Table of Content

21 December 2024, Volume 45 Issue 6

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Speech recognition for standard Chinese-speaking bimodal cochlear implant users in competitive noise

Zhang Xinyi, Chen Jingyuan, Chen Biao, Zou Xinyue, Shi Ying, Zhang Lifang, Liu Ping, Kong Ying, Li Yongxin

2024, 45(6):  938-945.  doi:10.3969/j.issn.1006-7795.2024.06.002

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Objective  To investigate the utilization of competitive speech by standard Chinese bimodal cochlear implant (BIM) users under  talker sex and spatial.Methods  The speech reception thresholds (SRT) of 11 standard Chinese BIM users were tested under 4 different spatial competitive speech noises. The four spatial competitive speech noise environments were recorded as middle male voice, middle female voice, two sides male voice and two sides female voice according to the gender and orientation of the masked noise. Subjects were assessed with BIM and cochlear implantation (CI) alone hearing assistance. The target sound is one male voice directly in front (0°), and the masking sound is two male or two female voices, coming from separately directly in front (0°) or from both sides (±90°).Results  There was no significant difference in SRT between the two groups (P> 0.05). The BIM group obtained masking release (MR) under talker sex cues, spatial cues, and talker sex+spatial cues, while the CI group obtained MR under talker sex, but masking inhibition under spatial cues and talker sex + spatial cues. There were no significant differences in MR between the three cues. There was no significant difference in MR between BIM group and CI group under talker sex cues and spatial cues, but there was difference between BIM group and CI group under talker sex+spatial cue (P= 0.013).Conclusions  Standard Chinese BIM users can use talker sex cues and spatial cues to separate competitive noise, but there is no significant difference in the ability to use talker sex and spatial cues between BIM and CI alone hearing aid, and the ability to use talker sex + spatial cues under BIM is better than that of cochlear alone hearing aid.

Long-term outcomes after cochlear implantation with customized electrodes via transmastoid slotted labyrinthotomy approach in patients with common cavity deformity

Zhang Lifang, Wei Xingmei, Kong Ying, Yang Mengge, Gao Zhencheng, Xue Shujin, Lu Simeng, Chen Biao, Chen Jingyuan, Shi Ying, Li Yongxin

2024, 45(6):  946-955.  doi:10.3969/j.issn.1006-7795.2024.06.003

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Objective  To investigate the long-term development of auditory and speech function after cochlear implantation (CI) using the transmastoid slotted labyrinthotomy approach (TSLA) with customized electrodes in patients with common cavity deformity (CCD).Methods  Thirty-six children with CCD, all of whom underwent unilateral CI, were included in this study, and 61 children match on age who underwent unilateral CI but with normal inner ear structure were selected as a control group from Beijing Tongren Hospital, Capital Medical University. The auditory and speech performance of all subjects were assessed by the professionals staff with uniform standardized training using the following assessment tools: Categories of Auditory Performance (CAP), Speech Intelligibility Rating (SIR), Infant-Toddler Meaningful Auditory Integration Scale/Meaningful Auditory Integration Scale (IT-MAIS/MAIS), and Meaningful Use of Speech Scale (MUSS). Assessments were performed at pre-surgery and 1, 3, 6, 12, 18, 24, 36, 48, 60, 72, and 84 months after CI switch-on.Results  The generalized estimating equation analysis suggested that the preoperative and postoperative auditory speech rehabilitation effects of the subjects in this study were statistically significant in terms of group, time, and their interaction effects (P<0.05). The differences in CAP scores of the CCD group  were statistically significant among preoperative and postoperative 1, 3, 6, 12, and 18 months after switch-on (P<0.05), while the increase stabilized among 24, 36, 48, and 60  months (P>0.05). The percentages of IT-MAIS/MAIS scores were significantly different among preoperative and postoperative 1, 3, 6, 12, and 24 months after switch-on (P< 0.05), with no significant difference among 24, 36, 48, and 60 months (P>0.05). SIR scores were not significantly different  among preoperative and 1, 3 months after switch-on (P>0.05), but significantly different among 6, 12, and 18 months after switch-on (P<0.05), again it showed no significantly difference among 18, 24, 36, 48, and 60 months after switch-on (P> 0.05). The percentages of MUSS score was not significantly different among preoperative and 1, 3 months after switch-on (P>0.05), among 3, 6, 12, and 18 months after switch-on (P<0.05), and among 24, 36, 48, and 60 months after switch-on (P>0.05).Compared with the control group, CCD group had significantly lower CAP scores and percentage of IT-MAIS/MAIS scores from 1 to 60 months after switch-on (P<0.05), and significantly lower SIR scores and percentage of MUSS scores from 3 to 60 months after switch-on (P<0.05). Conclusions  CI via the TSLA with customized electrodes can be effective in achieving long-term auditory and speech benefits in CCD children, but the development of auditory speech function is delayed after CI compared with that of children without structural abnormality of the inner ear. The development of auditory performance in children with CCD after CI shows a trend of rapid growth within 2 years of switch-on, and then a trend of slow growth after 2 years. The development of their speech ability shows a trend of rapid growth from 6 months to 18 months after switch-on, and then a trend of slow growth from 18 months to 7 years.

Anatomical characteristics of cochlear hypoplasia and postoperative outcomes of cochlear implantation

Xue Shujin, Wei Xingmei, Gao Zhencheng, Kong Ying, Lu Simeng, Chen Biao, Shi Ying, Cui Danmo, Li Yongxin

2024, 45(6):  956-965.  doi:10.3969/j.issn.1006-7795.2024.06.004

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Objective  To assess the morphological characteristics of the bony structure of the cochlea in patients with different subtypes of cochlear hypoplasia (CH) and to explore the relationship between the auditory and speech rehabilitation outcomes following cochlear implantation (CI) in patients with CH and the subtype of malformation as well as anatomical characteristics.Methods  Clinical data of CI patients diagnosed with CH at Beijing Tongren Hospital, Capital Medical University were collected and their postoperative outcomes were followed up. Temporal bone computed tomography (CT) 3D reconstruction technology was used to reconstruct 3D images of the cochlea in patients with different subtypes. Measurements and analyses were conducted on the cochlear length, cochlear width, cochlear height, cochlear volume, basal turn length, and cochlear duct length. A questionnaire was used to evaluate auditory and speech rehabilitation two years postoperatively. The study investigated the effects of different subtypes and cochlear nerve development on postoperative outcomes and explored the relationship between cochlear anatomical parameters and postoperative results.Results  Among 53 patients, a total of 102 ears were identified with CH malformations, with 9 ears having unique cochlear morphology that could not be classified into specific subtypes. Significant differences were found in the anatomical parameters among different CH subtypes (P<0.05). 54.90% of CH patients had concomitant cochlear nerve deficiency (CND). Postoperative follow-up was conducted on 38 of the patients. There were no significant differences in postoperative outcomes among different CH subtypes, but the presence of CND showed significant differences in  Categories of Auditory Performance （CAP）, the Speech Intelligibility Rating （SIR）  and  Meaningful Use of Speech Scale（MUSS） scores (P<0.01). In CH patients with normal cochlear nerve development, there was a positive correlation between postoperative outcome scores and several cochlear anatomical parameters.Conclusions  CH patients exhibit complex variations in cochlear morphology and a high probability of concurrent CND, resulting in significant individual differences in postoperative outcomes. Preoperative temporal bone CT 3D reconstruction can help in evaluating cochlear morphology, differential diagnosis of various subtypes, and identification of unique cochlear morphologies in CH patients. Patients with CND have poorer outcomes compared to those with normal cochlear nerve development. When cochlear nerve development is normal, better cochlear development correlates with better postoperative results. It is essential to perform a differential diagnosis and comprehensive evaluation of cochlear morphology and cochlear nerve development in CH patients preoperatively, to make reasonable predictions about surgical methods and postoperative outcomes.

A longitudinal study on the impact of cochlear implantation on vestibular function in children with inner ear malformations: a comparative analysis based on the test of  vestibular evoked myogenic potentials

Shen Mengya, Xue Shujin, Wei Xingmei, Kong Ying, Sun Jiaqiang, Li Yongxin

2024, 45(6):  980-988.  doi:10.3969/j.issn.1006-7795.2024.06.006

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Objective  To analyze the impact of cochlear implantation (CI) on vestibular evoked myogenic potentials (VEMPs) in children with congenital sensorineural hearing loss (SNHL), focusing on the potential changes in vestibular function after surgery.Methods  A total of 78 pediatric patients with SNHL, who were treated at Beijing Tongren Hospital, Capital Medical University between January 2021 and February 2023, were enrolled. The cohort was divided into two groups based on inner ear anomalies: 39 SNHL patients with normal inner ear structure and 39 patients with inner ear malformations, including 6 patients with large vestibular aqueduct syndrome, 13 patients with Mondini malformation, 5 patients with  vestibulocochlear  nerve deficiency, 2 patients with vestibular sac malformation, and 2 with narrow internal auditory canal. All patients underwent VEMPs test was performed preoperatively (T0) within one week, and at 1 month (T1), 6 months (T2), and 1 year (T3) post-CI. Chi-square tests and analysis of variance were applied to compare the differences in VEMPs parameters, including response rate, latencies, and amplitude, across all follow-up time and between the two groups.Results  Complete postoperative follow-up of cervical VEMP (cVEMP) was achieved in all 78 patients, The T0 cVEMP response rate was 69.23%, which significantly declined to 46.15%, 41.03%, and 58.97% at T1, T2, and T3, respectively (χ²=4.768, P=0.003). Notably, the P1 and N1 latencies significantly shortened at T1 (P=0.07, P=0.046). Among 48 patients who completed postoperative ocular VEMP (oVEMP) follow-up, the overall preoperative response rate was 75%, increasing to 81.25% at T1 but decreasing to 62.5% at both T2 and T3. The overall oVEMP response rate also showed a statistically significant difference pre- and post-CI (χ²=9.720, P=0.021). The duration of CI significantly influenced cVEMP-P1 latency, amplitude, and rectified amplitude (P=0.043 4, P=0.041, P=0.041, P<0.001), as well as oVEMP amplitude(P=0.043). No significant differences were observed in cVEMP response rates, latencies, or amplitudes at T3 compared to T0. However, oVEMP amplitudes at T2 and T3 were significantly different from T0 (P=0.038). No significant differences were observed in VEMP parameters between the inner ear malformation and non-malformation groups across T1-T3.Conclusions  VEMPs serve as a valuable tool for assessing vestibular function before and after CI in children with SNHL. The duration of CI is a crucial factor influencing VEMPs changes.  Inner ear malformations may impact otolithic function post-CI, with a more pronounced effect observed over time. The VEMP test results could provide insights for selecting the optimal side for CI placement.

Surgical technique of cochlear implantation in patients with facial nerve developmental abnormalities obstructing round window

Cui Danmo, Xue Shujin, Wei Xingmei, Chen Biao, Zou Xinyue, Li Yongxin

2024, 45(6):  989-994.  doi:10.3969/j.issn.1006-7795.2024.06.007

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Objective  To  explore the application of  the surgical technique of cochlear implantation (CI) in patients with facial nerve developmental abnormalities obstructing round window. Methods  A retrospective analysis  of medical history, audiological data, imaging data and surgical methods was conducted on the clinical data of 6 severely or extremely severely deaf patients with facial nerve developmental abnormalities obstructing round window from March 2009 to July 2023. Results  Among the 6 patients, 1 patient underwent oval window implantation, 2 patients underwent retro-facial approach implantation, and 3 patients underwent ear canal or ear canal/posterior combined approach implantation. Six patients were successfully implanted with electrodes. One patient showed no significant change in facial paralysis after surgery compared to before, and the others did not experience facial nerve damage after surgery. all 6 patients experienced complications such as collapse of the posterior wall of the external auditory canal and cerebrospinal fluid ear fistula. Conclusions  When abnormal facial nerve development is found during CI surgery in patients with severe or extremely severe hearing loss, various pathways can be selected based on the shape of the facial nerve to complete cochlear electrode implantation.

Surgical techniques and postoperative outcomes of cochlear implantation for incomplete partition type I with cerebrospinal fluid leak

Xue Shujin, Wei Xingmei, Chen Biao, Gao Zhencheng, Cui Danmo, Shi Ying, Chen Jingyuan, Kong Ying, Li Yongxin

2024, 45(6):  995-1000.  doi:10.3969/j.issn.1006-7795.2024.06.008

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Objective  To explore the surgical technique for cochlear implantation and simultaneous repair of cerebrospinal fluid (CSF) leaks in patients with incomplete partition type I (IP-I) combined with CSF leakage, as well as the postoperative control of CSF leaks and auditory-verbal rehabilitation outcomes. Methods  A retrospective analysis was conducted on the clinical data and postoperative follow-up results of 8 patients with IP-I combined with CSF otorrhea. All patients underwent cochlear implantation and simultaneous repair of CSF otorrhea via a transmastoid lateral semicircular canal approach. Antibiotic treatment was administered within the first week postoperation, and cochlear implants were activated one month post-surgery, followed by auditory-verbal rehabilitation training. Results  Cochlear implant electrodes were successfully implanted in all patients. The follow-up period ranged from 1 to 17 years, during which no patients experienced recurrent CSF otorrhea, and all patients had varying degrees of auditory benefit. Conclusions  The surgical method of cochlear implantation with simultaneous repair of CSF otorrhea via a transmastoid lateral semicircular canal approach effectively resolved  symptoms associated with IP-I combined with CSF leakage, prevented the recurrence of CSF leaks, and aided in hearing reconstruction.

Advance of cochlear implantation for inner ear malformation

Wei Xingmei, Li Yongxin

2024, 45(6):  1001-1007.  doi:10.3969/j.issn.1006-7795.2024.06.009

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Inner ear malformation (IEM) primarily refers to malformations of the bony labyrinth. Currently, patients with IEM can benefit from cochlear implantation (CI), but the surgical difficulty and risks are greater compared to those with normal cochleae. This article summarizes the technical challenges of CI surgery in IEM patients, such as the prevention and management strategies for facial nerve malformations, cerebrospinal fluid otorrhea, and electrode malposition, as well as surgical strategies regarding electrode selection and the choice of implantation side. We also discusses the characteristics of postoperative outcomes and programming. Furthermore, using bibliometrics, this article highlights the research hotspots in CI surgery for IEM patients and forecast the future of research prospects.

Effect of autophagy inhibitor 3-MA on inflammatory response in the brain of rats with cerebral ischemia/reperfusion injury

An Qi, Yang Nan, Zhu Yuequan, Shi Wenjuan, Huang Minqi, Zhao Yongmei

2024, 45(6):  1008-1015.  doi:10.3969/j.issn.1006-7795.2024.06.010

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Objective  To investigate the effects of the autophagy inhibitor 3-methyladenine (3-MA) on C-X-C chemokine receptor type 2 (CXCR2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and cyclooxygenase-2 (COX2) in the ischemic brain tissue of rats subjected to transient focal cerebral ischemia/reperfusion, in order to explore the role of autophagy in inflammation during cerebral ischemia/reperfusion injury. Methods  The male Sprague Dawley rats were randomized into: sham group, middle cerebral artery occlusion (MCAO) group and MCAO+3-MA (3-MA) group, with n=5 for each group. A model of MCAO was induced by using the intraluminal suture method. The rats underwent 90 minutes of ischemia. Rats in 3-MA group were intraperitoneally injected with 10 mg/kg of 3-MA before MCAO. All groups of rats underwent reperfusion for 24 h. After reperfusion time, the rats were quickly decapitated, and their brains were removed. The levels of CXCR2 protein in the ischemic brain tissue were detected by Western blotting. The number of positive cells of TNF-α, IL-1β, and COX2 were detected by immunofluorescence staining in the ischemic penumbra, and the cellular localization of IL-1β and COX2 was evaluated respectively. Results  ①Compared with sham group, the level of CXCR2 protein was upregulated obviously in the ischemic brain tissue of MCAO rats after 24 h reperfusion (P < 0.05). The level of CXCR2 protein decreased significantly in the ischemic brain tissue of 3-MA group compared with that of MCAO group (P < 0.05). ②There were few TNF-α, IL-1β, and COX2 positive cells in the sham group. Compared with sham group, the number of TNF-α, IL-1β, and COX2 positive cells in the ischemic penumbra of MCAO group rats obviously increased after 24 h of reperfusion (P < 0.05). Compared with MCAO group, the number of positive cells of TNF-α, IL-1β and COX2 decreased significantly in the ischemic penumbra of the MCAO+3-MA group rats (P  < 0.05). ③The IL-1β and COX2 positive cells were colocalized with NeuN, a general neuronal marker, in the ischemic penumbra of cerebral ischemia/reperfusion rats. Conclusions  The autophagy inhibitor 3-MA may attenuate inflammation by inhibiting the expression levels of chemokine receptor CXCR2, as well as the number of positive cells of TNF-α, IL-1β, and COX2 inflammatory factors in ischemic brain tissue of MCAO rats after reperfusion, indicating that autophagy is one of the factors that promote the inflammatory response after ischemia.

Effect of mitochondrial reactive oxygen species inhibitor EUK-134 on mitochondrial associated proteins PGC-1α and VDAC1 in rats with cerebral ischemia-reperfusion injury

Li Yakun, Li Wei, Yang Xueqi, Shi Wenjuan, Zhu Yuequan, Zhao Yongmei

2024, 45(6):  1016-1022.  doi:10.3969/j.issn.1006-7795.2024.06.011

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Objective  To investigate the effects of Eukarion-134 (EUK-134), a scavenger of reactive oxygen species (ROS), on peroxisome proliferator activated receptor gamma coactivator-1α (PGC-1α) and mitochondrial voltage-dependent anion channel 1 (VDAC1) in middle cerebral artery occlusion (MCAO) and reperfusion rats, and to explore the impact of ROS generation on mitochondrial structure and function after cerebral ischemia. Methods  Healthy male Sprague Dawley (SD) rats were divided into three groups with a random number table method: Sham group, MCAO group, and MCAO+EUK-134 (EUK-134) group, with 6 rats in each group. A model of MCAO was induced with the intraluminal suture method. The rats underwent 90 min of MCAO and then were reperfused for 24 h by withdrawal of the filament. The heart rate, mean arterial pressure, and temperature were maintained in the normal range during surgery. EUK-134(10 mg/kg) was injected subcutaneously in rats of the EUK-134 group, and rats in the sham and MCAO groups received equal volumes of solvent. The expression of PGC-1α in ischemic brain tissue was assessed by Western blotting. Immunofluorescence staining was applied to detect the expression of VDAC1 in the ischemic penumbra of rats. The ROS positive cells were labeled with an oxidant-sensing fluorescent probe (2′,7′-dichlorofluorescin diacetate, H2DCF-DA) staining, and double staining for VDAC1 and ROS were performed. Results  ① The expression of PGC-1α protein level in the ischemic brain tissue of rats in the MCAO group after 24 h reperfusion was significantly lower than that of the sham group (P<0.05). The PGC-1α protein level in the ischemic brain tissue of the EUK-134 group was significantly higher than that of the MCAO group (P<0.05).  ② After 24 h reperfusion, the number of VDAC1 positive cells in the ischemic penumbra of the MCAO group increased significantly compared to the sham group (P<0.05), while the number of VDAC1 positive cells in the ischemic penumbra of the EUK-134 group was significantly lower than that of the MCAO group (P<0.05). VDAC1 positive cells were colocalized with the neuronal marker NeuN in the brain ischemic penumbra. ③ In the MCAO group, VDAC1 positive cells were colocalized with ROS in the ischemic penumbra, and the number of VDAC1/ROS double positive cells was considerably increased compared to that of the sham group (P<0.05). The number of VDAC1/ROS double positive cells in the penumbra of EUK-134 treated rats decreased significantly compared to the MCAO group (P<0.05). Conclusions  The ROS scavenger EUK-134 could maintains mitochondrial function by affecting the expression of the mitochondrial biogenic regulator PGC-1α and the substance transport channel VDAC1, thereby ameliorating cerebral ischemia-reperfusion injury.

Effect of remimazolam and propofol on postoperative delirium in elderly patients undergoing cerebral endovascular surgery

Liu Yang, Gao Chao, Wang Xiaojie, Zhang Liang, Wu Anshi

2024, 45(6):  1023-1028.  doi:10.3969/j.issn.1006-7795.2024.06.012

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Objective  To compare the effects of remimazolam and propofol on postoperative delirium （POD） in elderly patients undergoing cerebral endovascular surgery. Methods  A controlled clinical trial was conducted on patients who underwent cerebral endovascular surgery in Beijing Chaoyang Hospital, Capital Medical University from June 2023 to April 2024. The patients were divided into remimazolam group (group R) and propofol group (group P). A total of 106 patients were included, with 53 in each group. The primary outcome was the incidence of POD from 30 min to 7 days after extubation between the two groups. The secondary outcomes included  the  time to recovery from anesthesia, the incidence of delayed extubation, the incidence of cardiovascular adverse events, the use of vasoactive drugs and the antagonist flumazenil, and the Quality of Recovery-15 (QoR-15) questionnaire at 48 h after surgery. Results A total of 103 patients (51 in group R and 52 in group P)  finally completed in the study. There was no statistical difference in the incidence of POD (5.88% vs 3.85%) between the two groups within 7 days after surgery (P >0.05). The incidence of intraoperative hypotension and bradycardia was significantly lower in group R (19.60%, 9.80%) than in group P (53.85%, 25.00%) (P =0.001 3，P =0.042). Compared with that in group P, the number of cases using norepinephrine and ephedrine,  in group R was significantly lower (P =0.020, P =0.033). There was no statistical difference in the time to recovery from anesthesia and  dose not increase the dosage of flumazenil antagonists between the two groups (P >0.05). There was no statistical difference in QoR-15 at 48 h after surgery between the two groups (P >0.05). Conclusions  The anesthetization with remimazolam show more stable hemodynamics dose not prolong  the time to recovery from anesthesia and  does not increase  the incidence of POD in elderly patients undergoing cerebral endovascular surgery.

Effects of GLP-1 receptor agonists on cognitive function in patients with type 2 diabetes mellitus after acute ischemic stroke

Li Xingmao, Li Xiu, Wang Ting, Zhao Xin, Wang Deyang, Shang Haiyan, Zhao Yongmei, Li Sen

2024, 45(6):  1029-1037.  doi:10.3969/j.issn.1006-7795.2024.06.013

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Objective  To investigate the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RA) on cognitive function in patients with type 2 diabetes mellitus (T2DM) after acute ischemic stroke.  Methods  A case-control study was conducted, involving 249 patients with acute ischemic stroke combined with T2DM. The patients were divided into two groups based on whether they had regularly used GLP-1 RA (with semaglutide as a representative) or not (insulin therapy). Baseline demographic characteristics, biochemical test results, and blood glucose monitoring levels during hospitalization were recorded. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and patients with a score below 26 were excluded. A total of 219 eligible patients were followed up 3 months after the stroke, and cognitive function was reassessed using the MoCA score, with a score below 22 indicating post-stroke cognitive impairment (PSCI). Binary Logistic regression analysis was used to compare the cognitive function scores between the two groups and to analyze the differences in ankle-brachial index and derived time in range (dTIR) between patients with different scores.  Results  By the end of the study, 32 out of 110 patients in the GLP-1 RA group developed PSCI, with an incidence rate of 29.09%. In the non-GLP-1 RA group, 45 out of 109 patients developed PSCI, with an incidence rate of 41.28%. Cognitive function scores showed that semaglutide intervention significantly reduced the incidence of PSCI. Binary Logistic regression analysis indicated that the odds ratio for semaglutide intervention was 2.285, while that for the dTIR parameter was 0.985.  Conclusions  GLP-1 RA therapy can reduce the severity of PSCI in patients with ischemic stroke combined with T2DM.

Prediction and analysis of cross immune genes between oral squamous cell carcinoma and Sjogren's syndrome

Yuan Wensi, Wu Yaheng, Wu Dongxue, Zhou Yan

2024, 45(6):  1038-1049.  doi:10.3969/j.issn.1006-7795.2024.06.014

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Objective  To screen the cross immune genes (CIGs) and immune infiltration status of oral squamous cell carcinoma (OSCC) and Sjogrens syndrome (SS) in the transcriptional level by bioinformatics analysis to provide scientific basis for diagnosis and therapy of OSCC in SS patients. Methods  OSCC and SS datasets were downloaded from GEO database. The differentially expressed genes (DEGs) in OSCC and SS were screened by limma R package combined with Venn map, and then the CIGs were obtained by cross screening with immune gene datasets. Least absolute shrinkage and selection operator (LASSO) regression was used to screen core CIGs. The CIBERSORT R package was used to analyze the type and ratio of the infiltrated immune cells. Results  We screened 2 885 DEGs by OSCC dataset and 2 472 DEGs by SS dataset, then 55 CIGs were predicted via further intersecting with DEGs; second cross screening following LASSO regression analysis showed that RASGRP3 was a potential core CIG, and was upregulated in both OSCC and SS. Besides, immune infiltration of memory CD4⁺T cells, macrophage and activated natural killer (NK) cells were associated with RASGRP3 levels in OSCC and SS. Conclusions  The oncogene RASGRP3 can serve as a potential therapeutic target and biomarker for SS and OSCC. RASGRP3 was closely related to CD4⁺T cells, macrophage and activated NK cells, which might provide a new idea for exploring the immunotherapy strategy of OSCC for SS patients.

Observation on the improvement of Si-Miao-Yong-An decoction based on KAS-seq sequencing and its promotion of wound healing in mice with diabetic foot

Li Xuehui, Chen Hangyu, Ma Ruiyao, Lin Jian, Li Linlin

2024, 45(6):  1050-1061.  doi:10.3969/j.issn.1006-7795.2024.06.015

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Objective  Based on modern scientific technology, the Si-Miao-Yong-An decoction was improved to verify its effect in promoting the healing of diabetic foot wounds.   Methods  The kethoxal-assisted single stranded DNA sequencing (KAS-seq)  technology was utilized to detect wound tissues from diabetic foot patients and normal wound tissues, to screen for key genes associated with diabetic foot. Combining network pharmacology, targeted traditional Chinese medicines were identified based on these key genes to modify the traditional formula Si-Miao-Yong-An decoction. Finally, the therapeutic effect of the modified formula was verified through an animal model of diabetic foot.  Results  Through clinical sample sequencing analysis, 8 key genes, including CREB1, GRID2, PIK3R3, DRD2, ADORA1, TNFSF11, EDNRB, HTR1B were obtained. These genes were targeted to Huang Bai, Cang Zhu, Di Huang, and Ban Xia, four traditional Chinese medicines combined in the prescription. On the 7th day of intragastric intervention, the wound healing efficiency of the S+ group mice was significantly higher than that of the control group (P<0.05), and on the 12th day, the wound healing rate of the S+ group mice was significantly higher than that of the S group (P<0.05). The target points of the modified prescription were more enriched in the neural system, hypoxia, and blood circulation regulation-related pathways compared to the original prescription. Conclusions  Compared to the original prescription, the modified prescription has a better effect on promoting the healing of diabetic foot wounds. The related mechanism may be associated with the regulation of inflammation, improvement of peripheral nerve damage, and promotion of wound healing pathways. This approach also provides a new perspective and a basis in modern scientific theory for the clinical application and modification of traditional Chinese medicine prescriptions.

The p38 MAPK signaling pathway mediates the reduction of apoptosis, inflammation and oxidative stress levels in AD mice by cerebroprotein

Gou Dongyun, Liang Jiayi, Guo Ziyu, Yan Fangyuan, Wang Shuaixiang , Qu Shuo, Gao Yan, Zhang Yujia, Ma Xiaowei

2024, 45(6):  1062-1070.  doi:10.3969/j.issn.1006-7795.2024.06.016

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Objective  Our objective was to examine the potential of cerebroprotein hydrolysate for injection I (CH-I) in mitigating oxidative stress, apoptosis, and neuroinflammation in an Alzheimer's disease (AD) model, while also gaining a better understanding of the underlying mechanisms. Methods  AD mouse model was established through the intrahippocampal injection of amyloid-β_1-42. The experiment consisted of four groups: Control (Con) group, Aβ group, Aβ+CH-I group, and CH-I group. The learning and memory abilities of the mice were assessed using the new object recognition experiment and Y-maze. Enzyme-linked immunosorbent assay was employed to measure the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thioredoxin, and catalase (CAT) in brain tissue. Additionally, Tunel staining was utilized to evaluate the levels of cell apoptosis. Aβ group and Aβ+CH-I group were extracted for RNA-seq and bioinformatics analysis and verification.Western blotting analysis was conducted to detect proteins associated with the pathway ［c-Jun N-terminal kinase (JNK),  mitogen-activated protein kinase (MAPK), p38 MAPK］. Results  In comparison to the Con group and the Aβ+CH-I group, the Aβ group exhibited a significant decrease in the proportion of time allocated to exploring novel arms/objects. Moreover, the Aβ group displayed significantly lower levels of SOD and GSH-Px activities in mice, in contrast to both the Con group and the Aβ+CH-I group, with statistically significant distinctions. The RNA-seq analysis demonstrated a significant downregulation of the MAPK signaling pathway in the Aβ+CH-I group compared to the Aβ group. Additionally, the Aβ+CH-I group exhibited noteworthy reductions in apoptosis levels, p38 MAPK protein, and inflammation levels when compared to the Aβ group. Conclusions  CH-I exerts neuroprotective effects through the modulation of the p38 MAPK signaling pathway, thereby conferring neuronal resistance against oxidative stress and apoptosis. 

Correlation analysis of plasma YAP level with stroke prognostic factors and post-stroke inflammation

Shen Tong, Li Fangfang, Fan Junfen, Luo Yumin

2024, 45(6):  1071-1078.  doi:10.3969/j.issn.1006-7795.2024.06.017

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Objective  This study aims to investigate the relationship of peripheral yes-associated protein (YAP) level in patients with acute ischemic stroke (AIS) with prognostic influencing factors and inflammatory indicators. Methods  AIS patients admitted to Xuanwu Hospital of Capital Medical University from November 2018 to May 2019 were enrolled in this study. Expression levels of YAP and inflammatory markers in plasma were detected, and the clinical data and 3-month prognostic data of the patients were collected by experienced neurologists. According to the 3-month modified Rankin Scale (mRS) score, the patients were divided into good outcome group (mRS≤2, n=92) and poor outcome group (mRS>2, n=67). Multivariate Logistic regression analysis was used to identify independent risk factors related to AIS prognosis. Furthermore, Spearman correlation analysis and partial correlation analysis were conducted to explore the relationship of YAP concentration with these prognostic influencing factors and inflammatory indicators. Results Compared with the good outcome group, the poor outcome group exhibited significantly higher white blood cell counts, neutrophil counts, and neutrophil-lymphocyte ratios (NLR), along with significantly lower lymphocyte counts (P<0.05). Logistic regression results indicated that older age (OR=1.04, P=0.013), diabetes mellitus (OR=3.87, P=0.004), and higher admission National Institutes of Health Stroke Scale (NIHSS) scores (OR=1.36, P<0.001) are risk factors for prognosis. Correlation analysis showed that plasma YAP levels were positively correlated with lymphocyte counts (r=0.22, P=0.006), IL-1β (r=0.418, P<0.001), IL-2 (r=0.310, P<0.001), IL-5 (r=0.417, P<0.001), and IL-10 (r=0.189, P=0.017), while being negatively correlated with neutrophil counts (r=－0.17, P=0.027), NLR (r=－0.24, P=0.002), IL-2R (r=－0.259, P<0.001), IL-16 (r=－0.334, P<0.001), and (hepatocyte growth factor, HGF) (r=－0.317, P<0.001). Partial correlation analysis indicated that the correlation between YAP protein levels and IL-2, IL-16, and HGF was not affected by other variables (P<0.05). Conclusions  There is a significant correlation between plasma YAP levels and various inflammatory indicators, suggesting that YAP may be involved in the regulation of inflammatory response after stroke.

Effect of monocyte/high density lipoprotein-cholesterol ratio  combined with body mass index in evaluating insulin resistance

Zhu Yingna, Li Xiaohui, Yuan Mingxia

2024, 45(6):  1079-1087.  doi:10.3969/j.issn.1006-7795.2024.06.018

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Objective  To explore the value of monocyte/high density lipoprotein-cholesterol ratio (MHR) combined with body mass index (BMI) in evaluating insulin resistance (IR) in the patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods  A total of 400  T2DM patients who were newly diagnosed in Department of Endocrinology, Beijing Friendship Hospital, Capital Medical University, were enrolled in the study from January 2022 to December 2023. The inflammatory markers included white blood cell, neutrophile granulocyte, lymphocyte, monocyte and high sensitivity C-reactive protein (HsCRP) were examined, together with metabolic indicators included blood glucose, insulin and lipid. According to median value of homeostasis model assessment of insulin resistance (HOMA-IR), participants were divided into high-HOMA-IR and low-HOMA-IR group. According to the MHR tertiles, three groups were divided into Q1(MHR≤0.25)、Q2(0.25<MHR≤0.34) and Q3(MHR>0.34) for analysis and comparison. Spearman correlation analysis and multiple logistic regression were used to analyze the relationship between MHR, BMI and IR. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of MHR combined with BMI on IR.  Results  Both the HsCRP level ［2.77 (1.06，5.46) vs 1.43(0.69, 2.94), P<0.001］ and the MHR in high-HOMA-IR group ［0.32 (0.26, 0.41) vs 0.27 (0.21, 0.34)］ was significantly higher than that of low-HOMA-IR group (P<0.001). HOMA-IR in MHR Q3 group was significantly higher than that in Q2 and Q1 groups (P<0.001). Spearman correlation analysis showed that HOMA-IR was positively correlated with MHR (r=0.294, P<0. 001)、HsCRP (r=0.281, P<0. 001) and BMI (r=0.501, P<0.001). Logistic regression analysis showed that MHR and BMI were independent influencing factors of HOMA-IR, the OR values are respectively 1.766(95%CI:1.189-2.625, P= 0.005) and 1.192 (95%CI:1.052-1.351, P = 0.006).  ROC curve analysis showed that compared with MHR and BMI, the area under ROC curve by the combined coefficient of MHR and BMI was the largest 0.754 (95%CI:0.706-0.801), with the highest efficiency in the diagnosis of insulin resistance.  Conclusions  MHR combined with BMI has a higher efficiency for evaluating IR in the patients with newly diagnosed T2DM, which could be used as a simple indicator to evaluate IR in these patients.

Development and reliability and validity testing of a health comprehensive evaluation scale for elder population in medical institutions of Beijing

Zhao Wenzhi, Peng Lu, Zhang Xiaowei, Wang Xin, Yang Liuqing, Shi Hanping

2024, 45(6):  1088-1094.  doi:10.3969/j.issn.1006-7795.2024.06.019

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Objective  To develop a health comprehensive evaluation scale for elder population seeking medical advice or care in medical institutions of Beijing and test the reliability and validity.  Method  To put together an initial scale through literature review, expert seminar and Delphi expert consultations. There were 60 elderly patients selected to participate the pre-experiment to and the initial scale improved. Total of 461 elderly patients were analyzed in the preliminary testing of validity and reliability and item discrimination, correlation analysis, exploratory factor analysis and internal consistency check was conducted for items screening. Total of  347 elderly patients were recruited in the second testing, and test-retest reliability, rater consistence reliability and predictive validity was conducted. Result  There were 5 dimensions (clinical complexity;medication treatment; diet, nutrition, and lifestyle; signs and symptoms;functional status) and  26 items contained in the formal scale. For the whole scale the split-half reliability was 0.631, and the Cronbach's α coefficient was 0.665, and the test-retest reliability was 0.739, and the rater consistence reliability was 0.747. There was significant correlation between score of the scale and common blood tests index (albumin, hemoglobin), physical examination index (body mess index, grip strength, calf circumference), nutritional screening scale, and hospitalization duration.Conclusions  The preliminary work was finished by developing a health comprehensive evaluation scale with acceptable reliability and validity, which was suitable for elder population seeking medical advice or care in medical institutions of Beijing.

A study on the  correlation between serum visfatin and coronary artery calcification in maintenance hemodialysis patients

Jiao Jian, Wang Xiaoqi, Shao Feng, Yuan Dan, Li Zhongxin

2024, 45(6):  1095-1099.  doi:10.3969/j.issn.1006-7795.2024.06.020

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Objective  To investigate the correlation between serum visfatin and coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients. Methods  In this cross-sectional study, the general data of MHD patients in Beijing Luhe Hospital, Capital Medical University  were collected from July 1, 2023 to February 29, 2024. The serum visfatin level were detected.CAC level was evaluated by low-dose chest multi spiral  computed tomography (CT). According to the results of CT, the patients were divided into 2 groups, clinical characteristics were compared between 2 groups, multivariate Logistic regression was used to analyze the independent influencing factors of CAC. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of influencing factors for CAC in MHD patients. Results  Totally 135 MHD patients were enrolled in this study and divided into non-CAC group (n=39) and CAC group (n=96).There were significant differences in age, diabetes mellitus, visfatin, blood glucose, serum sodium and urea clearance index(Kt/V)  between the two groups (P<0.05). Multivariate Logistic regression analysis showed that older age, higher serum visfatin level and diabetes were independent risk factors for CAC in MHD patients. ROC curve showed that the area under the curve (AUC) of serum visfatin for predicting CAC in MHD patients was 0.751 (P<0.01), which had high predictive value. Conclusions  Increased serum visfatin level is an independent risk factor for CAC, and may be a potential biomarker for predicting CAC in MHD patients.

Association between plasma trimethylamine-N-oxide level and type 2 diabetes mellitus

Li Xiaojing, Liu Hongzhou, Dong Song, Wang Hong

2024, 45(6):  1100-1105.  doi:10.3969/j.issn.1006-7795.2024.06.021

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Objective  To investigate the association of plasma trimethylamine-N-oxide (TMAO) with type 2 diabetes mellitus (T2DM). Methods  The total of 119 T2DM inpatients at the Department of Endocrinology, Aerospace Center Hospital from July 2021 to October 2021 were enrolled in the present study. The 55 healthy subjects who had physical examinations in Aerospace Center Hospital during the same period were also collected as the control group. General data of all subjects were recorded. Concentrations of plasma TMAO were measured by the enzyme-linked immunosorbent assay. The relationship between plasma TMAO and T2DM was analyzed. Results  The patients with T2DM were older and had higher systolic blood pressure, diastolic blood pressure, triglyceride, fasting blood glucose and glycosylated hemoglobin.On the other side, serum albumin, high density lipoprotein-cholesterol, and low density lipoprotein-cholesterol were lower in the T2DM group than in the control group (P<0.05). As compared with the control group, the T2DM patients showed a significantly higher plasma TMAO ［(137.83±11.80) pg/mL vs (122.65±10.93) pg/mL, P<0.05)］. Logistic regression analysis found that age (OR=1.268, 95%CI: 1.055－1.523, P=0.011) and plasma TMAO concentration (OR=1.186, 95%CI: 1.005－1.399, P=0.043) were independently associated with T2DM after adjustment for confounding factors. Conclusions  T2DM patients showed a higher plasma TMAO level, and T2DM was associated with plasma TMAO.

Investigation of glucose metabolism abnormalities and related influencing factors in patients with different stages of chronic kidney disease

Zhang Lan, Ma Yingchun

2024, 45(6):  1106-1110.  doi:10.3969/j.issn.1006-7795.2024.06.022

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Objective  To investigate the prevalence of glucose metabolism abnormalities and related influencing factors in patients with different stages of non-diabetic chronic kidney disease (CKD). Methods  A total of 140 patients with CKD in each stage of the Department of Nephrology, Beijing Bo’ai Hospital, China Rehabilitation Research Center, were selected from April 2020 to April 2022. Among them, 34 were early in CKD (CKD1-3a), 35 were in middle (CKD3b-4), and late stage (CKD5) was 71 cases. The demographic data and clinical biochemical indexes of the patients were recorded, and oral glucose tolerance test (OGTT)  was performed to measure blood glucose, insulin and C-peptide levels at 0, 1, and 2 h, a total of 71 patients completed the OGTT. Results  ① The prevalence of impaired glucose tolerance in the early, middle and late stages of CKD was 42.1%, 41.2%, and 37.1%；The prevalence of dominant diabetes in the early, middle and late stages of CKD was 42.1%, 17.6%, 34.3%;and the abnormal fasting blood glucose in the early, middle, and late stages of CKD was 29.4%, 14.3%, and 14.1%; ② Factors such as gender, blood albumin (ALB), hemoglobin, blood pressure, and blood lipid were corrected, and multivariate Logistic regression analysis revealed that the influencing factors of abnormal glucose metabolism in CKD patients were age, body mass index (BMI), and uric acid, the OR value was 1.057, 1.132, 1.007, with P values was 0.028, 0.035, and 0.012, respectively. That is, the risk of abnormal glucose metabolism increased by about 57% for every 10 years of age, 13.2% for every 1 kg/m2 of BMI, and 70% for every 100 μmol/L of uric acid. Conclusions  ①The prevalence of impaired glucose tolerance in CKD patients is as high as 39.4%, and the proportion of patients with new-onset diabetes is 32.4%, which are significantly higher than the general population (15.5% and 9.7%). ②Patients with CKD have abnormal glucose metabolism in the early stage. ③The influencing factors of abnormal glucose metabolism in CKD patients are age, BMI and uric acid.

Advances in clinical application and perioperative studies of glucagon-like peptide-1 receptor agonists

Wang Tianyuan, Yu Yun, Han Ruquan

2024, 45(6):  1115-1121.  doi:10.3969/j.issn.1006-7795.2024.06.024

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Glucagon-like peptide-1 receptor agonists (GLP-1RA) have an important therapeutic role in controlling blood glucose levels in patients with type 2 diabetes mellitus (T2DM)  and reducing body weight in obese patients. Recent studies have showed that by acting on GLP-1R distributed throughout the body, the drug may also have some effect on other important systems of the body, such as reducing the incidence of cardiovascular events, delaying the progression of chronic kidney disease, and increasing the risk of adverse events in the digestive system. As the use of this drug increase in the population, the potential for patients to experience an increase in perioperative adverse events such as delayed gastric emptying and the occurrence of reflux aspiration needs to be emphasized. This article summarizes the pharmacological characteristics of these drugs and their perioperative studies as follows.

Artificial intelligence: a powerful enabler for the new era of chemistry, pharmacy and medical research—the 2024 Nobel Prize in Chemistry

Lu Yu, Yu Shufan, Jiang Bingyin, Wang Yuji

2024, 45(6):  1131-1137.  doi:10.3969/j.issn.1006-7795.2024.06.026

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On Oct. 9, 2024, the Royal Swedish Academy of Sciences has announced that half of the 2024 Nobel Prize in Chemistry was awarded to American chemist David Baker for his contributions to computational protein design, while the other half was jointly awarded to Demis Hassabis and John M. Jumper of London-based artificial intelligence company Google DeepMind for their contributions to protein structure prediction.