1.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
2.Reliability and validity of the Chinese version of Amyotrophic Lateral Sclerosis Impairment Multidomain Scale
Shilei WAN ; Dan YANG ; Nianquan LIU ; Qianping JIANG ; Dandan XU ; Yan ZHAO ; Jing ZHOU
Journal of Chongqing Medical University 2025;50(11):1578-1586
Objective:To translate Amyotrophic Lateral Sclerosis Impairment Multidomain Scale(AIMS)into Chinese,and to investi-gate its reliability and validity among Amyotrophic Lateral Sclerosis(ALS)patients.Methods:A total of 161 ALS patients who were registered in the registry system of Integrated Traditional Chinese and Western Medicine Treatment Center for Motor Neuron Disease in Hubei Provincial Hospital of Traditional Chinese Medicine from August 2023 to July 2024 were enrolled as subjects,and the Chinese version of AIMS was used for investigation after translation and revision.The Rasch model was used to assess the unidimensionality,in-ternal consistency,content validity,construct validity,and criterion-related validity of the questionnaire,and the classical test theory was used for item analysis,test-retest reliability analysis,and criterion-related validity analysis.Results:Unidimensionality testing showed that all three dimensions of AIMS have good unidimensionality.For all items except item 18,information-weighted fit statis-tic mean square(Infit MNSQ)and outlier-sensitive fit statistic mean square(Outfit MNSQ)ranged from 0.5 to 1.5,and point-measure correlation(PT-Measure)ranged from 0.63 to 0.87.The threshold between adjacent options of each item was>1.4 logit.Wright maps showed that item difficulties ranged from-2.24 to 2.08 logit,and the differential item functioning analysis showed that the absolute values of differences between patients across different char-acteristic subgroups were<1 logit.The overall scale and each di-mension had a reliability of>0.9,with an individual reliability of>0.7.The dimension of respiration had a separation index of 1.56,while the overall scale and the other dimensions had a separation in-dex of>2.The item analysis showed that the correlation coefficient between the items in each dimension and their respective dimen-sions ranged from 0.622 to 0.865(P<0.01).The overall scale and the dimensions of medulla oblongata,motor,and respiration had a test-retest reliability of 0.994,0.970,0.990,and 0.972,respectively(P<0.01).The criterion-related validity analysis showed that the correlation coefficients of total score and the score of each dimension between the Chinese version of AIMS and the revised version of AIMS were 0.863,0.829,0.876,and 0.755,respectively(P<0.01).Conclusion:The Chinese version of AIMS has a good degree of fit-ting and relatively high levels of reliability and validity,with moderate item difficulty,reasonable option settings,and high overall qual-ity,and it is suitable for the functional assessment of ALS patients in China.
3.A retrospective study of the efficacy of endovascular therapy for acute symptoms of internal carotid artery occlusion
Pinyuan ZHANG ; Jiren ZHANG ; Dongman ZHAO ; Shilei QI ; Guoying DU ; Jian YANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(6):916-924
Objective To explore the influencing factors of poor prognosis after successful recanalization of symptomatic acute internal carotid artery occlusion(AICAO)by applying endovascular therapy(EVT)technology.Methods We made a retrospective analysis of the clinical and imaging data of 62 symptomatic AICAO patients.After collateral evaluation and recanalization therapy,we obtained flat CT and DSA images,together with the findings of the collateral circulation assessment.At 24.0±6.0 hours after surgery,head plain CT scans were reexamined,and at 14 days after surgery or at discharge,neurological function was assessed using the NIHSS scale.Using the modified Rankin scale,we assessed neurological function and prognosis over a 90-day period.Results Each of the 62 patients had a TICI grade of 2b or 3 and was successfully recanalized.On average,it took 124.36±66.31 minutes from puncture to recanalization.Two instances involved iatrogenic dissection,while twelve cases had intraoperative distal thrombus escape episodes.Of all the patients,32 ones(51.6%)had a fair prognosis,whereas 30 patients(48.4%)had a bad prognosis.The two patient groups differed significantly in the ASPECT score,preoperative NIHSS score,intraoperative balloon catheter usage,postoperative 24 hour and 14 days NIHSS score,postoperative 14 days neurological function,and all-cause mortality within 90 days(all P<0.05).The best intervention threshold for preoperative NIHSS score was 11.5 points,and both the preoperative NIHSS score and intraoperative BGC utilization were independent predictors influencing poor outcome.Conclusion The preoperative NIHSS score and intraoperative BGC usage are independent predictors of 90-day poor prognosis in AICAO patients with symptomatic AICAO who underwent successful recanalization via endovascular therapy.
4.A retrospective study of the efficacy of endovascular therapy for acute symptoms of internal carotid artery occlusion
Pinyuan ZHANG ; Jiren ZHANG ; Dongman ZHAO ; Shilei QI ; Guoying DU ; Jian YANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(6):916-924
Objective To explore the influencing factors of poor prognosis after successful recanalization of symptomatic acute internal carotid artery occlusion(AICAO)by applying endovascular therapy(EVT)technology.Methods We made a retrospective analysis of the clinical and imaging data of 62 symptomatic AICAO patients.After collateral evaluation and recanalization therapy,we obtained flat CT and DSA images,together with the findings of the collateral circulation assessment.At 24.0±6.0 hours after surgery,head plain CT scans were reexamined,and at 14 days after surgery or at discharge,neurological function was assessed using the NIHSS scale.Using the modified Rankin scale,we assessed neurological function and prognosis over a 90-day period.Results Each of the 62 patients had a TICI grade of 2b or 3 and was successfully recanalized.On average,it took 124.36±66.31 minutes from puncture to recanalization.Two instances involved iatrogenic dissection,while twelve cases had intraoperative distal thrombus escape episodes.Of all the patients,32 ones(51.6%)had a fair prognosis,whereas 30 patients(48.4%)had a bad prognosis.The two patient groups differed significantly in the ASPECT score,preoperative NIHSS score,intraoperative balloon catheter usage,postoperative 24 hour and 14 days NIHSS score,postoperative 14 days neurological function,and all-cause mortality within 90 days(all P<0.05).The best intervention threshold for preoperative NIHSS score was 11.5 points,and both the preoperative NIHSS score and intraoperative BGC utilization were independent predictors influencing poor outcome.Conclusion The preoperative NIHSS score and intraoperative BGC usage are independent predictors of 90-day poor prognosis in AICAO patients with symptomatic AICAO who underwent successful recanalization via endovascular therapy.
5.Anatomical variations and it's imaging characteristics of frontal recess cells in patients with frontal sinus related headache
Chengyao LIU ; Xiangdong WANG ; Qinggang XU ; Shilei CUI ; Zhongyan LIU ; Yan ZHAO ; Luo ZHANG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(4):242-247
OBJECTIVE To determine the prevalence of frontal recess cells variations in patients with frontal sinus associated headache according to the International Frontal Sinus Anatomy Classification(IFAC).METHODS A retrospective study was conducted on the CT scans of sinuses in patients with frontal sinus associated headache.We reviewed 46 patients with frontal sinus-related headache who had clinical symptoms and were relieved after nasal endoscopic surgery.The development of frontal recess cells in the frontal recess drainage area was analyzed,and the variation of middle meatus and sinus involvement were analyzed in the same time.The Anatomical variations and imaging characteristics of frontal recess cells development in patients with frontal sinus associated headache were analyzed.RESULTS A total of 92 sinus CT profiles were analyzed in 46 patients.The most common cells were agger nasi cell(ANC)(100%,92/92),followed by supra bulla cell(SBC)(78.3%,72/92),supra agger cell(SAC)(67.4%,62/92),supra bulla frontal cell(SBFC)(27.2%,25/92),supra agger frontal cell(SAFC)(20.7%,19/92),frontal septal cell(FSC)(8.7%,8/92)and supraorbital ethmoid cell(SOEC)(0%,0/92).In the conventional frontal sinus drainage area,SAFC(P=0.0108),SAC(P=0.0104)and SAFC(P=0.0088)in the IFAC classification were significantly associated with the occurrence of frontal sinus associated headache.At the same time,the middle concha bullosa also showed a significant correlation with the occurrence of frontal sinus associated headache in the lower segment of the frontal recess drainage channel(P=0.0390).CONCLUSION In the frontal recess drainage channel,the abnormal development of SAC,SAFC,SBFC and the middle concha bullosa are significantly correlated with frontal sinus associated headache.
6.Small cell carcinoma of the ovary of hypercalcaemic type: a clinicopathological analysis of sixteen cases
Jing ZHAO ; Rongkui LUO ; Tingting CHEN ; Jing LIN ; Jie ZHANG ; Shilei ZHANG ; Xianrong ZHOU ; Xiang TAO ; Yan NING
Chinese Journal of Pathology 2024;53(12):1210-1216
Objective:To investigate the clinicopathological, molecular pathological features, and family genetic pedigree of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT).Methods:A total of 16 cases of SCCOHT diagnosed in Obstetrics and Gynecology Hospital of Fudan University from January 2013 to January 2023 were collected. The clinicopathologic features, SMARCA4/2/B1 protein expression, outcomes and SMARCA4 gene detection were reported. A follow-up study was also carried out.Results:The average age at diagnosis was 28.7 years (range 17-38 years). The preoperative calcium level was evaluated in 3 of 6 patients. The tumor was unilateral in all 16 cases, ranged from 8 to 26 cm (average 15.8 cm) in the greatest dimension. Extraovarian spread was present in 7 cases. In 10 cases, the tumors were initially misinterpreted as other ovarian neoplasms. BRG1 and BRM expression by immunohistochemistry were all lost in detected cases, while INI1 exhibited retained nuclear expression. All BRM-negative SCCOHTs also lacked BRG1 protein,but retained INI1 expression. SCCOHTs were only focally positive for EMA, CKpan, Calretinin, SALL4, and diffusely positive for WT1. Two of nine cases exhibited mutation-type p53 immunoreactivity. Ki-67 index was 58% on an average. ER, PR, FOXL2, α-inhibin, chromogranin A and LCA were negative in all the cases. SMARCA4 sequencing was available in 8 cases of SCCOHT, which revealed a germline SMARCA4 mutation in one patient, and others carried somatic mutation. Furthermore, two daughters, mother and an aunt of a patient with germline mutation were reported to be SMARCA4 mutation carriers. Follow-up was available for 15 patients, and the 6-month, 1-year and 2-year survival rate was 65.8%, 45.1%, and 22.6%, respectively. For patients in FIGO stages Ⅱ+Ⅲ, 6-month, 1-year survival rate was 53.6% and 35.7% respectively, compared to 80% (6-month) and 60% (1-year) in patients of staged I ( P=0.358). Conclusions:With dismal prognosis of SCCOHT, accurate diagnosis is necessary. The typical age distribution, a panel of various staining results, especially concomitant loss of BRG1 and BRM may be of diagnostic aid and can be used to distinguish SCCOHT from its histological mimics. After the diagnosis of SCCOHT, genetic testing and genetic counseling are recommended.
7.Protective Mechanism of Paeoniflorin on Mice with Ulcerative Colitis Based on AMPK/mTOR Autophagy Pathway
Xin DAI ; Rou LI ; Yang HU ; Yuhang WANG ; Ruizhu ZHAO ; Jiaxuan FENG ; Shilei LOU ; Cong SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):45-53
ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis (UC) through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) autophagy pathway. MethodUC mouse model was established by allowing mice freely drink 4% DSS, and 56 BALB/c male mice were randomly divided into model group, AMPK inhibitor group (20 mg·kg-1), paeoniflorin (50 mg·kg-1) + inhibitor (20 mg·kg-1) group, and high dose (50 mg·kg-1), medium dose (25 mg·kg-1), and low dose (12.5 mg·kg-1) paeoniflorin groups. After seven days of drug intervention, the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight, disease activity index (DAI) changes, and Hematoxylin-eosin (HE) staining results. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum of mice in each group, and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 (LC3) content in the colon, AMPK, mTOR proteins, and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot, and the mRNA expression levels of AMPK, mTOR, Beclin1, LC3, and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the blank group, the model group showed a decrease in body mass, an increase in DAI score, and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum (P<0.01), while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue, and those of p-mTOR/mTOR were up-regulated (P<0.01). The mRNA expression levels of AMPK and LC3 were down-regulated, while the mRNA expression levels of mTOR and p62 were up-regulated (P<0.01). Compared with the model group and the paeoniflorin + inhibitor group, the mice treated with paeoniflorin showed an increase in body mass, a decrease in DAI score, a reduction in pathological damage to colon tissue, and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum (P<0.05). The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated, while the protein levels of p-mTOR/mTOR were down-regulated (P<0.01). The mRNA expression levels of AMPK, Beclin1, and LC3 were up-regulated, while the mRNA expression of mTOR and p62 were down-regulated (P<0.01). The colon tissue of the inhibitor group was severely damaged, and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group. ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.
8.Effect of gastrogin on AMPK/TRPA1 signaling pathway in rats with neuropathic pain
Xue SUN ; Shilei WANG ; Yanyu LU ; Yang ZHAO
Chinese Journal of Anesthesiology 2024;44(3):329-333
Objective:To evaluate the effect of gastrogin on AMP-activated protein kinase (AMPK)/transient receptor potential anchor protein 1 (TRPA1) signaling pathway in rats with neuropathic pain.Methods:Thirty-six SPF-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-230 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation+ normal saline group (SHAM group), neuropathic pain+ normal saline group (NP group), and neuropathic pain+ gastrogin group (GAS group). Neuropathic pain was induced by chronic constrictive injury to sciatic nerve under 2% isoflurane anaesthesia. The sciatic nerve was only exposed but not ligated in SHAM group. Gastrogin 100 mg/kg was intraperitoneally injected for 14 consecutive days after developing the model in GAS group, while the equal volume of normal saline was given instead in SHAM and NP groups. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before developing the model (T 0) and 1, 3, 5, 7, 10 and 14 days after developing the model (T 1-6). The rats were anesthetized and sacrificed following the measurement of pain thresholds at T 4 and T 6. The lumbar segment (L 4-6) of the spinal cord was removed for determination of TRPA1 mRNA expression (by quantitative real-time polymerase chain reaction), expression of TRPA1, AMPK and p-AMPK (by Western blot), expression of TRPA1 (by immunofluorescence staining) and expression of tumor necrosis-alpha(TNF-α), interleukin-1beta(IL-1β) and c-fos (by immunohistochemistry). Results:Compared with SHAM group, MWT and TWL were significantly decreased at T 1-6, the expression of TRPA1 mRNA, TRPA1, TNF-α, IL-1β and c-fos was up-regulated, the expression of p-AMPK was down-regulated ( P<0.05), and no significant change was found in AMPK expression in NP group ( P>0.05). Compared with NP group, MWT at T 3-6 and TWL at T 2-6 were significantly increased, the expression of TRPA1 mRNA, TRPA1, TNF-α, IL-1β and c-fos was down-regulated, and p-AMPK expression was up-regulated ( P<0.05), and no significant change was found in AMPK expression in GAS group ( P>0.05). Conclusions:The mechanism by which gastrogin reduces neuropathic pain may be related to modulating the expression of the AMPK/TRPA1 signaling pathway in rats.
9.The mediating effect of personality traits between job stress and mental symptoms among firefighters
Shilei WANG ; Jie ZHAO ; Fanhua KONG
China Occupational Medicine 2024;51(1):49-53
ObjectiveTo explore the mediating effect of personality traits between job stress and mental symptoms among firefighters. Methods A total of 974 firefighters in Shandong Province were selected as the research subjects using convenience sampling method. The Job Stress Scale, Brief Version of Chinese Big Five Personality Inventory and Symptom Checklist 90 were used to investigate their job stress, personality traits and mental symptoms. Results Job stress was found at a relatively high level in 39.7% of the firefighters, and 19.2% of the firefighters had high level of neurotic personality trait tendency. The positive detection rate of mental symptoms was 9.9% among firefighters. The score of job stress of the firefighters had a positive correlation with neuroticism and the score of mental symptoms (all P<0.01). The score of job stress and mental symptoms of the firefighters had a negative correlation with the personality traits score of extraversion, openness, agreeableness, and conscientiousness (all P<0.05). Neuroticism played a partially positive mediating effect between job stress and mental symptoms, and its mediating effect accounted for 39.6% of the total effect. Extraversion, agreeableness and conscientiousness played a partially negative mediating effect between work stress and mental symptoms, and the mediating effect accounted for 12.0%, 17.8% and 8.4% of the total effect respectively. There was no mediating effect of openness between job stress and mental symptoms. Conclusion Neurotic personality trait may enhance the negative effects of work stress on firefighters' mental health.
10.Mechanism of Huanglian Jiedutang in Inhibiting Activation of NLRP3 Inflammasomes and Ameliorating Acute Liver Injury in Septic Mice
Ruizhu ZHAO ; Zhengyang HUA ; Yuhang WANG ; Xinyue REN ; Dingxing FAN ; Shilei LOU ; Hui YAN ; Cong SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):27-34
ObjectiveTo explore the mechanism of Huanglian Jiedutang in inhibiting the pyroptosis mediated by NOD-like receptor protein 3 (NLRP3) inflammasomes and alleviating the acute liver injury (ALI) induced by lipopolysaccharide (LPS) in the mouse model of sepsis. MethodFifty-four male C57BL/6 mice were randomized into blank, model, low- (3.08 g·kg-1), medium- (6.15 g·kg-1), and high-dose (12.30 g·kg-1) Huanglian Jiedutang, and positive control (dexamethasone) groups (n=9). The mice were administrated with Huanglian Jiedutang at different doses by gavage for 7 days, and then LPS (15 mg·kg-1) was injected intraperitoneally for the modeling of sepsis. In the positive control group, dexamethasone (0.05 g·kg-1) was injected intraperitoneally 1.5 h after modeling, and the mouse sepsis score (MSS) was recorded 12 h after modeling. The mice were sacrificed for the collection of blood and liver tissue samples. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were measured by a biochemical analyzer. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-18 in the serum were measured by enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the pathological changes in the liver tissue. The content of NLRP3 was observed by the immunofluorescence assay. The expression of apoptosis-associated speck-like protein containing CARD (ASC) was detected by immunohistochemistry. The protein levels of NLRP3, ASC, Caspase-1, and gasdermin D (GSDMD) in the liver tissue were determined by Western blot. Real-time quantitative polymerase chain reaction(Real-time PCR) was employed to determine the mRNA levels of GSDMD, Caspase-1, IL-1β, and IL-18. ResultCompared with the blank group, the model group showed elevated levels of ALT and AST (P<0.01) and risen levels of inflammatory cytokines in the serum (P<0.01). In addition, the modeling resulted in edema and necrosis in the liver, and up-regulated the protein levels of GSDMD, NLRP3, ASC, and Caspase-1 (P<0.01) and the mRNA levels of GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.01). Compared with the model group, the drug intervention groups showed reduced content of inflammatory cytokines (P<0.01), alleviated pathological damage in the liver tissue, and down-regulated protein levels of GSDMD, NLRP3, ASC, and Caspase-1 (P<0.05,P<0.01) and mRNA levels of GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.05,P<0.01) in the liver tissue. ConclusionHuanglian Jiedutang can inhibit pyroptosis and reduce inflammation by inhibiting the activation of NLRP3 inflammasomes, thus demonstrating a therapeutic effect on acute liver injury in the mouse model of sepsis induced by LPS.

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