Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

OBJECTIVE: To determine the prevalence of lumbar spondylolysis (LS) and the proportion of spondylolytic spondylolisthesis (SS) in China, and to evaluate the musculoskeletal status of patients with LS and SS. METHODS: Spine Computed Tomography (CT) images were collected from community populations aged 40 and above in a nationwide multi-center project. LS was diagnosed, and SS was graded by an experienced radiologist. Bone mineral density (BMD) and paraspinal muscle parameters were quantified based on CT images. RESULTS: One hundred and seventeen patients of a total of 3,317 individuals were diagnosed with LS, corresponding to a prevalence rate of 3.53%. 63 of the 1,214 males (5.18%) and 54 of the 2,103 females (2.57%) were diagnosed with LS. SS occurred in 64/121 vertebrae (52.89%). BMD was not associated with LS ( P = 0.341). The L5 extensor paraspinal muscle density was higher in the LS group than in the non-LS group. In the LS group, patients with SS had a smaller L5 paraspinal extensor muscle cross-sectional area than those without SS ( P = 0.003). CONCLUSION The prevalence of LS in Chinese adults was 3.53%, with prevalence rates of 5.18% in males and 2.57% in females. Patients with LS have higher muscle density, whereas those with SS have smaller muscle cross-sectional areas at the L5 level.
Humans ; Male ; Female ; Middle Aged ; China/epidemiology* ; Prevalence ; Adult ; Lumbar Vertebrae/diagnostic imaging* ; Spondylolysis/diagnostic imaging* ; Aged ; Bone Density ; Tomography, X-Ray Computed ; Aged, 80 and over ; Spondylolisthesis/epidemiology* ; East Asian People

The anti-inflammatory efficacy of Callicarpa nudiflora extract were evaluated upon lipopolysaccharide (LPS)-induced infective inflammation in rats. Pathological changes of lung and colon tissues observed with hematoxylin-eosin (H&E) staining, together with inflammatory factors in serum, including nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were applied to assess the mitigating effects of C. nudiflora water extract on model rats. The experimental protocol strictly adhered to the guidelines of the Ethics Committee of Animal Research of Guangdong Pharmaceutical University (Approval: gdpulac2022132). Quality markers with anti-inflammatory activities were recognized by network pharmacology analysis. Subsequently, a reliable method for simultaneously quantifying six components was established. As a result, the pathological injury on lung and colon tissues of model rats induced by LPS were improved by C. nudiflora water extract. Compared with model group, C. nudiflora extract had decreased the release of proinflammatory factors in serum, including TNF-α and IL-6, and reduced the NO (P < 0.01). Network pharmacological analysis obtained 83 chemical components, 466 component targets, 584 disease targets and 129 action targets, which were mainly concentrated in 624 biological processes such as inflammatory response and positive regulation of nitric oxide biosynthesis, as well as 162 pathways such as phosphatidylinositol-3-hydroxykinase-protein kinase (PI3K-Akt) signal pathway and Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signal pathway. Upon analyzing their specificity, effectiveness, detectability, and quantity transfer rule from herb to extract, 6-hydroxyluteolin 7-glucoside, cynaroside, caffeic acid, acteoside, isoacteoside, and forsythoaside B were identified as the quality markers. Their anti-inflammatory activities were verified with LPS-induced inflammation model of RAW264.7 cells. Then contents of these 6 quality markers in 16 batches of C. nudiflora were determined. Thereby, the anti-inflammatory efficacy of C. nudiflora extract were confirmed in vivo, 6-hydroxyluteolin 7-glucoside, cynaroside, caffeic acid, acteoside, isoacteoside, and forsythoaside B were identified as anti-inflammatory ingredients, which can be used as quality control indicators for the herb and related formulation.

Objective:To understand the medical care of patients with sporadic Creutzfeldt-Jakob disease in China and its relationship with survival time.Methods:A retrospective analysis was performed on data of 150 patients with sporadic Creutzfeldt-Jakob disease diagnosed by China′s Creutzfeldt-Jakob Disease Surveillance Network during the period of January 1, 2021 to December 31, 2022 in this study, and telephone follow-up with family members was used to obtain information of the patients′ care, treatment, and survival after diagnosis. Survival was estimated by life table method, median survival time and 95% confidence interval ( CI) were calculated by Kaplan-Meier method, log-rank method was used to compare the difference in survival time between different groups, and multifactorial analysis was performed by COX proportional risk regression model regarding the influencing factors on patients′ survival time. Results:The median survival time of 150 patients with sporadic Creutzfeldt-Jakob disease was 6 months, and the cumulative lifetime survival rates at 2, 6, 12, and 18 months were 62%, 39%, 22%, and 9%, respectively. The result of univariate analysis showed that the differences in survival time between groups with the presence or absence of cortical blindness in the first symptom, the presence or absence of respiratory support (oxygen therapy), the presence or absence of adjunctive medication, and the presence or absence of tube feeding (nasogastric) were meaningful ( P<0.1). Multifactorial COX regression analysis showed that the risk of death in patients without adjuvant medication was 1.429 times higher than that in patients with adjuvant medication (95.0% CI: 1.014-2.014), and the risk of death in patients without tube feeding (nasal feeding) was 1.479 times higher than that in patients with tube feeding (nasal feeding) (95% CI: 1.052-2.081). Conclusions:Whether or not adjuvant medication is administered and whether or not tube feeding (nasogastric) is used are factors that affect survival time in patients with sporadic Creutzfeldt-Jakob disease, and the administration of appropriate adjuvant medication and tube feeding (nasogastric) may contribute to prolonging survival time in patients with sporadic Creutzfeldt-Jakob disease.

Coronary artery bypass grafting (CABG) is one of the most effective revascularization treatments for coronary heart disease. Secondary prevention strategies, which rely on antiplatelet and lipid-lowering drugs, are crucial after CABG to ensure the durability of revascularization treatment effects and prevent adverse cardiovascular and cerebrovascular events in the medium to long term. Previous research conducted by Professor Zhao Qiang's team from Ruijin Hospital of Shanghai Jiao Tong University, known as the DACAB study, indicated that dual antiplatelet therapy (DAPT, specifically ticagrelor+aspirin) after CABG can enhance venous graft patency. However, it remains uncertain whether DAPT can further improve the medium to long-term clinical outcomes of CABG patients. Recently, the team reported the medium to long-term follow-up results of the DACAB study, termed the DACAB-FE study, finding that DAPT administered after CABG can reduce the incidence of major cardiovascular events over five years and improve patients' medium to long-term clinical outcomes. This article will interpret the methodological highlights and significant clinical implications of the DACAB-FE study.

Objective To investigate the survival time of patients diagnosed with sporadic Creutzfeldt-Jakob disease in China between 2020 and 2022 and explore the associated factors influencing survival.Methods A retrospective analysis was conducted on clinically diagnosed cases with complete information on sporadic Creutzfeldt-Jakob dis-ease diagnosed by the China Creutzfeldt-Jakob disease surveillance network from 2020 to 2022,baseline information of patients was obtained from the case files,telephone follow-up was used to obtain the treatment and survival status of the patients after the diagnosis,life-table method was used for estimating the survival rate,Kaplan-Meier method was used for calculating the median survival time and the 95％CI,Cox regression model was used for univariate and multivariate analyses were used to screen for factors influencing survival time.Results The median survival time of the 300 patients was 5 months(95％CI:4.165-5.835).Univariate analysis revealed that factors such as age at onset,regional distribution,presence of corticobasal or extrapyramidal symptoms as initial manifestations,number of initial symptoms,presence of corticobasal or extrapyramidal functional abnormalities,number of major clinical manifestations,presence of typical electroencephalogram findings,and use of nasal feeding during the course of the disease were potential factors influencing survival time(P＜0.1).Multivariate analysis showed that the risk of death in patients with onset age＞65 years was 1.350 times higher than in patients with onset age ≤65 years(P=0.021,95.0％CI:1.046-1.742).Patients without pyramidal or extrapyramidal dysfunction had a 0.674-fold lower risk of death compared to those with these symptoms(P=0.020,95.0％CI:0.483-0.939).Patients who did not receive nasal feeding had a 1.817-fold higher risk of death compared to those who did(P＜0.001,95.0％CI:1.406-2.349).Conclusion Age at onset,the presence of pyramidal or extrapyramidal functional abnormalities,and the use of nasal feeding during the disease course are factors influencing the survival time of pa-tients clinically diagnosed with sCJD.

Background: Clinical chemistry tests are most widely used in clinical laboratories, and diverse measurement systems for these analyses are available in China. We evaluated the imprecision of clinical chemistry measurement systems based on internal QC (IQC) data. Methods: IQC data for 27 general chemistry analytes were collected in February each year from 2013 to 2022. Four performance specifications were used to calculate pass rates for CVs of IQC data in 2022. Boxplots were drawn to analyze trends of CVs, and differences in CVs among different groups were assessed using the Mann–Whitney U-test or Kruskal– Wallis test. Results: The number of participating laboratories increased significantly from 1,777 in 2013 to 5,425 in 2022. CVs significantly decreased for all 27 analytes, except creatine kinase and lipase. Triglycerides, total bilirubin, direct bilirubin, iron, and γ-glutamyl transferase achieved pass rates > 80% for all goals. Nine analytes with pass rates < 80% based on 1/3 allowable total error were further analyzed; the results indicated that closed systems exhibited lower CVs than open systems for all analytes, except total protein. For all nine analytes, differences were significant between tertiary hospitals and non-tertiary hospitals and between accredited and non-accredited laboratories. Conclusions The CVs of IQC data for clinical chemistry have seen a continuous overall improvement in China. However, there is ample room for imprecision improvement for several analytes, with stricter performance specifications.

Objective To explore the correlation between systemic family dynamics characteristics and adolescent depressive symptoms,and the mediating role of negative life events between them.Methods A cross-sectional study was conducted on 124 adolescent patients diagnosed with depressive disorder according to the international classification of diseases(ICD)-10 criteria at the Psychosomatic Medicine Department of Shanghai East Hospital Affiliated to Tongji University from September 2021 to February 2023.The second edition of the Scale of Systematic Family Dynamics(SSFD),Children's Depression Inventory(CDI),and Adolescent Self-Rating Life Events Checklist(ASLEC)were utilized to evaluate the family dynamics characteristics,depressive symptoms,and negative life events.Canonical correlation analysis was performed to explore the relationships between 4 dimensions of SSFD[family atmosphere(FA),individuation(IN),system logic(SL),illness concept(IC)]and 5 factors of CDI(low self-esteem,negative emotion,anhedonia,inefficiency,interpersonal problem).A mediation effect analysis using Bootstrap test was conducted to analyze the mediating role of negative life events between family dynamics and adolescent depressive symptoms.Results The scores for FA,SL,and IN in SSFD were negatively correlated with the total score of CDI(r=-0.359,-0.256,-0.291,P<0.01),and negatively correlated with the total score of ASLEC too(r=-0.318,-0.371,-0.406,P<0.01).However,a positive correlation was observed between the total scores of ASLEC and CDI(r=0.633,P<0.01).Canonical correlation analysis between the 4 dimensions of SSFD and the 5 factors of CDI revealed one pair of statistically significant canonical variables(U1,V1)with a canonical correlation coefficient of 0.483(P<0.05).This indicates that the canonical variable U1 of SSFD was primarily influenced by FA,while the canonical variable V1 of CDI was mainly affected by low self-esteem and interpersonal problems.The mediating analysis showed that the effects of FA,IN,and SL scores on CDI total score were all weak(-0.147,-0.117,-0.102,respectively)but statistically significant(P<0.05).The direct effect of IN and SL scores on CDI total score was not statistically significant(P>0.05),while the direct effect of FA score on CDI total score was statistically significant(-0.076,P<0.05).Additionally,the mediating effect of ASLEC between the scores of FA,IN,SL and CDI total score were all significant(-0.071,-0.095,-0.087,respectively)(P<0.05).Conclusions Adolescent depressive symptoms may be influenced by systemic family dynamics characteristics and negative life events.Negative life events mediate the influence of FA,IN,and SL on depressive symptoms.However,the IC is not related to depressive symptoms in adolescents.

Objective To develop an intelligent positioning system for mobile medical equipment in the operating room based on Bluetooth technology to enhance medical equipment management efficiency.Methods The intelligent positioning system for mobile medical equipment used received signal strength indication(RSSI)algorithm and multi-gateway trajectory filtering algorithm to realize Bluetooth positioning,which was composed of Bluetooth gateways,Bluetooth beacons,Bluetooth labels and a background data processing platform.The Bluetooth gateway consisted of an active power over ethernet(POE)module,a DC power module,a CPU,a Wi-Fi module and a Bluetooth module;the Bluetooth beacon included a beacon control unit,a Bluetooth transmitter module and a Bluetooth receiver module;the Bluetooth label was made up of a microcontroller unit(MCU),a Bluetooth module,an anti-temper switch and a accelerometer;the data processing platform had the front end developed with Vue architecture and the back end with Java language.Results The system developed could accurately locate the medical equipment in the operating room without electromagnetic interference to other medical devices.Conclusion The system developed gains advantages in high positioning accuracy,low electromagnetic interference,high stability and reliability and low cost,which improves the positioning and management efficiency of medical equipment under the premise of ensuring safety.[Chinese Medical Equipment Journal,2023,44(9):29-32]

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Antiviral Agents/adverse effects* ; Esophageal and Gastric Varices/complications* ; Liver Cirrhosis/complications* ; Treatment Outcome ; Gastrointestinal Hemorrhage/complications* ; Hepatitis B/drug therapy*