Advances in relationship between pyroptosis and pulmonary arterial hypertension and therapeutic drugs / 中国药理学通报

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Effect of exogenous hydrogen sulfide on hypoxia/reoxygenation injury in glomerular mesangial cells and its mechanism / 中国药理学通报

Aim To explore the effect of exogenous hydrogen sulfide ( H2 S ) on hypoxia/reoxygenation ( H/R) injury in glomerular mesangial cells and elucidate its relevant mechanism. Methods H/R induced mouse mesangial cell line ( SV40MES13 ) to establish cell damage model. Cell viability was detected by cell proliferation kit ( CCK8 ), the content of H

Effect of Government Guidelines and Corporate Governance on Telework Adoption and Occupational Health Measures in Taiwanese-Listed Companies

Background@#Telework adoption in Taiwan has surged because of government guidelines during the COVID-19 pandemic. This study examined the disclosure practices of Taiwanese-listed companies, assessing their adherence to government telework guidelines and their correlation with corporate governance, focusing on occupational health measures. @*Methods@#We conducted a guideline-adherent cohort analysis of the 2020 and 2021 sustainability reports of 295 Taiwanese-listed companies. We assessed their disclosure of corporate measures for teleworking in alignment with two government guidelines, specifically occupational health measures. Using the McNemar test and general estimating equation analysis, we compared the 2020 and 2021 responses and examined their associations with corporate governance rankings. @*Results@#Telework adoption increased significantly from 2020 to 2021, with 68% of companies reporting new work modes. The mentioning of government guidelines also increased to 67% by 2021. Companies with higher governance rankings were more likely to adopt online occupational health measures, including occupational health services (RR = 2.03; 95% CI = 1.41–2.94; p < 0.001) and mental health promotion activities (RR = 2.01; 95% CI = 1.06–3.82; p = 0.032), than those with low rankings. Although on-site and online occupational health services increased, home workspace assessments did not. @*Conclusion@#Our findings highlight significant upward trends in the disclosure of telework measures following the issuance of government guidelines. Corporate governance is significantly associated with the implementation of occupational health measures. Amid the evolution of teleworking, both government guidelines and corporate governance have become essential for shaping work arrangements and ensuring workforce well-being.

Effect of circDNMT1 regulating miR-377-3p/PUM1 axis on proliferation,apoptosis and epithelial-mesenchymal transition of triple-negative breast cancer cells / 局解手术学杂志

Objective To investigate the effects of circDNMT1 on the proliferation,apoptosis and epithelial-mesenchymal transition(EMT)of triple-negative breast cancer(TNBC)cells by regulating miR-377-3p/PUM1 axis.Methods The TNBC tissues and adjacent normal tissues of 24 patients with TNBC treated in Danzhou People's Hospital from 2018 to 2021 were collected.qRT-PCR and Western blot were used to detect the expression of circDNMT1,miR-377-3p,and PUM1 protein in tissue and mouse normal breast epithelial cell line HC11 and TNBC cell lines 4T1,Eph41424,and JC.4T1 cells were divided into the 4T1 group(untransfected),the si-NC group(transfected with si-NC),the si-DNMT1 group(transfected with si-DNMT1),the si-DNMT1+anti-NC group(simultaneously transfected with si-DNMT1 and anti-NC),and the si-DNMT1+anti-miR-377-3p group(simultaneously transfected with si-DNMT1 and anti-miR-377-3p).qRT-PCR was used to detect the expression of circDNMT1 and miR-377-3p of 4T1 cells in each group;CCK-8 was used to detect the proliferation of 4T1 cells in each group;flow cytometry was used to detect the apoptosis of 4T1 cells in each group;Western blot was used to detect the expression of PUM1,EMT-related proteins and apoptosis-related proteins of 4T1 cells in each group;TargetScan website was used to predict the binding sites of miR-377-3p with circDNMT1 and PUM1;dual luciferase report was used to verify the targeting relationships of miR-377-3p with circDNMT1 and PUM1.After inoculation with 4T1 cells,BALB/c mice were randomly divided into the blank control group(injected with equal amount of normal saline),the negative control group(injected with si-NC via tail vein),the DNMT1 silencing group(injected with si-DNMT1 via tail vein),the combined control group(injected with si-DNMT1 and anti-NC via tail vein),and the combined silencing group(injected with si-DNMT1 and anti-miR-377-3p via tail vein),the tumor massess of mice were recorded and the morphological changes of tumors were observed by hematoxylin-eosin staining.Results circDNMT1 and PUM1 were up-regulated in TNBC tissues and cells,and miR-377-3p was down-regulated.The expression difference was most obvious in 4T1 cells,so 4T1 cells were selected for subsequent experiments.Compared with the 4T1 group and the si-NC group,the expression of miR-377-3p,the apoptosis rate of 4T1 cells,the expression levels of Bax,cleaved caspase-3 and E-cadherin protein of 4T1 cells in the si-DNMT1 group were significantly increased(P<0.05),the circ-DNMT1 level,the expression level of PUM1 protein,OD values at 24 hours and 48 hours,the expression level of Bcl-2,N-cadherin,Vimentin protein were significantly decreased(P<0.05).Compared with the si-DNMT1 group and the si-DNMT1+anti-NC group,the expression of miR-377-3p,the apoptosis rate of 4T1 cells,the expression levels of Bax,cleaved caspase-3 and E-cadherin proteins of 4T1 cells in the si-DNMT1+anti-miR-377-3p group were significantly decreased(P<0.05),the expression level of PUM1 protein,OD values at 24 hours and 48 hours,the expression levels of Bcl-2,N-cadherin,Vimentin proteins were significantly increased(P<0.05).Compared with the miR-NC+WT-circDNMT1 group,the cell luciferase activity in the miR-377-3p mimic+WT-circDNMT1 group was significantly decreased(P<0.05);compared with the miR-NC+WT-PUM1 group,the cell luciferase activity in the miR-377-3p mimic+WT-PUM1 group was significantly decreased(P<0.05).The tumor cells in the blank control group and the negative control group were densely arranged with clear boundary;the tumor cells in the DNMT1 silencing group and the combined control group were loosely arranged,the nuclei were pyknotic,and the cell fragments were increased;the tumor cells in the combined silencing group were densely arranged and the boundaries tended to be clear.Compared with the blank control group and the negative control group,the tumor mass of mice in the DNMT1 silencing group was significantly decreased(P<0.05).Compared with the DNMT1 silencing group and the combined control group,the tumor mass of mice in the combined silencing group was significantly increased(P<0.05).Conclusion Silencing circDNMT1 may inhibit the expression of PUM1 by up-regulating miR-377-3p,thereby inhibiting the proliferation and EMT of TNBC cells,and promoting cell apoptosis.

Osteopontin activates the PI3K/AKT pathway by upregulating LGALS3BP in promotion of hepatoma cell migration / 中国比较医学杂志

Objective To investigate the effect and mechanism of osteopontin(OPN)in hepatoma cell migration through galectin-3 binding protein(LGALS3BP).Methods Human hepatoma cell lines SMMC-7721,SMMC-P(stably transfected with empty eukaryotic expression vectors),and SMMC-OPN(stably transfected with the OPN gene)were cultured.mRNA expression levels of OPN and LGALS3BP were measured by RT-qPCR.Western blot assays were used to analyze the relative protein expression of OPN and LGALS3BP and PI3K/AKT pathway.Wound healing assays were performed to explore the cell migration ability.After transfection with LGALS3BP-targeting small interfering RNA(si-LGALS3BP)or negative control small RNA(si-NC)into SMMC-OPN cells,cell migration and relative expression of PI3K/AKT pathway-related proteins were assessed.Results Compared with SMMC-7721 and SMMC-P,the migratory ability of SMMC-OPN cells was significantly reinforced,and expression of LGALS3BP was obviously upregulated at both mRNA and protein levels.Moreover,relative expression of p-PI3K/PI3K and p-AKT/AKT proteins was significantly increased.Wound healing assays showed that the si-LGALS3BP obviously suppressed the migratory ability of SMMC-OPN cells.Furthermore,relative expression of p-PI3K/PI3K and p-AKT/AKT proteins in SMMC-OPN cells was significantly decreased after transfection of si-LGALS3BP.Conclusions OPN activates the PI3K/AKT pathway by upregulating LGALS3BP expression to promote hepatoma cell migration.

Research Progress of Regulatory T Cells in the Pathogenesis of Multiple Myeloma --Review / 中国实验血液学杂志

The multiple myeloma (MM), the second most common hematologic malignancy, is malignant proliferative disease of plasma cells. Although the application of many targeted drugs has significantly prolonged the survival time of MM patients, it is still an incurable disease. In recent years, the immunosuppression caused by interaction between tumor microenvironment(TME) and tumor cells has attracted people's attention gradually. As a kind of immunosuppressive cells in TME, regulatory T cells (Treg) play an important role in the progress of MM. Treg is related to the proliferation and metastasis of tumors, and can lead to the progress of MM by promoting the angiogenesis and generating immunosuppressive TME. In this review, we briefly summarized the latest research progress on the impact of Treg on the pathogenesis of MM.

Measuring and analysis of the shoulder circumferences of 840 adults' permanent teeth crown preparations / 中华口腔医学杂志

Objective: To measure and analyze the shoulder circumferences of adults' permanent teeth crown preparations based on data collected through the intraoral scanning, so as to provide dental anatomy data for clinical diagnosis and analysis. Methods: Intraoral scanning data of 840 complete crown preparations were collected, and were entrusted to the World Dental Laboratory Co., Ltd. in Fuzhou between March 2021 and June 2022. Except the data of the third molar, the rest data were categorized in terms of 14 tooth positions in the upper and lower jaw (each category involved 30 samples from male group and 30 samples from female group). Image measurement software was used to measure the shoulder circumferences of permanent teeth crown preparations. And analysis was conducted to reveal the difference of shoulder circumference diameters between male and female groups. And then they were grouped according to the mean value at each tooth position, on the premise that the difference between the maximum and minimum values and the mean value of the entire group was≤±1.00 mm. Analysis were further conducted to determine the differences of shoulder circumference diameters between each dental position and the differences between male and female in the same groups. Results: Bivariate analysis of variance showed that gender had no effect on the shoulder circumference of full crown preparations (F=0.55, P=1.457), while tooth position had a significant impact on the shoulder circumference of full crown preparations (F=273.15, P<0.001). The samples were classified into 5 groups according to the mean values of shoulder circumference diameters relating to each tooth position. Statistical analysis showed that Group 1, covering maxillary lateral incisor, mandibular central incisor and mandibular lateral incisor, had shoulder circumference with diameters of (16.62±2.21) mm; Group 2, consisting of maxillary central incisor, maxillary cusp, mandibular cusp, mandibular first premolar and mandibular second premolar, had diameters of (20.78±2.48) mm; Group 3, consisting of maxillary first premolar and maxillary second premolar, had diamerters of (22.09±2.72) mm; Group 4, covering maxillary first molar, maxillary second molar and mandibular first molar, had diamerters of (30.21±2.67) mm; while group 5, with mandibular second molar alone its member, had diamerters of (31.34±3.18) mm. The difference among the 5 groups was statistically significant (P<0.05). Conclusions: Significant differences of shoulder circumference diameters could be found between different tooth positions, while at the same tooth position, the differences between male and female are not significant. The 14 tooth positions could be grouped into 5 groups according to their shoulder circumference diameters. Future research could take the grouping as reference.

Platelet Removal Efficiency by Leukocyte Filter in Red Blood Cell Units at Different Storage Periods / 中山大学学报(医学科学版)

ObjectiveThe aim of this study is to investigate change of platelet count in red blood cell （RBC） units at different storage periods and explore the efficiency of platelet removal by leukocyte filter. MethodsA total of 58 RBC units were divided into four groups according to different storage periods： 1 week Group （16）， 2 weeks Group （16）， 3 weeks Group （14） and 4 weeks Group （12）. RBC units in the four groups were filtered through leukocyte filter. The RBC samples before and after filtration were obtained. The platelet count was detected by automatic blood cell counter and the efficiency of platelet removal was calculated. RBC samples before filtration were made into blood cell smears. The blood cell smears were dyed with Wright-Giemsa stain， and the morphology of platelets was observed through a microscope. ResultsThe platelet count in RBC units stored for 1， 2， 3 and 4 weeks was （286.5±62.34）×109/L， （238.0±57.37）×109/L， （193.6±56.21）×109/L and （167.8±24.76）×109/L， respectively. Platelet count in blood stored for 3 weeks （P<0.01） and 4 weeks （P <0.000 1） were significantly lower than those stored for 1 weeks. When observed in the blood smears of RBC units at different storage periods， platelets with normal morphology were distributed in clump and scattered style. The platelet removal rates of the four groups were （80.13±9.06） %， （76.41±10.13） %， （77.78±9.30） % and （70.63±9.39） %， respectively， with no significant difference （P >0.05）. ConclusionsPlatelet count in RBC units decreases gradually as the storage period increases， but most platelets still remain in RBC units of late storage periods （3 weeks and 4 weeks）. The leukocyte filter is able to remove most of the platelets， and the removal efficiency is similar among the groups.

Tumoral calcinosis on thigh in a hemodialysis patient and literature review / 中华肾脏病杂志

The paper reported a patient under maintained hemodialysis for 11 years, with a large mass appeared in the right thigh after local injury. The mass was clinically considered as tumoral calcinosis combined with clinical, imaging and pathological findings. Several treatments such as enhancing dialysis adequacy, low calcium dialysate, calcimimetic agent, non-calcium- phosphorus binding agents, parathyroidectomy and intravenous infusion of sodium thiosulfate could not vanish the mass. Finally, the lump was surgically removed. The treatment of tumoral calcinosis in the hemodialysis patient can provide a instruction for similar situations in clinical practice.

Clinical significance of flow cytometry in detection of minimal residual disease in cerebrospinal fluid / 中南大学学报(医学版)

Objective:Central nervous system leukemia(CNSL)is one of the main causes of recurrence and death in patients with acute leukemia.This study aims to dynamically monitor minimal residual disease(MRD)in cerebrospinal fluid and bone marrow of patients with different types of acute leukemia by flow cytometry(FCM),and to compare the timeliness and consistency of MRD detection between the 2 methods to further explore the application value of monitoring MRD in cerebrospinal fluid. Methods:A total of 199 patients with acute leukemia admitted to the Guangdong Provincial people's Hospital between October 2018 and January 2022 were retrospectively analyzed,and multiparametric FCM method was adopted to summarize and analyze MRD in cerebrospinal fluid of patients with different types of leukemia and MRD in cerebrospinal fluid and bone marrow specimens of the same patients,and its role in assessing the prognostic value of patients was discussed. Results:Among the 199 acute leukemia cases,a total of 31 cases(15.58%)were positive MRD in the cerebrospinal fluid,of which 18 cases(58%)were detected earlier than the corresponding bone marrow specimens.Among the 19 patients with acute T lymphoblastic leukemia,134 patients with acute B lymphoblastic leukemia,and 46 patients with acute myeloid leukemia counted,there were 4,18,and 9 patients with positive MRD in the cerebrospinal fluid.The Kappa value of the concordance test between the results of cerebrospinal fluid MRD and bone marrow MRD in different types of acute leukemia was only 0.156,demonstrating a low concordance between them. Conclusion:Dynamic monitoring of cerebrospinal fluid MRD by FCM can be used as a monitoring index for central nervous system leukemia,and monitoring cerebrospinal fluid can detect MRD earlier compared with bone marrow,which complements each other as a sensitive index for evaluating prognosis with significant guidance in clinic.

Analysis of characteristics and risk factors of bacterial infection in patients undergoing liver transplantation for liver failure / 中华消化外科杂志

Objective:To analyze the pathogens distribution, drug resistance and risk factors of bacterial infection in patients undergoing liver transplantation for liver failure.Methods:The retrospective case-control study was conducted. The clinical data of 88 patients with liver failure who underwent liver transplantation in The First Affiliated Hospital of Xi′an Jiaotong University from July 2020 to June 2023 were collected. There were 57 males and 31 females, aged (44±9)years. Observation indicators:(1) incidence and pathogens distribution of bacterial infection in patients undergoing liver transplantation for liver failure; (2) drug resistance of bacteria; (3) risk factors of bacterial infection in patients undergoing liver transplantation for liver failure. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers and percentages. Univariate analysis was conducted using the chi-square test or Fisher exact probability. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Incidence and pathogens distribution of bacterial infection in patients undergoing liver transplantation for liver failure. Of 88 patients, 40 cases had bacterial infection after liver transplantation, with the incidence as 45.45% and occurrence time as postoperative 18(range, 1-57)days. Of the 40 cases with bacterial infection after liver transplantation, 9 cases had single strain infection and 31 cases had mixed bacterial infection. A total of 135 strains of different pathogenic bacteria were isolated from 40 patients, 106 of which were Gram-negative bacteria, 29 were Gram-positive bacteria. Of the Gram-negative bacteria, the top 4 pathogenic bacteria were 37 strains of Acinetobacter baumannii, 35 strains of Klebsiella pneumoniae, 11 strains of Pseudomonas aeruginosa, 9 strains of Stenotrophomonas maltophilia. Of the Gram-positive bacteria, there were 22 strains of Enterococcus faecium, 3 strains of Staphylococcus aureus, 3 strains of Staphylococcus epidermidis, 1 strain of Staphylococcus haemolyticus. Of the 135 strains of pathogenic bacteria, 64 strains were isolated from respiratory tract, 26 strains were from abdomen, 23 strains were from biliary tract, 16 strains were from blood, 6 strains were from other sites. (2) Drug resistance of bacteria. Of the Gram-negative bacteria, Acinetobacter baumannii had a resistance rate of lower than 30.0% to colistin, tigacyclinei, minocycline, a resistance rate of 30.0%-50.0% to amikacin and tobramycin, a resistance rate of over 70.0% to cefotetan, ceftazidime, cefepime, cefoperazone/sulbactam, piperacillin/tazobactam, meropenem, imipenem, ciprofloxacin, cotrimoxazole, levofloxacin. Klebsiella pneumoniae showed a resistance rate of lower than 30.0% to ceftazidime/avibactam, colistin, tigacyclinei and a resistance rate of more than 70.0% to other tested antibiotics. Pseudomonas aeruginosa showed a resistance rate of more than 50.0% to meropenem, imipenem, levofloxacin and a resistance rate of lower than 50.0% to other tested antibiotics. Stenotrophomonas maltophilia showed a resistance rate of lower than 30.0% to cotrimoxazole, levofloxacin, minocycline. Klebsiella oxytoca showed a resistance rate of more than 50.0% to piperacillin/tazobactam, cefoperazone/sulbactam and a resistance rate of lower than 50.0% to other tested antibiotics. The resistance rate of Escherichia coli to amikacin, tobramycin, ceftazidime/avibactam, colistin, and tigecycline was less than 30.0%, and the resistance rate to other tested antibiotics was more than 50.0%. Of the Gram-positive bacteria, Staphylococcus aureus showed a resistance rate of 0 to tigacyclinei, vancomycin, teicoplanin, linezolid, a resistance rate of lower than 50.0% to gentamicin and ciprofloxacin, and a resistance rate of more than 50.0% to erythromycin, penicillin G, ampicillin, tetracycline, levofloxacin. Staphylococcus showed a resistance rate of more than 50.0% to erythromycin, penicillin G, oxacillin, and a resistance rate of 0 to other tested antibiotics. (3) Risk factors of bacterial infection in patients undergoing liver transplantation for liver failure. Results of multivariate analysis showed that preoperative model for end-stage liver disease score ≥30 was an independent risk factor for bacterial infection in patients undergoing liver transplantation for liver failure ( odds ratio=6.440, 95% confidence interval as 2.155-19.248, P<0.05). Conclusions:The incidence of bacterial infection in patients undergoing liver transplantation for liver failure is high, with the most common sites of respiratory tract and abdomen. The pathogenic bacteria are mainly Gram-negative bacteria, which show an extensive and high drug resistance. Preoperative model for end-stage liver disease score ≥30 was an independent risk factor for bacterial infection in patients undergoing liver transplantation for liver failure.

Astragaloside Ⅳ Induces Autophagy and Apoptosis in Nasopharyngeal Carcinoma Cells via PI3K/Akt/mTOR Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and underlying molecular mechanism of astragaloside-Ⅳ （AS-Ⅳ） on autophagy and apoptosis of nasopharyngeal carcinoma cells. MethodIn experiments in vitro， the effect of AS-Ⅳ on the autophagy of nasopharyngeal carcinoma cells was observed by monodansylcadaverine （MDC） staining and transmission electron microscopy （TEM）. In experiments in vivo， immunofluorescence （IF） and Western blot were used to detect the changes in autophagy and apoptosis and the expression of key proteins in the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway after the establishment of a xenograft tumor model in nude mice. ResultAfter 5-8F cells were treated with AS-Ⅳ of different doses （5， 10， 20 μmol·L-1）， the fluorescence intensity of autophagy in AS-Ⅳ groups significantly increased as compared with that in the blank group. The fluorescence expression of autophagy in AS-Ⅳ groups was the strongest after intervention for 24 hours， and the fluorescence expression in the 10 μmol·L-1 AS-Ⅳ group was the most obvious. The autophagy activator rapamycin （RAPA） induced more autophagosomes in 5-8F cells under the transmission electron microscope， and 3-methyladenine （3-MA）， an autophagy inhibitor， did not induce autophagosome formation in 5-8F cells under the transmission electron microscope as compared with the results in the blank group. In the 10 μmol·L-1 AS-Ⅳ group， the intracellular structure and cell membrane were intact and clear， and autophagosome formation was observed. Compared with the blank group， the AS-Ⅳ groups showed inhibited tumor volume （P<0.05， P<0.01）， potentiated fluorescence signals of microtubule-associated protein l light chain 3 type Ⅱ/microtubule-associated protein l light chain 3 type Ⅰ （LC3 Ⅱ/Ⅰ） and cleaved Caspase-3 （P<0.05， P<0.01）， increased expression levels of the mammalian homolog of yeast ATG6 （Beclin-1）， LC3 Ⅱ/Ⅰ， cleaved Caspase-3， and cleaved PARP （P<0.05， P<0.01）， down-regulated expression of ubiquitin-binding protein （p62） （P<0.05， P<0.01）， and reduced protein expression levels of phosphorylated PI3K （p-PI3K）， phosphorylated Akt （p-Akt）， and phosphorylated mTOR （p-mTOR） （P<0.05， P<0.01）. ConclusionAS-Ⅳ can induce autophagy and apoptosis of nasopharyngeal carcinoma cells， and the mechanism is presumably attributed to the activation of the PI3K/Akt/mTOR signaling pathway.

Development of comprehensive vitality scale for the elderly based on classical test theory and analytic hierarchy process / 生理学报

The present study aims to construct an elderly vitality index evaluation system and develop a comprehensive vitality evaluation scale for the elderly to reasonably evaluate the vitality level of the elderly in China, so as to provide a reference for promoting the realization of "active aging" and "healthy aging". Literature research and in-depth interview were used to collect the senile vitality sensitive indexes. The indexes were screened and corrected by Delphi expert consultation method, item analysis method based on classical test theory, factor analysis method, and reliability and validity analysis method. The analytic hierarchy process was used to calculate the weight of each level of indexes. An elderly vitality evaluation system including 4 first-level indexes and 24 second-level indexes was constructed. The consistency test results of all levels of indicators showed that the consistency index (CI) and consistent ratio (CR) were both less than 0.1, which met the requirements and showed satisfactory consistency. The weights of exercise vitality, nutritional vitality, psychological vitality and social vitality were 0.263, 0.141, 0.455 and 0.141, respectively. In conclusion, the comprehensive vitality scale constructed for the Chinese elderly is reliable and scientific, and can be used to evaluate the vitality of the elderly.

Phenotypes and ATP7B gene variants in 316 children with Wilson disease / 中华儿科杂志

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ2 test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.

Research on the antioxidant activity of metabolites from a sponge-derived fungus Alternaria sp. F49 / 药学学报

To study the chemical constituents from the the deep-sea fungus Alternaria sp. F49. Seven compounds were isolated from the EtOAc extract by using silica gel, Sephadex LH-20, ODS and HPLC methods. Based on the spectroscopic analysis, their structures were identified as (8R)-5-O-methyl-orcinotriol (1), orcinotriol (2), α-acetylorcinol (3), 3'-hydroxyalternariol 5-O-methyl ether (4), altenusiol (5), altenusin (6), and 5'-methoxy-6-methyl-biphenyl-3,4,3'-triol (7). (8R)-5-O-Methyl-orcinotriol (1) is a new phenolic compound which has never been reported in the literature. Compounds 4-7 showed strong DPPH free radical scavenging activity; whereas compounds 1-7 showed strong ABTS free radical scavenging activity.

Joint association of sedentary behavior and physical activity on anxiety tendency among occupational population in China / 北京大学学报(医学版)

OBJECTIVE@#To investigate the status and influencing factors of anxiety tendency among occupational population in China and to examine the joint association between sedentary behavior and physical activity with anxiety tendency.@*METHODS@#The data were from the 2021 Asia Best Workplace (Chinese mainland) program. The Generalized Anxiety Tendency scale was used to assess employees' anxiety status, and Logistic regression was used to analyze the factors influencing anxiety tendency and calculate the odds ratio (OR) within different groups. The OR of sitting for each sitting-physical activity (PA) combination group and within PA strata were calculated to explore the joint association.@*RESULTS@#A total of 11 903 workers with an average age of 32.9 years were included in this study. Among them, 3 562 workers had anxiety tendency (29.9%) and the prevalence of those under 40 years old (30.6%) was significantly higher than the other age group (26.7%). 41.0% of the respondents had the moderated to vigorous physical activity. Their average daily sitting time was 9.4 h, and the percentage of those who exceeded 8 h sitting reached 73.9% in the past week. The analysis of Logistic regression showed that smoking (OR=1.24, 95%CI: 1.23-1.39), longer sedentary time and lower physical activity level were risk factors for anxiety tendency, and longer average daily sleep time (OR=0.56, 95%CI: 0.51-0.61) was a protective factor. The joint association analysis and stratified analysis of physical activity and sedentary behavior with anxiety tendency showed that increased sedentary time combined with decreased physical activity intensity was significantly associated with increased risk of anxiety tendency (range of OR: 1.64-3.14). The threshold for sedentary time in total as a risk factor for anxiety tendency gradually decreased as physical activity intensity increased.@*CONCLUSION@#The anxiety tendency and sedentary behavior among the occupational population should recieve more attention. Lack of physical activity and sedentary behavior are both risk factors for anxiety tendency, and strengthening the intensity of physical activity can attenuate the harmful effects of sedentary behavior on anxiety tendency.

Effect and Safety of Penetrating Moxibustion in Treatment of Migraine without Aura: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To observe the clinical effect of penetrating moxibustion on migraine without aura (MO) patients.@*METHODS@#Totally 60 MO patients from the Acupuncture Clinic of the Third Affiliated Hospital of Henan University of Chinese Medicine were collected from November 2015 to February 2017. All patients were assigned to a treatment group and a control group using a random number table, 30 cases in each group. The treatment group was treated with penetrating moxibustion, and the control group was treated with mild moxibustion, thrice a week for 4 consecutive weeks. The total effective rate, Visual Analogue Scale (VAS) scores, headache intensity, and Migraine Specific Quality of Life Questionnaire (MSQ) scores of patients after treatment were compared between the two groups. The moxibustion sensation and reaction after moxibustion were observed, and the adverse reactions were evaluated. All patients were followed up at 4 and 16 weeks after treatment.@*RESULTS@#The total effective rate of the treatment group was significantly higher than that of the control group (93.33% vs. 80.00%, P0.05).@*CONCLUSIONS@#Penetrating moxibustion can significantly relieve pain and improve quality of life of MO patients. After penetrating moxibustion, flushing and sweating of patients were obvious, and the curative effect was superior to the mild moxibustion.

The regulation role of PDK/Akt signaling pathway in berberine combined with ginsenoside Rg3 induced apoptosis of nasopharyngeal carcinoma cells / 中国药理学通报

Aim To study the effect of berberine combined with ginsenoside Rg3 on the apoptosis of nasopharyngeal carcinoma ( NPC ) cells, and to discuss the role of the PDK/Akt signaling pathway in this process. Methods Real time cellular analysis (RTCA)_fluorescence double-staining flow cytometry and Hoechst 33342 staining were used to detect the effects of ber¬ berine combined with ginsenoside Rg3 on the proliferation and apoptosis of NPC cells. Western blot was used to examine the effects of drugs on the expressions of apoptosis-related proteins and the key proteins of PI3K/Akt signaling pathway. Results Berberine combined with ginsenoside Rg3 inhibited the proliferation and induced cell apoptosis of NPC cells. Expressions of PI3K p 11 0 α and p-Akt were significantly down-regulated in combined drug group. After activation of PI3K/Akt signaling pathway, the effect of berberine combined with ginsenoside Rg3 on inhibiting CNE2 cell proliferation and inducing apoptosis was reduced. Compared with combination group, the levels of Survivin, PCNA and Bcl-2 were relatively enhanced, while the level of Bax declined (P < 0. 05). Conclusions Berberine combined with ginsenoside Rg3 may play a role in inhibiting the proliferation and inducing apoptosis of NPC cells through PI3K/Akt signaling pathway.

SPOP-mediated Non-degradative Ubiquitination / 中国生物化学与分子生物学报

Protein post-translational modification is a precondition guaranteeing normal exertion of protein functions. Ubiquitination is an important post-translational modification that maintains normal protein levels and activity. Numerous researches show that the E3 ubiquitin ligase speckle-type POZ protein (SPOP) displays mutations in many tumors and genetic diseases. Mainly concentrated in the MATH structural domain that recognizes substrates, these mutations influence the binding between SPOP and substrates, and further influence their protein levels, positioning and activities, thus disturbing the normal physiological functions. Wild-type SPOP binds the substrates, most of which enter the proteasome pathway for decomposition after being ubiquitinated by SPOP, but some substrates are also influenced functionally. Herein we review the ubiquitination types and functions of SPOP substrates, including the ubiquitin-proteasome system (UPS), structure, functions and molecular pathways of SPOP, and non-degradative ubiquitinated modification of SPOP. The emphasis will be laid on the molecular mechanisms of the signaling pathways mediated by the three non-degradative substrates of SPOP, that is, myeloid differentiation primary response gene 88 (MyD88)-mediated NF-κB pathway, X-chromosome silence signal pathway of histone macroH2A1 (macroH2A. 1 histone, macroH2A1), and inverted formin 2 (INF2)mediated chondriokinesis pathway, in inhibiting tumorigenesis and development. We expect to provide a new perspective for precise targeted therapies of tumors.

Clinical characteristics and outcome of COVID-19 in elderly patients / 西安交通大学学报(医学版)

【Objective】 To investigate the clinical characteristics， treatment and outcome of elderly patients with COVID-19. 【Methods】 We made a retrospective analysis of the clinical data of elderly patients with COVID-19 admitted by the National Anti-epidemic Medical Team of The First Affiliated Hospital of Xi’an Jiaotong University in Department of the seventh ward of Renmin Hospital of Wuhan University between February 9 and March 15， 2020. We fully extracted the patients’ demographics， epidemiological characteristics， clinical manifestations， laboratory examination， imaging performance， treatment and outcomes. 【Results】 In this study we included a total of 30 patients（18 males and 12 females）， with an average age of（71.1±14.4） years. Their underlying diseases included cardiovascular and cerebrovascular diseases（23 patients）， chronic pulmonary disease（3 patients）， digestive disease（2 patients）， diabetes mellitus（3 patients）， and chronic kidney disease（1 patients）. Before admission， 22 patients received oral medication. The initial symptoms were fever and cough. The peak body temperature averaged（38.4±0.6）℃ The mean time from symptom onset to hospitalization was 15.0±7.7 days. The clinical classification was mainly severe type in 26 patients（87%）. Laboratory examination revealed lower lymphocyte count（0.7±0.2）×109/L， and higher blood D-D dimer lever（6.9±13）μg/L. Serum lactate dehydrogenase（LDH） significantly increased（310±136）U/L. Serum C-reactive protein（61±52）mg/L and erythrocyte sedimentation rate（ESR）（66±38）mmol/L slightly increased. Imaging performance revealed that diffuse lesions were located in bilateral pulmonary parenchyma（22 patients） and in single pulmonary parenchyma（7 patients）. Ground-glass opacity was found in all the patients， and the average number of CT examination during hospitalization was 3.5±1.3. Viral load revealed that nucleic acid in nasopharyngeal swabs of 30 patients was all positive， nucleic acid in the feces of 6 patients was positive， and nucleic acid in nasopharyngeal swab of 1 patient was positive， whose nucleic acid in alveolar lavage fluid was negative. Serum IgG antibody level was（157.5±29.2）AU/mL and IgM antibody level was（69.0±148.7）AU/mL. Complications included ARDS in 5 patients， AKI in 5 patients， cardiac injury in 3 patients， shock in 2 patients， nosocomial infection in 3 patients， coagulation disorder in 3 patients， and gastrointestinal bleeding in 3 patients. Finally， 5 patients received non-invasive mechanical ventilation and 2 patients received invasive mechanical ventilation. Another 2 patients underwent CRRT and 1 patient received CRRT plus ECMO. Of the 3 patients with critical type， 2 died and 1 survived. There were 25 patients who turned from severe type into normal type/light type， and 1 patient finally died（turned from severe type into critical type）. In the end， 15 patients were cured and discharged. The average time of viral nucleic acid from positive to negative was 12.4±5.6 and the average time of lesion absorption in computer tomography was 16.9±5.8 days. The total hospital stay was 22.9±8.1 days， and the 28-day mortality rate was 6.7%. 【Conclusion】 COVID-19 in elderly patients is mostly severe and its initial symptoms are still fever and cough. Patients should be immediately hospitalized when symptoms develop. The time of viral nucleic acid transformation and imaging improvement is longer than that of others. The mortality in critically ill patients is higher than that of others. Clinicians should pay more attention to the elderly people.