ObjectiveTo analyze the epidemiological and clinical characteristics of surveillance cases in a sentinel hospital for pertussis in Jiangxi Province in 2019, and to provide corresponding references for the prevention and control of pertussis. MethodsCase investigation of pertussis was conducted among sentinel hospital surveillance cases, collecting their basic information, epidemiological characteristics, clinical characteristics, and other information. ResultsA total of 125 pertussis surveillance cases were investigated in 2019, including 73 clinically diagnosed cases (58.40%) and 52 confirmed cases (41.60%). The age of onset was mainly concentrated in children under 5 years old (108 cases, 86.40%), with the largest number of cases in infants aged less than 1-year-old (48 cases, 38.40%). Most cases had a history of receiving pertussis vaccine before onset (110 cases, 88.00%), and the intervals between the onset date and the date of last dose of pertussis vaccine in the 1‒2 doses group were significantly shorter than that in the 3‒4 doses group (U=-5.990, P<0.001). Probable household transmission of pertussis was found in 3 cases. All cases had cough symptoms, mainly manifested as whooping cough (77 cases, 61.60%), in addition to other main clinical manifestations, such as fever (76 cases, 60.80%), vomiting (30 cases, 24.00%), conjunctival congestion (27 cases, 21.60%), and inspiratory whoop (16 cases, 12.80%). A total of 73 cases (58.40%) experienced complications, including 1 death case. All the cases had multiple medical visit experiences before this visit, with an interval of 2 (0,3) days between the onset date and the first visit date. The misdiagnosis rate at the first medical visit was 88.00% (110/125), and the misdiagnosis rate of the first visit in secondary and primary hospitals was significantly higher than that in tertiary hospitals, exhibiting a statistically significant difference (χ²=21.582, P<0.001). ConclusionThe clinical symptoms of pertussis cases are often atypical, and the first diagnosis is prone to misdiagnosis, so it’s necessary to further strengthen the early diagnosis capabilities for pertussis cases in healthcare institutions, especially in the primary healthcare institutions.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Sepsis-induced lung injury is a common type of sepsis complicated with multiple organ dysfunction syndrome， whose uncontrolled inflammatory response and oxidative stress are the key pathological mechanisms. As an important pathway of anti-inflammatory and anti-oxidative stress， the nuclear factor-erythroid 2-related factor 2 （Nrf2） signaling pathway is very important in the occurrence and development of sepsis-induced lung injury. This review summarizes relevant research conducted over the past decade on the regulation of the Nrf2 signaling pathway by traditional Chinese medicine （TCM） to ameliorate sepsis- induced lung injury. It has been found that 14 kinds of TCM effective ingredients （including five types of compounds： flavonoids， terpenes， alkaloids， saponins， phenols） and 6 kinds of compound preparations （including three types of formulas： heat-clearing and detoxifying formulas， purgative formulas for promoting bowel movement， and formulas for reinforcing vital qi and consolidating the constitution） can inhibit inflammatory responses and oxidative stress by activating Nrf2 signaling pathway and intervening in related pathways such as those involving Kelch-like ECH-associated protein 1， heme oxygenase-1， antioxidant response element and AMP-activated protein kinase， thereby alleviating sepsis-induced lung injury.

[摘 要] 目的：探讨白蛋白结合型紫杉醇联合PD-1抑制剂用于治疗一线化疗失败的骨与软组织肉瘤的疗效及安全性。方法：回顾性分析北京积水潭医院骨肿瘤科2017年8月至2020年8月收治的一线化疗失败的晚期骨与软组织肉瘤患者。患者接受白蛋白结合型紫杉醇（125~140 mg/m2，第1天和第8天）与PD-1抑制剂（信迪利单抗或特瑞普利单抗，每21 d一次）联合治疗。每2个治疗周期评估1次疗效，按RECIST 1.1标准评估肿瘤疗效，按NCI-CTCAE5.0标准评估不良反应。结果：共20名患者纳入研究，完成1至8个治疗周期，中位治疗周期数为3个。所有患者均可评估疗效，完全缓解4例（20%），部分缓解0例，稳定9例（45%），疾病进展7例（35%）。客观缓解率（ORR）为20%，疾病控制率（DCR）为65%。中位无进展生存期（PFS）为3.0个月。治疗期间主要不良反应包括2级白细胞减少（40%）、1-2级神经毒性反应（20%），以及2级甲状腺功能减退（10%）。结论：白蛋白结合型紫杉醇联合PD-1抑制剂治疗为一线化疗失败的晚期骨与软组织肉瘤患者提供了一种潜在的治疗选择，其不良反应可控，值得开展更大样本的前瞻性研究进一步验证其疗效。

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Objective·To investigate the effect of Astragali Radix on T lymphocyte subsets and cytokine expression in Hashimoto's thyroiditis patients with normal thyroid function.Methods·A total of 120 Hashimoto's thyroiditis patients with normal thyroid function and complete data were selected from January 2020 to December 2020 in Jinshan Branch of Shanghai Sixth People's Hospital.The patients were randomly divided into intervention group(n=60)and control group(n=60)by the method of random number table.The treatment plan of the control group was iodine appropriate state diet,and the intervention group was combined with oral Astragali Radix solution(150 mL per time,twice/d)on the basis of the treatment of the control group.The two groups were treated for 6 months.The changes in peripheral blood serum T lymphocyte subsets(CD3+,CD4+,CD8+,and CD4+/CD8+),cytokines[interleukin-2(IL-2),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)],hypersensitive C-reactive protein(hs-CRP),erythrocyte sedimentation rate(ESR),thyroid function,autoantibody,liver and kidney function,and other biochemical indexes were compared before and after treatment between the two groups.Adverse reactions were observed during the treatment.The factors influencing the change amplitude of thyroid peroxidase antibody(TPOAb)were analyzed by multifactor linear regression.Results·Finally,118 patients,with 59 cases in each group,were included in the study.After 6 months of treatment,the intervention group showed significant improvements in the proportions of CD4+ T cells,the ratio of CD4+/CD8+,and the levels of IL-2,TNF-α,IL-10,hs-CRP,ESR,TPOAb,and thyroglobulin antibody(TGAb)compared to the values before treatment and in the control group(P<0.05).There were no statistically significant differences on the above indicators before and after treatment in the control group(P>0.05).No serious adverse reactions were observed in the intervention group.Multiple linear regression analysis results showed that the use of Astragali Radix,increase of CD4+ level,increase of CD4+/CD8+ ratio,and decrease of hs-CRP level were influencing factors for the decrease of TPOAb level(β=-0.393,P=0.029;β=-0.513,P=0.010;β=-0.351,P= 0.035;β=0.434,P=0.023).Conclusion·Astragali Radix can improve the levels of CD4+ T cells,CD4+/CD8+ratio,IL-2,TNF-α,IL-6,and IL-10 in Hashimoto's thyroiditis patients with normal thyroid function,and it is safe to use.

BACKGROUND:Filamin B(FLNB)can crosslink the actin cytoskeleton into a dynamic structure that is essential for the directional movement of cells.It can regulate the proliferation,differentiation and apoptosis of chondrocytes.However,the effect of FLNB on osteoblast proliferation,migration and apoptosis has not been reported. OBJECTIVE:To investigate the effect of FLNB on the proliferation,migration and apoptosis of MC3T3-E1 cells. METHODS:The adenoviral vectors for knockdown of FLNB expression(sh-FLNB1,sh-FLNB2,sh-FLNB3)were constructed and infected with MC3T3-E1 cells.After screened by puromycin drug,the efficiency of FLNB knockdown was detected by western blot and RT-PCR.The MC3T3-E1 cell line with the best efficiency of FLNB knockdown was selected as the stable transient cell line of MC3T3-E1 for subsequent experiments.The cells were divided into blank group,mc3t3 group,sh-NC group(empty vector),and sh-FLNB group(sh-FLNB lentivirus).The blank group was cultured in cell-free α-MEM complete medium;the mc3t3 group was cultured in α-MEM complete medium alone;and the sh-NC and sh-FLNB groups were cultured with α-MEM medium containing 2.5 μg/mL puromycin.After 3 days of culture,cell counting kit-8 assay and cell scratch assay were used to detect the proliferation and migration ability of MC3T3-E1;flow cytometry was used to detect cell apoptosis;and RT-PCR was used to detect the expression of apoptosis-related genes. RESULTS AND CONCLUSION:Western blot and RT-PCR results showed that the efficiency of FLNB knockdown was the best in the sh-FLNB3(P<0.000 1),which was used as a stable cell line for subsequent experiments.Cell counting kit-8 data showed that the proliferative ability of MC3T3 cells was significantly weakened after knockdown of FLNB(P<0.05).Cell scratch assay results showed that the migration ability of MC3T3 cells was significantly decreased after knockdown of FLNB.Flow cytometry and RT-PCR results showed that the apoptotic rate of MC3T3-E1 cells increased after knockdown of FLNB,the expression of pro-apoptotic factor Bax increased significantly,and the expression of anti-apoptotic factor Bcl-2 decreased significantly(P<0.05).To conclude,knockdown of FLNB can reduce the proliferation ability of MC3T3-E1 cells,decrease the migration ability of the cells,and increase cell apoptosis.

BACKGROUND:Currently,there is no drug that can completely cure osteoarthritis and its pathogenesis is still unclear.Circular RNAs(circRNAs)are differentially expressed in patients with osteoarthritis and are closely associated with various pathological processes in osteoarthritis.circRNAs play an important role in various physiological and pathological processes,such as chondrocyte homeostasis,extracellular matrix formation,and inflammatory response. OBJECTIVE:To mainly review the effects of circRNAs on pathological factors related to osteoarthritis,as well as the types and expression levels of circRNAs in osteoarthritis. METHODS:Related articles published from 1976 to August 2023 were retrieved from CNKI,WanFang,VIP,PubMed,Medline,Web of Science and Elsevier databases.The keywords were"osteoarthritis,circular RNA,non-coding RNA,synovial tissue,chondrocytes"in Chinese and English,respectively.All the relevant articles were screened,summarized,analyzed,and finally 69 papers were included in the review. RESULTS AND CONCLUSION:circRNAs are non-coding RNAs widely found in eukaryotic cells,with covalently closed continuous loop structure,but with no 5'hat structure and 3'poly A tail,which are involved in multi-gene and multi-target regulatory networks and cannot be degraded by nucleic acid exonucleases(RNase R).circRNAs have a high abundance,high conservativeness and stability,and cell and tissue specificity.circRNAs have biological functions such as acting as molecular sponges for miRNAs,regulating linear RNA transcription and RNA shearing,interacting with RNA-bound proteins,and translating proteins.circRNAs regulate chondrocyte apoptosis and proliferation,degradation of cartilage extracellular matrix,and inflammation and other physiopathologic processes.circRNAs are expected to become biomarkers and potential therapeutic targets for clinical diagnosis and prognosis of osteoarthritis,and may become a new strategy for clinical treatment of osteoarthritis in the future.

Objective:To explore the risk factors of neck work-related musculoskeletal disorders (WMSDs) among automobile manufacturing enterprise workers, and construct the risk prediction model.Methods:In May 2022, a cluster convenience sampling method was used to selet all front-line workers from an automobile manufacturing factory in Xiangyang City as the research objects. And a questionnaire survey was conducted using the modified Musculoskeletal Disorders Questionnaire to analyze the occurrence and exposure to risk factors of neck WMSDs. Logistic regression was used to analyze the influencing factors of workers' neck WMSDs symptoms, and Nomogram column charts was used to construct the risk prediction model. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve, the Bootstrap resampling method was used to verify the model, Hosmer-Lemeshow goodness of fit test was used to evaluate the model, and the Calibration curve was drawn.Results:A total of 1783 workers were surveyed, and the incidence of neck WMSDs symptoms was 24.8% (442/1783). Univariate logistic regression showed that age, female, smoking, working in uncomfortable postures, repetitive head movement, feeling constantly stressed at work, and completing conflicting tasks in work could increase the risk of neck WMSDs symptoms in automobile manufacturing enterprise workers ( OR=1.37, 95% CI: 1.16-1.62; OR=2.85, 95% CI: 1.56-5.20; OR=1.50, 95% CI: 1.18-1.91; OR=1.18, 95% CI: 1.02-1.37; OR=1.34, 95% CI: 1.04-1.72; OR=1.62, 95% CI: 1.21-2.17; OR=1.48, 95% CI: 1.13-1.92; P<0.05). While adequate rest time could reduce the risk of neck WMSDs symptoms ( OR=0.56, 95% CI: 0.52-0.86, P<0.05). The risk prediction model of neck WMSDs of workers in automobile manutacturing factory had good prediction efficiency, and the area under the ROC curve was 0.72 (95% CI: 0.70-0.75, P<0.001) . Conclusion:The occurrence of neck WMSDs symptoms of workers in automobile manufacturing factory is relatively high. The risk prediction model constructed in this study can play a certain auxiliary role in predicting neck WMSDs symptoms of workers in automobile manufacturing enterprise workers.

Objective To investigate the influencing factors for chronic pancreatitis(CP)complicated by pancreatogenic portal hypertension(PPH),and to establish a predictive model.Methods A retrospective analysis was performed for the clinical data of 99 patients with CP complicated by PPH who were hospitalized in The First Affiliated Hospital of Kunming Medical University,Chuxiong Yi Autonomous Prefecture People's Hospital,Wenshan People's Hospital,and Puer People's Hospital from January 2017 to December 2022,and these patients were enrolled as PPH group.The incidence density sampling method was used to select 198 CP patients from databases as control group.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.The Least Absolute Shrinkage and Selection Operator(LASSO)regression model was used to identify the potential predictive factors for CP complicated by PPH,and the predictive factors obtained were included in the multivariate Logistic regression analysis to obtain independent risk factors,which were used to establish a nomogram prediction model.The receiver operating characteristic(ROC)curve,the calibration curve,and the Hosmer-Lemeshow goodness-of-fit test were used to perform internal validation of the model,and the clinical decision curve was used to assess the clinical practicability of the model.Results There were significant differences between the two groups in sex,history of recurrent acute pancreatitis attacks,acute exacerbation of CP,bile duct stones,peripancreatic fluid accumulation,pseudocysts,pulmonary infection,elevated C-reactive protein(CRP),elevated procalcitonin,fibrinogen(FIB),neutrophil-lymphocyte ratio(NLR),gamma-glutamyl transpeptidase,total bilirubin,direct bilirubin,low-density lipoprotein(LDL),serum amylase,D-dimer,and serum albumin(all P<0.05).The predictive variables obtained by the LASSO regression analysis included sex,recurrent acute pancreatitis attacks,bile duct stones,peripancreatic fluid accumulation,pulmonary infection,pseudocysts,CRP,NLR,FIB,and LDL.The multivariate Logistic regression analysis showed that sex(odds ratio[OR]=2.716,P<0.05),recurrent acute pancreatitis attacks(OR=2.138,P<0.05),peripancreatic fluid accumulation(OR=2.297,P<0.05),pseudocysts(OR=2.805,P<0.05),and FIB(OR=1.313,P<0.05)were independent risk factors for CP complicated by PPH.The above factors were fitted into the model,and the Bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.787(95%confidence interval:0.730—0.844),and the calibration curve was close to the reference curve.The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good degree of fitting(χ2=7.469,P=0.487).The clinical decision curve analysis showed that the prediction model had good clinical practicability.Conclusion Male sex,recurrent acute pancreatitis attacks,peripancreatic fluid accumulation,pseudocysts,and FIB are independent risk factors for CP complicated by PPH,and the nomogram model established has good discriminatory ability,calibration,and clinical practicability.