ObjectiveTo screen key genes associated with neuroblastoma （NB） diagnosis and prognosis using the Gene Expression Omnibus （GEO） database， and to investigate the expression and clinical significance of nucleoporin 93 （NUP93） in NB tissues. MethodsNB gene chip data （GSE73517， GSE49710， GSE19274） were retrieved from the GEO database. Differentially expressed genes （DEGs） commonly upregulated in high-risk groups were screened. The R2 database was then used to assess the prognostic value of DEGs that were commonly upregulated in the MYCN amplification group. Finally， NUP93 expression levels in the tissues from 60 NB， 25 ganglioneuroblastoma （GNB）， and 26 ganglioneuroma （GN） cases were measured by immunohistochemistry . ResultsTwenty-five DEGs were identified as commonly upregulated in high-risk groups. Among these， 10 genes （SIVA1， NUP93， STIP1， LSM4， RAI14， MYOZ3， KNTC1， TNFRSF10B， TACC3 and CEP152） showed significantly higher expression in MYCN-amplified subgroups （P＜0.05）. Survival analysis revealed that high NUP93 expression was associated with shorter overall survival （HR = 4.0， 95% CI： 3.0，5.3， P = 1.80 × 10⁻³⁴）. Immunohistochemistry results revealed that NUP93 expression in NB tissues was significantly higher than in GNB and GN tissues （P＜0.001）. NUP93 expression was positively correlated with high mitosis-karyorrhexis index （MKI； P=0.040）， poor differentiation （P＜0.001）， and MYCN expression （r_s = 0.793， P ＜0.001）. ConclusionsHigh expression of NUP93 is associated with high MKI and poor differentiation， and predicts unfavorable prognosis in patients with NB， suggesting it may promote tumor progression by regulating MYCN. NUP93 has the potential to be a novel diagnostic biomarker and therapeutic target for NB.

OBJECTIVE To explore the effects of CD20 coding gene （MS4A1） polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020， with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software， including rs1051461， rs17155034， rs4939364， and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors（demographic， clinical， and genotypic variables） in patients and the steady-state trough concentration of rituximab during the first course of treatment， followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival （PFS） and overall survival （OS）. Using MS4A1 genotype and tumor stage as independent variables， Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL，which was significantly lower than 21.95 μg/mL in AA+AC carriers （P＜0.05）. The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers， CT+TT carriers had significantly prolonged PFS and OS （P＜0.05）. The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype （HR＝4.406， 95%CI：1.743-11.137， P＜0.05） and tumor Ⅲ&Ⅳ （HR＝3.233， 95%CI： 1.413-7.399， P＜0.05） were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab， and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.

Chikungunya fever （CHIKF） is a mosquito-borne infectious disease caused by Chikungunya virus （CHIKV） infection. The acute phase of CHIKF is mainly characterized by fever， severe polyarthralgia， and rash. Most cases are self-limited， however， atypical manifestations and chronic complications also occur in a minor proportion of cases. High-risk cases are at risk of complicating with severe condition. For these years， the emergence and spread of CHIKF place it as an international public health disease. This article summarizes the current knowledge and advances about CHIKF， with a focus on the diagnosis， differential diagnosis， evaluation， treatment， prevention and control. For individuals with a history of traveling to CHIKF prevalence areas within 12 days， presenting with fever， arthralgia， and rash， combined with laboratory tests such as positive IgM antibody， specific IgG antibody， CHIKV isolation， or viral nucleic acid testing in acute stage， could establish the diagnosis. Differential diagnosis with infection caused by similar viruses such as dengue virus and Zika virus should be considered too. Regarding treatment， there is no specific antiviral drug available currently. Supportive method is the dominating treatment， with non-steroidal anti-inflammatory drugs used to alleviate fever and arthralgia. The core strategy in prevention and control of CHIKF is to interrupt the transmission and eliminate mosquitoes. To meet challenges posed by the spread of CHIKF， the future researches should emphasize on developing specific antiviral drugs， safe and effective vaccines， and convenient and accurate diagnostic means.

In environmental epidemiological research, extensive non-random environmental exposures and complex confounding biases pose significant challenges when attempting causal inference. In recent years, the introduction of causal inference methods into observational studies has provided a broader range of statistical tools for causal inference research in environmental epidemiology. The instrumental variable (IV) approach, as a causal inference technique for effectively controlling unmeasured confounding factors, has gradually found application in the field of environmental epidemiological research. This article reviewed the basic principles of IV and summarized the current research progress and limitations of applying IV for causal inference in environmental epidemiology. IV application in the field of environmental epidemiology is still in the initial stage. Rational use of IV and effective integration with other causal inference methods will become the focus of the development of causal inference in environmental epidemiology. The aim of this paper is to provide a methodological reference and basis for future studies involving causal inference to target population health effects of environmental exposures in China.

ObjectiveTo explore the function of DANCR during the differentiation of human embryonic stem cells （hESC） toward definitive endoderm （DE）. MethodsThe in vitro DE differentiation system was established and its efficiency was verified. The correlation between the expression level of DANCR and DE differentiation process was detected. Using lentivirus system， we stably knocked down DANCR in hESC. The shDANCR hESC line was applied to DE differentiation， using qPCR and Western blot to detect the expression of DE marker genes SOX17 and FOXA2， and that of primitive streak marker genes Brachyury （T）， EOMES， MIXL1 and GSC. Dual luciferase reporter assay and qPCR were used to confirm the interaction between DANCR and the WNT pathway during DE differentiation. ResultsThe in vitro differentiation system mimicked DE differentiation efficiently. And the expression of DANCR was gradually downregulated during differentiation. DANCR was efficiently knocked down in the shDANCR hESC line （P < 0.001）. Compared with those in the control group， the expression levels of primitive markers Brachyury （T）， EOMES， MIXL1 and GSC， as well as DE markers SOX17 and FOXA2， were significantly decreased in shDANCR groups （P < 0.05）. Furthermore， the transcriptional activity of the WNT pathway in shDANCR groups was lower than that in the control group （P < 0.05）. And RNA levels of downstream genes of the WNT pathway， FZD5， FZD8， SFRP1， FRZB and ANKRD6， were significantly decreased in shDANCR groups （P < 0.05）. However， differences in protein levels of the TGFβ pathway effectors SMAD2/3 and p-SMAD2 were statistically insignificant in shDANCR and control groups （P > 0.05）. Forced activation of β-CATENIN rescued DANCR knock down-induced deficiency in DE differentiation. ConclusionsThe expression of DANCR decreases during DE differentiation. DANCR may promote DE differentiation through modulating the activity of the WNT pathway.

Bone Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*

AIM To explore the effect of Compound Fo'ercao Mixture on TLR4/MyD88/NF-κB signaling pathway in a rat model of chronic obstructive pulmonary disease(COPD).METHODS Rats were randomly divided into the blank group(n=10),and the model group(n=50)for the establishment of a rat model of COPD by 12-week cigarette smoke exposure combined with intratracheal injection of LPS.The successful rat models were randomly divided into the model group,the dexamethasone group(0.5 mg/kg)and the low,medium and high dose Compound Fo'ercao Mixture groups(6.8,13.6 and 27.2 g/kg),with 10 rats in each group.After 24 weeks of drug intervention,the rats had their lung function detected by animal lung function meter;their pathological changes of lung tissue observed by HE staining;their serum TNF-α,IL-1β,IL-6,and MDA levels and SOD activity detected by ELISA;their pulmonary mRNA expressions of TLR4,MyD88,NF-κB and caspase-3 detected by RT-qPCR;and their pulmonary protein expressions of TLR4,MyD88,NF-κB and TNF-α detected by Western blot.RESULTS Compared with the blank group,the model group displayed obviously pulmonary ventilation dysfunction,damaged lung tissue and bronchus,decreased SOD activity(P＜0.01);increased serum TNF-α,IL-1β,IL-6 and MDA levels(P＜0.01);and increased pulmonary expressions of TLR4,MyD88,NF-κB and caspase-3 mRNA and TLR4,MyD88,NF-κB and TNF-α proteins(P＜0.01).Compared with the model group,all Compound Fo'ercao Mixture groups shared improvement in lung function indices levels and lung tissue damage;decrease in the levels of serum TNF-α,IL-1β,IL-6 and MDA(P＜0.05,P＜0.01);and decrease in the pulmonary expressions of TLR4,MyD88,NF-κB and caspase-3 mRNA and TLR4,MyD88,NF-κB and TNF-α protein(P＜0.05,P＜0.01)in a dose-dependent manner.CONCLUSION Compound Fo'ercao Mixture can improve the lung dysfunction and pathological injury in a rat model of COPD,and its mechanism may be associated with the regulated TLR4/MyD88/NF-κB signaling pathway.

Objective:To construct a leadership evaluation indicator system for managers in primary healthcare institutions.Methods:This study was a qualitative research. Based on the Chinese Academy of Sciences′ Five Forces Model of Leadership, the framework of the leadership evaluation indicator system for primary healthcare institution managers was initially constructed through literature review, expert interviews, surveys, and group discussions. From November 2020 to June 2021, 19 experts were invited to participate in two rounds of Delphi expert consultations. Based on the consultation results, the leadership evaluation indicator system for primary healthcare institution managers was developed, and the analytic hierarchy process (AHP) was used to determine the weight of each indicator.Results:Nineteen consulting experts were included in the study, 13 of whom were aged 40 years or older, and seven of whom had 20 years or more of professional experience. The response rates of the two rounds of Delphi expert consultation questionnaires were 18/19 and 19/19, respectively; the authority coefficients of the experts were 0.92 and 0.91, respectively. In the second round of consultation, the coordination coefficients of each level of indicators were 0.640, 0.557, and 0.512 ( P<0.05), respectively. The constructed leadership indicator system for managers of primary healthcare institutions included five primary indicators, 16 secondary indicators, and 44 tertiary indicators. The primary indicators, in order of their weight, were "influence"(0.299),"decisiveness"(0.245),"control"(0.156),"inspiration"(0.150), and "foresight"(0.150). Conclusions:This study is a preliminary construction of a leadership evaluation indicator system for managers of primary healthcare institutions, which can be a reference for the training and evaluation of relevant talents.

Objective:To evaluate the reliability and validity of a questionnaire assessing the leadership qualities of primary healthcare institution managers, and to further clarify the current state of leadership development among management teams of community health service centers in Shanghai.Methods:The study was a cross-sectional survey. It was conducted from August to December 2021, and used a stratified sampling method. Using a self-developed questionnaire for primary healthcare institution managers, we surveyed 279 individuals from 10 community health service centers in Shanghai, including management teams, middle-level cadres, general practitioners, and staff from health administrative departments in their respective districts. Leadership qualities were evaluated on five dimensions: inspiration, decisiveness, control, influence, and foresight. Cronbach′s α coefficient and split half coefficient were used to analyze the reliability of the questionnaire, and confirmatory factor analysis was used to assess the structural validity of the scale.Results:The overall Cronbach′s α reliability of the questionnaire for the comprehensive management of community health service centers was 0.96, and the Spearman-Brown split-half coefficient was 0.94. The validity analysis yielded a KMO value of 0.975, the RMSEA for factor analysis was 0.085, and the adaptation indexes all met the model adaptation conditions. Of the 279 participants, 174 were female (62.4%), 257 held a mid-level or higher professional title (92.1%). The overall leadership score of the community health service center management teams was (4.43±0.59), with the dimensions ranked from highest to lowest as follows: inspiration (4.52±0.55), decisiveness (4.46±0.62), control (4.44±0.60), influence (4.42±0.63), and foresight (4.32±0.69). The foresight score was significantly lower than the other four dimensions (all P<0.05). Conclusions:The questionnaire used to assess the leadership qualities of primary healthcare institution managers is reliable and valid. The development of leadership qualities among management teams of community health service centers in Shanghai is unbalanced, with foresight being the weakest dimension.

Objective:To investigate the current status of research on the construction of leadership indicator system in the medical field at home and abroad, and to analyze the characteristics of the indicator system therein.Methods:This was a bibliometric study. The group applied subject keywords to search relevant literature on the construction of leadership indicator system in the medical field at home and abroad on English websites PubMed, Web of Science, Google Scholar, CINAHL, Scopus and Chinese websites Baidu Academic, CNKI, CQVIP, Wanfang Data Knowledge Service Platform, with a time frame of 2016-2023. The basic characteristics of the literature, the theoretical framework of the research application and the research theme were extracted, and the content of the indicator system in the literature was reviewed and summarized.Results:A total of 21 literatures were included, including 7 Chinese literatures and 14 English literatures. Of these literatures, 10 focused on physician leadership, 5 on medical manager leadership, and 2 on general practitioner leadership. Among 16 research literatures, 9 informed the theoretical basis of leadership, and 4 literatures were applied research. Five main themes were identified: leadership studies of individual healthcare administrators, leadership development in healthcare, interest and attitudes of healthcare workers towards leadership learning, applications of leadership in healthcare, and the impact of leadership in healthcare on patients and healthcare organizations.Conclusions:At present, research on the construction of the leadership indicator system in the medical field presents is diverse, with differences in theoretical basis and content. The original and empirical research is still insufficient.