Objective: To elucidate the biological basis of traditional Chinese medicine (TCM) syndromes from the perspective of “same syndrome, different diseases” in patients with chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC), thereby providing a complementary approach for the diagnosis and treatment of chronic liver diseases (CLD). Methods: To investigate the dynamic characteristics of TCM syndromes in CLD, transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) was performed from patients with CHB, LC, or HCC presenting with three TCM syndromes: liver gallbladder dampness heat syndrome (LGDHS), liver depression spleen deficiency syndrome (LDSDS), and liver kidney Yin deficiency syndrome (LKYDS). These participants were recruited at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between August 1, 2018 and December 31, 2021. Differentially expressed genes (DEGs) were identified using the random variance model (RVM) F test with false discovery rate (FDR) correction. Principal component analysis (PCA) and unsupervised hierarchical clustering were applied to visualize sample grouping. Dynamic network biomarkers (DNB) analysis was employed to detect critical transition stages during syndrome evolution, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to characterize the functional roles and pathway involvement of the DNB members. Random forest (RF) analysis and the area under the receiver operating characteristic (ROC) curves (AUC) were used to rank the importance of candidate genes. External validation was performed using microarray data from an independent CLD cohort (GSE89377) and RNA-seq data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset. Additionally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed on an independent cohort of LC patients to validate the expression levels of the candidate genes. Results: The study included a total of 132 participants. DNB analysis identified LDSDS stage as a critical tipping point during TCM syndrome evolution across CHB, LC, and HCC. The phosphoinositide 3-kinase/protein kinase B (PI3K-AKT) signaling pathway was consistently enriched in the DNB analysis across all three types of CLD, suggesting its potential involvement in the critical transition of TCM syndromes. Among the 24 core DNB members of the PI3K-AKT pathway, four genes—integrin subunit beta 1 (ITGB1), collagen type IV alpha 1 chain (COL4A1), collagen type IV alpha 2 chain (COL4A2), and DNA damage inducible transcript 3 (DDIT3)—were identified by RF analysis (Gini score > 1) and ROC analysis. ROC analysis demonstrated high discriminative ability for distinguishing LGDHS from LKYDS in CHB patients, with AUC of 0.7891 for ITGB1, 0.7070 for COL4A1, 0.7148 for COL4A2, and 0.8945 for DDIT3. In the independent CLD cohort (GSE89377), all four genes showed significant stepwise upregulation from normal to CHB, LC, and HCC (all P < 0.05). In the TCGA-LIHC dataset, their expression progressively increased with tumor stage. RT-qPCR validation in an independent LC cohort (30 LGDHS vs. 30 LKYDS) confirmed that ITGB1, COL4A2, and DDIT3 were significantly upregulated in LKYDS compared with LGDHS (P = 0.0152, 0.0186, and 0.0247, respectively), whereas COL4A1 showed a non-significant upward trend (P = 0.1201). Conclusion This study introduces a novel approach to understanding the molecular features underlying TCM syndrome evolution in CLD. The PI3K-AKT pathway and four identified genes (ITGB1, COL4A1, COL4A2, and DDIT3) play crucial roles in the transition from excess (LGDHS) to deficiency (LKYDS) via the critical LDSDS stage. These findings offer potential quantitative biomarkers and therapeutic targets for TCM syndrome differentiation and may help arrest syndrome progression in CLD.

ObjectiveTo analyze the epidemiological characteristics of long COVID and to investigate its main influencing factors by examining individuals infected with SARS-CoV-2 between March and June 2022 in two communities in Shanghai, to lay the foundation for further research on the mechanism and clinical treatment of long COVID, and to provide the basis for the development of inexpensive, convenient, and feasible prevention and intervention strategies. MethodsA cross-sectional study was conducted, enrolling 6 410 individuals infected with SARS-CoV-2. Data were collected through a questionnaire survey. The incidence and common symptoms of long COVID were analyzed, along with their associations with demographic characteristics, medical history, and behavioral factors. A logistic regression model was used to identify the major factors associated with the development of long COVID symptoms. ResultsThe overall incidence rate of long COVID among the study population was 13.9%. The most commonly reported symptoms included fatigue (65.1%), attention disorders (23.1%), and cough (16.9%). The analysis showed that having underlying chronic diseases (OR=2.580, 95%CI: 2.165‒3.074), a history of allergies (OR=1.418, 95%CI: 1.003‒1.971), current smoking (OR=1.461, 95%CI: 1.013‒2.079), ever smoking (OR=2.462, 95%CI: 1.687‒3.551), a greater number of symptoms during the acute phase [1 symptom (OR=1.778, 95%CI: 1.459‒2.162), 2 symptoms (OR=2.749, 95%CI: 2.209‒3.409), ≥3 symptoms (OR=7.792, 95%CI: 6.333‒9.593)] and aggravated symptoms during the acute phase (OR=1.082, 95%CI: 1.070‒1.094) were factors associated with a higher risk of developing long COVID symptoms. Additionally, individuals who had consumed alcohol in the past year (OR=1.914, 95%CI: 1.344‒2.684) were more prone to objective long COVID symptoms. Among individuals under 50 years of age, females (OR=1.427, 95%CI: 1.052‒1.943) were more likely to develop objective long COVID symptoms. ConclusionThis study has identified the diversity of long COVID symptoms, which involve multiple organs and systems, including fatigue, attention disorders, cough, and joint pain. It has also revealed associations between long COVID and various demographic factors (e.g., age, gender), personal medical history (e.g., underlying chronic diseases, history of allergies), acute-phase characteristics (e.g., number and severity of symptoms), and behavioral factors (e.g., smoking, alcohol consumption). These findings highlight the need for further research and ongoing surveillance of long COVID and may inform the development of more targeted health management strategies for specific populations.

Objective: To investigate the trend in disease burden of injuries among children and adolescents in China from 1990 to 2021, so as to provide a basis for formulating prevention and control strategies and reducing this disease burden. Methods: Data on mortality, disability-adjusted life years (DALY) rate, incidence, and prevalence of injuries among children and adolescents aged <20 years in China from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. All rates were standardized using the GBD 2021 world standard population. The trend in incidence of disease burden of injuries among children and adolescents across differents genders and ages from 1990 to 2021 was evaluated using average annual percent change (AAPC). Results: From 1990 to 2021, the standardized mortality (AAPC=-5.435%), standardized DALY rate (AAPC=-5.311%), standardized incidence (AAPC=-0.466%), and standardized prevalence (AAPC=-0.810%) of injuries among children and adolescents in China showed downward trends (all P<0.05). Among these, the standardized mortality of animal contact (AAPC=-9.138%) and the standardized DALY rate of medical side effects (AAPC=-8.389%) decreased at a relatively fast pace, while the standardized incidence of falls (AAPC=0.083%) and the standardized prevalence of exposure to natural forces (AAPC=2.656%) showed upward trends (all P<0.05). The standardized mortality, standardized DALY rate, standardized incidence and standardized prevalence of injuries were higher in males than in females. The trend in males showed a downward trend (all P<0.05), consistent with the total population. The crude incidence of injuries in the group aged 15-<20 years showed an upward trend (AAPC=0.391%, P<0.05), while the trend in the group aged 10-<15 years was not statistically significant (P>0.05). The crude incidence of injuries in the groups aged 5-<10 years and <5 years showed downward trends (AAPC=-0.488% and -2.275%, both P<0.05). In 2021, the <5 years age group had the highest crude mortality and crude DALY rate of injuries, at 13.94/100 000 and 1 257.26/100 000, respectively. The 15-<20 years age group exhibited the highest crude incidence and crude prevalence, at 4 874.05/100 000and 4 050.35/100 000, respectively. Drowning and falls were major components of the disease burden across all age groups. Conclusions From 1990 to 2021, the disease burden of injuries among children and adolescents in China showed an overall downward trend. The disease burden was consistently higher in males than in females. Children aged <5 years face a high risk of fatality and disability, while adolescents aged 15-<20 years experience a high incidence and frequency of injuries. Drowning and falls were key priorities for prevention and control.

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

OBJECTIVE To establish a core competency evaluation system for drug clinical trial quality management personnel in China and validate its application. METHODS Based on the scope of work， responsibilities， and role positioning of quality management personnel in drug clinical trials， a preliminary draft of the core competency evaluation system was constructed through literature analysis and expert consultation. The draft was refined through a Delphi method involving 17 experts who provided feedback and revisions， ultimately forming a complete evaluation system. The developed system was applied to conduct electronic surveys from March to May 2024 among 110 quality management personnel from 38 drug clinical trial institutions， comparing their scores on indicator importance and self-assessed capabilities. RESULTS The response rate of both rounds of questionnaire survey was 100%， with Kendall’s W coefficients of 0.256 and 0.277 （P＜0.001 for both）， and an expert authority coefficient of 0.946. The finalized evaluation system for core competencies of clinical trial quality management personnel comprised 9 primary indicators， covering individual professional competence， communication skills， implementation condition verification， informed consent process review， clinical trial execution monitoring， adverse event disposal， reporting and documentation， trial record examination， trial report auditing， and inspection of other tasks， and 107 secondary indicators. Empirical research revealed significant discrepancies between importance scores and self-assessed competency scores across 70 indicators among 110 respondents （P＜0.05）. Indicators with relatively notable gaps between importance scores and self-assessed competency scores included in-depth understanding of Good Clinical Practice （GCP） requirements （0.34-point gap）， familiarity with national and institutional clinical trial inspection priorities （0.24-point gap），etc. CONCLUSIONS The indicator system constructed in this study has good scientificity and reliability. Clinical trial quality management personnel demonstrate deficiencies in multiple critical competencies， highlighting the urgent need for targeted training programs to enhance their overall professional capabilities.

ObjectiveTo analyze the epidemiological characteristics and influencing factors of SARS-CoV-2 reinfection by conducting follow-up investigations among community residents who experienced their first SARS-CoV-2 infection between March and June 2022, so as to provide a scientific basis for predicting future epidemic trends and adjusting prevention and control strategies. MethodsA cohort study was conducted in Xuhui District, Shanghai. A total of 1 208 individuals with a documented primary SARS-CoV-2 infection between March and June 2022 were enrolled and followed-up longitudinally. Data were collected using structured questionnaire surveys to assess the reinfection rate, incidence density, and clinical manifestations of SARS-CoV-2 reinfection. A logistic regression model was used to analyze the influencing factors of SARS-CoV-2 reinfection. ResultsA total of 497 SARS-CoV-2 reinfection cases were observed among the 1 208 research subjects, with a reinfection rate of 41.14% and an incidence density of 0.63 cases per 1 000 person-days. The cumulative reinfection rates at 6, 9, 12, 15, and 18 months following the initial infection were 0.08%, 15.31%, 19.04%, 33.53%, and 38.25%, respectively. Compared with the primary infection, reinfection was more likely to be symptomatic, with a greater severity of fever, dry cough, sore throat, and runny nose. Being female, younger age, and symptom duration ≥7 days during the primary infection were identified as influencing factors for SARS-CoV-2 reinfection, while a higher socioeconomic status can reduce the risk of SARS-CoV-2 reinfection. ConclusionSARS-CoV-2 reinfection is relatively common and often symptomatic. Age, gender, income level, and the duration of symptoms during the primary infection are identified as infuencing factors for SARS-CoV-2 reinfection. Continuous monitoring of reinfection in the population is recommended, along with the development of effective strategies to mitigate the impact of reinfection.

Objective To observe the value of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies.Methods Totally 118 fetuses with intracranial anomalies diagnosed through cranial MRI/induced labor specimen dissection who underwent prenatal ultrasound examination were retrospectively enrolled.Two-dimensional,three-dimensional ultrasound and microvascular flow imaging manifestations of fetal intracranial anomalies were observed,and the accuracy of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies was analyzed.Results The accuracy of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies was 93.22％(110/118),of isolated and non-isolated intracranial anomalies was 97.47％(77/79)and 84.62％(33/39),respectively.Six fetuses were missed diagnosis of malformations of cortical development(1 fetus of tuberous sclerosis,4 of abnormal morphology of the sulci gyrus and 1 of schizencephaly)and 1 fetus of intracranial softening lesion,while posterior fossa arachnoid cyst in 1 fetus was misdiagnosed as mega cisterna magna.Conclusion The accuracy of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies was relatively high.

Objective To observe prenatal ultrasonic findings of fetal malformation of cortical development(MCD).Methods Totally 37 singleton fetuses with MCD diagnosed by fetal cranial MRI and/or genetic examination were retrospectively enrolled,and prenatal ultrasonic manifestations were observed.Results Among 37 fetuses,29(29/37,78.38％)were found with abnormal Sylvian fissure,26(26/37,70.27％)with widened/asymmetrical lateral ventricles,22(22/37,59.46％)with abnormal surface sulci,14(14/37,37.84％)with abnormal cavity of septum pellucidum(CSP)/corpus callosum(CC),11(11/37,29.73％)with midline deviation/curvature,11(11/37,29.73％)with widened subarachnoid space,10(10/37,27.03％)with head circumference＜2 standard deviation below mean value,9(9/37,24.32％)with abnormalities in the cerebellar hemisphere/vermis,7(7/37,18.92％)with abnormal echoes in the brain parenchyma,7(7/37,18.92％)with midline cysts and 2(2/37,5.41％)with enlarged ganglion eminence.Conclusion Fetal MCD mainly presented as abnormal Sylvian fissure,widened/asymmetrical lateral ventricles and abnormal surface sulci,which might accompanied by abnormal CSP/CC,midline deviation/curvature,widened subarachnoid space and abnormal head circumference in prenatal ultrasound.

This study investigates the feasibility of the VP8*protein as a subunit vaccine target for porcine rotavirus A(PoRVA),a major causative agent of diarrhea in piglets.The VP8* genes of PoRVA P[13]and P[23]genotype strains were amplified by RT-PCR.These genes were then liga-ted into the pET-28a(+)vector,yielding recombinant plasmids pET-28a-XJWF1-VP8*-P[23]and pET-28a-ShXYW13-VP8*-P[13].These plasmids were subsequently transformed into BL21(DE3)competent cells.The VP8*protein,induced by IPTG,was purified using affinity chroma-tography,and its expression and purification were verified by SDS-PAGE and Western blot.The purified VP8* protein was used to immunize mice,and serum samples were collected after three immunizations.Cross-neutralization assays were conducted to evaluate the ability of the VP8*protein immune serum to neutralize different genotype strains.The results demonstrated the ex-pression of soluble VP8*protein,with SDS-PAGE and Western blot analyses showing that the purified VP8*protein existed in both monomeric(27 kDa)and homodimeric(54 kDa)forms.ELISA results indicated that high levels of antibodies were produced in mice immunized with VP 8*-P[13]and VP8*-P[23]after three immunizations.Serum cross-neutralization assays revealed that the neutralizing titers of PoRVA VP8*-P[13]and VP8*-P[23]immune sera against homol-ogous genotype strains ranged from 1∶4 800 to 1∶19 200,significantly higher than those against heterologous genotype strains(1∶1 200).This suggests that the VP8*protein of different geno-type strains exhibits both antigenic conservation and distinct variability.The data obtained in this study provide a solid foundation for further exploration of the antigenic structure of the PoRVA VP8* protein and the development of novel subunit vaccines.

Objective:To observe and assess the clinical value of electrophysiology of ocular surface in the diagnosis and treatment of blepharospasm in Meige syndrome (MS).Methods:A single-center, cross-sectional study. A total of 413 patients diagnosed with MS and undergoing surgical treatment at the Henan Provincial Meige Syndrome Diagnosis and Treatment Center of the Henan Provincial Third People′s Hospital from May 2022 to December 2023 were included as the MS group. A total of 110 age- and gender-matched spouses of patients and community volunteers were selected as the control group. The bioelectricity detection program of the electrooculogram was used; the frequency bandwidth was set at 0.3 to 300.0 Hz. Surface electrodes were employed to record the surface electrophysiological manifestations of the corrugator supercilii muscle and the lower orbicularis oculi muscle, as well as the conditions and temporal characteristics of spasm waves. Based on the amplitude and waveform of the electrophysiology of ocular surface signals, it can be classified into 0-4 grades. The blepharospasm was divided into conditionally induced type, spastic type, reverse spastic type, and oro-ocular elicited type. All patients were treated with neural circuit occlusion, and the postoperative follow-up time was 4.1 (0.5-19.0) months. The distribution of different grades of electrophysiology of ocular surface in the MS and control group at baseline were observed, as well as within the MS group at the last follow-up visit. Additionally, the blepharospasm grades in the MS group were also assessed. The comparison of the distribution of the number of eyes with different grades of electrophysiology of ocular surface between groups was conducted using the Mann-Whitney U test. Results:At baseline, in the MS group, the number of cases with corrugator supercilii muscle amplitudes and morphologies graded from 0 to 4 were as follows: 15 (3.60%, 15/413) for grade 0, 95 (23.00%, 95/413) for grade 1, 142 (34.38%, 142/413) for grade 2, 127 (30.75%, 127/413) for grade 3, and 34 (8.24%, 34/413) for grade 4. In the control group, the corresponding numbers of individuals were 82 (74.54%, 82/110) for grade 0, 24 (21.82%, 24/110) for grade 1, 4 (3.64%, 4/110) for grade 2, 0 (0.00%, 0/110) for grade 3, and 0 (0.00%, 0/110) for grade 4. For the orbicularis oculi muscle, there were 35 cases (8.47%) in grade 0, 124 cases (30.03%) in grade 1, 150 cases (36.32%) in grade 2, 90 cases (21.79%) in grade 3, and 14 cases (3.39%) in grade 4 in the MS group. In the control group, there were 86 cases (78.18%) in grade 0, 24 cases (21.82%) in grade 1, and 0 cases in grades 2, 3, and 4. There were statistically significant differences in the distribution of the number of eyes with different electrophysiology of ocular surface grading of the corrugator supercilii muscle and the orbicularis oculi muscle between the MS and control group ( Z=-14.51, -13.86; P<0.001). Meanwhile, there were statistically significant differences in the distribution of the number of eyes with different electrophysiology of ocular surface grading of the corrugator supercilii muscle and the orbicularis oculi muscle between preoperation and at the last follow-up in the MS group ( Z=-16.52, -17.36; P<0.001). In the MS group, there were 61 (14.77%, 61/413), 306 (74.09%, 306/413), 27 (6.54%, 27/413) and 19 (4.60%, 19/413) cases of blepharospasm conditionally induced type, spasm type, reverse spasm type and oro-ocular elicited type, respectively. Conclusion:The electrophysiology of the ocular surface can objectively reflect the activity of periocular neuromuscular.