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 explore the clinical manifestations, auxiliary examinations, treatment, and outcomes of autoimmune-associated epilepsy (AAE) with anti-glutamic acid decarboxylase 65 (GAD65) antibodies.Methods:Nine patients diagnosed with AAE with anti-GAD65 antibodies between July 2019 and December 2023 at the Department of Neurology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, were enrolled. Their clinical data and prognosis were retrospectively analyzed.Results:The onset age of these 9 cases was 13.0-59.0 (29.0±13.4) years, with 8 females and 1 male. The main clinical phenotypes at onset included limbic encephalitis/extralimbic encephalitis (6 cases) and chronic epilepsy (3 cases, of whom 1 case was accompanied with stiff person syndrome). The former often demonstrated T 2/fluid attenuated inversion recovery (FLAIR) hyperintensities and enlargement of hippocampus and amygdala (5 cases), and may present with concomitant meningoencephalitis (2 cases) or hypertrophic pachymeningitis (1 case). The latter showed normal (2 cases) or increased T 2/FLAIR signals in the hippocampal tails (1 case) in magnetic resonance imaging. Electroencephalogram findings were usually characterized by slow activities (6 cases) and temporal epileptiform discharges (6 cases). Five cases concurrently presented with one or more other autoimmune diseases, including the autoimmune polyendocrine syndrome type Ⅱ in 1 case. All cases received first-line immunotherapy and 7 cases received long-term immunosuppressive agents. Eight cases were followed up for 5-45 months and 2 cases experienced relapse of autoimmune encephalitis (presented with new-onset seizures). At the last follow-up, all cases achieved favourable outcomes according to the modified Rankin Scale scores (all≤2) and 4 patients had reduced seizures, of whom 2 were seizure-free. Conclusions:Anti-GAD65 antibody-positive AAE is mainly composed of postencephalitic epilepsy and chronic temporal lobe epilepsy. The co-occurrence of systemic autoimmune diseases is common, and meningeal lesions sometimes can be involved in MRI findings. Patients usually have poor response to immunotherapy and anti-seizure medication,and some postencephalitic epilepsy patients who receive early immunotherapy and long-term immunosuppressants can achieve sustained seizure freedom.

The World Health Organization (WHO) classification serves as the internationally recognized standard for diagnosing and classifying hematopoietic and lymphoid tissue tumors(WHO-HEAM). Since 2001, it has undergone multiple upgrades and revisions, updating, clarifying, and refining previous tumor diagnostic and classification standards while incorporating numerous new genetic and molecular biological subtypes. In 2022, two classification proposals emerged due to a wealth of clinical and scientific research results: the fifth edition of the WHO hematopoietic and lymphoid tissue classification (WHO-HAEM5), published in Leukemia journal; and the International Consensus Classification (ICC), published in Blood journal. These two schemes differ in their approach to classifying hematopoietic and lymphoid tissue tumors, posing challenges for clinical laboratory diagnosis and treatment.

Objective To compare and explore the differences between the eight batches of drugs in the centralized procurement list and the 2018 edition of the national essential medicine list,and to provide reference for updating and improving the national essential medicine list and the national centralized procurement list of drugs.Methods The category,generic name variety,specification,and other information of drugs included in the centralized drug procurement were collected and compared with the 2018 edition of the national essential medicine list,and the reasons for differences were analyzed.Results A proportion of 39%of centralized procurement drugs were listed in national essential medicines.Forty pharmacological classifications were not involved in the drugs of centralized procurement.Only anticoagulant and thrombolytic drugs with dual attributes accounted for a smaller variety proportion than the specification proportion.Conclusion There are some differences between the centralized procurement list and the 2018 edition of the national essential medicine list,which have some rationality,but also some problems to be solved.

Objective To explore the current status of medication literacy among urban elderly patients with chronic diseases in Anhui Province,aiming to reveal the factors influencing their medication literacy,and to propose targeted measures for improvement.Methods This research involved 381 participants aged 60 and above.It was conducted in Anhui province between December,2022 and January,2023,with data collected through face-to-face interviews by pharmacists.Single-factor analysis and ordinal multi-class logistic regression analysis were conducted to determine factors affecting medication literacy.Results Medication literacy cognition and medication literacy behavior were rated as good among urban older adults in Anhui province of the 294 valid questionnaires.Those who did not understood package insert exhibited significantly lower medication literacy behavior than those who fully understood[estimate=-1.224,95%CI=(-2.130,-0.317),P<0.01].Elderly patients with chronic diseases faced issues such as an inability to read or understand drug instructions in the investigation.90.48%of elderly patients with chronic diseases never heard or seldom heard of medication guidance services.Conclusion Medication literacy among urban elderly patients with chronic diseases is generally good in Anhui province.The ability to understood drug instructions significantly influenced the medication literacy of urban elderly patients with chronic diseases.Modifying the drug instructions to meet the reading needs of the elderly patients with chronic diseases and developing pharmaceutical care could effectively enhance rational drug use among this demographic.

Objective:To study the role and specific mechanisms of glucose-6-phosphate dehydrogenase (G6PD), a key enzyme for glycometabolism, mediated reduction stress in arsenic-induced malignant transformation of cells.Methods:Immortalized human skin keratinocyte-forming cells (HaCaT cells) were treated with sodium arsenite (NaAsO 2) at a concentration of 0.0 (control group) and 1.0 μmol/L (arsenic group), and malignant transformation indicators were tested using cell growth kinetics assay, cell scratch assay, and soft agar colony formation assay. At different stages of arsenic treatment (0, 1, 7, 14, 21, 28, 35 passages of cells), the effects of NaAsO 2 on glycometabolism in HaCaT cells were determined using corresponding reagent kits and Western blot, including glucose-6-phosphate (G6P), lactate, acetyl CoA, G6PD levels, as well as protein expression levels of hexokinase 2 (HK-2), 6-phosphofructose-2-kinase/fructose-2, 6-diphosphatase 3 (PFKFB3), pyruvate dehydrogenase kinase 1 (PDK1), 6-phosphoglucose dehydrogenase (PGD), and G6PD. Mitochondria were extracted, and the effects of NaAsO 2 on HaCaT cells and mitochondrial redox [reduced nicotinamide adenine dinucleotide phosphate (NADPH)/nicotinamide adenine dinucleotide phosphate (NADP +) ratio, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio] were determined using corresponding reagent kits. The effect of G6PD on reduction stress and NaAsO 2-induced malignant transformation of HaCaT cells was determined using small interfering RNA (siRNA) intervention method. Results:Compared 1.0 μmol/L NaAsO 2-cultured HaCaT cells up to 35 generations (T-HaCaT cells) with matching passage 0.0 μmol/L NaAsO 2-cultured HaCaT cells [(33.797 ± 0.280) h, 0.177 ± 0.015, 13.667 ± 2.625], the multiplication time [(24.042 ± 0.479) h] was shorter ( t = 30.45, P < 0.001), the cell migration rate (0.396 ± 0.039) was higher ( t = 9.08, P < 0.001), and the number of colonies formed in soft agar (73.667 ± 4.450) was higher ( t = 20.11, P < 0.001). Compared with matching passage control group cells and 0 generation of the same group, G6P level in the arsenic group was higher at passages 1, 7, 14, 21, 28 and 35 ( P < 0.05), lactate and G6PD levels were higher at passages 14, 21, 28 and 35 ( P < 0.05), acetyl CoA level was lower at passages 21, 28 and 35 ( P < 0.05), and protein expression levels of HK-2, PFKFB3, PDK1, PGD, and G6PD were higher at passages 7, 14, 21, 28 and 35 ( P < 0.05). The NADPH/NADP + ratio of cells was higher at passages 1, 14, 21, 28 and 35 ( P < 0.05), GSH/GSSG ratio was higher at passages 21, 28 and 35 ( P < 0.05). The ratio of mitochondrial NADPH/NADP + was higher at passages 1, 7, 21, 28 and 35 ( P < 0.05), the GSH/GSSG ratio was higher at passages 1, 7, 14, 21, 28 and 35 ( P < 0.05). G6PD expression was silenced by siRNA in T-HaCaT cells, compared with the T-HaCaT con siRNA-treated group, the T-HaCaT G6PD siRNA-treated group had lower NADPH/NADP + and GSH/GSSG ratios in both cells and mitochondria ( P < 0.05), longer cell multiplication time, lower cell migration rate, and fewer soft agar colonies ( P < 0.05). Conclusion:During the malignant transformation of HaCaT cells induced by NaAsO 2, G6PD and other enzymes related to glycometabolism are activated, leading to reprogramming of glycometabolism, resulting in an imbalance of cell redox homeostasis and enhanced reduction stress in cells and mitochondria, thereby promoting NaAsO 2 induced malignant transformation of HaCaT cells.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

ObjectiveTo elucidate the principles and methods of the Bayesian probabilistic linkage model， and to demonstrate the effect of applying the model in linking birth and death data. MethodsThrough the Shanghai birth and death registration system， data of 199 025 infants born in 2017 and 1 512 infants who died in 2017 and 2018 were collected. After cleaning the data， the data were divided into monthly blocks and fully linked. The Jaro-Winkler algorithm and Euclidean distance were employed to measure the similarity of fields for matching. A Bayesian probabilistic linkage model was constructed and the linking effect was evaluated using a confusion matrix. ResultsUsing the Bayesian probabilistic linkage model， the birth and death data of infants were effectively linked， revealing that 36.71% of infants who died in Shanghai were born outside the city， and the probability of infant death was 2.6‰. The confusion matrix of the test set showed a recall rate of 0.86， precision of 0.76， and an F-score of 0.81. ConclusionThe practical application of Bayesian probabilistic linkage demonstrates a good model performance， enabling the establishment of birth-death cohorts that more accurately reflect the true levels of infant mortality. Utilizing this technique to integrate data from different departments can effectively improve research efficiency in the field of public health.

Objective:To explore the recurrence pattern and prognosis of cervical cancer after radical chemoradiotherapy.Methods:Clinical and follow-up data of 1 359 patients with stage Ⅰ-ⅣA (International Federation of Gynecology and Obstetrics 2009 staging) who received radical radiotherapy in Zhejiang Cancer Hospital from August 2011 to December 2017 were retrospectively analyzed. The survival and prognostic factors of 249 patients with recurrence / metastasis with detailed data were analyzed. The primary endpoint was post-recurrence / metastasis survival time. Kaplan-Meier method was used to calculate the survival rate, log-rank test was used for single factor analysis, and Cox model was used for multi-factor analysis.Results:The distant metastasis rate of 249 patients was 77.5%, and the local recurrence rate was 36.9%. According to the location of metastasis and recurrence, 56 cases with recurrence in the field of radiotherapy alone were assigned into group A, 157 cases with recurrence outside the radiation field alone were allocated into group B (56 cases with lymph node recurrence in group B1, 78 cases with blood metastasis in group B2, and 23 cases with lymph node and blood metastasis simultaneously in group B3), and 36 cases with combined recurrence and metastasis in and out of the field of radiotherapy were assigned into group C. The median survival time of patients in groups A, B1, B2, B3 and C was 13, 24, 13, 11 and 9 months, respectively (all P<0.001). According to the interval from initial diagnosis to recurrence / metastasis, 110 cases were classified in ≤1 year group, 74 cases in >1-2 years group, and 65 cases in >2 years group. The median survival time of patients in the three groups was 11, 14, and 22 months, respectively (all P<0.001). According to the management of recurrence / metastasis, 138 cases received palliative treatment, 15 cases received local treatment, 45 cases received systemic treatment, and 51 cases received combined treatment. The median survival time of patients among four groups was 9, 37, 20 and 32 months, respectively (all P<0.001). The results of multi-factor analysis showed that age, recurrence / metastatic site, retreatment methods, time interval between initial treatment and recurrence /metastasis were the independent prognostic factors affecting the survival (all P<0.05). Conclusions:Distant metastasis is the main failure pattern after radical radiotherapy. Patients with metastasis out of irradiated regions, especially those with only lymph node metastasis, have good prognosis. Active retreatment and time interval between initial diagnosis and recurrence / metastasis are important prognostic factors.

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.