ObjectiveTo analyze the epidemiological characteristics of patients with hepatitis C in Jinhua City, Zhejiang Province from 2005 to 2023, so as to provide a scientific basis for the prevention and control of hepatitis C. MethodsThe data on patients with hepatitis C, as well as whose current address is in Jinhua City, from 2005 to 2023 were collected from the infectious disease surveillance system of the China Disease Control and Prevention Information Management System. Descriptive epidemiological methods were used to analyze the temporal, spatial and demographic distribution characteristics of hepatitis C. ResultsA total of 2 326 cases of hepatitis C were reported in Jinhua from 2005 to 2023, including 2 death cases, with an average annual incidence rate of 2.19/100 000, showing a trend which rose first and then declined and then rose again. Hepatitis C was reported all the year round without significant seasonal pattern. In terms of the number of reported cases and the average annual incidence rate, Yiwu City ranked the first place. From 2005 to 2023, a total of 1 438 (61.82%) male cases and 888 (38.18%) female cases were reported, and the reported incidence rate was higher for males (2.62/100 000) than that for females (1.74/100 000), showing a statistically significant difference (χ²=92.937, P<0.001). Most cases aged between 30 to <50 years old (1 175, 50.52%), and the incidence rate of hepatitis C among the age group of 40‒<50, 50‒<60, 60‒<70 years old was showing an upward trend, with farmers (1 024, 44.02%) as the main occupation . ConclusionThe prevalence of hepatitis C in Jinhua City is generally at a low level, with an incidence rate of increasing and then decreasing, but rise up again after 2019. Therefore, epidemic surveillance and health education among the male, middle-aged and elderly people and farmers, as well as the key regions where the migrant workers flows in should be enhanced.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

Objective To investigate and analyze the distribution of serum cytokeratin 19 fragment antigen 21-1(CYFRA21-1)and squamous cell carcinoma-associated antigen(SCCA)levels in healthy pregnant women during pregnancy and to assess their diagnostic value for cervical cancer in pregnancy.Methods A total of 441 healthy pregnant women and 69 patients with cervical cancer in pregnancy who attended the Obstetrics and Gynecology Hospital of Fudan University from Jan 2021 to May 2024 were selected,and 165 healthy women in the Physical Examination Center of the Obstetrics and Gynecology Hospital of Fudan University were included in the same period as the control group.The healthy pregnant women were divided into 143 in early pregnancy(T1 group),147 in middle pregnancy(T2)and 151 in late pregnancy(T3).Serum CYFRA21-1 and SCCA values were detected and analyzed in all groups.One-way ANOVA,independent samples t-test,Mann-Whitney U-test,Kruskal-Wallis H-test,logistic analysis,and ROC curves were used for comparative analysis.Results The CYFRA21-1 and SCCA values were 1.66(1.19-2.17)ng/mL and 0.8(0.6-1.0)ng/mL in the control group,3.07(2.11-4.14)ng/mL and 0.9(0.7-1.3)ng/mL in the healthy pregnant women group,and were 4.33(2.99-7.60)ng/mL and 1.8(0.9-8.5)ng/mL in the patients with cervical cancer in pregnancy group,respectively.There was a statistically significant difference in the two serum values between every two groups(P<0.05).CYFRA21-1 levels were 3.13(2.46-4.05)ng/mL,1.89(1.50-2.53)ng/mL and 4.19(3.48-5.43)ng/mL in the T1,T2,and T3 groups,respectively;and SCCA levels were 0.9(0.7-1.1)ng/mL,0.7(0.6-1.0)ng/mL and 1.2(0.8-1.7)ng/mL,respectively.The results of T1 and T3 groups were higher than those of the control group(P<0.05);however,there was no statistically significant difference between the results of the T2 group and those of the control group(P>0.05).The areas under the ROC curves for the diagnosis of cervical cancer in pregnancy for CYFRA21-1,SCCA,human epididymis protein 4(HE4),anti-carcinoembryonic antigen(CEA)and joint indicators were 0.684,0.724,0.612,0.791 and 0.913,with sensitivities of 36%,48%,38%,57%and 73%,specificities of 96%,97%,89%,86%and 99%,respectively.The cut-off values of each indicator were 6.05 ng/mL,2.60 ng/mL,51.45 pg/mL and 1.75 ng/mL,respectively.Conclusion Serum CYFRA21-1 and SCCA levels were higher in pregnant women during early and late pregnancy compared with non-pregnant individuals,while they were not statistically different from non-pregnant women during mid-trimester.CYFRA21-1 and SCCA have diagnostic value for patients with cervical cancer during pregnancy.

Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Objective To explore the correlations between serum Mas-related G protein-coupled receptor X2 (MRGPRX2), interleukin (IL)-4, IL-5, IL-6, IL-13, IL-23 and IL-33 levels and chronic spontaneous urticaria (CSU). Methods The clinical characteristics and laboratory data from 55 patients with CSU and 21 healthy controls at Huashan Hospital, Fudan University from February 2021 to September 2023 were collected. The disease activity and severity of CSU patients were assessed. Serum level of MRGPRX2 was tested using enzyme-linked immunosorbent assay (ELISA), and levels of IL-4, IL-5, IL-6, IL-13, IL-23, and IL-33 were measured using Luminex multiplex assay in all subjects. Spearman correlation analysis was used to evaluate the correlations between biomarkers and other parameters in CSU patients, and logistic regression analysis was performed to identify factors influencing CSU. Results CSU patients exhibited significantly higher serum levels of MRGPRX2 (2.41[0, 11.51] ng/mL vs 0[0, 2.86] ng/mL, P＝0.015) and IL-23 (0.09[0.04, 0.56] pg/mL vs 0.05[0.03, 0.08] pg/mL, P＝0.033) than healthy controls. There was no difference in levels of other cytokines between the two groups. There was no difference in levels of MRGPRX2 and cytokines between severe and non-severe CSU patients. Correlation analysis showed that serum MRGPRX2 levels in CSU patients were positively correlated with IL-4 (r＝0.345, P＝0.010) and IL-6 (r＝0.395, P＝0.003) levels. Logistic regression analysis indicated that MRGPRX2≥0.055 ng/mL and IL-23≥0.135 pg/mL were independent risk factors for CSU (P＜0.05). Conclusions Serum levels of MRGPRX2 and IL-23 in CSU patients are elevated, which may be involved in the pathogenesis of CSU.