Objective: To discuss the epidemiological characteristics of hand foot mouth disease (HFMD) among children in Jiujiang City, and its correlation with meteorological factors, so as to provide scientific evidence for developing targeted HFMD prevention and control measures. Methods: HFMD incidence data among children and meteorological factor records from Jiujiang City during 2019-2023 were collected. Pearson correlation analysis and Quasi-Poisson regression analysis of generalized additive model were used to analyze the relationship between the number of cases and meteorological factors, calculating correlation coefficients (r) and excess risk (ER). Results: The annual reported children HFMD cases in Jiujiang City during 2019-2023 were 4 299, 4 671, 2 560, 3 230, and 3 584, respectively. Except for a peak in autumn-winter in 2020, outbreaks occurred mainly in spring and summer in other years. The majority of cases involved scattered children (71.11%) and children in daycare centers (26.64%). Pearson correlation analysis showed that total case counts, cases among scattered children, and cases among children in daycare centers were positively correlated with average temperature ( r =0.36, 0.39, 0.23), maximum temperature ( r =0.32, 0.36, 0.20), minimum temperature ( r =0.37, 0.41, 0.24), and average relative humidity ( r =0.19, 0.20, 0.15) (all P <0.05). Quasi-Poisson regression analysis of generalized additive model revealed that total cases, cases among scattered children, and cases among daycare children were positively associated with average temperature ( r =0.05, 0.06, 0.03) and average relative humidity ( r =0.03, 0.02, 0.02) (all P <0.01). Excess incidence risk analysis indicated that for every 10 ℃ increase in average temperature, the ER (95% CI ) values were 72.16 (45.91-103.14), 79.76 (52.99- 111.23 ) and 39.30 (14.45-69.54) among total children, scattered children and daycare children, respectively; for every 10% increase in average relative humidity, the ER (95% CI ) values were 28.69 (12.22-47.56), 27.81 (12.01-45.84) and 24.42 (5.56-46.65), respectively. Conclusions The incidence level of HFMD among children in Jiujiang City is positively correlated with the average temperature and average relative humidity. Higher temperature and humidity are associated with an increased risk of excess HFMD incidence in scattered children compared to children in daycare centers.

Objective To investigate the screening results and factors affecting abnormal detection rates among high-risk groups of esophageal cancer and to explore effective intervention measures. Methods We investigated and collected the information on gender, education level, age, marital status, symptoms of reflux esophagitis (heartburn, acid reflux, belching, hiccup, foreign body sensation in the pharynx, and difficulty swallowing), consumption of pickled vegetables, salt use, and esophageal cancer incidence of villagers in a natural village in Wenfeng District, Anyang City, Henan Province. Changes in reflux esophagitis symptoms in the high-incidence area of esophageal cancer before and after 16 years were observed, and the relationship of such changes with esophageal cancer was analyzed. Results In 2008, 711 cases were epidemiologically investigated, including 213 cases with one of the symptoms of reflux esophagitis such as heartburn, acid reflux, belching, hiccups, foreign body sensation in the pharynx, and difficulty swallowing (sorted in accordance with the abovementioned symptoms; if there are multiple symptoms, then the former is taken); 55 cases with at least two related symptoms, among which the most symptom was heartburn in 108 cases (15.1%); followed by acid reflux, belching, etc. In 2024, the same group of people was investigated, and eight people were missing because of relocation. A total of 703 people were successfully investigated, of which 189 cases (26.8%) had one of the symptoms of reflux esophagitis, such as heartburn (sorted in accordance with relevant symptoms, if there are multiple symptoms, then the former will be selected); 167 cases (23.7%) had at least two related symptoms, among which the most symptom was heartburn in 139 cases (19.7%); followed by acid reflux. Over 16 years, among the 703 people investigated, 45 cases had esophageal cancer and they had one or more of the abovementioned symptoms. No significant differences in the reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.26); no significant differences in the composition of reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.299). Conclusion The detection rate of reflux esophagitis-related symptoms in the population in a high-risk area of esophageal cancer has not decreased in the past 16 years, and the high-risk factors still exist. Esophageal cancer is closely related to reflux esophagitis, and clinical practice can provide early diagnosis and treatment for high-risk population.

Objective:To explore the relationships between physical activity and cognitive impairment in older adults aged ≥65 years in longevity areas in China.Methods:A total of 6 081 older adults aged ≥65 years from the Healthy Ageing and Biomarkers Cohort Study in China in 2021 were included in this study. Information about their demographic characteristics, lifestyles, and chronic disease histories were collected, the intensity of physical activity was evaluated by using Physical Activity Scale for the Elderly, and the cognitive function was evaluated by using Mini-Mental State Examination Scale (Chinese version). Multifactorial logistic regression model was used to analyze the associations between different levels and types of physical activity and cognitive impairment in older adults.Results:In the 6 081 older adults, 1 829 (30.1%) had cognitive impairment. After adjusting for confounders, older adults with T2 and T3 levels of physical activity had lower risks for cognitive impairment compared with those with T1 levels of physical activity, with ORs of 0.47 (95% CI: 0.40-0.55) and 0.22 (95% CI: 0.18-0.28). The results of different types of physical activities showed that the ORs in leisure activity T2 and T3 groups were 0.52 (95% CI: 0.44-0.63) and 0.49 (95% CI: 0.41-0.58), and the ORs in housework activity T2 and T3 groups were 0.36 (95% CI: 0.30-0.42) and 0.19 (95% CI: 0.16-0.24). There was no significant association between work-related activity and cognitive impairment. Conclusion:There is a negative association between the intensity level of physical activity and cognitive impairment, and active leisure and household activities might reduce the risk for cognitive impairment.

Objective·To detect immunoglobulin(Ig)expression levels in newly diagnosed multiple myeloma(MM)patients before and after induction therapy,and to explore the clinical significance of Ig expression levels and their dynamic changes in relation to treatment efficacy,infection occurrence,and prognosis.Methods·Clinical data from 142 MM patients treated at the Department of Hematology,The First Affiliated Hospital of Soochow University between August 2018 and September 2020 were analyzed.Baseline Ig expression levels and post-induction changes following bortezomib-lenalidomide-dexamethasone(VRD)regimen were assessed.Immunoparesis was defined as uninvolved Igs below the laboratory lower limit of normal.Patients were stratified by immunoparesis severity(mild,moderate,severe,extremely severe).ANOVA,rank-sum tests,and x2 tests were used to analyze correlations with baseline characteristics.The relationship between the improvement in immunoparesis and the induction efficacy,infection occurrence,and prognosis was analyzed based on the dynamic changes in immunoparesis.Results·Normal Igs were severely reduced in newly diagnosed MM patients.Immunoparesis was present in 128 patients(90.1%),with severe or extremely severe immunoparesis accounting for 76.1%.Patients with extensive immunoparesis(all uninvolved Ig levels below the lower normal limit)were more likely to have severe immunoparesis(P<0.05).There were no statistically significant differences in age,gender,presence of severe renal insufficiency,and high-risk cytogenetics among MM patients with different degrees of immunoparesis(P>0.05),but there were statistically significant differences in MM staging(P=0.008)and typing(P=0.010).Most patients with severe immunoparesis were at stage Ⅱ/Ⅲ based on the Revised International Staging System(R-ISS)and were of the IgG type.At diagnosis,the levels of the involved Ig or light chain were negatively correlated with normal Ig levels(P<0.05).Improvement in immunoparesis after induction therapy was positively correlated with treatment response(P=0.006).The infection rate was high(26.8%),but no significant correlation was found between immunoparesis and infection occurrence(P>0.05).After induction therapy,patients showing improvement in immunoparesis had significantly longer progression-free survival(PFS)(median PFS:not reached vs 38 months,P=0.025),but no significant impact on overall survival(OS)was observed(P=0.450).Conclusion·Immunoparesis is common and severe in newly diagnosed MM patients,with severity correlating with disease stage and subtype.VRD therapy can partially reverse immunoparesis,and improvement is positively associated with treatment response and PFS benefit.Infection risk appears unrelated to immunoparesis severity and warrants comprehensive prevention strategies.Humoral immune deficiency may serve as a prognostic indicator in MM,but its impact on OS requires further investigation.

Objective:To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.Methods:This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.Results:Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min -1· (1.73 m 2) -1, n=160], mild [≥60 ml·min -1· (1.73 m 2) -1 to <90 ml·min -1· (1.73 m 2) -1, n=55], moderate [≥30 ml·min -1· (1.73 m 2) -1 to <60 ml·min -1· (1.73 m 2) -1, n=39], and severe impairment [<30 ml·min -1· (1.73 m 2) -1, n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence ( P<0.05). Despite younger age ( P=0.001) and higher transplant rates ( P=0.041) in severe cases, overall response rates ( ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups ( P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5–4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min -1· (1.73 m 2) -1], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13–0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment ( P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2–65 months). Multivariate analysis identified 1q21+ ( OR=3.58, 95% CI: 1.17–11.02, P=0.026) and light-chain subtype ( OR=2.86, 95% CI: 1.08–7.69, P=0.036) as independent predictors of poor renal response. Conclusion:VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background: Acetaminophen (APAP)-induced hepatotoxicity has attracted considerable attention in clinical settings due to the limited treatment options available. Liensinine stands out as a key alkaloid known for its pharmaceutical activities. However, the role of liensinine in mitigating APAP-induced liver injury remains unclear. Objective: The aim of the study was to explore the protective effects of liensinine against APAP-induced liver injury. Methods: C57BL/6 male mice were treated with a dose of 200 mg/kg N-acetylcysteine or varying doses of liensinine (10 or 20 mg/kg) for seven consecutive days. APAP (400 mg/kg, i.g.) was then administered to induce liver damage for 12 hours. Blood samples and hepatic tissues were collected for further analysis. Liver enzyme levels and histopathological analysis were employed to assess liver injury. RNA-seq was conducted to evaluate the dynamic changes in gene expression. Biochemical assays were used to measure oxidative stress and inflammation, while the TUNEL assay was performed to assess hepatocyte apoptosis. Results: The results demonstrated that the administration of liensinine mitigated serum liver enzyme levels and tissue damage resulting from APAP overdose. Transcriptome analysis revealed significant and coordinated changes in genes related to the peroxisome proliferator-activated receptor signaling pathway, mitogen-activated protein kinase signaling pathway, and apoptosis pathway in response to APAP-induced hepatotoxicity. The expression alterations of key genes within these three pathways, associated with inflammation, oxidative stress, and cell apoptosis, were reversed by liensinine, indicating its potential in alleviating APAP-induced liver damage through multiple signaling pathways. This suggests the diverse therapeutic effects of liensinine, including inflammation suppression, oxidative stress reduction, and cell apoptosis inhibition. Indeed, pretreatment with liensinine effectively reduced inflammatory cytokines, oxidative stress indicators, and apoptotic cells induced by APAP. Conclusions: Liensinine mitigates APAP-induced hepatotoxicity in mice through multifaceted pathways, providing anti-inflammatory, antioxidant, and anti-apoptotic benefits.

Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.