Objective To identify factors affecting and key environmental factors of the Oncomelania hupensis snail density in the Yangtze River Delta region using machine learning methods. Methods Administrative village-level O. hupensis snail survey data in the Yangtze River Delta (including Shanghai Municipality, Jiangsu Province, Zhejiang Province and Anhui Province) from 2011 to 2021 were retrieved from the Information Management System for Parasitic Disease Control of Chinese Center for Disease Control and Prevention. Environmental factor data were captured from the Google Earth Engine platform, including elevation, slope, terrain, normalized difference vegetation index (NDVI), vegetation type, soil type, total petroleum hydrocarbon (TPH), ammonium nitrogen, inorganic nitrogen, dissolved oxygen, pH of water, chemical oxygen demand (COD) and inorganic phosphorus, and climatic factor data in the study region were retrieved from the Copernicus Climate Data Store, including annual precipitation, aridity index and annual mean temperature (AMT). O. hupensis snail survey data in the Yangtze River Delta region from 2011 to 2021 were randomly divided into a training set (70%) and a test set (30%), and five machine learning models were selected for machine learning model construction and comparative analysis of the O. hupensis snail density using the software R 4.3.0, including random forest (RF), eXtreme gradient boosting (XGBoost), support vector machine (SVM), gradient boosting machine (GBM) and neural network (NN). The XGBoost model was employed to construct a predictive model for the O. hupensis snail density, and the impact of each environmental factor on O. hupensis snail distribution was quantified. The SHapley Additive exPlanations (SHAPs) values were calculated to estimate the average contribution of each variable to the model prediction, and the core environmental factors affecting the O. hupensis snail population density were screened. Results Among the five machine learning models, the XGBoost model exhibited the optimal comprehensive performance, with the coefficient of determination (R²) of 0.855, mean squared error (MSE) of 0.188, root mean squared error (RMSE) of 0.434 and mean absolute error (MAE) of 0.155, respectively. Analysis of factors affecting the O. hupensis snail density with the XGBoost model showed that among the 16 environmental factors, the top four high-impact factors ranked by SHAPs values included annual precipitation, elevation, aridity index and NDVI, with cumulative SHAPs contributions of 75%, which was higher than that of other environmental factors. If NDVI was higher than 0.6, the O. hupensis snail density increased with NDVI and peaked if NDVI was 0.8 (1.60 snails/0.1 m²). The O. hupensis snail density increased with elevation if the elevation ranged from 14 to 40 m, and slowly rose if the annual precipitation ranged from 900 to 1 300 mm, and then increased rapidly to the peak (1.52 snails/0.1 m²) if the annual precipitation ranged from 1 300 to 1 500 mm. In addition, the O. hupensis snail density increased rapidly to the maximum (1.60 snails/0.1 m²) if the aridity index ranged from 0.8 to 1.1, and decreased gradually if the aridity index exceeded 1.1. Conclusions The XGBoost model shows excellent performance in prediction of the O. hupensis snail density and identification of key environmental factors in the Yangtze River Delta region. Annual precipitation, elevation, aridity index and NDVI are key environmental factors affecting the distribution and density of O. hupensis snails in the Yangtze River Delta region.

The frequent extreme climatic events post multifaceted impacts on the distribution of Oncomelania hupensis, the intermediate host of Schistosoma japonicum in the context of global climate change. This article systematically reviews the effects of four types of extreme climatic events, including floods, droughts, heat waves, and cold waves, on the survival, reproduction, and distribution of Oncomelania hupensis. Floods may expand suitable snail habitats, and increase both emerging and re-emerging snail habitats; however, the impact of floods on O. hupensis density is characterized by a lag effect of a decline followed by a rise. Droughts may cause fragmentation of suitable O. hupensis snail habitats, reduced O. hupensis snail egg production rates, and increased O. hupensis snail mortality, and heat waves may cause an increase in O. hupensis snail mortality, a reduction in numbers of O. hupensis snail populations and shrinking of O. hupensis snail distribution, while cold waves may cause a reduction in O. hupensis snail density and a rise in O. hupensis snail mortality. Extreme climate events pose both shortand long-term effects on the distribution of O. hupensis. Intensified surveillance of O. hupensis snails is required in high-risk environments.

ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

ObjectiveTo evaluate the clinical efficacy of Shenqi Yangxin decoction in the treatment of ischemic cardiomyopathy （ICM） with Qi and Yin deficiency and blood stasis syndrome and its effect on serum hydrogen sulfide （H₂S） and calcium ion （Ca²⁺）. MethodsA total of 64 ICM patients with Qi and Yin deficiency and blood stasis syndrome who met the inclusion criteria were randomly divided into a control group （n=32） and a treatment group （n=32）. All patients received conventional Western medicine treatment. The treatment group was additionally given Shenqi Yangxin decoction. The TCM syndrome score， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， left ventricular ejection fraction （LVEF）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， 6-minute walk test （6MWT）， New York Heart Association （NYHA） cardiac function classification， and serum H₂S and Ca²⁺ levels were compared between the two groups pre- and post-treatment. ResultsTwo cases dropped out from each group during the study. Finally， 30 patients in each group were included in the analysis. There were no significant differences in age， gender， course of coronary heart disease， underlying diseases， and laboratory tests between the two groups. Compared with baseline， the TCM syndrome score， MLHFQ score， and NT-proBNP in both treatment group and control group decreased significantly （P<0.01）， LVEF， 6MWT， and H₂S increased significantly （P<0.01）， and serum Ca²⁺ increased （P<0.05）. Compared with the control group after treatment， the MLHFQ score and NT-proBNP in the treatment group decreased （P<0.05）， the TCM syndrome score decreased significantly （P<0.01）， LVEF， 6MWT， and serum Ca²⁺ increased （P<0.05）， and H₂S increased significantly （P<0.01）. The improvement degree of the NYHA cardiac function classification in the treatment group was higher than that in the control group， but there was no significant difference. ConclusionShenqi Yangxin decoction is effective in treating ICM patients with Qi and Yin deficiency and blood stasis， which could significantly improve cardiac function and quality of life， and its therapeutic effect may be related to the regulation of serum H₂S and Ca²⁺ levels.

Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

To understand the progress of, summarize the lessons learned from and analyze the challenges in the national schistosomiasis elimination program of China in 2024, this article presented the endemic situation of schistosomiasis and national schistosomiasis surveillance results in the People’s Republic of China in 2024. By the end of 2024, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to consolidate schistosomiasis elimination achievements, and 7 provinces of Jiangsu, Sichuan, Yunnan, Hubei, Hunan, Anhui and Jiangxi maintained the criteria of schistosomiasis transmission interruption. A total of 450 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2024, including 26 061 endemic villages covering 73 630 500 residents at risk of infections. Among the 450 counties (cities, districts) endemic for schistosomiasis, 388 (86.22%) achieved the criteria of schistosomiasis elimination and 62 (13.78%) achieved the criteria of transmission interruption. In 2024, a total of 4 102 624 individuals received immunological tests for schistosomiasis in China, with 44 823 sero-positives identified (1.09% seroprevalence), and a total of 169 722 individuals received parasitological examinations, with 1 egg-positives detected. A total of 27 321 cases with advanced schistosomiasis were documented in China by the end of 2024. In 2024, a total of 575 686 bovines were raised in schistosomiasis-endemic villages of China, and 113 842 bovines received immunological tests, with 235 sero-positives detected (0.21% seroprevalence), while no egg-positives were identified among the 167 475 bovines receiving parasitological examinations. In 2024, snail survey was performed covering an area of 680 498.27 hm² in China, and 190 778.66 hm² snail habitats were identified, including 59.09 hm² emerging snail habitats and 704.23 hm² reemerging snail habitats. In 2024, a total of 19 665 schistosomiasis patients receiving chemotherapy with praziquantel in China, and expanded chemotherapy was given to humans at 571 722 person-times and to bovines at 306 740 herd-times. In addition, snail control with chemical treatment covered 117 111.37 hm² snail habitats across China in 2024, and the actual area of chemical treatment was 66 562.95 hm², while environmental improvements were performed in snail habitats covering an area of 1 374.26 hm². The national schistosomiasis surveillance results showed that the mean prevalence rates of Schistosoma japonicum infections were both 0 among humans and bovines in China in 2024, and no S. japonicum infection was detected in snails. These data demonstrated that the prevalence of schistosomiasis remained at a low level in China in 2024; however, the areas of snail habitats remained high and the number of fenced cattle showed a slight increase. To address these risks, it is imperative to maintain the integrated strategy with an emphasis on management of the source of S. japonicum infection and intensified snail control in high-risk areas, and to reinforce schistosomiasis surveillance and forecast and snail control in high-risk areas.

Objective: To evaluate the platelet transfusion requirements in children with high-risk stage Ⅳ neuroblastoma undergoing autologous hematopoietic stem cell transplantation (ASCT), and to identify risk factors for increased transfusion needs and prolonged time to platelet transfusion independence. Methods: This single-center retrospective clinical study included 96 children with high-risk stage Ⅳ neuroblastoma who underwent ASCT from January 2019 to May 2024 in our hospital. Relevant clinical data were collected and analyzed, including age, gender, body surface area, platelet count (PLT) on stem cell infusion day (day 0), conditioning regimen, CD34 stem cell dose, platelet transfusion requirements during transplantation, and time to platelet transfusion independence post-transplant. Results: All 96 (100%) children received transfusion after ASCT. From day 0 to transfusion independence, the median number of platelet transfusion was 3 (2, 4.50), and the median volume of platelet transfused was 3 (2, 4.25) units. Platelet transfusion was required in almost all children in pseudo-healing stage (day 4 to day 6) and polar stage (day 7 to day 14), with transfusion rates as high as 83.33%(n=80) and 100%(n=96), respectively. The median time to platelet transfusion independence post-transplant was 13(11,17) days. Multivariate analysis showed that PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, the use of “busulfan+ melphalan” conditioning regimen, and CD34 stem cell dose<4.0×10 /kg were associated with significantly increased platelet requirements and numbers of transfusion (P<0.05). PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, and CD34 stem cell dose<4.0×10 /kg were associated with significantly delayed platelet transfusion independence (P<0.05). Age, sex, and blood type showed no statistically significant association (P>0.05) with post-transplant platelet transfusion requirements or time to transfusion independence in neuroblastoma patients. Conclusion: This study provided quantitative data for platelet transfusion after ASCT in children with high-risk stage Ⅳ neuroblastoma, and identified PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, CD34 stem cell dose<4.0×10 /kg were risk factors for increased platelet transfusions and delayed transfusion independence. Furthermore, the use of the BuMel (busulfan-melphalan) conditioning regimen was also found to contribute to increased transfusion requirements.

Objective: To evaluate the platelet transfusion requirements in children with high-risk stage Ⅳ neuroblastoma undergoing autologous hematopoietic stem cell transplantation (ASCT), and to identify risk factors for increased transfusion needs and prolonged time to platelet transfusion independence. Methods: This single-center retrospective clinical study included 96 children with high-risk stage Ⅳ neuroblastoma who underwent ASCT from January 2019 to May 2024 in our hospital. Relevant clinical data were collected and analyzed, including age, gender, body surface area, platelet count (PLT) on stem cell infusion day (day 0), conditioning regimen, CD34 stem cell dose, platelet transfusion requirements during transplantation, and time to platelet transfusion independence post-transplant. Results: All 96 (100%) children received transfusion after ASCT. From day 0 to transfusion independence, the median number of platelet transfusion was 3 (2, 4.50), and the median volume of platelet transfused was 3 (2, 4.25) units. Platelet transfusion was required in almost all children in pseudo-healing stage (day 4 to day 6) and polar stage (day 7 to day 14), with transfusion rates as high as 83.33%(n=80) and 100%(n=96), respectively. The median time to platelet transfusion independence post-transplant was 13(11,17) days. Multivariate analysis showed that PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, the use of “busulfan+ melphalan” conditioning regimen, and CD34 stem cell dose<4.0×10 /kg were associated with significantly increased platelet requirements and numbers of transfusion (P<0.05). PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, and CD34 stem cell dose<4.0×10 /kg were associated with significantly delayed platelet transfusion independence (P<0.05). Age, sex, and blood type showed no statistically significant association (P>0.05) with post-transplant platelet transfusion requirements or time to transfusion independence in neuroblastoma patients. Conclusion: This study provided quantitative data for platelet transfusion after ASCT in children with high-risk stage Ⅳ neuroblastoma, and identified PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, CD34 stem cell dose<4.0×10 /kg were risk factors for increased platelet transfusions and delayed transfusion independence. Furthermore, the use of the BuMel (busulfan-melphalan) conditioning regimen was also found to contribute to increased transfusion requirements.

Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

Height， as one of the crucial indicators for assessing children’s growth and development， has consistently been a global focus. With economic development and improvements in social living standards， the clinical management needs for children with short stature have been increasingly growing. While growth hormone brings hope to children with short stature， it also triggers ethical challenges such as medical standardization， expansion of indications， equitable accessibility， and informed consent. To avoid the ethical issues related to the use of pediatric growth hormone， multidimensional and comprehensive clinical management should be implemented for children with short stature， including strictly adhering to medical standards and ethical guidelines， enhancing public awareness， and promoting the standardized development of recombinant human growth hormone （rhGH） therapy and ethics.