Objective To investigate the prevalence of Schistosoma japonicum infections in wild rodents in schistosomiasis-endemic areas of China, so as to provide insights into formulation of technical guidelines for monitoring of and the precise control strategy for S. japonicum infections in wild rodents during the elimination phase. Methods Two administrative villages where schistosomiasis was historically highly prevalent were selected each from Dongzhi County, Anhui Province, and Duchang County, Jiangxi Province as study villages. Wild rodents were captured from study villages with baited traps or cages at night in June and September, 2021. The number of rodents captured was recorded, and the rodent species was characterized based on morphologi-cal characteristics. Liver tissues were sampled from captured rodents for macroscopical observation of the presence of egg granu- lomas, and S. japonicum infection was detected simultaneously using liver tissue homogenate microscopy, examinations of mesenteric tissues for parasites, and modified Kato-Katz thick smear technique (Kato-Katz technique). A positive S. japonicum infection was defined as detection of S. japonicum eggs or adult worms by any of these methods. The rate of wild rodent capture and prevalence of S. japonicum infections in wild rodents were compared in different study villages and at different time periods, and the detection of S. japonicum infections in wild rodents was compared by different assays. Results The overall rate of wild ro- dent capture was 8.28% (237/2 861) in Dongzhi County, and the wild rodent capture rates were 9.24% (133/1 439) and 7.31% (104/1 422) in two study villages (χ² = 3.503, P = 0.061), and were 8.59% (121/1 409) and 7.99% (116/1 452) in June and September, 2021, respectively (χ² = 0.337, P = 0.561). The overall rate of wild rodent capture was 3.72% (77/2 072) in Duchang County, and the wild rodent capture rates were 6.91% (67/970) and 0.91% (10/1 102) in two study villages (χ² = 51.901, P < 0.001), and were 4.13% (39/945) and 3.37% (38/1 127) in June and September, 2021, respectively (χ² = 0.815, P = 0.365). Rattus norvegicus was the predominant rodent species captured in both counties, accounting for 70.04% (166/237) of all captured wild rodents in Dongzhi County and 88.31% (68/77) in Duchang County. No S. japonicum infection was detected in wild rodents captured in Duchang County. Nevertheless, the overall prevalence of S. japonicum infections was 51.05% (121/237) in wild rodents captured in Dongzhi County, with prevalence rates of 50.38% (67/133) and 51.92% (54/104) in two study villages (χ² = 0.098, P = 0.755), and 54.31% (63/116) and 47.93% (58/121) in September and June, 2021, respectively (χ² = 0.964, P = 0.326). Of 237 wild rodents captured in Dongzhi County, there were 140 (59.07%) rodents with visible hepatic egg granulomas, 117 (49.47%) tested positive for S. japonicum eggs by liver tissue homogenate microscopy, 34 (14.35%) tested positive for S. japonicum eggs with Kato-Katz technique; however, no adult S. japonicum worms were detected in mesenteric tissues. In addition, hepatic egg granulomas were found in all wild rodents tested positive for S. japonicum eggs with liver tissue homogenate microscopy. Conclusions The rate of wild rodent capture and prevalence of S. japonicum infection in wild rodents vary greatly in schistosomiasis-endemic areas of China, and the prevalence of S. japonicum infection is slightly higher in wild rodents captured in autumn than in summer. Liver tissue is recommended as the preferred sample for surveillance of S. japonicum infection in wild rodents, and a combination of macroscopical observation of hepatic egg granulomas and liver tissue homogenate microscopy may be a standard method for surveillance of S. japonicum infection in wild rodents.

Objective To analyze the effect of Hsa-circ-0101216 on gemcitabine(GEM)chemotherapy resistance in pancreatic cancer and its mechanism.Methods Differentially expressed circRNAs between GEM-resistant pancreatic cancer cells and parent cells were screened using the GEO database.Pancreatic cancer GEM resistant cell lines(BxPC-3-GEM and Capan-1-GEM)were constructed by intermittent concentration gradient method.qRT-PCR was used to detect the expression of Hsa-circ-0101216 in cells.GEM resistant pancreatic cancer cell lines were taken and divided into sh-circ-0101216 group(knockdown of circ-0101216),sh-NC group(transfected with sh-NC),and blank control group(untreated).CCK-8 assay and EdU proliferation assay were used to detect the half inhibitory concentration(IC50)of GEM and proliferation ability of cells in each group.Western blotting was performed to detect the expression of multidrug resistance-related protein 1(MRP1),breast cancer resistance protein(BCRP),and human equilibrative nucleoside transporter-1(hENT-1).A subcutaneous xenograft tumor model of human pancreatic cancer in nude mice was constructed,and sh-NC+GEM group and sh-circ-0101216+GEM group(n=6)were set up.The volume and weight of xenograft tumor in nude mice were compared between the two groups.Western blotting and immunohistochemistry were used to detect the expression of MRP1,BCRP,and hENT-1 proteins in xenograft tumor tissues,and EDU proliferation assay was used to detect the proliferation ability of tumor cells.Results The GEO database screening showed that Hsa-circ-0101216 was up-regulated in GEM-resistant pancreatic cancer cell lines.Pancreatic cancer GEM-resistant cell lines were successfully constructed,and the expression levels of Hsa-circ-0101216 and the IC50 value in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly higher than those in parental cells(P<0.05).In sh-circ-0101216 group,the IC50 values of GEM,cell viability,EdU positivity rate,and the expression levels of MRP1 and BCRP proteins in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly lower than those in blank control group and sh-NC group,while the expression level of hENT-1 protein was significantly higher(P<0.05 or P<0.001).In sh-circ-0101216+GEM group,the weight and volume of subcutaneous xenograft tumors in nude mice,the expression levels and positive expression rates of MRP1 and BCRP proteins in tumor tissues,and the EdU positive rate were significantly lower than those in sh-NC+GEM group,while the expression level and positive expression rate of hENT-1 protein were significantly higher(P<0.05).Conclusions Hsa-circ-0101216 is highly expressed in GEM-resistant pancreatic cancer cell lines.Its knockdown can inhibit the proliferation of pancreatic cancer cells and enhance the chemosensitivity of pancreatic cancer cells to GEM.The mechanism may be related to the regulation of transmembrane transporter protein expression.

AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

Objective:To analyze the influencing factors of postoperative pulmonary embolism (PE) in patients undergoing hepatectomy.Methods:Clinical data of 171 patients undergoing hepatectomy at the Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Kunming Medical University from January 2018 to November 2024 were retrospectively analyzed, including 95 males and 76 females, aged (52.0±12.6) years. The pathology of patients included hepatolithiasis, hepatic hemangioma, liver abscess, focal nodular hyperplasia of liver, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, etc. According to whether PE occurred after hepatectomy, patients were divided into PE group ( n=64) and control group ( n=107). Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of PE after hepatectomy. The receiver operating characteristic (ROC) curve was used to analyze the effect of each index on predicting PE after hepatectomy. Results:Multivariate logistic regression analysis showed that red blood cell volume distribution width ( OR=1.399, 95% CI: 1.223-1.601) and systemic inflammation response index (SIRI) on postoperative day (POD) 3 ( OR=1.317, 95% CI: 1.124-1.544) and D-dimer on POD1 ( OR=1.208, 95% CI: 1.026-1.421) were associated with a higher risk of PE after hepatectomy (all P<0.05). The area under the ROC curve of SIRI on POD3, D-dimer on POD1, and red blood cell volume distribution width on POD3 on predicting PE after hepatectomy was 0.763 (95% CI: 0.689-0.838), 0.744 (95% CI: 0.668-0.820) and 0.796 (95% CI: 0.727-0.864), respectively. Conclusion:Red blood cell volume distribution width on POD3, SIRI on POD3 and D-dimer on POD1 are the risk factors of PE after hepatectomy. These three indicators have certain predictive value for PE after hepatectomy.

Objective:To investigate the composition of immune cells and fibroblastic reticular cells (FRCs) in the lymph nodes (LNs) follicles of human immunodeficiency virus (HIV)-infected individuals with varying immune statuses, and their association with HIV replication.Methods:Neck LNs samples were collected from 4 treatment-naive, newly diagnosed HIV-infected individuals with diverse immune statuses. RNA in situ sequencing was employed, with imaging achieved via rolling circle amplification and fluorescence labeling. By integrating cell segmentation and nuclear staining, single-cell data from up to one hundred thousand cells were generated per paraffin tissue section. Using lymphoid follicles as the unit of analysis, compositional changes in immune cells and FRCs were characterized, and their correlations with viral replication were evaluated. Results:The peripheral blood CD4 + T cell counts of samples LN_1, LN_2, LN_3, and LN_4 exhibited a sequential decrease. A total of 31, 15, 16, and 18 structurally intact follicles were identified in each sample, respectively. In the follicles of LN_1, the proportion of HIV-replicating cells positively correlated with cDCs abundance ( R2=0.2, P=0.011), and HIV RNA signals were spatially colocalized with cDCs and FRCs. In the follicles of LN_2, HIV RNA molecules showed preferential enrichment within FRCs. In sample LN_3, HIV RNA enrichment was observed in both cDCs and CD4 + T cells. In sample LN_4, the proportion of cells with HIV replication was positively correlated with the proportions of the following cells: cDCs ( R2=0.38, P=0.006 4), CD4 + T cells ( R2=0.28, P=0.025), and FRCs ( R2=0.26, P=0.029), and HIV RNA molecules were detected in cDCs, CD4 + T cells, and FRCs. LN_1 and LN_2 samples showed a trend toward negative correlation between HIV-replicating cell proportion and CD8 + T cells proportion. LN_4 sample demonstrated a significant positive correlation between HIV-replicating cell proportion and CD8 + T cells proportion ( R2=0.23, P=0.046). Conclusions:RNA in situ sequencing technology reveals unique distribution patterns of immune cells and viral replication in LNs follicles of HIV-infected individuals. The follicular immune microenvironment exhibits distinct characteristics associated with peripheral blood CD4 + T cell counts, providing novel insights into the spatial dynamics of HIV persistence and immune cell interactions during infection.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Objective To investigate the structural changes and influencing factors of the average inpatient cost per admis-sion in public hospitals in Guangdong Province.Methods Grey relational analysis and structural variation degree analysis were used to analyze the correlation and changes between the average inpatient cost per admission and various cost components in public hospitals of Guangdong Province from 2017 to 2023.Results The average inpatient cost per admission in public hospitals of Guangdong Province showed an overall upward trend from 2017 to 2023,with an average annual growth rate of 3.84％.Among the components,laboratory test fees and examination fees grew at average annual rates of 6.17％and 6.68％,respectively.The top four cost components with the highest grey relational degree with the average inpatient cost were laboratory test fees(0.867),exam-ination fees(0.835),nursing fees(0.784),and treatment fees(0.728).The top four components with the largest structural vari-ation values were surgery fees(2.57％),medical material fees(1.77％),laboratory test fees(1.56％),and examination fees(1.45％).Conclusion The growth of the average inpatient cost per admission has slowed,and the cost structure has been opti-mized to some extent.However,the relatively rapid increase in laboratory test and examination fees has a significant impact on the cost structure.It is necessary to deepen the coordinated governance of healthcare,medical insurance,and medicine,strengthen the leveraging role of medical insurance payment,improve the external governance system and scientific compensation mechanism,and combine these with refined hospital management to promote reasonable cost control and high-quality development in public hospitals.

Objective:To analyze the imaging features of testicular conventional ultrasonography（US），shear wave elastography（SWE），and contrast-enhanced ultrasonography（CEUS）in subtypes of spermatogenic dysfunction（focal，arrest，and exhausted），and to evaluate the diagnostic efficacy of testicular multimodal ultrasound.Methods:A prospective study enrolled 310 spermatogenic dysfunction patients（focal type group： n=77，arrest type group： n=20，exhaustive type group： n=213）and 30 healthy volunteers（control group）at Shanghai General Hospital between October 2023 and December 2024. All patients underwent preoperative testicular US，SWE，and CEUS examinations，followed by microdissection testicular sperm extraction. Ultrasound parameters were compared among groups，and receiver operating characteristic（ROC）curves were plotted to assess the diagnostic efficacy of multimodal ultrasound for different subtypes. Results:①Testicular volume：The arrest group exhibited significantly greater volume compared to the focal group and the exhausted group（all P<0.05）. No statistically significant difference was observed between the arrest group and the normal group（ P>0.05）. ②Mean Young's modulus（Emean）：The arrest group exhibited significantly lower Emean compared with both the focal and exhausted groups（all P<0.05），but showed no significant difference versus the normal group（ P>0.05）. ③CEUS quantitative parameters：The arrival time（AT）and time to peak（TTP）in the exhausted group were higher than those in the normal group，while the peak intensity（PI）and area under the time-intensity curve（AUC）were lower（all P<0.05）. No significant differences were found in AT，TTP，or AUC among the three spermatogenic dysfunction subgroups（all P>0.05）. ④CEUS perfusion patterns：The focal group predominantly exhibited a mottled pattern（70.13%，54/77）. Both the arrest group（90.00%，18/20）and the normal group（93.33%，28/30）predominantly exhibited an rich pattern. The exhausted group predominantly exhibited a sparse pattern（56.34%，120/213）. ⑤ROC curve analysis showed that for differentiating the arrest group from the focal type group and the exhaustive type group，the combination of Emean，testicular volume，and CEUS perfusion pattern yielded an AUC of 0.931，with a sensitivity of 95.00% and specificity of 85.86%. For differentiating the focal type group from the exhaustive type group，the combination of testicular echogenicity，CEUS perfusion pattern，and Emean yielded an AUC of 0.833，with a sensitivity of 81.82% and specificity of 75.12%. Conclusions:Multimodal ultrasonography can comprehensively characterize the imaging features of different subtypes of spermatogenic dysfunction，holding promise as a noninvasive predictive tool.

Objective To explore the application value of a novel portable endoscope to perform upper gastrointestinal tract examinations in primary medical units.Methods A total of 532 subjects receiving portable endoscope examination were enrolled for analysis.The primary outcome was the success rate of operation.The secondary outcomes were the operation time,examination results,polyp removal and biopsy pathology results,and the subjective evaluation.Results In 532 cases,2 were withdrawn midway after the endoscope was inserted into the esophagus due to the patients'inability to tolerate the examination.Additionally,6 cases did not undergo examination of the descending part of the duodenum because of serious reactions during the procedure.Ultimately,524 cases successfully completed the upper gastrointestinal examination,and the success rate was 98.5％.The average examination time was(4.7±1.8)min,and the average time for disposal sheath wearing and removing was(4.2±1.4)min.The most common lesions were chronic non-atrophic gastritis(85.1％,451/530),reflux esophagitis(14.7％,78/530)and bile reflux(14.0％,74/530).A total of 10 cases of polyp removal were completed,and the polyp removal rate was 71.4％(10/14).Biopsy pathological diagnosis was completed in 44 cases,and the biopsy rate was 8.3％(44/530).The main discomfort symptoms during the examination were nausea(53.6％,285/532),vomiting(51.1％,272/532),and sore throat(38.5％,205/532),the main discomfort symptoms after the examination were sore throat(27.8％,148/532),nausea(19.5％,104/532),and vomiting(14.7％,78/532).No serious adverse events such as gastrointestinal bleeding,perforation,cardiac or pulmonary complications occurred.Conclusion The novel portable endoscope can safely and effectively complete the diagnosis and treatment of upper gastrointestinal diseases in primary medical units,while saving the decontamination process.However,the incidence of discomfort is high during examinations.Further optimization of the operation methods is needed.

Objective To investigate the relationship between systemic lupus erythematosus(SLE)and hypothyroidism using bidirectional two-sample Mendelian randomization(MR)method.Methods The Genome-Wide Association Study data of SLE and hypothyroidism were obtained online.Independent single nucleotide polymorphisms closely related to SLE were screened as instrumental variable(Ⅳ),and outlier values were tested and eliminated by MR-PRESSO tool of R 4.3.1 software.The inverse variance weighted(IVW),MR-Egger,weighted mode(WM),weighted median(WME)and simple mode(SM)were used for MR analysis,and the values of odds ratio(OR)and 95％confidence interval(95％CI)were used to evaluate whether there was an association between SLE and hypothyroidism.The Cochran's Q heterogeneity test was performed for the results of IVW and MR-Egger,the pleiotropy test was performed by Egger-intercept method,and the sensitivity analysis was performed by elimination test one by one.F value was calculated to evaluate whether there was a weak Ⅳ bias.Results MR analysis results showed that there was a positive causal relationship between SLE and hypothyroidism in the overall population,and the results calculated by IVW,MR-Egger,WM and WME were statistically significant,with OR(95％CI)being 1.004(1.002-1.005),1.004(1.001-1.008),1.004(1.002-1.007),and 1.004(1.002-1.006),respectively.The heterogeneity test results for IVW and MR-Egger were P=0.086 and P=0.098,respectively,indicating no heterogeneity;the Egger-intercept result was P=0.295,indicating no pleiotropy;sensitivity analysis showed MR results were stable;and all F values were greater than 10,indicating no weak Ⅳ bias.Conclusion Compared with healthy people,the risk of hypothyroidism in patients with SLE is significantly higher.