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.

This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Tumor is one of the major diseases that endanger people’s health. At present, the treatments used for tumor include surgery, chemotherapy, radiotherapy and so on. Nonetheless, the traditional treatments have some disadvantages, such as insufficient treatment effect, liable to cause multidrug resistance, toxicity and side effect. Further research and exploration of tumor treatment schemes are still necessary. As the energy converter of cells, mitochondria are currently considered to be one of the most important targets for the design of new drugs for tumor, cardiovascular and neurological diseases. Nano-drug delivery carriers have the characteristics of being easily modified with active targeting groups, and it can achieve accurate targeted drug delivery to cells and organelles. This paper reviews the application of mitochondrial targeted nanoparticles in tumor diagnosis and treatment from the aspects of inhibiting tumor cell proliferation, promoting tumor cell apoptosis, inhibiting tumor recurrence and metastasis, and inducing cell autophagy.

Objective To investigate the effect of dihydromyricetin(DMY)on myocardial oxidative damage in exhaustive exercise mice.Methods C57BL/6 mice were divided into control group,model group,positive control group and low,medium and high dose experimental groups and with 10 mice in each group.Mice in control group and model group were intragastricated with distilled water;20,40 and 80 mg·kg-1 dihydromyricetin were given by gavage in low,medium and high dose experimental groups,while mice in positive control group were intragastricated with 100 mg·kg-1 Vitamin C once a day for 4 weeks.After administration,superoxide dismutase(SOD),malondialdehyde(MDA)and lactate dehydrogenase(LDH)were detected by the kit.The expression of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)protein were detected by Western blot.Results SOD levels in control group,model group and low,medium,high dose experimental groups and positive control group were(57.81±6.92),(26.85±2.74),(33.68±4.52),(39.74±3.95),(48.97±4.26)and(39.22±3.54)U·mg-1;MDA were(4.72±0.36),(10.48±1.68),(8.75±0.82),(6.43±0.71),(5.11±0.48)and(6.36±0.64)nmol·mg-1;LDH were(268.71±23.94),(726.58±81.26),(621.32±47.59),(479.12±50.24),(337.91±34.99)and(486.15±50.98)U·L-1;Nrf2 protein expression were 0.75±0.06,0.19±0.02,0.30±0.04,0.47±0.05,0.63±0.06 and 0.49±0.06;the protein expression of HO-1 were 0.83±0.08,0.27±0.05,0.39±0.04,0.52±0.03,0.77±0.07 and 0.55±0.06,respectively.There were statistically significant differences between control group and model group(all P＜0.05);there were statistically significant differences in the above indexes between model group and positive control group,low dose experimental group,medium dose experimental group,high dose experimental group(all P＜0.05).Conclusion Dihydromyricetin can delay myocardial oxidative injury in exhaustive exercise mice,which may be related to Nrf2/HO-1 pathway.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.
Animals ; Mice ; Rats ; Proto-Oncogene Proteins c-akt ; Network Pharmacology ; Alzheimer Disease/drug therapy* ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases/genetics* ; Tandem Mass Spectrometry ; Drugs, Chinese Herbal/pharmacology*

【Objective】 To establish a practical and feasible blood management (PBM) model for clinical liver transplant patients, so as to optimize the perioperative blood usage and improve patient prognosis and survival rate. 【Methods】 Led by the Medical Department, a questionnaire survey Establishment and Implementation of a Blood Management Model for Organ Transplant Patients on the importance of establishing a PBM model for liver transplant patients in clinical practice was conducted among 71 staff from relevant departments such as the Anesthesiology Department, Hepatobiliary Department, Blood Transfusion Department, and ICU Medical Department. After statistical analysis, the important items of PBM for liver transplant patients were determined, and a (trial) plan was organized by the Medical Department and training was conducted by Blood Transfusion Department for medical staff training from departments as Anesthesiology, Hepatobiliary and Pancreatology, and ICU; PBM measures for liver transplant patients before, during and after surgery were determined by the Anesthesiology Department, Hepatobiliary and Pancreatic Department, and ICU; PBM was fully implemented in the experimental group with liver transplant patients in our hospital in 2021 as subjects; 30 cases of liver transplantation performed in our hospital in 2020 were selected as the control group, and the general data, preoperative laboratory examination results, and preoperative, intraoperative, and postoperative blood transfusion of the two groups of patients were compared. 【Results】 Compared with the control group, the experimental group did not receive any blood component transfusion before surgery. Intraoperative blood transfusion volume of allogeneic components: red blood cells(U) were 12.75(8.75, 18.63) vs 15.25(8.38, 26.13)(P>0.05), apheresis platelet (treatment volume) was 0(0, 2) vs 1(0, 4.25)(P>0.05), plasma(U) was 2 300(1 550, 3 763) vs 3 650(2 075, 5 400)(P<0.05); cryoprecipitate(U) was 0(0, 10) vs 10(0, 30)(P<0.05); Postoperative blood transfusion volume of allogeneic components were as follows: red blood cells(U) 8.00(3.38, 12.88) vs 11.25(4.75, 19.63)(P>0.05), platelets were not transfused, plasma(U) was 0(0, 0) vs 0(0, 600)(P>0.05), and cryoprecipitates were not transfused. 【Conclusion】 The establishment of PBM model for liver transplant patients and the application of its management measures before, during and after transplantation significantly reduced the intraoperative blood transfusion volume and improved the prognosis of patients after transplantation.

OBJECTIVE: To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC). METHODS: According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy. RESULTS: EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA. CONCLUSION EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.
Mice ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Electroacupuncture ; Beclin-1 ; Signal Transduction ; Constipation/therapy* ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Neuroglia/metabolism* ; Mammals/metabolism*