OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

Cholangiocarcinoma (CCA) is a malignancy characterized by tumor cells originating in the liver or bile ducts, exhibiting features of cholangiocyte differentiation. It poses a significant clinical challenge due to the limited diagnostic and therapeutic options available. Robust animal models are essential for advancing our understanding of CCA pathogenesis and developing effective treatments. This review provides a comprehensive overview of CCA mouse models, highlighting various approaches, including chemical induction, genetically engineered models, and tumor xenografts. Each model is discussed in terms of its establishment techniques, pathological characteristics, and research significance, with a focus on intrahepatic CCA. Chemical induction models, such as diethylnitrosamine- and azoxymethane-induced models, offer insights into tumorigenesis processes, whereas genetically modified models involving alterations in key genes such as Kirsten rat sarcoma viral oncogene homolog, tumor protein 53, and isocitrate dehydrogenase serve as important tools for studying the molecular mechanisms underlying CCA. Xenograft models, including patient-derived xenografts, bridge the gap between experimental research and clinical applications, allowing for precise therapeutic evaluations. By comparing these models, this review underscores their respective advantages and limitations, paving the way for future studies aiming to optimize and innovate CCA modeling strategies.

ObjectiveTo explore the effects of Qingxin Jieyu granules on ventricular remodeling of mice after myocardial infarction， and their regulatory role in mitophagy. MethodsSixty male C57BL/6 mice were randomly assigned to six groups： sham-operated group， model group， Qingxin Jieyu granules low-， medium-， and high-dose groups （1.3， 2.6， 5.2 g·kg^-1）， and sacubitril valsartan sodium group （0.03 g·kg^-1）， with 10 mice per group. Except for the sham-operated group， all other groups utilized left anterior descending coronary artery ligation to build a myocardial infarction model. Ultrasound was used to measure left ventricular parameters， including end-diastolic and end-systolic diameters （LVIDd， LVIDs）， diastolic and systolic posterior wall thickness （LVPWd， LVPWs）， end-diastolic and end-systolic volumes （LV Vold， LV Vols）， left ventricular ejection fraction （LVEF）， and fractional shortening （LVFS）. Additionally， the heart mass index and heart weight/tibia length ratio of mice were calculated. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify brain natriuretic peptide （BNP）， creatine kinase isoenzyme （CK-MB）， angiotensinⅡ （AngⅡ）， and lactate dehydrogenase （LDH） levels in the serum of mice. Histological analysis using hematoxylin-eosin （HE） and Masson staining was conducted to examine morphological changes in myocardial tissue. Immunohistochemistry assessed the expression of vascular growth factors， including basic fibroblast growth factor （bFGF） and vascular endothelial growth factor （VEGF）. Transmission electron microscopy was used to scrutinize mitochondrial morphology in the myocardial tissue of mice. Western blot was performed to analyze the expression of phosphorylated adenosine monophosphate activated protein kinase （p-AMPK） and phosphorylated mammalian target of rapamycin （p-mTOR） proteins in myocardial tissue from each experimental group. ResultsCompared to the sham-operated group， the model group mice exhibited significantly elevated levels of LV Vold， LV Vols， LVIDd， LVIDs， cardiac mass index， heart weight/tibia length ratio， BNP， LDH， and p-mTOR protein expression （P<0.05）， along with decreased levels of LVPWd， LVPWs， LVEF， LVFS， and p-AMPK protein expression （P<0.05）. The model group also displayed substantial inflammatory cell infiltration， collagen deposition in myocardial cells， reduced expression of bFGF and VEGF， mitochondrial swelling， and cristae fragmentation. Compared to the model group， the sacubitril/valsartan group and mid-dose Qingxin Jieyu granules group showed significant reductions in LVIDs， LV Vold， LV Vols， BNP， CK-MB， LDH， and p-mTOR protein expression （P<0.05）， coupled with increases in LVEF， LVFS， and p-AMPK expression （P<0.05）. Improvements were observed across all treatment groups， including reduced inflammatory cell infiltration and collagen deposition， increased bFGF and VEGF expression， alleviated mitochondrial swelling， and the presence of autophagosomes and lysosomes. ConclusionThe results show that Qingxin Jieyu granules can regulate mitochondrial autophagy in myocardial tissue and inhibit ventricular remodeling to improve cardiac performance， by up-regulating the p-AMPK expression in the myocardial tissue of mice with ventricular remodeling after myocardial infarction， and down-regulating the p-mTOR expression.

ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress （CRS） and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank， model， positive drug （diazepam， 1 mg·kg^-1）， and low-， medium-， and high-dose （0.75， 1.5， 3 g·kg^-1， respectively） Fufang Kangjiaolv capsules groups. After 14 days of administration， the elevated plus maze test， open field test， light and dark box test， and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats， and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of zonula occludens-1 （ZO-1） and occludin in the colon of rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the colon， serum， and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1， occludin， nuclear factor-κB p65 （NF-κB p65） in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze， the time and frequency of rats entering the central area of the open field， the time of entering the open box， the times of passing through the light and dark box， and the number of unburied beads （P<0.05， P<0.01）. Compared with the model group， Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees， and the high-dose group had the best effect， with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze （P<0.05）， the number of rats entering the central area in the open field （P<0.05）， the time of entering the open box， the times of passing through the light and dark boxes， and the number of unburied beads （P<0.01）. Moreover， the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes， Deferribacterota， Romboutsia， and Phascolarctobacterium， while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota， Bacteroides， norank f norank o Clostridia UCG-014， and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group， the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon （P<0.01）， elevated levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated protein level of NF-κB p65 in the colon and hippocampus （P<0.01）， and down-regulated protein level of BDNF in the hippocampus （P<0.05）. Compared with the model group， high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon （P<0.01）， lowered the levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated the protein levels of ZO-1 （P<0.01） and occludin （P<0.05） in the colon， down-regulated the protein level of NF-κB p65 in the colon and hippocampus （P<0.05）， and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance， up-regulating the expression of tight junction proteins in the colon， repairing intestinal mucosal mechanical barrier， and down-regulating NF-κB/BDNF signaling pathway， thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis， providing a new idea for further research.

ObjectiveTo investigate the potential mechanism of Liangxue Tuizi Formula （凉血退紫方， LXTZF） in treating Henoch-Schönlein Purpura （HSP） by examining its regulatory effect on neutrophil extracellular trap （NETs） dysregulation via the rapidly accelerated fibrosarcoma kinase （RAF）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsSeventy Wistar rats were randomly allocated into a blank control group （n=14） and a modeling group （n=56）. Rats in the modelling group underwent an eight-week modelling period to establish HSP rat models with blood-heat syndrome via modified ovalbumin （OVA） induction method combined with oral administration of heat-property Chinese herbal medicine. Fifty successfully modeled rats were subsequently randomly divided into five groups （n=10 per group）， model group， compound glycyrrhizin group， LXTZF group， RAF inhibitor group， and LXTZF + RAF agonist group. Additionally， 10 rats were selected from the original blank control group for the final experiment. From the 11th week of modelling， rats in the blank control group and the model group received 1 ml/（100 g·d） ultrapure water via oral administration， in addition to 0.5 ml/（kg·d） 0.9% sodium chloride solution via intraperitoneal injection. The LXTZF group and the compound glycyrrhizin group received 7.5 g/（kg·d） LXTZF granule suspension via gavage， 13.5 mg/（kg·d） compound glycyrrhizin suspension via gavage， respectively. The RAF inhibitor group received 1 mg/（kg·d） GW5074 suspension via intraperitoneal injection and ultrapure water via oral administration； the LXTZF + RAF agonist group received 7.5 g/（kg·d） LXTZF granule suspension via gavage and 1 mg/（kg·d） paclitaxel suspension via intraperitoneal injection. All administrations were performed once daily for 4 weeks. After intervention， skin tissue histopathology was examined by hematoxylin and eosin （H&E） staining， immunoglobulin A （IgA） deposition was assessed via immunofluorescence， serum levels of neutrophil elastase （NE）， tumor necrosis factor-α （TNF-α）， and vascular cell adhesion molecule-1 （VCAM-1） were measured using enzyme-linked immunosorbent assay （ELISA）， serum myeloperoxidase （MPO） level was determined by a colorimetric assay； the mRNA expression levels of RAF， MEK， and ERK in skin tissue were detected by real-time quantitative polymerase chain reaction （RT-qPCR）； and the protein expression of RAF， MEK， ERK， as well as phosphorylated MEK （p-MEK） and phosphorylated ERK （p-ERK）， were analyzed by Western Blot. ResultsSkin tissue in the blank control group rats remained normal， whereas the model group exhibited neutrophil infiltration and haemorrhage with red blood cell rupture. In all drug intervention groups， neutrophil infiltration and haemorrhagic exudation reduced markedly， with LXTZF group demonstrating the most pronounced improvement. Compared with the blank control group， rats in the model group exhibited enhanced IgA fluorescence intensity in skin tissue， elevated serum levels of NE， MPO， TNF-α and VCAM-1， increased mRNA expression of RAF， MEK， ERK1 and ERK2， as well as heightened RAF protein levels and p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with the model group， the drug intervention groups exhibited reduced IgA fluorescence intensity in skin tissue， along with decreased serum levels of NE， MPO， TNF-α， and VCAM-1 （P＜0.05）. In LXTZF group and RAF inhibition groups， reduced mRNA expression of RAF， MEK， ERK1， and ERK2 was observed in rat skin tissue， alongside decreased RAF protein levels and reduced p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with LXTZF + RAF agonist group， the compound glycyrrhizin group， LXTZF group， and RAF inhibitior group exhibited reduced IgA fluorescence intensity in skin tissue， decreased serum NE， MPO， TNF-α， and VCAM-1 levels， and decreased MEK mRNA expression and p-MEK/MEK ratio （P＜0.05）. ConclusionThe potential mechanism by which LXTZF treats Henoch-Schönlein purpura with blood heat syndrome may involve blocking the RAF/MEK/ERK signaling pathway in skin tissue， and suppressing excessive formation of NETs， thereby reducing IgA deposition in dermal microvessels and attenuating systemic inflammatory responses.

The receptor-binding region(RBD)of the spike protein(S)on the surface of porcine epi-demic diarrhea virus(PEDV)is a critical structural domain mediating viral invasion of host cells and serves as a key target for inducing neutralizing antibodies.In order to prepare antibodies that can be used to study the biological function of PEDV RBD and develop novel diagnostic and thera-peutic methods,recombinant RBD protein expressed in Sf9 insect cells was utilized as an immuno-gen to immunize BALB/c mice.Monoclonal antibodies(mAbs)were generated via hybridoma tech-nology,and positive hybridoma clones were screened using indirect ELISA.The reactivity of the mAbs was subsequently characterized.The results of ELISA,Western blot,and indirect immuno-fluorescence assay(IFA)showed that three monoclonal antibodies screened(3E5,4F9 and 5A5)had good reactivity with the virus and RBD protein.Antibody subtype results showed that 3E5 and 4F9 were of IgG1 subtypes and 5A5 was of IgM subtype.Neutralization assay further revealed that 3E5 monoclonal antibody had viral neutralizing activity.In this study,three monoclonal antibodies against PEDV RBD proteins were successfully prepared,providing the basis for the study of the bi-ological function of RBD proteins,PEDV serologic detection and vaccine development.

Epidemiology research has found that ABO blood group and the gene coding ABO glycosyltransferases are associated with many human diseases. The activity of ABO glycosyltransferases varies with different blood types, mediating different glycosylation modifications. The variation in glycosylation level might be the risk factor of specific disease. Based on the literature retrieval and analysis, glycosylation levels regulated by ABO glycosyltransferases mainly affect the ABH blood group antigens and von Willebrand factor (vWF). By modulating key glycosylation components, ABO glycosyltransferases partly determine the activity or expression levels of the ABH antigens and vWF, thereby affecting the development and progression of diseases. Exploring the pathogenic mechanisms of ABO glycosyltransferases can improve the understanding of the molecular pathology of related diseases and provide reference for clinical research and application.

Objective:To investigate the safety and efficacy of urinary microbiota transplantation（UMT）in treating interstitial cystitis（IC）.Methods:A retrospective analysis of the clinical data of three patients with IC treated with UMT at the Central Hospital of Jiangnan University from May 2022 to August 2024. Three women（45，62，79 years）presented with urinary frequency（10 - 90 min intervals），urgency，dysuria，lower abdominal pain，and non-organic sleep disorder，with nocturia（2 - 15 episodes）causing sleep difficulty. Disease durations were 3，6，and 21 years. Prior antibiotic therapy failed. Preoperative urinalysis/culture（x2）ruled out bacterial cystitis，and diagnosed as interstitial cystitis（IC），with one of transient positive urine culture. Preoperative scores for case 1 were self-rating depression scale（SDS）of 49，self-rating anxiety scale（SAS）of 31，interstitial cystitis symptom index（ICSI）of 5，interstitial cystitis problem index（ICPI）of 2，brief urological problem scale of 50，genitourinary pain assessment scale of 10，and pain catastrophizing scale（PCS）of 0. For case 2，the scores were 60 of SDS，66 of SAS，9 of ICSI，11 of ICPI，50 of brief urological problem scale，28 of genitourinary pain assessment scale，and 34 of PCS. For case 3，the scores were 44 of SDS，48 of SAS，11 of ICSI，5 of ICPI，33 of brief urological problem scale，27 of genitourinary pain assessment scale，and 21 of PCS. Preoperative bladder hydro-distention showed mucosal hemorrhage including central block hemorrhage（Case 1），numerous spots（Case 2），and distinct sheets（Case 3）. Preoperative urine 16S rRNA sequencing revealed low diversity，increased Gardnerella/ Bacteroides（opportunistic），and decreased Bacillus/ Streptococcus（beneficial）. Two healthy young female donors had normal comprehensive tests covering blood/urine/stool，coagulation，CRP，immunity，liver/kidney function，lipids，infectious diseases，hormones，tumor markers，urine culture，TOUCH，and expanded quantitative urine culture. Donor urine 16S rRNA showed low pathogenic（ Gardnerella/ Bacteroides）abundance. Donor midstream morning urine was catheter-collected，centrifuged，and the bacterial pellet resuspended in saline. Recipients underwent bladder irrigation pre-UMT. On UMT day，donor bacterial suspension was instilled via catheter with adverse event monitoring. Follow-up included clinic visits at 1 month and 1 year for symptom assessment，scale scoring，cystoscopy evaluating mucosal inflammation，hydrodistension checks，and telephone tracking of urinary symptoms every 2 - 3 months. Prognosis was assessed by symptom relief，scale score reduction，and mucosal recovery. Results:No adverse reactions occurred within 24 hours post-UMT in all 3 cases. Two patients showed same-day urinary urgency reduction；three reported relief from urinary frequency/urgency on postoperative day 7，with 2 - 3 hour daytime intervals and 0 - 5 nocturnal voids. Two patients experienced lower abdominal pain alleviation. Postoperative Week 1 urinalysis and urine cultures revealed no abnormalities. The 16S rRNA test showed a decrease in the abundance of harmful bacteria（e.g.， Cupriavidus，Ureaplasm，Mycobacterium，Pseudomonas）and an increase in the abundance of beneficial bacteria（ Dietzia，Halomonas，and Streptococcus），and the overall urobacterial structure was significantly improved and similar to that of the donor. Case 1 was followed up for 20 months，and the lab tests were normal，with SDS scales of 38，SAS of 20，ICSI of 3，ICPI of 2，brief urological problem scale of 44，genitourinary pain assessment scale of 10，PCS of 0，at 9 months post-op follow-up，indicating physical and mental improvement. The bladder hydro-distention revealed intact mucosa with only mild inflammation，which improved versus preoperative situation. Case 2 was followed up for 15 months，and the lab tests were normal，with SDS scales of 44，SAS of 34，ICSI of 4，ICPI of 2，brief scale of urinary problems of 0，genitourinary pain assessment scale of 9，PCS of 7，at 2 months post-op follow-up，showing improved anxiety/depression and quality of life. The hydro-distention showed decreased scattered hemorrhagic dots and mucosal inflammation. Case 3 was followed up for 13 months，with an increased leukocytes of urine and the other being normal for lab tests，and SDS scales of 35，SAS of 46，ICSI of 13，ICPI of 13，brief scale of urinary problems of 10，genitourinary pain assessment scale of 33，PCS of 11，at 13 months post-op follow-up，indicating physical and mental improvement. The hydro-distention revealed mucosal congestion，marked submucosal vasodilation，and inflammation decreased compared with preoperative situation. Conclusions:UMT alleviates urinary frequency，urgency，and pain in IC patients with sustained effects，significantly improves urine microecology，and shows no adverse events，positioning it as a viable intervention for IC.

Objective To explore the bronchoscopic manifestations of invasive pulmonary fungal disease(IPFD)and evaluate the safety and efficacy of interventional therapy effect.Methods A retrospective analysis was conducted on the clinical data of 35 patients with IPFD who underwent bronchoscopy from May 12,2018 to May 12,2025 to observe the bronchoscopic manifestations and interventional therapy of IPFD.Results 35 patients' clinical data were collected,including 22 males and 13 females,with an age of(53±14)years.The underlying diseases included:10 cases of hematological malignancies,5 cases of long-term use of glucocorticoids,4 cases of type 2 diabetes,2 cases of lung malignancies,and 1 case of organ transplant patient.Chest CT showed that there were 19 cases of lung lesions involving a single lobe and 16 cases involving multiple lobes.The main manifestations under bronchoscopy were 29 cases with mucosal hyperemia and edema(82.9％),22 cases with necrotic substances blocking the lumen(62.9％),17 cases with a large amount of viscous purulent secretions(48.6％),16 cases with partial bronchial stenosis or occlusion(45.7％),9 cases with mucosal necrosis(25.7％),5 cases with mucosal hemorrhage(14.3％),and 3 cases with fungal globules(8.6％).Among them,32 cases(91.4％)received systemic antifungal treatment,17 cases(48.6％)received local amphotericin B perfusion treatment by bronchoscopy,10 cases(28.6％)had the lesion removed by biopsy forceps,6 cases(17.1％)had the lesion frozen by cryoprobe,and 4 cases(11.4％)received argon plasma coagulation treatment.The clinical symptoms of 28 cases(80.0％)improved significantly,and the lung imaging lesions shrank or regressed.Four cases(11.4％)had stable lesions.Three cases(8.6％)did not complete the treatment.Conclusion IPFD is more common in immunosuppressed hosts,bronchoscopy often presents with necrotic substances blocking the lumen,accompanied by purulent secretions,bronchial lumen stenosis,local mucosal hyperemia,edema or necrosis.Systemic antifungal drugs combined with interventional therapy under bronchoscopy have high safety and good therapeutic effects.

Cardiovascular disease is the leading cause of death worldwide,with atherosclerosis(AS)-its core pathological manifestation-representing a multifactorial-driven chronic inflammatory disorder.The pathogenesis of AS involves intricate pathological mechanisms including dyslipidemia,inflammatory cascades,and plaque vulnerability,whose complexity necessitates animal models capable of accurately recapitulating specific pathological features.Genetically engineered murine models have emerged as pivotal tools for deciphering AS mechanisms,owing to their genetic manipulability,phenotypic traceability,and molecular conservation with human pathophysiology.This review provides a systematic overview of current methodologies for establishing AS mouse models,with particular emphasis on evaluating the pathological fidelity of dietary induction approaches,genetic modification strategies[notably apolipoprotein E(ApoE)-/-and low density lipoproteins receptor(LDLr)-/-models],and physical injury paradigms.