Increasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans ; Male ; Penis/abnormalities* ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome ; Child ; Plastic Surgery Procedures/methods*

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

Objective To Explore the effect of expression of peroxidase reductase 4(PRDX4)on cervi-cal lymph node metastasis in oral squamous cell carcinomas(OSCC)and its relationship with prognosis.Methods Using bioinformatics databases to explore the expression,prognosis analysis,and related pathway prediction of PRDX4 gene in head and neck squamous cell carcinoma.At the same time,clinical and pathologi-cal data including cervical lymph node metastasis were collected from 124 OSCC patients,the expression of PRDX4 was detected in 124 OSCC tissues using immunohistochemical experimental methods.Results Analy-sis of online bioinformatics databases showed that PRDX4 was highly expressed in head and neck squamous cell carcinoma and significantly correlated with tumor grade.The immunohistochemical results showed that the occurrence of cervical lymph node metastasis was significantly correlated with the intensity of PRDX4 stai-ning in 124 OSCC cases studied,and high expression of PRDX4 was an independent risk factor for cervical lymph node metastasis in OSCC(P=0.010).The staining intensity of PRDX4 was significantly correlated with the presence of multiple lymph node metastasis(P=0.020)and the the maximum diameter of lymph node metastasis(P=0.031),but not related to the invasion of lymph nodes outside the membrane.Survival a-nalysis showed that strong PRDX4 positivity was significantly correlated with poor disease-free survival(DFS)rate and overall survival(OS)rate in OSCC patients.Conclusion OSCC patients with strong expres-sion of PRDX4 have a higher incidence of cervical lymph node metastasis and a poorer prognosis.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective To explore the behavioral patterns and hippocampal neurogenesis of CHD8+mice,and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.Methods Genotype of wild type(WT)and CHD8+/-mice was identified.Weight measurement was conducted on both male and female mice of the WT and CHD8+/-strains.Subsequently,a battery of behavioral tests was administered,which included three-chamber test,self-grooming test,nesting test,Y-maze spontaneous alternation test,food burial test,open-field test and light-dark transition test.Afterwards,the mice were administered 2％pentobarbital sodium(2 ml/kg)to induce anesthesia.Their brains were frozen with 4％paraformaldehyde,removed for photography and analysis to identify any alterations in brain size.Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.Results Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8(CHD8)protein in both male and female mice with CHD8+genotype,as compared to WT mice.There were no notable disparities in body weight between male and female WT and CHD8+mice,as well as in brain size.The three-chamber social behavior test revealed that both male and female CHD8+/-mice had social deficiencies(P＜0.05).During the open field test,there was no significant difference in the total distance moved by male and female WT and CHD8+/-mice.However,the amount of time spent in the central region was considerably lower in CHD8+/-mice compared to the WT mice(P＜0.01).Furthermore,the light-dark transition test revealed that both male and female CHD8+/-mice spent considerably less time investigating the white box compared to the WT mice(P＜0.05).Nevertheless,there were no notable alterations found in self-grooming,nesting,spontaneous alternation of Y-maze,and food burial experiments.In addition,Western blotting result demonstrated a significant drop in doublecortin(DCX)expression(P＜0.001),and immunofluorescent staining revealed a notable reduction in the number of DCX+cells(P＜0.01)in the hippocampus of CHD8+/-mice.Conclusion CHD8+/-mice exhibit social disorders and anxiety-like behaviors,with a decrease in the number of newly generated neurons in the hippocampus and neurogenesis disorders.

OBJECTIVE: To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines. METHODS: In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function. CONCLUSION Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use* ; Colorectal Neoplasms/metabolism* ; Glycolysis/drug effects* ; Animals ; Humans ; Apoptosis/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Glucose/metabolism* ; Cell Cycle/drug effects* ; Mice, Inbred BALB C ; Mice ; HCT116 Cells ; Lactic Acid

Objective To evaluate the prognosis and safety of patients with advanced pancreatic ductal adenocarcinoma(PDAC)who received I-125 seed implantation in treatment with anti-PD-1 monoclonal antibody+chemotherapy.Methods A retrospective analysis was conducted on patients with stage Ⅳ metastatic PDAC who received anti-PD-1 combined chemotherapy treatment at Yixing Hospital,Jiangsu University from Jan 2021 to Jun 2023.Patients were divided into two groups based on whether they received I-125 seed implantation:the I-125 seed implantation+anti-PD-1 monoclonal antibody+Chemotherapy group(IPC group)and the anti-PD-1 monoclonal antibody+chemotherapy group(PC group).The follow-up period ranged from 2 to 24 months,with a median follow-up time of 9 months.The prognosis of patients was analysed in combination with peripheral blood biomarkers.The peripheral lymphocyte subsets of patients in different treatment groups were preliminarily analysed by flow cytometry.Results A total of 13 patients were included,with 5 in the IPC group and 8 in the PC group.Progression-free survival(PFS)and overall survival(OS)in the IPC group were significantly longer than those in the PC group.The treatment in the IPC group was relatively safe,adverse reactions were controllable.The neutrophil-lymphocyte ratio(NLR)and CD4/CD8 ratio indicated that the prognosis of the IPC patients was better.The levels of regulatory T cells(Treg)and active regulatory T cells(aTreg)cells in the IPC patients were reduced after treatment compared with those of the PC patients.Conclusion The addition of I-125 seed implantation can improve the prognosis of patients with advanced PDAC who receive anti-PD-1 monoclonal antibody+chemotherapy,the post-treatment levels of patients'circulating aTreg cells are reduced,and the combination therapy has good safety.

Objective To evaluate the safety and feasibility of percutaneous mitral balloon valvuloplasty with the assistance of arterio-venous circuit.Methods From January 2015 to October 2022,a total 25 patients[19 females,6 males;age(61.60±9.00)years]were included,who were diagnosed with rheumatic heart disease and severe mitral stenosis.A transseptal puncture was performed to establish a femoral arterio-venous circuit,followed by graded dilation with Inoue balloon(diameters:22.00 mm to 28.00 mm).The target was a mitral valve area≥1.50 cm2 with mild or less regurgitation.Results The arterio-venous circuit was established,and mitral balloon valvuloplasty was successfully completed in all 25 patients.Among them,20 patients experienced difficulty with transvalvular crossing using the balloon catheter with conventional methods,16 patients had valvular severe calcification,and 3 patients presented with a left atrial appendage thrombus despite of more than 6-month anticoagulation therapy with warfarin.The mean balloon diameter was(25.00±1.40)mm.The mitral valve area increased from(0.91±0.15)cm2 preoperatively to(1.70±0.14)cm2 postoperatively(P＜0.001).Mean left atrial pressure decreased from(27.00±7.50)mmHg to(16.36±4.07)mmHg(P＜0.001),and mean pulmonary artery pressure decreased from(40.84±13.81)mmHg to(25.00±7.12)mmHg(P＜0.001).All patients showed significant symptom improvement with no complications.Conclusions Arterio-venous circuit for percutaneous mitral balloon valvuloplasty is safe and feasible.This technique can serve as an alternative to standard technique for patients with complex mitral stenosis.