Background: The surgical neck of the humerus is located approximately 2–3 cm distal to the anatomical neck (collum anatomicum) at the junction of the greater and lesser tubercles and the humeral shaft. Owing to the transition between cortical and cancellous bones, this region is biomechanically vulnerable and prone to fractures, particularly in older adults. Fractures of the surgical neck of the humerus are classified under the International Classification of Diseases, 10th Revision (ICD-10), with diagnostic codes S42.21.3, S42.22, and S42.23. National statistics indicate that 210,763 new trauma cases were reported in Mongolia in 2023, representing an 11.6% increase compared to the previous year, of which 11,452 cases (5.4%) involved shoulder and humeral injuries. Aim: This study aimed to compare the clinical effects of traditional Mongolian bone-setting therapy and surgical treatment on pain intensity, shoulder function, range of motion, and activities of daily living in patients with surgical neck of the humerus fractures. Materials and Methods: Based on the Department of Traditional Therapies of the Mongolian National University of Medical Sciences (MNUMS) and the Department of Orthopedic Trauma of the Inner Mongolia International Hospital, Inner Mongolia Autonomous Region, China, a total of 60 patients diagnosed with surgical neck fractures of the humerus were enrolled in this study between January 2024 and December 2025. The patients were randomly assigned into two groups: a Mongolian traditional bone-setting therapy group (n=30) and a surgical treatment group (n=30). Assessments were conducted before treatment and at 1 month and 3 months after treatment. Shoulder joint range of motion, activities of daily living, and muscle strength were evaluated using the Constant–Murley score, while pain intensity was assessed using the Visual Analog Scale (VAS). The collected data were systematically analyzed, and the therapeutic outcomes of the two treatment modalities were comprehensively compared and summarized. Result: The baseline demographic and clinical characteristics were comparable between the groups. In the traditional bone-setting group, VAS scores decreased significantly, whereas Constant–Murley scores improved markedly at both follow-up points. The overall outcomes in the traditional bone-setting group were significantly better than those in the surgical group (P<0.05). Conclusion Traditional Mongolian bone-setting therapy offers rapid pain relief, superior long-term functional recovery, and fewer complications, making it a valuable treatment option, particularly for elderly patients and those unsuitable for surgery.

Background: Mongolian traditional bone-setting is a non-surgical treatment method for fractures; however, there is a lack of evidencebased research evaluating its effectiveness, which forms the basis of our study. Aim: To study the therapeutic efficacy of traditional bonesetting treatment for surgical neck fractures of the humerus. Materials and Methods: From June 2023 to June 2025, 120 patients diagnosed with surgical neck fractures of the humerus and treated at the Inner Mongolia International Mongolian Hospital were randomly divided into a traditional bone-setting group (n=64) and a surgical treatment group (n=56). Shoulder and upper limb function were evaluated at 1, 3, and 6 months after treatment using the Constant–Murley score, Oxford Shoulder Score (OSS), and Visual Analog Scale (VAS) for pain. Result: A total of 120 patients with surgical neck fractures of the humerus were divided into two groups, with no significant differences in the baseline characteristics (p>0.05).In the traditional bone-setting group, pain (VAS) decreased more rapidly at 1–3 months (p<0.01), while activities of daily living and functional outcomes improved significantly at 3–6 months (p<0.01). At 6 months, shoulder function (Constant–Murley score) was significantly improved (p=0.049).In contrast, the surgical group showed faster recovery in joint range of motion and muscle strength in the early stage; however, by 6 months, the outcomes between the two groups were comparable. Conclusion In the treatment of surgical neck fractures of the humerus, no significant difference was observed between traditional bone-setting and surgical treatment in terms of shoulder range of motion and muscle strength recovery. However, the advantages of traditional bone-setting lie in its ability to relieve pain more rapidly, promote faster functional recovery, improve activities of daily living, and achieve better long-term outcomes than modern bone-setting. Therefore, traditional bone setting is a safe and effective treatment method that aligns with modern theories of bone healing and rehabilitation principles and holds significant value for wider clinical application and further research in the management of surgical neck fractures of the humerus.

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals ; Mice ; Network Pharmacology ; Resveratrol/administration & dosage* ; Male ; Sepsis-Associated Encephalopathy/genetics* ; Signal Transduction/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Endothelium, Vascular/metabolism* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Humans ; Sepsis/complications* ; Oxidative Stress/drug effects*

OBJECTIVE: To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization (MR) study. METHODS: A two-sample MR study was performed using summarized statistics from the genome-wide association studies (GWAS) conducted in reproductive traits, as well as GWAS data on overall psoriasis, psoriatic arthritis (PsA), and psoriasis vulgaris (PV). Besides univariable MR (UVMR), multivariable MR and two-step MR was used to calculate the independent effects and quantify the proportion mediated by education or body mass index (BMI). RESULTS: Genetically predicted early age at first sexual intercourse (AFS) led to an increased risk of overall psoriasis [odds ratio ( OR) _UVMR: 0.54]; 36.13% of this effect was mediated through BMI and 47.79% through educational attainment. The direct negative casual association between age at first birth (AFB)-PsA was dominant ( OR _UVMR: 0.76), with 49.61% proportion of the mediation due to BMI. The mediating effect was found for BMI on the AFS-PV relationship, which accounted for 26.27% of the proportion. AFS was inversely associated with the risk of overall psoriasis and PV, with considerable mediation by BMI and educational attainment. CONCLUSION Early AFB may cause a higher risk of PsA, while the AFS-PsA association was fully mediated by BMI.
Humans ; Body Mass Index ; Psoriasis/etiology* ; Mendelian Randomization Analysis ; Educational Status ; Female ; Genome-Wide Association Study ; Risk Factors ; Male ; Reproduction ; Adult

To establish a method for detecting Toxoplasma gondii based on recombinant polymerase amplification(RPA)technology and apply it to clinical sample validation of pet cats.Using the 529 repeat sequence of the Toxoplasma gondii gene as the target gene sequence,primers and probes were designed,and the Rep-529 recombinant plasmid was constructed as the standard.A fluorescent RPA reaction system was established.Dilute the plasmid standard 10 times to different concentrations as the detection template for sensitivity testing;Specific testing was conducted using genomic DNA from several parasitic spe-cies,including Toxoplasma gondii,Cryptosporidium,Neosporidium,Trichinella spiralis,Giardia flagellata,Babesia bo-vis and Theileria annulata as templates;Simultaneously,fluorescence RPA and RT-PCR were used to detect 52 positive and 40 negative cats clinical samples,and the coincidence rate of the detection results of the two methods were compared and ana-lyzed.The RPA reaction system was successfully established using PTRep recombinant plasmid as the standard,ToxD-F/ToxD-R as the primer,and RepD-P as the fluorescent probe.The reaction temperature was constant at 39 ℃,the reaction time was 30 minutes,and the detection sensitivity was 1 copy/μL.There is no significant cross reaction with parasites such as Cryptosporidium,Neosporidium,Trichinella spiralis,Giardia,Babesia bovis and Theileria annulata,and the specificity is good.A total of 92 clinical fecal samples from cats were tested,and the positive coincidence rate of fluorescence RPA detection method was higher than that of conventional RT-PCR method(98.08％vs.82.69％),and the difference of the positive rate was not statistically significant(X2=1.392,P＞0.05).The fluorescence RPA detection method for Toxoplasma gondii suc-cessfully established in this study has the characteristics of being fast,sensitive,specific,accurate,and reliable.It can be used as a rapid clinical detection kit for Toxoplasma gondii in cats and other animals,providing new technical support for the subsequent epidemiological monitoring and precise clinical diagnosis of toxoplasmosis in cats,other animals,and humans in the future.

To establish a method for detecting Toxoplasma gondii based on recombinant polymerase amplification(RPA)technology and apply it to clinical sample validation of pet cats.Using the 529 repeat sequence of the Toxoplasma gondii gene as the target gene sequence,primers and probes were designed,and the Rep-529 recombinant plasmid was constructed as the standard.A fluorescent RPA reaction system was established.Dilute the plasmid standard 10 times to different concentrations as the detection template for sensitivity testing;Specific testing was conducted using genomic DNA from several parasitic spe-cies,including Toxoplasma gondii,Cryptosporidium,Neosporidium,Trichinella spiralis,Giardia flagellata,Babesia bo-vis and Theileria annulata as templates;Simultaneously,fluorescence RPA and RT-PCR were used to detect 52 positive and 40 negative cats clinical samples,and the coincidence rate of the detection results of the two methods were compared and ana-lyzed.The RPA reaction system was successfully established using PTRep recombinant plasmid as the standard,ToxD-F/ToxD-R as the primer,and RepD-P as the fluorescent probe.The reaction temperature was constant at 39 ℃,the reaction time was 30 minutes,and the detection sensitivity was 1 copy/μL.There is no significant cross reaction with parasites such as Cryptosporidium,Neosporidium,Trichinella spiralis,Giardia,Babesia bovis and Theileria annulata,and the specificity is good.A total of 92 clinical fecal samples from cats were tested,and the positive coincidence rate of fluorescence RPA detection method was higher than that of conventional RT-PCR method(98.08％vs.82.69％),and the difference of the positive rate was not statistically significant(X2=1.392,P＞0.05).The fluorescence RPA detection method for Toxoplasma gondii suc-cessfully established in this study has the characteristics of being fast,sensitive,specific,accurate,and reliable.It can be used as a rapid clinical detection kit for Toxoplasma gondii in cats and other animals,providing new technical support for the subsequent epidemiological monitoring and precise clinical diagnosis of toxoplasmosis in cats,other animals,and humans in the future.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Background and aims Cancer cachexia is prevalent in various cancers and is associated with chemotherapy toxicity. However, limited data exist on the relationship between cachexia and immune-related adverse events (irAEs). The aim of this study is to explore the correlation between cancer cachexia and irAEs and its possible mechanism. Methods A murine model of orthotopic hepatocellular carcinoma (HCC) with cachexia was developed to evaluate the impact of T-cell infiltration into multiple tumor-free organs on the occurrence of irAEs. Single-cell RNA sequencing of thymic stromal cells was performed. Additionally, patients with advanced cancers receiving anti-programmed cell death protein 1/ligand 1 (PD-1/L1) antibody treatment were followed to investigate the relationship between cachexia and irAEs. Results Inflammatory cell infiltration was observed in multiple tumor-free organs of cachexic HCC mice but not in non-cachexic controls. Immunofluorescence confirmed that the infiltrating cells included CD4+ and CD8+ T cells. Morphological assessment and hematoxylin–eosin staining revealed thymic atrophy in cachexic HCC mice. Single-cell RNA sequencing of thymic stromal cells showed a reduction in medullary thymic epithelial cells (mTECs) II and III in cachexic mice. Autoimmune regulator (Aire) downregulation was accompanied by decreased expression of tissue-restricted antigens in mTECs. T cells from cachexic HCC mice induced organ-specific inflammation and T-cell infiltration in multiple organs of tumor-free mice. Following anti-mouse PD-1 antibody treatment, the incidence of inflammation in multiple organs markedly increased in cachexic HCC mice and in tumor-free mice that had received T cells from the cachexic HCC mice. Flow cytometry and immunofluorescence analyses revealed enrichment of thymic monocytic myeloid-derived suppressor cells (M-MDSCs) in cachexic HCC mice. M-MDSCs infiltrated the thymus in cachexic mice with cancer, and they induced apoptosis of mTECs from tumor-free mice in vitro via nitric oxide production. Transfer of M-MDSCs led to inflammatory cell infiltration in multiple organs and thymic involution in tumor-free mice without affecting body weight. Sixty-four patients with advanced cancer receiving anti-PD-1/L1 therapy were enrolled. Patients who developed irAEs had higher levels of circulating M-MDSCs than those who did not. Moreover, patients with cachexia (body mass index (BMI) < 20 kg/m2 or ≥5% weight loss over the past 6 months) had elevated M-MDSC levels. Patients with both high M-MDSC levels and low BMI or weight loss ≥5% experienced more irAEs (hazard ratio: 2.333; 95% confidence interval: 1.231–4.423). Conclusions M-MDSCs in cachexic mice induced mTEC apoptosis through nitric oxide production, impairing T-cell negative selection and promoting autoimmune T-cell infiltration into tumor-free organs. Cancer cachexia-related M-MDSCs may serve as predictive biomarkers for irAEs in patients with advanced cancer. Graphical abstract