Varicocele (VC) is a common cause of male infertility, yet there is a lack of molecular information for VC-associated male infertility. This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients. Twenty infertile males with VC and twenty-three age-matched healthy controls (HCs) were recruited from Peking Union Medical College Hospital (Beijing, China) between October 2019 and April 2021. Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry. Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs. The top enriched pathways among these significantly different metabolites are protein digestion and absorption, aminoacyl-transfer RNA (tRNA) biosynthesis, and biosynthesis of amino acids. Different key lipid species, including triglyceride (TG), diacylglycerol (DG), ceramides (Cer), and phosphatidylserine (PS), varied between VC and HC groups. The distinct metabolites and lipids were moderately correlated. DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility (area under the curve [AUC] = 0.893), positively correlating with sperm count, concentration, and motility. Furthermore, DL-3-phenyllactic acid is the only metabolite shared by all four comparisons (VC vs HC, VC-induced oligoasthenospermia [OAS] vs VC-induced asthenospermia [AS], OAS vs HC, and AS vs HC). DL-3-phenyllactic acid significantly decreased in OAS than AS. Metabolite-targeting gene analysis revealed carbonic anhydrase 9 (CA9) might be the strongest candidate associated with the onset and severity of VC. The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs. DL-3-phenyllactic acid could be a promising biomarker.
Humans ; Male ; Varicocele/complications* ; Infertility, Male/etiology* ; Semen/metabolism* ; Lipidomics ; Adult ; Metabolomics ; Case-Control Studies ; Biomarkers/metabolism*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

To improve the quality evaluation system of Hibisci Mutabilis Folium, this study established high performance liquid chromatography(HPLC) fingerprints of Hibisci Mutabilis Folium and evaluated the quality differences of medicinal materials from different places of production by chemometrics. Furthermore, a content measurement method of differential components was established based on quantitative analysis of multi-components by single-marker(QAMS). The fingerprints of 17 batches of Hibisci Mutabilis Folium from different places of production were constructed, with a total of 19 common peaks marked and seven components confirmed. The similarity between the sample fingerprints and the reference fingerprints ranged from 0.890 to 0.974. By utilizing principal component analysis(PCA), hierarchical cluster analysis(HCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA), the chemical patterns of fingerprints were identified. Five components that could be used to evaluate the quality differences of Hibisci Mutabilis Folium were screened, namely peak 6(quercetin 3-O-β-robinobioside), peak 7(rutin), peak 9(kaempferol-3-O-β-robinobioside), peak 10(kaempferol-3-O-rutinoside), and peak 14(tiliroside). The relative correction factors of isoquercitrin, kaempferol-3-O-β-robinobioside, kaempferol-3-O-rutinoside, kaempferol-3-O-β-D-glucoside, and tiliroside were measured with rutin as the internal reference. The QAMS method was established for the content measurement of six flavonoids, and the results showed there was no significant difference compared to the results obtained by an external standard method. In summary, the HPLC fingerprints and QAMS method established in the study, demonstrating stability and accuracy, can provide a reference for the overall quality evaluation of Hibisci Mutabilis Folium.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Principal Component Analysis

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the intervention effect of dance therapy on the psychological symptoms and psychological craving in methamphetamine-dependent women.Methods:A total of 60 methamphetamine de-pendents in a women's drug rehabilitation center were divided into intervention group and control group(1 person dropped out).The intervention group was trained for 8 dance movements,during which the control group did not in-tervene.The Zhang Tuoji and Chen Huichang's Temperament Scale,Symptom Self-Rating Scale(SCL-90)and Amphetamine Craving Scale(DSQ)were used to evaluate the temperament type,psychological symptoms and psy-chological craving.Results:The differences of SCL-90 depression and anxiety scores(post-intervention score-base-line score)and DSQ total scores were higher in the intervention group than in the control group(Ps＜0.05).The choleric temperament scores were negatively correlated with the differences of DSQ total scores(r=-0.45,P＜0.05),and the melancholic temperament scores were positively correlated with the differences of SCL-90 hostility dimension scores(r=0.41,P＜0.05).Conclusion:Dance therapy could improve the psychological symptoms and psychological craving of women dependent on methamphetamine,with varying effects across different temperament types.

Objective To explore the clinical effect of 3D-printed interbody fusion cage applied in anterior cervical decompression and bone graft fusion for the treatment of cervical spondylotic myelopathy.Methods A total of 100 patients with cervical spondylotic myelopathy who underwent anterior cervical fusion surgery in our hospital from June 2020 to June 2023 were selected as the research subjects,they were randomly divided into the 3D group and the control group according to the random number table method,with 50 cases in each group.Patients in the 3D group were implanted with a 3D-printed interbody fusion cage which was made of microporous metal materials,while patients in the control group were implanted with intervertebral fusion cage which was made of polyetheretherketone material.The surgery-related indicators,cervical imaging parameters,cervical spinal cord function,cervical axial function and surgical complications of patients between the two groups were compared.Results There was no statistically significant difference in the operation time,intraoperative blood loss or length of hospital stay of patients between the two groups(P>0.05).The height of the cervical fusion segments and the Cobb angle of the fusion segments of patients in both groups at each time point after the operation were significantly increased compared with those before the operation(P<0.05).The height of the cervical fusion segments and the Cobb angle of the fusion segments of patients 1 month,3 months,and 6 months after the operation in the 3D group were all greater than those in the control group(P>0.05).The subjective symptom score and the total score of the Japanese orthopaedic association(JOA)of patients 6 months after the operation in the 3D group were higher than those in the control group(P<0.05).The cervical axial function of patients 6 months after the operation in the 3D group was better than that in the control group(P<0.05).The incidence of surgical complications in the 3D group was lower than that in the control group(P<0.05).Conclusion The use of 3D-printed interbody fusion cage during the anterior cervical decompression and bone graft fusion for patients with cervical spondylotic myelopathy can significantly improve the clinical symptoms of patients,achieve better cervical axial function,and have fewer complications.

Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P＜0.05,P＜0.01),and the high-dose EPL group reduced the serum RF in mice(P＜0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P＞0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P＜0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P＜0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P＜0.01).EPL significantly increased the pro-tein expression of Bcl-2(P＜0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P＜0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.

This study investigated the potential pathogenicity and genetic characteristics of ST314 Salmonella Kentucky(S.Ken-tucky)isolates from a broiler slaughterhouse.Antimicrobial susceptibility testing and whole-genome sequencing(WGS)were used to determine antimicrobial resistance,virulence factors,and the presence of antimicrobial resistance genes(ARGs)and mobile genetic elements(MGEs)among the isolates.The three multidrug resistant(MDR)isolates exhibited high resistance to multiple antimicrobial agents.The F4-2S strain exhibited resistance to 14 drugs across seven categories,whereas the F4T strain showed resistance to 13 drugs in the same number of categories.In contrast,the Y23 strain was resistant to nine drugs in six categories.Notably,F4-2S dem-onstrated high homology with F4T:both possessed 13 ARGs distributed across nine categories,in addition to a wide range of virulence factors,including secretion systems and effector proteins.The presence of IncR and IncX1 plasmids significantly enhanced both the antimicrobial resistance and pathogenicity of the isolates.The genome map of Y23 revealed a chromosome alongside two plasmids.The chromosome containedonly one resistance gene but several virulence factors,including the type III secretion system(T3SS),which is crucial for bacterial invasion.The plasmid pY23-1 contained eight types of 19 ARGs.Comparative analysis indicated that pY23-1 ex-hibited high homology with pZ1323SSL0055 and pSAL-045,all of which contained multiple ARGs,thus suggesting critical roles of these genes in the evolution of bacterial resistance.In conclusion,ST314 S.Kentucky demonstrated a complex mechanism of resis-tance coupled with significant pathogenic potential.The ARGs and MGEs in the plasmid contributed to the emergence and dissemina-tion of antimicrobial resistance.The multiple virulence factors present in the chromosome may be key factors driving the increasing virulence of ST314 S.Kentucky.

Objective To explore the clinical effect of 3D-printed interbody fusion cage applied in anterior cervical decompression and bone graft fusion for the treatment of cervical spondylotic myelopathy.Methods A total of 100 patients with cervical spondylotic myelopathy who underwent anterior cervical fusion surgery in our hospital from June 2020 to June 2023 were selected as the research subjects,they were randomly divided into the 3D group and the control group according to the random number table method,with 50 cases in each group.Patients in the 3D group were implanted with a 3D-printed interbody fusion cage which was made of microporous metal materials,while patients in the control group were implanted with intervertebral fusion cage which was made of polyetheretherketone material.The surgery-related indicators,cervical imaging parameters,cervical spinal cord function,cervical axial function and surgical complications of patients between the two groups were compared.Results There was no statistically significant difference in the operation time,intraoperative blood loss or length of hospital stay of patients between the two groups(P>0.05).The height of the cervical fusion segments and the Cobb angle of the fusion segments of patients in both groups at each time point after the operation were significantly increased compared with those before the operation(P<0.05).The height of the cervical fusion segments and the Cobb angle of the fusion segments of patients 1 month,3 months,and 6 months after the operation in the 3D group were all greater than those in the control group(P>0.05).The subjective symptom score and the total score of the Japanese orthopaedic association(JOA)of patients 6 months after the operation in the 3D group were higher than those in the control group(P<0.05).The cervical axial function of patients 6 months after the operation in the 3D group was better than that in the control group(P<0.05).The incidence of surgical complications in the 3D group was lower than that in the control group(P<0.05).Conclusion The use of 3D-printed interbody fusion cage during the anterior cervical decompression and bone graft fusion for patients with cervical spondylotic myelopathy can significantly improve the clinical symptoms of patients,achieve better cervical axial function,and have fewer complications.

Objective:To comprehensively evaluate the application of Common Data Model (CDM) of Observational Medical Outcomes Partnership (OMOP) in China, and provide reference for the implementation of data standardization and evidence sharing in China.Methods:PubMed, Embase, Web of Science, CNKI, VIP, WanFang and SinoMed databases were used for literature retrieval to collect the research papers of OMOP CDM application for data standardization in China until March 15, 2023. The information about institutions, types and numbers of patients were extracted.Results:A total of 14 research papers, including 9 in English and 5 in Chinese, were selected. The research papers published since 2018 were collected, which focused on patients with hypertension, diabetes, and depression. A total of 12 institutions or platforms transformed data into OMOP CDM. Jiangsu Provincial People's Hospital was the first one to apply the CDM and demonstrated its feasibility in China. Additionally, the regional information system in Yinzhou District of Ningbo, Zhejiang Province, standardized the multi-dimensional data of patients with diabetes and hypertension. Based on this platform, a series of prediction models for complications in patients with diabetes were constructed. Another major database in Beijing Anding Hospital applied OMOP CDM to analyze the characteristics of patients with late-life depression and dementia.Conclusions:This study analyzed the application of OMOP CDM in China. Through in-depth analysis of specific cases, the study provided guidance for the future cross-regional evidence sharing and collaboration.