Surgical methods for varicocele remain controversial. This study intends to evaluate the efficacy and safety of different surgical approaches for treating varicocele through a network meta-analysis (NMA). PubMed, Embase, Cochrane, and Web of Science databases were thoroughly searched. In total, 13 randomized controlled trials (RCTs) and 24 cohort studies were included, covering 9 different surgical methods. Pairwise meta-analysis and NMA were performed by means of random-effects models, and interventions were ranked based on the surface under the cumulative ranking curve (SUCRA). According to the SUCRA, microsurgical subinguinal varicocelectomy (MSV; 91.6%), microsurgical retroperitoneal varicocelectomy (MRV; 78.2%), and microsurgical inguinal varicocelectomy (MIV; 76.7%) demonstrated the highest effectiveness in reducing postoperative recurrence rates. In this study, sclerotherapy embolization (SE; 87.2%), MSV (77.9%), and MIV (67.7%) showed the best results in lowering the risk of hydrocele occurrence. MIV (82.9%), MSV (75.9%), and coil embolization (CE; 58.7%) were notably effective in increasing sperm motility. Moreover, CE (76.7%), subinguinal approach varicocelectomy (SV; 69.2%), and SE (55.7%) were the most effective in increasing sperm count. SE (82.5%), transabdominal laparoscopic varicocelectomy (TLV; 76.5%), and MRV (52.7%) were superior in shortening the length of hospital stay. The incidence rates of adverse events for MRV (0), SE (3.3%), and MIV (4.1%) were notably low. Cluster analyses indicated that MSV was the most effective in the treatment of varicocele. Based on the existing evidence, MSV may represent the optimal choice for varicocele surgery. However, selecting clinical surgical strategies requires consideration of various factors, including patient needs, surgeon experience, and the learning curve.
Humans ; Male ; Embolization, Therapeutic/methods* ; Microsurgery/methods* ; Randomized Controlled Trials as Topic ; Sclerotherapy/methods* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; Varicocele/surgery*

AIM To study the chemical constituents from Citri reticulatae Pericarpium Viride and their anti-triple negative breast cancer activities in vitro.METHODS The ethanolic extract of Citri reticulatae Pericarpium Viride was isolated and purified by silica gel,polyamide,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-triple negative breast cancer activities were screened by SRB assay,and their effects on the proliferation of triple negative breast cancer cell lines HCC1806,HCC1937 and MDA-MB-231 in vitro were evaluated.RESULTS Twenty compounds were isolated and identified as nobiletin(1),tangeritin(2),5,4'-dihydroxy-7,8-dimethoxy flavonoid(3),naringenin(4),artemetin(5),5-demethynobiletin(6),3,5,6,7,8,3',4'-pentamethoxy flavonoid(7),5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone(8),xanthomicrol(9),p-hydroxycinnamic acid(10),5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone(11),pectolinarigenin(12),4'-dihydroxy-5,6,7-tetramethoxyflavone(13),hispidulin(14),4',5,6,7-tetramethoxy-flavone(15),1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol(16),umbelliferone(17),5-hydroxymethyl furfural(18),hydroquinone(19),1H-indole-3-carbaldehyde(20).Compound 8 showed a significant inhibitory effect with the IC50 value of(5.36±0.24)μmol/L on HCC1806 cells.CONCLUSION Compound 20 is isolated from genus Citrus for the first time,8,12-13,16-17 are isolated from this plant for the first time.Compound 8 show inhibitory effects on the proliferation of HCC1806,HCC1937 and MDA-MB-231 cells in vitro and have the strongest activities.Compounds 3-4,11-12,15,17 and 19 show strong inhibitory effect on HCC1806 cells.Compounds 15,19 also inhibit the proliferation of HCC1937 cells in vitro.

Objective:To explore the genetic testing outcomes of a fetal family with Thyroid secretion disorder type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations.Methods:One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method. 10-15 mL of fetal amniotic fluid, and 2-3 mL of peripheral blood from the parents, sister, and grandfather of the fetus were collected, and genomic DNA was extracted for trio whole-exome sequencing (trio-WES). The Sanger sequencing was utilized to validate candidate variants for family verification. According to the Standards and Guidelines for the Interpretation and Reporting of Sequence Variants of the American Society of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG guidelines), the pathogenicity of the detected variants was classified. This study has been approved by the Medical Ethics Committee of Gansu Maternal and Child Health Hospital [Ethics No.(2021)GSFY(65)].Results:The fetal ultrasound indicated the nuchal translucency (NT) thickening, and the thyroid function test results of the sister showed an increase in thyroid stimulating hormone and a decrease in free thyroid hormone. Simultaneously, there were cafe-au-lait macules of various sizes in multiple parts of the body of the sister, and the mother had a similar cafe-au-lait macules phenotype. The trio-WES results revealed that there was a c. 413dupA(p.Tyr138*) frameshift mutation in exon 4 and c. 573G>A(p.Trp191*) nonsense mutation in exon 5 of the fetal DUOXA2, which were inherited from the mother and father, respectively. In accordance with the ACMG guidelines, they were classified as pathogenic variant (PVS1+ PM2_Supporting+ PM3) and likely pathogenic variant (PVS1+ PM2_Supporting), respectively. And the nonsense mutation c. 6972C>A(p.Tyr2264*) was detected in exon 46 of the NF1 in the fetus, inherited from the mother. The genetic testing results of the first sister and proband in this case were consistent, and the DUOXA2 and NF1 of the second sister were both wild-type. According to the ACMG guidelines, c.6972C>A(p.Tyr2264*) was classified as pathogenic variant (PVS1+ PS4_Supporting+ PP4+ PM2_Supporting). Conclusion:The mutations in the DUOXA2 gene c. 413dupA(p.Tyr138*) and c. 573G>A(p.Trp191*), and the NF1 gene c. 6972C>A(p.Tyr2264*) might be the genetic causes of TDH5 combined with familiar NF1 in proband. The discovery of the DUOXA2 gene c. 573G>A(p.Trp191*) enriches the spectrum of pathogenic gene variations.

Aromatic immunity in traditional Chinese medicine(TCM) is the medical knowledge accumulated in the process of people's struggling with diseases. It plays an important role in plague prevention, disease treatment, health preservation, and rehabilitation, and has profound TCM basic theoretical support and abundant modern scientific evidence. With the in-depth promotion of the Healthy China initiative and the succession of health needs in the post-COVID-19 era, how to practice the health concept of aromatic immunity in TCM and develop its health service resources with high quality has become an important proposition to be discussed urgently. This paper summarizes the cognitive process, puts forward the basic concept, discusses the scientific connotation and clinical application value, and looks forward to the future development trend of aromatic immunity in TCM, aiming to provide guidance for the development of great health products and promote the application of aromatic immunity in TCM in serving people's health.
Medicine, Chinese Traditional/methods* ; Humans ; COVID-19/immunology* ; China ; Drugs, Chinese Herbal/therapeutic use* ; SARS-CoV-2

Diabetic kidney disease(DKD)with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression.Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials.In this study,we integrated large-scale plasma proteomics,genetic-driven causal inference,and experimental validation to identify prioritized targets for DKD using the UK Biobank(UKB)and FinnGen cohorts.Among 2844 diabetic patients(528 with DKD),we identified 37 targets significantly associated with incident DKD,supported by both observational and causal evi-dence.Of these,22％(8/37)of the potential targets are currently under investigation for DKD or other diseases.Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4(IGFBP4),family with sequence similarity 3 member C(FAM3C),and prostaglandin D2 synthase(PTGDS)—were associated with a 4.35,3.51,and 3.57-fold increased likeli-hood of developing DKD,respectively.In addition,population-level protein-altering variants(PAVs)analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD,through the classic NLR family pyrin domain containing 3(NLRP3)-caspase-1-gasdermin D(GSDMD)apoptotic axis.Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

OBJECTIVE: To explore the genetic testing outcomes of a fetal family with Thyroid dyshormonogenesis type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations. METHODS: One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method. 10-15 mL of fetal amniotic fluid, and 2-3 mL of peripheral blood from the parents, sister, and grandfather of the fetus were collected, and genomic DNA was extracted for trio whole-exome sequencing (trio-WES). The Sanger sequencing was utilized to validate candidate variants for family verification. According to the Standards and Guidelines for the Interpretation and Reporting of Sequence Variants of the American Society of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG guidelines), the pathogenicity of the detected variants was classified. This study has been approved by the Medical Ethics Committee of Gansu Maternal and Child Health Hospital [Ethics No.（2021）GSFY（65）]. RESULTS: The fetal ultrasound indicated the nuchal translucency (NT) thickening, and the thyroid function test results of the sister showed an increase in thyroid stimulating hormone and a decrease in free thyroid hormone. Simultaneously, there were cafe-au-lait macules of various sizes in multiple parts of the body of the sister, and the mother had a similar cafe-au-lait macules phenotype. The trio-WES results revealed that there was a c.413dupA (p.Tyr138*) frameshift mutation in exon4 and c.573G>A (p.Trp191*) nonsense mutation in exon5 of the fetal DUOXA2, which were inherited from the mother and father, respectively. In accordance with the ACMG guidelines, they were classified as pathogenic variant (PVS1+PM2_Supporting+PM3) and likely pathogenic variant (PVS1+PM2_Supporting), respectively. And the nonsense mutation c.6972C>A (p.Tyr2264*) was detected in exon46 of the NF1 in the fetus, inherited from the mother maternal grandfather. The genetic testing results of the first sister and proband in this case were consistent, and the DUOXA2 and NF1 of the second sister were both wild-type. According to the ACMG guidelines, c.6972C>A (p.Tyr2264 *) was classified as pathogenic variant (PVS1+PS4_Supporting+PP4+PM2_Supporting). CONCLUSION The mutations in the DUOXA2 gene c.413dupA (p.Tyr138*) and c.573G>A (p.Trp191*), and the NF1 gene c.6972C>A (p.Tyr2264*) might be the genetic causes of TDH5 combined with familiar NF1 in proband. The discovery of the DUOXA2 gene c.573G>A (p.Trp191*) enriches the spectrum of pathogenic gene variations.
Humans ; Female ; Pedigree ; Pregnancy ; Neurofibromatosis 1/complications* ; Male ; Genetic Testing ; Adult ; Thyroid Dysgenesis/genetics* ; Fetus ; Exome Sequencing ; Mutation

OBJECTIVE: To investigate the clinical phenotype and genetic etiology of a patient with primary infertility accompanied by Oocyte maturation defect (OOMD). METHODS: A 24-year-old female patient who visited the Reproductive Medicine Center of Gansu Provincial Maternity and Child Care Hospital in April 2024 was selected as the study subject. Whole-exome sequencing (WES) was performed on the proband and her husband. Candidate gene variants were validated in the family using Sanger sequencing, and compound heterozygous variants were confirmed through vector construction. Candidate variants were classified for pathogenicity according to the "Standards and Guidelines for the Interpretation of Sequence Variants" established by the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Hospital [Ethics No.: (2023) GSFYLS(78)]. RESULTS: The proband, a 24-year-old female, had been unable to conceive for four years without contraception after marriage. She had undergone two ovarian stimulation cycles using the antagonist protocol and the PPOS protocol, respectively. A total of 74 oocytes were retrieved, with all showing OOMD and some oocytes exhibiting abnormal morphology and poor quality. WES results revealed two heterozygous missense variants in exons 14 and 16 of the PATL2 gene: c.1127G>A (p.R376Q) and c.1388C>G (p.A463G). Family validation results indicated that the missense variant in exon 14 was inherited from the proband's father, while the variant in exon 16 was de novo. CONCLUSION The compound heterozygous variants of the PATL2 gene probably underlay the OOMD and infertility in this proband. Further analysis based on the variant sites and protein structures is needed to determine whether PATL2 gene variants can fully affect oocyte development, thereby providing a personalized treatment plan for the proband.
Female ; Humans ; Young Adult ; Exome Sequencing ; Infertility, Female/genetics* ; Oocytes/metabolism* ; Pedigree ; Phenotype

Intervertebral disc degeneration(IDD)is a prevalent clinical degenerative disease that currently can only be treated through conservative and surgical treatments,which only alleviate symptoms and are not significantly effective.In recent years,nanoparticles have been widely studied in the biomedical field due to their biodegradability,biocompatibility,extended body circulation,sustained and controlled release,and precise drug targeting.Nanoparticle drug delivery systems have the potential to deliver a range of therapeutic agents including proteins,drugs,genes,and cells,thereby promoting tissue and cell repair and regeneration,which offers hope for IDD treatment.However,there are still challenges in translating experimental data into practical therapies applicable to humans.This review summarizes recent research progress on drug delivery systems for IDD treatment based on nanoparticles and provides insights and prospects for the challenges faced by nanoparticles,aiming to provide a reference for the clinical translation of nanoparticle-based treatment for IDD.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To investigate the technical capacity and service quality of occupational health technical service institutions (hereinafter referred to as "occupational health institutions") in Guangdong Province. Methods All occupational health institutions in Guangdong Province that had valid occupational health service qualifications and within the validity period were included for analysis. Data on basic information, employed personnel, and results of professional technical capacity assessments across occupational health institutions were obtained through the Guangdong Provincial Occupational Health Technical Quality Control Center. Results A total of 99 institutions with 2 732 technical staff were included in this study. Occupational health institutions in Guangdong Province were mainly distributed in the Pearl River Delta region, accounting for 87.9% (87/99) of the total. The number of public and private health institutions was 23 and 76, accounted for 23.2% and 76.8% respectively. In terms of technical personnel, the percentage of individuals worked in public or private health institutions was 24.1% and 75.9%, respectively. Personnel titles were predominantly intermediate level and no title, accounting for 38.7% and 26.4%, respectively. Individuals with a bachelor′s degree or above accounted for 67.4%. Engineering and other professionals accounted for 35.4% and 30.5%, respectively. Private institutions undertook 97.3% of testing and evaluation workload related to occupational hazard in the province. The number of occupational health institutes acquiring category Ⅰ and Ⅱ service license were 97 and 13. Among institutions participating in inter-laboratory comparisons, the overall pass rates for quantitative items were 95.5% in public and 70.3% in private institutions, while the pass rates for qualitative items were 100.0% and 94.5%, respectively. Conclusion Occupational health institutions in Guangdong Province face issues such as imbalanced regional distribution, uneven development, and insufficient technical competence and testing capacity of professional personnel. Health authorities at all levels should continue to strengthen supervision and quality control to solidify the technical foundation and comprehensively enhance service capacity and quality.