Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

This study explored the prescription pattern of traditional Chinese medicine(TCM) in the treatment of hypertensive left ventricular hypertrophy(LVH), so as to provide a relevant theoretical basis for the clinical diagnosis and treatment of hypertensive LVH. The study systematically searched the databases of CNKI, Wanfang, VIP, and SinoMed to screen out the qualified literature on TCM treatment of hypertensive LVH and used Microsoft Excel 2021 to establish the relevant prescription database. It also counted the frequency, property, flavor, and meridian affiliation of TCM in the prescriptions and classified their efficacy. The study used Lantern 5.0 and Rstudio software to analyze the hidden structural models and association rules of the high-frequency TCM with a frequency of >3.50% and adopted Origin 2024 software to visualize the data, so as to explore the prescription pattern of TCM in treating hypertensive LVH. The results showed that a total of 128 TCM prescriptions were included, involving 163 TCM with a total frequency of 1 242. The high-frequency TCM included Salviae Miltiorrhizae Radix et Rhizoma, Uncariae Ramulus Cum Uncis, Gastrodiae Rhizoma, Poria, and Chuanxiong Rhizoma, with the main efficacy from blood-activating and stasis-resolving herbs, tonic herbs, and liver-calming and wind-extinguishing herbs. The latent structure analysis(LSA) identified 10 latent variables, 20 latent classes, 7 comprehensive clustering models, and 23 core prescriptions. It was speculated that the common syndromes of hypertensive LVH included blood stasis obstructing the collaterals, ascending hyperactivity of liver Yang, Yin deficiency with Yang hyperactivity, and intermingled phlegm and blood stasis. The association rule analysis yielded 33 strong association rules, with the highest comprehensive association rule being Gastrodiae Rhizoma→Uncariae Ramulus Cum Uncis. Hypertensive LVH is characterized by asthenia in origin and asthenia in superficiality, with Yin deficiency and Qi deficiency as the origin and blood stasis and phlegm as the superficiality. Clinical treatment focuses on activating blood circulation, resolving stasis, tonifying Qi, and nourishing Yin, combined with syndrome-specific therapies such as calming wind and stopping convulsions, clearing heat, eliminating dampness and resolving phlegm, and promoting diuresis and reducing swelling.
Drugs, Chinese Herbal/therapeutic use* ; Data Mining ; Humans ; Hypertension/complications* ; Hypertrophy, Left Ventricular/physiopathology* ; Medicine, Chinese Traditional ; Drug Prescriptions

In this study, the pharmacodynamic components and potential pharmacological functions of Danzhi Xiaoyao Formula in treating nervous system diseases were investigated by hippocampal component characterization and network pharmacology. After rats were administrated with Danzhi Xiaoyao Formula by gavage, high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) was employed to explore the components in the hippocampus of rats. Fifty-seven components were identified in the hippocampus of rats by comparing the extract of Danzhi Xiaoyao Formula, herbal components in the hippocampus after administration, and blank samples. KEGG and GO analyses predicted 74 core targets including GSK3B, MAPK1, AKT, IL6. These targets were involved in PI3K/Akt, NF-κB, MAPK, JAK/STAT, Wnt, and other signaling pathways. The results indicated that Danzhi Xiaoyao Formula may ameliorate other nervous system diseases enriched in DO, such as neurodegenerative diseases, cerebrovascular diseases, and mental and emotional disorders by mediating target pathways, inhibiting inflammation, reducing neuronal damage, and alleviating hippocampal atrophy. The relevant activities exhibited by this formula in nervous system diseases such as Alzheimer's disease, Parkinson's disease, and diabetic neuropathy have extremely high development value and are worthy of further in-depth research. This study provides a theoretical basis and practical guidance for expanding the application of Danzhi Xiaoyao Formula in the treatment of nervous system diseases.
Drugs, Chinese Herbal/administration & dosage* ; Animals ; Rats ; Hippocampus/metabolism* ; Network Pharmacology ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Rats, Sprague-Dawley ; Male ; Nervous System Diseases/genetics* ; Humans ; Signal Transduction/drug effects*

OBJECTIVES: To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL). METHODS: A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors. The patients received ABVD regimen or Chinese Pediatric HL-2013 regimen chemotherapy. Early treatment response and long-term efficacy were assessed, and prognostic factors were analyzed using the Cox proportional hazards regression model. RESULTS: The overall complete response (CR) rates after 2 and 4 cycles of chemotherapy were 42% and 68%, respectively. Compared with the ABVD regimen group, patients treated with the HL-2013 regimen in the R1 group showed significantly higher CR rates after both 2 and 4 cycles (P<0.05). However, no statistically significant differences in CR rates were observed between the two regimens in the R2 and R3 groups (P>0.05). The 5-year event-free survival (EFS) rate, overall survival rate, and freedom from treatment failure rate were 83%±4%, 97%±2%, and 88%±4%, respectively. Cox analysis indicated that the presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy were independent risk factors for lower EFS rates (P<0.05). CONCLUSIONS Pediatric HL generally has a favorable prognosis. The presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy indicate poor prognosis.
Humans ; Hodgkin Disease/pathology* ; Male ; Child ; Female ; Adolescent ; Retrospective Studies ; Child, Preschool ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Infant

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

AIM:Using bioinformatics analysis and experiment validation to explore the differential expres-sion genes related to abnormal lipid metabolism in hepatocellular carcinoma(HCC)and the molecular mechanism of pachymaran affecting pyroptosis through squalene epoxidase(SQLE)/nucleotide-binding oligomerization domain-like re-ceptor protein 3(NLRP3)/gasdermin D(GSDMD)signaling pathway.METHODS:(1)The GEO,GSEA,DAVID,STRING and GEPIA databases were employed to screen abnormal lipid metabolism-related differentially expressed genes in HCC.(2)The tumor tissues from HCC patients(n=9)were collected to verify the differential expression of SQLE.(3)The inhibitory effect of pachymaran on the viability of human HCC cell line HepG2 was measured by CCK-8 assay.(4)The HepG2 cells were divided into control group and pachymaran(800 mg/L)group.The cell migration was analyzed by wound-healing assay,and RT-qPCR was used to measure SQLE mRNA expression.(5)The HepG2 cells with overexpres-sion of SQLE(OE-SQLE)were divided into 5 groups as follows:control group,overexpression negative control(OE-NC)group,OE-SQLE group,OE-NC+pachymaran group,and OE-SQLE+pachymaran group.The mRNA and protein expres-sion levels of SQLE and pyroptosis-related factors were determined by RT-qPCR and Western blot.Colorimetric method and ELISA were used to measure lactate dehydrogenase(LDH),interleukin-1β(IL-1β)and IL-18 levels.The necrosis of HepG2 cells was analyzed by flow cytometry.RESULTS:The SQLE gene was screened through bioinformatics analysis,and its mRNA expression was significantly increased in tumor tissues from HCC patients(P＜0.01).In cell experiments,treatment with 800 mg/L pachymaran for 48 h had a significant inhibitory effect on HepG2 cell viability,and the expres-sion of SQLE mRNA was reduced(P＜0.01).After overexpression of SQLE,the mRNA and protein levels of pyroptosis-re-lated factors,necrotic rate,and LDH,IL-1β and IL-18 levels were significantly decreased(P＜0.05).After treatment with pachymaran,the above indicators were significantly increased(P＜0.05).CONCLUSION:The SQLE is abnormal-ly highly expressed in HCC,and pachymaran can affect the growth of HCC cells by activating the NLRP3/GSDMD pyropto-sis pathway through SQLE.