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: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

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*

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

Objective To study the effects of Chrysanthemum Flos on blood pressure of spontaneously hypertensive rats(SHR)and evaluate its antioxidant activity in vitro and in vivo.Methods SHR were randomly divided into model,control and experimental-L,-H groups with 10 rats per group,and 10 WKY rats as blank group.Experimental-H,-L groups were given 2.10 and 0.525 g·kg-1 Chrysanthemum Flos extract by gavage;control group received 5.25 mg·kg-1 losartan by gavage;blank and model groups were given the same volume of 0.9％NaCl solution by gavage.Rats in each group were gavaged once a day for 8 weeks.After 8 weeks of continuous intragastric administration,the systolic blood pressure(SBP)and diastolic blood pressure(DBP)were observed.The contents of catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GSH)and malondialdehyde(MDA)in serum were measured with kit colorimetry method.The in vitro free radical scavenging rates of Chrysanthemum Flos extract were detected by 1,1-diphenyl-2-picrylhydrazyl(DPPH)and 2,2'-amino-di(2-ethyl-benzothiazoline sulphonic acid-6)ammonium salt(ABTS)methods.Results The SBP of blank,model,control and experimental-H,-L groups were(132.00±2.45),(204.00±4.55),(171.00±2.16),(181.00±3.74)and(184.67±4.78)mmHg;the DBP were(73.33±4.03),(175.67±3.40),(120.33±0.94),(125.33±2.87)and(125.67±2.36)mmHg;the contents of serum CAT were(9.24±3.99),(8.40±2.98),(9.24±2.42),(8.59±2.70)and(8.49±1.47)U·mL-1;the contents of serum SOD were(122.40±12.30),(75.30±28.37),(125.39±31.35),(110.92±26.14)and(103.37±22.31)U·mL-1;the contents of serum GSH were(117.93±10.18),(78.29±23.68),(118.57±26.08),(109.89±20.52)and(98.73±14.71)U·mL-1;the contents of serum MDA were(8.36±2.08),(8.45±3.38),(8.22±3.04),(7.09±3.21)and(7.24±3.32)nmol·L 1,respectively.Compared with model group,the differences of above indicators in control group and experimental-H,-L groups were statistically significant(P＜0.05,P＜0.01).Chrysanthemum Flos extract showed certain free radical scavenging ability in vitro.The highest scavenging rates of DPPH and ABTS were 90.29％and 92.67％,respectively.Conclusion Chrysanthemum Flos extract had good antihypertensive activity.The antioxidation ability might be its antihypertensive mechanisms.

Objective To analyze the influence of midazolam and propofol on sedation effect and blood gas indicators in elderly patients undergoing mechanical ventilation after cardiopulmonary bypass(CPB)cardiac surgery.Methods The elderly patients with mechanical ventilation after CPB cardiac surgery were grouped according to cohort method,including midazolam group(group M),propofol group(group P)and midazolam-propofol combined administration group(group M-P).Group M was treated with midazolam(intravenous injection of 0.05-0.10 mg kg-1 midazolam for sedation induction,and then continuously intravenous injection of 0.05-0.15 mg·kg-1·h-1 midazolam by micropump),and group P was treated with propofol(intravenous injection of 0.5 mg·kg-1 propofol for sedation induction,and then continuously intravenous injection of 0.5-2.0 mg·kg-1·h-1 propofol by micropump),and group M-P was given combined administration of midazolam and propofol(intravenous injection of 0.02-0.05 mg·kg-1 midazolam and 0.2-0.5 mg·kg-1 propofol for sedation induction and then continuously intravenous pump of 0.05-0.1 mg·kg-1 midazolam and 0.5-0.8 mg·kg·h-1 propofol).The sedation effect,blood gas indicators,hemodynamic indicators,extubation time,intensive care unit(ICU)stay time and treatment cost were compared among the three groups,and the adverse drug reactions during sedation therapy were recorded.Results There were 43 cases in group M,44 cases in group P,39 cases in group M-P.The drug onset times in groups M,P and M-P were(77.94±12.05),(18.18±5.20)and(21.25±9.36)s;the times to achieve satisfactory sedation effect were(42.57±11.41),(22.63±8.17)and(23.98±10.25)min;the recovery times after withdrawal were(59.30±14.86),(19.83±5.44)and(22.16±6.29)min;the extubation times were(1.61±0.20),(1.45±0.22)and(1.37±0.15)d;the ICU stay times were(2.17±0.29),(1.91±0.36)and(1.84±0.25)d;the treatment costs were(186.59±60.83),(922.97±164.34)and(375.03±71.16)thousand yuan;and the total incidence rates of adverse drug reactions were 34.88％,4.55％and 7.69％respectively,all with significant difference(all P＜0.05).There were no statistically significant differences in mean arterial pressure(MAP),heart rate(HR),oxygen saturation(SpO2),partial pressure of oxygen(PaO2),partial pressure of carbon dioxide(PaCO2)at T0,T1,T2,T3 and T4 among the three groups(all P＞0.05).Conclusion Combined administration of midazolam and propofol in elderly patients underwent mechanical ventilation after CPB cardiac surgery has a significant sedation effect,and it is conducive to reducing the dosages of sedative drugs,and it has small impact on blood gas indicators and hemodynamic indicators of patients.Compared with midazolam alone,it is more beneficial to shortening the extubation time and ICU stay and reducing the total incidence rate of adverse drug reactions,and compared with propofol alone,it is more beneficial to reducing treatment cost,and is a more ideal sedation administration model.

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

[Objective] To investigate the clinical features and treatment of renal cell carcinoma unclassified with medullary phenotype (RCCU-MP), so as to improve the clinical understanding of this disease. [Methods] The clinical data of 2 patients with pathological diagnosis of renal medullary carcinoma (RMC) in Zhujiang Hospital during 2019 and 2023 were retrospectively analyzed, and relevant literature was reviewed. [Results] Both patients had symptoms of backache, and imaging examination indicated renal space-occupying lesions.Case 1 was diagnosed as RMC by renal biopsy, and case 2 was pathologically diagnosed as RMC after surgery.Both cases lacked evidence of sickle cell trait or sickle cell disease, and were finally diagnosed as RCCU-MP.Case 1 did not receive antineoplastic therapy and died 5 months after diagnosis.Case 2 underwent laparoscopic nephrectomy, and then received gemcitabine + paclitaxel chemotherapy + immunotherapy.The patient's tumor progressed gradually after first-line treatment was abandoned due to concurrent hematologic infection, and he eventually died 7 months after surgery. [Conclusion] The clinical features of RCCU-MP are partially similar to those of RMC.The diagnosis of RCCU-MP requires pathological examinations and should exclude sickle cell trait or sickle cell disease.Due to the aggressive nature of the tumor, the prognosis of patients is poor.

AIM:To establish a model of meibomian gland dysfunction in rats induced by eyeliner tattoo and investigate its potential mechanisms.METHODS:A total of 40 SD rats were selected, with 30 randomly chosen to have eyeliner tattoo applied their right eyes and designated as the eyeliner group. The remaining 10 rats were not given any treatment and served as the normal group. The corneal morphology of both groups was observed using a slit lamp at 1, 2, and 4 wk after establishment, and the tear film break-up time(BUT), Schirmer I test(SIt), corneal fluorescein staining score, and corneal irregularity score were calculated. The corneal Placido rings were examined using an ocular surface analyzer, and the corneal tissue structures of both groups were observed under a confocal microscope. After 4 wk and completion of clinical indicator recording, the eyeballs and upper and lower eyelid tissues were taken for pathological examination. The meibomian gland structures were observed through HE staining, the conjunctival goblet cells were observed using PAS staining, and the lipid droplets were observed with ORO staining.RESULTS:The slit lamp examination results showed that the eyeliner group rats exhibited in situ black pigmentation in the eyelids, with no eyelid deformation or scarring. The corneal epithelium was rough, with positive fluorescein staining, presenting as spotty staining that worsened over time. Compared with the normal group, the BUT was significantly shortened, tear secretion volume was significantly decreased, and the corneal fluorescein staining score and corneal irregularity score were significantly increased at 1, 2, and 4 wk after modeling in the eyeliner group(all P<0.01). The corneal confocal microscopy results showed a decrease in corneal epithelial cells in the eyeliner group, with the appearance of abnormally bright cells, and inflammatory cell infiltration visible in the stromal layer. The ORO staining results revealed a decrease in lipid droplets in the eyeliner group, showing a downward trend with increasing observation time. The HE staining results showed that pigment blocked the meibomian gland openings in the eyeliner group, and the density of meibomian gland acini showed a downward trend over time. The PAS staining results showed a decreasing trend in the number of PAS-positive cells in the eyeliner group.CONCLUSION:Eyeliner tattoo can induce meibomian gland dysfunction, and the blockage of meibomian gland openings caused by the pigment particles used may be an important cause of meibomian gland dysfunction.