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: Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment. METHODS: The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process. RESULTS: The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC. CONCLUSIONS This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Combined Modality Therapy ; Perioperative Care

Objective : To investigate the role of single nucleotide polymorphisms(SNP) of glutathione peroxidase 4(GPX4) gene in the risk of non-cardia gastric cancer. Methods: A total of 1 031 samples were selected, including 506 normal examiners and 525 patients with non-cardia gastric cancer.GPX4rs4807542, rs713041, rs2074451 and rs3746162 were genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Unconditional Logistic regression was used to analyze the relationship between each SNP with the risk of non-cardia gastric cancer under the four genetic models. Results : The CT+TT genotype of rs713041 reduced the risk of non-cardia gastric cancer compared with the CC genotype(OR=0.699, 95%CI: 0.537-0.910). The GT+TT genotype of rs2074451 reduced the risk of non-cardia gastric cancer compared with the GG genotype(OR=0.681,95%CI: 0.520-0.893). The G-C-G-C haplotype, constructed by the four SNPs ofGPX4, was related to an increased risk of non-cardia gastric cancer(OR=1.262, 95%CI: 1.035-1.539), and G-T-T-C haplotype was related to a decreased risk of non-cardia gastric cancer(OR=0.784, 95%CI: 0.656-0.937). The fourth-order interaction ofGPX4rs4807542, rs713041, rs2074451 and rs3746162 played a synergistic effect in the risk of non-cardia gastric cancer(P<0.05). Conclusion GPX4rs713041 and rs2074451 are related to non-cardia gastric cancer susceptibility. The G-C-G-C haplotype composed ofGPX4rs4807542, rs713041, rs2074451 and rs3746162 is a risk factor for non-cardia gastric cancer, while the G-T-T-C haplotype is a protective factor. The interaction betweenGPX4rs4807542, rs713041, rs2074451 and rs3746162 is closely connected with the occurrence of non-cardia gastric cancer.

Objective To investigate the relationship between the expression of keratin 15(KRT15)and keratin 18(KRT18)proteins in colorectal cancer tissue and their clinicopathological features and prognosis.Methods A total of 97 patients with colorectal cancer who underwent surgical treatment in a hospital from June 2018 to June 2019 were selected as the study objects.Immunohistochemistry was used to detect the ex-pression of KRT15 and KRT18 protein in colorectal cancer tissues and adjacent tissues,and the differences of KRT15 and KRT18 protein expression in colorectal cancer patients with different clinicopathological features were compared.The patients with colorectal cancer were followed up for 3 years after discharge,and their o-verall survival(OS)during the follow-up period was analyzed.Kaplan-Meier survival curve and Log-rank test were used to analyze the difference in OS rate among colorectal cancer patients with different KRT15 and KRT18 protein expression.Univariate and multivariate COX proportional regression analysis was performed to analyze the factors affecting the prognosis of patients with colorectal cancer.Results The positive expres-sion rates of KRT15 and KRT18 protein in colorectal cancer tissues were higher than those in adjacent tis-sues,and the difference was statistically significant(P＜0.05).The positive expression rates of KRT15 and KRT18 protein in colorectal cancer tissues of patients with low differentiation,TNM Ⅲ stage,perineural inva-sion and preoperative carcinoembryonic antigen(CEA)level ≥5 ng/mL were higher than those of patients with medium-high differentiation,TNM Ⅰ-Ⅱ stage,without perineural invasion and preoperative CEA level＜5 ng/mL,the difference was statistically significant(P＜0.05).The 3-year OS rates of colorectal cancer patients with positive expression of KRT15 and KRT18 protein were 64.29％and 60.00％respectively,which were lower than those of patients with negative expression of KRT15 and KRT18 protein(83.64％and 85.96％respec-tively),and the difference was statistically significant(x2=6.497,7.987,P＜0.05).Multivariate COX pro-portional regression analysis showed that TNM stage Ⅲ,positive expression of KRT15 protein and positive expression of KRT18 protein were risk factors affecting the survival of patients with colorectal cancer(P＜0.05).Conclusion The expression of KRT15 and KRT18 protein in colorectal cancer tissues can provide ref-erence for prognosis assessment of patients with colorectal cancer.

BACKGROUND:The preoperative planning of traditional X-ray films is often inaccurate,which can lead to some intraoperative and postoperative complications,increase the operation time and intraoperative blood loss,and to some extent affect the surgical outcome of total hip arthroplasty. OBJECTIVE:To investigate the accuracy and effectiveness of artificial intelligence preoperative planning in total hip arthroplasty. METHODS:Sixty patients who underwent primary total hip arthroplasty on the affected side were selected.30 of them used artificial intelligence 3D preoperative planning(trial group)and 30 used conventional X-ray film 2D preoperative planning(control group),and there were no statistically significant differences between the two groups in terms of gender,age,condition and other general data(P>0.05).The actual intraoperative prosthesis placement and preoperative planning prosthesis matching,intraoperative operation time,intraoperative blood loss,bilateral femoral eccentric distance difference,bilateral joint eccentric distance difference and bilateral lower limb length difference,and Harris score at 3 months after operation were compared between the two groups,and the accuracy and application effect of the two preoperative plans were analyzed. RESULTS AND CONCLUSION:(1)Patients in both groups were followed up for 4-6 months postoperatively.One patient in the control group had a posterior dislocation of the prosthesis at 5 days postoperatively,which recovered after performing manual repositioning without re-dislodgement.The rest of the patients did not have postoperative complications or postoperative death.(2)Complete matching rate of the prosthesis on the acetabular side and femoral side was significantly better in the trial group than that in the control group(P<0.05).(3)Operation time and intraoperative blood loss were significantly less in the trial group than those in the control group(P<0.05).(4)The difference in bilateral lower limb length between the two groups was statistically significant(P<0.05),and the difference in bilateral femoral eccentric distance and bilateral joint eccentric distance was not statistically significant(P>0.05).(5)Harris score of patients in the trial group was significantly higher than that in the control group 3 months after operation(P<0.05).(6)These results confirm that compared with traditional film planning,artificial intelligence preoperative planning can predict the prosthesis type more accurately,shorten the operation time,reduce intraoperative blood loss,diminish the occurrence of postoperative bilateral lower limb inequality,and accelerate postoperative recovery.

AIM:To investigate the regulatory role of retinoid X receptor(RXR)in oxidative stress response of rat type Ⅱ alveolar epithelial cells(AECII)induced by hypoxia/reoxygenation(HR).METHODS:The AECII were di-vided into control(C)group,HR group,HR+solvent dimethyl sulfoxide(DMSO)group(HD group),HR+RXR agonist 9-cis-retinoic acid(9-RA)group(RA group),and HR+RXR antagonist HX531 group(HX group).Cell Counting Kit-8(CCK-8)method was used to measure the cell viability.Immunofluorescence staining was used to detect the expression of surfactant protein A(SP-A)and RXRα in AECII.Kits were detected to the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in cells.Transmission electron microscopy was used to observe the ultrastructural changes of the cells.Western blot was used to detect the protein level of nuclear factor E2-related factor 2(Nrf2).RT-PCR was used to detect the expression level of Nrf2 mRNA.RESULTS:Compared with C group,the cell viability and SOD activity in HR,HD,RA and HX groups were decreased significantly(P<0.05),the MDA content were increased significantly(P<0.05),the Nrf2 mRNA and protein expression levels were decreased significantly(P<0.05 or P<0.01),and the immuno-fluorescence expression of RXRα was significantly increased(P<0.01).Compared with HR and HX groups,the cells in RA group showed significantly increased cell viability(P<0.05),increased SOD activity(P<0.05),decreased MDA con-tent(P<0.05),increased Nrf2 mRNA and protein expression levels(P<0.01),and significantly increased immunofluo-rescence expression of RXRα(P<0.01).CONCLUSION:Hypoxia/reoxygenation can aggravate the oxidative stress re-sponse of rat AECII,and RXR agonist intervention can alleviate HR-induced rat AECII injury by inhibiting oxidative stress.

Diabetes is a common chronic non-infectious disease. Diabetic patients not only suffer from metabolic disorders, but are also prone to immune deficiencies and are at a higher risk of being infected with human papillomavirus (HPV). Many studies at home and abroad have shown that the HPV infection rate of patients with diabetes is higher than that of non-diabetic patients. Patients with diabetes can benefit from HPV vaccination, and the tolerance is good. HPV vaccination is recommended for diabetic patients. This article reviews the research on diabetes, HPV infection, and HPV vaccine, which will provide references for HPV vaccination in diabetic patients.

OBJECTIVE To provide a reference for pharmaceutical care in patients with hemorrhagic transformation after cerebral infarction complicated with atrial fibrillation. METHODS Clinical pharmacists participated in the treatment practice of a patient with hemorrhagic transformation after cerebral infarction complicated with atrial fibrillation. Because the patient had a hemorrhagic transformation after cerebral infarction after stent implantation and arterial thrombolysis， the clinical pharmacists recommended stopping antiplatelet drugs and giving plasma and cold precipitation； because D-dimer was significantly elevated， the clinical pharmacists recommended anticoagulant therapy with low-molecular heparin. Due to the patient’s recurrence of hemorrhagic transformation after cerebral infarction， the clinical pharmacists recommended discontinuing rivaroxaban and administering human prothrombin complex concentrate. RESULTS The physician adopted the clinical pharmacists’ recommendation. After treatment， the patient’s condition tended to improve steadily and was allowed to be discharged with medication. CONCLUSIONS The clinical pharmacists assessed the individualized risk and optimized the patient’s medication regimen by suggesting discontinuation of antiplatelet and anticoagulant drugs， carrying out pharmaceutical care such as coagulation index monitoring， determining the time and indications for restarting anticoagulation， and pharmaceutical monitoring， to ensure the safety and efficacy of the patient’s medication.

ObjectiveTo investigate the mechanism of neferine（Nef） in promoting vascular regeneration against cerebral ischemia through modulation of mitochondrial calcium uniporter（MCU） ion channel. MethodTaking the area of subintestinal vessels in microvascular deficiency zebrafish as an index， the vascular regenerative efficacy of Nef was evaluated， and the median effective concentration（EC₅₀） was calculated. Rats were randomly divided into a sham operation group， a model group， a positive drug group（butylphthalide， 6 mg·kg^-1）， and Nef low， medium， and high dose groups（0.125， 0.625， 3.125 μg·kg^-1）. Except for the sham operation group， the middle cerebral artery occlusion（MCAO） model was established in other groups. After modeling， the groups were administered the corresponding dose of drugs by gavage， while the sham operation and model groups received equal volumes of saline， once a day for 7 consecutive days. Neurobehavioral scores were assessed for each group of rats， and the infarct rate of ischemic brain tissue was calculated by 2，3，5-triphenyltetrazolium chloride（TTC） staining. The regional cerebral blood flow（rCBF） of each group was measured using a speckle contrast imaging. Immunofluorescence and Western blot were conducted to detect the expression of vascular endothelial growth factor（VEGF）， platelet endothelial cell adhesion molecule-1（CD31）， and hypoxia-inducible factor-1α（HIF-1α） proteins in each group. Human umbilical vein endothelial cells（HUVECs） were divided into the normal group， model group， positive drug group（astragaloside Ⅳ， 10 μmol·L^-1）， and Nef group （32 nmol·L^-1）. In the verification of mitochondrial protection of Nef and its mechanism in promoting vascular regeneration， the spermine（MCU agonist） and Nef+spermine group were added. HUVECs model of oxygen-glucose deprivation（OGD） was established in all groups except the normal group， the cell viability was assessed using 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide（MTT） assay， and cell migration ability was evaluated through scratch and tube formation assays. Fluorescent probes（Rhod-2 AM， Fluo-3 AM， JC-1， Calcein AM） and a cellular energy metabolism analyzer were used to analyze the mitochondrial protective effects of Nef. Molecular docking was performed to predict the binding ability of Nef with MCU and HIF-1α， and Western blot was used to detect the effects of Nef on the protein expressions of MCU， B-cell lymphoma-2 associated X protein（Bax）， Caspase-3 and HIF-1α in the OGD model HUVECs. ResultThe results of vascular regeneration in microvascular deficiency zebrafish showed that compared to the normal group， the area of subintestinal vessels in the model group significantly decreased（P<0.01）. Compared to the model group， different concentrations of Nef could significantly increase the area of subintestinal vessels（P<0.01）， with the maximum tolerated concentration of 10.24 μmol·L^-1 and the EC₅₀ of 0.23 μmol·L^-1. Anti-cerebral ischemia results on MCAO rats showed that compared to the sham operation group， the model group had a significant decrease in rCBF and a significant increase in infarct rate， while CD31 expression significantly decreased（P<0.01）， and VEGF and HIF-1α protein expressions significantly increased（P<0.05）. Compared to the model group， the treated groups showed significant increases in rCBF， significant reductions in infarct volume， and significant increases in CD31， VEGF， and HIF-1α protein expression（P<0.01）. Cell experiment results showed that compared to the normal group， the model group had decreased cell viability and migration ability， increased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， reduced mitochondrial permeability transition pore（MPTP） opening， and decreased mitochondrial energy metabolism capability， with increased expressions of MCU， Bax， Caspase-3 and HIF-1α proteins（P<0.05， P<0.01）. Compared to the model group， the Nef group showed increased cell viability and migration ability， decreased intracellular Ca²⁺ and mitochondrial Ca²⁺ levels， increased MPTP opening， enhanced mitochondrial energy metabolism capability， decreased expressions of MCU， Bax and Caspase-3 proteins， and increased HIF-1α protein expression（P<0.05， P<0.01）. ConclusionNef can stabilize mitochondrial membrane potential and inhibit mitochondrial apoptosis. By down-regulating the expression of MCU， it suppresses the activation of intracellular Bax and Caspase-3 while activating the HIF-1α signaling pathway， enhancing the expression of VEGF and CD31， thereby promoting vascular regeneration to treat ischemic brain injury.

Objective: To investigate the effects of 3-phosphoinositide-dependent protein kinase-1(PDK1) on the purkinje cells(PCs) in aging mice. Methods: The footprint test, elevated beam-walk test and rotarod test were used to measure the gait traits, motor balance and motor coordination of mice. Immunoflourescence was used to detect the structure of the cerebellum and the morphology of cells in the cerebellum. The expression level of PDK1, protein kinase C gamma(PKCγ) and protein kinase B(also known as AKT) and the phosphorylation of ribosomal protein S6(rpS6) in the cerebellum were detected by Western blot. Results: The mice showed motor defects in the overlap between forelimb and hindlimb, motor balance and motor coordination ability in an age-dependent manner. Furthermore, the cerebellum and the soma size of the PCs decreased in an age-dependent manner. However, the density of the PCs was not affected by age. Additionally, the expression level of the PDK1, PKCγ, AKT and the phosphorylation of rpS6 in the cerebellum were reduced with age. Conclusion The cerebellar size and the cell soma size of PCs decrease in the old mice. These effects may contribute to the reduction of the expression of PKCγ and AKT and the phosphorylation of rpS6 in the old mice, ultimately affecting the cerebellar motor coordination.