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*

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective:To investigate the effectiveness and safety of endovascular therapy for patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion with early neurological deterioration (END).Methods:Patients with AIS due to anterior circulation large vessel occlusion with END underwent endovascular therapy under the multimodal imaging guidance in the Department of Neurology, Huai'an First Hospital Affiliated to Nanjing Medical University from June 2019 to April 2023 were collected retrospectively. The modified Thrombolysis in Cerebral Infarction (mTICI) grading was used to evaluate the vascular recanalization, and grade 2b or 3 was defined as successful recanalization. At 90 days after onset, the modified Rankin Scale (mRS) was used to evaluate the functional outcome, and 0-2 was defined as a good outcome. The patients with onset to femoral artery puncture time ≤24 hours and >24 hours were compared.Results:A total of 19 patients were enrolled, including 13 males, aged 61.16±11.75 years. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 4 (interquartile range, 2-5), and the median NIHSS score at END was 13 (interquartile range, 10-20). Twelve patients (63.2%) received intravenous thrombolysis before END. Median baseline Alberta Stroke Project Early CT Score (ASPECTS) was 8 (interquartile range, 7-9); 18 patients (94.7%) achieved successful recanalization, and 2 (10.5%) experienced symptomatic intracranial hemorrhage (sICH). At 90 days after onset, the mRS scores: 0-2 in 12 cases (63.2%), 3 in 4 cases (21.1%), 5 in 1 case (5.2%), and 6 (death) in 2 cases (10.5%). There were 10 patients (52.6%) in the group with onset time to femoral artery puncture ≤24 hours, and 9 patients (47.4%) in the group with onset time >24 hours. There was significant difference between the two groups only in the ASPECTS ( P=0.035), but there were no significant differences in the postprocedural recanalization rate, sICH incidence rate, and good outcome rate at 90 days. Conclusion:Endovascular therapy under the guidance of multimodal imaging is safe and feasible for AIS patients with END due to anterior circulation occlusion.

Objective:To discuss the medication law in prescriptions of Professor Shao Nianfang in the treatment of kidney deficiency and bone marrow loss in senile dementia based on data mining.Methods:Medical cases of kidney deficiency and bone marrow loss in senile dementia in the Geriatric Hospital of Shandong University of Traditional Chinese Medicine from 1st Jan. 2014 to 31st Oct, 2019 were collected. Through hospital electronic medical records system prescription statistics, using ancient and modern medical case cloud platform (V1.2.4), medication frequency, property ans taste, efficacy analysis, correlation rule analysis, clustering analysis and complex network analysis were performed.Results:Totally 110 cases were included in medical cases, involving 238 kinds of Chinese materia medica. The top 10 Chinese materia medica with use frequency were Poria, Acori Tatarinowii Rhizoma, Corni Fructus, Dioscoreae Rhizoma, Rehmanniae Radix Praeparata, Alpiniae Oxyphyllae Fructus, Rehmanniae Radix, Astragali Radix, Chuanxiong Rhizoma, Atractylodis Macrocephalae Rhizoma; the properties were mainly mild, warm slight cold, and cold; the tastes were mainly sweet, bitter, pungent, and light; the meridians were mainly spleen, liver, lung and kidney meridians; the efficacy was clearing dampness and promoting diuresis, clearing heat and promoting blood circulation, calming mind, clearing heat and detoxification, reducing dampness and promote appetizing, tonifying spleen; the association analysis found 15 groups of drug combinations used more than 25 times, they were: Corni Fructus and Poria, Corni Fructus and Dioscoreae Rhizoma, Dioscoreae Rhizoma and Corni Fructus, Rehmanniae Radix Praeparata and Corni Fructus, Dioscoreae Rhizoma and Poria, Astragali Radix and Poria, Alismatis Rhizoma and Poria, Moutan Cortex and Poria, Rehmanniae Radix Praeparata and Poria, Rehmanniae Radix and Poria, Polygalae Radix and Acori Tatarinowii Rhizoma, Moutan Cortex and Corni Fructus, Moutan Cortex and Dioscoreae Rhizoma, Alismatis Rhizoma and Corni Fructus, Alismatis Rhizoma and Dioscoreae Rhizoma; clustering analysis identified four groups of new prescriptions, the first group: Poria, Rehmanniae Radix, Rehmanniae Radix Praeparata, Alismatis Rhizoma, Moutan Cortex, Corni Fructus, Dioscoreae Rhizoma; the second group: Acori Tatarinowii Rhizoma, Cistanches Herba, Morindae Officinalis Radix; the third group: Alpiniae Oxyphyllae Fructus, Chuanxiong Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle; the fourth group: Atractylodis Macrocephalae Rhizoma, Codonopsis Radix, Astragali Radix, Angelicae Sinensis Radix; the results of complex network analysis showed that the core prescription was modified Liuwei Dihuang Pills. Conclusion:This study found that in view of kidney deficiency and bone marrow loss in senile dementia, Professor Shao pays attention to strengthening the healthy qi, and focuses on tonifying deficiency, taking into account the methods of clearing dampness, clearing heat, detoxification, removing blood stasis and restoring consciousness. The four new prescriptions found in the study can provide a reference for modified medication for syndrome differentiation.

Objective To analyze the target volume margins and positioning errors in the radiotherapy for nasopharyngeal carcinoma(NPC)using the cone-beam computed tomography(CBCT)of Halcyon linear accelerator for providing a reference for the margin from clinical target volume to planning target volume(CTV-to-PTV margin)in the radiotherapy for NPC using Halcyon linear accelerator,hence improving treatment precision and effectiveness.Methods A total of 117 NPC patients who received volumetric modulated arc therapy using Halcyon linear accelerator from May 2020 to June 2022 in Jinshazhou Hospital of Guangzhou University of Chinese Medicine were enrolled.The 3861 CBCT images collected from the patients were matched with the CT images to obtain the correction values of the treatment couch in lateral(Lat),longitudinal(Lng)and vertical(Vrt)directions for positioning error analysis.The CTV-to-PTV margin was obtained by the equation(margin =2.5∑+0.7δ).Results The positioning errors in the radiotherapy for NPC using Halcyon linear accelerator were 0.10(0.00,0.10)cm,0.10(0.00,0.20)cm and 0.20(0.10,0.30)cm in Lat,Lng and Vrt directions,respectively.The CTV-to-PTV margins in Lat,Lng and Vrt directions were 0.12,0.12 and 0.09 cm,respectively.Conclusion Low positioning errors can be achieved for NPC patients undergoing image-guided treatment using Halcyon linear accelerator.

Objective To observe and analyze the effect of HbA1c level on macular microcirculation in patients with type 2 diabetes mellitus (T2DM).Methods A cross-sectional study.One hundred and twenty-four T2DM patients (124 eyes) without diabetic retinopathy who diagnosed by the examination of fundus color photography in Lixiang Eye Hospital Of Soochow University during September to December 2017 were enrolled in this study.There were 59 males (59 eyes) and 65 females (65 eyes),with the mean age of 65.06±7.99 years old.All patients underwent BCVA,fundus color photography,and OCT angiography (OCTA).The history of diabetes,hypertension and dyslipidemia were recorded in detail.According to the HbA 1 c level,patients were divided into three groups,HbA1c ideal control group (group A,HbA1c ＜7％,67 eyes),HbA1c control group (group B,7％≤HbA1c≤9％,44 eyes),and HbA1c poor control group (group C,HbA1c＞9％,13 eyes),respectively.The 3 mm × 3 mm range of the macular area was scanned by OCTA instrument.The vascular density (VD) and skeleton density (SD) of nonsegmented retinal layer (NRL),superficial retinal layer (SRL) and deep retinal layer (DRL) in the macular area and foveal avascular zone (FAZ) area,non-circularity index,axial rate (AR) of SRL were measured.The correlation between HbA1c,BCVA and VD,SD ofNRL,SRL,DRL was analyzed statistically with Spearman correlation test.The correlation between systemic factors and the above indicators was analyzed statistically with linear regression analysis.Results The results of linear regression analysis showed that HbA1 c was significantly correlated with VD (t=-3.237,-3.156,-2.050) and SD (t=-0.3.45,-3.034,-2.248) of NRL,SRL and DRL (P＜0.05);but no correlation with FAZ,non-circularity index and AR (t=1.739,0.429,1.155;P＞0.05).The differences of VD (F=6.349,5.981,3.709),SD (F=7.275,6.085,1.904) and AR (F=0.027) of NRL,SRL and DRL in group A,B and C were statistically significant (P＜0.05);but the differences of FAZ (F=1.904),non-circularity index (F=0.280) was not statistically significant (P＞0.05).Significant differences (P＜0.05) of VD and SD of NRL were found between group A and B (t=1.987,2.201),group A and C (t=3.365,3.572),group B and C (t=2.010,2.076).Significant differences (P＜0.05) of VD and SD of SRL were found between group A and B (t=2.087,2.168),group A and C (t=3.197,3.194).There were significant differences (P＜ 0.05) in SD of DRL between group A and B (t=2.239),group A and C (t=-2.519).There was significant difference in VD of DRL between group A and C (t=2.363).The results of Spearman correlation analysis showed that HbA1c was negatively correlated with VD (r=-0.273,-0.255,-0.222;P=0.002,0.004,0.013) and SD (r=-0.275,-0.236,-0.254;P＜0.05) ofNRL,SRL,DRL;positively correlated with FAZ and BCVA (r=0.221,0.183;P＜0.05).BCVA was negatively correlated with VD (r=-0.210,-0.190,-0.245) and SD (r=-0.239,-0.207,-0.296) of NRL,SRL,and DRL (P＜0.05),but not correlated with FAZ (r=0.099,P＞0.05).Conclusion The decrease of macular perfusion and the morphological change of FAZ accompanied by HbA1c increased.

Objective To discuss the feasibility,safety and efficacy of robot-assisted laparoscopic buccal mucosal ureteroplasty in the treatment of long segment upper ureteral stricture.Methods Five patients with complex ureteral strictures were treated with robot-assisted laparoscopic buccal mucosa ureteroplasty (5 males;right side,2 cases;left side,3 cases) in our hospital from March to July of 2017.The patients aged 25-40 years with median of 35 years old.The median body mass index was 23.5 kg/m2 (19-29 kg/m2).Data of surgical conditions,postoperative complications,and follow-up were collected.Results All patients were treated with robot-assisted laparoscopic buccal mucosa ureteroplasty and the operations were uneventful.The median length of stricture of upper ureter were 3 cm (2-6 cm).The median operation time was 360 min (200-400 min),median blood loss was 100 ml (50-200 ml),drainage tube retained time was 5 d(2-9 d),post-operative hospital stay was 11 d(7-12 d),and the median creatinine value was 85 μmol/L (76-98 μmol/L).No urine leakage,infection,buccal mucosa necrosis or other serious complications occurred after surgery.Five patients' CT examnation showed improved hydronephrosis 3 weeks post-operatively.DJ stent was removed 3 months after surgery in 2 patients,and 1 patient presented with no hydronephrosis,another one with mild hydronephrosis.DJ stent was removed 6 months after surgery in the other 3 patients with improved hydronephrosis.Conclusions Robot-assisted laparoscopic buccal mucosal ureteroplasty for the treatment of long segment upper ureteral stricture is a safe and feasible procedure,with a good short-term effectiveness and without severe complications.

Objective To optimize the sulfated modification conditions for Rhizoma Smilacis Glabrae polysaccharides (RSGP),and to investigate the possibility of enhancing the activity of RSGP after sulfating modification.Methods RSGP was modified by cholorosulfonic acid-pyridine.With the yield,carbohydrate content and sulphate substitution degree as the observation indexes,L9 (34)orthogonal design was used to optimize reaction time,reaction temperature and reagent ratio.The degree of sulphate substitution was determined by barium chloride turbitimetry,and the carbohydrate content was detected by sulfuric acid-phenol method.Then the structures of the sulfated modified products were analyzed by infrared radiation (IR) spectrum.Methyl thiazolyl tetrazolim(MTT)assay was used to determine the anti-tumor activity of sulfated RSGP on HepG2 and MCF-7 cell lines.Results The optimized modification conditions of RSGP were sulfating RSGP with cholorosulfonic acid-pyridine in the ratio of 1:6 for 4.5 hours at 60 ℃.The MTT assay results showed that the sulfated RSGP could inhibit the growth and proliferation of human liver cancer HepG2 cell line and human mammary cancer MCF-7 cell line in concentrationdepending manner.Conclusion It is feasible for sulfating modification of RSGP with cholorosulfonic acid-pyridine,and sulfating modification can enhance the anti-tumor activitv of RSGP.

Objective To observe the clinical efficacy of L-carnitine combined with trimetazidine in the treatment of chronic heart failure.Methods The clinical data of 700 patients with chronic heart failure were retrospectively analyzed.According to different treatment methods,they were divided into four groups:A,B,C,D.181 cases of A group used L-camitine combined with trimetazidine treatment on the basis of routine treatment.177 cases of B group received L-carnitine treatment on the basis of routine treatment.175 cases of C group received trimetazidine treatment on the basis of routine treatment.167 cases of D group received conventional treatment.Then,the clinical efficacy of the four groups was compared.Results The total effective rates of A,B,C,D groups were 83.43％,76.84％,73.71％,62.28％,respectively.The total effective rate of A group was obviously higher than the other groups,the difference was statistically significant(x2 =22.40,P ＜0.05).There was no significant difference in total effective rate between B group and C group (x2 =0.46,P ＞ 0.05),but both B and C groups were obviously better than group D (x2=4.37,5.13,all P ＜ 0.05).The data before and after treatment in four groups were significantly improved,such as 6MWT,NT-proBNP,LVEF and FS(A group:t =33.856,37.474,17.722,31.250,B group:t =27.328,31.559,6.863,25.581,C group:t =23.430,32.640,9.524,16.923,D group:t =15.863,9.602,3.061,10.169,all P ＜ 0.01).In the above four indicators,those in A group were obviously better than B group,C group and D group (F =5.884,38.621,4.357,13.770,all P ＜ 0.01).Conclusion L-carnitine combined with trimetazidine can improve the abnormal metabolism of myocardium,optimize the energy metabolism pathway of myocardium,improve the short-term cardiac function of patients markedly.L-carnitine combined with trimetazidine is worthy of promoting joint use.

Objective Our purpose was to investigate the pathogenic gene mutation of a Han Chinese family with vitreous amyloidosis.Methods The 9 individuals(proband,1 affected member and 7 unaffected members) of the family were selected and their DNA was extracted from peripheral blood.The 4 exons of transthyretin(TTR) gene were amplified by polymerase chain reaction(PCR) technique.The amplified products of TTR gene were sequencing by Sanger technique.We also selected 100 unrelated healthy individual as the control group.Results By DNA sequencing,a heterozygous mutation was found in 4 of the 9 subjects from the family.The transition of adenine to cytosine(AAG ＞ ACG) was detectable in exon 2 of TTR,which changed the amino acid composition at codon 35 (Lys35Thr).This mutation did not presented in control group.Conclusion The heterozygosis mutation of TTR gene Lys35Thr should be a pathogenic mutation for the family with vitreous amyloidosis.