ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.

ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.

Objective:To investigate the efficacy and safety of oral maintenance therapy with tegafur for residual lesions in patients with locally advanced esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy.Methods:A retrospective cohort study was conducted. A total of 38 patients with locally advanced ESCC who had residual lesions after receiving albumin bound paclitaxel combined with platinum chemoradiotherapy from March 2019 to September 2021 in Jiangsu Province Suqian Hospital were selected. All patients were divided into the maintenance treatment group (20 cases) and the non-maintenance treatment group (18 cases) based on whether they received oral maintenance therapy with tegafur after chemoradiotherapy. The progression-free survival (PFS) of both groups was compared and the adverse reactions of the maintenance treatment group were analyzed.Results:There were no statistically significant differences in baseline data between the 2 groups (both P > 0.05). The 1, 2, 3-year PFS rates for the maintenance treatment group were 95.0%, 78.1%, and 58.3%, respectively, with a median PFS time of 33.65 months (95% CI: 29.04-38.26 months); the 1, 2, 3-year PFS rates in the non-maintenance treatment group were 88.9%, 54.5%, and 12.1%, respectively, with a median PFS time of 25.08 months (95% CI: 20.97-29.18 months); there was a statistically significant difference in PFS between the 2 groups ( χ2 = 5.36, P = 0.021). The common adverse reactions in the maintenance treatment group included hematological adverse reactions, hand foot syndrome, decreased appetite, and fatigue. The more common adverse reactions were neutropenia [85.0% (17/20)] and leukopenia [65.0% (13/20)]; 9 cases experienced grade 3-4 adverse reactions, which were relieved by adjusting the dosage or discontinuing the medication. Conclusions:Oral maintenance therapy with tegafur may improve the survival of ESCC patients with residual lesions after chemoradiotherapy and the adverse reactions are controllable.

Objective:To investigate the efficacy and safety of oral maintenance therapy with tegafur for residual lesions in patients with locally advanced esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy.Methods:A retrospective cohort study was conducted. A total of 38 patients with locally advanced ESCC who had residual lesions after receiving albumin bound paclitaxel combined with platinum chemoradiotherapy from March 2019 to September 2021 in Jiangsu Province Suqian Hospital were selected. All patients were divided into the maintenance treatment group (20 cases) and the non-maintenance treatment group (18 cases) based on whether they received oral maintenance therapy with tegafur after chemoradiotherapy. The progression-free survival (PFS) of both groups was compared and the adverse reactions of the maintenance treatment group were analyzed.Results:There were no statistically significant differences in baseline data between the 2 groups (both P > 0.05). The 1, 2, 3-year PFS rates for the maintenance treatment group were 95.0%, 78.1%, and 58.3%, respectively, with a median PFS time of 33.65 months (95% CI: 29.04-38.26 months); the 1, 2, 3-year PFS rates in the non-maintenance treatment group were 88.9%, 54.5%, and 12.1%, respectively, with a median PFS time of 25.08 months (95% CI: 20.97-29.18 months); there was a statistically significant difference in PFS between the 2 groups ( χ2 = 5.36, P = 0.021). The common adverse reactions in the maintenance treatment group included hematological adverse reactions, hand foot syndrome, decreased appetite, and fatigue. The more common adverse reactions were neutropenia [85.0% (17/20)] and leukopenia [65.0% (13/20)]; 9 cases experienced grade 3-4 adverse reactions, which were relieved by adjusting the dosage or discontinuing the medication. Conclusions:Oral maintenance therapy with tegafur may improve the survival of ESCC patients with residual lesions after chemoradiotherapy and the adverse reactions are controllable.

Objective To investigate the effects of a 45％high-fat diet(HFD)with isocaloric intake on energy metabolism and endurance exercise capacity in SD rats.Methods Twenty-four male SD rats were randomly divided into normal chow diet group(CON),HFD group,normal chow diet+exercise training group(CONT),and HFD+exercise training group(HFDT).The CON and CONT groups received normal chow diet,while the HFD and HFDT groups received a 45％high-fat diet with isocaloric intake.The HFDT and CONT groups underwent an endurance training of moderate-intensity running for 6 weeks.Body weight,fat mass,and lean mass were measured weekly.Energy expenditure and basal metabolic rate during rest and exercise states were measured using Pheno Master/Calo Treadmill system.Blood glucose,lipids,and creatine kinase levels were detected after the exhaustion test.Results In 6 weeks after intervention,the endurance exercise capacity was significantly enhanced in the HFDT group than the CONT group(P＜0.05).There were no obvious differences in body weight and body composition among the groups under isoenergetic feeding conditions.At rest,no statistical differences were observed in total energy expenditure and basal metabolic rate among the groups.However,prior to the 4th week,the CON group primarily metabolized carbohydrates while the HFD group primarily metabolized fats.But the carbohydrate metabolism was decreased and then increased,and the substrate metabolism rates eventually reached similar levels between the 2 groups on the 5th to 6th week.The HFDT group primarily metabolized fats while the CONT group primarily metabolized carbohydrates,with significant differences persisting after 6 weeks of training(P＜0.05).HFD led to elevated levels of serum cholesterol,triglycerides(TG),and high-density lipoprotein cholesterol(HDL-C),but,endurance training resulted in decreased lipid levels in the HFDT group,accompanied by an increase inβ-hydroxybutyrate(βHB)level(P＜0.05).Isoenergetic diets had no significant differences in their effects on liver and kidney function or muscle damage indicators.Conclusion An isoenergetic HFD can improve fat utilization ability and extend endurance exercise time in rats without altering body composition or affecting liver and kidney function.

Objective To develop a nutritional formula on enhancing the endurance of heavy load exercise,and evaluate its efficacy comprehensively.Methods Sixty C57BL/6J male mice were randomly divided into control group(CON group)and low-,medium-and high-dose nutritional formula groups(LDF,MDF and HDF groups),with 15 mice in each group.Each group received intervention with nutritional formula at corresponding dose for 2 weeks,and underwent adaptive training and heavy load exercise in the 1 st and 2nd weeks,respectively.Exhaustion exercise time,skeletal muscle antioxidant indicators(SOD,MDA,PC and GSH),fatigue related indicators(serum URA,LDH and LA),muscle glycogen,and serum exercise injury related indicators(ALT,AST,CK and CK-MB)were measured and detected in the mice,and comprehensive evaluation was conducted according to relevant evaluation standards.Results The LDF group,MDF group and HDF group had significantly prolonged running exhaustion time than the CON group(P＜0.05),with the HDF group showing the greatest improvement(P＜0.05).Compared with the CON group,the activities of SOD and GSH in the skeletal muscles were significantly increased(P＜0.05),while the levels of MDA and PC in skeletal muscles were obviously decreased in the 3 doses of nutritional formula groups(P＜0.05).PAS staining of the skeletal muscles displayed that the glycogen content was significantly increased in the MDF group and the HDF group than the CON group(P＜0.05),and the highest increase was observed in the HDF group(P＜0.05).Biochemical test revealed that the levels of LDH,LA,ALT,AST,CK,and CK-MB were remarkably lower in the 3 doses of nutritional formula groups than the CON group(P＜0.05).Conclusion The nutritional formula can significantly improve the endurance and skeletal muscle antioxidant capacity in mice under heavy load exercise,and has anti-fatigue and-injury protection effects.This nutritional formula can be used to support physical fitness during heavy load endurance exercise.

Rotator cuff injury often leads to shoulder pain and dysfunction. For the injured rotator cuff tendon without continuous interruption, conservative treatment is often used. However, the shoulder is used frequent in daily life, which makes that the rotator cuff injury generally shows gradual aggravation and eventually progresses to complete tear due to poor blood supply of the rotator cuff tendon tissue and weak repair ability. In order to reverse the pathophysiological changes after rotator cuff injury and promote the repair of injured rotator cuff tendon, a series of conservative treatments for rotator cuff injury have been explored. Extracorporeal shock wave therapy (ESWT) is one of the representative treatments, but its molecular biological mechanism in promoting rotator cuff repair is still unclear. Therefore, the authors review the progress of ESWT for rotator cuff injury from aspects of the molecular biological mechanism and clinical application status, so as to provide a reference for future researches and clinical application of ESWT.

【Objective】 To investigate the predictive value of high preoperative neutrophile-lymphocyte ratio (NLR) for the prognosis of nonurothelial carcinoma of the bladder (NUBC) after radical cystectomy (RC). 【Methods】 Clinical and follow-up data of NUBC patients undergoing RC during Jan.2005 and Dec.2020 were collected. The optimal cut-off value of NLR was determined with the receiver operating characteristic (ROC) curve. The survival curve was drawn with Kaplan-Meier method to compare the differences in cancer specific survival (CSS) and overall survival (OS) between the high-NLR and low-NLR groups. The independent risk factors of CSS and OS were screened with Cox proportional hazard regression model. 【Results】 Of the 62 eligible cases,34 (54.8%) were diagnosed with adenocarcinoma,17 (27.4%) with squamous cell carcinoma, 6 (9.7%) with small cell carcinoma and 5 (8.1%) with sarcoma. Kaplan-Meier analysis results showed high NLR was associated with poor CSS (P=0.001) and OS (P<0.001). Cox regression results indicated that high NLR (HR=2.42, 95%CI: 1.12-5.23, P=0.025) and advanced pathologic tumor stage (HR=3.21, 95%CI:1.53-6.74,P=0.002) were independent risk factors of unfavorable CSS. Similarly, high NLR (HR=2.75, 95%CI: 1.35-5.56, P=0.005) and advanced pathologic tumor stage (HR=2.81, 95%CI:1.43-5.57, P=0.003) were independent risk factors of unfavorable OS. 【Conclusion】 As an independent risk factor of unfavorable CSS and OS in NUBC patients undergoing RC, high preoperative NLR is of great value in the prediction of long-term prognosis and may help to optimize individualized treatment.

The spatiotemporal distribution of growth factors in bone tissue-engineered repair and reconstruction is critical. Growth factors can be used in bone tissue engineering through different encapsulation methods. Different encapsulation methods make growth factors have different release kinetics. At present, the common physical entrapment, easily degradable carrier and simple spatial structure usually result in poor sustained release of growth factors by burst release. The optimization of release methods of growth factors enables their release at different times and spaces in a biomimetric manner, which is conducive to improving the effect of tissue repair and avoiding the adverse effects of excessive factors. Starting from the necessity of spatiotemporal sustained release of growth factors, the authors summarize growth factors can attain spatiotemporal sustained release by being directly immobilized on the surface of the carrier, encapsulated in the carrier, encapsulated in the microparticles and encapsulated in the carrier by the microparticles and review the spatiotemporal sustained release of growth factors in different encapsulation methods, so as to provide a reference for optimizing spatiotemporal release of growth factor in bone tissue engineering.

Objective:To investigate the characteristics of gonads, the incidence of gonadal tumors and the detection results of SRY gene and Y chromosome microdeletions in 45, X/46, XY chimeras. Methods:The medical records of 45, X/46, XY karyotype or its variant in Jiangxi Children′s Hospital from January 2013 to December 2019 were analyzed retrospectively and analyze the gonadal phenotype and oleculardetection of 45, X/46, YX karyotype.Results:Among the 30 patients with 45, X/46, XY karyotype or its variant, the age of treatment was under 18 years old, with 11 males and 19 females.Fourteen of the patients had undergone prophylactic gonadectomy.Six male cases of unilateral testis and contralateral striated gonads were detected.Pathological section suggested that the gonadal tissue contained testis and ovary in 3 cases, adrenal gland tissue with translocation in 2 cases, and bilateral striated gonad in 8 cases, and both sexes were female.Pathological section indicated that the gonad tissue contained both epididymis and ovary tissue in 1 case, and gonadoblastoma in 1 case.There were 1 case of ovarian dysplasia with granulomatous hyperplasia and 1 case with proliferative nevus cells (mixed nevus). No follicle was found in all patients with B-ultrasound and pathological sections.Among the 11 male children, 5 cases were positive by SRY gene detection.Seven cases by Y chromosome microdeletion detection displayed that 3 cases had partial Y chromosome deletion and 4 cases had no deletion; 10 cases among 19 cases of social gender female patients were detected by SRY gene detection and 9 cases were positive and 1 case was negative; 7 cases were detected by Y chromosome microdeletion and the results are 2 cases with Y chromosome partial deletion, 4 cases with Y chromosome no deletion and 1 case with Y chromosome whole deletion. Conclusions:Most patients with 45, X/46, XY chimera have abnormal gonadal tissue, which has the risk of gonadal tumor, especially among female patients.Most patients had positive SRY gene and had no or partial deletion of Y chromosome.In view of the increased risk of gonadal tumors in these patients, early prophylactic gonadectomy is recommended.