Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

Objective To compare the short-term efficacy and safety of inflatable video-assisted mediastinoscopic transhiatal esophagectomy (IVMTE) and minimally invasive transthoracic esophagectomy (MITE) in the treatment of esophageal cancer. Methods The Cochrane Library, EMbase, PubMed, Wanfang Database, VIP, and CNKI were searched. Literatures related to the short-term efficacy and safety of IVMTE and MITE in the treatment of esophageal neoplasms published from the establishment of the database to December 2023 were searched and meta-analysis was conducted by using RevMan5.4. Quality of case control study or cohort study was assessed by the Newcastle-Ottawa Scale (NOS) and quality of randomized controlled trial was assessed by Cochrane Handbook. Results A total of 14 studies (12 case control studies and 1 prospective cohort study wiht NOS score more than 7 points and 1 randomized controlled trial wiht low bias risk) were included, comprising 1 163 patients, with 525 in the IVMTE group and 638 in the MITE group. The results of meta-analysis revealed that the IVMTE group exhibited significantly shorter operative time [MD=−60.42, 95%CI (−83.78, −37.07), P<0.001] and postoperative hospital stay [MD=−2.44, 95%CI (−2.93, −1.94), P<0.01] compared to the MITE group. Moreover, intraoperative blood loss [MD=−34.67, 95%CI (−59.11, −10.23), P=0.005], three-day postoperative drainage [MD=−286.66, 95%CI (−469.93, −103.40), P=0.002], incidence of postoperative pulmonary infection [OR=0.38, 95%CI (0.26, 0.56), P<0.001], lung leakage rate [OR=0.12, 95% CI (0.02, 0.63), P=0.01] and overall complication rate [MD=0.41, 95%CI (0.22, 0.75), P=0.004] were all lower in the IVMTE group compared to those in the MITE group. However, the MITE technique demonstrated superiority over IVMTE regarding intraoperative lymph dissection number [MD=−3.52, 95%CI (−6.36, –0.68), P=0.02] and intraoperative recurrent laryngeal nerve injury [OR=1.78, 95%CI (1.22, 2.60), P=0.003]. No significant difference was observed between both methods concerning anastomotic fistula. Conclusion Compared to MITE, IVMTE has advantages such as shorter operation time, less intraoperative blood loss, shorter hospital stay, less postoperative drainage within 3 days, and a lower incidence of pulmonary complications. In terms of laryngeal recurrent nerve injury and lymphatic dissection, MITE operation offers more benefits.

Objective To explore the mechanism of ginsenoside Rg1 in alleviating heat stress-induced testicular injury in mice.Methods A total of 20 C57BL/6 male mice(6～8 weeks old)were randomly divided into 4 groups(n=5).The mice from the control group and heat stress(HS)group were intraperitoneally injected with 10 mL/(kg·d)0.9％normal saline for 14 d,while those in the HS+Rg1 group and the Rg1 group were given an intraperitoneal injection of 20 mg/(kg·d)for 14 d,and then on the 7th day after administration,the mice in the HS group and the HS+Rg1 group had the lower abdomen put into a 43 ℃ water bath for 30 min as a single heat stress after being anesthetized with 4％chloral hydrate.Mouse spermatocytes GC-2spd(ts)were divided into control group(routine culture for 48 h),HS group(placed in a 43 ℃ water bath for 30 min after 36 h of conventional culture,and cultured till the end of 48 h),HS+Rg1 group(50 μmol/L Rg1 treatment followed by heat stress injury),and Rg1 group(no heat stress injury).In 1 d after modeling,the eyeball blood samples were collected to detect serum testosterone with ELISA,and the testicles were extracted to observe the morphology and weighed to calculate the testicular index.HE staining was used to observe the histopathology of testis,and corresponding reagents and kits was employed to detect the content of malondialdehyde(MDA)and activities of catalase(CAT)and superoxide dismutase(SOD)in testis tissue.After the epididymal sperm were collected,the sperm concentration and motility were analyzed by computer-assisted sperm analysis(CASA)system.In in vitro experiments,cell apoptosis was detected with TUNEL staining,the protein levels of Nrf2,Keap1,HO-1,Bax,Bcl-2 and Caspase3 were detected with Western blotting,and the mRNA levels of GCLC,GCLM and NQO1 were detected by RT-qPCR.Results Rg1 prevented the decreases in testicular weight and testicular index caused by heat stress,reduced the damage of testicular tissue structure,prevented the decrease of sperm concentration and vitality,antagonized the decreasd number of Leydig cells and serum testosterone level,reduced the accumulation of MDA in testicular tissue,and enhanced the activities of CAT and SOD.Rg1 treatment alleviated the apoptosis of GC-2spd(ts)cells,down-regulated the expression of Bax,Caspase3 and Keap1 proteins,enhanced the expression of Bcl-2,Nrf2 and HO-1 proteins,and increased the transcriptional levels of Nrf2 target genes GCLC,GCLM and NQO1.Conclusion Rg1 has no significant effect on the structure and function of mouse testes,but it can effectively improve the ability of mouse testes to resist heat stress injury,which may be related to the activation of Nrf2 signaling pathway,the improvement of antioxidant enzyme activity,and the reduction of apoptosis of spermatogenic cells.

Objective To investigate the clinical efficacy and safety of 1 565 nm non-ablative fractional laser combined with topical minoxidil and oral finasteride in the treatment of patients with androgenetic alopecia(AGA).Methods Seventy-five male AGA patients with Norwood-Hamilton classification grade Ⅱ-Ⅲ,were randomly assigned into three groups:the control group 1,the control group 2 and the experimental group,with 25 cases in each group.Patients in the control group 1 received topical 5%minoxidil(1 mL,twice daily).Patients in the control group 2 were treated with both topical 5%minoxidil and oral finasteride(1 mg,once daily).Patients in the experimental group received a combined therapy of 1 565 nm non-ablative fractional laser in addition to topical 5%minoxidil and oral finasteride.Hair overall efficacy was evaluated using a 7-point rating scale after 24 weeks of treatment.Hair diameter and density were measured using a dermoscope.Patient satisfaction was assessed post-treatment,and adverse reactions were recorded.Results The overall efficacy of hair in the experimental group was superior to the control group 1 and the control group 2.There were no significant differences in hair density and hair diameter before treatment between the three groups(P＞0.05).After treatment,hair diameter and density increased in all three groups compared to baseline values(P＜0.05),and the hair diameter and hair density of the experimental group were higher than those of the control group 1 and the control group 2(P＜0.05).Patient satisfaction in the experimental group was higher than that in the control group 1 and the control group 2(P＜0.05).Patients in the experimental group experienced tolerable pain and burning sensations during laser treatment,and the symptoms were self-alleviated within a few hours.There were no serious adverse reactions reported in any group.Conclusion The combination therapy of 1 565 nm non-ablative fractional laser,5%minoxidil,and finasteride demonstrates significantly better efficacy in the treatment of AGA than minoxidil and finasteride alone drug therapy.

Objective:To explore the influencing factors of clinical pregnancy outcomes in patients with hydrosalpinx undergoing in vitro fertilization-embryo transfer(IVF-ET) after interventional embolization and whether residual hydrops has an adverse impact on pregnancy outcomes.Methods:Clinical data from 65 patients who underwent interventional embolization and IVF-ET for hydrosalpinx at the Third Affiliated Hospital of Zhengzhou University from March 2021 to October 2022 were collected retrospectively. The hydrops index was quantified by the ratio of the widest diameter to the pelvic transverse diameter of the intraoperative hydrops, and the patient′s age, body mass index(BMI), follicle-stimulating hormone(FSH), lutenizing hormine(LH), estradiol(E2), automated matetials hangling(AMH), endometrial thickness at the time of transplantation, the number of transplanted embryos, embryo type, and location of the hydrosalpinx were recorded. In addition, the clinical pregnancy outcomes of the first transplantation after embolization were followed. Two independent samples t-test, rank sum test and chi-square test were used to analyze the difference of the above indexes among different clinical pregnancy outcomes by SPSS 25.0. The receiver operating characteristic (ROC) curves and Youden index were used to calculate the cut-off value of the water accumulation index. Results:Among 65 patients, the clinical pregnancy rate was 63.1%(41/65), among the 45 patients who underwent embryo transfer before embolization without success, the clinical pregnancy rate after embolization was 62.2%(28/45). Based on data analysis, it showed that IVF-ET clinical pregnancy outcomes were not associated with age, BMI, FSH, LH, E2, AMH, endometrial thickness at the time of transplantation, the number of transplanted embryos, embryo type, as well as location of hydrosalpinx( P>0.05), but associated with hydrosalpinx index( P<0.001). ROC curve analysis showed that the hydrops index could be used as a predictor of pregnancy outcome, and the area under the curve was 0.825, and the optimal cut-off value of the hydrops index was 12.925% based on the Youden index analysis result. Conclusions:Interventional embolization of hydrosalpinx may improve clinical pregnancy rates. When the hydrosalpinx is large enough, it could adversely affected IVF-ET clinical pregnancy, and further aspiration of hydrosalpinx should be performed prior to transplantation.

Objective:To investigate the factors contributing to frailty in very elderly patients with multimorbidity.Methods:This cross-sectional study enrolled 119 very elderly patients with multimorbidity who were hospitalized in the Department of Geriatrics of Huadong Hospital Affiliated to Fudan University from August 2022 to March 2023.The study aimed to understand the basic status of multimorbidity by collecting general information, the number and types of diseases, and frailty status.The subjects were divided into frail and non-frail groups through comprehensive geriatric assessment.Various factors including gender, age, Tinetti balance gait score, risk of sarcopenia, dementia, depression, risk of deep vein thrombosis, dysphagia, comorbidity index, medication count, Basic Activities of Daily Living(BADL)score, Instrumental Activities of Daily Living(IADL)score, Nutritional Risk Screening 2002(NRS-2002)score, Norton pressure injury risk assessment score, and Social Support Rating Scale(SSRS)score were compared.The correlation between each factor and the occurrence of frailty was analyzed using univariate analysis and multivariate Logistic regression analysis.Results:A total of 119 elderly inpatients with multimorbidity, with an average age of 90.8±5.9 years old, were included in the study.The incidence of frailty was 68.9%(82 cases).Univariate analysis revealed significant statistical differences between the frail group and the non-frail group in various factors including age( t=-3.131, P=0.002), Tinetti score( Z=-5.544, P<0.001), risk of sarcopenia( χ2=39.205, P<0.001), dysphagia( χ2=5.937, P=0.015), Charlson comorbidity index( Z=-2.565, P=0.010), medication count( Z=-3.325, P<0.001), BADL( Z=-5.871, P<0.001), IADL( Z=-5.062, P<0.001), Norton score( Z=-5.922, P<0.001), and SSRS social support( Z=-2.637, P=0.008).Multivariate logistic regression analysis showed that the Tinetti score( OR=0.843, 95% CI: 0.737-0.966, P=0.014), decreased muscle strength( OR=11.226, 95% CI: 2.157-58.432, P=0.004), sarcopenia( OR=18.084, 95% CI: 2.041-106.211, P=0.009), Norton score( OR=0.462, 95% CI: 0.254-0.838, P=0.011), and medication count( OR=1.153, 95% CI: 1.000-1.329, P=0.049)were independently associated with frailty. Conclusions:In very elderly patients with multimorbidities, the occurrence of frailty is notably increased.Frailty is linked to multiple risks including falls, muscle weakness/sarcopenia, pressure ulcer risk, and polypharmacy, and these risks are independent of other factors.

Objectives:Aimed to establish a rapid, high-throughput, automated method for determining the creatine kinase (CK-MM) isoform levels.Methods:Magnetic beads labeled with anti-CK-MM antibodies were combined with alkaline phosphatase-based chemiluminescence detection. Clinical and diagnostic performance validation of the assay was determined by analysis of 998 and 75 dried blood spot samples from healthy newborns and Duchenne muscular dystrophy (DMD) patients, respectively, and the CK activity was also determined. The blank and detection limits, cross-reactivity, recovery rate of the method, intra-and inter-assay coefficient, and the hook effect were evaluated.Results:Blank and detection limits were 17.4 and 39.3 ng/ml, respectively. Cross-reactivity toward CK-MB and CK-BB isoforms was 0.2% and 0.02%, respectively. Intra-and inter-assay coefficients of variation were<1%. Mean recovery was 100.32%, with no hook effect in CK-MM levels<50 000 ng/ml. Overall, the mean CK-MM concentrations in newborns and DMD patients were (27.05±0.97) and (3 720±300.5) ng/ml, respectively. A significant positive correlation between the dried blood spot detected CK-MM levels and total CK enzyme activity, evaluated in corresponding serum samples from the 75 DMD patients, was observed ( r=0.91, P<0.001), ?which is in good agreement with the clinical. Conclusions:An assay for rapid quantitative determination of CK-MM that meets clinical newborn screening requirements was established. It had a good value for application.

Primary ciliary dyskinesia (PCD) is a highly heterogeneous recessive inherited disorder. FAP54, the homolog of CFAP54 in Chlamydomonas reinhardtii, was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella. A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes. Through whole-exome sequencing, compound heterozygous variants c.2649_2657delinC (p. E883Dfs*47) and c.7312_7313insCGCAGGCTGAATTCTTGG (p. T2438delinsTQAEFLA) in a new suspected PCD-relevant gene, CFAP54, were identified in an individual with PCD. Two missense variants, c.4112A>C (p. E1371A) and c.6559C>T (p. P2187S), in CFAP54 were detected in another unrelated patient. In this study, a minigene assay was conducted on the frameshift mutation showing a reduction in mRNA expression. In addition, a CFAP54 in-frame variant knock-in mouse model was established, which recapitulated the typical symptoms of PCD, including hydrocephalus, infertility, and mucus accumulation in nasal sinuses. Correspondingly, two missense variants were deleterious, with a dramatic reduction in mRNA abundance from bronchial tissue and sperm. The identification of PCD-causing variants of CFAP54 in two unrelated patients with PCD for the first time provides strong supportive evidence that CFAP54 is a new PCD-causing gene. This study further helps expand the disease-associated gene spectrum and improve genetic testing for PCD diagnosis in the future.
Mice ; Animals ; Humans ; Male ; Kartagener Syndrome/metabolism* ; Cilia/metabolism* ; Semen ; Genetic Testing ; RNA, Messenger ; Mutation

【Objective】 To evaluate the efficacy and safety of different doses and frequencies of oral Sildenafil in the treatment of erectile dysfunction (ED). 【Methods】 The randomized,open clinical trial included 120 ED patients who met the inclusion and exclusion criteria. The patients were randomly divided into the following groups:on-schedule (25 mg/day),on-demand (50 mg,taken irregularly half an hour before each sexual life),new regular group (25 mg/day,50 mg more before each sexual life),regular group (100 mg/time,twice/week). All treatments lasted for 8 weeks. The follow-up indexes included the five-item International Index of Erectile Function (IIEF-5),Erection Hardness Scale (EHS) and Sexual Encounter Profile (SEP2/3). The adverse reactions were recorded. 【Results】 The IIEF-5 scores of the four groups were significantly higher than those after baseline treatment (P<0.001),but there was no significant difference among the four groups (P>0.05). In terms of effective rate,at the 16th week,there were significant differences between the on-demand group (10.7%) and new regular group (62.1%),and between the on-demand group (10.7%) and regular group (50.0%) (P<0.001). In terms of EHS, the percentage of grade 4 patients in regular group was significant higher than that in the on-demand group at the 8th week and 16th week (all P<0.05). In terms of positive rate of SEP-3,there was a significant difference between the on-demand group and regular group (P=0.042) at the 16th week. In the course of treatment,there were transient adverse reactions such as headache,blurred vision,stuffy nose and back pain,which did not affect the treatment. 【Conclusion】 All of the four treatment methods of oral sildenafil showed good efficacy. Both regular group and new regular group maintained good clinical efficacy during the follow-up,which is better than that of the on-demand group. The new regular scheme can be used as a new,safe and effective treatment option.

Adenosine triphosphate (ATP) regeneration systems are essential for efficient biocatalytic phosphoryl transfer reactions. Polyphosphate kinase (PPK) is a versatile enzyme that can transfer phosphate groups among adenosine monophosphate (AMP), adenosine diphosphate (ADP), ATP, and polyphosphate (Poly P). Utilization of PPK is an attractive solution to address the problem of ATP regeneration due to its ability to use a variety of inexpensive and stable Poly P salts as phosphate group donors. This review comprehensively summarizes the structural characteristics and catalytic mechanisms of different types of PPKs, as well as the variations in enzyme activity, catalytic efficiency, stability, and coenzyme preference observed in PPKs from different sources. Moreover, recent advances in PPK-mediated ATP regeneration systems and protein engineering of wild-type PPK are summarized.
Adenosine Triphosphate/metabolism* ; Adenosine Monophosphate ; Polyphosphates/metabolism* ; Catalysis ; Regeneration