Mitofusin 2 (MFN2) residing on the outer mitochondrial membrane is a pivotal factor participating in mitochondrial fusion and maintaining mitochondrial morphology. Due to its multifaceted cellular functions, MFN2 is implicated in the pathogenesis of diverse maladies, notably type 2 Charcot-Marie-Tooth disease, which has catalyzed a surge in pharmaceutical endeavors directed towards MFN2. This article reviews the function of MFN2 and its role in a variety of diseases, outlines the current status of drug discovery against MFN2, and summarizes potential drug molecules currently in preclinical research, aiming to provide some reference for the research and development of drugs and therapies targeting MFN2.

Objective: To explore the clinical safety and efficacy of a single-position robot-assisted radical nephroureterectomy (RRUN) in the treatment of upper tract urothelial carcinoma (UTUC). Methods: A retrospective study was conducted on 136 UTUC patients who underwent RRUN (n=35) and laparoscopic radical nephroureterectomy (LRUN，n=101) in our hospital during Dec.2020 and Aug.2023.The perioperative and safety indicators of the two groups were compared.The intravesical recurrence-free survival (IVRFS)，recurrence-free survival (RFS)，and overall survival (OS) of the two groups were compared using Kaplan-Meier method. Results: There were no significant differences in the baseline data between the two groups (P>0.05).All surgeries were successfully completed without conversion to open surgery.RRUN demonstrated superior perioperative outcomes compared to LRUN in overall postoperative complication rate [37.1%(13/35) vs. 56.4%(57/101)]，postoperative hospital stay [6(5,7) days vs. 7(6,8) days]，and catheter indwelling time [3(2，4) days vs. 4(3，5) days]，with statistically significant differences (P<0.05).Safety indicators of both surgical approaches were similar (P>0.05).Survival analysis showed no significant difference in oncological outcomes between the two groups [IVRFS (1 year：92.1%，2 years：85.2%)，RFS (1 year:82.4%，2 years:74.9%)，OS (1 year:90.6%，2 years:84.2%)] (P>0.05). Conclusion: Compared with retroperitoneal LRUN，single-position RRUN for UTUC demonstrates comparable safety and oncological efficacy，while offering significant advantages in perioperative outcomes such as reducing postoperative complication rate and shortening hospital stay.

Idiopathic pulmonary fibrosis （IPF）， as a progressive lung disease， has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs， which are ineffective and induce side effects， failing to meet the clinical needs. Therefore， developing safer and more effective drugs has become an urgent task， which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization， epithelial-mesenchymal transition （EMT）， oxidative stress， and autophagy， while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory， Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore， the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood， warming Yang and tonifying Qi， and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization， restoring redox balance， inhibiting EMT， and regulating cell autophagy. However， few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field， we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines， we focus on exploring systemic treatment options for IPF， with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.

Objective To evaluate the safety, effectiveness and feasibility of robotic-assisted kidney transplantation (RAKT). Methods Clinical data of 16 patients who underwent kidney transplantation were collected. Among them, 8 recipients received RAKT (RAKT group) and 8 cases underwent open kidney transplantation (OKT) with the contralateral kidney from the same donor (OKT group). Perioperative status and the recovery of renal allograft function were compared between two groups. Results All patients successfully completed the surgery. In the RAKT group, no patient was converted to open surgery. The operation time in the RAKT group was longer than that in the OKT group (P=0.015). No significant differences were observed in the serum creatinine levels before surgery and upon discharge between two groups (both P>0.05). In the OKT group, one recipient developed delayed graft function (DGF), and the remaining recipients did not experience perioperative complications. No significant difference was noted in the short-term recovery of renal allograft function between two groups (P>0.05). Conclusions Postoperative recovery of the recipients in the RAKT group is equivalent to that of their counterparts in the OKT group. RAKT is a safe and effective procedure for the team expertise in kidney transplantation.

Objective:To systematically evaluate the clinical efficacy of Ruiyun procedure for hemorrhoids(RPH)combined with milligan-morgan hemorrhoidectomy(MMH)in the treatment of mixed hemorrhoids compared with MMH alone.Methods:Relevant literature was retrieved from China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their establishment to Jan 2023 using computers.Clinical randomized controlled trials(RCTs)of RPH combined with MMH and MMH alone in the treatment of mixed hemorrhoids were selected and analyzed,and meta-analysis was conducted using RevMan5.3 software.Results:A total of 30 RCTs were included,involving 4 609 patients.Results of Meta-analysis showed that there were statistically significant differences in surgical efficacy(RR=1.05,95% CI:1.02-1.08,P= 0.003),postoperative margin edema(RR=0.36,95% CI:0.27-0.49,P＜0.01),postoperative anal pain(RR=0.35,95% CI:0.23-0.53,P＜0.01),postoperative rectal bleeding(RR=0.35,95% CI:0.17-0.72,P=0.004),postoperative anal stenosis(RR=0.26,95% CI:0.11-0.59,P=0.001)and postoperative urinary retention(RR=0.77,95% CI:0.63-0.93,P=0.007)between RPH combined with MMH group and MMH group.Conclusion:Compared with MMH alone,RPH combined with MMH in the treatment of mixed hemorrhoids can reduce the incidence of postoperative side effects,such as postoperative margin edema,anal pain,rectal bleeding,anal stenosis,and urinary retention,with a relatively higher efficiency.

Objective To investigate the mechanism of inducing macrophage polarization induced by acupoint effect of electroacupuncture to promote the repair of acute skeletal muscle injury.Methods 45 SD rats were randomly divided into blank group,model group,electroacupuncture group(EA group),sodium chrominate group (DSCG group) and electroacupuncture+sodium chrominate group (hereinafter referred to as EA+DSCG group),with 9 rats in each group. The rats in the EA group and the EA+DSCG group were subjected to EA intervention at the right "Chengshan" (BL57) and "Yanglingquan"(GB34),with a frequency of 2 Hz/100 Hz. The gait changes of rats were recorded by animal gait analyzer. The morphological changes of the right gastrocnemius were observed by HE staining. The changes of mast cell aggregation and degranulation in local skin muscles of "chengshan" point were observed by toluidine blue staining. The expressions of Pax7,MyoD and skin mast cells and 5-HT in the right gastrocnemius were detected by immunofluorescence method. The positive expressions of CD68 and CD206 in right gastrocnemius macrophage was observed by immunohistochemical staining.Results Compared with blank group,the wiggle time of the right hind leg in model group and DSCG group increased,stride length decreased,HE staining showed inflammatory cell infiltration,myocyte enlargement,degeneration and necrosis. The degranulation rate of local skin mast cells in "Chengshan" (BL57) area increased,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD,CD68 and CD206 increased (P<0.05). Compared with model group,the wiggle time of the right hind leg in EA group and EA+DSCG group decreased,stride length increased,HE staining showed that inflammatory cell infiltration was reduced,muscle cells were uniform in size and arranged neatly. Mast cell degranulation rate increased significantly in EA group,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased (P<0.05). Compared with EA+DSCG group,the degranulation rate of mast cells and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased in EA group (P<0.05). Conclusion EA "Chengshan" (BL57) and "Yanglingquan" (GB34) can stimulate acupuncture points to locally induce mast cell degranulation,promote the polarization of macrophages,and then activate muscle satellite cells to play the regulatory process of repairing skeletal muscle injury.

To investigate the differences in postoperative short-term complications and long-term prognosis of pancreatic cancer(PC) patients after total pancreatectomy(TP) and pancreaticoduodenectomy(PD).

Objective:To evaluate the economy of recombinant human thrombopoietin(rhTPO)combined with conventional therapy compared with conventional therapy in the treatment of sepsis-associated thrombocytopenia(SIT)from the perspective of China's health service system.Methods:The decision tree model was constructed,and the minimum cost analysis and cost-effectiveness analysis were used to evaluate the economy based on the characteristics of sepsis.The economy was judged by two willingness to pay thresholds,and then the stability of the results was tested by sensitivity analysis.Results:rhTPO combined with conventional therapy can save 520.58 yuan for each 1％increase in survival rate compared with conventional therapy alone,which is an absolute advantage program.The single factor sensitivity analysis showed that the daily cost of ICU medical service and the duration of CRRT in the control group and the daily cost of ICU medical service in the experimental group had a great influence on the results,and the stability of the parameter outcome was good.The probability sensitivity analysis showed that when the willingness to pay threshold changes ranged 0～268 074 yuan,rhTPO has a 100％economical probability.Conclusion:Under the existing evidence,rhTPO combined with conventional treatment for SIT treatment is more economical on the basis of improving survival rate and equal safety.

Objective:To investigate the association of exposure to PM 2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods:We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM 2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM 2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results:A 10 μg/m 3 increase in PM 2.5 exposure during pregnancy was associated with a decrease of 0.025 ( β=-0.025, 95% CI: -0.048- -0.001) in HC Z-score, 0.026 ( β=-0.026, 95% CI: -0.049- -0.003) in AC Z-score, and 0.028 ( β=-0.028, 95% CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% ( RR=1.085, 95% CI: 1.010-1.165) and 13.5% ( RR=1.135, 95% CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM 2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO 42-) and ammonium consistently correlated with decreased HC Z-score. SO 42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions:Our findings demonstrated that exposure to PM 2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.

[Objective]To explore the mechanism of Qifu Qiangxin Decoction mitigating myocardial damage in heart failure(HF)mice with heart-kidney Yang deficiency syndrome.[Methods]Thirty C57BL/6 mice were randomly divided into Sham surgery group(Sham group),HF model(HF)group,low-dose Qifu Qiangxin Decoction(HF+QL)group,high-dose Qifu Qiangxin Decoction(HF+QH)group and western medicine[HF+angiotensin converting enzyme inhibitors(ACEI)]group,six in each group.In Sham group,the skin was cut open after anesthesia,the heart was exposed,the left anterior descending coronary artery was not in ligation,and then sutured.The rest were used to establish a mouse model of HF with heart-kidney Yang deficiency syndrome after myocardial infarction(MI)by ligating the left anterior descending coronary artery and swimming in cold water,then treated for 15 days.After treatment,the state of the mice was recorded,left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),ejection fraction(EF)and left ventricular fractional shortening(LVFS)were measured by echocardiography to evaluate cardiac function;hematoxylin-eosin(HE)staining was used to evaluate the morphological of myocardial tissue;the serum levels of B-syndrome natriuretic peptide(BNP)were measured by enzyme linked immunosorbent assay(ELISA);terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)was used to detect cardiomyocyte apoptosis;Western blot was used to determine the expression levels of apoptosis related proteins,autophagy related proteins and adenosine monophosphate-activated protein kinase/mammalian target of rapamycin(AMPK/mTOR)signaling pathway related proteins in mice myocardial tissue.[Results]Qifu Qiangxin Decoction can relieve the symptoms of HF in mice.Compared with Sham group,EF and LVFS values of mice in HF group were significantly decreased,while LVEDV and LVESV were significantly increased(P＜0.01).Compared with HF group,EF and LVFS values in each group were significantly increased,while LVEDV and LVESV were significantly decreased(P＜0.01),moreover,HF+QH group had a better effect than that of HF+QL group.According to HE staining,extensive necrotic myocardial tissue was observed in HF group compared with Sham group,and ELISA showed a significant increase in BNP levels(P＜0.01).Compared with HF group,the pathological conditions of myocardial tissue were relieve in each group,and the level of BNP was also significantly reduced(P＜0.01).TUNEL staining and Western blot results showed that the level of apoptosis in HF group was significantly increased compared with Sham group(P＜0.05).Compared with HF group,the apoptosis level of the each group was significantly reduced(P＜0.05).Therefore,Qifu Qiangxin Decoction could significantly reduce the level of cardiomyocyte apoptosis.Western blot detection of autophagy-related proteins and AMPK/mTOR signaling pathway related proteins showed that Qifu Qiangxin Decoction could significantly enhance autophagy level and regulate AMPK/mTOR signaling pathway in a concentration-dependent manner.[Conclusion]Qifu Qiangxin Decoction can regulate AMPK/mTOR signaling pathway,inhibit cell apoptosis and induce autophagy,thus protecting cardiomyocytes and mitigating myocardial injury.