OBJECTIVE To explore the renal protective mechanism of Shenbining granules on IgA nephropathy （IgAN） rats based on mitochondrial quality control system. METHODS IgAN rat model was established by the method of “bovine serum albumin+carbon tetrachloride+lipopolysaccharide”. The model rats were randomly divided into model group， prednisone acetate group （6.25 mg/kg）， Shenbining equal-dose group （4.1 g/kg） and Shenbining high-dose group （20.5 g/kg）. The normal rats were taken as the normal control group， with 12 rats in each group. Rats were given corresponding drugs or distilled water intragastrically in each group， once a day， for 4 consecutive weeks. After the last medication， the 24 h total urinary protein （24 h- UTP） and erythrocyte count in urine were determined， and the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， albumin （ALB） and alanine transaminase （ALT） were also detected. The histopathological changes in the kidneys and changes in IgA deposition in the mesangial area of the kidney were observed. mRNA and protein expression levels of PTEN-induced putative kinase 1 （PINK1）， E3 ubiquitin ligase（Parkin）， microtubule-associated protein 1 light chain-3 （LC3）， dynamin-related protein 1 （Drp1） and mitofusin 2 （Mfn2） were detected in the kidney tissues of rats. RESULTS Compared with model group， 24 h-UTP， urinary erythrocyte count， ALT， BUN and Scr levels， LC3-Ⅱ/LC3-Ⅰ mRNA ratio， mRNA and protein expressions of Drp1 were reduced significantly in prednisone acetate group， Shenbining equal-dose group and Shenbining high-dose group （P＜0.05）； ALB level， LC3-Ⅱ/LC3-Ⅰ protein ratio， mRNA and protein expressions of PINK1， Parkin and Mfn2 were increased significantly （P＜0.05）； the pathological morphology of kidney tissue in rats was significantly improved， and IgA deposition was significantly reduced. CONCLUSIONS Shenbining granule may reduce renal pathological injury in IgAN rats and protect renal function by activating the PINK1/Parkin pathway， enhancing mitochondrial autophagy， and correcting mitochondrial kinetic disorders.

Objective:To evaluate the impact of self-crosslinked hyaluronic acid (SCH) gel on endometrium recovery after artificial abortion.Methods:A multicenter, prospective randomized controlled trial was conducted across 18 hospitals from December 2021 to February 2023, involving 382 women who underwent artificial abortion. Participants were randomly allocated to receive either treatment with SCH gel (SCH group) or no treatment (control group) in a 1∶1 ratio. The primary outcome was endometrium thickness in 14 to 18 days after the first postoperative menstruation. Secondary outcomes included changes in menstrual volume during the first postoperative menstruation, menstruation resumption within 6 postoperative weeks, time to menstruation resumption, duration of the first postoperative menstruation, and incidence of dysmenorrhea.Results:Baseline characteristics of participants were comparable between the two groups (all P>0.05), with 95.3% (182/191) in SCH group and 92.7% (177/191) in the control group completed the study. The postoperative endometrial thickness in SCH group was significantly greater than that in the control group [(9.78±3.15) vs (8.95±2.32) mm; P=0.005]. SCH group also had significantly fewer participants with reduced menstrual volume [23 cases (12.6%, 23/182) vs 31 cases (17.5%, 31/177); P=0.038]. Although SCH group experienced less dysmenorrhea during the first postoperative menstrual period, this difference was not statistically significant [28.5% (51/179) vs 37.1% (65/175); P=0.083]. Outcomes were similar between SCH group and the control group regarding the proportion of participants who resumed menstruation within 6 weeks postoperatively, time to menstruation resumption, and duration of the first postoperative menstruation ( P=0.792, 0.485, and 0.254, respectively). No serious adverse events were observed during the study period, and no adverse events were attributed to SCH gel treatment. Conclusion:The application of SCH gel after artificial abortion is safe and might aid in the recovery of the endometrium.

OBJECTIVE To study the nephrotoxicity of the extracts from different parts o f Miao medicine Wikstroemia indica in healthy rats ，and to provide reference for the study of its toxicity mechanism and clinical drug use. METHODS Using 70％ ethanol as solvent ，total ethanol extract of W. indica was extracted with diacolation method. After dispersing the above extract with water，the fractions of corresponding fractions were obtained with petroleum ether ，ethyl acetate and n-butanol，and the rest was the extract of water fraction. SD rats were randomly divided into total ethanol extract group ，petroleum ether fraction group ，ethyl acetate fraction group ，n-butanol fraction group ，water fraction group and blank group ，with 12 rats in each group （half male and half female ）. The rats in the administration groups were given the corresponding dose of drug solution intragastrically （total ethanol extract 317.520 mg/kg，petroleum ether fraction 7.875 mg/kg，ethyl acetate fraction 78.435 mg/kg，n-butanol fraction 53.865 mg/kg and water fraction 76.545 mg/kg），once a day ，for conse- cutive 2 weeks，and then stopped taking drug for 2 weeks； rats in the blank group were given equal volume of 1.0％ . sodium carboxymethyl cellulose solution intragastrically. Duringthe experiment ，the general conditions of rats were observed. The samples of urine （on the 14th and 28th day ），serum and bilateral renal tissues （on the 15th and 29th day ）were taken respectively，the renal index was calculated ，the levels of @qq.com renal function indexes in serum and urine were detected ，and the pathomorphological changes of renal tissues were observed. RESULTS During administration ，compared with blank group ，the rats in the total ethanol extract group and ethyl acetate fraction group showed poisoning behavior and activity characteristics such as mental depression ，decreased activity and diet ，thin stool and decreased body mass. The mental state of the rats in the petroleum ether fraction group ，n-butanol fraction group and water fraction group were slightly worse than that in blank group，and slightly decreased activity and diet as well as thin stool ，and slowly increased body mass were found ；however，there was no significant difference in anal temperature in each group. After 2 weeks of administration ，the renal index in total ethanol extract group ，the serum levels of N-acetylglucosaminidase（NAG），urea nitrogen （BUN）and creatinine （Cr）in total ethanol extract group and ethyl acetate fraction group ，serum level of NAG in n-butanol fraction group and serum level of Cr in water fraction group ，as while as NAG levels in urine of rats in total ethanol extract group and petroleum ether fraction group ，NAG and urinary protein levels in urine of rats in ethyl acetate fraction group were increased significantly （P＜0.05 or P＜0.01）. In the pathomorphological observation ，renal tubules showed different degrees of unclear structure ，cell swelling and a few cell necrosis in the total ethanol extract group ，petroleum ether fraction group and ethyl acetate fraction group ，accompanying by glomerular pyknosis，renal tubular sclerosis and inflammatory cell infiltration ，compared with blank group. After drug withdrawal ，the mental state of rats in the administration groups were significantly improved ，the amount of activity and diet increased ，and the stool tended to be normal. Two weeks after drug withdrawal and recovery ，the levels of above indexes in serum and urine of rats in administration groups returned to be close to that in blank group （P＞0.05）；the glomerular structure of rats in each administration group gradually recovered clearly ，and cell swelling and inflammatory cell infiltration were rare in total ethanol extract group ， petroleum ether fraction group and ethyl acetate fraction group. CONCLUSIONS The total ethanol extract ，petroleum ether fraction and ethyl acetate fraction of Miao medicine W. indica have certain nephrotoxicity and reversibility. The toxic component may

Purpose: This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in metastatic breast cancer (MBC) patients. Materials and Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matching of multicenter cohort study evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. This study is registered with PROSPERO: CRD42017071858 and ClinicalTrials.gov: NCT04258163. Results: A total of 2,867 patients from 15 RCTs and 760 patients from multicenter cohort were included. The results from meta-analysis showed that chemotherapy maintenance improved progression-free survival (PFS) (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.54 to 0.73; p < 0.001; moderate-quality evidence) and overall survival (OS) (HR, 0.87; 95% CI 0.78 to 0.97; p=0.016; high-quality evidence) than observation. In the cohort study, for hormone receptor–positive MBC patients, chemotherapy maintenance improved PFS (HR, 0.67; 95% CI, 0.52 to 0.85; p < 0.001) and OS (HR, 0.55; 95% CI 0.42 to 0.73; p < 0.001) compared with observation, and endocrine therapy maintenance also improved PFS (HR, 0.65; 95% CI, 0.53 to 0.80; p < 0.001) and OS (HR, 0.55; 95% CI, 0.44 to 0.69; p < 0.001). There were no differences between chemotherapy and endocrine therapy maintenance in PFS and OS (all p > 0.05). Regardless of the continuum or switch maintenance therapy, showed prolonged survival in MBC patients who were response to first-line treatment. Conclusion This study provided evidences for survival benefits of chemotherapy and endocrine therapy maintenance in MBC patients, and there was no difference efficacy between chemotherapy and endocrine therapy maintenance for hormone receptor–positive patients.

Objective:To evaluate the effect and mechanism of bone regeneration in distraction osteogenesis zone after the repair of sciatic nerve in rats.Methods:Between January 2021 and August 2021, 60 healthy adult male Sprague-Dawley rats were divided randomly into 3 groups: Group A, B, and C. In groups B and C, right sciatic nerve transection and anastomosis were performed. Then after 8 and 12 weeks, the 3 groups were treated with extension external fixation (Ilizarov technique) of right femur osteotomy to make distraction osteogenesis model. Electrophysiological changes of peripheral nerves were monitored by electromyography (EMG) pre-and postoperatively in all the femoral lengthening rats. The formation of callus was examined by X-ray every week after operation. The rats were sacrificed on 2nd, 4th, 6th weeks after the bone transport operation. Four-point bending test and histological staining examination were carried out to determine the osteogenesis in the distracted area. SPSS 21.0 was used for statistical analysis. Data of measurement were expressed as (Mean±SD). A non-parametric test was used to assess the statistical difference between groups. Graphs were plotted by GraphPad Prism 8.0 and considered statistically significant when P<0.05. Results:The results of Sciatic nerve function index (SFI), Compound muscle action potential (CMAP) and Motor nerve conduction velocity (MNCV) in group A were better than the group B and group C in both of before and after the surgery. At the 2nd and 4th weeks of the consolidation stage, X-ray showed that bone formation in group B was superior to groups A and C; HE and Safranin O staining showed that local capillary and cartilage formation in group B was significantly more than in groups A and C; Immunohistochemical staining showed that the expression levels of Osteopontin(Opn) and Osteocalcin(Ocn) in the distraction area of group B were higher than that of groups A and C. At the 6th week of the consolidation stage, the four-point bending test showed that the bone quality of group B was better than groups A and C. The differences of the results between groups shown above had statistical significance ( P<0.05). Conclusion:Bone regeneration in the distraction area of the bone lengthening group with sciatic nerve injury was better than that of the bone lengthening group without a never injury. This might be in relation to the fact that a distractive osteogenesis caused the secondary injury to the repaired nerve. The electrophysiological results showed that periodic changes took place in the repaired sciatic nerve caused by the stretch of femoral lengthening, and the injurious changes of sciatic nerve would be gradually relieved in 6th week after surgery.

OBJECTIVE: To investigate the serological and molecular characteristics of a pedigree carrying an allele for ABO*BW.11 blood subgroup. METHODS: The ABO blood type of 9 pedigree members were determined by serological methods. Exons 6 and 7 of the ABO gene were amplified by PCR and directly sequenced. The patient and her father were also subjected to clone sequencing analysis. RESULTS: Serological tests demonstrated that the proband and her younger brother had an ABw subtype, whilst her father and two daughters had Bw subtype. Clone sequencing found that the exon 7 of the ABO gene of the proband had a T>C substitution at position 695, which was identified as a BW.11 allele compared with the reference sequence B.01. This BW.11 allele was also identified in the proband's father, brother and two daughters. Due to allelic competition, the A/BW.11 and BW.11/O alleles demonstrated significantly different phenotypes. CONCLUSION The c.695T>C substitution of the ABO gene may lead to allelic competition in the Bw11 subtype. Combined molecular and serological methods is helpful for precise blood grouping.
ABO Blood-Group System/genetics* ; Alleles ; Female ; Genotype ; Humans ; Male ; Pedigree ; Phenotype

OBJECTIVE: Neoadjuvant chemotherapy (NACT) for the treatment of epithelial ovarian cancer (EOC) has remained controversial. This meta-analysis was performed to systematically assess the efficacy and safety of NACT versus primary debulking surgery (PDS) in patients with EOC.METHODS: PubMed, Embase, ClinicalTrials.gov, and Cochrane Library were queried to assess the therapeutic value of NACT versus PDS in EOC. Electronic databases were queried by using the keywords “ovarian cancer/neoplasms”, “primary debulking surgery”, and “neoadjuvant chemotherapy”.RESULTS: The available trials were pooled, and hazard ratios (HRs), relative risk ratios (RRs) and associated 95% confidence intervals (95% CIs) were determined. Sixteen trials involving 57,450 participants with EOC (NACT, 9,475; PDS, 47,975) were evaluated. We found that NACT resulted in markedly decreased overall survival than PDS in patients with EOC (HR=1.30; 95% CI=1.13–1.49; heterogeneity: p<0.001, ²=82.7%). Furthermore, our results demonstrated that the NACT group displayed increased completeness of debulking removal (RR=1.69, 95% CI=1.32–2.17; heterogeneity: p<0.001, ²=81.9%), and reduced risk of postsurgical death (RR=0.18, 95% CI=0.06–0.51; heterogeneity: p=0.698, ²=0%) and major infection (RR=0.29, 95% CI=0.17–0.51; heterogeneity: p=0.777, ²=0%) compared with patients administered PDS.CONCLUSIONS: This meta-analysis indicated that NACT results in increased completeness of debulking removal, and reduced risk of postsurgical death and major infection compared with PDS, while PDS is associated with improved survival in comparison with NACT in EOC patients.TRIAL REGISTRATION: PROSPERO Identifier: CRD42019120625
Cytoreduction Surgical Procedures ; Drug Therapy ; Humans ; Neoadjuvant Therapy ; Odds Ratio ; Ovarian Neoplasms ; Population Characteristics

OBJECTIVE：To compare the content changes of active/toxic ingredient genkwanin in ethanol extract from Wikstroemia indica before and after processing with “sweat soaking method ”and the effects of processing method on its anti-oxidation ability. METHODS ：HPLC method was adopted to determine the content of genkwanin in W. indica before and after processing with “sweat soaking method ”. The separation was performed on Diamonsil C 18 column with 0.2％ phosphoric acid solution-methanol as mobile phase （gradient elution ）at the flow rate of 1 mL/min. The column temperature was 30 ℃ and detection wavelength was set at 346 nm. The sample size was 20 µL. SD rats were randomly divided into blank group ，W. indica raw product ethanol extract group （317.52 mg/kg，called“raw-product group ”as short ）and W. indica processed product ethanol extract group （317.52 mg/kg，called“processed-product group ”as short ），with 6 rats in each group. Blank group was given constant volume of 1.0％CMC-Na solution intragastrically ，and administration groups were given relevant medicine suspension intragastrically；all of them were given 20 mL/kg，once a day ，for consecutive 14 days. The contents of serum oxidant stress indexes（MDA，CAT，SOD）in rats were determined by ELISA. RESULTS ：The linear range of genkwanin were 0.147-27.360 μg （r＝0.999 9）；RSDs of precision ，reproducibility and stability tests were all lower than 3％ ；average recoveries were 98.64％-98.92％（RSD＜1％，n＝3）. Before and after processing with “sweat soaking method ”，average contents of genkwanin in W. indica were 0.377 6 and 0.234 0 mg/g. Compared with blank group ，the serum content of SOD in raw-product group was increased significantly ，while CAT content was decreased significantly （P＜0.05 or P＜0.01）；the serum content of MDA was decreased significantly in processed-product group ，while SOD content was increased significantly （P＜0.05 or P＜0.01）. MDA content of processed-product group was significantly lower than that of raw-product group ，while SOD content was significantly higher than raw-product group （P＜0.05）. CONCLUSIONS ：After proce ssing with “sweat soaking method ”，the content of genkwanin in W. indica is decreased ，and antioxidant activity is increased .“Sweat soaking method ”processes certain function of “reducing toxicity and increasing efficiency ”.

OBJECTIVE: Neoadjuvant chemotherapy (NACT) for the treatment of epithelial ovarian cancer (EOC) has remained controversial. This meta-analysis was performed to systematically assess the efficacy and safety of NACT versus primary debulking surgery (PDS) in patients with EOC. METHODS: PubMed, Embase, ClinicalTrials.gov, and Cochrane Library were queried to assess the therapeutic value of NACT versus PDS in EOC. Electronic databases were queried by using the keywords “ovarian cancereoplasms”, “primary debulking surgery”, and “neoadjuvant chemotherapy”. RESULTS: The available trials were pooled, and hazard ratios (HRs), relative risk ratios (RRs) and associated 95% confidence intervals (95% CIs) were determined. Sixteen trials involving 57,450 participants with EOC (NACT, 9,475; PDS, 47,975) were evaluated. We found that NACT resulted in markedly decreased overall survival than PDS in patients with EOC (HR=1.30; 95% CI=1.13–1.49; heterogeneity: p<0.001, ²=82.7%). Furthermore, our results demonstrated that the NACT group displayed increased completeness of debulking removal (RR=1.69, 95% CI=1.32–2.17; heterogeneity: p<0.001, ²=81.9%), and reduced risk of postsurgical death (RR=0.18, 95% CI=0.06–0.51; heterogeneity: p=0.698, ²=0%) and major infection (RR=0.29, 95% CI=0.17–0.51; heterogeneity: p=0.777, ²=0%) compared with patients administered PDS. CONCLUSIONS This meta-analysis indicated that NACT results in increased completeness of debulking removal, and reduced risk of postsurgical death and major infection compared with PDS, while PDS is associated with improved survival in comparison with NACT in EOC patients.TRIAL REGISTRATION: PROSPERO Identifier: CRD42019120625

GGGGCC repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9ORF72 produce five dipeptide repeat (DPR) proteins by an unconventional repeat-associated non-ATG (RAN) translation. Within the five DPR proteins, poly-PR and poly-GR that contain arginine are more toxic than the other DPRs (poly-GA, poly-GP, and poly-PA). Here, we demonstrated that poly-PR peptides transferred into cells by endocytosis in a clathrin-dependent manner, leading to endoplasmic reticulum stress and cell death. In SH-SY5Y cells and primary cortical neurons, poly-PR activated JUN amino-terminal kinase (JNK) and increased the levels of p53 and Bax. The uptake of poly-PR peptides by cells was significantly inhibited by knockdown of clathrin or by chlorpromazine, an inhibitor that blocks clathrin-mediated endocytosis. Inhibition of clathrin-dependent endocytosis by chlorpromazine significantly blocked the transfer of poly-PR peptides into cells, and attenuated poly-PR-induced JNK activation and cell death. Our data revealed that the uptake of poly-PR undergoes clathrin-dependent endocytosis and blockade of this process prevents the toxic effects of synthetic poly-PR peptides.