Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective To investigate the effects of long non coding RNA(lncRNA)metastasis associated lung adenocarcinoma transcript 1(MALAT1)on the proliferation and osteogenic differentiation of human periodontal ligament stem cells(PDLSCs)by regulating the miR-150-5p/X-box binding protein 1(XBP1)axis.Methods Quantitative real-time PCR(qRT-PCR)was used to detect the expression of lncRNA MALAT1,miR-150-5p and XBP1 mRNA in undifferentiated and differentiated PDLSCs.The third generation PDLSCs were divided into control group,pcDNA group,pcDNA-lncRNA MALAT1 group,anti-miR-NC group,anti-miR-150-5p group,pcDNA-lncRNA MALAT1+mimic NC group and pcDNA-lncRNA MALAT1+miR-150-5p mimic group.The expression of lncRNA MALAT1,miR-150-5p and XBP1 mRNA of PDLSCs were detected by qRT-PCR.CCK-8 and the clone formation assay were used to detect the proliferation of PDLSCs.P-nitrophenolphosphate substrate method was used to detect alkaline phosphatase(ALP)activity.Alizarin red staining was applied to detect the formation rate of mineralized nodules.Western blot was used to detect XBP1,Cyclin D1,osteocalcin(OCN),Runt related transcription factor 2(RUNX2)and osteopontin(OPN)proteins.Dual luciferase assay was used to verify the targeting relationship between lncRNA MALAT1 and miR-150-5p,and between miR-150-5p and XBP1 was validated.Results Compared with the undifferentiated group,the expression of lncRNA MALAT1(1.95±0.14 vs 1.00±0.00)and XBP1 mRNA expression(1.63±0.12 vs 1.00±0.00)increased in the differentiated PDLSCs,the expression of miR-150-5p decreased(0.26±0.01 vs 1.00±0.00)in differentiated group,with the differences were statistical significance(t=16.622,12.860,181.262,all P<0.001).Overexpression of lncRNA MALAT1 or down-regulation of miR-150-5p could promote the proliferation and osteogenic differentiation of human PDLSCs(t=13.693～45.518),miR-150-5p mimic reversed the effects of overexpression of lncRNA MALAT1 on proliferation and osteogenic differentiation of PDLSCs(t=9.229～27.854),and the differences were statistically significant(all P<0.05),respectively.Dual luciferase assay confirmed that overexpression of miR-150-5P reduced the luciferase activity in transfected lncRNA MALAT1-WT and XBP1-WT cells(t=56.546,89.826,all P<0.001).Conclusion Overexpression of lncRNA MALAT1 may promote XBP1 expression by downregulating miR-150-5p,thereby promoting proliferation and osteogenic differentiation of human PDLSCs.

Objective To investigate the efficacy of treating adhesive small intestinal obstruction using blind insertion of a nasal ileus catheter in combination with continuous enteral nutrition.Methods The data of patients with adhesive small intestinal obstruction admitted to our department from January 2022 to December 2023 were retrospectively collected.Group A was treated with blind insertion of a nasal jejunal decompression catheter,whereas Group B was managed with a nasogastric tube.Continuous enteral nutrition was initiated after the resolu-tion of intestinal obstruction in both groups.The nutritional indices,abdominal improvement,inflammatory markers,and complication rates were compared between the two groups before and after treatment.Results In terms of nutritional indices,the scores for Alb,Pa,and NRS2002 in Group A were significantly higher than those in Group B on the 7th day(P<0.05).Regarding abdominal improvement indices,Group A demonstrated significantly better outcomes than Group B in daily average decompression drainage volume,daily average reduction in abdominal circumference,relief time for abdominal distension and pain,recovery time for exhaust,defecation,time to resump-tion of enteral nutrition,and total hospitalization duration(P<0.05).Concerning inflammatory indices,CRP,IL-6,and WBC levels in Group A were significantly lower than those in Group B on both the 4th and 7th days post-treatment(P<0.05).With regard to complications,Group A exhibited fewer cases of EN intolerance,reflux,and conversion due to conservative treatment ineffectiveness compared to Group B(P<0.05).Conversely,Group B had fewer instances of water and electrolyte imbalance compared to Group A(P<0.05).Conclusion Adhesive small intestinal obstruction treated with blind insertion of a nasal ileus catheter combined with continuous enteral nutrition is a safe and effective approach,making it worthy of promotion in clinical practice.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective:To investigate the value of pelvic floor reconstruction with gluteus maximus myocutaneous flap in second-stage surgery for patients with failed perineal wound healing after pelvic exenteration (PE).Methods:This was a descriptive case series study. The clinical data of 24 patients with locally advanced (LARC) or recurrent (LRRC) rectal cancer who underwent PE and had long-term nonunion of postoperative perineal wounds were collected from the department of colorectal surgery of the Second Affiliated Hospital of Navy Medical University (Shanghai Changzheng Hospital) from January 2022 to January 2023. The specific operation methods of pelvic reconstruction by gluteus maximus myocutaneous flap are as follows: the necrotic tissue of the perineal wound was debrided and rinsed repeatedly, the gluteus maximus muscle was cut and separated from the gluteus superior and inferior arteries, the middle muscle pedicle was retained, part of the skin and muscle were separated from the medial margin, part of the epidermis was removed, the muscle and subcutaneous tissue at the medial margin of the flap were fixed to the medial edge of the wound, negative pressure suction tubes were placed above and below the wound cavity and in the muscle space on the right side, and the subcutaneous muscle and fat layer were sutured. The skin was sutured intersegmentally, and a negative pressure suction device was placed on the wound surface. After surgery, the patient should remain prone, and the drainage tube should be placed for at least 7 days. The drainage tube can be removed after 24-hour drainage is less than 30 ml. Perineal wound healing and complications related to gluteal major myocutaneous flap were observed.Result:The median reconstruction time of 24 patients was 180 (150 ~ 230) minutes, and the median intraoperative blood loss was 100 (30 ~ 200) ml. 91.7% (22/24) patients had successful healing of perineal wound within 30 d after operation. After a follow-up of 6 months, no complete or partial flap necrosis occurred. The incidence of complications related to gluteus maximus myocutaneous flap was 8.3% (2/24). One patient had flap infection and sinus tract, and one patient had flap sinus tract. All patients healed after debridement under local anesthesia.Conclusion:For LARC/LRRC patients with poor perineal wound healing after PE, pelvic floor reconstruction with gluteus maximus myocutaneous flap in second-stage operation is safe and feasible, and could successfully close the perineal wound, and has a low incidence of postoperative flap-related complications.

Objective To investigate the efficacy of treating adhesive small intestinal obstruction using blind insertion of a nasal ileus catheter in combination with continuous enteral nutrition.Methods The data of patients with adhesive small intestinal obstruction admitted to our department from January 2022 to December 2023 were retrospectively collected.Group A was treated with blind insertion of a nasal jejunal decompression catheter,whereas Group B was managed with a nasogastric tube.Continuous enteral nutrition was initiated after the resolu-tion of intestinal obstruction in both groups.The nutritional indices,abdominal improvement,inflammatory markers,and complication rates were compared between the two groups before and after treatment.Results In terms of nutritional indices,the scores for Alb,Pa,and NRS2002 in Group A were significantly higher than those in Group B on the 7th day(P<0.05).Regarding abdominal improvement indices,Group A demonstrated significantly better outcomes than Group B in daily average decompression drainage volume,daily average reduction in abdominal circumference,relief time for abdominal distension and pain,recovery time for exhaust,defecation,time to resump-tion of enteral nutrition,and total hospitalization duration(P<0.05).Concerning inflammatory indices,CRP,IL-6,and WBC levels in Group A were significantly lower than those in Group B on both the 4th and 7th days post-treatment(P<0.05).With regard to complications,Group A exhibited fewer cases of EN intolerance,reflux,and conversion due to conservative treatment ineffectiveness compared to Group B(P<0.05).Conversely,Group B had fewer instances of water and electrolyte imbalance compared to Group A(P<0.05).Conclusion Adhesive small intestinal obstruction treated with blind insertion of a nasal ileus catheter combined with continuous enteral nutrition is a safe and effective approach,making it worthy of promotion in clinical practice.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Constipation,a common functional gastrointestinal disorder,not only severely impairs patients'quality of life but is also highly comorbid with psychiatric conditions such as anxiety and depression.Emerging evidence indicates that gut microbiota dysbiosis is a critical link connecting these two disease states.On one hand,dysbiosis exacerbates constipation by affecting host metabolism and intestinal function;on the other,it plays a central role in the pathophysiology of mood disorders.This complex interaction is primarily mediated through the"microbiota-gut-brain axis."Therefore,elucidating the intrinsic relationship among anxiety,depression,gut microbiota,and constipation has become a frontier of interdisciplinary research.

Adipocytic tumors are the most common type of soft tissue tumors,which can be divided into lipomas and liposarcomas.Studies have found that benign lipomas resected from the same site can transform into liposarcomas,especially atypical lipomatous tumors(ALT),suggesting an underlying biological association.In this case,the patient underwent resection of a right neck mass in our hospital in 2017,and the pathology showed fibrolipoma.One year later,the mass recurred at the original site but was not treated.By 2023,the mass had significantly enlarged and extended deeply.MRI showed that the lesion had an unclear boundary with the surrounding fat,suggesting liposarcoma.Puncture and molecular pathology showed MDM2 gene amplification,and the diagnosis of ALT was made,which was confirmed by pathology after complete surgical resection.It can be seen that adipocytic tumors have great differences in biological behavior,and benign lipomas can transform into liposarcomas(especially ALT).Clinically,it is necessary to combine imaging,pathology and molecular detection(such as MDM2/CDK4)for differentiation to formulate treatment plans.

AIM To observe the effects of Hugan Tablets on high-fat diet induced non-alcoholic fatty liver disease(NAFLD)in a mouse model,and the autophagy,pyroptosis and the PI3K/Akt/mTOR signaling pathway as well.METHODS The C57BL/6 mice were randomly divided into the normal group,the model group,the Hugan Tablets group(0.7 g/kg)and the Yishanfu group(0.23 g/kg),with 10 mice in each group.The NAFLD mouse model was established by 16 weeks feeding of high-fat diet.From the 13th week,the mice started their corresponding dosing of the drug by gavage followed by killing of the mice at the end of 16th week and collection of their serum and liver tissue samples.The mice had their serum ALT,AST,TG,TC,LDL levels,liver TG,TC,NEFA,MDA levels and activities of SOD and GSH-Px detected;their serum levels of IL-1β,IL-6 and TNF-αdetected by ELISA;their hepatic pathological changes observed using HE staining and oil red O staining;and their hepatic protein expressions of ACC,CPT1A,FAS,p-PI3K,p-Akt,p-mTOR,P62,LC3,NLRP3,GSDMD and Caspase1 detected by Western blot.RESULTS Compared with the model group,the Hugan Tablets group displayed decreased body weight and hepatosmatic index level(P＜0.01);decreased levels of serum ALT,AST,TG,TC,LDL,IL-6,IL-1β and TNF-α(P＜0.05,P＜0.01);increased hepatic levels of TG,TC,NEFA and MDA(P＜0.05);decreased activities of SOD and GSH-Px(P＜0.05);improved pathological changes of hepatic lipid deposition and hepatocytic ballooning and decreased NAS score and oil red O staining area(P＜0.01);decreased hepatic protein expressions of ACC1,FAS,NLRP3,Caspase1,GSDMD,P62,p-PI3K,p-Akt and p-mTOR(P＜0.05,P＜0.01);and increased protein expressions of CPT1A and LC3(P＜0.01).CONCLUSION Hugan Tablets can effectively prevent and control the development of high-fat diet induced NAFLD in mice,and the mechanism may be associated with the promotion of autophagy in hepatocytes and the inhibition of pyroptosis via the inhibition of PI3K/Akt/mTOR signaling pathway.