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.

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.

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 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.

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.

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.

The growth of puberty height is affected by many factors, among which the role of sex hormones is particularly important. The height increase in puberty accounts for about 20% of the final height in adulthood. It was previously believed that the final height of patients with disorders of sexual development was impaired due to the disorder of sex hormones. However, there are more classifications and subtypes of disorders of sexual development, and the growth patterns of patients with different subtypes of disorders of sexual development are also different. This article briefly reviews puberty bone growth, the effect of sex hormones on puberty bones, the sex hormone spectrum and growth pattern of patients with common disorders of sexual development, and the effect of growth hormone therapy.

OBJECTIVE To evaluate the ameliorative effect of Juanbi Tongluo Oral Liquid on sciatic neuronal apoptosis in Type 2 diabetic model mice.METHODS The Type 2 diabetes mouse model was established by feeding with high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin(STZ).The mice were treated with metformin(200 mg·kg-1·d-1),low dose(3.9 g·kg-1·d-1)and high dose(7.8 g·kg-1·d-1)Juanbi Tongluo Oral Liquid for 35 days.The latency of response to thermal stimu-lation was detected by hot plate,and the values of blood glucose insulin and glycosylated hemoglobin were determined.Biochemical kits were used to detect the expression of serum total cholesterol(T-CHO),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and oxidation product malondialdehyde(MDA).The expression of tumor cytokine α(TNF-α),interleukin(IL)-1β,IL-6 and IL-10 in serum of mice were detected by ELISA method;the injury of sciatic nerve of model mice was detected by HE staining;the apoptosis of sciatic nerve was detected by TUNEL method;and the expression of neurofilament protein NF-L,apoptosis(cleaved Caspase-3,Caspase-3)and oxidative stress(Nrf2,HO-1)signal pathway proteins in sciatic nerve of model mice were detected by Western blot method.RESULTS High-dose Juanbi Tongluo Oral Liquid shortened the latent period of heat pain response in model mice(P<0.01);downregulated fasting blood glucose and glycated hemoglobin(P<0.01),and upregulated fasting plasma insulin in model mice(P<0.01);downregulated serum T-CHO,TG,and LDL-C levels(P<0.01),upregulated HDL-C levels(P<0.01);downregulated serum pro-inflammatory factors TNF-α,IL-1β and IL-6 levels(P<0.05),upregulated the anti-inflammatory cyto-kine IL-10 level(P<0.01);inhibited sciatic nerve structural damage and apoptosis(P<0.05);downregulated the ratio of cleaved Caspase-3 to Caspase-3 in the apoptosis pathway(P<0.01);upregulated the expression of neurofilament proteins NF-L and NF-H in sciatic nerve tissue(P<0.05,P<0.01);and upregulated the expression of antioxidant stress proteins Nrf2 and HO-1(P<0.01).CONCLUSION Juanbi Tongluo Oral Liquid can improve sciatic neuronal apoptosis of Type 2 diabetic mice,which may be related to its effect on improving oxidative stress and inflammatory stress.

The growth of puberty height is affected by many factors, among which the role of sex hormones is particularly important. The height increase in puberty accounts for about 20% of the final height in adulthood. It was previously believed that the final height of patients with disorders of sexual development was impaired due to the disorder of sex hormones. However, there are more classifications and subtypes of disorders of sexual development, and the growth patterns of patients with different subtypes of disorders of sexual development are also different. This article briefly reviews puberty bone growth, the effect of sex hormones on puberty bones, the sex hormone spectrum and growth pattern of patients with common disorders of sexual development, and the effect of growth hormone therapy.