This paper dicusses the significance of drug clinical trials,and summarises the experiences in policy making,personnel trainning,supervising and management in drug clinical trials at the First People's Hospital of Changzhou,which may provide reference for drug clinical trials in China.

Inguinal incarcerated hernia in adults is a common acute abdomen in hernia and abdominal wall surgery. If not treated in time, it is easy to progress to constrictive hernia, lead to intestinal ischemic necrosis, cellulitis of tegmental tissue outside the hernia, hernia sac empyema, intestinal fistula, and even cause toxic shock, with significantly increased mortality. The types of incarceration are different and the corresponding management methods are different. Based on the proposal of the concept of musculopubic foramen hernia repair, inguinal incarcerated hernia includes incarcerated indirect hernia, incarcerated direct hernia, incarcerated femoral hernia, etc. At present, there is no uniform standard for the comprehensive treatment of different types of inguinal incarcerated hernia, and the clinical management strategies of adult inguinal incarcerated hernia still face serious challenges.

Objective:To monitor the cerebral vascular blood flow parameters in the early stage of simulated acute exposure to high altitude hypoxia by transcranial color Doppler (TCCD), and to evaluate the change trend of cerebral hemodynamics and cerebrovascular reactivity.Methods:Sixty-four healthy volunteers were selected to observe the changes of peak systolic flow velocity(Vs), end diastolic flow velocity(Vd), mean flow velocity(Vm), resistance index (RI) and pulsatility index (PI) of middle cerebral artery (MCA) 30 minutes after they quickly entered the simulated altitude of 4 500 meters. Combined with breath holding test, breath holding index (BHI) was used to evaluate cerebrovascular reactivity (CVR), and subjects were divided into ≤30 years old group and >30 years old group, and the changes of CVR after hypoxia of the two groups were compared.Results:In the early stage of hypoxic environment, compared with baseline, SpO 2 decreased, heart rate increased, and blood flow velocity of middle cerebral artery(Vs, Vd, Vm) increased significantly, BHI showed a decreasing trend (all P<0.01). After hypoxia, the BHI rate of change in >30 years old was lower than that of the subjects ≤30 years old ( P<0.05). After breath holding, cerebral blood flow velocity increased significantly, PI and RI decreased significantly (all P<0.01). Conclusions:Cerebral blood flow is very sensitive to hypoxia. The application of TCCD technology can evaluate the trend of cerebral blood flow dynamics and cerebrovascular reserve capacity in real time and accurately, which is helpful to provide objective basis and research basis for the prevention and treatment of high altitude hypoxia.

BACKGROUND:Numerous basic and clinical trials have confirmed that the low survival rate after bone marrow mesenchymal stem cell transplantation is a serious constraint on its long-term therapeutic effect.Previous studies have shown that apoptosis-related factors play an important role in the apoptosis of bone marrow mesenchymal stem cells,of which apoptosis-inducing factor may be a key factor. OBJECTIVE:Bone marrow mesenchymal stem cells,of which apoptosis-inducing factor was knocked down,were transplanted into infarcted myocardium of mice,aiming to certify the importance of apoptosis-inducing factor in the survival of bone marrow mesenchymal stem cells to further recover cardiac function after infarction. METHODS:Firstly,bone marrow mesenchymal stem cells were infected with LV-AIF-shRNA lentivirus to down-regulate the expression of apoptosis-inducing factor protein.Flow cytometry,western blot assay,and RT-qPCR were used to detect the infection efficiency of lentivirus.CCK-8 assay was used to detect the cell viability of bone marrow mesenchymal stem cells with apoptosis-inducing factor knockdown under hypoxic and ischemic conditions.Then,with the mouse model of acute myocardial infarction constructed,the normal bone marrow mesenchymal stem cells and bone marrow mesenchymal stem cells with apoptosis-inducing factor gene knockdown were transplanted into the model,respectively.The expression of apoptosis-inducing factor was examined by fluorescence immunoassay.Serum brain natriuretic peptide levels were detected by ELISA.Cardiac ultrasound was used to detect cardiac function.Myocardial fibrosis was observed by Masson staining.The expression of SRY gene was detected by RT-qPCR in apoptosis-inducing factor-knocked bone marrow mesenchymal stem cells after transplantation,reflecting cell survival. RESULTS AND CONCLUSION:(1)Bone marrow mesenchymal stem cells with apoptosis-inducing factor gene knockdown were successfully established by LV-AIF-shRNA lentivirus infection,following 97.7%of infection efficiency,and notably decline of the expression of apoptosis-inducing factor(P<0.001).(2)Under ischemia and hypoxia,the cell viability of apoptosis-inducing factor knockdown bone marrow mesenchymal stem cells was significantly increased compared with normal bone marrow mesenchymal stem cells.(3)Compared with normal bone marrow mesenchymal stem cells after transplantation,the survival number of bone marrow mesenchymal stem cells in the infarcted myocardium after apoptosis-inducing factor gene knockdown was significantly increased to 3.71 times(P<0.001),and the apoptosis-inducing factor protein expression and myocardial fibrosis degree in the infarcted area were significantly reduced.(4)Compared with normal bone marrow mesenchymal stem cells,the serum brain natriuretic peptide level of bone marrow stem cells with apoptosis-inducing factor gene knockdown after transplantation was significantly decreased(P<0.05),and left ventricular ejection fraction and left ventricular shortening fraction were significantly improved(P<0.05).(5)These findings confirm that apoptosis-inducing factor gene knockdown can reduce myocardial fibrosis and improve cardiac function after acute myocardial infarction via enhancing the bone marrow mesenchymal stem cell viability and increasing the bone marrow mesenchymal stem cell survival after transplantation in the donor.

Objective To explore the feasibility of peritoneal dialysis catheter placement assisted by flexible ureteroscope.Methods A retrospective analysis was conducted on clinical data of 54 cases of end-stage renal disease receiving peritoneal dialysis catheter placement from May 2019 to March 2023.The placement method was chosen by the patient.In the conventional group,23 cases were guided by a metal guide wire for insertion of the peritoneal dialysis catheter,while in the flexible ureteroscope group,31 cases were guided by flexible ureteroscope instead of guide wire for insertion of the peritoneal dialysis catheter.The success rate of catheterization,surgical time,use of postoperative analgesic,complications related to peritoneal dialysis catheter,and postoperative creatinine decrease were compared between the two groups.Results The catheter placement was successfully performed in both groups.The total incidence of complications related to peritoneal dialysis catheter in the flexible ureteroscope group was lower than that in the conventional group[6.5%(2/31)vs.30.4%(7/23),χ2 =3.878,P =0.049].Between the conventional group and the flexible ureteroscope group,there were no statistically significant differences in the surgical time,postoperative analgesic usage,and the decrease of creatinine at 2 weeks after surgery(P>0.05).The median postoperative follow-up period was10 months(range,3-24 months)in the two groups,and there were no complications such as peritoneal leakage,intestinal perforation,or intraperitoneal bleeding.Conclusion The placement of peritoneal dialysis catheter guided by the flexible ureteroscope instead of metal guide wire is a safe,visible,and accurate method,which can reduce complications related to peritoneal dialysis catheter,and detect and manage comorbidities in the abdominal cavity.