OBJECTIVE To study the pharmacodynamics and pharmacokinetics of semaglutide(Sem)capsules in type 2 diabetic model rats.METHODS Male SD rats were divided into the normal control group,type 2 diabetic model group and model+Sem capsules(0.839,1.678 and 2.517 mg·kg-1)groups.A type 2 diabetic rat model was induced by high sugar and high fat diet feeding combined with ip given streptozotocin(STZ)injection.Seven days after modeling,the model+Sem capsules group was ig given Sem capsules at the corresponding dose in a fasting state,once a day,for 14 d.Body mass,fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)levels were regularly mea-sured in each group of rats.Plasma from rats in the model+Sem capsules 0.839,1.678 and 2.517 mg·kg-1 groups at different time points was collected at the end of the continuous administration of Sem capsules,and the content of Sem in the plasma of rats was determined by liquid chromatography-tandem mass spectrometry.Concentration-time curves were plotted,and the main pharmacokinetic parameters were fitted by the WinNonlin non-atrial model method.RESULTS Compared with the model group,the body mass of rats in model+Sem capsules dosing groups decreased significantly after 7 and 14 d of Sem capsules intervention(P<0.05,P<0.01),so did FBG(P<0.01)and the HbA1c level(P<0.01).Meanwhile,FBG and HbA1c levels of rats in model+Sem capsules 1.678 and 2.517 mg·kg-1 groups were not significantly different from those of the normal control group after 14 d of Sem capsules intervention,suggesting that FBG and HbA1c levels were basically restored to normal.Phar-macokinetic results showed that the elimination half-life(t1/2)of Sem in plasma after ig administration of Sem capsules 0.839,1.678,and 2.517 mg·kg-1 for 14 d in rats was 7.40±1.34,7.48±0.33 and(8.23±0.90)h,respectively,the peak concentration(Cmax)was 18±9,81±23 and(256±53)μg·L-1,time to peak(Tmax)was 0.06±0.13,1.56±0.88,(1.50±1.00)h,respectively,the area under the curve(AUC0-t)was 158±76 μg·h·L-1,858±310 and(3795±1539)μg·h·L-1,and the accumulation index was 1.12±0.05,1.12±0.01 and 1.15±0.04,respectively.CONCLUSION Sem capsules ig administrated can effectively reduce body mass,FBG and HbA1c levels in type 2 diabetic model rats,and lead to glucose reduction and by mass loss.After 14 d of continuous administration of Sem capsules,there is no accu-mulation of semaglutide in rats in the dose range of 0.839-2.517 mg·kg-1,and the exposure increases with the dose.

Extracorporeal membrane oxygenation (ECMO) is an important treatment for extracorporeal cardiopulmonary life support for clinically critical patients. Currently, ECMO tubing is commonly fixed by tie-wraps or tourniquets, which have shortcomings such as easy loosening and potential damage to the tubing. Improper fixation of the catheter can lead to a series of adverse events, such as accidental disconnection of the tubing, rupture of the tubing, tubing folding, and air ingress into the tubing. In order to overcome the above problems, the research team of Zhongda Hospital, Southeast University invented a device for ECMO line fixation and obtained a national utility model patent of China (patent number: ZL 2019 2 2282849.3). The tool is mainly composed of several devices, including a line fixation clamp, a clip fixation device, and a base plate, which is uniquely designed and easy to operate. During ECMO therapy, this device ensures effective stabilization of the ECMO tubing, preventing unexpected incidents due to catheter loosening and facilitating the observation of ECMO catheter insertion markings. Pipeline can be effectively fixed to avoid the occurrence of accidents due to the loosening of the catheter, and at the same time, it is convenient to observe the placement scale of the ECMO catheter. The novelty and uniqueness of the fixation device materials also effectively prevent the occurrence of pressure injuries during its use.

Objective To elucidate the influence of two procedures aortic root remodeling using a straight tubular artificial vessel while preserving the aortic valve and the Florida sleeve procedure on the biomechanics of the aortic root.Methods Five finite element models of the aortic root were reconstructed using computed tomography angiography images,including two cases of aortic root remodeling(A1 and A2),two cases of the Florida sleeve procedure(B1 and B2),and one control group without aortic root pathology(C).Numerical simulations were performed to obtain the blood flow and pressure distribution result to assess the differences in the hemodynamics of the aortic root.Results There were no significant differences in the peak systolic velocity between the two procedures and the control.However,the flow velocity after aortic root remodeling was smoother,similar to the model of the control group,with a more stable average aortic pressure and wall shear stress.In the Florida sleeve procedure,high-speed blood flow affected the vessel wall,leading to various degrees of wall shear stress and pressure concentrations along the aortic wall.Conclusions After aortic root replacement with valve preservation,blood flow patterns in the reconstructed aortic root depended on postoperative changes in sinus geometry.Both surgical procedures showed favorable blood flow patterns;however,the flow pattern after aortic root remodeling was more stable than that after the Florida sleeve procedure.

Malignant tumors in children are one of the most important diseases that threaten the health and quality of life of children and are the second most common cause of death in children.With the continuous improvement and progress of treatment technology, the long-term survival rate of children with tumor has been significantly improved, but both the disease itself and the treatment can impair the immune function of children, which makes them vulnerable to various infectious diseases and secondary serious complications, and even become a source of infection, endangering the health of others. Vaccination is the most cost-effective measure to prevent infectious diseases. For children with normal immune functions, the benefits of vaccination usually outweigh the disadvantages. However, there is a lack of detailed data on the vaccination situation, efficacy and safety of vaccine use for such immunocompromised tumor survivors, and there are no authoritative and uniform vaccination recommendations. This article reviewed and summarized the literature and consensus of some domestic and foreign scholars on current status of post-treatment vaccination status, efficacy and safety of vaccination for children with tumors after treatment, with the aim of providing a reference for the practice in this field in China.

Deconvolution of potential drug targets of the central nervous system (CNS) is particularly challenging because of the complicated structure and function of the brain. Here, a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging. This strategy can map various substances including exogenous drugs, isotopically labeled metabolites, and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways. The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts, and can increase glutamate decarboxylase activity to elevate γ-aminobutyric acid (GABA) levels in the hypothalamus, agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation. These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.

Objective: To investigate the incidence of adverse events following immunization (AEFI) of human papillomavirus (HPV) vaccines in Hangzhou City from 2017 to 2021, so as to provide insights into safety monitoring and evaluation for HPV vaccines. Methods: The AEFI caused by immunization of bivalent (HPV2), quadrivalent (HPV4) and nonavalent HPV vaccines (HPV9) reported in Hangzhou City from 2017 to 2021 were captured from the AEFI Surveillance Module of Chinese Disease Control and Prevention Information System, and HPV vaccination data were captured from the Zhejiang Municipal Immunization Information Management System. The incidence, temporal distributions and clinical symptoms of AEFI were analyzed. Results: Totally 922 310 doses of HPV vaccines were immunized in Hangzhou City from 2017 to 2021, and 232 cases with AEFI were reported, with an overall incidence rate of 25.15/105 doses. The reported incidence rates of AEFI caused by HPV2, HPV4 and HPV9 vaccination were 31.13/105 doses, 25.93/105 doses and 22.01/105 doses, respectively. General reactions and abnormal reactions were predominant AEFI, and the reported incidence rates of general reactions and abnormal reactions were 21.58/105 doses and 2.60/105 dose, respectively. AEFI predominantly occurred 0 to 1 day post-immunization (165 cases, 71.12%), and the main clinical symptoms included local swelling of injection sites, hard tubercle and fever, with reported incidence rates of 10.30/105 doses, 5.96/105 doses and 6.18/105 doses, respectively. Conclusions Low incidence of AEFI was reported following HPV vaccination in Hangzhou City from 2017 to 2021, and all AEFI were mild. The safety of HPV2, HPV4 and HPV9 remains high.

OBJECTIVE: To explore the genetic basis for a patient presenting with renal insufficiency. METHODS: The patient was subjected to whole exome sequencing, and the candidate variant was verified by Sanger sequencing. Transcriptional activity of the PAX2 gene was analyzed by using a PRS4-EGFP reporter plasmid. RESULTS: Genetic testing revealed that the patient has carried a novel de novo heterozygous variant c.418C>T (p.Arg140Trp) of the PAX2 gene. The influence of c.389C>G (p.Pro130Arg), c.478G>A (p.Ala160Thr), c.418C>G (p. Arg140Gly) and c.418C>T (p.Arg140Trp) variants on the transcriptional activity was also evaluated. Functional study has illustrated that the PAX2-P130R, PAX2-R140G and PAX2-R140W variants all had a significant inhibitory effect on the transcriptional activity, but not the PAX2-A160T variant. CONCLUSION The isolated renal hypoplasia of the proband is probably due to the likely pathogenic variant of the PAX2 gene.
Coloboma/genetics* ; Genetic Testing ; Humans ; Mutation ; PAX2 Transcription Factor/genetics* ; Renal Insufficiency/genetics* ; Vesico-Ureteral Reflux

Objective:To study the collapse of the contralateral femoral head after the total hip arthroplasty (THA) in patients with bilateral steroid-induced femoral head necrosis leg-length discrepancy (LLD) influences.Methods:A total of 108 patients with bilateral steroid-induced femoral head necrosis who were treated in Honghui Hospital Affiliated to Xi′an Jiaotong University from June 2014 to June 2016 underwent THA surgery on the hip joints that had symptoms and developed to Association Research Circulation Osseous (ARCO) Ⅲ. At the same time, the non-surgical hip-preserving treatment of the non-collapsed femoral head developed to the ARCO Ⅱ stage was performed. The follow-up period was 2 years, and 98 cases were finally included. According to the size of the leg-length discrepancy [LLD<3 mm group ( n=50), LLD≥3 mm group ( n=48)] and the type of leg-length discrepancy[non collapse side longer group ( n=58) and shorter group ( n=58)], the collapse of the femoral head and the THA were observed. Results:Finally, a total of 56 cases of femoral head collapse occurred in the non collapse side of the hip, of which 50 cases underwent THA within 24 months. There were significant statistical differences in THA and femoral head collapse between LLD<3 mm group and LLD≥3 mm group, non collapse side longer group and non collapse side shorter group ( P<0.05). The 2-year survival rate without collapse in the LLD<3 mm group and LLD≥3 mm group were 52.1% and 34.0%, respectively, and the 2-year survival rates in the longer and shorter non-collapsed limb groups were 56.9% and 22.5%, respectively. Compared with patients with moderate lesions, the survival rate of femoral heads in patients with larger lesions was lower ( OR: 4.25, 95% CI: 1.55-11.26; P=0.003). LLD<3 mm group ( OR: 0.24, 95% CI: 0.06-0.50; P<0.01) or non collapse side longer group ( OR: 0.13, 95% CI: 0.04-0.29; P<0.01) had lower risk of contralateral femoral head collapse after THA. Conclusions:For patients with bilateral steroid-induced femoral head necrosis who have collapsed lateral THA, postoperative leg-length discrepancy extremities is a potential risk factor for collapse of non-collapsed femoral head. LLD<3 mm and avoiding shortening of the uncollapsed limb may reduce the risk of collapse of the uncollapsed femoral head.

The administration of nanoparticles (NPs) first faces the challenges of evading renal filtration and clearance of reticuloendothelial system (RES). After that, NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor cells. As long as possible to prolong the time of NPs remaining in tumor tissue, NPs release active agent and induce pharmacological action. This review provides a comprehensive summary of the physical and chemical properties of NPs and the influence of various biological factors in tumor microenvironment, and discusses how to improve the final efficacy through adjusting the characteristics and structure of NPs. Perspectives and future directions are also provided.

OBJECTIVE: To compare the mRNA level of cell proliferation-related genes Twist1, SIRT1, FGF2 and TGF-β3 in placenta mesenchymal stem cells (PA-MSCs), umbilical cord mensenchymals (UC-MSCs) and dental pulp mesenchymal stem cells (DP-MSCs). METHODS: The morphology of various passages of PA-MSCs, UC-MSCs and DP-MSCs were observed by microscopy. Proliferation and promoting ability of the three cell lines were detected with the MTT method. Real-time PCR (RT-PCR) was used to determine the mRNA levels of Twist1, SIRT1, FGF2, TGF-β3. RESULTS: The morphology of UC-MSCs and DP-MSCs was different from that of PA-MSCs. Proliferation ability and promoting ability of the PA-MSCs was superior to that of UC-MSCs and DP-MSCs. In PA-MSCs, expression level of Twist1 and TGF-β3 was the highest and FGF2 was the lowest. SIRT1 was highly expressed in UC-MSCs. With the cell subcultured, different expression levels of Twist1, SIRT1, FGF2, TGF-β3 was observed in PA-MSCs, UC-MSCs and DP-MSCs. CONCLUSION Up-regulated expression of the Twist1, SIRT1 and TGF-β3 genes can promote proliferation of PA-MSCs, UC-MSCs and DP-MSCs, whilst TGF-β3 may inhibit these. The regulatory effect of Twist1, SIRT1, FGF2 and TGF-β3 genes on PA-MSCs, UC-MSCs and DP-MSCs are different.
Cell Differentiation ; Cell Proliferation/genetics* ; Cells, Cultured ; Dental Pulp/cytology* ; Female ; Fibroblast Growth Factor 2/genetics* ; Humans ; Mesenchymal Stem Cells/cytology* ; Nuclear Proteins/genetics* ; Placenta/cytology* ; Pregnancy ; Sirtuin 1/genetics* ; Transforming Growth Factor beta3/genetics* ; Twist-Related Protein 1/genetics* ; Umbilical Cord/cytology*