Objective To evaluate the bone repair capacity ofpolylactic acid-polyglycolic acid copolymer (PLGA)/collagen type Ⅰ (CoI) microspheres combined with BMSCs after being injected in intertrochanteric bone defect of osteoporotic female rats.Methods Prepared PLGA microspheres.The microspheres were coated with Col.BMSCs of the third passage were cultured with PLGA/CoI microspheres.Forty 3-month-old female SD rats were ovariectomized to establish osteoporotic animal models.The osteoporotic rats were randomly divided into 5 groups,including SHAM group,PBS group,Cell group,MS group and Cell+ MS group.There were 8 rats in each group.Different material was injected into the intertrochanteric bone defect site which was made with electric drill.Four rats of each group were sacrificed at 1 month and 3 months post-operation.The fenora were taken to measure the intertrochanteric bone mineral density (BMD) with DEXA and evaluate trabecular stucture with Micro CT.Results After 7 days of coculture,BMSCs seeded on PLGA/CoI microspheres had nice adherance and proliferation.There was no difference of BMC and BMD among all groups at 1 month post-operation.Tb.Th of Cell+MS group was higher than that of PBS group and MS group at 1 month post-operation.％Tb.Ar of Cell+MS group was higher than that of Cell group and MS group at 1 month post-operation.Tb.Sp of Cell+MS group had a tendence to decrease compared with other groups but there was no statistical difference at 1 month post-operation.After 3 months of operation,the BMC of Cell+MS group had a tendence to increase compared with that of PBS group and MS group but showed no statistical difference.BMD and Tb.Th of Cell+MS group was higher than those of other groups.％Tb.Ar of Cell+MS group was higher than that of SHAM group and PBS group.Tb.Sp of Cell+MS group had a tendence to reduce compared with other groups but showed no statistical difference.Conclusion The bone defect of osteoporotic site can be repaired 1 month after the injection of the PLGA/CoI microspheres combined with BMSCs.The trabecular reconstruction and bone quality of osteoporotic site can be improved 3 months after the injection.

Objects:To investigate the current situation of counselors'implementation and their attitude to informed consent in Beijing.Methods:Eleven counselors who worked in Beijing were interviewed,the average of their working years was (7.4 ± 4.4).A semi-structured interview was used to learn about their practicing processes in and viewpoints on informed consent,and their interview transcripts were analyzed through qualitative method.Results:The results could be categorized into four categories,including the content of informed consent,the influential factors of informed consent,problems and confusions,and the significance of informed consent.The crucial role of informed consent in psychotherapy was generally recognized by counselors,and they could obey the related rules as well.The therapists had some confusion and problems about informed consent,such as the form and length,the consent for special population and online consultation.Conclusion:Basically,the counselors in Beijing could comply with the ethical standards of informed consent.However,they also suggest that certain limitations of these rules should be noticed.

Objective To investigate the effect of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) on the proliferation, migration and tumor immune microenvironment of colorectal cancer cells and its possible molecular mechanism. Methods The Cancer Genome Atlas (TCGA) database was used to analyze the expression levels of IGF2BP2 and MYC in colorectal cancer and adjacent tissues. The expression of IGF2BP2 in HCT-116 and SW480 human colorectal cancer cells was silenced by RNA interference (RNAi), and the silencing effect was detected by quantitative real-time PCR. After knocking down IGF2BP2, colony formation assay, CCK-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were employed to detect cell colony formation and proliferation ability. Transwell^TM assay was used to detect cell migration ability. Quantitative real-time PCR was used to detect the mRNA expression of IGF2BP2, MYC, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and interleukin-10 (IL-10). The protein expression of IGF2BP2 and MYC was detected by western blot. The binding ability of IGF2BP2 and MYC in HCT-116 cells was detected by quantitative real-time PCR after RNA immunoprecipitation. Results The results of TCGA database showed that the expression of IGF2BP2 and MYC in colorectal cancer tissues was significantly higher than that in adjacent tissues, and the survival time of colorectal cancer patients with high expression of IGF2BP2 was shorter. After silencing IGF2BP2, the viability, proliferation and migration of HCT-116 and SW480 cells were decreased. The mRNA expression of MYC, TGF-β and IL-10 in IGF2BP2 knockdown group was significantly decreased, while the expression of TNF-α mRNA was increased. The expression of MYC protein and the stability of MYC mRNA were significantly decreased. RIP-qPCR results showed that IGF2BP2 could bind to MYC mRNA. Conclusion Knockdown of IGF2BP2 inhibits colorectal cancer cell proliferation, migration and promotes tumor immunity by down-regulating MYC expression.
Humans ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Colorectal Neoplasms/metabolism* ; Gene Expression Regulation, Neoplastic ; Interleukin-10/metabolism* ; RNA, Messenger ; RNA-Binding Proteins/metabolism* ; Transforming Growth Factor beta/genetics* ; Tumor Microenvironment/immunology* ; Tumor Necrosis Factor-alpha/metabolism* ; Proto-Oncogene Proteins c-myc/metabolism*

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K⁺ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.

ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension， synthesize and update the evidence， form expert consensus， and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure （CNKI）， WanFang Data Knowledge Service Platform （WanFang）， Vip Chinese Science and Technology Journal Database （VIP）， Chinese Biomedical Literature Service System （Sinomed）， National Library of Medicine （PubMed）， Cochrane Library， Web of Science， and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31， 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment， Development， and Evaluation profiler （GRADEprofiler） 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included， and the results of literature quality evaluation and risk of bias showed that 70.31% （45/64） of the studies indicated some risks， and 29.69% （19/64） indicated high risks. Compared with conventional western medicines， the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure （SBP） and diastolic pressure （DBP）， increase the effective rate of antihypertensive， reduce the incidence of adverse reactions， endothelin-1， and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive， and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive， without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive， and Xinmaitong capsules decreased DBP， with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally， four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension， antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety， but they are mostly weak recommendations in terms of efficacy， and more high-quality evidence is needed.