BACKGROUND:A large number of studies have confirmed that tissue engineering scaffolds can almost completely repair osteochondral defects.However,when osteochondral defects are complicated with infection,even after thorough debridement in the early stage,the repair effect of simple osteochondral tissue engineering scaffolds is often unsatisfactory. OBJECTIVE:To prepare fibroin/chitosan/nano-hydroxyapatite scaffold loaded with vancomycin hydrochloride sustained release microspheres,and to investigate the repair effect on infected osteochondral defect in distal femur of rabbit. METHODS:(1)Vancomycin hydrochloride sustained release microspheres were prepared by emulsified solvent evaporation method.The sustained-release microspheres of different weights(7.5,10,and 12.5 mg)were mixed with fibroin protein-chitosan nanohydroxyapatite solution,and the scaffolds of fibroin protein/chitosan/nano-hydroxyapatite were prepared by chemical crosslinking method.The porosity,water absorption and expansion rate,hot water loss rate of the scaffolds,and drug sustained-release in vitro were characterized.(2)Forty-five New Zealand white rabbits were randomly divided into blank group,control group,and experimental group,with 15 rabbits in each group.The osteochondral defect and infection model of the distal femur of the right hind limb was established in both groups.The blank group was not treated,and the control group was implanted with fibroin protein-chitosan-nano-hydroxyapatite scaffold.Vancomycin hydrochloride sustained-release microspheres(10 mg)of fibroin/chitosan/nano-hydroxyapatite scaffold were implanted in the defect of the experimental group.The levels of C-reactive protein and leukocytes in blood samples were detected 1 week after operation.At 4,8 and 12 weeks after operation,the tissue of the operative area was taken for gross observation and pathological observation. RESULTS AND CONCLUSION:(1)With the increase of sustained-release microspheres content,the porosity of scaffolds decreased,and there was significant difference among groups(P＜0.05).There were no significant differences in the pore size,water absorption expansion rate and hot water loss rate among the three groups(P＞0.05).Vancomycin hydrochloride was released sustainably in vitro for more than 30 days in all three groups of scaffolds.(2)The levels of C-reactive protein and leukocytes in blood samples of the experimental group were lower than those of the blank group and control group(P＜0.05).The repair of gross cartilage in the experimental group was significantly better than that in the blank group and the control group.Hematoxylin-eosin,Masson,Alcian blue and type Ⅱ collagen immunohistochemical stainings showed that the osteochondral repair effect of the experimental group was significantly better than that of the blank group and the control group at each time point.(3)The results showed that fibroin/chitosan/nano-hydroxyapatite scaffolds loaded with vancomycin hydrochloride sustained-release microspheres could effectively promote the repair of open osteochondral defects.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:Through comprehensive analysis of symptoms and signs, biochemistry, imaging, and dynamic tests, to explore the diagnosis and differential diagnosis of thyrotropin-secreting pituitary adenoma(TSH adenoma) and syndrome of resistance to thyroid hormone(RTH).Methods:A retrospective analysis was conducted on clinical data from 14 patients who visited the First Affiliated Hospital of Zhengzhou University from July 2016 to September 2022, exhibiting elevated levels of free thyroxine(FT4) and free triiodothyronine(FT3) in the presence of increased TSH.Results:There were 7 cases of TSH adenoma and 7 cases of RTH, with the average age of diagnosis at 40.0 years and 26.6 years, respectively. Thirteen patients showed thyrotoxicosis or occasional palpitation, some with pituitary occupancy manifestations or abnormal growth and development; One patient presented with neck thickening. Sex hormone binding globulin was elevated in 3 cases of TSH adenoma. Pituitary magnetic resonance imaging showed that all 7 cases of TSH adenoma were macroadenomas and 1 case of RTH was microadenoma. The octreotide suppression test in 13 patients was inhibited, but there was a significant difference in the inhibition rate of 24 h/2 h TSH inhibition rate of TSH adenoma and RTH, ranging from 46.6% to 83.9% and 4.6% to 28.8% respectively. Six cases of RTH had thyroid hormone receptor β mutation.Conclusion:Syndrome of inappropriate secretion of thyrotropin is a rare condition, mainly including TSH adenoma and RTH. The diagnosis and differentiation of the two conditions require comprehensive assessment incorporating family history, symptoms and signs, laboratory tests, dynamic test, and genetic test. Among these, the 24 h/2 h TSH inhibition rate of octreotide suppression test can effectively distinguish TSH adenoma from RTH.

Continuing medical education for general practitioners is an important measure to upgrade the quality of primary health care services in China, which is still facing various challenges and need to be further developed and improved. This article analyzes the status quo and existing problems of continuing medical education for general practitioners in China, and proposes suggestions based on the concept of people centered and integrated health care (PCIC), including faculty development, training contents, assessment methods, and experience learning, to provide references for the improvement of continuing medical education for general practitioners.

OBJECTIVE To investigate the effects and mechanism of galangin （GAL） on hepatocyte apoptosis in rats with obstructive jaundice （OJ） based on the Janus kinase 2 （JAK2）/signal transduction and activator of transcription 3 （STAT3） signaling pathway. METHODS Taking male SD rats as the object， the OJ model was established by double ligation of common bile duct， and 48 rats with successful modeling were randomly separated into OJ model group （model group）， low-dose GAL group （GAL-L group）， high-dose GAL group （GAL-H group） and high-dose GAL+JAK2 activator colivelin group （GAL-H+ colivelin group）， with 12 rats in each group； another 12 SD rats with laparotomy/abdominal closure without ligation were selected as sham operation group （sham group）. Each administration group was given relevant medicine intragastrically and/or intraperitoneally， once a day， for 7 consecutive days. After the last medication， the morphology of liver tissue in rats was observed； the serum levels of total bilirubin （TBIL）， direct bilirubin （DBIL）， alanine transaminase （ALT） and γ -glutamyltransferase （GGT）， as well as the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in mail：guoweishengjcy@126.com liver tissue were detected. The apoptotic rate of liver tissue cells， the expression levels of signaling pathway-related proteins （phosphorylated JAK2， JAK2， phosphorylated STAT3， STAT3） and apoptosis-related proteins [B cell lymphoma 2 （Bcl-2）， Bcl-2 related X protein （Bax）] were determined. RESULTS Compared with sham group， congestion of liver sinusoids， damage to liver lobules， disordered arrangement and swollen morphology of liver cells， the disappearance of nucleoli， and significant infiltration of inflammatory cells and fibrous tissue proliferation were observed in model group； the serum levels of TBIL， DBIL， ALT and GGT， the level of MDA in liver tissue， the apoptosis rate of liver cells， the protein expression of Bax， and the protein phosphorylation levels of JAK2 and STAT3 in liver tissue of model group were increased significantly （P＜0.05）； the level of SOD and the protein expression of Bcl-2 in liver tissue were decreased significantly （P＜0.05）. Compared with the model group， the pathological injuries of liver tissue were relieved in GAL-L group and GAL-H group， all quantitative indicators had significantly improved， and the effect of GAL-H group was more significant （P＜ 0.05）. Colivelin could significantly reverse the improvement effects of GAL on liver injury and related indicators of OJ rats （P＜ 0.05）. CONCLUSIONS GAL may inhibit liver cell apoptosis in OJ rats， improve liver function and alleviate oxidant stress， the mechanism of which may be associated with inhibiting JAK2/STAT3 signaling pathway.

Objective To study the cellular senescence and molecular mechanism of olaparib in MCF-7 breast cancer cells.Methods The effects of olaparib on the proliferation and migration of MCF-7 cells were detected dynamically by real-time cell analysis(RTCA)technology.The effects of olaparib on the Senescence was detected by using the senescence-associated β-galactosidase(SA-β-gal).Quantitative polymerase chain reaction was used to analyze the effects of olaparib on the expression levels of genes encoding the senescence-associated factors p16,p21,C/EBP homologous protein,interleukin(IL)-6,IL-8,plasminogen activator inhibitor 1,phosphatase and tensin homolog deleted on chromosome 10,p27,retinoblastoma gene,Ki67,and E2F1.The effects of olaparib on the expression levels of the senescence-associated proteins p21,γH2AX,pRB,cyclin D1,insulin-like growth factor binding protein 3,and Ki67 were analyzed by Western Blot.Results Olaparib inhibited the proliferation and migration and induced the senescence of MCF-7 cells.Long-term(96 h)treatment with olaparib significantly up-regulated the gene expression levels of p16,p21,p27,C/EBP homologous protein,IL-6,IL-8,plasminogen activator inhibitor 1,phosphatase and tensin homolog deleted on chromosome 10,and retinoblastoma protein(P＜0.01)and significantly down-regulated the gene expression levels of Ki67 and E2F1(P＜0.01)in MCF-7 cells.Olaparib significantly increased protein expression levels of p21,γH2AX,and insulin-like growth factor binding protein 3 in MCF-7 cells(P＜0.01,P＜0.01,P＜0.05)and significantly decreased cyclin D1,pRB,and Ki67 levels(P＜0.05,P＜0.01,P＜0.05).Conclusions Olaparib can inhibit proliferation and migration and induce senescence in MCF-7 breast cancer cells.

Periodontitis is a chronic inflammatory and destructive disease in which plaque acts as an initiator.Recruitment of host im-mune cells and production of multiple inflammatory mediators leads to periodontal tissue damage.Programmed cell death(PCD)is a self-destructive process that is actively initiated by cells under specific conditions and can be mainly categorized into apoptosis,necrop-tosis,autophagy,pyroptosis,ferroptosis,cuproptosis,etc.Different types of programmed cell death have their own distinctive roles in periodontitis.In this review,we summarizes the characteristics of different types of PCD and their role in the progression of periodonti-tis,in order to provide new research ideas on the pathogenic mechanism of periodontitis and more references for the precise treatment of periodontitis.

Transcatheter tricuspid valve intervention is the new frontier of interventional cardiology. The LuX-Valve is a radial force-independent orthotopic tricuspid valve replacement device developed in China. The LuX-Valve Plus transcatheter tricuspid valve replacement (TTVR) system is changed from the trans-atrial to the transjugular approach, which further reduces trauma and pulmonary complications compared with the first generation LuX-Valve. The first-in-human study has been completed at Zhongshan Hospital, Fudan University and an exploratory multicentre clinical study is underway. Echocardiography plays an important role in pre-TTVR screening, intraoperative guidance and postoperative evaluation and follow-up, especially two-dimensional transoesophageal echocardiography (2D-TEE) and three-dimensional transoesophageal echocardiography (3D-TEE). However, there is a lack of appropriate intraoperative guidance and assessment protocols. In this study, we briefly described the protocols and imaging considerations for intraoperative 2D-TEE and 3D-TEE to ensure the successful implantation of TTVR.

Objective:To explore the β-amyloid (Aβ) deposition pattern of subjects with the preclinical Alzheimer′s disease (AD), community-derived amnestic mild cognitive impairment (aMCI) and normal cognition (NC) from communities of Shanghai.Methods:According to the inclusion and exclusion criteria, 273 subjects (104 males, 169 females; age (64.2±7.6) years) were recruited from Shanghai community and memory clinics from December 2018 to July 2020. All subjects underwent MRI, 18F-AV45 PET imaging and neuropsychological scale tests and were grouped into AD, aMCI and NC groups based on clinical diagnosis. Differences in demographic information, the neuropsychological scale tests′ scores and positive rate of Aβ deposition among each group were analyzed by one-way analysis of variance or χ2 test. Aβ deposition patterns of AD and MCI groups were analyzed at voxel level, and the differences of Aβ deposition among different groups were compared. Results:Among 273 patients, the positive rates of Aβ deposition in AD, aMCI and NC groups were 84.4%(38/45), 36.4%(20/55) and 23.1%(40/173), respectively ( χ2=58.37, P<0.001). Among AD, aMCI, NC and NC (Aβ-) groups ( n=132), the education years of AD group was the lowest ((9.7±4.6) years; F=8.86, P<0.001). In addition, there were significant differences in the scores of several neuropsychological scale tests among AD, aMCI, NC groups and NC (Aβ-) group ( F values: 27.68-235.50, all P<0.001). Compared with subjects in NC(Aβ-) group, the Aβ depositions in the aMCI and AD groups were widely distributed in the whole cerebral cortex; and AD group had higher Aβ deposition in bilateral frontal, parietal, temporal, occipital lobe, cingulate gyrus and precuneus than aMCI group. Conclusions:The positive rate of Aβ deposition in the preclinical AD population from the Shanghai community is obtained. There are significant different Aβ deposition patterns in subjects at different stages of AD.

Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer;hence,new and efficient strategies are necessary.In this study,a supramolecular nanoreactor(DOC@TA-Fe3+)based on tannic acid(TA),iron ion(Fe3+),and docetaxel(DOC)with microtubule inhibition,reactive oxygen species(ROS)generation,and glutathione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,the DOC@TA-Fe3+nanoreactor escapes from the lysosomes to release payloads.The subsequent Fe3+/Fe2+conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration.Additionally,Fe3+can consume gluta-thione to repress the activity of GPX4 to induce ferroptosis.Meanwhile,the released DOC controls microtubule dynamics to activate the apoptosis pathway.The superior in vivo antitumor efficacy of DOC@TA-Fe3+nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model.Therefore,the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.