Objective To explore the risk factors of early femoral head necrosis in patients with femoral neck fracture after operation,and to establish a nomogram prediction model.Methods A total of 167 patients with femoral neck fracture from Jan-uary 2020 to April 2022 were selected and divided into necrosis group and non-necrosis group according to whether femoral head necrosis occurred in the early postoperative period.There were 21 males and 17 females in the necrosis group,aged from 33 to 72 years old,with an average of(53.49±10.96)years old,and the time from injury to operation ranged from 40 to 67 hours,with average time of(53.46±7.23)hours.There were 72 males and 57 females in the non-necrosis group,aged from 18 to 83 years,with an average of(52.78±12.55)years old,and the time from injury to operation was 18 to 65 hours,with an aver-age time of(39.88±7.79)hours.The potential influencing factors,including patient gender,diabetes mellitus,hypertension,chronic liver disease,posterior inclination angle of the femoral head,operation mode,fracture displacement,fracture line loca-tion,preoperative braking traction,screw arrangement mode,reduction quality,age,body mass index(BMI),and injury to operation time were subjected to single factor analysis.Logistic multivariate regression analysis was conducted for factors with a significance level of P＜0.05.Results The incidence of femoral head necrosis in 167 patients with femoral neck fracture was 22.76％.The following factors were identified as independent risk factors for early postoperative femoral head necrosis in pa-tients with femoral neck fractures:coexisting diabetes[OR=5.139,95％CI(1.405,18.793),P=0.013],displaced fracture[OR=3.723,95％CI(1.105,12.541),P=0.034],preoperative immobilization[OR=3.444,95％CI(1.038,11.427),P=0.043],quality of reduction[OR=3.524,95％CI(1.676,7.411),P=0.001],and time from injury to surgery[OR=1.270,95％CI(1.154,1.399),P=0.000].The Hosmer-Lemeshow goodness-of-fit test(x2=3.951,P=0.862),the area under the receiver operator characteristic(ROC)curve was 0.944[P＜0.001,95％CI(0.903,0.987)],with a sensitivity of 89.50％,the specificity was 88.40％,the maxi-mum Youden index was 0.779,and the overall trend of the model correction curve was close to the ideal curve.Model regres-sion equation was Z=1.637 × diabetes+1.314× fracture displacement+1.237 × preoperative braking traction+1.260 × reduc-tion quality+0.239 ×injury to operation time-18.310.Conclusion The occurrence of early femoral head necrosis in patients with femoral neck fracture postoperatively is affected by multiple factors.The risk early warning model established according to the factors has good predictive efficacy.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Morinda officinalis oligosaccharides (MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan (5-HTP) → serotonin (5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan; meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation, and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide, as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome

Objective To understand the epidemiological characteristics of COVID-19 epidemic in Huangpu District of Shanghai, and to provide scientific evidence for prevention and control of COVID-19. Methods Descriptive statistics were used to study the suspected and confirmed cases of COVID-19 reported from January 21 through March 10, 2020 in Huangpu District, Shanghai. Results A total of 120 suspected cases of COVID-19 were reported, of which 12 were diagnosed and 108 were excluded.The first confirmed case was reported on January 21, and the last case was on February 10; the majority (11/12) of the confirmed cases were reported from January 21 through February 1.The average duration of time from the symptom onset to the first medical visit was 2.6 days, whereas the average duration from the first medical visit to the hospital diagnosis was 2.2 days.There were 15 suspected cases with a confirmed history of residence or tourism in Wuhan, in which 6 were confirmed cases.Moreover, 5 suspected cases had a confirmed history of contact with other confirmed cases, in which 3 were confirmed cases.Thus, exposure in Wuhan and exposure to confirmed cases were the most significant risk factors at this stage of the epidemic. Conclusion The 12 cases identified in Huangpu District of Shanghai are all adults, half of whom had confirmed history of exposure in Wuhan.The first cluster of COVID-19 cases in Shanghai is documented in Huangpu District.Epidemiological investigation reveals that the confirmed cases might be infectious the day before the symptom onset.

Bile Duct Diseases ; Biliary Atresia/surgery* ; Cysts ; Humans ; Infant ; Liver Failure ; Portoenterostomy, Hepatic ; Retrospective Studies

Objective　The active protein of traditional Chinese medicine has anti-tumor effect, and salvia miltiorrhiza is an important anti-tumor traditional Chinese medicine. Here, the effect of Salvia miltiorrhiza lectin protein (SMLP) on the apoptosis of gastric cancer cells was studied.　Methods　SMLP expressed and purified from prokaryotic cells was used to treat the gastric cancer cells SGC-7901. The experiment was divided into the control group (untreated) and the SMLP treatment group (final concentration of 10 μmol / L of SMLP was treated for 24 h). Real-time RT-PCR and Western blot were used to detect the changes of apoptosis gene expression. Flow cytometry and Hoechst staining were applied to detect the apoptotic status. Caspase-3 and Caspase-9 activity assay kits were used to detect the apoptotic level.　Results　The result of RT-PCR showed that the mRNA level of Bax in the SMLP treatment group was significantly higher than in the control group (1.00±0.12 vs 0.67±0.10）(P<0.05). After treatment with SMLP to gastric cancer cells, the activity and expression level of cleaved Caspase-3 and Caspase-9 were increased significantly compared with the control group (P<0.05). The cell nucleus in the control group was bigger and rounder, with smooth surface and uniform staining, whilst in the SMLP-treated group, the cell nucleus became deeper with pyknosis, representing typical morphological characteristics of apoptosis. The early apoptosis level in the control group was 6.55%, and the SMLP treatment group reached 10.18%, showing an increase in the level of apoptosis.　Conclusion　SMLP expressed and purified in vitro can promote the apoptosis of gastric cancer cells, which is of great significance for further revealing the function of plant lectin and investigating the anti-tumor effect on the protein of traditional Chinese medicine.

OBJECTIVETo study if programmed death-ligand 1 (PL-L1) expression in breast cancer cell activates PD-L1/PD-1 pathway in dendritic cells to inhibit dendritic cell maturation.

METHODSHuman monocytes were induced to differentiate into immature dendritic cells using GM-CSF and IL-4, and further to mature dendritic cells using TNF-α. PD-L1-expressing breast cancer cell line MDA-MB-231 was co-cultured in contact with the dendritic cells to observe the effects of the breast cancer cells on the maturation of the dendritic cells. A PD-L1 blocking antibody was applied to the co-culture, and the changes in the inhibitory effect of the MDA-MB-231 cells on dendritic cell maturation was observed. TNF-α-induced dendritic cells were treated with a recombinant human PD-L1 protein to study the effect of PD-L1/PD-1 pathway activation on the maturation of dendritic cells. The expression of PD-L1 in MDA-MB-231 cells and the dendritic cell maturation marker HLA-DR and CD83 were analyzed using flow cytometry.

RESULTSMDA-MB-231 cell line showed PD-L1 positivity on the cell membrane cells at a rate as high as (99.7∓0.15)%. In mature dendritic cells, the positivity rates for HLA-DR and CD83 were (88.8∓6.96)% and (18.36∓3.07)%, respectively, but in the co-culture system, the positivity rates of the dendritic cells were significantly decreased to (42.76∓10.52)% (P<0.01) and (9.93∓2.74)% (P<0.05), respectively, indicating that MDA-MB-231 cells inhibited the maturation of dendritic cells. Following treatment with a PD-L1 antibody isotype control, the percentages of HLA-DR- and CD83-positive cells in the co-culture were (45.17∓10.19)% and (10.15∓2.54)%, which were significantly increased to (63.46∓1.72)% and (16.46∓2.58)% after treatment with PD-L1 antibody, respectively (both P<0.05). Compared with the mature dendritic cell controls, the cells treated with the recombinant human PD-L1 protein exhibited significantly lowered percentages of HLA-DR-positive [from (84.23∓4.18)% to (2.56∓2.39)%, P<0.05] and CD83-positive cells [(87.26∓1.54)% to (60.67∓1.63)%, P<0.05].

CONCLUSIONThe effect of PD-L1 antibody therapy on triple negative breast cancer can be partially mediated by blocking PD-L1 expression on breast cancer cell membrane, which attenuates the inhibition of dendritic cell maturation in the cancer microenvironment.

AIM:To determine the role of nuclear receptor subfamily 6,group A,member 1 (NR6A1) in vascular smooth muscle cell (VSMC) apoptosis.METHODS:NR6A1 protein was over-expressed in the VSMCs by infection of adenovirus.The effect of NR6A1 on the viability of VSMCs was measured by MTT assay.DAPI staining,TUNEL staining and caspase activity assay were conducted.DNA microarray was used to quickly screen the target genes of NR6A1.The effect of receptor-interacting serine/threonine-protein kinase 3 (RIPK3) silencing on NR6A1-induced apoptosis of the VSMCs was further analyzed.RESULTS:Adenovirus-mediated over-expression of NR6A1 induced the apoptosis of VSMCs.The RIPK3 gene expression was up-regulated by NR6A1 over-expression in the VSMCs.NR6A1-induced VSMC apoptosis was inhibited by RIPK3 silencing.CONCLUSION:NR6A1 promotes VSMC apoptosis by up-regulating the RIPK3 gene expression.

To investigate the effects of cordycepin on proliferation and invasion of pancreatic cancer stem cells (Pan CSC) and its mechanisms, MTT assay was used to investigate the effect of cordycepin on proliferation of Pan CSC. Inverted microscope was used to observe the morphologic change of cells. Propidium iodide staining methods was employed to observe the cell apoptosis. Cell scratch method was used to detect the ability of migration of Pan CSC in each group. RT-PCR and Western blot were used to determine the expression of apoptosis gene and epithelial-mesenchymal transitions (EMT) gene. The growth of Pan CSC was inhibited by cordycepin in a dose-and time-dependent manner, with IC₅₀ 107.364 and 48.472 μmol·L^-1 at 24 and 48 h, respectively. Moreover, the cell migration was inhibited at the same time. RT-PCR and Western blot results showed that cordycepin decreased the expression of Bcl-2 and activated pro-apoptotic gene levels such as Bax,p53, caspase-3. Furthermore, cordycepin reduced the expression of EMT genes by up-regulation of E-cadherin and down-regulation of N-cadherin. Cordycepin has the ability to inhibit Pan CSC proliferation and invasion by activating p53 pathway as well as suppressing the EMT. This study provides a new basis for inhibition of pancreatic cancer stem cells in the treatment of pancreatic cancer.