Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b.Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases.It is involved in regulating the pathological process of myocardial infarction,myocardial ischemia/reperfusion injury,cardiac hypertrophy,atrial fibrillation,diabetic cardiomyopathy,atherosclerosis,pulmonary hyperten-sion,cerebral ischemia/reperfusion injury,Parkinson's disease,and Alzheimer's disease.Obviously,miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases.However,the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed.Therefore,in this review,we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases.Drugs targeting miR-135b for the treatment of diseases and related patents,highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases,have been discussed.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective:To discuss the molecular association pattern of Shenling Baizhu Powder for type 2 diabetes (T2DM) and ulcerative colitis through network pharmacology method based on the theory of "treating different diseases with same method" in TCM.Methods:The TCMSP and ETCM Chinese medicine chemical composition databases were used to obtain the chemical composition and predict the targets of Shenling Baizhu Powder. The OMIM, GeneCards, DrugBank and TTD disease databases were used to obtain the disease targets of T2DM and ulcerative colitis. The intersection targets of chemical composition of Shenling Baizhu Powder, T2DM and ulcerative colitis were obtained by Bioinformatics platform. Cytoscape 3.8.2 software was used to map the "Chinese materia medica-component-target" network and "effective component- intersection target" network. The GO enrichment analysis and KEGG pathway analysis of the intersection targets were performed with the STRING platform. The intersection target protein-protein interaction network was constructed by STRING database, and core targets were obtained using the CytoNCA plugin of Cytoscape 3.8.2 software. AutodockTools software was applied to validate the molecular docking between the core chemical components and the core targets of Shenling Baizhu Powder.Results:Totally 176 chemical components of Shenling Baizhu Powder, 226 corresponding targets, 11 478 T2DM targets, 4 857 Ulcerative targets of ulcerative colitis, and 162 intersection targets of medicinal chemistry components and diseases were obtained. 1 789 related biological processes, 163 molecular functions, 92 cell constituents, and 192 signaling pathways were obtained by GO enrichment analysis and KEGG pathway analysis. The signaling pathways were mainly about AGE-RAGE, TNF, IL-17,MAPK, PI3K-Akt signaling pathways, etc. The core components of Shenling Baizhu Powder were mainly sitosterol, luteolin, kaempferol, naringenin, beta-carotene, etc. The core targets were EGFR, ALB, IL1B, CASP3, ESR1, VEGFA, PTGS2, TNF, IL6, MYC, AKT 1, JUN, TP53, etc. The core chemical components had tight correlation with the core targets by the molecular docking.Conclusions:By acting on core targets such as TNF, IL1B, IL6, AKT1, VRGFA, PTGS2, MYC, JUN, TP53, and regulating IL-17 signaling pathway, TNF signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, etc., Shenling Baizhu Powder improves tissue inflammation damage, mucosal barrier damage, immune regulation imbalance, intestinal flora dysbiosis, insulin resistance, apoptosis, oxidative stress and other biological processes. Therefore Shenling Baizhu Powder can treat T2DM and ulcerative colitis with the same method.

Objective To explore left ventricular longitudinal systolic function changes during perioperative period of coronary artery bypass graft(CABG).Methods Totally 41 patients with confirmed coronary artery disease(CAD)who underwent CABG were prospectively enrolled.The preoperative left ventricular global longitudinal strain(GLS),as well as GLS on the day of CABG,on the 3rd and 7th day postoperation were measured.According to preoperative left ventricular GLS,the patients were divided into 3 groups,i.e.normal group(group A,GLS≤-18.1％,n=6),mildly decreased group(group B,-18.1％＜GLS≤-14.0％,n=22)and severely decreased group(group C,GLS＞-14.0％,n=13).Repeated measures analysis of variance,generalized estimating equation and multiple comparisons were used to analyze left ventricular systolic function in different perioperative time points.Results No significant difference of GLS was found among different time points during perioperative period of CABG in group A and C(all adjusted P＞0.05).In group B,GLS on postoperative days were lower than that before CABG(all adjusted P＜0.001),and the lowest value was observed on the day of CABG postoperatively,while no significant difference of GLS was found between the 3rd and 7th day postoperation(adjusted P=1.00).Compared with those before CABG,the longitudinal strain(LS)of basal segment on the day of CABG postoperatively and 3rd day postoperation,of middle segment and apical segment at all postoperative time points were lower(all adjusted P＜0.05),while of the apical segment on the day of CABG postoperatively decreased most obviously.No significant difference of LS of each ventricular segment was found between the 3rd nor the 7th day postoperation(all adjusted P＞0.05).Conclusion GLS decreased significantly on the day of CABG postoperatively but partially recovered within the following week in CAD patients with mildly decreased preoperative GLS.CABG had the most pronounced effect on LS of apical segment in left ventricle.

Objective:To explore the application value of transrectal ultrasound images classification network model of prostate cancer based on deep learning in the classification of benign and malignant prostate tissue in transrectal ultrasound images.Methods:A total of 1 462 two-dimensional images of transrectal prostate biopsy with clear pathologic results(including 658 images of malignant tumor, 804 images of benign tumor) from 203 patients with suspicious prostate cancer(including 89 cases of malignant tumor, 114 cases of benign tumor) were collected from May 2018 to May 2021 in the First Affiliated Hospital of Jinan University. They were divided into the training database, validation database, and test database. And the training and validation database were used to train and obtain the intelligence-assisted diagnosis network model, and then the test database was used to test the network model and two ultrasound doctors of different ages. With pathologic diagnosis as the gold standard, the diagnostic performance among them was evaluated.Results:①The sensitivity of network model was 66.7% the specificity was 91.9%, the accuracy was 80.5%, the precision(positive predictive value) was 87.1%. The area under the ROC curve was 0.922. ②The accuracy of the junior and senior ultrasound doctors was 57.5%, 62.0%; the specificity was 62.0%, 66.3%; the sensitivity was 51.5%, 56.8%; the precision was 53.1%, 58.1%, respectively. ③The accuracy, sensitivity, specificity, precision of classification: the network model > the ultrasound doctors, the differences were significant( P<0.05); the senior ultrasound doctor>the junior ultrasound doctor, the differences were not significant( P>0.05). Conclusions:The intelligence-assisted diagnosis network model based on deep learning can classify benign and malignant prostate tissue in transrectal ultrasound images, improve the accuracy of ultrasound doctors in diagnosing prostate cancer. It is of great significance to improve the efficiency of screening for patients with high clinical suspicion of prostate cancer.

Objective: To compare the effect of scalp acupuncture and scalp acupuncture plus acupuncture exercise therapy (AET) on walking ability in children with spastic cerebral palsy (CP). Methods: A total of 60 spastic CP children with gross motor function classification system (GMFCS) grades Ⅰ-Ⅲ were divided into a control group and an observation group by the random number table method, with 30 cases in each group. Both groups were treated with the same conventional rehabilitation and scalp acupuncture therapy for CP. The control group received conventional rehabilitation first and then scalp acupuncture. The observation group received AET, which was to receive the conventional rehabilitation and scalp acupuncture simultaneously. Before and after treatment, the clinical efficacy was evaluated by the modified Ashworth scale (MAS) score, scores of dimensions D and E of the gross motor function measure (GMFM) scale, walking speed, and walking distance. Results: During treatment, there were 2 dropouts in the observation group. After 3 courses of treatment, the MAS scores in both the control group and observation group decreased compared with the same group before treatment (P<0.05), and the scores of dimensions D and E of the GMFM, walking speed, and walking distance were increased (P<0.05); the between-group comparison showed that the MAS score in the observation group was lower than that in the control group (P<0.05), and the scores of dimensions D and E of the GMFM, walking speed, and walking distance in the observation group were higher or longer than those in the control group (P<0.05). Conclusion: W ith the same treatments, scalp acupuncture combined with AET is superior to the conventional scalp acupuncture method in reducing lower-limb muscle tone, improving standing balance ability, and walking stability in children with spastic CP.

Objective To investigate the effect of circular RNA hsa_circ_0001922 on the proliferation, migration and invasion of prostate cancer cell PC-3 and its underlying molecular mechanism. Methods qRT-PCR and RNA FISH were used to detect the expression level and localization of hsa_circ_0001922 in PC-3 cells respectively. After hsa_circ_0001922 was targeted inhibited, clone formation, Transwell assay and scratch assay were used to detect the proliferation, migration and invasion abilities of PC-3 cells. qRT-PCR and Western blot were used to detect the expression levels of EMT pathway-related molecules after inhibiting hsa_circ_0001922. Results The expression of circular RNA hsa_circ_0001922 was increased in PC-3 cells (P < 0.01) and it existed in the cytoplasm and nucleus. The invasion, migration and invasion abilities were significantly weakened (P < 0.05) after inhibiting hsa_circ_0001922; the expression of E-cadherin mRNA increased (P < 0.05) while the mRNA level of Vimentin decreased (P < 0.05). The results of Western blot were consistent with the above (both P < 0.05). Conclusion The circular RNA hsa_circ_0001922 may promote the proliferation, migration and invasion of PC-3 cells through the EMT pathway.

ObjectiveTo investigate the association of high-density lipoprotein cholesterol (HDL-C) with the prognosis of patients with alcohol-related hepatocellular carcinoma (HCC) after radical treatment. MethodsA retrospective analysis was performed for the clinical data of 43 patients with alcohol-related HCC who were admitted to The Fifth Medical Center of Chinese PLA General Hospital and underwent radical treatment from January 2008 to July 2015, and according to HDL-C level, the patients were divided into normal group with 26 patients and abnormal group with 17 patients. The two groups were compared in terms of basic information, laboratory markers, imaging indices, Barcelona Clinic Liver Cancer tumor stage, and Child-Pugh class of liver function. The t-test test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves and the log-rank test was used for comparison between groups. Univariate and multivariate Cox proportional hazards models were used to analyze independent risk factors for prognosis. ResultsThere was a significant difference in prealbumin between the two groups (162.38±60.86 mg/L vs 120.06±64.08 mg/L, t=2.184, P=0.035). Number of tumors (hazard ratio ［HR］=2.839, 95%confidence interval ［CI］: 1.120~7.200,P=0.028), tumor size (HR=2.634, 95%CI: 1.062~6.529,P=0037), and HDL-C level (HR=2.400, 95%CI: 1.040~5.537,P=0.040) were independent risk factors for the overall survival of patients with alcohol-related HCC. There were significant differences in 1-, 3-, and 5-year cumulative survival rates between the normal group and the abnormal group (88.5%/72.4%/55.7% vs 70.6%/43.7%/17.5%, χ2=5.881, P=0.015). ConclusionThe reduction in HDL-C level might indicate poor prognosis of patients with alcohol-related HCC.