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.

Objective To explore the clinical efficacy of azithromycin sequential therapy(AST)combined with infantile massage(IM)in children with chronic cough after mycoplasma pneumoniae infection(CCAMP)phlegm-heat closed lung syndrome(PHCLS),and provide a new scheme for the clinical diagnosis and treatment of CCAMP.Methods The study retrospectively collected children with CCAMP-PHCLS diagnosed in the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from March 2022 to March 2023.According to the treatment regimes,the children were divided into AST group and AST+IM group.The differences in cough symptoms integral and inflammatory factors(IL-6,PCT and CRP)between the two groups of CCAMP-PHCLS children were observed and compared.In addition,the total time to disappearance of clinical symptoms/signs,negative conversion of serum MP antibody(MP-IgM),total treatment response rate and incidence of adverse reactions were compared between the two groups.Results A total of 98 CCAMP-PHCLS children were collected,49 in each group.There were no significant differences between the AST+IM group and AST group in daytime cough symptoms points,nighttime cough symptoms points,serum IL-6 content,serum PCT content,and serum CRP content before treatment(P>0.05).After treatment,the daytime cough symptoms,serum IL-6,serum PCT and serum CRP in both groups significantly decreased compared to before treatment,and the above indicators in the AST+IM group were lower than those in the AST group(P<0.05).In terms of clinical characteristics,CCAMP-PHCLS children lost cough,fever and lung rales in the AST+IM group were shorter than the AST group(P<0.05),and the MP-IgM conversion rate was significantly higher than the AST group(P<0.05).In addition,in terms of clinical efficacy and safety,the total response rate of CCAMP-PHCLS in the AST+IM group was significantly higher than that in the AST group(P<0.05),while the incidence of adverse reactions of CCAMP-PHCLS in the AST+IM group was significantly lower than that in the AST group(P<0.05).Conclusion IM combined with AST has significant efficacy and high safety in children with CCAMP.The potential possible mechanism is that IM mediate production of inflammatory factors,and improves airway inflammation,thus alleviating clinical symptoms and signs.

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.

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.

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).

Primary liver cancer (PLC) has the features of insidious onset and difficulties in early diagnosis, with limited and ineffective therapeutic options. Chimeric antigen receptor (CAR) T-cell therapy is a genetically modified T-cell therapy that recognizes tumor-specific antigens and activates T cells to exert a tumor-killing effect. CAR T-cell therapy has made great progress in the treatment of hematological tumors and has achieved a good clinical effect in the field of solid tumors in recent years, and although CAR T-cell therapy has developed from the first to the fifth generation, there are still many challenges in the field of solid tumors. This article comprehensively reviews the mechanisms of CAR T-cell therapy for PLC and related research advances, including the main targets such as GPC3, AFP, MUC1, and NKG2D in CAR T-cell therapy for PLC, CAR T-cell therapy for PLC and oncolytic virus, and combined treatment with immune checkpoint inhibitors, as well as the advances in the biological, preclinical, and clinical studies on these targets and treatment modalities and the challenges and solutions for CAR T-cell therapy in the treatment of PLC, so as to provide a reference for the future clinical development of CAR T-cell therapy in liver cancer.

Objective:To explore the molecular mechanism of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair for depression and Alzheimer disease (AD) with the same treatment through network pharmacology. Methods:Effective components of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were retrieved from TCMSP, TCMID and ETCM databases. The disease targets of depression and AD were retrieved from GeneCards, TTD and CTD databases. Targets of action of drugs on active components were predicted through SwissTargetPrediction, and then the intersection targets of medicinal pair and the diseases were taken. Cytoscape 3.6.1 was used to construct the interaction network of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair on "component-common target-disease". The enrichment analysis of GO function and KEGG pathway was carried out with the help of Metascape platform, and molecular docking verification was carried out. Results:Through searching the databases and literature, 78 compounds in Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were obtained, corresponding to 41 targets of different diseases with the same treatment. The GO function was mainly concentrated in response to lipopolysaccharide and cellular response to nitrogen compound. The KEGG pathway was mainly concentrated in lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on. The core targets were PTGS2, ESR2, etc. Molecular docking showed that most of the core components could form stable conformation with the core targets. Conclusions:Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair has the characteristics of multi-component, multi-target and multi-pathway in the same treatment of depression and AD. Through their core components of senegenin, 1-carbobutoxy-β-carboline, 6-hydroxy-1,2,3,7-tetramethoxyxanthone, kaempferol and etc., the pair can act on PTGS2 and other targets, regulate lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on, and play a therapeutic role in depression and Alzheimer's disease with the same treatment.

Objective:To investigate the pharmacological effects and molecular mechanisms of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma for the treatment of ulcerative colitis based on the network pharmacology and molecular docking methods.Methods:TCMSP database was applied to get the active components of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma, and SwissTargetPrediction database was applied to predict their targets; OMIM, DrugBank, TTD, PharmGKB and GeneCards databases were used to obtain the disease targets of ulcerative colitis; Venn Diagram website was used to draw the venn diagrams of drug-disease intersecting targets; drug-component-target network diagrams were created in Cytoscape 3.8.2, and the targets and active components with high correlation in the network were analyzed; protein interaction networks of intersecting targets were constructed using the String platform, and the NetworkAnalyzer plug-in in Cytoscape 3.8.2 was applied to Topology analysis and screening of core targets were performed using the Metascape platform; GO and KEGG analysis were performed using the Metascape platform; molecular docking validation was performed using vina inside pyrx software.Results:A total of 14 active components of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma were screened, and the core components were kaempferol, stigmasterol, hederagenin, α-amyrin; 148 drug targets, 1 307 disease targets and 50 drug-disease intersection targets were obtained; there were 23 core points such as ESR1, PTPN2, PIK3R1, SRC, EGFR, and AKT1. The results of GO analysis indicated that the targets were mainly located in the cell membrane region and were involved in the regulation of biological functions such as monooxygenase and oxidoreductase activities, as well as the regulation of hormones and lipids, etc. The results of KEGG pathway enrichment analysis revealed that the main enrichment pathways were PI3K-Akt, JAK-STAT and MAPK signaling pathways. The molecular docking results showed that the main components, kaempferol and serpentine, could bind stably to several core targets such as PIK3R1 and ESR1. Relevant literature has verified the pharmacological action of each core component.Conclusions:Kaempferol, hederagenin and α-amyrin are the active components of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma. They play therapeutic roles in improving immune dysregulation, reducing inflammatory response, inhibiting epithelial cell apoptosis and repairing mucosal damage by regulating targets such as PIK3R1, PTPN2 and ESR1, and modulating PI3K-Akt pathway, JAK-STAT pathway and MAPK pathway.

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.

Bile acid metabolism, gut microbiota, and bile acid receptors are involved in the development and progression of hepatocellular carcinoma (HCC). There are substantial increases in the levels of some bile acids, such as glycocholic acid, taurocholic acid, and taurochenodeoxycholic acid, in the liver tissue of HCC mice and the serum and feces of HCC patients. Bile acid metabolism due to the imbalance of the abundance of bacteria producing bile salt hydrolases and Clostridium in the intestine and the change in immune microenvironment may also promote the development of HCC. Moreover, some bile acid receptors, such as farnesoid X receptor, G protein-coupled bile acid receptor 1, pregnane X receptor, constitutive androstane receptor, and sphingosine-1-phosphate receptor 2, have been shown to participate in the development and progression of HCC through various pathways. Each link of bile acid metabolism plays a different role in the progression of HCC, and a systematic elaboration of the interaction between these links may help to deepen the understanding of the pathogenesis of HCC and develop the biological targets for early diagnosis, prognosis prediction, and precise treatment.