ObjectiveTo evaluate the efficacy and safety of first-line transcatheter arterial chemoembolization （TACE） combined with targeted therapy and immunotherapy in the treatment of patients with stage Ⅱb/Ⅲa hepatocellular carcinoma （HCC） based on China Liver Cancer Staging （CNLC）. MethodsA total of 198 patients who received first-line TACE combined with targeted therapy and immunotherapy or received TACE alone from January 2015 to December 2022 in the First Affiliated Hospital of Soochow University were enrolled in this study， and after propensity score matching， there were 50 patients in combination group and 50 patients in TACE group. The Kaplan-Meier method was used to calculate median overall survival （mOS） and median progression-free survival （mPFS）. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate objective response rate （ORR） and disease control rate （DCR）， and Common Terminology Criteria for Adverse Events v5.0 was used to evaluate adverse events. The chi-square test was used for comparison of categorical data between two groups； the t-test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to estimate survival time and calculate 95% confidence interval （CI）， and the Log-rank test was used for comparison of mOS and mPFS between two groups. ResultsThe combination group had an mOS of 30.1 months （95%CI： 21.9‍ ‍—‍ ‍38.3）， and the TACE group had an mOS of 14.5 months （95%CI： 11.0 ‍—‍‍ ‍18.0）， with a significant difference between the two groups （χ²=17.8， P<0.001）； the combination group had an mPFS of 10.3 months （95%CI： 8.8‍ ‍—‍ ‍11.8）， and the TACE group had an mPFS of 7.1 months （95%CI： 5.8‍ — ‍8.4）， with a significant difference between the two groups （χ²=10.4， P<0.001）. There were significant differences between the combination group and the TACE group in ORR （84% vs 58%， P<0.05） and DCR （94% vs 80%， P<0.05）. There was no significant difference between the combination group and the TACE group in the incidence rate of adverse events （24% vs 16%， P=0.317）， and no adverse event-related deaths were observed in either group. ConclusionCompared with TACE alone， TACE combined with targeted therapy and immunotherapy has a better efficacy in the treatment of patients with CNLC stage Ⅱb/Ⅲa HCC， without increasing the incidence rate of severe adverse events.

BACKGROUND:At present,wrist protection products designed in and outside China have not solved the contradiction between protecting the wrist joint from injury and maintaining the flexible movement of the wrist joint. OBJECTIVE:To investigate the biomechanical mechanism of dorsiflexion injury of the wrist joint in elderly people after falls,and to provide a biomechanical basis for the prevention and treatment of wrist injury in elderly people after falls. METHODS:A 65-year-old man was selected to obtain the original data by uninterrupted CT scan of the middle and lower 2/3 of his left forearm up to the end of the finger.A finite element model of wrist dorsiflexion was established using ANSYS 12.0 finite element software.The palm surface of the model was constrained,and the model at a velocity load of 2 m/s in the direction of vertical downward was given to simulate the injury state of the palm when the elderly fall.The stress distribution of the soft tissues and bones of the wrist joint and the change of the stress with time were observed after the load was applied. RESULTS AND CONCLUSION:(1)A realistic and effective finite element model of the dorsal extension position of the wrist joint of the elderly was established.The soft tissue stresses were mainly concentrated in the small fissure of the palm and the dorsal side of the wrist after loading.The skeletal stresses were mainly concentrated in the lower end of the ulnar radius dorsally.The stresses in the lower end of the radius were the greatest.The palmar stresses were mainly concentrated in the middle and lower 1/3 of the radius and the hook bone.The stress distribution of the ulnar radius was asymmetric,and the stresses in the radius were more concentrated.(2)The results of the study are consistent with the clinical situation of a fallen wrist injury in elderly people,and can be used to explain the mechanism of wrist dorsiflexion injury,which can provide the biomechanical basis for the design of wrist protection devices that can be used to prevent wrist injury induced by falling and the treatment of wrist injury in elderly people.

BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.

ObjectiveTo investigate the ability of the modified albumin-bilirubin （mALBI） grade in predicting the prognosis of patients with Child-Pugh A unresectable hepatocellular carcinoma （uHCC） after transcatheter arterial chemoembolization （TACE） combined with immunotherapy and anti-angiogenic drugs （hereafter referred to as targeted immunotherapy）. MethodsA retrospective analysis was performed for the data of 76 patients with Child-Pugh A uHCC who met the inclusion criteria and underwent TACE combined with targeted immunotherapy in The First Affiliated Hospital of Soochow University from January 2020 to January 2023， and according to the mALBI grade， they were divided into mALBI 1/2a group with 38 patients and mALBI 2b group with 38 patients. The primary endpoint was overall survival （OS）， and the secondary endpoints were progression-free survival （PFS）， objective response rate （ORR）， and disease control rate （DCR）. Evaluation criteria included complete remission， partial remission， stable disease， and progressive disease. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical variables between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of median OS （mOS） and median PFS （mPFS） between groups. The univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors for prognosis. ResultsThere were significant differences in albumin and tumor burden between the two groups （both P<0.05）. The 76 patients had an mOS of 25.2 months （95% confidence interval ［CI］： 18.4 — 32.0）， an mPFS of 9.4 months （95%CI： 7.1 — 11.7）， an ORR of 63.2%， and a DCR of 82.9%. The mOS was 30.1 months （95%CI： 19.8 — 40.4） in the mALBI 1/2a group and 19.5 months （95%CI： 7.1 — 31.9） in the mALBI 2b group， and there was a significant difference in mOS between the two groups （χ²=4.490， P=0.034）. The mALBI 1/2a group had an mPFS of 10.2 months （95%CI： 8.4 — 12.0）， an ORR of 71.1%， and a DCR of 86.8%， while the mALBI 2b group had an mPFS of 7.6 months （95%CI： 4.6 — 10.6）， an ORR of 55.3%， and a DCR of 78.9%； there were no significant differences in mPFS， ORR， and DCR between the two groups （all P>0.05）. ECOG status， tumor burden， mALBI grade， portal vein invasion， and extrahepatic metastasis were independent risk factors for mOS in patients undergoing TACE combined with targeted immunotherapy （all P<0.05）. There were no treatment-related deaths. ConclusionThe mALBI grade has a good value in predicting the survival of patients with Child-Pugh A uHCC undergoing TACE combined with targeted immunotherapy.

Transcriptomics technology has shown remarkable application effects in multiple disease fields, but its application in severe burns, especially in the field of burn sepsis, is still superficial. The use of transcriptomics and big data methods to solve the long-standing challenges of severe burns, especially in the field of burn sepsis, has great prospects and significance. This article comprehensively discusses the application value, current status, and future prospects of transcriptomics in the study of severe burns, especially burn sepsis, in order to provide new ideas for the treatment of severe burns.

Objective:To establish a general method for the simultaneous determination of hydroxyphenyl esters and quaternary ammonium bacteriostatic agents in eye drops.Methods:The chromatographic analysis was per-formed on an Agilent C18 column(4.6 mm ×250 mm,5 μm)with 1％triethylamine solution(pH adjusted to 5.0 with phosphoric acid)as mobile phase A and methanol as mobile phase B.Gradient elution was performed at col-umn temperature of 40 ℃.The detection wavelength was 214 nm,the flow rate was 1 mL·min-1,and the injec-tion volume was 20 μL.Results:Methylparaben,ethylparaben,propylparaben,butylparaben,benzalkonium chlo-ride and benzalkonium bromide were 0.11-559.0,0.10-513.0,0.10-258.8,0.11-270.5,1.07-537.0 and 1.03-512.8 μg·mL-1,respectively.The linear range was good(r＞0.999).The average recoveries of meth-ylparaben,benzalkonium bromide and benzalkonium chloride were 104.7％(RSD=1.3％),102.6％(RSD=1.1％)and 100.9％(RSD=1.1％),respectively.The contents of bacteriostatic agent in 100 batches of eye drops from 36 varieties of 12 enterprises were determined,and the accurate results were obtained.Conclusion:This meth-od provides a reference for the content quality control and safety evaluation of bacteriostatic agents in eye drops.

Abstract OBJECTIVE To analyze the inflammation-related molecular targets of Pien Tze Huang in the treatment of hepatocellular carcinoma and to preliminary explore its mechanism. METHODS Obtain the ingredients and targets of Pien Tze Huang through TCMSP and BATMAN databases. Obtain the disease targets of hepatocellular carcinoma through Genecards, OMIM and TCGA databases. Take the intersection of compound targets and disease targets to get Pien Tze Huang’s target for the treatment of hepatocellular carcinoma. Obtain the related genes of inflammation pathway from the GSEA database, and then analyze the correlation between Pien Tze Huang’s therapeutic targets for hepatocellular carcinoma and inflammation-related genes to screen out inflammation-related targets, and explore the mechanism through GO and KEGG enrichment analysis. Then, single-factor cox analysis and LASSO regression were performed to construct related prognostic models. The 10 core targets were screened out through the protein-protein interaction(PPI) network. The model gene and the core target were intersected. The core compounds were screened out through the drug-compound-target network. Perform molecular docking verification between the core compound and the target. Construct a nomogram to assess the prognosis of patients. RESULTS Obtained 162 Pien Tze Huang targets, 522 hepatocellular carcinoma targets, 20 Pien Tze Huang therapeutic targets for hepatocellular carcinoma, and 16 inflammation-related targets. The enrichment analysis of GO and KEGG showed that their effects were mainly through biological functions such as monooxygenase activity, oxidoreductase activity, and chemical carcinogenesis-receptor activation. The ROC curve of the prognosis model calculated AUC as 0.780 in 1 year, 0.688 in 3 years, and 0.642 in 5 years, indicating that the model was reliable. The prognostic model intersects with the core target of PPI to get 5 targets: PON1, IGF2, NQO1, CCNB1 and IGFBP3. The nomogram was constructed using CCNB1, NQO1, and T staging, and its c-index was 0.726, indicating the reliability of the model. The drug-compound-target network suggested that quercetin was the core compound and targets the above two genes. CONCLUSION Pien Tze Huang’s treatment of hepatocellular carcinoma mainly uses quercetin to target CCNB1 and NQO1 to exert anti-inflammatory effects, and its prognostic model can be used to predict the survival of patients.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To screen the differentially co-expressed genes in the mRNA expression profile of colon cancer by combined application of weighted gene co-expression network analysis(WGCNA) and differential gene expression analysis, and to analyze the relationship between differentially co-expressed genes and prognosis.Methods:The transcriptomics data of the cancer genome atlas (TCGA)-colon adenocarcinoma (COAD) dataset and chip expression profile data of GSE68468 dataset were downloaded from TCGA and gene expression omnibus (GEO) databases based on bioinformatics methods, and differentially expressed gene (DEG) and the most significantly related weighted gene modules between normal tissues and colon cancer tissues were screened. Then, the differentially co-expressed genes related to colon cancer were screened out according to the intersection of differential genes and weighted genes. A protein-protein interaction (PPI) network was constructed, and the top ten core differentially co-expressed genes according to the maximal clique centrality (MCC) score were screened out by MCC calculation method. The expression of core genes in normal tissues and colon cancer tissues were further verified by TCGA-COAD dataset. Kaplan-Meier survival analysis was used to investigate the correlation between core genes and overall survival time and disease-free survival time of patients. The survival-related differentially co-expressed genes were verified by immunohistochemical staining in human protein atlas (HPA) database.Results:A total of 3 481 DEG of the TCGA-COAD dataset and 7 275 DEG of the GSE68468 dataset were screened out, and totally 237 differentially co-expressed genes were obtained. Ten core differentially co-expressed genes were obtained by the MCC calculation method of the PPI network, which were chloride channel accessory 1 ( CLCA1), mitogen-activated protein kinase 3, glucagon ( GCG), solute carrier family 26 member 3 ( SLC26 A3), nuclear receptor subfamily 1 group H member 4 ( NR1 H4), fatty acid binding protein 1 ( FABP1), guanylate cyclase activator 2A ( GUCA2 A), uridine diphosphate glucuronosyltransferase family 2 member A3 ( UGT2 A3), carnitine palmitoyltransferase 2 ( CPT2) and membrane spanning 4-domains A12 ( MS4 A12). Compared with those of the normal tissues, CLCA1, GCG, SLC26 A3, NR1 H4, FABP1, GUCA2 A, UGT2 A3, CPT2 and MS4 A12 of colon cancer tissues of the TCGA-COAD dataset were all down-regulated (all P<0.05). Among them, the overall survival time and disease-free survival time of patients with colon cancer with high expression of CLCA1 were both longer than those with low expression (both P<0.05). The results of immunohistochemical staining also verified the accuracy of the results at the protein level. Conclusions:CLCA1 may play a key role in the development of colon cancer, and it can be used as a potential biomarker for further diagnosis and treatment.

Objective:To establish virus culture method and full genome sequencing method for severe acute respiratory syndrome coronavirus (2019-nCoV), and to illuminate the variation of 2019-nCoV.Methods:The pharyngeal swab specimens were inoculated into Vero-E6 cells for isolation, and the cytopathic effect were observed day by day, and the result of virus isolation were confirmed by Real-Time RT-PCR. Some isolated viruses were diluted 10 times to detect the virus titer. Full-genome of 2019-nCoV was sequenced with the whole genome capture technology and next generation sequencing technology. Phylogenetic analysis and molecular characterization for obtained 2019-nCoV sequences were undertaken.Results:Twenty-two 2019-nCoV strains were isolated with Vero-E6 cell line in the Biosafety Level-3 Laboratory (BSL-3). Eighteen full-genome sequences obtained (almost 29 000 nucleotide) were analyzed with 99.94%~100% identity and 28 nucleotides and 20 amino acids variations. Phylogenetic analysis showed that the 2019-nCoV sequences belonged to different clades, including clade S and clade L with Europe lineage L. I and Europe lineage L. II.1. Furthermore, 5 of 18 2019-nCoV harbor the D614G mutation.Conclusions:2019-nCoV were successfully isolated with Vero-E6 cells, and partially illuminated the phylogenetic characteristics, which provided a basis for subsequent drug screening and biological characteristics research. Continuous monitoring and analysis of the sequences of new cases would be vital to understand the genetic evolution and rates of substitution of the 2019-nCoV.