Comprehensive treatment strategy for hepatocellular carcinoma based on surgical treatment in the era of targeted therapy and immunotherapy / 中华消化外科杂志

Hepatocellular carcinoma is still a severe threat to people′s health of China. Most patients have advanced disease at the time of first diagnosis and lose the opportunity of radical surgery. In the past, the traditional medical drug treatment and radiotherapy are ineffective, which make the treatment of hepatocellular carcinoma into a bottleneck. With the emergence of target therapy represented as tyrosine kinase inhibitors and immunotherapy represented by programmed death-1 antibody and programmed death-ligand 1 antibody, the treatment of hepatocellular carcinoma has entered a new era and patients with advanced hepatocellular carcinoma have seen a new hope. The systemic therapy represented by target therapy and immunotherapy has not only greatly improved the survival of patients with advanced hepatocellular carcinoma, but also changed the treatment concept of hepatocellular carcinoma from single-drug therapy to combined therapy with multiple means. The treatment of hepatocellular carcinoma has changed from the era of surgery as the king to the era of surgery as the mainstay of whole-process management and comprehensive treatment. The authors review previous studies and their own experience to elaborate on the comprehensive treat-ment strategy for hepatocellular carcinoma based on surgical treatment in the era of targeted therapy and immunotherapy.

Diagnosis and treatment of kidney transplant recipients infected with novel coronavirus Omicron variant: a single-center experience of 181 cases / 中华器官移植杂志

Objective:To explore the risk factors associated with the clinical progression of COVID-19 infection in kidney transplant(KT)recipients during the spread of Omicron variant and evaluate the effectiveness of anti-RNA virus agents in blocking the clinical progression of COVID-19 in these recipients.Methods:Retrospective analysis was conducted for the clinical data on COVID-19 infection in 232 KT recipients followed up from December 4, 2022 to January 31, 2023 at Department of Renal Transplantation, Organ Transplantation Center, Beijing Tsinghua Changgung Hospital.Inclusion criteria were age ≥18 years and stable kidney function without renal replacement therapy.The follow-up time was 30 days after COVID-19 infection.Based upon whether or not there was an infection of COVID-19, KT recipients were divided into two groups of infection(181 cases)and non-infection(51 cases). In infection group, recipients were further assigned into two sub-groups of disease progression(n=23)and stable(158 cases)according to whether or not there was a progression to severe disease.Various factors such as gender, age, body mass index(BMI), time after transplantation, underlying diseases(history of hypertension, diabetes mellitus, coronary heart disease & chronic lung disease), smoking history and dosing of anti-RNA virus agents were collected.Pearson χ2 test or Fisher's exact probability method was utilized for examining enumeration data while Mann-Whitney U test for measurement data.Univariate Logistic regression analysis was conducted and variables with P<0.05 were included into multifactorial Logistic regression analysis to identify independent risk factors for clinical progression of COVID-19 infection in KT recipients. Results:Among 232 KT recipients, infection rate of COVID-19 was 78.0%(181/232). The clinical classification was mild(112 cases), moderate(46 cases), severe(21 cases)and critical(n=2 cases). The severe rate was 12.7%(23/181). After infection with COVID-19, the proportion of KT recipients aged ≥65 years progressing from mild/moderate to severe was higher than those aged<65 years[38.5%(5/13)vs 10.7%(18/168)]. The difference was statistically significant( P=0.014); The proportion of diabetic KT recipients progressing from mild/moderate to severe was higher than those without diabetes[19.1%(13/68)vs 8.8%(10/113)]. The difference was statistically significant( P=0.045). Univariate Logistic analysis showed similar results.Age≥65 years( OR=5.21, 95% CI: 1.54-17.64, P=0.008)or diabetes mellitus( OR=2.44, 95% CI: 1.003-5.911, P=0.049)were the risk factors for COVID-19 infection recipients progressing from mild/moderate to severe disease.Multivariate Logistic analysis revealed that age ≥65 years( OR=4.03, 95% CI: 1.14-14.34, P=0.031)was an independent risk factor for COVID-19 infection recipients progressing from mild/moderate to severe.Among 181 cases of COVID-19 mild/medium infected patients, 18 cases received nimativir/ritonavir and 10 cases had azvudine for anti-RNA virus treatment.However, none of them progressed to severe; 153 cases did not use anti-RNA virus drugs and 23 cases(15.0%)progressed to severe disease and the difference was statistically significant( P=0.028). Among 23 severe cases, 14 cases received nirmatrelvir/ritonavir and 2 cases had azivudine for anti-RNA virus treatment.The former did not progress to critical disease while 1 case in the latter progressed to critical illness and death; 1/7 recipients not using anti-RNA virus agents progressed to critical illness and died while another 6 cases did not progress to critical illness. Conclusions:KT recipients aged ≥65 years or diabetes mellitus have a greater risk of progression from mild/moderate to severe disease after COVID-19 infection.Among them, age ≥65 years is an independent risk factor for patients with COVID-19 infection to progress from mild/moderate to severe.Antiviral treatment with nirmatrelvir/ritonavir or azivudine in KT recipients during mild/moderate stage of COVID-19 infection can significantly reduce the rate of severe disease.Treatment with Nirmatrelvir/Ritonavir is still effective in the severe stage.

Gene transcriptome sequencing in schizophrenia / 中华神经医学杂志

Schizophrenia is a mental illness that can seriously affect a patient's cognitive and social communication. Because schizophrenia is affected by multiple factors, the cause of schizoophrenia is still unclear. Gene transcriptome sequencing (RNA-seq) is a new research method to study the morphological structure, and gene differential expression and function; RNA-Seq can sequence hundreds of thousands to millions of DNA molecules at a time, providing more effective data for biological transcription information. This paper reviews the principles and technical characteristics of RNA-Seq, and application of RNA-Seq in schizophrenia, which provide new ideas for schizophrenia research.

RNA-seq analysis of amygdala tissue in social isolation rearing models of schizophrenia / 中华神经医学杂志

Objective:To investigate the gene transcription level changes in the amygdala of social isolation rearing models of schizophrenia to determine the pathogenic genes and their related pathways of schizophrenia.Methods:A total of 29 3-week-old SPF C57BL/6J male mice were randomly divided into control group ( n=16) and model group ( n=13); 4 mice were raised in each transparent mouse cage in the control group, and 1 mouse was raised in each transparent mouse cage in the model group; mice in each cage could see their surrounding mice but could not touch each other. Mice in both groups were fed for 4 weeks and then subjected to open field experiment, pre-pulse inhibition experiment and new object recognition experiment within one week. After the experiment, mice were sacrificed by spinal dislocation, and the amygdala was taken for transcriptome sequencing. The topGO software was used for gene ontology (GO) functional enrichment analysis of differentially expressed genes (DEGs), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using KEGG database. Results:(1) Animal experiment: compared with the control group, the model group had significantly increased movement distance in the open field experiment ([1 239.20±106.35] m vs. [1 845.53±143.65] m, t=3.464, P=0.002), significantly decreased activity time in the central region 5 min before experiment ([13.15±1.41] s vs. [8.47±1.19]) s, t=2.464, P=0.020). Compared with the control group, the model group had significantly lower percentage of deficient prepulse inhibition (PPI) of 78 dB ([22.28±1.53] % vs. [14.59±2.75] %, t=2.629, P=0.013), and deficient PPI of 88 dB ([32.83±3.39] % vs. [18.44±3.07] %, t=3.081, P=0.005). Compared with the control group, the model group had significantly decreased ratio of time exploring new objects/time exploring former objects ([80.5±2.2]% vs. [71.0±3.6]%, t=2.356, P=0.026). (2) Bioinformatics analysis: a total of 96 DEGs were found, of which 42 were with up-regulated expressions ( Th, Crlf1, etc.), and 54 were with down-regulated expressions ( Prkcd, etc.). Th and Crlf1 were positively correlated ( r=0.940, P=0.018). GO enrichment results suggested that DEGs were enriched in projection function of plasma membrane boundary cells, neuronal differentiation, and cell apoptosis. KEGG enrichment results suggested that DEGs were enriched in WNT signaling pathway, apoptosis pathway and tyrosine metabolism pathway. Protein network interaction analysis suggested that Wnt6, Tcf712, Pitx2, Tcf7 and Cd4 were key proteins. Conclusion:DEGs such as Th, Prkcd, Lrrc74b, Fadd, Wnt6, Ror2, Notum, and Tcf7l2, and their related signaling pathways may be related to schizophrenia in the amygdala of social isolation rearing mice.