Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

O-acetyl-L-homoserine (OAH) is a promising platform compound for the production of L-methionine and other valuable compounds, while its low yield and low conversion rate limit the industrial application. To solve these problems, we constructed a strain for high OAH production with the previously constructed L-homoserine producer Escherichia coli HS33 as the chassis by systematic metabolic engineering. Firstly, PEP accumulation, pyruvate utilization, and OAH synthesis pathway (overexpressing aspB, aspA, and thrA^C1034T) were enhanced to obtain an initial strain accumulating 13.37 g/L OAH. Subsequently, the co-factor synthesis genes were integrated to supply reducing power and energy, which increased the yield to 15.79 g/L. The OAH yield of the engineered strain OAH28 was further increased to 17.49 g/L by strengthening the acetic acid reuse pathway, improving the supply of acetyl-CoA, and regulating the expression of MetX from different sources. Finally, in a 5 L fermenter, OAH28 achieved an OAH titer of 47.12 g/L, with a glucose conversion rate of 32% and productivity of 0.59 g/(L·h). The results lay a foundation for increasing the OAH production by metabolic engineering and give insights into the industrial production of OAH.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Homoserine/biosynthesis* ; Fermentation

Objective:To translate the Self-Confidence Scale for Clean Intermittent Self-Catheterization (SCSCISC) into Chinese and test its reliability and validity.Methods:Following the Brislin questionnaire translation principles, the English version of SCCSISC was translated, back translated, culturally adapted, consulted with experts, and pre-surveyed to form the Chinese version of SCCSISC. From June to September 2023, 237 patients with neurogenic bladder admitted to the First Hospital of Shanxi Medical University were selected as survey subjects by the convenient sampling method. The critical ratio method was used for project analysis, and Cronbach's α coefficient, split half reliability, and test-retest reliability were used to evaluate the reliability of the scale. Content validity and construct validity were used to test the validity of the scale.Results:The Cronbach's α coefficient of the Chinese version of SCCSISC was 0.976, the split half coefficient was 0.962, and the test-retest reliability was 0.876. The item-level content validity index ( I- CVI) of the Chinese version of SCCSISC was 0.86 to 1.00, and the scale-level content validity index ( S- CVI) was 0.93, with Kappa consistency coefficients above 0.74. Two common factors were extracted through exploratory factor analysis, with a cumulative variance contribution rate of 73.42%. Conclusions:The Chinese version of SCCSISC has good reliability and validity, and can be used as a tool for self-confidence measurement of clean intermittent self-catheterization among patients with neurogenic bladder in China.

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Proteomics ; COVID-19/prevention & control* ; Vaccination ; Antibodies ; Antibodies, Viral ; Antibodies, Neutralizing

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine and metabolic disease, and its pathogenesis is closely related to inflammation, insulin resistance, and metabolic disorders. Bilirubin is the final product of the destruction and degradation of senescent red blood cells in the body. In addition, bilirubin can be not only used to evaluate liver function damage and cytotoxicity, but also can anti-inflammatory, antioxidant, alleviate metabolic disorders, etc. Recently, studies have found a certain correlation between low levels of bilirubin and PCOS: the level of bilirubin in patients with PCOS is low, and the anti-inflammatory and antioxidant properties of bilirubin may play a protective role in the pathogenesis of PCOS.

Objective:To translate the Intermittent Catheterization Difficulty Questionnaire (ICDQ) into Chinese, and to test its reliability and validity in neurogenic bladder patients.Methods:After translation, back-translation, cross-cultural debugging, expert consultation and pre-investigation, a Chinese version of ICDQ was formed. A total of 248 patients with neurogenic bladder clean intermittent self-catheterization who were treated and followed up in the First Hospital of Shanxi Medical University in October 2022 were selected as research objects by the convenient sampling method, and the Chinese version of ICDQ was used for investigation. The critical ratio method was used for project analysis. Content validity and structure validity were used to test the validity of the questionnaire. Cronbach's α coefficient, split half reliability coefficient and retest reliability coefficient were used to test the reliability of the questionnaire. A total of 248 questionnaires were sent out in this study, and 238 were effectively collected, with a recovery rate of 95.97% (238/248) .Results:The Cronbach's α coefficient of the Chinese version of ICDQ was 0.857, the split half coefficient was 0.711, and the retest reliability coefficient was 0.954. The content validity index of the Chinese version of ICDQ item level was 0.860 to 1.000, and the content validity index of the scale level was 0.930. Seven common factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 77.38%. The results of confirmatory factor analysis showed RMSEA < 0.080, GFI, AGFI, TLI, CFI > 0.800. Conclusions:Through confirmatory factor analysis, the Chinese version of ICDQ shows that the model fitting indicators of the scale meet the corresponding requirements, indicating that the scale has high structural validity and overall model fitting. It can be used as an evaluation tool for intermittent self catheterization difficulties in patients with neurogenic bladder.

OBJECTIVE To eval uate the effectiveness ，safety and economy of deferasir ox for the treatment of iron overload in thalassemia with rapid health technology assessment ，and to provide evidence-based basis for rational clinical use. METHODS Retrieved from Chinese and English database/website as PubMed ，Embase，Cochrane Library ，NHS EED ，CADTH，CNKI and Wanfang database ，health technology assessment （HTA），systematic evaluation/meta-analysis and pharmacological studies about deferasirox versus deferoxamine/deferiprone for the treatment of iron overload in thalassemia were collected from the inception to June 2021. Based on literature screening and data extraction ，the quality of literature about HTA reports ，systematic evaluation/ Meta-analysis and pharmacoeconomic research were evaluated with HTA checklist ，A Measurement Tool to As sess Systematic Reviews，standard scale of economic evaluation report. The effectiveness and safety results were described quantitatively ，and the economic evaluation results were described qualitatively. RESULTS One HTA report ，five systematic evaluation/meta-analysis and five pharmacoeconomic studies were selected from 1 569 literature. Included HTA reports ， systematic evaluation/meta-analysis，pharmacoeconomic studies were high in quality. Most studies reported that 30 mg/（kg·d） deferasirox was E-mail：aydgs@126.com better than deferoxamine in reducing the levels of s erum ferritin and liver iron overload ；ADR induced by deferasirox were mainly gastrointestinal irritation symptoms ，skin itching ，joint pain，transaminase elevation ，etc.，which generally did not affect subsequent treatment. There was no statistical significance in severe ADR between deferoxamine group and deferasirox group [RR ＝0.96，95％CI（0.85，1.08），P＝0.52]. Compared with deferoxamine，deferasirox had higher cost-effectiveness ；but deferasirox was less likely to be cost-effective than deferiprone. CONCLUSIONS Deferasirox has good effectiveness and safety for iron overload in thalassemia ，and has good economic advantages in Britain and Iran ，compared with deferoxamine.

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 for the mutation types of the FOXL2 in 4 families with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), and explore their genotype-phenotype correlations.Methods:To retrospectively analyze the result of FOXL2 gene detection by fluorescence quantification PCR, Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA) in probands and families of BPES from January 2018 to January 2021, obtain mutation sites of pathogenic genes.Results:4 BPES families (8 cases) including 4 males and 4 females, with age ranged form 4 to 52 years (mean 24). The proband of family 1 has fragment deletion of Chr3∶138, 944, 224-138, 947, 137 region of FOXL2 gene. Proband of family 2 has heterozygosity deletion upstream of the 5’end of FOXL2 gene. There are missense mutations of c. 241 T>C(p.Y81 H)in proband and affected mother of family 3. There are c. 672_701dup(p.A224_A234dup) in-frame duplication mutations in proband and affected mother of family 4.Conclusions:Identification of causative mutations in the BPES patients has provided a basis for genetic counseling and reproductive guidance. The fragment deletion of Chr3∶138, 944, 224-138, 947, 137 region of FOXL2 gene and heterozygosity deletion upstream of the 5’end of FOXL2 gene are all new mutations that have not been reported. The novel mutations have enriched the mutation spectrum of the FOXL2 gene.