Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

INTRODUCTION: Ultrasonography (US) is the current standard of care for imaging surveillance in patients at risk of hepatocellular carcinoma (HCC). Magnetic resonance imaging (MRI) has been explored as an alternative, given the higher sensitivity of MRI, although this comes at a higher cost. We performed a cost-effective analysis comparing US and dual-sequence non-contrast-enhanced MRI (NCEMRI) for HCC surveillance in the local setting. METHODS: Cost-effectiveness analysis of no surveillance, US surveillance and NCEMRI surveillance was performed using Markov modelling and microsimulation. At-risk patient cohort was simulated and followed up for 40 years to estimate the patients' disease status, direct medical costs and effectiveness. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio were calculated. RESULTS: Exactly 482,000 patients with an average age of 40 years were simulated and followed up for 40 years. The average total costs and QALYs for the three scenarios - no surveillance, US surveillance and NCEMRI surveillance - were SGD 1,193/7.460 QALYs, SGD 8,099/11.195 QALYs and SGD 9,720/11.366 QALYs, respectively. CONCLUSION Despite NCEMRI having a superior diagnostic accuracy, it is a less cost-effective strategy than US for HCC surveillance in the general at-risk population. Future local cost-effectiveness analyses should include stratifying surveillance methods with a variety of imaging techniques (US, NCEMRI, contrast-enhanced MRI) based on patients' risk profiles.
Humans ; Adult ; Carcinoma, Hepatocellular/diagnostic imaging* ; Liver Neoplasms/diagnostic imaging* ; Cost-Effectiveness Analysis ; Cost-Benefit Analysis ; Quality-Adjusted Life Years ; Magnetic Resonance Imaging/methods*

Objective To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.Methods The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR,and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0.Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1.Breast cancer MCF-7 cells were transfected via liposome,miR-6838-5p mimic,miR-6838-5p inhibitor,DDR1 siRNA,DDR1-overexpresisng vector,or both miR-6838-5p mimic and DDR1-overexpressing vector,and the changes in cell proliferation were examined with CCK-8 and EdU assays;Western blotting was used to detect the expression of DDR1.The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.Results The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells.In MCF-7 cells,miR-6838-5p overexpression induced significant inhibition of cell proliferation.Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1(P<0.01).Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells,and DDR1 overexpression promoted proliferation of the cells;co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation.In the tumor-bearing nude mice,the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.Conclusion Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.

Objective To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.Methods The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR,and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0.Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1.Breast cancer MCF-7 cells were transfected via liposome,miR-6838-5p mimic,miR-6838-5p inhibitor,DDR1 siRNA,DDR1-overexpresisng vector,or both miR-6838-5p mimic and DDR1-overexpressing vector,and the changes in cell proliferation were examined with CCK-8 and EdU assays;Western blotting was used to detect the expression of DDR1.The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.Results The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells.In MCF-7 cells,miR-6838-5p overexpression induced significant inhibition of cell proliferation.Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1(P<0.01).Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells,and DDR1 overexpression promoted proliferation of the cells;co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation.In the tumor-bearing nude mice,the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.Conclusion Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.

Objective To investigate the effect of comprehensive nursing measures on preventing venous thromboembolism(VTE)in elderly patients.Methods A total of 182 inpatients from the First Affiliated Hospital of Guangxi Medical University from January 2021 to December 2022 were selected and divided into observation group(92 cases)and control group(90 cases)according to random number table method.Patients in control group were given VTE prevention by conventional methods,and patients in observation group were given VTE comprehensive preventive measures.After the implementation of preventive measures,VTE prevention compliance and health self-management"knowledge-attitude-practice"were compared between two groups.Results There was no significant difference in the assessment of VTE risk level between two groups(P>0.05).The compliance of observation group was significantly better than that of control group(P<0.05).There were statistically significant differences between two groups in understanding and mastering VTE prevention knowledge,believing that VTE prevention measures were difficult to adhere to,and implementing VTE prevention according to medical advice(P<0.05).Patients in observation group had better health self-management.Conclusion The comprehensive nursing intervention of patients participating in VTE risk assessment and jointly implementing thrombosis prevention measures between nurses and patients can improve the compliance of VTE prevention and health self-management ability of elderly patients,which is of great significance for reducing the occurrence of VTE.

Objective To investigate the current situation of the construction of geriatrics in second and third level gen-eral hospitals in Guangxi,analyze the existing problems,and propose suggestions.Methods A self-developed"Survey on the Current Situation of Geriatrics Construction"was used to conduct a questionnaire survey on 250 second and third level general hospitals in Guangxi from April to September 2021.Results A total of 98 geriatrics were established in 196 general hospitals,and the overall number met national requirements.Among them,36 are independent institutions,including 24 tertiary hospitals and 12 secondary hospitals,with 2 172 beds and 1 764 medical staff.Conclusion In the future,Guangxi should ensure the high-quality construction of geriatrics,reasonably allocate geriatric human resources,enhance disciplinary medical service capa-bilities,strengthen overall two-way health connections,and vigorously promote the construction and development of geriatrics in Guangxi.

Drug delivery with customized combinations of drugs, controllable drug dosage, and on-demand release kinetics is critical for personalized medicine. In this study, inspired by successive opening of layered structures and compartmentalized structures in plants, we designed a multiple compartmentalized capsular structure for controlled drug delivery. The structure was designed as a series of compartments, defined by the gradient thickness of their external walls and internal divisions. Based on the careful choice and optimization of bioinks composed of gelatin, starch, and alginate, the capsular structures were successfully manufactured by fused deposition modeling three-dimensional (3D) printing. The capsules showed fusion and firm contact between printed layers, forming complete structures without significant defects on the external walls and internal joints. Internal cavities with different volumes were achieved for different drug loading as designed. In vitro swelling demonstrated a successive dissolving and opening of external walls of different capsule compartments, allowing successive drug pulses from the capsules, resulting in the sustained release for about 410 min. The drug release was significantly prolonged compared to a single burst release from a traditional capsular design. The bioinspired design and manufacture of multiple compartmentalized capsules enable customized drug release in a controllable fashion with combinations of different drugs, drug doses, and release kinetics, and have potential for use in personalized medicine.

Scleroglucan is a high-molecular water-soluble microbial exopolysaccharide and mainly applied in the fields of petroleum, food, medicine and cosmetics. The high molecular weight of scleroglucan produced by microbial fermentation leads to low solubility, high viscosity and poor dispersibility, thus bringing a series of difficulties to extraction, preservation and application. It is important to explore suitable degradation method to adjust the molecular weight of scleroglucan for expanding its industrial application. Taking Sclerotium rolfsii WSH-G01 as a model strain, in which functional annotations of the glucanase genes were conducted by whole genome sequencing. Based on design of culture system for culture system for differential expression of β-glucanase, endogenous β-glucanase genes in S. rolfsii WSH-G01 were excavated by transcriptomics analysis. Functions of these potential hydrolases were further verified. Finally, 14 potential endogenous hydrolase genes were obtained from S. rolfsii. After heterologous overexpression in Pichia pastoris, 10 soluble enzymes were obtained and 5 of them had the activity of laminarin hydrolysis by SDS-PAGE and enzyme activity analysis. Further investigation of the 5 endogenous hydrolases on scleroglucan degradation showed that enzyme GME9860 has positive hydrolysis effect. The obtained results provide references not only for obtaining low and medium molecular weight of scleroglucan with enzymatic hydrolysis, but also for producing different molecular weight of scleroglucan during S. rolfsii fermentation process with metabolic engineering.
Basidiomycota/genetics* ; Glucans ; Hydrolysis ; Saccharomycetales

Objective:To investigate the correlation of mRNA expression levels and DNA methylation levels of Alu-mediated p21 transcriptional regulator (APTR) with hepatitis B virus infection.Methods:One hundred patients with HBV infection admitted in Affiliated Hospital of Yunnan University during January to December 2019 were enrolled in the study, including 50 patients with chronic hepatitis B (CHB group) and 50 asymptomatic HBV carriers (ASC group); and 50 healthy subjects were also enrolled as the healthy control group. The DNA methylation levels of APTR gene were detected by methylation-sensitive high-resolution melting (MS-HRM); the expression levels of APTR mRNA were detected by fluorescence real-time quantitative PCR (qRT-PCR). Pearson correlation or Spearman rank correlation was used for correlation analysis.Results:There were significant differences in the APTR DNA methylation levels among the CHB, ASC and healthy control groups {[12.02 (9.30, 23.32)]%, [10.02 (8.46, 17.44)]% and [8.86 (7.82, 11.57)]%, χ2=13.360, P<0.01}. The APTR DNA methylation levels were significantly higher in CHB group than those in healthy control group( Z=31.480, P<0.01). There were significant differences in the APTR mRNA expression levels among CHB, ASC and healthy control groups (2.38±1.41, 5.78±2.78 and 5.70±2.66, F=33.720, P<0.01). The APTR mRNA expression levels were significantly lower in CHB group than those in healthy control and ASC groups ( t=7.808 and 7.724, both P<0.01). Correlation analysis showed that the DNA methylation level of APTR gene was negatively correlated with mRNA expression levels ( r=-0.305, P<0.01) in all subjects. The DNA methylation level of APTR gene was positively correlated with HBsAg level ( r=0.231, P=0.022), and the mRNA expression level was negatively correlated with HBsAg level ( r=-0.245, P=0.014) in patients with HBV infection. Conclusion:There are differences in DNA methylation and mRNA expression of APTR gene in different stages of HBV infection, suggesting that APTR gene may be involved in the immune regulation of HBV infection.