Real world drug treatment models for pregnancy complicated with urinary tract infection in China from 2018 to 2022: a cross-section analysis.

Objective: Urinary tract infection (UTI) is common in pregnant women. The selection of anti-infection plans during pregnancy must take into account the dual factors of patient pregnancy status and urinary tract infection anti-infection treatment, as well as the efficacy, cost, risk, and potential adverse reactions associated with each method applied to individual patients. Consequently, there are numerous drugs from which to choose; presently, there is no unified conclusion regarding the choice of drug therapy, and there is a lack of long-term drug treatment for UTI during pregnancy. Our objective is to investigate the actual drug treatment patterns of UTI patients during pregnancy in China over the past 5 years, with a particular emphasis on the trend and rationality of antibiotic use in these patients over the past 5 years. Method: We conducted a cross-sectional analysis of data from a China Medical Association-supervised hospital prescription analysis cooperation initiative. From January 2018 to December 2022, the information is extracted from prescriptions/medical orders of patients with UTI during pregnancy. Using a primary anatomical therapeutic chemistry (ATC) classification code and the US Food and Drug Administration (FDA) classification, we quantified the frequency of drug use and drug types. We also calculated the prevalence of the most frequently prescribed antibacterial medications and assessed the efficacy of anti-infection plans based on drug labels and guidelines. Results: Among the 563 patients included in this research, Chengdu (36.59%), Guangzhou (27.72%), and Shanghai (8.70%) were the top three cities. Over the course of 5 years, the average age was 29.60% ± 6.59 years, with approximately 60.21% of women between the ages of 25 and 34. Each patient's primary anti-infection medications were statistically analyzed. Cephalosporins (403, 71.58%), enzyme inhibitors (66, 11.72%), and penicillins (34, 6.04%) were the first few categories, followed by the most commonly used cephalosporins. Cefuroxime, ceftriaxone, and cefdinib, rounded out the top five. Cefoxitin and cefaclor. According to the 5-year change in dosage, cephalosporins have always ranked first. Three of the top five most expensive drugs are cephalosporins, carbapenems, and enzyme inhibitors. Teicoplanin, tigecycline, nifurtel, linezolid, and quinolones ranked among the top five in terms of per-patient drug costs for patients receiving comprehensive treatment drugs. Conclusion: In the 5 years of research, the average age of patients who visit a doctor has not increased substantially, but the opportunity cost of female fertility has increased, which has severely impeded the fulfillment of fertility desires. The selection of medications is generally reasonable, and the dosage of the first-line cephalosporins recommended by the guidelines is relatively high in this study. The dosage of furantoin and fosfomycin, which are more prevalent in urinary tract infections, is however relatively low. In addition, some expensive pharmaceuticals may increase patients' financial burden. On the premise of meeting clinical needs, future research will focus on how to further improve the level of rational drug use in outpatient clinics, attain economical, safe, and effective drug use, and thus reduce the economic burden on patients.

Gene polymorphism and prediction of toxicity to platinum-based chemotherapy in patients with gynecologic cancer.

The relationship between single nucleotide polymorphisms (SNPs) at various loci and adverse drug reactions (ADRs) in patients with gynecologic cancer receiving platinum-based chemotherapy (PPCT) remains unexplored. This research aimed to investigate the correlation between SNPs at several loci (e.g., GSTP1 rs1695, MTHFR rs1801133, XPC rs2228001, TP53 rs1042522, and ERCC1 rs3212986) and ADRs in patients with gynecologic cancer receiving PPCT. A total of 244 patients with gynecologic cancer who received first-line PPCT were included in this retrospective study. Blood fluorescence quantitative polymerase chain reaction was used to detect genotypes. Logistic regression, Pearson's Chi-square test, and Fisher's exact test were used to explore the correlations between these SNPs and the occurrence of ADRs. The logistic regression results showed that different genotypes of the five genes had no statistical significance in the overall grade greater than or equal to 3 ADRs. The results of Pearson's Chi-square test showed the same results. On specific adverse reactions, we found that the rs1042522 GG genotype significantly increased the risk of grade greater than or equal to 3 leucopenia compared with the CG and the CC genotypes (p = 0.002). The rs1695 AG genotype showed higher correlation for grade greater than or equal to 3 neutropenia (p = 0.020). The rs2228001 CC genotype also had a higher risk for grade greater than or equal to 3 neutropenia (p = 0.003). This study found that whereas the overall grade greater than or equal to 3 adverse reactions in patients with gynecologic cancer receiving PPCT were not associated with SNPs, specific SNPs (rs1042522 GG, rs1695 AG, and rs2228001 CC) were linked to higher risks of leucopenia and neutropenia, indicating their potential as predictors of hematotoxicity in PPCT-treated patients with gynecologic cancer.

nH115a, a novel inhibitor of the La protein: Effect on expression of multiple RNAs in hepatitis B virus-infected hepatoma cells and embryotoxicity profile.

The La protein binds to RNA and protects replication of the hepatitis B virus (HBV). We recently developed the compound nH115a, an inhibitor of the La protein that has high stability and anti-HBV activity. However, the mechanism, by which this compound inhibits HBV infection and its safety to embryos, remains unclear. Our goal was to examine the molecular mechanism, by which nH115a inhibits HBV infection, and to characterize its embryotoxicity. Microarray experiments using HepG2. 2. 15 cells (established by transfecting an HBV plasmid into HepG2 hepatoma cells) and bioinformatics analyses were used to measure the effect of nH115a on the expression of lncRNAs, mRNAs, and circRNAs. The embryonic stem cell test was used to assess the embryotoxicity of nH115a. nH115a significantly altered the expression of 2402 lncRNAs, 338 mRNAs, and 559 circRNAs. Gene Ontology (GO) analysis indicated the differentially expressed transcripts functioned in interleukin-2 production, I-SMAD binding, RNA-induced silencing complex (RISC), NLRP3 inflammasome complex assembly, cytoplasmic sequestering of nuclear factor kappa-B (NF-κB), and death receptor binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the most enriched pathways included transforming growth factor-ß (TGF-ß) signaling, pathways in cancer, ubiquitin mediated proteolysis, p53 signaling, antigen processing and presentation, Fc gamma R-mediated phagocytosis, and B cell receptor signaling. The results of the embryonic stem cell test indicated that nH115a exhibited weak embryotoxicity. In conclusion, immune responses, TGF-ß/SMAD signaling, and cancer-related pathways may function in the nH115a-mediated inhibition of HBV replication. Keywords: hepatitis B virus; La protein; inhibitor; nH115a.

La protein contributes to cells proliferation and migration and serves as a potential therapeutic target for hepatocellular carcinoma.

AIM: La protein is a multifunctional RNA-binding protein involved in RNA metabolism that has been reported to promote the growth of some solid tumors. However, potential role of La in hepatocellular carcinoma (HCC) has not been fully elucidated. This study aimed to investigate the expression of La and its function in HCC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were conducted to detect the expression levels of La mRNA and protein in HCC cells and tissues. The proliferation capability of cells was clarified by Cell Counting Kit-8 and clone formation assays. Wound healing assay was carried out to assess cell migration ability. Related protein expressions were also analyzed by western blot. RESULTS: Analysis of our clinical samples showed that La mRNA and protein expression of HCC tissues was higher than those of corresponding adjacent tissues, consistent with the result of microarray datasets from Oncomine database. La was also significantly overexpressed in eight HCC cells, compared with normal hepatocytes. According to in vitro experiments, we demonstrated that knockdown of La inhibited HCC cell proliferation and migration. CONCLUSIONS: Our results revealed that La expression is elevated both at the RNA and protein levels in HCC. Highly expressed La significantly promotes tumorigenesis of HCC, suggesting that La may be a potential therapeutic target for the treatment of HCC.

Study on the structure optimization and anti-hepatitis B virus activity of novel human La protein inhibitor HBSC11.

In our previous study, Methyl pyrazolo[1,5-a] pyridine-2-carboxylate (HBSC11) was shown to combine with La protein, which conferred anti-hepatitis B virus (HBV) effects. The purpose of this study was to optimize, synthesize, and evaluate the anti-HBV activity of HBSC11. The methyl group of HBSC11 was substituted with hydrophobic, hydrophilic, and tricyclic groups to generate novel HBV inhibitors with desirable potency. On in vitro evaluation, several derivatives exhibited good anti-HBV activity compared with control. In particular, compound 5a reduced the level of HBV antigen by approximately 50%, which was similar to the activity of entecavir. In a mouse model, 5a showed 98.9% inhibition rate for HBV DNA, 57.4% for HBsAg, and 46.4% for HBeAg; the corresponding rates in the control group were 90.8, 3.8, and 9.8%, respectively. In addition, prediction of binding modes and physicochemical properties showed that 5a formed hydrogen bonds with La protein and conformed well to the Lipinski's rule of five. Our results suggest that 5a is a potential new anti-HBV drug.

Patient compliance with antimicrobial drugs: A Chinese survey.

BACKGROUND: Antimicrobial therapy is among the mainstream treatment modalities employed in clinical settings. Antimicrobial sensitivity of the pathogen and patient compliance are key determinants of the efficacy of antimicrobial therapy. OBJECTIVE: In this study, we sought to investigate the factors that affect patient compliance to antimicrobial therapy in a Chinese teaching hospital to enhance patient compliance and to prevent abuse and misuse of antibiotics by patients. METHODS: A questionnaire survey was conducted among patients willing to answer all the questions who were prescribed antimicrobial drugs orally, and for whom at least half of the duration of therapy was not under the supervision of a doctor or nurse. Data analyses were performed using Kruskal-Wallis test and multivariate logistic regression. RESULTS: A total of 720 patients participated in the survey; of these, 714 patients provided complete data and were included in the analysis. Up to 86.97% of patients showed noncompliance to antimicrobial therapy (total compliance score < 8), whereas 13.03% of patients showed good compliance (total compliance score = 8). On multivariate analyses, understanding of the treatment was an important factor associated with compliance. CONCLUSIONS: A range of factors were associated with compliance to antimicrobial therapy, including understanding of the treatment, gender, age, home address, education level, and family income.

Alteration of microRNA profiles by a novel inhibitor of human La protein in HBV-transformed human hepatoma cells.

A pyrazolopyridine HBSC11 was previously identified as a novel inhibitor of human La protein with anti-hepatitis B virus (HBV) activity. However, the underlying mechanism(s) of HBV inhibition by HBSC11 remains unclear. This study aimed to examine the regulation of microRNA (miRNA) by HBSC11 in HBV-transformed human hepatoma HepG2.2.15 cells using microarray and quantitative real-time PCR. Target genes of the differentially expressed miRNAs were predicted and subjected to bioinformatics analysis. Results showed that HBSC11 significantly upregulated the expression of miR-3912-5p, miR-6793-5p, and miR-7159-5p in HepG2.2.15 cells. Target genes of the three miRNAs were mainly involved in the regulation of nucleic acid-templated transcription, negative regulation of gene expression, nucleic acid binding transcription factor activity and regulation of phosphorylation. In addition, target genes were enriched in certain regulatory pathways related to HBV infection and HBV-associated disease progression, such as the transforming growth factor (TGF)-ß, Wnt, and p53 signaling. Our study demonstrates the involvement of miR-3912-5p, miR-6793-5p, and miR-7159-5p and the potential modulation of specific pathways (TGF-ß, Wnt, and p53 signaling) in HBSC11-mediated inhibition of HBV replication. This study provides insight into the molecular mechanism of the action of HBSC11 against HBV infection and will support the development of antiviral drugs targeting La protein.

New anti-hepatitis B virus drugs under development and evaluation.

PURPOSE OF REVIEW: Although available therapies can effectively inhibit hepatitis B virus (HBV) replication in patients with active chronic hepatitis B (CHB) infection, therapeutic efficacy is limited because of potential drug resistance, and an inability to mediate viral clearance and to rectify immune impairment in CHB patients. This review will summarize the state-of-the-art for anti-HBV drugs and focus on potential drugs and targets under development and evaluation. RECENT FINDINGS: New developing drugs are evaluated for their antiviral effects in the areas of interference with the viral replication cycle, elimination of covalently closed circular DNA, modulation of host immunity and identification of the La protein and its regulator casein kinase as possible targets for the development of anti-HBV therapies. SUMMARY: These novel compounds and targets have showed great inhibitory effects on HBV replication in vitro and in animal models. Several novel therapies are promising in early clinical trials. Potentially, combination of newly developing and current antiviral drugs may cure CHB in the clinic.

Anti-HBV Drugs: Progress, Unmet Needs, and New Hope.

Approximately 240 million people worldwide are chronically infected with hepatitis B virus (HBV), which represents a significant challenge to public health. The current goal in treating chronic HBV infection is to block progression of HBV-related liver injury and inflammation to end-stage liver diseases, including cirrhosis and hepatocellular carcinoma, because we are unable to eliminate chronic HBV infection. Available therapies for chronic HBV infection mainly include nucleos/tide analogues (NAs), non-NAs, and immunomodulatory agents. However, none of them is able to clear chronic HBV infection. Thus, a new generation of anti-HBV drugs is urgently needed. Progress has been made in the development and testing of new therapeutics against chronic HBV infection. This review aims to summarize the state of the art in new HBV drug research and development and to forecast research and development trends and directions in the near future.

The use of vancomycin in the treatment of adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infection: a survey in a tertiary hospital in China.

BACKGROUND: Vancomycin is frequently used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA). OBJECTIVES: To determine MRSA infection status and the use of vancomycin in its treatment at a teaching hospital in China. METHODS: We retrospectively reviewed 140 cases of MRSA infection that were treated from January 2013 to October 2014. We analyzed the etiology of MRSA infection and the use of vancomycin in these cases. RESULTS: MRSA infection mainly occurred in elderly patients concomitant with a variety of diseases, which incidence was more in men than women. More cases of MRSA infection were encountered in the ICU than in other departments. The positive culture results for MRSA were obtained in the sputum (38.57%), pharyngeal swab (19.29%), blood (5.71%), and wound secretion (11.43%) samples. The MRSA patients were sensitive to vancomycin, with the minimum inhibitory concentration (MIC) being 1 µg/mL in 53.80% of the cases and 2 µg/mL in 44.10% of the cases, respectively. Among the 35 (25%) cases treated with vancomycin, 23 were cured, while 3 died and 7 (20%) were considered as an unreasonable application. CONCLUSIONS: MRSA infection mainly appeared in patients admitted to the ICU. The MIC of vancomycin had a tendency to increase gradually.