Associations between the use of red yeast rice preparations and adverse health outcomes: An umbrella review of meta-analyses of randomized controlled trials.

BACKGROUND: Red yeast rice (RYR), a natural lipid-lowering agent, is widely used in clinical practice. However, the existing meta-analyses concerning the safety of RYR preparations have yielded inconsistent results, and the credibility of the evidence has not been quantified. OBJECTIVE: This study was designed to evaluate the existing evidence and offer a comprehensive understanding of the associations between the use of RYR preparations and various adverse health outcomes. SEARCH STRATEGY: Seven literature databases were searched from inception to May 5, 2023, using medical subject headings and free-text terms (e.g., "red yeast rice," "Xuezhikang," and "Zhibitai"). INCLUSION CRITERIA: Meta-analyses that investigated and quantitatively estimated associations between the use of RYR preparations and adverse health outcomes were included in this study. DATA EXTRACTION AND ANALYSIS: Two researchers independently extracted data using a standardized data collection table; any disagreements were resolved by consulting a third researcher. Based on the participant, intervention, comparator and outcome (PICO) framework in each eligible meta-analysis, a series of unique associations between the use of RYR preparations and adverse health outcomes were determined. The associations' effect estimates were re-evaluated using random-effect models. RESULTS: Fifteen meta-analyses, comprising 186 (164 unique) randomized controlled trials, were identified. Based on A MeaSurement Tool to Assess Systematic Reviews version 2, 3 (20%) and 12 (80%) of these meta-analyses had low and critically low confidence, respectively. A total of 61 unique associations between the use of RYR preparations and adverse health outcomes were extracted from eligible meta-analyses. Based on the random-effect models, 10 (16.4%) associations indicated a significant protective effect of RYR preparations against adverse health outcomes, while 5 (8.2%) indicated an increased risk of adverse health outcomes related to uric acid, alanine transaminase and aspartate transaminase levels. The other 46 (75.4%) associations showed no significant difference between the use of RYR preparations and control treatments. Regarding the credibility of the evidence, 21 (34.4%), 34 (55.7%) and 6 (9.8%) associations showed moderate, low and very low credibility, respectively. CONCLUSION: The evidence examined in this study suggests that RYR preparations are safe; however, the credibility of the evidence was not high. Further high-quality evidence is required. Please cite this article as: Ma ZY, Yang SP, Li Y, Xu TT, Yang YL, Yang HY, Li HB, Zhou LJ, Diao Y, Li SY. Associations between the use of red yeast rice preparations and adverse health outcomes: An umbrella review of meta-analyses of randomized controlled trials. J Integr Med. 2024; 22(2): 126-136.

Visible-Light-Promoted Desulfurization to Synthesize Deoxyglycosides.

In this study, we have successfully applied a visible-light-promoted desulfurization method to the synthesis of deoxysugars, especially 1-deoxyglycose, 2,4-deoxyglycosides, and 2-deoxyglycosides with exclusive α-configuration. Compared to the reported desulfurization under UV light (500 W mercury lamp), this desulfurization under visible light (20 W blue LED) is easy to operate since it does not require a dedicated photochemical reactor, occurs under very mild conditions, and is able to avoid many of the side reactions that often occur during the UV-induced desulfurization.

Efficacy and mortality of ceftazidime/avibactam-based regimens in carbapenem-resistant Gram-negative bacteria infections: A retrospective multicenter observational study.

OBJECTIVES: Limited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data. METHODS: This multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors. RESULTS: A total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of<20 mL/min), cardiovascular diseases, and digestive system diseases were independent risk factors for poor clinical efficacy of CAZ/AVI-based regimens. Bloodstream infection (BSI), patients with the adjusted doses of CAZ/AVI, and CAZ/AVI co-administration with carbapenem were independently associated factors of bacterial clearance by CAZ/AVI-based regimens. Age, total hospital stays, use of mechanical ventilation, and cumulative CAZ/AVI dose were independent factors associated with all-cause mortality. CONCLUSION: CAZ/AVI was an effective drug in treating CR-GNB infection. CAZ/AVI that is mostly excreted by the kidney and is accumulated in renal impairment should be renally adjusted. Renal dysfunction and the adjusted dose of CAZ/AVI were associated with efficacy. Clinicians should individualize CAZ/AVI regimen and dose by the level of renal function to achieve optimal efficacy and survival. The efficacy of CAZ/AVI in the treatment of CR-GNB infection, as well as the implementation of individualized precision drug administration of CAZ/AVI according to patients' different infection sites, renal function, bacterial types, bacterial resistance mechanisms, blood concentration monitoring and other conditions need to be further studied in multicenter.

His bundle pacing versus left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing: a prospective crossover comparison.

BACKGROUND: His bundle pacing (HBP) and left bundle branch pacing (LBBP) both provide physiologic pacing which maintain left ventricular synchrony. They both improve heart failure (HF) symptoms in atrial fibrillation (AF) patients. We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term. METHODS: Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality. Echocardiographic measurements, New York Heart Association (NYHA) classification, quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up. Left ventricular function including the left ventricular endo-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and right ventricular (RV) function quantified by tricuspid annular plane systolic excursion (TAPSE) were all assessed. RESULTS: Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled (69.1 ± 8.1 years, 53.6% male, LVEF 59.2% ± 13.7%). The LVESV was improved by both pacing modalities in all patients (n = 23) and the LVEF was improved in patients with baseline LVEF at less than 50% (n = 6). The TAPSE was improved by HBP but not LBBP (n = 23). CONCLUSION: In this crossover comparison between HBP and LBBP, LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node (AVN) ablation. HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.

SnCl4 Promoted Efficient Cleavage of Acetal/Ketal Groups with the Assistance of Water in CH2Cl2.

Acetalization and deacetalation are a pair of routine manipulations to protect and deprotect the 4- and 6-hydroxyl groups of glycosides in the synthesis of glycosyl building blocks. In this study, we found that treatment of SnCl4 with various carbohydrates containing acetal/ketal groups with the assistance of water in CH2Cl2 led to deacetalization/deketalization products in almost quantitative yields. In addition, for substrates containing both acetal/ketal and p-methoxylbenzyl groups, we also found that the p-methoxylbenzyl group was selectively cleaved by the use of a catalytic amount of SnCl4, while the acetal/ketal groups remained. Furthermore, based on this, 4,6-benzylidene glycosides can be conveniently converted to 4,6-OAc or 4-OH, 6-OAc glycosides.

Drug resistance characteristics of pathogenic bacteria in neonatal bloodstream infections from a hospital in Chuzhou, Anhui, 2017-2021 / 中国热带医学

@#Abstract： Objective　To investigate the distribution and antimicrobial resistance profile of the bacterial strains isolated from blood cultures in neonatal septicemia children of Neonatology Department, the First People's Hospital of Chuzhou during Jan. 2017-Dec. 2021, in order to guide clinical rational drug use. Methods　The distribution and the results of antimicrobial susceptibility tests and characteristics of the pathogenic bacteria isolated from blood culture samples in neonatal septicemia children in the First Hospital of Chuzhou from Jan. 2017 to Dec. 2021 were retrospectively analyzed. The results were analyzed with WHONET 5.6 software, according to the Clinical and Laboratory Standards Institute (CLSI) 2021 breakpoints. 　Results　A total of 189 strains were isolated from the 4 538 sample of blood cultures, the positive rate was 4.2%, including 59(31.2%) Gram-negative bacterial strains, 130 (68.8%) Gram-positive bacterial strains. The most frequently isolates were coagulase-negative staphylococci（64.0%), Serratia liquefaciens (15.9%), Escherichia coli (3.2%), Acinetobacter lwoffii (2.6%) and Delftia acidovorans (2.6%). The prevalence of methicillin-resistant isolates was 81.8%(99/121) in coagulase-negative Staphylococci and 25.0%（1/4） in Staphylococcus aureus. No staphylococcal strains were found resistant to vancomycin, quinupristin-dalfopristin or linezolid. The sensitivity of the antibacterial drug monitored by Serratia liquefaciens was 100.0%.Conclusions　Gram-positive bacterial are the main pathogen of neonatal septicemia, and is highly resistant to the common antibacterial drugs. The clinical should choose antibacterial agents reasonably according to drug sensitivity.

Microfluidics applications for high-throughput single cell sequencing.

The inherent heterogeneity of individual cells in cell populations plays significant roles in disease development and progression, which is critical for disease diagnosis and treatment. Substantial evidences show that the majority of traditional gene profiling methods mask the difference of individual cells. Single cell sequencing can provide data to characterize the inherent heterogeneity of individual cells, and reveal complex and rare cell populations. Different microfluidic technologies have emerged for single cell researches and become the frontiers and hot topics over the past decade. In this review article, we introduce the processes of single cell sequencing, and review the principles of microfluidics for single cell analysis. Also, we discuss the common high-throughput single cell sequencing technologies along with their advantages and disadvantages. Lastly, microfluidics applications in single cell sequencing technology for the diagnosis of cancers and immune system diseases are briefly illustrated.

Cystatin-B Negatively Regulates the Malignant Characteristics of Oral Squamous Cell Carcinoma Possibly Via the Epithelium Proliferation/Differentiation Program.

Disturbance in the proteolytic process is one of the malignant signs of tumors. Proteolysis is highly orchestrated by cysteine cathepsin and its inhibitors. Cystatin-B (CSTB) is a general cysteine cathepsin inhibitor that prevents cysteine cathepsin from leaking from lysosomes and causing inappropriate proteolysis. Our study found that CSTB was downregulated in both oral squamous cell carcinoma (OSCC) tissues and cells compared with normal controls. Immunohistochemical analysis showed that CSTB was mainly distributed in the epithelial structure of OSCC tissues, and its expression intensity was related to the grade classification. A correlation analysis between CSTB and clinical prognosis was performed using gene expression data and clinical information acquired from The Cancer Genome Atlas (TCGA) database. Patients with lower expression levels of CSTB had shorter disease-free survival times and poorer clinicopathological features (e.g., lymph node metastases, perineural invasion, low degree of differentiation, and advanced tumor stage). OSCC cell models overexpressing CSTB were constructed to assess the effects of CSTB on malignant biological behaviors and upregulation of CSTB inhibited cell proliferation, migration, and invasion in vitro. Weighted gene correlation network analysis (WGCNA) and gene set enrichment analysis (GSEA) were performed based on the TCGA data to explore potential mechanisms, and CSTB appeared to correlate with squamous epithelial proliferation-differentiation processes, such as epidermal cell differentiation and keratinization. Moreover, in WGCNA, the gene module most associated with CSTB expression (i.e., the brown module) was also the one most associated with grade classification. Upregulation of CSTB promoted the expression levels of markers (LOR, IVL, KRT5/14, and KRT1/10), reflecting a tendency for differentiation and keratinization in vitro. Gene expression profile data of the overexpressed CSTB cell line were obtained by RNA sequencing (RNA-seq) technology. By comparing the GSEA enrichment results of RNA-seq data (from the OSCC models overexpressing CSTB) and existing public database data, three gene sets (i.e., apical junction, G2/M checkpoint, etc.) and six pathways (e.g., NOTCH signaling pathway, glycosaminoglycan degradation, mismatch repair, etc.) were enriched in the data from both sources. Overall, our study shows that CSTB is downregulated in OSCC and might regulate the malignant characteristics of OSCC via the epithelial proliferation/differentiation program.

Untargeted and targeted gingival metabolome in rodents reveal metabolic links between high-fat diet-induced obesity and periodontitis.

AIM: To characterize gingival metabolome in high-fat diet (HFD)-induced obesity in mice with/without periodontitis. METHODS: HFD-induced obesity mouse model was established by 16-week feeding, and a lean control group was fed with low-fat diet (n = 21/group). Both models were induced for periodontitis on the left sides by molar ligation for 10 days, whereas the right sides were used as controls. Gingival metabolome and arginine metabolism were analysed by non-targeted/targeted liquid chromatography-mass spectrometry. RESULTS: Of 2247 reference features, presence of periodontitis altered 165 in lean versus 885 in HFD mice; and HFD altered 525 in absence versus 1435 in presence of periodontitis. Compared with healthy condition, periodontitis and HFD had distinct effects on gingival metabolome. Metabolomic impacts of periodontitis were generally greater in HFD mice versus lean controls. K-medoids clustering showed that HFD amplified the impacts of periodontitis on gingival metabolome in both intensity and extensity. Ten metabolic pathways were enriched, including 2 specific to periodontitis, 5 specific to HFD and 3 shared ones. Targeted validation on arginine metabolism confirmed the additive effects between HFD and periodontitis. CONCLUSION: The obese population consuming excessive HFD display amplified metabolic response to periodontitis, presenting a metabolic susceptibility to exacerbated periodontal destruction.

Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice.

The occurrence of lipotoxicity during obesity-associated cardiomyopathy is detrimental to health. Salvianolic acid A (SAA), a natural polyphenol extract of Salvia miltiorrhiza Bunge (Danshen in China), is known to be cardioprotective. However, its clinical benefits against obesity-associated cardiomyocyte injuries are unclear. This study aimed at evaluating the protective effects of SAA against lipotoxicity-induced myocardial injury and its underlying mechanisms in high fat diet (HFD)-fed mice and in palmitate-treated cardiomyocyte cells (H9c2). Our analysis of aspartate aminotransferase and creatine kinase isoenzyme-MB (CM-KB) levels revealed that SAA significantly reversed HFD-induced myocardium morphological changes and improved myocardial damage. Salvianolic acid A pretreatment ameliorated palmitic acid-induced myocardial cell death and was accompanied by mitochondrial membrane potential and intracellular reactive oxygen species improvement. Analysis of the underlying mechanisms showed that SAA reversed myocardial TLR4 induction in HFD-fed mice and H9c2 cells. Palmitic acid-induced cell death was significantly reversed by CLI-95, a specific TLR4 inhibitor. TLR4 activation by LPS significantly suppressed SAA-mediated lipotoxicity protection. Additionally, SAA inhibited lipotoxicity-mediated expression of TLR4 target genes, including MyD88 and p-JNK/MAPK in HFD-fed mice and H9c2 cells. However, SAA did not exert any effect on palmitic acid-induced SIRT1 suppression and p-AMPK induction. In conclusion, our data shows that SAA protects against lipotoxicity-induced myocardial damage through a TLR4/MAPKs mediated mechanism.

Effect of the Standardized Management of Cancer Pain on Patients with Bone Metastasis of Lung Cancer in China.

OBJECTIVE: This study investigates the effect of the standardized management of cancer pain on patients with bone metastasis of lung cancer in China. PATIENTS AND METHODS: A total of 123 patients with bone metastasis of lung cancer were selected from the Respiratory Department of the Affiliated Hospital of North China University of Science and Technology. Among these patients, 62 patients who had not received standardized management of cancer pain from March 12, 2018, to September 11, 2018, were selected as the control group. In contrast, 61 patients who had received the standardized management of cancer pain from September 12, 2018, to March 11, 2019, were selected as the observation group. The former cohort accepted the conventional management of cancer pain, while the latter accepted the strict, standardized management of cancer pain. The demographic statistics, disease characteristics, and painkiller application of patients in these two groups were analyzed. Then, the analgesic effect and level of satisfaction were compared between these two groups. RESULTS: No significant differences were noticed between these two groups in terms of age, gender, smoking status, type of pathology, education level, previous treatment, and the Eastern Cooperative Oncology Group score, as well as other demographic and disease characteristics. As for the use of painkillers, opioid analgesics accounted for a higher proportion in the observation group than in the control group. Compared with the control group, pain improvement and patient satisfaction after analgesic treatment were significantly higher in the observation group (p < 0.05). CONCLUSION: The standardized management of cancer pain can considerably alleviate the pain of patients with bone metastasis of lung cancer and improve their quality of life. Furthermore, this type of management can increase satisfaction.

[Application of infrared thermal imaging technology in the design of free anterolateral thigh perforator flap transplantation].

OBJECTIVE: To explore clinical effect of infrared thermal imaging technology for the treatment of free anterolateral thigh perforator flap transplantation. METHODS: From June 2014 to June 2018, 31 patients with skin defect at various degrees treated by free anterolateral thigh perforator flap transplantation, including 21 males and 10 females aged from 16 to 59 years old with an average age of(35.3±1.5) years old, the courses of disease ranged from 2 to 4 weeks with an average of (1.8±0.6) weeks. The number of perforating branch, the position of the perforating branch, the perforating branch vitality detected by Doppler blood stream detector and parameters of thermal imaging image in order to guide design of skin flap, and compared results with the data of perforator arteries observed during the operation. RESULTS: Totally 52 branches of perforating arteries were detected by Doppler blood stream detector during operation, and 38 perforator branches were confirmed in operation, the accuracy rate was 73.1%. Thirty-eight branches of perforating arteries were detected by infrared thermography during operation, and 35 branches of perforating branches were confirmed in operation, the accuracy rate was 92.1%; there were statistical difference. The most dynamic perforating pivot found by Doppler blood stream detector was confirmed by intraoperative diagnosis, with an accuracy rate of 80.6%. The most dynamic perforating pivot found by infrared thermography is confirmed by intraoperative diagnosis, with an accuracy rate of 100%; there were statistical difference. Thirty-one flaps were survived without vascular crisis occurred. All patients were followed up from 6 to 18 months with an average of(10.7±1.2) months. The flaps survived with soft texture and good blood circulation, the defect was not bloated, the color of skin flap was basically the same as that of the normal skin, and the limbs appearance and function recovered well. CONCLUSIONS: Infrared infrared thermal imaging technology could be used as a new technology in localization of perforator artery in free anterolateral thigh perforator flap transplantation.

Joint Exploration of Favorable Haplotypes for Mineral Concentrations in Milled Grains of Rice (Oryza sativa L.).

Grain minerals in rice, especially those in milled grains, are important sources of micro-nutrition elements, such as iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), and selenium (Se), and of toxic heavy metal elements, especially cadmium (Cd), for populations consuming a rice diet. To date, the genetic mechanism underlying grain mineral concentrations (GMCs) in milled grain remains largely unknown. In this report, we adopted a set of 698 germplasms consisting of two subsets [indica/Xian (X-set) and japonica/Geng (G-set)], to detect quantitative trait loci (QTL) affecting GMC traits of Fe, Zn, Cd, Mn, Cu, and Se in milled grains. A total of 47 QTL regions, including 18 loci and 29 clusters (covering 62 Cd loci), responsible for the GMCs in milled grains were detected throughout the genome. A joint exploration of favorable haplotypes of candidate genes was carried out as follows: (1) By comparative mapping, 10 chromosome regions were found to be consistent with our previously detected QTL from linkage mapping. (2) Within eight of these regions on chromosomes 1, 4, 6, 7, and 8, candidate genes were identified in the genome annotation database. (3) A total of 192 candidate genes were then submitted to further haplotype analysis using million-scale single nucleotide polymorphisms (SNPs) from the X-set and the G-set. (4) Finally, 37 genes (19.3%) were found to be significant in the association between the QTL targeting traits and the haplotype variations by pair-wise comparison. (5) The phenotypic values for the haplotypes of each candidate were plotted. Three zinc finger (like) genes within two candidate QTL regions (qFe6-2 and qZn7), and three major GMC traits (Fe, Zn, and Cd) were picked as sample cases, in addition to non-exhausted cross validations, to elucidate this kind of association by trait value plotting. Taken together, our results, especially the 37 genes with favorable haplotype variations, will be useful for rice biofortification molecular breeding.

Assembly of an early-matured japonica (Geng) rice genome, Suijing18, based on PacBio and Illumina sequencing.

The early-matured japonica (Geng) rice variety, Suijing18 (SJ18), carries multiple elite traits including durable blast resistance, good grain quality, and high yield. Using PacBio SMRT technology, we produced over 25 Gb of long-read sequencing raw data from SJ18 with a coverage of 62×. Using Illumina paired-end whole-genome shotgun sequencing technology, we generated 59 Gb of short-read sequencing data from SJ18 (23.6 Gb from a 200 bp library with a coverage of 59× and 35.4 Gb from an 800 bp library with a coverage of 88×). With these data, we assembled a single SJ18 genome and then generated a set of annotation data. These data sets can be used to test new programs for variation deep mining, and will provide new insights into the genome structure, function, and evolution of SJ18, and will provide essential support for biological research in general.

[Advance in therapy for Duchenne/Becker muscular dystrophy].

Duchenne/Becker muscular dystrophy (DMD/BMD) is the most common X-linked recessive inherited neuromuscular disease, characterized by progressive muscle weakness. Mutations in the dystrophin gene are responsible for this disease. Treatment for this disease has always been a topic of interest. With the development of diagnosis and treatment technology of molecular biology, promising therapies have been developed. This review article summarizes the advance in traditional therapy, cell transplantation and gene therapy for this disease.