tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application.

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding RNAs (ncRNAs) produced by the specific cleavage of precursor or mature tRNAs. tsRNAs are involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting the occurrence and development of various human diseases, including cancers. Recent studies have shown that tsRNAs play an important role in tumorigenesis by regulating biological behaviors such as malignant proliferation, invasion and metastasis, angiogenesis, immune response, tumor resistance, and tumor metabolism reprogramming. These may be new potential targets for tumor treatment. Furthermore, tsRNAs can exist abundantly and stably in various bodily fluids (e.g., blood, serum, and urine) in the form of free or encapsulated extracellular vesicles, thereby affecting intercellular communication in the tumor microenvironment (TME). Meanwhile, their abnormal expression is closely related to the clinicopathological features of tumor patients, such as tumor staging, lymph node metastasis, and poor prognosis of tumor patients; thus, tsRNAs can be served as a novel type of liquid biopsy biomarker. This review summarizes the discovery, production, and expression of tsRNAs and analyzes their molecular mechanisms in tumor development and potential applications in tumor therapy, which may provide new strategies for early diagnosis and targeted therapy of tumors.

Clinical evaluation of a multiplex droplet digital PCR for pathogen detection in critically ill COVID-19 patients with bloodstream infections.

BACKGROUND: Nosocomial bloodstream infections (nBSI) have emerged as a clinical concern for physicians treating COVID-19 patients. In this study, we aimed to evaluate the effectiveness of a multiplex ddPCR in detecting bacterial pathogens in the blood of COVID-19 critically ill patients. METHODS: This prospective diagnostic study included RT-PCR-confirmed COVID-19 patients admitted to our hospital from December 2022 to February 2023. A multiplex ddPCR assay was used to detect common bacterial pathogens and AMR genes in blood samples of the patients, along with antimicrobial susceptibility testing (AST). The diagnostic performance of the ddPCR assay was evaluated by comparing the results with those obtained through blood culture and clinical diagnosis. Additionally, the ability of ddPCR in detecting bacterial resistance was compared with the AST results. RESULTS: Of the 200 blood samples collected from 184 patients, 45 (22.5%) were positive using blood culture, while 113 (56.5%) were positive for bacterial targets using the ddPCR assay. The ddPCR assay outperformed blood culture in pathogen detection rate, mixed infection detection rate, and fungal detection rate. Acinetobacter baumannii and Klebsiella pneumoniae were the most commonly detected pathogens in COVID-19 critically ill patients, followed by Enterococcus and Streptococcus. Compared to blood culture, ddPCR achieved a sensitivity of 75.5%, specificity of 51.0%, PPV of 30.9%, and NPV of 87.8%, respectively. However, there were significant differences in sensitivity among different bacterial species, where Gram-negative bacteria have the highest sensitivity of 90.3%. When evaluated on the ground of clinical diagnosis, the sensitivity, specificity, PPV and NPV of ddPCR were 78.1%, 90.5%, 94.7%, and 65.5%, respectively. In addition, the ddPCR assay detected 23 cases of blaKPC, which shown a better consistent with clinical test results than other detected AMR genes. Compared to blaKPC, there were few other AMR genes detected, indicating that the application of other AMR gene detection in the COVID-19 critically ill patients was limited. CONCLUSION: The multiplex ddPCR assay had a significantly higher pathogen detection positivity than the blood culture, which could be an effective diagnostic tool for BSIs in COVID-19 patients and to improve patient outcomes and reduce the burden of sepsis on the healthcare system, though there is room for optimization of the panels used.- Adjusting the targets to include E. faecalis and E. faecium as well as Candida albicans and Candida glabrata could improve the ddPCR' s effectiveness. However, further research is needed to explore the potential of ddPCR in predicting bacterial resistance through AMR gene detection.

[Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis].

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

Mitochondrial Transplantation: A Unique Treatment Strategy.

ABSTRACT: Mitochondrial transplantation (MT) refers to the process of introducing isolated mitochondria into a damaged area of the heart or other organs. In the past decade, this technique has been continuously updated as the fundamental research on the repair of damaged cells or tissues. In particular, in the field of heart protection from ischemia-reperfusion injury, the MT therapy has been developed to the clinical trial stage. Generally speaking, the goal of therapeutic intervention is to replace damaged mitochondria or increase the transfer of mitochondria between cells so as to improve mitochondrial dysfunction. In this review, we summarized the studies on MT conducted at different time nodes and outlined a range of different methods for delivering mitochondria into the target site. Finally, we described the applications of MT in different diseases and discussed the clinical studies of human MT currently in progress and the problems that need to be overcome. We hope to provide new ideas for the treatment of mitochondrial defect-related diseases.

Different visual evoked potentials in neuromyelitis optica spectrum disorder-related optic neuritis and idiopathic demyelinating optic neuritis: a prospective longitudinal analysis.

BACKGROUND: To investigate different visual evoked potential (VEP) patterns in neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) and idiopathic demyelinating optic neuritis (IDON). METHODS: This was a longitudinal, prospective, case-control study. Eighty-four Chinese patients with acute optic neuritis were enrolled, including 26 NMOSD-ON patients and 58 IDON patients. All the patients underwent best-corrected visual acuity (BCVA) and full-field pattern reversal VEP recordings at the onset, 1 month, 3 months, and 6 months. RESULTS: Within 15' checks, the NMOSD-ON patients had more severe VEP amplitude reduction at 6 months (2.39 ± 4.63 µV vs. 6.96 ± 8.88 µV, P = 0.034). However, the IDON patients showed more frequently normal VEP response at 3 months (24.0% vs. 4.5%, P = 0.017), and only prolonged P100 peak latency with normal amplitude (L) at 6 months (30.0% vs. 57.8%, P = 0.048). Within 60' checks, no significant difference in VEP parameters between the two groups was found at each follow-up (P > 0.05). CONCLUSIONS: The NMOSD-ON patients showed more severe axonal damage and worse axonal recovery than the IDON patients. VEP elicited by smaller check size was more sensitive to visual pathway abnormality in NMOSD-ON.

Myocardial Ischemia-Reperfusion Injury: Therapeutics from a Mitochondria-Centric Perspective.

Coronary arterial disease is the most common cardiovascular disease. Myocardial ischemia-reperfusion injury caused by the initial interruption of organ blood flow and subsequent restoration of organ blood flow is an important clinical problem with various cardiac reperfusion strategies after acute myocardial infarction. Even though blood flow recovery is necessary for oxygen and nutrient supply, reperfusion causes pathological sequelae that lead to the aggravation of ischemic injury. At present, although it is known that injury will occur after reperfusion, clinical treatment always focuses on immediate recanalization. Mitochondrial fusion, fission, biogenesis, autophagy, and their intricate interaction constitute an effective mitochondrial quality control system. The mitochondrial quality control system plays an important role in maintaining cell homeostasis and cell survival. The removal of damaged, aging, and dysfunctional mitochondria is mediated by mitochondrial autophagy. With the help of appropriate changes in mitochondrial dynamics, new mitochondria are produced through mitochondrial biogenesis to meet the energy needs of cells. Mitochondrial dysfunction and the resulting oxidative stress have been associated with the pathogenesis of ischemia/reperfusion (I/R) injury, which play a crucial role in the pathophysiological process of myocardial injury. This review aimed at elucidating the mitochondrial quality control system and establishing the possibility of using mitochondria as a potential therapeutic target in the treatment of I/R injuries.

Combination of levulinic acid and sodium dodecyl sulfate on inactivation of foodborne microorganisms: A review.

The combination of levulinic acid and sodium dodecyl sulfate (SDS) in recent years has shown considerable promise as an antimicrobial intervention. Both ingredients have been designated by the U.S. Food and Drug Administration (FDA) as Generally Recognized as Safe (GRAS) for being used as a flavoring agent and multipurpose food additive, respectively. The use of levulinic acid and SDS alone has limited antimicrobial efficacy on tested microorganisms, and synergism between levulinic acid and SDS has been observed. The postulated mechanism of action of the synergistic effect is presented. The antimicrobial efficacy of levulinic acid plus SDS remains high even when organic materials are present. The other features, including penetration, foamability, and being readily soluble, extend its potential applications to disinfection of difficult-to-access areas and control of foodborne pathogens both in a planktonic state and in a biofilm. These features indicate that the levulinic acid plus SDS combination may have the potential to be applied within the food processing environment on a large scale.

Verrucosispora rhizosphaerae sp. nov., isolated from mangrove rhizosphere soil.

An actinomycete strain, 2603PH03T, was isolated from a mangrove rhizosphere soil sample collected in Wenchang, China. Phylogenetic analysis of the 16S rRNA gene sequence of strain 2603PH03T indicated high similarity to Verrucosispora gifthornensis DSM 44337T (99.4%), Verrucosispora andamanensis (99.4%), Verrucosispora fiedleri MG-37T (99.4%) and Verrucosispora maris AB18-032T (99.4%). The cell wall was found to contain meso-diaminopimelic acid and glycine. The major menaquinones were identified as MK-9(H4), MK-9(H6) and MK-9(H8), with MK-9(H2), MK-10(H2), MK-9(H10) and MK-10(H6) as minor components. The characteristic whole cell sugars were found to be xylose and mannose. The phospholipid profile was found to contain phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol mannoside, phosphatidylinositol, phosphatidylserine and an unidentified phospholipid. The DNA G+C content was determined to be 70.1 mol%. The results of physiological and biochemical tests and low DNA-DNA relatedness readily distinguished the isolate from the closely related species. On the basis of these phenotypic and genotypic data, strain 2603PH03T is concluded to represent a novel species of the genus Verrucosispora, for which the name Verrucosispora rhizosphaerae sp. nov. is proposed. The type strain is 2603PH03T (=CCTCC AA 2016023T = DSM 45673T).

McTwo: a two-step feature selection algorithm based on maximal information coefficient.

BACKGROUND: High-throughput bio-OMIC technologies are producing high-dimension data from bio-samples at an ever increasing rate, whereas the training sample number in a traditional experiment remains small due to various difficulties. This "large p, small n" paradigm in the area of biomedical "big data" may be at least partly solved by feature selection algorithms, which select only features significantly associated with phenotypes. Feature selection is an NP-hard problem. Due to the exponentially increased time requirement for finding the globally optimal solution, all the existing feature selection algorithms employ heuristic rules to find locally optimal solutions, and their solutions achieve different performances on different datasets. RESULTS: This work describes a feature selection algorithm based on a recently published correlation measurement, Maximal Information Coefficient (MIC). The proposed algorithm, McTwo, aims to select features associated with phenotypes, independently of each other, and achieving high classification performance of the nearest neighbor algorithm. Based on the comparative study of 17 datasets, McTwo performs about as well as or better than existing algorithms, with significantly reduced numbers of selected features. The features selected by McTwo also appear to have particular biomedical relevance to the phenotypes from the literature. CONCLUSION: McTwo selects a feature subset with very good classification performance, as well as a small feature number. So McTwo may represent a complementary feature selection algorithm for the high-dimensional biomedical datasets.

Spatial diversity processing mechanism based on the distributed underwater acoustic communication system.

To address the problem of unreliable single-link underwater acoustic communication caused by large signal delays and strong multipath effects in shallow water environments, this paper proposes a distributed underwater acoustic diversity communication system (DUA-DCS). DUA-DCS employs a maneuverable distributed cross-medium buoy network to form multiple distributed, non-coherent, and parallel communication links. In the uplink, a receiving diversity processing mechanism of joint decision feedback equalizer embedded phase-locked loop and maximum signal-to-interference ratio combining (DFE-PLL-MSIRC) is proposed to achieve waveform-level diversity combining of underwater signals. A phase-locked loop module is embedded in each branch of the decision feedback equalizer to eliminate the residual frequency and phase errors after Doppler compensation. Meanwhile, the combining coefficients are determined based on the maximum signal-to-interference ratio criterion, taking into account the residual inter-symbol interference after equalization, resulting in efficient and accurate computation. Additionally, the combined decision values are fed back to the feedback filters in each branch to ensure more accurate feedback output. Simulation and lake experiment results demonstrate that, compared to the single-link communication system, DFE-PLL-MSIRC can achieve a diversity gain of more than 5.2 dB and obtain about 3 dB more diversity gain than the comparison algorithm. And the BER of DFE-PLL-MSIRC can be reduced by at least one order of magnitude, which is lower by at least 0.6 order of magnitude compared to the comparison algorithm. In the downlink, a transmitting diversity processing mechanism of complex orthogonal space-time block coding (COSTBC) is proposed. By utilizing a newly designed generalized complex orthogonal transmission matrix, complete transmission diversity can be achieved at the coding rate of 3/4. Compared to the single-link communication system, the system can achieve a diversity gain of more than 6 dB.

High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson's disease: a randomized controlled trial.

Background: Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson's disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD. Methods: This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes. Results: Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1. Conclusion: High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.

Exosome derived from tumor-associated macrophages: biogenesis, functions, and therapeutic implications in human cancers.

Tumor-associated macrophages (TAMs), one of the most abundant immune cell types in the tumor microenvironment (TME), account for approximately 50% of the local hematopoietic cells. TAMs play an important role in tumorigenesis and tumor development through crosstalk between various immune cells and cytokines in the TME. Exosomes are small extracellular vesicles with a diameter of 50-150 nm, that can transfer biological information (e.g., proteins, nucleic acids, and lipids) from secretory cells to recipient cells through the circulatory system, thereby influencing the progression of various human diseases, including cancer. Recent studies have suggested that TAMs-derived exosomes play crucial roles in malignant cell proliferation, invasion, metastasis, angiogenesis, immune responses, drug resistance, and tumor metabolic reprogramming. TAMs-derived exosomes have the potential to be targeted for tumor therapy. In addition, the abnormal expression of non-coding RNAs and proteins in TAMs-derived exosomes is closely related to the clinicopathological features of patients with cancer, and these exosomes are expected to become new liquid biopsy markers for the early diagnosis, prognosis, and monitoring of tumors. In this review, we explored the role of TAMs-derived exosomes in tumorigenesis to provide new diagnostic biomarkers and therapeutic targets for cancer prevention.

Study on the mechanism of action of colchicine in the treatment of coronary artery disease based on network pharmacology and molecular docking technology.

Objective: This is the first study to explore the mechanism of colchicine in treating coronary artery disease using network pharmacology and molecular docking technology, aiming to predict the key targets and main approaches of colchicine in treating coronary artery disease. It is expected to provide new ideas for research on disease mechanism and drug development. Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Swiss Target Prediction and PharmMapper databases were used to obtain drug targets. GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), DrugBank and DisGeNET databases were utilized to gain disease targets. The intersection of the two was taken to access the intersection targets of colchicine for the treatment of coronary artery disease. The Sting database was employed to analyze the protein-protein interaction network. Gene Ontology (GO) functional enrichment analysis was performed using Webgestalt database. Reactom database was applied for Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking was simulated using AutoDock 4.2.6 and PyMOL2.4 software. Results: A total of 70 intersecting targets of colchicine for the treatment of coronary artery disease were obtained, and there were interactions among 50 targets. GO functional enrichment analysis yielded 13 biological processes, 18 cellular components and 16 molecular functions. 549 signaling pathways were obtained by KEGG enrichment analysis. The molecular docking results of key targets were generally good. Conclusion: Colchicine may treat coronary artery disease through targets such as Cytochrome c (CYCS), Myeloperoxidase (MPO) and Histone deacetylase 1 (HDAC1). The mechanism of action may be related to the cellular response to chemical stimulus and p75NTR-mediated negative regulation of cell cycle by SC1, which is valuable for further research exploration. However, this research still needs to be verified by experiments. Future research will explore new drugs for treating coronary artery disease from these targets.

Wall shear stress and its role in atherosclerosis.

Atherosclerosis (AS) is the major form of cardiovascular disease and the leading cause of morbidity and mortality in countries around the world. Atherosclerosis combines the interactions of systemic risk factors, haemodynamic factors, and biological factors, in which biomechanical and biochemical cues strongly regulate the process of atherosclerosis. The development of atherosclerosis is directly related to hemodynamic disorders and is the most important parameter in the biomechanics of atherosclerosis. The complex blood flow in arteries forms rich WSS vectorial features, including the newly proposed WSS topological skeleton to identify and classify the WSS fixed points and manifolds in complex vascular geometries. The onset of plaque usually occurs in the low WSS area, and the plaque development alters the local WSS topography. low WSS promotes atherosclerosis, while high WSS prevents atherosclerosis. Upon further progression of plaques, high WSS is associated with the formation of vulnerable plaque phenotype. Different types of shear stress can lead to focal differences in plaque composition and to spatial variations in the susceptibility to plaque rupture, atherosclerosis progression and thrombus formation. WSS can potentially gain insight into the initial lesions of AS and the vulnerable phenotype that gradually develops over time. The characteristics of WSS are studied through computational fluid dynamics (CFD) modeling. With the continuous improvement of computer performance-cost ratio, WSS as one of the effective parameters for early diagnosis of atherosclerosis has become a reality and will be worth actively promoting in clinical practice. The research on the pathogenesis of atherosclerosis based on WSS is gradually an academic consensus. This article will comprehensively review the systemic risk factors, hemodynamics and biological factors involved in the formation of atherosclerosis, and combine the application of CFD in hemodynamics, focusing on the mechanism of WSS and the complex interactions between WSS and plaque biological factors. It is expected to lay a foundation for revealing the pathophysiological mechanisms related to abnormal WSS in the progression and transformation of human atherosclerotic plaques.

Meta-analysis and trial sequential analysis of acupoint catgut embedding in the treatment of ulcerative colitis: Acupoint catgut embedding treating ulcerative colitis meta-analysis.

BACKGROUND: Although anti-inflammatory and immunomodulatory measures have delayed the progression of ulcerative colitis (UC) to a certain extent, the adverse drug reactions and recurrence after recovery still trouble clinicians. Acupoint catgut embedding is a possible alternative strategy for the treatment of UC, but its clinical efficacy remains controversial. Therefore, this study systematically evaluated the clinical efficacy and safety of acupoint catgut embedding compared with conventional western medicine in the treatment of UC. METHODS: VIP, Wanfang, China National Knowledge Infrastructure, China Biology Medicine, PubMed, Embase, Web of Science, the Cochrane Library databases were searched. And the publication time of the literature was limited from the time that the database was established to February 2022. Two researchers independently screened the literature, extracted data, and assessed risk of bias as required. Meta-analysis was performed with Revman 5.3. Trial sequential analysis (TSA) was performed with TSA 0.9.5.10 Beta. Publication bias was assessed by Stata 15.0. And evidence quality was appraised with GRADEpro3.6. RESULTS: A total of 10 studies were listed, with a total sample size of 782 cases. Meta-analysis showed that compared with conventional western medicine, acupoint catgut embedding can effectively improve the total effective rate of clinical symptoms (relative risk [RR] = 1.16, 95% confidence interval [CI] = [1.09,1.24], P < .00001), endoscopic total effective rate (RR = 1.16, 95%CI = [1.08,1.25], P < .0001), clinical symptom cure rate (RR = 1.80, 95%CI = [1.37,2.38], P < .0001), and endoscopic cure rate (RR = 1.97, 95%CI = [1.36,2.86], P = .0004) of UC, but the adverse event rate (RR = 0.20, 95%CI = [0.01,4.00], P = .29) was similar. Trial sequential analysis indicated that the efficacy endpoint was conclusive. Harbord test confirmed no significant publication bias. The quality of evidence for these outcomes ranges from low to medium. CONCLUSION: The clinical efficacy of acupoint catgut embedding in the treatment of UC is superior to that of conventional western medicine, and the safety may be equivalent to that of conventional western medicine, which has the value of further research and exploration.

Optimal dose of tirzepatide for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis.

Objective: The purpose of this study is to evaluate the optimal dose of tirzepatide (TZP) for the treatment of type 2 diabetes mellitus (T2DM) by meta-analysis and trial sequential analysis (TSA). Methods: Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022. Mean differences (MD) and 95% confidence intervals (95%CI) were used for continuous variables, and relative risk (RR) and 95%CI were used for dichotomous variables. Results: Compared with TZP 5 mg, meta-analysis showed that TZP 10 mg significantly reduced glycosylated hemoglobin type A1c (HbA1c) (MD -0.24, 95%CI -0.31~-0.17, P < 0.00001), fasting serum glucose (FSG) (MD -5.82, 95%CI -8.35~-3.28, P < 0.00001) and weight (MD -2.47, 95%CI -2.95~-1.98, P < 0.00001), and TZP 15 mg significantly reduced HbA1c (MD -0.37, 95%CI -0.44~-0.29, P < 0.00001), FSG (MD -8.52, 95%CI -11.07~-5.98, P < 0.00001) and weight (MD -4.63, 95%CI -5.45~-3.81, P < 0.00001). Compared with TZP 10 mg, TZP 15 mg dramatically reduced HbA1c (MD -0.12, 95%CI -0.19~-0.05, P = 0.001), FSG (MD -2.73, 95%CI -5.29~-0.17, P = 0.04) and weight (MD -2.18, 95%CI -2.67~-1.70, P < 0.00001). The TSA indicated that the benefits observed in the current information set were conclusive, except for the FSG of "TZP 15 mg vs. TZP 10 mg". In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP. Compared with TZP 5 mg, TZP 10 mg increased total adverse events (RR 1.06, 95%CI 1.01~1.11, P = 0.03) and gastrointestinal (GI) AEs (RR 1.17, 95%CI 1.03~1.33, P = 0.02), and TZP 15 mg increased total AEs (RR 1.10, 95%CI 1.05~1.15, P = 0.0001). There were no significant differences in total AEs and GI AEs for TZP 15 mg compared to TZP 10 mg. The TSA demonstrated that the total AEs of "TZP 15 mg vs. TZP 5 mg" were conclusive. Conclusions: TZP 15 mg >TZP 10 mg > TZP 5 mg in terms of lowering glycemia and reducing weight. TZP 5 mg > TZP 10 mg = TZP 15 mg in terms of safety. On this basis, we recommend TZP 5 mg as the first-choice dose for patients with T2DM to minimize AEs while reducing glycemia and weight. If patients cannot effectively control their glycemia after taking TZP 5 mg, it is recommended to take TZP 15 mg directly to achieve the best effect of glycemic reduction. However, most of the included studies have the background of basic medication, the independent efficacy and safety of different doses of TZP still need to be tested. Systematic review registration: Unique Identifier: CRD42022341966.

Efficacy and safety of dorzagliatin for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis.

Objective: To evaluate the efficacy and safety of dorzagliatin in the treatment of type 2 diabetes mellitus (T2DM) by using meta-analysis and trial sequential analysis (TSA). Method: Search for clinical trials of dorzagliatin for T2DM in eight databases, with a time limit of build to July 2022. The included studies that met the requirements were carried out for meta-analysis and TSA. Results: In terms of efficacy endpoints, meta-analysis showed that dorzagliatin decreased glycated hemoglobin A1c(HbA1c) [mean difference (MD) -0.65%, 95% confidence interval (CI) -0.76 ~ -0.54, P < 0.00001], fasting plasma glucose (FPG) (MD -9.22 mg/dL, 95% CI -9.99 ~ -8.44, P < 0.00001), 2 h postprandial glucose (2h-PPG) (MD -48.70 mg/dL, 95% CI -55.45 ~ -41.96, P < 0.00001), homeostasis model assessment 2 of insulin resistance (HOMA2-IR) (MD -0.07, 95% CI -0.14 ~ -0.01, P = 0.03) and increased homeostasis model assessment 2 of ß-cells function (HOMA2-ß) (MD 2.69, 95% CI 1.06 ~ 4.31, P = 0.001) compared with placebo. And TSA revealed that the benefits observed for the current information set were conclusive, except for HOMA2-IR. In comparison with placebo, dorzagliatin increased triglyceride(TG) (MD 0.43 mmol/L, 95% CI 0.30 ~ 0.56, P < 0.00001), total cholesterol (TC) (MD 0.13 mmol/L, 95% CI 0.05 ~ 0.21, P = 0.001), body weight (MD 0.38 kg, 95% CI 0.12-0.63, P = 0.004) and body mass index (BMI) (MD 0.14 kg/m2, 95% CI 0.05-0.24, P = 0.003), while low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were comparable. And TSA demonstrated that TG, TC, body weight, and BMI were conclusive. In terms of safety endpoints, dorzagliatin increased total adverse events (AEs) [risk ratio (RR) 1.56, 95% CI 1.06 ~ 2.30, P = 0.03], while serious AEs, hyperlipidemia, and hypoglycaemia were all comparable. And TSA indicated that the results need to be confirmed by additional studies. Harbord regression showed no publication bias. Conclusion: Dorzagliatin was effective in lowering glycemia, reducing insulin resistance and improving islet ß-cells function without affecting blood pressure, LDL-C, and HDL-C. Although dorzagliatin caused a mild increase in TG and TC, it did not increase the incidence of hyperlipidemia, and the small increases in body weight and BMI were not clinically significant enough. In terms of safety, the total AEs caused by dorzagliatin may be a cumulative effect of single AEs, with no drug-related adverse event being reported at a higher incidence than placebo alone. Dorzagliatin's serious AEs, hyperlipidemia, and hypoglycemia are comparable to that of placebo, and dorzagliatin has a good safety profile. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371802 identifier: CRD42022371802.

[Clinical study of the effect of fixed Twin-block on adolescent skeletal Class â ¡ malocclusion].

PURPOSE: To evaluate the retention ability of fixed Twin-block appliance and its clinical effect on adolescent skeletal ClassⅡmalocclusion. METHODS: Twenty-six skeletal ClassⅡdivision 1 adolescents (M:12, F: 14; age:11~13 years, average: 11.8 years) were chosen and fixed Twin-block appliance was used to guide the mandibular protrusion for one year. Before and after treatment, cephalometric films were taken to observe the skeletal, dental and soft tissue changes. Graphpad Prism 6.0 software was used for Student's t test. RESULTS: There was no loosening or destruction of the appliance during the treatment and the profile of all cases was improved significantly. The indexes that showed significant difference(P<0.05) included the mandibular length and position (Co-Gn, SNB, ANB, Pog-VL, Pos-VL) , the inclination and position of the maxillary incisors(U1-VL, U1-SN), the sagittal position of the mandibular dentition(L1-VL, L6-VL). The indexes that showed insignificant difference(P>0.05) included the mandibular plane(MP-SN), the length and position of the maxilla (SNA, A-VL) , the vertical position of the maxillary incisor(U1-HL), the position of the maxillary posterior teeth(U6-VL, U6-HL), the mandibular incisor inclination(IMPA) and the vertical position of the mandibular dentition(L6-MP,L1-MP). CONCLUSIONS: Fixed Twin-block appliance can enhance the mandibular anchorage, effectively promote the mandibular growth and improve the facial profile.

Nitrogen-doped porous carbon encapsulating iron nanoparticles for enhanced sulfathiazole removal via peroxymonosulfate activation.

Developing novel catalyst with both high efficiency and stability presents an enticing prospect for peroxymonosulfate (PMS) activation. In this paper, nitrogen-doped porous carbon encapsulating iron nanoparticles (CN-Fe) was fabricated by a facile carbothermal reduction process using polyaniline (PANI) and α-Fe2O3 as the precursors. The stubborn antibiotics, sulfathiazole (STZ), was employed as a target pollutant, demonstrating that CN-Fe coupled with PMS could achieve 96% removal efficiency and even 57% mineralization rate of STZ within 40 min. More importantly, the rate constant of CN-Fe was calculated to be 0.07665 min-1, which was 6 times higher than that of the commercial α-Fe2O3 catalyst. Furthermore, CN-Fe also presented a favorable catalytic performance for removing other organic pollutants including phenolic compounds and organic dyes. Interestingly, the catalytic activity of the used CN-Fe catalyst could be regenerated after thermal treatment (600 °C) and the as-synthesized CN-Fe catalyst exhibited excellent long-term stability with almost no loss of activity after storage for three months. The catalytic mechanism in the CN-Fe/PMS system was elucidated by electron paramagnetic resonance (EPR), linear sweep voltammetry (LSV), radical and electron trapping tests, which confirmed that sulfate radicals (SO4-), hydroxyl radicals (OH), superoxide radicals (O2-) and singlet oxygen (1O2) were generated in the oxidation process with the assistance of electron transfer between PMS and catalyst. To our knowledge, this was the first attempt for the application of PANI-derived CN-Fe hybrid materials as PMS activators and the findings would provide a simple and promising strategy to fabricate highly efficient and environment-benign catalysts for wastewater remediation.

[Study on the practice and effect of target teaching method in teaching of dental technology interns].

PURPOSE: To standardize the teaching process of interns in dental technology so as to make the learning progress and process goals more clearly and improve the teaching quality. METHODS: Thirty-two junior interns were selected from medical colleges and universities from 2014 to 2017, based on same learning ability, learning attitude, learning achievement and hands-on ability ，they were randomly divided into 2 groups. The experimental group adopted the goal teaching method, using relevant teaching materials, applying theory to practice closely, and trying to standardize practice. The control group entered the production lines directly without teaching materials, the students were all owed only to see, think and manipulate. The data were analyzed with SPSS 18.0 software package. RESULTS: The exam scores of the students in the experimental group were significantly higher than that of the students in the control group. Moreover, the satisfaction with the teaching methods of the experimental group was significantly higher than that of the control group (P<0.05). CONCLUSIONS: The target teaching method is effective in teaching dental technology. Students clearly understand the study progress, process goals and their operational performance is significantly improved.