International Journal of Clinical Practice最新文献

Background. This study employed integrated network pharmacology approach to explore the mechanisms underlying the protective effect of colchicine against acute lung injury (ALI). Methods. We analyzed the expression profiles from 13 patients with sepsis-related ALI and 21 controls to identify differentially expressed genes and key modules. ALI-related genes were curated using databases such as DisGeNET, Therapeutic Target, and Comparative Toxicogenomics Database to curate ALI-related genes. Drug target fishing for colchicine was conducted using the DrugBank, BATMAN-TCM, STITCH, and SwissTargetPrediction. Potential drug-disease interactions were determined by intersecting ALI-associated genes with colchicine target genes. We performed comprehensive pathway and process enrichment analyses on these genes. A protein-protein interaction network was constructed, and topological analysis was executed. Additionally, an ALI mouse model was established to evaluate the effect of colchicine on CXCL12 and CXCR4 levels through western blot analysis. Results. Analysis revealed 23 potential colchicine-ALI interaction genes from the intersection of 253 ALI-associated genes and 389 colchicine targets. Functional enrichment analysis highlighted several inflammation-related pathways, such as cytokine-mediated signaling pathway, CXCR chemokine receptor binding, NF-kappa B signaling pathway, TNF signaling pathway, and IL-17 signaling pathway. The protein-protein interaction network demonstrated complex interactions for CXCL12 and CXCR4 among other candidate genes, with significant topological interaction degrees. In vivo studies showed that colchicine significantly reduced elevated CXCL12 and CXCR4 levels in ALI mice. Conclusion. Our findings suggest that colchicine’s therapeutic effect on ALI might derive from its anti-inflammatory properties. Further research is needed to explore the specific mechanisms of colchicine’s interaction with sepsis-induced ALI.

Aim. This study aimed to explore how varying inspiratory muscle training workloads affect exercise capacity, health-related quality of life (HrQoL), depression, peripheral and respiratory muscle strength, pulmonary function, dyspnea, fatigue, and physical activity levels in hypertension (HT) patients. Methods. A randomized, controlled three-arm study. Forty-five patients (58.37 ± 8.53 y, 7F/38M) with HT received IMT (7 days/8 weeks) by POWERbreathe® Classic LR device and were randomized to control group (CG, 10% maximal inspiratory pressure (MIP), n: 15), low-load group (LLG, 30% MIP), and high-load group (HLG, %50 MIP). Exercise capacity, HrQoL, depression, peripheral and respiratory muscle strength, pulmonary function, fatigue, physical activity level, dyspnea, and sleep quality were evaluated before and after the training. Results. Exercise capacity, physical functioning, peripheral muscle strength, and resting dyspnea were statistically significantly improved in HLG and LLG after the training compared to CG (p < 0.05). Similar improvements in perception of depression, fatigue, and sleep quality were seen within and between the groups (p > 0.05). Statistically significant differences were found within all the groups in terms of MIP and PEF values of respiratory functions (p < 0.05). The superior improvement in the physical activity level was found in the HLG (p < 0.05). Discussion. High-load IMT was particularly effective in increasing physical activity level, peripheral muscle strength, exercise capacity, and improved HrQoL. Low-load IMT was effective in reducing dyspnea and improving respiratory function. Device-guided breathing exercises decreased blood pressure, improved sleep quality, and strengthened respiratory muscles. IMT, an efficient method, is suggested for inclusion in rehabilitation programs due to its capacity to increase physical activity, exercise capacity, and peripheral muscle strength, enhance HrQoL and respiratory function, and alleviate dyspnea. Also, the efficacy of IMT should be investigated with different training protocols such as endurance IMT or functional IMT in HT patients.

Background. During the COVID-19 pandemic, there was increased adoption of telepharmacy, which has proven benefits. This study was conducted to assess the knowledge and perception of the community pharmacists of Aseer region, Saudi Arabia, towards telepharmacy services and evaluate their willingness to adopt telepharmacy in clinical practice during the COVID-19 pandemic. Materials and Methods. A cross-sectional study was conducted using an online self-administered structured anonymous questionnaire on the community pharmacists of Aseer region, Saudi Arabia. It covers demographics, computer access and literacy, knowledge and perception, and willingness to practice telepharmacy. Results were expressed as frequencies, percentages, and mean. The comparison between the classes of the demographic variables and the scores was done via Kruskal–Wallis and Mann–Whitney tests. Result. About half of the pharmacists in our study showed average knowledge about telepharmacy, the practical application of telepharmacy technology, and telepharmacy guidelines with a percentage of 53%, 52%, and 47%, respectively). Majority of the participants showed high perception towards telepharmacy in Saudi Arabia, while 93% of the pharmacists in Saudi Arabia agreed that the implementation of telepharmacy technology is appropriate due to the current COVID-19 pandemic. Only a significant relation was found between gender and computer access, literacy, and perceptions towards telepharmacy with p values of 0.033 and 0.026, respectively. Conclusion. The majority of the community pharmacists exhibited a positive perception and are willing to practice the concept of telepharmacy despite having a below average knowledge of telepharmacy. A future study involving the entire kingdom of Saudi Arabia could help identify the gaps in the knowledge, perception, and willingness to practice telepharmacy on a broader scale and thus promote telepharmacy adoption in the entire kingdom.

Objective. We conducted a meticulous bioinformatics analysis leveraging expression data of 226 PANRGs obtained from previous studies, as well as clinical data from AML patients derived from the HOVON database. Methods. Through meticulous data analysis and manipulation, we were able to categorize AML cases into two distinct PANRG clusters and subsequently identify differentially expressed genes (PRDEGs) with prognostic significance. Furthermore, we organized the patient data into two corresponding gene clusters, allowing us to investigate the intricate relationship between the risk score, patient prognosis, and the immune landscape. Results. Our findings disclosed significant associations between the identified PANRGs, gene clusters, patient survival, immune system, and cancer-related biological processes and pathways. Importantly, we successfully constructed a prognostic signature comprising nineteen genes, enabling the stratification of patients into high-risk and low-risk groups based on individually calculated risk scores. Furthermore, we developed a robust and practical nomogram model, integrating the risk score and other pertinent clinical features, to facilitate accurate patient survival prediction. Our comprehensive analysis demonstrated that the high-risk group exhibited notably worse prognosis, with the risk score proving to be significantly correlated with infiltration of most immune cells. The qRT-PCR results revealed significant differential expression patterns of LGR5 and VSIG4 in normal and human leukemia cell lines (HL-60 and MV-4-11). Conclusions. Our findings underscore the potential utility of PANoptosis-based molecular clustering and prognostic signatures as predictive tools for assessing patient survival in AML.

Background. Amino acid metabolism, including ATP production, nucleotide synthesis, and redox homeostatic processes, are associated with proliferation and differentiation of tumor cells. This study aimed to identify novel prognostic biomarkers and potential therapeutic targets of amino acid metabolism-related genes for stomach adenocarcinoma (STAD). Methods. RNA sequencing transcriptome data in the TCGA-STAD (training set) and GTEx datasets (validation set) were used. The LIMMA R program enabled the differentially expressed amino acid metabolism-related genes (AAMRGs) to be found. A prognostic risk score model based on clinical phenotypic features was built using LASSO regression and step multi-Cox analyses. Gene set enrichment analysis (GSEA) was used to find potential molecular pathways associated with STAD. Hierarchical cluster analysis was used to evaluate pyrimidine metabolism. Cultured STAD cells assessed the proliferation of STAD and upregulation of GPX3 expression by CCK8 and flow cytometry. Transwell and wound healing assays assessed the impact of GPX3 on invasion and migration of STAD cells. Western blot and qRT-PCR were used to measure changes in pyrimidine metabolism-related markers and active molecules involved in the AMPK/mTOR signaling pathway. Results. Three AAMRGs, DNMT1, F2R, and GPX3, could independently predict the course of STAD. Pyrimidine metabolism appeared to be significantly associated with these by GSEA and clustering analyses. Pyrimidine metabolism was negatively correlated with GPX3. Functional studies using an overexpressed GPX3 plasmid showed an enhanced migration and invasion of STAD cells as well as the expression of genes associated with pyrimidine metabolism and the AMPK/mTOR signaling pathway. By using a CAD siRNA, it was found that that GPX3 affected 5-fluorouracil resistance during de novo synthesis of pyrimidine through the CAD-UMPS signaling axis. Conclusions. GPX3 which regulates the level of pyrimidine metabolism through the AMPK/mTOR pathway was found to be closely associated with STAD. Our findings demonstrate GPX3 is a reliable biomarker for the prognosis of amino acid metabolism and a probable target for STAD therapy.

Background of the Study. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in western countries. Lifestyle interventions are recommended as the primary therapy for NAFLD. Methodology. In this clinical trial, NAFLD patients were enrolled in a 12-month dietary intervention aimed to improve their eating habits according to the Mediterranean pattern, with scheduled appointments every three months. After the exclusion of steatosis, healthy subjects were recruited and received general advice based on current Italian food-based dietary guidelines. Results. One hundred and fifty five subjects aged 20–59 years underwent (i) liver ultrasound (US), (ii) clinical and anthropometric evaluations, (iii) blood tests, and (iv) assessment of dietary habits. According to US evaluation, 73 of them had severe, moderate, or mild liver steatosis (NAFLD patients) and 82 had no liver steatosis (healthy controls). Fifty-eight NAFLD patients and 73 controls completed the study. Among NAFLD patients, 26 (45%) downgraded steatosis severity, 12 of which achieved complete steatosis regression (21%). Three of the healthy controls developed NAFLD. The NAFLD patients improved their dietary habits and reduced BMI and waist circumference, during the study period, more than healthy controls. Liver steatosis remission/regression was independent of changes in BMI or liver enzymes and was more frequent among patients with mild steatosis at baseline. Conclusions. Mediterranean dietary advices, without a personalised meal planning, were efficient in reducing/remitting NAFLD, especially among patients with mild disease, which argues in favour of early identification and lifestyle intervention. This trial is registered with NCT03300661.

Background. Bloodstream infection is amongst the leading causes of mortality for critical postoperative patients. However, data, especially from developing countries, are scary. Clinical decision-making tools for predicting postoperative bloodstream infection-related mortality are important but still lacking. Objective. To analyze the distribution of pathogens and develop a nomogram for predicting mortality in patients with postoperative bloodstream infection in the surgical intensive care unit. Methods. The clinical data, infection and pathogen-related data, and prognosis of patients with PBSI in the SICU from January 2017 to January 2022 were retrospectively collected. The distribution of pathogens and clinical characteristics of patients with PBSI were analyzed. The patients were assigned to a died group and a survived group according to their survival status. Independent predictors for mortality were identified by univariate and multivariate analyses. A nomogram for predicting PBSI-related death was developed based on these independent predictors. Calibration and decision-curve analysis were established to evaluate the nomogram. We collected postoperative patients admitted to our center from February 2022 to June 2023 as external validation sets to verify the nomogram. We also add the Brier score to further validate the model. Results. In the training set, 7128 patients admitted to the SICU after different types of surgery were collected. A total of 198 patients and 308 pathogens were finally enrolled. The mean age of patients with PBSI was 64.38 ± 16.22 (range 18–90) years, and 56.1% were male. Forty-five patients (22.7%) died in the hospital. Five independent predictors including BMI, APACHE II score, estimated glomerular filtration rate (eGFR), urine volume in the first 24 hours after surgery, and peak temperature before positive blood cultures were selected to establish the nomogram. The area under the receiver operating characteristic curve for the prediction model was 0.922. Calibration curve and decision curve analysis showed good performance of the nomogram. Seventy patients with PBSI were collected as an external validation set, and thirteen patients died in this set. The external validation set was used to validate the nomogram, and the results showed that the AUC was 0.930 which was higher than that in the training set indicating that the nomogram had a good discrimination. The brier score was 0.087 for training set and 0.050 for validation set. Conclusions. PBSI was one of the key issues that clinicians were concerned and could be assessed with a good predictive model using simple clinical factors.

Burn injuries are considered an important public health problem in the world. Burns are considered the fourth most common kind of trauma in the world, after traffic accidents, falls, and interpersonal violence. Various biochemical agents are involved in the burn healing process such as cytokines (such as IL-6 and TNF-α), antioxidants, and liver and kidney damage biomarkers. Cichorium intybus L. and milk thistle extracts showed a wide range of pharmacological activities such as significant antimicrobial effect and antioxidant activity, as well as anti-inflammatory, antidiabetic, antiproliferative, antiprotozoal, and hepatoprotective effect. Also, these two herbs possess blood-cleansing, detoxifying, laxative, and invigorating activities. Some research confirmed that the preparations of the extract are very suitable for the treatment of nonalcoholic fatty liver disease. This is a double-blind randomized controlled clinical trial. Patients with 2nd and 3rd degree burns have been selected to participate in the study according to the inclusion criteria. A total of 60 patients were selected and divided into intervention and control groups (30 patients in each group). Patients in the intervention group received chicory seed syrup 10 cc three times a day and 1 placebo capsule, and those in the control group received placebo syrup (10 cc three times a day) and one Livergol (140 mg of silymarin in each capsule) capsule. Lab data such as liver function tests, albumin, creatinine, BUN, and hemoglobin were checked every 3 days and 1 week after discharge. The treatment lasted for 4 weeks. According to the results of the study, although the average of liver enzymes at the end of the study does not show a significant difference between the two groups, the level of liver enzymes in each group decreased on the 15th day of the study compared to the first day. This trial is registered with IRCT20180609040016N1.

Background. Volume overload is a fatal complication for people undergoing hemodialysis. Therefore, regulating a patient’s “dry weight” based on their fluid status is imperative. Clinical experiences are too subjective to accurately judge a patient’s fluid status, but techniques have emerged for improved fluid control in the two decades. Specifically, lung ultrasonography (LUS) uses a unique aspect of ultrasound images, the B-lines, to evaluate extravascular lung water, which has increasingly attracted attention. However, the role of B-line quantification in predicting short-mid-term death and/or cardiovascular complications is unclear. Methods. Patients undergoing MHD at the hemodialysis center of Zhejiang Provincial People’s Hospital from October 1, 2020, to February 28, 2021, were examined using LUS and a bioelectrical impedance analysis before and after dialysis, and related clinical data were collected. All patients were followed up for one year after the examination, and deaths and first cardiovascular events (e.g., stroke, myocardial infarction, and heart failure) during this period were recorded. Results. 98 patients were enrolled and divided into three groups in relation to their mild (<16 B-lines), moderate (16–30 B-lines), or severe (>30 B-lines) hypervolemia, defined by the number of B-lines. The long-term survival rate was significantly lower in the severe group than in the mild and moderate groups. LUS and bioelectrical impedance-related parameters (e.g., extracellular water-to-water ratio) were closely related to cardiac ultrasound parameters (left ventricular ejection fraction) (P < 0.001). The optimal B-line cutoff value on LUS for predicting fluid overload (defined clinically) in patients on hemodialysis was 11.5 lines (AUC = 0.840, 95% confidence interval 0.735–0.945, P < 0.001), and the diagnostic sensitivity and specificity were both 76.5%. During the one-year follow-up period, ten deaths and six cardiovascular events occurred. The survival rate was significantly lower in the severe group than in the mild group (log-rank test χ² = 10.050, P = 0.002) but did not differ between the severe and moderate groups (χ² = 2.629, P = 0.105). Conclusion. LUS is a cheap, noninvasive, simple, and repeatable volume-monitoring method that can assist with individualized fluid volume management in patients undergoing MHD. LUS results may also help to predict the short-mid-term survival rate of patients to a certain extent.

Background. Perioperative sleep disorders exert a severe adverse impact on postoperative recovery. Recently, some observational studies reported that acupuncture-point stimulation (APS) provided benefits for promoting perioperative sleep quality. However, the effects of APS on perioperative sleep disorders following general anesthesia have not been thoroughly assessed by any systematic study and meta-analysis. Therefore, we conducted this systematic review and meta-analysis to reveal the effects of APS on perioperative sleep disorders. Methods. Eight databases (Chinese: CNKI, VIP, CBM, and Wanfang; English: PubMed, Embase, Web of Science, and Cochrane Library) were thoroughly searched to find randomized controlled trials (RCTs) that indicated a link between APS and the occurrence of perioperative sleep disorders. We applied RevMan 5.4 (Cochrane Collaboration) and Stata 16.0 (Stata Corp) to conduct our meta-analysis. In addition, the trial sequential analysis (TSA) tool was utilized to estimate the validity and reliability of the data. Results. In this study, nine RCTs with 719 patients were conducted. Compared to the control group, APS significantly improved perioperative subjective sleep quality (SMD: −1.36; 95% CI: −1.71 to −1.01; P < 0.00001). Besides, it increased perioperative TST (preoperative period MD = 24.29, 95% CI: 6.4 to 42.18, P = 0.0008; postoperative period MD = 45.86, 95% CI: 30.00 to 61.71, P < 0.00001) and SE (preoperative MD = 3.62, 95% CI: 2.84 to 4.39, P < 0.00001; postoperative MD = 6.43, 95% CI: 0.95 to 11.73, P < 0.00001). The consequence of trial sequential analysis further confirmed the reliability of our meta-analysis results. Conclusion. According to the currently available evidence, APS could effectively improve perioperative sleep quality and play an essential role in decreasing the incidence of perioperative sleep disorders.