Objective: The current meta-analysis aimed at updating evidence regarding the therapeutic potential of probiotics against autism spectrum disorder (ASD) symptoms and identifying outcome confounders. Methods: Following PRISMA guidelines, randomized placebo-controlled trials retrieved from PubMed, Embase, Cochrane CENTRAL, and ScienceDirect were analyzed for effect size of primary outcomes (i.e., overall behavioral symptom changes) expressed as standardized mean difference (SMD) and odds ratios (ORs) for continuous and categorical variables, respectively, with 95% confidence interval (CI). Results: Meta-analysis of eight studies (465 participants, mean age: 6.03, range: 1.5−45, female: 17.4%) revealed total ASD symptom improvements in the probiotic group compared to placebos (SMD: −0.19, 95% CI: −0.38 to −0.01, p = 0.04, I2 = 0%, eight studies, 465 participants, certainty of evidence [COE]: low). Subgroup analyses showed probiotics-associated improvements only in studies recruiting predominantly preschool children (SMD: −0.30, 95% CI:−0.59 to −0.01, p = 0.04, three studies, 191 participants) or those using probiotics for over three months (SMD:−0.39, 95% CI: −0.73 to −0.06, p = 0.04, three studies, 144 participants) without difference between multipleand single-strain probiotics. No difference was noted in overall dropouts between individuals treated with probiotics and those taking placebos (OR: 0.98, p = 0.94, eight studies, I2 = 0%, 464 participants, COE: low). Despite a low risk of bias in most studies, COE was deemed low from limited trials and inconsistencies on sensitivity analysis. Conclusion The current study showed an association between probiotics use and an improvement in ASD symptoms, mainly in those aged below six or over three-month treatments. More large-scale investigations are warranted to support our findings.

Background: EGFR exon 20 insertions account for 1% to 10% of EGFR mutations in nonsmall-cell lung cancer (NSCLC) and are known to confer resistance to traditional tyrosine kinase inhibitors. However, the prognostic significance of these mutations in early-stage resected NSCLC remains unclear. This study assesses outcomes in patients with resected NSCLC harboring EGFR exon 20 insertions, comparing them to patients with common EGFR mutations and those with wild-type EGFR. Methods: We retrospectively reviewed 3,235 patients who underwent resection for NSCLC at Tri-Service Hospital between 2008 and 2021. After excluding cases lacking EGFR testing, incomplete data, or advanced-stage disease, 44 patients with exon 20 insertions were matched to 602 patients with common EGFR mutations and 729 with wild-type EGFR. Clinical characteristics, disease-free survival (DFS), and overall survival (OS) were analyzed using the Kaplan-Meier method, with statistical comparisons performed using the log-rank test. Cox proportional hazards models were used to identify independent prognostic factors. Results: Patients with exon 20 insertions were younger and more frequently presented with stage IA disease. The 5-year DFS was 79% in the exon 20 insertion group, compared to 81% in the common mutation group and 83.9% in the wild-type group. The 5-year OS was 78.5% for exon 20, 91.9% for common mutations, and 91% for wild-type. While no significant differences in DFS or OS were observed between groups, the exon 20 insertion group had a higher incidence of secondary cancers. Multivariable analysis indicated that exon 20 insertion was independently associated with worse OS, but not with DFS. Conclusion EGFR exon 20 insertions do not significantly shorten DFS, but are associated with inferior OS in early-stage resected NSCLC. Given the limited treatment options, the role of adjuvant therapy warrants further investigation.

BACKGROUND: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH. METHODS: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded. RESULTS: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH. CONCLUSIONS: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT02164526.
Coronary Artery Disease/epidemiology* ; Creatinine ; Heart Failure/complications* ; Humans ; Hypertension, Pulmonary/complications* ; Nitrates ; Prevalence ; Prognosis ; Prospective Studies ; Registries ; Risk Factors ; Stroke Volume ; Ventricular Function, Left

The present study aimed to evaluate the effects of virtual reality (VR) simulations combined with bedside assignments on nurses’ self-efficacy in providing pre-treatment educational services. Between March 2019 and November 2020, we conducted a study of VR educational materials that were developed to cover information about the treatment of oral cancers. The effects of the VR simulation, the thinking-path tracking map method, and bedside assignments on the nurses’ treatment decision-related knowledge were evaluated in a ward for oral cancer patients at Taipei Veterans General Hospital, Taipei, Taiwan. The blended training model significantly increased nurses’ familiarity (P<0.01) and confidence (P<0.03) regarding their knowledge of treatments and treatment decision-related knowledge. This model also significantly increased their confidence in their skills in bedside pre-treatment education for admitted oral cancer patients (P<0.002). Oral cancer-specific VR materials enhanced the effectiveness of skills training among nurses in the oral cancer ward.

The present study aimed to evaluate the effects of virtual reality (VR) simulations combined with bedside assignments on nurses’ self-efficacy in providing pre-treatment educational services. Between March 2019 and November 2020, we conducted a study of VR educational materials that were developed to cover information about the treatment of oral cancers. The effects of the VR simulation, the thinking-path tracking map method, and bedside assignments on the nurses’ treatment decision-related knowledge were evaluated in a ward for oral cancer patients at Taipei Veterans General Hospital, Taipei, Taiwan. The blended training model significantly increased nurses’ familiarity (P<0.01) and confidence (P<0.03) regarding their knowledge of treatments and treatment decision-related knowledge. This model also significantly increased their confidence in their skills in bedside pre-treatment education for admitted oral cancer patients (P<0.002). Oral cancer-specific VR materials enhanced the effectiveness of skills training among nurses in the oral cancer ward.

Purpose: Senior nursing and medical interns’ lack of familiarity and confidence with respect to practicing universal precaution for the prevention of occupational needlestick or sharp injuries may harm themselves. Trainees’ self-reported needlestick or sharp injury rate was known to be especially high during the first 2 months of internship in Taiwan. This prospective cohort study aimed to assess the effect of newly developed virtual reality (VR) game, which uses Gagne’s learning model to improve universal precaution for needlestick or sharp injury prevention and decrease the rates of needle stick or sharp injuries in new-coming medical and nursing interns in Taiwan. Methods: From 2017 to 2019, the VR system was developed and applied in training of 59 new-coming nursing and 50 medical interns. Occupational needlestick or sharp injury prevention was sought to be achieved through a game of right and wrong choices for safe or unsafe universal precaution behaviors. Results: In comparison with medical interns, a higher proportion of nursing interns had past experiences of deep occupational needlestick or sharp injury. Before VR training, the familiarity and confidence for needlestick or sharp injury prevention were higher among nursing interns than medical interns. Trainees with past experiences of deep needlestick or sharp injury exhibited better performance on the accuracy rate and time needed to complete 20 decisions than those without past experiences in VR practice. All trainees showed an improved performance after VR training. A high proportion of trainees reported that the VR-based training significantly decreased their anxiety about needlestick or sharp injury prevention. Conclusion This self-developed VR game system using Gagne’s flow improved universal precaution for needlestick or sharp injury prevention and reduced the needlestick or sharp injury rates in the first 2 months of nursing and medical internship.

Purpose: In contrast to the core part of the clinical interviewing and physical examination (PE) skills course, corresponding to the basic, head-to-toe, and thoracic systems, learners need structured feedback in the cluster part of the course, which includes the abdominal, neuromuscular, and musculoskeletal systems. This study evaluated the effects of using Dreyfus scale-based feedback, which has elements of continuous professional development, instead of Likert scale-based feedback in the cluster part of training in Taiwan. Methods: Instructors and final-year medical students in the 2015–2016 classes of National Yang-Ming University, Taiwan comprised the regular cohort, whereas those in the 2017–2018 classes formed the intervention cohort. In the intervention cohort, Dreyfus scale-based feedback, rather than Likert scale-based feedback, was used in the cluster part of the course. Results: In the cluster part of the course in the regular cohort, pre-trained standardized patients rated the class climate as poor, and students expressed low satisfaction with the instructors and course and low self-assessed readiness. In comparison with the regular cohort, improved end-of-course group objective structured clinical examination scores after the cluster part were noted in the intervention cohort. In other words, the implementation of Dreyfus scale-based feedback in the intervention cohort for the cluster part improved the deficit in this section of the course. Conclusion The implementation of Dreyfus scale-based feedback helped instructors to create a good class climate in the cluster part of the clinical interviewing and PE skills course. Simultaneously, this new intervention achieved the goal of promoting medical students’ readiness for interviewing, PE, and self-directed learning.

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.
Animals ; Bile Ducts ; Cell Death ; Cholestasis ; Hepatocytes ; Humans ; Hydrogen ; In Vitro Techniques ; Ligation ; Liver ; Mice ; Nerve Growth Factor ; Phosphotransferases ; Rodentia ; Sirtuin 1

Objective: To explore the effects of cardiac support on delayed resuscitation in extensively burned patients with shock. Methods: Clinical data of 62 extensively burned patients with shock on admission, admitted to the 159th Hospital of PLA (hereinafter referred to as our hospital) from January 2012 to January 2017, were retrospectively analyzed. They were divided into cardiac support group (n=35) and control group (n=27) according to the use of deslanoside and ulinastatin. All patients were treated with routine fluid resuscitation based on the formula of the Third Military Medical University till post injury hour (PIH) 48. Patients in cardiac support group were given slow intravenous injection of deslanoside which was added in 20 mL 100 g/L glucose injection with first dose of 0.4 to 0.6 mg, 0.2 to 0.4 mg per 6 to 8 h, no more than 1.6 mg daily, and slow intravenous injection of 1×10⁵U ulinastatin which was added in 100 mL 50 g/L glucose injection, once per 12 h. Other treatments of patients in the two groups followed the same conventional procedures of our hospital. The following data of the two groups of patients were collected. (1) The data of urine volume per hour within PIH 48, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), blood lactic acid, base excess, hematocrit, and albumin at PIH 48 were recorded. (2) The input volumes of electrolyte, colloid within the first and second 24 hours post burn and the total fluid input volumes within PIH 48 were recorded. (3) The data of creatine kinase, creatine kinase isoenzyme-MB, lactate dehydrogenase, total bile acid, alanine aminotransferase, aspartate aminotransferase, β₂-microglobulin, urea nitrogen, and creatinine at PIH 48 were recorded. (4) The complications including cardiac failure, pulmonary edema, pleural effusion, seroperitoneum, renal failure, sepsis, and death were also recorded. Data were processed with independent sample ttest, Fisher′s exact test, Pearson chi-square test, or continuous correction chi-square test. Results: (1) There were no statistically significant differences in urine volume within PIH 48, heart rate, MAP, CVP, hematocrit, or albumin at PIH 48 between the patients of two groups (t=0.150, 0.488, 0.805, 0.562, 1.742, 0.696, P>0.05). While the levels of blood lactic acid and base excess were respectively (4.2±2.2) and (-4.3±2.0) mmol/L in patients of cardiac support group, which were significantly better than (5.9±1.7) and (-6.0±3.1) mmol/L in patients of control group (t=3.249, 2.480, P<0.05 or P<0.01). (2) There was no statistically significant difference in input volume of colloid within the first 24 hours post burn between the patients of two groups (t=0.642, P>0.05). The input volume of electrolyte within the first 24 hours post burn, the input volumes of electrolyte and colloid within the second 24 hours post burn, and the total fluid input volume within PIH 48 of patients in cardiac support group were significantly less than those in control group (t=2.703, 4.223, 3.437, 2.515, P<0.05 or P<0.01). (3) The levels of creatine kinase, creatine kinase isoenzyme-MB, lactate dehydrogenase, total bile acid, alanine aminotransferase, aspartate aminotransferase, β₂-microglobulin, urea nitrogen, and creatinine of patients in cardiac support group at PIH 48 were significantly lower than those in control group (t=3.066, 3.963, 3.225, 2.943, 2.431, 3.084, 4.052, 2.915, 3.353, P<0.05 or P<0.01). (4) The occurrences of pleural effusion and seroperitoneum and mortality of patients in cardiac support group were significantly lower than those in control group (χ²=5.514, 6.984, 4.798, P<0.05 or P<0.01). There were no statistically significant differences in cardiac failure, pulmonary edema, renal failure, and sepsis between the patients of two groups [χ²=1.314 (sepsis), P>0.05]. Conclusions The cardiotonic and cardiac protection treatments in delayed resuscitation of extensively burned patients with shock contribute to improving the cellular anonic metabolism, reducing the volume of fluid resuscitation, and mitigating the ischemic and hypoxic damage to organs, so as to lay foundation for decreasing further complication incidences and mortality.

Objective To explore the correlation among ST-2,adiponectin(APN),positive growth dif-ferentiation factor -15(GDF-15)and senile heart failure,and to investigate the diagnostic values of these indica-tors. Methods Totally 129 patients(15 patients of NYHA Ⅰ,60 of NYHA Ⅱ,28 of NYHA Ⅲ and 26 of NYHAⅣin study group)with heart failure and 30 control subjects(control group)were enrolled in the study.Se-rum levels of ST-2,APN and GDF-15 were determined by ELISA,and their correlation with senile heart failure was analyzed.Results Compared with those in control group,serum levels of ST-2,APN and GDF-15 in study group were significantly increased(P<0.05).There were significant differences in serum levels of ST-2,APN and GDF-15 among patients of different classifications in study group(P<0.05)and the higher level of cardiac func-tion,the higher serum ST-2,APN and GDF-15. There was a positive correlation among serum ST-2,APN and GDF-1. Conclusions The serum levels of ST-2,APN and GDF-1 are positively related to the severity of senile heart failure,thus it could be served as the index of diagnosis,curative effect monitoring and prognosis of patients with heart failure.