Effects of a multilevel intervention of resistance training with or without beta-hydroxy-beta-methylbutyrate in medical ICU patients during entire hospitalisation: a four-arm multicentre randomised controlled trial.

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. METHODS: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis. RESULTS: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. CONCLUSIONS: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. TRIAL REGISTRATION: ChiCTR2200057685 was registered on March 15th, 2022.

ent-Atisane Diterpenoids from Euphorbia helioscopia and Their Anti-inflammatory Activities.

Phytochemical investigation on the anti-inflammatory fraction extracted from the whole plant of Euphorbia helioscopia L. led to the isolation of three new ent-atisane diterpenoids (1-3) and five known analogues (4-8). The structures and absolute configurations of the new compounds were elucidated by comprehensive analysis of the NMR, MS, IR, ECD, and X-ray crystallography. It is worth mentioning that compound 3 belongs to a rare class of ent-atisane diterpenoid featuring a hydroxyl group at C-9. Bioactivity investigation showed that compounds 4, 7, and 8 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner, which indicates their anti-inflammatory potential.

Anti-leukemic effect and molecular mechanism of 11-methoxytabersonine from Melodinus cochinchinensis via network pharmacology, ROS-mediated mitochondrial dysfunction and PI3K/Akt signaling pathway.

Melodinus cochinchinensis (Lour.) Merr. is a Yunnan endemic folk medicine. Our previous study showed that 11-methoxytabersonine (11-MT) isolated from M. cochinchinensis has strong cytotoxicity on human T-ALL cells, but its molecular mechanism has not been studied. In current study, the cytotoxicity and possible mechanism of 11-MT on T-cell acute lymphoblastic leukemia was explored using network pharmacology and molecular biology techniques. 11-MT significantly inhibited the cell proliferations on different four human T-ALL cells (MOLT-4, Jurkat, CCRF-CEM, and CEM/C1 cells). 11-MT triggered ROS accumulation, calcium concentration and cell apoptosis, and decreased the mitochondrial membrane potential (MMP) in human T-ALL cells, especially MOLT-4 cells. Western blot analysis showed that it can induce MOLT-4 cell apoptosis by up-regulating PI3K/Akt signaling pathway. Therefore, 11-MT induces human T-ALL cells apoptosis via up-regulation of ROS-mediated mitochondrial dysfunction and down-regulation of PI3K/Akt/mTOR signaling pathway.

Two New Eremophilane-Type Sesquiterpenoids from Ligularia sagitta.

Two new eremophilane-type sesquiterpenoids, sagittacins F and G (1 and 2), together with one known isomer of sagittacin F (3) were isolated from the leaves and stems of Ligularia sagitta. Their structures were elucidated by interpretation of spectroscopic data and the absolute configurations of 1 and 3 were determined by X-ray spectroscopy. Compound 1 belongs to a rare class of eremophilane-type sesquiterpenoid featuring an α-oriented hydroxy group at C-1. A nitric oxide (NO) production inhibitory assay was applied to evaluate their anti-inflammatory activities by using LPS-induced RAW 264.7 cells. Compounds 2 and 3 exhibited modest NO production inhibitions with IC50 values of 45.15±2.72 and 49.83±2.34 µM, respectively.

Metabolomics as a potential method for predicting thyroid malignancy in children and adolescents.

PURPOSE: To identify potential metabolic biomarkers for distinguishing malignant and benign thyroid nodules in children and adolescents using a metabolomics approach. METHODS: A total of 96 consecutive patients (median age 14.29 ± 2.31 years, range 9-18 years) who underwent thyroidectomy and 40 healthy controls were enrolled. Patients were assigned to the papillary thyroid carcinoma and benign thyroid adenoma groups according to postoperative pathologic biopsy. Plasma samples were preoperatively collected, and multivariate analysis was performed to identify differential metabolites. RESULTS: Papillary thyroid carcinoma could be distinguished not only from healthy serum but also from benign thyroid adenoma according to the metabolic profiles. A total of 17 metabolites were identified. Compared with those from benign thyroid adenoma patients and healthy controls, the metabolites from papillary thyroid carcinoma patients, including leucine, lactate, alanine, glycine, acetate, lysine and choline, were increased, while glucose was decreased. CONCLUSION: The metabolomics method based on proton nuclear magnetic resonance has great potential for identifying papillary thyroid carcinoma in children and adolescents. Lactate and glycine may be used as potential serum markers for the diagnosis of papillary thyroid carcinoma.

Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma : A matched-pair multicenter analysis of outcomes.

PURPOSE: The benefit of adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (NPC) is controversial. This study compared concurrent chemoradiotherapy plus AC (CCRT/AC) with CCRT. METHODS: Pair-matched analysis based on eight clinicopathological features of 244 patients treated with platinum-based CCRT/AC or CCRT alone was performed. Survival outcomes were assessed using the Kaplan-Meier method and log-rank test. Toxicities and response rates were compared using Fisher's exact test. RESULTS: Four-year overall survival, progression-free survival, distant failure-free survival, and locoregional failure-free survival were 72 %, 61 %, 71 %, and 81 %, respectively, for the CCRT arm, compared to 74 % (hazard ratio, HR 0.89; 95 % confidence interval, CI 0.64-1.23; P = 0.474), 62 % (HR 0.91, 95 % CI 0.68-1.20, P = 0.489), 73 % (HR 0.84, 95 % CI 0.59-1.18, P = 0.316), and 84 % (HR 0.84, 95 % CI 0.52-1.24, P = 0.323), respectively, for the CCRT/AC arm. Cox multivariate regression analysis demonstrated AC was not an independent prognostic factor. Overall, there was a higher incidence of grade 3-4 toxicities in the CCRT/AC arm. The most common grade 3-4 adverse events in the CCRT/AC arm were vomiting (27 %), nausea (43 %), leukopenia/neutropenia (23 %), thrombocytopenia (8.8 %), and anemia (6.2 %). CONCLUSION: Addition of AC to CCRT increased toxicities but did not improve survival in locoregionally advanced NPC.

Parasite densities modulate susceptibility of mice to cerebral malaria during co-infection with Schistosoma japonicum and Plasmodium berghei.

BACKGROUND: Malaria and schistosomiasis are endemic and co-exist in the same geographic areas, even co-infecting the same host. Previous studies have reported that concomitant infection with Schistosoma japonicum could offer protection against experimental cerebral malaria (ECM) in mice. This study was performed to evaluate whether alterations in parasite density could alter this protective effect. METHODS: Mice were inoculated with 100 or 200 S. japonicum cercariae followed by infection with high or low density of Plasmodium berghei ANKA strain eight weeks after the first infection. Then, parasitaemia, survival rate and blood-brain-barrier (BBB) damage were assessed. Interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, IL-13, IL-10, and TGF-ß levels were determined in splenocyte supernatants using enzyme-linked immunosorbent assay (ELISA). Cell surface/intracellular staining and flow cytometry were used to analyse the level of CD4(+)/CD8(+) T cells, CD4(+)CD25(+)Foxp3(+) Tregs, IL-10-secreting Tregs, and IL-10(+)Foxp3-CD4(+) T cells in the spleen, and CD4(+)/CD8(+) T cells infiltrating the brain. RESULTS: Co-infection with low density P. berghei and increased S. japonicum cercariae significantly increased the levels of IL-4, IL-5, IL-13, TGF-ß and Tregs, but significantly decreased the levels of IFN-γ and the percentage of CD4(+) T cells and CD8(+) T cells in the spleen and CD8(+) T cell infiltration in the brain. Increased worm loads also significantly decreased mortality and BBB impairment during ECM. When challenged with higher numbers of P. berghei and increased cercariae, the observed cytokine changes were not statistically significant. The corresponding ECM mortality and BBB impairment also remained unchanged. CONCLUSIONS: This study demonstrates that protection for ECM depends on the numbers of the parasites, S. japonicum and P. berghei, during co-infection. Alterations in the regulatory response appear to play a key role in this adaptation.

Right atrial pressure alterations during echocardiography-guided-catheterization predict tricuspid valvular impairment: a novel method for the creation of a rabbit model of Staphylococcus aureus endocarditis.

BACKGROUND: We previously reported the use of a catheter system to damage the tricuspid valve and create infectious endocarditis (IE) in an animal model. The current study aims to create a faint IE model suitable for antibiotic prophylaxis using a low bacterial inoculum. We also aim to explore a way to quantitatively assess valvular impairment and to predict the success of the IE models during catheterization. METHODS: Ninety rabbits were assigned to two groups according to the density of bacteria inoculated (1 × 10(5) CFU for Group A and 1 × 10(4) CFU for Group B). A catheter system consisting of a polyethylene catheter and a guide wire were used to damage the valve. The catheter system was passed through the rabbits' tricuspid valves under echocardiographic guidance. A pressure transducer was used to assess right atrial pressure (P(RA)) before and just after valvular damage to calculate the pressure alterations (ΔP(RA)). The animals in group A and B were divided into 3 subgroups according to the ΔP(RA) (0-5 mmHg for Groups A1 and B1; 5-10 mmHg for Groups A2 and B2; 10-15 mmHg for Groups A3 and B3). Staphylococcus aureus (ATCC 29213) inoculation was performed 24 hr after cardiac catheterization. RESULTS: Faint IE was confirmed in 20%, 93.3%, 26.7%, 6.7%, 20%, and 33.3% of the rabbits in Groups A1, A2, A3, B1, B2, and B3, respectively. There was no difference in the LV/RV ratio and VTR of the No-IE, faint-IE, and severe IE animals. Faint IE rabbits had a larger ΔPRA than No-IE rabbits (7.81 ± 1.21 vs. 2.48 ± 1.0, P < 0.01, for Group A; 7.60 ± 1.32 vs. 2.98 ± 1.08, P < 0.01, for Group B). The ΔPRA of severe IE and faint IE rabbits was significantly different (13.11 ± 1.31 vs. 7.81 ± 1.21, P < 0.01, for Group A; 12.73 ± 1.44 vs.7.60 ± 1.32, P < 0.01, for Group B). CONCLUSION: ΔP(RA) could be used to assess valvular impairment. Controlling the value of ΔP(RA) during catheterization and inoculating of an appropriate dose of bacteria was associated with a successful IE model.

Pre-existing Schistosoma japonicum infection alters the immune response to Plasmodium berghei infection in C57BL/6 mice.

BACKGROUND: Since helminths and malaria parasites are often co-endemic, it is important to clarify the immunoregulatory mechanism that occurs during the process of co-infection. A previous study confirmed that dendritic cells (DCs) are involved in the establishment and regulation of the T-cell-mediated immune response to malaria infection. In the current study, distinct response profiles for splenic DCs and regulatory T cell (Treg) responses were assessed to evaluate the effects of a pre-existing Schistosoma japonicum infection on malaria infection. METHODS: Malaria parasitaemia, survival rate, brain histopathology and clinical experimental cerebral malaria (ECM) were assessed in both Plasmodium berghei ANKA-mono-infected and S. japonicum-P. berghei ANKA-co-infected mice. Cell surface/intracellular staining and flow cytometry were used to analyse the level of splenic DC subpopulations, toll-like receptors (TLRs), DC surface molecules, Tregs (CD4⁺CD25⁺Foxp3⁺), IFN-γ/IL-10-secreting Tregs, and IFN-γ⁺/IL-10⁺-Foxp3⁻CD4⁺ T cells. IFN-γ, IL-4, IL-5, IL-10 and IL-13 levels were determined in splenocyte supernatants using enzyme-linked immunosorbent assay (ELISA). RESULTS: The co-infected mice had significantly higher malaria parasitaemia, compared with the mono-infected mice, on days 2, 3, 7 and 8 after P. berghei ANKA infection. Mono-infected mice had a slightly lower survival rate, while clinical ECM symptoms, and brain pathology, were significantly more severe during the period of susceptibility to ECM. On days 5 and 8 post P. berghei ANKA infection, co-infected mice had significantly lower levels of CD11c⁺CD11b⁺, CD11c⁺CD45R/B220⁺, CD11c⁺TLR4⁺, CD11c⁺TLR9⁺, CD11c⁺MHCII⁺, CD11c⁺CD86⁺, IFN-γ-secreting Tregs, and IFN-γ⁺Foxp3⁻CD4⁺ T cells in single-cell suspensions of splenocytes when compared with P. berghei ANKA-mono-infected mice. Co-infected mice also had significantly lower levels of IFN-γ and higher levels of IL-4, IL-5, and IL-13 in splenocyte supernatants compared to mono-infected mice. There were no differences in the levels of IL-10-secreting Tregs or IL-10⁺Foxp3⁻CD4⁺ T cells between co-infected and mono-infected mice. CONCLUSIONS: A Tregs-associated Th2 response plays an important role in protecting against ECM pathology. Pre-existing S. japonicum infection suppressed TLR ligand-induced DC maturation and had an anti-inflammatory effect during malaria infection not only by virtue of its ability to induce Th2 responses, but also by directly suppressing the ability of DC to produce pro-inflammatory mediators.

A rabbit model of right-sided Staphylococcus aureus endocarditis created with echocardiographic guidance.

BACKGROUND: The most widely used experimental models of infective endocarditis (IE) are the rabbit and rat models, in which cardiac valve lesions are induced by a polyethylene catheter introduced into the left ventricle through the aortic valve. Our study was designed to create a rabbit model of IE right-sided with echocardiographic guidance. METHODS: Thirty rabbits underwent both catheterization and inoculation (group A). These were divided into three subgroups of ten based on the time of catheter removal (immediately, after 24 h, and after death or moribundity for groups, A(1), A(2), and A(3), respectively). Ten inoculated-only and ten catheterized-only rabbits served as controls. A catheter system consisted of a polyethylene catheter and a guide wire inside it. This system was passed through the rabbits' tricuspid valves under echocardiographic guidance to damage them. The ratio of left ventricle to right ventricle (LV/RV) was measured in a four-chamber view before catheterization and at the time of death or moribundity. The peak velocity of tricuspid regurgitation (V(TR)) was measured in a four-chamber view at the time of catheterization and at the time of death or moribundity. Staphylococcus aureus (ATCC 29213) inoculation was performed 24 h after right heart catheterization to produce IE. RESULTS: IE was confirmed in 28 of 30 rabbits by macroscopic and histologic examination of tricuspid valves, blood cultures, and bacterial count in cardiac vegetations. Cardiac vegetations were confirmed in 25 of 28 IE rabbits by echocardiography. Enlargement of right ventricle dimension with a significantly decreased LV/RV ratio was confirmed in all IE rabbits at the time of death or moribundity than at the initial state (1.11 ± 0.35 vs. 1.95 ± 0.39, P < 0.01; 1.21 ± 0.34 vs. 1.98 ± 0.35, P < 0.01; 1.04 ± 0.31 vs. 2.00 ± 0.41, P < 0.01 for groups A(1), A(2), and A(3), respectively). V(TR) was significantly higher in all the IE rabbits at the time of death or moribundity than at the time of catheterization (1.89 ± 0.46 vs 0.76 ± 0.45, P < 0.01; 2.04 ± 0.73 vs 0.68 ± 0.66, P < 0.01; 2.24 ± 0.51 vs 0.87 ± 0.55, P < 0.01 for group A(1), A(2), and A(3), respectively). CONCLUSION: The models described herein closely reproduced the pathogenesis and pathophysiology of right heart catheter-induced endocarditis in humans. Echocardiographic guidance is helpful in the process of right heart catheterization. Some echocardiographic parameters, such as V(TR) and the LV/RV ratio could be used to assess the success or failure of the IE models.

[Mutational spectrum of phenylalanine hydroxylase gene and identification of novel mutations in patients with hyperphenylalaninemia in Jiangsu province].

OBJECTIVE: To study the characteristics of phenylalanine hydroxylase (PAH) gene mutations in patients with hyperphenylalaninemia from Jiangsu province by DNA sequencing, and to analyze the spectrum of PAH gene mutations. METHODS: A total of 70 patients and their parents were included in this study. All of the 13 exons and flanking introns of the PAH gene were analyzed with DNA sequencing. RESULTS: Forty five types of mutations were identified, which included 4 novel mutations (L37P, H107R, Q267L, S391T). A total of 125 mutations were identified in 140 alleles (89.3%). All mutations were detected in exons 2-3, 5-7, 9-12 and introns 2, 4, 7 and 8. Most mutations were found in exons 6, 7 and 12. EX6-96A > G, R243Q and R241C were the most common mutations. CONCLUSION: The mutational spectrum of Jiangsu province seems to be different from other regions. The spectrum can offer reliable information for genetic diagnosis of patients with hyperphenylalaninemia.

[Development and application of a method for molecular diagnosis of 21-hydroxylase deficiency].

OBJECTIVE: To develop a method for elucidating genetic basis of 21-hydroxylase deficiency. METHODS: Sanger sequencing of entire 21-hydroxylase coding gene CYP21A2 was carried out to detect point mutations, and multiplex ligation-dependent probe amplification (MLPA) and locus-specific PCR/enzyme restriction method were used to detect large deletions and conversion mutations. RESULTS: Nine children were analyzed. Point mutations of the CYP21A2 gene have been identified as: IVS2 13A/C>G (9 alleles), p.Arg356Trp (1 allele), Cluster E6 (1 allele), p.Gln318X (1 allele), and Prom conv (1 allele). While the former 4 mutations are pathogenic, the role of Prom conv mutation in the pathogenesis was uncertain. Three cases had entire CYP21A2 gene deletions (3 alleles), three had CYP21A1P/CYP21A2 chimeric mutations (3 alleles). The genotypes of all patients were determined. And all of the mutations were inherited from parents. CONCLUSION: A rational method for detecting point mutations and large deletions/conversions of CYP21A2 gene has been established.

Berberine enhances autophagic flux by activating the Nrf2 signaling pathway in bovine endometrial epithelial cells to resist LPS-induced apoptosis.

Berberine exerts many beneficial effects on lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (BEECs). Recently, we also found that berberine shows significant antiapoptotic and autophagy-promoting activities, but the underlying mechanism has not been elucidated. This research explored the association between the antiapoptotic and autophagy-promoting activities of berberine in LPS-treated BEECs. BEECs were first preconditioned with an inhibitor of autophagic flux (chloroquine [CQ]) for 1 h, treated with berberine for 2 h, and then incubated with LPS for 3 h. Cell apoptosis was assessed by flow cytometry, and autophagy activities were assessed by immunoblot analysis of LC3II and p62. The results indicated that the antiapoptotic activity of berberine was notably inhibited in LPS-treated BEECs after preconditioning with CQ for 1 h. Furthermore, to determine whether berberine promoted autophagy by activating the nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway, we assessed autophagy in LPS-treated BEECs after preconditioning with a signaling pathway inhibitor of Nrf2 (ML385). The results indicated that the enhanced autophagy activity induced by berberine was partially reversed in LPS-treated BEECs after the Nrf2 signaling pathway was disturbed by ML385. In conclusion, berberine enhances autophagic flux to allow resistance to LPS-induced apoptosis by activating the Nrf2 signaling pathway in BEECs. The present study may provide new insight into the antiapoptotic mechanism of berberine in LPS-induced BEECs.

Awareness and practice of preventive measures among healthcare workers in medical institutions in Beijing during influenza season on the eve of COVID-19 epidemic: A cross-sectional survey.

BACKGROUND: Influenza is an acute respiratory infectious disease caused by the influenza virus, which poses a certain threat to humans due to its short incubation period, fast transmission and strong infectivity. OBJECTIVES: To evaluate the awareness and prevention behavior against influenza among healthcare workers on the eve of the coronavirus disease 2019 (COVID-19) epidemic in Beijing, China. MATERIAL AND METHODS: Using the cross-sectional research design based on the principle of convenience sampling, an online questionnaire survey on the knowledge of flu, vaccination, medical protection behavior, and flu medication was conducted between January and February 2020. Healthcare workers from different healthcare facilities and different job positions in Beijing participated in this survey. RESULTS: A total of 1910 healthcare workers from different medical institutions and jobs were included in the study. The mean age of the participants was 32.69 ±8.72 years (range: 18-64 years). There were significant differences in knowledge about clinical signs about flu and prevention approaches among different age groups, individuals with different work experience and job titles (χ2 = 8.903-32.839; p < 0.05). Personnel with different job positions and education levels differed only in the knowledge about clinical signs of flu and identification of high-risk populations. A multivariate logistic regression analysis revealed that age (odds ratio (OR) = 0.979, 95% confidence interval (95% CI): 0.966-0.992) and education level (OR = 0.736, 95% CI: 0.588-0.921) were risk factors for hand hygiene practices, whereas job position (OR = 1.757, 95% CI: 1.146-2.695) and awareness of high-risk populations (OR = 1.405, 95% CI: 1.096-1.800) were protective factors influencing hand hygiene practices (p < 0.05). The only factor influencing mask wearing was the education level (OR = 0.610, 95% CI: 0.450-0.828). CONCLUSION: The knowledge level and preventive behavior of healthcare workers before the outbreak of COVID-19 has been insufficient.

Identification and antibiotic susceptibility of microorganisms isolated from diabetic foot ulcers: A pathological aspect.

Diabetic foot ulcers infected with microorganisms increase the risk of amputation. The presence of drug-resistant bacteria in diabetic foot ulcers creates a big challenge during the treatment. The objective of the present study was to determine the bacterial prevalence and antibiotic resistance among bacteria isolated from Chinese patients with diabetic foot ulcers. The present study studied the microbial colonization of diabetic foot ulcers of patients from a single center in China. Wound swabs from 89 patients with diabetic foot ulcers were collected and the presence of microorganisms detected. The isolated microorganisms were subjected to antibiotic susceptibility testing by the disk diffusion method. Of 89 patients, 56 (62.9%) were male and 33 (37.1%) were female, the mean age of patients was 53.2±5.4 years, the mean duration of diabetes was 14.8±2.9 years, the mean random blood sugar was 301±87 mg/dl, mean HbA1c was 7.9±1.4%. Patients with Wanger ulcer grade III (36.0%; P=0.034) and patients within the weight range of 51-75 kg (59.6%; P=0.012) were significantly higher. The prevalence rate of diabetic foot ulcers was 11.3%. Among 153 microorganisms, gram-positive bacteria (52.3%) were more prevalent than gram-negative bacteria (44.4%). Most of the patients with polymicrobial infection were classified to have Wanger III ulcer grade diabetic foot ulcers. Staphylococcus aureus (38.2%) was the most predominant bacteria isolated followed by Staphylococcus epidermidis (29.2%) and Escherichia coli (28.1%). Most of the gram-positive and gram-negative bacteria were resistant to dicloxacillin (73.8%, P=0.021) and cefotaxime (50%), respectively and ~53.4% of the isolates were multi-drug resistance isolates, 61.8% of the Staphylococcus aureus were identified as methicillin-resistant Staphylococcus aureus and 61.8% of the gram-negative bacteria were extended-spectrum ß-lactamase producers. Staphylococcus aureus and Escherichia coli were the predominant gram-positive and gram-negative bacteria isolated, respectively. Penicillin resistance was significantly higher among the gram-negative bacteria (P=0.019). Staphylococcus aureus and Escherichia coli were the predominant gram-positive and gram-negative bacteria isolated and levofloxacin and nitrofurantoin were the most effective antibiotics among the gram-positive and gram-negative bacterial isolates, respectively.

Magnetic resonance imaging radiomics-based prediction of clinically significant prostate cancer in equivocal PI-RADS 3 lesions in the transitional zone.

Purpose: This bi-institutional study aimed to establish a robust model for predicting clinically significant prostate cancer (csPCa) (pathological grade group ≥ 2) in PI-RADS 3 lesions in the transition zone by comparing the performance of combination models. Materials and methods: This study included 243 consecutive men who underwent 3-Tesla magnetic resonance imaging (MRI) and ultrasound-guided transrectal biopsy from January 2020 and April 2022 which is divided into a training cohort of 170 patients and a separate testing cohort of 73 patients. T2WI and DWI images were manually segmented for PI-RADS 3 lesions for the mean ADC and radiomic analysis. Predictive clinical factors were identified using both univariate and multivariate logistic models. The least absolute shrinkage and selection operator (LASSO) regression models were deployed for feature selection and for constructing radiomic signatures. We developed nine models utilizing clinical factors, radiological features, and radiomics, leveraging logistic and XGboost methods. The performances of these models was subsequently compared using Receiver Operating Characteristic (ROC) analysis and the Delong test. Results: Out of the 243 participants with a median age of 70 years, 30 were diagnosed with csPCa, leaving 213 without a csPCa diagnosis. Prostate-specific antigen density (PSAD) stood out as the only significant clinical factor (odds ratio [OR], 1.068; 95% confidence interval [CI], 1.029-1.115), discovered through the univariate and multivariate logistic models. Seven radiomic features correlated with csPCa prediction. Notably, the XGboost model outperformed eight other models (AUC of the training cohort: 0.949, and validation cohort: 0.913). However, it did not surpass the PSAD+MADC model (P > 0.05) in the training and testing cohorts (AUC, 0.949 vs. 0.888 and 0.913 vs. 0.854, respectively). Conclusion: The machine learning XGboost model presented the best performance in predicting csPCa in PI-RADS 3 lesions within the transitional zone. However, the addition of radiomic classifiers did not display any significant enhancement over the compound model of clinical and radiological findings. The most exemplary and generalized option for quantitative prostate evaluation was Mean ADC+PSAD.

Conversion and origin of normal and abnormal temperature dependences of kinetic isotope effect in hydride transfer reactions.

The effects of substituents on the temperature dependences of kinetic isotope effect (KIE) for the reactions of the hydride transfer from the substituted 5-methyl-6-phenyl-5,6-dihydrophenanthridine (G-PDH) to thioxanthylium (TX(+)) in acetonitrile were examined, and the results show that the temperature dependences of KIE for the hydride transfer reactions can be converted by adjusting the nature of the substituents in the molecule of the hydride donor. In general, electron-withdrawing groups can make the KIE to have normal temperature dependence, but electron-donating groups can make the KIE to have abnormal temperature dependence. Thermodynamic analysis on the possible pathways of the hydride transfer from G-PDH to TX(+) in acetonitrile suggests that the transfers of the hydride anion in the reactions are all carried out by the concerted one-step mechanism whether the substituent is an electron-withdrawing group or an electron-donating group. But the examination of Hammett-type free energy analysis on the hydride transfer reactions supports that the concerted one-step hydride transfer is not due to an elementary chemical reaction. The experimental values of KIE at different temperatures for the hydride transfer reactions were modeled by using a kinetic equation formed according to a multistage mechanism of the hydride transfer including a returnable charge-transfer complex as the reaction intermediate; the real mechanism of the hydride transfer and the root that why the temperature dependences of KIE can be converted as the nature of the substituents are changed were discovered.

Hypertrophic Obstructive Cardiomyopathy with SAM Phenomenon: A Case Report and Literature Review.

Background: Hypertrophic cardiomyopathy (HCM) is defined by the presence of left ventricular hypertrophy (LVH) in the absence of other potentially causative cardiac, systemic, syndromic, or metabolic diseases [1]. It is the most common genetic abnormality of the myocardium, with an anaesthetized prevalence ranging from 1:500 to as high as 1:200 [2-4]. It is the primary cause of sudden cardiac death (SCD) among teenagers and athletes. Patient: A 56-year-old man presented with chest tightness and palpitations which had been occurring post-activity for the previous 6 months. The patient was advised to be admitted. He underwent echocardiography, cardiac magnetic resonance (CMR), coronary angiography (CAG) examination, and left ventriculography. He was diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) with systolic anterior motion (SAM) phenomenon. Results: Echocardiography results showed that the interventricular septal thickness was 14-16 mm and that there were 2 degrees of SAM of the mitral valve. This resulted in severe stenosis of the left ventricular outflow tract (LVOT) and moderate to severe mitral insufficiency. Left ventriculography confirmed mitral regurgitation (MR) associated with HOCM with SAM phenomenon. Under the protection of a permanent pacemaker, the patient was treated with alcohol septal ablation (ASA). After discharge, the symptoms of chest tightness and palpitation did not recur. Conclusion: Beneficial effects were observed when patients with HOCM and SAM were treated with ASA under the condition of a permanent pacemaker.

Research landscape on 3D printing applications in healthcare within Southeast Asian countries: a systematic scoping review protocol.

INTRODUCTION: Three-dimensional (3D) printing plays a significant role as a promising technological advancement in modern healthcare settings. 3D printing has been incorporated by many sectors worldwide including in Southeast Asian countries. However, there is a paucity of research, especially in the healthcare pertaining to 3D printing activity in the Southeast Asian region. Thus, a scoping review is conducted to gain insight into 3D printing healthcare research landscape in the Southeast Asian region. METHODS AND ANALYSIS: The methodology draws on Arksey and O'Malley's seminal framework for the scoping review. The literature search will be conducted by using keywords to find suitable published literature. The existing literature will be searched using selected electronic databases such as PubMed/MEDLINE, CINAHL, Scopus, ProQuest and Web of Science from the years 2011 and 2021. The selected publications will focus on 10 Southeast Asian countries: Malaysia, Indonesia, Singapore, Thailand, Brunei, Philippines, Laos, Vietnam, Cambodia and Myanmar. Two reviewers will be performing title and abstract screening for the criteria of each publication, in which they will be working independently of each other. The included publication will undergo a full-text review and references cited will be examined for relevance using the same inclusion criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram will guide throughout the process. Data will be extracted, analysed and charted within each category from the selected publications for each Southeast Asian country. ETHICS AND DISSEMINATION: The results of this scoping review will illustrate an overview of the 3D printing healthcare research in the Southeast Asian context, which can be a guide for the advancement of 3D printing that can be accentuated in future research. The results will undergo dissemination which will be submitted for publication in a scientific journal.

Hypoglycemic and hypolipidemic effects of Epigynum auritum in high fat diet and streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Epigynum auritum is mainly distributed in Southwest China, and has been used as a "dai" folk medicine with promising Besides, the leaves and barks of E. auritum have detoxifying, analgesic and relieving swelling effects. Previous studies evidenced that E. auritum was rich in pregnanes and their glycosides. However, the hypoglycemic and hypolipidemic effects of the extract from E. auritum (EAE) and its molecular mechanism are still not studied. AIM OF THE STUDY: The aim of this study is to investigate the hypoglycemic and hypolipidemic effects of EAE on high-fat diet and streptozocin-induced type 2 diabetic rats. MATERIALS AND METHODS: The high-fat diet and streptozocin induced type 2 diabetic model was established. The diabetic rats were treated with 70% ethanol extract of E. auritum (100 and 300 mg/kg/d) or metformin (DMBG, 100 mg/kg/d) every day for 4 weeks. Fasting blood glucose was recorded weekly. The phenotypic changes were evaluated by the measurement of biochemical indexes and immunohistochemical. The expressions of signaling-related proteins were explored by western blotting. RESULTS: EAE could effectively regulate the metabolism of glucose and lipids in diabetic rats by increasing insulin sensitivity. In addition, EAE ameliorated the oxidative stress damage and further mitigated the liver, kidney, and pancreatic damage. Mechanism research results show that EAE treatment increased the phosphorylation of Akt, AMPK and GSK-3ß, up-regulated the expression of GLUT-2, GLUT-4 and PPAR-α, and reduced PPAR-γ and FAS expressions. CONCLUSION: EAE exhibited significant hypoglycemic and hypolipidemic effects in HFD/STZ-induced diabetes rats. The mechanism may be related to the effective upregulation of AMPK/Akt/GSK-3ß pathway and the decreased expression of PPAR-γ and FAS. It could be a promising natural product with potential value for the development of drugs to prevent or treat type 2 diabetic.