A novel PDGFR inhibitor WQ-C-401 prevents pulmonary vascular remodeling in rats with monocrotaline-induced pulmonary arterial hypertension.

Platelet-derived growth factor (PDGF) is one of the most important cytokines associated with pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). PDGF receptor (PDGFR) inhibition exerted therapeutic effects on PAH in clinical trials, but serious side effects warrant the withdrawal of existing drugs. In this study, a novel highly selective PDGFR inhibitor WQ-C-401 was developed, and its effects on PDGFR signaling pathway and pulmonary vascular remodeling in PAH were investigated. Cell proliferation assays and Western blot analysis of PDGFRα/ß phosphorylation showed that WQ-C-401 inhibited PDGFR-mediated cell proliferation assay and suppressed PDGFR phosphorylation in a concentration-dependent manner. DiscoverX's KinomeScanTM technology confirmed the good kinome selectivity of WQ-C-401 (S score (1) of PDGFR = (0.01)). In monocrotaline (MCT)-induced PAH rats, intragastric administration of WQ-C-401 (25, 50, 100 mg/kg/d) or imatinib (50 mg/kg/d, positive control) significantly decreased right ventricular systolic pressure (RVSP). Histological analysis demonstrated that WQ-C-401 inhibited pulmonary vascular remodeling by reducing muscularization and fibrosis, as well as alleviated right ventricular hypertrophy in MCT-treated rats. In addition, WQ-C-401 suppressed MCT-induced cell hyperproliferation and CD68+ macrophage infiltration around the pulmonary artery. In vitro, WQ-C-401 inhibited PDGF-BB-induced proliferation and migration of human pulmonary arterial smooth muscle cells (PASMCs). Moreover, Western blot analysis showed that WQ-C-401 concertration-dependently inhibited PDGF-BB-induced phosphorylation of ERK1/2 and PDGFRß Y751, decreased collagen Ⅰ synthesis and increased alpha smooth muscle actin (α-SMA) expression in PASMCs. Collectively, our results suggest that WQ-C-401 is a selective and potent PDGFR inhibitor which could be a promising drug for the therapeutics of PAH by preventing pulmonary vascular remodeling.

Engineering c-Met-CAR NK-92 cells as a promising therapeutic candidate for lung adenocarcinoma.

Mesenchymal-epithelial transition factor (C-Met) has been acknowledged as a significant therapeutic target for treating lung adenocarcinoma (LUAD). However, the potential application of chimeric antigen receptors (CAR)-modified natural killer (NK) cells targeting c-Met in LUAD is rarely explored. In this study, bioinformatic databases were searched and a tissue microarray (TMA) was enrolled to investigate expression status and prognostic role of c-Met in LUAD. Then, four types of c-Met-CAR structures were designed and prepared. The engineering CAR-NK cells containing c-Met-CARs were transfected, verified and characterized. The tumor-inhibitory role of c-Met-CAR-NK cells was finally evaluated in vitro and in vivo. The results demonstrated that c-Met expression elevated and confirmed that high c-Met expression was significantly associated with unfavorable prognosis in LUAD. Then, C-Met-CAR-NK cells were successfully constructed and DAP10 designed in CAR structure was a favorable stimulator for NK cell activation. CCN4 containing DAP10 co-stimulator exhibited the strongest cytotoxicity compared with other CAR-NK cells. Furthermore, CCN4 cells also exerted the prominent tumor-inhibitory effect on xenograft tumor growth. Collectively, this study suggests that DAP10 is a potent stimulator in CAR structure for NK cell activation, and CCN4-based immunotherapy may represent a promising strategy for the treatment of c-Met-positive LUAD.

7-Guanidinyl Coumarins: Synthesis, Photophysical Properties, and Application to Exploit the Pd-Catalyzed Release of Guanidines.

Molecular manipulation of guanidino-containing biomolecules in a cellular environment is fundamental to exploiting protein function and drug release, but currently, there is a lack of suitable methods for reaction screening and monitoring. To exploit the potential of the fluorescent method in this respect, herein, we evaluated a novel array of 7-guanidinyl coumarins by incorporating different substituted guanidino moieties into a coumarin scaffold. These compounds were prepared by guanidinylation reagent S-methylisothiourea or TFA-protected pyrazole-carboxamidine. Examination of their photophysical properties revealed that the fluorescence emission of alkyloxycarbonyl-substituted guanidinyl coumarin was significantly enhanced as compared with the unsubstituted analogue. This dramatic fluorescence difference enabled preliminary exploitation of the Pd-catalyzed release of allyloxycarbonyl (Alloc)-caged guanidinyl coumarin-6 in living cells.

Facile access to S-methyl dithiocarbamates with sulfonium or sulfoxonium iodide as a methylation reagent.

Efficient access to S-methyl dithiocarbamates was achieved with sulfonium or sulfoxonium iodide as a methylation reagent. This method is reliable for the synthesis of dithiocarbamates from primary or secondary amines, with sulfoxonium iodide demonstrating more robust methylation capability than sulfonium iodide. Moreover, it also enables facile access to S-trideuteromethyl dithiocarbamates via sulfoxonium metathesis between sulfoxonium iodide and DMSO-d6 with high yields.

Regioselective Access to 2-Iminoimidazolidines via AgF-Mediated Cascade Reactions.

A convergent access to substituted 2-iminoimidazolidines from aromatic amines and N-propargyl S-methylthiourea is developed via Ag(I)-mediated cascade guanylation-cyclization reactions. This method features high regioselectivity, excellent efficiency, and mild reaction conditions. Subsequent deprotection of the Boc (tert-butyloxycarbonyl) group under acidic conditions provides expedient access to aryl 2-aminoimidazole derivatives in a convenient manner.

Effects of tightening torque on screw stress and formation of implant-abutment microgaps: A finite element analysis.

STATEMENT OF PROBLEM: The mechanical behavior of the conical connection implant with different torque levels requires evaluation. PURPOSE: The purpose of this finite element analysis study was to investigate the impact of abutment screw torque on the formation of microgaps at the implant-to-abutment interface of a conical connection under oblique loading. This is important because it is thought that bacteria can invade the internal implant space through the abutment-implant microgaps, causing peri-implantitis. MATERIAL AND METHODS: Three-dimensional finite element analyses of the conical implant-abutment connection were performed by using screw torques of 20 Ncm and 30 Ncm. Oblique loads from 10 N to 280 N were applied to the prosthesis placed on the implant. The maximum von Mises stress in the abutment screw, the microgap formation process, and the critical load for bridging the internal implant space were evaluated. RESULTS: The stresses in the abutment screw under oblique loading had limited sensitivity to the screw torque. However, the residual stress in the screw with a 30-Ncm torque was 35% higher than that with a 20-Ncm torque in the absence of an external load. The area in contact at the implant-to-abutment interface decreased with increasing load for both torque values. The critical load for bridging the internal implant space was 160 N for a screw torque of 20 Ncm and 220 N for a screw torque of 30 Ncm. The maximum gap size was approximately 470 µm with all the loads. CONCLUSIONS: Increasing the screw torque can reduce the formation of microgaps at the implant-to-abutment interface. However, this will result in higher mean stress in the abutment screw, which may reduce its fatigue life and consequently that of the prosthesis. Further research is needed to evaluate the relationship between the abutment screw torque and microleakage in implant-supported restorations.

Prediabetes and the risk of heart failure: A meta-analysis.

AIM: To determine the role of prediabetes in the incidence of heart failure (HF). MATERIALS AND METHODS: We searched electronic databases (PubMed, Embase, Google Scholar and OpenGrey) for studies up to 31 December 2020. Studies were included for meta-analysis if they reported adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the risk of HF for prediabetes compared with normoglycaemia. Prediabetes was defined as impaired fasting glucose (IFG) according to the World Health Organization (WHO) criteria (IFG-WHO), or according to the American Diabetes Association (ADA) definition (IFG-ADA), impaired glucose tolerance (IGT), raised HbA1c according to the ADA criteria (HbA1c-ADA), or according to the International Expert Committee (IEC) recommendation (HbA1c-IEC). RESULTS: A total of 15 studies comprising 9,827,430 individuals provided data for this analysis. The median follow-up duration of the included studies was 8.0 years. Compared with normoglycaemia, prediabetes was associated with an increased risk for HF: IFG-ADA (RR: 1.09, 95% CI: 1.05-1.13), IFG-WHO (RR: 1.18, 95% CI: 1.07-1.30), IGT (RR 1.58, 95% CI 1.04-2.39), HbA1c-ADA (RR 1.28, 95% CI 1.16-1.41) or HbA1c-IEC (RR 1.40, 95% CI 1.09-1.79), respectively. CONCLUSIONS: Prediabetes is associated with an increased risk of HF. Future studies are needed to evaluate effective treatments for prediabetes to prevent the development and progression of HF.

Ag(I)-Catalyzed rapid access to 2-amino-4-methylenethiazolines with potential applications in bioconjugation chemistry.

An Ag(i)-catalyzed tandem addition-cyclization of isothiocyanate and propargylamine was successfully applied to the synthesis of 2-amino-4-methylenethiazolines. This route features an unprecedented fast reaction rate with full conversion reached within 10 min at room temperature for aromatic isothiocyanates and excellent chemoselectivity for exocyclic products. The application of this strategy is further highlighted by the accelerated bioconjugation of propargylamine with fluorescein isothiocyanate (FITC) under Ag(i)-catalysis.

Characteristics of regulatory T-cell function in patients with chronic hepatitis B and C coinfection.

Regulatory T cells (Tregs) affect the pathogenesis and disease progression of chronic viral hepatitis. This study evaluated the frequency and function of Tregs in patients with chronic HBV/HCV coinfection. Seventy-four untreated HBV/HCV co-infected patients were enrolled in this study. These subjects were divided into four subgroups: HBV-active/HCV-active (BACA), HBV-inactive/HCV-active (BICA), HBV-active/HCV-inactive (BACI) and HBV-inactive/HCV-inactive (BICI). Treg frequency was calculated as the fraction of CD4+ Foxp3+ T cells among CD4+ T cells. Treg-mediated inhibition was measured as percent of inhibition of T-cell proliferation. The expression of interferon (IFN)-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-10 with/without Treg inhibition was also studied. Among the patients, there were 8 cases of BACA (10.8%), 38 of BICA (51.4%), 14 of BACI (18.9%) and 14 of BICI (18.9%). The frequency of CD4+ Foxp3+ T cells was comparable between the four groups. The inhibitory function of Tregs among the patients in the BACA and BICA was higher than that in the BICI (BACA vs BICI, P = .0210; BICA vs BICI, P = .0301). Patients in the BACA and BICA had higher fibrosis-4 (FIB-4) scores and serum ALT levels and lower serum albumin levels than those of the other groups. ALT abnormality was significantly and independently associated with a higher Treg immunosuppressive ability. The IFN-γ expression of the effector T cells in the BACA was higher than that of the other groups. In conclusion, the inhibitory function of Tregs is higher among the HBV/HCV co-infected patients with active HCV infection. ALT abnormality plays a dominant role in Treg function.

Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients.

BACKGROUNDS: Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection. AIMS: This study evaluated the function of Tregs in CHC patients receiving the standard direct-acting antiviral agents (DAA) treatment. METHODS: CHC patients (n = 20) who received DAA treatment, clinical data, and function of Tregs were checked at baseline, Week 4, end of treatment (EOT), and 12 weeks after EOT (SVR 12). Treg-mediated inhibition was measured. The cytokine expression and fold change of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-ß with/without Treg inhibition were also detected. RESULTS: The cohort included 14 females with a mean age of 59.8 ± 11.5 years. Nineteen had HCV genotype 1. The HCV RNA level was 6.17 ± 0.70 log IU/mL. All patients reached the sustained virologic response. The frequency of CD4+Foxp3+T cells decreased from baseline to EOT and returned at SVR 12. The inhibitory function of Tregs decreased during treatment and then restored (baseline vs. EOT, P = 0.0393; EOT vs. SVR 12, P = 0.0052). The cytokine expression and fold change of IFN-γ and TNF-α were highest at EOT and then decreased at SVR 12. The fold change of IL-10 was lowest at EOT and then increased at SVR 12. The fold change of TGF-ß was significantly increased at Week 4 and SVR 12 compared to baseline. CONCLUSIONS: The frequency and inhibitory function of Tregs declined gradually from baseline to EOT and then increased from EOT to SVR 12 in CHC patients receiving DAA therapy. The expression of IFN-γ, TNF-α, IL-10, and TGF-ß parallelled Treg function.

Treatment of Ankylosing Spondylitis With a Bushen-Qiangdu-Zhilv Decoction: A Case Report With a 3-year Follow-up.

Context • Ankylosing spondylitis (AS) is a refractory rheumatic disease, characterized by sacroiliitis and structural damage, and over decades, it can lead to joint fusion, frequently followed by significant spinal deformity and disability. However, to date, no method has been found to be effective in relieving or blocking structural damage to joints. Objective • The study intended to show that a decoction of Bushen-Qiangdu-Zhilv (BQZ), a therapy used in traditional Chinese medicine (TCM), can provide an alternative treatment for AS patients. Design • The research team performed a case study. Setting • The study was conducted at Guangdong Provincial Hospital of TCM in Guangzhou, China. Participant • The case study involved a 33-y-old male patient with active AS who visited the research team's clinic. Intervention • The patient took the BQZ orally 2 ×/d at 30 min after breakfast and 30 min after dinner. The patient returned to the clinic for consultation monthly. The patient took 2 servings/d for 10 mo and then received continuous BQZ treatment of the maintenance dosage for a period of approximately 3 y until December 2013. The maintenance dosage of BQZ was 3 or 4 decoctions per wk. Outcome Measures • The study used a number of measurements to evaluate the outcomes of treatment: (1) disease activity-the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); (2) functional condition-the Bath Ankylosing Spondylitis Functional Index (BASFI); (3) inflammation-ratings of morning stiffness and night pain, serum C-reactive protein (CRP) concentration measured by means of particle-enhanced immunonephelometry, and erythrocyte sedimentation rate (ESR) value as detected using the Westergren method; (4) spinal mobility-the Bath Ankylosing Spondylitis Metrology Index (BASMI); and (5) global assessments by patient and physician. Results • The participant showed improvements in inflammatory symptoms and recovery from structural damage after receiving the TCM therapy for 3 y. Conclusions • The study has shown that the long-term use of BQZ not only can lead to an improvement in inflammatory symptoms and quality of life but also can help to restore function after structural damage in AS patients.

Impact of an Early Decrease in Systolic Blood Pressure on The Risk of Contrast-Induced Nephropathy after Percutaneous Coronary Intervention.

BACKGROUND: The early postprocedural period was thought to be the rush hour of contrast media excretion, causing rapid and prolonged renal hypoperfusion, which was the critical time window for contrast-induced nephropathy (CIN). METHODS: 349 consecutive patients were enrolled into the study. The relation between an early postprocedural decrease in systolic blood pressure (SBP) and the risk of CIN was assessed using multivariate logistic regression. RESULTS: A postprocedural decrease in SBP was observed in 63% of patients and CIN developed in 28 (8.0%) patients. The CIN group had a lower postprocedural SBP (114.5±13.5 vs. 123.7±15.6mmHg, P=0.003) and a greater postprocedural decrease in SBP (16.2±19.1 vs. 5.9±18.7mmHg, P=0.005) than the no-CIN group. ROC analysis revealed that the optimum cutoff value for the SBP decrease in detecting CIN was >10mmHg (sensitivity 60.7%, specificity 59.5%, AUC=0.66). Multivariate logistic regression analysis found that a postprocedural decrease in SBP >10mmHg was a significant independent predictor of CIN (OR 2.368, 95%CI: 1.043-5.379, P=0.039), after adjustment for other risk factors. CONCLUSION: An early moderate postprocedural decrease in SBP may increase the risk of CIN in patients undergoing PCI.

Traditional Chinese medicine versus western medicine as used in China in the management of rheumatoid arthritis: a randomized, single-blind, 24-week study.

This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.

Anti-inflammatory activity of extracts of Bushen-Qiangdu-Zhilv decoction, a Chinese medicinal formula, in M1-polarized RAW264.7.

BACKGROUND: Bushen-Qiangdu-Zhilv Decoction (BQZ) is one of famous traditional Chinese medical formula for treating ankylosing spondylitis (AS). However, the mechanisms underlying effects of BQZ remains unknown. Pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1, play an important role in AS. We therefore evaluated if BQZ could affect the expression of these cytokines. METHODS: Crude extracts were prepared and fractioned with petroleum ether (PE), ethyl acetate (EA), n-butanol (BU) and finally water (ACE). The stability of the extracts was confirmed by high-pressure liquid chromatography (HPLC) analysis. M1-polarized RAW264.7 was induced and subsequently treated with BQZ extracts. Quantitative real-time PCR experiments were performed to measure mRNA expression of TNF-α and IL-1. RESULTS: It was found that TNF-α could be significantly suppressed by ACE extracts, whereas IL-1 was dramatically inhibited by BU extracts, which was further confirmed by dose-dependent experiments. Importantly, MTS assays showed that both ACE and BU extracts had a low cytotoxicity. CONCLUSION: Altogether, our study indicates that BQZ decoction exerts anti-AS effects via its anti-inflammatory activity and may have a low side-effect. Further analysis of the extracts of BQZ decoction could lead to a discovery of some novel drugs adding to therapeutic strategy for AS patients.

[Relationship between carbon dioxide combining power and contrast- induced acute kidney injury in patients with ST segment elevation myocardial infarction undergoing emergency percutaneous coronary intervention].

OBJECTIVE: To study the relationship between carbon dioxide combining power(CO2-CP) and contrast-induced acute kidney injury (CI-AKI) in patients with ST segment elevation myocardial infarction and undergoing percutaneous coronary intervention. METHODS: We retrospectively analyzed 174 patients admitted to our hospital from March 2012 to August 2013 with ST segment elevation myocardial infarction and underwent emergency percutaneous coronary intervention. Patients were divided into three tertiles according to pre-operative CO2-CP: T1 (CO2-CP < 22.62 mmol/L), T2(CO2-CP 22.62-24.30 mmol/L), T3(CO2-CP > 24.30 mmol/L). Baseline clinical data, CI-AKI incidence, in-hospital mortality and dialysis rate were compared among groups. An increase in serum creatinine of >26.4 µmol/L and/or >50% from baseline within 48 hours after contrast exposure was defined as CI-AKI. Univariate logistic regression analysis was used to identify the risk factors of CI-AKI. The relationship between CO2-CP and CI-AKI was assessed by multivariate logistic regression analysis. Receiver operating characteristic curve was used to identify the optimal cutoff of the CO2-CP for predicting CI-AKI. RESULTS: CI-AKI occurred in 25 (14.4%) patients, and lower CO2-CP was related to higher incidence of CI-AKI (27.6% (16/58) in group T1, 5.3% (3/57) in group T2, 1.7 % (1/59) in group T3, P = 0.002) and higher in-hospital mortality (10.3% (6/58) vs. 0 and 1.7% (1/59), P = 0.010). Dialysis rate was similar among 3 groups (5.2% (3/58) vs. 0 and 1.7% (1/59), P = 0.168). The incidence of CI-AKI was significantly associated with CO2-CP < 22.00 mmol/L in univariate analyses (OR = 6.767, 95% CI 2.731-16.768, P < 0.001). After adjusting for potential confounding risk factors, CO2-CP < 22.00 mmol/L remained significantly associated with the incidence of CI-AKI (OR = 5.835, 95%CI 1.800-18.914, P = 0.003) in multivariate logistic regression. ROC analysis revealed that the optimal cutoff of CO2-CP to predict CI-AKI was 22.00 mmol/L (sensitivity 64.0%, specificity 79.1%, AUC = 0.714). CONCLUSIONS: Pre-percutaneous coronary intervention CO2-CP in patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention is related to CI-AKI. CO2-CP < 22.00 mmol/L predicts higher risk of CI-AKI in this patient cohort.

Research progress on the mechanism of acute hypertriglyceridemic pancreatitis.

ABSTRACT: The incidence rate of hypertriglyceridemia pancreatitis (HTGP) has experienced a notable increase in recent years, with eclipsing alcohol as the second leading cause of acute pancreatitis (AP). HTGP is often associated with more severe local and systemic complications. Recognized as a metabolic disorder hypertriglyceridemia (HTG), holds significant relevance in the pathogenesis of HTGP, yet its mechanisms are not fully understood. Both primary (genetic) and secondary (acquired) factors contribute to elevated triglyceride (TG) levels, which concurrently influence the progression of HTGP. This article presents a comprehensive review of the evolving research on HTGP pathogenesis, encompassing lipid synthesis and metabolism, calcium signal transduction, inflammatory mediators, endoplasmic reticulum stress, autophagy, mitochondrial injury by fatty acids, oxidative stress response, genetic factors, and gene mutations. By unraveling the intricate mechanisms underlying HTGP, this article aims to enhance physicians' understanding of the disease and facilitate the development of potential targeted pharmacological interventions for patients.

Body composition and metabolic syndrome in patients with type 1 diabetes.

BACKGROUND: In recent years, the prevalence of obesity and metabolic syndrome in type 1 diabetes (T1DM) patients has gradually increased. Insulin resistance in T1DM deserves attention. It is necessary to clarify the relationship between body composition, metabolic syndrome and insulin resistance in T1DM to guide clinical treatment and intervention. AIM: To assess body composition (BC) in T1DM patients and evaluate the relationship between BC, metabolic syndrome (MS), and insulin resistance in these indi-viduals. METHODS: A total of 101 subjects with T1DM, aged 10 years or older, and with a disease duration of over 1 year were included. Bioelectrical impedance analysis using the Tsinghua-Tongfang BC Analyzer BCA-1B was employed to measure various BC parameters. Clinical and laboratory data were collected, and insulin resistance was calculated using the estimated glucose disposal rate (eGDR). RESULTS: MS was diagnosed in 16/101 patients (15.84%), overweight in 16/101 patients (15.84%), obesity in 4/101 (3.96%), hypertension in 34/101 (33.66%%) and dyslipidemia in 16/101 patients (15.84%). Visceral fat index (VFI) and trunk fat mass were significantly and negatively correlated with eGDR (both P < 0.001). Female patients exhibited higher body fat percentage and visceral fat ratio compared to male patients. Binary logistic regression analysis revealed that significant factors for MS included eGDR [P = 0.017, odds ratio (OR) = 0.109], VFI (P = 0.030, OR = 3.529), and a family history of diabetes (P = 0.004, OR = 0.228). Significant factors for hypertension included eGDR (P < 0.001, OR = 0.488) and skeletal muscle mass (P = 0.003, OR = 1.111). Significant factors for dyslipidemia included trunk fat mass (P = 0.033, OR = 1.202) and eGDR (P = 0.037, OR = 0.708). CONCLUSION: Visceral fat was found to be a superior predictor of MS compared to conventional measures such as body mass index and waist-to-hip ratio in Chinese individuals with T1DM. BC analysis, specifically identifying visceral fat (trunk fat), may play an important role in identifying the increased risk of MS in non-obese patients with T1DM.

Evolution of Microstructure and Mechanical Properties of Ti-6Al-4V Alloy under Heat Treatment and Multi-Axial Forging.

The mechanical properties of various Ti-6Al-4V alloys are influenced by their respective microstructures. This study generated an ultrafine-grain (UFG) Ti-6Al-4V alloy featuring bimodal grain distribution characteristics achieved through initial heat treatment, multi-axial forging (MF), and annealing. The study also extensively examined the evolution process of the alloy's microstructure. By subjecting the materials to heat treatments at 900 °C with air cooling and 950 °C with air cooling, both materials were found to be consisted of primary α (αp) and transformed ß (αs+ß) regions with different proportions. Following MF, the sample treated at 900 °C displays a microstructure featuring UFGs of α+ß surrounding larger micron-sized αp grains. On the other hand, the sample treated at 950 °C displays a microstructure distinguished by twisted αs lamellar and fragmented ß grains surrounding larger micron-sized αp grains. Following annealing, no significant grain growth was observed in the sample. The geometrically necessary dislocations (GNDs) within the UFGs were eliminated, though some GNDs persisted within the αp grains. The samples undergoing the 900 °C heat treatment, MF, and subsequent annealing exhibited elevated strength (1280 MPa) and total elongation (10.7%). This investigation introduces a novel method for designing the microstructure of the Ti-6Al-4V alloy to achieve superior performance.

Identification of cotton pest and disease based on CFNet- VoV-GCSP -LSKNet-YOLOv8s: a new era of precision agriculture.

Introduction: The study addresses challenges in detecting cotton leaf pests and diseases under natural conditions. Traditional methods face difficulties in this context, highlighting the need for improved identification techniques. Methods: The proposed method involves a new model named CFNet-VoV-GCSP-LSKNet-YOLOv8s. This model is an enhancement of YOLOv8s and includes several key modifications: (1) CFNet Module. Replaces all C2F modules in the backbone network to improve multi-scale object feature fusion. (2) VoV-GCSP Module. Replaces C2F modules in the YOLOv8s head, balancing model accuracy with reduced computational load. (3) LSKNet Attention Mechanism. Integrated into the small object layers of both the backbone and head to enhance detection of small objects. (4) XIoU Loss Function. Introduced to improve the model's convergence performance. Results: The proposed method achieves high performance metrics: Precision (P), 89.9%. Recall Rate (R), 90.7%. Mean Average Precision (mAP@0.5), 93.7%. The model has a memory footprint of 23.3MB and a detection time of 8.01ms. When compared with other models like YOLO v5s, YOLOX, YOLO v7, Faster R-CNN, YOLOv8n, YOLOv7-tiny, CenterNet, EfficientDet, and YOLOv8s, it shows an average accuracy improvement ranging from 1.2% to 21.8%. Discussion: The study demonstrates that the CFNet-VoV-GCSP-LSKNet-YOLOv8s model can effectively identify cotton pests and diseases in complex environments. This method provides a valuable technical resource for the identification and control of cotton pests and diseases, indicating significant improvements over existing methods.

[The relationship between hyperuricemia and contrast-induced nephropathy in patients with chronic kidney disease undergoing percutaneous coronary intervention].

OBJECTIVE: To investigate the relationship between hyperuricemia and contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). METHODS: A total of 446 consecutive patients with CKD undergoing PCI in Guangdong general hospital were enrolled in this study. Patients were divided into hyperuricemic group (n = 205) and normouricemic group (n = 241).Hyperuricemia was defined as serum uric acid > 420 µmol/L for male, > 357 µmol/L for female. CIN was defined as ≥ 44.2 µmol/L or ≥ 25% increase from baseline Serum creatinine within 48-72 hours after contrast medium exposure, and that was not attributable to other causes.In hospital incidences of CIN and the major adverse cardiac events were compared between the two groups. The relationship between the incidence of CIN and hyperuricemia was evaluated by multivariate logistic regression analysis. RESULTS: CIN occurred in 16.6% (74/446) of patients, and incidence of CIN was significantly higher in the hyperuricemic group than in the normouricemic group [23.9% (49/446) vs. 10.4% (25/446) , P = 0.000]. Patients who developed CIN had higher in hospital mortality [14.9% (11/74) vs. 1.3% (5/372), P = 0.000]. Need for renal replacement therapy, acute heart failure, intra-aortic balloon pump use and the hypotension after PCI were significantly higher in the hyperuricemic group compared with normouricemic group (P < 0.01 or P < 0.05) . Multivariate analysis indicates that hyperuricemia (OR = 1.9, 95%CI:1.1-3.5, P = 0.037), age > 75 years (OR = 3.2, 95%CI:1.8-5.7, P = 0.000) , emergent PCI (OR = 2.9, 95%CI:1.6-5.1, P = 0.000) and anemia (OR = 2.1, 95%CI:1.2-3.8, P = 0.012) were predictors of CIN in patients with CKD. CONCLUSION: Hyperuricemia is the independent risk predictor of CIN in patients with CKD undergoing PCI.