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Growing evidences have confirmed the effect of Sacubitril/Valsartan (SV) on antihypertension and cardiac protection in general population. However, there was no prospective study about the effect and safety of SV on resistant hypertension and myocardial work in hemodialysis patients. In this single‐center, prospective, before‐after study, enrolled patients were endured with resistant hypertension for more than 6 months. Participants were initially instructed to take SV 50 mg twice daily, and the dosage was gradually increased up to 100 mg twice daily. The primary outcomes were blood pressure (BP) control, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), myocardial work (MW), fatigue and life quality. In addition, the adverse events were also recorded in this cohort. A total of 18 patients (34–64 years old) was finally enrolled and completed in this study. The SV‐based regimen provided significantly mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (‐20.7/‐8.3 mm Hg), respectively. The cardiac remodeling parameters were partially improved. Compared to the baseline, NT‐proBNP was significantly reduced at week 4 (8119.50 [3710.75, 29300] pg/ml to 7216.50 [4124.75, 17455.00] pg/ml, p = .046), which was much lower at week 12 (3130.50 [2244.50, 9565.70] pg/ml, p = .037). Global MW index was higher at week 12 compared to the baseline (p = .026). MW efficiency was also improved accordingly compared to the baseline, even though the statistical difference was not significant (p = .226). Life quality and fatigue were improved at week 12 compared to the baseline (all p = .000). There was no serious adverse events were observed. SV safely and effectively controlled resistant hypertension and improved MW as well as life quality in hemodialysis patients.

The hydroxyapatite nanoparticles (nHAPs) were synthesized rapidly by the self-assembled dual-frequency ultrasonic method. The ultrasonic time and power effect on the morphology and phase composition of nHAPs were investigated through field-emission scanning electron microscopy (FE-SEM), X-ray diffraction, energy dispersive spectrometer (EDS) spectrometer, and Fourier transform infrared spectroscopy, which showed that the most uniform nanoparticles were obtained when the ultrasonic time was 30 min and the ultrasonic power was 280 W. Cytotoxicity and hemolysis tests showed that an indistinctive cytotoxic effect was within the concentration of 25–400 μg/mL and the hemolytic ratio was below 2.0% at concentration of 25–200 μg/mL, respectively, revealing a good biocompatibility of nHAPs. By loading tetracycline hydrochloride onto nHAPs spheres, the drug release results showed that the drug loading and encapsulation efficiency were (26.34 ± 2.99)% and (52.68 ± 5.98)%, respectively. The drug-loaded sample shows a slow-release property, indicating that nHAPs may be promising as drug carriers.

Chronic obstructive pulmonary disease （COPD） is a leading cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. By the year 2020, COPD will be the third leading cause of mortality and the fifth leading cause of disability worldwide, In a population based study conducted at multiple international sites, approximately 10% of participants 40 years of age or older were found to have airflow obstruction of at least moderate severity according to spirometric criteria. In China, the overall prevalence of COPD in individuals 40 years of age or older was 8.2%.m COPD is a slowly progressive respiratory disease, which, although preventable and treatable, is not curable. The final years for patients with advanced COPD are characterized by progressive functional decline, frequent exacerbations, poor quality of life, increasing dependency on informal caregivers and on the health care system. According to the literature, 5-year survival from diagnosis is estimated to be 78% in men and 72% in women with mild disease, but only 30% in men and 24% in women with advanced COPD.

Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a “shield” in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.

In Arabidopsis, the salt overly sensitive (SOS) pathway, consisting of calcineurin B-like protein 4 (CBL4/SOS3), CBL-interacting protein kinase 24 (CIPK24/SOS2) and SOS1, has been well defined as a crucial mechanism to control cellular ion homoeostasis by extruding Na+ to the extracellular space, thus conferring salt tolerance in plants. CBL10 also plays a critical role in salt tolerance possibly by the activation of Na+ compartmentation into the vacuole. However, the functional relationship of the SOS and CBL10-regulated processes remains unclear. Here, we analyzed the genetic interaction between CBL4 and CBL10 and found that the cbl4 cbl10 double mutant was dramatically more sensitive to salt as compared to the cbl4 and cbl10 single mutants, suggesting that CBL4 and CBL10 each directs a different salt-tolerance pathway. Furthermore, the cbl4 cbl10 and cipk24 cbl10 double mutants were more sensitive than the cipk24 single mutant, suggesting that CBL10 directs a process involving CIPK24 and other partners different from the SOS pathway. Although the cbl4 cbl10, cipk24 cbl10, and sos1 cbl10 double mutants showed comparable salt-sensitive phenotype to sos1 at the whole plant level, they all accumulated much lower Na+ as compared to sos1 under high salt conditions, suggesting that CBL10 regulates additional unknown transport processes that play distinct roles from the SOS1 in Na+ homeostasis.

To evaluate the efficacy and safety of upadacitinib in the treatment of moderate-to-severe atopic dermatitis (AD), and provide reference for rational clinical medication. PubMed, Medline, Embase, Web of Science, Clinical Trials Website, and Cochrane Library databases were searched from the time of establishment until January 6, 2024, to compile a list of all randomized controlled trials (RCTs) including upadacitinib in the treatment of moderate-to-severe AD. The quality of the included studies was evaluated using the Cochrane Systematic Review. Review Manager 5.3 software was utilized for statistical analysis of outcome measures. A total of five studies were included in the meta-analysis. The results revealed that the 15 mg and 30 mg upadacitinib significantly improved Eczema Area and Severity Index (EASI) 75% {[Odds Ratio (OR) = 8.58, 95% confidence interval (CI) (5.84-12.60), P < 0.00001] [OR = 15.62, 95% CI (10.89-22.42), P < 0.00001]}, Numerical Rating Scale (NRS) ≥ 4 {[OR = 7.13, 95% CI (5.63-9.01), P < 0.00001] [OR = 11.30, 95% CI (8.93-14.31), P < 0.00001]}, and Investigator's Global Assessment (IGA) 0/1 {[OR = 8.63, 95% CI (6.60-11.27), P < 0.00001] [OR = 16.04, 95% CI (12.26-20.99), P < 0.00001]} compared to placebo. In terms of safety, although 15 mg and 30 mg upadacitinib significantly increased the overall adverse events rate compared to placebo {[OR = 1.31, 95% CI (1.09-1.58), P = 0.004] [OR = 1.85, 95% CI (1.54-2.21), P < 0.00001]}, there was no significant difference in the serious adverse events rate {[OR = 0.73, 95% CI (0.41-1.29), P = 0.28] [OR = 0.69, 95% CI (0.39-1.23), P = 0.21]} and withdrawal rate due to adverse events {[OR = 0.66, 95% CI (0.39-1.11), P = 0.12] [OR = 0.85, 95% CI (0.52-1.38), P = 0.50]} compared to placebo. This meta-analysis preliminarily suggests that upadacitinib is effective and safe for usage in the treatment of moderate-to-severe AD. Additionally, upadacitinib can instantly relieve itchiness and effectively reduce symptoms and signs, with its 30-mg dose being more effective than the 15-mg dose.

Economically underdeveloped areas in western China are hotspots of tuberculosis, especially among students. However, the related spatial and temporal patterns and influencing factors are still unclear and there are few studies to analyze the causes of pulmonary tuberculosis in students from the perspective of space. We collected data regarding the reported incidence of pulmonary tuberculosis (PTB) among students at township level in Nanning, from 2012 to 2018. The reported incidence of pulmonary tuberculosis among students in Nanning was analyzed using spatial autocorrelation and spatial scan statistical analysis to depict hotspots of PTB incidence and spatial and temporal clustering. Spatial panel data of the reported incidence rates and influencing factors at district and county levels in Nanning were collected from 2015 to 2018. Then, we analyzed the spatial effects of incidence and influencing factors using the spatial Durbin model to explore the mechanism of each influencing factor in areas with high disease prevalence under spatial effects. From 2012 to 2018, 1609 cases of PTB were reported among students in Nanning, with an average annual reported incidence rate of 14.84/100,000. Through the Joinpoint regression model, We observed a steady trend in the percentage of cases reported each year (P>0.05). There was spatial autocorrelation between the annual reported incidence and the seven-years average reported incidence from 2012 to 2018. The high-incidence area was distributed in the junction of six urban areas and spread to the periphery, with the junction at the center. The population of college students, per capita financial expenditure on health, per capita gross domestic product, and the number of health technicians per 1,000 population were all influencing factors in the reported incidence of PTB among students. We identified spatial clustering of the reported incidence of PTB among students in Nanning, mainly located in the urban center and its surrounding areas. The clustering gradually decreased from the urban center to the surrounding areas. Spatial effects influenced the reported incidence of PTB. The population density of college students, per capita health financial expenditure, gross domestic product (GDP) per capita, and the number of health technicians per 1,000 were all influencing factors in the reported incidence of PTB among students.

Purpose To verify whether radiomics techniques based on dual-modality ultrasound consisting of B-mode and superb microvascular imaging (SMI) can improve the accuracy of the differentiation between gallbladder neoplastic polyps and cholesterol polyps. Methods A total of 100 patients with 100 pathologically proven gallbladder polypoid lesions were enrolled in this retrospective study. Radiomics features on B-mode ultrasound and SMI of each lesion were extracted. Support vector machine was used to classify adenomas and cholesterol polyps of gallbladder for B-mode, SMI and dual-modality ultrasound, respectively, and the classification results were compared among the three groups. Results Six, eight and nine features were extracted for each lesion at B-mode ultrasound, SMI and dual-modality ultrasound, respectively. In dual-modality ultrasound model, the area under the receiver operating characteristic curve (AUC), classification accuracy, sensitivity, specificity, and Youden’s index were 0.850 ± 0.090, 0.828 ± 0.097, 0.892 ± 0.144, 0.803 ± 0.149 and 0.695 ± 0.157, respectively. The AUC and Youden’s index of the dual-modality model were higher than those of the B-mode model ( p  < 0.05). The AUC, accuracy, specificity and Youden’s index of the dual-modality model were higher than those of the SMI model ( p  < 0.05). Conclusions Radiomics analysis of the dual-modality ultrasound composed of B-mode and SMI can improve the accuracy of classification between gallbladder neoplastic polyps and cholesterol polyps.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients. A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results. In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model. Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.