Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To explore the influencing factors of renal injury in elderly patients with cor pulmonale, and to provide information for the prevention of renal injury in patients with cor pulmonale. Methods A total of 309 elderly patients with cor pulmonale over 60 years old treated in our hospital from June 2019 to December 2020 were included in the study. According to the patients with renal injury , they were divided into cor pulmonale renal injury group (case group) and cor pulmonale non renal injury group (control group). The basic information of the two groups and the influencing factors of potential renal injury in the past were collected, The influencing factors of renal injury in elderly patients with cor pulmonale were analyzed by univariate analysis and regression model. Results The single factor analysis of the case group was higher than that of the control group, with a male age of 80 years, smoking history, family history of diabetes, concurrent infection, diabetes mellitus and left ventricular ejection fraction (LVEF) <56.00% ratio. The difference between the case group and the control group was higher than that of the control group (P<0.05). The above univariate analysis results were brought into the multiple regression model. The final multiple regression analysis showed that age > 80 years old (or = 3.142), smoking history (or=2.115) , concurrent infection (or=4.263) , and excessive systolic blood pressure (or=2.279) were the risk factors potentially increasing the risk of renal injury, which were statistically significant (P < 0.05). Conclusion Elderly patients with cor pulmonale over 80 years old , with smoking history and abnormal blood pressure , as well as those complicated with infection , have an increased risk of renal injury. It is worthy of clinical attention and relevant preventive measures to improve the prognosis of patients.

Objective To understand the epidemiological characteristics and psychological factors of senile arrhythmia in Xining area, and provide theoretical basis for the prevention and treatment of senile arrhythmia. Methods A total of 518 elderly patients treated in the department of Cardiology in Xining area from June 2018 to June 2020 were selected and divided into control group (without arrhythmia) and study group (with arrhythmia) according to whether the patients were complicated with arrhythmia. All subjects underwent 24h electrocardiographic monitoring to record heart rate, heart rate lead electrocardiogram and 24h dynamic electrocardiogram examination. Refer to the patient's medical records for general information, including age, gender, coronary heart disease, hypertension, etc.; Psychological factors such as depression, anxiety, sleep and quality of life were analyzed. The correlation between PSQI score, HAMA-14 score, HAMD-17 score and arrhythmia was analyzed by Pearson correlation analysis. Results Among 518 patients, 305 (58.89%) were complicated with arrhythmia, including 155 males and 150 females, with an average age of 76.15±3.79. Atrial arrhythmia accounted for 38.36% (117/305), sinus tachycardia accounted for 28.52% (87/305). Ventricular arrhythmias accounted for 11.48% (35/305); The incidence of arrhythmia in 70-79 year olds was significantly higher than that in 60-69 year olds (χ²=8.358 , P<0.05). The incidence of arrhythmia in rural area was significantly higher than that in urban area (χ²=6.801, P<0.05). There was no significant difference in the incidence of arrhythmia between male and female (χ²=1.534, P>0.05). The incidence of arrhythmia was significantly higher in patients with hypertension and coronary heart disease (χ²=16.401, χ²=9.772 , P<0.05). There were significant differences in PSQI score, HAMA-14 score, HAMD-17 score between the two groups (P<0.05). Pearson correlation analysis showed that PSQI score, HAMD-14 score and HAMD-17 score were positively correlated with the occurrence of arrhythmia in the elderly population in Xining area, with correlation coefficients r=0.417 , 0.607 , 0.653 (P<0.05). Conclusion The incidence of arrhythmia increases in the elderly population in Xining area, mainly in the rural elderly population, which is associated with depression and anxiety and sleep disorders and other psychological factors. Early detection and early intervention can improve the response to treatment and accessibility.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis. METHODS: Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups. RESULTS: Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed. CONCLUSION: Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis. CLINICAL TRIAL REGISTRATION https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies ; Brain Neoplasms/genetics*

Pulmonary hypertension is a rapidly progressing disease of the lung vasculature with poor prognosis, ultimately leading to right heart failure and death. The remodeling of small pulmonary arteries represents an important pathological characteristic of pulmonary hypertension. Pulmonary arterial smooth muscle cells (PASMCs) located in the middle layer of pulmonary artery exhibit hyperproliferation and resistance to apoptosis, which is the main initiator of pulmonary vascular remodeling and similar to that seen in tumor cells. In this review we focus on the signaling pathways that play a key role in PASMCs proliferation and the latest research progress on inhibitors targeting cell proliferation pathways to provide a new perspective for the treatment of PH．

Pulmonary hypertension (PH) is a kind of disease characterized by progressive increase of pulmonary vascular resistance and occlusive vascular remodeling. Hypoxic inductive factor-2α (HIF-2α) plays an important role in the abnormal proliferation of pulmonary vascular cells and pulmonary vascular remodeling. This review focuses on the role of HIF-2α in pulmonary hypertension at the cellular and the global level, and candidates targeting HIF-2α for the treatment of pulmonary hypertension, in order to better understand the pathogenesis of PH and find effective treatments.

Objective:To observe the clinical efficacy of modified Banxia Xiexintang on nonalcoholic fatty liver （NAFLD） and the regulatory effect on insulin resistance （IR）. Method:One hundred and forty patients were randomly divided into control group and observation group. A total of 63 patients in control group completed the therapy （4 patients fell off or were lost to follow-up， 3 were eliminated）， while 65 patients in observation group completed the therapy （5 patients fell off or were lost to follow-up， none was eliminated）. Both groups' patients got lifestyle intervention， liver protection and lipid regulation. Patients in control group got Huazhi Rougan granule， 1 pack/time， 3 times/day. Patients in observation group got modified Banxia Xiexintang， 1 dose/day. And the course of treatment for the two groups was 12 weeks， and a 12 week follow-up was recorded. Before and after treatment and during the follow-up， fat content of liver was recorded by instantaneous elastic recorder， fasting blood glucose （FBG） and fasting insulin （FINS） were detected， and insulin sensitivity index （ISI）， insulin resistance index （HOMA-IR） and islet β cell function index （HOMA-β） were detected. After treatment， B-mode ultrasonography and ratio of liver/spleen CT were detected. And levels of alanine transaminase （ALT）， aspartate transaminase （AST）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， adiponectin， leptin， serine protease inhibitor （Vaspin）， tumor necrosis factor （TNF）-α and interleukin-6 （IL-6） were detected. And the safety was evaluated. Result:CAP and HOMA-IR in observation group were lower than those in control group after treatment and during the follow-up （P<0.01）， and ISI and HOMA-β were higher than those in control group （P<0.01）. Amelioration of indexes of blood lipid was better than those in control group （P<0.01）. Levels of ALT， AST， FBG and FINS were lower than those in control group （P<0.01）. Scores of traditional Chinese medicine （TCM） syndromes were lower than those in control group （P<0.01）， ratio of liver/spleen CT and adiponectin was higher than that in control group （P<0.01）. Levels of TNF-α， IL-6， vaspin and leptin were lower than those in control group （P<0.01）. B-ultrasound efficacy and fat content of liver were superior to those of control group （P<0.05）. There were no serious adverse events and drug-related adverse reactions. Conclusion:Modified Banxia Xiexintang can regulate glucose and lipid metabolism， improve insulin sensitivity and HOMA-β cell function， improve IR， regulate adipocytokines and inflammatory factors， relieve clinical symptoms and liver fat content， and improve CT ratio of liver/spleen， with a better clinical efficacy and safety.

Drug screening against Candida albicans has become more urgent due to the increasing incidence of infection and the development of drug-resistant strains. The microfluidic chip technique has shown great potential for high-throughput drug screening. In this study we developed a concentration gradient microfluidic chip platform for drug screening against Candida albicans. The generated concentration gradient on this platform was investigated qualitatively by monitoring the distribution of the fluorescent tracer fluorescein sodium and quantitatively by following the distribution of the model drug fluconazole as analyzed by HPLC; the effect of different flow conditions on the concentration gradient were determined. The ratio of the two aqueous phase flow rates was determined in the subsequent drug screening studies. Alamar Blue, an indicator of cell viability, was used in the susceptibility test for amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, terbinafine, 5-fluorocytosine and caspofungin as carried out on the established chip platform. The MIC range of the drugs, which was consistent with the MIC values of the CLSI-recommended standard, were obtained quickly and efficiently through the use of this platform, indicating that this new platform can quickly screen a series of antibacterial drugs in one run. In addition, the strain of Candida albicans we used showed resistance to terbinafine in our platform assay, consistent with the results of a 96-well plate assay, indicating that the platform can also be used for rapid screening of resistant strains.