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.

ObjectiveTo investigate the effects of Fangji Fulingtang on macrophage polarization and oxidative stress in the mouse model of myocardial fibrosis. MethodThe mouse model of myocardial fibrosis was established by subcutaneous injection of isoproterenol （ISO， 5 mg·kg^-1·d^-1）. Fifty C57BL/6J mice were randomly assigned into control （0.9% NaCl）， model （0.9% NaCl）， low- and high-dose （3.315 g·kg^-1·d^-1 and 13.26 g·kg^-1·d^-1， respectively） Fangji Fulingtang （FFD-L and FFD-H， respectively）， and metoprolol tartrate （Meto， 15 mg·kg^-1·d^-1） groups， with 10 mice each group. After 2 weeks of treatment， the heart appearance， cardiac weight index （CWI）， heart weight （HW）/tibia length （TL） ratio， and myocardial histopathological alterations were observed. Meanwhile， the serum levels of creatine kinase-MB （CK-MB）， transforming growth factor-β₁ （TGF-β₁）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6， IL-10， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） were measured by enzyme-linked immunosorbent assay （ELISA）. The expression levels of CD86 and CD206 were observed by immunohistochemical staining. ResultCompared with the model group， the FFD-L， FFD-H， and Meto groups showed improved heart appearance， decreased CWI and HW/TL ratio （P<0.01）， lowered serum levels of CK-MB， TGF-β₁， TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， and elevated IL-10 level （P<0.05）. Furthermore， the three groups showed reduced infiltration of inflammatory cells， myocardial injury， collagen deposition， and myocardial fibrosis， decreased CD86， SOD， and GSH （P<0.01）， and increased CD206 and MDA （P<0.01）. ConclusionFangji Fulingtang can mitigate ISO-induced myocardial fibrosis by regulating macrophage polarization and oxidative stress.

Objective:To analyze the local recurrence patterns after concurrent chemoradiotherapy (CCRT) for thoracic esophageal squamous cell carcinoma (ESCC) through image fusion, and to explore the risk factors of local recurrence and its relationships with dosimetric indices.Methods:A retrospective analysis was conducted for 209 thoracic ESCC patients who received radical CCRT in Fourth Hospital of Hebei Medical University during 2016-2019. For the patients diagnosed as the local recurrence of esophageal lesions, their CT images were fused with the original planning CT images using image registration software to identify the recurrence sites. Through 1∶1 propensity score matching (PSM) of the clinal data of patients with local recurrence (the recurrence group, nbefore = 81, nafter = 62) and those without local recurrence (the recurrence-free group, nbefore = 128, nafter=62), the dose and volume parameters of the treatment plans for the two groups were compared. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and the Cox regression model to analyze the factors affecting the overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Results:All patients had 1-, 3-, and 5-year OS rates of 80.9%, 42.6%, and 33.0%, respectively, 1-, 3-, and 5-year PFS rates of 67.9%, 34.0%, and 27.9%, respectively, and 1-, 3-, and 5-year RFS rates of 71.3%, 39.2%, and 30.5%, respectively. T stage, N stage, and radiation dose were independent prognostic factors for the OS, PFS, and RFS ( HR = 1.42-1.87, P < 0.05) of the patients, respectively. Among 68 patients with local recurrence, 62 cases (91.2%) suffered recurrence within the gross tumor volume (GTV). The dose and volume parameters of patients with local recurrence, such as GTV- D95%, clinical target volume (CTV)- D95%, GTV- D50%, CTV- D50%, and planning target volume (PTV)- D50%, GTV- V60, CTV- V60, and PTV- V60, were significantly lower than those of patients free from the local recurrence ( t=1.90-2.15, P < 0.05). Conclusions:Local recurrence of patients with thoracic ESCC after radical CCRT occurs mainly within the GTV. Increasing radiation doses may contribute to their survival benefits. The D50% for each target volume in the radiotherapy plan may be related to local recurrence, and it is necessary to conduct further research.

Objective:To analyze the factors influencing the poor effect of short-term electrical spinal cord stimulation in the treatment of postherpetic neuralgia (PHN).Methods:The medical records of PHN patients of either sex, aged 40-85 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, who received short-term electrical spinal cord stimulation from July 2017 to July 2022, were retrospectively collected. The therapeutic effect was evaluated using the modified MacNab criteria at 3 months after operation, and the patients were divided into good efficacy group (excellent and good efficacy) and poor efficacy group (fair and poor efficacy). General information, disease course, lesion site, complicated diseases, ossification of the yellow ligament in the diseased spinal segment, severity of pain in the herpetic stage, standard antiviral therapy in the herpetic stage (for more than 7 days) and use of neurotrophic drugs in the herpetic stage (for more than 7 days) were collected. Multivariate logistic regression analysis was used to screen the influencing factors for the poor effect of electrical spinal cord stimulation in the treatment of PHN.Results:A total of 168 patients were eventually enrolled, among which 69 had poor curative effect, and the rate of poor curative effect was 41.1%. The results of multivariate logistic regression analysis showed that the patient′s age ( OR=2.230, P=0.015), course of disease ( OR=2.191, P=0.027), complication with diabetes mellitus( OR=8.859, P=0.010), ossification of ligamentum flavum at the same segment ( OR=6.602, P=0.019), severity of pain in the herpetic stage ( OR=5.788, P=0.038) and non-standard antiviral therapy in the herpetic stage ( OR=6.765, P=0.021) were the influencing factors for the poor effect of electrical spinal cord stimulation in the treatment of PHN. Conclusions:Age, course of disease, complication with diabetes mellitus, ossification of ligamentum flandum at the same segment, severity of pain in the herpetic stage and non-standard antiviral therapy in the herpetic stage are the factors influencing the poor effect of short-term electrical spinal cord stimulation in the treatment of PHN.

Objective:To analyze the correlation between peripheral blood eosinophil (EOS) level and clinical characteristics of patients with pneumoconiosis complicated with chronic obstructive pulmonary disease (COPD) .Methods:From January 2007 to November 2020, newly diagnosed patients with pneumoconiosis complicated with COPD in Beijing Chaoyang Hospital, were retrospectively analyzed. These patients were stratified into EOS<100 cells/μl group and EOS≥100 cells/μl group, taking 100 cells/μl as the cut-off value. Demographic characteristics, clinical symptoms, lung function and laboratory indexes were compared between the two groups.Results:The median EOS count of patients with pneumoconiosis complicated with COPD was 100 (40, 180) cells/μl. 50.2% (160/319) had blood eosinophil counts ≥100 cells/μl, and 11.0% (35/319) had blood eosinophil counts ≥300 cells/μl. In comparison with EOS<100 cells/μl group, EOS≥100 cells/μl group were older ( P=0.035), had higher body mass index ( P=0.008), and had lower forced respiratory volume in the first second ( P=0.017), had higher the ratio of residual volume to total lung volume ( P=0.010), and had lower diffusing capacity of the lung for carbon monoxide ( P=0.008). Arterial partial pressure of oxygen was significantly reduced in EOS≥100 cells/μl group ( P=0.039). The peripheral blood EOS count was negatively correlated with forced vital capacity, forced breathing volume in the first second, carbon monoxide diffusion, peak expiratory flow, and maximum mid expiratory flow as a percentage of expected values ( rs=-0.22, -0.18, -0.19, -0.19, -0.19, P=0.000, 0.001, 0.003, 0.008, 0.002), and positively correlated with the ratio of residual air volume to total lung volume ( rs=0.17, P=0.002) . Conclusion:There was a correlation between blood EOS count and pulmonary function parameters, can proide reference for the diagnosis and treatment of chnoric obstuctive pulmmory disease in clinical practice.

Objective:To analyze the correlation between peripheral blood eosinophil (EOS) level and clinical characteristics of patients with pneumoconiosis complicated with chronic obstructive pulmonary disease (COPD) .Methods:From January 2007 to November 2020, newly diagnosed patients with pneumoconiosis complicated with COPD in Beijing Chaoyang Hospital, were retrospectively analyzed. These patients were stratified into EOS<100 cells/μl group and EOS≥100 cells/μl group, taking 100 cells/μl as the cut-off value. Demographic characteristics, clinical symptoms, lung function and laboratory indexes were compared between the two groups.Results:The median EOS count of patients with pneumoconiosis complicated with COPD was 100 (40, 180) cells/μl. 50.2% (160/319) had blood eosinophil counts ≥100 cells/μl, and 11.0% (35/319) had blood eosinophil counts ≥300 cells/μl. In comparison with EOS<100 cells/μl group, EOS≥100 cells/μl group were older ( P=0.035), had higher body mass index ( P=0.008), and had lower forced respiratory volume in the first second ( P=0.017), had higher the ratio of residual volume to total lung volume ( P=0.010), and had lower diffusing capacity of the lung for carbon monoxide ( P=0.008). Arterial partial pressure of oxygen was significantly reduced in EOS≥100 cells/μl group ( P=0.039). The peripheral blood EOS count was negatively correlated with forced vital capacity, forced breathing volume in the first second, carbon monoxide diffusion, peak expiratory flow, and maximum mid expiratory flow as a percentage of expected values ( rs=-0.22, -0.18, -0.19, -0.19, -0.19, P=0.000, 0.001, 0.003, 0.008, 0.002), and positively correlated with the ratio of residual air volume to total lung volume ( rs=0.17, P=0.002) . Conclusion:There was a correlation between blood EOS count and pulmonary function parameters, can proide reference for the diagnosis and treatment of chnoric obstuctive pulmmory disease in clinical practice.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

Medical microbiology is one of the compulsory courses of basic medical sciences, which lays an important theoretical foundation for the follow-up study of infectious diseases, contagions, tumors, and so on. The course of medical microbiology in our college adhered to the concept of student-centered, diversified teaching, scientific evaluation, and continuous improvement. Teaching design was a cross-link of general theories, specific chapters, clinical cases, theory and practice, and the ideological and political education throughout the curriculum. Lectures adopted the mode of offline teaching (such as flipped classroom, case analysis, and comprehensive experimental design), online assistance (such as classroom test, stage test, extracurricular homework, and questionnaire survey), and combined process evaluation. This teaching mode also reflected the deep integration of information technology and classroom teaching. With the development and construction in these years, medical microbiology has completed the renewal of curriculum resources, the construction of online question bank, the construction and design of ideological and political case bank, and process evaluation (10 points of usual score + 10 points of case study + 10 points of experimental performance + 100 points of final examination multiplied by 70%). There was no significant difference in the results of qustionnaire survey in terms of the improvement of independent learning ability, curriculum evaluation system and satisfaction feedback. Students in Batch 2019 were most satisfied with the teaching of keeping pace with the times and the guidance of positive outlook on life and values.

BACKGROUND: Lung cancer is the leading cause of cancer-related death, of which non-small cell lung cancer (NSCLC) is the most common type. Immune checkpoint inhibitors (ICIs) have now become one of the main treatments for advanced NSCLC. This paper retrospectively investigated the effect of peripheral blood inflammatory indexes on the efficacy of immunotherapy and survival of patients with advanced non-small cell lung cancer, in order to find strategies to guide immunotherapy in NSCLC. METHODS: Patients with advanced non-small cell lung cancer who were hospitalized in The Affiliated Cancer Hospital of Nanjing Medical University from October 2018 to August 2019 were selected to receive anti-PD-1 (pembrolizumab, sintilimab or toripalimab) monotherapy or combination regimens. And were followed up until 10 December 2020, and the efficacy was evaluated according to RECIST1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were followed up for survival analysis. A clinical prediction model was constructed to analyze the predictive value of neutrophil-to-lymphocyte ratio (NLR) based on NLR data at three different time points: before treatment, 6 weeks after treatment and 12 weeks after treatment (0w, 6w and 12w), and the accuracy of the model was verified. RESULTS: 173 patients were finally included, all of whom received the above treatment regimen, were followed up for a median of 19.7 months. The objective response rate (ORR) was 27.7% (48/173), the disease control rate (DCR) was 89.6% (155/173), the median PFS was 8.3 months (7.491-9.109) and the median OS was 15.5 months (14.087-16.913). The chi-square test and logistic multi-factor analysis showed that NLR6w was associated with ORR and NLR12w was associated with ORR and DCR. Further Cox regression analysis showed that NLR6w and NLR12w affected PFS and NLR0w, NLR6w and NLR12w were associated with OS. CONCLUSIONS In patients with advanced non-small cell lung cancer, NLR values at different time points are valid predictors of response to immunotherapy, and NLR <3 is often associated with a good prognosis.
Aged ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Biomarkers/blood* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Female ; Humans ; Immunotherapy/methods* ; Inflammation/blood* ; Leukocyte Count ; Lung Neoplasms/pathology* ; Lymphocytes ; Male ; Middle Aged ; Neutrophils ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Survival Analysis ; Treatment Outcome