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.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.

Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.

Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.

The rapid development of medical application of ionizing radiation has seen a range of safety and protection problems that might be of importance. This paper aims to introduce the current situation and existing problems in the public medical exposure, and to propose the relevant suggestions, based on a combination of judgment of medical radiation exposure justification, quality assurance and control of equipment in radiodiagnosis and radiotherapy, occupational protection of radiation workers, and health effects on patients undergoing radiodiagnosis and radiotherapy.

Objective To observe the clinical efficacy of heat-sensitive moxibustion plus point-toward-point needling in treating poststroke strephenopodia.Method Eighty patients with poststroke strephenopodia were randomized into a treatment group intervened by heat-sensitive moxibustion plus point-toward-point needling and a control group intervened by rehabilitation, 40 cases in each group. In addition to the basic treatment, the treatment group was given heat-sensitive moxibustion plus point-toward-point needling, and the control group was given rehabilitation treatment. Holden's Functional Ambulation Classification (FAC), Fugl-Meyer Assessment (FMA) of the lower-limb motor function, and Tinetti Gait Assessment (TGA) were adopted for evaluation of the two groups, and the clinical efficacies were compared.ResultThe effective rate was 90.0% in the treatment group versus 77.5% in the control group, and the difference was statistically significant (P<0.05); after the treatment,there was a significant difference in comparing the Holden's FAC between the two groups (P<0.05); the FMA score changed significantly after the treatment in both groups (P<0.05), and there was a significant difference in comparing the FMA score between thetwo groups after the treatment (P<0.05); the TGA score changed significantly after the intervention in both groups (P<0.05), and there was a significant difference in comparing the TGA score between the two groups after the intervention (P<0.05).ConclusionHeat-sensitive moxibustion plus point-toward-point needling can produce a significant efficacy in treating poststroke strephenopodia, as it can enhance the effective rate and improve the lower-limb motor function.

Objective To investigate the clinical efficacy of intermittent liver-nourishing and mind-regulating acupuncture in preventive treatment of migraine. Method One hundred and twenty migraine patients were randomly allocated to treatment and control groups, 60 cases each. The treatment group received intermittent liver-nourishing and mind-regulating acupuncture and the control group took flunarizine hydrochloride capsules orally. The migraine score, the visual analogue scale (VAS) score and the headache severity rating score were recorded in the subjects before treatment and at the end of treatment and the 4-week, 8-week, 12-week, 16-week and 20-week follow-ups. The Self-Rating Anxiety Scale (SAS) score and the Self-Rating Depression Scale (SDS) were recorded before and after treatment.Result After one course of treatment, the total efficacy rate was 98.3% in the treatment group and 89.5% in the control group; there was a statistically significant difference between the two groups (P<0.05). There was a statistically significant difference in the migraine score between before treatment and at the end of treatment in the two groups (P<0.05) and between the two groups at the same follow-ups (P<0.05). There was a statistically significant difference in the VAS score between before treatment and at the end of treatment in the two groups (P<0.05) and between the two groups at the same follow-ups (P<0.05). There were statistically significant differences in the SAS and SDS scores between before treatment and at the end of treatment in the two groups (P<0.05) and between the two groups after treatment (P<0.05).Conclusion Intermittent liver-nourishing and mind-regulating acupuncture has marked efficacy in preventive treatment of migraine. It can increase the total efficacy rate and reduce the number of relapses.

Animals ; Cellular Reprogramming ; genetics ; DNA Transposable Elements ; genetics ; Genetic Vectors ; genetics ; Genome ; genetics ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Mutagenesis

Objective Gynecologic minimally invasive surgery has become popular in the treatment of tumor therapy in re-cent years, but improper application can result in tumor metastasis.In this paper, we presented 6 uterine neoplasm cases of tumor me-tastasis after minimally invasive surgery and analyzed the causes and the preventive measures. Methods Retrospective analysis was made on the clinical data and pathology characteristics of the 6 uterine neoplasm cases of tumor metastasis after primary minimally inva-sive surgery in our department from January 1, 2013 to 2015 June 30, and related literature were reviewed. Results The ages of 6 patients were 39-52 years old.The primary operation methods included 2 cases of hysteroscopic myomectomy, 3 cases of laparoscopic myomectomy and 1 case of radiofrequency ablation.The pathological diagnosis after primary operations were 4 cases of uterine sarcoma ( low grade endometrial stromal sarcoma in 2 cases and leiomyosarcoma in 2 cases) who were found metastatic tumor at 3-16 months after primary surgery and finally died of the disease and 2 cases of uterine fibroids who were found metastatic tumor in abdominal cavity and puncture hole at 60 months and 108 months respectively after primary operation followed by a good prognosis after the second surgi-cal resection. Conclusion Owing to uterine neoplasm by hysteroscopy, laparoscopy often needs certain pressure and morcellation which may result in easy plantation of crushing tumor tis-sue or metastasis with circulation and puncture under pressure.Ra-diofrequency ablation lack of histopathologic diagnosis has heating effect which is inclined to speed up the spread and transfer of tumor cells once it is diagnosed as malignant.Therefore, clinicians should know the defects and risk of being lack of histopathologic diagno-sis, diagnostic curettage pathology and fast pathology to avoid tumor metastasis induced by minimally invasive surgery.