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.

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

OBJECTIVE: We aimed to analyze the current indoor radon level and estimate the population risk of radon-induced lung cancer in urban areas of China. METHODS: Using the passive monitoring method, a new survey on indoor radon concentrations was conducted in 2,875 dwellings across 31 provincial capital cities in Chinese mainland from 2018 to 2023. The attributable risk of lung cancer induced by indoor radon exposure was estimated based on the risk assessment model. RESULTS: The arithmetic mean (AM) and geometric mean (GM) of indoor radon concentrations were 65 Bq/m³ and 55 Bq/m³, respectively, with 13.6% of measured dwellings exceeding 100 Bq/m³ and 0.6% exceeding 300 Bq/m³. The estimated number of lung cancer deaths induced by indoor radon exposure was 150,795, accounting for 20.30% (95% CI: 20.21%-20.49%) of the lung cancer death toll. CONCLUSION This study provided the most recent data on national indoor radon levels in urban areas and the attributable risk of lung cancer. These results served as an important foundation for further research on the disease burden of indoor radon exposure and radon mitigation efforts.
Radon/analysis* ; China/epidemiology* ; Air Pollution, Indoor/analysis* ; Lung Neoplasms/etiology* ; Humans ; Cities/epidemiology* ; Air Pollutants, Radioactive/adverse effects* ; Neoplasms, Radiation-Induced/etiology* ; Risk Assessment ; Radiation Monitoring

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO_2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO_2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO_2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

Objective:To explore the clinical features and risk factors of systemic lupus erythematosus(SLE) concomitant with interstitial lung disease(ILD) in children.Methods:A retrospective analysis was performed.A total of 111 hospitalized children diagnosed with SLE in the Department of Rheumatology and Immunology, Children′s Hospital of Soochow University from February 2016 to November 2018 were selected as the research subjects and divided into the SLE-ILD group(18 cases) and the SLE-non-ILD group(93 cases)according to the lung high-resolution CT manifestations. T-test and Wilcoxon rank sum test were used to compare and analyze the general situation, clinical manifestations and laboratory results.Multivariate Logistic regression was used to analyze the risk factors of SLE-ILD. Results:The prevalence of SLE-ILD was 16.2%(18/111 cases). There were significant differences between the SLE-ILD group and the SLE-non-ILD group in the course of disease [14.00 (12.00-24.25) months vs.1.00(1.00-2.00) months], the incidence of serositis [55.6%(10/18 cases) vs.8.6%(8/93 cases)], post-activity shortness of breath [83.3%(15/18 cases) vs.25.8%(24/93 cases)], nervous system damage [27.8%(5/18 cases) vs.6.5%(6/93 cases)], cardiovascular system damage [38.9%(7/18 cases) vs.9.7%(9/93 cases)], the occu-rrence of increased erythrocyte sedimentation rate [66.7%(12/18 cases) vs.31.2%(29/93 cases)], the decreased C 3[88.9%(16/18 cases) vs.62.4%(58/93 cases)], positive anti neutrophil cytoplasmic antibody (ANCA) [88.9%(16/18 cases) vs.18.3%(17/93 cases)], positive anti-Sm antibody [61.1%(11/18 cases) vs.15.1%(14/93 cases)] and anti ribonucleoprotein antibody (anti RNP antibody)[66.7%(12/18 cases) vs.16.1%(15/93 cases)](all P<0.05). Logistic regression analysis demonstrated that serositis( OR=30.535, 95% CI: 2.167-430.336, P=0.011), shortness of breath after exercise( OR=55.115, 95% CI: 1.117-2 579.852, P=0.041), positive ANCA( OR=65.090, 95% CI: 4.488-944.071, P=0.002) and positive anti-RNP antibody( OR=10.007, 95% CI: 1.362-73.500, P=0.024) were risk factors for SLE-ILD. Conclusions:The longer the course of SLE, the higher the incidence of ILD; serositis, shortness of breath after exercise, positive ANCA and positive anti RNP antibody may be risk factors for SLE-ILD.

Objective To investigate the effect of nucleus localization signal linked nucleic kinase substrate short peptide-conjugated chitosan (NNSCS)-mediated human miR-140 gene local transfection on the repair of articular cartilage defect in rabbits.Methods Eukaryotic expression plasmid GV268-miR-140 was constructed,and then negative controls GV268 and GV268-miR-140 were respectively combined with NNSCS to form NNSCS/GV268 and NNSCS/GV268-miR-140 complexes.Eighteen healthy male New Zealand white rabbits were randomly divided into transgenic group (Group A),negative control group (Group B),and sham operation group (Group C),with 6 rabbits per group.Both Groups A and B were prepared for the total cartilage damage model of femur trochlear,and Group C only exposed the articular surface of the femur trochlear.One week after operation,Group A was treated with NNS CS/GV268-miR-140 complex,Group B was given NNS CS/GV268 complex,and Group C was given equal amount of isotonic saline,twice a week for 7 weeks.The experimental animals were sacrificed at the end of the eighth week after operation.Real time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression of miR-140,Sox9,Aggrecan and Hdac4 in the defect area.HE staining,safranine O/fast green staining,and Aggrecan immunohistochemical staining were used to evaluate cartilage repair in the defect area.Results RT-qPCR showed the expression of miR-140 in Group A (3.16 ± 0.37) was significantly higher than that in Group B (1 ± 0.24) and in Group C (1.24 ± 0.18) (P ＜ 0.05).The miR-140 expression in Group A obviously up-regulated the expression of SOx9 gene (4.38 ± 0.66) compared with Group B (1.04 ± 0.04) and Group C (1.19 ± 0.3),(P ＜ 0.05).The miR-140 expression in Group A obviously up-regulated the expression of Aggrecan gene (3.63 ± 0.58) (P ＜0.05) compared with Group B (1.21 ± 0.14) and Group C (1.34 ± 0.13).The miR-140 expression in Group A obviously down-regulated the expression of Hdac4 (0.37 ±0.06) compared with Group B (0.81 ± 0.06) (P ＜ 0.05).According to results of HE staining,safranine O/fast green and Aggrecan,cartilage repair was evident in Group A,while fibrous tissue proliferation and inflammatory cell infiltration were seen in the defect region in Group B,showing no cartilage repair.Conclusions NNS CS can carry exogenous genes into chondrocytes and the genes can abundantly express locally.High expression of miR-140 might significantly improve the repair of articular cartilage defect in vivoby up-regulating expressions of Aggrecan and Sox9 as well as down-regulating Hdac4 expression.

Objective To investigate the influence of co-culture of microglia and neural stem cells (NSCs) on differentiation from NSCs into dopaminergic neurons in vitro.Methods (1) The microglia from neonatal SD rats was purified and identified.After the NSCs were isolated from 14-day pregnant SD rats,the cells were cultured and identified.(2) The identified NSCs were randomly divided into 2 groups:simple NSCs culture group and NSCs+microglia co-culture group.After the cells in both groups were cultured for 6 days,immunofluorescence assay and Westem blotting were performed to detect the protein expression of TH,DAT and Pitx3,the factors associated with the differentiation and maturity of dopaminergic neurons.(3) PCR was used to detect the gene transcription of TH,DA T and Pitx3 in the cells from the 2 groups and differences were compared between the 2 groups.Results (1)The staining of CD1 1b/c in the microglia mixed cultured in the neonatal SD rats was positive,with a purity of above 95％;the staining of NSCs identified via nestin was positive in the 14-day pregnant SD rats.(2) The immunofluorescence assay showed that the amounts of positive proteins of TH,DAT and Pitx3 in the NSCs+microglia co-culture group were significantly larger than in the simple NSCs culture group (P＜0.05).The Western blotting showed that the protein expression levels ofTH,DAT and Pitx3 in the NSCs+microglia co-culture group were significantly higher than in the simple NSCs culture group (P＜0.05).(3) The PCR detection showed that the gene transcription levels of TH,DA T and Pitx3 in the NSCs+microglia co-culture group were significantly higher than in the simple NSCs culture group (P＜0.05).Conclusion Co-culture of NSCs and microglia via Transwell may promote differentiation from NSCs into dopaminergic neurons.

Objective To evaluate the efficacy and safety of tacrolimus (TAC) for treatment of Henoch-SchSnlein purpura nephritis in children.Methods Forty children with Henoch-SchSnlein purpura nephritis (pathological grade Ⅲ-Ⅵ) in Children's Hospital Affiliated to Soochow University from January 2013 to June 2016 were selected and divided into TAC group (n =19) and cyclophosphamide (CTX) group (n =21).The children in TAC group were given TAC orally;the children in CTX group were given CTX pulse therapy intravenously.The 24 h urine protein,urine red blood cell count,serum albumin,serum creatinine and blood urea nitrogen of children before treatment and after 6 months treatment were observed and compared between the two groups.The treatment effects and adverse reactions of patients were observed and compared between the two groups.Results There was no statistic difference in the 24 h urine protein,urine red blood cells count,serum albumin,blood creatinine and blood urea nitrogen levels of children between the two groups before treatment (P ＞ 0.05).The 24 h urinary protein and urine red blood cells count of children after 6 months of treatment in the two groups were significantly lower than those before treatment (P ＜ 0.05);there was no statistic difference in the serum albumin,serum creatinine and blood urea nitrogen levels of children in the two groups before treatment and after 6 months of treatment (P ＞ 0.05).Mter 6 months of treatment,the 24 h urine protein and urine red blood cells count of children in TAC group were significantly lower than those in the CTX group (P ＜ 0.05);there was no statistic difference in the serum albumin,serum creatinine and blood urea nitrogen levels of children between the two groups (P ＞ 0.05).After 6 months treatment,the effective rate of children in the TAC group was significantly higher than that in the CTX group (x2 =4.607,P ＜ 0.05).The incidence of adverse reactions of children in the TAC group was significantly lower than that in the CTX group (x2 =4.043,P ＜ 0.05).Conclusion TAC is effective in treatment of Henoch-Sch(o)nlein purpura nephritis in children.It is easy to take,and has less adverse reactions.

Objective: To investigate the clinical and genetic character of Chinese children with the aarF domain containing kinase 4 (ADCK4)-associated glomerulopathy. Methods: Applying next generation sequencing to detect possible gene mutation(renal disease associated monogene was pooled as one panel) in 69 children with steroid-resistant nephrotic syndrome (SRNS) or persistent proteinuria of unknown origin. Sanger sequencing was used to confirm the significant mutations found in the children and to validate these mutation sites in their patients. Using online software (PolyPhen2, SIFT, Mutation Taster) to predict whether the detected missense mutations were disease causing or not. Collecting and analyzing clinical data of children with ADCK4-associated glomerulopathy, which included onset age, clinical manifestation, and renal pathology. Results: The ADCK4 gene mutation was detected in 8 children with a positive rate of 11.6% (8 out of 69), among which 3 patients carried homozygous c.748G>C mutation, 3 patients carried homologous c.737G>A mutation, 1 patient carried compound heterozygous mutation(c.748G>C and c.737G>A), and 1 patient carried compound heterologous mutation(c.551A>G and c.737G>A). Collectively, there were only 3 mutation sites found in total 8 patients, in which the mutation sites of c.748G>C and c.737G>A had high detection frequency in these 8 patients. These 3 mutation sites were all missense mutation which were predicted to be disease causing by online software and not reported before. The average onset age was 6.5 years (2 years-11.75 years). Four patients presented with SRNS and the other 4 presented with persistent proteinuria. All 8 patients had no extrarenal manifestation, renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in most patients, among which 3 cases had gone to end-stage renal disease (ESRD) at disease onset, and 2 cases progressed to ESRD 2 and 5 years after onset respectively. Seven patients had received glucocorticoid and/or immunosuppressive drug while only one patient getting partial response. All 8 patients were treated with large amount of coenzyme Q₁₀ (15 mg·kg^-1·d^-1) after definite diagnosis of ADCK4 mutation-some patients had acquired encouraging curative effect. Conclusions ADCK4-associated glomerulopathy is not rare especially in the children with SRNS. The onset age is relatively old and the extrarenal manifestation is less common. FSGS is a main pathology type. Patients usually have no response to immunosuppressive therapy, but may benefit from addition of large amount of coenzyme Q₁₀. Some patients may only manifest with insidious proteinuria, causing the early diagnosis to be difficult, which deserves more attention. Three new missense mutations expand disease causing mutation repertoire of ADCK4 gene, among which the two sites of c.748G>C and c.737G>A may be mutation hotspot of ADCK4-associated glomerulopathy in Chinese population, and need further study.