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.

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

CRISPR, as an emerging gene editing technology, has been widely used in multiple fields due to its convenient operation, less cost, high efficiency and precision. This robust and effective device has revolutionized the development of biomedical research at an unexpected speed in recent years. The development of intelligent and precise CRISPR delivery strategies in a controllable and safe manner is the prerequisite for translational clinical medicine in gene therapy field. In this review, the therapeutic application of CRISPR delivery and the translational potential of gene editing was firstly discussed. Critical obstacles for the delivery of CRISPR system in vivo and shortcomings of CRISPR system itself were also analyzed. Given that intelligent nanoparticles have demonstrated great potential on the delivery of CRISPR system, here we mainly focused on stimuli-responsive nanocarriers. We also summarized various strategies for CIRSPR-Cas9 system delivered by intelligent nanocarriers which would respond to different endogenous and exogenous signal stimulus. Moreover, new genome editors mediated by nanotherapeutic vectors for gene therapy were also discussed. Finally, we discussed future prospects of genome editing for existing nanocarriers in clinical settings.

Objective:To investigate the expression of miRNA-34b (miR-34b) in non-small cell lung cancer (NSCLC) tissues and its effect on proliferation and invasion of human NSCLC A549 cells in vitro.Methods:The specimens of cancer tissues and paracancerous normal epithelial tissues (more than 5 cm from the edge of the tumor) were collected from 40 NSCLC patients in Shanxi Province Cancer Hospital from June 2015 to March 2017. A549 cells were transfected with miR-34b mimics (experimental group) and irrelevant sequences (negative control group), respectively. The expression of miR-34b in tissues and each group of A549 cells was detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The proliferation activity of A549 cells in the experimental group and the negative control group was detected by methyl thiazolyl tetrazolium (MTT) assay, and the invasion ability of A549 cells in the two groups was detected by Transwell assay.Results:The relative expression of miR-34b in NSCLC tissues was lower than that in paracancerous normal epithelial tissues (0.52±0.06 vs. 1.05±0.17), and the difference was statistically significant ( P < 0.001). The relative expression of miR-34b in A549 cells of the experimental group was higher than that in the negative control group, and the difference was statistically significant ( P < 0.05). MTT assay showed that the cell proliferation ability (absorbance value) of A549 cells in the experimental group was lower than that in the negative control group after cultured for 24 and 48 hours (both P < 0.01). Transwell assay showed that the number of invaded A549 cells in the experimental group was less than that in the negative control group [(49.53±5.03) cells vs. (121.00±12.06) cells, P < 0.01]. Conclusions:The expression of miR-34b is low in NSCLC tissues, and the up-regulation of miR-34b expression can inhibit the proliferation and invasion of NSCLC A549 cells.

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 investigate the association of FAT atypical cadherin 1 (FAT1) with clinicopathological parameters and prognosis in esophageal squamous cell carcinoma (ESCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 124 patients with ESCC who were admitted to Shanxi Cancer Hospital from January 2011 to December 2015 were collected. There were 85 males and 39 females, aged from 40 to 72 years, with a median age of 60 years. The ESCC tissues surgically removed and adjacent tissues specimens were collected to prepare tissue microarray for immunohistochemical staining. The 5 cases of ESCC tissues and adjacent tissues were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR). Observation indicators: (1) the expression of FAT1 protein in ESCC and adjacent tissues; (2) the expression of FAT1 RNA in ESCC and adjacent tissues; (3) the expression of FAT1 protein in ESCC tissues and its association with clinicopathological parameters; (4) follow-up and survival. Follow-up using outpatient examination and telephone interview was conducted to detect survival of patients up to February 13, 2019. The survival time was from surgical date to tumor-related death or endpoint of follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non parameter rank sum test. The Kaplan-Meier method was used to calculate survival time, and Log-rank test was used for survival analysis. Results:(1) The expression of FAT1 protein in ESCC and adjacent tissues: of 124 specimens, the 107 cases of ESCC tissues and 93 cases of adjacent tissues were finally obtained because of exfoliative tissues. There were 76 cases of ESCC tissues and corresponding adjacent tissues matched. Results of immuno-histochemical staining showed that FAT1 protein was expressed in both ESCC and adjacent tissues and was brown after staining. FAT1 was located in cytomembrane, with high expression of FAT1 as ≥75 and low expression as <75. The relative expression levels of FAT1 protein in ESCC and adjacent tissues were 68±42 and 77±37, showing a significant difference between ESCC and adjacent tissues ( t=2.380, P<0.05). (2) The expression of FAT1 RNA in ESCC and adjacent tissues: results of qRT-PCR showed that the relative expression levels of FAT1 RNA in 5 cases of ESCC and adjacent tissues were 1.6±0.4 and 2.5±0.3, with a significant difference between them ( t=3.560, P<0.05). (3) The expression of FAT1 protein in ESCC tissues and its association with clinicopathological parameters: of the 107 ESCC patients, 58 cases had high expression of FAT1. There were 42 and 16 cases with high expression of FAT1 in 65 non-drinking patients and 42 drinking patients, respectively, showing a significant difference between them ( χ2=7.229, P<0.05). (4) Follow-up and survival: 96 of 107 ESCC patients were followed up for 38.0?94.9 months, with a median follow-up time of 45.9 months. Survival analysis showed that the survival time of patients with high FAT1 expression was 24 months, versus 22 months of patients with low FAT1 expression, indicating no significant difference between them ( χ2=1.773, P>0.05). Results of subgroup analysis showed that the survival time was 24 months and 21 months of female patients with high and low FAT1 expression, 23 months and 22 months of non-smoking patients with high FAT1 expression and low FAT1 expression, 23 months and 21 months of non-drinking patients with high FAT1 expression and low FAT1 expression, respectively, showing significant differences between them ( χ2=8.769, 12.827, 10.724, P<0.05). Conclusions:The expression of FAT1 in ESCC tissues is low. Female, non-smoking and non-drinking ESCC patients with high FAT1 expression have good survival.

Objective:To explore the practical effect of multi-disciplinary treatment learning (MDT-L) combined with PBL+CBL teaching on the clinical clerkship of neurosurgery.Methods:In the study, 30 neurosurgery clinical interns accepted by Wuhan Third Hospital from January 2019 to December 2019 were set as the control group, and 30 neurosurgery clinical interns from January 2020 to December 2020 were set as the research group. The control group implemented conventional teaching, and the research group used MDT-L combined with PBL+CBL teaching. After the clerkship, the two groups' clinical clerkship results, changes of comprehensive abilities before and after clerkship, professional quality after clerkship, and satisfaction with teaching methods were compared. SPSS 26.0 was used for t test and chi-square test. Results:After the clerkship, the theoretical knowledge and operational skills assessment scores of the research group were significantly higher than those of the control group ( P<0.05). There was no statistically significant difference in the scores of the two groups in learning interest, analytical ability, communication skills, innovation ability and file management ability before the clerkship ( P>0.05). While, after the clerkship, the comprehensive ability scores of the above dimensions of the two groups increased, and the comprehensive ability scores of the study group were all higher than those of the control group ( P<0.05). After the clerkship, the scores of professional ability, problem analysis and solving ability, mastery of diagnosis and treatment procedures, scoring of medical documents writing and total scoring of professional quality in the study group were all higher than those in the control group ( P<0.05). The satisfaction scores of the study group on the attractiveness, effectiveness and practicality of the teaching method were higher than those of the control group ( P<0.05). Conclusion:The application of MDT-L combined with PBL+CBL teaching in neurosurgery clinical clerkship can not only improve the performance of internship, but also enhance the comprehensive ability of interns and improve their professional quality and satisfaction.

Objective To investigate the expressions of Th17 lymphocytes and interleukin-17 (IL-17) in peripheral blood of patients with non-small cell lung cancer (NSCLC) and its clinical significance. Methods Sixty patients with primary and untreated NSCLC were enrolled and designed as experimental group, at the same time, 60 healthy volunteers were collected as control group. Flow cytometry (FCM) was used to detect the level of Th17 lymphocytes. Enzyme linked immunosorbent assay (ELISA) was used for detecting the level of IL-17. The relationship between the expression levels of Th17 and IL-17 in peripheral blood and clinicopathological features was compared between the two groups. Results The peripheral blood levels of Th17 lymphocytes and IL-17 in the experimental group [(1.7±1.2) ％, (8.3±2.5) pg/ml] were higher than those in the control group [(0.9 ±0.6) ％, (5.4 ±1.2) pg/ml] (P< 0.05). The peripheral blood expression of Th17 lymphocytes and IL-17 in patients with smoking history [(1.8±1.2) ％, (8.8±3.7) pg/ml] were higher than those in patients without smoking history [(1.6±1.2)％, (8.0±2.2) pg/ml], and the peripheral blood expression of Th17 lymphocytes and IL-17 were higher in patients with squamous-cell carcinoma [(1.8 ±1.2) ％, (9.4 ±4.7) pg/ml] than those in patients with adenocarcinoma [(1.6±1.1) ％, (7.3±3.9) pg/ml], furthermore, they were also higher in patients with stage Ⅲ-Ⅳ than those in patients with stage Ⅰ-Ⅱ (P < 0.05). Conclusion Th17 lymphocytes and IL-17 play certain roles in the occurrence and progression of NSCLC.

Objective To analyze the efficacy and hemodynamic changes in patients with complex symptomatic middle cerebral artery stenosis after Solitaire AB stent implantation.Methods From June 2013 to June 2016,7 consecutive patients with complex symptomatic middle cerebral artery stenosis treated with Solitaire stents at the Department of Neurology,the Third People's Hospital of Hubei Province were enrolled retrospectively.The stenosis rate ≥70% was confirmed by digital subtraction angiography (DSA).Of the 7 patients,5 were male and 2 were female,with an average age of 70±8 years.The general data of the patients were documented,including clinical symptoms,modified Rankin scale(mRS)score,stenosis degree,vascular pathways LMA classification and Mori typing for stenosis,and postoperative residual stenosis or restenosis.The hemodynamic parameters at day 1,7,and 3 months before and after procedure were compared.Results All patients were successfully implanted with the Solitaire AB stents.(1) Of the 7 patients,the Mori type A of stenosis lesions was in 4 cases,B in 2 cases,and C in 1 case.The LMA typing of vascular approaches were Type Ⅲ in 3 cases,type Ⅱ in 4 cases.The preoperative stenosis rate was 80±7%,the residual stenosis rate was 24±13%,and there were no operation-related complications.No ischemic events occurred during the follow-up period.(2) Before stent implantation and at 1 d,7 d,and 3 months after procedure,the peak systolic velocity (PSV) were 297±41,144±34,145±27,and 143±40 cm/s,respectively,the end diastolic velocity (EDV) were 159±22,68±16,68±14,and 66±17 cm/s,respectively,and the pulse index (PI) were 0.67±0.06,0.80±0.08,0.80±0.07,and 0.82±0.06,respectively.PSV,EDV,and PI at 1 d,7 d,and 3 months were improved compared with before procedure (all P<0.05),There were no significant differences at all time points in the pairwise comparison PSV and EDV and PI at all time points after the procedure (all P>0.05).Conclusions Initial analysis showed that no procedure-related complications were observed in the treatment of vascular tortuosity and complex middle cerebral artery stenosis with the Solitaire stents.The short-term curative effect is exact;However,it still needs to be validated further.

Objective To establish acute peritonitis induced by monosodium urate (MSU) of in mice and observe the significance of mitochondrial deoxyribonucleic acid (mtDNA) expression in the inflammatory processes.Methods The mouse models of acute peritonitis were made by intraperitoneal injection of MSU.Sixty-four male C57BL16 mice were randomly divided into the MSU group which were treated with 0.2 ml of 15 mg/ml MSU solution by i.p.injection and the control group which were treated with 0.2 ml of PBS.Respectively four mice from MSU group and four mice from control group were killed 2 hours, 4 hours, 6 hours, 8 hours 12 hour, 16 hours, 20 hours and 24 hours later and whole blood, peritoneal lavage and peritoneum were collected respectively.Four the mice from the MSU group and four mice from the control group were killed and whole blood, peritoneal lavage and peritoneum were collected.Immunoflourescence study of peritoneum tissues was performed.The levels of interleukin (IL)-1β, IL-18 in plasma and peritoneal lavage were examined by enzyme linked immunosorbent assay (ELISA).DNA was extracted from blood and peritoneal lavage, and mtDNA level was detected by using real-time polymerase chain reaction (PCR).The data was analyszied by multivariate analysis of variance.Results As compared with those killed at other time points from the MSU groups and the control group, the levels of IL-1β [(27.0±2.0) pg/ml vs (26.8±2.1) pg/ml], IL-18 [(673±454) pg/ml vs(752±495) pg/ml] in plasma and peritoneal lavage were increased progressively in those which were killed after i.p.injection of 2 hours and 4 hours from in the MSU group (F=22.778, P＜0.05;F=6.660, P＜0.05).The mtDNA in plasma and peritoneal lavage of the mice began to be expressed 4 hours after i.p.injection 4 hours from in the MSU group.The peak level was detected in those i.p.injected MSU 6 hours later [(9.85±4.59)×106 copies, (7.81±3.43)×106 copies].Then 8 hours later the mtDNA began to slowly decreased.At these three time points, the mtDNA were all increased progressively than those at the other time points of the MSN group or at all time points of the control group (F=6.719, P＜0.05;F=11.181, P＜0.05).By immunoflourescence study, there were neutrophil extracellular traps (NETs) were formed 12 hours later in the MSU group and aggregated NETs were found 24 hours later.Conclusion In the inflammatory processes of acute peritonitis induced by MSU of in mice, with the expression of mtDNA increasing, the inflammation is relieved, and aggregated NETs are formed in the end.Expression of mtDNA may be one for the protective factors of the inflammation induced by MSU.