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.

Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

Objective To make clear the patients in minimally invasive surgery through explo-ring effects of pneumoperitoneum and pulmonary infection on the airway pressure of patients with dif-ferent body mass index (BMI)under general anesthesia.Methods A total of 849 cases of patients with trachea cannula in pneumoperitoneum surgery inr general anesthesia under different position were studied.To observe the changes of airway pressure and the ratio of pulmonary infection within one week of patients in general anesthesia.Propofol,Remifentanil and Atracrium were used in general an-esthesia.BIS and TOF were used to detect the degree of muscle relaxation.Results The airway pres-sure was increased obviously in patients of Head-down Tilt under same pneumoperitoneum pressure(P<0.05);the airway pressure was increased in patients with BMI>30 kg/m2 (P <0.05).There was no obvious increase in pulmonary infection rate in all patients.Conclusion Pneumoperitoneum could increase airway pressure and pulmonary infection of patients with low head position and BMI > 30 kg/m2 under same pneumoperitoneum pressure.Therefore,shorten the operation time and decreased pneumoperitoneum pressure could be used to prevent pulmonary infection.

OBJECTIVETo observe the clinical efficacy differences between regular acupuncture combined with acupuncture at trigone of urinary bladder and simple regular acupuncture for treatment of urination dysfunction induced by spinal cord injury.

METHODSSixty patients were randomized into an observation group and a control group, 30 cases in each one. The control group was treated with regular acupuncture at Sanyinjiao (SP 6), Zusanli (ST 36), Zhongwan (CV 12) and Tianshu (ST 25), etc. Based on the treatment of control group, the observation group was additionally treated with intensive needling at trigone of urinary bladder, once a day, 30 min per treatment. Ten treatments were considered as one course, and there was an interval of two days between courses, 4 courses of treatment were given in two groups. The improvement of urination function in two groups was evaluated, and the efficacy of urination function in two groups was compared.

RESULTSAfter treatment, the times of urine leakage, maximum urine output, bladder capacity and residual urine were all improved in two groups (all P<0.05). The improvement of times of urine leakage, bladder capacity and residual urine in the observation group was superior to that in the control group (all P<0.05). The total effective rate was 96.7% (29/30) in the observation group, which was superior to 83.3% (25/30) in the control group (P<0.05).

CONCLUSIONThe efficacy of regular acupuncture combined with intensive needling at trigone of urinary bladder on urination dysfunction induced by spinal cord injury is significantly superior to that of simple regular acupuncture.

Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Spinal Cord Injuries ; complications ; Treatment Outcome ; Urination ; Urination Disorders ; etiology ; physiopathology ; therapy ; Young Adult

Objective To systematically analyze and evaluate the association between the peptidylarginine deiminaseⅣ(PADI4) gene and rheumatoid arthritis (RA) based on the published data,and to provide evidence for the pathogenesis of RA.Methods By selecting five SNPs in PADI4 (rs11203366,rs11203367,rs874881,rs2240340,rs1748033) which had been extensively examined.Meta-analysis on each SNP was performed step by step according to Hugenet manual to investigate the association of the polymorphisms of the PADI4 gene with RA.Results This Meta-analysis enrolled 15 659 RA patients and 22 019 healthy controls from 21 studies worldwide.It demonstrated that rs11203366,rs11203367,rs2240340 and rs 1748033 confered susceptibility to RA in Asian ethnicity (P＜0.01,0.03,＜0.01,＜0.01),while rsl1203366,rsl1203367 and rs874881 confered susceptibility to RA in Caucasian of European ancestry (P=0.0002,0.004,0.03).It also shown that no significant association between rs874881 and RA in the Asian ethnicity populations (P=0.2),or rs2240340,rs1748033 and RA in Caucasian of European ancestry (P=0.18,0.1 ).A linkage disequilibrium study was also performed.The LD study showed that rs11203366,rs11203367,rs874881,rs2240340 and rs1748033 were in linkage disequilibrium both in the Asian ethnicity and Caucasian,which was basically inconsistent with the results of Meta-analysis.The conflicting results should be explained by many aspects such as bias in sample selection,genotyping,and the stratification.Conclusion The PADI4 genotype is partially associated with RA,and the underling mechanisms need further study.Haplotype based research and Metaanalysis would be valuable.

Objective To explore the association between HLA-Cw alleles with systemic lupuserythematosus. Methods Polymerase chain reaction-sequence specific primer method was used to analyze thedistribution of HLA-Cw01-08 alleles among 108 patients with SLE and 102 healthy controls. The allelefrequencies was compared between various patient groups and the control population. Results The frequencyof HLA-Cw07 alleles in patients with SLE was significantly increased in patients with SLE. Conclusion Theresults indicate that HLA-Cw07 may be the susceptible alleles or may be closely linked to the susceptiblegenes for SLE.

OBJECTIVE:To optimize the extraction technics of liver-strengthening cholagogue oral preparation.METHODS:The effects of the four factors-the quantity of the added water,the decoction time,the decoction times and the alcohol precipitation concentration on the extraction results were determined with content of total flavonoids taken as index.RESULTS:The best extracting condition was the following,the amount of the added water was 10 times that of the medicinal materials,the decoction duration was 60min,the alcohol precipitation concentration was 50%and the decoction was carried out twice.CONCLUSION:The preparation under this technics is of high clarity and stable contents.