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 systematically evaluate the risk of major bleeding and major adverse cardiac events(MACE)in patients with acute coronary syndrome(ACS)after combined use of novel oral anticoagulants(NOAC)and antiplatelet therapy. Methods Randomized controlled trials( RCTs)about NOAC treatment for ACS patients with basic antiplatelet therapy in related databases(up to July 2018)were searched. The outcome indicators included major bleeding events ( safety indicators ) and MACE ( effectiveness indicators). Quality of methodology was evaluated using bias risk assessment tool of Cochrane collaboration networks. Meta﹣analysis was performed using RevMan 5. 3 software. Results A total of 6 RCTs were entered,including comparative studies of single antiplatelet therapy(SAPT)or dual antiplatelet therapy(DAPT)combined with NOAC and combined with placebo or warfarin,involving 20 070 patients. Drugs used in the trial group included apixaban,rivaroxaban,and dabigatran etexilate. The quality evaluation showed that 4 of the 6 RCTs were with low risks of bias and 2 with high risks of bias. The meta﹣ analysis showed that the risk of clinical major bleeding events in patients in the SAPT+NOAC group was significantly higher than that in the SAPT+placebo group[3. 14%(44/1 402)vs. 1. 07%(19/1 770), RR＝3. 47,95% CI:2. 01﹣5. 97,P﹤0. 001]. The incidence of clinical major bleeding events in patients in the DAPT+NOAC group was significantly higher than that in the DAPT+placebo group[5. 72%(387/6 761)vs. 2. 79%(251/8 984),RR＝2. 59,95% CI:1. 73﹣3. 86,P﹤0. 001],but significantly lower than that in the DAPT+warfarin group[17. 22%(422/2 450)vs. 25. 68%(627/2 442),RR＝0. 68, 95% CI:0. 56﹣0. 82,P﹤0. 001]. The risk of MACE in patients in the SAPT+NOAC group was significantly lower than that in the SAPT+placebo group[8. 61%(121/1 405)vs. 12. 20%(217/1 779),OR＝0. 69, 95% CI:0. 55﹣0. 88,P ＝0. 003];there were no significant differences in the risks of MACE between patients in the DAPT+NOAC group and the DAPT+placebo group or DAPT+warfarin group(P﹥0. 05 for both). Conclusions Combination of anticoagulants and SAPT or DAPT in ACS patients may all increase the risk of clinical major bleeding,but combination of SAPT and NOAC may reduce the risk of MACE,and should be used after weighing. For patients who must be treated with triple antithrombotic therapy,DAPT combined with NOAC can be chosen and warfarin should be avoided.

Objective To systematically evaluate the risk of major bleeding and major adverse cardiac events(MACE)in patients with acute coronary syndrome(ACS)after combined use of novel oral anticoagulants(NOAC)and antiplatelet therapy. Methods Randomized controlled trials( RCTs)about NOAC treatment for ACS patients with basic antiplatelet therapy in related databases(up to July 2018)were searched. The outcome indicators included major bleeding events ( safety indicators ) and MACE ( effectiveness indicators). Quality of methodology was evaluated using bias risk assessment tool of Cochrane collaboration networks. Meta﹣analysis was performed using RevMan 5. 3 software. Results A total of 6 RCTs were entered,including comparative studies of single antiplatelet therapy(SAPT)or dual antiplatelet therapy(DAPT)combined with NOAC and combined with placebo or warfarin,involving 20 070 patients. Drugs used in the trial group included apixaban,rivaroxaban,and dabigatran etexilate. The quality evaluation showed that 4 of the 6 RCTs were with low risks of bias and 2 with high risks of bias. The meta﹣ analysis showed that the risk of clinical major bleeding events in patients in the SAPT+NOAC group was significantly higher than that in the SAPT+placebo group[3. 14%(44/1 402)vs. 1. 07%(19/1 770), RR＝3. 47,95% CI:2. 01﹣5. 97,P﹤0. 001]. The incidence of clinical major bleeding events in patients in the DAPT+NOAC group was significantly higher than that in the DAPT+placebo group[5. 72%(387/6 761)vs. 2. 79%(251/8 984),RR＝2. 59,95% CI:1. 73﹣3. 86,P﹤0. 001],but significantly lower than that in the DAPT+warfarin group[17. 22%(422/2 450)vs. 25. 68%(627/2 442),RR＝0. 68, 95% CI:0. 56﹣0. 82,P﹤0. 001]. The risk of MACE in patients in the SAPT+NOAC group was significantly lower than that in the SAPT+placebo group[8. 61%(121/1 405)vs. 12. 20%(217/1 779),OR＝0. 69, 95% CI:0. 55﹣0. 88,P ＝0. 003];there were no significant differences in the risks of MACE between patients in the DAPT+NOAC group and the DAPT+placebo group or DAPT+warfarin group(P﹥0. 05 for both). Conclusions Combination of anticoagulants and SAPT or DAPT in ACS patients may all increase the risk of clinical major bleeding,but combination of SAPT and NOAC may reduce the risk of MACE,and should be used after weighing. For patients who must be treated with triple antithrombotic therapy,DAPT combined with NOAC can be chosen and warfarin should be avoided.

Objective To systematically evaluate the correlation between sodium-glucose co-tran-sporter 2(SGLT2)inhibitors and fracture risk in type 2 diabetes mellitus(T2DM)patients. Methods The related databases were searched. The randomized controlled trials(RCTs)which the outcome index included fracture in T2DM patients treated with SGLT2 inhibitors from the inception to August 2017 were enrolled into the study. The documents were selected according to the inclusion and exclusion criteria. After the data extraction and evaluation of methodological quality of RCTs,Meta-analysis was conducted using Rev Man 5.3 software. Results A total of 12 RCTs involving 28 181 patients were entered,including 17 747 patients in the test group(SGLT2 inhibitors)and 10 434 in the control group. The drugs used in the test group were canagliflozin(7 RCTs)and empagliflozin(5 RCTs). The drugs used in the control group were non-SGLT2 inhibitors including metformin,glimetazide and/or placebo. The results of Meta-analysis showed that the incidence of fractures in the test group was significantly higher than that in the control group[5.05%(897/17 747)vs. 4.40%(459/10 434),RR=1.27,95%CI:1.14-1.42,P<0.01]. Subgroup analysis showed that the incidence of fractures in the canagliflozin group was significantly higher than that in the control group[6.21%(679/10 938)vs. 5.28%(365/6 913),RR=1.31,95%CI:1.15-1.48,P<0.01]. There were no significant differences in the incidence of fractures between the empagliflozin group and the control group[3.20%(218/6 809)vs. 2.67%(94/3 521),RR=1.44,95%CI:0.35-5.90, P=0.61]. Conclusions Canagliflozin(a kind of SGLT2 inhibitors)can increase the incidence of fractures. It is suggested that the risk assessment should be done before medication for the benefit of patients.

Objective To analyze the relationship between glutathione S-transferase P1 (GSTP1) 313A＞G polymorphism and the adverse reactions induced by cyclophosphamide (CP). Methods The clinical research literature about the relationship between GSTP1 313A＞G polymorphism and the adverse reactions induced by CP were collected from related domestic and foreign databases up to July,2017. The quality of the literature was evaluated by STREGA criterion. The meta-analysis was conducted by RevMan 5.2 software and the results were expressed as relative risk (RR)and 95% confidence interval (CI). Results A total of 7 articles were included in the meta-analysis and their quality evaluation results were reliable (all scores≥3),involving 1 305 patients. The results of meta-analysis showed that the differences of incidence of leukopenia,neutropenia,anemia,thrombocytopenia,myelosuppression,and infection after the treatments of CP combined with other chemotherapeutics between the patients with GSTP1 313A＞G AA genotype and GSTP1 313A＞G AG/GG genotype were not statistically significant (P＞0.05 for all);the incidence of gastrointestinal reactions in patients with GSTP1 313A＞G AA genotype was significantly lower than that in patients with GSTP1 313A＞AG/GG genotype (RR＝0.46,95%CI:0.22-0.97,P＝0.004);the incidence of myelosuppression after the treatment of CP alone in patients with GSTP1 313A ＞G AA genotype was significantly lower than that in patients with GSTP1 313A＞G AG/GG genotype (RR＝0.27, 95%CI:0.08-0.91,P＝0.03). Conclusion The gastrointestinal reactions induced by CP combined with other chemotherapeutics and myelosuppression induced by CP alone may be related to the polymorphism of GSTP1 313A＞G.

Objective To systematically evaluate the correlation between sodium-glucose co-tran-sporter 2(SGLT2)inhibitors and fracture risk in type 2 diabetes mellitus(T2DM)patients. Methods The related databases were searched. The randomized controlled trials(RCTs)which the outcome index included fracture in T2DM patients treated with SGLT2 inhibitors from the inception to August 2017 were enrolled into the study. The documents were selected according to the inclusion and exclusion criteria. After the data extraction and evaluation of methodological quality of RCTs,Meta-analysis was conducted using Rev Man 5.3 software. Results A total of 12 RCTs involving 28 181 patients were entered,including 17 747 patients in the test group(SGLT2 inhibitors)and 10 434 in the control group. The drugs used in the test group were canagliflozin(7 RCTs)and empagliflozin(5 RCTs). The drugs used in the control group were non-SGLT2 inhibitors including metformin,glimetazide and/or placebo. The results of Meta-analysis showed that the incidence of fractures in the test group was significantly higher than that in the control group[5.05%(897/17 747)vs. 4.40%(459/10 434),RR=1.27,95%CI:1.14-1.42,P<0.01]. Subgroup analysis showed that the incidence of fractures in the canagliflozin group was significantly higher than that in the control group[6.21%(679/10 938)vs. 5.28%(365/6 913),RR=1.31,95%CI:1.15-1.48,P<0.01]. There were no significant differences in the incidence of fractures between the empagliflozin group and the control group[3.20%(218/6 809)vs. 2.67%(94/3 521),RR=1.44,95%CI:0.35-5.90, P=0.61]. Conclusions Canagliflozin(a kind of SGLT2 inhibitors)can increase the incidence of fractures. It is suggested that the risk assessment should be done before medication for the benefit of patients.

Objective To analyze the relationship between glutathione S-transferase P1 (GSTP1) 313A＞G polymorphism and the adverse reactions induced by cyclophosphamide (CP). Methods The clinical research literature about the relationship between GSTP1 313A＞G polymorphism and the adverse reactions induced by CP were collected from related domestic and foreign databases up to July,2017. The quality of the literature was evaluated by STREGA criterion. The meta-analysis was conducted by RevMan 5.2 software and the results were expressed as relative risk (RR)and 95% confidence interval (CI). Results A total of 7 articles were included in the meta-analysis and their quality evaluation results were reliable (all scores≥3),involving 1 305 patients. The results of meta-analysis showed that the differences of incidence of leukopenia,neutropenia,anemia,thrombocytopenia,myelosuppression,and infection after the treatments of CP combined with other chemotherapeutics between the patients with GSTP1 313A＞G AA genotype and GSTP1 313A＞G AG/GG genotype were not statistically significant (P＞0.05 for all);the incidence of gastrointestinal reactions in patients with GSTP1 313A＞G AA genotype was significantly lower than that in patients with GSTP1 313A＞AG/GG genotype (RR＝0.46,95%CI:0.22-0.97,P＝0.004);the incidence of myelosuppression after the treatment of CP alone in patients with GSTP1 313A ＞G AA genotype was significantly lower than that in patients with GSTP1 313A＞G AG/GG genotype (RR＝0.27, 95%CI:0.08-0.91,P＝0.03). Conclusion The gastrointestinal reactions induced by CP combined with other chemotherapeutics and myelosuppression induced by CP alone may be related to the polymorphism of GSTP1 313A＞G.

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