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.

To investigate the effect of mitochondrial division inhibitor 1(Mdivi-1)on imiquimod(IMQ)-induced psoriasis-like skin inflammation in mice and its mechanism,female 8-week-old C57BU6 mice were recruited and randomly divided into control group,IMQ model group,IMQ+Mdivi-1 experiment group.IMQ was used to induce the psoriasis-like skin inflammation model in mice.The mice in the experiment group were injected intraperitoneally(i.p.)with Mdivi-1,and the mice in the control group and model group were injected with the same volume of solvent.The mice were sacrificed on the 7th day for sampling.Psoriasis area and severity index(PASI)score was used to evaluate the severity of skin lesions in each group;the reactive oxygen species(R0S)content in skin tissue was detected by fluorescence staining of frozen section;HE staining was used to observe the histomorphologic change of skin lesions;immunohistochemical staining was used to detect the expression of dynamin-related protein 1(Drp1)in the skin of mice;Western blot was used to detect the protein levels of Drp1,NLRP3 and IL-1β in the skin tissues of mice in each group;and the expressions of IL-17A and IL-18 in mouse serum were detected by ELISA.Data showed that the model group had typical psoriatic lesions such as erythema,scale and thickening,and the Mdivi-1 group demonstrated obvious reduction of the lesions.The PASI score of the experiment group was significantly lower than that of the model group.HE staining indicated that the epidermal thickness of the back skin in the treatment group was significantly lower than that in the model group,and Munro microabscess was significantly reduced.R0S fluorescence staining indicated that ROS content in the experiment group was significantly lower than that in the model group;immunohistochemical results showed that the expression of Drp1 protein in the experiment group was significantly lower than that in the model group;Western blot results showed that the expression levels of Drp1,NLRP3 and IL-1 β in the experiment group were significantly lower than those in the model group;ELISA results indicated that the expressions of IL-17A and IL-18 in serum of mice in the experiment group were lower than those in the model group.Taken together,Mdivi-1 can reduce mitochondrial damage and ROS production by inhibiting the expression of Drp1,thereby reducing the production of NLRP3 inflammasome,down-regulating IL-1 β,IL-18 and IL-17A,and alleviating the IMQ-induced psoriasis-like skin inflammation in mice.

Objective:To investigate the predictive value for major adverse cardiovascular events (MACE) occurring within 1 year in patients with old myocardial infarction(OMI) using characteristics of myocardial scar derive from dual-energy CT (DECT) post-processing technique.Methods:OMI patients who received coronary CT angiography following dual-energy CT with late iodine enhancement (LIE-DECT) in the Second Affiliated Hospital of Nantong University from November 2019 to October 2022 were continuously included, and the images of all enrolled patients were reconstructed using 40 keV monoenergetic plus (Mono+) map, LIE (representing myocardial scar) was quantified on left ventricular short-axis images, including the LIE segments, the LIE score, and the LIE degree. All enrolled patients were followed up for MACE, defined as hospitalization for heart failure, malignant arrhythmia, and cardiac death. Regression analysis was used to investigate the relationship between the quantified value of myocardial scar and the occurrence of MACE, and receiver operating characteristic curve (ROC) was used to evaluate the efficacy of quantified value of myocardial scar in predicting MACE. The area under the curve (AUC) was compared using the DeLong test.Results:Finally, 231 patients with OMI were included, and MACE occurred in 37 cases (16.0%) within 1 year after LIE-DECT examination. The LIE segments 5 (4, 7), the LIE score 27 (13, 49) and the LIE degree 9.4%(7.5%, 15.5%) in the MACE group were higher than those in the non-MACE group 3 (2, 5), 9 (6, 15) and 6.7%(6.3%, 7.9%) (all P<0.001). Multivariable logistic regression analysis showed that after adjusting for confounders, the LIE segments ( OR=2.118, P<0.001), the LIE score ( OR=3.168, P<0.001), and the LIE degree ( OR=3.092, P<0.001) remained risk factors for the development of MACE. On ROC analysis, AUC of LIE segments, LIE score and LIE degree were 0.715, 0.822 and 0.806 (all P<0.001), with sensitivities of 81.1%, 86.5%, and 91.9%, and specificities of 53.6%, 69.6%, and 60.8%, respectively. DeLong′s test showed that the predictive efficacy of LIE score and LIE degree was higher than that of LIE segments ( Z=2.63, P=0.008; Z=1.96, P=0.049), and there were no significant differences in the predictive efficacy of LIE score and LIE degree ( Z=0.60, P=0.551). Conclusion:The LIE segments, the LIE score and the LIE degree detected by LIE-DECT 40 keV Mono+maps are risk factors for the occurrence of MACE in patients with OMI and have good efficacy in predicting the occurrence of MACE, which can be used as important indicators for assessing the clinical prognosis of OMI.

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*

Tumor radiotherapy is established on the basis of clinical oncology, radio-physics and radiobiology, and has become one of the three major therapeutic methods for malignant tumors. With the pace of socialist construction in China, the subject of radiotherapy in Shanxi province has developed from scratch and from small to large for more than 60 years. Remarkable achievements have been made in the establishment of departments, the updating of technical equipment, the increase of employees and clinical scientific research. This article reviews and summarizes the development history of tumor radiotherapy in Shanxi province.

Objective To explore the mechanism that Staphylococcus aureus(S.aureus) α-toxin(Hla) regulate miR-142 expression and inhibit macrophage phagocytosis.Methods BALB/C mice and RAW264.7 cells were infected with wild type S.aureus(WT S.aureus),Hla deletion S.aureus(△HlaS.aureus) or phosphate buffered saline(PBS),and the expression level of miR-142 of skin tissues and cells were detected.miR-142 mimics and inhibitor were then applied in the RAW264.7 culture to examine the effect on phagocytosis.Direct targeting of miR-142 on protein kinase Cα(PKCα) was assessed by luciferase assay and western blotting.Results miR-142 expression in △HlaS.aureus group were significantly down-regulated than WT S.aureus group(P<0.05).MiR-142 mimics inhibited RAW264.7 phagocytosis ability and inhibitor enhanced RAW264.7 phagocytosis ability.PKCα was directly targeted by miR-142.MiR-142 mimics significantly decreased the mRNA expression levels of PKCα in RAW264.7 cells(P<0.05).Conclusion Hla could promote miR-142 expression in macrophages.MiR-142 could inhibit macrophage phagocytosis through down-regulated PKCα.

Objective To evaluate the diagnostic and therapeutic value and safety of transcatheter arterial angiography and embolization in patients with endoscopic refractory gastrointestinal bleeding.Methods Thirty-one cases of endoscopic refractory gastrointestinal bleeding were performed DSA and treated with transcatheter arterial angiography and embolization.The safty and efficacy was evaluated.Results Angiographic positive rate of bleeding was 80.65％ (25/31);28 cases was treated with embolization.The success rate of first embolization was 75.00％ (21/28),and the total success rate was 82.14 ％ (23/28) by the second embolization.Seven patients received surgical resection after interventional therapy,including 2 cases of jejunal stromal tumors and 5 cases of gastric malignant tumors.Four cases of gastric cancer patients underwent rebleeding within 30 days after interventional therapy,of which 2 died of heart or lung function failure due to basic diseases.Except for 1 patient of anastomotic bleeding after gastrointestinal anastomosis occurred anastomotic fistula after embolization,who recovery with the support treatment,no other cases occurred serious gastrointestinal ischemic necrosis.Conclusion Interventional diagnosis and treatment for gastrointestinal bleeding hemostasis is effective and safety,and also can achieve good results especially for malignant gastric tumor hemorrhage,which can be used for endoscopic refractory gastrointestinal bleeding patients.

Objective To design and construct a controlled adenovirus vector in degradating by itself after induction for solving the problem of stimulating host immune and producing replication adenovirus and providing a secure exogenous gene vectors for clinical practice. Methods Based on the traditional adenovirus vector AdEasyTM system, we inserted the Cre gene which belongs to Cre-LoxP system into the downstream of Tet-On inducible expression system. Two LoxP sites were inserted into two sides of the shuttle plasmid′s right arm genome. Then, the full-length human insulin gene was inserted HindIII enzyme site. After the recombinant adenovirus infected the rat bone marrow-derived mesenchymal stem cells , fluorescent protein expression and insulin secretion were detected before or after induction by Dox. Results A new controlled recombinant adenovirus vector carrying human insulin gene was constructed successfully, and was named AdEasyN/INS. After the transfection of this new vector into QBI-293A cells and rat bone marrow mesenchymal stem cells , green fluorescent protein could be observed. After induction by Dox, both of the ratio of fluorescent cells/total cell and the levels of insulin significantly decreased. Conclusion Construction and preliminary validation of a controlledrecombinant adenovirus vector carrying human insulin gene is constructed successfully , it could infect rat bone marrow mesenchymal stem cells, and degradate by itself after Dox induction, realize the controllability of exogenous gene carrier.

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.