Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective To investigate the effect of different radiotherapy doses on the prognosis of patients with stage cT1-4N0M0 esophageal squamous cell carcinoma(ESCC)who received radical radio(chemo)therapy categorized into subgroups with different tumor local factors.Methods A retrospective analysis was conducted on 256 patients with clinically nonmetastatic esophageal squamous cell carcinoma.The optimal cutoff for tumor local factors was determined.The relationship between latest treatment efficacy and tumor local factors was analyzed,and independent indicators affecting patient overall survival(OS)were examined using multivariate analysis.The subgroup analysis was performed to determine the correlation between selected factors and radiation therapy doses.Results The shorter the X-ray length of esophageal tumor lesion and the smaller the lesion canal wall thickness and gross tumor volume(GTV),the better the latest treatment efficacy of the patients(χ2=9.066,10.310,15.661,respectively,P=0.011,0.006,P＜0.001).Multivariate analysis results showed that GTV(P＜0.001),radiation dose(P=0.038),and latest treatment efficacy(P＜0.001)were independent predictors of the patients'OS,and the latter two were also independent predictors of the patients'progression-free survival(PFS)(P=0.033,＜0.001).Subgroup analysis further showed that high doses of radiotherapy(over 60 Gy)resulted in good OS(χ2=5.040,4.588,5.400,P=0.025,0.032,0.020)and PFS(χ2=6.089,4.353,6.459,P=0.014,0.037,0.011)in the subgroup with maximum wall thickness below 3.7 cm,with esophageal lesions with GTV below 37.34 cm3,or not receiving simultaneous chemotherapy.Conclusion Local tumor factors are important prognostic factors of ESCC patients treated with radical radio(chemo)therapy.Patients with thin lesion walls and small tumor volumes may greatly benefit from high doses of radiation(over 60 Gy).

The liver is one of the essential hubs for maintaining the homeostasis of the organism.Liver aging not only heightens its susceptibility to acute injuries and chronic liver diseases, but also triggers a " chain reaction" of multi-organ aging and dysfunction.With the continuous deepening of the aging population in China, how to prevent, monitor, and evaluate the occurrence, development, and prognosis of liver aging has become an important issue in the field of geriatrics research.Thus, the identification and widespread application of liver aging biomarkers is the key to solving this problem.Therefore, this article reviews the research progress of liver aging-related biomarkers, aiming to provide a basis for the precise prevention and targeted intervention of liver diseases related to aging.

Objective To investigate the effect of different radiotherapy doses on the prognosis of patients with stage cT1-4N0M0 esophageal squamous cell carcinoma(ESCC)who received radical radio(chemo)therapy categorized into subgroups with different tumor local factors.Methods A retrospective analysis was conducted on 256 patients with clinically nonmetastatic esophageal squamous cell carcinoma.The optimal cutoff for tumor local factors was determined.The relationship between latest treatment efficacy and tumor local factors was analyzed,and independent indicators affecting patient overall survival(OS)were examined using multivariate analysis.The subgroup analysis was performed to determine the correlation between selected factors and radiation therapy doses.Results The shorter the X-ray length of esophageal tumor lesion and the smaller the lesion canal wall thickness and gross tumor volume(GTV),the better the latest treatment efficacy of the patients(χ2=9.066,10.310,15.661,respectively,P=0.011,0.006,P＜0.001).Multivariate analysis results showed that GTV(P＜0.001),radiation dose(P=0.038),and latest treatment efficacy(P＜0.001)were independent predictors of the patients'OS,and the latter two were also independent predictors of the patients'progression-free survival(PFS)(P=0.033,＜0.001).Subgroup analysis further showed that high doses of radiotherapy(over 60 Gy)resulted in good OS(χ2=5.040,4.588,5.400,P=0.025,0.032,0.020)and PFS(χ2=6.089,4.353,6.459,P=0.014,0.037,0.011)in the subgroup with maximum wall thickness below 3.7 cm,with esophageal lesions with GTV below 37.34 cm3,or not receiving simultaneous chemotherapy.Conclusion Local tumor factors are important prognostic factors of ESCC patients treated with radical radio(chemo)therapy.Patients with thin lesion walls and small tumor volumes may greatly benefit from high doses of radiation(over 60 Gy).

The liver is one of the essential hubs for maintaining the homeostasis of the organism.Liver aging not only heightens its susceptibility to acute injuries and chronic liver diseases, but also triggers a " chain reaction" of multi-organ aging and dysfunction.With the continuous deepening of the aging population in China, how to prevent, monitor, and evaluate the occurrence, development, and prognosis of liver aging has become an important issue in the field of geriatrics research.Thus, the identification and widespread application of liver aging biomarkers is the key to solving this problem.Therefore, this article reviews the research progress of liver aging-related biomarkers, aiming to provide a basis for the precise prevention and targeted intervention of liver diseases related to aging.

Objective:To explore the association between thyroid function and chronic kidney disease (CKD) in adults.Methods:A cross-sectional study was conducted in adults who received health checkup in the First Affiliated Hospital of Shandong First Medical University from January to December in 2021. Clinical data were collected, including age, gender, height, weight, blood pressure, etc. And blood glucose, blood lipid, blood creatinine, blood uric acid, routine urine function, thyroid function (free triiodine, free thyroxine, thyroid stimulating hormone) were measured. Multivariate logistic regression model was used to investigate the correlation between thyroid function indicators and the onset of CKD; and receiver operator characteristic (ROC) curve was used to explore the ability of thyroid function indicators in evaluating CKD.Results:In the study, 46 342 adults with an average age of (47.6±14.3) years were enrolled, of which 56.2% were males. The prevalence of DeGFR (eGFR<60 ml·min -1·(1.73 m 2) -1), proteinuria and CKD was 1.15%, 0.53% and 1.58%, respectively. The TSH subgroup analysis showed that the prevalence of DeGFR, albuminuria and CKD in the hypothyroidism group was significantly increased to 1.07%, 2.36% and 3.20%, respectively (all P<0.05). After adjusting for confounding factors, multivariate logistic regression analysis showed that FT3 was negatively associated with CKD ( OR=0.63, 95% CI: 0.54-0.74), however FT4 ( OR=1.05, 95% CI: 1.03-1.07) and TSH ( OR=1.03, 95% CI: 1.01-1.04) were positively correlated with CKD. Similar results were obtained in the subgroup without hypertension and diabetes ( P<0.05). The ROC analysis indicated that FT3 had a better capability for evaluating CKD than FT4 and TSH, with an area under the curve of 0.63, a cut-off value of 4.18 pmol/L, and a sensitivity and specificity of 57.5% and 62.6%, respectively. Conclusions:Thyroid function status is closely associated with the onset of CKD in the adult population receiving health check-up. FT3 is a risk factor for the onset of CKD.

Objective To investigate the effect of percutaneous balloon mitral valvuloplasty under echocardiographic guidance for patients with moderate to severe mitral stenosis during pregnancy. Methods A retrospective observational study was conducted to include pregnant women who were diagnosed with moderate to severe mitral stenosis and underwent percutaneous balloon mitral valvuloplasty under echocardiographic guidance in Fuwai Hospital from August 2018 to June 2022, and their baseline characteristics, surgical outcomes, echocardiographic results, and follow-up results were analyzed. Results A total of 3 pregnant women aged 30-35 years, with gestational age of 19-26 weeks, and New York Heart Association (NYHA) function class Ⅲ were included. All the procedures were successfully performed. The mitral valve orifice area increased from 0.9 cm2 preoperatively to 2.1 cm2 postoperatively. The mean transvalvular pressure gradient decreased from 15.0 mm Hg preoperatively to 6.7 mm Hg postoperatively. No perioperative adverse events occurred. The follow-up time ranged from 3 to 48 months. All patients delivered uneventfully and returned to normal life, with maternal-fetal safety. Conclusion Percutaneous balloon mitral valvuloplasty under echocardiographic guidance is a feasible and effective procedure for the treatment of patients with moderate to severe mitral stenosis in pregnancy, with satisfactory maternal-fetal outcomes.

Objective:To investigate the ocular characteristics and treatment prognosis of ocular immune reconstruction inflammatory syndrome (IRIS) in patients with cytomegalovirus retinitis (CMVR) complicated with acquired immunodeficiency syndrome (AIDS).Methods:A serial case-observational study was conducted.Seventeen eyes from 15 male 21-to 43-year-old AIDS patients combined with CMVR, who were diagnosed with IRIS at Beijing You'an Hospital, Capital Medical University from February 2016 to December 2018 were included.The best corrected visual acuity (BCVA) of patients was recorded, and the intraocular pressure and anterior segment was measured with a non-contact tonometer and a slit-lamp microscope, respectively.The ocular fundus was observed by fundus photography and optical coherence tomography (OCT). Reverse transcription polymerase chain reaction was used to measure the cytomegalovirus deoxyribonucleic acid (CMV-DNA) content in the aqueous humor during the occurrence of IRIS.The flow cytometry was employed to determine the peripheral blood CD4 + T lymphocyte count before highly active antiretroviral therapy (HAART) and during the occurrence of IRIS.All patients were followed for 3 to 25 months, with an average of 15 months.The HAART time of patients was 17 to 104 days, with an average of (66.1±27.4) days.Patients with anterior segment inflammatory reactions were given the anti-inflammatory and mydriatic treatment.Patients with severe vitreous opacity were intravitreally injected with 4 mg of triamcinolone.Patients with macular edema were given 0.5 mg intravitreal injection of conbercept.The study adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Beijing You'an Hospital, Capital Medical University (No.[2017]11). Written informed consent was obtained from each patient prior to any examination. Results:Anterior segment inflammation (Tyndall effect, KP, post-iris adhesion) was found in 9 eyes, vitreous opacities to varying degrees in 11 eyes, and macular edema in 2 eyes.The CMV-DNA content was negative (<500 copies/ml) in 15 eyes.The CD4 + T lymphocyte count in peripheral blood during IRIS was 67 (51, 99) cells/μl, which was significantly higher than 17(6, 20) cells/μl before HAART treatment ( Z=-4.48, P<0.01). Two of the 15 AIDS patients had tuberculosis.The BCVA of the patients was improved from 0.30 (0.10, 0.55) before treatment to 0.50 (0.35, 0.60) after treatment, and the difference was statistically significant ( Z=-2.34, P=0.019). Conclusions:The anterior and posterior segment may be involved in IRIS patients with AIDS and CMVR, and the corresponding ocular treatment is effective.

Objective:To investigate the clinical manifestations of acquired immunodeficiency syndrome(AIDS) patients with initial-stage cytomegalovirus (CMV) retinitis (CMVR).Methods:Retrospective case series study. From July 2017 to November 2019, 21 patients with 22 eyes of AIDS combined with CMVR in the initial stage of AIDS and CMVR diagnosed in the eye examination in the study. Among them, there were 19 males with 19 eyes and 2 females with 3 eyes; the average age was 34.3±9.6 years. The average CD4 + T lymphocyte count of patients was 26.1±23.2/μl. Routine fundus screening revealed 17 cases, and the contralateral eye disease was found in 4 cases. There were 13 cases of CMVR in both eyes (61.9%, 13/21). Among them, both eyes were in the initial stage of CMVR, and the contralateral eyes were in the early stage of CMVR in 12 cases. The contralateral eye included 2 cases of human immunodeficiency virus-related retinal microangiopathy, 1 case of optic disc edema, and 5 cases of no obvious abnormality on fundus examination. All patients underwent slit lamp microscopy and ultra-wide-angle fundus photography examination. At the same time, 18 eyes underwent optical coherence tomography (OCT). Blood CMV-DNA detection was performed in 17 cases within 1 week before the first diagnosis; aqueous CMV-DNA detection was performed in 7 eyes within 1 week after the first diagnosis. Within 1 week after the fundus examination, 8 eyes of 8 cases and 8 eyes of 7 cases were received and not received systemic anti-CMV treatment; the treatment status was unknown in 6 cases and 6 eyes. After treatment, 18 eyes of 17 cases were followed up. The follow-up time was 0.5-28 months. Results:There were no obvious abnormalities in the anterior segment examination of all the affected eyes; the vitreous body was transparent. The fundus lesions were less than 1 optic disc diameter (DD), and they were white granular, clustered, with blurred edges. Among them, there were granular satellite lesions around the lesion in 18 eyes (81.8%, 18/22). The lesions were located in 19 eyes (86.4%, 19/22) in zone 2, 1 eye in zone 1 and 2 (4.5%, 1/22), and 2 eyes in zone 3 (9.1%, 2/22). In 18 eyes that underwent OCT examination, 12 eyes failed to obtain image data because the lesion was not in the conventional scanning range; the other 6 eyes showed the inner or full retina thickened or atrophy depression, structural destruction, accompanied by local vitreous punctate strong reflection. Among the 17 patients who underwent blood CMV-DNA testing, 1 (5.9%, 1/17) and 16 (94.1%, 16/17) cases were CMV-DNA negative and positive, respectively. The 7 eyes that underwent the CMV-DNA test of aqueous humor were all negative. Among the 18 eyes who were followed up, the lesions did not expand, and gradually subsided and absorbed in 4 eyes (22.2%, 4/18); the varying degrees of lesion enlargement in 14 eyes (77.8%, 14/18).Conclusion:The patients with AIDS and CMVR at the initial stage have no obvious ocular symptoms; the fundus shows white granular lesions less than 1 DD with blurred edges.

Objective:To explore the efficacies of bevacizumab monotherapy and combination therapy of bevacizumab with irinotecan, semustine and cisplatin in patients with recurrent high-grade glioma.Methods:Seventy patients with recurrent high-grade glioma admitted to our hospital from January 2011 to November 2019 were chosen in our study; 38 patients received bevacizumab monotherapy, 13 patients accepted bevacizumab and semustine combination therapy, 11 patients received bevacizumab and cisplatin combination therapy, and 8 patients accepted bevacizumab and irinotecan combination therapy. Survival statuses (progression-free survival [PFS] and overall survival [OS]) of these patients were retrospectively analyzed.Results:The median OS and median PFS of the enrolled patients were 12.83 months and 6.23 months, respectively. The median OS and median PFS of patients accepted bevacizumab monotherapy were 10.92 months and 5.03 months, respectively. The median OS and median PFS of patients accepted bevacizumab and semustine combination therapy were 16.30 months and 6.77 months, respectively. The median OS in patients accepted bevacizumab and irinotecan combination therapy and patients accepted bevacizumab and cisplatin combination therapy was 11.90 months and 14.40 months, respectively.Conclusion:Bevacizumab by different therapy methods enjoys good efficacy; bevacizumab monotherapy or combination therapy can be recommended for recurrent high-grade glioma.