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 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 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 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.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective:To observe the ultra-wide-angle fundus imaging characteristics of acquired immunodeficiency syndrome (AIDS) combined with cytomegalovirus retinitis (CMVR).Methods:This study was a retrospective study. From July 2017 to November 2019, 124 eyes of 86 patients diagnosed with AIDS and CMVR at the Department of Ophthalmology, Beijing You'an Hospital, Capital Medical University, were included in the study. Among them, 80 patients were males (93.0%) and 6 patients were females (7.0%) with 17-58 years old. The average age was (36.86±8.82) years old. There were 48 cases (55.8%) in one eye and 38 cases (44.2%) in both eyes. All the affected eyes underwent indirect ophthalmoscope fundus examination and Aalborg ultra-wide-angle fundus photography examination. According to the characteristics of CMVR in ultra-wide-angle fundus images, it can be divided into classic type, granular type, frost-like dendritic vasculitis and optic neuroretinitis. We observed and analyzed the type of fundus of the affected eye. According to the position of the vortex vein in the fundus image and record of the lesion as the posterior pole or peripheral part, the scope of the lesion was divided into ≤1 quadrant, >1 quadrant and ≤2 quadrants (1-2 quadrants), >2 quadrants and ≤3 quadrants (2-3 quadrants), >3 and ≤4 quadrants (3-4 quadrants). The upper and lower vascular arches or disc edges of the macula were used as boundaries to record whether the macular area or optic disc was involved. At the same time, we recorded whether the vitreous body had obvious turbidity. The comparison of CD4 + T lymphocyte count between patients of different types was performed by one-way analysis of variance, and the comparison of the positive rate of blood CMV-DNA was performed by the χ2 test; pairwise comparisons between groups were performed by the least significant difference method. Results:Among the 124 eyes, CMVR was classified into 35 eyes (28.2%) with classic type, 68 eyes with granular type (54.8%), 3 eyes with frost-like dendritic vasculitis (2.4%), and 18 eyes with optic neuroretinitis (14.5%). The lesion involved 83 eyes (66.9%) at both the posterior pole and the periphery, 22 eyes (17.7%) confined to the posterior pole, and 19 eyes (15.3%) confined to the periphery; the extent of the lesion was ≤1 quadrant in 76 eyes (61.3%), 23 eyes (18.5%) in 1-2 quadrants, 7 eyes (5.6%) in 2-3 quadrants, and 18 eyes (14.5%) in 3-4 quadrants. 54 eyes (43.5%) showed lesions involving the macular area; 52 eyes (41.9%) had lesions involving the optic disc; 33 eyes (26.6%) showed obvious vitreous inflammatory opacities. Among 86 patients, the average number of CD4 + T lymphocytes in 82 patients was 1 to 168 cells/μl, with an average of 33.60±40.02 cells/μl; the remaining 4 patients (4.7%) were unknown. There was no statistically significant difference in the positive rate of CD4 + T lymphocyte count and blood CMV-DNA load between patients in different subtypes groups ( F=0.863, 0.926; P=0.462, 0.431). Conclusion:The ultra-wide-angle fundus images of AIDS combined with CMVR have certain characteristics, which can manifest as classic, granular, frost-like dendritic vasculitis and optic neuroretinitis.

Objective To summarize the clinical characteristics of papillary thyroid microcarcinoma with diameter ≤ 5 mm. Methods The clinical data of 259 papillary thyroid microcarcinoma patients who had underwent radical thyroidectomy from January 2015 to December 2017 were retrospectively analyzed. The patients were divided into 2 groups according to the preoperative tumor diameter: ＞5 mm group (88 cases) and ≤ 5 mm group (171 cases); then according to the lymph node metastasis, the 2 groups were divided into non-lymph node metastasis sub-group and lymph node metastasis sub-group. The reason of lymph node metastasis was analyzed. Results There were no statistical difference in gender composition, age and combined Hashimoto thyroiditis rate between ＞5 mm group and≤5 mm group (P＞0.05). The rates of T3-4 stage, N1a-1b stage and multifocal tumors in＞5 mm group were significantly higher than those in ≤ 5 mm group: 34.1% (30/88) vs. 18.7% (32/171), 45.5% (40/88) vs. 22.8% (39/171) and 39.8% (35/88) vs. 22.8% (39/171), and there were statistical differences (P＜0.05 or＜0.01). In＞5 mm group, lymph node metastasis sub-group had 40 cases, non-lymph node metastasis sub-group had 48 cases; the rate of T3-4 stage in lymph node metastasis sub-group was significantly higher than that in non-lymph node metastasis sub-group: 55.0% (22/40) vs. 16.7% (8/48), and there was statistical difference (P＜0.01). In≤5 mm group, lymph node metastasis sub-group had 39 cases, and non-lymph node metastasis sub-group had 132 cases; the rate of T3-4 stage in lymph node metastasis sub-group was significantly higher than that in non-lymph node metastasis sub-group:51.3% (20/39) vs. 9.1% (12/132), and there was statistical difference (P＜0.01). In＞5 mm group and≤5 mm group, there were no statistical difference in gender composition, age, combined Hashimoto thyroiditis rate and multifocal tumors rate between 2 sub-groups (P＞0.05). Conclusions The clinical behavior of papillary thyroid microcarcinoma with diameter ≤ 5 mm has a less aggressive nature compared to that＞5 mm. Tumor capsular invasion or extra thyroidal extension has a great influence on lymph node metastasis in thyroid papillary microcarcinoma of different diameter.

Objective To compare the clinical utility of alpha-fetoprotein (AFP) and des-gammacarboxyprothrombin (DCP) in diagnosing hepatocellular carcinoma (HCC) in patients with a hepatic mass.Methods From January 2015 to May 2015,141 patients were diagnosed to have a liver tumor after imaging examinations in the Hepatobiliary Surgical General Hospital of PLA,Beijing,China.Preoperative AFP and DCP were measured using commercial assay kits.The reference standard was either pathologic or clinical diagnosis of HCC.The performance of AFP and DCP in diagnosing HCC was determined using receiver operating characteristic curve analysis.Results Of 141 patients,98 were diagnosed to have HCC and 43 without.The levels of AFP were significantly higher in patients with HCC than those without [80.0(3.9-1 375.0) μg/L vs.2.1 (1.6-3.2) μg/L,Z =6.98,P ＜ 0.01].Similar results were observed in the levels of DCP [141.5 (24.0-978.0) AU/L vs.19.0 (14.0-25.5) AU/L,Z =5.18,P ＜ 0.01].Receiver operating curves (ROC) indicated the cut-off value with the best sensitivity and specificity was 3.6 μg/L for AFP and 35 AU/L for DCP.The difference in the area under ROC between AFP and DCP was not statistically significant (0.87 vs.0.78,Z =1.72,P =0.085).The sensitivity and specificity for detection of HCC in patients with a hepatic mass were 56.1％ and 95.4％ for AFP ＞ or =20 μg/L,69.4％ and 83.7％ for DCP ＞ or =40 AU/L,respectively.The level of AFP was associated with DCP in patients with HCC (x2 =9.12,P ＜ 0.01,r =0.292) and parallel testing of AFP and DCP gave an optimal sensitivity of 79.6％ with a specificity of 81.4％ in diagnosing HCC.Conclusions DCP is a useful biomarker and it gave an equal performance as AFP in diagnosing HCC in patients with a liver mass in this study.Parallel testing of AFP and DCP effectively increased the diagnostic sensitivity.Although the biomarkers only marginally improved the diagnostic results,it could be useful in diagnosing HCC in individuals who had atypical imaging results.