OBJECTIVE To evaluate the efficacy and safety of letermovir in preventing cytomegalovirus （CMV） infection after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. METHODS A retrospective cohort study was conducted， enrolling patients who underwent allo-HSCT at the Department of Hematology， Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine， from August 30， 2022， to February 21， 2024. Patients who initiated letermovir prophylaxis within 28 days post-transplantation were assigned to the experimental group （99 cases）， while those who did not initiate letermovir within this period were assigned to the control group （18 cases）. The incidence and clinical characteristics of CMV infection （including the number of wangranran@xinhuamed.com.cn CMV infection cases， the number of cases progressing to CMV disease， recurrent CMV disease， onset time of CMV infection， and treatment duration）， immune function recovery within 120 days post-transplantation， and the occurrence of transplantation-related complications （including CD4+ and CD8+ T-cell recovery， Epstein-Barr virus infection， acute graft-versus-host disease， human herpesvirus 6 infection， and posttransplant lymphoproliferative disorders） and adverse events were recorded. Univariate and multivariate Cox regression analyses were performed to identify factors influencing CMV infection. RESULTS A total of 117 patients were included， among whom 15 developed CMV infection， 5 progressed to CMV disease， and 2 experienced recurrent CMV disease. The CMV infection rate in the experimental group was significantly lower than that in the control group （P＜0.001）， and the onset time of CMV infection was significantly delayed （P＝0.014）. The proportion of patients with CD4+ T-cell counts ≥200 cells/μL in the experimental group was significantly lower than that in the control group （P＝0.022）. During the follow-up period， elevated creatinine levels were observed in 1 patient， and nausea and vomiting were observed in 2 patients. Multivariate Cox regression analysis revealed that the use of high-dose corticosteroids was a risk factor for CMV infection （HR＝6.230， 95%CI of 1.255-30.926， P＝0.025）， while initiating letermovir within 28 days post-transplantation was a protective factor （HR＝0.125， 95%CI of 0.045-0.348， P＜0.001）. CONCLUSIONS Early initiation of letermovir after allo-HSCT significantly reduces the CMV infection rate and delays the onset of infection， with favorable short-term safety.

Objective:To compare the performance and surgical outcomes of domestic single-use digital flexible ureteroscopes with reusable digital flexible ureteroscopes in treatment of upper urinary stones.Methods:A prospective, single-blind, multicenter and randomized controlled study was performed from September 2018 to June 2019. Eligible patients were randomly assigned, in a ratio of 1∶1, to either experimental group or control group. The inclusion criteria for the study were: aged 18-75 years, solitary upper urinary stone with stone size between 0.8 and 2.0 cm and CT value less than 1 400 HU, negative preoperative urine culture and normal renal function. Exclusion criteria included: patients with acute urinary tract infection, intransitable urethral strictures, impassable ureteropelvic junction obstructions, systemic hemorrhagic disease, coagulation function abnormalities or bleeding tendency, severe hypertension or cardiopulmonary insufficiency, severe hip malformation and difficulty in meeting the demand of operation position and pregnant and lactation women. The device used in the experimental group was a domestic single-use digital flexible ureteroscope, and the device used in the control group was an imported Olympus digital flexible ureteroscope. The qualified rate of clinical comprehensive evaluation (including image quality and operational performance), the rate of device failure, the stone-free rate and the occurrence rate of adverse events (including increase in urine red blood cell and white blood cell counts, postoperative hematuria, nausea, vomiting, dizziness, and fever) in the two groups were recorded.Results:A total of 186 eligible study cases were collected from the People's Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University, and the First Affiliated Hospital of Guangzhou Medical University. 90 cases in the final experimental group and 88 cases in the control group completed the trial and were included in the evaluation. There were no statistically significant differences among age [(48.40±11.36) vs. (47.40±12.53)years old, P=0.594], male to female ratio (62/28 vs. 56/32, P =0.874), BMI [(24.8±2.1) kg/m 2 vs. (25.1±2.0)kg/m 2,P =0.331], hydronephrosis (no/slight vs. mild/severe) (62/28 vs. 65/23, P =0.874), stone location and stone size [(12.8±4.7) mm vs. (11.9±5.2) mm, P =0.227]. There were no significant differences in terms of qualified rate of clinical comprehensive evaluation [98.9% (89/90) vs. 100.0% (88/88), P =0.991], lithotripsy success rate [84.4% (76/90) vs. 84.1% (74/88), P =0.888], device failure/defect rate (both 0%), and the incidence of adverse events [50.0% (45/90) vs. 52.0% (51/88), P =0.894]. The highest incidence of adverse events in two groups was the increase of red blood cells and white blood cells of routine urine after operation. There was no serious adverse event in the experimental group and 1 serious adverse event in the control group. Conclusions:There was no significant difference in image quality, device failure/defect rate, lithotripsy success rate, and adverse event rate between single-use digital flexible ureteroscopes and reusable digital flexible ureteroscopes for lithotripsy of upper ureteral and pelvic stones. Domestic single-use digital flexible ureteroscopes have good safety and effectiveness in the treatment and microscopy of upper urinary tract stones.

Objective:To explore the clinical characteristic and risk factors of subcutaneous tophus among hospitalized gout patients.Methods:The clinical data of 646 inpatients with gout from April 2014 to December 2019 in Tianjin Medical University Chu Hsien-I Memorial Hospital were retrospectively analyzed. The patients were divided into tophus group (172 cases) and non-tophus group (474 cases) according to the presence of subcutaneous tophus. The body height, body mass, waist circumference, hip circumference and blood pressure were measured. The total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), urea nitrogen, creatinine, uric acid and C-reactive protein (CRP) were detected; urine was collected for 24 h to detect uric acid. The body mass index (BMI), estimated glomerular filtration rate (eGFR) and uric acid excretion fraction (FUA) were counted. Binary Logistic regression analysis was used to analyze the independent risk factors of subcutaneous tophus among hospitalized gout patients.Results:The proportion of male, course of disease, number of joint involved in attack, rate of smoking history, rate of drinking history, smoking amount, alcohol consumption volume, length of time spent drinking, length of time spent smoking, LDL-C, urea nitrogen, serum creatinine and serum uric acid in tophus group were significantly higher than those in non-tophus group: 98.84% (170/172) vs. 94.09% (446/474), 10 (5, 16) years vs. 5 (2, 9) years, 6 (4, 8) joints vs. 3 (2, 5) joints, 66.86% (115/172) vs. 58.44% (277/474), 65.70% (113/172) vs. 57.38% (272/474), 11 (0, 20) cigarettes /d vs. 10 (0, 20) cigarettes/d, 100 (0, 250) ml/d vs. 50 (0, 162) ml/d, 10 (0, 26) years vs. 0 (0, 20) years, 20 (0, 30) years vs. 10 (0, 20) years, (3.44 ± 0.98) mmol/L vs. (3.25 ± 0.97) mmol/L, 5.81 (4.61, 7.46) mmol/L vs. 5.38 (4.39, 6.66) mmol/L, 89.4 (74.3, 107.5) μmol/L vs. 85.1 (72.5, 98.9) μmol/L and 514.4 (452.9, 595.2) μmol/L vs. 499.0 (404.8, 572.4), the onset age, red blood cell, hemoglobin and eGFR were significantly lower than those in non-tophus group: (37.78 ± 10.56) years old vs. (40.17 ± 13.06) years old, (4.72 ± 0.74) × 10 9/L vs. (4.88 ± 0.56) × 10 9/L, (141.15 ± 17.19) g/L vs. (146.00 ± 13.06) g/L and 87.7 (65.9, 108.4) ml/min vs. 93.3 (75.9, 113.1) ml/min, and there were statistical differences ( P<0.05 or <0.01); there were no statistical differences in family history of diabetes, family history of hypertension, family history of gout, BMI, waist-hip ratio, blood pressure, FUA, white blood cell, TC, TG, HDL-C and CRP between 2 groups ( P>0.05). The patients were grouped according to the course of disease, the incidences of tophus in patients with course of disease ≤5.0 years, 5.1 to 10.0 years and >10.0 years were 15.34% (50/326), 27.67% (44/159) and 48.45% (78/161), and there was statistical difference ( χ2 = 60.59, P<0.01); the patients were grouped according to the quartiles of serum uric acid, the incidences of tophus in patients with serum uric acid <424.05 μmol/L, 424.05 to 505.24 μmol/L, 505.25 to 576.17 μmol/L and ≥576.18 μmol/L were 14.91% (24/161), 32.72% (53/162), 29.01% (47/162) and 29.81% (48/161), and there was statistical difference ( χ2 = 15.70, P<0.01). Binary Logistic regression analysis result showed that the course of gout, smoking amount, number of joint involved in attack, serum uric acid and LDL-C were the independent risk factors of subcutaneous tophus among hospitalized gout patients ( OR = 1.069, 1.020, 1.317, 1.002 and 1.262; 95% CI 1.032 to 1.097, 1.006 to 1.032, 1.223 to 1.417, 1.000 to 1.003 and 1.033 to 1.541; P<0.01 or <0.05). Conclusions:The duration of disease, number of involved joint, serum uric acid level, unhealthy lifestyles and lipid metabolism disorders are the independent risk factors of subcutaneous tophus among hospitalized gout patients.

OBJECTIVE: To establish a mouse model bearing orthotopic temozolomide (TMZ)-resistant glioma that mimics the development of drug resistance in gliomas METHODS: Seventy-eight adult C57BL/6 mice were randomly divided into 6 groups ( RESULTS: The mouse models bearing TMZresistant glioma was successfully established. The cells from the high-dose induced group showed a significantly higher colony-forming rate than those from the high-dose control group ( CONCLUSIONS Progressive increase of TMZ doses in mice bearing orthotopic gliomas can effectively induce TMZ resistance of the gliomas.
Animals ; Antineoplastic Agents, Alkylating/pharmacology* ; Brain Neoplasms/drug therapy* ; Cell Line, Tumor ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Glioma/drug therapy* ; Mice ; Mice, Inbred C57BL ; Temozolomide/therapeutic use*

【Objective】 To explore the effect of Zhikepipa Mixture on the treatment of COVID-19 through network pharmacology analysis and molecular docking technology. 【Methods】 First, we performed the network pharmacology method to screen active compounds and targets so as to explore the mixture’s potential mechanisms in the treatment of COVID-19. In line with ADME screening index, like oral bioavailability (OB) ≥30% or drug likeness index (DL) ≥0.18, the active compounds against COVID-19 related targets were selected to construct the 'herb-compound-target’ network. Mechanism prediction of Zhikepipa mixture in the treatment of COVID-19 was analyzed by the interaction of the target sites, the bioinformatic annotation, and the metabolic pathway. Then, we used a molecular docking model to evaluate the binding ability between active compounds and 2019-nCoV (SARS-CoV-2) 3-chymotrypsin-like cysteine protease (3CL^pro) receptor-binding domain (PBD ID 6LU7), which was involved in mediating viral replication and transcription functions. 【Results】 The'herb-compound-target’ network showed 34 key compounds and 30 disease targets after overlapping with disease targets. The network topology analysis showed that those selected compounds with higher degree would produce marked anti-inflammatory effects by regulating 30 targets like PTGS1, IL1B, IL6, IL10, CXCL8 and JUN. AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway were involved in regulating hepatitis B and diabetic complications. In addition, Folium eriobotryae and Radix stemonae played important roles in the network. The molecular docking results showed that nine compounds were identified with higher docking score rank against 2019-nCoV 3CL^pro protease, and most of them were attributed to flavonoids. 【Conclusion】 Zhikepipa Mixture could exhibit both anti-inflammatory and anti-virus actions through multi-component, multi-target, and multi-pathway.

Objective:To study the effect of Pterostilbene on endoplasmic reticulum stress and apoptosis in human renal tubular epithelial cells (HK-2 cells) induced by oxalate.Methods:From January 2019 to January 2020, HK-2 cells were divided into a control group (cultured with normal medium), an oxalate group (cultured with a medium containing 4 mmol/L of oxalate), and an intervention group of Pterostilbene (containing 4 mmol/L of oxalate + Pterostilbene 5, 10, and 20 μmol/L mixed medium were cultured at the same time), and the following tests were performed after 12 hours of treatment. Pterostilbene (5, 10, and 20 μmol/L) intervention group for cell viability test, lactate dehydrogenase cytotoxicity test, reduced glutathione, superoxide dismutase, malondialdehyde, hydrogen peroxide enzyme, total antioxidant capacity detection experiments to explore the degree of oxidative damage, and Western blotting experiments to explore the protein expression of ATF6, GRP78, DDIT3, caspase12, Clevead caspase 3/9; Pterostilbene (10 μmol/L) intervention group to detect mitochondrial membrane potential, caspase 3 enzyme activity, apoptosis rate, reactive oxygen detection to detect the apoptosis, reactive oxygen level, and qRT-PCR to detect ATF6, GRP78, DDIT3 of cells mRNA expression.Results:CCK-8 and lactate dehydrogenase toxicity test results showed that the cell activity of the oxalate group was significantly lower than that of the control group [(45.6±3.1)% vs. 100.0%, P<0.001]; the lactate dehydrogenase [(330.2±11.1)U/L vs. (2.6±6.7) U/L, P<0.001] of the oxalate group was higher than that of the control group increased obviously; the cell viability[ (57.2±1.7)%, (67.2±3.4)%, (78.9±1.8)%] of Pterostilbene intervention group (5, 10, 20 μmol/L) significantly increased compared with oxalate group ( P<0.05); lactate dehydrogenase [(288.1±4.3)U/L, (260.9±5.5)U, (202.7±10.2)U/L] in Pterostilbene intervention group (5, 10, 20 μmol/L ) was significantly lower than oxalate group ( P<0.05). The results of the five biochemical indexes of malondialdehyde, reduced glutathione, total superoxide dismutase, catalase, and total antioxidant capacity showed that the cell damage state was consistent with the experimental results of CCK-8 and lactate dehydrogenase. The active oxygen test results showed that the oxalate group had a significantly higher active oxygen level (76.3±4.9 vs. 6.2±1.7, P<0.01); the active oxygen level (39.5±5.4) of the Pterostilbene intervention group(10 μmol/L) was significantly lower than oxalate group ( P<0.01). The flow cytometry and caspase3 enzyme activity showed an increase in apoptosis rate and caspase3 activity in line with the trend of reactive oxygen levels. Mitochondrial membrane potential results showed that the oxalate group had a significantly lower mitochondrial membrane potential (0.76±0.15 vs. 7.84±0.26, P<0.01), and the mitochondrial membrane potential (2.26±0.27) of the Pterostilbene intervention group (10 μmol/L) was significantly higher than oxalate group( P<0.01). Western blot analysis showed that the relative expression of ATF6, DDIT3, GRP78, caspase12 and Cleaved caspase3/9 protein in the oxalate group was significantly higher than that in the control group. The relative expression of ATF6, DDIT3, GRP78, caspase12, Cleaved caspase3/9 protein in the Pterostilbene intervention group was significantly lower than that in the oxalate group ( P<0.05). qRT-PCR results showed that the mRNA expression trends of ATF6, DDIT3 and GRP78 in the three groups were consistent with the results of Western blotting. Conclusion:Pterostilbene can effectively inhibit the endoplasmic reticulum stress and apoptosis of HK-2 cells induced by oxalate.

Four hundred and four male patients with primary gout were enrolled. According to the degree of nonalcoholic fatty liver diseases (NAFLD), the patients were divided into simple gout ( n=121), gout combined with mild NAFLD ( n=149) and gout combined with moderate-severe NAFLD ( n=134). The height, weight, waist, hip, blood pressure and blood biochemistry parameters of patients were measured. The degree of NAFLD was negatively correlated with the age of patients in three groups. The BMI, ratio of waist/hip, count of red cells, hemoglobin, hematocrit, red blood cell distribution width ( SD and CV), triglyceride, alanine aminotransferase and HOMA-IR were increased with the increasing of NAFLD severity (all P<0.05). Red blood cell count, hemoglobin, alanine aminotransferase, serum uric acid increased with the increasing of NAFLD severity (all P<0.05). Platelet, serum urea nitrogen and serum creatinine were decreased with the increase of NAFLD severity. Logistic regression showed that BMI, hemoglobin and HOMA-IR were independent risk factors for NAFLD. The prevalence and the severity of NAFLD was increased with increasing quadrates of hemoglobin. Taking group Q1 as a control, OR of NAFLD in group Q2 was 1.166(95 %CI:0.638-2.133), OR in group Q3 was 2.011(95 %CI:1.122-3.605)and OR in group Q4 was 3.120(95 %CI:1.613-6.034). The result indicates that hemoglobin levels are associated with the development and the severity of NAFLD in male patients with primary gout.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Interventional bronchoscopy is widely used in histopathological diagnosis of airway disorders.Hemorrhage is the most frequently encountered and difficult-to-manage complication during bronchoscopy,and massive hemorrhage could be life-threatening.There were differences in the incidence of hemorrhage caused by different interventional procedures.At present,the prevention of bleeding induced by intervention is relatively lacking,and the choice of treatment may be not the same in different endoscopy centers.We review the prevention and treatment of hemorrhage complicated by interventional bronchoscopy in this article,which may help to improve the understanding and management ability of hemorrhage during bronchoscopy.

Objective To study the MRI findings of superficial siderosis of the central nervous system(SSCNS)and to improve the understanding of SSCNS imaging features.Methods MRI images of 21 cases were retrospectively reviewed.MRI plain scan (T1WI,T2WI)and diffusion weighted imaging(DWI)were performed in all patients;T2* weighted angiography(SWAN)scan was performed in 8 patients.Results On T1WI of 21 cases,only 4 cases showed infratentorial superficial siderosis which appeared as linear hypointense signal in sulci cerebelli and around brainstem.On T2WI of 21 cases,18 cases presented with linear hypointense signal on cerebral surface.On DWI of 21 cases,20 cases showed linear hypointense signal on cerebral surface,and the other one case showing negative signal on DWI presented hypointense signal on SWAN.On SWAN of 8 cases,more lesions were found in more regions.Conclusion SSCNS has characteristic findings on MRI.SWAN is sensitive to superficial siderosis.MRI is a reliable method for the assessment of SSCNS.