COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

[Abstract] Objective: Elevated levels of soluble PD-L1 (sPD-L1) are associated with worse prognosis of renal cell carcinoma and multiple myeloma. However, the regulatory roles and functions of sPD-L1 in advanced melanoma are not fully understood. This study was designed to evaluate the association between circulating sPD-L1 concentrations and prognosis of patients with advanced acral or mucosal melanoma. Methods: A total of 102 untreated patients with advanced acral and mucosal melanoma admitted to Peking University Cancer Hospital between January 2012 and December 2015 were enrolled in this study. In the meanwhile, peripheral blood samples were obtained from 40 healthy donors. Circulating sPD-L1 concentrations were determined using an enzyme-linked immunosorbent assay. Results: The advanced melanoma cohort included 58 acral melanoma patients and 44 mucosal melanoma patients. The pre-treatment concentration of sPD-L1 (2.91±2.23 ng/ml) in plasma of patients group was elevated as compared with that in healthy donors (0.59 ng/ml). The concentration of sPD-L1 in serum was significantly upregulated in 39/102 (38.2%) patients and significantly associated with increased LDH level (P=0.021) and number of Tregs (P=0.017). The overall survival rates of patients with high or low concentrations of sPD-L1 were statistically different (8.5 months [high level] vs 11.6 months [low level], P=0.022). Conclusion: sPD-L1 concentration is elevated in patients with advanced acral or mucosal melanoma, which may play an important role in predicting prognosis.

[Abstract] Objective: To explore the expression patterns of melanoma lineage antigens and nuclear antigen Ki-67 and their correlations with survival in melanoma patients. Methods: A retrospective analysis was conducted to analyze the pathological data of melanoma patients treated at the Department of Melanoma, Peking University Cancer Hospital from February 2008 to August 2020, mainly including the expression patterns of melanoma lineage antigens (S-100, HMB-45, Melan-A) and Ki-67, demographics, clinical features and survival. The correlation between expression patterns of melanoma lineage antigens, Ki-67 and melanoma-specific survival (MSS) was analyzed. Results: In total, 603 patients were included in this study. The median follow-up time was 47.4 months. The positive rates of S-100, HMB, and Melan-A were 92.8%, 92.1% and 90.0%, respectively. The percentages of patients with melanoma lineage antigen scores (S-100, HMB-45 and Melan-A was scored each, as 1 when positive and 0 when negative) of 0, 1, 2, and 3 were 0.5%, 5.0%, 15.6%, and 78.8%, respectively. The percentages of patients with Ki-67 scores of 0, 1, 2, and 3 were 43.0%, 36.3%, 16.3%, and 4.5%, respectively. Ki-67 was highly expressed in mucosal and progressive melanomas. In a multivariate analysis, Ki-67 expression was an independent prognostic factor for poorer MSS (HR=1.506, 95%CI: 1.248-1.818, P<0.001) as the incidence of MSS event increased by 50% per 25% increase in Ki-67 expression, whereas there was no statistical correlation between melanoma lineage antigen expression and MSS (HR=0.991, 95%CI: 0.759-1.293, P=0.94). Conclusion: High expressions melanoma lineage antigens are ubiquitous in melanoma tissues, and Ki-67 is an independent prognostic factor for MSS.

OBJECTIVE: To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics. METHODS: Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes. RESULTS: The expression level of miR-181b in CLL patients was significantly lower than that in control group (P＜0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P＜0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging. CONCLUSION The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.
Apoptosis Regulatory Proteins ; Cell Proliferation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; Prognosis

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective:To explore the prognostic value of PD-L1 expression level in patients with metastatic renal cell carcinoma (mRCC).Methods:The clinicopathological and survival data of patients with mRCC in our hospital from Jan 2014 to Apr 2016 were retrospectively analyzed including 46 males and 15 females. The median age of these patients was 56 years(range: 29-75 years), with 41 patients ≤60 years and 20 patients >60 years. The baseline data before the systemic therapy showed 36 patients(59.0%)had 1 metastatic organ and 25 patients (41.0%) had equal or more than 2 organs to be metastasized. Among them, 17 patients(27.9%)had lung metastasis and 54 patients(88.5%)had liver metastasis. Abnormal baseline LDH occurred in 4 patients and 52 patients had normal LDH. Favorite and intermediate risk patients categorized by MSKCC risk stratification accounted for 59.6%(34 patients)and 40.4%(23 patients), respectively. Six patients(9.8%)experienced distant metastasis at initial diagnosis, with 4 of them undergoing primary site resection, and the other 55 patients undergoing radical nephrectomy. PD-L1 expression was detected by the immunohistochemical staining method. PD-L1 staining rate ≥1% detected on the tumor cell membrane was defined as positive expression. The correlation between PD-L1 expression and clinicopathological characteristics were compared. Kaplan-Meier method and log-rank test were used to compare the differences about DFS and OS under different factors. Cox proportional hazards regression model is used for multivariable analysis of survival data.Results:The detailed pathological types of the 61 patients with renal cell carcinoma were classified as 53 clear cell carcinomas, 3 papillary carcinomas, 1 collecting duct carcinoma, 2 translocation renal cell carcinomas and 2 being unclassified. There were 4, 20, 19 and 9 patients categorized as WHO/ISUP nuclear grade 1, 2, 3 and 4, and 26, 12, 20 and 2 patients were categorized as T 1, T 2, T 3 and T 4 stage, respectively. Five patients had regional lymph node metastasis(N+), and the other 56 patients had no regional lymph node metastasis(N-). The numbers of patients categorized as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ diseases according to TNM staging system were 20, 11, 21 and 8, respectively. The total PD-L1 positive rate was 24.6%(15/61). The corresponding PD-L1 expression rate of patients with WHO/ISUP nuclear grade 1-4 were 0(0 patient), 5.0%(1 patient), 31.6%(6 patients)and 44.4%(4 patients), respectively; With the increasing WHO/ISUP nuclear grade, the positive rate of PD-L1 gradually escalated with a linear correlation ( P=0.006). The PD-L1 expression of the normal and abnormal LDH group were 19.2%(10 patients)and 75.0%(3 patients), respectively, with significant difference( P=0.035). Univariate analysis of disease-free survival time(DFS)showed that the prognostic factors include PD-L1( P=0.045), age group( P=0.014), WHO/ISUP nuclear grade( P<0.001), T stage( P=0.015), N stage( P=0.026)and TNM stage( P=0.005). However multivariate analysis only suggested WHO/ISUP nuclear grade as the independent prognostic factors for DFS( HR=1.8, 95% CI 1.1-2.9, P=0.018). Either in univariate or multivariate analysis, PD-L1 was not a prognostic factor for overall survival (OS)of mRCC patients(univariate analysis: P=0.154; multivariate analysis: P=0.902). The independent prognostic factors of OS include WHO/ISUP nuclear grade( HR=3.0, 95% CI 1.1-8.0, P=0.033)and MSKCC risk stratification( HR=5.9, 95% CI 1.2-29.7, P=0.03). Conclusions:This study showed that the higher the WHO/ISUP nuclear grade of patients with mRCC, the higher the positive rate of PD-L1. PD-L1 expression was not the independent prognostic factor for DFS or OS of mRCC.

Objective: To investigate the clinical characteristics, treatment methods, and prognosis of metastatic papillary renal cell car-cinoma (pRCC). Methods: The clinical data of metastatic pRCC patients treated at the Department of Kidney Cancer and Melanoma, Pe-king University Cancer Hospital, were retrospectively analyzed. The prognosis of these patients was stratified through international metastatic renal cell carcinoma database consortium (IMDC) model. Survival and influencing factors were further analyzed using the Kaplan-Meier method and Cox proportional risk regression model. Results: From January 2003 to March 2018, 93 patients (median age, 50.0 years) were diagnosed with metastatic pRCC: 89 (95.7%) typeⅡcases and 4 (4.3%) typeⅠcases. The median follow-up dura-tion was 23.1 months, with 90, 44, and 14 patients having received first-line, second-line, and third-line treatments, respectively. The median overall survival (OS) of the 93 patients was (31.5±5.9) months [95% confidence interval (CI): 19.9-43.1], while the median OS of patients with low-, intermediate-, and high-risk (classified as per the International Metastatic Renal Cell Carcinoma Database Con-sortium [IMDC]) were (100.0±32.8), (38.3±8.2), and (16.4±1.2) months, respectively (high-risk vs. low/intermediate-risk, P<0.001; low-risk vs. intermediate-risk, P=0.015). The median progression free survival (PFS) with first-line treatment was (6.6±0.5) months. And the median PFS of the corresponding three groups stratified by IMDC score were (17.5±5.7), (7.1±2.3), and (5.2±1.5) months, respectively (high-risk vs . low-risk, P=0.002; high-risk vs . intermediate-risk, P=0.01). Conclusions: Metastatic pRCC is noted to have unique biologi-cal characteristics. The IMDC model can be used to predict the efficacy of first-line treatment using tyrosine kinase inhibitors as well as the prognosis of metastatic papillary renal cell carcinoma in such patients.

5-HT as an important neurotransmitter which takes part in the development of many diseases, including bronchial asthma,schizophrenia and bone metabolism as reported in literatures in recent years. Central 5-HT can inhibit sympathetic excitations and promote bone formation through Tph2. Lrp5 can reduce the level of peripheral 5-HT and act on Tph1 to promote bone formation. Peripheral 5-HT blocks the association between transcription factor FOXO1 and CREB and inhibits bone formation. Peripheral 5-HT can also promote IL-6 expression and induce bone reabsorption. LP533401 as a Tph1 inhibitor could effectively reduce the level of peripheral 5-HT and induce bone formation as reported. In this paper, we try to summarize the effect of 5-HT on bone metabolism and its mechanism, and further using 5-HT to regulate bone quantity effectively.

Objective The relationship between osteoblast autophagy induced by wear particles and secretion of inflammatory cytokines has not been illuminated.The purpose of this study was to investigate the effect of wear particles on the secretion of TNF -α and IL-6 by autophagy of osteoblasts in aseptic loosening. Methods The mouse MC3T3-E1 osteoblasts in logarithmic growth phase were divided into 5 groups:control group(in α-MEM medium),CoCrMo particle group(100 μg/mL CoCrMo particles was added in α-MEM medium),3-MA group(10 mmol/L autophagy inhibitor 3-MA prestimulated osteoblasts in α-MEM medium,3h later 100 μg/mL CoCrMo particles were added),the expression of autophagy marker protein LC-3 in osteoblasts was detected by Western blotting, and the levels of TNF-αand IL-6 were detected by ELISA. Results Compared with the control group,the expression level of auto-phagy marker protein LC-3 was significantly increased in CoCrMo particles group(P<0.05).Compared with CoCrMo particles group,the expression level of LC-3 in 3-MA group was significantly decreased(P<0.05).Compared with control group TNF-α[(0.95± 0.00)pg/mL]and IL-6[(4.67±0.23)pg/mL], CoCrMo particles group TNF-α[(10.35±3.63)pg/mL]and IL-6[(14.27±1.07)pg/mL]secretion level was significantly increased(P<0.05),compared with CoCrMo particles group,the effects of 10 mmol/L 3-MA group to TNF-α[(13.13±5.08)(14.71±5.46)pg/mL]and IL-6[(15.31±0.88),(16.75±3.87)pg/mL]secretion were not significant, while 10 mmol/L 3-MA group TNF-α[The secretion levels of(302.61±45.63)pg/mL]and IL-6[(216.67±27.71)pg/mL]in-creased significantly(P<0.01). Conclusion The osteoblast autophagy induced by CoCrMo particles can inhibit the secretion of in -flammatory cytokines TNF-αand IL-6 in osteoblasts.