Assessment of the Benefits of Targeted Interventions for Pandemic Control in China Based on Machine Learning Method and Web Service for COVID-19 Policy Simulation / 生物医学与环境科学（英文）

Taking the Chinese city of Xiamen as an example, simulation and quantitative analysis were performed on the transmissions of the Coronavirus Disease 2019 (COVID-19) and the influence of intervention combinations to assist policymakers in the preparation of targeted response measures. A machine learning model was built to estimate the effectiveness of interventions and simulate transmission in different scenarios. The comparison was conducted between simulated and real cases in Xiamen. A web interface with adjustable parameters, including choice of intervention measures, intervention weights, vaccination, and viral variants, was designed for users to run the simulation. The total case number was set as the outcome. The cumulative number was 4,614,641 without restrictions and 78 under the strictest intervention set. Simulation with the parameters closest to the real situation of the Xiamen outbreak was performed to verify the accuracy and reliability of the model. The simulation model generated a duration of 52 days before the daily cases dropped to zero and the final cumulative case number of 200, which were 25 more days and 36 fewer cases than the real situation, respectively. Targeted interventions could benefit the prevention and control of COVID-19 outbreak while safeguarding public health and mitigating impacts on people's livelihood.

Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC

Augmentation of anti-MDA5 antibody implies severe disease in COVID-19 patients

OBJECTIVETo identify the anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) in coronavirus disease 2019 (COVID-19) and its relationship with the severity and clinical outcomes of COVID-19. DESIGNRetrospective cohort study. SETTINGThree hospitals in China. PARTICIPANTS274 adult inpatients diagnosed with COVID-19 according to the Protocol for Prevention and Control of COVID-19 (Edition 7) of China and confirmed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) RNA testing, were included from three hospitals from Wuhan, Harbin and Beijing, China from 1 December 2019 to 19 April 2020. The Biobank of Myositis Registry Department of Rheumatology, Peking Union Medical College Hospital, provided the plasma of five patients with anti-MDA5 Ab-related dermatomyositis as positive control group. Demographic, clinical and laboratory data were collected from medical records. The anti-MDA5 Ab was determined by an ELISA assay and was verified by immunoblotting analysis. MAIN OUTCOME MEASURESIn hospital death of all cause. RESULTSThe positive rate of anti-MDA5 Ab in patients with COVID-19 was 48.2% (132/274) and the anti-MDA5 Ab positive patients tended to represent with severe disease (88.6% vs 66.9%, P<0.0001). The titer of anti-MDA5 Ab was significantly elevated in the non-survivals (5.95{+/-}5.16 vs 8.22{+/-}6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding to severe COVID-19 patients, we found that high titer of anti-MDA5 Ab ([≥]10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. CONCLUSIONAnti-MDA5 Ab was prevalent in the COVID-19 patients and high titer of this antibody is correlated with severe disease and unfavorable outcomes. Early screening and serially monitoring of anti-MDA5 Ab titer have the potential to predict the disease progression of COVID-19.

Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2

COVID-19 pandemic has infected millions of people with mortality exceeding 300,000. There is an urgent need to find therapeutic agents that can help clear the virus to prevent the severe disease and death. Identifying effective and safer drugs can provide with more options to treat the COVID-19 infections either alone or in combination. Here we performed a high throughput screen of approximately 1700 US FDA approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 24 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, and merfloquine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of >600, indicating wide therapeutic window compared to hydroxychloroquine which had safety index of 22 in similar experiments. Mechanistically, five of the effective compounds were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA approved compounds can provide much needed therapeutic options that we urgently need in the midst of the pandemic.Competing Interest StatementThe authors have declared no competing interest.View Full Text

Efficiency Analysis of EX16+10Y Kit on Detection of the Uygur Population in Xinjiang Province / 法医学杂志

Objective To analyse the efficiency of EX16+10Y kit on the forensic detection of the Uygur in Xinjiang province. Methods The blood samples were extracted from 4620 male individuals of Uygur in Xinjiang province, and amplified by EX16+10Y kit. The typing of amplification products was per-formed by 3130xl genetic analyzer. Results The genotyping graphs of 15 autosomal STR loci and 10 Y-chromosomal STR loci from 4620 male individuals of Uygur in Xinjiang province were acquired completely. The genotype distribution of 15 autosomal STR loci was consistent with Hardy-Weinberg equilibrium. The heterozygosity, polymorphism information content and discrimination power of STR loci were 0.637-0.838, 0.580-0.860 and 0.811-0.978, respectively. There were 766 haplotypes in 10 Y -chro-mosomal STR loci. Conclusion The test results of EX16+10Y kit is accurate and trustworthy, which can simultaneously be used for the individual identification and the screening of paternal pedigree in practical work.

Expression and characterization of ArgR, an arginine regulatory protein in Corynebacterium crenatum / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Corynebacterium crenatum MT, a mutant from C. crenatum AS 1.542 with a lethal argR gene, exhibits high arginine production. To confirm the effect of ArgR on arginine biosynthesis in C. crenatum, an intact argR gene from wild-type AS 1.542 was introduced into C. crenatum MT, resulting in C. crenatum MT. sp, and the changes of transcriptional levels of the arginine biosynthetic genes and arginine production were compared between the mutant strain and the recombinant strain.</p><p><b>METHODS</b>Quantitative real-time polymerase chain reaction was employed to analyze the changes of the related genes at the transcriptional level, electrophoretic mobility shift assays were used to determine ArgR binding with the argCJBDF, argGH, and carAB promoter regions, and arginine production was determined with an automated amino acid analyzer.</p><p><b>RESULTS</b>Arginine production assays showed a 69.9% reduction in arginine from 9.01 ± 0.22 mg/mL in C. crenatum MT to 2.71 ± 0.13 mg/mL (P<0.05) in C. crenatum MT. sp. The argC, argB, argD, argF, argJ, argG, and carA genes were down-regulated significantly in C. crenatum MT. sp compared with those in its parental C. crenatum MT strain. The electrophoretic mobility shift assays showed that the promoter regions were directly bound to the ArgR protein.</p><p><b>CONCLUSION</b>The arginine biosynthetic genes in C. crenatum are clearly controlled by the negative regulator ArgR, and intact ArgR in C. crenatum MT results in a significant descrease in arginine production.</p>

Comparative analysis of the pathogenic mechanisms of street rabies virus strains with different virulence levels / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To characterize two strains of street rabies virus (RABV) isolated from the brain tissue of cattle from Inner Mongolia. Differences in the histopathological and ultrastructural changes in the brain tissue of infected mice were determined to reveal variation in the pathogenesis of infection between street rabies virus strains.</p><p><b>METHODS</b>Ten-day-old mice were intracranially inoculated with one of three virus strains and brain tissue harvested when the mice were moribund. Various histopathological and ultrastructural markers of disease were then compared between the groups.</p><p><b>RESULTS</b>Infection with the street virus strain CNM1101C resulted in severe neuronal dendrites damage, but only mild cell apoptosis, T lymphocyte infiltration and microglial activation. Infection with the other street virus strain, CNM1103C, was characterized by cell apoptosis, T lymphocyte infiltration and microglial activation as well as dendrites damage. However, in comparison, infection with the attenuated virus strain CTN caused severe T lymphocyte infiltration, microglial activation and cell apoptosis, but left the neuronal dendrites intact.</p><p><b>CONCLUSION</b>The two street rabies virus strains isolated from cattle from Inner Mongolia had different levels of virulence and caused distinct pathological changes in infected mice. Therefore, we concluded that different pathogenic mechanisms exist between different RABV strains.</p>

AS-PCR assay for 20 mtDNA SNP typing and haplotype frequency / 法医学杂志

OBJECTIVE@#To develop a multiplex allele-specific PCR (AS-PCR) assay with three-color fluorescence labeling for mitochondrial DNA (mtDNA) SNP typing.@*METHODS@#Based on the principle of AS-PCR, the primer sets were designed for 20 SNP located on the coding region of mtDNA and divided into 2 groups labeled with FAM and HEX fluorescence, respectively. A primer set included two forward (reverse) allelic specific primers with different sizes and a generic reverse (forward) primer. Blood samples from 200 unrelated individuals were analyzed by AS-PCR and capillary electrophoresis. Three random samples at least for each SNP site were examined and verified by direct sequencing. The haplotype frequency was investigated.@*RESULTS@#Distinct electropherograms of 200 blood samples were obtained successfully. The typing results of direct sequencing were identical to those obtained from AS-PCR. The minimum detectable DNA concentration was 0.2 pg under the system of 10 microL. The sensitivity of the DNA concentrations ranged from 0.5 to 5 pg. The 200 individuals were assigned into 15 haplotype, and the haplotype diversity was 0.906 0.@*CONCLUSION@#AS-PCR is a simple, rapid and efficient method for mtDNA SNP typing, and can be applied to forensic practice.

Expression of microRNA-29b2-c cluster is positively regulated by MyoD in L6 cells / 中国医学科学杂志(英文版)

<p><b>OBJECTIVES</b>To evaluate the expression profile of myoD microRNA-29 (miR-29) family in L6 myoblast differentiated to myotube of L6 myotube treated by glucose and insulin, and to further probe the molecular mechanism of myoD regulating the expression of miR-29 clusters.</p><p><b>METHODS</b>The expression of myoD and miR-29 family was detected by using real-time PCR and Western blot analysis. The potential promoter and transcription factors binding sites of miR-29 clusters were predicted by Promoter scan and transcriptional factor search. The promoter sequence of miR-29b1-a and miR-29b2-c cluster was cloned into a luciferase reporter plasmid and the regulatory effect of myoD was analyzed by using dual luciferase reporter assay. Electrophoretic mobility shift assay was further conducted to indicate the binding of myoD on specific sequence. Moreover, overexpression of myoD was achieved by a recombinant adenovirus system (Ad-myoD). L6 cells were infected with Ad-myoD and real-time PCR was conducted to analyze the expression of miR-29b and miR-29c.</p><p><b>RESULTS</b>The expression levels of myoD, miR-29a, miR-29b, and miR-29c were increased in L6 myoblast differentiated to myotube. The expression of myoD, miR-29b, and miR-29c was up-regulated in L6 myotube treated with glucose and insulin, but miR-29a depicted no significant change. Dual luciferase reporter gene assay showed that myoD functioned as a positive regulator of miR-29b2-c expression and myoD could bind to the specific sequence located at the promoter region of miR-29b2-c cluster. Enforced expression of myoD led to a marked increase of miR-29b and miR-29c levels in L6 cells.</p><p><b>CONCLUSION</b>MyoD might act as a crucial regulator of myogenesis and glucose metabolism in muscle through regulating the expression of miR-29b2-c.</p>

Applications of the hospital statistics management system / 中国医疗器械杂志

The Hospital Statistics Management System is built on an Office Automation Platform of Shandong provincial hospital system. Its workflow, role and popedom technologies are used to standardize and optimize the management program of statistics in the total quality control of hospital statistics. The system's applications have combined the office automation platform with the statistics management in a hospital and this provides a practical example of a modern hospital statistics management model.

Expression of cyclooxygenase-2 in colorectal cancer and its clinical significance.

AIM: To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer. METHODS: A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2, anti-VEGF and anti-MMP-2 antibodies. The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathologic parameters was evaluated by chi-square test. RESULTS: Among 128 cases of colorectal cancer, 87 (67.9%) were positive for cyclooxygenase-2. The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion, stage of disease, and metastasis (lymph node and liver). Patients in T3-T4, stages III-IV and with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2, stages I-II and without metastasis (P<0.05). Among 45 cases of colorectal cancer with lymph node metastasis, the COX-2- positive rate was 86.7% (39/45) for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastatic lesions of the lymph nodes. VEGF expression was detected in 49 tumors (38.3%), and VEGF expression was closely correlated with COX-2 expression. The positive expression rate of VEGF (81.6%) in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2- negative group (18.4%, P<0.05). MMP-2 expression was detected in 88 tumors (68.8%), and MMP-2 expression was closely correlated with COX-2 expression. The positive expression rate of MMP-2 (79.6%) in the positive COX-2 group was higher than that in the negative COX-2 group (20.4%, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.

Study on the characteristics of apoptosis in the condyles of osteoarthritic temporomandibular joints / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the characteristics of apoptosis in the condyles of osteoarthritic temporomandibular joints, and investigate its role in the pathogenesis of the disease.</p><p><b>METHODS</b>Temporomandibular joint osteoarthrosis model of rabbits was created by partial resection of joint disc. The animal models were sacrificed in the 15th day, the 1st month, the 2nd month, the 3rd month, the 4th month, the 5th month, and the 6th month chronologically. Then the pathological condyles were sectioned and detected with TUNEL method to investigate the apoptosis within the tissue.</p><p><b>RESULTS</b>In the reactive repairing state of osteoarthrosis, the apoptosis cells mainly located in the superficial fibrous layer of articular cartilage. With the remodeling of articular cartilage and bone, the apoptosis cells gradually appeared in the proliferating layer, especially in the "clusters of chondrocytes". Accompanied with the severe damage and loss of articular cartilage, the phenomena of apoptosis decreased in the lower zone of cartilage and increased in the hypertrophic and calcified zone.</p><p><b>CONCLUSION</b>There were abundant phenomena of apoptosis within the condylar cartilage of osteoarthritic temporomandibular joint. Abnormal proliferation and abundant apoptosis would disturb the regulation mechanism in the cartilage matrix and lead to the osteoarthrosis.</p>

Cyclooxygenase-2 expression and angiogenesis in colorectal cancer.

AIM: Cyclooxygenase-2 is involved in a variety of important cellular functions, including cell growth and differentiation, cancer cell motility and invasion, angiogenesis and immune function. However, the role of cyclooxygenase-2 as an angiogenic factor in colorectal cancer tissue is still unclear. We investigated the relationship between cyclooxygenase-2 and angiogenesis by analyzing the expression of cyclooxygenase-2 in colorectal cancer tissue, as well as its association with vascular endothelial growth factor (VEGF) and microvascular density (MVD). METHODS: The expression of cyclooxygenase-2, VEGF, as well as MVD was detected in 128 cases of colorectal cancer by immunohistochemical staining. The relationship between the cyclooxygenase-2 and VEGF expression and MVD was evaluated. Our objective was to determine the effect of cyclooxygenase-2 on the angiogenesis of colorectal cancer tissue. RESULTS: Among 128 cases of colorectal cancer, 87 were positive for cyclooxygenase-2 (67.9 %), and 49 for VEGF (38.3 %), respectively. The microvessel counts ranged from 23 to 142, with a mean of 51.7 (standard deviation, 19.8). The expression of cyclooxygenase-2 was correlated significantly with the depth of invasion, stage of disease, metastasis (lymph node and liver), VEGF expression and MVD. Patients in T3-T4, stage III-IV and with metastasis had much higher expression of cyclooxygenase-2 than patients in T1-T2, stage I-II and without metastasis (P<0.05). The positive expression rate of VEGF (81.6 %) in the cyclooxygenase-2 positive group was higher than that in the cyclooxygenase-2 negative group (18.4 %, P<0.05). Also, the microvessel count (56+/-16) in cyclooxygenase-2 positive group was significantly higher than that in cyclooxygenase-2 negative group (43+/-12, P<0.05). The microvessel count in tumors with positive cyclooxygenase-2 and VEGF was the highest (60+/-18, 41-142, P<0.05), whereas that in tumors with negative cyclooxygenase-2 and VEGF was the lowest (39+/-16, 23-68, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by madulating the angiogenesis in colorectal cancer tissue and used as a possible biomarker.

Antitumor activity of different organic solvents extracts and plumbagin from plumbago zeylanica L. on EMT-6 breast cancer and transplanting S180 in vivo / 中国药理学通报

Aim To find out the effect of the different organic solvents extracts and plumbagin from Plumbago zeylanica L.on EMT-6 breast cancer of BALB/C mouse and transplanted S180 of KM mouse primarily.Method Experiments of animal transplanted tumor in vivo were adopted.Results ① The high dose of chloroform group and plumbagin group could inhibit the growth of EMT-6 breast cancer in BALB/C mice in vivo.Compared with that of physiological saline group,tumor weight has obviously lightened(P