Background::To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods::This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results::A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions::SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.Trial registration::Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1

ObjectiveTo explore the pharmacodynamic ingredients of Zhenqi Fuzheng granules （ZFG） for immunomodulatory through spectrum-effect relationship analysis， which provides experimental basis for improving the quality standard of ZFG. MethodEighteen batches of ZFG from six manufacturers were collected for analysis. The fingerprints were established by high performance liquid chromatography （HPLC）. Acetonitrile （A）-0.1% formic acid aqueous solution （B） were adopted as the mobile phase with gradient elution （0-15 min， 5%A； 15-23 min， 5%-8%A； 23-30 min， 8%-11%A； 30-45 min， 11%-18%A； 45-60 min， 18%-21%A； 60-67 min， 21%-23%A； 67-90 min， 23%-37%A）， the detection wavelength was 220 nm. Chemometric analysis such as similarity analysis and hierarchical cluster analysis （HCA） were subsequently used to analyze the similarities and chemical differences among these samples. A cyclophosphamide-induced immunodeficiency mouse model was used to evaluate the immune-enhancing effects of the products from different manufacturers. The spectrum-effect relationship between HPLC fingerprints and the immunomodulatory effects was examined using Spearman bivariate correlation analysis. HPLC coupled with mass spectrometry （HPLC-MSⁿ） was used to identify the spectrum-effect related peaks with electrospray ionization， positive and negative ion modes， and scanning range of m/z 100-1 500. ResultThe HPLC fingerprint of ZFG was established， and twenty peaks with good resolution were selected as common peaks. The results of quality analysis and pharmacodynamic test showed there were significant differences in both ingredients content and immune-enhancing effects of ZFG from different manufacturers. Through spectrum-effect relationship study， twelve peaks were screened as bioactive ingredients peaks. Thereafter， eight peaks among them were subsequently identified by HPLC-MSⁿ. They were salidroside （peak 2）， echinacoside （peak 5）， calycosin-7-glucoside （peak 6）， isomer of specnuezhenide （peak 7）， isonuezhenide （peak 9）， calycosin （peak 11）， nuezhenide G₁₃ or oleonuezhenide （peak 14）， and formononetin （peak 18）， respectively. ConclusionThere are differences in quality and efficacy of ZFG produced by different manufacturers. Through spectrum-effect relationship analysis， the medicinal ingredients of ZFG for immune-enhancing effects are screened， which can provide reference for the improvement of its quality standard.

【Objective】To explore the effects of liver dysfunction in the third trimester of pregnancy on maternal outcomes and identify the factors affecting the maternal prognosis.【Methods】We collected the clinical data of 1 113 women with liver dysfunction in the third trimester of pregnancy （case group） and 1 113 normal pregnancies （control group） from the Third Affiliated Hospital of Sun Yat-sen University between January 2015 and December 2018. We compared the rates of cesarean section，premature delivery，placental abruption，postpartum hemorrhage and maternal mortality in the two groups，conducted the univariate and multivariate analysis for the case group and determined the prognostic risk factors by using Logistic regression. Receiver operating characteristic（ROC）curve analysis was applied to estimate the value of each independent risk factor for predicting liver dysfunction-related maternal mortality. 【Results】The rates of cesarean section，premature delivery，placental abruption，postpartum hemorrhage in the case group were higher than those in the control group（P < 0.05），and the odds ratios（ORs）were 3.59 ，7.81 ，10.68 and 2.93 ，respectively. The maternal mortality in the case group（1.2%）was higher than that in the control group（0.0%）（P < 0.05）. Logistic analysis revealed that high total bilirubin（TBIL），low prothrombin activity（PTA）and low fasting plasma glucose（FPG）were independent risk factors for liver dysfunction- related maternal mortality. The ROC curve analysis indicated that when TBIL was 235.4 μmol/L，the Youden′ s index in maximum was 0.331 with sensitivity of 0.818 and specificity of 0.513. When PTA was 20.5% ，the Youden′ s index in maximum was 0.366 with sensitivity of 0.821 and specificity of 0.545. When FPG was 3.11 mmol/L，the Youden′s index in maximum was 0.405 with sensitivity of 0.769 and specificity of 0.636.【Conclusion】Liver dysfunction in the third trimester of pregnancy has adverse effects on maternal outcomes. TBIL ，PTA and FPG are the factors affecting the maternal prognosis and may have certain predictive value for maternal death.

Objective To investigate the epidemic character of injuries among rural left-behind children, so as to provide evidence for strategies and processes on preventing injuries. Methods Using stratified cluster sampling, a town was randomly selected from each of the two layers with different economic development levels in Qingxin district, Qingyuan city, Guangdong Province. The local left-behind children of 3-9 grades from 3 elementary schools and 3 middle schools were randomly selected from the local area. The student self-administered questionnaire was used to investigate the occurrence of injuries, personal circumstances, family environment and school situation in the past year. Data of injury situation, personal situation, family situation and school situation during last year were analysed by Chi-square and multiple logistic analysis. Results Injuries were reported to occur in 440 left-behind children, with an injury rate of 17.5%. Significant difference of injury rate was observed between groups divided by grades, being only-child in family, health conditions, anxiety, getting along with other students, teacher’s attitude to students, emphasizing security by teachers, knowledge level about injury, and injury-relative behaviors (all P<0.05). Multivariate logistic regression model results suggested that middle school, physical health, behavioral level, and relationship with classmates are protective factors, anxiety is a risk factor (OR=1.262,95%CI:1.009~1.577,P=0.041). Conclusions We have to take some comprehensive methods to prevent injuries that are influenced by all kinds of factors. While constructing an advantage circumstance to left-behind children, their awareness of security should also be improved to reduce the occurrence of injuries.

PURPOSE: In this study, we aimed to evaluate lymphocyte-activation gene-3 (LAG-3) expression and its prognostic value in neoadjuvant-treated triple-negative breast cancer (TNBC). METHODS: LAG-3, programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), and CD8⁺ tumor-infiltrating lymphocyte (TILs) levels were examined using immunohistochemistry in 148 preand 114 post-neoadjuvant chemotherapy (NACT) specimens of human TNBC tissue. Correlations between expression levels and clinicopathological features were analyzed. Prognostic values for combined detection in TNBC following NACT were evaluated. RESULTS: In pre-NACT specimens, LAG-3 expression showed a significant association with pathological complete response (pCR, p=0.038) and was correlated with PD-1 (p<0.001) and PD-L1 (p=0.008). In post-NACT specimens, high expression of LAG-3 showed significant effects on nodal status (p=0.023) and PD-1 (p<0.001). The expression of immune markers on TILs significantly increased following NACT. Multivariate analysis indicated that only nodal status (odds ratio [OR], 0.226; 95% confidence interval [CI], 0.079–0.644; p=0.005) and high quantities of CD8⁺TILs (OR, 3.186; 95% CI, 1.314–7.721; p=0.010) are independent predictors of pCR. Nodal status (hazard ratio [HR], 2.666; 95% CI, 1.271–5.594; p=0.010), CD8⁺TILs (HR, 0.313; 95% CI, 0.139–0.705; p=0.005), and the LAG-3-high/PD-L1-high group (HR, 2.829; 95% CI, 1.050–7.623; p=0.040) provided prognostic values for patients with TNBC following NACT. CONCLUSION: CD8+TILs were sensitive predictive markers in response to NACT. High expression of LAG-3 in residual tissues, especially in combination with PD-L1, was associated with poor prognosis.
Biomarkers ; Drug Therapy ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating ; Multivariate Analysis ; Neoadjuvant Therapy ; Polymerase Chain Reaction ; Prognosis ; Triple Negative Breast Neoplasms*

Objective:To evaluate the effectiveness and safety of endovascular treatment in solving symptomatic cerebral artery tandem lesions.Methods:From June 201 2 to February 201 4,1 2 cases (24 lesions)with symptomatic cerebral artery tandem lesions were accepted for the endovascular treatment. The distributions of the tandem lesions were as follows:the common carotid artery and internal carotid ar-tery (1 case),the internal carotid artery and the proximal of the carotid cavernous sinus segment (3 ca-ses),the internal carotid artery and the distal of the carotid cavernous sinus segment (4 cases),the in-tracranial segment of internal carotid artery and middle cerebral artery M1 segment (2 cases),the first segment of vertebral artery and intracranial segment of vertebral artery (2 cases).All of these cases were treated from distal lesions to proximal lesions except for tandem lesions in the internal carotid artery and the distal of the carotid cavernous sinus segment in order to obtain better support.Tandem lesions were treated in the same operation with local anesthesia or general anesthesia.The procedures of the 1 2 cases retrospectively were analyzed and the peri-operation complications and responsibility region recurrent is-chemic stroke incidents observed.Results:All tandem lesions were solved successfully all at once.There were no peri-operation complications or recurrent ischemic stroke incidents.There were no recurrent is-chemic stroke incidents or stent restenosis cases in the follow-up.Conclusion:It is safe and effective for selective endovascular treatment in solving symptomatic cerebral artery tandem lesions at the same time, but we should take careful preoperative evaluation and improve the operation plan.

Objective:To study the morphology of middle cerebral artery ( MCA ) M1 segment .Me-thods:We selected the MRA data of 794 MCA (400 of the left side and 394 of the right side ) from Ja-nuary 1, 2011 to June 30, 2011 consecutively and analyzed the morphology of the MCA M 1 segment in axial, anteroposterior and lateral view , measured the length of the M1 segment, and analyzed the simila-rity of the left and right side M1 segment morphology .Results:In axial, anteroposterior and lateral view , the MCA M1 segment showed C-shape >L-shape >S-shape .In axial view , it was about 373 ( 47%) M1 segment performance for the C-shape, of which 340 (42.8%) M1 segments showed bowing to the dorsal side, only 33 (4.2%) M1 segments showed bowing to the ventral side .In anteroposterior view, it was about 322 (40.6%) M1 segments of the performance of the C-shape, of which 262(33.0%) M1 segments showed a bowing to the superior , 60 (7.6%) showed bowing to the inferior .The similarity of the left and right MCA M1 segments was 27.2% (114/419) in axial view and 42.7% (179/419) in anteroposterior view.It was more similar in anteroposterior view than in axial view .Along with the increase of age, in the axial view, L-shape converted to C-shape very obviously, but only mildly elevated in S-shape .In anteroposterior view , the L-shape converted to the C-shape or S-shape along with the increase of age.Conclusion:The different morphology of MCA M1 segment in axial and anteroposterior view may be involved in the development of intracranial atherosclerosis .

Objective:To anslysis the hemodynamic states of vertebrobasilar dolichoectasia based on computational fluid dynamics technique.Methods:The original DICOM format image data from a patient with vertebrobasilar dolichoectasia (VBD), were imported by the Mimics software directly,and the 3D Objects were constructed.The simulation of model was made with Ansys software, the hemodynamic pa-rameters such as streamlines, wall shear stress( WSS) and wall pressure were described.Results:There was stable laminar flow in proximal basilar artery and was no blood flow mixed by bilateral vertebral arter-y.However, Spiral flows were appeared in distal tortuous basilar artery.The low WSS regions in the ver-tebra-basilar junction section and inferior segment of basilar artery were coincide with the high wall pres-sure regions.It could be speculated the initial growth regions might be located in the vertebra-basilar junction section and inferior segment of basilar artery.Local regions with low WSS and high wall pressure might be associated with the occurrence and development of VBD.Conclusion: CFD numerical simula-tion maybe can provide a theoretical basis for the role of hemodynamic factors in occurrence and develop-ment of VBD.

Objective:To analyze correlation factors of hemodynamic damage after carotid artery stenting.Methods:In this study, 66 cases (71 lesions) who undertook carotid artery stenting were col-lected and the correlation factors of hemodynamic damage were analyzed .Results:Hemodynamic damage emerged in 23 cases (32.4%), of which, 11.3%developed hypotension.The distance between bifurca-tion and lesions (P=0.002 0), plaque distribution (P=0.000 2), plaque character (P=0.001 9), post-dilation ( P =0.002 6 ) were associated with hemodynamic damage by single factor analysis . However, only eccentric plaque (P=0.015 3) and calcified plaque (P=0.009 7) were associated with hemodynamic damage by multiple factors analysis .All the patients could reach stable circulation by drugs during operation , and no cerebral ischemic events ( transient ischemic attack or stroke ) and cardiovascu-lar ischemic events happened .Conclusion: The distance between bifurcation and lesions , eccentric plaques, calcified plaques are correlation factors of hemodynamic damage .

Factor VII Deficiency ; complications ; Humans ; Liver Cirrhosis ; complications ; Male ; Middle Aged