Safety Evaluation of Tianzhi Granules in Treating Mild-to-moderate Vascular Dementia / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the safety of Tianzhi granules used in the treatment of mild-to-moderate vascular dementia. MethodA randomized， double-blind， double-simulated， positive drug/placebo parallel controlled multi-center phase Ⅳ clinical trial and an open multi-center phase Ⅳ clinical trial of Tianzhi granules in the treatment of mild-to-moderate vascular dementia were conducted. Safety data of 1 492 patients were included and analyzed according to inclusion and exclusion criteria. The main evaluation measures were the incidence rate of adverse events/adverse reactions， laboratory indicators， vital signs， and electrocardiogram （ECG） results. ResultA total of six adverse events possibly related to the test drug occurred in 520 patients of the double-blind trial， and the symptoms were all mild and recovered. The incidence of adverse events was not statistically different among Tianzhi granules， donepezil， and placebo groups. Nine adverse events possibly related to the test drug were observed in 972 patients of the open trial， and the symptoms were mild and recovered. Laboratory tests （blood routine， urine routine， liver function， kidney function， and coagulation） and vital signs were compared before treatment （baseline） and after treatment of 12 and 24 weeks， respectively. There was no statistical significance in the main indicators before and after treatment. In the double-blinded trial， there was no significant difference in safety indicators between different groups before and after treatment. The most frequent adverse reaction was gastrointestinal discomfort， with an incidence rate of 6.64‰. ConclusionAdverse reactions occasionally occur in patients using Tianzhi granules， and it is safe to use Tianzhi granules to treat mild-to-moderate vascular dementia clinically.

Targeting the stimulator of interferon genes (STING) in breast cancer.

Breast cancer has a high occurrence rate globally and its treatment has demonstrated clinical efficacy with the use of systemic chemotherapy and immune checkpoint blockade. Insufficient cytotoxic T lymphocyte infiltration and the accumulation of immunosuppressive cells within tumours are the primary factors responsible for the inadequate clinical effectiveness of breast cancer treatment. The stimulator of interferon genes (STING) represents a pivotal protein in the innate immune response. Upon activation, STING triggers the activation and enhancement of innate and adaptive immune functions, resulting in therapeutic benefits for malignant tumours. The STING signalling pathway in breast cancer is influenced by various factors such as deoxyribonucleic acid damage response, tumour immune microenvironment, and mitochondrial function. The use of STING agonists is gaining momentum in breast cancer research. This review provides a comprehensive overview of the cyclic guanosine monophosphate-adenosine monophosphate synthase-STING pathway, its agonists, and the latest findings related to their application in breast cancer.

Design, sensitivity and validity of wrist patient self-evaluation instrument / 中华骨科杂志

Objective:To design a patient self-rating wrist scale suitable for Chinese patients, and evaluate its reliability and validity.Methods:The primary entry pool was established by referring to the existing foreign scales and the opinions of domestic experts. Opinions of 11 hand surgeons and 10 patients with wrist diseases were referred to select better items into the primary scale. During September 2015 to November 2016, 100 inpatients with wrist diseases in the hand surgery department of Beijing Jishuitan Hospital were selected by convenient sampling method, and the primary scale was conducted on them. Eight indices including item response rate, item differentiation, item-dimension attribution, variability, responsiveness, overall item attribution, internal consistency and factor loading were summarized. All the 8 indices were evaluated to establish the wrist patient self-evaluation instrument for Chinese. Test-retest reliability, Cronbach coefficient, expert score, KMO value, explanatory power, χ 2/df, root mean square error of approximation (RMSEA) and comparative fit index (CFI) were used to evaluate the reliability and validity of the scale. Results:A total of 40 subjective items in the primary entry pool were selected to form the primary scale, including 32 items (A1-D4), and 4 dimensions (physiology, safety, pain and emotion). There were 92 valid scale results in 100 cases. All cases' response rate were over 90%. In terms of item differentiation, only the high grouping score [3.20±0.577 points (range, 1-3 points)] and the low grouping score [2.68±0.627 points (range, 2-5 points)] of item B10 had no statistical significance ( t=5.11, P=0.340). There were 17 items: A1, A2, A5, A6, A7, A8, A9, A10, A11, A12, B4, B6, B7, C5, D1, D2, and D3 were considered to be deleted according to the result of item-dimension attribution. A total of 11 items had a variation less than 0.65: A4 (0.645), A7 (0.593), B1 (0.590), B5 (0.617), B8 (0.578), B9 (0.612), B10 (0.526), D1 (0.644), D2 (0.320), D3 (0.169), D4 (0.526). A2, A4, A6, A8, B4, B6, D1, D2, D3, C2, C3, C4, C5, C6 did not meet the reactivity requirements. Items with factor loads less than 0.4: D2 (-0.051), D3 (-0.127), and D4 (0.267). C4 (0.026), C5 (0.023), D1 (0.103), D2 (0.434), D3 (0.387), D4 (0.062) did not meet the internal consistency requirements. In multiple linear regression analysis, 19 items were not included in the final regression equation. Based on the above analysis, D1, D2, and D3 were finally deleted and the rest 29 valid items were remained to form the wrist patient self-evaluation instrument for Chinese. Reliability and validity of the scale: the test-retest reliability of physiology, safety, pain, emotion dimensions were 0.984, 0.976, 0.985 and 0.802 ( P<0.001), respectively. Except for there was only one item in emotion dimension, the Cronbach coefficients of total score, physiology, safety and pain dimensions were 0.943, 0.973, 0.944 and 0.881, respectively. KMO was 0.894 ( P<0.001). Except for there was only one item in emotion dimension, whose validity could not be evaluated. The χ 2/df, CFI, RMSEA results were as follows, physiology: 5.152, 0.817, 0.022, respectively; safety: 5.378, 0.795, respectively; pain: 7.439, 0.865, 0.028, respectively. Conclusion:The wrist patient self-evaluation instrument for Chinese is consisted of 4 dimensions and 29 items. As a subjective wrist self-rating scale suitable for modern Chinese patients, the scale has good reliability and validity, and can be one of the choices of the subjective evaluation for Chinese patients with wrist diseases.

Total Glucosides of Paeony Regulate Immune Imbalance Mediated by Dermal Mesenchymal Stem Cells in Psoriasis Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the therapeutic effects of total glucosides of paeony (TGP) on psoriasis based on the immunomodulatory effect of dermal mesenchymal stem cells (DMSCs).@*METHODS@#A total of 30 male BALB/c mice were divided into 6 groups (n=5 in each) by a random number table method, including control, psoriasis model (model, 5% imiquimod cream 42 mg/d), low-, medium- and high-dose TGP (50, 100, and 200 mg/kg, L, M-, and H-TGP, respectively), and positive control group (2.5 mg/kg acitretin). After 14 days of continuous administration, the skin's histopathological changes, apoptosis, secretion of inflammatory cytokines, and proportion of regulatory T cells (Treg) and T helper cell 17 (Th17) were evaluated using hematoxylin-eosin (HE) staining, TdT-mediated dUTP nick end labeling staining, enzyme-linked immunosorbent assay, and flow cytometry, respectively. DMSCs were further isolated from the skin tissues of normal and psoriatic mice, and the cell morphology, phenotype, and cycle were observed. Furthermore, TGP was used to treat psoriatic DMSCs to analyze the effects on the DMSCs immune regulation.@*RESULTS@#TGP alleviated skin pathological injury, reduced epidermis layer thickness, inhibited apoptosis, and regulated the secretion of inflammatory cytokines and the proportion of Treg and Th17 in the skin tissues of psoriatic mice (P<0.05 or P<0.01). There was no significant difference in cell morphology and phenotype between control and psoriatic DMSCs (P>0.05), however, more psoriatic DMSCs remained in G0/G1 phase compared with the normal DMSCs (P<0.01). TGP treatment of psoriatic DMSCs significantly increased cell viability, decreased apoptosis, relieved inflammatory response, and inhibited the expression of toll-like receptor 4 and P65 (P<0.05 or P<0.01).@*CONCLUSION@#TGP may exert a good therapeutic effect on psoriasis by regulating the immune imbalance of DMSCs.

Cancer biology deciphered by single-cell transcriptomic sequencing

Tumors are complex ecosystems in which heterogeneous cancer cells interact with their microenvironment composed of diverse immune, endothelial, and stromal cells. Cancer biology had been studied using bulk genomic and gene expression profiling, which however mask the cellular diversity and average the variability among individual molecular programs. Recent advances in single-cell transcriptomic sequencing have enabled a detailed dissection of tumor ecosystems and promoted our understanding of tumorigenesis at single-cell resolution. In the present review, we discuss the main topics of recent cancer studies that have implemented single-cell RNA sequencing (scRNA-seq). To study cancer cells, scRNA-seq has provided novel insights into the cancer stem-cell model, treatment resistance, and cancer metastasis. To study the tumor microenvironment, scRNA-seq has portrayed the diverse cell types and complex cellular states of both immune and non-immune cells interacting with cancer cells, with the promise to discover novel targets for future immunotherapy.

Anlotinib combined with docetaxel for the treatment of advanced non-small cell lung cancer / 中国基层医药

Objective:To investigate the clinical efficacy and safety of anlotinib combined with docetaxel for the treatment of advanced non-small cell lung cancer.Methods:A total of 118 patients with advanced non-small cell lung cancer who received treatment in Jinhua Guangfu Cancer Hospital from March 2018 to June 2019 were included in this study. They were randomly assigned to receive treatment with either anlotinib combined with docetaxel (study group, n = 59) or docetaxel alone (control group, n = 59) for two treatment courses. Clinical efficacy, progression-free survival, 1-year survival rate, and adverse drug reactions were compared between the study and control groups. Results:There was no significant difference in the objective remission rate between the two groups (22.03% vs. 32.20%, χ2 = 1.544, P = 0.214). The disease control rate in the study group was significantly higher than that in the control group (88.14% vs. 69.49%, χ2 = 6.141, P = 0.013). Progression-free survival in the study group was significantly longer than that in the control group [6.92 months (95% CI: 3.83-9.54 months) vs. 3.84 months (95% CI: 2.08-6.17 months), χ2 = 5.934, P = 0.019). The 1-year survival rate in the study group was significantly higher than that in the control group [52.47% (31/59) vs. 32.20% (19/59), χ2 = 4.998, P = 0.025]. During the treatment, the proportion of patients having leucopenia, erythropenia, gastrointestinal adverse reactions and abnormal liver and kidney function in the study group was 20.34%, 13.56%, 28.81% and 5.08%, respectively, which was significantly higher than 16.95%, 10.17%, 23.73% and 3.39%, respectively in the control group ( χ2 = 0.211-0.835, P = 0.361-0.646). Conclusion:Arotinib combined with docetaxel can effectively inhibit the progression of non-small cell lung cancer, prolong the progression-free survival, increase the 1-year survival rate, and does not increase adverse drug reactions.

Osimertinib Re-challenge for EGFR-mutant NSCLC after Osimertinib-induced Interstitial Lung Disease: A Case Report / 中国肺癌杂志

Osimertinib-induced interstitial lung disease (ILD) is an uncommon, but fatal pulmonary toxicity in some patients. We report a case of a 64-year-old male with stage IV adeno-non-small cell lung cancer (NSCLC) harboring an exon 19 deletion in the epidermal growth factor receptor (EGFR) treated with osimertinib 80 mg/d for first-line targeted therapy. On day 60 after initiating treatment of osimertinib, the patient developed ILD. Osimertinib was discontinued immediately and oral prednisone 60 mg/d was initiated, ILD improved within 13 d. After balancing the risk and benefit, osimertinib was restarted concurrently with prednisone. The patient showed neither disease progression nor a recurrence of ILD for more than 16 months. Based on our case and literature review, retreatment with osimertinib under steroid coverage could be considered as an effective treatment option after careful risk-benefit assessment for patients with EGFR-mutant NSCLC.
.

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19. HIGHLIGHTSO_LILarge-scale scRNA-seq analysis depicts the immune landscape of COVID-19 C_LIO_LILymphopenia and active T and B cell responses coexist and are shaped by age and sex C_LIO_LISARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responses C_LIO_LICytokine storms with systemic S100A8/A9 are associated with COVID-19 severity C_LI

Single-cell landscape of immunological responses in COVID-19 patients

In COVID-19 caused by SARS-CoV-2 infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of five healthy donors and 13 COVID-19 patients including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in COVID-19 patients showed a strong interferon-alpha response, and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ Effector-GNLY (Granulysin), CD8+ Effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during the disease progression.

COVID-19 outbreak in Wuhan demonstrates the limitations of publicly available case numbers for epidemiological modelling.

Epidemiological models are widely used to analyse the spread of diseases such as the global COVID-19 pandemic caused by SARS-CoV-2. However, all models are based on simplifying assumptions and on sparse data. This limits the reliability of parameter estimates and predictions. In this manuscript, we demonstrate the relevance of these limitations by performing a study of the COVID-19 outbreak in Wuhan, China. We perform parameter estimation, uncertainty analysis and model selection for a range of established epidemiological models. Amongst others, we employ Markov chain Monte Carlo sampling, parameter and prediction profile calculation algorithms. Our results show that parameter estimates and predictions obtained for several established models on the basis of reported case numbers can be subject to substantial uncertainty. More importantly, estimates were often unrealistic and the confidence / credibility intervals did not cover plausible values of critical parameters obtained using different approaches. These findings suggest, amongst others, that several models are oversimplistic and that the reported case numbers provide often insufficient information.

Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction

The human coronavirus HCoV-19 infection can cause acute respiratory distress syndrome (ARDS), hypercoagulability, hypertension, extrapulmonary multiorgan dysfunction. Effective antiviral and anti-coagulation agents with safe clinical profiles are urgently needed to improve the overall prognosis. We screened an FDA approved drug library and found that an anticoagulant agent dipyridamole (DIP) suppressed HCoV-19 replication at an EC50 of 100 nM in vitro. It also elicited potent type I interferon responses and ameliorated lung pathology in a viral pneumonia model. In analysis of twelve HCoV-19 infected patients with prophylactic anti-coagulation therapy, we found that DIP supplementation was associated with significantly increased platelet and lymphocyte counts and decreased D-dimer levels in comparison to control patients. Two weeks after initiation of DIP treatment, 3 of the 6 severe cases (60%) and all 4 of the mild cases (100%) were discharged from the hospital. One critically ill patient with extremely high levels of D-dimer and lymphopenia at the time of receiving DIP passed away. All other patients were in clinical remission. In summary, HCoV-19 infected patients could potentially benefit from DIP adjunctive therapy by reducing viral replication, suppressing hypercoagulability and enhancing immune recovery. Larger scale clinical trials of DIP are needed to validate these therapeutic effects.

ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism

Respiratory disease caused by the 2019 novel coronavirus (2019-nCoV) pneumonia first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV and has been suggested to be also the receptor for 2019-nCoV. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike protein induced lung injury by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. Upon analysis of single cell-RNA sequencing data from control subjects and those with colitis or inflammatory bowel disease (IBD), we found that ACE2 expression in the colonocytes was positively associated with genes regulating viral infection, innate and cellular immunity, but was negatively associated with viral transcription, protein translation, humoral immunity, phagocytosis and complement activation. In summary, we suggest that ACE2 may play dual roles in mediating the susceptibility and immunity of 2019-nCoV infection.

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

Effectiveness of neuromuscular electrical stimulation combined with rehabilitation training for treatment of post-stroke limb spasticity.

BACKGROUND: This study aims to systematically explore the effectiveness of neuromuscular electrical stimulation (NMES) combined with rehabilitation training (RT) for the treatment of post-stroke limb spasticity (PSLS). METHODS: We will search Cochrane Library, MEDILINE, EMBASE, CINAHL, AMED, PsycINFO, WOS, Scopus, OpenGrey, and 4 Chinese databases from inception to the present without language restrictions. We will only consider randomized controlled trial on assessing the effectiveness and safety of NMES combined with RT for the treatment of PSLS. All included randomized controlled trials will be assessed using Cochrane risk of bias tool. Two researchers will independently perform study selection, risk of bias assessment, and data extraction, respectively. Any disagreements will be solved by a third researcher through discussion. RESULTS: Primary outcome is limb spasticity status. Secondary outcomes comprise of limb function, quality of life, and adverse events. CONCLUSION: This study will summarize the latest evidence of NMES combined with RT for the treatment of patients with PSLS. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019138900.

Effectiveness of neuromuscular electrical stimulation for wrist rehabilitation after acute ischemic stroke.

This study investigated the effectiveness of neuromuscular electrical stimulation (NMES) for patients with wrist dysfunction after acute ischemic stroke (AIS).A total of 82 patient cases with wrist dysfunction after AIS were selected in this study. Of these, 41 cases in the intervention group received physical training and NMES treatment. The other 41 cases in the control group received physical training only. The primary outcome was measured by Action Research Arm Test (ARAT) score. The secondary outcomes were measured by the Barthel Index (BI), and numerical rating scale (NRS).After 4-week treatment, patients in the intervention group neither improved arm function recovery, measured by ARAT score (P = .79), and activities of daily living, measured by BI scale (P = .62), nor reduced pain, measured by the NRS scale (P = .11), compared with patients in the control group.The results of this study demonstrated that NMES might not benefit for patients with wrist dysfunction after AIS after 4-week treatment.

Lead aVL in combination with lead V1:A new method for identifying premature ventricular contractions originating from aortic sinus cusp / 中国介入心脏病学杂志

Objective To explore the validity of lead aVL in combination with lead V1 for identifying idiopathic outflow tract premature ventricular contractions(PVCs)originating from aortic sinus cusp(ASC).Methods This study consecutively enrolled 102 idiopathic outflow tract PVCs patients who underwent radiofrequency catheter ablation at the Second Xiangya Hospital,Central South University between January 2015 and August 2017.We compared the QRS wave amplitudes in the surface twelve leads electrocardiography between PVCs originating from ASC and right ventricular outflow tract(RVOT).Results(1)The origin sites of PVCs were ASC(n=28,27.5％)and RVOT(n=74,72.5％).The lead V1R/S wave amplitude ratio and lead aVL S wave amplitude were significantly higher in the ASC group than in the RVOT group[(1.14±1.32)vs.(0.16±0.18),P＜0.001;(0.99±0.36)mV vs.(0.56±0.26)mV,P＜0.001].The areas under the receiver operating characteristic curve(AUCs)and 95％confidence intervals of V1R/S wave amplitude ratio and aVL S wave amplitude had relatively larger AUCs which were 0.894(0.824-0.964)and 0.831(0.749-0.912),with the cut-offs of 0.25 and 0.80 respectively.(2)The sensitivity,specificity and accuracy of the lead V1R/S wave amplitude ratio＞0.25 to identify ASC originating PVCs were 78.9％,83.7％and 82.4％,respectively.The sensitivity,specificity and accuracy of the lead aVL S wave amplitude＞0.80 mV were 78.6％,85.1％and 83.3％,respectively.The lead aVL S wave amplitude＞0.80 mV in combination with the lead V1R/S wave amplitude ratio＞0.25 was applied to developed a new diagnostic approach and the sensitivity,specificity and accuracy were 60.7％,93.2％and 84.3％,respectively.Conclusions Lead aVL in combination with lead V1 could be applied to develop a more accurate method for identifying ASC originating PVCs.

Structure and magnetic properties of icosahedral PdxAg13-x (x = 0-13) clusters.

In this article, we present a modified Velocity-Verlet algorithm that makes cluster system converge rapidly and accurately. By combining it with molecular dynamics simulations, we develop an effective global sampling method for extracting isomers of bimetallic clusters. Using this method, we obtain the isomers of icosahedral PdxAg13-x (x = 0-13). Additionally, using the first-principle spin-polarized density functional theory approach, we find that each isomer still retains its icosahedral structure because of strong s-d orbital hybridization, and the cluster is more stable when a Pd atom is at the center of the cluster. With increasing x value, the magnetic moment decreases linearly from 5.0 µB at x = 0, until reaching zero at x = 5, and then increases linearly up to 8.0 µB at x = 13. By calculating the atom-projected density of states (PDOS), we reveal that the magnetic moment of PdxAg13-x mainly originates from s electrons of Ag when 0 ≤ x < 5, and d electrons of Pd when 5 < x ≤ 13. The PDOS results also show that the PdxAg13-x tends to transform from a semiconductor state to semi-metallic state when x gradually increases from 0 to 13.

Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome.

Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients. In vitro experiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likely via a mechanism of inhibiting virus entry demonstrated by binding and entry assay. Localization of IFITM3 in late endosomes was also observed. In addition, we demonstrated that the transcription of IFITM3 is negatively regulated by an lncRNA negative regulator of interferon response (NRIR). Taken together, we conclude that IFITM3, negatively regulated by NRIR, inhibits HTNV infection, and its SNP rs12252 correlates with the plasma HTNV load and the disease severity of patients with HFRS.

Anti-proliferative and apoptotic effects of S1, a tetrandrine derivative, in human gastric cancer BGC-823 cells / 中国天然药物

The aim of the study was to investigate the anti-proliferation and apoptosis-inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer BGC-823 cells and explore the possible mechanism of action. The anti-proliferative activity was determined by MTT assay; the induction of cell cycle arrest and apoptosis were detected by flow cytometry. Quantitative real time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels in mitochondrial pathway. S1 significantly reduced cell viability and induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner. Further studies showed that S1 increased mRNA and protein expression of Bax and the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase-9 and procaspase-3, suggesting that the induction of apoptosis may be related to the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These findings suggested that S1 merits further investigation as a novel therapeutic agent for the treatment of human gastric cancer.

Effects of Melatonin on Synaptic Plasticity after Spinal Cord Injury in Rats / 中国康复理论与实践

Objective To observe the effects of melatonin on synaptic plasticity impaired by spinal cord injury in rats. Methods A total of 54 female Sprague-Dawley rats were divided into sham group (n=18), control group (n=18) and melatonin group (n=18). Spinal cord inju-ry model was established with modified Allen's method at T10 (10 g from 25 mm height). The number of neurons and the expression of the Nissl body were detected with immunofluorescence and Nissl staining. The expression of neurofilament-200 (NF-200), brain-derived neuro-trophic factors (BDNF), Synapsin I and growth-associated protein-43 (GAP-43) was detected with Western blotting. Results Seven days af-ter injury, the number of motoneurons, the expression of Nissl body in motoneurons, and the expression of BDNF, Synapsin I and GAP-43 decreased in the control group compared with those in the sham group, and they increased in the melatonin group compared with those in the control group. Conclusion Melatonin can repair the impaired synaptic plasticity, which might promote the functional recovery after spi-nal cord injury.