Effect of Qizhitongluo capsule on lower limb rehabilitation after stroke: A randomized clinical trial.

BACKGROUND: An individual's level of lower limb motor function is associated with his or her disability level after stroke, and motor improvement may lead to a better prognosis and quality of life. Data from animal models show that Qizhitongluo (QZTL) capsule facilitates recovery after focal brain injury. We aimed to validate the efficacy and safety of the QZTL capsule for promoting lower limb motor recovery in poststroke patients. METHODS: In this randomized, multicenter, double-blind, placebo- and active-controlled trial from 13 sites in China, participants with ischemic stroke and Fugl-Meyer motor scale (FMMS) scores of <95 were eligible for inclusion. Patients were randomly assigned in a 2:1:1 ratio to the QZTL group, Naoxintong (NXT) group or placebo group for 12 weeks at 15-28 days after the onset of stroke. The primary outcome was the change in the Lower Limb FMMS (FMMS-LL) score from baseline over the 12-week intervention period. RESULTS: 622 participants were randomly assigned to the QZTL group (309), NXT group (159), or placebo group (154). The FMMS-LL score increased by 4.81 points (95 % CI, 4.27-5.35) in the QZTL group, by 3.77 points (95 % CI, 3.03-4.51) in the NXT group and by 3.00 points (95 % CI, 3.03-4.51) in the placebo group at week 12. The QZTL group showed significantly larger improvements compared with the placebo group at each interview from weeks 4-12 (difference, 0.89 [0.30,1.49] at week 4, P = 0.0032; difference, 1.83[1.01,2.66] at 90 days poststroke, P < 0.0001; difference, 1.81[0.88,2.74] at week 12, P = 0.0001). CONCLUSION: The QZTL capsule is an effective treatment for lower limb motor impairment. The finding indicates that the QZTL capsule may be used as a potential new strategy for stroke rehabilitation.

Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1α.

BACKGROUND: Cumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer. However, the expression status and involvement of SNHG12 in renal cell carcinoma is still elusive. METHODS: The expression of SNHG12 was determined by q-PCR. The transcriptional regulation was interrogated by luciferase reporter assay. Cell viability was measured with CCK-8 kit. The anchorage-independent was evaluated by soft agar assay. Cell apoptosis was analyzed by Annexin V/7-AAD double staining. The migration and invasion were determined by trans-well assay and wound scratch closure. The in vivo tumor growth was monitored in xenograft mice model. Protein expression was quantified by immunoblotting. RESULTS: SNHG12 was aberrantly up-regulated in renal carcinoma both in vivo and in vitro. High expression of SNHG12 associated with poor prognosis. Deficiency of SNHG12 significantly suppressed cell viability, anchorage-independent growth and induced apoptosis. In addition, SNHG12 silencing inhibited migrative and invasive in vitro and xenograft tumor growth in vivo. Mechanistically, SNHG12 modulated HIF1α expression via competing with miR-199a-5p, which consequently contributed to its oncogenic potential. MiR-199a-5p inhibition severely compromised SNHG12 silencing-elicited tumor repressive effects. CONCLUSION: Our data uncovered a crucial role of SNHG12-miR-199a-5p-HIF1α axis in human renal cancer.

MiR-378 suppresses prostate cancer cell growth through downregulation of MAPK1 in vitro and in vivo.

Prostate cancer is one of the biggest health problems for the aging male. To the present, the roles of dysregulated microRNAs in prostate cancer are still unclear. Here, we evaluated the anti-proliferative role of miR-378 in prostate cancer. And, we found that the expression of miR-378 was significantly downregulated in clinical prostate cancer tissues. In vitro assay suggested that overexpression of miR-378-suppressed prostate cancer cell migration and invasion promoted cell apoptosis. Furthermore, we identified and validated MAPK1 as a direct target of miR-378. Ectopic expression of MAPK1 rescues miR-378-suppressed cell migration and invasion. In vivo assay demonstrated that the stably miR-378-overexpressed prostate cancer cells displayed a significantly reduction in tumor growth. Taken together, our data suggested that miR-378 may act as a potential therapeutic target against human prostate cancer.

Retraction Notice to: circFMN2 Sponges miR-1238 to Promote the Expression of LIM-Homeobox Gene 2 in Prostate Cancer Cells.

[This retracts the article DOI: 10.1016/j.omtn.2020.05.008.].

Transcriptome-based discovery of pathways and genes related to resistance against Fusarium head blight in wheat landrace Wangshuibai.

BACKGROUND: Fusarium head blight (FHB), caused mainly by Fusarium graminearum (Fg) Schwabe (teleomorph: Gibberellazeae Schwble), brings serious damage to wheat production. Chinese wheat landrace Wangshuibai is one of the most important resistance sources in the world. The knowledge of mechanism underlying its resistance to FHB is still limited. RESULTS: To get an overview of transcriptome characteristics of Wangshuibai during infection by Fg, a high-throughput RNA sequencing based on next generation sequencing (NGS) technology (Illumina) were performed. Totally, 165,499 unigenes were generated and assigned to known protein databases including NCBI non-redundant protein database (nr) (82,721, 50.0%), Gene Ontology (GO) (38,184, 23.1%), Swiss-Prot (50,702, 30.6%), Clusters of orthologous groups (COG) (51,566, 31.2%) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) (30,657, 18.5%), as determined by Blastx search. With another NGS based platform, a digital gene expression (DGE) system, gene expression in Wangshuibai and its FHB susceptible mutant NAUH117 was profiled and compared at two infection stages by inoculation of Fg at 24 and 48 hour, with the aim of identifying genes involved in FHB resistance. CONCLUSION: Pathogen-related proteins such as PR5, PR14 and ABC transporter and JA signaling pathway were crucial for FHB resistance, especially that mediated by Fhb1. ET pathway and ROS/NO pathway were not activated in Wangshuibai and may be not pivotal in defense to FHB. Consistent with the fact that in NAUH117 there presented a chromosome fragment deletion, which led to its increased FHB susceptibility, in Wangshuibai, twenty out of eighty-nine genes showed changed expression patterns upon the infection of Fg. The up-regulation of eight of them was confirmed by qRT-PCR, revealing they may be candidate genes for Fhb1 and need further functional analysis to confirm their roles in FHB resistance.

Automatic landmark detection and registration of brain cortical surfaces via quasi-conformal geometry and convolutional neural networks.

In medical imaging, surface registration is extensively used for performing systematic comparisons between anatomical structures, with a prime example being the highly convoluted brain cortical surfaces. To obtain a meaningful registration, a common approach is to identify prominent features on the surfaces and establish a low-distortion mapping between them with the feature correspondence encoded as landmark constraints. Prior registration works have primarily focused on using manually labeled landmarks and solving highly nonlinear optimization problems, which are time-consuming and hence hinder practical applications. In this work, we propose a novel framework for the automatic landmark detection and registration of brain cortical surfaces using quasi-conformal geometry and convolutional neural networks. We first develop a landmark detection network (LD-Net) that allows for the automatic extraction of landmark curves given two prescribed starting and ending points based on the surface geometry. We then utilize the detected landmarks and quasi-conformal theory for achieving the surface registration. Specifically, we develop a coefficient prediction network (CP-Net) for predicting the Beltrami coefficients associated with the desired landmark-based registration and a mapping network called the disk Beltrami solver network (DBS-Net) for generating quasi-conformal mappings from the predicted Beltrami coefficients, with the bijectivity guaranteed by quasi-conformal theory. Experimental results are presented to demonstrate the effectiveness of our proposed framework. Altogether, our work paves a new way for surface-based morphometry and medical shape analysis.

Combination treatment with FAAH inhibitors/URB597 and ferroptosis inducers significantly decreases the growth and metastasis of renal cell carcinoma cells via the PI3K-AKT signaling pathway.

Ferroptosis, a nonapoptotic form of programmed cell death characterized by significant iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating the potential of combinational strategies for treating cancer in the future. In this study, we explored the combinational effects of lipid metabolism compounds and ferroptosis inducers on renal cell carcinoma (RCC) cells. We found potent synergy of the fatty acid amide hydrolase (FAAH) inhibitor URB597 with ferroptosis inducer (1S, 3R)-RSL3 (RSL3) in inhibiting the growth and metastasis of RCC cells both in vitro and in vivo via induction of G1 cell cycle arrest and promotion of the production of lipid peroxides, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and cytosolic reactive oxygen species (ROS). In addition, inhibition of FAAH increased the sensitivity of RCC cells to ferroptosis. Genome-wide RNA sequencing indicated that the combination of URB597 and RSL3 has more significant effects on regulation of the expression of genes related to cell proliferation, the cell cycle, cell migration and invasion, and ferroptosis than either single agent alone. Moreover, we found that combinational treatment modulated the sensitivity of RCC cells to ferroptosis via the phosphatidylinositol 3 kinase (PI3K)-AKT signaling pathway. These data demonstrate that dual targeting of FAAH and ferroptosis could be a promising strategy for treating RCC.

Overexpression of RIN1 associates with tumor grade and progression in patients of bladder urothelial carcinoma.

Ras and Rab interactor 1 (RIN1) is an effector of H-Ras, which plays an important role in the development and progression of carcinomas, but it has not been reported in bladder cancer. Hence, the association of RIN1 expression with prognosis of bladder urothelial carcinoma (UC) was examined. RIN1 mRNA and protein expression in 20 paired UCs and the adjacent normal tissues was detected by quantitative reverse transcription polymerase chain reaction and Western blot. The expression of RIN1 protein in 96 specimens of UCs and 22 specimens of adjacent normal bladder tissues were analyzed by immunohistochemistry. The overall survival (OS) was assessed by univariate and multivariate analysis. Moreover, the progression-free survival (PFS) and recurrence-free survival (RFS), classified by the clinicopathologic features with RIN1 expression, were assessed by multivariate analysis. RIN1 mRNA and protein level was higher in UCs than in the adjacent normal tissues (P < 0.01). Enhanced RIN1 immunoexpression was associated with high histologic grades (P = 0.046), cancer progression (P = 0.047) as well as Ki-67 expression (P = 0.023). Furthermore, the 5-year survival rate was 29% in the subgroup with high level of RIN1 expression, while it was 43% in the subgroup with normal level of RIN1 expression (P < 0.05). Importantly, RIN1 level was revealed as the significant independent prognostic factor for death (P = 0.023) and progression (P = 0.003), but a weak contribution for recurrence (P = 0.063). Collectively, RIN1 expression could be a potential prognostic predictor for UC patients.

A fast-neutron induced chromosome fragment deletion of 3BS in wheat landrace Wangshuibai increased its susceptibility to Fusarium head blight.

Fusarium head blight (FHB), also called wheat scab, is an important disease in warm and humid regions worldwide, which not only reduces crop yield and grain quality, but also is a major safety concern in food and feed production due to mycotoxin contamination. Growing wheat cultivars with FHB resistance is one of the most economical and effective means to control the disease. Chinese wheat landrace Wangshuibai is an important resistant source from southern China. Several resistance QTLs in Wangshuibai were identified and mapped on chromosomes or chromosomal arms including 3BS, 4B, 6BS, 7AL, etc. In the present research, a mutant with increased FHB susceptibility, designated as NAUH117, was identified from the M(1) progenies of Wangshuibai irradiated by fast neutron. Genetic analysis of the F (1), F (2), and F (2:3) families from the reciprocal cross of Wangshuibai and NAUH117 indicated that NAUH117 was a recessive mutant. Genome-wide molecular marker analysis identified a deletion in the short arm of chromosome 3B of NAUH117, spanning the region of FL0.57 to FL1.00 that covers the locus of Fhb1 previously mapped on chromosome 3BS. Further molecular cytogenetics characterization by bi-color fluorescence in situ hybridization using three repetitive sequences, pSc119.2, pAs1 and GAA-satellite indicated that a multiple chromosome rearrangements occurred in chromosomes 3B, 6B, 3D, 4D, and 3A of the mutant. During these processes, a distal fragment of chromosome arm 3BS was eliminated, which is confirmed by molecular marker analysis. Four markers covered the deletion fragment were used for analysis of the F (2) population. The result showed that the 3BS deletion was only present in the susceptible plants, indicating that the deletion of 3BS fragment in NAUH117 increased susceptibility to FHB. The susceptible mutant will be valuable for the validation of the contribution of the resistant QTL located on 3BS, and for the characterization of the molecular mechanisms of FHB resistance in Wangshuibai.

[Effects of inhibiting RhoA by Stealth RNA on high glucose-induced RhoA/ROCK signaling pathway in human mesangial cells].

OBJECTIVE: To observe the effect of small interference RNA (Stealth RNAiTM siRNA) of RhoA on the inflammatory response and fibrosis in human mesangial cell (HMC) and explore the role of RhoA/ROCK signaling pathway in the process of diabetic nephropathy. METHODS: Synchronized HMC were divided into several groups. Lipofectamine(TM)2000 was employed to transfect RhoA-siRNA and RhoA-negative siRNA into the above cells. RhoA-siRNA could inhibit the expression of RhoA. The expressions of RhoA, ROCK-I, fibronectin (FN), connective tissue growth factor (CTGF) and tumor necrosis factor-alpha (TNF-α) were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and ELISA (enzyme-linked immunosorbent assay). RESULTS: (1) The expressions of RhoA, ROCK-I and CTGF mRNA were inhibited by RhoA siRNA transfection in high glucose-induced HMC. The expression of each mRNA was reduced 26% - 60% as compared with the high glucose-induced group (P < 0.05); (2) After RhoA siRNA transfection and culturing with high glucose for 48 h, FN, the secretions of CTGF and TNF-α significantly declined [FN: (1.99 ± 0.04) mg/L vs. (4.31 ± 0.13) mg/L, CTGF:(4.98 ± 0.17) mg/L vs. (6.06 ± 0.09) mg/L; TNF-α: (61.17 ± 2.59) ng/L vs.(91.76 ± 2.27) ng/L, all P < 0.05]. The levels of FN and CTGF almost decreased to those of normal glucose-induced HMC. CONCLUSION: The levels of FN, CTGF and TNF-α in high glucose-induced HMC may be lowered by inhibiting RhoA through RNA interference and reducing the accumulation of extracellular matrix, glomerular fibrosis and inflammation. Thus it provides a new intervention target for the prevention of diabetic nephropathy.

Standard Operating Procedures for Chinese Medicine Data Monitoring Committees of Clinical Studies.

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

[Establishment of non-parametric probabilistic model for evaluation of Chinese dietary exposure].

OBJECTIVE: To establish a non-parametric probabilistic model for evaluation of Chinese dietary exposure and to improve the assessment accuracy while integrating into the global risk assessment on food safety. METHODS: Contamination data was from the national food contamination monitoring program during 2000 - 2006, including heavy metals, pesticides and mycotoxins, amounting to 135 contaminants with 499 commodities and 487 819 samples. Food consumption data was obtained from the national diet and nutrition survey conducted in 2002 with three consecutive days by 24-hour recall method, and 66 172 consumers were included. Monte Carlo simulation was applied to derive the intake distribution, and the uncertainty of each percentile was estimated using the Bootstrap sampling. RESULTS: Different non-parametric probabilistic models for dietary exposure evaluation on heavy metals, pesticides and some of the toxins were established for Chinese people, and intake distributions with 95% confidence intervals of these contaminants were estimated. Taking acephate as an example, the results of its model shows that, for the 7 - 10 year-old children, the median dietary exposure in urban and rural areas were 1.77 microg x kg(-1) x d(-1) and 2.48 microg x kg(-1) x d(-1) respectively, with a 95% confidence interval of (1.59 - 2.06) microg x kg(-1) x d(-1) and (2.33 - 2.80) microg x kg(-1) x d(-1) respectively. CONCLUSION: The non-parametric probabilistic model can quantify the variability and uncertainty of exposure assessment and improve the assessment accuracy.

circFMN2 Sponges miR-1238 to Promote the Expression of LIM-Homeobox Gene 2 in Prostate Cancer Cells.

Circular RNAs (circRNAs) regulate gene expression in different malignancies. However, the molecular mechanisms that link circRNAs with the tumorigenesis of prostate cancer (PCa) are not well understood. In the present study, we attempted to provide a novel basis for targeted therapy for PCa from the aspect of circRNA-microRNA (miRNA)-mRNA interaction. We investigated the expression of circRNAs in 5 paired PCa tissues and adjacent non-tumor tissues by microarray analysis. We focused on hsa_circ_0005100, which is located on chromosome 1 and derived from FMN2, and thus we named it circFMN2. The qRT-PCR was used to detect circFMN2 and target miRNA expression in PCa tissues and cell lines. Biological functional experiments were performed to detect the effects of circFMN2 on the biological behavior of PCa cells in vivo and in vitro. Bioinformatic analysis was utilized to predict potential miRNA target sites on circFMN2. High expression of circFMN2 was associated with PCa progression. Function assays revealed that knockdown of circFMN2 significantly reduced PCa cell growth in vitro and in vivo. Finally, we found that circFMN2 acts as a competing endogenous RNA (ceRNA) for miR-1238 to regulate LIM-homeobox gene 2 (LHX2) expression. circFMN2 regulates the miR-1238/LHX2 axis to promote PCa progression.

Establish a Real-time Responsible Home Quarantine and Monitoring Management mHealth Platform.

Due to the global spreading of the COVID-19 virus, countries all over the world are faced with the need to conduct centralized quarantine or home quarantine for "persons who have been in contact with individuals diagnosed with the COVID-19 virus" and "visitors who have travel histories via COVID-19 hot zones". We have presented the community home quarantine service platform design that was utilized in Nanjing, China when the first wave of citizens returns to work after the Chinese New Year holidays on 10th Feb 2020. The main functions of the home quarantine monitoring system include (1) community grid management,(2) GPS positioning application in home isolation movement management,(3) Bluetooth body temperature patch data transmission integration, (4) health assessment scale (physical and mental health state) and (5) multilingual language options.

[Regression on order statistics and its application in estimating nondetects for food exposure assessment].

OBJECTIVE: To explore the application of regression on order statistics (ROS) in estimating nondetects for food exposure assessment. METHODS: Regression on order statistics was adopted in analysis of cadmium residual data set from global food contaminant monitoring, the mean residual was estimated basing SAS programming and compared with the results from substitution methods. RESULTS: The results show that ROS method performs better obviously than substitution methods for being robust and convenient for posterior analysis. CONCLUSION: Regression on order statistics is worth to adopt,but more efforts should be make for details of application of this method.

Developing Mobile Health Management System for Patients with Musculoskeletal Tumor.

This research provided a postoperative system for osteosarcoma which is seperated into two parts, Bone Patient and Bone Care. We focus on using smartphone features and proper interface design to facilitate self-monitoring, health analysis, and to make appointments. It achieves the effects of shared decision making (SDM). During the two weeks of research, we achieved satisfied with 4.03 ± 0.67 TAM score.

MiR-345 suppresses proliferation, migration and invasion by targeting Smad1 in human prostate cancer.

INTRODUCTION: The roles of dysregulated microRNAs in prostate cancer metastasis are still unknown. In this study, we found that the expression of miR-345 was significantly downregulated in prostate cancer and clinical prostate cancer tissues. MATERIALS, METHODS AND RESULTS: Overexpression of miR-345 in prostate cancer cells suppressed proliferation, migration and invasion. Using nude mice model, we revealed that miR-345 inhibits the growth of prostate cancer cells in vivo and in vitro. Furthermore, we identified and validated Smad1 as a direct target of miR-345. Ectopic expression of Smad1 without its 3'-UTR rescued miR-345-induced cell migration and invasion inhibition. CONCLUSION: Taken together, our data suggest that miR-345 exerts a suppressive effect on prostate cancer proliferation, invasion and migration through downregulation of Smad1.

[Investigation and confirmatory factor analysis of information collected with the four diagnostic methods in patients with bronchial asthma].

OBJECTIVE: To investigate the information acquired through the four diagnostic methods of traditional Chinese medicine in patients with bronchial asthma, and to classify the syndrome types. METHODS: Four hundred and thirty patients with bronchial asthma were randomly investigated. The information acquired through the four diagnostic methods was recorded and the database was established by Amos software, and then the data were analyzed by confirmatory factor analysis (CFA). RESULTS: After analyzing the data with 4 factors, 5 factors and 6 factors, we found that the results of CFA with 6 factors were in accordance with clinical practical experience. CONCLUSION: According to the results of CFA with 6 factors and with the standard regression coefficient 0.4 as primary and secondary critical points, the syndromes in patients with bronchial asthma can be classified into 5 types, which are syndromes of cold fluid retained in lung, phlegm-heat obstructing lung, wind-phlegm blocking lung, qi deficiency of lung and kidney and qi deficiency of spleen.

Dynamic Changes in Phenotypic Groups in Patients with Stable Angina Pectoris after Treatment with Xinxuekang Capsule: A Randomized Controlled Trial.

OBJECTIVE: To reveal the cutoff point and influencing factors in the dynamic change in phenotypic group in patients with stable angina pectoris (SAP) after Xinxuekang capsule treatment. METHODS: Five hundred and seventy-six SAP patients were randomly assigned to receive Xinxuekang (XXK) capsules or Compound Danshen (CDS) tablets for 8 weeks. Global similarity degree analysis and nonlinear mixed effects modeling (NONMEM) were employed to reveal the cutoff points and influencing factors in dynamic changes in the SAP phenotypic group. The phenotypic group was defined as the six phenotypes in SAP, including angina, choking sensation in the chest, palpitations, dark purple lips, ecchymosis on the tongue, and fine-choppy pulse, which were quantitatively evaluated on Days 0, 14, 28, 42, and 56. RESULTS: Variation in the six individual phenotypes and distribution of the SAP phenotypic profile were similar between the two experimental groups, but cutoff points for changes in the SAP phenotypic group were 7.28 and 10.73 weeks in XXK and CDS groups, respectively. Degree of severity of SAP as well as study site significantly affected the tendency for change in the SAP Xueyu Zheng in both XXK and CDS treatment groups. Different Chinese patent drugs affected the tendency for change in phenotypic group in patients with SAP. XXK was superior to CDS in controlling a clinical phenotypic group. CONCLUSION: Based on global similarity degree analysis and NONMEM, the cutoff point and influencing factors in phenomic variation of SAP may be determined, to improve the development and modification of treatment regimens.