Plasma microRNAs as potential biomarkers in diagnosis of acute venous thromboembolism.

OBJECTIVE: To assess the potential use of plasma microRNAs (miRNAs) in diagnosis of acute venous thromboembolism (VTE). METHODS: Using BGISEQ-500 sequencing technology, we analyzed the miRNA profile of paired plasma samples from the acute and chronic phases of four patients with unprovoked VTE. Using real-time quantitative polymerase chain reaction (RT-qPCR), we verified nine upregulated named miRNAs in the acute phase in the plasma samples of 54 patients with acute VTE and 39 controls. We then compared the relative expression of the 9 candidate miRNAs between the acute VTE and control group, and plotted the receiver operating characteristic (ROC) curves of the differentially expressed miRNAs. We chose the miRNA with the greatest area under curve (AUC) to evaluate the effect of miRNA on coagulation and platelet function in the plasma samples of 5 healthy volunteers. RESULTS: The plasma levels of miR-374b-3p, miR-660-5p, miR-378a-3p, miR-425-5p, miR-3613-5p, miR-130b-3p, miR-183-5p, and miR-103b were higher in patients with acute VTE than in the controls, with AUCs of 0.6776, 0.6614, 0.6648, 0.6885, 0.8048, 0.6871, 0.7298, and 0.7498, respectively, and P values of 0.0036, 0.0081, 0.0069, 0.0020,<0.0001, 0.0022, 0.0002, and < 0.0001, respectively. There were no significant differences in miR-193b-5p level between the acute VTE group and the control group. Fibrinogen (Fib), thrombin- antithrombin complex (TAT), tissue plasminogen activator-inhibitor complex (t-PAIC), and TAT/plasmin-α2-plasmin inhibitor complex (PIC) were decreased in the miR-3613-5p group when compared with the control group (P < 0.05) and the mean platelet aggregation rate was increased in the miR-3613 group (P < 0.05). CONCLUSION: miRNAs can be potential biomarkers for diagnosing acute VTE, and miR-3613-5p may be involved in the formation, coagulation, and platelet functions in acute VTE.

A multicenter clinical study on parent-implemented early intervention for children with global developmental delay.

Objective: Early identification and intervention for children with global developmental delay (GDD) can significantly improve their prognosis and reduce the possibility of developing intellectual disability in the future. This study aimed to explore the clinical effectiveness of a parent-implemented early intervention program (PIEIP) for GDD, providing a research basis for the extended application of this intervention strategy in the future. Methods: During the period between September 2019 and August 2020, children aged 3 to 6 months diagnosed with GDD were selected from each research center as the experimental group and the control group. For the experimental group, the PIEIP intervention was conducted for the parent-child pair. Mid-term and end-stage assessments were performed, respectively, at 12 and 24 months of age, and parenting stress surveys were completed. Results: The average age of the enrolled children was 4.56 ± 1.08 months for the experimental group (n = 153) and 4.50 ± 1.04 months for the control group (n = 153). The comparative analysis of the variation in the progress between the two groups by independent t-test showed that, after the experimental intervention, the developmental quotient (DQ) of locomotor, personal-social, and language, as well as the general quotient (GQ) of the Griffiths Mental Development Scale-Chinese (GDS-C), the children in the experimental group demonstrated higher progress than those in the control group (P < 0.05). Furthermore, there was a significant decrease in the mean standard score of dysfunctional interaction, difficult children and the total level of parental stress in the term test for the experimental groups (P < 0.001 for all). Conclusions: PIEIP intervention can significantly improve the developmental outcome and prognosis of children with GDD, especially in the areas of locomotor, personal-social, and language.

Clinical characterization of Lamb-Shaffer syndrome: a case report and literature review.

BACKGROUND: Lamb-Shaffer syndrome (LAMSHF, MIM 616,803) is a rare neurodevelopmental disorder due to haploinsufficiency of SOX5. Furthermore, studies about the clinical features of LAMSHF patients with same allele of c.1477C > T (p. R493*) are very limited. CASE PRESENTATION: We analyzed the phenotypes of one of our cases and two previously reported cases with c.1477C > T (p. R493*), and reviewed the correlating literature. A de novo heterozygous variation c.1477C > T (p. R493*) in SOX5 was identified in a 4 years and 2 months old boy with global development delay by trio-based whole exome sequencing. We compared our case and previously 2 cases reported with recurrent variation, the overlapping clinical features are global developmental delay or intellectual disability, language delay and scoliosis, but their other clinical characteristics are different. CONCLUSIONS: This study suggests that the clinical features of LAMSHF patients with recurrent variations in the SOX5 gene are different. It is suggested that the LAMSHF-related SOX5 gene should be screened and included as one of the candidate genes for neurodevelopmental disorders of unknown etiology.

Enhanced Alkaline Oxygen Evolution Using Spin Polarization and Magnetic Heating Effects under an AC Magnetic Field.

Renewable electricity from splitting water to produce hydrogen is a favorable technology to achieve carbon neutrality, but slow anodic oxygen evolution reaction (OER) kinetics limits its large-scale commercialization. Electron spin polarization and increasing the reaction temperature are considered as potential ways to promote alkaline OER. Here, it is reported that in the alkaline OER process under an AC magnetic field, a ferromagnetic ordered electrocatalyst can simultaneously act as a heater and a spin polarizer to achieve significant OER enhancement at a low current density. Moreover, its effect obviously precedes antiferromagnetic, ferrimagnetic, and diamagnetic electrocatalysts. In particular, the noncorrected overpotential of the ferromagnetic electrocatalyst Co at 10 mA cm-2 is reduced by a maximum of 36.6% to 243 mV at 4.320 mT. It is found that the magnetic heating effect is immediate, and more importantly, it is localized and hardly affects the temperature of the entire electrolytic cell. In addition, the spin pinning effect established on the ferromagnetic/paramagnetic interface generated during the reconstruction of the ferromagnetic electrocatalyst expands the ferromagnetic order of the paramagnetic layer. Also, the introduction of an external magnetic field further increases the orderly arrangement of spins, thereby promoting OER. This work provides a reference for the design of high-performance OER electrocatalysts under a magnetic field.

[Systematic review and Meta-analysis of efficacy and safety of Huachansu in treating cancer-related pain].

To evaluate the effectiveness and safety of Huachansu in the treatment of cancer-related pain,four Chinese databases( CNKI,VIP,Wan Fang,Sino Med) and three English databases( Cochrane Library,Medline,PubMed) were systematically and comprehensively retrieved since the establishment of each database to October 2018. Randomized controlled trials( RCTs) for the treatment of cancer-related pain with Huachansu were screened out according to pre-established inclusion criteria and exclusion criteria. Rev Man5. 3 software was used for Meta-analysis. A total of 241 articles were retrieved,and finally 10 studies were included. The total sample size was 1 293,including 648 in the experimental group and 645 in the control group. The overall quality of the included studies was generally low. The results of Meta-analysis showed that Huachansu combined with Western medicine acesodynes was superior to the single use of Western medicine acesodynes in the treatment of short-term pain relief,improvement of quality of life and reduction of constipation,nausea and vomiting,dizziness,drowsiness,anorexia and other adverse reactions. And it also has the advantage of a shorter onset time and longer duration time of analgesia,but cannot reduce the incidence of dysuria. Based on the findings,Huachansu had a certain effect in the treatment of cancer-related pain,and a significant positive effect on the improvement of quality of life and the reduction of adverse reactions. No serious adverse reactions occurred. However,due to the small number of studies included,the low quality of the included studies,published biases and other restrictions,the evidence in this study has a low quality,and the conclusion shall be adopted with caution. The effectiveness and safety of Huachansu in the treatment of cancer-related pain remained to be further confirmed in the future with a well-designed,rigorous,and standardized report,with a large sample size,multiple centers,and sufficient follow-up time for randomized controlled trials.

Effect of Compound Zhebei Granule () combined with chemotherapy on surface markers of leukemia stem cell in patients with acute myeloid leukemia.

OBJECTIVE: To observe the effects of Compound Zhebei Granule (, CZBG) combined with chemotherapy on surface markers of leukemia stem cell (LSC) in the bone marrow of patients with acute myeloid leukemia (AML). METHODS: Seventy-eight patients with AML received bone marrow aspiration and the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) cells were tested using flow cytometry method. A total of 24 refractory or relapsed AML patients were enrolled and treated with one cycle of standard chemotherapy combined with CZBG. Bone marrow samples were obtained before and after treatment, and the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) cells were examined by flflow cytometry. RESULTS: Compared with refractory or relapsed AML patients, patients achieved remission had a significant lower percentage of CD34(+) CD123(+) cells(P<0.01) and CD33(+) CD123(+) cells (P<0.01), indicating that controlling the LSC percentage may be important for patients with AML to achieve sustainable remission. Compared with those before treatment, the expression levels of CD34(+) CD123(+) were significantly decreased after CZBG combined with chemotherapy treatment (P<0.01). The percentages of CD34(+) CD123(+) cells and CD33(+) CD123(+) in patients achieving complete remission after CZBG combined with chemotherapy treatment were both significantly lower than those in patients with nonremission (P<0.01). CONCLUSION: CZBG combining chemotherapy could reduce the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) LSC, which might improve the clinical efficacy of refractory or relapsed AML.

[Expression of biomarkers related with bone marrow cells in patients with acute myelogenous leukemia].

This study was aimed to investigate the expression of biomarkers (PTEN, mTOR, NF-kB, CD44, PI3K) related with bone marrow cells in patients with acute myelogenous leukemia. The immunohistochemical method was used to detect the expression of PTEN, mTOR, NF-kB, CD44, PI3K in 20 patients. The AML patients were divided into remission group and non-remission group after calculating the percentage of leukemia cells in bone marrow. The results showed that by optical microscopy, the positive expression rates of PTEN, mTOR, NF-kB, CD44 and PI3K in remission group were 33.3%, 33.3%, 77.8%, 22.2%, 0, respectively; meanwhile, in non-remission group, the positive expression rates of above-menthioned biomarkers were 63.6%, 18.2, 90.9, 63.6%, 0, respectively. The percentage and mean OD for PTEN and CD44 were statistically different between the two groups (P < 0.05), but for mTOR, NF-kB and PI3K were not statistically differenly (P > 0.05). It is concluded that the high expression of PTEN and CD44 can be regarded as an important index for diagnosis and prognosis in acute myelogenous leukemia.

Evaluating autism in a Chinese population: the Clinical Autism Diagnostic Scale.

BACKGROUND: The purpose of this study was to report on the psychometric measures and discriminatory function of a new diagnostic test for autism spectrum disorders, the Clinical Autism Diagnostic Scale (CADS). METHODS: The CADS was used to test 216 children in the study, including 86 with low-functioning autism spectrum disorders (ASD), 16 children with high-functioning ASD, 16 with pervasive developmental disorder, not otherwise specified, 7 with Asperger syndrome, 65 with typical development, 11 children with language impairments and 15 with intellectual disabilities. Ages ranged from 38-73 months. Behaviors for the groups were compared across seven domains. RESULTS: The results indicated the instrument was reliable, valid, and successfully differentiated the different groups of children with and without autism. All ASD groups were found to display difficulties in the domains of sensory behaviors and stereotyped behaviors. The play and social domains were found to measure similar underlying concepts of behaviors, while the receptive language and expressive language domains were also found to measure similar underlying-language concepts. The group of children diagnosed as having low-functioning autism performed less well on all tested domains in the instrument than did the other three groups of children with ASD, and these other three groups each also presented unique patterns of behaviors and differed on individual domains. CONCLUSIONS: CADS is a reliable and valid test. It successfully differentiates the abilities of children with ASD at different levels of functioning.

[Clinical observation of Compound Zhebei Granule in improving the survival time of refractory acute leukemia patients].

OBJECTIVE: To observe the effects of Compound Zhebei Granule (CZG) as the main intervention and treatment protocol on the sustained remission time, the median survival time, the relapse rate, and the mortality rate of refractory acute leukemia (RAL) patients. METHODS: The RAL subjects, who were completely released after one standard chemotherapeutic course of the National Support Scheme (Chinese medicine interventions and standard chemotherapy of Western medicine in the peri-chemotherapy) were followed-up to get knowledge of the sustained remission time, the survival time, the relapse rate, and the morbidity. RESULTS: Totally 41 patients were finally accounted into the statistics, 20 in the treatment group and 21 in the control group. The sustained remission time was 172 days in the treatment group and 115 days in the control group, the median survival time was 363 days and 201 days respectively. The relapse rate of the treatment group within 3 months, 6 months,1 year, and the total relapse rate was 30.0%, 50.0%, 70.0%, and 90.0%, respectively, lower than that of the control group (being 42.8%, 76.2%, 90.5%, 90.5%, respectively). The mortality rate of the treatment group was 80.0%, 5.7% lower than that of the control group (85.7%). CONCLUSION: CZG could lengthen the sustained remission time for RAL patients, elevate their survival time, and reduce the relapse rate and the mortality rate.

[Mesenchymal stem cells release membrane microparticles in the process of apoptosis].

Though mesenchymal stem cells (MSC) have been clinically used to repair a variety of damaged tissues, the underlying mechanisms remain elusively as the majority of the ex vivo expanded MSC die shortly after transplantation. To explore the mechanism in which the death cells play tissue repair effect, apoptosis of rat bone marrow MSC was induced by culturing cells in the conditions of hypoxia or/and serum-free medium, and the subcellular structures in the supernatants were analyzed. The results showed that apoptosis occurred in the presence of either hypoxia or serum-free condition as well, and the apoptotic proportion reached up to (17.44 ± 2.15) after the cells were treated by hypoxia plus serum free culture for 72 hours. The flow cytometric analysis of the sub-cellular substances harvested by ultracentrifugation of the supernatants found that the MSC released substantial amount of membrane microparticles into the supernatants, which expressed CD29, CD44A and Annexin-V-binding phosphatidylserine. It is concluded that the MSC can release membrane microparticles after induction, the amount of these membrane microparticles was around 15-fold of the parent cell numbers. The membrane microparticles is the mediators in the cross-talk between the transplanted cells and their surrounding tissues. This study provides some novel information for the mechanisms of MSC therapy.

[Clinical study on effect of compound granule prescription of thunberg fritillary bulb in relieving post-chemotherapy bone marrow suppression in RAL patients].

OBJECTIVE: To observe the effect of compound granule prescription of thunberg fritillary bulb in relieving the post-chemotherapy bone marrow depression in refractory acute leukemia (RAL) patients. METHOD: Two hundred and thirty eight RAL patients collected from 7 third-grade class-A hospitals were randomly divided into the treatment group and the control group. Both groups were treated with conventional chemotherapy. They were administered with compound granule prescription of thunberg fritillary bulb or placebo three days before chemotherapy for consecutively 14 days. A standardized chemotherapy course was a treatment cycle. The changes in peripheral hemogram of two groups were detected before and after chemotherapy. RESULT: After the treatment, the white blood cell counts of the two groups were significantly different (P < 0.05), but there was no statistical significance in qualitative comparison. Before and after the treatment, the difference of the white cell counts of the two groups detected had significant statistics (P < 0.05). The white cell counts of both groups declined after chemotherapy, but the treatment group decreased more significantly than the control group. Before and after the treatment, there were no statistical significances in quantitative and qualitative comparisons both in HGB and PLT. After the treatment, HGB and PLT contents of both groups declined, but there was no statistical difference between the two groups. CONCLUSION: Compound granule prescription of thunberg fritillary bulb can relieve the bone marrow suppression in RAL patients caused by the chemotherapy, which is mainly reflected by the slowdown of reduction in white blood cells.

[Study on the compound Fritilaria thunbergii Miq particles to the subcellular accumulation ability and inducing apoptosis of K562/A02 cells].

OBJECTIVE: To investigate the effects of the Compound Fritillaria thunbergii Miq Particles (CFMP) to the sub-cellular accumulation ability and inducing the apoptosis of K562/A02 cells, explore the mechanism of the CFMP reserve the multi-drug resistance of K562/A02 cells. METHODS: Forty Wistar male rats were divided into the blank-serum group, the adriamycin (ADR) containing serum group, the CFMP high dose [8 g/ (kg x d)] group, the CFMP medium dose [4 g/(kg x d)] and the CFMP low dose [2 g/(kg x d)] group. The effects of different time of drug contained serum on sub-cellular accumulation of ADR and Rh123 were quantitative detected by flow cytometry. Cells apoptosis induced by different concentrations of CFMP contained serum were detected by flow cytometry with Annexin-V/PI staining method. RESULTS: Different concentrations of CFMP contained serum can inhibit the descend trend of the ADR and Rh123 fluorescence accumulation curve of K562/A02 cells with dose-dependence. The high-dose group showed superior inhibition than the other. Annexin-V/PI staining method exhibited that the rate of apoptosis of K562/A02 cells in blank-serum group was 1.40%. Different concentrations of CFMP contained serum induced the apoptosis of K562/A02 cells showed a dose-dependent manner, that is medium dose group presented 24.60% apoptosis, high dose group presented 11.21% apoptosis, and low dose group presented 5.71% apoptosis. CONCLUSION: CFMP can inhibit the descend trend of the ADR and Rh123 fluorescence accumulation curve of K562/A02 cells, induce the apoptosis of K562/A02 cells to achieve the reverse intention of multi-drug resistance.

[Autologous skeletal myoblast transplantation improves hemodynamics dogs with chronic heart failure dogs].

OBJECTIVE: To test the effects of autologous skeletal myoblast transplantation on the hemodynamics in dogs with coronary microembolization-induced chronic heart failure (CHF). METHODS: CHF models were successfully induced in 19 dogs and divided into ASMT group (n=9) and control group (n=10). The myoblasts were injected into the embolized region in the 9 dogs of the ASMT group, and saline was injected in the control dogs, and the hemodynamics of the dogs were evaluated 5 weeks after the injections. RESULT: Compared with saline injection, ASMT significantly increased dP/dtmax, MAP and LVSP (P<0.05) and decreased LVEDP (P<0.05) 5 weeks after myoblast transplantation. Desmin and Brd-U immunofluorescent staining showed myoblast survival at the injected sites in the dogs. CONCLUSION: ASMT provides mild improvements in the hemodynamics of dogs with CHF.

[Effects of compound Zhe-Bei granule (CZBG) combined with doxorubicin on expression of membrane transport proteins in K562/A02 cell xenografts].

This study was purposed to investigate the effects of compound Zhe-Bei granule (CZBG) combined with doxorubicin on expressions of P-gp, MRP, LRP in K562/A02 cell xenografts. Tumor xenograft model were established by injecting the multidrug resistant cell line K562/A02 in the axillary flank of BALB/c-nu-nu mice. CZBG-intragastric administration and doxorubicin-intraperitoneal injection in combination were given to the BALB/c-nu nude mice. The tumor xenografts were made into slice after the dissection, and the expression of P-gp, MRP, LRP in K562/A02 tumor xenografts in mice were investigated by immunohistochemical technique. The integral optical density (IOD) of P-gp, MRP, LRP in K562/A02 tumor xenografts were measured by Image Pro Plus 6.0. The results showed that as compared with the doxorubicin alone, the combination of the doxorubicin and CZBG with high, middle and low dosage could decrease IOD of P-gp, MRP in K562/A02 tumor xenografts with statistical significance (p < 0.05). The LRP expression in K562/A02 tumor xenografts was not observed in five groups. It is concluded that the combination of CZBG with doxorubicin decreases the expressions of P-gp, MRP in K562/A02 tumor xenografts of mice.

[Effect of compound Zhe-Bei granule (CZBG) combined with doxorubicin on cell apoptosis and expression of related proteins in K562/A02 multidrug resistance tumor xenografts in mice].

This study was purposed to investigate the effects of compound Zhe-Bei granule (CZBG) combined with doxorubicin (Dox) on the expression of BCL-2, BAX and cell apoptosis rate in K562/A02 multidrug resistant tumor xenografts. Tumor xenograft model was established by injecting the K562/A02 cells into the axillary flank of BALB/c nude mice. The cell apoptosis rate of xenografts was detected by flow cytometry with Annexin V-FITC/PI staining. The expressions of BCL-2 and BAX in xenografts were measured by immunohistochemistry staining. The value of integral optical density (IOD) was calculated according to staining image on slide. The results indicated that as compared with normal saline control group and Dox group, the high, middle, low dose of CZBG combined with Dox could increase the cell apoptosis rate of tumor xenografts with statistical significance (p < 0.05); and could decrease the IOD value of BCL-2 and increase the IOD value of BAX in xenografts with statistical significance (p < 0.05). It is concluded that CZBG combined with Dox can enhance the apoptosis rate in K562/A02 cells, down-regulate the expression of BCL-2 and up-regulate the expression of BAX, thereby, can reverse the multidrug resistance of K562/A02 cells by decreasing the ratio of BCL-2/BAX.

Clinical research of compound zhebei granules for increasing the therapeutic effect of chemotherapy in refractory acute leukemia patients.

OBJECTIVE: To observe the effects of Compound Zhebei Granules (CZG) in chemotherapy for refractory acute leukemia. METHOD: Using a randomized, double-blind and multi-central concurrent control clinical research project, the patients conformed with the diagnostic criteria, according to the drug randomized method, were divided into a CZG group and a control group. The patients of the two groups respectively took the observation drug or a placebo 3 days before chemotherapy, and the therapeutic effects were evaluated after one course of chemotherapy. According to the clinical research project, 137 patients were enrolled, including 71 cases in the CZG group and 66 cases in the control group. RESULTS: The clinical complete remission (CR) rate was 42.3% in the CZG group with a total effective rate of 73.2%, and it was 25.8% in the control group with a total effective rate of 53.0%, showing a statistically significant difference between the two groups (P < 0.05). CONCLUSION: CZG can increase the clinical remission rate for refractory acute leukemia during chemotherapy.

[Effects of Compound Zhebei Granule plus doxorubicin on mdr 1 gene expression in nude mice with K562/A02 tumor xenografts].

OBJECTIVE: To investigate the effects of Compound Zhebei Granule (CZBG), a compound traditional Chinese herbal medicine, combined with adriamycin (ADM) on mdr 1 gene expression in tumor xenografts in nude mice. METHODS: A tumor xenografts model was established by subcutaneously injecting multidrug resistance cell line K562/A02 into the axillary flank of BALB/c-nu mice. Sixty tumor-bearing nude mice were divided into untreated group, ADM group and high-, medium-, and low-dose CZBG plus ADM groups. The nude mice in the CZBG plus ADM groups were intragastrically administered with CZBG once per day and intraperitoneally injected with ADM once every other day. The nude mice in the untreated group and the ADM group were administered with normal saline or ADM respectively. The course of treatment was continuous for 14 days. The weight of tumor xenografts was measured after treatment and the inhibition rate of tumor xenografts was calculated. The mdr 1 gene expression in tumor xenografts was tested by quantitative polymerase chain reaction method. RESULTS: Compared with the untreated group, CZBG (high-, medium- and low-dose) plus ADM could significantly decrease the weight of tumor xenografts in nude mice (P<0.05). Compared with ADM, high- and medium-dose CZBG plus ADM could decrease the weight of tumor xenografts in nude mice with statistical significance (P<0.05). The high- and medium-dose CZBG plus ADM could also significantly decrease the mdr 1 gene expression in tumor xenografts as compared with ADM alone (P<0.05). CONCLUSION: CZBG at high- and medium-dose plus ADM can inhibit the growth of tumor xenografts and decrease the mdr 1 gene expression in tumor xenografts in nude mice.