Efficacy and safety of SIMPLE regimen in treatment of extranodal NK/T-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of SIMPLE regimen in the treatment of extranodal NK/T-cell lymphoma (ENKTCL).Methods:The clinical data of 11 patients with ENKTCL who were admitted to the University of Hong Kong-Shenzhen Hospital from January 2012 to January 2022 were retrospectively analyzed. The patients received 4-6 courses of SIMPLE (cisplatin, gemcitabine, ifosfamide, etoposide, dexamethasone, and pegasparaginase) regimen chemotherapy, and stage Ⅰ and Ⅱ patients who also received local radiotherapy after 2 or 3 courses of chemotherapy. Patients were evaluated for mid-treatment and end-of-treatment outcomes, and the adverse effects of patients were evaluated in each treatment cycle. The Kaplan-Meier method was used to analyze the progression-free survival (PFS) and overall survival (OS) of the 11 patients.Results:All 11 patients were nasal type, with the median age of 41 years old (26-67 years old), including 5 males and 6 females, 3 relapsed cases and 8 newly treated cases. Of the 10 patients evaluated for efficacy, 9 achieved complete remission and 1 achieved at least partial remission (efficacy was assessed based on follow-up). All 11 patients were followed up for a median time of 50 months (15-72 months) and 2 relapsed patients died due to disease progression. The expected 5-year PFS rate and OS rate of 11 patients were both 90.0%, and the expected 5-year OS rate was 100.0% and 66.6% in newly treated and relapsed patients, respectively. Common adverse effects were hematologic adverse reactions, infections, gastrointestinal symptoms, elevated transaminases, and hypofibrinogenemia, all of which were curable. There is no treatment-related death.Conclusions:The SIMPLE regimen for the treatment of ENKTCL has a high remission rate, the patients have long survival time, and the regimen is moderately well tolerated.

Potential of natural products containing 3-acyl tetramic acid as antibacterial precursors / 药学学报

The natural products containing 3-acyl tetramic acid units have a large number of complex and diverse structures, showing a variety of biological activities such as antibacterial, antiviral, anti-tumor and so on, especially antibacterial activity which are regarded as a potential reservoir of new antibiotics. In this paper, the antibacterial activities of various natural products containing 3-acyl tetramic acids and the new research hotspots and directions are reviewed.

Association between the trajectory of waist-to-height ratio from childhood to adulthood and the risk of adult hypertension / 中华健康管理学杂志

Objective:To analyze the trajectory of waist-to-height ratio (WHtR) from childhood to adulthood and its association with the risk of hypertension in adulthood.Methods:In this retrospective cohort study, based on the data of China Health and Nutrition Survey (CHNS) from 1991 to 2015, the group-based trajectory model was applied to identify the trajectory of WHtR in 1 794 subjects aged from 7 to 40 years living in 15 provinces, autonomous regions and municipalities in China. The subjects aged 18 years and above with a systolic blood pressure≥140 mmHg (1 mmHg=0.133 kPa) or diastolic blood pressure ≥90 mmHg or those currently taking antihypertensive drugs were defined as having adult hypertension. And further, the Poisson regression model was used to assess the effect of WHtR trajectory from childhood to adulthood on adult hypertension, and the “E-value” approach was employed to evaluate the potential impact of unobserved confounders on the robustness of the results.Results:Of all the subjects surveyed, 3 trajectory groups were identified, and 750 (41.8%), 958 (53.4%) and 86 (4.8%) subjects were identified as having persistent normal, slow-growing and fast-growing WHtR trajectory, respectively; the incidence of adulthood hypertension in the up-mentioned 3 trajectory groups was 2.1%, 4.7% and 14.0%, respectively ( P<0.001). The risk of adult hypertension in the slow-growing trajectory group ( RR=1.94, 95% CI: 1.12-3.36) and the fast-growing trajectory group ( RR=5.70, 95% CI: 2.65-12.24) were both significantly higher than that in the persistent normal group (both P<0.05). The results of sensitivity analysis showed that the results were relatively robust (E-value was 3.29 and 10.88, respectively). Conclusion:Different trajectories of WHtR from childhood to adulthood exist in the surveyed population, and the increase of WHtR would be positively correlated with the risk of adulthood hypertension.

Directed differentiation of human induced pluripotent stem cells into midbrain / 南方医科大学学报

OBJECTIVE@#To establish an efficient protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into functional midbrain dopaminergic progenitor cells (DAPs) in vitro.@*METHODS@#hiPSCs were induced to differentiate into DAPs in two developmental stages. In the first stage (the first 13 days), hiPSCs were induced into intermediate cells morphologically similar to primitive neuroepithelial cells (NECs) in neural induction medium containing a combination of small molecule compounds. In the second stage, the intermediate cells were further induced in neural differentiation medium until day 28 to obtain DAPs. After CM-DiI staining, the induced DAPs were stereotactically transplanted into the right medial forebrain bundle (MFB) of rat models of Parkinson's disease (PD). Eight weeks after transplantation, the motor behaviors of PD rats was evaluated. Immunofluorescence assay of brain sections of the rats was performed at 2 weeks after transplantation to observe the survival, migration and differentiation of the transplanted cells in the host brain microenvironment.@*RESULTS@#hiPSCs passaged stably on Matrigel showed a normal diploid karyotype, expressed the pluripotency markers OCT4, SOX2, and Nanog, and were positive for alkaline phosphatase. The primitive neuroepithelial cells obtained on day 13 formed dense cell colonies in the form of neural rosettes and expressed the neuroepithelial markers (SOX2, Nestin, and PAX6, 91.3%-92.8%). The DAPs on day 28 highly expressed the specific markers (TH, FOXA2, LMX1A and NURR1, 93.3-96.7%). In rat models of PD, the hiPSCs-DAPs survived and differentiated into TH+, FOXA2+ and Tuj1+ neurons at 2 weeks after transplantation. Eight weeks after transplantation, the motor function of PD rats was significantly improved as shown by water maze test (P < 0.0001) and apomorphine-induced rotation test (P < 0.0001) compared with rats receiving vehicle injection.@*CONCLUSION@#HiPSCs can be effectively induced to differentiate into DAPs capable of differentiating into functional neurons both in vivo and in vitro. In rat models of PD, the transplanted hiPSCs-DAPs can survive for more than 8 weeks in the MFB and differentiate into multiple functional neurocytes to ameliorate neurological deficits of the rats, suggesting the potential value of hiPSCs-DAPs transplantation for treatment of neurological diseases.

Heparin-binding hemagglutinin as a composition antigen of tuberculosis vaccine exerts protective immune effects by inducing IL-17 / 中华预防医学杂志

To explore the protective immune effect induced by mucosal delivery heparin-binding hemagglutinin (HBHA)-a candidate vaccine antigen of Mycobacterium tuberculosis. Female C57BL/6 mice were between 6 and 8 weeks of age before experimental use. Thirty mice received different immunization strategies and were randomly divided into the control group, the early secreting antigen target-6 (ESAT-6) intranasal immunization group, the HBHA intranasal immunization group, the BCG priming PBS control group, or BCG priming HBHA boost group, 6 mice in each group. In order to analyzed the immune effect, the concentrations of plasma Interleukin-17A (IL-17A) and other cytokines were measured by ELISA. Quantitative real-time PCR analyses were performed to detect the relative quantity (RQ) mRNA of IL-17A in the lung. The lung tissue sections were stained to detect the formation of the tertiary lymphoid structures. The chemokines contributed to formation of the tertiary lymphoid structures were also measured. Flow cytometry was used to detect the frequency of Th1 and Th17 cells in the system. Sixty mice in the BCG priming PBS control group and the BCG priming HBHA boost group were sacrificed at different time points after infection to count the lung bacterial burden. The concentrations of plasma IL-17A and relative quantity of lung IL-17A mRNA were highest in the BCG priming HBHA boost group [(14.76±4.73) pg/mL,RQ (12.27±6.71)], which was significantly higher than the control group [(5.57±2.95) pg/mL,RQ (1.30±0.97)] (t=4.213, P<0.001; t=5.984, P<0.001), and also significantly higher than the BCG priming PBS control group [(6.81±2.18) pg/mL,RQ (1.44±1.16)] (t=3.646 P=0.001; t=6.185 P<0.001). Compared with the BCG priming PBS control group (0.38±0.38)% the frequency of spleen Th17 cells were also significantly increased (t=-0.280 , P=0.048) in the BCG-primary HBHA boost group (1.02±0.34)%. In addition, HBHA boosting could promote better formation of the tertiary lymphoid structures in the lung, and decrease the bacterial load on the early stage after BCG challenge. Collectively, mucosal delivery of HBHA can effectively enhance the protective effect after BCG vaccination, and it is a potential candidate vaccine component.

Advance in emotion ability intervention of children with hearing impariment / 中国学校卫生

Abstract@#There are many problems in emotion ability development of hearing impaired children, such as emotion recognition, emotion expression obstacle, emotion understanding limitation and emotion regulation impropriety, etc., which seriously affect their social adaptation and mental health. Making systematic and individualized intervention programs can effectively promote the development of emotion ability of hearing impaired children. Based on the analysis of the characteristics and influencing factors of the emotion ability development of hearing impaired children, this paper reviews the existing intervention studies, and proposes future research directions in view of the deficiencies of existing studies, in order to provide reference for the research on emotion ability intervention of hearing impaired children.

Network pharmacology unveils spleen-fortifying effect of Codonopsis Radix on different gastric diseases based on theory of “same treatment for different diseases” in traditional Chinese medicine / 中草药·英文版

Objective: “Same treatment for different diseases” is a unique treatment strategy under the guidance of traditional Chinese medicine (TCM) theory. Codonopsis Radix (Codonopsis pilosula, Dangshen in Chinese) with spleen-fortifying effect was employed to understand the strategy of “Same treatment for different diseases”, based on its common mechanism in the treatment of gastric diseases including gastric ulcer, gastritis and gastric cancer via network pharmacology research. Methods: Network pharmacology research methods were used to analyze the interaction network and potential mechanisms of Dangshen in treating gastric ulcer, gastritis and gastric cancer. The active components and their target proteins of Dangshen were integrated from TCMSP, BATMAN-TCM databases. The targets of gastric ulcer, gastritis and gastric cancer were collected through GeneCards, PubMed, TDD and DisGeNET Database. Through screening, the key components and the key targets of Dangshen in treating gastric ulcer, gastritis and gastric cancer were obtained. After KEGG pathway analysis and GO analysis, the important pathways and biological processes were analyzed. Results: Through data and literature mining, the common and specific pharmaceutical effects and mechanism of Dangshen were summarized in these three gastric lesions. It was shown that Dangshen mainly acted on gastric ulcer, gastritis and gastric cancer through the overall regulation of the PI3K-AKT signaling pathway. With the development of the disease, it will gradually increase the control of inflammation through TNF, NF-κB and other inflammation-related signaling pathways to reduce inflammatory damage. For tumorigenesis, it pays more attention to inhibiting the ErbB signaling pathways to reduce the proliferation and migration of tumor cells. In addition, Dangshen's regulation of HIF-1 signaling pathway may also be beneficial for the treatment of gastric ulcer, gastritis and gastric cancer. Conclusion: Dangshen achieves spleen-fortifying effect on gastric diseases including gastric ulcer, gastritis and gastric cancer through multiple targets in multiple pathways, especially PI3K-AKT pathway and HIF-1 pathway. It could provide a scientific basis for understanding the strategy of “Same treatment for different diseases” in traditional Chinese medicine.

Common mechanism of Citrus Grandis Exocarpium in treatment of chronic obstructive pulmonary disease and lung cancer / 中草药·英文版

Objective: “Same treatment for different diseases” is a unique treatment strategy in traditional Chinese medicine. Two kinds of malignant respiratory diseases endanger human health-chronic obstructive pulmonary disease (COPD) and lung cancer. Citrus Grandis Exocarpium (Huajuhong in Chinese, HJH), a famous herbal, is always applied by Chinese medicine practitioners to dispersion the lung to resolve phlegm based on “syndrome differentiation and treatment” theory. However, the common mechanism for HJH's treatment of COPD and lung cancer is not clear. Methods: In this study, based on network pharmacology and molecular docking technology, the common mechanism of HJH in the treatment of COPD and lung cancer was studied. The active ingredients and related targets of HJH were integrated from TCMSP, BATMAN-TAM, STP, and Pubchem databases. The standard names of these targets were united by UniProt database. Targets of COPD and lung cancer were enriched through GeneCards, NCBI (Gene), Therapeutic Target Database, and DisGeNET (v7.0) databases. Then the intersection targets of HJH and diseases were obtained. The STRING network and the Cytoscape 3.7.2 were used to construct PPI network, the DAVID database was used to perform GO and KEGG analysis. Then Cytoscape 3.6.1 was used to build “ingredient-target-signal pathway” network. Finally, AutoDock 1.5.6 software was used to perform molecular docking of key proteins and molecules. Results: Eleven active ingredients in HJH were obtained by searching the database, corresponding to 184 HJH-COPD-lung cancer targets intersection. The results of biological network analysis showed that naringenin, the active component in HJH, could mainly act on target proteins such as AKT1, EGFR. Then through positive regulation of vasoconstriction and other biological processes, naringenin could regulate estrogen signaling pathway, VEGF signaling pathway, HIF-1 signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway to play an important role in the treatment of both COPD and lung cancer. Conclusion: Network pharmacology was employed to systematically investigate the active ingredients and targets of HJH in treatment of COPD and lung cancer. And then, the common pharmacodynamic network of HJH for the two malignant respiratory diseases was firstly described. Furthermore, naringenin was proved to strongly bind with AKT1 and EGFR. It may provide the scientific basis for understanding the “Same treatment for different diseases” strategy in traditional Chinese medicine and inspirit subsequent drug discovery for COPD, lung cancer and other malignant lung diseases.

Influence of IL-24 on monocyte activity in patients with non-small cell lung cancer / 中华微生物学和免疫学杂志

Objective:To investigate the influence of IL-24 on monocyte activity in patients with non-small cell lung cancer (NSCLC) in vitro. Methods:Twenty-five NSCLC patients and 20 healthy controls were enrolled in the current study. Peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) samples were collected to isolate monocytes. Expression of IL-22R1, IL-20R1 and IL-20R2 at mRNA level in monocytes was semi-quantified by real-time RT-PCR. Flow cytometry was used to detect the expression of Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and enzyme linked immunosorbent assay was performed to measure the levels of granzyme A, granzyme B and granzyme H after stimulating monocytes with recombinant human IL-24 (10 ng/ml and 100 ng/ml). The monocytes isolated from peripheral blood of NSCLC patients were co-cultured with A549 cells in vitro. Monocyte-induced target cell death in response to IL-24 stimulation was investigated and changes in the cytotoxicity of monocytes were also assessed after inhibiting granzyme B with Z-AAD-CMK. Student′s t test or LSD- t test was used for comparison. Results:IL-22R1 mRNA was not detected in monocytes. There were no remarkable differences in either IL-20R1 mRNA or IL-20R2 mRNA expression in monocytes between healthy controls and NSCLC patients, or between non-tumor site and tumor site ( P>0.05). FasL and TRAIL expression and granzyme secretion were significantly reduced in monocytes from peripheral blood and tumor sites of NSCLC patients as compared with those from controls ( P<0.05). IL-24 stimulation did not affect the expression of FasL or TRAIL or the secretion of granzyme A or granzyme H ( P>0.05). Low concentration of IL-24 (10 ng/ml) did not affect granzyme B secretion ( P>0.05), while high concentration of IL-24 (100 ng/ml) significantly elevated the secretion of granzyme B by monocytes ( P<0.05). Low concentration of IL-24 (10 ng/ml) did not affect the monocyte-induced target cell death ( P>0.05), while high concentration of IL-24 (100 ng/ml) promoted NSCLC patient-derived monocyte-induced target cell death ( P<0.05). Z-AAD-CMK stimulation suppressed the high concentration of IL-24-mediated elevation of monocyte cytolytic function ( P<0.05). Conclusions:High concentration of IL-24 promoted the cytolytic function of monocytes in NSCLC patients through elevating granzyme B secretion in vitro. However, IL-24 might not influence monocyte function in vivo.

Application of the method of judging small shadow intensity and CT reference film in the diagnosis of silicosis / 中华放射学杂志

Objective:To explore the application value of the method of judging the density of small shadows in the lung area by using CT and CT reference films for pneumoconiosis.Methods:The chest imaging data of 244 employees of a large copper company in Tongling City, Anhui Province who underwent occupational physical examination at Tongling Municipal Hospital in Anhui Province from January 2016 to December 2019 were retrospectively analyzed. Totally 244 cases underwent chest CT scan and chest DR radiography at the same time. The shape and size of the small shadows (the size of the circular and quasi-circular nodules in the lung area were represented by p, q, r, and the size of the irregular small shadows were represented by s, t, u), the overall density, the density of small shadows in each lung area, the large shadows, and the diagnosis stage were observed and compared. The small shadow density of each lung area was judged by the method of judging the small shadow density of CT lung area and the reference film, and other observation indicators were judged according to GBZ70-2015 Diagnosis of Occupational Pneumoconiosis. Results:There was a significant difference between CT and DR in judging s-shaped small shadows and no small shadows ( P<0.05), and there was no statistically significant difference in judging p, q, r, t, and u-shaped small shadows ( P>0.05). CT and DR had medium to high consistency in the judgment of the overall density of small shadows (Kappa=0.692, P=0.001), and the diagnostic coincidence rate was 82.38% (201/244). There was moderate to high agreement between CT and DR in the density of small shadows shown in the right upper, right lower, left upper, left middle, and left lower lung regions (Kappa ranged from 0.40 to 0.75, P<0.05), and the consistency in the right middle lung region was poor (Kappa=0.381, P=0.001). Eleven large shadows were detected in 8 cases by DR, 31 large shadows were detected in 23 cases by CT, and 20 (8.20%) large shadows were detected more frequently by CT than DR. The agreement between CT and DR for the diagnosis and staging of silicosis was excellent (Kappa=0.843, P=0.001), and the diagnostic coincidence rate was 91.80% (224/244). Conclusion:Applying the method of determining the density of small shadows in the lung area of pneumoconiosis and reference films, combined with GBZ70-2015 Diagnosis of Occupational Pneumoconiosis, can make a more accurate diagnosis of silicosis.

E cigarette usage and associated factors among Beijing primary and secondary school students / 中国学校卫生

Objective@#To understand current situation of e cigarette use and associated factors in primary and secondary school students in Beijing, in order to promote the construction of smoke free schools.@*Methods@#During April to June in 2019, PPS sampling was used to select primary schools, secondary schools and trade schools. In each selected school, randomly sampling method was conducted until the sample size was reached. There were 18 312 students included in the analysis. Surveillance information mainly included the current situation of electronic cigarette use and associated factors.@*Results@#Among primary and secondary school students who have known about e cigarettes, female students were less likely to use e cigarettes than male students ( OR = 0.47 , 95% CI =0.42- 0.54 ). After entering the second year of junior high school, the possibility of using e cigarettes increased. Smoke free home was associated less e cigarettes usage ( OR =0.78, 95% CI =0.69-0.88). Primary and secondary school students with average daily allowance of 30~<150 yuan and no less than 150 yuan were 1.43 (95% CI =1.22-1.67) times and 2.24 (95% CI =1.79-2.79) times more likely to use e cigarettes than those with 0-10 yuan allowance, respectively. The probability of using e cigarettes among primary and secondary school students who have not tried using cigarettes was only 16.4% compared with those who have tried cigarettes ( OR =0.16, 95% CI =0.14-0.19).@*Conclusion@#It is necessary to curb the prevalence of e cigarettes among primary and secondary school students. Actions need to be taken urgently to fill in the gaps or correct the mistakes in children and adolescents cognition of e cigarettes, and to adopt more innovative methods to scientifically guide children and adolescents to stay away from e cigarettes.

In vitro influence of IL-24 on functions of CD8 + T cells from patients with non-small cell lung cancer / 中华微生物学和免疫学杂志

Objective:To investigate the in vitro influence of IL-24 on the functions of CD8 + T cells from patients with non-small cell lung cancer (NSCLC). Methods:Twenty-eight NSCLC patients and 17 healthy individuals were enrolled in this study. Peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to isolate CD8 + T cells. Real-time reverse transcription-PCR was used to detect the expression of IL-24 receptors (IL-20R1, IL-20R2 and IL-22R1) at mRNA level in CD8 + T cells. Changes in the expression of perforin and granzyme B were measured by flow cytometry after stimulating purified CD8 + T cells with different concentrations of recombinant human IL-24 (10 ng/ml and 100 ng/ml). In vitro direct and indirect contact co-culture systems were established for CD8 + T cells and NSCLC cell line (NCI-H1882 cells). CD8 + T cells induced target cell death and expression of IFN-γ and TNF-α in response to IL-24 stimulation were analyzed. Student′s t test or LSD- t test was used for intergroup comparison. Results:The expression of IL-22R1 at mRNA level was not detected in CD8 + T cells. No significant difference in IL-20R1 or IL-20R2 expression at mRNA level in CD8 + T cells was observed between healthy individuals and NSCLC patients, or between non-tumor sites and tumor sites ( P>0.05). Perforin and granzyme B expression was significantly reduced in CD8 + T cells from peripheral bloods and tumor sites of NSCLC patients as compared with those from healthy individuals and non-tumor sites (all P<0.05). Low concentration of IL-24 (10 ng/ml) did not affect perforin or granzyme B expression in CD8 + T cells ( P>0.05), but high concentration of IL-24 (100 ng/ml) significantly enhanced the expression of perforin and granzyme B in CD8 + T cells from NSCLC patients ( P<0.05). In the direct contact co-culture system, increased ratio of dead target cells and up-regulated IFN-γ and TNF-α expression were induced after stimulating CD8 + T cells from tumor sites in NSCLC patients with high concentration of IL-24 (100 ng/ml), but low concentration of IL-24 (10ng/ml) had no significant influence on CD8 + T cell-induced target cell death and cytokine production. In the indirect contact co-culture system, neither target cell death nor cytokine production induced by CD8 + T cells was affected by IL-24 stimulation. Conclusions:High concentration of IL-24 promoted the in vitro cytolytic function of CD8 + T cells from NSCLC patients, but might not influence the in vivo functions of CD8 + T cells.

Regulatory mechanism of long noncoding RNA in the occurrence and development of leukemia: a review / 生物工程学报

Long noncoding RNAs (lncRNAs) are a class of RNA molecules that are greater than 200 nt in length and do not have protein-coding capabilities or encode micropeptides only. LncRNAs are involved in the regulation of cell proliferation, differentiation, apoptosis and other biological processes, and are closely associated with the occurrence, recurrence and metastasis of a variety of malignant hematologic diseases. This article summarizes the function, regulatory mechanism and potential clinical application of lncRNAs in leukemia. In general, lncRNAs regulate the occurrence and development of leukemia and the multi-drug resistance in chemotherapy through epigenetic modification, ribosomal RNA transcription, competitive binding with miRNA, modulating glucose metabolic pathway, and activating tumor-related signaling pathway. Studies on lncRNAs provide new references for understanding the pathogenesis of leukemia, uncovering new prognostic markers and potential therapeutic targets, and addressing the problems of drug resistance and post-treatment recurrence in patients in clinical treatment of leukemia.

Study on chemical constituents from fruiting bodies of Ganoderma calidophilum / 中国中药杂志

Chemical constituents were isolated and purified from fruiting bodies of Ganoderma calidophilum by various column chromatographic techniques, and their chemical structures were identified through combined analysis of physicochemical properties and spectral data. As a result, 11 compounds were isolated and identified as(24E)-lanosta-8,24-dien-3,11-dione-26-al(1), ganoderone A(2), 3-oxo-15α-acetoxy-lanosta-7,9(11), 24-trien-26-oleic acid(3),(23E)-27-nor-lanosta-8,23-diene-3,7,25-trione(4), ganodecanone B(5), ganoderic aldehyde A(6), 11β-hydroxy-lucidadiol(7), 3,4-dihydroxyacetophenone(8), methyl gentiate(9), ganoleucin C(10), ganotheaecolumol H(11). Among them, compound 1 is a new triterpenoid. The cytotoxic activities of all of the compounds against tumor cell lines were evaluated. The results showed that compounds 1, 3, 4 and 6 showed cytotoxic activity against BEL-7402, with IC_(50) values of 26.55, 11.35, 23.23, 18.66 μmol·L~(-1); compounds 1 and 3-6 showed cytotoxic activity against K562, with IC_(50) values of 5.79, 22.16, 12.16, 35.32, and 5.59 μmol·L~(-1), and compound 4 showed cytotoxic activity against A549, with IC_(50) value of 42.50 μmol·L~(-1).

Protection of Addition and Subtraction Therapy of Ditantang Combined with Taohong Siwutang to Brain Nerve of Patients with Cerebral Infarction and （Syndrome of Phlegm and Blood Stasis Blocking Collaterals） During Early Recovery / 中国实验方剂学杂志

Objective:To discuss clinical effect of addition and subtraction therapy of Ditantang combined with Taohong Siwutang to cerebral infarction and syndrome of phlegm and blood stasis blocking collaterals during early recovery， and to study protection to brain nerve. Method:One hundred and fifty-two patients were randomly divided into control group （76 cases） and observation group （76 cases） by random number table， 71 patients in control group completed the therapy （5 patients were falling off， missing visit or eliminated）， and 70 patients in observation group completed the therapy. Both groups' patients got comprehensive rehabilitation measures. Patients in control group got Zhongfeng Huichun pills， 1.5 g/time， 3 times/day. Patients in observation group got addition and subtraction therapy of Ditantang combined with Taohong Siwutang in the morning and at night， 1 dose/day. The treatment was continued for 12 weeks. Before and after treatment， scores of degree of neurological deficit， Barthel （BI） index， Fugl-Meyer scale （FMA）， modified Rankin scale （MRS） and syndrome of phlegm and blood stasis blocking collaterals were graded. And levels of malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， advanced oxidation protein products （AOPP）， vascular endothelial growth factor （VEGF）， brain-derived neurotrophic factor （BDNF） and neuron specific enolase （NSE）. And cerebral hemodynamics were detected， and peak flow velocity （VS）， vascular resistance index （RI）， pulsatility index （PI） and cerebrovascular reserve function （CVR） were recorded. Safety was evaluated. Result:After the 6th week and 12th week of treatment， scores of degree of neurological deficit， BI， FMA， MRS， syndrome of phlegm and blood stasis blocking collaterals， AOPP， MDA， NSE， RI and PI were lower than those in control group （P<0.01）， levels of SOD， GSH-Px， BDNF， VEGF， Vs and CVR were higher than those in control group （P<0.01）. The clinical effect was better than which in control group （Z=2.109， P<0.05）. Besides， there was no adverse reaction caused by Ditantang combined with Taohong Siwutang. Conclusion:Ditantang combined with Taohong Siwutang can ameliarate the hemodynamics， reduce the lipid peroxidation damage， regulate the neurovascular repair factor， so it can promote the repair of nerve tissue and function， clinically reduce the degree of nerve function defect， improve the ability of daily life and exercise when it used to cerebral infarction and syndrome of phlegm and blood stasis blocking collaterals during early recovery， and it is good for clinical effect and safe using.

Analysis of mental health status and influencing factors of MSM in AIDS patients / 中国医师杂志

Objective:To analyze the mental health status of men who have sex with men (MSM) population among acquired immunodeficiency syndrome (AIDS) patients.Methods:A face-to-face questionnaire survey was conducted to investigate the general information, symptom check list-90 (SCL-90) questionnaire and scale of 269 MSM patients with AIDS in the Eighth Hospital of Xi'an city from November 2015 to May 2016.Results:Among the 269 cases of MSM with human immunodeficiency virus (HIV)/AIDS, the majority were 20-40 years old, with higher education level, mostly unmarried and nonsingleton. The scores of each factor of SCL-90 were significantly higher than that of the norm, among which diet and sleep, interpersonal relationship, anxiety and depression were the most prominent; regression analysis showed that the main reason affecting the scores of each factor among AIDS patients was the low quality of life, and the patients with high education were more likely to have depression and anxiety.Conclusions:MSM has its own special characteristics among AIDS patients, and there are many psychological problems. Necessary psychological intervention measures should be given.

Virtual screening of small molecular inhibitors of SARS-CoV-2 3CL hydrolase based on high-throughput molecular docking and prediction of Chinese materia medica and its compound against COVID-19 / 中草药

Objective: Based on the systematic pharmacological database of traditional Chinese medicine (TCM) and the analysis platform TCMSP, the computer virtual screening technique was used to screen the small molecule inhibitors of SARS-CoV-2 3CL hydrolase from Chinese materia medica (CMM), and speculate the potential anti-COVID-19 novel coronavirus pneumonia TCMs and its compounds. Methods: SARS-CoV-2 3CL hydrolase protein was targeted in this study. Autodock Vina software and Python script were used to realize high-throughput molecular docking. Combined with “ADME-Lipinski” rules, the re-screening was carried out to optimize the active ingredients and speculate the key TCMs and compound prescriptions. Based on the perspective of network pharmacology, a component-target-pathway network was constructed to infer the mechanism of action of core drug pairs. Results: Taking the reference ligand as positive control, 66 natural micromolecule compounds with good pharmacokinetic properties were obtained. Twelve single TCMs, two Chinese medicine pairs of Glycyrrhizae Radix et Rhizoma-Mori Cortex and Lonicerae Japonicae Flos-Forsythiae Fructus, and 12 TCM prescriptions including Sangju Drink and modified Sangju Drink and Yinqiao Powder were selected as candidate schemes to fight against novel coronavirus pneumonia. Conclusion: This study is based on high-throughput molecular docking technology to virtually screen small molecule inhibitors of SARS-CoV-2 3CL hydrolase of CMM and Chinese medicines, innovatively analyze the potential molecular mechanism in combination with network pharmacology, and provide scientific guidance and theoretical basis for TCM to resist novel coronavirus pneumonia.

Macrolide-refractory Mycoplasma pneumoniae pneumonia and hemophagocytic lymphohistiocytosis: case report and literature review

Mycoplasma pneumoniae causes various extra-pulmonary complications. As a rare but fatal hematological complication, hemophagocytic lymphohistiocytosis (HLH) can be observed in children with M. pneumoniae infection. We report a case of a 6-year-old girl with HLH who was initially presumed to have macrolide-refractory M. pneumoniae pneumonia. Despite the combination treatment of antimicrobial and anti-inflammatory agents, she showed persistent fever, hepatosplenomegaly, and thrombocytopenia. Secondary HLH associated with M. pneumoniae should be considered if unexplained clinical deterioration is noted in children with macrolide-refractory M. pneumoniae pneumonia.

Macrolide-refractory Mycoplasma pneumoniae pneumonia and hemophagocytic lymphohistiocytosis: case report and literature review

Mycoplasma pneumoniae causes various extra-pulmonary complications. As a rare but fatal hematological complication, hemophagocytic lymphohistiocytosis (HLH) can be observed in children with M. pneumoniae infection. We report a case of a 6-year-old girl with HLH who was initially presumed to have macrolide-refractory M. pneumoniae pneumonia. Despite the combination treatment of antimicrobial and anti-inflammatory agents, she showed persistent fever, hepatosplenomegaly, and thrombocytopenia. Secondary HLH associated with M. pneumoniae should be considered if unexplained clinical deterioration is noted in children with macrolide-refractory M. pneumoniae pneumonia.

Synergistic role of JAK/STAT5 and PI3K/AKT signaling pathways in regulating eIF4B in acute leukemia / 生物工程学报

Human acute leukemia (AL) is a clonal malignancy with abnormal hematopoietic stem cells. Clinically, AL is very difficult to cure due to its sudden onset and short course of disease progression. Previous studies have shown that eukaryotic initiation factor 4B (eIF4B) plays a critical role in the development of chronic leukemia. However, the involvement of eIF4B in human acute leukemia is still largely unknown. Therefore, we studied eIF4B function and its regulatory mechanism in human acute leukemia. We found that phosphorylation levels of eIF4B in acute leukemia cells were significantly reduced in response to treatment with either LY294002 (PI3K inhibitor), AKTi (AKT inhibitor) or SMI-4A (Pim inhibitor). Co-treatment with inhibitors targeting JAK/STAT5/Pim and PI3K/AKT/mTOR signaling dramatically promoted apoptosis of acute leukemia cells by downregulating eIF4B phosphorylation. Furthermore, in vitro and in vivo functional experiments showed that eIF4B played an important anti-apoptosis role in the acute leukemia cells by regulating the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL. In contrast, silencing eIF4B inhibited the growth of acute leukemia cells as engrafted tumors in nude mice. Taken together, our results indicate the synergistic role of JAK/STAT5/Pim and PI3K/AKT/mTOR signaling pathways in regulating eIF4B phosphorylation in acute leukemia, and highlight eIF4B as a candidate therapeutic target for treatment of acute leukemia.