Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience / 中华血液学杂志

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

Meta-analysis and trial sequential analysis of modified Sangbaipi Decoction for treating acute exacerbation of chronic obstructive pulmonary disease / 中国中药杂志

The randomized controlled trials about modified Sangbaipi Decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) patients were collected from 7 databases( PubMed,CNKI,et al) from the establishment to December 5,2018. All the studies searched were strictly evaluated. Literatures were independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. To systematically review the efficacy of modified Sangbaipi Decoction in treating AECOPD,the Meta-analysis and trial sequential analysis were conducted by using Stata/SE 14. 0 and TSA 0. 9. 5. 10 Beta,respectively. A total of 25 RCTs involving 1 784 patients were included. According to the results of Meta-analysis,compared with the control groups,the trial group had a higher clinical efficacy in AECOPD patients( RR =1. 18,95%CI[1. 13,1. 22],P = 0),improved pulmonary functions including forced expiratory volume in one second( FEV1,WMD =0. 44,95%CI[0. 01,0. 87],P = 0. 046),and the forced vital capacity( FVC,WMD = 0. 42,95%CI[0. 07,0. 22],P = 0),but no statistical significance in the percentage of forced expiratory volume in one second( FEV1%,P = 0. 067) and the first seconds breathing volume percentage of forced vital capacity( FEV1/FVC,P = 0. 238); it improved the arterial oxygen partial pressure( PaO2,SMD =0. 85,95%CI[0. 41,1. 30],P = 0) and decreased the arterial partial pressure of carbon dioxide( PaCO2,SMD =-0. 94,95% CI[-1. 70,-0. 18],P= 0. 016); and in terms of inflammatory markers,it improved the white blood cell count( WBC,WMD=-0. 94,95%CI[-1. 17,-0. 70],P = 0). The trial sequential analysis showed that the studies included with the improvement of clinical efficacy had passed the conventional and TSA threshold,so as to further confirm the evidence. According to the findings,in addition to conventional Western medicine treatment,modified Sangbaipi Decoction could improve the efficiency in treating acute exacerbation patients with chronic obstructive pulmonary disease,increase PaO2,and decrease PaCO2,with a high safety but no effect on pulmonary function. However,restricted by the low quality of studies included,this conclusion shall be further verified by more high-quality clinical trials.

Systematically review of modified Sanzi Yangqin Decoction for treating acute exacerbation of chronic obstructive pulmonary disease / 中国中药杂志

The randomized controlled trials( RCTs) about modified Sanzi Yangqin Decoction in the treatment of patients with exacerbation of chronic obstructive pulmonary disease( AECOPD) were collected from 7 databases( PubMed,CNKI,etc.) till December25,2018 from their inception. All the studies searched were strictly evaluated and independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. In order to systematically review the efficacy and safety of modified Sanzi Yangqin Decoction for treating AECOPD,the Meta-analysis and trial sequential analysis were conducted by using Stata/SE 14. 0 and TSA 0. 9. 5. 10 Beta,respectively. A total of 22 RCTs involving 2 012 patients were included. The results of Meta-analysis suggested that: as compared with the control group,the clinical symptoms in AECOPD patients were improved( RR = 1. 19,95%CI[1. 15,1. 24],P = 0); the pulmonary functions including forced expiratory volume in one second( FEV_1)( SMD= 0. 96,95%CI[0. 39,1. 52],P= 0. 001),the percentage of forced expiratory volume in one second( FEV_1%)( SMD =0. 80,95%CI[0. 20,1. 41],P = 0. 009),forced vital capacity( FVC)( SMD = 0. 69,95% CI[0. 06,1. 31],P = 0. 032),first seconds breathing volume percentage of forced vital capacity( FEV_1/FVC) were improved( SMD = 0. 81,95%CI[0. 64,0. 97],P = 0);the arterial oxygen partial pressure( PaO_2) was improved( SMD= 0. 87,95%CI[0. 41,1. 32],P= 0); the arterial partial pressure of carbon dioxide( PaCO_2) was decreased( SMD =-0. 91,95%CI[-1. 33,-0. 49],P = 0) in the trial group. In addition,the incidence of adverse reactions in the experimental group was low,and there were no serious adverse events. The trial sequential analysis( TSA) showed that the studies included in the improvement of clinical efficacy had passed the conventional and TSA threshold at the same time,further confirming the efficacy of trial group. This research showed that,conventional Western medicine treatment,combined with modified Sanzi Yangqin Decoction in treating acute exacerbation patients with chronic obstructive pulmonary disease could improve the clinical efficiency and pulmonary functions,improve the PaO_2,decrease the PaCO_2,with a high safety. However,the quality of existing research is low,requiring more high quality clinical trials for further validation.

Molecular Mechanism of Belamcandae Rhizoma and Ephedrae Herba Couplet Medicines in Treating Asthma Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To analyze the effective active ingredients of Belamcandae Rhizoma and Ephedrae Herba couplet medicines(BREH)in the treatment of bronchial asthma based on network pharmacology, in order to predict their potential targets and explore the mechanism. Method:Active ingredients and predict their targets were collected from traditional Chinese medicine system pharmacology(TCMSP) database. Drugs-components-targets network and Proteins interations network were built by STRING database and Cytoscape software. ClusterProfiler and ClueGO was used to enrich the biological function and metabolic pathway of core targets. Finally, candidate targets were mapped onto the pictures of correlative pathways. Result:The 38 effectively active ingredients were screened out, including luteolin, stigmasterol, diosmetin, naringenin, quercetin, iristectorigenin A, isorhamnetin. There were 214 candidate targets relating to bronchial asthma, and 55 core ones were selected to be mainly studied, including RAC-alpha serine/threonine-protein kinase (Akt1), tumor necrosis factor (TNF), mitogen-activated protein kinase 1 (MAPK1), vascular endothelial growth factor A (VEGFA), interleukin-10 (IL-10), NF-kappa-B inhibitor alpha (NFKBIA), and a number of relevant gene ontology(GO) functions and Kyoto Encyclopedin of Genes and Genomes(KEGG) pathways were enriched. Conclusion:BREH may regulate the Th1, Th2 and Th17 cell differentiations, Asthma, IL-17, phosphatidylinositol-3-kinases(PI3K)/Akt, MAPK, NF-κB, VEGF signaling pathways, so as to interfere the process of cell metabolism, and inhibit gene expression of proinflammatory factor in the treatment of bronchial asthma.

Analysis on Mechanism of Shema Zhichuan Liquid in Treating Asthma Based on Network Pharmacology / 中国实验方剂学杂志

Objective: To explore the potential mechanism of Shema Zhichuan liquid in treatment of asthma by network pharmacology. Method: Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (TCM), systematic pharmacological database and analysis platform of TCM were employed to find the components in Shema Zhichuan liquid and their targets, and asthma-related genes were obtained from the comparative toxicogenomics database (CTD). The data set of Shema Zhichuan liquid-gene and asthma-gene were imported into the Draw Venn Diagram for intersection analysis. The obtained data set of Shema Zhichuan liquid-asthma-gene was imported into String 11.0 for protein-protein interaction (PPI) analysis, and was visualized by Cytoscape 3.6.1, and further important modules were analyzed with MCODE. DAVID 6.8 was used to analyze pathway enrichment and biological process of Shema Zhichuan liquid-asthma-gene. Result: A total of 399 components and 2 099 potential targets were obtained from Shema Zhichuan liquid, 98 asthma-related targets were retrieved, 45 common genes and 16 hub genes were screened, including transforming growth factor-β1(TGF-β1), heme oxygenase-1 (HMOX1), interleukin-4 (IL-4), etc. Enrichment analysis showed that the common biological processes of Shema Zhichuan liquid and asthma were related to inflammation, contraction and remodeling of airway, cell proliferation and apoptosis, etc. The common biological pathways mainly included tumor necrosis factor (TNF) signaling pathway, receptor with high affinity for immunoglobulin E (Fc epsilon RI) signaling pathway, nuclear transcription factor-kappa B (NF-κB) signaling pathway, nucleotide binding oligomerization domain (NOD)-like receptor signaling pathway and so on. Conclusion: Shema Zhichuan liquid serves as a multi-target, multi-pathway treatment for asthma, which can provide a reference for the further research and clinical application of this preparation.

Practice of Palliative Care:Experience of a Patient with Advanced Retroperitoneal Sarcoma at the End of Life / 中国医学科学院学报

According to the World Health Organization,palliative care is an approach that prevents and alleviates the pain of patients with life-threatening illness and improves the quality of life of patients and their families through early identification,assessment and treatment of pain and other physical,psychosocial and spiritual problems. It is the active holistic care accomplished by multidisciplinary team. This article describes the practice of the palliative care in a patient with advanced retroperitoneal sarcoma.

Effect of Zhifei mixture combined western drugs on symptoms and signs of children with mycoplasma pneumonia / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of three Chinese medical formulae (Zhifei Mixture I , Zhfei Mixture II, and Zhifei Mixture II) on main and secondary symptoms and signs of children with Totally 70 mycoplasma pneumonia in treating three types of children mycoplasma pneumonia.</p><p><b>METHODS</b>children with mycoplasma pneumonia were assigned to the control group (38 cases) and the treatment group (32 case). All patients were intravenously injected with Azithromycin and took Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution. Those in the treatment group additionally took Zhifei Mixture I , Zhfei Mixture II, and Zhifei Mixture Ill by syndrome typing. Their main and secondary symptoms and signs were observed before and after treatment (main symptoms and signs covered fever, cough, abundant sputum, short breath, and anoxia; secondary symptoms and signs covered aversion to cold, heart rate, facial complexion, spirit, appetite, and sweating).</p><p><b>RESULTS</b>Seven patients were lost in this study. Compared with before treatment in the same group, scores for main and secondary symptoms and signs decreased in the treatment group (P <0.01). The therapeutic effect on fever and cough was obviously better in the control group (P <0.01). The main and secondary symptoms and signs were more obviously improved in the treatment group than in the control group (P <0.01). Commpared with the control group, scores for main and secondary symptoms and signs decreased more in the treatment group (P <0.01). Patients' main and secondary symptoms and signs were more obviously improved (P <0.05).</p><p><b>CONCLUSIONS</b>Zhifei Mixture combined Western drugs could significantly improve main and secondary symptoms and signs of mycoplasma pneumonia children patients. Its efficacy was superior to that of using Western medicine alone.</p>

Effect of percutaneous intratumoral injection of lipiodol emulsion of chemotherapie agents on implanted VX2 tumor in rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the therapeutic effect of percutaneous intratumoral injection with lipiodol emulsion of chemotherapie agents (CALE) on implanted VX2 tumor in rabbits.</p><p><b>METHODS</b>Twelve New Zealand rabbits with implanted VX2 tumor (24 models) were divided into lipiodol group, chemotherapeutic agent group and CALE group with intratumoral injections of the corresponding agents. The pathological changes of all the lesions were observed and the expression of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) were evaluated 7 days after the operation.</p><p><b>RESULTS</b>Compared with the lipiodol group and chemotherapie agent group, intratumoral injection of CALE resulted in the highest tumor necrosis rate and greatest tumor necrosis (P<0.01). The labeling indices of PCNA and VEGF expressions in CALE group were markedly lower than those in the other two groups (P<0.01).</p><p><b>CONCLUSION</b>Percutaneous intratumoral injection of CALE is an effective ablation approach for treatment of malignant solid tumors.</p>

Optimal therapeutic window of hyperbaric oxygenation in neonatal rat with hypoxic-ischemic brain damage / 中华儿科杂志

<p><b>OBJECTIVE</b>Hyperbaric oxygenation (HBO) is an attractive procedure that has been used in treatment of hypoxic-ischemic encephalopathy (HIE). However, depending on the HBO protocol, especially the time point of starting treatment of HBO, different and conflicting results were obtained. This study was undertaken to search for the optimal therapeutic window of ABO in neonatal rat with hypoxic-ischemic brain damage (HIBD).</p><p><b>METHODS</b>Eighty-four healthy seven-day-old SD rats were used as research subjects and were randomly divided into seven groups with 12 in each: sham group, HI group, HI (1 h) + HBO group (HBO starting 1 h after HI), HI (3 h) + HBO group (HBO starting 3 h after HI), HI (6 h) + HBO group (HBO starting 6 h after HI), HI (12 h) + HBO group (HBO starting 12 h after HI), HI (24 h) + HBO group (HBO starting 24 h after HI). Single HBO treatment (2.5 atmospheres absolute, ATA for 1.5 h) was used in this study. Two indexes were used to assess the effect of HBO that included short-term (48 h after HI) histology change (the cell density in CA1 of hippocampus and cortex) and long-term (5 w and 6 w after HI) neurobehavioral testing (grip test and treadmill test for evaluating the deficits of sensor motor; step-down avoidance test for assessing the deficits of memory).</p><p><b>RESULTS</b>In HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO groups, neuron density of cortex and CA1 of hippocampus were 1981.76 +/- 299.55, 1841.53 +/- 241.21, 1525.78 +/- 189.00 and 4430.56 +/- 1180.31, 4507.54 +/- 1374.32, 3883.48 +/- 821.87, respectively, which were significantly higher than HIBD group (987.86 +/- 285.39 and 1813.59 +/- 295.33, P < 0.05, ANOVA). But in HI (12 h) + HBO and HI (24 h) + HBO, the neuron density of cortex and CA1 of hippocampus compared with those in HIBD group had no statistical significance (P > 0.05, ANOVA). In the sensor motor testing performed at 5 w after HI of rat, the grip time in grip test and the stay time in treadmill test of HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO groups were 193.39 +/- 51.19, 168.39 +/- 34.02, 168.95 +/- 34.93 and 130.34 +/- 42.56, 128.20 +/- 27.69, 125.74 +/- 36.99, respectively, which, compared with HIBD group, were significantly prolonged (P < 0.05, ANOVA). But in HI (12 h) + HBO and HI (24 h) + HBO groups, the time was not significantly longer compared with HI (P > 0.05, ANOVA). In the step-down avoidance test which was performed at 6 w after HI, the step-down latencies of HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO were 96.91 +/- 29.91, 90.35 +/- 28.44 and 76.46 +/- 38.70, respectively, which were significantly prolonged (P < 0.05, ANOVA), but in HI (12 h) + HBO and HI (24 h) + HBO, the latencies did not significantly increase compared with HIBD, P > 0.05, ANOVA.</p><p><b>CONCLUSIONS</b>The optimal therapeutic window of HBO in neonatal rat with HIBD was within the first 6 hours after HI. In this therapeutic window, HBO was highly effective in reducing the cell loss in CA1 of hippocampus and cortex.</p>

Effect of zhidan huayu oral liquid on mycoplasmal pneumonia in mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Chinese herbal medicine for activating blood circulation to remove stasis in treating mycoplasmal pneumonia (MP) in mice.</p><p><b>METHODS</b>One hundered and thirty-five BALB/C mice were randomly divided into the control group, the MP model groups IF1 and IF2, the Rexithromycin treated groups LH1 and LH2, and the Rexithromycin plus Zhidan Huayu oral liquid treated groups LZ1 and LZ2. The changes of pathologic scoring, graphic analysis and thrombus counting of lung were observed.</p><p><b>RESULTS</b>In the 3rd day of treatment, the pathologic scores in LH1 and LZ1 were significantly lower and their values of graphic analysis were significantly higher than those in IF1 (P < 0.01 and P < 0.05 respectively), but with inflammation of lung significantly milder than that in IF1. The difference of therapeutic effect between LH1 and LZ1 was insignificant. In the 4th day of treatment, pathologic scores in LZ2 was significantly lower and value of graphic analysis higher than those in IF2 respectively (P < 0.01), with the improvement better than that of LH2 (P < 0.05). In 3rd and 4th day of treatment, the difference of thrombus counting between the Rexithromycin treated groups and the model groups was insignificant (P > 0.05), but it was significantly lower in the combined treated groups than that in the model groups (P < 0.05).</p><p><b>CONCLUSION</b>Zhidan Huayu oral liquid could assist Rexithromycin to alleviate the condition of mice with MP, its mechanism may be related with the effect of reducing thrombosis and improving microcirculation.</p>