Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma / 中华肿瘤杂志

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

Effect of γδ T cells on the Proliferation, Apoptosis and Autophagy of Multiple Myeloma Cells / 中国实验血液学杂志

AbstractObjective: To investigate the effect of γδ T cells on the proliferation, apoptosis and autophagy of multiple myeloma cells.@*METHODS@#Peripheral blood mononuclear cells (PBMNC) were isolated from healthy volunteers, and stimulated with zoledronic acid (Zol) in combination with rhIL-2. Flow cytometry analysis was used to detected the purity of γδ T cells. γδ T cells were collected and co-cultured with RPMI-8226 or U-266 cells at different effector target ratios. The proliferation of RPMI-8226 or U-266 cell lines were detected by CCK-8. Cell cycle and cell apoptosis were detected by flow cytometry and Western blot．The expressions of autophagy-related proteins were detected by Western blot.@*RESULTS@#γδ T cells can be expanded in vitro. γδ T cells could inhibit the proliferation of RPMI-8226 or U-266 cells, induced cell cycle arrest and promoted apoptosis in an effector target-dependent manner. In addition, γδ T cells could induce autophagy of myeloma cells, inhibited the expression of autophagy-related PI3K, P-AKT and P-mTOR, while increased the expression of AMPK and Beclin-1.@*CONCLUSION@#γδ T cells can inhibit the proliferation of RPMI-8226 and U-266 myeloma cells, induce cell cycle arrest, promote apoptosis, and enhance autophagy in vitro. The mechanism may be related to inhibition of PI3K/AKT/mTOR signaling pathway and/or activation of AMPK/Beclin-1 signaling pathway.

Ethnopharmacology, Phytochemistry, Pharmacology, Toxicology and Clinical Applications of Radix Astragali / 中国结合医学杂志

Radix Astragali (RA), a traditional Chinese medicine from the dried root of Astragalus species, is widely distributed throughout the temperate regions of the world. The major bioactive constituents of RA are triterpene glycosides, flavonoids, saponins, and alkaloids, and these compounds mostly exert pharmacological activities on the cardiovascular, immune, respiratory, and hepatic systems. This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources, ethnopharmacology, phytochemistry, pharmacology, toxicology, clinical application, and patent release of RA. We hope this review can provide a guidance for further development of therapeutic agents from RA.

Saposhnikovia divaricata-An Ethnopharmacological, Phytochemical and Pharmacological Review / 中国结合医学杂志

Saposhnikovia divaricata (Turcz.) Schischk., a perennial herb belonging to the family Umbelliferae, is widely distributed in Northeast Asia. Its dried root (Radix Saposhnikoviae) is used as a Chinese herbal medicine for the treatment of immune system, nervous system, and respiratory diseases. Phytochemical and pharmacological studies have shown that the main constituents of S. divaricata are chromones, coumarins, acid esters, and polyacetylenes, and these compounds exhibited significant anti-inflammatory, analgesic, antioxidant, antiproliferative, antitumor, and immunoregulatory activities. The purpose of this review is to provide comprehensive information on the botanical characterization and distribution, traditional use and ethnopharmacology, phytochemistry, and pharmacology of S. divaricata for further study concerning its mechanism of action and development of better therapeutic agents and health products from S. divaricata.

Inter- and intra-observer variability for the assessment of coronary artery tree description and lesion EvaluaTion (CatLet©) angiographic scoring system in patients with acute myocardial infarction / 中华医学杂志(英文版)

BACKGROUND@#Previously, we developed a novel Coronary Artery Tree description and Lesion EvaluaTion (CatLet©) angiographic scoring system, which was capable of accounting for the variability in the coronary anatomy and assisting in the risk-stratification of patients with acute myocardial infarction (AMI). Our preliminary study revealed that the CatLet score better predicted clinical outcomes for AMI patients than the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score. However, the reproducibility of the CatLet score in both inter- and intra-observer remains to be evaluated.@*METHODS@#A total of 30 consecutive AMI patients, admitted in September of 2015, were independently assessed by two experienced interventional cardiologists to evaluate the inter-observer reproducibility of the CatLet score. Another set of 49 consecutive AMI patients, admitted between September and October in 2014, were assessed by one of the two interventional cardiologists on two occasions 3 months apart to evaluate the intra-observer reproducibility of the CatLet score. The weighted kappa was used to express the degree of agreement.@*RESULTS@#The weighted kappa values (95% confidence interval) for the intra- and inter-observer reproducibility of the CatLet Score were 0.82 (0.59-1.00, Z = 7.23, P 22). Regarding the adverse characteristics pertinent to lesions and dominance parameters, the kappa values for the inter-observer variability were 0.80 (0.56-1.00, Z = 6.47, P < 0.001) for total number of lesions, 0.57 (0.28-0.85, Z = 3.03, P < 0.001) for bifurcation, 0.69 (0.43-0.96, Z = 5.06, P < 0.001) for heavy calcification, 1.00 (0.72-1.00, Z = 6.93, P < 0.001) for tortuosity, 0.54 (0.26-0.82, Z = 3.78, P < 0.001) for thrombus, 0.69 (0.48-0.91, Z = 6.29, P < 0.001) for right coronary artery dominance, 0.69 (0.41-0.96, Z = 4.91, P < 0.001) for left anterior descending artery length, and 0.22 (0.06-0.51, Z = 1.56, P = 0.06) for diagonal size. Equivalent values for the intra-observer variability were moderate to almost perfect (range 0.54-1.00).@*CONCLUSIONS@#The reproducibility of the CatLet angiographic scoring system for evaluation of the coronary angiograms ranged from substantial to excellent. The high reproducibility of the CatLet angiographic scoring system will boost its clinical application to patients with AMI.

Effect of SARI Overexpression on Apoptosis of CBFL Cells and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of SARI overexpression on the proliferation and apoptosis of core binding factor leukemia (CBFL) cells and explore the potential molecular mechanisms.@*METHODS@#C-KIT N822K mutation status in Kasumi-1 cell line was detected by exon 17 sequencing. Then the SARI lentiviral vector (pGC-FU-SARI) was constructed, meanwhile Kasumi-1 cells were transfected with the SARI lentiviral vector. Quantitative PCR and Western blot were employed to identify efficacy of SARI overexpression after the transfection of cells. Cells were divided into three groups, including the cells infected with pGC-FU-SARI (OE group), the cells infected with pGC-FU-GFP (NC group) and the untreated cells (blank control group). Cell proliferative activity was tested by MTT assay, cell apoptosis was measured by flow cytometry (FCM) and the expression of apoptosis-related proteins: BCL-2,BAX,Cyto C,Caspase 9,Caspase 3,cleaved-Caspase 3,PARP and cleaved-PARP as well as PI3K/Akt pathway proteins: PI3K（p85）,p-PI3K（p85）,Akt and p-Akt were detected by Western blot.@*RESULTS@#The Kasumi-1 cells were detected to bear c-KIT N822K (T>A) mutation. The Kasumi-1 cells with SARI was overexpression were construeted successfully. Compared with NC group, the cell proliferation was decreased and cell apoptosis was increased; BCL-2 expression was reduced, BAX expression was enharued; cyto C expression appeared; the expression of Caspase 9 and Caspase 3 was down-regulated, the expression of cleaved Caspase 3 was up-regulated; the PARP expression was decreased, cleaved PARP expression was increased; the phosphorylation level of PI3K/Akt pathway proteins: p-PI3K/PI3K, p-Akt/Akt was down-regulated in OE group (P<0.05).@*CONCLUSION@#SARI gene may suppress the proliferation of CBFL cells, and induce their apoptosis through the mitochondrial pathway, which may be related with the inhibition of PI3K/Akt pathway.

Outcomes of Ebstein's Anomaly Patients Treated with Tricuspid Valvuloplasty or Tricuspid Valve Replacement: Experience of a Single Center / 中华医学杂志(英文版)

<p><b>Background</b>The incidence of Ebstein's anomaly is extremely low, and except for the Mayo Clinic, no cardiac center has reported on a sufficient number of patients. The aim of our study was to report the outcomes of Ebstein's anomaly patients treated with tricuspid valvuloplasty (TVP) or tricuspid valve replacement (TVR).</p><p><b>Methods</b>TVP or TVR was performed in 245 patients from July 2006 to April 2016. We reviewed patients' records and contacted patients via outpatient service and over the telephone.</p><p><b>Results</b>The mean follow-up time was 43.6 ± 32.6 months, and 224 (91.4%) patients underwent follow-up. The mean operative age was 31.2 ± 15.7 years. TVR was performed in 23 patients, and TVP was performed in 201 patients. The 30-day mortality rate was 1.3%, and the overall survival rate was 97.9% at 5 and 10 years. The early mortality rate of the TVP group was lower than that of the TVR group (0.5% vs. 8.7%, P = 0.028), and the overall mortality rate of the TVP group was lower than that of the TVR group, without statistical significance (1.0% vs. 8.7%). After propensity score matching, the rates of mortality and New York Heart Association class ≥ III were lower in the TVP group than those in the TVR group without statistical significance. Seven patients with Type B Wolff-Parkinson-White (WPW) syndrome underwent one-stage surgery, and arrhythmias disappeared. Six patients suffered from episodes of left ventricular outflow tract obstruction (LVOTO) during surgery. Severe LVOTO could be treated with reoperation of the atrialized right ventricle.</p><p><b>Conclusions</b>Ebstein's anomaly patients treated with TVP or TVR can experience optimal outcomes with midterm follow-up. However, TVP should be the first-choice treatment. Optimal outcomes can be obtained from one-stage operation in patients with Type B WPW syndrome. Severe LVOTO during surgery might be related to improper operation of the atrialized right ventricle.</p>

Clinical Analysis and Echocardiographic Evaluation of Paravalvular Leaks After Surgical Aortic Valve Replacement / 中国循环杂志

Objectives: To explore the clinical features and the value of echocardiographic examination of paravalvular leaks after surgical aortic valve replacement. Methods: A total of 123 patients (aged from 12-74 [mean age 45 ± 13] years) hospitalized in our hospital from 2002-03 to 2017-03 because of paravalvular leaks after surgical aortic valve replacement were included in this study. The first operation was performed in our hospital or other hospitals. All patients had a confirmed diagnosis of paravalvular leaks by transthoracic or transesophageal echocardiography. Among them, 28 cases received non-surgical treatment and paravalvular leaks were corrected by reoperation in 95 cases. Results: Diastolic paravalvular regurgitation was detected by color doppler echocardiography in most patients, and dehiscence between the artificial valve and adjacent tissue was evidenced by two-dimensional echocardiography in some patients. The causes of paravalvular leaks, defined by imaging modalities including echocardiography, operative findings and pathological results included: infective endocarditis in 45 patients, Bechet's syndrome in 23 patients, Takayasu arteritis in 4 patients, suspected diagnosis of immune system diseases in 5 patients, aortic dissection in 2 patients, suspected operative technical reasons in 3 patients, and unknown in 41 patients. There were 13 deaths in this cohort, 5 patients gave up the further treatment and self-discharged due to the serious disease conditions. During follow-up, mild degree or above paravalvular leaks were found in 27 patients, 1 patient suffered from heart failure, improvement or recovery were seen in 55 patients.Conclusions: The paravalvular leaks with significant clinical consequence is an important complication after surgical aortic valve replacement, and most patients need to be treated with reoperation. Despite reoperation, the recurrence rate remains high and the prognosis is poor. Infective endocarditis is the most common cause of paravalvular leaks in prosthetic aortic valves, followed by non-specific vasculitis. Echocardiography plays an important role on diagnosis and monitoring in these patients.

Study of a novel diagnostic assay for thoracic malignant tumor based on DNA image cytometry / 临床与实验病理学杂志

Purpose To explore the effects of ploidy analysis on thoracic neoplasms based on DNA image cytometry (DNA-ICM), and to look for a meaningful novel diagnostic assay for tumor patients. Methods 4 402 patients who were diagnosed with thoracic disease were recruited in 2 years. By the DNA-ICM analysis, all the specimens were diagnosed as three types——positive, equivocal and negative ones. The results of701 specimens were compared with biopsy and clinical followup. Results DNA aneuploidy detected by DNA-ICM were65％ in confirmed malignant samples, 64％ in equivocal malignancy, and 8％ in non-malignant diseases. The comprehensive performance of DNA-ICM in malignancy was 73％, 93％, 71％, 94％ respectively for sensitivity, specificity, positive predictive value and negative predictive value. OR analysis found that the risk ratio of aneuploidy in malignancy was 23.236 compared to non-malignancy. Conclusion DNA-ICM can be applied in thoracic malignancy and have more potential values to be explored in oncology.

Effect of PI3K/Akt/mTOR signal pathway-mediated N822K mutation on apoptosis induced by c-KIT inhibitor in AML cells / 中国免疫学杂志

Objective:To investigate the effect of c-KIT N822K mutation on the apoptosis of AML cells induced by c-KIT inhibitor and to explore the underlying molecular mechanisms.Methods: Kasumi-1 cells that carry the c-KIT N822K mutation were used as experimental group,and HL-60 and NB4 cells with non-c-KIT N822K mutation were used as control group.These AML cells were treated with 0,0.04,0.16 and 0.64 μmol/L c-KIT inhibitor sunitinib for 24 h,respectively.Apoptosis-related proteins and PI3K/Akt/mTOR pathway proteins were detected by Western blot,compared the changes of cell-related signal pathway proteins in each group.Results: With the increase of sunitinib concentration,the expression of apoptosis-related proteins Bax,CytoC,Caspase-9, Actived-Caspase-3 and PARP in HL-60 and NB4 cells were increased (P<0.05),and the expression of anti-apoptotic protein Bcl-2 was down-regulated (P<0.01).However,the trend of this change was obviously weakened in Kasumi-1 cells with N822K mutation.In Kasumi-1 cells,the phosphorylation levels of PI3K/Akt/mTOR pathway proteins such as PI3K,Akt,4EBP1 and mTOR were down-regulated in a dose-dependent manner(P<0.05),but not in HL-60 cells and NB4 cells.Conclusion:The constitutive activation of c-KIT induced by N822K mutation may affect the apoptosis induction of c-KIT inhibitor sunitinib to Kasumi-1 cells,which may be related to the inhibition of PI3K/Akt/mTOR pathway.