Alteration and significance of serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma: a retrospective study based on LEGEND-2 / 中华血液学杂志

Objective: To explore the dynamic changes in serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma (R/R MM) based on LEGEND-2. Methods: The data of patients with R/R MM who underwent BCMA-CAR-T therapy at our hospital between March 30, 2016, and February 6, 2018, were retrospectively collected. Serum lipid levels, controlled nutritional status (CONUT) score, and other clinical indicators at different time points before and after CAR-T-cell infusion were compared and analyzed. The best cut-off value was determined by using the receiver operator characteristic (ROC) curve. The patients were divided into high-CONUT score (>6.5 points, malnutrition group) and low-CONUT score groups (≤6.5 points, good nutrition group), comparing the progression-free survival (PFS) and total survival (OS) of the two groups using Kaplan-Meier survival analysis. Results: Before the infusion of CAR-T-cells, excluding triglycerides (TG), patients' serum lipid levels were lower than normal on average. At 8-14 d after CAR-T-cell infusion, serum albumin (ALB), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and apolipoprotein A1 (Apo A1) levels dropped to the minimum, whereas CONUT scores reached the maximum. In addition to TG, apolipoprotein B (Apo B) levels increased compared with baseline. After CAR-T-cell therapy, the patients' serum lipid levels significantly increased with well-improved nutritional status. Spearman's related analysis showed that TC, HDL, and ApoA1 levels after CAR-T-cell injection were significantly negatively correlated with the grade of cytokine-release syndrome (CRS) (r=-0.548, P=0.003; r=-0.444, P=0.020; r=-0.589, P=0.001). Furthermore, survival analysis indicated that the CONUT score was unrelated to PFS, and the median OS of patients with R/R MM in the high-CONUT score group was shorter than that in the low-CONUT score group (P=0.046) . Conclusions: During CAR-T-cell therapy, hypolipidemia and poor nutritional status were aggravated, which is possibly related to CRS. The patients' serum lipid levels and nutritional status were significantly improved after CAR-T-cell treatment. The CONUT score affected the median OS in patients treated with CAR-T-cells. Therefore, specific screening and intervention for nutritional status in patients receiving CAR-T-cell therapy are required.

Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors / 中华内科杂志

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Clinical study on the changes of left ventricular function and recovery after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension / 中华超声影像学杂志

Objective:To assess the configuration and systolic function of the left ventricle in patients with chronic thromboembolic pulmonary hypertension (CTEPH) by routine ultrasound, two-dimensional speckle tracking imaging and three-dimensional echocardiography, and to observe the recovery after pulmonary endarterectomy (PEA).Methods:The patients who were diagnosed with CTEPH, underwent PEA and had no left heart disease were enrolled as the CTEPH group ( n=30) in the China-Japan Friendship Hospital from November 2016 and June 2021. The right heart catheterization data before and after surgery were recorded. In the meantime, gender- and age-matched healthy individuals who sought for physical examination during the same period were included as the control group ( n=23). Echocardiography findings before and after PEA were comparatively analyzed and compared between the two groups, including left ventricular end-diastolic diameter (LVEDd), right and left ventricular cross-section ratio (RVd/LVd), left ventricular global longitudinal strain (LVGLS), left ventricular end-diastolic/systolic volume index (LVEDVi/LVESVi), left ventricular ejection fraction (LVEF) and left ventricular stroke volume (LVSV). Associations between the mean pulmonary arterial pressure (mPAP)/pulmonary vascular resistance (PVR) and left ventricular function were discussed. Results:When compared with the control group, the LVEDd, LVEDVi, LVESVi, LVSV, LVGLS and the mitral early to late diastolic flow velocity ratio (E/A) in the CTEPH group were lower (all P<0.05). There were no significant differences between the two groups regarding LVEF, cardiac output (CO), and cardiac index (CI) (all P>0.05). There were no statistical differences of the left ventricular volume and LVSV between PEA group and the control group (both P>0.05), while the LVGLS and E/A remained lower (both P<0.05). Correlation analysis showed negative associations between mPAP and LVSV as well as E/A ( r=-0.490, -0.455; both P<0.05). Conclusions:There are changes in left ventricular configuration with abnormal filling pattern and potential systolic dysfunction in CTEPH patients. The PEA surgery could lead to recovery of the left ventricular configuration and volume, but the filling pattern and LVGLS at follow-up can not recover completely.

Corrigendum to “Selection of quality markers of Jasminum amplexicaule based on its anti-diarrheal and anti-inflammatory activities: Effect-target affiliation-traceability-pharmacokinetics strategy” Chinese Herbal Medicines 11 (2019) 379–386 (Chinese Herbal Medicines (2019) 11(4) (379–386), (S167463841930070X), (10.1016/j.chmed.2019.08.002)) / 中草药·英文版

When this paper was first published the following ethical statement was omitted in error: All animal experimental protocols were approved by the Animal Ethics Committee of Guangdong Provincial Engineering Technology Institute of Traditional Chinese Medicine (Guangzhou, Guangdong, China, Approval NO: 048483). Further, all methods were performed in accordance with the relevant guidelines and regulations. NIH mice were purchased from the Guangdong Medical Laboratory Animal Center (Guangzhou, Guangdong, China, Certificate NO.44007200031795). The authors would like to apologise for any inconvenience caused.

Analysis of Chemical Constituents in Bushao Tiaozhi Capsules by UPLC-Q-TOF-MS / 中国实验方剂学杂志

Objective:To analyze the main chemical constituents of traditional Chinese medicine compound Bushao Tiaozhi capsules by using UPLC-Q-TOF-MS technology. Method:The separation was eluted with Waters CORTECS UPLC C18 column（2.1 mm×150 mm，1.6 μm） in a gradient mode， with methanol-0.1% formic acid as the mobile phase. The column temperature was 40 ℃，the flow rate was 0.24 mL·min-1，and the injection volume was 1 μL. The mass spectrometry condition was X500R QTOF mass spectrometry，the positive and negative electrospray ionization （ESI） was adopted for determine the chromatographic effluent，and the main chromatographic peaks were assigned and distinguished by Q-TOF. Result:A total of 53 chemical constituents were identified by reference confirmation，literature comparison，and high mass spectrometry data analysis. The chemical constituent cluster was composed of 21 flavonoids，10 phenolics，5 monoterpene glycosides，7 diterpene lactones and 10 sesquiterpenes. Furthermore，all of the constituents were surveyed and classified according to their medicinal materials derivation. Among them，the 5 flavonoids components（mangiferin，isoquercitrin，typhaneoside，isorhamnetin 3-O-neohesperidoside，tiliroside）were identified in Microctis Folium for the first time. Conclusion:This study shows that UPLC-Q-TOF-MS technology provides a simple，rapid，and accurate method for the identification of chemical constituents in Bushao Tiaozhi capsules. The identified chemical components mostly cover the main constituents of each medicinal material in the formula，so as to provide a new technological method and theoretical foundation for further defining the pharmacological basis and mechanism of action and optimizing the quality control of Bushao Tiaozhi capsules.

Cloning of New Antigen Gene MLAA-34 Promoter and Identification of Core Region in Acute Monocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To clone the promoter sequence of acute monocytic leukemia new antigen gene.MLAA-34 and identify its promoter core region.@*METHODS@#The full-length fragment of MLAA-34 gene promoter region was amplified by PCR, then was ligated into pGL3-Basic vector, and the recombinant plasmid was cloned. Constructed a series of MLAA-34 gene promoter 5' flanking region truncated plasmid. These recombinant plasmids were transfected into U937 and HEK293 cells, and the dual luciferase reporter gene was used to detect the promoter activity of each fragment to determine the minimum active region. Transcription factor binding sites were analyzed by bioinformatics methods.@*RESULTS@#The recombinant plasmid containing MLAA-34 promoter sequence and its truncated plasmid were successfully constructed, and the promoter activity was significantly increased as compared with the empty vector (P＜0.001). The minimal active region of MLAA-34 located between 402 bp and 200 bp. It contained multiple transcription factor binding sites such as E2F1, MZF-1, SP1, USF2 and STAT3.@*CONCLUSION@#The promoter of luciferase reporter gene has been successfully constructed with different deletion fragments of MLAA-34, and its core promoter region may contain multiple transcription factor sequence.

Selection of quality markers of Jasminum amplexicaule based on its anti-diarrheal and anti-inflammatory activities: Effect-target affiliation-traceability-pharmacokinetics strategy / 中草药·英文版

Objective: To investigate therapeutic mechanism in Jasminum amplexicaule (Oleaceae) and verify its main active component as quality control markers Methods: Established mouse models of diarrhea, intestinal angina, and inflammation were firstly used to select herb fractions with optimum efficacy, followed by an in vitro experiment to determine key targets associated with effects of J. amplexicaule extract. The selected fractions were isolated and purified, its components were identified, and the obtained compounds were verified for their effects on NF-κB and iNOS. Finally, effective compounds were administered to rats, their plasma pharmacokinetic parameters were calculated, and quality markers (QMs) reflecting therapeutic activities of J. amplexicaule were confirmed. Results: Trichloromethane and ethyl acetate fractions had significant anti-diarrheal, anti-inflammatory, and analgesic effects. The trichloromethane fraction also reduced BDNF, p38 MAPK, p-p38 MAPK, NF-κB p65, and p-NF-κB p65 levels in the ileum in a rhubarb-induced diarrhea mouse model. Additionally, it inhibited LPS-induced NF-κB transcription and nitric oxide (NO) production in RAW264.7 macrophages, which suppressed iNOS expression. Therefore, the trichloromethane fraction was further investigated. QMs candidate selection identified 17 compounds, and results of in-vitro therapeutic validation indicated that methyl caffeate and isochlorogenic acid B had the strongest anti-diarrheal, anti-inflammatory, and analgesic activities. After being validated by a UHPLC–MS-MS method, concentrations of these target compounds were accurately determined in the rat plasma and pharmacokinetic parameters were calculated. Cmax, tmax, and t1/2 were respectively 575.35 ng/mL (2.963 nmol/mL), 0.5 h, and 0.45 h for methyl caffeate and 262.03 ng/mL (0.5034 nmol/mL), 0.25 h, and 2.03 h for isochlorogenic acid B. Because these candidate compounds exhibited favorable pharmacokinetics, they were considered as QMs of J. amplexicaule. Conclusions: The present study accurately and effectively identified QMs of J. amplexicaule that act as indicators of efficacy and quality.

Garlicin Post-Conditioning Suppresses Adhesion Molecules in a Porcine Model of Myocardial Ischemia-Reperfusion Injury / 中国结合医学杂志

OBJECTIVES@#To evaluate whether garlicin post-conditioning can attenuate myocardial ischemiareperfusion injury in a catheter-based porcine model of acute myocardial infarction (AMI) by affecting adhesion molecules integrin β1/CD29 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31).@*METHODS@#Twenty-two swine were devided into 3 groups: 6 in a sham-operation group, and 8 each in the model and garlicin groups. AMI porcine model was established in the model and garlicin groups. The distal parts of the left anterior descending coronary artery in the animals of the model and garlicin groups were occluded by dilated balloon for 2 h, followed by reperfusion for 3 h. Garlicin (1.88 mg/kg) was injected over a period of 1 h, beginning just before reperfusion, in the garlicin group. Real-time polymerase chain reaction, immunohistochemistry and Western blot were carried out to detect mRNA and protein expressions of CD29 and CD31 3 h after reperfusion.@*RESULTS@#Hematoxylin-eosin staining showed a better myocardial structure in the garlicin group after reperfusion. Compared to the model group, garlicin inhibited both the mRNA and protein expression of CD29 and CD31 in reperfusion area and no-reflflow area (P<0.05 respectively).@*CONCLUSIONS@#Garlicin post-conditioning induced cardio-protection against myocardial ischemia-reperfusion injury in this catheter-based porcine model of AMI. The cardio-protective effect of garlicin is possibly owing to suppression of production of CD29 and CD31, by inhibition of the mRNA expression of CD29 and CD31.

Combined Effects of A Body Shape Index and Serum C-reactive Protein on Ischemic Stroke Incidence among Mongolians in China / 生物医学与环境科学（英文）

OBJECTIVE@#We aimed to evaluate the combined effects of a high body shape index (ABSI) and a high serum C-reactive protein (CRP) level on the incidence of ischemic stroke in a Mongolian population in China.@*METHODS@#A prospective cohort study was conducted among 2,589 participants from June 2002 to July 2012 in Inner Mongolia, China. The participants were categorized into 4 groups according to their level of ABSI and CRP. Cox proportional hazards models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for ischemic stroke among all groups.@*RESULTS@#The multivariate adjusted HRs (95% CI) of ischemic stroke for high ABSI and high CRP level were 1.46 (0.89-2.39) and 1.63 (0.95-2.79), respectively. Compared with the low ABSI/low CRP level group, the multivariate adjusted HRs (95% CI) of ischemic stroke in the low ABSI/high CRP, high ABSI/low CRP, and high ABSI/high CRP groups were 1.04 (0.46-2.35), 1.06 (0.58-1.95) and 2.52 (1.27-5.00), respectively. The HR of ischemic stroke for the high ABSI/high CRP level group was the highest and most statistically significant.@*CONCLUSION@#We found that participants with simultaneously high ABSI and high CRP levels had the highest risk of ischemic stroke in the Mongolian population. Our findings suggest that the combination of high ABSI and high CRP levels may increase the risk of ischemic stroke.

The protective effects of lycium barbarum polysaccharides on retinal neurons in diabetic rats and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To clarify whether lycium barbarum polysaccharides (LBP) have protective effects on retina neuronal cells in diabetic rats and to identify the related mechanism involved in this process.@*METHODS@#Eighteen SD rats were randomly divided into 3 groups ( n= 6): normal control group (NC), diabetes mellitus group (DM) and LBP-treatment group (DM+LBP). The diabetic rat model was induced by single intraperitoneal injection of streptozotocin (STZ). The rats in DM+LBP group were treated with LBP at the dose of 1 mg/kg by gavage, once a day for 12 weeks. After the treatment, the weight and blood glucose, the generation of reactive oxygen species (ROS), the surviving retinal ganglion cells (RGCs) and amacrine cells and the protein expressions of nuclear factor E2-related factor 2 (Nrf2) and the heme oxygenase-1 (HO-1) were detected.@*RESULTS@#The successful rate of diabetic model was 100%. Compared with NC group, the rats of DM group caused weight loss, elevated blood glucose, a marked increase of ROS generation and a significant decrease in the number of RGCs and amacrine cells (P＜0.01), and these effects were diminished or abolished by LBP treatment. Meanwhile, LBP significantly increased the expressions of Nrf2 and HO-1 in the retinas of diabetic rats (P＜0.01).@*CONCLUSION@#LBP can improve retinal oxidative stress and exert beneficial neuroprotective effects in diabetic rats, and its mechanism may be associated with the activation of the Nrf2/HO-1 antioxidant pathway.

Effects of Transcription Factor MZF-1 on Transcriptive Regulation of Acute Monocytic Leukemia-related Gene MLAA-34 / 中国实验血液学杂志

OBJECTIVE@#To investigate the transcriptional regulation of transcription factor MZF-1 on acute monocytic leukemia-related gene MLAA-34.@*METHODS@#The effect of MZF-1 on the transcriptional activity of MLAA-34 gene promoter was analyzed by luciferase reporter gene detection system and site-directed mutation technique. The EMSA and ChIP assay were used to verify whether MZF-1 directly and specifically binds to the core region of MLAA-34 promoter. The over-expression vector and interference vector of MZF-1 were constructed to transfect U937 cells, and RT-PCR and Western blot were used to detect the transcription and expression changes of MLAA-34 gene.@*RESULTS@#The transcription factor MZF-1 had a regulatory effect on MLAA-34 gene expression, and the relative luciferase activity was decreased after MZF-1 binding point mutation (P<0.01). EMSA and ChIP experiments demonstrated that MZF-1 could directly bind to MLAA-34 promoter and play a regulatory role. In the over-expression test, the increase of MZF-1 could up-regulate the expression of MLAA-34 (P<0.05). In the interference test, the decrease of MZF-1 could down-regulate the expression of MLAA-34 (P<0.05).@*CONCLUSION@#Transcription factor MZF-1 can bind to the transcriptional regulatory region on the promoter of MLAA-34 gene and promote the transcription of MLAA-34 gene in acute monocytic leukemia.

Detection of Novel Antigen MLAA-34 Gene Mutation in Acute Monocytic Leukemia and Its Correlation with Efficacy / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of all exone mutation in MLAA-34 gene with chemotherapeutic efficacy for leukemia.</p><p><b>METHODS</b>The expression level of MLAA-34 gene in 40 patients with AML-M5 and 5 healthy volunteers as control was detected by RT-PCR and its effect on chemotherapeutic efficacy were analyzed by RT-PCR; the effect of MLAA-34 gene mutation on overall survival (OS) and progression-free survival (PFS) of AML-M5 patients was analyzed by sequencing of all 12 exoues in MLAA-34 gene, the correlation between the mutation of prognostic genes important to leukemia and the mutation of MLAA-34 gene was explored.</p><p><b>RESULTS</b>The expression level of MLAA-34 gene was significantly up-regulated as compared with that of healthy volunteers, moreover this up-regulation was related with a C59T SNP site located in second exon of MLAA-34 gene, meanswhile this SNP site is affinitive to the well-known mdecular markers of AML, inclinding Fms-like tyrosine kinase (FLT-3) and DNA methyltransferase-3A(DNAMT3A). The AML-M5 patients with high expression of MLAA-34 gene poorly responded to chemotherapy, the AML-M5 patients with MLAA-34 C59T mulation had even more high expression of MLAA-34 gene and significantly short OS and PFS in comparison with those of patients without C59T mutation.</p><p><b>CONCLUSION</b>The C59T mutation in MLAA-34 gene is a high risk factor for recurrence of AML, and may be a cadidate target for treatment of AML.</p>

Echocardiographic study of right ventricular dysfunction in patients with chronic thromboembolic pulmonary hypertension: Comparison of the right ventricular free wall longitudinal strain and conventional parameters / 中华超声影像学杂志

Objective@#To compare the value of right ventricular (RV) free wall longitudinal strain (FWLS) by speckle tracking echocardiography (STE) and conventional parameters in evaluation of RV dysfunction in chronic thromboembolic pulmonary hypertension (CTEPH).@*Methods@#Sixty CTEPH patients were enrolled as group A and 45 pulmonary embolism (PE) patients with normal pulmonary pressure were enrolled as group B in this study. CTEPH patients were divided into 2 subgroups using the World Health Organization (WHO) function classification: patients with WHO Ⅰ-Ⅱ were designated as group A1 and those with WHO Ⅲ-Ⅳ were designated as group A2. Conventional RV functional parameters including tricuspid annular plane systolic excursion (TAPSE), tissue Doppler-derived tricuspid annular systolic velocity (S′), fractional area change (FAC), RV index of myocardial performance (RVIMP), and STE-derived RV FWLS were measured and compared. Clinical right heart failure (RHF) was defined as the presence of symptoms of heart failure and signs of systemic circulation congestion during hospitalization.@*Results@#Compared to group B, group A patients had significant enlarged right heart dimension and impaired RV systolic function parameters (all P<0.001). The TAPSE, S′, FAC, and RV FWLS showed significant differences between CTEPH patients with mild (group A1) and severe symptoms (group A2) (all P<0.01), while RVIMP showed no significant difference (P=0.188). On receiver operating characteristic analysis, FWLS had the largest AUC to identify RHF (AUC=0.864, P<0.001), when the cutoff value was 15.05%, the sensitivity was 85.71%, and the specificity was 64.29%, respectively. On binary logistic regression analysis, only right atria area (OR=1.212, 95%CI=1.004-1.48, P=0.046) and RV FWLS (OR=0.662, 95%CI=0.470-0.933, P=0.018) were identified as independent predictor of RHF.@*Conclusions@#Compared with conventional parameters, RV FWLS showed advantages in identifying abnormal RV function in CTEPH patients.

Establishment of UPLC fingerprints of Jasminum elongatum and determination of two constituents / 中成药

AIM To establish the UPLC fingerprints of Jasminum elongatum (Bergium) Wild.and to determine the contents of isochlorogenic acid B and ethylcaffeate.METHODS The analysis of methanol extract of J.elongatum was developed on a 25 ℃ thermostatic Agilent Ecplise XDB-C18 column (2.1 mm × 100 mm,1.7 μm),with the mobile phase comprising of acetonitrile-0.1％ methanoic acid flowing at 0.5 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS There were eighteen common peaks in the fingerprints of ten batches of samples,with the similarities of more than 0.85.Isochlorogenic acid B and ethylcaffeate showed good linear relationships within the ranges of 7.67-38.35 μg/mL (R2 =0.999 4),9.60-96.0 μg/mL (R2 =0.999 7),whose average recoveries were 98.61％,99.09％ with the RSDs of 0.84％,1.25％,respectively.CONCLUSION This stable and reliable method can be used for the quality control of J.elongatum.

The discovery of synergistic anti-tumor effect of the cannabinoid receptor agonists in combination with WIN55212-2 and exemestane / 国际药学研究杂志

Objective To discover antitumor drugs showing a synergistic effect with the cannabinoid receptor agonist sildenafil mesylate (WIN55212-2), so as to provide a new strategy for potential drug combinations for improving the life quality of cancer patients. Methods Firstly, the antitumor activity was tested for the combination of cannabinoid receptor 1 (CB1R) receptor agonist WIN55212-2 with each of 25 antitumor drugs using three tumor cell lines with high CB1R, HepG2, DU145 and HCT-8, by highthroughput assay. Then, the in vitro tumor colony-forming assay and 3D tumor spheroid assay were conducted to confirm the synergistic effect for the effective drug combination. Flow cytometry was used to investigate the effect of the synergistic drug combination on the apoptosis and cell cycle progression. Results Three drugs showed a synergistic inhibitory effect on the proliferation of tested tumor cells by combining with WIN55212-2, and among them, the combination of exemestane with WIN55212-2 displayed best effect, which showed a dose-dependent synergistic antitumor effect in the in vitro tumor colony-forming test and 3D tumor spheroid assay (CI＜1).Compared with the single-exemestane treatment, the combination of exemestane with WIN55212-2 significantly increased the apoptosis of HepG2 cells (P＜0.01) and caused G2/M phase arrest of the HepG2 cells. Conclusion The study is the first to report that the combination of exemestane with WIN55212-2 showed a synergistic anti-tumor activity on HepG2 cells, which was likely related to the promotion of apoptosis and induction of cell cycle arrest.

Polymorphism in rs2229783 of the Alpha 1(XI) Collagen Gene Is Associated with Susceptibility to but not Severity of Kashin-Beck Disease in a Northwest Chinese Han Population / 生物医学与环境科学（英文）

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. The purpose of this study was to explore whether genomic polymorphisms in the alpha 1(XI) collagen gene (COL11A1) were associated with the risk and severity of Kashin-Beck disease (KBD). Twenty-two single nucleotide polymorphisms (SNPs) in COL11A1 were genotyped in 274 KBD cases and 249 healthy controls using the Sequenom MassARRAY system. The expression of type XI collagen (COL11A) in the knee articular cartilage of 22 KBD patients and 21 controls was analyzed by immunohistochemistry. Our results showed that the frequency distribution of genotypes of the rs2229783 polymorphism in COL11A1 was significantly different between the KBD and control groups (P = 0.0003). Moreover, the expression level of COL11A in cartilage was significantly lower in the KBD group than in the controls (t = 2.637, P = 0.02). However, no association was found between the rs2229783 and the severity of KBD, suggesting a role of COL11A1 in the susceptibility to but not the severity of KBD.

Validation of the China-PAR Equations for Cardio-cerebrovascular Risk Prediction in the Inner Mongolian Population / 生物医学与环境科学（英文）

The objective of this study was to evaluate the usefulness of the China-PAR equations in predicting the 10-year risk of cardiovascular disease (CVD) in the Inner Mongolians population. A population-based, prospective cohort of 2,589 Mongolians were followed up from 2003 to 2012. Participants were categorized into 4 subgroups according to their 10-year CVD risks calculated using the China-PAR equations: < 5%, 5%-9.9%, 10%-19.9%, and ⪖ 20%. The China-PAR equations discriminated well with good C statistics (range, 0.76-0.86). The adjusted hazard ratios for CVD showed an increasing trend among the 4 subgroups (P for trend < 0.01). However, the China-PAR equations underestimated the 10-year CVD risk in Mongolians, and the calibration was unsatisfactory (Hosmer-Lemeshow χ2 = 19.98, P < 0.01 for men, χ2 = 46.58, P < 0.001 for women). The performance of the China-PAR equations warrants further validation in other ethnic groups in China.

Combined Effects of Family History of Cardiovascular Disease and Serum C-reactive Protein Level on the Risk of Stroke: A 9.2-year Prospective Study among Mongolians in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We aimed to evaluate the combined effect of a family history of cardiovascular disease (CVD) and high serum C-reactive protein (CRP) on the stroke incidence in an Inner Mongolian population in China.</p><p><b>METHODS</b>A prospective cohort study was conducted from June 2002 to July 2012, with 2,544 participants aged 20 years and over from Inner Mongolia, China. We categorized participants into four groups based on the family history of CVD and CRP levels.</p><p><b>RESULTS</b>We adjusted for age; sex; smoking; drinking; hypertension; body mass index; waist circumference; and blood glucose, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. Compared with the group with no family history of CVD/low CRP levels, the group with family history of CVD/high CRP levels had a hazard ratio (HR) of 1.78 [95% confidence interval (CI), 1.03-3.07; P = 0.039] of stroke, and an HR of 2.14 (95% CI, 1.09-4.20; P = 0.027) of ischemic stroke. The HRs of hemorrhagic stroke for the other three groups were not statistically significant (all P > 0.05).</p><p><b>CONCLUSION</b>Participants with both a family history of CVD and high CRP levels had the highest stroke incidence, suggesting that high CRP levels may increase stroke risk, especially of ischemic stroke, among individuals with a family history of CVD.</p>

Role of Jagged1-Hey1 Signal in Angiotensin II-induced Impairment of Myocardial Angiogenesis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Angiotensin II (Ang II) is a major contributor to the development of heart failure. However, the molecular and cellular mechanisms that underlie this process remain elusive. Inadequate angiogenesis in the myocardium leads to a transition from cardiac hypertrophy to dysfunction, and our previous study showed that Ang II significantly impaired the angiogenesis response. The current study was designed to examine the role of Jagged1-Notch signaling in the effect of Ang II during impaired angiogenesis and cardiac hypertrophy.</p><p><b>METHODS</b>Ang II was subcutaneously infused into 8-week-old male C57BL/6 mice at a dose of 200 ng·kg-1·min-1 for 2 weeks using Alzet micro-osmotic pumps. N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester (DAPT), a γ-secretase inhibitor, was injected subcutaneously during Ang II infusion at a dose of 10.0 mg·kg-1·d-1. Forty mice were divided into four groups (n = 10 per group): control group; Ang II group, treated with Ang II; DAPT group, treated with DAPT; and Ang II + DAPT group, treated with both Ang II and DAPT. At the end of experiments, myocardial (left ventricle [LV]) tissue from each experimental group was evaluated using immunohistochemistry, Western blotting, and real-time polymerase chain reaction. Data were analyzed using one-way analysis of variance test followed by the least significant difference method or independent samples t-test.</p><p><b>RESULTS</b>Ang II treatment significantly induced cardiac hypertrophy and impaired the angiogenesis response compared to controls, as shown by hematoxylin and eosin (HE) staining and immunohistochemistry for CD31, a vascular marker (P < 0.05 for both). Meanwhile, Jagged1 protein was significantly increased, but gene expression for both Jag1 and Hey1 was decreased in the LV following Ang II treatment, compared to that in controls (relative ratio for Jag1 gene: 0.45 ± 0.13 vs. 0.84 ± 0.15; relative ratio for Hey1 gene: 0.51 ± 0.08 vs. 0.91 ± 0.09; P < 0.05). All these cellular and molecular effects induced by Ang II in the hearts of mice were reduced by DAPT treatment. Interestingly, Ang II stimulated Hey1, a known Notch target, but did not affect the expression of Hey2, another Notch target gene.</p><p><b>CONCLUSIONS</b>A Jagged1-Hey1 signal might mediate the impairment of angiogenesis induced by Ang II during cardiac hypertrophy.</p>

Screening of Serum Peptidome-Based Biomarker for Multiple Myeloma Renal Impairment / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To screen serum peptide associated with renal impairment in patients with multiple myeloma(MM) and search early biomarker of MM renal impairment.</p><p><b>METHODS</b>The weak cation exchange magnetic bead combined with matrix assisted laser desorption/ionization time of flight mass spectrometry was used to compare and analyze serum peptidome of MM with or without renal impairment.</p><p><b>RESULTS</b>There were 18 peptide peaks with statistical significance in the molecular weight range from 700 to 10 000 Da(P<0.05), among them 7 peptides were upregulated and 11 were downregulated. The Quick Classifier diagnostic model composed of 3 peptides, which can strongly distinguish MM patients with or without renal impairment by means of Embedded Software. Its sensitivity and specificity were 97.14% and 94.12%, respectively. Peptides with molecular weight of 3908.85 Da and 3216.06 Da were significantly upregulated in MM patients with renal impairment, while the peptide with molecular weight of 2990.08 Da was significantly downregulated in MM patients with renal impairment.</p><p><b>CONCLUSION</b>Peptides associated with MM renal impairment obtained by serum peptidome technology can provide a new clue for early assessment and diagnosis of clinical MM renal impairment.</p>