Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

The In Vivo Intervention and Relative Mechanism of Genistein on the Inflammation and Thrombophilia in Lymphoma-Bearing Mice / 中国实验血液学杂志

OBJECTIVE@#To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.@*METHODS@#Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX）drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.@*RESULTS@#After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05).@*CONCLUSION@#Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.

Clinical features of fundus lesions of 74 patients with acquired immunodeficiency syndrome in Shenyang / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical features and factors of fundus lesions in patients with acquired immunodeficiency syndrome(AIDS)in Shenyang and the relationship between fundus lesions and CD4+T cell count.METHODS: Retrospective case study. A total of 74 cases with AIDS who were treated in the Central Hospital of Liaoning Electric Power Supply Co., Ltd., from January 2021 to December 2021 were selected. The fundus manifestation and CD4+T cell count of the patients were analyzed.RESULTS: The total detection rate of fundus lesions in AIDS patients was 58%. CD4+T cell count in the patients with fundus lesions was significantly lower than that in the patients with normal fundus [29(6, 55)/μL vs. 76(35, 103)/μL, P<0.01]. The rate of fundus lesions was the highest in the patients with CD4+T cell count ≤ 50/μL(74%). Logistic regression analysis showed that as the CD4+T cell count increased, the incidence of fundus lesions decreased(OR=0.977, 95%CI 0.964～0.991, P<0.01).CONCLUSION: Fundus lesions in AIDS patients related to CD4+T cell count. Decreasing CD4+T cell count was a risk factor of fundus lesions for AIDS patients. Routine fundus examination is important for the early diagnosis of fundus lesions in AIDS patients.

Clinical features, gene mutation profile and prognosis analysis of diffuse large B-cell lymphoma complicated with follicular lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathologic characteristics, gene mutation profile and prognostic influencing factors of diffuse large B-cell lymphoma (DLBCL) complicated with follicular lymphoma (FL) (DLBCL/FL).Methods:The clinicopathological data of 50 DLBCL/FL patients admitted to Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine from February 2018 to November 2021 were retrospectively analyzed. Targeted sequencing was performed to assess the mutation profile of 55 lymphoma-related genes. The clinicopathological characteristics were summarized to evaluate the short-term therapeutic efficacy of all patients. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS) of patients. Cox regression risk models were used to assess the factors affecting the OS and PFS.Results:Among 50 DLBCL/FL patients, 23 cases (46%) were male, 22 cases (44%) had an international prognosis index (IPI) score ≥ 2 points, 16 cases (32%) were double-expression lymphoma (DEL) and 4 cases (8%) were double-hit lymphoma (DHL). The complete response (CR) and overall response rates were 68% (34/50) and 78% (39/50), respectively after the first-line therapy. The median follow-up time was 23.3 months (5.1-50.9 months). The 2-year OS rate was 82.1% and 2-year PFS rate was 67.1%; and the median OS and PFS were not reached. Targeted sequencing results showed that the mutation frequencies of KMT2D, MYD88, TP53, BTG2, DTX1, EZH2, CD70, CREBBP, DUSP2, HIST1H1C, HIST1H1E and PRDM1 genes in this cohort were more than 15%. Multivariate Cox regression analysis showed that male ( HR = 4.264, 95% CI 1.144-15.896, P = 0.031) and IPI score ≥ 2 points ( HR = 6.800, 95% CI 1.771-37.741, P = 0.007) were independent risk factors of PFS in newly diagnosed DLBCL/FL patients, and TP53 mutation ( HR = 4.992, 95% CI 1.027-24.258, P = 0.046) was an risk influencing factor of OS. Conclusions:The proportion of male and female DLBCL/FL patients is similar, with a small proportion of DHL. Mutations of KMT2D, MYD88 and TP53 genes are commonly found in DLBCL/FL patients. Generally, DLBCL/FL patients can have a high overall response and good prognosis. Male and IPI score ≥ 2 points are the independent risk factors of PFS, and TP53 mutation is an independent risk factor of OS in DLBCL/FL patients.

Clinical characteristics and prognosis of primary and secondary diffuse large B-cell lymphoma of the pancreas / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods: Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes). Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival (OS) and progression-free survival (PFS) . Results: Overall, 80 patients were included; 12 patients had primary pancreatic DLBCL (PPDLBCL), and 68 patients had secondary pancreatic DLBCL (SPDLBCL). Compared with those with PPDLBCL, patients with SPDLBCL had a higher number of affected extranodal sites (P<0.001) and had higher IPI scores (P=0.013). There was no significant difference in the OS (P=0.120) and PFS (P=0.067) between the two groups. Multivariate analysis indicated that IPI intermediate-high/high risk (P=0.025) and double expressor (DE) (P=0.017) were independent adverse prognostic factors of OS in patients with pancreatic DLBCL. IPI intermediate-high/high risk (P=0.021) was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL. Targeted sequencing of 29 patients showed that the mutation frequency of PIM1, SGK1, BTG2, FAS, MYC, and MYD88 in patients with pancreatic DLBCL were all >20%. PIM1 (P=0.006 for OS, P=0.032 for PFS) and MYD88 (P=0.001 for OS, P=0.017 for PFS) mutations were associated with poor OS and PFS in patients with SPDLBCL. Conclusion: There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL. IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL. PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.

Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal Networks / 神经科学通报·英文版

Acetylcholine (ACh) is an important neuromodulator in various cognitive functions. However, it is unclear how ACh influences neural circuit dynamics by altering cellular properties. Here, we investigated how ACh influences reverberatory activity in cultured neuronal networks. We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses, but to a much lesser extent at high doses. Moreover, high doses of ACh caused a longer duration of evoked reverberation, and a higher occurrence of spontaneous activity. With whole-cell recording from single neurons, we found that ACh inhibited excitatory postsynaptic currents (EPSCs) while elevating neuronal firing in a dose-dependent manner. Furthermore, all ACh-induced cellular and network changes were blocked by muscarinic, but not nicotinic receptor antagonists. With computational modeling, we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations. Thus, ACh modulates network dynamics in a biphasic fashion, probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.

Combined application of field epidemiology and laboratory etiology analysis in the investigation of a foodborne disease outbreak in Xinjiang uygur Autonomous Region, 2016 / 中华预防医学杂志

Objectives: To analyze the causes of a foodborne outbreak in rural areas of Xinjiang between April 2 and April 5 in 2016. Methods: Cases and the relevant background information were obtained by consulting outpatient records of local health centers and regional people's hospitals and interviewing doctors and residents. All samples were collected by the laboratory test through epidemiological and food hygiene investigations. The χ2 test (Fisher's exact probability method) was used to compare differences in incidence rates. Molecular typing, virulence genes and single nucleotide polymorphisms (SNPS) were analyzed by using Pulsed Field Gel Electrophoresis (PFGE) and Whole Genome Sequencing (WGS). Results: A total of 142 cases were found in this study, with incidence rate at 5.7‰ (142/24 979). Among all cases, the main symptoms were nausea (94%), vomiting (92%) and abdominal pain (67%), and the incubation period was about 2 h (1-7.5 h). There were 16 Staphylococcus aureus isolates identified and all of them could produce A+C+E mixed enterotoxin. PFGE showed 100% homology. WGS further revealed that there were 9 and 1 strains contained by Sequence Type 1 (ST1) and ST5405, respectively. All ST1 strains were in the same clade on the genome tree. Among these, 7 strains shared close proximity (74 SNPs) and 2 strains shared close relationships as well (127 SNPs). The S. aureus isolates that caused the outbreak were introduced by a mutant isolate from the milk supply station. Conclusions: This foodborne outbreak was mainly caused by Staphylococcus aureus contamination.

Clinicopathological characteristics and prognostic analysis of patients with female genital tract diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathological characteristics, gene mutation profile, and prognostic factors of diffuse large B-cell lymphoma (DLBCL) in female genital tract.Methods:A retrospective analysis was performed on the clinicopathological data of 30 patients with female genital tract DLBCL who were admitted to Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from October 2003 to October 2021. Targeted sequencing was used to detect 55 lymphoma-related genes, and the gene mutation status of patients was evaluated. Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed by Cox proportional hazards model.Results:The median age of 30 female genital tract DLBCL patients at diagnosis was 58 years old (23-77 years old). The initial symptoms mainly included abdominal pain, distension, and masses (8 cases, 32%). Tumors most commonly located in the adnexal region (including ovaries and fallopian tubes) (13 cases, 45%), of which 9 cases were unilateral. Twenty-one cases (70%) had multiple extra-nodal involvements, 22 cases (73%) had Ann Arbor stage Ⅲ-Ⅳ, 8 cases (27%) had Eastern Cooperative Oncology Group (ECOG) score of ≥2, and 22 cases (73%) had elevated lactate dehydrogenase (LDH), 21 cases (70%) had International Prognostic Index (IPI) score of 3-5. Within 30 patients, 11 patients (37%) received surgery, and all patients received R-CHOP regimen-based chemotherapy. All 30 cases were evaluated for efficacy, the complete remission rate was 83% (25/30), the 5-year progression-free survival (PFS) rate was 69.7%, and the 5-year overall survival (OS) rate was 79.6%. Univariate analysis showed that ECOG score ≥2 was associated with worse OS ( P = 0.048). Among the 30 patients, 7 patients (23%) were primary and 23 patients (77%) were secondary. The proportions of patients with Ann Arbor stage Ⅲ-Ⅳ, IPI score 3-5 and elevated LDH in secondary patients were higher than those in primary patients (all P < 0.001), but there were no significant differences in PFS and OS between the two ( P values were 0.261 and 0.671). The targeted sequencing results of 16 patients showed that the mutation rates of PIM1, MYD88, KMT2D, TP53, CARD11, CCND3 and GNA13 were all > 20%, and TP53 mutation was associated with poorer PFS and OS ( P values 0.012 and 0.002). Conclusions:Female genital tract DLBCL is a rare invasive extranodal DLBCL with similar survival prognosis in primary and secondary patients. High-frequency mutations of PIM1, MYD88 and TP53 genes may provide new directions for treatment.

Inhibitory Effect of Interference with PD-L1 Expression on B-cell lymphoma in Mice / 中国实验血液学杂志

OBJECTIVE@#To investigate the potential inhibitory effect of interference with PD-L1 on B cell lymphoma in mice.@*METHODS@#Three shRNA vectors for mouse CD274 (PD-L1) were constructed and transiently transfected into 293T cells. RT-qPCR was used to validate the interference efficiency of CD274. The shRNA vector that interfere efficiently with CD274 expression was packaged by using lentivirus packaging system to generate shRNA lentivirus, and then transfected into A20 lymphoma cell line. The methyl thiazol terazolium (MTT) assay was used to detect proliferation after 48 h culture of CD274-sh A20 cells. Meanwhile, BALB/c mice were hypodermically infected with CD274-sh A20 cells. Infected mice were observed daily and assessed to visualize tumor by in vivo fluorescence imaging.@*RESULTS@#The proliferation rate of CD274-sh A20 cells in vitro was significantly lower than that of A20 cells (P<0.05). The tumor size detected by in vivo fluorescence imaging showed a significant reduce in tumor bearing mice with CD274-sh compared with other tumor bearing mice. And the weight and size of tumor in CD274-sh group were also significantly reduced compared with other group (P<0.05). Moreover, the survival time of tumor bearing mice in CD274-sh group was longer than that of the PD-L1 high expression group.@*CONCLUSION@#PD-L1 plays an important role in the incidence and the progression of lymphoma, and the shRNA-based PD-L1 knockdown can inhibit cell proliferation of A20 cells and partly suppress tumor growth.

Effect of miltirone on proliferation and apoptosis of leukemia THP-1 cells / 中国中药杂志

To investigate the toxicity and related mechanism of miltirone to human acute myeloid leukemia THP-1 cells. To be specific, the active components and targets of miltirone were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the target proteins were converted into standard gene names with UniProt. Acute leukemia-rela-ted target genes were screened from GeneCards and DisGeNET. Venn diagram was constructed with Venny 2.1 to yield the common targets of the disease and the drug. The protein-protein interaction(PPI) network was constructed by STRING and Cytoscape 3.8.2. THP-1 cells in the logarithmic growth phase were treated with dimethyl sulfoxide(DMSO), and 2.5, 5, 10, 15, and 20 μmol·L~(-1) miltirone for 24 h, respectively. The proliferation rate of cells was analyzed by carboxyfluorescein diacetate succinimidyl ester(CFSE), apoptosis rate by flow cytometry with Annexin V-PE/7 AAD staining, and cell morphology by acridine orange staining. Real-time quantitative PCR(qPCR) was employed to detect the mRNA levels of nuclear receptor coactivator 2(NCOA2), poly(ADP-ribose) polymerase-1(PARP1), B-cell lymphoma-2(Bcl-2)-associated X protein(Bax), Bcl-2, and cysteine aspartyl protease-3(caspase-3). The effect of miltirone on apoptosis was detected in presence of caspase inhibitor Z-VAD-FMK. A total of 26 targets of miltirone, 1 046 genes related to acute leukemia, and 6 common targets of the two were screened out. Flow cytometry result showed miltirone at 10 μmol·L~(-1) can inhibit proliferation and promote apoptosis of THP-1 cells. The typical manifestations of apoptosis, such as cell shrinkage, nuclear rupture, and chromatin agglomerate were displayed by acridine orange staining. The decreased mRNA levels of NCOA2 and PARP1 and increased Bax/Bcl-2 ratio and the activity of pro-apoptotic protein caspase-3 were observed. Z-VAD-FMK can attenuate the apoptosis-inducing effect of miltirone. This study indicates that miltirone can inhibit the proliferation and promote the apoptosis of THP-1 cells, by down-regulating NCOA2 and PARP1, raising Bax/Bcl-2 ratio, and activating caspase-3.

The application effect of enhanced recovery after surgery in laparoscopic colorectal cancer surgery in primary hospitals / 中华老年医学杂志

Objective:To evaluate the application efficacy of enhanced recovery after surgery(ERAS)in laparoscopic colorectal cancer surgery in primary hospitals.Methods:A total of 116 patients who underwent laparoscopic colorectal cancer surgery from January 2017 to December 2018 at our hospital were enrolled in this study.According to the perioperative rehabilitation program, 116 patients were divided into the group A(n=67, receiving enhanced recovery after surgery)and the group B(n=49, receiving traditional recovery after surgery).Results:The incidences of preoperative thirst and hunger were lower in the group A than in the group B(11.9% vs.53.1%, 16.4% vs.51.0%, χ2=23.10 and 15.83, respectively, P<0.001). The levels of CRP and blood glucose in the two groups were significantly higher after operation than before operation, and reached the peak values on the 3rd day after the operation.At different time points after operation, CRP levels and blood glucose levels were higher in the group B than in the group A(all P<0.05). On the 7th day after operation, blood glucose level was recovered to the preoperative level in the group A, while it was not so in the group B. The incidence of complication in the group A was similar to the group B(7.46% vs.12.2%, χ2=0.75, P>0.05). The hospitalization period was shorter and the hospitalization cost was less in the group A than in the group B(8.16±1.33)d vs.(15.39±2.81)d, (46100±1800)yuan vs.(56900±5600)yuan, t=10.98 and 9.96, P=0.000). Conclusions:The application of enhanced recovery after surgery is beneficial for perioperative safety, can reduce surgical stress response, promote postoperative recovery, shorten hospitalization time after surgery and reduce hospitalization costs in laparoscopic colorectal cancer surgery.

Forensic Analysis of Sudden Death Associated with Sexual Activity / 法医学杂志

OBJECTIVES@#To analyze the characteristics of sudden death associated with sexual activity to provide recommendations for forensic identification.@*METHODS@#A retrospective analysis was conducted on autopsy cases accepted by Forensic Identification Center of Huazhong University of Science and Technology from 1998 to 2018, and a total of 15 cases of sudden death associated with sexual activity were screened out. The general information, case data and pathological changes of 15 cases were collected to find the relationship between sexual activity and sudden death.@*RESULTS@#The ratio of male to female was 1.5∶1. The average age of males was 50.1 years and that of females was 35.0 years. Coronary artery diseases and brain diseases accounted for most of the cases (12/15). Sexual partners were associated with locations of deaths and body dumping behaviors.@*CONCLUSIONS@#Sudden death associated with sexual activity, although rare, may occur in people over 30 years old with pre-existing heart or brain diseases, which should be paid attention to in forensic practice.

Research progress and perspective in metabolism and metabolomics of psoriasis / 中华医学杂志(英文版)

Psoriasis is considered a systemic disease associated with metabolic abnormalities, and it is important to understand the mechanisms by which metabolism affects pathophysiological processes both holistically and systematically. Metabolites are closely related to disease phenotypes, especially in systemic diseases under multifactorial modulation. The emergence of metabolomics has provided information regarding metabolite changes in lesions and circulation and deepened our understanding of the association between metabolic reprogramming and psoriasis. Metabolomics has great potential for the development of effective biomarkers for clinical diagnosis, therapeutic monitoring, prediction of the efficacy of psoriasis management, and further discovery of new metabolism-based therapeutic targets.

Intratracheal Transplantation of Amnion-Derived Mesenchymal Stem Cells Ameliorates Hyperoxia-Induced Neonatal Hyperoxic Lung Injury via Aminoacyl-Peptide Hydrolase

Background and Objectives@#Bronchopulmonary dysplasia (BPD) has major effects in premature infants. Although previous literature has indicated that mesenchymal stem cells (MSCs) can alleviate lung pathology in BPD newborns and improve the survival rate, few research have been done investigating significantly differentially expressed genes in the lungs before and after MSCs therapy. The aim of this study is to identify differentially expressed genes in lung tissues before and after hAD-MSC treatment. @*Methods@#and Results: Human amnion-derived MSCs (hAD-MSCs) were cultured and met the MSCs criteria for cell phenotype and multidirectional differentiation. Then we confirmed the size of hAD-MSCs-EXOs and their expressed markers. An intratracheal drip of living cells showed the strongest effect on NHLI compared to cellular secretions or exosomes, both in terms of ameliorating pulmonary edema and reducing inflammatory cell infiltration. Through gene chip hybridization, PCR, and western blotting, acylaminoacyl-peptide hydrolase (APEH) expression was found to be significantly decreased under hyperoxia, and significantly increased after hAD-MSC treatment. @*Conclusions@#The intratracheal transplantation of hAD-MSCs ameliorated NHLI in neonatal rats through APEH.

Study on CYP2E1 gene polymorphism and the relationship between methylation level of its promoter region and liver injury induced by anti-tuberculosis drugs in Mongolian tuberculosis patients in Inner Mongolia / 医学研究生学报

ObjectiveThere are few studies on whether the occurrence of anti-tuberculosis drug-induced liver injury (ADIH) is associated with the polymorphism of CYP2E gene and methylation level. This study aims to CYP2E1 gene polymorphism and the relationship between the methylation level of the promoter region and ADIH in Mongolian tuberculosis (TB) patients.Methods A total of 135 Mongolian TB patients who received standardized treatment at the Tuberculosis Research Institute of Tongliao City, Inner Mongolia from November 2015 to June 2018 were selected. According to the ADIH criteria, TB patients with liver injury were selected as the ADIH group (n=45), and TB patients without liver injury were matched as the control group based on a ratio of 1∶2 (n=90). DNA extraction and polymerase chain reaction (PCR) were performed to amplify the CYP2E1 gene to determine the CYP2E1 rs2031920 genotype, and to analyze the CYP2E1 gene polymorphism and relationship between ADIH and promoter methylation level.Results There were no significant differences in the distribution of CYP2E1 rs2031920 genotype, C1 and C2 gene frequencies between the ADIH group and the control group (P>0.05). The overall methylation level in the promoter region of CYP2E1 gene in ADIH group (0.711±0.085) was significantly lower than that of the control group (0.759±0.062). Results of Logistic regression showed that the overall methylation level in the promoter region of CYP2E1 gene was the influencing factor for the occurrence of ADIH (P<0.005). For each 0.1 unit increase of methylation level, the risk of ADIH occurrence reduced by 0.388 times, and the OR (95% CI) value was 0.388 (between 0.204 and 0.739).Conclusion The overall methylation level in the promoter region of CYP2E1 gene was reduced in Mongolian ADIH patients, but the polymorphism of CYP2E1 gene was not related to the occurrence of ADIH. These results suggested that CYP2E1 methylation could be applied to the prevention and treatment of ADIH in patients with tuberculosis.

Study on CYP2E1 gene polymorphism and the relationship between methylation level of its promoter region and liver injury induced by anti-tuberculosis drugs in Mongolian tuberculosis patients in Inner Mongolia / 医学研究生学报

ObjectiveThere are few studies on whether the occurrence of anti-tuberculosis drug-induced liver injury (ADIH) is associated with the polymorphism of CYP2E gene and methylation level. This study aims to CYP2E1 gene polymorphism and the relationship between the methylation level of the promoter region and ADIH in Mongolian tuberculosis (TB) patients.Methods A total of 135 Mongolian TB patients who received standardized treatment at the Tuberculosis Research Institute of Tongliao City, Inner Mongolia from November 2015 to June 2018 were selected. According to the ADIH criteria, TB patients with liver injury were selected as the ADIH group (n=45), and TB patients without liver injury were matched as the control group based on a ratio of 1∶2 (n=90). DNA extraction and polymerase chain reaction (PCR) were performed to amplify the CYP2E1 gene to determine the CYP2E1 rs2031920 genotype, and to analyze the CYP2E1 gene polymorphism and relationship between ADIH and promoter methylation level.Results There were no significant differences in the distribution of CYP2E1 rs2031920 genotype, C1 and C2 gene frequencies between the ADIH group and the control group (P>0.05). The overall methylation level in the promoter region of CYP2E1 gene in ADIH group (0.711±0.085) was significantly lower than that of the control group (0.759±0.062). Results of Logistic regression showed that the overall methylation level in the promoter region of CYP2E1 gene was the influencing factor for the occurrence of ADIH (P<0.005). For each 0.1 unit increase of methylation level, the risk of ADIH occurrence reduced by 0.388 times, and the OR (95% CI) value was 0.388 (between 0.204 and 0.739).Conclusion The overall methylation level in the promoter region of CYP2E1 gene was reduced in Mongolian ADIH patients, but the polymorphism of CYP2E1 gene was not related to the occurrence of ADIH. These results suggested that CYP2E1 methylation could be applied to the prevention and treatment of ADIH in patients with tuberculosis.

Systematic Evaluation of Clinical Efficacy and Safety of Traditional Chinese Medicine for Post Stroke Cognitive Impairment / 中国实验方剂学杂志

Objective:To evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of post stroke cognitive impairment (PSCI). Method:Seven databases, including CNKI, WanFang, VIP, CBM, PubMed, The Cochrane library and ClinicalTrials.gov, were electronically searched for relevant randomized controlled trials (RCTs) of TCM in the treatment of PSCI. The Cochrane risk of bias assessment tool was used to evaluate the methodological quality of the included studies, descriptive analysis was carried out on the included studies, and the Meta quantitative analysis was carried out with RevMan 5.3 software. Result:A total of 16 RCTs were included with 1 296 participants, and they were assigned to the intervention group (n=649) and the control group (n=647). The results showed that TCM combined with western medicine group and TCM group were better than western medicine group in improving the scores of Montreal Cognitive Assessment (MoCA), Mini-mental State Examination (MMSE), Barthel Index (BI), Activity of Daily Living (ADL), Chinese stroke scale (CSS) and National Institutes of Health stroke scale (NIHSS) of PSCI patients, and no serious adverse events were observed. Conclusion:TCM has potential advantages in improving the cognitive function of patients with PSCI, and it also has certain efficacy in improving the daily living ability and neurological impairment symptoms, and no serious adverse events have been observed. Due to the low quality of methodology included in the studies, in order to provide reliable basis for clinical decision-making, high-quality of RCTs are still needed to study the efficacy and safety of TCM for PSCI.

Mechanism of Shengmaisan in Atrial Fibrillation Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To study the mechanism of Shengmaisan in treating atrial fibrillation by regulating relative genes and signaling pathways based on network pharmacology. Method:Target genes of Shengmaisan were obtained using Bioinformatics Analysis Tool for Molecular Mechanism of TCM（BATMAN-TCM） database，and target genes of atrial fibrillation were obtained through GeneCards，OMIM and DisGeNET databases. The target genes of Shengmaisan-atrial fibrillation intersection protein were obtained through the integration of the two groups of genes. STRING was used to build the protein-protein interaction network and visualize the results. The drug-disease intersection genes were introduced into the DAVID 6.8 database for gene ontology （GO） analysis and enrichment analysis based on the Kyoto Encyclopedia of Genes and Geomes （KEGG）. Result:A total of 159 active ingredients for Shengmai powder for atrial fibrillation were obtained. After the drug targets and the disease targets were intersected，206 common targets were obtained. PPI protein interaction network analysis showed that AKT1，TP53，PRKACA，IL-1B，TNF，INS，PPAR，RXR，F2，CACAN1C PKC might be the core targets of Shengmaisan in treating AF. GO enrichment analysis was used to identify 175 items （P<0.05），among which biological processes mainly included regulation of heart rate by cardiac conduction，membrane depolarization during action potential；cell components mainly included voltage-gated sodium/ potassium/calcium channel complex；molecular functions mainly included high-voltage-gated calcium channel activity，steroid hormone receptor activity. Through KEGG pathway enrichment analysis，100 signaling pathways were identified，mainly including cGMP/PKG signaling pathway，cAMP signaling pathway，serotonergic synapse，renin secretion，calcium signaling pathway. Conclusion:Based on the network pharmacology，Shengmaisan has multiple mechanisms in the prevention and treatment of atrial fibrillation. This study explores relevant signaling pathways，advantages and research directions of Shengmaisan in treatment of atrial fibrillation，so as to lay the foundation for further experimental verification.

Validation of fatty liver index and hepatic steatosis index for screening of non-alcoholic fatty liver disease in adults with obstructive sleep apnea hypopnea syndrome / 中华医学杂志(英文版)

BACKGROUND@#Obstructive sleep apnea hypopnea syndrome (OSAHS) is a contributing factor for non-alcoholic fatty liver disease (NAFLD). Non-invasive algorithms including fatty liver index (FLI) and hepatic steatosis index (HSI) have been used as a screening test for NAFLD in epidemiologic studies. The aim of this study is to compare the diagnostic accuracy of FLI and HSI for NAFLD detection in adults with OSAHS.@*METHODS@#We enrolled consecutive adult subjects who were newly diagnosed with OSAHS from March 2016 to January 2018. NAFLD was diagnosed by ultrasonography. The accuracy and cut-off point of the FLI and HSI to detect NAFLD were assessed by analyzing the area under the receiver operating characteristic (AUROC) curve and the maximum Youden index analysis, respectively.@*RESULTS@#The 326 subjects were diagnosed as NAFLD according to ultrasound findings, while 105 subjects who had normal abdominal ultrasonography were grouped as controls. Both FLI and HSI values were significantly higher in patients with NAFLD compared with controls. The AUROC of FLI and HSI for predicting NAFLD was 0.802 (95% confidence interval [CI] 0.762-0.839) and 0.753 (95% CI 0.710-0.793), respectively. The AUROC of FLI was significantly higher than that of HSI (P = 0.0383). The optimal cut-off value of FLI and HSI was 60 (sensitivity 66% and specificity 80%) and 35 (sensitivity 81% and specificity 60%), respectively.@*CONCLUSIONS@#Both FLI and HSI can serve as screening tools for NAFLD in OSAHS adults. The FLI shows better performance in diagnosing NAFLD than HSI.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry (No. ChiCTR-OOB-15007253), http://www.chictr.org.cn/showproj.aspx?proj=11606.

Expression Difference of RhoH Gene in Leukemia and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of RhoH gene in bone marrow cells of leukemia patients.@*METHODS@#31 cases of leukemia and 15 cases of non-tumor as controls were collected. The expression of RhoH in bone marrow cells was detected by real-time quantitative PCR (RQ-PCR). The median expression level of RhoH was used as the cut-off value. The newly diagnosed patients were divided into RhoH high expression group and low expression group. The relationship of different RhoH expression levels with clinical features and prognosis of newly diagnosed patients was analyzed.@*RESULTS@#The mRNA expression of RhoH in the bone marrow cells of 31 cases of leukemia was significantly lower than that in the control group, mRNA expression of RhoH in the ALL group was significantly lower than that in AML group (P＜0.05). Compared with the RhoH high expression group, the proportion of bone marraw blasts and LDH level in the RhoH low expression group was significantly increased (P＜0.05), but there were no significant differences in clinical features such as age, white blood cell count, hemoglobin level, platelets count, PCT and CRP level (P＞0.05). In AML, the recurrence rate after standard chemotherapy in RhoH low expression group was higher than that in high expression group, while the expression of RhoH not correlated with other prognostic genes of AML. In ALL, the recurrence rate in RhoH low expression group was not statistically significant different from that in high expression group.@*CONCLUSION@#RhoH may be involved in the genesis of acute leukemia. In AML, RhoH expression negatively correlates with recurrence rate, which can be used as a prognostic indicator independently. In ALL, RhoH may participate in the disease process through other mechanism.