Objective:To investigate the effect of pre-treatment plasma Epstein-Barr virus(EBV)DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH).Methods:The clinical characteristics,survival rate,and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study.Patients were divided into three groups,including the EBV DNA-negative group(＜5.0 × 102 copies/ml),lower EBV-DNA loads group(5.0 × 102-8.51 × 104 copies/ml),and higher EBV-DNA loads group(＞8.51 × 104 copies/ml),according to pre-treatment plasma EBV-DNA copy number.Cox regression model was established for screening prognostic factors.Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index(C-index)and calibration curves were calculated to verify model predictive and discriminatory capacity.Results:Among 171 adult sHLH patients,84 patients were not infected with EBV(EBV DNA-negative group),and 87 with EBV(EBV DNA-positive group,48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group).Consistent elevations in the levels of liver enzymes(ALT and AST),LDH,TG,β2-microglobulin and ferritin across the increasing of EBV-DNA load(all P＜0.05),while the levels of fibrinogen decrease(P＜0.001).The median follow-up time was 52 days(range 20-230 days),and 123 patients died.The overall survival(OS)rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group(median OS:40 days vs 118 days,P＜0.001).Higher EBV-DNA loads had worse OS(median OS:24 days vs 45 days vs 118 days,P＜0.0001 for trend)compared to lower EBV-DNA loads and EBV DNA-negative group.Multivariate Cox analysis revealed that higher EBV-DNA loads(P=0.005),fibrinogen≤ 1.5 g/L(P=0.012),ferritin(P=0.041),associated lymphoma(P=0.002),and anti-tumor based strategy(P=0.001)were independent prognostic factors for OS.The C-indexes of 30 day,90 days,365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability.Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women,ferritin＞5 000 μg/L,β2-microglobulin＞7.4 mmol/L and regardless of age,etiologies,HScore points.Conclusion:The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH.The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective:To explore the biochemical characteristics, virulence factors and other phenotypes of the strains of Yersinia pestis isolated in Jianchuan County Yunnan Province in 2017, and to analyze the nature and source of the new plague epidemic. Methods:Three strains of Yersinia pestis (JC109 rat, JC109 fleas and JC113) isolated from Daqing Village, Jinhua Town, Jianchuan County, Dali Prefecture, Yunnan Province in 2017, and 2 associated strains of Yersinia pestis (LJ01 in Yulong County, Lijiang City and LJ04 in Gucheng District of Lijiang City), 5 control strains ( Yersinia pestis JC1332, LJ485, BN2636, EV-76 and Yersinia pseudotuberculosis PST-1), preserved by the Central Laboratory of Yunnan Institute for Endemic Disease Control and Prevention were collected. The biochemical characteristics and ecotypes of Yersinia pestis were analyzed by using arabinose, rhamnose, denbiose, maltose and glycerol fermentation experiments and nitrate reduction experiments. Combining pigmentation factor (pgm), virulence antigen (VW) detection and nutritional requirements test results to determine the virulence of Yersinia pestis. Results:The Yersinia pestis JC109 rat, JC109 fleas and JC113 all fermented arabinose, maltose and glycerol, but didn't ferment rhamnose and denbiose; and the nitrate reduction test was positive. The ecological type belonged to the Himalayan Marmot plague strain of Qinghai-Tibet plateau. The virulence factors pgm and VW tests were positive, the nutritional requirement type was phenylalanine dependent and glutamate independent. It had the same phenotype as the LJ01 strain, but different from the JC1332 strain. Conclusions:The newly isolated strains in Jianchuan County are the same as those in the Lijiang Yulong wild rodent plague foci. This outbreak may have been imported from the Lijiang Yulong wild rodent plague foci to the south.

OBJECTIVE: To explore the karyotype features and genetic relationship among Schizonepeta tenuifolia Briq. from different producing origins. METHODS: The chromosome features of Schizonepeta tenuifolia Briq. from 11 different producing origins were analyzed by using root-tip squashing method and clustered by the karyotype resemblance-near coefficients. RESULTS: The Schizonepeta tenuifolia Briq. from 11 different producing origins all had 12 chromosomes. There were four types of karyotype formula: 2n=2x=12=4m+8sm, 2n=2x=12=8m+4sm, 2n=2x=12=6m+6sm and 2n=2x=12=4m+6sm+2st. The karyotypes of Yutianchun and Shanxi Schizonepeta tenuifolia Briq. were 2B type, and those of the other Schizonepeta tenuifolia Briq. were 2A type. The asymmetrical karyotype coefficients were not distinctively different, which ranged from 61% to 67%, and the karyotype of Sichuan Schizonepeta tenuifolia Briq. was the most primitive among all the samples, and the highest degree of evolution belonged to Anguoxia Schizonepeta tenuifolia Briq. The karyotype clustering analysis showed that Jiangsu and Sichuan Schizonepeta tenuifolia Briq had the highest karyotype resemblance-near coefficient (0.989) and the smallest evolutionary distance (0.011). The farthest genetic relationship existed between Zhejiang and Yutianchun Schizonepeta tenuifolia Briq., as shown by the minimum karyotype resemblance-near coefficient (0.792 5) and the maximum evolution distance (0.232 6). CONCLUSION: Karyotype is an important parameter for identification of medicinal plants. The genetic distances between 11 species of Schizonepeta tenuifolia Briq. are obtained by karyotype clustering analysis of karyotype resemblance-near coefficient. The results provide cytological information for the study of germplasms identification, genetic relationship and system evolution of Schizonepeta tenuifolia Briq.

The aim of this study was to investigate the knockdown efficiency of 2'-O-methylated (2'-OMe)-modified small interfering RNAs (siRNAs) on human rhinovirus 1B (HRV1B) replication and the interferon response. Thus, 24 2'-OMe-modified siRNAs were designed to target HRV1B. The RNA levels of HRV1B, Toll-like receptor 3, melanoma differentiation-associated gene 5, retinoic acid inducible gene-I, and interferons were determined in HRV1B-infected HeLa and BEAS-2B epithelial cells transfected with 2'-OMe-modified siRNAs. The results revealed that all 2'-OMe-modified siRNAs interfered with the replication of HRV1B in a cell-specific and transfection efficiency-dependent manner. Viral activation of Toll-like receptor 3, melanoma differentiation-associated gene 5, retinoic acid inducible gene-I, and the interferon response was detected. In conclusion, the 2'-OMe-modified siRNAs used in this study could interfere with HRV1B replication, possibly leading to the reactivation of the interferon response.
Gene Knockdown Techniques ; HeLa Cells ; Humans ; Interferons ; physiology ; RNA, Small Interfering ; Rhinovirus ; Virus Replication

OBJECTIVETo observe the dynamic time-phase expressions of key genes of brain-gut CaM signal pathway of spleen Qi deficiency rats and the intervention effect of Sijunzi decoction.

METHODMale Wistar rats were randomly divided into the normal control group, model 14 d, 21 d, 28 d groups, and Sijunzi decoction 14 d, 21 d, 28 d groups. Except for the normal control group, the remaining groups were included into the spleen Qi deficiency model with the bitter cold breaking Qi method (ig 7.5 g · kg⁻¹ · d⁻¹ of Rheum officinale, Fructus aurantii immaturus, Magnolia officinalis preparation) and the exhaustive swimming method. On the 7th day after the modeling, the Sijunzi decoction groups were orally administered with Sijunzi decoction 20 g · kg⁻¹ · d⁻¹. The expressions of key genes CaM/CaMK II of CaM signaling pathway in hippocampus and intestine at different time points by immunohistochemical method and Western blot. At the same time, the intervention effect of Sijunzi decoction on spleen Qi deficiency rats and its mechanism were analyzed.

RESULTSpleen Qi deficiency rats showed higher intestinal CaM/CaMK II expression and lower hippocampus CaM/CaMK II expression than normal rats (P < 0.05, P < 0.01). After the treatment of Sijunzi decoction, spleen Qi deficiency rats showed reduction in intestinal CaM/CaMK II expression and increase in hippocampus CaM/CaMK II expression (P < 0.05, P < 0.01).

CONCLUSIONThe formation of spleen Qi deficiency syndrome may be related to the high expression of CaM/CaMK II in small intestine tissues and its low expression in hippocampus tissues. Sijunzi decoction may achieve the therapeutic effect in spleen Qi deficiency syndrome by reducing the CaM/CaMK II expression in intestinal tissues and increasing it in hippocampus tissues.

Animals ; Brain ; drug effects ; enzymology ; metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; genetics ; metabolism ; Calmodulin ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Intestines ; drug effects ; enzymology ; metabolism ; Male ; Qi ; Rats ; Rats, Wistar ; Spleen ; drug effects ; Splenic Diseases ; drug therapy ; enzymology ; genetics ; metabolism

OBJECTIVE: To study variation of total flavonoids from nine different Bupleurum chinense introduced of different ground parts of different organs in different growth period, and explore the best harvest period and the optimal varieties. METHODS: The extraction conditions were optimized by microwave assisted method, UV-visible spectropholometry was used to determine the contents of total flavonoids. RESULTS: The optimum extraction conditions: the concentration of ethanol was 80%, each microwave time 40 s, microwave 10 times; the content of total flavonoids was difference in different growth period, fluctuated trend. The flower was the highest, with an average of 7.59% in the range of 4.65%-16.75%, the content of total flavonoids in nutrition growth phase; leaf>stem, in flowering stage; flower>leaf>stem; in fruiting stage; the content of Gansu Longxi, Liaoning Shenyang, Shandong Heze and Hebei Anguo Bupleurum: fruit>leaf>stem, other Bupleurum; leaf>stem>fruit; The higher the content of total flavonoids was in the flowering and fruiting of nine different Bupleurum chinense introduced, Gansu Longxi Bupleurum (flowering stage) was the highest, up to 27.41%. CONCLUSION: It is suggested that harvested in the flowering or fruiting stage, and carried on the comprehensive development and utilization.

The research aimed at investigating the physicochemical properties, stability and skin penetration in vitro of total alkaloids of Sophora flavescens nanoemulsion. Prepare total alkaloids of S. flavescens nanoemulsion and detect the determination of matrine and oxymatrine in the nanoemulsion using HPLC method. Transmission electron microscopy and laser particle size analyzer were utilized to detect the shape and size of the nanoemulsion respectively. And also the stability of nanoemulsion was studied under the conditions of low temperature (4 degrees C), normal temperature (25 degrees C) and high temperature (60 degrees C). Franz diffusion cell was used to research the transdermal absorption of nanoemulsion in vitro. The results found that the nanoemulsion we prepared presented appearance of rounded, uniform; its average diameter was (15.55 +/- 2.24) nm, and particle size distribution value was 0. 161; the appearance, diameter and percentage determination of total alkaloids of S. flavescens had no variations after 15 d under 4, 25, 60 degrees C respectively. The steady-state permeation rate was 4.564 1 microg x cm(-2) x h(-1), 24 h cumulative amount of penetration was 110.7 microg x cm(-2), which was 1.86 fold of 24 h cumulative amount of aqueous solution (59.41 microg x cm(-2)). All the results demonstrated total alkaloids of S. flavescens nanoemulsion had good permeability, and could provide a new preparation for its clinical application.
Alkaloids ; chemistry ; metabolism ; Animals ; Chemical Phenomena ; Drug Carriers ; chemistry ; Emulsions ; Male ; Nanostructures ; chemistry ; Rats ; Rats, Sprague-Dawley ; Skin Absorption ; Sophora ; chemistry