Application of PROTACs in Hematological Malignancies--Review / 中国实验血液学杂志

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional small molecules by utilizing the ubiquitin proteasome system (UPS) to degrade proteins of interest. PROTACs have exhibited unprecedented efficacy and specificity in degrading various oncogenic proteins because of their unique mechanism of action, ability to target "undruggable" and mutant proteins. A series of PROTACs have been developed to degrade multiple key protein targets for the treatment of hematologic malignancy. Notably, PROTACs that target BCL-XL, IRAK4, STAT3 and BTK have entered clinical trials. The known PROTACs that have the potential to be used to treat various hematological malignancies are systematically summarized in this review.

Excretion of three alkaloids from Simiao Pills in urine, feces, and bile between normal and type 2 diabetic rats / 中国中药杂志

This study investigated the differences in excretion kinetics of three alkaloids and their four metabolites from Simiao Pills in normal and type 2 diabetic rats. The diabetes model was established in rats by injection of streptozotocin, and the alkaloids in urine, feces, and bile of normal and diabetic rats were detected by LC-MS/MS to explore the effect of diabetes on alkaloid excretion of Simiao Pills. The results showed that 72 h after intragastric administration of the extract of Simiao Pills, feces were the main excretion route of alkaloids from Simiao Pills. The total excretion rates of magnoflorine and berberine in normal rats were 4.87% and 56.54%, which decreased to 2.35% and 35.53% in diabetic rats, which had statistical significance(P<0.05). The total excretion rates of phellodendrine, magnoflorine, and berberine in the urine of diabetic rats decreased significantly, which were 53.57%, 60.84%, and 52.78% of those in normal rats, respectively. After 12 h of intragastric administration, the excretion rate of berberine in the bile of diabetic rats increased significantly, which was 253.33% of that of normal rats. In the condition of diabetes, the excretion rate of berberine metabolite, thalifendine significantly decreased in urine and feces, but significantly increased in bile. The total excretion rates of jateorrhizine and palmatine in the urine increased significantly, and t_(1/2) and K_e changed significantly. The results showed that diabetes affected the in vivo process of alkaloids from Simiao Pills, reducing their excretion in the form of prototype drug, affecting the biotransformation of berberine, and ultimately increasing the exposure of alkaloids in vivo, which would be conducive to the hypoglycemic effect of alkaloids. This study provides references for the clinical application and drug development of Simiao Pills in diabetes.

Component identification and analysis in vivo of Sanhan Huashi formula / 中国中药杂志

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Recent advances in the study of a novel Omicron variant of SARS-CoV-2 / 中国热带医学

@#Abstract: Due to the continued emergence of multiple variants of SARS-CoV-2, the ongoing pandemic has resulted in severe mortality over the past two years. After the Alpha, Beta, Gamma and Delta variants, the most recent new variant of concern (VOC) strain to emerge is Omicron (B.1.1.529), which evolved as a result of the accumulation of a large number of mutations. The Omicron variant, which has a much higher transmission rate than the Delta variant, soon replaced the Delta variant and others, is now the dominant variant worldwide. The emergence of Omicron poses new challenges for the prevention and control of COVID-19 and has raised a number of concerns worldwide. Recently, cases of Omicron infection have been reported in several parts of China, and therefore this paper provides a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant, including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going COVID-19 pandemic successfully.

Retrospective Analysis of Serological Characteristics and Distribution of Patients with Mimicking Antibodies / 中国实验血液学杂志

OBJECTIVE@#To understand the characteristics of patients with mimicking specificity autoantibodies through the analysis of the causes of autoantibodies, specificity of antibodies, strategy of blood transfusion, effect of transfusion and distribution of antibodies in China and abroad.@*METHODS@#A total of 23 patients who applied for blood in our hospital from January 2017 to June 2019 were identified as mimicking specificity autoantibodies by antibody identification or absorption-elution test. The causes of mimicking specificity autoantibodies, antibody specificity, blood transfusion strategy and blood transfusion effect were analyzed. The relevant articles on antibodies published in China and abroad were summarized and sorted out, and the distribution of antibodies was analyzed.@*RESULTS@#All the 23 patients with mimicking specificity autoantibodies were Rh blood group system antibodies, of which mimicking anti-Ce autoantibodies were the most common (34.8%), followed by mimicking anti-e autoantibodies (26.1%), mimicking anti-D autoantibodies (21.7%), mimicking anti-C autoantibodies (8.7%) and mimicking anti-E autoantibodies (8.7%). Except for 2 cases with suspected history of blood transfusion, the other 21 cases had a history of blood transfusion / pregnancy. The most common cause of mimicking autoantibodies was drug, followed by infection and autoimmune diseases. The hemoglobin (Hb) of pretransfusion in the blood transfusion group was (48.4±23.9) g/L, which was significantly lower than (86.0±38.9) g/L in the non-transfusion group (P<0.01). Except for 2 cases who could not evaluate the effect of blood transfusion, the effective rate of transfusion was 100%. According to the retrospective statistics of 32 related articles published in China and abroad, the most type of mimicking antibodies were in Rh blood group system, accounting for 79.28%, among which anti-E was the main part of all mimicking autoantibodies, accounting for 21.95%. The following ones were in Kidd system MNSs system, and Kell system.@*CONCLUSION@#Combined with the clinical symptoms and the degree of difficulty of blood matching, the best strategy of blood transfusion should be selected to ensure the safety of blood transfusion.

Clinical features and risk factors associated with severe COVID-19 patients in China / 中华医学杂志(英文版)

BACKGROUND@#Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines.@*METHODS@#A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19.@*RESULTS@#A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004).@*CONCLUSIONS@#The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.

Comparative analysis of pharmacokinetics and intestinal absorption of six alkaloids between Sanmiao Pills and Simiao Pills in rats / 中国中药杂志

The present study investigated the differences in pharmacokinetics and intestinal absorption of six alkaloids in Sanmiao Pills and Simiao Pills in rats and explored the different efficacies of the two formulae. After oral administration of Sanmiao Pills and Simiao Pills in rats, blood samples were collected at different time points. Samples were prepared for the determination of six alkaloids in plasma by UPLC-MS/MS. The chromatography was performed on an ACE Excel 3 C_(18 )column with acetonitrile-0.1% formic acid in water as the mobile phase for gradient elution. Analytes were detected in the positive ion mode. Plasma concentrations and pharmacokinetic parameters were calculated. Intestinal absorption of alkaloids was investigated by single-pass intestinal perfusion and absorption parameters of ingredients were calculated. The results showed that the UPLC-MS/MS method for simultaneous determination of concentrations of six alkaloids in plasma was developed and validated by methodological investigations, such as specificity, calibration curves, precision, accuracy, recovery, matrix effect, and stability. The results of the pharmacokinetic assay revealed that C_(max) and AUC values of phellodendrine, berberine, magnoflorine, berberrubine, and jatrorrhizine in Simiao Pills were significantly increased, and CL/F values were reduced as compared with those in Sanmiao Pills, which indicated the increase in plasma concentrations of alkaloids. The intestinal absorption parameters K_(a )and P_(eff) values of phellodendrine, berberine, and jatrorrhizine in Simiao Pills were higher than those in Sanmiao Pills. The intestinal absorption and plasma concentrations of alkaloids in Simiao Pills were significantly higher than those in Sanmiao Pills, suggesting that the composition of Simiao Pills was more conducive to the alkaloids into the blood to resist inflammation and lower uric acid.

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

Background/Aims@#Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. @*Methods@#Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). @*Results@#Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. @*Conclusions@#Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

Assessment of the Severity of Coronavirus Disease:Quantitative Computed Tomography Parameters versusSemiquantitative Visual Score

Objective@#To compare the accuracies of quantitative computed tomography (CT) parameters and semiquantitative visualscore in evaluating clinical classification of severity of coronavirus disease (COVID-19). @*Materials and Methods@#We retrospectively enrolled 187 patients with COVID-19 treated at Tongji Hospital of Tongji MedicalCollege from February 15, 2020, to February 29, 2020. Demographic data, imaging characteristics, and clinical data werecollected, and based on the clinical classification of severity, patients were divided into groups 1 (mild) and 2 (severe/critical). A semiquantitative visual score was used to estimate the lesion extent. A three-dimensional slicer was used toprecisely quantify the volume and CT value of the lung and lesions. Correlation coefficients of the quantitative CT parameters,semiquantitative visual score, and clinical classification were calculated using Spearman’s correlation. A receiver operatingcharacteristic curve was used to compare the accuracies of quantitative and semi-quantitative methods. @*Results@#There were 59 patients in group 1 and 128 patients in group 2. The mean age and sex distribution of the two groupswere not significantly different. The lesions were primarily located in the subpleural area. Compared to group 1, group 2 hadlarger values for all volume-dependent parameters (p < 0.001). The percentage of lesions had the strongest correlation withdisease severity with a correlation coefficient of 0.495. In comparison, the correlation coefficient of semiquantitative scorewas 0.349. To classify the severity of COVID-19, area under the curve of the percentage of lesions was the highest (0.807;95% confidence interval, 0.744–0.861: p < 0.001) and that of the quantitative CT parameters was significantly higher thanthat of the semiquantitative visual score (p = 0.001). @*Conclusion@#The classification accuracy of quantitative CT parameters was significantly superior to that of semiquantitativevisual score in terms of evaluating the severity of COVID-19.

Detection of Autoimmune Hemolytic Anemia Induced by Salvianolate and Evaluation of Blood Transfusion Efficacy / 中国实验血液学杂志

OBJECTIVE@#To evaluate the characteristics of autoimmune hemolytic anemia caused by salvianolate by antibody detection and clinical index monitoring.@*METHODS@#Micro-column gel anti-human globulin method was used for irregular antibody screening and antibody identification. Salvianolate, sodium creatine phosphate and levocarnitine were used to sensitize red blood cells that were compatible with the patient's plasma, and the RBCs were used to test drug antibody in patient plasma respectively. The patient's clinical examination of hemolysis index and blood transfusion effect were analyed retrospectively.@*RESULTS@#The patients were positive for irregular antibody screening, and there were antoanti-Ce antibodies in serum. The erythrocytes sensitized with salvianolate in the patient's serum were positive, while those sensitized with sodium creatine phosphate and levocarnitine were negative.@*CONCLUSION@#Salvianolate causes drug-induced autoimmune hemolytic anemia in this patient.

Relationship between Electrical Conductivity and Related Biochemical Indicators of Rat Cerebrum Tissues and Postmortem Interval / 法医学杂志

Objective To explore the relationship between the electrical conductivity （EC） and biochemical indicators of rat cerebrum tissues and postmortem intervals （PMIs） and discuss the mechanism of applying EC to infer PMI. Methods Forty healthy Sprague-Dawley rats were sacrificed and stored in an environment of about 25 ℃. The whole cerebrum tissues of rats were removed respectively at different PMIs of 0, 1, 2, 3, 4, 5, 6, and 7 d, and then made into homogenized impregnation solution. The EC and related biochemical indicators （potassium, sodium, chloride, calcium, inorganic phosphorus, magnesium, uric acid, urea nitrogen and creatinine） in cerebrum tissue impregnation solution were determined, and the relationships among EC in impregnation solution, related biochemical indicators and PMI were analyzed. Results The EC in cerebrum tissues increased gradually with the extension of PMI, and the content of uric acid, urea nitrogen and inorganic phosphorus in its impregnation solution also increased gradually with the extension of PMI. The correlation of EC, uric acid, urea nitrogen, and inorganic phosphorus with PMI was relatively good （R2 was 0.95-0.99）, and there was a linear correlation between the content change of uric acid, urea nitrogen, inorganic phosphorus and EC （R2 was 0.97-0.99）. The changes of the other 6 kinds of biochemical indicators with the extension of PMI within 7 d after the rats' death were non-significant （P>0.05）. Conclusion The correlation between EC in cerebrum tissues, uric acid, urea nitrogen, inorganic phosphorus and PMI were relatively good, and combining various indicators can also improve the accuracy of PMI estimation.

Study on the physical growth status of birthweight discordant twins under 4 years old / 中国实用儿科杂志

OBJECTIVE: To study the physical growth characteristics of birthweight discordant twins(BDT)under 4 years old. METHODS: The physical growth characteristics of BDT under 4 years old born from September 2010 to December 2017 in child health care system of Children's Hospital of Chongqing Medical University were analyzed retrospectively. R 3.5.3 was used to clean up the database,analyze the distribution of different degree of birthweight discordance,and draw the fitting curves. More than 20% of birth weight difference was taken as inclusive criteria of BDT. BDT were divided into preterm or full-term groups,and low birthweight or normal birthweight groups respectively. SPSS 19.0 software was used for statistical analysis. RESULTS: A total of 141 pairs of BDT were included,accounting for 15.4%(141/916). The degree of birthweight difference in premature BDT was higher than that of full-term BDT(t=3.820,P<0.001). The growth discordance of preterm BDT lasted longer. Physical growth of low/very low birthweight BDT was slower than that of normal birthweight BDT under 4 years old. The growth status of BDT didn't reach the average level of WHO growth chart by the time of the last follow-up. CONCLUSION: Birthweight discordance of twins could have longlasting effects on further growth and development. Preterm twins have higher degree of birthweight discordance,and the growth discordance lasts longer. Low birthweight is an important reason for growth retardation of the lighter BDT.Growth of BDT should be monitored regularly to increase follow-up compliance.

Clinical Characteristics of Patients with Ph Mixed Phenotype Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical biological characteristics and prognosis of the patients with mixed phenotype acute leukemia with t(9;22)(q34;q11.2) and/or BCRABL1 (Ph MPAL).@*METHODS@#The morphological, immunological, cytogenetic, and molecular features of 33 in patients with Ph MPAL were retrospectively analyzed in our center from June 2002 to June 2016 according to the scoring proposal of European Group for the Classification of Acute Leukemia(EGIL )1998 and WHO 2008 criteria. All the cases were either treated with acute lymphoblastic leukemia (ALL) induction regimen or combined chemotherapy regimens for both acute lymphoblastic and acute myeloid leukemia,part of which also received tyrosine kinase inhibitor(TKI) and 5 cases underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission.@*RESULTS@#Ph MPAL occurred predominantly in male patients (ratio of M/F was 1.75∶1), and a high WBC counts at diagnosis; the WBC count was higher than 30×10/L in 25 patients( 75.8% )， and appeared higher than 100 ×10/L in 13 patients ( 39.4%). Among all the 33 PhMPAL patients, 32 (97.0%) had a myeloid / B-lymphoid (M/B) phenotype， and 1 case(3.0%) had a myeloid/ B-lymphoid/ T-lymphoid/ (M/B/T) phenotype. There was no patients displayed myeloid / T-lymphoid (M/T) or B-lymphoid/ T-lymphoid/ (B/T) phenotype. 19 of all cases(57.6%) met the diagnosis criteria of PhMPAL based on EGIL 1998 criteria, while the remaining 14 cases can be diagnosed as Ph MPAL by WHO 2008 classification,but excluded as PhMAPL by EGIL 1998.Karyotype analysis was successfully performed in 31 cases, and out of them 13 (41.9%) had a sole Ph chromosome, 10 (32.3%) had additional chromosome aberration and Ph chromosome was not found in 8 cases (25.8%) .In 31 patients the fusion gene BCR/ABL (P190、P210) was detected,including 17 (54.8%) cases with the p190 BCR/ABL transcript, 8 (25.8%) cases with the p210 BCR/ABL transcript, 4 (12.9%) expressing both transcripts and 2 (6.5%) without any one of these 2 transcripts. 24 out of 33 patients (77.4%) achieved complete remission after induction therapy. The median time achieving CR was 43(26-98)days. The CR rate of patients treated with and without imatinib after the first inducion treatment was 81.3% and 46.7%,respectively (P0.05). Within the 17 patients treated with imatinib at induction stage，2 of which became BCR/ABLnegative．At consolidation chemotherapy stage, 9 out of 16 patients became BCR/ABL negative, including 3 patients already subjected to HSCT. The median time reached to BCR/ABL negative was 2.87（1.13-9.20）months.@*CONCLUSION@#Ph MPAL is more common in male, and inclined to high WBC counts at diagnosis. Myeloid/B lymphoid phenotype is more common, and the prognosis of patients with PhMPAL is poor. Imatinib and allogeneic hematopoietic stem cell transplantation may improve survival of patients with PhMPAL.

Colour Doppler and biomarkers utility for renal damage due to congenital hydronephrosis

Objective: To determine colour doppler and serum biomarkers spectrum in children with congenital hydronephrosis

Study Design: An observational study

Place and Duration Of Study: Department of Pediatric Nephrology, West China 2nd University Hospital of Sichuan University and Key Laboratory of Birth Defects and Related Disease of Women and Children [Sichuan University], China, from January to December 2017

Methodology: A total of 95 children with hydronephrosis were selected as case group. According to the degree of hydronephrosis, the patients were divided into mild hydronephrosis group, moderate hydronephrosis group, and severe hydronephrosis group. Forty children with normal renal function were selected as normal comparison group. Peak systolic velocity [Vmax], end diastolic velocity [Vmin], resistance index [RI], pulsatility index [PI], and serum cystatin C [CysC], beta2-microglobulin [beta2-MG], and ?1-microglobulin [beta1-MG] of all subjects in both groups were recorded and compared

Results: The Vmax, Vmax of main renal artery [MRA] and interlobar renal artery [IRA] in case group were lower than those of normal group [all p<0.001]. RI of MRA and IRA in case group were higher than those of normal control group [both p<0.001]. There were no significant differences in the PI of MRA and IRA between the two groups [p=0.700, and 0.250 respectively]. The levels of serum CysC, beta2-MG and alpha1-MG in normal control group, mild hydronephrosis group, moderate hydronephrosis group, and severe hydronephrosis group were significantly different [all p<0.001], and the levels of serum CysC, beta2-MG, alpha1-MG were also different in children with different degrees of hydronephrosis

Conclusion: Combined detection of colour doppler and serum biomarkers CysC, beta2-MG and alpha1-MG in the diagnosis of renal damage in congenital hydronephrosis is feasible and reliable

Analysis on moisture transfer laws of Chaenomeles sinensis during drying process based on low-field NMR / 中草药

Objective To study the moisture transfer laws of Chaenomeles sinensis in different drying processes. Methods Using the non-destructive and non-invasive technique of low field-nuclear magnetic resonance (LF-NMR), the transverse relaxation time (T2) inversion spectrum of C. sinensis slice was monitored under different drying methods (hot air drying, drying after evaporation, segmental drying and drying in the shade) to analyze the changes of moisture migration. Results There were three different types water that were detected in C. sinensis (free water > bound water > immobilized water). The internal water distribution and water content changed during drying process. The moisture changes were similar in hot air drying, drying after steaming, and drying in shade, the total water gradually decreased, and the combining degree between moisture and non-water components enhanced. Steaming promoted the water loss rate of C. sinensis slice, the water loss rate was higher in drying after steaming than in hot air drying, and the difference was significant (P < 0.05). During the intermittent drying, the conversion of different states of water would occur in order to return to a relatively stable equilibrium. During the low temperature drying process, immobilized water content decreased and free water content increased. The low-temperature drying has less damage to the tissue, which is more conducive to the conversion of immobilized water into free water, and thus the water dissipated faster. During the early of drying, high temperature caused tissue structure damage, the bonding force between water and non-aqueous tissue would be strengthened because of the tissue shrinkage. Conclusion The three different types water content and peak area in T2 was positively correlated. The LF-NMR technique would provide useful guides for the investigation of water distribution and variation of C. sinensis, which will provide a theoretical basis for C. sinensis processing.

Development of Dipolar Proton Transfer Reaction Mass Spectrometer for Real-time Monitoring of Volatile Organic Compounds in Ambient Air / 分析化学

Volatile organic compounds (VOCs) in ambient air can participate in photochemical reactions, which lead to the generation of secondary pollutants such as ozone and aerosol. So real-time and accurate monitoring of atmospheric VOCs plays an important role in the study of the causes of air pollution. On the basis of proton transfer reaction mass spectrometry (PTR-MS) research, a novel dipolar proton transfer reaction mass spectrometer (DP-PTR-MS) for real-time and on-line monitoring atmospheric VOCs was developed. Compared with the conventional PTR-MS with one kind of reagent ion H3O+, DP-PTR-MS had three kinds of reagent ions H3O+, OH-, (CH)2COH+, which could be switched according to the actual detection need. So DP-PTR-MS can improve the qualitative ability and expand the detection range effectively. The reagent ion H3O+can be used for detecting VOCs whose proton affinities are greater than that of H2O. The reagent ion OH-can be used to identify VOCs cooperating with the reagent ion H3O+,and can also be used for detecting some inorganic substances such as CO2. The reagent ion (CH3)2COH+can be used for accurately detecting NH3under interference elimination circumstances. The limit of detection (LOD) and sensitivity of DP-PTR-MS were measured by using six kinds of standard gases. The results showed that the LOD for detecting toluene was 7×10-12(V/V) and the sensitivity for detecting ammonia has reached 126 cps/10-9 (V/V). The ambient air in Hefei city was on-line and real-time monitored for continuous 78 hours with DP-PTR-MS. The results showed that the newly developed DP-PTR-MS could be used for long-term and real-time monitoring atmospheric VOCs with the concentration of 10-12(V/V) level. DP-PTR-MS is an important tool for the study of the causes of atmospheric pollution and the monitoring of trace VOCs emissions.

Spectrum of somatic mutations and their prognostic significance in adult patients with B cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients' overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph+ B-ALL and Ph- B-ALL patients. Ph- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph+ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion: Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.

Biological pacemaker in treatment of bradycardiac arrhythmia: Research progress / 第二军医大学学报

Electronic pacemakers has become the preferred treatment for arrhythmia, especially for severe bradycardiac arrhythmia. Although the technology of electronic pacemaker was gradually improving, it still has some shortcomings. Over the past 10 years, research has confirmed that biological pacemaker can be created by gene therapy and cell therapy; with the development of molecular biology and cell biology, biological pacemaking technology has been continuously broken. Currently there are two approaches to construct biological pacemakers: one is to introduce pacemaker genes into mesenchymal stem cells, and the other is to induce pluripotent stem cells to sinoatrial node cells. In this paper, we reviewed the latest research progress of biological pacemakers, so as to analyze the existing problems in biological cardiac pacing and future research directions.

2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glycoside attenuates the apoptotic responses of hypoxia/reoxygenation injury in bronchial epithelial cells through MAPK, HIF-1α and p53 pathway / 药学学报

This study was designed to investigate the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glycoside(TSG)on hypoxia/reoxygenation(H/R)-induced oxidative stress injury and its potential mechanism in human bronchial epithelial cell(BEAS-2B)cells. BEAS-2B cells were exposed to H/R treatment. Level of intracellular ROS was detected using DCFH-DA probe and fluorescence microplate reader. Production of MDA and activity of SOD were evaluated with MDA and SOD kits. Nucleus was shaped by DAPI staining. Translocation of Bax to mitochondria was observed in MCF-7/GFP-Bax cells. Change in mitochondrial membrane potential was detected by JC-1 staining. Release of cytochrome C from mitochondria was detected by immunofluorescence. Expressions of mitochondrial/cytoplasmic Bax and cytochrome C, caspase-9, caspase-3, phosphorylated MAPK, HIF-1α and phosphorylated p53(p-p53)were determined by Western blotting. TSG significantly improved cell viability and reduced H/R-induced ROS production in BEAS-2B cells, while significantly decreased MDA production. It inhibited Bax translocation and nucleus fracture, reversed the decrease in mitochondrial membrane potential and inhibited the release of cytochrome C and following activation of caspase-9/caspase-3. Simultaneously, TSG down-regulated the signals of SAPK JNK1/2 and p38 MAPK without an impact in ERK1/2. It attenuated expression of HIF-1α and phosphorylation of p53. This study suggests that TSG could protect BEAS-2B against H/R-induced apoptosis, perhaps through the MAPK, HIF-1α and p53 pathways.

Association rules analysis for exploring combined medication characteristics of Fufang Kushen injection: real-world study based on 49 597 cases / 中国中药杂志

The present study aimed to analyze the association rules of Fufang Kushen injection in combined medications in the real world based on electrical medical records in hospital information system, and provide reference for its reasonable clinical application. The electrical medical records of the hospitalized patients using Fufang Kushen injection were extracted to analyze the frequency distribution characteristics in combined application with Western medicine, and analyze the specific association rules between these combinations by using Apriori algorithm. A total of 49 597 patients were included in the study, and its common combined medications included 5-HT receptor blockers, hepatic protector, antibiotics, chemotherapeutic drugs, immunomodulatory drugs, glucocorticoids, analgetics and proton pump inhibitors. The results revealed that the distribution characteristics in combined application and association combinations of Fufang Kushen injection had specific rules, consistent with the clinical orientation of this drug in treatment of malignant tumor. Such results may provide reference for reasonable application of Fufang Kushen injection in clinical treatment.