Analysis of typical experiences of public hospital salary system reform in Sichuan province / 中华医院管理杂志

Objective:To analyze the experiences and practice in the reform of public hospital salary system in Sichuan province, summarize the typical modes of such reform in the province, and provide references for further reform.Methods:As of October 29, 2021, the research group received 77 sets of typical experience materials submitted by the health commissions and public hospitals in Sichuan province on enforcing the reform of the public hospital salary system. The analysis framework was based on the five main elements proposed in the Guidance to Deepening the Reform of the Salary System of Public Hospitals for the purpose of furthering the reform. These five elements refer to " reasonably determining the level of salary in public hospitals" " fully implementing the autonomy of internal distribution in public hospitals " " establishing and improving the incentive and restraint mechanism for the remuneration of public hospital leaders" " improving the assessment and evaluation mechanism oriented to public welfare" and " funding sources ". A quantitative analysis was made on the typical experience materials using the social network analysis method, while a qualitative analysis was made on the typical experience materials using the content analysis method. Results:The results of social network analysis showed that the network density was 0.272; the highest point centrality was " fully implement the autonomy of internal distribution in public hospitals" (0.935), and the highest intermediary centrality was " improving the assessment and evaluation mechanism oriented to public welfare" (0.870), while the closeness to centrality of " establishing and improving the incentive and constraint mechanism for the salary of public hospital leaders" (0.434) and " funding sources" (0.421) were relatively low. The results of content analysis showed that the ones with higher frequency among all the typical experience materials were " fully implementing the autonomy of internal distribution of hospitals" (72 times) and " improving the assessment and evaluation mechanism oriented to public welfare" (67 times), while the ones with lower frequency were " establishing and improving the salary incentive and constraint mechanism for public hospital leaders" (17 times) and " funding sources" (14 times). In terms of unity and synergy, the typical models of public hospital salary system reform in the province could be categorized as the fine standard mode, the fair value mode, the autonomous synergy mode and the circular symbiosis mode.Conclusions:Deepening the reform of the salary system of public hospitals should unify the standards and improve the fair and refined assessment and evaluation mechanism; explore various forms of distribution and build an internal autonomous and synergistic incentive mechanism; pay attention to the weak remuneration incentive mechanism for hospital leaders and the problem of a relatively single source of funding.

Intervention effect of transcutaneous auricular vagus nerve stimulation on myocardial structural remodeling, electrical remodeling and apoptosis in rat heart failure model with preserved ejection fraction / 中华老年医学杂志

Objective:To observe the effect of percutaneous auricular vagus nerve stimulation on myocardial structural remodeling, electrical remodeling and apoptosis in rats of heart failure with preserved ejection fraction, and to explore the relationship between this effect and oxidative stress.Methods:The arteriovenous fistula was closed by ligation two weeks after establishment in SD rat.By increasing cardiac volume load in the short term, a rat model of heart failure with preserved ejection fraction was constructed.Forty rats were randomly divided into four groups, with 10 rats in each group: sham operation group(S), abdominal aorta-inferior vena cava fistula + closure group(AVF+ L), abdominal aorta-inferior vena cava fistula + closure+ percutaneous auricular vagus nerve stimulation group(AVF+ L+ tVNS)and abdominal aorta-inferior vena cava fistula + closure+ percutaneous auricular vagus nerve stimulation + acetylcholine M 2 receptor antagonist group(AVF+ L+ tVNS+ M -). Rats in the AVF+ L+ tVNS group received percutaneous vagal nerve stimulation on the basis of those in the AVF+ L group.Rats in the AVF+ L+ tVNS+ M - group received daily injection of acetylcholine M 2 receptor antagonist mesotramine(0.5mg/Kg)into tail vein on the basis of those in the AVF+ L+ tVNS group.The parameters of cardiac structural remodeling and electrical remodeling in each group were obtained by cardiac ultrasound and cardiac electrophysiological stimulator.Enzyme-linked immunosorbent assay(ELISA)was used to detect the values of B-type natriuretic peptide precursor(NT-proBNP)and oxidative stress-related indicators in each group.hematoxylin-eosin(HE)staining was used to observe the damage of myocardial structure, disorder of cell arrangement and infiltration of inflammatory cells.Cardiomyocyte apoptosis was observed by TdT-mediated dUTP nick end labeling(TUNEL)staining and apoptosis index was calculated.reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting were used to detect the mRNA and protein expression of B cell lymphoma / leukemia-2(BCL-2)and apoptosis promoting gene(BAX)in BCL-2 gene family. Results:The rats in the AVF + L group developed heart failure characterized by ventricular wall hypertrophy and diastolic dysfunction, and the left ventricular ejection fraction(LVEF)was >50 %.The rat heart failure model with preserved ejection fraction was successfully established.HE staining showed that the myocardial tissue structure damage, cell arrangement disorder and inflammatory cell infiltration were obvious in AVF+ L group, while the pathological changes of myocardial tissue in AVF+ L+ tVNs were significantly less than those in AVF+ L group.Compared with AVF+ L group, in the AVF+ L+ tVNs, the value of NT-proBNP decreased[(301.25 ± 16.07)ng/L vs.(79.33±5.63)ng/L, P<0.05], the value of E/A increased(1.28 ± 0.06 vs.1.66 ±0.05, P<0.05), the expression of BCL-2 mRNA[0.08(0.07, 0.08) vs.0.70(0.64, 0.76), P<0.05]and BCL-2 protein(0.19±0.03 vs.0.46±0.04, P<0.05)both increased, the expression of BAX mRNA(5.00±0.32 vs.2.14±0.36, P<0.05)and BAX protein(0.76±0.04 vs.0.43±0.05, P<0.05)both decreased, while the apoptotic index was also decreased(16.26±0.32 vs.7.04±0.24, P<0.05). Compared with AVF + L group, the indexes of myocardial structural remodeling, electrical remodeling and oxidative stress were decreased in AVF + L + tVNs group(P<0.05). Compared with AVF + L group, there was no significant difference in the above indexes in AVF + L + tVNS + M - group( P>0.05). Conclusions:tVNS can alleviate myocardial structural remodeling, electrical remodeling and apoptosis in HFpEF rats, which may be related to the reduction of oxidative stress response activity.

Clinical characteristics and related factors analysis of adrenal crisis occurred in children with primary nephrotic syndrome / 中华儿科杂志

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×109 vs. (11±5)×109/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

Successful treatment of acute leukemia by secondary transplantation after the first haploidentical hematopoietic stem cell transplantation failure / 器官移植

Objective To evaluate the feasibility of secondary transplantation for patients with acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation. Methods Two acute leukemia patients underwent the first haploidentical hematopoietic stem cell transplantation from two donors with thalassemia, and the number of collected CD34+ cells was 2.57×106/kg and 1.99×106/kg per donor, respectively. The first haploidentical hematopoietic stem cell transplantation failed. Secondary transplantation was performed from two non-thalassemia donors, and the number of collected CD34+ cells was 4.28×106/kg and 5.75×106/kg per donor, respectively. A reduced-intensity conditioning regimen consisting of fludarabine (Flu), busulfan (Bu) and antithymocyte globulin (ATG) was adopted for the secondary transplantation. Results For two recipients, the time of secondary transplantation of neutrophil and platelet was +12 d and +10 d, +10 d and +10 d, respectively. Up to the final follow-up (+1 062 d and +265 d after secondary transplantation), the primary diseases of both two recipients have been completely relieved without evident post-transplantation complications. Conclusions Secondary transplantation with reduced-intensity conditioning regimen may successfully treat acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation.

Analysis on the staff salary status in traditional Chinese medicine hospitals of Sichuan province in 2020 / 中华医院管理杂志

Objective:To analyze the staff salary status and the influencing factors in traditional Chinese medicine(TCM) hospitals implementing the salary system reform in Sichuan province in 2020, for reference in optimizing the salary system reform of such hospitals.Methods:Cluster sampling and institutional survey were used to collect the salary information of 26 TCM hospitals in 21 cities(prefectures)of Sichuan province implementing the salary system reform in 2020. Such information was then subject to descriptive analysis, while the influencing factors of salary were subject to one-way analysis of variance and generalized linear model multifactor analysis.Results:15 428 staff from 26 TCM hospitals were included as the research objects. In 2020, personnel expenditure accounted for 40.23% of the total expenditure, and 24.34% of which came from financial subsidy in 26 TCM hospitals. The average annual payable income per person was(149 312±74 288)yuan, 67.82% of which being performance pay. Analysis of variance showed that there were significant differences among the salary levels of staff in different economic regions, hospital grades, hospital levels, gender, educational background, position, seniority, performance pay ratio, employment in the government system and other natures, senior and other professional titles, doctors and other positions( P<0.05), and the differences were still statistically significant after adjustment by generalized linear model( P<0.05). Conclusions:The reform of the salary system of Sichuan TCM Hospitals has basically achieved equal pay for equal work, and the income of low-level personnel has been improved. However, the salary level was not very motivated and the salary structure was not guaranteed. It is necessary to strengthen financial precision subsidies, increase the proportion of personnel expenditure, so as to support the increase of the absolute value of salary in non-core economic areas, improve the salary structure, reasonably widen the salary gap among different educational backgrounds and positions, further optimize internal distribution, and ensure the sustainable development of Chinese medicine talents.

Analysis of salary characteristics and influencing factors of personnel expenditure in medical institutions in Sichuan province / 中华医院管理杂志

Objective:To analyze the salary characteristics of medical institutions and the influencing factors of personnel expenditure as found in the salary system reform of public hospitals in Sichuan province, for reference in furthering such reform in public hospitals.Methods:The data of personnel expenditure, business operation and medical services came from 96 medical institutions in 21 cities(prefectures)of Sichuan province from 2017 to 2020 by means of institutional survey. The average salary level and salary structure of medical staff were used to describe the salary characteristics, and the total salary was presented by the level of personnel expenditure. The measurement data was represented by M(IQR), the counting data was described by frequency and constituent ratio, and the influencing factors of personnel expenditure were analyzed by generalized linear mixed model. Results:From 2017 to 2020, the personnel expenditure of medical institutions increased by 13.04% annually. In 2020, the per capita salary level of medical staff was 151 900 yuan, while the basic salary and performance salary accounted for 16.20% and 54.60% of personnel expenditure respectively. The analysis results of the generalized linear mixed model showed that the average cost of patients per visit( β=0.596), the level of drugs and sanitary materials consumed per 100 yuan medical income( β=0.286), the number of medical visits( β=0.328), and the years [(2018, 2019, 2020) β=0.025, 0.052, 0.066] were positively correlated to personnel expenditure, while the average length of stay( β=-0.693), the proportion of medical service income( β=-0.392), and the balance rate of income and expenditure( β=-0.062)were negatively correlated to personnel expenditure( P<0.05). The proportion of fiscal subsidy revenue, regional GDP and asset-liability ratio were not the influencing factors of personnel expenditure( P> 0.05). Conclusions:In the reform of the salary system of the province, its salary level of medical institutions has surpassed the current wage ceiling of these institutions. As the salary distribution was mainly made based on the workload, the " baton" role of the salary system reform has begun to pay off. However, the basic guarantee role of compensation has not yet been fully leveraged.Further reform is needed in upgrading refined management, and timely dynamic adjustment of personnel expenditure in combination with the hospital's financial performance and cost analysis, and reasonably optimizing the level of medical staff compensation.

IL-6 exacerbates potential arrhythmia of Chan Su intravenous injection / 中国药理学通报

Aim To explore the arrhythmic risk of Chan Su intravenous injection(CS)and its underlying mechanismin in the absent or presence of IL-6.Methods The recording techniques of guinea pig in vivo ECG, the action potential, L-type Ca2+ and Na+ currents from left ventricular myocytes were used to analyze heart rate(HR), P-R, QRS and QTc intervals and the underlying mechanism.Results① CS at one time CRD(clinically relevant dose)insignificantly changed the guinea pig in vivo ECG.However, the IL-6(18.4 μg·kg-1)only and the combinational use of IL-6(18.4 μg·kg-1)plus CS(one time CRD)remarkably prolonged the P-R and QTc intervals.② The CS at one time CRC(clinically relevant concentration)had no significant change in the action potential duration at 90% repolarization level(APD90).The IL-6(20 μg·L-1)only and the combination of CS at one time CRC plus IL-6(20 μg·L-1)significantly prolonged APD90.③ Moreover, the IL-6(20 μg·L-1)combined with CS at one time CRC significantly inhibited the L-type Ca2+ current. CS at one, five, ten time CRC, IL-6(20 μg·L-1)alone and IL-6(20 μg·L-1)combined with CS had no significant effects on Na+current.Conclusions CS intravenous injection has low risk of arrhythmia in the clinical settings.However, in presence of high titer of IL-6 characterized by inflammation, CS may induce the atrioventricular conduction block due to the blockade effect on Ca2+ current by both of CS and IL-6.

Analysis of the equity of health human resource allocation for echinococcosis control based on Gini index / 中国血吸虫病防治杂志

OBJECTIVE@#To analyze the current status and evaluate the equity of health human resource allocation for echinococcosis control in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, so as to provide the empirical evidence for optimizing the health human resource allocation for echinococcosis control.@*METHODS@#A questionnaire survey was performed to collect the numbers of health human sources for echinococcosis control, including health workers, healthcare professionals, certified/assistant physicians and registered nurses, per 1 000 permanent residents, per 1 000 m2, per 1 000 residents screened using Bmode ultrasonography and per 1 000 echinococcosis patients in two highly endemic counties and three lowly endemic counties in Ganzi Tibetan Autonomous Prefecture, Sichuan Province from 2016 to 2019. The equity of health human resource allocation for echinococcosis control was evaluated by permanent residents and geographical areas using Lorenz curve and Gini index in Ganzi Tibetan Autonomous Prefecture from 2016 to 2019.@*RESULTS@#The numbers of health workers, healthcare professionals, certified/assistant physicians and registered nurses per 1 000 permanent residents, per 1 000 permanent residents, per 1 000 m2, per 1 000 residents screened using B-mode ultrasonography and per 1 000 echinococcosis patients were 0.99-, 1.06-, 1.78- and 1.88-fold; 3.38-, 3.67-, 6.00- and 6.00-fold; 1.64-, 1.74-, 3.22- and 3.18-fold; and 64.92-, 70.39-, 139.34- and 117.44-fold more in lowly endemic counties than in highly endemic countries in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, 2019. The Gini indexes of health human resource allocation for echinococcosis control were 0.371 to 0.397 by permanent residents and 0.477 to 0.591 by geographical areas in Ganzi Tibetan Autonomous Prefecture from 2016 to 2019, and the Gini indexes (0.469 to 0.730) for allocation of certified/assistant physicians and registered nurses were both higher than those of health workers and healthcare professionals (0.302 to 0.451) by both permanent residents and geographical areas.@*CONCLUSIONS@#The health human resource allocation for echinococcosis control showed general equity by permanent residents and poor equity by geographical areas in Ganzi Tibetan Autonomous Prefecture, Sichuan Province from 2016 to 2019.

Meta analysis of the effects of high intensity interval training on metabolic syndrome in overweight college students / 中国学校卫生

Objective@#In this study, a meta analysis was conducted to evaluate and compare the effects of different types of interval training, such as, repeated sprint training(RST), high intensity interval training(HIIT) and sprint interval training(SIT) on body index of overweight/obese college students and the effect of moderate intensity continuous training(MICT), so as to provide a reference for taking appropriate exercise measures.@*Methods@#The data was searched and selected from the database of Web of Science, PubMed, Scopus, The Cochrane Library and CNKI, and from the articles about random research on the effects of HIIT, SIT, RST, and MICT on overweight/obese college students for the evaluation of bias risk. And Stata 16.0 software was used for Meta analysis and network analysis.@*Results@#Totally 815 samples selected from 18 articles were included in the study. Meta analysis showed that HIIT( SMD=-0.26, 95%CI =-0.52--0.00, P <0.05) and SIT( SMD=-0.39, 95%CI =-0.72--0.07, P <0.05) could make greater effects on BMI than MICT. The differences between RST and MICT were of no statistical significance( SMD=0.28, 95%CI =0.32-0.87, P >0.05). According to the SUCRA method combined with effect size, the best effect on improving MetS related physiological indexes of overweight college students was found in SIT( SUCRA =79.3), followed by HIIT( SUCRA =78.2), RST( SUCRA =56.8), and MICT( SUCRA =35.7).@*Conclusion@#Compared with MICT, high intensity interval training can greatly improve BMI of the obese/overweight college students, and could achieve the optimal effect of reducing the fat by exercising through SIT.

Clinical observation of modified lower costa surgical approach for transversus abdominis plane block combined with rectus sheath block in peritoneal dialysis catheterization / 中国医师进修杂志

Objective:To explore the safety and effectiveness of modified lower costa surgical approach (mLS) for transversus abdominis plane block (TAPB) combined with rectus sheath block (RSB) in surgical incision peritoneal dialysis catheterization (PDC).Methods:Forty chronic kidney disease of stage 5 patients scheduled for PDC from January to December 2018 in Huadu District People′s Hospital of Guangzhou City were selected. The patients were divided into 3 groups by random digits table method, among whom 13 cases used mLS for TAPB combined with RSB (TAPB combined with RSB group), 13 cases used lateral approach combined with hip approach for TAPB (TAPB group), and 14 cases used local anesthesia (LA group). The mean arterial pressure, heart rate and pain visual analogue score (VAS) at skin incision (T 0), separation of rectus abdominis (T 1), peritoneal dialysis catheter placement (T 2) and suture of skin and subcutaneous tunnel (T 3) were recorded; and the total operation and anesthesia time, cases of rescue anesthesia, surgeon′s satisfaction with anesthesia, surgical and anesthesia related complication were recorded. Results:The VAS from T 0 to T 3 in TAPB combined with RSB group and TAPB group was significantly lower than that in LA group: (1.92 ± 0.95) and (3.00 ± 1.08) scores vs. (5.07 ± 0.62) scores, (1.31 ± 0.63) and (2.54 ± 0.66) scores vs. (3.86 ± 0.77) scores, (0.85 ± 0.69) and (1.77 ± 0.93) scores vs. (3.71 ± 0.61) scores, (1.38 ± 0.77) and (1.38 ± 0.87) scores vs. (3.64 ± 0.17) scores, the VAS of T 1 in TAPB combined with RSB group was significantly lower than that in TAPB group, and there were statistical differences ( P<0.05). There were no statistical differences in mean arterial pressure and heart rate among 3 groups ( P>0.05). The surgeon′s satisfaction with anesthesia from T 0 to T 3 in TAPB combined with RSB group and TAPB group were significantly higher than that in LA group: (3.12 ± 0.76) and (3.11 ± 0.65) scores vs. (2.09 ± 0.61) scores, (3.09 ± 0.82) and (2.68 ± 0.75) scores vs. (1.99 ± 0.66) scores, (3.35 ± 0.82) and (3.31 ± 0.75) scores vs. (2.37 ± 0.73) scores, (3.02 ± 0.82) and (3.01 ± 0.75) scores vs. (2.35 ± 0.63) scores, surgeon′s satisfaction with anesthesia of T 1 in TAPB combined with RSB group was significantly higher than that in TAPB group, and there were statistical differences ( P<0.05). The rescue anesthesia in LA group was in 2 cases. The total operation and anesthesia time in TAPB combined with RSB group was significantly shorter than that in TAPB group and LA group: (45.08 ± 9.62) min vs. (74.46 ± 7.29) and (69.71 ± 13.25) min, that in LA group was significantly shorter than that in TAPB group, and there were statistical differences ( P<0.05). The patients of 3 groups had no surgical and anesthesia related complication. Conclusions:In surgical incision PDC with mLS for TAPB combined with RSB, the effectiveness of intraoperative anesthesia is accurate, the operation time is short, the surgeon′s satisfaction with anesthesia is high, the blood pressure and heart rate are stable, and the security is high.

The positive inotropic effect of phosphodiesterase type 8 inhibitor of PF-04957325 in rats and its underlying mechanism / 中国药理学通报

Aim To investigate the inotropic effect of PF-04957325, a phosphodiesterase type 8 inhibitor, in normal rats and its underlying molecular mechanism. Methods The techniques of in vivo rat left ventricular pressure-volume loop (P-V loop) and isolated perfusion rat heart were used to analyze the hemodynamics and positive inotropic effect of rat hearts. The Ca transient induced by field stimulation was used to analyze the hemodynamics of sarcoplasmic reticulum (SR) Ca + uptaking. Western blot was used to analyze the phosphorylation levels of SR phospolamban (PLB) and ryanodine receptor type 2 (RyR2). Results The P-V loop experiment indicated that PF-04957325 (0.5 mg · kg

Positive inotropic effect of phosphodiesterase type 9 inhibitor PF-04449613 in rats and its underlying mechanism / 生理学报

This study aimed to explore the positive inotropic effect of phosphodiesterase type 9 (PDE9) inhibitor PF-04449613 in ratsand its cellular and molecular mechanisms. The heart pressure-volume loop (P-V loop) analysis was used to detect the effects of PF-04449613 on rat left ventricular pressure-volume relationship, aortic pressures and peripheral vessel resistance in healthy rats. The Langendorff perfusion of isolated rat heart was used to explore the effects of PF-04449613 on heart contractility. The cardiomyocyte sarcoplasmic reticulum (SR) Ca

Effects of RNA Targeting mPGES-1 on Proliferation and Apoptosis of K562/A Cells / 中山大学学报(医学科学版)

@#【Objective】 To explore the effects and the possible mechanism of RNA targeting membrane-bound prostaglandin E2 synthase l（mPGES- 1）on proliferation，apoptosis and drug resistance of leukemia cell line K562/A.【Methods】RNA interference was used to inhibit the expression of mPGES-1 of K562/A cells. Four groups were set up as follows：untreated group（K562/A），negative control group after interference（K562/A-NC），group after interference（K562/ A-KD），and group after interference with exogenous PGE2（K562/A-KD+PGE2）.Cell viability was assessed by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry. Concentration of PGE2 was detected by ELISA. Proteins expression was detected by western blot.【Results】The expression of mPGES- 1 in K562/A cells was significantly down- regulated and the synthesis of PGE2 decreased（P < 0.000 1）after RNA interference. After RNA interference，the proliferation of K562/A cells was inhibited and apoptosis increased，and the sensitivity to chemotherapy drugs was enhanced（P < 0.05）. Meanwhile，the expression of β-catenin and MDR1 was decreased（P < 0.01）. Exogenous PGE2 could reverse the effect of RNA interference on proliferation ，apoptosis and drug sensitivity in K562/A cells（P < 0.05），and up-regulate the expression of β-catenin and MDR1（P < 0.01）. XAV939，an inhibitor of β-catenin，could down-regulate the expression of β- catenin and MDR1 in an dose- dependent pattern in K562/A cells（P < 0.05）.【Conclusions】RNA interference of mPGES- 1 could inhibit proliferation，induce apoptosis and reverse drug resistance in K562/A cells. The mechanism was related to reducing the synthesis of PGE2 and thus down- regulating the expression of β- catenin and MDR1. Wnt/β- catenin signal pathway may participate in the regulation of MDR1 by mPGES-1/PGE2.

Advance in clinical research of radiotherapy for primary and metastatic liver malignancies / 肿瘤

Surgical treatment is the primary curative treatment for hepatocellular carcinoma and liver metastasis of colorectal cancer, but most patients are ineligible for the treatment upon initial diagnosis. And the overall efficacy of topical treatments such as radiofrequency ablation or transcatheter arterial chemoembolization remains limited. As an important supplementary treatment for surgery, radiotherapy plays an increasingly important role in the treatment of hepatic malignancies with the development of radiotherapy and the progress of liver cancer research. At the same time, the focus of liver radiation is on the safety of radiotherapy, especially the risk of radiation-induced liver disease. In this review, the recent advances in the clinical studies and safety of radiotherapy for hepatocellular carcinoma and liver metastasis of colorectal cancer were summarized.

Application of the selective bcl-2 inhibitor venetoclax in hematologic malignancies / 白血病·淋巴瘤

Resistance to apoptosis is a key carcinogenic mechanism in hematologic malignancies. bcl-2 is considered to be an important anti-apoptotic protein of endogenous apoptosis pathway and bcl-2 targeting inhibition has become one of research hotspots of anti-hematologic malignancies. Venetoclax, a selective bcl-2 inhibitor, has been used in the treatment of chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) and mantle cell lymphoma (MCL). This paper reviews the role of bcl-2 family in the regulation of apoptosis and advances of venetoclax in hematologic malignancies.

Analysis of incidence and influencing factors of stroke in Philadelphia chromosome-negative myeloproliferative neoplasms / 白血病·淋巴瘤

Objective:To investigate the occurrence of stroke and its associated risk factors in patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPN).Methods:The data of patients diagnosed as Ph-negative MPN in the Affiliated Yuebei People's Hospital of Shantou University Medical College from January 2016 to December 2019 were retrospectively analyzed. The occurrence of stroke in these patients and the clinical characteristics were summarized. Logistic regression was used to analyze the risk factors of stroke in MPN patients.Results:A total of 193 Ph-negative MPN patients were collected, including 103 males and 90 females. The median age of onset was 62 years old (24-93 years old). There were 129 patients (66.84%) with essential thrombocythemia, 46 patients (23.83%) with polycythemia vera, and 18 patients (9.33%) with primary myelofibrosis. In 193 patients with MPN, there were 31 patients (16.06%) with stroke, including 30 cases (15.54%) of ischemic stroke and 1 case (0.52%) of hemorrhagic stroke, and the incidence of ischemic stroke was higher than that of hemorrhagic stroke, the difference was statistically significant (χ 2 = 54.258, P < 0.01). Among the patients with stroke, JAK2V617F mutation was observed to be the most common driver mutation (80.65%, 25/31). The small-artery occlusive cerebral infarction was the most common in ischemic stroke (63.33%, 19/30). Compared with MPN patients without stroke, those with stroke displayed higher hemoglobin level [(156±35) g/L vs. (138±40) g/L] and concurrent JAK2V617F and CALR mutations rate [3.23% (1/31) vs. 0.62% (1/162)], and lower CALR mutation rate [3.23% (1/31) vs. 19.14% (31/162)], the differences were statistically significant (all P < 0.05). Logistic regression analysis revealed that hemoglobin ≥ median level (140 g/L) was a risk factor for stroke in MPN patients ( OR = 2.903, 95% CI 1.163-7.244, P = 0.022), and CALR mutation acted as a protective factor for stroke ( OR = 0.090, 95% CI 0.009-0.932, P = 0.044). Conclusions:Ischemic stroke is more common than hemorrhagic stroke in Ph-negative MPN patients, and the small-artery occlusive cerebral infarction is also more frequently found in these patients. Hemoglobin ≥140 g/L is a risk factor for stroke in MPN patients, and CALR mutation is a protective factor.

Clinical analysis of driver mutations in classical myeloproliferative neoplasms / 白血病·淋巴瘤

Objective:To explore the driver mutations in patients with classical myeloproliferative neoplasms (MPN) and their relationships with clinical characteristics.Methods:The clinical data of 186 patients with classical MPN in the Affiliated Yuebei People's Hospital of Shantou University Medical College from January 2013 to October 2019 who met the World Health Organization 2016 MPN diagnostic criteria were retrospectively analyzed. The mutations of diver genes JAK2, CALR and MPL and clinical characteristics, such as white blood cell count, hemoglobin, and platelet count in patients with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) were analyzed.Results:Among the 186 MPN patients, 100 were male and 86 were female, with a median age of onset of 62.0 years old (24.0-93.0 years old). There were 125 patients (67.20%) with ET, 44 patients (23.66%) with PV, and 17 patients (9.14%) with PMF. The JAK2V617F mutation was found in 133 patients (71.51%, 133/186). The JAK2V617F mutation rates in patients with ET, PV and PMF were 66.40% (83/125), 88.64% (39/44) and 64.71% (11/17), respectively. Two patients (1.08%, 2/186) with PV were found with JAK2 exon 12 mutation. The CALR exon 9 mutation was found in 32 patients (17.20%, 32/186), with the CALR mutation rates of 24.00% (30/125), 0 and 11.76% (2/17) in patients with ET, PV and PMF, respectively. The MPL exon 10 mutation was found in one ET patient (0.54%, 1/186). CALR mutated ET patients showed higher platelet count [(1 155±537)×10 9/L vs. (997±330)×10 9/L, t = -2.095, P = 0.038], and lower leukocyte count ( t = 2.434, P = 0.017) and hemoglobin ( t = 3.087, P = 0.003) than JAK2V617F mutated ET patients. Two cases of MPN had rare concurrent driver mutations, of which one ET patient with JAK2V617F and CALR mutations and one PMF patient with JAK2V617F and MPLW515L mutations. Conclusions:The detection result of driver mutations is an important basis for precision health care for MPN. Different types of MPN have different detection rates of driver mutations, which are of great significances for judging the clinical characteristics of patients.

Positive inotropic effect of Ivabradine in rats and its underlying mechanism / 医学研究生学报

ObjectiveIvabradine reduces heart rate by inhibiting If current of cardiomyocyte and is used clinically to treat stable angina pectoris and myocardial ischemia. However, the mechanism of positive inotropic effect by Ivabradine is still not well understood. This study aims to investigate the Ivabradine's positive inotropic effect both in vivo and in vitro and the underlying mechanism involved.Methods①A Millar catheter with double-pressure was inserted into the right carotid artery of general anesthesia rats. The pressure-volume of left ventricle, HR (heart rate) and aortic pressure were recorded as a blank group (n=7). The effect of Ivabradine (1 mg/kg) administrated via left external jugular vein was recorded as a drug treated group (n=7). The cardiac output, left ventricular and aortic pressure of the rats in the blank group A and the administration group A were compared, and the results were used to analyze the Ivabradine's inotropic effectin vivo.②Langendorff setup was used to analyze the left ventricular pressure of the isolated heart. The normal perfusion solution was used as the blank group (n=6), while the Ivabradine (10 μmol/L) perfusion was used as the treated group (n=6). In addition, the treatment of H89 (200 nmol/L) (a PKA inhibitor) was recorded as the blank group (n=6) and the combined use of H89 (200 nmol/L) and Ivabradine (10 μmol/L) was recorded as drug treated group (n=6). Following the above protocol, KN-93 (500 nmol/L) (a CaMKII inhibitor) or CA (10 nmol/L) (a protein phosphatase 1 and 2A inhibitor) was used to analyze the inhibitory effect on inotropic effect of Ivabradine (n=6 for each group). ③The field stimulation induced Ca2+ transient from cardiomyocyte was used to investigate the mechanism underlying the positive inotropic effect of Ivabradine (10 μmol/L).The perfusion orders and concentrations of Ivabradine or/and H89, KN-93 and CA were the same as that in isolated rat heart experiment (n= 6 for each group).Results① Ivabradine (1 mg/kg) significantly increased the left ventricular develop pressure (from 102.43±11.06 in blank group to 109.86±11.65 mmHg in ivabradine treated group, P<0.01, n=7) and cardiac output (from 33.72±1.96 in blank group to 36.27±2.22 mL/min in ivabradine treated group, P<0.01, n=7). It reduced the heart rate (from 348.56±10.02 in blank group to 324.17±11.33 beats/min in ivabradine treated group, P<0.01, n=7) and increased the systolic blood pressure (from 99.74±8.67 in blank group to 108.57±9.24 mmHg in Ivabradine treated group, P<0.01, n=7) without significant change in diastolic blood pressure. ② Ivabradine (1, 10 μmol/L) significantly increased the left ventricular developed pressure (LVDP) (P<0.05, n=6). The positive inotropic effect of Ivabradine was blocked by CaMKⅡ inhibitor of KN-93. ③ Ivabradine (10 μmol/L) significantly increased the amplitude of SR Ca2+ transient (P<0.01,n=6). The enhanced amplitude of Ca2+ transient was blocked by CaMKⅡ inhibitor of KN-93.ConclusionIvabradine shows a positive inotropic effect in rat hearts both in vivo and in vitro and its underlying mechanism involved the action which was mediated by CaMKⅡ.

Enteral nutrition support reduces toxicity of chemotherapy in patients with advanced or metastatic esophageal cancer / 北京大学学报(医学版)

OBJECTIVE@#To assess the impact of enteral nutrition support on response and toxicity of the first-line chemotherapy in those patients with advanced or metastatic esophageal cancer.@*METHODS@#We collected the clinical data of 118 patients with unresectable advanced or metastatic esophageal cancer who received the first-line chemotherapy in our center from July 2014 to December 2016. All these 118 esophageal cancer patients were then divided into two groups: the nutrition group (received enteral nutrition support in addition to chemotherapy) and the control group (received chemotherapy only). Differences were analyzed before and after chemotherapy in each of the nutritional indicators including Karnofsky performance status (KPS), weight, body mass index (BMI), hemoglobin (Hb), number of lymphocytes (Lymph), total protein (TP), albumin (Alb), triglycerides (TG), total cholesterol (TC) in both groups. And differences of the efficacy and toxicities of the first-line chemotherapy between the two groups were also analyzed.@*RESULTS@#(1) Weight, BMI and Hb were all significantly decreased after chemotherapy in the control group (P<0.001), while there was no significant change of weight and BMI in the nutrition group, just with Hb decrease only. However, there was no significant change of all the other nutrition indicators after chemotherapy in both groups. (2) Compared with the control group, the nutrition group had significantly lower incidence of grade 3 to 4 hematologic toxicities after chemotherapy (15.4% vs. 42.1%, P=0.004). In addition, the incidence of grade 3 to 4 nonhematologic toxicities after chemotherapy was also lower in the nutrition group but without statistical significance (0 vs. 9.2%, P=0.123). Logistic regression model was then used for multivariate analysis to identify the factors that affected the toxicity of chemotherapy in these patients, and the results showed that nutrition therapy was an independent influencing factor of grade 3 or higher hematological toxicity after chemotherapy in the patients with esophageal cancer (P=0.008, RR=6.048, 95%CI: 1.589-23.027). (3) The response rate of chemotherapy between the control group and the nutrition group had not significant difference.@*CONCLUSION@#Enteral nutrition support in addition to chemotherapy could improve nutrition status and reduce toxicity of chemotherapy in advanced or metastatic esophageal cancer patients.

Effects of XPO1 Inhibitor KPT-8602 on Proliferation and Apoptosis in U937 cells / 中山大学学报(医学科学版)

@#【Objective】To explore the effects and the possible mechanism of KPT- 8602，a novel selective inhibitor of nuclear export protein （XPO1），on proliferation，cell cycle and apoptosis in human histiocytic lymphoma cell line U937 cells.【Methods】U937 cells were treated with different concentrations of KPT- 8602. Cell viability was assessed by CCK-8 assay. The cell cycle distribution and the apoptosis rate were analyzed by flow cytometry. The proteins expression of XPO1，p-AKT，AKT，Cleaved Caspase-3，p21 were determined by Western blot. Fluorescence microscope was used in observing the intracellular location of XPO1. 【Results】 KPT- 8602 inhibited the growth of U937 cells in a dose- dependent（P<0.001）and time- dependent manner（P<0.001），but normal PBMC were unaffected. 48 h after treatment with KPT-8602，a higher proportion of cells in G1 phase was observed（P<0.001）and the apoptosis rate increased（P=0.016）with drug concentration in U937 cells. XPO1 protein expression of U937 cells was significantly higher than normal PBMC（P=0.003）. 48 h after treatment with KPT- 8602，the protein expression of XPO1 decreased（P=0.011），p-AKT decreased（P=0.011），and Cleaved Caspase- 3 increased（P=0.009）. In addition，the protein expression of p21，the cargo protein of XPO1，increased in both the nuclei and the cytoplasm（P<0.05）after treatment with KPT- 8602. XPO1 decreased in both the nuclei and the cytoplasm under the fluorescence microscope after treatment with KPT- 8602.【Conclusion】KPT- 8602 can inhibit the proliferation of U937 cells，block the cell cycle at G1 phase，and induce cell apoptosis，which may partially be attributed to the down-regulation of XPO1 and inhibition of PI3K/AKT signaling.