Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors / 中华肿瘤杂志

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

Impact of different referral timing on the pregnancy outcomes of severe pre-eclampsia in the referral system / 中华妇产科杂志

Objective:To explore the impact of different referral timing on postponing early-onset pre-eclampsia (PE), postponing severe pre-eclampsia (SPE), reducing SPE severe complications and improving maternal and neonatal outcomes by analyzing the pregnancy outcomes of SPE patients who were referred from primary hospitals to tertiary referral center in the referral system.Methods:The clinical data of 159 SPE patients who were referred from primary hospitals, treated and then terminated their pregnancy in Peking University Third Hospital from January 2020 to October 2021, were observed and analyzed in this clinical observational study. According to the clinical stage of PE at the time of referral, they were divided into four groups: 38 cases were referred after onset of SPE severe complications (SPE-C group), 72 cases were referred after onset of SPE (a-SPE group), 15 cases were referred after onset of PE (a-PE group) and 34 cases were referred after detection of PE early warning-signs (Warn-s group). And then these 159 cases were divided into different color groups according to the project management system for high-risk pregnant women. Patients of Red color (highest risk) and Orange color (higher risk) were required to be referred to tertiary hospitals (Red-Orange group, 113 cases), and patients of Yellow color (high risk) could be treated under tertiary hospitals (Yellow group, 46 cases). The maternal and neonatal outcomes of different referral timings were analyzed and compared.Results:(1) Pregnancy outcomes of different referral timings grouped by PE clinical stage at the time of referral: the later the referral timing, the higher the rate of SPE severe complications, the shorter the interval from referral to termination of pregnancy. The rate of SPE severe complications in the SPE-C group was significantly higher than those of the other three groups, and the interval from referral to termination of pregnancy in the SPE-C group was significantly shorter than those of the other three groups (all P<0.05). The referral gestational age of Warn-s group was earlier than those of the other three groups (all P<0.05). The average gestational ages for onset of SPE, termination of pregnancy, and onset of SPE severe complications were all after 34 gestational weeks, and were later than those of a-SPE group and SPE-C group; the rates of SPE onset before 34 gestational weeks, SPE severe complications onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, neonatal intensive care unit (NICU) hospitalization, and pregnancy giving up before 28 gestational weeks were lower than those of a-SPE group and SPE-C group, the length of NICU stay was shorter than those of a-SPE group and SPE-C group, and its rate of take-home-babies was 100%, significantly higher than those in a-SPE group and SPE-C group (all P<0.05). The gestational ages for onset of SPE and termination of pregnancy in a-PE group were later than those in a-SPE group and SPE-C group, the rates of SPE onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, and NICU hospitalization were lower than those of a-SPE group and SPE-C group, the length of NICU stay was shorter than those of a-SPE group and SPE-C group (all P<0.05). (2) Pregnancy outcomes of different referral timings grouped by the color classification of PE clinical characteristics: among the 159 cases of SPE, 113 cases (71.1%, 113/159) were in the Red-Orange group which were required to be referred to tertiary hospitals, and 46 cases (28.9%, 46/159) were in the Yellow group,which were not in the range of referral requirements, but actually referred to the tertiary hospital and eventually developed SPE. Gestational ages for onset of SPE, termination of pregnancy, and onset of SPE severe complications in the Yellow group were later than those of the Red-Orange group, while the rates of SPE onset before 34 gestational weeks, SPE severe complications onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, NICU hospitalization, and pregnancy giving up before 28 gestational weeks were lower than those of the Red-Orange group, the length of NICU stay was shorter than that of the Red-Orange group, and its rate of take-home-babies was higher than that in the Red-Orange group (all P<0.05). (3) Analysis of different clinical referral timings in the Yellow group: among these 159 SPE patients, 46 cases (28.9%, 46/159) would be excluded from the range of referral requirements which belonged to the Yellow color grade, but 6 cases still developed SPE severe complications (4 cases in Warn-s group and 2 cases in a-PE group), 17 cases were terminated pregnancy before 34 weeks of gestation (12 cases in Warn-s group and 5 cases in a-PE group), and 23 cases developed SPE before 34 weeks of gestation (17 cases in Warn-s group and 6 cases in a-PE group). (4) Multivariate analysis: referral after detection of PE early warning signs was the independent protective factor for postponing the onset of SPE severe complications ( P<0.05). Referral after detection of PE early warning signs and referral after onset of PE were both protective factors for postponing the onset of SPE and early-onset PE (all P<0.05). Conclusions:Different referral timing in the referral system is one of the key points that affect the maternal and neonatal outcomes of SPE. Referral after detection of PE early warning signs and timely referral after onset of PE would reduce early-onset PE, postpone the onset of SPE and reduce the severe complications of SPE. The clinical development and evolution of PE is really complicated, and referral based on specific clinical situations is better than referral based on fixed mode.

Application of Flow Cytometry Combined Fluorescence in Situ Hybridization to Indentify the Lymphocyte Subtypies with Epstein-Barr Virus Infection / 中国实验血液学杂志

OBJECTIVE@#To establish the technique that take the advantages of flow cytometry combined fluorescence in situ hybridization (Flow-FISH) to identify the Epstein-Barr virus(EBV) infected lymphocyte subtypies in patients' peripheral blood sample.@*METHODS@#Peripheral Blood monocyte from 9 patients with EBV infection enrolled at Children's Hospital in Chongqing Medical University were isolated by Ficoll-paque centrifugal separation. The expressions of EBER1, EBER2 in cell were detected by qRT-PCR. The surface markers of cell were detected by Flow cytometry after staining with their antibodies. The cell was treated Fix-Permeabilization Buffer before hybridization with fluorescent labeled probe at 37 ℃ overnight. The cell status, surface markers and targeted mRNA are detected by flow cytometry and fluorescence microscope.@*RESULTS@#It was optimized that the Fix-Permeabilization Buffer and recipe with 0.2% Tween-20 were picked out as providing a good cell integrity and high resolution of surface markers. Hybridization with 20% formamide and 7% dextran sulfate at 37 ℃ overnight is the optimal hybridization condition as a good hybridization effect, a detectable cell integrity and a high resolution of cell markers under flow cytometry detection. Finally, upon the established Flow-FISH method, lymphocyte subpopulations of the EBV+ cells from cell lines and blood samples of patients were identified successfully.@*CONCLUSION@#A Flow-FISH technology is established, which can be applied in the identification of EBV infected cell subtypes. This research provides a foundmental for its application in clinical test in EBV+ related proliferative diseases.

Clinical characteristics of severe pre-eclampsia in a single tertiary referral center / 中华妇产科杂志

Objective:To explore the feasibility and key point of improvement in preventing and postponing the onset of severe pre-eclampsia (SPE) and its severe complications in the tertiary referral system by analyzing the clinical characteristics of SPE in a single tertiary referral center.Methods:The clinical data of 217 patients with SPE who were hospitalized and terminated pregnancy in Peking University Third Hospital from January 2020 to December 2020 were retrospectively analyzed. The risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the characteristics and perinatal outcome.Results:(1) Clinical characteristics: among the 217 cases of SPE, 84 cases were in the referral group and 133 cases were in the central group. The gestational ages at SPE clinical diagnosis [31.5 weeks (28.1-34.6 weeks) vs 35.6 weeks (33.3-37.2 weeks); Z=-6.547, P<0.01], termination of pregnancy [32.3 weeks (29.5- 35.1 weeks) vs 36.3 weeks (34.4-37.5 weeks); Z=-6.554, P<0.01] and onset of SPE severe complications [30.6 weeks (26.4-32.7 weeks) vs 34.9 weeks (32.7-36.5 weeks); Z=-4.040, P<0.01] in the referral group were significantly earlier than those in the central group, the rates of ICU [10.7% (9/84) vs 3.8% (5/133); χ2 =4.126, P=0.042] and neonatal ICU hospitalization [72.9% (51/70) vs 54.7% (70/128); χ2 =6.286, P=0.012] were higher than those in the central group, while the live birth rate [83.3% (70/84) vs 96.2% (128/133); χ2 =10.736, P=0.001] was lower than that of the central group. (2) Analysis of risk factors: for the patient whose risk factors were obesity, advanced age or pre-eclampsia history, the gestational ages at SPE clinical diagnosis and termination of pregnancy in the referral group were significantly earlier than those in the central group ( P<0.05). For those with chronic hypertension, the gestational ages at severe complications onset in the referral group were significantly later than those in the central group ( P<0.05). For those without obvious risk factors, the gestational ages at SPE clinical diagnosis, termination of pregnancy and onset of SPE severe complications in the referral group were earlier than those in the central group ( P<0.05). (3) Analysis of severe complications: the top three severe complications in the referral group and the central group were hypertensive encephalopathy/cerebrovascular accident [20.2% (17/84) vs 7.5% (10/133)], HELLP syndrome [7.1% (6/84) vs 8.3% (11/133)] and placental abruption [8.3% (7/84) vs 7.5% (10/133)]. The rate of hypertensive encephalopathy/cerebrovascular accident in the referral group was significantly higher than that in the central group ( χ2 =7.645, P=0.006). (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (8.3%, 7/84), referral after onset of SPE (67.9%, 57/84), referral after detection of SPE early warning signs (14.3%, 12/84) and referral after detection of SPE risk factors in the 2nd and 3rd trimester (9.5%, 8/84). The earlier the referral, the longer the interval from clinical diagnosis to onset of severe complications, from referral to termination of pregnancy, and from referral to severe complications onset ( P<0.05). The earlier the referral, the lower the NICU hospitalization rates, the higher the live birth rates. The ICU hospitalization rate of referrals after severe complications onset was significantly higher than those of the other three referral timing groups ( P<0.05). Conclusions:SPE occurs in hospitals of different levels. Although tertiary referral center may postpone the onset of SPE and its severe complications, reduce the severity of SPE and prolong the gestational age, its awareness of prevention and control still needs to be further improved. Early identification of the risk of SPE and timely referral are important parts of improving SPE adverse outcomes in primary medical institutions. The significance and value of referral system need to be brought into full play.

Comparative analysis of high risk factors between early-onset pre-eclampsia and late-onset pre-eclampsia / 中华妇产科杂志

Objective:To explore the difference of high-risk factors between early-onset and late-onset pre-eclampsia, and to further understand high-risk factors of pre-eclampsia.Methods:Clinical data of pre-eclampsia pregnant women in 160 medical institutions in China in 2018 were retrospectively analyzed, including 8 031 cases of early-onset pre-eclampsia and 12 969 cases of late-onset pre-eclampsia. The proportion of high-risk factors, different body mass index (BMI) and age stratification between early-onset group and late-onset group were compared.Results:(1) Univariate analysis of high-risk factors: the proportions of high-risk factors in early-onset group and late-onset group were compared, and the differences were statistically significant (all P<0.05). Among them, the proportions of primipara and multiple pregnancy in early-onset group were lower than those in late-onset group, while the proportions of pregnant women with advanced age, irregular antenatal examination, obesity, family history of hypertension, pre-eclampsia, diabetes, kidney diseases, immune system diseases and assisted reproductive technology were higher than those in late-onset group. (2) Hierarchical analysis of BMI: the proportion of pregnant women with BMI≥24 kg/m 2 in early-onset group [48.2% (2 828/5 872) vs 45.5% (4 177/9 181), respectively; P=0.001] and the proportion of pregnant women with BMI ≥28 kg/m 2 in early-onset group [19.5% (1 143/5 872) vs 18.0% (1 656/9 181), respectively; P=0.028] were significantly higher than those in late-onset group. (3) Age stratification analysis: the proportion of pregnant women aged 35-39 years in the early-onset group [21.8% (1 748/8 023) vs 17.5% (2 110/12 068), respectively; P<0.01], the proportion of pregnant women 40-44 years old [6.8% (544/8 023) vs 5.4% (648/12 068), respectively; P<0.01], and the proportion of pregnant women ≥45 years old [0.7% (58/8 023) vs 0.5% (57/12 068), respectively; P=0.021] were significantly higher than those in the late-onset group. (4) Multivariate analysis: advanced age (≥35 years old), multiple pregnancy, irregular antenatal examination or transfer from other hospitals, family history of hypertension (including paternal, maternal and parental lines), previous history of pre-eclampsia, kidney diseases, immune system diseases (systemic lupus erythematosus, antiphospholipid antibody syndrome) and assisted reproductive technology pregnancy were the risk factors affecting the severity of pre-eclampsia (all P<0.05). Conclusion:Pregnant women with high risk factors such as age ≥35 years old, BMI ≥24 kg/m 2 before pregnancy, family history of hypertension, history of pre-eclampsia, chronic kidney diseases, immune diseases (mainly including systemic lupus erythematosus and antiphospholipid syndrome) and assisted reproductive technology are more likely to have early-onset pre-eclampsia.

Preliminary study of human serum albumin level in early warning onset of preeclampsia / 中华妇产科杂志

Objective:To observe the dynamic changes of human serum albumin (HSA) level during pregnancy and study the early warning significance of HSA level on the onset of preeclampsia (PE) .Methods:Totally 369 PE pregnant women (PE group) and 309 normal pregnant women (control group) without PE who admitted in Haidian Maternal and Child Health Hospital from January 2013 to December 2017 were selected. HSA levels were tested before meeting the criterion of PE in the first trimester, the early-third trimester and the late-third trimester, the difference between the two groups were compared. The relationship between the HSA level and the incidence of complications in PE patients was analyzed.Results:(1)The mean values of HSA level in PE group and control group were (41.9±3.1) versus (40.0±2.2) g/L, (34.2±2.7) versus (35.4±2.7) g/L and (33.7±2.9) versus (36.7±3.3) g/L in the first trimester,the early-third trimester and the late-third trimester respectively,the difference in the first trimester was no significance ( P>0.05), while the differences in the early-third trimester and the late-third trimester were both significant (all P<0.05). (2) The HSA level during pregnancy of PE group showed a continuous downward trend, while the control group was V-shaped trend. The receiver operating characteristic (ROC) curve analysis showed that PE could be early warned by the decrease of HSA level in PE group [area under curve (AUC)=0.742, cut-off value=5.97 g/L, sensitivity 70.8%, specificity 62.8%], the same result was in severe PE (AUC=0.756, cut-off value=6.85 g/L, sensitivity 70.8%, specificity 72.0%). The level of HSA was negatively correlated with the incidence of complications ( r=-0.19, P<0.01). Conclusions:Excessive decrease of HSA level is an early warning factor for PE onset. The higher the baseline of HSA level and the greater the extent of pregnancy decline, the risk of PE in pregnant women is higher. The lower of HSA level in PE, the incidence of complications is higher. The excessive decrease of HSA level may be the first clinical manifestation before the onset of clinical symptoms of PE, so it may be the warning factor and one of the laboratory indicators in the PE sub-clinical stage.

Preliminary study of human serum albumin level in early warning onset of preeclampsia / 中华妇产科杂志

Objective@#To observe the dynamic changes of human serum albumin (HSA) level during pregnancy and study the early warning significance of HSA level on the onset of preeclampsia (PE) .@*Methods@#Totally 369 PE pregnant women (PE group) and 309 normal pregnant women (control group) without PE who admitted in Haidian Maternal and Child Health Hospital from January 2013 to December 2017 were selected. HSA levels were tested before meeting the criterion of PE in the first trimester, the early-third trimester and the late-third trimester, the difference between the two groups were compared. The relationship between the HSA level and the incidence of complications in PE patients was analyzed.@*Results@#(1)The mean values of HSA level in PE group and control group were (41.9±3.1) versus (40.0±2.2) g/L, (34.2±2.7) versus (35.4±2.7) g/L and (33.7±2.9) versus (36.7±3.3) g/L in the first trimester,the early-third trimester and the late-third trimester respectively,the difference in the first trimester was no significance (P>0.05), while the differences in the early-third trimester and the late-third trimester were both significant (all P<0.05). (2) The HSA level during pregnancy of PE group showed a continuous downward trend, while the control group was V-shaped trend. The receiver operating characteristic (ROC) curve analysis showed that PE could be early warned by the decrease of HSA level in PE group [area under curve (AUC)=0.742, cut-off value=5.97 g/L, sensitivity 70.8%, specificity 62.8%], the same result was in severe PE (AUC=0.756, cut-off value=6.85 g/L, sensitivity 70.8%, specificity 72.0%). The level of HSA was negatively correlated with the incidence of complications (r=-0.19, P<0.01).@*Conclusions@#Excessive decrease of HSA level is an early warning factor for PE onset. The higher the baseline of HSA level and the greater the extent of pregnancy decline, the risk of PE in pregnant women is higher. The lower of HSA level in PE, the incidence of complications is higher. The excessive decrease of HSA level may be the first clinical manifestation before the onset of clinical symptoms of PE, so it may be the warning factor and one of the laboratory indicators in the PE sub-clinical stage.

Effect of eccentricity of overnight orthokeratology lenses on axial growth and visual quality / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To explore the effect of eccentricity of overnight orthokeratology(OK)lenses on 2-year eye axial growth and visual quality.<p>METHODS:Based on the degree of eccentricity of OK lenses, patients were divided into three groups: a low degree of eccentricity group(degree of eccentricity ≤0.5 mm), a group of moderate eccentricity(eccentric degree >0.5-≤1.0 mm)and a group with a high degree of eccentricity(eccentric degree >1-≤1.5 mm). The degree of eccentricity of the OK lens, spherical equivalent(SE), the uncorrected visual acuity after wearing OK lenses(UCVA), axial length before and after wearing OK lenses(AL), total higher-order aberrations(HOA), comas, and spherical aberrations(SA)for 3 mm pupils were analyzed. The difference among the three groups for all parameters was compared using the Kruskal-Wallis H Rank-Sum test.<p>RESULTS:The study retrospectively analyzed 75 cases(139 eyes). In the low eccentricity group(53 eyes), the mean age was 11.4±2.4 years, SE was -3.24±1.48 D, and AL was 24.85±1.01 mm. In the moderate eccentricity group(53 eyes), the mean age was 11.4±2.2 years, SE was -3.22±1.29 D, and AL was 25.15±0.92 mm. In the high eccentricity group(31 eyes), the mean age was 11.5±1.9 years, SE was -3.54±1.43 D, and AL was 24.95±0.84mm. After two years, there was no significant difference in the changes of the axis among the three groups(<i>P</i>=0.089). The HOA, SA, and coma in the high eccentric group were significantly higher than in the middle eccentric group(<i>P</i><0.05). The HOA, SA, and coma in the high eccentric group were also significantly higher than those in the low eccentric group(<i>P</i><0.05).<p>CONCLUSION:For OK lenses, it is unnecessary to strictly require the absolute centralization of the lens position. An unnecessary change of the lenses may delay the eye-axis control. However, the balance between axial control and visual quality should be assessed.

Clinical features of 109 cases of novel coronavirus pneumonia / 中华传染病杂志

Objective@#To observe theepidemiology, clinical manifestations, laboratory tests, imaging findings, treatment and prognosis of patients with novel coronavirus pneumonia.@*Methods@#Clinical data of 109 patients with suspected and definite novel coronavirus pneumonia admitted to Wuhan Sixth Hospital from December 24, 2019 to January 28, 2020 were retrospectively analyzed. Statistical analysiswas performed by using t test or chi-square test.@*Results@#Among the 109 patients, 48 (44%) were male and 61 (56%) were female, with the average age of (52.5±10.8) years. Fifty-four patients (49.5%) had definite contact history. Among the 109 patients, 104 (95.5%) presentedwith fever, 37(33.7%) with headache, 78 (71.9%) with general pain, 88 (80.8%) with fatigue and poor appetite, 23 (21.3%) with diarrhea, 94 (86.5%) withcoughing, 23 (21.3%) with shortness of breath, 57 (52.8%) withpalpitation, 45 (41.5%) with chest distress, 4 (3.3%) with chest pain, 40 (37.0%) with lung rales. Forty-two cases (38.5%) had leukocyte count <4×109/L, 58 cases (53.2%) had lymphocyte count <1.5×109/L, 7 cases (24.8%) had hemoglobin <120g/L, 37 cases(33.9%) had LDH >230 mmol/L, 29 cases (26.6%) had brain natriuretic peptide precursor>300 ng/mL, 87 cases (79.8%) had hypersensitive C-reactive protein >10mg/L, 26 cases (23.9%) had D-dimer >0.5 mg/L, 35 cases (32.1%) had coagulation disorder. The leukocyte counts, LDH, brain natriuretic peptide precursor and D-dimer of severe/critical cases[(11.33±4.87)×109/L, (527.51±260.87) mmol/L, (722.88±189.56) ng/mL, (1.89±4.24) mg/L, respectively] were all significantly higher than those of common cases [(4.02±1.49)×109/L, (159.75±30.31)mmol/L, (428.22±124.76)ng/mLand (0.41±0.22)mg/L, respectively], while the lymphocyte count of severe/critical cases [(0.60±0.17)×109/L] was significantly lower than common cases [(1.13±0.43)×109/L] (t=11.36, 11.33,9.81,2.81 and 7.77,all P<0.05). On admission, chest CT showed that 27 cases (24.8%) of pneumonia were unilateral, 82 cases (75.2%) werebilateral, and most of them were ground glass. The pneumonia progressed in a short time and reached the peak within 10 days. The comprehensive treatment included antiviral drugs, prevention ofbacterialinfection and supportive treatment, and glucocorticoid and respiratory support treatment wereadministrated when necessary.@*Conclusions@#The novel coronavirus pneumonia is characterized by highly infectious, rapid progress, and diverse clinical and imaging features. Early diagnosis and active comprehensive treatment could improve theprognosis and reduce themortality.

Establishment of "quantitative analysis of multi-components by single marker" method for phenolic acids in compound Danshen Tablets and its application in mass transfer law / 中国中药杂志

To construct a quality management model for the whole industry chain of compound Danshen Tablets,and quality control system for all key links in the production of compound Danshen Tablets. In this paper,with salvianolic acid B as internal reference substance,three batches of mix standards were prepared,and three sets of relative correlation factors between salvianolic acid B and other phenolic acids were calculated in parallel. Finally,the correlation factors are obtained on average. The quality transfer process was studied by optimizing the concentration of Salvia miltiorrhiza extract. The results showed that RSD among three sets of relative correlation factors ranged between 1. 7%-4. 1%,with no significant difference between the quantitative result of two methods. In addition,the quality transfer study showed that with the rise of the concentration temperature,the content of phenolic acid components changed,which had a significant effect on the salvianolic acid B at more than 80 ℃. It was suggested to rationally control the concentration temperature during the industrial production. The results of this study provide a methodology for the establishment of the quality control system for the whole industry chain of compound Danshen Tablets,and quality control methods for the improvement of the quality of medicinal materials and finished medicine products.

Analysis of standard decoction of salt-processed Psoraleae Fructus / 中国中药杂志

The traditional Chinese medicine standard decoction is prepared on the basis of the theory of traditional Chinese medicine and clinical application. With reference to the modern extraction method,the single decoction of traditional Chinese medicine is prepared by the standardized process,and the establishment of its quality standards is conducive to standardizing clinical medication. This research is to set an evaluation standard for the quality of salt-processed Psoraleae Fructus standard decoction. Twelve batches of salt-processed Psoraleae Fructus standard decoctions were prepared. The contents of psoralen and isopsoralen were determined,the transfer and extract rates were calculated,and the pH value was measured; HPLC fingerprint method was established for analysis. The results of the 12 batches of samples revealed that the transfer rates of psoralen and isopsoralen were 17. 10%-26. 40%,14. 70%-22. 70%,respectively; the extract rate was between 14. 7%-27. 0%,and the pH value was between 5. 4-6. 9. Moreover,7 common chromatographic peaks were determined based on fingerprint by using similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine( 2012 A).The similarities of the 12 batches of samples were analyzed and compared,and the results showed that the similarities were all higher than0. 9. In this study,the preparation method for salt-processed Psoraleae Fructus decoction was standard,with high similarities in fingerprint. This study build a convenient and reliable method of comprehensive quality evaluation,with a high precision,stability and repeatability,which can provide a reference for the quality control of salt-processed Psoraleae Fructus dispensing granules.

Predictive Factors of Early Weight Loss after Laparoscopic Sleeve Gastrectomy / 中国医学科学院学报

Objective To explore the clinical factors that can be used to predict the early weight loss after laparoscopic sleeve gastrectomy(LSG).Methods The clinical data of 64 obese patients undergoing LSG in Peking Union Medical College Hospital from August 2015 to January 2018 were retrospectively analyzed.We analyzed the relationship between different clinical factors and early weight loss,determined the independent predictors based on models,and estimated their test power by using the receiver operating characteristic(ROC)curves.Results Correlation analysis indicated that preoperative body mass index(=0.000,=0.000,=0.000),waist circumference(WC)(=0.000,=0.000,=0.000),whole body fat volume(=0.000,=0.006,=0.003),homeostatic model assessment for insulin resistance(HOMA-IR)(=0.000,=0.000,=0.002),and hypersensitive C-reactive protein(hsCRP)(=0.004,=0.002,=0.025)were negatively correlated with excess weight loss percentage(EWL %) after 3,6 and 12 months.Also,hsCRP after 6 months showed negative correlation with EWL % after 1 year(=0.029).Binary Logistic regression analysis showed that WC was an independent predictor of early weight loss(=0.018).ROC analysis showed that when the optimal cutoff value is 142.5 cm for WC, index was highest,with a sensitivity of 80% and a specificity of 87%.Patients were further divided into low WC group and high WC group based on this optimal cutoff value.The low WC group had significantly higher EWL% than the high WC group 3 months(=6.677,=0.000),6 months(=6.157,=0.000),and 1 year(=4.006,=0.000)after surgery.The low WC group also had significantly lower hsCRP than high WC group 6 months after surgery(=-3.510,=0.000).HOMA-IR showed no significant difference between these two groups(=-0.821,=0.412).Conclusions WC is an independent predictor of weight loss early after LSG.The patients with low WC have better weight loss effectiveness.

Role of mammalian target of rapamycin signaling pathway in regulation of fatty acid oxidation in a preeclampsia-like mouse model treated with pravastatin / 中华医学杂志(英文版)

BACKGROUND@#Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several studies show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastatin (Pra) can promote FAO in Nω-nitro-L-arginine methyl ester (L-NAME) PE-like mouse model in our previous study. This study aimed to investigate the effect of mTOR signaling pathway in PE-like model treated with Pra.@*METHODS@#Pregnant mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from gestational 7th to 18th day. Giving Pra (L-NAME + Pra, Control + Pra, n = 8) or normal saline (NS; L-NAME + NS, Control + NS, n = 8) from gestational 8th to 18th day, the mice were sacrificed on day 18 and their liver and placental tissues were collected. Then the activation of mTOR and its substrates in the liver and placenta were detected. And the association between mTOR activation and serum free fatty acid (FFA) levels and the expression of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) were evaluated using Pearson correlation test. Differences between groups were analyzed using independent t-test or one-way analysis of variance (ANOVA).@*RESULTS@#Both in the maternal liver and placenta, the activation of mTOR protein and its effect on substrates increased significantly in the L-NAME + NS group and decreased significantly in the L-NAME + Pra group. The p-mTOR/mTOR protein ratio decreased in the L-NAME + Pra group significantly than that in the L-NAME + NS group both in liver and placenta (liver: 0.74 ± 0.08 vs. 0.85 ± 0.06, t = 2.95, P < 0.05; placenta: 0.63 ± 0.06 vs. 0.77 ± 0.06, t = 4.64, P < 0.05). The activation of mTOR protein in the liver and placenta negatively correlated with the expression of LCHAD in the L-NAME + NS group (liver: r = -0.745, P < 0.05; placenta: r = -0.833, P < 0.05) and that in the maternal liver negatively correlated with the expression of LCHAD (r = -0.733, P < 0.05) and positively with the serum FFA levels (r = 0.841, P < 0.05) in the L-NAME + Pra group.@*CONCLUSION@#The inhibition of mTOR signaling pathway might be involved in the regulation of FAO in mouse model treated with Pra.

Expression level and Clinical Significance of Serum SE-CAD and Matriptase in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the expression level of the serum soluble E cadherin (SE-CAD) and Matriptase and its clinical significance for evaluation of the disease condtions and prognosis in patients with acute myeloid leukemia (AML).@*METHODS@#One hundred and ten patients diagnosed as AML in our hospital were divided into 3 groups: newly diagnosed group (38 cases), remission group (40 cases) and recurrence group (32 cases). The expression levels of serum matriptase were detected by Western blot, and the expression levels of serum SE-CAD were detected by ELISA. The serum levels of serum SE-CAD and matriptase among 3 groups were compared. Followin-up for one year, according to the outcome of patients, all the patients were divided into 2 groups: the survival group and death group. The serum levels of SE-CAD and Matriptase were compared between 2 groups. The correlation of serum levels of SE-CAD and matriptase with the survival of AML patients was analyzed by multivariate Logistic analysis. The evaluation value of the serum levels of SE-CAD and matriptase for the prognosis of the patients with AML were analyzed by receiver operating characteristic curves (ROC).@*RESULTS@#The serum levels of SE-CAD and matriptase were siginificantly different among 3 groups (P＜0.05). The serum levels of SE-CAD and matriptase in remission group were lowest (P＜0.05), and the serum levels of SE-CAD and matriptase were not different between newly diagnoses and recurrence groups (P＞0.05). Multivariate Logistic analysis showed that the serum levels of SE-CAD and matriptase were independent risk factors for the prognosis of AML patients (OR=3.157, P＜0.05, OR=2.426, P＜0.05). By follow-up for 1 year, the serum expression levels of SE-CAD and Matriptase in survival group were lower than that in death group. ROC curve showed that when the cut-off value of matriptase level was 0.73 and SE-CAD level was 3.42 ng/ml, the AUC of predictions for the poor prognosis in AML patients was 0.849 (P＜0.05), the sensitivity was 85.6% (95%CI: 0.810~0.924) and specificity was 89.6% (95%CI: 0.849~0.941).@*CONCLUSION@#The serum levels of SE-CAD and matriptase can perfectly evaluate the condition and short-term prognosis of the patients with AML.

Effect of Puerarin in Reducing Insulin Resistance in HepG2 Cells via PI3K/Akt/GSK-3β Signal Transduction Pathway / 中国实验方剂学杂志

Objective: To observe the effect of puerarin on phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β) in insulin resistant HepG2 cells. Method: HepG2 cells were treated with palmitic acid 0.5 mmol·L-1 and insulin 9×10-4 U·L-1 to induce insulin resistant condition for 24 h. Cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay to determine the concentration of puerarin. This experiment included normal control group, model control group and puerarin groups of different doses (40, 80, 160,320 μg·L-1). Glucose detection kit was used to detect the content of glucose in cell culture supernatant. Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels in supernatant of cell culture medium were detected by enzyme-linked immunosorbent assay (ELISA). Hepatic glycogen assay kit was used for detecting the hepatic glycogen content in HepG2 cells. Western blot was applied to detect protein expression levels of PI3K, Akt, p-Akt, GSK-3β and p-GSK-3β. Result: Compared with those in the normal control group, the glucose consumption rate was significantly down-regulated in HepG2 cells in the model control group (PPα and IL-6 were increased in supernatant of cell culture medium (PPβ protein expression was up-regulated (PPα and IL-6 were reduced in supernatant of cell culture medium (PPβ protein expression was down-regulated, but its phosphorylation inactivation was increased (PConclusion: Puerarin alleviates the insulin resistance of HepG2 cells by strengthening the PI3K/Akt/GSK-3β signal transduction process and increasing the glycogen content in hepatocytes.

Different effects of pravastatin on sFlt-1, PlGF and VEGF in different preeclampsia-like mouse models / 中华妇产科杂志

Objective@#To explore the pathways of preeclampsia by investigating different effects of pravastatin (Pra) on and soluble FMS tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in different preeclampsia (PE)-like mouse models.@*Methods@#C57BL/6J mice were randomly subcutaneously injected with N-nitro-L-arginine methyl ester (L-NAME) or intraperitoneally injected with lipopolysaccharide (LPS) as PE-like mouse model, saline as normal pregnancy control (Con) respectively, daily at gestational 7-18 days. Pra was given daily at gestational 8-18 days in each model group and the mice were divided into Pra (L-NAME+Pra, LPS+Pra, Con+Pra) and saline (L-NAME+NS, LPS+NS, Con+NS) groups. Liver,placental tissue and blood of pregnant mice were collected on the 18th day of pregnancy. The levels of VEGF, PlGF and sFlt-1 in the liver, placenta and serum of mice in each group were compared by western blot, ELISA and real-time fluorescence quantitative PCR (RT-PCR).@*Results@#(1) ELISA: Serum VEGF (205.70±3.43, 154.60±2.31) and PlGF (131.5±3.75, 101.50±4.31) levels were significantly increased in L-NAME+Pra group compared with L-NAME+NS group (all P<0.05). Serum VEGF (202.30±4.90, 144.50±6.71) and PlGF (121.50±3.86, 95.41±4.08) levels were significantly higher in LPS+Pra group than those in LPS+NS group (all P<0.05). Serum sFlt-1 level in LPS+Pra group was significantly lower than that in LPS+NS group (3.01±0.50, 776.60±80.06), serum sFlt-1 level in L-NAME+Pra group was significantly lower than that in L-NAME+NS group (2.60±0.06, 583.70±9.83; all P<0.05). (2) Western blot: the expression levels of PlGF (1.344±0.118, 0.664±0.143) and VEGF (1.34±0.12, 0.66±0.14) in the liver of mice in the L-NAME+Pra group were significantly higher than those in the L-NAME+NS group (all P<0.05), but the expression levels of PlGF and VEGF in the placenta of L-NAME+Pra group were not significantly different from those of L-NAME+NS group (all P>0.05). The expression levels of PlGF and VEGF in placenta and liver of pregnant mice in LPS+Pra group were not significantly different from those in LPS+N group (all P>0.05). (3) RT-PCR: the mRNA expression of PlGF and VEGF in placenta and liver of L-NAME+Pra group were not significantly different from those in L-NAME+NS group (all P>0.05). The mRNA expression levels of PlGF and VEGF in placenta and liver of LPS+Pra group were not significantly different from those of LPS+NS group (all P>0.05).@*Conclusions@#Pra has different regulatory effects on vascular endothelial function in different PE-like models. It reveals that different pathogenesis and pathways exist in different PE-like changes.

Study on secondary metabolites of endophytic fungus Aspergillus ochraceus from Polygonatum cyrtonema / 中草药

Objective: To investigate the secondary metabolites of Aspergillus ochraceus, an endophytic fungus isolated from Polygonatum Cyrtonema. Methods: Compounds were isolated and purified from the EtOAc extract by using chromatography technology and their structures were established on the basis of comprehensive spectroscopic analysis. Results: A total of 15 compounds were obtained and their structures were elucidated as 6,7-dihydroindolizin-8(5H)-one (1), polygonatine A (2), 8-oxo-5,6,7,8-tetrahydro-3-indolizinyl methyl acetate (3), 8-hydroxyketone (4), cyclo-(L-Leu-L-Ile) (5), alternariol (6), seco- patulolide C (7), n-butyl-β-D-fructopyranoside (8), Nb-acetyltryptamine (9), N-trans-cinnamoyltyramine (10), 5-hydroxy- methylfurfural (11), 5,7-dihydroxy-6,8-dimethyl-3-(4’-hydroxybenzyl) chroman-4-one (12), 5,7-dihydroxy-6-methyl-8- methoxy-3- (4’-hydroxybenzyl) chroman-4-one (13), 25R-3-β-hydroxyspirost-5-en-12-one (14), and 25S-3-β-hydroxyspirost-5-en-12-one (15). Conclusion: All chemical constituents are isolated from A. ochraceus for the first time.

Changes of Rheb gene and protein expression in preeclampsia-like mouse model treated with pravastatin / 中华妇产科杂志

Objective To explore whether pravastatin (Pra) inhibits mammalian target of rapamycin (mTOR) signal pathway by regulating Ras homolog enriched in brain (Rheb) protein through the comparison of gene and protein expression changes of Rheb in liver and placenta in preeclampsia (PE)-like mouse model treated with Pra. Methods C57BL/6J pregnant mice were randomly divided into two groups. The PE group was established by injecting N-nitro-L-arginine methyl ester (L-NAME) daily at gestational 7-18 days, saline was injected as contol group (Con);then giving mice Pra (PE+Pra, Con+Pra group, n=8) or normal saline (PE+N, Con+N group, n=8) every day from the 8th gestational day of pregnancy. The maternal liver and placenta tissues were collected on the 18th day of pregnancy. Western blot, real-time quantitative PCR and immunohistochemistry were used to compare the levels of Rheb protein and mRNA expression in the liver and placenta. Results (1)The results of western blot:there were no significant differences in Rheb protein expression between PE+N group (liver:0.706±0.123;placenta:0.866±0.128) and Con+N group (liver:0.732 ± 0.123; placenta: 0.909 ± 0.097), and the differences between PE+Pra group (liver: 0.669 ± 0.134;placenta:0.940 ± 0.221) and PE+N group were not significant either in liver or in placenta (all P>0.05). (2) The results of real-time quantitative PCR:when PE+N group (liver:1.026 ± 0.480;placenta:1.102 ± 0.361) compared with Con+N group (liver:1.058±0.389;placenta:1.067±0.400), PE+Pra group (liver:0.735±0.356;placenta:0.822±0.304) compared with PE+N group, there were no significant differences either in liver or in placenta (all P>0.05). (3) The results of immunohistochemistry: Rheb protein expression did not change significantly in maternal liver and placenta, there were no significant differences in protein expression levels between PE+N group and Con+N group, and between PE+Pra group and PE+N group (all P>0.05). Conclusion The inhibition of Pra on mTOR signaling pathway in some PE-like model may be independent of the expression of Rheb gene and protein.

Different effects of pravastatin on sFlt?1, PlGF and VEGF in different preeclampsia?like mouse models / 中华妇产科杂志

Objective To explore the pathways of preeclampsia by investigating different effects of pravastatin (Pra) on and soluble FMS tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in different preeclampsia (PE)?like mouse models. Methods C57BL/6J mice were randomly subcutaneously injected with N?nitro?L?arginine methyl ester (L?NAME) or intraperitoneally injected with lipopolysaccharide (LPS) as PE?like mouse model, saline as normal pregnancy control (Con) respectively, daily at gestational 7-18 days. Pra was given daily at gestational 8-18 days in each model group and the mice were divided into Pra (L?NAME+Pra, LPS+Pra, Con+Pra) and saline (L?NAME+NS, LPS+NS, Con+NS) groups. Liver,placental tissue and blood of pregnant mice were collected on the 18th day of pregnancy. The levels of VEGF, PlGF and sFlt?1 in the liver, placenta and serum of mice in each group were compared by western blot, ELISA and real?time fluorescence quantitative PCR (RT-PCR). Results (1) ELISA: Serum VEGF (205.70±3.43, 154.60±2.31) and PlGF (131.5±3.75, 101.50± 4.31) levels were significantly increased in L?NAME+Pra group compared with L?NAME+NS group (all P<0.05). Serum VEGF (202.30 ± 4.90, 144.50 ± 6.71) and PlGF (121.50 ± 3.86, 95.41 ± 4.08) levels were significantly higher in LPS+Pra group than those in LPS+NS group (all P<0.05). Serum sFlt?1 level in LPS+Pra group was significantly lower than that in LPS+NS group (3.01±0.50, 776.60±80.06), serum sFlt?1 level in L?NAME+Pra group was significantly lower than that in L?NAME+NS group (2.60±0.06, 583.70±9.83;all P<0.05). (2) Western blot: the expression levels of PlGF (1.344±0.118, 0.664±0.143) and VEGF (1.34±0.12, 0.66 ± 0.14) in the liver of mice in the L?NAME+Pra group were significantly higher than those in the L?NAME+NS group (all P<0.05), but the expression levels of PlGF and VEGF in the placenta of L?NAME+Pra group were not significantly different from those of L?NAME+NS group (all P>0.05). The expression levels of PlGF and VEGF in placenta and liver of pregnant mice in LPS+Pra group were not significantly different from those in LPS+N group (all P>0.05). (3) RT?PCR: the mRNA expression of PlGF and VEGF in placenta and liver of L?NAME+Pra group were not significantly different from those in L?NAME+NS group (all P>0.05). The mRNA expression levels of PlGF and VEGF in placenta and liver of LPS+Pra group were not significantly different from those of LPS+NS group (all P>0.05). Conclusions Pra has different regulatory effects on vascular endothelial function in different PE?like models. It reveals that different pathogenesis and pathways exist in different PE?like changes.

Screening and management of polycystic ovary syndrome in adolescence / 中国实用妇科与产科杂志

Polycystic ovary syndrome is one of the common gynecological endocrine diseases.The mech⁃anism is unclear.Many patients of polycystic ovary syndrome have their first onsets during adolescence,who may encounter various problems in reproduction and metabolism later,including infertility,spontaneous abortion and gestational diabetes.We summarized the early screening and management of polycystic ovary syndrome in adolescence.