Correlation between PAFAH1B3 Expression Level and Risk of Disease Progression After Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the association between the expression level of platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3 ) gene in bone marrow CD138+ cells of patients with multiple myeloma (MM) treated with autologous hematopoietic stem cell transplantation (AHSCT) and the prognosis within 2 years.@*METHODS@#147 MM patients treated with AHSCT in The First and The Second Affiliated Hospital of Nantong University from May 2014 to May 2019 were included in the study. Expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells of the patients was detected. Patients with disease progression or death during 2 years of follow-up were included in progression group, and the rest were included in good prognosis group. After comparing the clinical data and PAFAH1B3 mRNA expression levels of the two groups, the patients were divided into high PAFAH1B3 expression group and low PAFAH1B3 expression group based on the median PAFAH1B3 mRNA expression level of the enrolled patients. Progression-free survival rate (PFSR) between the two groups was compared by the Kaplan-Meier method. The related factors of prognosis within 2 years were analyzed by univariate analysis and multivariate COX regression analysis.@*RESULTS@#At the end of follow-up, there were 13 patients lost to follow-up. Finally, 44 patients were included in the progression group and 90 patients were included in the good prognosis group. Age in the progression group was higher than that in the good prognosis group, the proportion of patients with CR+VGPR after transplantation in the progression group was lower than that in the good prognosis group, and there was a statistical difference between two groups in the cases distribution of ISS stage (all P<0.05). PAFAH1B3 mRNA expression level and the proportion of patients with LDH>250U/L in the progression group were higher than those in the good prognosis group, and platelet count in the progression group was lower than that in the good prognosis group (all P<0.05). Compared with the low PAFAH1B3 expression group, the 2-year PFSR of the high PAFAH1B3 expression group was significantly lower (log-rank χ2=8.167, P=0.004). LDH>250U/L (HR=3.389, P=0.010), PAFAH1B3 mRNA expression (HR=50.561, P=0.001) and ISS stage Ⅲ(HR=1.000, P=0.003) were independent risk factors for prognosis in MM patients, and ISS stage Ⅰ (HR=0.133, P=0.001) was independent protective factor.@*CONCLUSION@#The expression level of PAFAH1B3 mRNA in bone marrow CD138+ cells is related to the prognosis of MM patients treated with AHSCT, and detecting PAFAH1B3 mRNA expression can bring some information for predicting PFSR and prognostic stratification of patients.

Effect of Scutellarin on Proliferation of Acute Myeloid Leukemia Cells and Its Related Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of scutellarin (SCU) on proliferation, cell cycle and apoptosis of acute myeloid leukemia (AML) cells and its related molecular mechanism.@*METHODS@#Human AML HL-60 cells were cultured in vitro. The cells were treated with SCU at the concentration of 0, 2, 4, 8, 16, 32, 64 μmol/L, and the inhibition rate of cell proliferation was detected by CCK-8 method. Then HL-60 cells were treated with SCU at the concentration of 4, 8, 16 μmol/L, and the negative control group (NC group) was set. The cell cycle distribution and apoptosis were detected by flow cytometry, and the expression of cell cycle, apoptosis and JAK2/STAT3 pathway related proteins were detected by Western blot.@*RESULTS@#SCU significantly inhibited the proliferation of HL-60 cells in a concentration- and time-dependent manner(r =0.958,r =0.971). Compared with NC group, the proportion of cells in G0/G1 phase and apoptosis rate of HL-60 cells in 4, 8, 16 μmol/L SCU group were significantly increased, and the proportion of cells in S phase was significantly decreased (P <0.05). The relative protein expression levels of p21, p53, caspase-3 and Bax were significantly increased, while the relative protein expression levels of CDK2, cyclin E and Bcl-2 were significantly decreased (P <0.05). The ratio of p-JAK2/JAK2 and p-STAT3/STAT3 were significantly decreased (P <0.05). The changes of above-mentioned indexes were concentration dependent.@*CONCLUSION@#SCU can inhibit the proliferation of AML cells, induce cell cycle arrest and apoptosis, and its mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.

Prospective study of apatinib combined with chemoradiotherapy for head and neck squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC).Methods:37 patients orally received apatinib at 250 mg/d during concurrent chemoradiotherapy until completion of radiotherapy, complete remission assessed by imaging examination, the onset of unacceptable toxicity or death. Baseline characteristics, objective response rates (ORR) and adverse events were assessed in all enrolled patients with complete baseline and safety data. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic factors were statistically identified using Cox regression models.Results:The ORR was 85%(95% CI: 72%-98%). The median PFS was 17.9 months and the 2-year OS rate was 62%(95% CI: 48%-80%). Ineffective short-term efficacy ( HR=0.035, 995% CI: 0.02-0.652, P=0.025) was an independent risk factor for poor OS. In addition, ineffective short-term efficacy ( HR=0.104, 95% CI: 0.017-0.633, P=0.014) and lymphocytopenia ( HR=17.539, 95% CI: 2.040-150.779, P=0.009) were independent risk factors for poor PFS. Common adverse events (>60%) included lymphocytopenia (76%), leukopenia (68%) and irradiation-induced mucosal injury (65%). The most common treatment-associated grade 3 adverse event was lymphopenia (49%). Conclusions:Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity. For patients with advanced HNSCC, short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.

Onset and Recurrence Characteristics of Chinese Patients with Noncardiogenic Ischemic Stroke in Chinese Medicine Hospital / 中国结合医学杂志

OBJECTIVE@#To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China.@*METHODS@#A prospective, multicenter and registry study was carried out in 2,558 patients at 7 representative clinical sub-centers during November 3, 2016 to February 17, 2019. A questionnaire was used to collect information of patients regarding CM syndromes and constitutions and associated risk factors. Additionally, stroke recurrence was defined as a primary outcome indicator.@*RESULTS@#A total of 327 (12.78 %) patients endured recurrence events, 1,681 (65.72%) were men, and the average age was 63.33 ± 9.45 years. Totally 1,741 (68.06%) patients suffered first-ever ischemic stroke, 1,772 (69.27%) patients reported to have hypertension, and 1,640 (64.11%) of them reported dyslipidemia, 1,595 (62.35%) patients exhibited small-artery occlusion by The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Specifically, 1,271 (49.69%) patients were considered as qi-deficient constitution, and 1,227 (47.97%) patients were determined as stagnant blood constitution. There were 1,303 (50.94%) patients diagnosed as blood stasis syndrome, 1,280 (50.04%) patients exhibited phlegm and dampness syndrome and 1,012 (39.56%) patients demonstrated qi deficiency syndrome. And 1,033 (40.38%) patients declared intracranial artery stenosis, and 478 (18.69%) patients reported carotid artery stenosis. The plaque in 1,508 (41.36%) patients were of mixed. Particularly, 41.09% of them demonstrated abnormal levels of glycated hemoglobin levels.@*CONCLUSIONS@#Recurrence in minor and small-artery stroke cannot be ignored. Hypertension, dyslipidemia, abnormal HbA1c, intracranial artery stenosis and carotid plaque were more common in stroke patients. Particularly, phlegm-dampness and blood stasis syndromes, as well as qi deficiency and blood stasis constitutions, were still the main manifestations of stroke. (Trial registration at ClinicalTrials.gov No. NCT03174535).

Influence of online and offline Satir family therapy on emotions of adolescents with depressive disorder and their parents / 中华行为医学与脑科学杂志

Objective:To explore the influence of online and offline family therapy based on the Satir model on emotions of adolescents with depressive disorder and their parents in remote areas.Methods:A total of 98 cases adolescents with depressive disorder treated in the psychosomatic medicine of the Second Affiliated Hospital of Nanchang University from January 2021 to June 2021 and their parents were selected as the objects. The adolescents with depressive disorder and their parents were randomly divided into the control group (49 parents and 49 adolescents) and the observation group (49 parents and 49 adolescents). The control group received the medical treatment (sertraline 100 mg/d) and the routine health education, while the observation group received the online and offline Satir family therapy on the basis of the intervention of the control group. Generalized anxiety disorder-7 (GAD-7) and patient health questionnaire-9 (PHQ-9) were used to investigate the negative emotions of the parents of the two groups before and 12 weeks after the intervention. The screen for child anxiety related emotional disorders (SCARED) and depression self-rating scale for childhood (DSRS) were used to investigate the negative emotions of the adolescents before and 12 weeks after the intervention.The SPSS 20.0 software was used for statistical analysis. t test was used to compare the SCARED scale score and DSRS score changes of the adolescents in the two groups, and χ 2 test was used to compare the proportional changes of parents' anxiety and depression. Results:The scores of SCARED (51.55±12.69 vs 36.82±7.69, t=15.839) and DSRS (25.08±4.81 vs 16.88±2.16, t=13.047) of adolescents in the control group were significantly different before and after the intervention (both P<0.05). The scores of SCARED (51.16±15.84 vs 31.31±7.72, t=14.385) and DSRS (24.12±4.81 vs 14.08±2.03, t=14.723) of adolescents in the observation group were significantly different before and after the intervention (both P<0.05). After the intervention, the scores of SCARED and DSRS in the observation group were lower than those in the control group ( t=3.540, 6.609, both P<0.05). Before intervention, there was no significant difference in the proportion of anxiety and depression between the parents of the two groups (χ 2=1.837, 3.547, both P>0.05). After 12 weeks of intervention, there was a statistically significant difference in the proportion of anxiety and depression between the two groups, which were lower in the observation group than those in the control group (χ 2=5.995, 4.009, both P<0.05). Conclusion:Online + offline family therapy based on the Satir model can not only effectively reduce anxiety and depression of adolescents, but also effectively reduce anxiety and depression of their parents.It is especially suitable for outpatient management of children with depressive disorder in remote areas.

Survival and safety evaluation of surgery combined with chemoradiotherapy for advanced hypopharyngeal carcinoma / 国际肿瘤学杂志

Objective:To compare the survival rate and adverse reactions of patients with advanced hypopharyngeal squamous cell carcinoma undergoing surgery combined with chemoradiotherapy, and to analyze the prognostic factors of patients.Methods:The clinicopathologic data of 78 patients with advanced hypopharyngeal squamous cell carcinoma admitted to the Department of Radiation Oncology of the First Affiliated Hospital of Bengbu Medical University from August 2013 to December 2018 were retrospectively analyzed. The patients were divided into surgery combined with chemoradiotherapy group ( n=27) and chemoradiotherapy group ( n=51) according to different treatment methods. The median follow-up time was 46 months (20-84 months). The main observation indicators were overall survival (OS), progression-free survival (PFS) and local control rate (LCR). Cox regression model was used to analyze the prognostic factors. Results:Until July 31, 2020, 51 of the 78 patients with advanced hypopharyngeal squamous cell carcinoma died, including 6 cases of local recurrence, 11 cases of distant metastasis, and 34 cases of other causes (15 cases of hemorrhage, 15 cases of cachexia, and 4 cases of other diseases). In the surgery combined with chemoradiotherapy group, 12 patients died, accounting for 44.44%. In the chemoradiotherapy group, 39 patients died, accounting for 76.47%. The 1-, 3- and 5-year OS rates of 78 patients were 57.7%, 36.3% and 27.2% respectively, the 1-, 2- and 3-year PFS rates were 49.5%, 38.7% and 32.6% respectively, and the 1-, 2- and 3-year LCR were 53.4%, 40.0% and 34.2% respectively. The 1-, 3- and 5-year OS rates in the surgery combined with chemoradiotherapy group were 74.1%, 50.1% and 44.6%, and those in the chemoradiotherapy group were 49.0%, 29.3% and 12.8%, with a statistically significant difference ( χ2=5.142, P=0.023). The 1-, 2- and 3-year PFS rates in the surgery combined with chemoradiotherapy group were 62.1%, 54.3% and 44.4%, and those in the chemoradiotherapy group were 43.1%, 30.6% and 26.7%, with no statistically significant difference ( χ2=3.222, P=0.073). The 1-, 2- and 3-year LCR of the surgery combined with chemoradiotherapy group were 69.8%, 54.3% and 44.4%, and those in the chemoradiotherapy group were 45.1%, 32.9% and 29.6%, with no statistically significant difference ( χ2=3.576, P=0.059). The results of univariate analysis showed that tumor T stage ( χ2=7.140, P=0.008), N stage ( χ2=4.493, P=0.034) and treatment method ( χ2=5.142, P=0.023) were all independent influencing factors of the OS of patient with advanced hypopharyngeal squamous cell carcinoma; T stage ( χ2=5.807, P=0.016) and N stage ( χ2=6.587, P=0.010) were both independent influencing factors of PFS. The results of multivariate analysis showed that tumor T stage ( HR=2.121, 95% CI: 1.142-3.938, P=0.017), N stage ( HR=2.088, 95% CI: 1.144-3.811, P=0.016) and treatment method ( HR=0.430, 95% CI: 0.226-0.815, P=0.010) were all independent prognostic factors of the OS of patients with advanced hypopharyngeal squamous cell carcinoma; T stage ( HR=1.884, 95% CI: 1.011-3.510, P=0.046) and N stage ( HR=1.904, 95% CI: 1.058-3.429, P=0.032) were both independent prognostic factors of PFS. During the treatment period, there were statistically significant differences in the incidences of radioactive pharyngitis [7.41% (2/27) vs. 39.22% (20/51), χ2=8.821, P=0.003] and radioactive dermatitis [3.70% (1/27) vs. 29.41% (15/51), χ2=7.156, P=0.007] between the surgery combined with chemoradiotherapy group and the chemoradiotherapy group. However, there were no statistically significant differences in the incidences of radioactive oral mucositis [11.11% (3/27) vs. 17.65% (9/51), χ2=0.186, P=0.666], bone marrow suppression [37.04% (10/27) vs. 50.98% (26/51), χ2=1.381, P=0.240], pharynx infection [11.11% (3/27) vs. 5.88% (3/51), χ2=0.143, P=0.706] and tracheal fistula [7.41% (2/27) vs. 0 (0/51), P=0.117] between the two groups. Conclusion:The 1-, 3- and 5-year OS rates in the surgery combined with chemoradiotherapy group are higher than those in the chemoradiotherapy group, and the incidences of adverse reactions are low. T stage, N stage and treatment method are independent prognostic factors for OS of advanced hypopharyngeal squamous cell carcinoma patients, while T stage and N stage are independent prognostic factors for PFS.

Coronavirus disease 2019 vaccines: landscape of global studies and potential risks / 中华医学杂志(英文版)

With the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the importance of vaccines in epidemic prevention and public health has become even more obvious than ever. However, the emergence of multiple severe acute respiratory syndrome coronavirus 2 variants worldwide has raised concerns about the effectiveness of current COVID-19 vaccines. Here, we review the characteristics of COVID-19 vaccine candidates in five platforms and the latest clinical trial results of them. In addition, we further discuss future directions for the research and development of the next generation of COVID-19 vaccines. We also summarize the serious adverse events reported recently after the large-scale vaccination with the current COVID-19 vaccines, including the thromboembolism caused by the AstraZeneca and Johnson & Johnson vaccines.

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials / 中华医学杂志(英文版)

BACKGROUND@#The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.@*METHODS@#Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.@*RESULTS@#In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.@*CONCLUSIONS@#Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

Synthetic drug use，sexual behavior and associated factors among men who have sex with men in Shanghai / 上海预防医学

Objective:To understand the status of synthetic drug use， high-risk sexual behavior and associated factors among men who have sex with men （MSM） in Shanghai. Methods:MSM subjects were recruited， by a team of non-governmental organizations （NGO）， at MSM places and voluntary counseling and testing clinics from May to December 2018. The subjects completed a self-administered questionnaire survey on social-demographic， ways to make friends， synthetic drug use， high-risk sexual behavior， and HIV/STD testing history. They also received tests of HIV and syphilis. According to the use of synthetic drugs， they were divided into user group and non-user group. Results:A total of 209 subjects were recruited. Among them， 43.1% （90/209） used at least one synthetic drug. 81.3% （170/209） of MSM used internet dating software. The proportion of synthetic drug use was higher among the subjects in 30-34 age group， residence registered in other provinces， with university degree or above， occupation of cadres and staff members， monthly income of more than 10 000 yuan， making friends through gay bars， and acquaintance with male partners. The registered residence in other provinces （OR=3.006） and making friends through gay bars （OR=3.588） were independent factors. The top three synthetic drugs were Rush （90.0%， 81/90）， Viagra （8.9%， 8/90） and “capsule 0” （7.8%， 7/90）. The proportion of having sex after using synthetic drugs was 89.5% （17/19）. The frequency of high-risk sexual behaviors such as oral sex， anal sex without condom and group sex was once a day per person on average. Conclusion:The use of synthetic drugs is prevalent among MSM， and the frequency of high-risk sexual behaviors after use is high. Warning education on the dangers of synthetic drug use and mobilization for HIV testing should be carried out with the help of new media technology. Special attention should be paid to MSM people in high-income occupations and gay bars.

Association between pulse pressure and new-onset diabetes in hypertensive patients / 中华心血管病杂志

Objective: To determine the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Methods: In this prospective cohort study, hypertensive patients from the Kailuan Study, who were diagnosed in 2006-2007 check-up, were screened for enrollment. Participants who finished the biennial follow-up until December 31, 2017 were finally included in this analysis. The primary outcome was incident diabetes development. The pulse pressure variables were divided into quartiles (Q1-Q4), and the Kaplan-Meier curve was used to examine and estimate the cumulative incidence of new-onset diabetes among quartiles. Cox proportional hazards regression model was performed to explore the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Results: During an average follow-up of 8.17 years, 6 617 new-onset diabetes were identified out of the 32 917 hypertensive patients with no history or evidence of diabetes in 2006-2007 check-up. Participants were classified into quartiles according to pulse pressure levels as follows: Q1 group(<41 mmHg (1mmHg=0.133kPa))(n=7 995); Q2 group(41-<51 mmHg) (n=8 196); Q3 group (51-<61 mmHg) (n= 8 270); Q4 group (≥61 mmHg) (n=8 456). The cumulative incidences of new-onset diabetes across the quartiles were 16.94%, 19.61%, 21.07%, and 22.33%, respectively, with the incidence density was 20.27, 23.20, 24.92, and 26.10 per 1 000 person-years, respectively. The cumulative incidence of new-onset diabetes increased in proportion with increasing pulse pressure levels (P<0.01 by the Log-rank test). After multivariate adjustment, compared with the first quartile, the hazard ratios for new-onset diabetes in the third and fourth quartiles were 1.13 (95%CI 1.04-1.22, P<0.01) and 1.14 (95%CI 1.05-1.24, P<0.01), respectively. The risk of new-onset diabetes increased 5%(HR=1.05, 95%CI 1.02-1.08, P<0.01) with the fractional pulse pressure increased per 1 SD (0.13). Findings from the three sensitivity analyses were consistent with the main results in this cohort. Conclusions: Pulse pressure at baseline is positively associated with the incidence of new-onset diabetes among hypertensive individuals, and pulse pressure is an independent risk factor for the development of diabetes in hypertensive patients.

Neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane in male offspring rats / 中国职业医学

OBJECTIVE: To observe the neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane(1-BP) on the offspring rats by the breast-feeding route. Method A total of eight specific pathogen free female rats and their 64 male newborn rats were divided into the control group and the exposure group, with four lactation female rats and their 32 male newborn rats in each group. The female rats in exposure group were intragastrically administered with 700.00 mg/kg body mass of 1-BP during lactation, and the control group was given equal volume of corn oil for 21 days, once a day. The body mass of female rats and their offspring rats were measured during the exposure period. After exposure, the Morris water maze and the open field tests were performed in male offspring. The blood samples of offspring were collected for blood routine and blood biochemical indexes detection. The histopathological examination was performed in the hippocampus in the male offspring. RESULTS: A litter of eight pups in the exposure group began to die one day after the mother rat was exposed to 1-BP, and all rats died on the ninth day after exposure. There was no significant difference in the body mass of female rats between the exposure group and the control group(P>0.05). The body mass of offspring rats in the exposure group was lower than that in the control group at the same time point from the first day to the 21 st day of the female rats exposed to 1-BP(all P<0.05). In the orientation navigation experiment, the escape latency time on the first, the second day and the total distance on the first day in the offspring of the exposure group were significantly prolonged than those in the control group at the same time points(all P<0.05). The number of times of crossing the platform of offspring rats in the exposure group was less than that in the control group in the spatial exploration test(P<0.01). In the open field test, there was not statistical significance of the activity, rest time ratio, total distance, the distance ratio and time ratio in the central region in the offspring between the two groups(all P>0.05). The counts of white blood cells, neutrophils, lymphocytes, and average red blood cell width, platelet ratio and average platelet volume of the offspring of the exposure group decreased(all P<0.05), the serum levels of globulin, total protein, triacylglycerol and total bilirubin decreased(all P<0.05), and the albumin/globulin ratio and serum glucose level increased(all P<0.05), when compared with that of the control group. Histopathological examination results showed that the nerve fibers were loose in the hippocampal dentate gyrus area, and there were necrotic neurons and loss of nerve fibers in the CA1 area of the offspring rats. CONCLUSION: Maternal exposure to 1-BP during lactation can induce neurotoxicity and hematotoxicity to offspring rats. The neurotoxicity mainly caused damage to the central nerve system, which affected the learning and memory function of the offspring rats. The reason may be related to the damage caused by 1-BP on the hippocampal function.

Variations of gut microbiome composition under different preservation solutions and periods / 生物工程学报

Gut microbiota is closely related to human health, and its composition can give us health information. The large-scale population sampling is required on gut microbiome research; however, fresh feces samples are not easy to obtain, and rapid low-temperature freezing is difficult to achieve. With the development of technology, preservation solutions are widely used for sample collection, storage, and transport under normal temperature conditions. Preservation solutions can be used in large scale sample collection, wide geographical distribution, diverse on-site sampling conditions, heavy workload, and poor transportation conditions. In this study, five healthy volunteers were recruited. After collecting their fresh stool samples, effect of 5 different commercial preservation solutions was evaluated at room temperature. Samples in different preservation solutions after placing fresh stool samples at the 0, 1, 3, 7, 15, and 30 days were collected. All samples were tested by 16S rRNA V3-V4 high-throughput sequencing to analyze the influence of microbiome composition in different preservation solutions. The results show that different preservation solutions had distinct effects on the gut microbiome composition. Compared with the control, different preservation solutions had little effect on the amount of OUTs; preservation solutions A, B and C were closer to the control in the composition of the gut microbiota, but preservation solution D significantly changed the composition by increasing Actinobacteria and Firmicutes abundance. With the time, all solutions tended to reduce the diversity of the microbiota. Preservation solution E significantly reduced the diversity of the flora; on the 30th day, all five solutions changed the composition; the individual differences in the composition of the gut microbiome were the main factors affecting the similarity of each sample, and were derived from different stools donors. The same samples, no matter which storage solution and storage time, were directly closer to each other. Different storage solutions had different effects on the content of Gram-positive bacilli, Gram-positive cocci and Gram-negative bacteria. Storage solutions C and E reduced the abundance of Bifidobacterium, whereas storage solution D increased; except that preservation solution E relatively reduced the abundance of Lactobacillus, but the preservation solution A, B, C, and D were all closer to the control. Except for the greater difference in preservation solution D, preservation solution C was the closest to the control group on Streptococcus; preservation solution D reduced Ruminococcaceae UCG 003 than the control group. However, other preservation solutions were not much different from the control group; different preservation solutions increased the abundance of Escherichia-Shigella than the control group, and preservation solutions A and B increased the abundance of Klebsiella, but preservation solution C, D, and E were closer to the control group. Overall, preservation solution C performed better in stabilizing the composition of the gut microbiota. This study provides reference for standardized microbiome projects. Subsequent research can choose a targeted preservation solution and preservation time based on this study.

Expert consensus on Injection of Breviscapine in clinical practice / 中国中药杂志

With the advancement of the aging process, cerebrovascular disease has become China's first cause of death. Injection of Breviscapine is a type of traditional Chinese medicine injections published in the Chinese Pharmacopoeia of 2015 Edition and the National Basic Medical Insurance, Industrial Injury Insurance and Maternity Insurance Drug Catalogue, and used to treat ischemic cerebrovascular disease in clinic. In order to further improve clinicians' understanding of the drug and guidance of its rational clinical use, we gave full consideration of clinical research evidences and expert experience, followed the procedures developed based on expert consensus of Chinese Academy of Traditional Chinese Medicine, and then offered recommendations for clinical problems summarized by clinical first-line investigations and evidence-based clinical problems according to internationally accepted evidence grading and recommendation standards, i.e. Grade. As for clinical problems without evidence, we reached through nominal group method, and formed consensus recommendations. Safety issues of Injection of Breviscapine, such as indication, syndrome, dosage, course of treatment, precautions, suggestions and contraindications, were defined to improve clinical efficacy, promote rational drug use and reduce drug risks. This consensus needs to be revised in the future based on emerging clinical issues and evidence-based updates in practical applications.

Effect and Safety of Hydroxysafflor Yellow A for Injection in Patients with Acute Ischemic Stroke of Blood Stasis Syndrome: A Phase II, Multicenter, Randomized, Double-Blind, Multiple-Dose, Active-Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To assess the effect and safety of Hydroxysafflor Yellow A for Injection (HSYAI) in treating patients with acute ischemic stroke (AIS) and blood stasis syndrome (BSS).@*METHODS@#A multicenter, randomized, double-blind, multiple-dose, active-controlled phase II trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups (25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group (Dengzhan Xixin Injection (, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale (mRS) score ⩽1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale (NIHSS) score ⩽1, Barthel Index (BI) score ⩾95, and BSS score reduced ⩾30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment.@*RESULTS@#Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium- and high-dose HSYAI groups with mRS score ⩽1 at days 90 after treatment were significantly larger than the control group (P0.05).@*CONCLUSIONS@#HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium (50 mg/d) or high dose (75 mg/d) might be the optimal dose for a phase III trial. (Registration No. ChiCTR-2000029608).

Meta-analysis on effectiveness of live attenuated influenza vaccine against seasonal influenza in children / 中华流行病学杂志

To evaluate the effectiveness of live attenuated influenza vaccine (LAIV) in the prevention of seasonal influenza in children aged 2-17 years. Literature retrieval of case-control studies on the effectiveness of LAIV against seasonal influenza in children published from January 2003 to November 2018 was conducted through Web of Science, PubMed, and ScienceDirect databases. The Stata 13.1 software was used for Meta-analysis. A total of 14 studies were included in this study, and all were test-negative design (TND) studies. Our Meta-analysis showed that the effectiveness of LAIV in children was 49 (95: 40-57). Subgroup analysis found that the protection rate of LAIV was 35 against influenza A (H1N1) pdm09 (95: 5-56), 35 against influenza A (H3N2) (95: 21-46), and 71 against influenza B (95: 55-82). The protection rates of trivalent LAIV and quadrivalent LAIV in children were 56 (95: 48-63) and 44 (95: 27-57), respectively. The protection rates of LAIV in Europe and North America were 65 (95: 47-77) and 46 (95: 36-55), respectively. LAIV has a certain preventive effect on seasonal influenza in children aged 2-17 years.

Clinical evaluation of tumor-stroma ratio in pseudomyxoma peritonei from the appendix / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effect of tumor-stroma ratio (TSR) on disease progression and prognosis of pseudomyxoma peritonei (PMP) from the appendix.@*METHODS@#The study included 30 PMP patients with complete individual patient data, who underwent cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Beijing Shijitan Hospital. Image-Pro Plus was used to quantitatively analyze the proportion of tumor and stromal areas in hematoxylin-eosin staining pathological images, from which TSR was derived. Correlation studies were conducted to evaluate the relationships between TSR and clinicopathological features, immunohistochemical characteristics, and prognosis of PMP.@*RESULTS@#Among 30 PMP patients, there were 16 males (53.3%) and 14 females (46.7%), with the mean age of (54.9±2.3) years. There were 15 cases (50.0%) of low-grade mucinous carcinoma peritonei (LMCP) and high-grade mucinous carcinoma peritonei (HMCP), respectively, with vascular tumor emboli occurring in 4 cases (13.3%), nerve invasion occurring in 3 cases (10.0%), and lymphatic metastasis occurring in 4 cases (13.3%). The median peritoneal cancer index (PCI) score was 36 (range: 3-39). The median TSR was 8% (range: 2%-24%), with TSR≤10% in 19 cases (63.3%) and TSR>10% in 11 cases (36.7%). Immunohistochemistry showed that 16 cases (53.3%) had Ki67 label index ≤ 50% and 14 cases (46.7%) > 50%. The mutation rate of p53 was 56.7% and the loss rate of MMR protein was 11.8%. In addition, the expression rates of MUC2, MUC5AC, CDX2, CK7, and CK20 were 66.7%, 100.0%, 82.6%, 56.0%, and 92.3%, respectively. There were significant correlations between TSR and histopathological types, nerve invasion, Ki67 label index, and p53 mutation (P<0.05 for all). At the end of the last follow-up, 21 patients (70.0%) died and 9 patients (30.0%) survived, including 6 patients survived with tumor. The median overall survival (OS) was 12.7 months (95%CI: 10.4-11.5 months), and the 1-, 2-, and 3-year survival rates were 60.5%, 32.3%, and 27.7%, respectively. The median OS was 19.4 months (95%CI: 3.0-35.9 months) in the TSR≤10% group, versus 12.6 months (95%CI: 0.7-24.5 months) in the TSR>10% group (χ2=3.996, P=0.046).@*CONCLUSION@#TSR is correlated with histopathological types, tumor proliferation, invasion behaviors and prognosis of PMP, thus could be a new prognostic indicator for PMP.

Preoperative GGT, ALT/AST relates to clinicopathological features and prognosis after radical surgery for hepatocellular carcinoma / 中华普通外科杂志

Objective To investigate the relationship between preoperative GGT γ-glutamyl transferase),ALT/AST with clinicopathological features and prognosis after radical surgery of hepatocellular carcinoma(HCC).Methods The clinical data of 187 HCC patients undergoing radical resection in our hospital were retrospectively analyzed.Survival analysis was performed using the Kaplan-Meier analysis method to estimate the survival rate,and Log-rank analysis was used to compare survival rates between groups.Cox proportional hazards model was used for univariate and multivariate survival analysis.Results The Kaplan-Meier curves showed that HCC patients with normal GGT leval and higher ALT/AST ratio had a longer survival time than those with higher GGT leval and those with lower ALT/AST ratio (all P ＜ 0.05).The multivariate analyses showed that GGT leval and TNM staging were independent factors in predicting overall survival time in HCC patients.Conclusions GGT is a predictive index of overall survival of HCC patients.

The intervention of ginkgo biloba extract on monocrotaline-induced right ventricular hypertrophy in rats and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To study the protective effects of ginkgo biloba extract on the right ventricular hypertrophy.@*METHODS@#Seventy-two SD male rats were randomly divided into 3 groups: control group(CON), monocrotaline-induced right ventricular hypertrophy group (MCT) and ginkgo biloba extract treated group (EGB) (n=24 in each group). Group MCT and group EGB were intraperitoneally injected with 2%MCT at the dose of 60 mg /kg on the first day. From the second day, group MCT was injected with 2 ml 0.9% sodium chloride, and 60 mg/kg ginkgo leaf extract was administered to the stomach in group EGB. The control group was injected with 2 ml 0.9% sodium chloride on the first day. After 3 weeks, in each group,cardiac hemodynamic changes were measured, heart weight index was calculated, and myocardial pathological changes were observed by HE staining. The expression of TRPC6 was detected by real-time polymerase chain reaction (real-time -PCR) and Western blot.@*RESULTS@#Compared with the control group, the right ventricular systolic pressure (RVSP) was increased significantly in the MCT group(P＜0.01), the maximum or decline rate of descent (RV ±dp/dt) of the right ventricle pressure was increased significantly(P＜0.01), while the EGB group had the same trend as all the indexes in the group MCT, but the amplitude of all indicators in group EGB were decreased significantly than those of group MCT(P＜0.01), and the right ventricular hypertrophy index (RVMI) in group EGB was significantly lower than that in group MCT(P＜0.01).Group MCT showed typical myocardial hypertrophy performance by HE staining, and the right ventricular myocytes in group EGB were significantly improved than that in group MCT, and the mRNA and protein expression levels of TRPC6 in the right ventricle of group MCT and group EGB were increased(P＜0.01), while the EGB group was significantly lower than that of the MCT group(P＜0.01).@*CONCLUSION@#Ginkgo biloba extract may inhibit the signal pathway of CaN / NFAT in cardiac myocytes by reducing the expression of TRPC6 protein, and then play an early protective effect on myocardial hypertrophy.

Prospects of Application of Microbial Biofilm to Estimate PMI of Corpses in Water / 法医学杂志

In forensic pathology, the estimation of postmortem interval （PMI） has always been a difficult issue, and there is still lack of effective methods to estimate PMI of corpses in water. Microbial biofilm refers to the microbial population attached to non-biological or biological surfaces by microorganisms during microbial growth, that has a three-dimensional structure, surrounded by extracellular polymers and matrix networks created by itself. A series of community succession phenomena of microorganisms occur during the occurrence and development of microbial population. The microbial community and its succession process of this kind of biofilm attached to the surface of a corpse in water may become a new basis for estimation of the PMI of corpses in water. This review elucidates on the concept, classification, research methods, and influencing factors of biofilm and analyzes its application prospects in PMI estimation of corpses in water, which would provide new ideas for the researches in this field.

Research Progress of Aquatic Corpse Decomposition and Postmortem Submersion Interval Estimation / 法医学杂志

Human corpses can be found in a variety of aquatic environments. The decomposition of corpses in aquatic environments is different from those on land. A large number of factors influence the decomposition process in water, therefore postmortem submersion interval （PMSI） is difficult to estimate. To date, while studies on aquatic corpses are obviously fewer than those on terrestrial corpses, there are many problems in practical work. This review summarizes the stages and influencing factors of aquatic corpse decomposition, and introduces the relevant research progress of PMSI estimation based on decomposition stages, postmortem phenomena, aquatic insects, biofilm, and physical and chemical methods, in order to provide reference for aquatic decomposition researches and practices.