Role of Flow Cytometry in the Diagnosis of Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the immunological phenotype of chronic myeloid leukemia (CML), and explore its characteristics and significance.@*METHODS@#The immunophenotypes of 40 CML children and 40 controls were analyzed by multicolor flow cytometry. CD45/SSC, as the basic gate, was used to delineate neutrophils. Then, the distribution of cluster differentiation (CD) molecules on the surface of granulocytes was analyzed in three ranges (≥1%, ≥5%, and ≥20%), and the expression rates of CD molecules (≥1% included in the statistical analysis) and the mean fluorescence intensity (MFI) were compared between the two groups.@*RESULTS@#The proportion of granulocytes in the CML group was (82.1±6.4)%, which was significantly higher than (57.8±11.8)% in the control group (P <0.001). The expression rates of CD15/CD11b/CD33/CD13 in CML and control groups were high, and both distributed in the range of ≥20%. The differentiation trajectory of CD33/CD13 was normal and there were no significant differences in the expression rate and MFI between the two groups. However, both the expression rate of CD11b and CD15 MFI in the CML group were significantly lower than those in the control group (P <0.001). There were no significant differences in the expression rate and MFI of CD10 between the two groups, and the expression levels of CD10 between the two groups were consistent in different distributions. In the CML group, there was a large number of cases with abnormal high expression of CD56, 52.5% of the cases had a CD56 expression rate of ≥5%, and 42.5% had a CD56 expression rate of ≥20%, while the control group did not express CD56 (<1%). The expression distribution of CD117 was different between the two groups. In the range of expression rate ≥5%, there were 35.0% cases in the CML group, while only 2.5% in the control group. The expression rate of CD117 in the CML group was higher than that in the control group (P <0.001), though there was no significant difference in MFI.@*CONCLUSION@#The immunophenotyping of CML is characterized by increased proportion of mature neutrophils, decreased CD15 MFI, decreased proportion of CD11b and abnormal high expression of CD56 and CD117. Flow cytometric analysis of immunophenotype can effectively distinguish normal granulocytes from chronic granulocytes, and help in the diagnosis of CML.

Etiology composition and prognosis of pediatric chronic critical illness in a pediatric intensive care unit / 中国当代儿科杂志

OBJECTIVES@#To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU).@*METHODS@#The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed.@*RESULTS@#Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05).@*CONCLUSIONS@#The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.

Genetic analysis of a Chinese pedigree affected with Congenital dysfibrinogenemia due to variant of FGG gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the coagulation deficit and genetic basis for a Chinese pedigree affected with Congenital dysfibrinogenemia (CD).@*METHODS@#Peripheral venous blood samples of the proband and her family members (including 4 individuals from three generations) were subjected to routine blood test and assays of liver and kidney functions and viral hepatitis to exclude related diseases. Clauss method and DFg-PT method were used to determine the fibrinogen activity (Fg:C), and an immunoturbidimetric assay was used to determine the level of fibrinogen antigen (Fg:Ag). All of the exons (22 in total) and their flanking sequences of the FGA, FGB and FGG genes were amplified by PCR and directly sequenced. Variants in the coding regions of the three genes and transcriptional splicing sites were screened by using Mutation SurveyorTM software.@*RESULTS@#The Clauss method showed that Fg:C was significantly reduced in the proband and her father, whilst her mother and son were normal. With the DFg-PT method, the proband, her parents and son were all within the normal range. The Fg:C/Fg:Ag ratio of the proband and her father was lower than 0.7, whilst her mother and son were above 0.7. No significant change in the prothrombin time, activated partial thromboplastin clotting time and thrombin time was noted. Two genetic variants were detected, which included a homozygous missense variant in the FGA gene [c.991A>G (p.Thr331Ala)], which was predicted to be benign, and a heterozygous missense variant of the γ chain of the FGG gene [c.1211C>G (p.Ser404Phe)], which is located in a conserved region and unreported in the CLINVAR/HGMD/EXAC/1000G databases and literature.@*CONCLUSION@#This pedigree has conformed to the autosomal dominant inheritance of CD. The c.1211C>T (p.Ser404Phe) missense variant of the γ chain of the FGG gene probably underlay the pathogenesis of CD in this pedigree. The variant was unreported previously and named as "Fibrinogen Harbin II Ser404Phe".

Effect of transcutaneous acupoint electrical stimulation at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy / 中国针灸

OBJECTIVE@#To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy.@*METHODS@#A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (PETCO2) and minimum value of oxygen saturation (SpO2) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T0), at the start of surgery (T1), thoracic exploration (T2) and lobectomy (T3), as well as 30 min (T4) and 60 min (T5) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups.@*RESULTS@#The maximum value of PETCO2, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO2 in the observation group was higher than that of the control group (P < 0.01). At T1-T5, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01).@*CONCLUSION@#For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.

Analysis of disease characteristics and hospitalization burden of elderly patients with cerebrovascular disease based on home page of medical records / 中华老年医学杂志

Objective:To analyze the disease characteristics and hospitalization burden of elderly inpatients with cerebrovascular disease, so as to provide basis for disease prevention, diagnosis, treatment and rehabilitation of elderly patients with multiple chronic conditions.Methods:The data of the first page of medical records of elderly inpatients with cerebrovascular disease from 2015 to 2020 in a comprehensive tertiary hospital in Jiangsu Province were retrospectively collected.Descriptive analysis, variance analysis and multiple linear regression analysis were carried out for the research objects using SPSS statistics and Python complex network methods.Results:A total of 14 657 elderly inpatients with cerebrovascular disease were included.From 2015 to 2020, the number of hospitalizations increased from 1 268 to 4 733, the average number of hospitalizations increased from 2.0 to 2.9, the average length of stay decreased from 11.9 days to 9.1 days, and the average number of illnesses increased from 1.9 to 4.9.The five most common comorbidities associated with cerebrovascular diseases were hypertension, diabetes, ischemic heart disease, other types of heart disease and other respiratory diseases.From 2015 to 2020, the average hospitalization costs of elderly cerebrovascular inpatients decreased from 20588.1 Chinese yuan(CYN)to 15580.9 Chinese yuan(CYN). The hospitalization cost was mainly composed of drug cost(46.6%), diagnosis cost(28.2%)and treatment cost(20.2%). There were significant differences in the average hospitalization expenses among patients with different gender, age, number of admissions, length of stay and number of diseases( P<0.05 for all). Gender, age, number of hospitalizations and length of stay had an impact on hospitalization expenses. Conclusions:The number of inpatients, comorbidities, and hospitalized times of elderly patients with cerebrovascular disease showed an increasing trend, while the number of hospitalization days and the average hospitalization cost showed a downward trend.Comorbidities associated with cerebrovascular diseases should be one of the concerns of chronic disease management in the elderly.

Mechanism of Erhuang Quzhi Granules in the treatment of non-alcoholic fatty liver based on NF-kB/NLRP3 signaling pathway / 中国药理学通报

Aim To explore the therapeutic effect of Erhuang Quzhi Granules on non-alcoholic fatty liver disease ( NAFLD) mouse model induced by Western diet ( WD) combined with low-dose CCl

Clinical characteristics of definite vestibular migraine diagnosed according to criteria jointly formulated by the Bárány Society and the International Headache Society

Abstract Objective: To investigate the clinical features of patients with definite vestibular migraine (dVM). Methods: A total of 91 patients with vestibular symptoms accompanied by migraines/migrainelike symptoms were enrolled and diagnosed according to the criteria of the Bárány Society and the International Headache Society. Baseline data were collected. Videonystagmography and immune-related laboratory tests were performed. Results: Among the 91 patients, 62 (68.1%) had dVM (11 men, 51 women). Among dVM patients, migraine occurred earlier than vestibular symptoms in 42 (67.7%) patients. Spontaneous vertigo occurred in 41 (66.1%) patients. Induced vertigo occurred in 21 (33.9%) patients. Motion sickness occurred in 33 (53.2%) patients. Central oculomotor dysfunction was observed in 11 (17.7%) patients. Caloric test revealed unilateral horizontal semicircular canal dysfunction in 12 (19.4%) patients. Severe intolerance during the test occurred in 44 (71.0%) patients with dVM. 12 (19.4%) patients showed abnormal immune-related indicators. Conclusion: dVM is more common in women. The onset of migraine precedes that of vestibular symptoms, which are often accompanied by photophobia and phonophobia. Motion sickness and severe caloric test intolerance can contribute to the diagnosis of dVM. Immunological indicators are abnormal in some patients with dVM, dVM may be secondary or an accompanying disorder, but the causal relationship needs further investigation. Level of evidence: IV.

Analysis of hospitalization expenses and its influencing factors of elderly patients with hypertension at tertiary general hospitals in Jiangsu province / 中华医院管理杂志

Objective:To analyze the hospitalization expenses of elderly patients with hypertension and its influencing factors, so as to provide reference for optimizing the medical service management of elderly patients with hypertension.Methods:Medical record home page data of all hypertension inpatients of elderly patients at two tertiary general hospitals in Jiangsu province from 2017 to 2020 were retrieved. These data were used to analyze the basic information, hospitalization expenses and their influencing factors. Descriptive analysis was used for all data, variance analysis was used for one-way analysis, and multiple linear regression was used for multivariate analysis.Results:A total of 20 596 elderly inpatients with hypertension were included in this study. The number of patients was increased from 1 476 in 2017 to 10 771 in 2020. Among them, the number of inpatients with≥2 diseases increased from 1 105(74.86%) to 10 564(98.08%); From 2017 to 2020, the average hospitalization expenses of elderly inpatients with hypertension were 11 500 yuan, 13 600 yuan, 13 800 yuan and 14 100 yuan respectively, increasing year by year; Gender, age, number of hospitalizations, hospitalization days and number of diseases were the influencing factors of hospitalization expenses( P<0.05), and the hospitalization expenses increased with the increase of hospitalization days, number of diseases and age. Conclusions:The number of elderly patients with hypertension, the incidence of comorbidity, and the average hospitalization cost in tertiary hospitals in Jiangsu province were increasing year by year. There were many factors affecting the hospitalization cost. The author suggested that the treatment of elderly patients with hypertension should be shifted to prevention, so as to reduce the economic burden of disease and improve their quality of life.

Expression and clinical significance of minichromosome maintenance protein 3(MCM3) in gastric cancer tissues / 国际生物医学工程杂志

Objective:To study the expression level and clinical significance of minichromosome maintenance protein 3(MCM3) in human gastric cancer.Methods:The expression levels of MCM3 mRNA and protein in gastric cancer and adjacent normal tissues were analyzed using public databases such as TCGA, CCLE and HPA. The clinicopathological features of 69 patients with gastric cancer were retrospectively analyzed, and the expression levels of MCM3 protein in tumor tissues and adjacent normal tissues were detected by immunohistochemical staining, and the relationship between it and clinicopathological features was analyzed. The interaction network of MCM3 proteins was analyzed using the STRING database.Results:The expression levels of MCM3 mRNA and protein in gastric cancer tissues were significantly higher than those in adjacent normal tissues ( P<0.05), and its high expression was correlated with the size of gastric cancer tumors ( P<0.05). In gastric cancer tissue, the expression of MCM3 was correlated with the expression level of proliferating cell nuclear antigen (PCNA) ( R=0.61, P<0.01), and there may be a protein-protein interaction. Conclusions:MCM3 plays an important role in gastric cancer by interacting with PCNA, and it is expected to become a new diagnostic and therapeutic target.

Determining the protective effects of Ma-Mu-Ran Antidiarrheal Capsules against acute DSS-induced enteritis using 16S rRNA gene sequencing and fecal metabolomics / 中国天然药物

Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) is traditional Chinese medicine that has been used to treat diarrhea caused by acute enteritis (AE) and bacillary dysentery in Xinjiang (China) for many years. However, the potential therapeutic mechanism of MMRAC for AE and its regulatory mechanism on host metabolism is unclear. This study used fecal metabolomics profiling with GC/MS and 16S rRNA gene sequencing analysis to explore the potential regulatory mechanisms of MMRAC on a dextran sulfate sodium salt (DSS)-induced mouse model of AE. Fecal metabolomics-based analyses were performed to detect the differentially expressed metabolites and metabolic pathways. The 16S rRNA gene sequencing analysis was used to assess the altered gut microbes at the genus level and for functional prediction. Moreover, Pearson correlation analysis was used to integrate differentially expressed metabolites and altered bacterial genera. The results revealed that six intestinal bacteria and seven metabolites mediated metabolic disorders (i.e., metabolism of amino acid, carbohydrate, cofactors and vitamins, and lipid) in AE mice. Besides, ten altered microbes mediated the differential expression of eight metabolites and regulated these metabolisms after MMRAC administration. Overall, these findings demonstrate that AE is associated with metabolic disorders and microbial dysbiosis. Further, we present that MMRAC exerts protective effects against AE by improving host metabolism through the intestinal flora.

Therapeutic effect and mechanism of Erhuang quzhi granules on non-alcoholic fatty liver disease in mice / 药学学报

Erhuang quzhi compounds is one of the protecting liver and inhibiting toxin prescriptions series summarized by Jinqi Yuan and other famous doctors of traditional Chinese medicine during the long-term clinical practice. It is very effective for non-alcoholic fatty liver disease (NAFLD), but its mechanism is not clear. This research investigated mechanism of Erhuang quzhi granules (EQG) in the treatment of NAFLD. All the animal welfare and experimental procedures are in accordance with the regulations of the Animal Ethics Committee of the First Affiliated Hospital of Shihezi University. Mouse models of NAFLD were established by feeding with methionine and choline deficient diet (MCDD) for five weeks. While feeding MCDD, the treatment groups were given EQG (16.25 g·kg-1·d-1) and atorvastatin (ATO, 7.20 mg·kg-1·d-1) by gavage. The effects of EQG on serum biochemical indices, liver pathological changes, and inflammatory cytokines in mice of NAFLD were investigated. Quantitative real-time PCR (qPCR), immunocytochemistry (ICH) and Western blot assays were used to detect the levels of mRNA and protein associated with nuclear factor kappa B/Nod-like receptor protein 3 (NF-κB/NLRP3) in liver. The results showed that EQG significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and improved the level of low-density lipoprotein cholesterol (LDL-C). The result of hematoxylin-eosin (HE) staining showed that EQG reduced lipid deposition in livers of mice. Meanwhile, EQG notably decreased the levels of interleukin (IL)-1β, IL-6, IL-18 and tumor necrosis factor-α (TNF-α), and mRNA levels of NF-κB, NLRP3, IL-1β, TNF-α, down-regulated the expression of F4/80, IκB kinase β (IKKβ), NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) and inhibited the activation of NF-κB and cysteinyl aspartate specific proteinase-1 (caspase-1). These findings announced that EQG could improve NAFLD via NF-κB/NLRP3 pathway possibly, which provides a theoretical basis for the further development and utilization of EQG in clinic.

Expression of MCM4/PCNA in gastric cancer and its potential as a potential biomarker / 国际生物医学工程杂志

Objective:To analyze the expressions of minichromosome maintenance protein 4(MCM4) and proliferating cell nuclear antigen (PCNA) in gastric cancer tissues, to explore the relationship between MCM4/PCNA and gastric cancer, and to investigate the possibility of MCM4/PCNA as a potential biomarker for gastric cancer.Methods:Bioinformatics methods were used to analyze the mRNA expressions of MCM4 and PCNA in gastric cancer tissues and adjacent normal tissues. The clinicopathological data of 69 patients with gastric cancer who underwent surgery were retrospectively analyzed. The expression levels of MCM4 and PCNA in gastric cancer tissues and adjacent normal tissues were detected by immunohistochemistry, and their relationship with the clinicopathological characteristics of gastric cancer patients was analyzed.Results:The mRNA levels of MCM4 and PCNA in gastric cancer tissues are significantly higher than those in adjacent normal tissues (all P<0.05). The expression of MCM4 is correlated with the tumor size of gastric cancer ( P=0.037), but there is no significant correlation with gender, age and tumor grade (all P>0.05). Both MCM4 and PCNA proteins are highly expressed in gastric cancer patients. Conclusions:The expression levels of MCM4 and PCNA have a clear correlation with the occurrence of gastric cancer. MCM4 and PCNA are expected to be potential biomarkers for the diagnosis and treatment of gastric cancer.

Comparison of the Consistency and Difference of Three Detection Methods in Blood Concentration Monitoring of Mycophenolic Acid / 中国药房

OBJECTIVE：To investigate the consistency and difference of f luorescence immunochromatographic and liquid chromatography-tandem mass spectrometry （LC-MS/MS）and enzyme multiplied immunoassay technique （EMIT）in the blood concentration monitoring of mycophenolic acid. METHODS ：Fluorescence immunochromatography ，LC-MS/MS and EMIT were used to detect the blood concentration of mycophenolic acid in 61 blood samples of children treated with mycophenolate mofetil ester orally at different time points. Kolmogorov-Smirnov method ，Wilcoxon pairing test ，Passing-Bablok regression ，Cusum method，Spearman correlation analysis ，Bland-Altman scatter diagram were adopted for statistical analysis. RESULTS ：Blood concentrations of mycophenolic acid ，which were determined by fluorescence immunochromatography ，LC-MS/MS and EMIT ， showed non-normal distribution. Passing-Bablok regression analysis showed that regression equation of fluorescence immunochromatography and LC-MS/MS ，fluorescence immunochromatographic method and EMIT were CFI=0.928 3CLC-MS/MS+0.961 7 and CFI＝0.880 7CEMIT－0.488 2（FI means fluorescence immunochromatographic ）. Spearman correlation analysis showed that the correlation coefficients between fluorescence immunochromatography and LC-MS/MS ，fluorescence immunochromatography and EMIT were 0.968 and 0.929， respectively （P＜0.000 1）. Bland Altman scatter plot analysis showed that 3.28％ of the 358341451@qq.com difference between fluorescence immunochromatography and LC-MS/MS was outside the consistency limit （±1.96SD）， and 1.64％ of the difference between fluorescence immuno- chromatography and EMIT was outside the consistency limit （± 1.96SD）. Wilcoxon pairing test showed that the results of fluorescence immunochromatography were higher than those of LC-MS/MS （Z＝3.76，P＝0.000 2）and lower than those of EMIT （Z＝－5.96，P＜0.000 1）. CONCLUSIONS ：Fluorescence immunochromatography shows good consistency and correlation with LC-MS/MS and EMIT ；the blood concentrations of mycophenolic acid detected by fluorescence immunochromatography were higher than those by LC-MS/MS and lower than those by EMIT . It can be used for bedside rapid detection. When using the test results of different methods for clinical medication ，the differences of test methods need to be considered.

Luteolin inhibits H2O2 -induced cellular senescence via modulation of SIRT1 and p53

Luteolin, a sort of flavonoid, has been reported to be involved in neuroprotective function via suppression of neuroinflammation. In this study, we investigated the protective effect of luteolin against oxidative stress-induced cellular senescence and its molecular mechanism using hydrogen peroxide (H2O2)-induced cellular senescence model in House Ear Institute-Organ of Corti 1 cells (HEI-OC1). Our results showed that luteolin attenuated senescent phenotypes including alterations of morphology, cell proliferation, senescence-associated β-galactosidase expression, DNA damage, as well as related molecules expression such as p53 and p21 in the oxidant challenged model. Interestingly, we found that luteolin induces expression of sirtuin 1 in dose- and time-dependent manners and it has protective role against H2O2 -induced cellular senescence by upregulation of sirtuin 1 (SIRT1). In contrast, the inhibitory effect of luteolin on cellular senescence under oxidative stress was abolished by silencing of SIRT1. This study indicates that luteolin effectively protects against oxidative stress-induced cellular senescence through p53 and SIRT1. These results suggest that luteolin possesses therapeutic potentials against age-related hearing loss that are induced by oxidative stress.

Luteolin inhibits H2O2 -induced cellular senescence via modulation of SIRT1 and p53

Luteolin, a sort of flavonoid, has been reported to be involved in neuroprotective function via suppression of neuroinflammation. In this study, we investigated the protective effect of luteolin against oxidative stress-induced cellular senescence and its molecular mechanism using hydrogen peroxide (H2O2)-induced cellular senescence model in House Ear Institute-Organ of Corti 1 cells (HEI-OC1). Our results showed that luteolin attenuated senescent phenotypes including alterations of morphology, cell proliferation, senescence-associated β-galactosidase expression, DNA damage, as well as related molecules expression such as p53 and p21 in the oxidant challenged model. Interestingly, we found that luteolin induces expression of sirtuin 1 in dose- and time-dependent manners and it has protective role against H2O2 -induced cellular senescence by upregulation of sirtuin 1 (SIRT1). In contrast, the inhibitory effect of luteolin on cellular senescence under oxidative stress was abolished by silencing of SIRT1. This study indicates that luteolin effectively protects against oxidative stress-induced cellular senescence through p53 and SIRT1. These results suggest that luteolin possesses therapeutic potentials against age-related hearing loss that are induced by oxidative stress.

Study on effect of SuperTab 40LL on compression characteristics of musk sustained-release mini-tablets based on mathematical models / 中国中药杂志

In this paper, co-processed lactose SuperTab 40 LL was selected as fillers to study the preparation of musk sustained-release mini-tablets in the Xihuang multiple-unit drug release system. Musk sustained-release tablets containing different proportions of SuperTab 40 LL and MCC were prepared under various pressures, and then the compressibility and compactibility of these prescriptions were evaluated by Walker, Heckel and Ryshkewitch-Duckworth equations. In addition, the fluidity of the prescriptions was evaluated by parameters of Kawakita equation. There was a comprehensive analysis of the effect of SuperTab 40 LL on musk sustained-release mini-tablets combined with the appearance of SuperTab 40 LL and their tensile strength. The results shown that SuperTab 40 LL had better compression process through the Heckel equation, and the direct compression process of drug powders with excipients can be analyzed by the Kawakita and Ryshkewitch-Duckworth equations. As a new type of co-processed lactose, SuperTab 40 LL had a good fluidity and compactibility. SuperTab 40 LL may undergo particle crushing and plastic deformation during the compression process, which increased the contact area and bonding sites between the particles, and aggregated and shaped the mixed powder easy. Moreover, MCC showed a synergistic effect, and the combined application with SuperTab 40 ll could effectively improve the fluidity and compressibility of the musk sustained-release powder. When the ratio of SuperTab 40 LL and MCC was 2∶1, musk sustained-release mini-tablets had a high drug loading capacity and good compactibility in line with the design objectives.

Effect of acupuncture for regulating spleen and stomach on aspirin resistance in patients with type 2 diabetes mellitus: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture for regulating spleen and stomach on aspirin resistance in patients with type 2 diabetes mellitus (T2DM) and explore the effect mechanism.@*METHODS@#A total of 68 T2DM patients complicated with aspirin resistance were randomized into an observation group and a control group, 34 cases in each one. On the base of the conventional treatment for diabetes, aspirin enteric-coated tablets were prescribed for oral administration, 100 mg each time, once daily in the control group. In the observation group, on the basis of the treatment as the control group, acupuncture was used for regulating spleen and stomach at Zhongwan (CV 12), Zusanli (ST 36), Yinlingquan (SP 9), Hegu (LI 4), etc., once daily. The treatment for 1 week was as one course and 4 courses of treatment were required totally in two groups. Before and After treatment, the indexes of platelet function (platelet aggregation rate [PAG] and salicylic acid concentration), the indexes of vascular endothelial function (6-keone prostaglandin F1α[6-keto-PGF1α], thromin B2 [TXB2] and cyclooxysynthase-2 [COX-2]), blood glucose (fasting plasma glucose [FPG], 2 h plasma glucose [2h PG] and glycosylated hemoglobin [HbA1c]), insulin resistance index (HOMA-IR), blood lipid indexes (total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) and the total score of TCM symptoms were observed in the patients of two groups. Clinical therapeutic effect and safety was compared in the patients between the two groups after treatment and the recurrence rate of cardiocerebrovascular events was followed up 6 months after treatment.@*RESULTS@#After treatment, PAG, salicylic acid concentration, TXB2, COX-2, FPG, 2h PG, HbA1c, HOMA-IR, LDL-C, TC, TG and the total scores of TCM symptoms were all reduced as compared with those before treatment in the two groups (@*CONCLUSION@#Acupuncture for regulating spleen and stomach combined with aspirin enteric-coated tablets relieve insulin resistance and reduces blood glucose and lipid as well as the recurrence rate of cardiocerebrovascular events in the patients with T2DM, which is probably related to the regulation of insulin resistance and the improvement of vascular endothelial function. This combined therapy achieves the better effect on aspirin resistance as compared with simple aspirin enteric-coated tablets.

Effect of electroacupuncture at Neiguan (PC 6) on pulmonary function during one-lung ventilation in patients with lobectomy / 中国针灸

OBJECTIVE@#To observe the protective effect of electroacupuncture (EA) at Neiguan (PC 6) on pulmonary function during one-lung ventilation (OLV) in patients with lobectomy, and explore its action mechanism.@*METHODS@#Sixty patients with lobectomy were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with general anesthesia, and OLV was given when surgery began; when the surgery finished, air was removed from the thoracic cavity and two-lung ventilation was performed. On the basis of the treatment in the control group, the patients in the observation group were treated with EA (disperse-dense wave, 2 Hz/100 Hz of frequency) at Neiguan (PC 6) 30 min before anesthesia induction until the end of the surgery. The pulmonary function indexes [arterial partial pressure of oxygen (PaO@*RESULTS@#Compared with T@*CONCLUSION@#EA at Neiguan (PC 6) has protective effects on lung injury induced by OLV after lobectomy, and its mechanism may be related to the improvement of oxidative stress and inflammatory response.

Pharmacokinetic/pharmacodynamic modeling of the antitumor action of bispecific CD3/EpCAM antibody M701 in human colorectal cancer xenograft mice / 药学学报

M701 is a bispecific CD3/EpCAM T-cell engager antibody for the treatment of malignant ascites. We developed a population pharmacokinetic/pharmacodynamic (PK/PD) model to quantitatively describe and predict the antitumor effect of M701 in human colorectal cancer xenograft mice. We developed the M701 PK model based on plasma concentration data after i.v. administration. A tumor growth model for human colorectal cancer xenograft was developed to evaluate the antitumor effect of M701. We additionally simulated the inhibitory effect of M701 on tumor volume under different dose regimens based on a PK/PD model. A two-compartment model was developed to predict the PK in human colorectal cancer xenograft mice. The relationship between the M701 concentration and tumor growth inhibition was characterized by a combined Simeoni tumor growth/transit compartment model. The estimated pharmacodynamic parameters were related to the tumor growth characteristics λ0 (0.212 d-1) and λ1 (0.044 7 cm3·d-1), to the drug potency k2 (0.071 5 mL·ng-1·d-1), and to the kinetics of tumor cell death k1 (2×10-5 d-1). A model visual predictive check showed that both the PK model and the tumor growth model closely fit the observed data. Simulated tumor growth after administration of M701 (0.5 mg·kg-1 every 6 days and 0.25 mg·kg-1 every 3 days) could be effectively inhibited. This population PK/PD model of M701 provides insight into the antitumor effect of M701 and supports the further therapeutic development of M701.

Bioinformatics analysis of differentially expressed circRNAs and microRNA-1 in HepG2 cells / 医学研究生学报

ObjectivecircRNAs play an important role in tumor development, but the relationship between circRNAs and hepatocellular carcinoma remains to be further explored. The present study aimed to bioinformatically analyze the target gene of microRNA-1. Another aim was to screen circRNAs that are associated with target genes and differentially expressed in hepatocellular carcinoma cells, as well as provide theoretical basis for clinical screening of molecular markers and targeted therapies related to hepatocellular carcinoma.MethodsThe miRNA related database used for the prediction of microRNA-1 target genes, and the bioinformatic analysis of the target genes of microRNA-1 involved functional enrichment analysis and signal transduction pathway enrichment. Then, the circRNAs, which are related to the downstream target genes of microRNA-1, are screened through the circRNA database.ResultsThe number of microRNA-1 target genes was 230 in miRNA related database. Through GO analysis, it was found that the target genes of microRNA-1 had a strong tendency in regulation, and were mainly enriched in three aspects: biological function, biological process and cell localization.The target genes of microRNA-1 are involved in the function of proteins, regulation of biosynthesis, cofactor binding, enzyme regulation and other biological processes. Predicted target genes of miRNA-1 were significantly enriched in cancer signaling pathways, hepatitis B occurrence, endocytosis and splicing pathways. Further, 21 circRNAs related to the target gene of microRNA-1 were found in three circRNA databases, wherein hsa_circ_0004651 was highly expressed in hepatocellular carcinoma cell line HepG2 and its pavent gene was hnRNPD.ConclusionMicroRNA-1 influence the occurrence of hepatocellular carcinoma development through the regulation of protein and enzyme. Hsa_circ_0004651 may affect the development of hepatocellular carcinoma with microRNA-1 and its parental gene hnRNPD.