Pingxiao capsule inhibits lung metastasis of triple-negative breast cancer and sensitizes breast cancer to radiotherapy.

OBJECTIVES: To investigate the anticancer effect of Pingxiao capsule (, PXC) on the treatment of breast cancer and . METHODS: The inhibition of PXC on cell viability and proliferation was determined by cell counting kit-8, EdU assay and colony formation assay, respectively. The effect of PXC on cell apoptosis was detected by using flow cytometry. The suppression of PXC on cell migration and invasion was investigated by chamber assay. To investigate the underlying molecular mechanisms, the expression of proteins related to epithelial to mesenchymal transition (EMT) was analyzed by Western blotting in breast cancer cells and by immunohistochemistry in tumor tissues. The anticancer effect of PXC was evaluated by using MDA-MB-231 xenograft model and 4T1 metastatic breast cancer model. RESULTS: Our results indicated that triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and MDA-MB-468 were sensitive to PXC. PXC potently inhibited the proliferation, colony formation, migration, and invasion of MDA-MB-231 and MDA-MB-468 cells . Then, MDA-MB-231 xenograft model depicted that PXC significantly reduced tumor size and weight compared with Control. 4T1 lung metastasis model showed that PXC significantly inhibited breast cancer cell spreading to lungs in mice. Mechanistically, PXC inhibited EMT process by reducing cadherin turnover in TNBC. Furthermore, PXC in combination with 8 Gy X-ray treatment obviously promoted the induction of apoptosis, and suppressed cell proliferation. CONCLUSION: PXC could inhibit the proliferation and invasion of TNBC both and , and exerted its anti-metastatic effect by regulating cadherin turnover, Furthermore, it sensitized the TNBC cells to radiotherapy. The data supported further development of PXC as an adjuvant-therapy agent for TNBC.

Application of flipped classroom based on effective teaching theory in clinical teaching of nursing students in otolaryngology and head and neck surgery / 中华医学教育探索杂志

Objective:To investigate the effect of flipped classroom teaching based on effective teaching theory in the clinical teaching of otolaryngology and head and neck surgery.Methods:A total of 35 nursing students who received clinical teaching in Department of Otolaryngology and Head and Neck Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University Medical College, from June 2019 to June 2020 were selected as control group, and 35 nursing students who received clinical teaching from July 2020 to July 2021 were selected as study group. The students in the control group received traditional teaching, and those in the observation group received flipped classroom teaching based on effective teaching theory. The two groups were compared in terms of the scores of theoretical knowledge and practical operation after teaching, abilities of self-learning, analysis and problem-solving, innovative thinking, teamwork, and nurse-patient communication before and after treatment, and the degree of satisfaction with teaching among nursing students. SPSS 24.0 was used to perform the t-test and the chi-square test. Results:After teaching, the study group had significantly higher scores of theoretical knowledge and practical operation than the control group (94.24±3.25/94.65±3.41 vs. 89.54±3.36/88.76±3.37, P < 0.05). After teaching, both groups had significant increases in the scores of self-study ability, analysis and problem-solving ability, innovative thinking ability, teamwork ability, and nurse-patient communication ability, and the study group had significantly higher scores of these abilities than the control group ( P < 0.05). The study group had a significantly higher satisfaction rate of teaching than the control group [94.29% (33/35) vs. 71.43% (25/35)]. Conclusion:In the clinical teaching of nursing students in otolaryngology and head and neck surgery, the application of flipped classroom teaching based on effective teaching theory can improve the understanding of theoretical knowledge and practical operation ability, with significant increases in comprehensive ability and degree of satisfaction with teaching, and therefore, it has a good application value.

Evaluation of immunoprotection against coronavirus disease 2019:Novel variants,vaccine inoculation,and complications / 药物分析学报

The strikingly rapidly mutating nature of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)genome has been a constant challenge during the coronavirus disease 2019(COVID-19)pandemic.In this study,various techniques,including reverse transcription-quantitative polymerase chain reaction,antigen-detection rapid diagnostic tests,and high-throughput sequencing were analyzed under different scenarios and spectra for the etiological diagnosis of COVID-19 at the population scale.This study aimed to summarize the latest research progress and provide up-to-date understanding of the methodology used for the evaluation of the immunoprotection conditions against future variants of SARS-CoV-2.Our novel work reviewed the current methods for the evaluation of the immunoprotection status of a specific population(endogenous antibodies)before and after vaccine inoculation(adminis-tered with biopharmaceutical antibody products).The present knowledge of the immunoprotection status regarding the COVID-19 complications was also discussed.Knowledge on the immunoprotection status of specific populations can help guide the design of pharmaceutical antibody products,inform practice guidelines,and develop national regulations with respect to the timing of and need for extra rounds of vaccine boosters.

Prediction of human intestinal absorption properties based on artificial intelligence / 中国药科大学学报

@#Human intestinal absorption (HIA) is a crucial indicator for measuring the oral bioavailability of drugs.This study aims to use artificial intelligence methods to predict and evaluate the HIA of drugs in the early stages of drug discovery, thus accelerating the drug discovery process and reducing costs.This study used MOE''s 2D, 3D descriptors, and ECFP4 (extended connectivity fingerprints) to characterize the molecules and established eight models, including support vector machine (SVM), random forest (RF), and deep neural network (DNN).The results showed that the SVM model constructed using a combination of 2D, 3D descriptors and ECFP4 fingerprints was the optimal model according to comprehensive evaluation of various evaluation indicators.The area under the receiver operating characteristic curve (AUC), Matthews correlation coefficient, and Kappa coefficient of the optimal model were 0.94, 0.75, and 0.74, respectively.In conclusion, this study established a robust and generalizable machine learning model for predicting HIA properties, which can provide guidance for early molecular screening and the study of pharmacokinetic properties of drugs.

Effects of Ligusticum Chuanxiong extract on MPP+-induced SH-SY5Y cells in Parkinson’s syndrome model via miR-23a-3p/SNCA axis / 西安交通大学学报(医学版)

【Objective】 To explore the effects of Ligusticum Chuanxiong extract on MPP+-induced SH-SY5Y cell damage and Parkinson’s syndrome. 【Methods】 1-methyl-4phenylpyridine ion (MPP+) interfered with SH-SY5Y to establish a cell model of elderly Parkinson’s syndrome (SH-SY5Y-MPP+). After intervention with Ligusticum Chuanxiong extract, cell proliferation and apoptosis as well as miR-23a-3p and SNCA expressions were detected. In addition, the changes of SH-SY5Y-MPP+ after regulating the expression of miR-23a-3p and SNCA were observed, and the relationship between miR-23a-3p and SNCA was verified by dual luciferase reporter. 【Results】 The cell proliferation capacity of SH-SY5y-MPP+ was significantly lower than that of SH-SY5Y, while the apoptosis rate was higher than that of SH-SY5Y (P<0.05). Under the intervention of Ligusticum Chuanxiong extract, the proliferation ability of SH-SY5Y-MPP+, and Bcl-2 and SNCA protein increased, the apoptosis rate, miR-23a-3p, and Bax proteins decreased (P<0.05). Both silencing miR-23a-3p and increasing SNCA could promote the proliferation of SH-SY5Y-MPP+ and inhibit apoptosis, while increasing miR-23a-3p and silencing SNCA were the opposite (P<0.05). The online target gene prediction website found that miR-23a-3p and SNCA had complementary sites that could bind, and the dual luciferase reporter enzyme showed that the firefly activity of SNCA-wt was significantly inhibited after the miR-23a-3p mimic sequence was transfected (P<0.05). After increasing miR-23a-3p, the expression of SNCA protein in SH-SY5Y-MPP+ decreased, while silencing miR-23a-3p was the opposite (P<0.05). Rescue experiments showed that the intervention effect of Ligusticum Chuanxiong extract on SH-SY5Y-MPP+ was completely reversed by increasing miR-23a-3p or silent SNCA (P>0.05); the effect of increasing miR-23a-3p on SH-SY5Y-MPP+ increased SNCA reversion (P>0.05). 【Conclusion】 Ligusticum Chuanxiong extract can affect the biological behavior changes of SH-SY5Y induced by MPP+ by regulating the miR-23a-3p/SNCA axis, which may be a new direction for the treatment of elderly Parkinson’s syndrome in the future.

Analysis of the current situation of research ability, cognition, and needs of medical staff in a grade A tertiary hospital in Xinjiang / 中华医学科研管理杂志

Objective:To understand the research ability, cognition, and training needs of clinical medical staff in a grade A tertiary hospital in Xinjiang and to analyze the influencing factors.Methods:A convenience sampling method was applied to survey the clinical medical staff of our hospital with a questionnaire including general information, a self-assessment scale of research ability, and a survey of research cognition and training needs. A total of 618 questionnaires were collected with 609 valid returned responses, resulting in an effective return rate of 98.54%. Univariate and multiple linear regression analysis were applied to analyze the influencing factors of the total score of clinical medical staff's research ability.Results:The total score of research ability of 609 clinical medical personnel was 60.73±13.59. The results of multiple linear regression showed that participation in scientific research conferences, enthusiasm for scientific research activities, and the need for scientific research training all had positive effects on the self-assessment of scientific research ability, which together explained 52% of the total variance (adjusted R2=0.520, P<0.001). The top three " very important" options for medical staff research training were data analysis, research design, and research topic selection. Conclusions:Medical staff research skills need to be improved and there is a strong need for research training. Managers should refine scientific research management initiatives and provide hierarchical and targeted scientific research training to improve the overall medical staff's scientific research literacy and research ability, thereby promoting the progress of medical care in hospitals.

miR-7/TGF-β2 axis sustains acidic tumor microenvironment-induced lung cancer metastasis

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Correlation between the expressions of serum microRNA-29c-3p, microRNA-378a-3p and serum inflammatory factors, myocardial injury indexes and echocardiographic indexes in sepsis patients with myocardial injury and the value of prognosis evaluation / 中国医师进修杂志

Objective:To investigate the correlation between the expressions of microRNA (miR)-29c-3p, miR-378a-3p and serum inflammatory factors, myocardial injury indexes and echocardiographic indexes in sepsis patients with myocardial injury, and analyze the value of prognosis evaluation.Methods:Prospective research methods were used. Two hundred and eighty-six patients with sepsis in Handan Central Hospital from February 2019 to October 2021 were selected. The serum levels of miR-29c-3p and miR-378a-3p were detected by polymerase chain reaction, and serum Troponin I (TnI), creatine kinase isoenzyme MB (CK-MB), myoglobin (Mb), B-type brain natriuretic peptide (BNP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and procalcitonin (PCT) were detected. The left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), stroke output (SV), cardiac output (CO) and the ratio of early diastolic maximum mitral valve velocity to atrial systolic maximum velocity (E/A) were measured by echocardiography. Serum TnI≥0.15 μg/L was defined as myocardial injury, the survival status within 28 d of hospitalization in patients with myocardial injury was recorded, and the acute physiology and chronic health Ⅱ evaluation (APACHE Ⅱ) and sequential organ failure assessment (SOFA) were evaluated. Pearson method was used for correlation analysis; Multivariate Logistic regression was used to analyze the independent risk factors of death within 28 d of hospitalization in sepsis patients with myocardial injury; the receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of miR-29c-3p and miR-378a-3p in predicting the death within 28 d of hospitalization in septic patents with myocardial injury patients.Results:Among 286 patients with sepsis, 131 had myocardial injury (myocardial injury group), and 155 had no myocardial injury (non-myocardial injury group). The miR-29c-3p, Mb, CK-MB, BNP, TnI, TNF-α, IL-6, IL-1β, PCT, CRP, LVEDD and LVESD in myocardial injury group were significantly higher than those in non-myocardial injury group: 5.02 ± 1.69 vs. 2.01 ± 0.57, (102.35 ± 23.56) μg/L vs. (32.15 ± 9.12) μg/L, (25.01 ± 6.09) U/L vs. (13.02 ± 4.16) U/L, (905.23 ± 135.49) ng/L vs. (92.31 ± 26.35) ng/L, (0.23 ± 0.05) μg/L vs. (0.12 ± 0.02) μg/L, (13.41 ± 3.71) μg/L vs. (3.26 ± 0.95) μg/L, (9.02 ± 2.46) ng/L vs. (4.18 ± 1.03) ng/L, (71.45 ± 15.29) ng/L vs. (30.02 ± 6.39) ng/L, (1.05 ± 0.21) μg/L vs. (0.72 ± 0.13) μg/L, (21.35 ± 6.13) mg/L vs. (16.23 ± 4.57) mg/L, (37.45 ± 3.39) mm vs. (34.01 ± 2.15) mm and (50.12 ± 3.49) mm vs. (44.17 ± 3.02) mm, the miR-378a-3p, LVEF, SV, CO and E/A were significantly lower than those in non-myocardial injury group: 1.67 ± 0.36 vs. 3.02 ± 0.79, (46.32 ± 3.26)% vs. (56.24 ± 4.98)%, (48.21 ± 2.81) ml vs. (56.02 ± 3.49) ml, (3.11 ± 0.29) L/min vs. (4.15 ± 0.31) L/min and 0.98 ± 0.21 vs. 1.19 ± 0.32, and there were statistical differences ( P<0.01). Pearson correlation analysis result showed that miR-29c-3p was positive correlation with TNF-α, IL-6, IL-1β, PCT, CRP, Mb, CK-MB, BNP, TnI, LVEDD and LVESD in sepsis patients with myocardial injury ( P<0.01 or <0.05), and it was negative correlation with LVEF, SV, CO and E/A ( P<0.01); miR-378a-3p was negative correlation with TNF-α, IL-6, IL-1β, PCT, CRP, Mb, CK-MB, BNP, TnI, LVEDD and LVESD ( P<0.01 or <0.05), and it was positive correlation with LVEF, SV, CO and E/A P<0.01). Among 131 sepsis patients with myocardial injury, 55 patients died within 28 d of hospitalization (death subgroup), and 76 patients survived (survival subgroup). The mechanical ventilation rate, continuous renal replacement therapy rate, APACHE Ⅱ, SOFA, miR-29c-3p, Mb, CK-MB, TnI, BNP, TNF-α, IL-6, IL-1β, PCT, CRP, LVEDD and LVESD in death subgroup were significantly higher than those in survival subgroup, the miR-378a-3p, LVEF, SV, CO and E/A were significantly lower than those in survival subgroup, and there were statistical differences ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that APACHE Ⅱ, TnI, miR-29c-3p were independent risk factors for death within 28 d of hospitalization in sepsis patients with myocardial injury ( OR = 1.203, 2.451 and 1.394; 95% CI 1.085 to 1.334, 1.498 to 4.008 and 1.141 to 1.702; P<0.01); and the miR-378a-3p an independent protective factor for death within 28 d of hospitalization in sepsis patients with myocardial injury ( OR = 0.367, 95% CI 0.217 to 0.622, P<0.01). ROC curve analysis result show that the best cut-off values of miR-29c-3p and miR-378a-3p for predicting the death within 28 d of hospitalization in sepsis patients with myocardial injury were 5.00 and 1.65; the area under the curve of miR-29c-3p combined with miR-378a-3p for predicting the death within 28 d of hospitalization in septic patients with myocardial injury was significantly larger than that of the two separate applications (0.890 vs. 0.695 and 0.732), with a sensitivity of 87.0%, a specificity of 87.3%, and an accuracy of 86.8%. Conclusions:The expression of serum miR-29c-3p is increased and the expression of miR-378a-3p is decreased in sepsis patients with myocardial injury. The expressions of miR-29c-3p and miR-378a-3p are related to the degree of myocardial injury, echocardiogram indexes, the levels of inflammatory factors and prognosis. The miR-29c-3p and miR-378a-3p can be used as potential prognostic indexes for sepsis patients with myocardial injury.

A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

The outbreak of COVID-19 has emerged as a global pandemic. The unprecedented scale and severity call for rapid development of effective prophylactics or therapeutics. We here reported Nanobody (Nb) phage display libraries derived from four camels immunized with the SARS-CoV-2 spike receptor-binding domain (RBD), from which 381 Nbs were identified to recognize SARS-CoV-2-RBD. Furthermore, seven Nbs were shown to block interaction of human angiotensin converting enzyme 2 (ACE2) with SARS-CoV-2-RBD-variants, bat-SL-CoV-WIV1-RBD and SARS-CoV-1-RBD. Among the seven candidates, Nb11-59 exhibited the highest activity against authentic SARS-CoV-2 with ND50 of 0.55 g/mL. Nb11-59 can be produced on a large-scale in Pichia pastoris, with 20 g/L titer and 99.36% purity. It also showed good stability profile, and nebulization did not impact its stability. Overall, Nb11-59 might be a promising prophylactic and therapeutic molecule against COVID-19, especially through inhalation delivery. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/242867v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@e4434org.highwire.dtl.DTLVardef@9fee79org.highwire.dtl.DTLVardef@1e15bb1org.highwire.dtl.DTLVardef@4adb0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

Genotype-phenotype analysis of a homozygous familial hypercholesterolemia pedigree / 中华儿科杂志

Objective@#To analyze the genetic characteristics of a five generations pedigree with homozygous familial hypercholesterolemia (HoFH).@*Methods@#Prospective study. Twenty family members included a proband diagnosed as familial hyperlipidemia at the cardiology Department of Xi′an Children′s Hospital in October 2018 were research object. Clinical data were collected. Genome DNAs were extracted. Whole exons sequencing was performed on the proband using target capture next generation sequencing. Candidate gene mutation sites identified by bioinformatics were verified by Sanger sequencing in the family members. The genotype-phenotype correlation of the pedigree was analyzed between heterozygous mutation carriers and non-carriers.@*Results@#The proband was a 7-years and 10-month-old boy. He was born with a roundgreen bean size yellow skin protuberance in the skin of the coccyx. Since the age of 3-4 years old, xanthoma-like lesions with a diameter of 0.5-1.5 cm gradually appeared in the skin of bilateral elbow joints, knee joints and Achilles tendon. The height, weight and intellectual development of the child were the same as those of normal children at the same age. No similar xanthoma-like lesion was found in the other family members. The proband′s total cholesterol (TC) reached 18.16-21.24 mmol/L, and his low density lipoproteincholesterol (LDL-C) was 14.08-15.51 mmol/L. Carotid ultrasonography showed diffuse sclerotic plaques in bilateral carotid and vertebral arteries, and color Doppler echocardiography revealed aortic valve thickening and calcification. Gene testing identified that the proband carried a homozygous mutation C. 418G>A (p. E140K) in LDLR gene inherited from his parents who had a consanguineous marriage and carried a heterozygous mutation of LDLR-E140K, respectively.The TC, LDL-C and apolipoproteinB (ApoB) of LDLR-E140K gene heterozygous carriers ((8.40±0.13), (6.79±0.01) and (1.95±0.05) mmol/L, respectively) were significantly higher than those of non-carriers ((4.59±0.28), (3.35±0.39) and (0.86±0.10) mmol/L, t=7.269, 4.595, 6.311, respectively, P<0.05).@*Conclusions@#LDLR-E140K gene homozygous mutation is first reported to be associated with most severe phenotype HoFH. The genotype-phenotype analysis of the pedigree shows that the clinical phenotype of the proband with homozygous mutation is the most serious, and all the heterozygous mutation carriers present with hypercholesterolemia phenotype. The investigation confirms that LDLR-E140K is the pathogenic variation of familial hyperlipidemia.

Clinical and genetic analysis of a Chinese pedigree affected with Smith-Lemli-Opitz syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and pathogenic variants in a Chinese pedigree affected with Smith-Lemli-Opitz syndrome.@*METHODS@#Peripheral blood samples were collected from five members, including two affected ones, from the pedigree for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing as well as reverse transcription sequencing at the RNA level.@*RESULTS@#The proband and another affected child from the pedigree showed mental retardation, dyskinesia, microcephaly, micrognathia, anteverted nares, and 2/3 toe syndactyly. The proband also had hypospadia, single upper incisor, and lower serum cholesterol level. Both children were found to harbor a paternally derived c.278C>T (p.T93M) variant and a maternally derived c.907G>A (p.G303R) variant of the DHCR7 gene. Both were known pathogenic mutations.@*CONCLUSION@#The compound heterozygous mutations of c.278C>T (p.T93M) and c.907G>A (p.G303R) of the DHCR7 gene probably underlay the disease in this pedigree. Above finding has enabled early diagnosis and treatment of Smith-Lemli-Opitz syndrome.

Analysis of genotype-phenotype correlation for a novel MYH7-D554Y mutation identified in an ethnic Han Chinese pedigree affected with hypertrophic cardiomyopathy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genotype-phenotype correlation of a MYH7-D554Y mutation identified in an ethnic Han Chinese pedigree affected with hypertrophic cardiomyopathy.</p><p><b>METHODS</b>Ninety six cardiovascular disease-related genes were detected in the proband by exonic amplification and high-throughput sequencing. Suspected mutations were verified by Sanger sequencing among 300 healthy controls as well as family members of the proband. The pathogenicity and conservation of the detected mutations were analyzed with ClustalX, MutationTaster, PolyPhen-2, Provean and SIFT software.</p><p><b>RESULTS</b>Four of the 5 first-degree relatives of the proband were diagnosed with hypertrophic cardiomyopathy. The proband has featured extremely hypertrophic left ventricular wall with a maximal thickness of 35 mm. Genetic testing showed that four of them have carried a heterozygous c.1660G>T (p.Asp554Tyr) mutation of the MYH7 gene, who the remaining one was phenotypically normal and did not carry the mutation. The mutation has not been recorded by the Human Gene Mutation Database (HGMD) and other databases. Bioinformatics analysis suggested that the mutation site is highly conserved and that the mutation is pathogenic.</p><p><b>CONCLUSION</b>The p.Asp554Tyr mutation of the MYH7 gene probably underlies the hypertrophic cardiomyopathy in this pedigree.</p>

A prospective cohort study on triglycerides levels and risk of acute pancreatitis / 中华消化杂志

Objective To investigate the effects of fasting serum triglycerides (TG) levels at different baseline on the risk of new-onset acute pancreatitis (AP) in in-service and retired employees of Kailuan Group.Methods A total of 125 178 in-service and retired employees of Kailuan Group who received health check-ups from 2006 to 2009 and had no AP history but had complete TG data were prospectively enrolled.According to quantile level,the baseline serum fasting TG level of study subjects were divided into ＜1.01 mmol/L group (n=42 128),1.01 to 1.64 mmol/L group (n=41 711) and ＞ 1.64 mmol/L group (n=41 339).The incidence of new-onset AP of these three groups was analyzed.The survival curve was plotted by Kaplan-Meier method.The cumulative incidence rate was calculated and tested by log-rank method.And multivariate Cox proportional hazards regression model was performed to calculate hazard ratios (HR) of baseline fasting serum TG level for AP.Results After followed up for (7.36±1.23) years,a total of 193 cases of AP occurred.The incidences of AP in ＜1.01 mmol/L group,1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group were 1.43 events/10 000 person-years,2.37 events/10 000 person-years and 2.49 events/10 000 person-years,respectively.The cumulative incidence rates of AP in ＜1.01 mmol/L group,1.01 to 1.64 mmol/L group and ＞1.64 mmol/L group were 0.10％ (44/42 128),0.18％ (73/41 711) and 0.18％ (76/41 339),respectively,and the difference was statistically significant (x2 =9.998,P=0.007).The results of multivariate Cox proportional hazards regression model analysis indicated that the risk of AP increased in 1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group compared with that of ＜1.01 mmol/L group,HR and 95％ confidence interval (CI) were 1.56 (1.07 to 2.29) and 1.57 (1.06 to 2.32),respectively.After excluded onset AP within one year,with a control group of ＜1.01 mmol/L group,the results of multivariate Cox proportional hazards regression model analysis indicated that the HR and 95％CI for AP of 1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group were 1.70 (1.11 to 2.58) and 1.69 (1.10 to 2.60),respectively.Conclusion Baseline fasting serum TG levels over 1.01 mmol/L may increase the risk of AP.

Updated insights into the pathogenesis of sepsis / 医学研究生学报

Sepsis and septic shock are common critical diseases in the ICU, which have a high mortality and seriously affect the patients'' quality of life.The pathogenesis of sepsis is very complicated and involves the changes in the functions of multiple systems and organs.Recently, the investigation into the potential mechanisms underlying the development of sepsis is becoming a hotspot all over the world.The author presents an overview on the advances in the studies of the pathogenesis of sepsis, relating to the imbalance of inflammatory response, immune dysfunction, abnormal blood coagulation, nerve-endocrine-immunity network, mitochondrial function damage, endoplasmic reticulum stress, autophagy, and genetic polymorphism, in order to provide some theoretical evidence for the prevention and treatment of sepsis in clinical practice.

Clinical effect of tacrolimus for Henoch-Sch(o)nlein purpura nephritis in children / 新乡医学院学报

Objective To evaluate the efficacy and safety of tacrolimus (TAC) for treatment of Henoch-SchSnlein purpura nephritis in children.Methods Forty children with Henoch-SchSnlein purpura nephritis (pathological grade Ⅲ-Ⅵ) in Children's Hospital Affiliated to Soochow University from January 2013 to June 2016 were selected and divided into TAC group (n =19) and cyclophosphamide (CTX) group (n =21).The children in TAC group were given TAC orally;the children in CTX group were given CTX pulse therapy intravenously.The 24 h urine protein,urine red blood cell count,serum albumin,serum creatinine and blood urea nitrogen of children before treatment and after 6 months treatment were observed and compared between the two groups.The treatment effects and adverse reactions of patients were observed and compared between the two groups.Results There was no statistic difference in the 24 h urine protein,urine red blood cells count,serum albumin,blood creatinine and blood urea nitrogen levels of children between the two groups before treatment (P ＞ 0.05).The 24 h urinary protein and urine red blood cells count of children after 6 months of treatment in the two groups were significantly lower than those before treatment (P ＜ 0.05);there was no statistic difference in the serum albumin,serum creatinine and blood urea nitrogen levels of children in the two groups before treatment and after 6 months of treatment (P ＞ 0.05).Mter 6 months of treatment,the 24 h urine protein and urine red blood cells count of children in TAC group were significantly lower than those in the CTX group (P ＜ 0.05);there was no statistic difference in the serum albumin,serum creatinine and blood urea nitrogen levels of children between the two groups (P ＞ 0.05).After 6 months treatment,the effective rate of children in the TAC group was significantly higher than that in the CTX group (x2 =4.607,P ＜ 0.05).The incidence of adverse reactions of children in the TAC group was significantly lower than that in the CTX group (x2 =4.043,P ＜ 0.05).Conclusion TAC is effective in treatment of Henoch-Sch(o)nlein purpura nephritis in children.It is easy to take,and has less adverse reactions.

Isoflavone preventing ultraviolet radiation induced skin injuries of mice / 第二军医大学学报

Objective To explore the protective effect of external use of isoflavone cream on ultraviolet radiation induced skin injuries of mice and its mechanisms.Methods A total of 48 male ICR mice were randomly assigned to vehicle (control),ultraviolet radiation (UV),2％ isoflavone+UV and 3％ isoflavone+-UV groups,with 12 mice in each group,and the naked skin of mice in the four groups were treated with sesame oil (15 min),sesame oil (15 min) in combined UV (first radiation with 1.55 J/cm2 long-wave ultraviolet [UVA] for 18 min,and then with 0.95 J/cm2 middle-wave ultraviolet [UVB] for 11 min),2％ isoflavone (15 min) in combined UV and 3％ isoflavone (15 min) in combined UV,respectively.After radiation for 7 days,the UV-exposed skins were obtained to observe the morphological and histological changes using H-E staining.The contents of interleukin (IL)-1β,IL-6,tumor necrosis factor α (TNF-α),malondialdehyde (MDA),superoxide dismutase (SOD) and catalase (CAT) in the skins were determined using ELISA or corresponding kits.Results (1) UV irradiation caused erythema and crusting in skin,and inflammatory cell infiltration in the dermis and fractured elastic fiber were observed microscopically.Isoflavone pretreatment effectively ameliorated these damages in mice skin.(2) Compared with the control group,contents of IL-1β,IL-6 and TNF-α in the UV group were significantly increased (P＜0.05);however,the contents of IL-1β,IL-6 and TNF-α were significantly reversed by isoflavone pretreatment (P＜0.05,P＜0.01).(3) Compared with the control group,the skin MDA content in the UV group was significantly increased (P＜0.05),SOD and CAT contents were significantly decreased (P＜0.05);however,the isoflavone pretreatment significantly reversed the alterations of MDA,SOD and CAT (P＜0.05,P＜0.01).Conclusion Isoflavone exerts protective effects against the ultraviolet induced skin damage in mice through alleviating lipid peroxidation,oxidative stress and inflammatory response.

Analysis of genotype and phenotype correlation of MYH7-V878A mutation among ethnic Han Chinese pedigrees affected with hypertrophic cardiomyopathy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the phenotype-genotype correlation of MYH7-V878A mutation.</p><p><b>METHODS</b>Exonic amplification and high-throughput sequencing of 96-cardiovascular disease-related genes were carried out on probands from 210 pedigrees affected with hypertrophic cardiomyopathy (HCM). For the probands, their family members, and 300 healthy volunteers, the identified MYH7-V878A mutation was verified by Sanger sequencing. Information of the HCM patients and their family members, including clinical data, physical examination, echocardiography (UCG), electrocardiography (ECG), and conserved sequence of the mutation among various species were analyzed.</p><p><b>RESULTS</b>A MYH7-V878A mutation was detected in five HCM pedigrees containing 31 family members. Fourteen members have carried the mutation, among whom 11 were diagnosed with HCM, while 3 did not meet the diagnostic criteria. Some of the fourteen members also carried other mutations. Family members not carrying the mutation had normal UCG and ECG. No MYH7-V878A mutation was found among the 300 healthy volunteers. Analysis of sequence conservation showed that the amino acid is located in highly conserved regions among various species.</p><p><b>CONCLUSION</b>MYH7-V878A is a hot spot among ethnic Han Chinese with a high penetrance. Functional analysis of the conserved sequences suggested that the mutation may cause significant alteration of the function. MYH7-V878A has a significant value for the early diagnosis of HCM.</p>

Progress of small molecule anti-tumor covalent drugs / 中国药科大学学报

@#Covalent drugs are a type of inhibitors which exert their biological functions by irreversibly binding to the target through covalent bonds. With the marketing of kinase inhibitor covalent drugs against tumor, covalent drugs have regained the attention for drug discovery and have become a recent hotspot of anti-tumor drugs. In this paper, the action mechanisms, pharmacological advantages and the development strategies of modern covalent drugs are discussed and the recent research progress of anti-tumor covalent inhibitors is summarized, which provides a reference for the design of new anti-tumor covalent drugs.

Study on the relationship between serum ferritin level at different trimester of pregnancy and gestational diabetes mellitus / 中国医师杂志

Objective To investigate the association between serum ferritin(SF) level at early and mid trimester of pregnancy and gestational diabetes mellitus (GDM) and insulin resistance (IR).Methods A total of 192 cases of women who were accepted antenatal examination from the first trimester of pregnancy at Yueqing People Hospital from July,2012 to October,2013 was prospectively analyzed and followed up.All cases were divided into two groups:96 cases of GDM pregnant women who were diagnosed as GDM at mid trimester of pregnancy as GDM group,and 96 cases of pregnant women with normal glucose tolerance at the same time as the control,normal glucose tolerance (NGT group).The differences in clinical data were compared between two groups.The relationship between SF level and fasting plasma glucose (FPG),fasting insulin (FINS),homeostasis model assessment insulin resistance (HOMA-IR),and C-peptide was investigated with Spearman rank correlation analysis.The predictive values of SF and relative variables to GDM were calculated by receiver operating characteristic curve (ROC) or Logistic regression analysis.Results (1) There was statistically significant difference in body weight and body mass index (BMI) at prepregnancy and mid trimester of pregnancy,Hb,FPG,FINS,SF,and C-peptide at the first trimester of pregnancy,SF level and FPG and HOMA-IR and C-peptide at mid trimester of pregnancy between two groups (P ＜ 0.01 or P ＜ 0.05).(2) As showed by Spearman rank correlation analysis,there was statistical correlation between SF at mid trimester of pregnancy,and FPG,FINS,HOMA-IR and C-peptide (P ＜0.01 or P ＜ 0.05);while no statistical correlation was found between SF at the first trimester of pregnancy and the same factors above (P ＞ 0.05).(3) The area under the ROC curve of SF at mid trimester of pregnancy for GDM was 0.653.The sensitivity and specificity were 68.8％ and 59.4％ in predicting GDM at the cut-off value of 16.61 ng/ml.As showed by Logistic regression analysis,high level of SF at mid trimester of pregnancy was a independent risk factor for GDM.Odds ratio (OR) was 1.032 (95％ CI:1.008 ～ 1.058,P ＜ 0.01).Conclusions The relationship between SF at different trimester of pregnancy and GDM is variant.There is relationship between high level SF of mid trimester of pregnancy in GDM pregnant women and IR.The level of SF might predict the occurrence of GDM.

Relationship between electrocardiographic and genetic mutation (MYH7-H1717Q, MYLK2-K324E and KCNQ1-R190W) phenotype in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relationship between electrocardiographic (ECG) and genetic mutations of patients with hypertrophic cardiomyopathy (HCM), and early ECG changes in HCM patients.</p><p><b>METHODS</b>Clinical, 12-lead ECG and echocardiographic examination as well as genetic examinations were made in a three-generation Chinses HCM pedigree with 8 family members (4 males). The clinical characterization and ECG parameters were analyzed and their relationship with genotypes in the family was explored.</p><p><b>RESULTS</b>Four missense mutations (MYH7-H1717Q, MYLK2-K324E, KCNQ1-R190W, TMEM70-I147T) were detected in this pedigree. The proband carried all 4 mutations and 5 members carried 2 mutations. Corrected QTc interval of KCNQ1-H1717Q carriers was significantly prolonged and was consistent with the ECG characterization of long QT syndrome. MYLK2-K324E and KCNQ1-R190W carriers presented with Q wave and(or) depressed ST segment, as well as flatted or reversed T waves in leads from anterolateral and inferior ventricular walls. ECG results showed ST segment depression, flat and inverted T wave in the gene mutation carriers with normal echocardiographic examination results. ECG and echocardiographic results were normal in TMEM70-I147T mutation carrier.</p><p><b>CONCLUSIONS</b>The combined mutations of the genes associated with cardiac ion channels and HCM are linked with the ECG phenotype changes in this HCM pedigree. The variations in ECG parameters due to the genetic mutation appear earlier than the echocardiography and clinical manifestations. Variation in ECG may become one of the indexes for early diagnostic screening and disease progression of the HCM gene mutation carriers.</p>