Risk factors for 28-day mortality in patients with sepsis related myocardial injury in the intensive care unit / 中国医师杂志

Objective:To analyze and explore the independent risk factors of 28-day mortality in patients with septic myocardial injury.Methods:A retrospective cohort study was conducted to collect clinical data of 505 patients diagnosed with sepsis related myocardial injury admitted to the intensive care unit (ICU) of the Affiliated Hospital of Jining Medical University from January 2015 to December 2020. According to the 28-day survival status of patients, they were divided into survival group and death group. COX multivariate regression analysis was used to analyze the influencing factors of the 28-day mortality rate of sepsis related myocardial injury patients, and receiver operating characteristic (ROC) curves were drawn to evaluate the effectiveness of independent risk factors in predicting the 28-day mortality rate of sepsis related myocardial injury patients.Results:A total of 505 patients with sepsis myocardial injury were included, of which 282 survived on 28 days and 223 died, with a mortality rate of 44.16%. COX multivariate regression analysis showed that Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, blood lactate (LAC), oxygenation index (PaO 2/FiO 2), admission heart rate, and albumin were independent risk factors for sepsis associated myocardial injury mortality at 28 days (all P<0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of SOFA score was 0.766 2, and the 95% confidence interval (95% CI) was 0.724 5-0.807 9; The predictive value of 28-day mortality in sepsis associated myocardial injury patients was superior to APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin [The AUC values were 0.754 1(0.711 5-0.796 7), 0.752 6(0.710 1-0.795 1), 0.697 0(0.649 7-0.744 2), 0.623 2(0.573 7-0.672 7), and 0.620 3(0.570 8-0.669 7), respectively]. Conclusions:SOFA score, APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin are independent risk factors for the 28-day mortality rate of sepsis related myocardial injury. Clinical practice should identify these factors early, intervene early, and improve patient prognosis.

Predictive value of serum neurofilament light chain on neurologic function in out-of-hospital cardiac arrest patients / 中华急诊医学杂志

Objective:To determine the predictive value of serum neurofilament light chain (NfL) on neurologic function in out-of-hospital cardiac arrest (OHCA) patients.Methods:The clinical data of 96 OHCA patients admitted to Cangzhou Central Hospital from January 2018 to March 2022 were retrospectively analyzed. According to the Glasgow-Pittsburgh cerebral performance category (CPC) upon hospital discharge, the patients were divided into the favorable neurologic function (grade 1-2) and poor neurologic function (grade 3-5) groups. The difference of serum NfL was compared between the two groups, and the relationship between serum NfL and neurologic function was assessed using correlation analysis and logistic regression analysis. The area under the curve (AUC), sensitivity, and specificity of serum Nfl were calculated by receiver operating characteristic (ROC) curve. Hanley & McNeil method test was used to compare the difference of AUCs between serum NfL and neuron specific enolase (NSE).Results:Twenty-six percent (25/96) patients were discharged with favorable neurologic function. Serum NfL in the favorable neurological function group was significantly lower than that in the poor neurologic function group (47.6 pg/mL vs. 261.4 pg/mL, P<0.001). Correlation analysis showed that serum NfL was positively correlated with neurologic function ( r=0.69, P<0.001). Logistic regression analysis showed that serum NfL was independently associated with neurological function ( OR=0.92, 95% CI: 0.86-0.98; P=0.010). ROC curve indicated that the AUC of serum NfL in predicting poor neurologic function was 0.95 (95% CI: 0.92-0.99), with a sensitivity of 84.5% and a specificity of 100% at the cutoff value of 80.0 pg/mL. The AUC of serum NSE in predicting poor neurologic function was 0.79 (95% CI: 0.69-0.89), with a sensitivity of 67.6% and a specificity of 80.0% at the cutoff value of 45.1 ng/mL. A pairwise comparison using Hanley & McNeil method showed that the AUC of serum NfL in predicting poor neurologic function was higher than that of NSE ( Z=3.22, P=0.001). Conclusions:Serum NfL is helpful for clinician to predict neurologic function in OHCA patients.

A real-world study of the effects of endocrine therapy on liver function in breast cancer / 中华外科杂志

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.

Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin.@*METHODS@#Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively.@*RESULTS@#Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05).@*CONCLUSION@#Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

Quality assessment of pharmacoeconomic evaluation literature in China from 2018 to 2022 / 中国药房

OBJECTIVE To analyze existing problems of pharmacoeconomic evaluation research in China and to improve the standardization and scientificity of research， so as to provide more high-quality evidence for government decision-making. METHODS Retrieved from CNKI， Wanfang database， VIP， PubMed， Web of Science from 2018 to 2022， the literature related to pharmacoeconomic evaluation in China was collected； Excel 2016 software was used to extract the key information of the included literature which met inclusion criteria. The Quality of Health Economic Studies （QHES） scale was used to evaluate the quality of the included literature. RESULTS A total of 113 pieces of literature were included in this study， involving 85 pieces of Chinese literature and 28 pieces of English literature. The overall score of QHES included literature was 65.7， of which the average score of Chinese literature was 62.0 and English literature was 76.9. The median quality scores for the literature in 2018， 2019， 2020， 2021 and 2022 were 62.0， 70.5， 59.3， 71.0， and 73.0， respectively. Of these， 65 pieces of literature reported the research perspective； 36 reported the discount rate indistinctly； 25 provided unclear definitions of thresholds； and 53 used two sensitivity analysis methods. Among different items of the QHES scale， item 2 （research perspective）， item 8 （time range and discount rate）， item 14 （potential bias） and item 16 （sources of funding） had low percentage of scores. CONCLUSIONS From 2018 to 2022， pharmacoeconomic evaluation literature published by Chinese academics has generally shown a fluctuating upward trend in terms of quality， but there is still some room for improvement. The main problems in current pharmacoeconomics research in China include unclear understanding of the research perspective， single measurement of cost and health outcomes， unreasonable design of time horizon， indistinct description of the threshold or discount rate， and lack of sensitivity analysis.

Comparison of mental health status of pregnant women with assisted reproductive technology and natural pregnancy / 中国实用护理杂志

Objective:To explore whether assisted reproductive technology (ART) can affect the mental health of pregnant women during pregnancy.Methods:Convenient sampling method was used to select 500 pregnant women who underwent prenatal examination in Dalian Women and Children′s Medical Group from July 2019 to July 2020, including 193 cases of ART pregnant women (observation group) and 307 cases of natural pregnant women (control group). PEM-D psychosomatic holistic diagnosis and treatment system combined with Symptom Checklist- 90 (SCL-90), 7- item Generalized Anxiety Disorder Scale (GAD-7), 9-item Patient Health Questionnaire (PHQ-9) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate and compare the mental health status between the two groups.Results:The total score of SCL-90 in the observation group was (154.34 ± 14.42), which was significantly higher than that in the control group (142.42 ± 14.39), the difference was statistically significant ( t=5.35, P<0.05). The scores of anxiety, depression and paranoia in the observation group were (2.17 ± 0.47), (2.15 ± 0.68), (1.78 ± 0.45), which were significantly higher than those in the control group (1.95 ± 0.52), (1.77 ± 0.55), (1.58 ± 0.39), the differences were statistically significant ( t=2.86, 3.88, 3.20, all P<0.015). The scores of GAD-7 and PHQ-9 in the observation group were (6.72 ± 2.44), (5.43 ± 2.54), which were significantly higher than those in the control group (5.76 ± 2.47), (3.74 ± 1.66), the differences were statistically significant ( t=2.52, 3.57, both P<0.05). There was no significant difference in PSQI scores between the two groups ( P>0.05). Conclusions:ART affects the mental health of pregnant women, especially increases the level of depression and anxiety. We should provide corresponding psychological support and help for these pregnant women to reduce their depression and anxiety level.

Exploratory research of the value of abbreviated comprehensive geriatric assessment in elderly breast cancer patients / 中华老年医学杂志

Objective:To explore the value and feasibility of abbreviated comprehensive geriatric assessment(aCGA)grading in elderly patients with breast cancer.Methods:From June 2019 to January 2020, elderly patients with breast cancer aged 65 years and above were enrolled.Eastern Cooperative Oncology Group(ECOG)score and aCGA classification were performed respectively.Clinical characteristics, score distribution and differences between the two assessment methods were compared and analyzed.Results:A total of 61 cases of breast cancer patients aged 65 years and above were included in our study.According to the assessment of aCGA, grade A accounted for 65.5%(40/61), grade B accounted for 27.9%(17/61), and grade C accounted for 6.6%(4/61), among which 82.0%(50/61 cases)of the patients had complications.And the most common complications were hypertension, cardiovascular disease and diabetes.Among the 50 patients with ECOG score 0-1, 74.0%(37/50)were aCGA grade A, and 26.0%(13/50)were aCGA grade B.Conclusions:According to the aCGA grading, about two thirds of breast cancer patients over 65 years old are assessed as grade A, which indicates that they might have better tolerance during the treatment.However, among the patients with 0-1 score according to the ECOG score, some patients still have a slightly worse grade(aCGA grade B, which shows slightly worse health condition), suggesting that the refinement degree of ECOG score may be insufficient, and the health damage of some patients may be underestimated.

Analysis of allocation of antipsychotics in regions with different economic levels in Shandong province / 中国药房

OBJECTIVE To investigate the allocation of antipsycho tics in regions with different economic levels in Shandong province，and to provide reference for strengthening the management of antipsychotics allocation and promoting the balance of regional allocation. METHODS The procurement information of the secondary and tertiary public medical institutions in Shandong province from 2016 to 2019 was collected from the Drug Centralized Bidding and Procurement Information Platform of Shandong Provincial Medical Institutions. The procurement varieties of antipsychotics ，allocation proportion and procurement cost per 10 000 people were analyzed in area with different economic levels in Shandong province. RESULTS From 2016 to 2019，there were 18 kinds of antipsychotics purchased by secondary and tertiary public medical institutions in Shandong province （9 kinds of first- and second-generation antipsychotics respectively ），and the average number of purchased varieties were 3.50-4.42. The average number of purchased varieties in undeveloped areas （3.59-4.48 kinds）were slightly higher than that in developed areas （3.41-4.36 kinds）. In these four years ，average allocation proportion of antipsychotics was 17.19％，and most of them showed a fluctuating increase （the average annual increase ranged 4.64％-38.34％）. The allocation proportion of second-generation antipsychotics was higher in developed areas than that in undeveloped areas. The purchasing cost per 10 000 people showed an upward trend of fluctuation ， ranging from 2.45 to 7 440.20 yuan. Among the 18 antipsychotics procured from 2016 to 2019，61.11％，61.11％，83.33％ and 72.22％ of them were procured by developed areas with higher procurement costs per 10 000 people than by undeveloped areas. The total procurement cost of essential medicine per 10，000 people in developed areas （11 382.99-39 650.90 yuan）was also higher than that in undeveloped areas （8 353.15-30 561.77 yuan）. CONCLUSIONS The allocation proportion of antipsychotics is low in Shandong province ，and the allocation proportion of second-generation antipsychotics in developed areas are higher than that in undeveloped areas.

Research progress in anti-colorectal cancer mechanism of berberine / 药学学报

Colorectal cancer (CRC) is a common malignancy burdening people globally, with increasing morbidity and mortality nowadays, due to the alternation in the diet type and lifestyle in modern society. Berberine, a type of benzylisoquinoline alkaloid, is widely present in numerous medicinal plants, particularly including Coptidis Rhizoma. Mounting evidence reveals that berberine possesses an array of pharmacological effects, such as anti-inflammation, anti-bacterium, anti-cancer, anti-diabetes mellitus and so on. In particular, berberine exhibits substantial inhibition on various types of cancers including CRC. Hereby, we sought to systematically review the suppressive effect of berberine on CRC through the diminishment of the proliferation and metastasis, induction of apoptosis, arrest of cell cycle, regulation of inflammatory reaction, the reverse of chemotherapeutic resistance and restoration of gut microbiota in CRC, so as to shed light on the in-depth mechanisms underlying the treatment of CRC with berberine in the clinical setting.

UHPLC-Q-Exactive Orbitrap MS/MS-based rapid identification of chemical components in substance benchmark of Kaixin San / 中国中药杂志

Ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS/MS) was used for rapid identification of the chemical components in Kaixin San substance benchmark. The gradient elution was performed through a Waters ACQUITY~(TM) BEH C_(18) column(2.1 mm×150 mm, 1.7 μm) with water-acetonitrile as mobile phase, a column temperature of 30 ℃, a flow rate of 0.3 mL·min~(-1), and a sample size of 1 μL. The scanning was performed in the negative ion mode. The complex component groups in Kaixin San substance benchmark were quickly and accurately identified and clearly assigned based on the comparison of the retention time and MS data with those of the reference substance as well as the relative molecular weight of the same or similar components in the mass spectrum database and literature. A total of 77 compounds were identified, including 26 saponins, 13 triterpenoid acids, 20 oligosaccharide esters, 5 xanthones, and 13 other compounds. The qualitative method established in this study can systematically, accurately, and quickly identify the chemical components in Kaixin San substance benchmark, which can provide a basis for the further analysis of its active components in vivo and the establishment of its quality control system.

Screening and influence of common psychological disorders in the perinatal period / 中国实用护理杂志

With the change of medical model, the impact of common psychological disorders on the occurrence, development and treatment has been paid more attention to. If the diagnosis is not timely, it can result in serious long-term effects on the wellbeing of women, their partners and infants. We reviewed the recent foreign studies on the common psychological problems of perinatal women and summarize the epidemiology, identification and interventions, so as to understand the impact on the offspring. It is of great significance to strengthen the training for health professionals in wider psychosocial assessment and to adopt effective intervention methods to alleviate the adverse psychological state of perinatal women.

Correlation between serum level of miRNA-106a expression with clinicopathological characteristics and prognosis of patients with renal cell carcinoma / 中华医学遗传学杂志

OBJECTIVE@#To analyze the expression of microRNA-106a(miR-106a) in renal cell carcinoma (RCC) and its correlation with clinicopathological characteristics and prognosis of patients.@*METHODS@#Serum samples of 64 patients with newly diagnosed RCC were collected as the study group, and serum samples of 40 healthy individuals were used as the control group. Real-time fluorescence quantitative PCR was used to determine the expression level of miR-106a in each group. The correlation between miR-106a expression and clinicopathological characteristics of the patients was studied with single factor analysis and multiple Logistic regression model. Kaplan-Meier survival curve was used to analyze its correlation with the prognosis of patients.@*RESULTS@#Before surgery, compared with the control group (1.17± 0.58), RCC patients with high- (9.15± 0.96) and low-expression(3.45± 0.37) had increased expression of miR-106a. Postoperatively, the expression level of miR-106a in both groups of patients decreased to 1.53± 0.18 and 1.75± 0.21, respectively. The area under the curve (AUC) of the diagnostic value of serum miR-106a for RCC was 0.782 (95% CI: 0.661-0.902). With an optimal cutoff value of 0.531, the sensitivity was 78.10% and the specificity was 75.00%. Serum miR-106a level of RCC patients with TNM stage T3 or T4, clinical stage II or III, lymph node metastasis, and recurrence were significantly increased. The high expression of serum miR-106a in RCC patients has an independent relationship with the tumor TNM stage and lymph node metastasis. Of the 64 follow-up patients, 4 were lost and 30 had died. Among them, the median survival time of patients in the miR-106a high expression group was 30 months, which was significantly shorter than that of the low expression group (52 months).@*CONCLUSION@#The serum level of miR-106a is elevated in RCC patients, and may be used as a molecular marker for the diagnosis of RCC. High serum expression of miR-106a is an independent predictor for tumor TNM stage and lymph node metastasis, as well as an independent predictor for poor prognosis of RCC patients.

Active components and action mechanism of Shenmai Injection in treatment of atrial fibrillation based on network pharmacology and molecular docking / 中国中药杂志

This study aims to explore the active components and molecular mechanism of Shenmai Injection in the treatment of atrial fibrillation(AF) based on the application of network pharmacology and molecular docking technology. The chemical components of single herbs of Shenmai Injection were collected from TCMSP and TCMID, with the standard chemical name and PubChem CID(referred to as CID) obtained from PubChem database. The active components were screened using SwissADME, and their targets were predicted using SwissTargetPrediction. Targets related to AF treatment were identified using GeneCards, OMIM, and other databases. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. The single herb-active component-potential target network was constructed using Cytoscape, and the clusterProfiler R function package was used to perform the gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment. The protein-protein interaction(PPI) network of intersection targets was generated based on the STRING database. The hub target protein was identified by visualization using Cytoscape, and then docked to its reverse-selected active components. The analysis showed that there were 65 active components with 681 corresponding targets in Shenmai Injection, 2 798 targets related to AF treatment, and 235 intersection targets involving 2 549 GO functions and 153 KEGG pathways. Finally, hub target proteins, including RAC-alpha serine/threonine-protein kinase(AKT1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA), and estrogen receptor 1(ESR1), were screened out by PPI network visualization. The molecular docking was performed for 39 active components screened out in reverse, among which 30 active components de-monstrated high affinity. Among them, homoisoflavanoids CID 10871974, CID 5319742, and CID 10361149 had stronger affinity docking with AKT1. This study preliminarily indicates that Shenmai Injection treats AF through multiple components, multiple targets, and multiple pathways. Homoisoflavonoids of Ophiopogon japonicus are its important active components, which target AKT1 to regulate metabolism, inflammation, and apoptosis in AF treatment.

Progress of Tumor Infiltrating Lymphocytes in Immunotherapy of Triple Negative Breast Cancer / 中国医学科学院学报

Breast cancer has become the most common cancer for women in China.Lack of effective therapeutic targets,triple negative breast cancer(TNBC)has poorer prognosis compared with other subtypes of breast cancer.Tumor infiltrating lymphocytes(TILs)are a group of heterogeneous lymphocytes around the tumor,which are believed as immunoreactive products of host immune response to tumor antigens.At present,there have been reports on the predictive effect of TILs on the prognosis of breast cancer,and the available studies focus mainly on TNBC.This article briefly reviews the recent progress of tumor infiltrating lymphocytes in immunotherapy of TNBC.

Application Value of Abbreviated Comprehensive Geriatric Assessment in Elderly Female Breast Cancer Patients / 中国医学科学院学报

Objective To evaluate the application value of abbreviated comprehensive geriatric assessment(aCGA)in elderly female breast cancer patients. Methods Eight aspects of the traditional CGA were simplified to form the aCGA assessment table,based on which the patients were classified into three grades of A,B and C according to the total scores.This study enrolled the elderly female patients with breast cancer aged 70 years and above who were treated in PUMC Hospital from June 2018 to January 2020.Eastern Cooperative Oncology Group(ECOG)scoring and aCGA grading were performed respectively,and the results of the two methods were compared. Results Of the 162 patients,111(68.5%)were classified by the aGGA method as grade A,43(26.5%)as grade B,and 8(5.0%)as grade C;131(80.9%)cases have concurrent diseases,and the most common complications were hypertension(

Distribution of bacteria infected by metagenomic sequencing technology in maxillofacial space / 华西口腔医学杂志

OBJECTIVES@#This study aimed to compare and analyze the consistency and difference between metageno-mic next-generation sequencing (mNGS) and conventional bacterial culture in the detection of pathogenic microorganisms in maxillofacial space infection, as well as to provide a new detection method for the early clinical identification of pathogenic bacteria in maxillofacial space infection.@*METHODS@#The clinical data of 16 patients with oral and maxillofacial space infections in the First Affiliated Hospital of Zhengzhou University from March 2020 to June 2020 were collected. mNGS and conventional bacterial culture methods were used to detect pus. We then analyzed and compared the test results of the two methods, including the test cycle, positive detection rate, anaerobic bacteria, facultative anaerobes and aerobic bacteria detection rates, distribution of pathogenic bacteria, relative species abundance, and resistance genes.@*RESULTS@#The average inspection period of mNGS was (18.81±3.73) h, and the average inspection period of bacterial culture was (83.25±11.64) h, the former was shorter than the latter (@*CONCLUSIONS@#Compared with conventional bacterial culture, mNGS has the characteristics of short test time, high sensitivity, and high accuracy. Thus, it is a new detection method for the early identification of pathogenic bacteria in maxillofacial space infection and is beneficial to the early clinical diagnosis and treatment of the disease.

Clinical analysis of methylmalonic acidemia presented with hemolytic uremic syndrome in children / 中华实用儿科临床杂志

Objective:To understand clinical characteristics, treatment effects and prognosis of children with methylmalonic acidemia (MMA) presented with hemolytic uremic syndrome(HUS).Methods:The medical records of children with MMA were collected in Beijing Children′s Hospital, Capital Medical University from January 2012 to January 2019, the clinical manifestations, laboratory, imaging material, inspection results, renal pathological, gene analysis, treatment effect, and prognosis of MMA children with renal damage were analyzed, and were followed-up for 1-7 years.Results:Thirty cases were diagnosed as MMA with secondary renal damage.Eight cases(26.67%) showed as MMA-HUS.Age was from 1 month and 14 days to 12 years and 10 months old.There were 4 males and 4 females.The concentration of urine methylmalonic acid increased by 10-62 times.All were combined with hyperhomocysteine(HCY). The level of serum methylmalonic acid(1.5-11.8 mg/L), propylene carnitine(6.33-9.77 μmol/L)and the ratio of propylene /ethylene carnitine (0.24-0.29)were increased.Manifested as the mental and physical development retardation, anemia, jaundice, renal dysfunction, platelet reduction, hematuria, proteinuria in 8 cases, hypertension in 6 cases, frequent vomiting and convulsions in 2 cases.Two cases had a positive family history.Renal pathology showed that mesangial cells and mesangial matrix proliferation broadening, electron dense deposits no mesangial area, renal tubular epithelial cell swelling degeneration, immunofluorescence was negative.Two cases were genetically analyzed. One case was a CblC type MMACHC compound heterozygous mutation[c.80A>G(p.Q27R); c.217C>T(p.R73X)] and CblX type HCFC1 heterozygous mutation [c.3757G>A(p.R1253C)] double mutation; 1 case was a CblC type MMACHC compound heterozygous mutation[c.365A>T(p.H122L); c.609 G>A(p.W203X)]. Children diagnosed were treated with vitamin B 12, etc.Four cases of children gave up.The others, after treatment, were improved. Conclusions:MMA-HUS might be associated with multiple organ failure.Early diagnosis was the key, timely treatment could effectively control the disease, improve the prognosis.It should be followed up for ever.

Mechanism of ursolic acid in regulating colorectal cancer cell HCT116 autophagy through hedgehog signaling pathway / 中国中药杂志

To prove that ursolic acid(UA)could activate the autophagy of colorectal cancer HCT116 cells by inhibiting hedgehog signaling pathway. The effect of UA on the viability of HCT116 cells was determined by MTT assay. The effect of UA on the proliferation and migration of HCT116 cells was detected by crystal violet staining and scratch test. In the study on autophagy, the time points were screened out first: the autophagy fluorescence intensity of UA acting on HCT116 at different time points were detected by Cell Meter~(TM) Autophagy Assay Kit; Western blot was used to detect the expression of autophagy protein P62 at different time points. Then, Cell Meter~(TM) Autophagy Assay Kit was used to detect the effect of UA on autophagy fluorescence intensity of HCT116 cells. The effect of different doses of UA on the expressions of LC3Ⅱ and P62 proteins in HCT116 cells were detected by Western blot. Further, AdPlus-mCherry-GFP-LC3 B adenovirus transfection was used to detect the effects of UA on autophagy flux of HCT116 cells; UA combined with autophagy inhibitor chloroquine(CQ) was used to detect the expression of LC3Ⅱ by Western blot. In terms of mechanism, the effect of UA on hedgehog signaling pathway-related proteins in HCT116 cells was detected by Western blot. The results showed that UA inhibited the activity, proliferation and migration of HCT116 cells. UA enhanced the fluorescence intensity of autophagy in HCT116 cells, while promoting the expression of LC3Ⅱ and inhibiting the expression of P62, in a time and dose dependent manner. UA activated the autophagy in HCT116 cells, which manifested that UA resulted in the accumulation of fluorescence spots and strengthened the fluorescence intensity of autophagosomes; compared with UA alone, UA combined with autophagy inhibitor CQ promoted the expression of LC3Ⅱ. UA reduced the expressions of PTCH1, GLI1, SMO, SHH and c-Myc in hedgehog signaling pathway, while increased the expression of Sufu. In conclusion, our study showed that UA activated autophagy in colorectal cancer HCT116 cells, which was related to the mechanism in inhibiting hedgehog signaling pathway activity.

Ursolic acid ameliorates azoxymethane/dextran sulfate sodium-caused colorectal cancer by inhibition of Wnt signaling cascade / 中国药理学与毒理学杂志

OBJECTIVE To investigate the pharmacological effect of ursolic acid (UA) on colitis-associated colorec?tal cancer (CAC) and its underlying mechanism based on the Wnt signaling pathway. METHODS The CAC model in mice was established by azoxymethane (AOM) combined and dextran sulfate sodium salt (DSS), accompanied by treat?ment with various dosages of UA and concomitant appraisal of body weight, stool and physical state of the mice. After the sacrifice of the mice, the tumor and length of the colorectum were measured, followed by retrieval of the liver, spleen, thymus and tumor tissue for downstream assays. The levels of inflammatory factors interleukin-6 (IL-6), IL-1βand C-reactive protein (CRP) in the tumor and serum were examined by enzyme-linked immunosorbent assay (ELISA). The pathological changes of colorectal tissues were observed by HE staining. The levels in tumors of Wnt/β-catenin sig?naling pathway-related proteins Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry (IHC). The mRNA expressions of Wnt4, GSK-3β,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, Bax, caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR (RT-qPCR). The protein levels of Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, phospho-β-catenin, phospho-GSK-3β, Bcl-2 and Bax in tumors were probed by analyzed by Western blotting (WB). Also, RNA-seq was employed to assess the gut microbiota in the mice. RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC, evidenced by improved physical state, body weight, survival rate, colorectal length, the mass of liver, thy?mus, spleen, and decreased CAC load and colorectal mass. UA attenuated the levels of IL-6, IL-1β and CRP in the mouse serum and colorectal tumor in a dose-dependent manner. HE staining showed that UA lessened carcinogenesis in the colorectum, with lower infiltration of lymphocytes, versus the control. IHC indicated that UA mitigated the expres?sion of Wnt4,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and promoted the GSK-3βexpression, compared with the control. Furthermore, UA diminished the mRNA expressions of Wnt4, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and heightened the mRNA levels of GSK-3β, caspase-3, capase-9 and Bax in CAC. The results of mRNA expressions were verified by WB analysis, which revealed that UA impeded the protein expression of Wnt4,β-catenin, c-Myc, cyclin D1, Bcl-2, TCF4, LEF1, and elevated the protein levels of GSK-3βand Bax, phospho-β-catenin in mouse CAC. In addi?tion, UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC. CONCLU?SION Ursolic acid may protect against CAC, potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.

Scutellarin induces apoptosis of colorectal cancer HCT116 cells via Hippo signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of scutellarin on the apoptosis of human colorectal cancer cells via the Hippo signaling pathway in vitro. METHODS MTT colorimetric method was used to detect the influence of scutellar?in on the survival rate of HCT116 cells. And the effect of scutellarin at various concentrations on cell morphology was observed by microscopy. Cell scratch experiment was used to detect the influence of scutellarin on the migration of HCT116 cells. Hoechst33342/PI double staining method was used to detect the effect of scutellarin on the apoptosis of HCT116 cells. Western blotting method was used to assess the action of scutellarin on the expressions of Hippo signal?ing pathway-related proteins Mst1, Lats1, YAP1, p-YAP(Ser127), TAZ, and its downstream effector proteins c-Myc and cyclin D1, as well as apoptosis-related proteins Bcl-2 and Bax in HCT116 cells. RESULTS Scutellarin significantly affected the morphology of HCT116 cells and reduced the survival rate of HCT116 cells. Hoechst33342/PI double stain?ing showed that scutellarin effectively induced the apoptosis of HCT116 cells. Western blotting analysis showed that the expression levels of Hippo signaling pathway-related proteins Mst1, Lats1, YAP1, TAZ and its downstream effector pro?teins c-Myc, cyclin D1 were down-regulated in a concentration-dependent manner by scutellarin, and the expression of p-YAP (ser127) was up-regulated. Moreover, scutellarin substantially lessened the expression level of apoptosis-related protein Bcl-2, and promoted the protein level of Bax. CONCLUSION Scutellarin may inhibit the proliferation and migra?tion of HCT116 cells, while induce its apoptosis, potentially by activation of Hippo signaling pathway.