Role of apical sodium-dependent bile acid transporter in hepatobiliary diseases / 临床肝胆病杂志

Apical sodium-dependent bile acid transporter （ASBT） is a key transporter responsible for intestinal reabsorption of bile acid and plays an important role in maintaining bile acid and cholesterol homeostasis， and its expression is regulated by various factors including transcription factors， nuclear receptors， and intestinal microflora. The abnormal expression and function of ASBT can lead to disorders in the metabolism of bile acid and cholesterol， causing a variety of hepatobiliary diseases. At present， ASBT has attracted wide attention as a therapeutic target. This article elaborates on the biological characteristics and expression regulation mechanism of ASBT and reviews the role of ASBT in hepatobiliary diseases， in order to provide a new direction for the treatment of related diseases.

Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes / 药学学报

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

Study on mechanism of Hippo/YAP pathway inhibition by salvianolic acid B in HuH-7 cells / 中国药理学通报

Aim To investigate whether salvianolic acid B ( Sal B) has inhibitory effect on hepatoma HuH- 7 cells and explore whether it works via Hippo/YAP signaling pathway. Methods HuH-7 cells were induced by TGF-β1 (9 pmol · L

Research progress in ferroptosis pathways and ubiquitination modification of ferroptosis-related molecules / 中国药理学通报

Ferroptosis is an iron-dependent cell death caused by phospholipid peroxidation damage of polyunsaturated fatty acids on cell membranes and involves several pathways, including the iron homeostasis regulatory pathway, the cystine glutamate reverse transporter (system Xc) pathway and the voltage-dependent anion channel (VDAC) pathway. Ferroptosis is involved in the development of several diseases (e. g. myocardial infarction, stroke, cancer and degenerative diseases). The ubiquitination is an important post-translational modification of various protein molecules in the organism. Studies have shown that regulating the ubiquitination of ferroptosis pathway-related molecules can control cellular ferroptosis. Targeting the ubiquitination of ferroptosis pathway-related molecules can effectively promote or inhibit ferroptosis, which is expected to be a new strategy for the treatment of cancer or cardiovascular diseases. In this paper we review the progress of the ferroptosis pathways and the ubiquitination modification of ferroptosis-related molecules.

The influencing Factors of Doctor-patient Shared Decision Making: A Qualitative Study / 中国医学伦理学

To explore the barriers and facilitators of shared decision making, 23 clinicians were selected for semi-structured interviews by purpose sampling and convenience sampling with phenomenological methods in qualitative research, and 7-step of Colaizzi was used to analyze the interview data. Three themes and twelve subthemes were extracted, included: individual factors of doctors (role cognition, perceived outcomes, communication skills, clinical expertise, cognitive bias) , individual factors of patients (general information, lack of disease knowledge, willingness to participate in decision making) and environmental factors (clinical situation, social environment, resources and social influence) . There were many barriers and facilitators in the implementation of doctor-patient shared decision making. It is necessary to scientifically analyze and actively deal with the influence of each factor, and find reasonable countermeasures to promote the clinical implementation of shared decision making.

Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats

Abstract Objectives: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. Methods: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autoly-sosome, by EM) and pyroptosis (IL-1β, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. Results: After the treatment wound area rate, IL-1β by ELISA, and IL-1β, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. Conclusions: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.

Biological Functions of CD24 in Malignant Tumor and its Application as a Novel Anti-tumor Target / 中国生物化学与分子生物学报

CD24 is a highly glycosylated protein that is linked to the plasma membrane via a glycosylphosphatidylinositol anchor. As a universally expressed protein on immune cells, CD24 is also overexpressed in nearly 70% of human cancers including hepatocellular carcinoma, lung cancer and bladder cancer et al. Studies revealed that CD24 is involved in regulating cell proliferation, migration and invasion in cancer cells by interacting with P-selectin, activating Wnt and MAPK signaling pathway or other signaling molecules. Therefore, CD24-targeted siRNA or antibody has a great potential to exert anti-tumor effects by blocking the interaction. There are currently several agents or regiments targeting CD24 for the treatment of patients with various kinds of cancers that are undergoing assessment in the preclinical study at present. Recent studies revealed that CD24 was able to interact with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which located on the surface of macrophages, to compose a novel immune checkpoint. The binding of CD24 to Siglec-10 elicits an inhibitory signaling cascade, limits macrophage phagocytosis, evades immune surveillance, and promotes tumor growth, which suggested that CD24 may be a potential target in anti-tumor immunotherapy. In this review, we introduced the structure and function of CD24 and its role in cancer progression and anti-tumor immunity. Moreover, the progression in developing novel anti-cancer drugs or treatment strategies with the target of CD24 was summarized, which aims to provide a new insight in CD24-targeting therapy.

Analysis on influencing factors of leg work-related musculoskeletal disorders among shipbuilding workers / 中国职业医学

{L-End}Objective To investigate the current status and influencing factors of leg work-related musculoskeletal disorders (WMSDs) in shipbuilding workers. {L-End}Methods A total of 3 393 shipbuilding workers from Guangdong Province, Liaoning Province, Shandong Province, and Beijing City were selected as the research subjects using the convenience sampling method. The Chinese Version of the Musculoskeletal Disorders Questionnaire was used to investigate the prevalence of leg WMSDs in the past year. A multivariate logistic regression model was used to analyze the influencing factors of leg WMSDs. {L-End}Results The prevalence of leg WMSDs in the research subjects was 11.3% (382/3 393). The result of multivariate logistic regression showed that the risk of leg WMSDs was higher in workers with a length of service >10 years than those with a length of service <5 years (P<0.05). Workers with frequent used of vibration tools at work had higher the risk of leg WMSDs (all P<0.05). Workers who did the same work every day, had insufficient rest time, had a shortage of department staff, and those who often repeated the same leg movements had a higher risk of leg WMSDs (all P<0.05). The risk of leg WMSDs in workers who sometimes stand for a long time was lower than that in workers who rarely stand for a long time (P<0.01). {L-End}Conclusion Length of service, rarely long-standing work, use of vibration tools at work, daily engagement in the same work, in-adequate rest time, shortage of department staff, and frequent repetition of the same leg movements are all influencing factors for leg WMSDs in shipbuilding workers.

Study on the relationship between local muscle fatigue and related metabolic biomarkers in simulated manual lifting / 中国职业医学

{L-End}Objective To analyze the local muscle response under continuous ergonomic workload by simulating manual lifting, and to screen the sensitive metabolic biomarkers during fatigue process. {L-End}Methods A total of 13 healthy male volunteers were selected as the study subjects using simple random sampling method. Study subjects underwent repetitive simulated manual lifting for four periods (T1 to T4), each lasting 12 minutes. The degree of work-related fatigue in the forearm, upper arm, shoulder, back, and leg muscles, and the whole body was accessed using Borg 6-20 Rating of Perceived Exertion (RPE) Scale. The venous blood samples were collected from elbow between each two periods to detect the levels of eight metabolic biomarkers: ammonia, lactate, creatine kinase, lactate dehydrogenase (LDH), C-terminal telopeptide of type Ⅰ collagen (CTX-Ⅰ), C-terminal telopeptide of type Ⅱ collagen (CTX-Ⅱ), cartilage oligomeric matrix protein (COMP), and calcium ions. {L-End}Results The RPE scores of the study subjects for the muscles of five body parts and the whole body increased with the increasing lifting periods (all P<0.01). Fatigue was observed in all target muscles, with overall body fatigue occurring in the T2 period. The levels of ammonia, lactate, creatine kinase, LDH, COMP, and calcium ions in the serum of study subjects were higher in the T1 to T4 periods than in the T0 period (all P<0.05). The serum CTX-Ⅰ level was higher in the T1 and T3 periods than that in the T0 period (all P<0.05) , and the serum CTX-Ⅱ level was higher in the T1, T2 and T4 periods than that in the T0 period (all P<0.05). The level of these eight serum metabolic biomarkers fluctuated during the T1 to T4 periods. The serum creatine kinase level increased with the period of lifting (all P<0.05). The serum lactate level was higher in the T3 period than those in the T1 and T2 periods (all P<0.05). The serum LDH and calcium ion levels were higher in the T2 to T4 periods than that in the T1 period (all P<0.05). The serum COMP level was higher in the T2 and T3 periods than that in the T1 period (all P<0.05). Except for CTX-Ⅰ, the levels of other seven metabolic markers in serum were higher in individuals after fatigue than before fatigue (all P<0.05). {L-End}Conclusion Serum metabolic biomarkers such as ammonia, lactate, creatine kinase, calcium ions, LDH, CTX-Ⅱ, and COMP exhibit significant changes before and after fatigue. These metabolic biomarkers could be used as sensitive biomarkers for evaluating muscle fatigue during repetitive works.

Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on SIRT2 expression / 浙江大学学报·医学版

OBJECTIVES@#To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma (CCA) based on the expression of silence information regulator 2 (SIRT2).@*METHODS@#The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases. Gene set enrichment analysis (GSEA) was used to explore potential mechanisms of SIRT2 in CCA. The expression of SIRT2 protein in CCA tissues and normal tissues (including 44 pairs of specimens) was also detected by immunohistochemistry (IHC) staining in 89 resectable CCA patients who underwent surgical treatment in The First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021. The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed. A survival prediction model for patients with resectable CCA was constructed with COX regression results, the calibration curve and the time-dependent receiver operating characteristic curve (ROC) were used to evaluate the performance of the constructed model, and the predictive power between this model and the AJCC/TNM staging system (8th Edition) was compared.@*RESULTS@#SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases. IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues. GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway, such as fatty acid metabolism, oxidative phosphorylation, amino acid metabolism, etc. SIRT2 expression level was related to serum triglycerides level, tumor size and lymph node metastasis (all P<0.05). The survival analysis results showed that the patients with higher SIRT2 expression had a significant lower overall survival (OS) than patients with lower SIRT2 expression (P<0.05). Univariate COX regression analysis suggested that pathological differentiation, clinical stage, postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients (all P<0.05). Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients (both P<0.05). A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed. The C-index of the model was 0.675, and the area under the time-dependent ROC curve (AUC) for predicting survival in the first, second, and third years was 0.879, 0.778, and 0.953, respectively, which were superior to those of AJCC/TNM staging system (8th Edition).@*CONCLUSIONS@#SIRT2 is highly expressed in CCA tissues, which is associated with poor prognosis in patients with resectable CCA. The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system (8th Edition) in prediction of survival of postoperative CCA patients.

Form Properties of Moving Targets Bias Smooth Pursuit Target Selection in Monkeys / 神经科学通报·英文版

During natural viewing, we often recognize multiple objects, detect their motion, and select one object as the target to track. It remains to be determined how such behavior is guided by the integration of visual form and motion perception. To address this, we studied how monkeys made a choice to track moving targets with different forms by smooth pursuit eye movements in a two-target task. We found that pursuit responses were biased toward the motion direction of a target with a hole. By computing the relative weighting, we found that the target with a hole exhibited a larger weight for vector computation. The global hole feature dominated other form properties. This dominance failed to account for changes in pursuit responses to a target with different forms moving singly. These findings suggest that the integration of visual form and motion perception can reshape the competition in sensorimotor networks to guide behavioral selection.

Causes of Abnormal Hemoglobin Electrophoresis / 中国实验血液学杂志

OBJECTIVE@#To investigate the possible causes of abnormal hemoglobin electrophoresis results.@*METHODS@#The hemoglobin electrophoresis results of 5 696 patients in the First Affiliated Hospital of Chengdu Medical College from September 2018 to July 2021 were collected, and the abnormal results and clinical significance were analyzed.@*RESULTS@#The results of 486 patients (accounting for 8.53%) were abnormal, of which 300 cases had increased HbA2, 135 cases had decreased HbA2, 44 cases had increased F alone, and 7 cases had abnormal hemoglobin bands. Among the 486 patients, 246 patients were thalassemia gene positive (the positive rate was 50.62%), including 29 cases of α thalassemia, 208 cases of β thalassemia and 9 cases of αβ thalassemia. Among the patients with elevated HbA2, 68.67% were detected β thalassemia, 3.00% αβ thalassemia, 9.33% were suspected to be caused by macrocytosis, 6.33% by thyroid dysfunction, and 12.67% by uncertainty of the method. Among the patients with reduced HbA2, 21.48% were detected α thalassemia, 60.00% iron deficiency anemia, 8.15% were suspected to be caused by thyroid dysfunction, and 10.37% by uncertainty of the method. Among the patients with elevated F alone, the results of thalassemia gene detection were negative, 40.91% of them were suspected to be caused by macrocytosis, 27.27% by hereditary persistence of fetal hemoglobin, 29.55% by special physiological condition of pregnant women, and 2.27% by hyperthyroidism. Abnormal hemoglobin bands were detected in 7 patients, including 4 cases of hemoglobin D, 2 cases of hemoglobin E, and 1 case of hemoglobin J.@*CONCLUSION@#Thalassemia, iron deficiency anemia, macrocytosis such as megaloblastic anemia and non-severe aplastic anemia, thyroid dysfunction, hereditary persistence of fetal hemoglobin, abnormal hemoglobin diseases, the uncertainty of the method are all important causes of abnormal hemoglobin electrophoresis results. In clinical work, the patient's indicators should be comprehensively analyzed to determine the possible cause.

A cohort study of vincristine-induced peripheral neuropathy in children / 中国当代儿科杂志

OBJECTIVES@#To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN.@*METHODS@#The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups.@*RESULTS@#A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05).@*CONCLUSIONS@#There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.

Berberine targets the electron transport chain complex I and reveals the landscape of OXPHOS dependency in acute myeloid leukemia with IDH1 mutation / 中国天然药物

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1mi.

Effect of MG53 on Cardiac Function Affected by Acute Doxorubicin-Induced Cardiotoxicity in Mice and Its Mechanism / 中山大学学报(医学科学版)

ObjectiveThis study was designed to explore the effect of MG53 on cardiac function affected by acute doxorubicin （DOX）-induced cardiotoxicity （DIC） in mice and its possible mechanism. MethodsIn vivo， C57BL/6 mice were injected intraperitoneally with twenty mg/kg DOX for one week to induce the acute DIC. In vitro， neonatal rat cardiomyocytes （NRCs） were treated with 1 μmol/L DOX to induce DIC. A small animal ultrasound imaging system was used to evaluate cardiac function， and the left ventricular changes in ejection fraction （EF） and fraction shortening （FS） were measured. qPCR technology was used to evaluate cardiac remodeling related factors ANP， BNP and α-MHC， autophagy-related factors Beclin1 and LC3， and apoptosis-related factor CASPASE3. Autophagy-related protein levels of Beclin1， LC3 and apoptosis-related protein levels of caspase3 were assessed by Western Blot. Transmission electron microscopy （TEM） was used to detect autophagosomes in heart tissues. TUNEL assay kit was used to detect apoptosis in neonatal murine cardiomyocytes. ResultsThe small animal ultrasound imaging revealed cardiac function was significantly reduced by doxorubicin in the DOX group and DOX+AAV9-NC group compared with the sham group （EF： Sham： 86.06 ± 2.08 vs. DOX：58.97 ± 1.62， P < 0.000 1； Sham： 86.06 ± 2.08 vs. DOX+AAV9-NC： 59.00 ± 1.86， P < 0.000 1. FS： Sham： 45.47 ± 1.95 vs. DOX：30.68 ± 1.21， P < 0.000 1； Sham： 45.47 ± 1.95 vs. DOX+AAV9-NC： 30.79 ± 1.13， P < 0.000 1）. However， the overexpression of MG53 with adeno-associated virus9 （AAV9） ameliorated cardiac dysfunction （EF： DOX+AAV9-MG53： 66.93 ± 1.78 vs. DOX+AAV9-NC： 59.00 ± 1.86， P < 0.000 1. FS： DOX+AAV9-MG53： 36.35 ± 1.33 vs. DOX+AAV9-NC： 30.79 ± 1.13， P < 0.000 1）. TEM showed autophagosomes were increased in the DOX+AAV9-MG53 group compared with the DOX group and DOX+AAV9-NC. qPCR results suggested that MG53 down-regulated the mRNA expression of cardiac remodeling related genes. Additionally， Western blot results confirmed that the protein level of caspases3 was decreased and Beclin1 and LC3 expression was increased in the DOX+AAV9-MG53 group compared with those in the DOX group and DOX+AAV9-NC group （caspase： DOX+AAV9-MG53： 1.49 ± 0.13 vs. DOX+AAV9-NC： 2.49 ± 0.46， P = 0.000 2； Beclin-1： DOX+AAV9-MG53：0.82 ± 0.02 vs. DOX+AAV9-NC： 0.62 ± 0.05， P < 0.000 1； LC3： DOX+AAV9-MG53： 0.83 ± 0.04 vs. DOX+AAV9-NC： 0.40 ± 0.05， P < 0.000 1）. In contrast， knockdown of MG53 significantly up-regulated the protein level of Caspase3 and significantly down-regulated the protein level of Beclin1 and LC3 （caspase： DOX+si-MG53： 4.52 ± 0.28 vs. DOX+si-NC： 3.37 ± 0.08， P < 0.000 1； Beclin-1： DOX+si-MG53： 0.34 ± 0.06 vs. DOX+si-NC： 0.54 ± 0.07， P = 0.026 2； LC3： DOX+si-MG53： 0.41 ± 0.12 vs. DOX+si-NC： 0.70 ± 0.07， P = 0.001 5）. TUNEL analysis showed overexpression of MG53 significantly inhibited the apoptosis of cardiomyocytes （DOX+Ad-MG53： 9.41 ± 0.53 vs. DOX+Ad-NC： 29.34 ± 7.29， P < 0.000 1）， and knockdown of MG53 significantly facilitate the apoptosis of cardiomyocytes （DOX+si-MG53： 71.34 ± 5.90 vs. DOX+si-NC： 32.19 ± 9.91， P < 0.000 1）. ConclusionMG53 inhibits cardiac apoptosis and enhances autophagy， which delays cardiac remodeling and ameliorates cardiac dysfunction.

Optimization of the preparation process of ethanol extracts from Centipeda minima and study on its anti-inflammatory activity of different extraction sites / 中国药房

OBJECTIVE To optimize the preparation technology of ethanol extracts from Centipeda minima， and investigate the anti-inflammatory activities of different extraction sites. METHODS Single factor test and response surface methodology were adopted to investigate the effects of ethanol volume fraction， extraction time， solid-liquid ratio and extraction times on the heating reflux extraction technology of total triterpenoids ethanol extract using the extraction rate of total triterpenoids of C. minima as indexes， optimize the extraction technology and carry out validation. Using dexamethasone as positive control drug， the effects of different extraction sites of C. minima （petroleum ether part， ethyl acetate part， n-butanol part， water part） on nitric oxide （NO） production in mononuclear macrophage RAW 264.7 cells of mice induced by lipopolysaccharide （LPS） were compared； the half inhibitory concentration （IC50） was calculated. RESULTS The optimal extraction technology of total triterpenoids ethanol extracts of C. minima was as follows： ethanol volume fraction of 70%， solid-liquid ratio of 1∶40 （g/mL）， extraction time of 2.0 h and extraction times of 3 times. The 3 times of validation tests showed that average extraction rate of total triterpenoids of C. minima was 1.134%， relative error of which with the predicted value was 0.02%. The petroleum ether part and ethyl acetate part of C. minima could inhibit the generation of NO in RAW 264.7 cells induced by lipopolysaccharide to different degrees. IC50 values of NO production were 2.44 μg/mL and 2.22 μg/mL， respectively， and both of them were lower than those of positive control drug dexamethasone （7.65 μg/mL）. CONCLUSIONS The optimized preparation process of ethanol extracts from C. minima is stability and feasibility. The petroleum ether part and ethyl acetate part have obvious anti-inflammatory effects.

Phenotype-genotype analysis of the autosomal recessive hereditary hearing loss caused by OTOA variations / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.

Research, development and application of collagen: a review / 生物工程学报

Collagen, which widely exists in skin, bone, muscle and other tissues, is a major structural protein in mammalian extracellular matrix. It participates in cell proliferation, differentiation, migration and signal transmission, plays an important role in tissue support and repair and exerts a protective effect. Collagen is widely used in tissue engineering, clinical medicine, food industry, packaging materials, cosmetics and medical beauty due to its good biological characteristics. This paper reviews the biological characteristics of collagen and its application in bioengineering research and development in recent years. Finally, we prospect the future application of collagen as a biomimetic material.

TRPV4-induced Neurofilament Injury Contributes to Memory Impairment after High Intensity and Low Frequency Noise Exposures / 生物医学与环境科学（英文）

OBJECTIVE@#Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN.@*METHODS@#Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.@*RESULTS@#The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.@*CONCLUSION@#TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.

Epidemiological and etiological characteristics of active surveillance of foodborne illness / 公共卫生与预防医学

Objective To realize the epidemiological and pathogenic characteristics of foodborne illness in Shiyan in 2019 and provide targeted measures for the prevention and control work of the foodborne illness． Methods The active surveillance data of foodborne illness in shiyan in 2019 were collected and analyzed. The Salmonella strains isolated from the patients with foodborne illness were tested with serotyping，PFGE molecular classification and drug sensitivity test respectively according to《National foodborne illness surveillance workbook 2019》. Result A total of 3 191 cases of foodborne illness were analyzed. The pre-school children were the highest-risk group of foodborne diseases. Grain and grain product was the main suspicious contaminated food．The main location of eating place was family. A total of 330 samples were tested. The positive detection rate of foodborne illness was 20.30%（73/330）.The main pathogen were Rotavirus and Salmonella,and the detection rates were 11.21%(37/330) and 4.85%(16/330) respectively. The pre-school children were the group with the highest detection rate, which was 57.27% (63/110). The dominant serotype of the 14 Salmonella strains isolated from patients were Salmonella typhimurium and Salmonella enteritis. 14 different genotypes were obtained through PFGE classification and clustering. 64.29% (9/14) of Salmonella strains were multidrug-resistant strains. The drug resistance rates of ampicillin and tetracycline were the highest, which were 71.43%（11/14）and 64.29%（10/14）respectively. Conclusions The publicity and education of food safety should be strengthened and the surveillance network system of food-borne disease should be further improved according to the epidemiological and pathogenic characteristics of foodborne illness in Shiyan in 2019, and the use of clinical antibiotics should be controlled reasonably as well.