Aim To establish thioacetamide(TAA)-induced mouse intrahepatic cholangiocarcinoma(ICC)model and investi-gate the characteristics so as to provide an experimental basis for exploring the pathological mechanisms of ICC and evaluating new drugs for ICC treatment.Methods C57BL/6J mice were ran-domly divided into the normal controls(NC)and TAA group.The mice in the NC group were fed with sterilized water,while those in the model group with 600 mg·L-1 TAA solution for 32 weeks.Blood was collected from the eyeballs of the anesthetized mice and used for detecting serum ALT,AST,DBIL,and TBIL levels.The morphology of mice livers was observed.The patho-logical changes in liver tissue were observed using HE,Sirius red,Masson,and Prussian blue staining.CK7,CK19,Ki67,CD68,TNF-α,and α-SMA levels were detected by immunohis-tochemistry staining.The mRNA and protein levels of ICC mark-ers were detected by RT-qPCR and Western blot.HNF4α+CK19+cells in liver tissue were detected by immunofluorescence assay.Results We found tumor nodules on the surface of livers in the mice treated with TAA.The pathological results showed inflammatory cell infiltration,tubular shape of tumor cells with arrangement and hepatic fibrosis.The levels of ALT,AST,DBIL,TBIL in serum were upregulated after TAA induction.Meanwhile,ICC markers CK7 and CK19,and the proliferative marker Ki67 were upregulated in liver tissue induced by TAA.CD68,a marker of macrophage,and TNF-α level were also up-regulated in liver tissue of TAA-treated mice.The α-SMA-posi-tive staining was increased,suggesting the activation of hepatic stellate cells(HSCs).Most interestingly,HNF4α+CK19+bi-phenotype cells were found in liver tissue of TAA-treated mice,suggesting that the biphenotype cells originated from hepatocytes.Conclusions TAA can be used to induce the ICC model in mice,with the characteristics of inflammatory cell infiltration,HSCs activation,liver fibrosis,and hepatocyte transformation in-to ICC cells,etc.,which is similar to that in human ICC.Therefore,the mouse ICC model can be used for exploring the mechanisms of ICC and evaluating the effects of endogenous mol-ecules and new drugs on ICC.

Objective To propose a human life signal separation and reconstruction method based on optimized variational mode decomposition(VMD)to improve the accuracy and timeliness of the life detection radar in extracting and separating human life signals such as heartbeat and respiration.Methods Firstly,the particle swarm optimization algorithm was used to optimize the parameters of VMD,and the human life signal was decomposed into a series of intrinsic mode functions(IMFs);secondly,the alignment entropy of each IMF was calculated,the noise was removed based on the alignment entropy threshold,and the remaining components were reconstructed to form human life signals;finally,the method proposed was compared with infinite impulse response(IIR)filtering,VMD and complete ensemble empirical mode decomposition with adaptive nosie(CEEMDAN)to verify its performance.Results Under different noise levels the proposed method outperformed IIR filtering,VMD and CEEMDAN in evaluation metrics of signal-to-noise ratio and root-mean-square error,and behaved better than CEEMDAN in terms of computational time-consumption.Conclusion The proposed method realizes rapid separation and reconstruction of vital signals such as heartbeat and respiration while effectively filtering out the noise,which has broad application prospects in the fields of non-contact vital signs detection of bum/scald patients,infectious disease patients and newborns and the search and rescue of buried casualties after a disaster.[Chinese Medical Equipment Journal,2024,45(3):9-15]

OBJECTIVES: To investigate the value of CCKBR^fl/fl villin-Cre mice as a mouse model of salt-sensitive hypertension (SSH). METHODS: In the first part, 2-month-old CCKBR^fl/fl villin-Cre mice (CKO) and control CCKBR^fl/fl mice (WT) were fed with normal diet (0.4% NaCl) or high salt diet (4% NaCl), separately for 6 weeks. In the rescue study, one week of hydrochlorothiazide or saline injection were treated with the CKO mice fed high salt diet. The blood pressure, biochemical indexes, and the expression of small intestinal sodium transporters (NHE3, NKCC1, eNaC) was detected. The organ injury markers (MMP2/MMP9) and the histopathological changes of kidneys were observed, whereas the changes of duodenal sodium absorption were detected by small intestinal perfusion in vivo. RESULTS: The CCKBR^fl/fl villin-Cre mice with high salt intake exhibited high blood pressure, increased duodenal sodium absorption and urinary sodium excretion, and with renal injury. The protein expression of NHE3, NKCC1 and eNaC were also significant increase in the intestine of CKO-HS mice. Treatment with hydrochlorothiazide remarkably attenuated the elevated blood pressure by high salt absorption in the CCKBR^fl/fl villin-Cre mice, but no significant histopathological changes were observed. CONCLUSIONS These results support a crucial role of intestinal Cckbr deficiency on SSH development and the diuretic antihypertension effect in CCKBR^fl/fl villin-Cre mice. The CCKBR^fl/fl villin-Cre mice with the high salt intake may serve as a stable model of salt-sensitive hypertensive induced by sodium overloading.

AIM: To analyze the relationship between ocular signs and quality of life in patients with thyroid-associated ophthalmopathy(TAO).METHODS:A total of 356 patients with TAO who treated at a general hospital in Chengdu from October 2019 to December 2019 were selected. Their basic information and ocular signs(intraocular press, visual acuity, exophthalmos and eyelid retraction)were collected. In addition, the Graves Ophthalmopathy Quality of Life Scale(GO-QOL)was used to evaluate patients' quality of life.RESULTS:The median of visual function and social psychology of patients with TAO were 87.50 and 68.75 respectively. It was indicated that TAO patients' visual function scores were related to intraocular pressure, visual acuity and eyelid retraction(all P<0.05), social psychology scores were related to visual acuity(P<0.05), the high intraocular pressure had a significant influence on patients' visual function scores(P=0.001), and different visual acuity had a significant influence on the social psychology scores of patients with TAO(P=0.012).CONCLUSION:High intraocular pressure and impaired vision can reduce TAO patients' quality of life. Hence, medical staff should pay attention to the ocular signs during symptom management, especially the high intraocular pressure and low visual acuity, actively treating and preventing adverse ocular signs, so as to improve the quality of life of patients with TAO.

Objective To analyze the epidemic trend of hepatitis B virus (HBV) in 18 minority nationalities in Yunnan Province from 2009 to 2018, so as to explore the ethnic differences in the incidence of HBV in Yunnan Province. Methods Based on the reported incidence data of hepatitis B in China's disease prevention and control information system from 2009 to 2018, descriptive epidemiology method was used to describe and analyze the incidence of hepatitis B in different ethnic groups, and K-means clustering method was used to explore and analyze the annual average incidence of hepatitis B in different ethnic groups. Results From 2009 to 2018, the average incidence of hepatitis B in Yunnan Province was 44.26/100 000, which was much lower than the overall level of China every year; the average incidence of hepatitis B in ethnic groups was 41.27/100 000, slightly lower than the overall level of Yunnan every year. The prevalence of hepatitis B was different in different ethnic groups. The average incidence of Wa was significantly higher than others (95.26/100 000), and Jingpo was the lowest (22.51/100 000). According to the incidence of hepatitis B, different ethnic groups were divided into three categories: high incidence ethnic group, middle incidence ethnic group and low incidence ethnic group. Conclusion There are ethnic differences in the incidence of hepatitis B in Yunnan Province. The incidence of hepatitis B in some ethnic groups is higher than that in the whole country all the year round, which is the key population in the prevention and control of hepatitis B.

Objective: To analysis and identify the chemical components in Trichosanthis Fructus by UPLC-LTQ-Orbitrap-MS. Method: Samples of Trichosanthis Fructus were extracted by ultrasonic with 70% methanol after smashing and sifting by 40 mesh sieve. Thermo Scientific^TM Dionex^TM UltiMate^TM 3000 Rapid Separation LC system performed UPLC separations with Waters HSS T3-C₁₈(2.1 mm×100 mm,1.8 μm) column. The mobile phase was 0.1% formic acid water(A)-methanol(B) with a gradient elution. The volume flow was 0.3 mL ·min^-1. A Thermo Scientific^TM LTQ-Orbitrap mass spectrometer equipped with a ESI probe was employed. The samples were respectively scanned in MS¹ and MS² mode of positive and negative ions. According to the chromatographic peak separation,mass signal intensity,and the number of molecular ions in MS¹ model,the extraction condition,chromatogram and mass spectrum parameters were optimized. The chemical compounds were identified by the accurate mass measurement of molecular ions and fragment ion and comparation with reference substance. Result: 91 chemical compositions in Trichosanthis Fructus were totally identified,including 14 amino acids,5 monoterpenoids,5 tetracyclic triterpenoids,1 pentacyclic triterpene,14 flavonoids, 17 organic acids,3 polysaccharides,7 nucleotides,7 alkaloids and nitrogen compounds,2 volatile components,1 phytosterol,5 other compositions. Conclusion: The established UPLC-LTQ-Orbitrap-MS method can be used to quickly analyze and identify the main chemical constituents of Trichosanthis Fructus. The chemical information concerning the constituents in Trichosanthis Fructus could be helpful to the quality control and further studies of Trichosanthis Fructus.

Objective: To observe the effect of modified Chaihu Shugantang on the expression of miRNA-204 in hippocampus of epileptic mice, and to explore its mechanism of neuroprotection. Method: The sixty mice were randomly divided into 6 groups:normal group, model group (pilocarpine 180 mg·kg^-1), and modified Chaihu Shugantang group (7 g·kg^-1·d^-1), modified Chaihu Shugantang+miRNA-204 mimic group (7 g·kg^-1·d^-1+ 2 μL), modified Chaihu Shugantang+miRNA-204 inhibitor group (7 g·kg^-1·d^-1+2 μL), carbamazepine group (30 mg·kg^-1·d^-1),each was given intragastric administration for 2 weeks,using pilocarpine to cause epilepsy in mice, respectively, add flavor to Bupleurum after intragastric administration, inhibition and overexpression of miRNA-204, the mice were sacrificed and their hippocampus tissues were harvested.The indicators of each group were observed, Real-time quantitative PCR detecting system (Real-time PCR) was used to detect mouse hippocampal miRNA-204 expression, Western blot analysis of autophagy-related protein microtubule-associated protein light chain 3 (LC3), autophagy-associated marker protein 7 (ATG7) expression, hematoxylin pathological condition of hippocampus in each group was observed by hematoxylin-eosin(HE)staining.The autophagy of hippocampus in each group was observed by transmission electron microscopy. Result: Compared with normal group, the expression of miRNA-204 was significantly decreased in model group (P<0.01), the pathological changes in the hippocampal C1 area were the most obvious, the expression of ATG7, LC3Ⅱ/LC3Ⅰ was increased (P<0.01), and the autophagy was small. Compared with model group, the expression of miRNA-204 in the hippocampus of the modified Chaihu Shugantang group was increased (P<0.05), the pathological changes in the hippocampal C1 area were alleviated, the expression of ATG7, LC3Ⅱ/LC3Ⅰ was decreased (P<0.05), and the autophagy was small. The number of body decreased,the expression of miRNA-204 in hippocampus of modified Chaihu Shugantang+miRNA-204 mimic group was significantly increased (P<0.01), the pathological changes in hippocampal C1 area were the lightest, and the expression of ATG7, LC3Ⅱ/LC3I was decreased (P<0.01), the number of autophagosomes was the least.Compared with modified Chaihu Shugantang group, the above-mentioned indicators of modified Chaihu Shugantang+miRNA-204 inhibitor group had the same change trend and the change range decreased (P<0.05). Conclusion: Modified Chaihu Shugantang can improve the pathological changes of hippocampus in mice with epilepsy and play a neuroprotective role. The mechanism may be to increase the expression of miRNA-204 in hippocampus of mice with epilepsy, inhibit excessive autophagy of neurons and reduce apoptosis.

BACKGROUND: Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy. METHODS: Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy. RESULTS: A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified. CONCLUSIONS We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.
Animals ; Asian Continental Ancestry Group ; Cardiomyopathies ; genetics ; pathology ; Desmin ; genetics ; Electrocardiography ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Muscular Dystrophies ; genetics ; pathology ; Mutation ; genetics ; Pedigree ; Phenotype

Objective To investigate and control the outbreak of infection caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) in a gastroenterology intensive care unit (ICU), so as to provide reference for the prevention and control of clinical multidrug-resistant organisms (MDROs).Methods Epidemiological investigation was conducted on 3 patients with CRKP infection in a gastroenterology ICU on January 21-31, 2018, specimens were collected with environmental biology monitoring method, CRKP in environment was searched, homology between patients and environmental isolates were analyzed by pulsed-field gel electrophoresis (PFGE).Results Three patients were all isolated CRKP from sputum and blood specimens, all were male, with adjacent beds in the same ward, and treated by the same doctor.The number of isolated CRKP and infection rate in January 2018 were higher than those in other months, infection rate was significantly different (χ2=13.67, P＜0.01).A total of 102 environmental specimens were collected, including air and surface of objects, only 1 of which (nurse's uniform) was isolated 1 strain of KP.PFGE typing of KP isolated from patients and environment showed that there were two genotypes A and B, KP isolated from uniform of a nurse, hydrops abdominis and blood specimen of patient at bed 07, blood specimen of patient at bed 08, as well as sputum and blood specimen of patient at bed 09 were all type A, KP isolated from sputum specimen of patient at bed 07 was type B, KP isolated from hydrops abdominis in patient at bed 09 was not be typed.After comprehensive intervention, CRKP was not no longer isolated from 3 patients, and there was no new case in the ward.Conclusion Imperfect implementation of prevention and control measures for MDROs by health care workers may be an important cause for the spread of CRKP.

This study focuses on the protective effect of germacrone on human umbilical vein endothelial cells(HUVECs) damaged by H2O2-induced oxidative stress and its possible mechanisms. The oxidative damage model was established by using 500 μmol•L⁻¹ H2O2 to treat HUVECs for 3 hours, and then protected with different concentrations of germacrone for 24 hours. The effect of germacrone on cell viability of HUVECs damaged by H2O2 was detected by MTT. The contents of PGI2, TXB2, ET-1, t-PA, PAI-1, TNF-α and IL-6 were detected by ELISA. The content of NO was detected by using nitrate reductase method. Colorimetry was used to detect NOS and GSH-Px. The contents of MDA, SOD and LDH were detected by TBA, WST-1 and microplate respectively. Apoptosis was observed by Hoechst 33258 fluorescent staining. The mRNA expressions of Bax, Bcl-2 and Caspase-3 in cells were detected by RT-PCR. The results showed that the cell damage rate was 52% after treated with 500 μmol•L⁻¹ H2O2 for 3 hours. The cell activity was increasing with the rise of germacrone concentration within the range of 20-200 mol•L⁻¹. Compared with normal group, the contents of PGI2, NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were lower after damaged with H2O2. The contents of PAI-1, ET-1, IL-6, TNF-α, TXB2, LDH, MDA, Bax mRNA and Caspase-3 mRNA expressions were increased. Compared with model group, the contents of PGI2, NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were increased after treated with germacrone. The contents of PAI-1, ET-1, IL-6, TNF-α, TXB2, LDH, MDA, Bax mRNA and Caspase-3 mRNA expressions were lower after treated with germacrone. According to Hoechst 33258 fluorescence staining, compared with normal group, the cell membrane and the nucleus showed strong dense blue fluorescence, and the number of cells significantly decreased in model group. Compared with model group, blue fluorescence intensity decreased in drug group. The above findings demonstrate that germacrone may improve the effect on HUVECs damaged by H2O2-induced oxidative stress by resisting oxidation and inhibiting cell apoptosis.