Primary cilia support cartilage regeneration after injury / 国际口腔科学杂志·英文版

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.

Risk Factors and Predictive Model for Severe Myelosuppression due to Chemotherapy in Triple-negative Breast Cancer / 中山大学学报(医学科学版)

ObjectiveTo investigate the risk factors and construct a predictive model for severe myelosuppression due to chemotherapy in triple negative breast cancer （TNBC）. MethodsPatients with TNBC who received anthracycline combined with cyclophosphamide sequential paclitaxel chemotherapy regimen at the Second Affiliated Hospital of Nanchang University from September 2， 2016 to September 2， 2021 were selected and assigned to severe myelosuppression group and no/mild myelosuppression group. The χ2 test and binary logistic regression were used to analyze the risk factors for severe myelosuppression due to chemotherapy and to develop a prediction model. Hosmer-Lemeshow test and receiver operating characteristic （ROC） curve were used to evaluate the predictive efficiency of the regression model. Kappa consistency test was used to verify the regression model externally. ResultsA total of 207 patients who met the inclusion were enrolled and 106 patients （51%） had severe myelosuppression. Binary logistic regression multivariate analysis showed that age 40 to 60 years （OR = 3.463， 95% CI： 1.144 to 10.486， P = 0.028）， age >60 years （OR = 3.474， 95% CI： 1.004 to 12.020， P = 0.049）， body mass index （BMI） 18.5 to 24.0 （OR = 1.445， 95% CI： 0.686 to 3.087， P = 0.328）， BMI <18.5 （OR = 3.582， 95% CI： 1.260 to 10.182， P = 0.017）， tumor TNM stage Ⅱ （OR = 1.698， 95% CI： 0.831 to 3.468， P = 0.146）， tumor TNM stage Ⅲ （OR = 2.943， 95% CI： 1.199 to 7.227， P = 0.019）， previous diabetes （OR = 2.441， 95% CI： 1.076 to 5.539， P = 0.033）， low pre-treatment albumin level （OR = 2.759， 95% CI： 1.141 to 6.669， P = 0.024） and low pre-treatment lymphocytes （OR = 3.428， 95% CI： 1.689 to 6.958， P = 0.001） were independent risk factors for severe myelosuppression due to chemotherapy. The χ2 value for the logistic regression model Hosmer-Lemeshow test was 11.507， P= 0.175， the area under the ROC curve was 0.763， standard error 0.033， 95% CI： 0.698-0.828， P=0.000. External validation showed that the prediction model had a specificity of 88% and a sensitivity of 80%； the kappa value was 0.679， standard error 0.081， P=0.000. conclusionThis logistic regression model had high predictive efficacy and is useful for clinicians to predict whether patients with TNBC develop severe myelosuppression.

Effects of different field processing methods on volatile components of Chuanxiong Rhizoma: an exploration based on headspace gas chromatography-mass spectrometry / 中国中药杂志

The volatile oil of Chuanxiong Rhizoma(CX) is known as an effective fraction. In order to seek a suitable method for processing CX and its decoction pieces, this study selected 16 volatile components as indices to investigate how different processing methods such as washing/without washing, sun-drying, baking, oven-drying and far-infrared drying at different temperatures affected the quality of CX and its decoction pieces(fresh CX was partially dried, cut into pieces, and then dried) by headspace gas chromatography-mass spectrometry(GC-MS), cluster analysis, principal component analysis and comprehensive weighted scoring. The results showed that the rapid washing before processing did not deteriorate the volatile components of CX. Considering the practical condition of production area, oven-drying was believed to be more suitable than sun-drying, baking, and far-infrared drying. The CX decoction pieces with a thickness of 0.3-0.4 cm were recommended to be oven-dried at 50 ℃. The integrated processing(partial drying, cutting into pieces, and drying) did not cause a significant loss of volatile components. For the fresh CX, the oven-drying at 60 ℃ is preferred. The temperature should not exceed 60 ℃, and drying below 60 ℃ will prolong the processing time, which will produce an unfavorable effect on volatile components. This study has provided the scientific evidence for field processing of CX, which is conducive to realizing the normalization and standardization of CX processing in the production area and stabilizing the quality of CX and its decoction pieces.

Short-term efficacy of superficial X-ray treatment for infantile maxillofacial hemangioma / 华西口腔医学杂志

OBJECTIVES@#This study aimed to explore the short-term clinical efficacy and factors influencing low-dose superficial X-ray for treating infantile maxillofacial hemangioma.@*METHODS@#Retrospective analysis was conducted on 161 cases of infants with maxillofacial hemangioma treated with superficial X-ray in the Laser Center of Dermatology Department of Sichuan Provincial People's Hospital from January 2015 to December 2017. Clinical efficacy was analyzed by comparing the photos before and after treatment. Patients were further divided into groups according to different genders, age at the start of treatment, preterm birth or low birth weight, hemangioma site, longest diameter of hemangioma, and type of hemangioma to analyze whether differences existed in clinical efficacy and therapeutic dose between different groups.@*RESULTS@#Twelve months after the end of treatment, the overall cure rate was 93.8%, and the significant efficiency was 97.5%. The clinical efficacy was related to the age of children at the beginning of treatment and the type of hemangioma (@*CONCLUSIONS@#Low-dose superficial X-ray is safe and effective for the treatment of infantile maxillofacial hemangioma. Age and type of hemangioma at the time of treatment are the factors influencing therapeutic dose and clinical efficacy.

The application of multi-teaching mode based on MOOC in the practice course of epidemiology / 上海预防医学

At present， there is little research on the new teaching mode for the practice course of epidemiology. Based on the situation， this paper mainly discussed how the MOOC （Massive Open Online Course）-based multi-teaching mode was applied to the practice course of Epidemiology. The structure of this multi- teaching mode consisted of case base construction， class preparation， class presentation and learning evaluation. Thus， MOOC， flipped Class Mode and other new teaching modes were integrated into traditional face-to-face teaching. In addition， this paper also demonstrated the implementation of the multi-teaching mode in the teaching of preventive medicine. It is worth exploring how to integrate MOOC into the teaching of the practice course of epidemiology in the future.

Prevalence of multiple anxiety disorder and associated factors among adolescents three years after Ya’an Earthqhake / 中国学校卫生

Objective@#To examine the prevalence of multiple anxiety disorder of adolescents in Lushan, Sichuan and to provide the scientific reference for a long-term psychological intervention and rehabilitation for adolescents after earthquake.@*Methods@#In May 2016, 3 741 students were sampled in two middle schools and two high schools in Lushan county. Self-report questionnaice regarding exposure to earthquake, Screen for Child Anxiety Related Emotional Disorders (SCARED), and negative life events questionnaire (ASLES) were administered to the subjects.@*Results@#The prevalence of anxiety symptoms of adolescents in Lushan, Sichuan was 42.3%, among which panic disorder was 36.3%; generalized anxiety was 29.5%, separation anxiety was 40.3%, social anxiety was 26.1%, school fear was 32.4%. Junior school students resported more symptoms of separation anxiety than high school students (χ2=33.09, P<0.01). The results of Logistic regression showed that girls (OR=2.34, 95%CI=2.00-2.74, P<0.01), high negative life events (OR=2.87, 95%CI=2.60-3.17, P<0.01), trapped in earthqnakes (OR=1.77, 95%CI=1.18-2.67, P<0.01), parents injured (OR=1.22, 95%CI=1.03-1.43, P=0.02), experienced extreme fear (OR=1.78, 95%CI=1.52-2.08, P<0.01) were associated with higher risk of anxiety disorder.@*Conclusion@#High prevalence of anxiety disorder among adolescent following disaster need to be alerted. Adolescents among female victim or those experienced extreme fear emotion or high frequencies of negative life events, need specific intervention.

Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

BACKGROUND@#Adjuvant (chemo)radiotherapy (A(C)RT) may be an important supplement to surgery for extrahepatic cholangiocarcinoma (EHCC). However, whether all patients would achieve benefits from A(C)RT and which adjuvant regimen, adjuvant radiotherapy (ART) or adjuvant chemoradiotherapy (ACRT), would be preferred, are still undetermined. The low incidence of EHCC makes it difficult to carry out randomized controlled trials (RCTs); therefore, almost all clinical studies on radiotherapy are retrospective. We have conducted a meta-analysis of these retrospective studies.@*METHODS@#We conducted a meta-analysis of current retrospective studies using PubMed, Embase, and ClinicalTrials databases. All studies published in English that were related to A(C)RT and which analyzed overall survival (OS), disease-free survival (DFS), or locoregional recurrence-free survival (LRFS) were included. Estimated hazard ratios (HRs) were calculated for OS, DFS, and LRFS.@*RESULTS@#Data from eight studies including 685 patients were included. Our analysis showed that A(C)RT significantly improved OS (HR 0.69, 95% confidence interval (CI) 0.48-0.97, P=0.03), DFS (HR 0.60, 95% CI 0.47-0.76, P<0.0001), and LRFS (HR 0.27, 95% CI 0.17-0.41, P<0.00001) of EHCC overall. In subgroups, patients with microscopically positive resection margin (R1) could achieve a benefit from A(C)RT (HR 0.44, 95% CI 0.27-0.72, P=0.001). No statistically OS difference was observed in negative resection margin (R0) subgroup (HR 0.98, 95% CI 0.30-3.19, P=0.98).Significant OS benefit was found in patients who received concurrent ACRT (HR 0.40, 95% CI 0.26-0.62, P<0.0001), while the result of ART without chemotherapy showed no significant benefit (HR 1.14, 95% CI 0.29-4.50, P=0.85). In the distal cholangiocarcinoma subgroup, no significant difference was seen when ACRT and ART were included (HR 0.61, 95% CI 0.14-2.72, P=0.52), but a significant difference was seen when analyzing the concurrent ACRT only (HR 0.29, 95% CI 0.13-0.64, P=0.002).@*CONCLUSIONS@#A(C)RT may improve OS, DFS, and LRFS in EHCC patients, especially in those with R1 resection margins. ACRT may be superior to ART especially in distal patients.

Comparative study on free and bound phenolic acids before and after drying of Salvia miltiorrhiza / 中国中药杂志

There were significant differences in phenolic acid content between fresh and dried Salvia miltiorrhiza before and after drying. That is to say, the content of phenolic acid in S. miltiorrhiza significantly increased with the increase of dehydration during the drying process.In order to investigate the differences and transformation of free and bound phenolic acids before and after the drying process of S.miltiorrhiza, we studied hydrolysis method, hydrolysates and hydrolysis regularity of phenolic acids in S.miltiorrhiza. UPLC method was used to determine four main hydrolysates of bound phenolic acids, namely danshensu, caffeic acid dimer(SMND-309), caffeic acid, przewalskinic acid A(prolithosperic acid), and three main free phenolic acids in S.miltiorrhiza, namely rosmarinic acid, lithospermic acid, salvianolic acid B. The results of the acid-base hydrolysis experiment of salvianolic acid showed that the alkaline hydrolysis effect was significantly better than acid hydrolysis. The optimal alkaline hydrolysis condition was hydrolysis at 70 ℃ for 4 h with 2 mol·L~(-1) NaOH solution containing 1% ascorbic acid(Vit C). The hydrolysates of free phenolic acids were the same with the hydrolysates of bound phenolic acids. Fresh S.miltiorrhiza contains a low level of free phenolic acids and a high level of bound phenolic acids, which were exactly opposite to dried S.miltiorrhiza. It was suggested that a large amount of bound phenolic acids was accumulated during the growth of S.miltiorrhiza. These bound phenolic acids were coupled with polysaccharides on the cytoderm through ester bonds to form insoluble phenolic acids, which was not easy to be detected by conventional methods. However, during drying and dehydration processes, the bound phenolic acids were converted to a large amount of free phenolic acids under the action of the relevant enzyme.

FBX8 degrades GSTP1 through ubiquitination to suppress colorectal cancer progression.

F-box only protein 8 (FBX8), as a critical component of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases, has been associated with several malignancies through interacting with a member of proteins. However, the substrates of FBX8 for destruction in the progression of colorectal carcinoma (CRC) need to be explored. Here, we show that loss of FBX8 accelerates chemical-induced colon tumorigenesis. FBX8 directly targets GSTP1 for ubiquitin-mediated proteasome degradation in CRC. GSTP1 promotes the proliferation, invasion, and metastasis of CRC cells. Furthermore, GSTP1 is upregulated in CRC tissue samples and predicts poor prognosis of CRC patients. The inactivation of FBX8 negatively correlated with increased levels and stability of GSTP1 in clinical CRC tissues and FBX8 knockout transgenic mice. These findings identify a novel ubiquitination pathway as FBX8-GSTP1 axis that regulates the progression of CRC, which might be a potential prognostic biomarker for CRC patients.

Prevalence and influencing factors of myopia for the Chinese junior high school students / 中华疾病控制杂志

Objective To analyze the mechanism of the influencing factors of myopia for junior high school students in China. Methods Based on the follow-up to 7 119 students in the 3 waves of questionnaire survey of the Chinese Education Panel Survey in junior high school stage, and the variables on students’ myopia status, myopia influencing factors, and two kinds of risk behaviors of myopia including near visual activities and outdoor activities, the mediation effects of the myopia risk behaviors were tested by Logistic regression model. Results The myopia prevalence of 9th graders before junior high school graduation was 66.36%. Time on writing homework significantly increased the risk of myopia，the odds ratio (OR) was 1.17，the 95% confidence interval (CI) was 1.13-1.21, and the time on outdoor sports significantly decreased the risk of myopia (OR=0.80，95% CI:0.75-0.86). Before and after including the risk behaviors into the model, the myopia risk OR(95% CI) of female centralized from 1.84(1.66-2.04) to 1.69(1.51-1.88), the myopia risk OR(95% CI) of urban students’centralized from 1.19(1.03-1.37) to 1.16(1.00-1.34), the myopia risk OR(95% CI) of only children’centralized from 1.20(1.06-1.36) to 1.18(1.04-1.33). With reference to not myopic for both parents, the myopia risk OR(95% CI) of students having one myopic parent centralized from 2.47(2.12-2.88) to 2.44(2.09-2.85), the myopia risk OR(95% CI) of students having parent without myopic centralized from 4.25(3.09-5.86) to 4.13(3.00-5.69). Conclusions Gender, urban and rural, only child, and myopic parents are influencing factors of myopia. These factors have effects on myopia via two kinds of risk behaviors including outdoor activities and near visual activities.

Culture and identification of tumor stem cells from surgically resected colorectal cancer tissues / 南方医科大学学报

OBJECTIVE@#To obtain cancer stem cells (CSCs) from surgically resected colorectal cancer specimens and identify their stem cell characteristics.@*METHODS@#Colorectal cancer tissue specimen obtained from a patient undergoing radical resection of colorectal cancer were implanted in nude mice, and the xenograft was harvested 1 month later to obtain purified tumor cells by enzyme digestion and adherent culture. The CSCs were screened by limiting dilution method and serum-free culture to identify their phenotypes. Soft agar colony assay was used to assess the proliferative ability of the CSCs and human colorectal cancer cell line SW480. The tumorigenic ability of the isolated CSCs and SW480 cells was evaluated by observing their subcutaneous tumor formation in nude mice. Western blotting and immunofluorescence assay were used to detect the immunophenotype of the CSCs and SW480 cells.@*RESULTS@#The primary cultured CSCs from clinical specimens of colorectal cancer underwent differentiation in the presence of serum in the culture. Soft agar colony formation assay showed that the CSCs had a colony formation rate above 50%, significantly higher than the rate of colorectal cancer SW480 cells (4.41%; < 0.01). In nude mice, subcutaneous injection of 500 CSCs was sufficient to result in subcutaneous tumor formation, while the injection of 500 SW480 cells failed to form any subcutaneous tumors. The CSCs expressed CD133 and CD44 but not CK7, while SW480 cells expressed CK7 but not CD133 or CD44.@*CONCLUSIONS@#CSCs can be derived by primary culture of cancer cells obtained from surgically resected colorectal cancer tissue followed by serum-free culture, and the CSCs obtained have self-renewal and differentiation abilities.

Primary intraosseous hematopoietic pseudotumor: clinicopathological analysis and 9-year follow-up of 3 cases / 南方医科大学学报

We analyzed the clinicopathological data of 3 cases of primary intraosseous hematopoietic pseudotumor (IHPT), which had been previously misdiagnosed as malignancies or metastases both clinically and pathologically. Two of the patients received close follow-up for 132 and 100 months, and one patient was lost to follow-up, and the tumors were confirmed to be benign in all the 3 cases. IHPT is a rare benign intraosseous solid lesion consisting of tissues resembling normal hematopoietic tissue, and can be easily misdiagnosed as malignancy. Understanding the clinicopathological features and the outcomes of the disease can facilitate the clinical decisions on individualized diagnosis and therapeutic regimens.

Study on dynamic changes of chemical constituents during different drying processes of Salvia miltiorrhiza / 中国中药杂志

There is no consensus on the drying methods of Salvia miltiorrhiza in ancient and modern times,especially on the content of phenolic acid in fresh S. miltiorrhiza. In order to further explore the content of main components in fresh S. miltiorrhiza and study the dynamic changes during the drying process,the content of main components was used as the index in this study to evaluate the processing method,drying method,correlation between dehydration rate and component content for fresh S. miltiorrhiza. In addition,the sealed and unsealed parallel control groups were set to carry out verification test during the drying process. UPLC method was used for determination of seven main components including rosmarinic acid,lithosperic acid,salvianolic acid B,cryptotanshinone,tanshinoneⅠ,methylene salianolate and tanshinone ⅡAin S. miltiorrhiza. The results showed that the fresh S. miltiorrhiza contained low levels of phenolic acid,and the content of phenolic acid increased significantly with the increase of dehydration rate during drying process,while the change of tanshinone was not obvious. In the comparison of three drying methods,we found that drying at 50 ℃ was better than drying in the sun,and drying in the sun was superior to drying in the shade. So,drying at 50 ℃ was the best drying method. The correlation between dehydration and phenolic acid content of S. miltiorrhiza was analyzed by verification test and SPSS software,which further proved that the dehydration rate was significantly positively correlated with the content of phenolic acid components. This study provides reference for the production processing and drying methods of S. miltiorrhiza medicinal materials,which is of great significance for improving the quality of S. miltiorrhiza.

Consistency of different physicians in diagnosis of malignant breast lesions with breast CEUS predictive model: A multicenter study / 中国医学影像技术

Objective To explore the consistency of different physicians in diagnosis of malignant breast lesions with breast CEUS predictive model.Methods Totally 953 patients with solitary breast nodule from multicenter who underwent ultrasound and CEUS were collected.The research team was composed by the initial group (one junior physician from each hospital),check group (one or two physicians who had at least two-year experience of CEUS examination from each hospital),research group (two senior physicians from Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) and cross-blinded group (one or two vice directors or chief physicians from each hospital).At first,the lesions were classified according to the breast imaging reporting and data system (BI RADS) by the initial group and the check group,then new BI RADS classifications were performed by research group and cross blind group with breast CEUS predictive model.The consistency of different physicians in diagnosis of malignant breast lesions was analyzed.Results Among 953 patients,benign lesions were found in 451 patients (451/953,47.32％),malignant lesions were found in 435 patients (435/953,45.65％),and precancerous lesions were found in 67 patients (67/953,7.03％).The accuracy of the initial group,check group,research group and cross-blinded group was 71.67％(683/953),74.92％(714/953),80.17％ (764/953) and 83.42 ％ (795/953),respectively.The consistency of different physicians for diagnosis of malignant breast lesions between initial group and check group was good (Kappa =0.82,P＜0.001),while between initial group and crossblinded group,initial group and research group were both moderate (Kappa =0.56,0.41;all P＜0.001).The consistency of different physicians for diagnosis of malignant breast lesions between cheek group and cross-blinded group,between check group and research group were both moderate (Kappa =0.68,0.51;all P＜0.001).The consistency between research group and cross-blinded group with breast CEUS predictive model was moderate (Kappa =0.74,P＜ 0.001).Conclusion The consistency of different physicians in diagnosis of malignant breast lesions with breast CEUS predictive model was moderate.

Involvement of interaction between TRPC1 and Orai1 in calcium sensing receptor-mediated calcium influx and nitric oxide generation in human umbilical vein endothelial cells / 生理学报

The present study was to investigate the role of the interaction between canonical transient receptor potential channel 1 (TRPC1) and calcium release-activated calcium modulator 1 (Orai1) in extracellular Ca-sensing receptor (CaR)-induced extracellular Ca influx and nitric oxide (NO) production. Human umbilical vein endothelial cells (HUVECs) were incubated with CaR agonist Spermine [activating store-operated calcium channels (SOC) and receptor-operated calcium channels (ROC)] alone or in combination with the following reagents: CaR negative allosteric modulator Calhex231 plus ROC analogue TPA (activating ROC and blocking SOC), Ro31-8220 (PKC inhibitor that activates SOC and blocks ROC) or Go6967 (PKCs and PKCµ inhibitor that activates SOC and blocks ROC). The protein expressions and co-localization of TRPC1 and Orai1 were determined using immunofluorescent staining. The interaction between TRPC1 and Orai1 was examined by co-immunoprecipitation. We silenced the expressions of their genes in the HUVECs by transfection of constructed TRPC1 and Orai1 shRNA plasmids. Intracellular Ca concentration ([Ca]) was detected using Ca indicator Fura-2/AM, and NO production was determined by DAF-FM staining. The results showed that TRPC1 and Orai1 protein expressions were co-located on the cell membrane of the HUVECs. Compared with Spermine+Ca group, Calhex231+ TPA+Spermine+Ca, Ro31-8220+Spermine+Ca and Go6976+Spermine+Ca groups exhibited down-regulated protein expressions of TRPC1 and Orai1 in cytoplasm and decreased co-localization on the cell membrane. Co-immunoprecipitation results showed that the interaction between TRPC1 and Orai1 was reduced by Calhex231 plus TPA, Ro31-8220 or Go6976 addition in the Spermine-stimulated HUVECs. Double knockdown of Trpc1 and Orai1 genes significantly decreased [Ca] level and NO production in all of the Spermine+Ca, Calhex231+TPA+Spermine+Ca, Ro31-8220+Spermine+Ca and Go6976+Spermine+Ca groups. These results suggest that TRPC1/Orai1 may form a complex that mediates Ca influx and No production via SOC and ROC activation.

Comparison on sensitivity and specificity of serum miR-122 as biomarkers of drug-induced liver injury / 中国药理学与毒理学杂志

OBJECTIVE To make a comparison of sensitivity and specificity between serum miR-122 and traditional biomarkers of drug-induced liver injury. METHODS Acetaminophen (APAP, 1250 mg · kg-1, ig), α-naphthylisothiocyanate (ANIT, 150 mg · kg-1, ig), methionine-choline deficient diet (MCDD, free feeding) and carbon tetrachloride (CCl4, 50%, ip) were used to establish hepatocellular injury, cholestasis, steatosis and fibrosis models, respectively, which were used to evaluate the sensitivity of serum miR-122 as a biomarker of drug-induced liver injury, when compared with the traditional biomarkers. Isoprenaline hydrochloride (IH) and gentamicin (GM) were used to establish myocardial and renal injury models, respectively, which were used to evaluate the specificity of serum miR-122, when compared with the tradi-tional biomarkers. Serum and liver tissues were collected at different time points during the study. Tradi-tional biomarkers such as glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT) and total bilirubin (TBIL) were measured with an automatic biochemistry analyzer. MiR-122 was detected with real- time quantitative PCR. Histopathological examination with HE staining was performed for liver tissues. RESULTS Serum miR-122 increased significantly earlier [miR-122 was signifi-cantly increased (>2 fold) at 1.5 h, 3 h, 2 weeks and 4 weeks after treatment in the four models respec-tively, while no significant increase (<2 fold) was observed for GPT, GOT and TBIL at 6 h, 12 h, 3 weeks and 6 weeks after treatment in the four models respectively] and more signficantly (the maximum fold change for miR-122 was 235.8, 202.7, 73.8 and 600.3 for the four models, respectively. For the GPT, the maximum fold change was 9.5, 3.9, 2.5 and 6.6, respectively; 6.0, 2.4, 1.4 and 3.5 respectively for GOT; 2.6, 2.3, 1.2 and 1.8 respectively for TBIL) than that of traditional biomarkers in hepatocellular injury, cholestasis, steatosis and fibrosis models, when compared with the control group. In the myocar-dial injury model, a significant increase of GOT was observed after IH treatment (2.1 fold), while no change was observed for serum miR-122. In the renal injury model, no false positive results were observed for serum miR-122. CONCLUSION Serum miR-122 can be used as a biomarker of drug-induced liver injury and serum miR-122 is more sensitive and specific than traditional biomarkers (such as GPT, GOT and TBIL).

Preparation of anti-EGFR-PEG-SPIO molecular probe and its targeting MRI for lung adenocarcinoma cells / 中国医学影像技术

Objective To observe the targeting function of high affinity anti-EGFR monoclonal antibody (Cetuximab)conjugated superparamagnetic iron oxide-dopamine (anti-EGFR-PEG-SPIO) lung cancer cells via epidermal growth factor receptor (EGFR),as well as the feasibility for surveillance of tumor targeting with MRI.Methods Nanoparticles (NPs)of anti-EGFR-PEG-SPIO and PEG-SPIO were prepared,and the morphology of nanoparticles was observed with transmission electron microscope (TEM).The hydrodynamic diameter and R2 values of nanoparticles before and after conjugation with anti-EGFR were performed with dynamic light scattering (DLS) and MRI.MRI was performed in incubation with anti-EGFR-PEG-SPIO and PEG-SPIO after 2 h in vitro.The cellular uptake of anti-EGFR-PEG-SPIO and PEG-SPIO was further evaluated using Prussian blue staining and TEM.Results Anti-EGFR-PEG-SPIO and PEG-SPIO showed signal intensity of H460 cells on T2WI,decreased significantly compared with PEG-SPIO.The rate of signal intensity change was -58.2％,-82.7％,-94.4％ and-98.3％,respectively,at iron concentrations of (0,10,20,40,80 μg/ml) of antiEGFR-PEG-SPIO.Prussian blue staining and TEM showed that a lot of intracellular irons of anti-EGFR-PEG-SPIO were observed in H460 cells,but few of PEG-SPIO.Conclusion The effect of active targeting via anti-EGFR in EGFR overexpressed cells can be achieved with anti-EGFR-PEG-SPIO in H460 cells in vitro,and the targeting delivery process could be monitored with 3.0T MRI.

Interaction between STIM1 and Orai1 in calcium-sensing receptor-media-ted calcium influx and nitric oxide generation / 中国病理生理杂志

AIM:To investigate the interaction of Ca 2+-sensing proteins , stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1), in Ca2+-sensing receptor (CaSR)-mediated extracellular Ca2+ influx and production of nitric oxide ( NO).METHODS: Human umbilical vein endothlial cells (HUVECs) were incubated with CaSR agonist spermine [activating store-operated calcium channels (SOC) and receptor-operated calcium channels ( ROC) ] alone or combined with CaSR negative allosteric modulator Calhex 231+ROC analogue TPA (activating ROC, blocking SOC), protein kinase C (PKC) inhibitor Ro 31-8220, or PKCα/β1 selective inhibitor Go 6976 (activate SOC, blocking ROC).The protein expression of STIM1 and Orai1 was determined by the method of immu-nofluorescence .The interaction between STIM 1 and Orai1 was examined by co-immunoprecipitation .The second to third passages of HUVECs were divided into STIM 1 and Orai1 short hairpin RNA group ( shSTIM1+shOrai1 group ) , vehicle-STIM1+vehicle-Orai1 group and control group , and then incubated with the 4 different treatments above .The intracellular Ca2+concentration ( [ Ca2+] I ) was detected using the fluorescent Ca 2+indicator Fura-2/AM.The production of NO was also determined by DAF-FM DA fluorescent probe .RESULTS:The protein expression of STIM 1 and Orai1 was located in the cytoplasm.Compared with control group , the localization of STIM1 and Orai1 in the cytoplasm was reduced after the HUVECs were incubated with Calhex 231+TPA, Ro 31-8220 or Go 6976, and the interaction of STIM1 and Orai1 was de-creased significantly .The [ Ca2+] I and the net NO fluorescence intensity in shSTIM 1+shOrai1 group were significantly re-duced after the 4 different treatments (P<0.05).CONCLUSION:STIM1 and Orai1 are components of SOC and ROC in store-and receptor-operated Ca 2+entry and NO generation .

Application of transvaginal ultrasound in diagnosis and treatment of cesarean scar pregnancy / 上海交通大学学报（医学版）

Objective · To investigate the performance of transvaginal ultrasound (TVS) on cesarean scar pregnancy (CSP), and evaluate the value of TVS combined with MRI in the diagnosis and treatment of CSP. Methods · A retrospective analysis was made in 42 patients with CSP in Shanghai General Hospital in recent 3 years. The TVS performance, MRI results, and clinical data of the patients were analyzed. Results · In all 42 cases, 36 were diagnosed as CPS. TVS missed one case, and misdiagnosed 5 cases, which diagnostic accuracy was 85.7%. Thirty-six cases were tested by MRI, therein 32 cases were diagnosed correctly, 3 cases missed, 1 case misdiagnosed, which diagnostic accuracy rate was 88.9%. Among the 36 CSP cases, 30 were simple sac type and 6 were mixedmass type. For the simple sac type, different treatment was chosen according to the muscle thickness of the lower uterine segment incision measured by TVS. When it was more than 3 mm, suction surgery was used. But when it was no more than 3 mm, MRI examination was further used, and the surgical resection or uterine artery embolism+MTX+suction surgery was chosen. Conclusion · Both TVS and MRI have a high diagnostic accuracy for CSP, and TVS combined with MRI can provide important reference for CSP treatment options.

Interaction between STIM1 and Orai1 in calcium-sensing receptor-media-ted calcium influx and nitric oxide generation / 中国病理生理杂志

AIM:To investigate the interaction of Ca 2+-sensing proteins , stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1), in Ca2+-sensing receptor (CaSR)-mediated extracellular Ca2+ influx and production of nitric oxide ( NO).METHODS: Human umbilical vein endothlial cells (HUVECs) were incubated with CaSR agonist spermine [activating store-operated calcium channels (SOC) and receptor-operated calcium channels ( ROC) ] alone or combined with CaSR negative allosteric modulator Calhex 231+ROC analogue TPA (activating ROC, blocking SOC), protein kinase C (PKC) inhibitor Ro 31-8220, or PKCα/β1 selective inhibitor Go 6976 (activate SOC, blocking ROC).The protein expression of STIM1 and Orai1 was determined by the method of immu-nofluorescence .The interaction between STIM 1 and Orai1 was examined by co-immunoprecipitation .The second to third passages of HUVECs were divided into STIM 1 and Orai1 short hairpin RNA group ( shSTIM1+shOrai1 group ) , vehicle-STIM1+vehicle-Orai1 group and control group , and then incubated with the 4 different treatments above .The intracellular Ca2+concentration ( [ Ca2+] I ) was detected using the fluorescent Ca 2+indicator Fura-2/AM.The production of NO was also determined by DAF-FM DA fluorescent probe .RESULTS:The protein expression of STIM 1 and Orai1 was located in the cytoplasm.Compared with control group , the localization of STIM1 and Orai1 in the cytoplasm was reduced after the HUVECs were incubated with Calhex 231+TPA, Ro 31-8220 or Go 6976, and the interaction of STIM1 and Orai1 was de-creased significantly .The [ Ca2+] I and the net NO fluorescence intensity in shSTIM 1+shOrai1 group were significantly re-duced after the 4 different treatments (P<0.05).CONCLUSION:STIM1 and Orai1 are components of SOC and ROC in store-and receptor-operated Ca 2+entry and NO generation .