Involvement of intracellular organelle stress, autophagy and ferroptosis in cobalt chloride-induced vascular smooth muscle cell injury / 中国临床药理学与治疗学

AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.

Use of anticoagulant mechanical methods after laparoscopic sleeve gastrectomy for obese patients / 中华普通外科杂志

Objective:To investigate anticoagulant effects of mechanical methods in obese patients undergoing laparoscopic sleeve gastrectomy (LSG).Methods:In this prospective study, 54 obese patients receiving LSG were enrolled . All patients were given post-op mechanical methods for thrombogenic interventions. BMI and the operation-related factors were recorded. Venous blood specimens were taken from each patient before surgery, at the end of pneumoperitoneum (i.e., 0 h after surgery), at 24 hours after surgery for prothrombin time (PT) and activated partial thromboplastin time (APTT), fibrinogen (FIB) and D-dimer (D-D).Results:All 54 obese patients successfully underwent LSG. No severe complications were observed. Before operation, the mean BMI was (43.49±8.29) kg/m 2. DVT-2600 device was applied in all patients for 3 consecutive days after surgery. The PT values increased at 0 h, 24 h after surgery [(12.4±1.2) s, (12.4±0.8) s vs. (11.2±0.8) s, P=0, 0]. The APTT values at 0 h, 24 h after surgery decreased [(29.7±3.6) s, (29.0±3.1) s vs.(31.2±3.3) s, P=0.020, 0.001]. However, the D-D values increased at 0 h,24 h after operation [(213±143) ng/ml ,(445±237) ng/ml vs. (85±108) ng/ml, P=0, 0]. All patients were followed up for 1 month, and no thrombosis -related complications were observed. Conclusion:Mechanical methods for obese patients after LSG can help decrease the risk of deep venous thrombosis.

Clinical research progress on Traditional Chinese Medicine treating diabetes mellitus with depression / 国际中医中药杂志

The ways of treating diabetes mellitus with depression by using Traditional Chinese Medicine (TCM) include internal treatment, external treatment and combining internal and externalmethod, mostly based on the viscera syndrome differentiation and Qi blood phlegm stasis syndrome differentiation, focusing on soothing the liver qi and regulating, liver and spleen. The internal treatments mainly include self-made prescriptions or classic prescriptions, such as Jiawei-Xiaoyao Powder, Danggui-Shaoyao Decoction, Wendan Decoction, etc; External treatments mainly include common acupuncture, ear acupuncture, scalp acupuncture, abdominal acupuncture, acupoint application, etc. The above treatments can improve the symptoms of depression, and control the blood glucose level.

Overoxidized poly(3,4-ethylenedioxythiophene)-gold nanoparticles-graphene-modified electrode for the simultaneous detection of dopamine and uric acid in the presence of ascorbic acid / 药物分析学报

An innovative,ternary nanocomposite composed of overoxidized poly(3,4-ethylenedioxythiophene)(OPEDOT),gold nanoparticles (AuNPs),and electrochemically reduced graphene oxide (ERGO) was prepared on a glassy carbon electrode (GCE) (OPEDOT-AuNPs-ERGO/GCE) through homogeneous chemical reactions and heterogeneous electrochemical methods.The morphology,composition,and structure of this nanocomposite were characterized by transmission electron microscopy,scanning electron microscopy,X-ray diffraction,and X-ray photoelectron spectroscopy.The electrochemical properties of the OPEDOT-AuNPs-ERGO/GCE were investigated by cyclic voltammetry using potassium ferricyanide and hexaammineruthenium(Ⅲ) chloride redox probe systems.This modified electrode shows excellent electro-catalytic activity for dopamine (DA) and uric acid (UA) under physiological pH conditions,but inhibits the oxidation of ascorbic acid (AA).Linear voltammetric responses were obtained when DA concentrations of approximately 4.0-100 μM and UA concentrations of approximately 20-100 μM were used.The detection limits (S/N=3) for DA and UA were 1.0 and 5.0 μ.M,respectively,under physiological conditions and in the presence of 1.0 mM of AA.This developed method was applied to the simultaneous detection of DA and UA in human urine,where satisfactory recoveries from 96.7％ to 105.0％were observed.This work demonstrates that the developed OPEDOT-AuNPs-ERGO ternary nano-composite,with its excellent ion-selectivity and electro-catalytic activity,is a promising candidate for the simultaneous detection of DA and UA in the presence of AA in physiological and pathological studies.

Follow up study on sleep behavior, chronotype and emotional symptoms of college students in Anhui Province / 中国学校卫生

Objective@#To explore the relationships between sleep behaviors, chronotype and emotional symptoms including depression and anxiety symptoms among college students.@*Methods@#Freshmen and sophomore from one university in Anhui Province were recruited through cluster sampling method. The baseline survey was conducted in November 2020, and the follow up survey was conducted 2 months later. The Morning and Evening Questionnaire 5 (MEQ-5) was used to assess chronotype. The Insomnia severity Index (ISI) and Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) were used to evaluate sleep behaviors. Depression Anxiety Stress Scale (DASS-21) was used to assess depression and anxiety symptoms, respectively. The detection rate of depression and anxiety among college students with different demographic characteristics, different sleep chronotypes and sleep behavior were compared, and the association between sleep behavior, chronotypes and depression and anxiety symptoms was analyzed.@*Results@#The detection rates of depressive and anxiety symptoms were higher in the college students with daytime sleepiness and insomnia( χ 2=12.39，22.68；40.14，29.46， P <0.01). Logistic regression results showed that at the baseline daytime sleepiness and insomnia were positively associated with depression ( OR =3.03, 5.23) and anxiety symptoms ( OR =3.74, 4.24), respectively ( P ＜0.05), however, no association was found between chronotype and symptoms of depression and anxiety ( P ＞0.05). Follow up survey results were consistent with baseline.@*Conclusion@#Daytime sleepiness and insomnia are risk factors for depression and anxiety symptoms among college students. It is suggested that keeping healthy sleep behaviors play an important role in mental health promotion among college students in the future.

Relationship between serum retinol binding protein, stromal cell derived factor-1 and renal function in patients with diabetic nephropathy / 国际外科学杂志

Objective:To investigate the relationship between serum retinol binding protein (RBP), stromal cell derived factor-1 (SDF-1) and renal function in patients with diabetic nephropathy (DKD).Methods:The patients with type 2 diabetes mellitus (T2DM) admitted to Yantai Affiliated Hospital of Binzhou Medical College from October 2017 to October 2020 were prospectively selected, 438 patients were divided into simple T2DM group ( n=276)and DKD group( n=162) according to the presence or absence of DKD, according to the ratio of urinary albinin/creatinine (UACR) were divided into normal( n=25), microalbuminuria ( n=75) and macroalbuminuria group ( n=62), according to the estimated glomerular filtration rate (eGFR) were divided into G1 stage ( n=28), G2 stage ( n=27), G3A + G3B stage ( n=35), G4 stage ( n=39)and G5 stages( n=33). The relationship between RBP, SDF-1 and renal function index UACR, serum uric acid (UA), blood urea nitrogen (BUN), β 2-microglobulin (β 2-MG) and serum creatinine (Scr) was analyzed. Measurement data of normal distribution were expressed as Mean± standard deviation ( Mean± SD). Independent sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups.Chi-square test was used to compare the enumeration data between groups. Receiver operating characteristic curve (ROC) was used to analyze the discriminant value of RBP and SDF-1 for DKD. Pearson was used for correlation analysis among indicators. Multivariate linear regression analysis was used to analyze the influencing factors of RBP. Results:In the DKD group, the duration of diabetes was longer, the levels of RBP, UACR, UA, BUN, β 2-MG, Scr were high, SDF-1 and eGFR were lower, with statistically significant differences compared with the simple T2DM group( P<0.05).The areas under the curve of RBP and SDF-1 to distinguish DKD were 0.903 and 0.868, and the optimal cut-off values was 70.71 mg/L and 5.69 ng/mL. With the increase of urinary albumin and clinical stage, the levels of RBP, UACR, UA, BUN, β 2-MG, Scr increased gradually, while SDF-1 and eGFR decreased gradually, and the differences were statistically significant ( P<0.05).RBP was positively correlated with UACR, UA, BUN, β 2-MG and Scr in DKD patients ( r=0.764, 0.787, 0.693, 0.577, 0.801, P<0.000 1), and negatively correlated with EGFR ( r=-0.782, P<0.000 1). SDF-1 was negatively correlated with UACR, UA, BUN, β 2-MG and Scr ( r=-0.744, -0.794, -0.666, -0.605, -0.820, P<0.000 1), and positively correlated with EGFR ( r=0.767, P<0.000 1). The multiple linear regression equation was RBP=29.852+ 0.007UACR+ 0.101UA+ 0.497BUN+ 0.034Scr-0.083eGFR ( P<0.001). Conclusion:RBP and SDF-1 have certain discriminant value for DKD patients in T2DM population, and the degree of DKD renal function injury is positively correlated with RBP and negatively correlated with SDF-1, the increase of UACR, UA, BUN, Scr and the decrease of eGFR are risk factors for the increase of RBP.

Analysis of the safety and feasibility of two closed thoracic drainage methods after video-assisted thoracoscopic lung volume reduction surgery / 中国胸心血管外科临床杂志

@#Objective    To investigate the effects of closed thoracic drainage with single tube or double tubes after video-assisted thoracoscopic lung volume reduction surgery. Methods    Retrospective analysis was performed on 50 patients (39 males, 11 females) who underwent three-port thoracoscopic lung volume reduction surgery in our hospital from January 2013 to March 2019. Twenty-five patients with single indwelling tube after surgery were divided into the observation group and 25 patients with double indwelling tubes were divided into the control group. Results    There was no significant difference in pulmonary retension on day 3 after surgery, postoperative complications, the patency rate of drainage tube before extubation, retention time or postoperative hospital stay (P>0.05). Postoperative pain and total amount of nonsteroidal analgesics use in the observation group was less than those in the control group (P<0.05). Conclusion    It is safe and effective to perform closed thoracic drainage with single indwelling tube after video-assisted thoracoscopic lung volume reduction surgery, which can significantly reduce the incidence of related adverse drug reactions and facilitate rapid postoperative rehabilitation with a reduction of postoperative pain and the use of analgesic drugs.

Laparoscopic sleeve gastrectomy for patients with type 2 diabetes mellitus / 中华普通外科杂志

Objectives To investigate the efficacy of laparoscopic sleeve gastrectomy (LSG)for patients of type 2 diabetes mellitus (T2DM).Methods Between Jun 2013 and Jun 2017,39 T2DM patients were enrolled in this study and underwent LSG.The clinical data of all patients were collected.The fasting plasma glucose (FPG),glycosylated hemoglobin (HbAl c),C-peptide,fasting insulin (FINS),glucagon-like peptide-1 (GLP-1) as well as BMI of all patients were measured before and at 1,6 months after surgery.Results All patients underwent LSG surgery successfully.The mean levels of FPG,HbAlc,C-peptide,FINS and BMI of all patients decreased at 6 months after surgery respectively compared to those before surgery [(6.4 ± 1.2) mmol/L vs.(9.6 ± 2.3) mmol/L,t =9.455,P =0.000;(6.0 ± 0.7) ％ vs.(7.5 ±1.0)％,t=10.538,P=0.000;(2.7±2.2)ng/ml vs.(4.0±2.6) ng/ml,t=3.491,P=0.001;(9.2 ±6.3) μIU/L vs.(15.5 ±11.1) μIU/L,t=4.902,P=0.000;(32.0 ±6.1) kg/m2 vs.(41.0 ± 7.5) kg/m2,t =10.826,P =0.000],however the mean GLP-1 of all patients increased after surgery compared to that before surgery [(4.0 ± 2.1) pmol/L vs.(3.1 ± 2.2) pmol/L,t =-4.242,P =0.000].At 6 months after surgery,32 patients achieved complete remission of T2DM,5 patients gained partial remission of T2DM and 2 patients got no remission of T2DM.Conclusions LSG is effective for obesity patients as well as patients suffering from T2DM.

Correlation between the infiltration of tumor-associated macrophages in the tissues of breast carcinoma and the expressions of vascular endothelial growth factors / 肿瘤研究与临床

Objective To investigate the correlation between the infiltration of tumor-associated macrophages (TAM) in breast cancer and the expressions of vascular endothelial growth factors (VEGF). Methods The expressions of CD163 (TAM marker) and VEGF in 45 postoperative tissue specimens of primary breast cancer in Affiliated Hospital of Guilin Medical University from January 2014 to January 2018 were examined by using immunohistochemistry EnVision method. Then TAM was counted under light microscope and the expression of VEGF was determined by using semi quantitative integration method. Correlation between the expression of TAM and VEGF and their relationships with clinicopathological parameters were also analyzed. Results TAM infiltration (the number of TAM under per high power field) in breast cancer patients (≤ 51 years old) was significantly more than that in breast cancer patients (> 51 years old) [(78.1±11.9)/HP vs. (69.7±14.0)/HP, t=2.167, P=0.036]. TAM infiltration in breast cancer patients with lymph node metastasis was more than that in breast cancer patients without lymph node metastasis [(79.2 ± 11.8)/HP vs. (70.2±13.6)/HP, t= 2.362, P= 0.023]. The positive rate of VEGF in breast cancer with lymph node metastasis was significantly higher than that in breast cancer without lymph node metastasis [100.00 ％(20/20) vs. 68.00％(17/25),χ2=5.749, P=0.017]. Pearson correlation analysis showed that the expression of VEGF was positively correlated with TAM infiltration (r 2 = 0.800, P< 0.05). Conclusion TAM infiltration and the expression of VEGF can be used to predict the malignant degree of breast cancer, and can be used as a potential intervention target for adjuvant therapy and clinical prognosis of breast cancer.

Diagnosis and surgical treatment of patients with femoral vein compression from synovial cyst of hip joint / 中华普通外科杂志

Objective To investigate the diagnosis,treatment and outcomes of femoral vein compression by the synovial cyst of the hip joint.Methods A retrospective study was performed on 13 patients with femoral vein compression from the hip joint synovial cyst between March 2010 and June 2017.Results All the patients received Doppler ultrasound exam.Five (38％) patients received CT.Eight (61.6％) patients received MRI.Surgeries were performed and successful in 12 cases,the synovial cysts were completely removed.All postoperative pathologic results were confirmed as synovial cyst.The median follow-up time was 24 months without recurrence.One patient treated by percutaneous needle aspiration suffered from early cyst recurrence one month after the procedure.Conclusions Surgical excision is the preferred treatment method,postoperative symptoms improve significantly without cyst recurrence.

Application of virtual reality technology in teaching course of radiotherapy technology / 中华放射肿瘤学杂志

Objective To discuss the necessity and feasibility of application of virtual reality (VR) technology in the teaching course of radiotherapy technology based on the contradictions between the theory and practice of current teaching mode.Methods After in-depth analysis of the characteristics of the existing disciplinary teaching mode,VR technology was introduced to design software,glasses,operating handles and establish a special interactive platform. The teaching courses could be delivered via mobile phone side AR, helmet and AR, touch screen and PC virtual simulation with VR virtual simulation, etc. Six processes of radiotherapy were tested through online courses and offline groups to analyze the feasibility of this technology applied in the training of radiotherapy professionals. Results After the design of software and hardware and the analysis of test results,the online teaching could be utilized to write interactive programs,build virtual experience scenes, create course resource database and construct practical training courses and teaching system. The offline practice test could be applied to the simulation learning of feedback of the whole process, which possessed feasibility and development value. It could be applied to the theory and practice teaching of radiation therapy technology,making the teaching more convenient,vivid and intuitive. Conclusions VR technique combined with radiotherapy technology training can be delivered through online and offline teaching courses of theory and practice by using the plane and virtual simulation technology, which is convenient, quick and highly efficient and deserves widespread application.

A cohort study on body mass index and risk of all-cause mortality among hypertensive population / 中华流行病学杂志

Objective To investigate the relationship between body mass index (BMI) and all-cause mortality in hypertensive population.Methods All participants were selected from a prospective cohort study based on a rural population from Henan province,China.Cox proportional hazards regression models were used to estimate the associations of different levels of BMI stratification with all-cause mortality.Restricted cubic spline models were used to detect the doseresponse relation.Results Among the 5 461 hypertensive patients,a total of 31 048.38 person-years follow-up was conducted.The median of follow-up time was 6 years,and 589 deaths occurred during the follow-up period.Compared to normal weight group (18.5 kg/m2＜BMI＜24.0 kg/m2) the multivariate-adjusted hazard ratios for all-cause mortality associated with BMI levels (＜ 18.5 kg/m2,24-28 kg/m2,and ≥28 kg/m2) were 0.83 (95％CI:0.37-1.87),0.81 (95％CI:0.67-0.97),and 0.72 (95％CI:0.56-0.91),respectively.The dose-response analysis showed a nonlinear,reverse "S" shaped relationship (non-linearity P＜0.001).Conclusion Overweight or obese might have a protective effect on all-cause mortality in hypertensive population,which supports the "obesity paradox" phenomenon.

Age-related modification effect on the association between body mass index and the risk of hypertension: A Cohort Study on Chinese people living in the rural areas / 中华流行病学杂志

Objective To study the modification effect of age on the association between body mass index and the risk of hypertension.Methods People age ≥ 18 years old were selected by clusters,from a rural area of Henan province.In total,20 194 people were recruited at baseline during 2007 and 2008,and the follow-up study was completed from 2013 to 2014.Logistic regression model was used to assess the risk of incident hypertension by baseline BMI and age-specific BMI.Results During the 6-year follow-up period,1 950 hypertensive persons were detected,including 784 men and 1 166 women,with cumulative incidence rates as 19.96％,20.51％,and 19.61％,respectively.Compared with those whose BMI＜22 kg/m2,the RRs of hypertension were 1.09 (0.93-1.27),1.17 (1.01-1.37),1.34 (1.14-1.58) and 1.31 (1.09-1.56) for participants with BMI as 22-,24-,26-and ≥28 kg/m2,respectively.In young and middle-aged populations,the risk of hypertension gradually increased with the rise of BMI (trend P＜0.05).However,in the elderly,the increasing trend on the risk of hypertension risk was not as significantly obvious (trend P＞0.05).Conclusion The effect of BMI on the incidence of hypertension seemed to depend on age.Our findings suggested that a weight reduction program would be more effective on young or middle-aged populations,to prevent the development of hypertension.

A cohort study on body mass index and risk of all-cause mortality among hypertensive population / 中华流行病学杂志

Objective To investigate the relationship between body mass index (BMI) and all-cause mortality in hypertensive population.Methods All participants were selected from a prospective cohort study based on a rural population from Henan province,China.Cox proportional hazards regression models were used to estimate the associations of different levels of BMI stratification with all-cause mortality.Restricted cubic spline models were used to detect the doseresponse relation.Results Among the 5 461 hypertensive patients,a total of 31 048.38 person-years follow-up was conducted.The median of follow-up time was 6 years,and 589 deaths occurred during the follow-up period.Compared to normal weight group (18.5 kg/m2＜BMI＜24.0 kg/m2) the multivariate-adjusted hazard ratios for all-cause mortality associated with BMI levels (＜ 18.5 kg/m2,24-28 kg/m2,and ≥28 kg/m2) were 0.83 (95％CI:0.37-1.87),0.81 (95％CI:0.67-0.97),and 0.72 (95％CI:0.56-0.91),respectively.The dose-response analysis showed a nonlinear,reverse "S" shaped relationship (non-linearity P＜0.001).Conclusion Overweight or obese might have a protective effect on all-cause mortality in hypertensive population,which supports the "obesity paradox" phenomenon.

Age-related modification effect on the association between body mass index and the risk of hypertension: A Cohort Study on Chinese people living in the rural areas / 中华流行病学杂志

Objective To study the modification effect of age on the association between body mass index and the risk of hypertension.Methods People age ≥ 18 years old were selected by clusters,from a rural area of Henan province.In total,20 194 people were recruited at baseline during 2007 and 2008,and the follow-up study was completed from 2013 to 2014.Logistic regression model was used to assess the risk of incident hypertension by baseline BMI and age-specific BMI.Results During the 6-year follow-up period,1 950 hypertensive persons were detected,including 784 men and 1 166 women,with cumulative incidence rates as 19.96％,20.51％,and 19.61％,respectively.Compared with those whose BMI＜22 kg/m2,the RRs of hypertension were 1.09 (0.93-1.27),1.17 (1.01-1.37),1.34 (1.14-1.58) and 1.31 (1.09-1.56) for participants with BMI as 22-,24-,26-and ≥28 kg/m2,respectively.In young and middle-aged populations,the risk of hypertension gradually increased with the rise of BMI (trend P＜0.05).However,in the elderly,the increasing trend on the risk of hypertension risk was not as significantly obvious (trend P＞0.05).Conclusion The effect of BMI on the incidence of hypertension seemed to depend on age.Our findings suggested that a weight reduction program would be more effective on young or middle-aged populations,to prevent the development of hypertension.

Treatment principles and surgical skills in laparoscopic subtotal cholecystectomy for acute cholecystitis / 中华肝胆外科杂志

Objective To study the treatment principles and surgical skills in laparoscopic subtotal cholecystectomy (LSC) for acute cholecystitis.Methods We retrospectively analyzed the clinical data of patients who underwent LSC for acute cholecystitis from Jan.2006 to Dec.2015 at the Beijing Shijitan Hospital,Capital Medical University.We dissected any serious pericholecystic adhesions according to the principle that "It is better that the gallbladder rather than other tissue is injured",and the technique that "After the gallbladder anterior wall is excised,the gallbladder ampulla and duct are split along the longitudinal direction of the cholecystic duct,then the opened cholecystic duct is sutured inside the gallbladder".Results LSC was completed successfully in 96 patients.There were no conversion to open surgery,and no bile duct injury.The mean surgery time was (108.0 ± 37.0) min,the mean blood loss was (121.0 ± 62.0) ml,the mean peritoneal drainage was (105.0 ± 32.0) ml.The drainage tube was removed at a mean of (3.4 ±1.2) d after surgery.The mean hospitalization time after surgery was (6.1 ± 2.2) d.Surgical complications occurred in 2 patients with bleeding after surgery.One patient underwent laparoscopic exploration to stop bleeding.Another patient underwent conservative treatment and the bleeding stopped spontaneously.There were 3 patients who had mild bile leakage.All these patients recovered well after drainage.No patient developed bile duct stenosis or obstructive jaundice on follow-up.Conclusions LSC for acute cholecystitis was safe.Bile duct injuries could be avoided if we follow the principle of "It is better that the gallbladder rather than other tissue is injured" and the technique of "After the gallbladder anterior wall is excised,the gallbladder ampulla and duct are split along the longitudinal direction of the gallbladder,then the opened cholecystic duct is sutured inside the gallbladder".

Cyclized Oligopeptide Targeting LRP5/6-DKK1 Interaction Reduces the Growth of Tumor Burden in a Multiple Myeloma Mouse Model

PURPOSE: Dickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents. In this study, we developed a cyclized oligopeptide against DKK1-low density lipoprotein receptor-related protein (LRP) 5/6 interaction and tested the effects of the oligopeptide on tumor burden. MATERIALS AND METHODS: A cyclized oligopeptide based on DKK1-LRP5/6 interactions was synthesized chemically, and its nuclear magnetic resonance structure was assessed. Luciferase reporter assay and mRNA expressions of osteoblast markers were evaluated after oligopeptide treatment. MOPC315.BM.Luc cells were injected into the tail vein of mice, after which cyclized oligopeptide was delivered subcutaneously 6 days a week for 4 weeks. RESULTS: The cyclized oligopeptide containing NXI motif bound to the E1 domain of LRP5/6 effectively on surface plasmon resonance analysis. It abrogated the Wnt-β-catenin signaling inhibited by DKK1, but not by sclerostin, dose dependently. RT-PCR and alkaline phosphatase staining showed increased expressions of osteoblast markers according to the treatment concentrations. Bioluminescence images showed that the treatment of cyclized oligopeptide reduced tumor burden more in oligopeptide treated group than in the vehicle group. CONCLUSION: The cyclized oligopeptide reported here may be another option for the treatment of tumor burden in multiple myeloma.

Effects of Single Vitamin D₃ Injection (200,000 Units) on Serum Fibroblast Growth Factor 23 and Sclerostin Levels in Subjects with Vitamin D Deficiency

BACKGROUND: Vitamin D deficiency remains common in all age groups and affects skeletal and non-skeletal health. Fibroblast growth factor 23 is a bone-derived hormone that regulates phosphate and 1,25-dihydroxyvitamin D homeostasis as a counter regulatory factor. 1,25-Dihydroxyvitamin D stimulates fibroblast growth factor 23 synthesis in bone, while fibroblast growth factor 23 suppresses 1,25-dihydroxyvitamin D production in the kidney. The aim of this study was to evaluate the effects of vitamin D₃ intramuscular injection therapy on serum fibroblast growth factor 23 concentrations, and several other parameters associated with bone metabolism such as sclerostin, dickkopf-1, and parathyroid hormone. METHODS: A total of 34 subjects with vitamin D deficiency (defined by serum 25-hydroxyvitamin D levels below 20 ng/mL) were randomly assigned to either the vitamin D injection group (200,000 units) or placebo treatment group. Serum calcium, phosphate, urine calcium/creatinine, serum 25-hydroxyvitamin D, fibroblast growth factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were serially measured after treatment. RESULTS: Comparing the vitamin D injection group with the placebo group, no significant changes were observed in serum fibroblast growth factor 23, parathyroid hormone, or dickkopf-1 levels. Serum sclerostin concentrations transiently increased at week 4 in the vitamin D group. However, these elevated levels declined later and there were no statistically significant differences as compared with baseline levels. CONCLUSION: Serum fibroblast factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were not affected significantly by single intramuscular injection of vitamin D₃.

Treatment principles and surgical skills in laparoscopic subtotal cholecystectomy for acute cholecystitis / 中华肝胆外科杂志

Objective To study the treatment principles and surgical skills in laparoscopic subtotal cholecystectomy (LSC) for acute cholecystitis.Methods We retrospectively analyzed the clinical data of patients who underwent LSC for acute cholecystitis from Jan.2006 to Dec.2015 at the Beijing Shijitan Hospital,Capital Medical University.We dissected any serious pericholecystic adhesions according to the principle that "It is better that the gallbladder rather than other tissue is injured",and the technique that "After the gallbladder anterior wall is excised,the gallbladder ampulla and duct are split along the longitudinal direction of the cholecystic duct,then the opened cholecystic duct is sutured inside the gallbladder".Results LSC was completed successfully in 96 patients.There were no conversion to open surgery,and no bile duct injury.The mean surgery time was (108.0 ± 37.0) min,the mean blood loss was (121.0 ± 62.0) ml,the mean peritoneal drainage was (105.0 ± 32.0) ml.The drainage tube was removed at a mean of (3.4 ±1.2) d after surgery.The mean hospitalization time after surgery was (6.1 ± 2.2) d.Surgical complications occurred in 2 patients with bleeding after surgery.One patient underwent laparoscopic exploration to stop bleeding.Another patient underwent conservative treatment and the bleeding stopped spontaneously.There were 3 patients who had mild bile leakage.All these patients recovered well after drainage.No patient developed bile duct stenosis or obstructive jaundice on follow-up.Conclusions LSC for acute cholecystitis was safe.Bile duct injuries could be avoided if we follow the principle of "It is better that the gallbladder rather than other tissue is injured" and the technique of "After the gallbladder anterior wall is excised,the gallbladder ampulla and duct are split along the longitudinal direction of the gallbladder,then the opened cholecystic duct is sutured inside the gallbladder".

Molecular cytogenetic analysis of a case with ring chromosome 3 syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the genetic cause for a child with developmental delay and congenital heart disease through molecular cytogenetic analysis.</p><p><b>METHODS</b>G-banded karyotyping and chromosomal microarray analysis (CMA) were performed for the patient and his parents.</p><p><b>RESULTS</b>The proband's karyotype was detected as ring chromosome 3, and a 3q26.3-25.3 deletion encompassing 45 genes has been found with CMA. Testing of both parents was normal.</p><p><b>CONCLUSION</b>Clinical phenotype of the patient with ring chromosome 3 mainly depends on the involved genes. It is necessary to combine CMA and karyotyping for the diagnosis of ring chromosome, as CMA can provide more accurate information for variations of the genome.</p>