Objective To investigate the efficacy of laparoscopic cholecystectomy(LC) followed by endoscopic retrograde cholangiopancreaticography(ERCP) for gallbladder and bile duct stones.Methods A total of 58 patients with both gallbladder and bile duct stones received endoscopic sphincterotomy(EST) in our hospital.After the stones were removed,LC was performed on the patients.Results Of the 58 patients,56 were successfully treated with EST and LC.Two cases were unsuccessful owing to difficulty in intubation during ERCP in one and failure to remove all the stones from the bile duct in the other.These two patients were then cured by LC combined with electronic choledochoscopy.Perioperative complications included bleeding during EST in 1,acute edematous pancreatitis in 2,and mild infection of the puncture site in 1.The overall complication rate was 7.1%(4/56).Retained common bile duct stone was observed in 1 patient,and was successfully removed by subsequent ERCP.Conclusions LC combined with ERCP is a safe and effective minimal invasive method for the treatment of concurrent gallstones and bile duct stones.

Swine is an ideal model for diabetes studies. Insulin and insulin resistance are closely related with diabetes. To investigate the effect of SOCS-3 in insulin resistance, porcine primary adipocyte was treated with insulin (100 nmol/L) and dexamethasone (300 nmol/L) to induce insulin resistance. The simi-quantitative PCR results suggested that insulin increased GLUT4, PPARgamma and SOCS-3 gene expression in primary culture porcine adipocytes and no change of OB gene expression. Under insulin resistance conditions, SOCS-3 and OB gene expression were up-regulated, whereas GLUT4 and PPARgamma gene expression were down-regulated in primary porcine adipocytes. The overexpression of PPARgamma gene resulted in the increase of GLUT4 expression by insulin. Different expression levels of SOCS-3 determined the inhibitory effects of insulin signaling. Induction of insulin resistance by dexamethasone was not only due to inhibition of glucose transportation, but also repression of insulin signaling. SOCS-3 might be a potential gene to block the insulin resistance.
Adipocytes ; cytology ; metabolism ; Animals ; Cells, Cultured ; Dexamethasone ; pharmacology ; Glucose Transporter Type 4 ; biosynthesis ; genetics ; Insulin ; pharmacology ; Insulin Resistance ; Leptin ; biosynthesis ; genetics ; PPAR gamma ; biosynthesis ; genetics ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; biosynthesis ; genetics ; Swine

Objective: To investigate the clinical features and genetic characteristics of patients with TBC1D24 gene mutations. Method: The clinical data of a patient with novel TBC1D24 compound heterozygous mutations from Children′s Hospital of Fudan University were collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and Pubmed (up to April 2016) by using search terms "TBC1D24" "epilepsy" . The clinical features, electroencephalogram (EEG) and prognosis of the patients with TBC1D24 gene mutations were studied. Result: The patient was a boy with non-consanguineous healthy parents.He had an acute episode of focal continuous myoclonus lasting a few hours with consciousness preserved at the age of 3 months.Myoclonic jerks alternatively affected the eyelids, either the right or left limbs, sometimes triggered by fever or fatigue.The frequency was once 3-7 days.At the age of 6 months he was found to have myoclonus seizures with onset from a unilateral eyes lid and limb lasting 10 more minutes and subsequently affected four extremities or the trunk.They occurred once 3-4 months with perserved consciousness and lasted from several hours to up to ten more hours.They mostly disappeared during sleep.He had ataxia and mild mental retarding.Paroxysmal anomalies were not found on ictal traces.A novel compound heterozygous mutation of TBC1D24 gene, c. 730G>A, p.A244T and c. 1571G>C, p.R524P were found in the patient.Further study showed that c. 730G>A mutation was inherited from his father and c. 1571G>C from his mother. These two were not reported in public databases and predicted deleterious by Mutation Taster and polyphen-2.Literature relevant to TBC1D24 published all around the world was reviewed, no Chinese cases with TBC1D24 gene mutations had been reported. The total of 24 cases including the present case with TBC1D24 gene mutation were reported.Among them, 11 cases had compound heterozygous mutations and 13 cases had homozygous mutations.Ten mutations were identified, including 1 termination mutation, 1 frameshift mutation and 8 missense mutations. Conclusion TBC1D24 gene mutational analysis should be performed on patients with early-onset focal continuous myoclonus, if the etiology was unclear.

Cognitive dysfunction,predominantly a consequence of neurodegenerative disorders,is a burgeoning health issue.Odor molecules have the unique ability to circumvent the blood-brain barrier through the olfactory pathway,exerting a direct influence on cognitive-related brain regions including the entorhinal cortex,hippocampus,and amygdala,without transiting through the thalamus.These olfactory molecules,mostly sourced from natural plant essential oils,are character-ized by significant volatility,minimal adverse reactions,and abundant availability.Hence,research into and applications of olfactory stimulation in improving cognitive dysfunction have raised widespread concerns.This article reviews the rela-tionship between the olfactory pathway and cognitive brain regions,and explores the mechanism by which natural plant es-sential oils alleviate cognitive dysfunction through olfactory stimulation in order to provide a reference for improving cogni-tive function via olfactory stimulation.

Objective:To investigate the role and mechanism of dopamine receptor D2(DRD2)in the immune microenvironment of breast cancer. Methods:The xenograft model of breast cancer is established using female C57BL/6J mice and murine breast cancer EO771 cells.Mice with transplanted tumor were treated by intraperitoneal injection of the specific antagonist of DRD2,thioridazine,while PBS was injected intraperitoneally in the control group.siDRD2 targeting DRD2 gene was intratumorally injected to tumor-bearing mice[negative control siRNA(siNC)was injected to the control group].The percentage of Ki-67 positive cells and CD4+T lymphocytes in tumor tissue was examined by immunohistochemical analysis.The proportion of CD45+CD4+T lymphocytes,CD45+CD4+IFNγ+Th1 cells and CD45+CD4+IL-1 7+Th17 cells was detected by flow cytometry. Results:Compared with the control group,the tumor volume(P＜0.05),tumor mass(P＜0.001)and the proportion of Ki-67 positive cells(P＜0.001)in tumor tissue were decreased in the thioridazine-treated group.The proportion of CD45+immune cells(P＜0.05)and CD4+T lymphocytes(P＜0.001)in thioridazine-treated group was higher than that in the control group.The proportion of Th1 cells(CD45+CD4+IFNγ+)increased(P＜0.001)in thioridazine-treated group.There was no significant changes in the proportion of Th1 7 cells(CD45+CD4+IL-1 7+)(P＞0.05).Compared with the control group(siNC),the tumor volume(P＜0.05),tumor mass(P＜0.001)and the proportion of Ki-67 positive cells(P＜0.001)were decreased in siDRD2 group.The proportion of tumor infiltrating CD4+T lymphocytes(P＜0.001)and Th1 cells(P＜0.001)in the siDRD2 group was higher than that in the siNC group,whereas the change in the proportion of Th1 7 cells was not statistically significant(P＞0.05). Conclusion:Down-regulation of DRD2 could promote the differentiation of Th1 cells and inhibit the proliferation of breast cancer cells in a mouse breast cancer model.

Breast cancer is the most diagnosed cancer in women worldwide and the leading cause of most cancer-related deaths,posing a serious threat to women′s health worldwide.At present,although the prognosis of some patients with breast cancer has improved,the emergence of drug resistance and the metastasis and recurrence of breast cancer are still the main reasons for poor prognosis.CD36 is a multiligand transmembrane glycoprotein expressed on various cell types.In recent years,studies have confirmed that CD36 can reshape the lipid metabolism of cancer cells;promote the differentiation of tumor-related macrophages into M2 type and recruitment into tumor tissues;regulate the function of Treg cells,CD8+T cells,DCs,and other immune cells,and thus promote tumor development.In addition,CD36 is also associated with breast cancer stem cells,metastasis-initiating cells,and breast drug resistant cells.Therefore,CD36 could be an important potential therapeutic target for breast cancer.

Objective To study the influence of rosemary essential oil inhalation on the memory of mice experiencing sleep deprivation and to delineate the possible mechanisms involved.Methods C57BL/6J mice were randomly divided into four experimental groups in this study:a control group(Con),a control group with rosemary essential oil inhalation(Con+REO),a sleep deprivation group(SD)and a sleep deprivation group with rosemary essential oil inhalation(SD+REO).A 72-hour sleep deprivation model was induced using the multiple platform water environment method,with the Con+REO and SD+REO groups exposed to rosemary essential oil inhalation.Cognitive function was evaluated through Y-maze and novel object recognition tests.The hippocampal tissue was analyzed for superoxide dismutase(SOD)activity and the concentrations of malondialdehyde(MDA)and glutathione(GSH).ELISA was used to determine the levels of norepinephrine(NE),dopamine(DA),and serotonin 5-hydroxytryptamine(5-HT)in the hippocampus.The expression levels of postsynaptic density 95(PSD95)and brain-derived neurotrophic factor(BDNF)in the hippocampus were determined using immunoblotting techniques.Results Compared with the Con and Con+REO groups,the SD group demonstrated a significant reduction in the spontaneous alternation percentage in the Y-maze as well as the novel object recognition index.Additionally,there was a pronounced decrease in hippocampal SOD activity and GSH content,a substantial elevation in MDA levels,and a decrease in the levels of DA,NE,and 5-HT.The expressions of PSD95 and BDNF proteins also decreased.In comparison with the SD group,the SD+REO group exhibited a significant increase in the spontaneous alternation percentage in the Y-maze and the novel object recognition index.There was also a marked increase in hippocampal SOD activity and GSH content,a reduction in MDA levels and elevated levels of NE and DA.Moreover,the expressions of PSD95 and BDNF proteins were upregulated.Conclusion The inhalation of rosemary essential oil enhances the memory of sleep-deprived mice,and the underlying mechanism may involve the mitigation of oxidative stress within the hippocampal tissue,the modulation of neurotransmitter levels,and the facilitation of synaptic plasticity.

Objective To understand the situation of iodine deficiency disorders and iodine nutrition of children in Yunnan Province after the implementation of new standard of salt iodine,and provide the basic data for prevention and control of iodine deficiency disorders.Methods Using multistage sampling method,Yunnan provincial evaluations for iodine deficiency disorders elimination were carried out.According to the comparative analysis of 2010 (pre-adjustment) and 2015 (post-adjustment) evaluation results,the changes of the median of salt iodine,the coverage rate of iodized salt,the qualified rate of iodized salt,the rate of qualified iodized salt consumption,goiter rate of school children aged 8-10 and the median of urinary iodine were evaluated.Salt iodine was tested using the "Salt Industry General Test Method for Determination of Iodine" (GB/T 13025.7-1999);thyroid volume examination of children using B-scan ultrasonography,thyroid volume calculation and enlargement judgment using "Diagnostic Criteria for Endemic Goiter" (WS 276-2007);and urinary iodine detection using "Urinary Iodine Arsenic Cerium Catalytic Spectrophotometry" (WS/T 107-2006).Results The medians of salt iodine in 2010 and 2015 were 30.6 and 22.4 mg/kg,respectively,the difference was statistically significant (U =317 503.50,P ＜ 0.01).The coverage rates of iodized salt in 2010 and 2015 were 99.6％ (1 681/1 688) and 98.9％ (2 592/2 622),the qualified rates of iodized salt were 98.6％ (1 657/1 681) and 89.7％ (2 325/2 592),and the rates of qualified iodized salt consumption were 98.2％ (1 657/1 688) and 88.7％ (2 325/2 622),and the differences were statistically significant (x2 =6.42,125.11,130.18,P ＜ 0.01);the rates of children goiter in 2010 and 2015 were 0.8％ (25/3 272) and 1.4％(44/3 245),respectively;the medians of urinary iodine of children were 289.0 and 157.3 μg/L,respectively,the difference was statistically significant (U =1 121 669.50,P ＜ 0.01).Conclusion After decreasing of salt iodine level starting from 2012 in Yunnan Province,the children iodine nutrition condition is in a more proper level.

Objective To investigate the influence from natural and constrained modal of the hip joint on internal fixation after implantation of hollow screws and locking plates for treating femoral neck fractures. Methods CT image data of a patient with femoral neck fracture were analyzed, boundary of the hip joint was extracted to generate a three-dimensional (3D) model of the hip joint, and the assembly of common internal fixation models and hip joint models was established. Finite element simulation was then conducted, with focus on vibration characteristics. Results Vibration had a certain effect on internal fixation stability of hollow screws and locking plates. The occurrence of torsion would destroy the fixation environment of hollow screws and locking plates, resulting in a small displacement at the fracture end. In a constrained state, the modal frequency range was lower. Deformation of the vibration shape mostly occurred at proximal end of the femoral head, leading to the loosening phenomenon of internal fixation and prosthesis. A method for judging the stability of internal fixation was proposed from the perspective of vibration characteristics, and it was found that the stability of internal fixation with hollow screws was better than that of proximal locking plates. Conclusions For choosing internal fixation, influences from natural frequency of the screw and plate should be considered, so as to avoid natural frequency of the femur, which may cause resonance. The results can be used as a guidance for the selection of internal fixation materials and the design of structure and configuration.

Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.