Association between thyroid function and nonalcoholic fatty liver disease: a dose-response meta-analysis.

Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Trial registration: Registered number in PROSPERO: CRD42023405052.

Changes in the Biomechanical Properties of Corneal Stromal Lens after Collagen Crosslinking Induced by EDC-NHS.

Introduction: To evaluate the changes of lens antidilatation, antiedema, and antienzymolysis ability after different concentrations of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC-NHS)-induced collagen cross-linking. Methods: Corneal stromal lenticules (n = 100) obtained from small incision lenticule extraction (SMILE) procedures were divided into 5 groups: no treatment (control); EDC/NHS (5%/2.5%); EDC/NHS(5%/5%); EDC/NHS (10%/5%); riboflavin and ultraviolet-A light (UVA). Collagen crosslinking was induced using EDC-NHS and UVA. Biomechanical assessments including inflation test, enzymatic degradation resistance, and light transmittance were evaluated posttreatment. Results: (1) Lenticule apex displacement ranked: control Group > UVA Group > Group (5%/5%) > Group (5%/2.5%) > Group (10%/5%) (Friedman test, p < 0.0001). (2) Light transmittance was significantly higher in the crosslinked groups versus control, with EDC/NHS superior to UVA riboflavin. After 15 minutes in PBS, light transmittance decreased due to swelling; however, crosslinked groups maintained significantly higher transmittance versus control. (3) Following crosslinking, enzymatic resistance improved significantly, with the EDC-NHS crosslinking group was significantly better than the UVA cross-linking group. Conclusions: EDC/NHS crosslinking enhanced lenticule stiffness, antiedema, and enzymatic resistance and without compromising the transparency of the lens. Moreover, EDC/NHS crosslinking efficacy exceeded UVA riboflavin crosslinking in improving lenticule biomechanical properties.

Balanced medial-lateral wall vs selective 3-wall orbital decompression for sight-threatening Graves's orbitopathy: a clinical retrospective cohort study from 2016 to 2022.

PURPOSE: Although urgent orbital decompression surgery for sight-threatening Graves' orbitopathy unresponsive to available medical treatments continues to evolve, post-operative new-onset or worsened pre-operative strabismus or diplopia remains a significant complication. At present, the optimal surgical technique remains debatable. Here, we sought to compare long-term outcomes after balanced medial-lateral wall versus selective 3-wall decompression as an urgent treatment for unresponsive sight-threatening GO. METHODS: This retrospective study examined the post-operative outcome of 102 eyes (57 patients) that underwent urgent orbital decompression for sight-threatening GO. Treatment effectiveness was measured by visual acuity, proptosis, perimetry, and strabismus/diplopia, while fundus findings were detected by fundus color photography and optical coherence tomography and followed up for more than 12 months. RESULTS: Fifty-seven patients (102 orbits) with an average age of 52.7 ± 10.2 years were evaluated. Balanced medial-lateral wall (BMLW-OD) or selective 3-wall decompression(S3W-OD) were performed in 54 and 48 eyes, respectively. Twelve months after orbital decompression, all parameters significantly improved in both groups, including best-corrected visual acuity (BCVA), mean defect of visual field (VF-MD), pattern standard deviation of visual field (VF-PSD), and proptosis (all P < 0.01). However, new-onset esotropia occurred in 25.8% and 3.8% of patients who underwent BMLW-OD surgery or S3W-OD, respectively. Moreover, 6.5% and 38.5% of patients improved after decompression in the medial-lateral wall decompression group and the selective 3-wall decompression group, respectively. CONCLUSIONS: We demonstrated that S3W-OD provides a lower rate of new-onset strabismus/diplopia as compared with BMLW-OD surgery, while still allowing for satisfactory visual outcomes. TRIAL REGISTRATION NUMBER:  : NCT05627401. Date of registration: November 25, 2022.

Establishment of risk prediction model for postoperative liver injury after non-liver surgery based on different machine learning algorithms / 陆军军医大学学报

Objective To construct a machine learning prediction model for postoperative liver injury in patients with non-liver surgery based on preoperative and intraoperative medication indicators.Methods A case-control study was conducted on 315 patients with liver injury after non-liver surgery selected from the databases developed by 3 large general hospitals from January 2014 to September 2022.With the positive/negative ratio of 1 ∶3,928 cases in corresponding period with non-liver surgery and without liver injury were randomly matched as negative control cases.These 1243 patients were randomly divided into the modeling group(n=869)and the validation group(n=374)in a ratio of 7∶3 using the R language setting code.Preoperative clinical indicators(basic information,medical history,relevant scale score,surgical information and results of laboratory tests)and intraoperative medication were used to construct the prediction model for liver injury after non-liver surgery based on 4 machine learning algorithms,k-nearest neighbor(KNN),support vector machine linear(SVM),logic regression(LR)and extreme gradient boosting(XGBoost).In the validation group,receiver operating characteristic(ROC)curve,precision-recall curve(P-R),decision curve analysis(DCA)curve,Kappa value,sensitivity,specificity,Brier score,and F1 score were applied to evaluate the efficacy of model.Results The model established by 4 machine learning algorithms to predict postoperative liver injury after non-liver surgery was optimal using the XGBoost algorithm.The area under the receiver operating characteristic curve(AUROC)was 0.916(95%CI:0.883～0.949),area under the precision-recall curve(AUPRC)was 0.841,Brier score was 0.097,and sensitivity and specificity was 78.95%and 87.10%,respectively.Conclusion The postoperative liver injury prediction model for non-liver surgery based on the XGBoost algorithm has effective prediction for the occurrence of postoperative liver injury.

Prediction of isocitrate dehydrogenase status of glioma via diffusion tensor imaging parameters and clinical features / 实用放射学杂志

Objective To noninvasively predict isocitrate dehydrogenase(IDH)status of glioma via combining imaging and clini-cal features before surgery,so as to provide basis for individualized clinical treatment decision.Methods A total of 47 patients with glioma confirmed by pathological and molecular genetic tests were included,including 20 with IDH mutant type and 27 with IDH wild type.After diffusion tensor imaging(DTI)scanning,fractional anisotropy(FA)and mean diffusivity(MD)values of tumor paren-chyma were calculated.Combining DTI parameters with MRI morphological features of tumor,blood neutrophil/lymphocyte ratio(NLR)and patient's age,binary logistic regression model was established to effectively predict IDH status of glioma patients before surgery.Results There were significant differences in FAmean/FANAWM,MDmin,NLR,tumor location and age between IDH mutant type and IDH wild type groups(P<0.05).The binary logistic regression model concluding,FAmean/FANAWM,MDmin,cystic degeneration,NLR and age,predicted IDH status of glioma with area under the curve(AUC)of 0.961 and 95%confidence interval(CI)of 0.914-1.00.Conclusion The regression model established via combining DTI,MRI morphological features and blood NLR has great performance in classifying IDH status of glioma,and can help predict IDH status noninvasively before surgery,so as to assist clinical individualized treatment.

Correlation between Serum CD73 and Motor Dysfunction in Patients with Parkinson's Disease / 医学研究杂志

Objective To explore the expression level of serum CD73 in Parkinson's disease(PD)patients and the correlation be-tween serum CD73 and the severity of motor dysfunction.Methods A total of 97 PD patients and 71 healthy controls were included.Bas-ic data of the subjects were collected,including age,gender,smoking history,and the condition of dose taking.Disease course,H&Y stage,and UPDRS-Ⅲ score of PD patients were also collected.PD patients were divided into mild PD group,and moderate and severe PD group according to H&Y stage.The fasting venous blood of the subjects was collected for serum CD73detection.Binary Logistic regres-sion analysis was used to analyze the correlation between PD and factors such as age,gender,and serum CD73.Receiver operating char-acteristic curve analysis was used to predict the diagnostic value of serum CD73.Pearson correlation was used to analyze the correlation between serum CD73 level,H&Y stage,and UPDRS-Ⅲ score in PD patients.Results The level of serum CD73 in PD patients was significantly lower than that in healthy controls.Binary Logistic regression showed that the decrease in the level of serum CD73 was an in-dependent risk factor for PD.The level of serum CD73 lower than 2.85U/L was more sensitive to the diagnosis of PD.In PD patients,the higher the H&Y stage,the lower the serum CD73 level;Pearson correlation analysis showed that the serum CD73 level was negatively cor-related with the H&Y stage and UPDRS-Ⅲ score.Conclusion The reduction of serum CD73 level can significantly increase the risk of PD,and the lower the level of serum CD73,the more serious the motor dysfunction of PD patients.

Application of deep learning technology in the diagnosis of gastrointestinal stromal tumors / 中国医科大学学报

Gastrointestinal stromal tumor(GIST),with a certain malignant potential,are currently the most common subepithelial tumors of the gastrointestinal tract.Early diagnosis and prediction of malignant potential are very important for the formulation of a treatment plan and determining the prognosis of GIST.Deep learning technology has made significant progress in the diagnosis of digestive tract diseases,and it can also effectively assist physicians in diagnosing GIST and predicting their malignant potential,preoperatively.The application of deep learning technology in the diagnosis of GIST includes CT,gastrointestinal endoscopy and endoscopic ultrasound.This paper aims to review the application of deep learning technology in the diagnosis and prediction of malignant potential of GIST.

Deep Learning-Based Segmentation of Extra-Pelvic Organs and Metastases in Advanced Prostate Cancer Based on MET-RADS-P / 中国医学影像学杂志

Purpose To explore the feasibility of the deep learning-based segmentation of extra-pelvic region and metastases in advanced prostate cancer based on metastasis reporting and data system for prostate cancer(MET-RADS-P).Materials and Methods Four datasets(68,91,57 and 263 patients with head,neck,chest and abdomen metastases,respectively)from Jan 2017 to Jan 2022 in Peking University First Hospital were retrospectively collected for the development of the classification model of scanning range and segmentation model of different regions and metastases according to the scanning sites(head,neck,chest and abdomen).In addition,90 patients with prostate cancer confirmed by pathology and underwent whole-body MRI were collected for external validation of the developed model.The manual annotation of the regions and metastases were used as the"reference standard"for the model evaluation.The evaluation indexes included dice similarity coefficient(DSC)and volumetric similarity(VS).Results In the external validation set,the classification accuracy of head,neck,chest and abdomen were 100%(90/90),98.89%(89/90),96.67%(87/90)and 94.44%(85/90),respectively.The range of DSC,VS values of the segmentation model for organs in different regions were(0.86±0.10)-(0.99±0.01),(0.89±0.10)-(0.99±0.01),respectively.The range of DSC,VS values of the segmentation model for metastases in different regions were(0.65±0.07)-(0.72±0.13),(0.74±0.04)-(0.82±0.13),respectively.Conclusion The 3D U-Net model based on deep learning may achieve the segmentation of extra-pelvic region and metastasis in advanced prostate cancer.

Value of 18F-PSMA-1007 PET/CT-based radiomics model for differential diagnosis between prostate cancer and benign prostatic hyperplasia / 中华核医学与分子影像杂志

Objective:To evaluate the value of prostate specific membrane antigen (PSMA) PET/CT-based radiomics models in differentiation between prostate cancer and benign prostatic hyperplasia (BPH).Methods:Data from 50 patients with prostate cancer (age: (70.0±8.8) years) and 25 patients with BPH (age: (66.9±9.4) years) who underwent 18F-PSMA-1007 PET/CT imaging and prostate biopsy in the First Affiliated Hospital of Xi′an Jiaotong University from May 2020 to September 2022 were retrospectively collected. Patients were divided into the training set ( n=53) and test set ( n=22) in the ratio of 7∶3 by using random seed number. The ROIs were delineated based on PET and CT images, and radiomics features were extracted respectively. Feature selection was performed using the minimum redundancy and maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithm. PET and PET/CT radiomics models were generated using logistic regression. ROC curve analysis was employed for model evaluation. In addition, comparisons of the 2 radiomics models with parameters including the ratio of free prostate specific antigen (fPSA)/total prostate specific antigen (tPSA), PET metabolic parameters, as well as prostate cancer molecular imaging standardize evaluation (PROMISE) were conducted (Delong test). Results:A total of 7 features were included in the PET radiomics model, and 3 CT-based features and 4 PET-based features were included in the PET/CT radiomics model. The AUCs of PET and PET/CT radiomics models in the training set and test set were 0.941, 0.914 and 0.965, 0.914, respectively, which were higher than those of fPSA/tPSA (0.719 and 0.710), SUV max(0.748 and 0.800), peak of SUV (SUV peak, 0.722 and 0.771), metabolic tumor volume (MTV, 0.640 and 0.595), total lesion uptake (TLU, 0.525 and 0.476) and PROMISE (0.644 and 0.667)[ z values for the training set: from -6.26 to -3.13, all P<0.01; z values for the test set: from -3.16 to -1.08, P>0.05 (fPSA/tPSA, SUV max, SUV peak) or P<0.05 (MTV, TLU, PROMISE)]. The differential diagnostic accuracy, sensitivity and specificity of PET and PET/CT radiomics models in the test set were 86.36%(19/22), 13/15, 6/7 and 90.91%(20/22), 15/15, 5/7, respectively. Conclusion:Compared with the clinical and PET parameters, PSMA PET/CT-based radiomics model can further improve the efficiency of differential diagnosis between prostate cancer and BPH.

A case of tubulointerstitial nephritis and uveitis syndrome complicated with Fanconi syndrome and literature review / 中华肾脏病杂志

The clinical diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome combined with Fanconi syndrome is relatively rare. The paper reports a 47-year-old female patient of TINU syndrome with hypokalemia, hypophosphatemia, hypouricemia and renal impairment as initial symptoms followed by uveitis. Serological tests showed that the patient also met the diagnostic criteria of Fanconi syndrome. Renal tissue pathology confirmed tubular interstitial injury, manifested as interstitial nephritis with acute tubular injury. Ophthalmic examination confirmed iritis in the right eye. After excluding other primary diseases, the patient was diagnosed as TINU syndrome with Fanconi syndrome. After glucocorticoid therapy, ocular symptoms, renal impairment and electrolyte disturbance were significantly improved.

Outcomes of total cavopulmonary connection in the treatment of functional single ventricle with heterotaxy syndrome: A propensity score matching study / 中国胸心血管外科临床杂志

@#Objective To comprehensively analyze the clinical outcomes of total cavopulmonary connection (TCPC) in the treatment of functional single ventricle combined with heterotaxy syndrome (HS). Methods A retrospective analysis was conducted on the patients with functional single ventricle and HS who underwent TCPC (a HS group) in Guangdong Provincial People's Hospital between 2004 and 2021. The analysis focused on postoperative complications, long-term survival rates, and identifying factors associated with patient survival. Early and late postoperative outcomes were compared with matched non-HS patients (a non-HS group). Results Before propensity score matching, 55 patients were collected in the HS group, including 42 males and 13 females, with a median age of 6.0 (4.2, 11.8) years and a median weight of 17.0 (14.2, 28.8) kg. Among the patients, there were 53 patients of right atrial isomerism and 2 patients of left atrial isomerism. Eight patients underwent TCPC in one stage. TCPC procedures included extracardiac conduit (n=39), intracardiac-extracardiac conduit (n=14), and direct cavopulmonary connection (n=2). Postoperative complications included infections in 27 patients, liver function damage in 19 patients, and acute kidney injury in 11 patients. There were 5 early deaths. The median follow-up time was 94.7 (64.3, 129.8) months. The 1-year, 5-year, and 10-year survival rates were 87.2%, 85.3%, and 74.3%, respectively. After propensity score matching, there were 45 patients in the HS group and 81 patients in the non-HS group. Compared to the non-HS group, those with HS had longer surgical and mechanical ventilation time, higher infection rates (P<0.05), and a 12.9% lower 10-year survival rate. Multivariate Cox regression analysis identified asplenia was a risk factor for mortality (HR=8.98, 95%CI 1.86-43.34, P=0.006). Conclusion Compared to non-HS patients, patients with HS have lower survival rates after TCPC, and asplenia is an independent risk factor for the survival of these patients.

Prediction and validation of common targets in atherosclerosis and non-small cell lung cancer influenced by atorvastatin.

BACKGROUND: Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology. METHODS: The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease-target-component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients. RESULTS: We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin. CONCLUSIONS: This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.

Sex- and reproductive status-specific relationships between body composition and non-alcoholic fatty liver disease.

BACKGROUND: Sex and reproductive status differences exist in both non-alcoholic fatty liver disease (NAFLD) and body composition. Our purpose was to investigate the relationship between body composition and the severity of liver steatosis and fibrosis in NAFLD in different sex and reproductive status populations. METHODS: This cross-sectional study included 880 patients (355 men, 417 pre-menopausal women, 108 post-menopausal women). Liver steatosis and fibrosis and body composition data were measured using FibroScan and a bioelectrical impedance body composition analyzer (BIA), respectively, and the following parameters were obtained: liver stiffness measurement (LSM), controlled attenuation parameter (CAP), waist circumference (WC), body mass index (BMI), percent body fat (PBF), visceral fat area (VFA), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), fat mass (FM), fat free mass (FFM), and FFM to FM ratio (FFM/FM). Multiple ordinal logistic regression (MOLR) was used to analyze the independent correlation between body composition indicators and liver steatosis grade and fibrosis stage in different sex and menopausal status populations. RESULTS: Men had higher WC, ASM, ASMI, FFM, and FFM/FM than pre- or post-menopausal women, while pre-menopausal women had higher PBF, VFA, and FM than the other two groups (p < 0.001). Besides, men had greater CAP and LSM values (p < 0.001). For MOLR, after adjusting for confounding factors, WC (OR, 1.07; 95% CI, 1.02-1.12; P = 0.011) and FFM/FM (OR, 0.52; 95% CI, 0.31-0.89; P = 0.017) in men and visceral obesity (OR, 4.16; 95% CI, 1.09-15.90; P = 0.037) in post-menopausal women were independently associated with liver steatosis grade. WC and visceral obesity were independently associated with liver fibrosis stage in men (OR, 1.05; 95% CI, 1.01-1.09, P = 0.013; OR, 3.92; 95% CI, 1.97-7.81; P < 0.001, respectively). CONCLUSIONS: Increased WC and low FFM/FM in men and visceral obesity in post-menopausal women were independent correlates of more severe liver steatosis. In addition, increased WC and visceral obesity were independent correlates of worse liver fibrosis in men. These data support the sex- and reproductive status-specific management of NAFLD.

Retrospective analysis of 217 fatal intoxication autopsy cases from 2009 to 2021: temporal trends in fatal intoxication at Tongji center for medicolegal expertise, Hubei, China.

This retrospective analysis of fatal intoxication case autopsies was performed at Tongji Center for Medicolegal Expertise in Hubei (TCMEH) from 2009 to 2021 to obtain up-to-date information on intoxication cases. The objective was to describe important data about evolving patterns in intoxication occurrences, enhance public safety policies, and assist forensic examiners and police in more efficient handling of such cases. Analyses based on sex, age, topical exposure routes, toxic agents, and mode of death were performed using 217 records of intoxication cases collected from TCMEH as a sample, and the results were compared with reports previously published (from 1999 to 2008) from this institution. Deaths from intoxications occurred at a higher rate in males than in females and were most common among individuals aged 30-39 years. The most frequent method of exposure was oral ingestion. The causative agents of deadly intoxications have changed when compared to the data from the previous 10 years. For instance, deaths from amphetamine overdoses are becoming more prevalent gradually, whereas deaths due to carbon monoxide and rodenticide intoxication have declined dramatically. In 72 cases, pesticides continued to be the most frequent intoxication cause. A total of 60.4% of the deaths were accidental exposure. Men died from accidents at a higher rate than women, although women were more likely to commit suicide. Particular focus is needed on the use of succinylcholine, cyanide, and paraquat in homicides.

Exploring the Mechanism of Yi-Jing Decoction in Treating Polycystic Ovary Syndrome by Using Network Pharmacology.

BACKGROUND: Yi-Jing decoction (YJD), a traditional Chinese medicine prescription, has been reported to be effective in the treatment of polycystic ovary syndrome (PCOS). However, the underlying mechanisms of YJD in treating PCOS are still unclear. OBJECTIVE: In the present work, the effective ingredients of YJD and their treatment mechanisms on PCOS were systematically analyzed. METHODS: The effective ingredients of YJD and targets of PCOS were selected from public databases. The network pharmacology method was used to analyze the ingredients, potential targets, and pathways of YJD for the treatment of PCOS. RESULTS: One hundred and three active ingredients were identified from YJD, of which 82 were hit by 65 targets associated with PCOS. By constructing the disease-common targetcompound network, five ingredients (quercetin, arachidonate, beta-sitosterol, betacarotene, and cholesterol) were selected out as the key ingredients of YJD, which can interact with the 10 hub genes (VEGFA, AKT1, TP53, ALB, TNF, PIK3CA, IGF1, INS, IL1B, PTEN) against PCOS. These genes are mainly involved in prostate cancer, steroid hormone biosynthesis, and EGFR tyrosine kinase inhibitor resistance pathways. In addition, the results of molecular docking showed that the ingredients of YJD have a good binding affinity with the hub genes. CONCLUSION: These results demonstrate that the treatment of PCOS by YJD is through regulating the levels of androgen and insulin and improving the inflammatory microenvironment.

Curcumol inhibits breast cancer growth via NCL/ERα36 and the PI3K/AKT pathway.

Background: Breast cancer (BC) is the most common malignancy worldwide. ERα36 (ERα66 variant) is expressed in many breast cancer cells, especially highly expressed in tamoxifen (TAM)-resistant cell lines and triple-negative breast cancer, and our previous work revealed that nucleolin (NCL) is a protein target of curcumol. This study is aimed at investigating the effect and mechanism of curcumol on ERα36 positive breast cancer cells, and the relationship between curcumol's target protein NCL and ERα36. Study design: Application of in vivo and in vitro studies to reveal the mechanism of curcumol in inhibiting BC growth and the relationship between curcumol's target protein NCL and ERα36. Methods: The anti-tumor effect of curcumol was quantified via an MTT assay, colony formation and cycle arrest, respectively. The expressions of ERα36, NCL and the proteins involved in PI3K/AKT signaling were evaluated by western blotting. The interaction between two proteins was detected using co-immunoprecipitation (Co-IP) and an immunofluorescence assay. A mouse xenograft model was established to verify the role of ERα36 in breast cancer cells and curcumol's effect on ERα36 positive cancer cells. Results: Curcumol inhibited the cell growth, caused cell cycle arrest, decreased cell cycle related proteins and inactivated the PI3K/AKT pathway in ERα36 positive breast cancer cells. There is a positive correlation between NCL and ERα36 in breast cancer cells. In addition, ERα36 bound to NCL; the two proteins were distributed in the nucleus, cytoplasm and plasma membrane, where their expression was obviously decreased by curcumol. Moreover, NCL silenced by NCL siRNA blocked the cell cycle progress and inhibited the activation of PI3K/AKT in MDA-MB-231 cells, while overexpressed ERα36 increased the expression of NCL, promoted the cell cycle progress and enhanced the activity of PI3K/AKT in MCF-7 cells. NCL knockdown or ERα36 overexpression attenuated the effect of curcumol on breast cancer cells. Conclusion: Curcumol reduced the proliferation of breast cancer cells by targeting NCL/ERα36 and inactivating the PI3K/AKT pathway.

Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica.

BACKGROUND: Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. METHODS: We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. RESULTS: Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. CONCLUSIONS: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.

Research progress of familial hereditary prostate cancer / 中华泌尿外科杂志

Hereditary prostate cancer has the highest hereditary rate in men cancers. Genes associated with hereditary prostate cancer susceptibility include mismatch repair genes (MLH1, MSH2, MSH6 and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2), and single nucleotide polymorphisms and copy number variants also play a role in genetic mutations. Early onset, rapid disease progression and locally advanced stage are the main features of hereditary prostate cancer. Patients with potentially hereditary prostate cancer would benefit from undergoing genetic testing or counseling. This article reviews the current status of the prevalence, incidence characteristics, and etiology of familial hereditary prostate cancer and other research advances.

Role of TLR4/NF-κB signaling pathway in long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal rats / 中华麻醉学杂志

Objective:To evaluate the role of Toll-like receptor 4 (TLR4)/nuclear transcription factor κB (NF-κB) signaling pathway in long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal rats.Methods:Seventy-five SPF healthy newborn Sprague-Dawley rats of either sex, aged 6 days, weighing 12-20 g, were divided into 3 groups ( n=25 each) using a random number table method: control group (group C), multiple exposures to sevoflurane anesthesia group (group S) and TLR4 inhibitor plus multiple exposures to sevoflurane anesthesia group (group I+ S). The rats in group S and group I inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. TLR4 inhibitor TAK-242 10 mg/kg was intraperitoneally injected before each exposure to sevoflurane in group I, and the equal volume of normal saline was given instead in the other two groups. The spontaneous activity was evaluated by open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. After the behavioral test, the blood samples from the abdominal aorta were collected, and then the rats were sacrificed under deep anesthesia to isolate the hippocampal tissues for measurement of the levels of S100β and neuron-specific enolase (NSE) in serum and hippocampal interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) (by enzyme-linked immunosorbent assay), expression of TLR4, NF-κB p65 and phosphorylated NF-κB p65 (p-NF-κB p65) (by Western blot) and for microscopic examination of the pathological changes of hippocampal CA1 region after HE staining. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the TLR4 expression was up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was increased, the levels of serum S100β protein and NSE and hippocampal IL-1β, IL-6 and TNF-α were increased ( P<0.05), and the pathological changes in the hippocampal CA1 region were aggravated in group S. Compared with group S, the escape latency was significantly shortened, the number of crossing the original platform was increased, TLR4 expression was down-regulated, the ratio of p-NF-κB p65/NF-κB p65 was decreased, the levels of S100β and NSE in serum and hippocampal IL-1β, IL-6 and TNF-α were decreased ( P<0.05), and the pathological changes in hippocampal CA1 area were significantly attenuated in group P. Conclusions:The mechanism by which multiple exposures to sevoflurane anesthesia induces long-term cognitive impairment is related to activation of TLR4/NF-κB signaling pathway and increase in hippocampal inflammatory responses in neonatal rats.