Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.

Objective To investigate the efficacy of sakubatril valsartan combined with tolvaptan in the treatment of heart failure patients with reduced ejection fraction(HFrEF)and the effects on echocardiography and cardiovascular events.Methods According to the random number table method,400 patients with HFrEF admitted to the First People's Hospital from September 2017 to January 2022 were divided into the control group and the combination group with 200 cases each.Both groups were given conventional treatment,based on which the control group was given sacubitril valsartan and the combination group was given sacubitril valsartan combined with tolvaptan.The efficacy,echocardiographic indexes[left ventricular ejection fraction(LVEF),left ventricular end-diastolic internal diameter(LVEDD),left ventricular end-systolic internal diameter(LVESD)],myocardial injury indexes[serum brain natriuretic peptide(BNP),high-sensitivity troponin T(hs-CTnT),growth transforming factor-15(GDF-15)],urine output,neuroendocrine factors[antidiuretic hormone(ADH),angiotensin(PRA),angiotensin Ⅱ(Ang Ⅱ)],cardiovascular events and adverse effects were compared between the two groups.Results The total effective rate was 94.50%(189/200)higher in the combined group than 86.00%(172/200)in the control group(P＜0.05);LVEF was high-er in the combined group than in the control group after treatment,and LVEDD and LVESD were lower than in the control group(P＜0.05);BNP,hs-CTnT,GDF-15,ADH PRA,and Ang II were lower in the combined group than in the control group,and urine volume was higher than in the control group(P＜0.05);at 6-month follow-up after treatment,there were no statistically significant differences in the rehospitalization rate of heart failure,the incidence of non-fatal infarction,post-discharge cardiovascular mortali-ty and all-cause mortality in the combined group compared with those of the control group(P＞0.05);there were no statistically significant differences in the incidence of adverse events in the combined group compared with that of the control group(P＞0.05).Conclusion Sacubitril valsartan combined with tolvaptan is effective in treating HFrEF,by reducing myocardial inju-ry,promoting urination,and improving patients'cardiac function without increasing the risk of cardiovascular events and adverse reactions.

A 55-year-old male patient was admitted to the hospital due to "recurrent chest pain for 8 months, with worsening symptoms for 2 weeks". After admission, comprehensive relevant examinations led to the consideration of a giant chronic left ventricular pseudoaneurysm caused by myocardial infarction with non-obstructive coronary arteries. Surgical treatment was performed at our hospital. We discuss the diagnosis and treatment of this patient.

Objective:To investigate the efficacy and safety of recombinant human endostatin(Endostar)combined with platium-contained chemotherapeutic agents in advanced non-small cell lung cancer(NSCLC)patients over 60 years old.Methods:93 advanced NSCLC patients from January 2019 to June 2021 were selected as the research objects.The patients received three days of continuous intravenous infusion of Endostar(210 mg for 72 hours)combined with platinum-containing chemotherapy.The efficacy and toxicities were evaluated according to Response Evaluation Criteria in Solid Tumors(RECIST)version1.1 and National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE version 4.0), respectively.Follow-up data were obtained to perform the Kaplan-Meier survival analysis.Results:In our study, the objective remission rate(ORR)and disease control rate(DCR)were 38.7% and 78.5%, respectively.The median progression-free survival(PFS)and overall survival(OS)were 6.8 months and 16.5 months, respectively.A Multivariate analysis showed that tumor staging and TP53 mutation were independent prognostic factors related to PFS and OS in advanced NSCLC patients.Adverse reactions related to Endostar during treatment included arrhythmia in 2 cases(2.2%), myocardial ischemia in 1 case(1.07%)and bloody sputum in 1 case(1.07%), all of which were Grade 1 or Grade 2.Conclusions:The application of three days continuous intravenous infusion of Endostar combined with platium-contained chemotherapeutic agents is worthy to be recommended for clinical application in elderly patients with advanced NSCLC due to its high effective rate and survival advantage, as well as good safety.

Chinese, as a logographic language, fundamentally differs from alphabetic languages like English. Previous neuroimaging studies have mainly focused on alphabetic languages, while the exploration of Chinese reading is still an emerging and fast-growing research field. Recently, a growing number of neuroimaging studies have explored the neural circuit of Chinese reading. Here, we summarize previous research on Chinese reading from a connectomic perspective. Converging evidence indicates that the left middle frontal gyrus is a specialized hub region that connects the ventral with dorsal pathways for Chinese reading. Notably, the orthography-to-phonology and orthography-to-semantics mapping, mainly processed in the ventral pathway, are more specific during Chinese reading. Besides, in addition to the left-lateralized language-related regions, reading pathways in the right hemisphere also play an important role in Chinese reading. Throughout, we comprehensively review prior findings and emphasize several challenging issues to be explored in future work.
Brain/diagnostic imaging* ; Brain Mapping ; China ; Connectome ; Language ; Magnetic Resonance Imaging/methods* ; Reading

To explore the mechanisms by which AKR1C3 induces tumor resistance, human breast cancer cell strain MCF-7/DOX resistant to doxorubicin, MCF-7/ AKR1C3 cells for overexpression of AKR1C3 and MCF-7/DOX-KD cells for knockdown of AKR1C3 in MCF-7/DOX cells were established. Western blot analysis found that AKR1C3 was expressed at a higher level in MCF-7/DOX than MCF-7 wild type cells. Similarly, CCK-8 and DAPI confirmed that MCF-7/ AKR1C3 cells were more resistant to DOX than AKR1C3 wild types as the IC50 was increased 6 times in MCF-7/AKR1C3 cells more than in AKR1C3 wild type cells. Meanwhile, colony formation ability was also enhanced after AKR1C3 was over-expressed in MCF-7 cells.Cytoplasmic/nuclear separation analysis and IF further found that β-catenin nuclear translocation mediated by AKR1C3 was the main reason contributing to the occurrence of DOX-resistant breast cancer cells. β-catenin inhibitor, XAV939, could reverse the AKR1C3 induced doxorubicin resistance in MCF-7 cells.Results indicated that AKR1C3 could be a potential therapeutic target in breast cancer cells.

Objective To preliminary explore the feasibility of three‐dimensional transesophageal echocardiography ( 3D‐T EE) as images data source for 3D printing model by comparing the 3D‐T EE with CT of the aortic root Digital Imaging and Communications in M edicine ( DICOM ) data into 3D printing models respectively . Methods Fifteen patients w ho underwent surgical aortic valve replacement in the hospital were enrolled ,and the aortic root 3D‐T EE and CT DICOM data were obtained in perioperative . T he images were imported into M imics software to generate digital model standard tessellation language file ,and to print the aortic root models by 3D printer . T he structural morphology of both 3D‐T EE and CT models were qualitatively evaluated respectively . T he aortic annular area ,perimeter ,maximal diameter and minimal diameter of the original data , digital model , model and aortic valve replacement were quantitatively evaluated ,and the consistency of each parameter value were analyzed . T he mean diameter of 3D‐T EE and CT model were calculated . T he correlation of mean diameter with the number of replacement was analyzed . Results ①Both 3D‐TEE and CT images data were successfully printed into 3D models ,and the positive rate of aortic valve structure were 93 .3% ( 14/15) and 80 .0% ( 12/15) respectively . ②T he measured values of the aortic annular 3D‐T EE and digital model were smaller than CT ,CTdigital model and replacement ( P＜0 .05) ,and the measurement consistency among groups was high . ③ T he parameter values of 3D‐T EE model were smaller than CT model ( P ＜0 .05 ) ,and the measured values were all within the consistency range . T he mean diameters were highly correlated with the replacement values ( r ＞ 0 .95 , P ＜ 0 .05 ) . Conclusions 3D printing aortic root model based on 3D‐TEE image data is of high feasibility .

Objective: To preliminary explore the feasibility of three-dimensional transesophageal echocardiography (3D-TEE) as images data source for 3D printing model by comparing the 3D-TEE with CT of the aortic root Digital Imaging and Communications in Medicine(DICOM) data into 3D printing models respectively. Methods: Fifteen patients who underwent surgical aortic valve replacement in the hospital were enrolled, and the aortic root 3D-TEE and CT DICOM data were obtained in perioperative. The images were imported into Mimics software to generate digital model standard tessellation language file, and to print the aortic root models by 3D printer. The structural morphology of both 3D-TEE and CT models were qualitatively evaluated respectively. The aortic annular area, perimeter, maximal diameter and minimal diameter of the original data, digital model, model and aortic valve replacement were quantitatively evaluated, and the consistency of each parameter value were analyzed. The mean diameter of 3D-TEE and CT model were calculated. The correlation of mean diameter with the number of replacement was analyzed. Results: ①Both 3D-TEE and CT images data were successfully printed into 3D models, and the positive rate of aortic valve structure were 93.3% (14/15) and 80.0% (12/15) respectively. ②The measured values of the aortic annular 3D-TEE and digital model were smaller than CT, CTdigital model and replacement (P<0.05), and the measurement consistency among groups was high. ③The parameter values of 3D-TEE model were smaller than CT model (P<0.05), and the measured values were all within the consistency range. The mean diameters were highly correlated with the replacement values (r>0.95, P<0.05). Conclusions 3D printing aortic root model based on 3D-TEE image data is of high feasibility.

Objective: To investigate the accuracy and repeatability of contrast-enhanced transthoracic echocardiography for measurements of right ventricular structure and function. Methods: The apical four-chamber views and the three-dimensional full-volume images of the right heart were collected from 12 beagles with unenhanced and contrast-enhanced transthoracic echocardiography. The intimal display rate of the right ventricular segments, right ventricular end diastolic longitudinal dimension (RVLD), right ventricular end diastolic area (RVEDA), right ventricular end systolic area (RVESA) and right ventricular fractional area change (RVFAC) were evaluated respectively with two-dimensional unenhanced and contrast-enhanced echocardiography. Right ventricular three-dimensional full-volume images were processed and analyzed by TomTec software, and right ventricular end diastolic volume (RVEDV), right ventricular end systolic volume (RVESV) and right ventricular ejection fraction (RVEF) were measured respectively with three-dimensional unenhanced and contrast-enhanced echocardiography. The measurements of pathological specimen were taken as the gold standard, the accuracies of measuring RVEDVand RVLD by different methods were evaluated. All indexes were measured repeatedly by the same observer and different observers to assess the intraobserver and interobserver reproducibilities of different methods. Results: ①The intimal display rate of the right ventricular segments was higher with contrast-enhanced echocardiography than that with unenhanced echocardiography (P<0.05). ②The measurements of RVEDV by three-dimensional contrast-enhanced echocardiography correlated well with the measurements by anatomical specimens. And the correlation was higher (0.916 vs 0.843), the consistency was better than that by unenhanced echocardiography. The measurements of RVLD by two-dimensional contrast-enhanced echocardiography correlated well with the measurements by anatomical specimens. And the correlation was higher (0.928 vs 0.850), the consistency was better than that by unenhanced echocardiography. ③For inter- and intraobservers reproducibilities, the interclass correlation coefficients of RVLD, RVEDV, RVESV, RVEF, RVEDA, RVESA, RVFAC with contrast-enhanced echocardiography were higher and 95% confidence interval ranges were smaller than those with unenhanced echocardiography. Conclusions Contrast-enhanced transthoracic echocardiography can improve the accuracy and repeatability for measurements of right ventricular structure and function, providing a new evaluation method for patients with poor image quality of the right ventricle in clinical practice.