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Rong Chen,1 Wenbin Yang,2 Jing Sun,3 Yuan Liu,4 Qing An,2 Feijuan Zhang,2 Zhuanli Bai,5 Qi Luan2 1College of Life Sciences, Northwest University, Xi’an, 710069, People’s Republic of China; 2Department of Dermatology, Xi’an No.3 Hospital, the Affiliated Hospital of Northwest University, Northwest University, Xi’an, 710069, People’s Republic of China; 3Department of Anesthesiology, Northwest Women’s and Children’s Hospital, Xi’an, 710061, People’s Republic of China; 4Center of Medical Genetics, Northwest Women’s and Children’s Hospital, Xi’an, 710061, People’s Republic of China; 5Department of Plastic and Aesthetic Maxillofacial Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Qi Luan, Department of Dermatology, Xi’an No.3 Hospital, the Affiliated Hospital of Northwest University, Northwest University, Xi’an, 710069, People’s Republic of China, Tel/Fax +86-29-61816090, Email luanq@sina.com Zhuanli Bai, Department of Plastic and Aesthetic Maxillofacial Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email zhuanlibai@xjtu.ecu.cnBackground: Hyaluronic acid (HA)-based fillers are applied to treat facial wrinkles and volume loss. Many efforts have been made to improve properties of HA to prolong the duration in aesthetic indications. A new cross-linking technique called “Tri-Hyal”, could make HAs to achieve desired rheological characteristics. HAs synthesized by Tri-Hyal are triple cross-linked and sustained-release, which could increase duration of promoting skin rejuvenation after injection.Purpose: To evaluate the efficiency and persistence of HAs with Tri-Hyal on skin rejuvenation and further investigate underlying mechanisms, we compared the performances of cross-linked HA (AF) based on Tri-Hyal with another highly acceptable HA filler (Res) in vivo and in vitro.Methods: Male BALB/c mice were divided into three groups, treated with AF, Res and vehicle, respectively. Skin biopsies were taken on day 0, 30, 90 and 180 after injection and hematoxylin and eosin (H&E), Masson’s trichrome (MT), immunohistochemical (IHC) stainings for CD31, TGF-β and MMP9 were performed. EdU incorporation, cell counting kit-8 (CCK-8), SA-β-Gal staining and activity were measured by biochemical analysis. RFP-GFP-LC3 adeno virus was used for autophagic flux detection. Protein levels of CD44, P62 and LC3I/II were detected by Western blot. Reactive oxygen species (ROS) level was detected by flow cytometry with DCFH-DA probe.Results: The AF synthesized by Tri-Hyal showed persistent dermal structural correction without attenuation up to 6 months, which was illustrated by skin thickness, formation of elastic fibers and vascular density. Consistently, in fibroblasts the AF improved cell proliferation and slowed the senescent in vitro. Furthermore, it promoted cellular autophagy to reduce ROS level, which would account for its function in skin renewal.Conclusion: The HA with Tri-Hyal could stimulate the production of extracellular matrix components more persistently than traditional HA fillers. In terms of mechanisms, it delayed senescence in dermal fibroblasts through reducing oxidative stress mediated by induction of autophagy.Keywords: skin rejuvenation, fibroblasts, senescence, ROS, autophagy

Rong Wan,1 Shengwei Cai,2 Dejian Pan,2 Weilin Yang,2 Rengui Zhou2 1Department of Quality Management, The 904th Hospital of Joint Logistic Support Force (Anhui Medical University Affiliated Wuxi Clinical College), Wuxi, 214044, People’s Republic of China; 2Department of Oncology, The 904th Hospital of Joint Logistic Support Force (Anhui Medical University Affiliated Wuxi Clinical College), Wuxi, 214044, People’s Republic of ChinaCorrespondence: Rong Wan, Department of Quality Management, The 904th Hospital of Joint Logistic Support Force (Anhui Medical University Affiliated Wuxi Clinical College), Xing Yuan North Road 101, Wuxi, 214044, People’s Republic of China, Tel +86 051085142023, Fax +86 051085142601, Email yings2007@21cn.comIntroduction: Postoperative delirium (POD) is one of the prevalent and potentially fatal clinical conditions, leading to high disability and mortality in older patients, as well as increased duration of hospital stay and more hospitalization expenses. There were no effective drugs in the clinical management of POD, and an absence of evidence-based medicine concerning the treatment of POD.Materials and Methods: The present study explored whether atorvastatin (Ato) can decrease the occurrence rate of POD. The present research included patients over the age of 60 who were hospitalized to critical care units (ICUs) following surgery for malignant tumors. Patients received Ato (40mg/day) or placebos utilizing a computer-based random sequencing (in a 1:1 ratio). The primary outcome measure was the occurrence of delirium within the first seven days following surgery.Results: A total of 230 individuals were classified into two groups, namely the placebo group (n=123) and the Ato group (n=107). Patients belonging to two groups had similar baseline clinical data, and there were no statistically significant differences between them. The occurrence of delirium in the Ato group was remarkably reduced unlike the case in the placebo group. 30-day all-cause mortality did not vary significantly between the two groups. Pulmonary infection and Bedsore were significantly decreased in the Ato group than the placebo group, there were no statistically significant differences between the two groups in rhabdomyolysis and abnormal liver enzymes. In terms of medication responses, there were no statistically significant differences between the two groups. Ato patients had remarkably shortened hospital stays and spent remarkably less on hospitalization expenditures in comparison with those in the placebo group.Conclusion: The findings from the present research indicated that Ato can decrease the occurrence of delirium following surgical operation of malignant tumors among elderly patients, it also can reduce the duration of hospitalization, hospital cost, and post-surgical complications, but not improve 30-day all-cause mortality.Registration Number: ChiCTR-IPR-17011984.Keywords: atorvastatin, 30-day all-cause mortality, postoperative delirium, RCT, outcome

Ziyu Li,1 Wei Yang,1 Yong Yang,1 Jianbo Wu,2 Pei Luo,3 Yong Liu1,4,5 1Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, People’s Republic of China; 4Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, People’s Republic of China; 5Medical Equipment Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Yong Liu, Email liuyong@swmu.edu.cnBackground: Astragaloside IV is the most important bioactive component of Radix Astragali. Previous studies have shown that astragaloside IV plays an important role in the control of early- and mid-stage diabetes and late diabetic nephropathy. However, it is disappointing that the in vivo solubility of astragaloside IV and its bioavailability after oral administration are very low. We recently obtained a new water-soluble derivative of astragaloside IV-astragaloside formic acid (LS-102), which has higher bioavailability than the parent compound. In our previous study, we found that there was a significant inflammatory response in the perirenal adipose tissue of mice with obesity-related nephropathy induced by a high-fat diet (HFD), which was related to macrophage infiltration. We hypothesized that in model mice with obesity-related nephropathy, LS-102 effectively regulated the inflammatory response and pathological changes in obesity-related nephropathy through macrophages in perirenal adipose tissue. If this hypothesis is true, the effects of LS-102 and astragaloside IV on TGF-β 1/Smad signal transduction will be further investigated.Methods: In this study, adipose stem cells and an HFD-induced obesity-related nephropathy mouse model were used to observe the regulatory effect of LS-102 on perirenal fat inflammation and the mechanism. Adipose mesenchymal stem cells were extracted from mice that were fed a normal diet and those with obesity-related nephropathy. The effects of LS-102 on the proliferation of two kinds of cells were measured by the CCK-8 method. The levels of tumor necrosis factor-α (TNF-a) and plasminogen activator inhibitor-1 (PAI-1) were measured by ELISA. Obesity-related nephropathy mice were randomly divided into five groups: the HFD group, the LAS group (HFD+low concentration of astragaloside IV [10 mg/kg], intragastrically [ig]), the HAS group (HFD+high concentration of astragaloside IV [40 mg/kg], ig), the L102 group (HFD+low concentration of LS-102 [10 mg/kg], ig) and the H102 group (HFD+high concentration of LS-102 [40 mg/kg], ig). Body weight was measured, and the levels of serum glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), serum creatinine (Crea) and blood urea were measured. The kidneys were stained with HE, PAS and Masson’s trichrome. Perirenal adipose tissue was harvested to examine the expression of CD68, LCA, CD11C, TNF-a, TGF-β 1, Fn1, Smad2, Smad3, Smad4, and Smad7 by immunohistochemical staining, and F4/80 was examined by immunofluorescence staining.Results: LS-102 significantly inhibited the in vitro secretion of TNF-a and PAI-1 by adipose stem cells in a concentration-dependent manner (P < 0.05). In vivo, the body weights in the LAS group, HAS group, L102 group and H102 group were significantly lower than those in the HFD group (P < 0.05). Except for that in the HFD group, the volume of perirenal adipocytes in the other groups was small and uniform (P < 0.05). Compared with the LAS, HAS, L102 and H102 groups, the HFD group had a larger glomerular cross-sectional area, proliferation of mesangial cells and the mesangial matrix, and increased matrix area/glomerular area (P < 0.05). The effect of LS-102 was better than that of astragaloside IV at the same concentration (P < 0.05). Compared with those in the HFD group, glucose, HDL-C, LDL-C and urea levels in the LAS group, HAS group, L102 group and H102 group were significantly decreased (P < 0.05). The expression of F4/80, CD68, LCA, TNF-a, CD11C, and PAI-1 in perirenal adipose tissue in the HFD group was significantly higher than that in the LAS group, HAS group, L102 group and H102 group (P < 0.05). Compared with those in the HFD group, the expression levels of TGF-β 1 and Fn1 in the HAS group, L102 group and H102 group were significantly increased (P < 0.05). Compared with the HFD group, the HAS group, L102 group and H102 group had decreased immunopositive rates of Smad2, Smad3 and Smad4 (P < 0.05). At the same concentration, the effect of LS-102 was better than that of astragaloside IV (P < 0.05). There was no significant difference in the expression of Smad7 among the different experimental groups (P > 0.05).Conclusion: Astragaloside IV and LS-102 improved the inflammatory reaction in perirenal adipose tissue and renal pathological changes in obesity-related nephropathy model mice and inhibited the TGF-β 1/Smad signaling cascade. At the same concentration, the effect of LS-102 was better than that of astragaloside IV. These results suggest that LS-102 has a better protective effect against obesity-related nephropathy. LS-102 may be a new type of traditional Chinese medicine for the clinical treatment of obesity and its related metabolic diseases.Keywords: LS-102, obesity-related nephropathy, inflammation, macrophages, PAI-1, TGF-β 1, Smads

Zhen Liu,1 Hao Tang,1 Huaming Xu,1 Guoping Lu,2 Wensu Yang,1 Zhaoxin Xia,1 Yi Zhu,1 Shenwang Ni,1 Wanqi Men,1 Jilu Shen1 1The Fourth Affiliated Hospital of Anhui Medical University Laboratory Department, Hefei, People’s Republic of China; 2Laboratory Department of Fuyang Hospital Affiliated to Anhui Medical University, Fuyang, Anhui, 236000, People’s Republic of ChinaCorrespondence: Jilu Shen, The Fourth Affiliated Hospital of Anhui Medical University Laboratory, No. 100 Huaihai Avenue, Xinzhan District, Hefei, Anhui Province, 230012, People’s Republic of China, Tel +86 151 5515 2963, Email shenjilu@ahmu.edu.cnAim: To reduce the inspection time for urinary tract pathogens and provide a rapid and effective therapeutic plan for clinical anti-infection treatment, this study developed a rapid identification (ID) and antimicrobial sensitivity test (AST) method by DOT-MGA.Methods: We grouped midstream urine samples with single bacteria according to the number of bacteria (≤ 5/5– 15/≥ 15) under per oil microscope after Gram staining. Then we adopted differential centrifugation to process the grouped samples to collect precipitate. MALDI-TOF MS was performed using precipitate directly or after short-term culture. If succeed, we resuspended the precipitate into droplets with or without antibiotics at a MALDI target. Four hours later, mass spectrometer (MS) was used to identify the culture on the target and to analyse AST.Results: Samples (count ≥ 15), which precipitate can be directly identified by MS; otherwise, the precipitate need a short-term cultured for 3– 6 h before ID. The consistency of the ID results between conventional culture and the precipitate is 100%. Compared with broth microdilution method, DOT-MGA for predicting AST had a high consistency. EA and CA for IPM, LEV, CAZ, NIT, and FOT were 100%/100%, 98%/90%, 98%/92%, 100%/90%, 98%/94%, respectively. No VME was observed in all tests. Besides, MIC50 for the five antibiotics by DOT-MGA and broth microdilution method were ≤ 1/≤ 0.5,> 2/2,≤ 4/≤ 2,≤ 32/≤ 16,≤ 64/≤ 32 and MIC90 were ≤ 1/≤ 0.5, > 2/> 4, 16/16, 128/128, 128/64.Conclusion: This study can shorten the ID time (minimum 0.5h) and AST (minimum 4h) of the main pathogens of urinary tract infection to 5– 10 hours, which greatly reduce the inspection time and provide substantial help for the rapid diagnosis and treatment of patients with urinary tract infection.Keywords: MALDI-TOF, DOT-MGA, rapid drug susceptibility test, urinary tract infection, antibiotics resistance

Mengxuan Li,1,&ast; Nan Che,2,&ast; Yu Jin,1 Jinhua Li,3 Wanshan Yang2 1Human Anatomy and Histoembryology, Yanbian University College of Medicine, Yanji, People’s Republic of China; 2Department of Pathology, Yanbian University College of Medicine, Yanji, People’s Republic of China; 3Department of Drug and Device Clinical Trials Institution, Affiliated Hospital of Yanbian University, Yanji, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wanshan Yang, Department of Pathology, Yanbian University College of Medicine, No. 977, Gongyuan Road, Yanji City, 133002, People’s Republic of China, Tel +8613944390633, Email yangwsh@ybu.edu.cn Jinhua Li, Department of Drug and Device Clinical Trials Institution, Affiliated Hospital of Yanbian University, No. 1827, Juzi Road, Yanji City, 133000, People’s Republic of China, Tel +8613843360437, Email 13843360437@163.comBackground: Aerobic glycolysis plays an important role in bladder cancer (BLCA) progression and chemoresistance. Cyclin-dependent kinase inhibitor-3 (CDKN3), a dual-specificity protein tyrosine phosphatase, has aberrant upregulation in multiple cancer types and is associated with tumorigenesis. However, the role of CDKN3 in BLCA progression and glycolysis has not been elucidated.Purpose: In this study, we investigated the effect and underlying mechanisms of CDKN3 on bladder cancer chemoresistance.Results: This study confirmed that CDKN3 was overexpressed in BLCA tissues and promoted proliferation and migration. Additionally, our results showed a CDKN3-dependent mechanism on chemoresistance; chemoresistance cells were transformed into chemosensitivity cells by CDKN3 knockdown. Additionally, we showed that CDKN3 knockdown decreased glycolysis by inhibiting LDHA expression in BLCA chemoresistance cells. The results also proved that LDHA was an important mediator of CDKN3-regulated BLCA resistance. LDHA overexpression reversed glycolysis inhibition and chemosensitivity induced by CDKN3 downregulation.Conclusion: These data collectively identified a vital role of CDKN3 in glycolysis and chemoresistance by regulating LDHA expression in BLCA cells, providing a possible therapeutic strategy for treating BLCA.Keywords: bladder cancer, glycolysis, CDKN3, chemoresistance

Jian Chen,1 Xiaoyun Liu,1 Jian Lan,1 Tingchao Li,2 Chaokun She,1 Qingyun Zhang,1 Wei Yang3 1Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi City, Guizhou Province, People’s Republic of China; 2Pathology Department, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi City, Guizhou Province, People’s Republic of China; 3Imaging Department, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi City, Guizhou Province, People’s Republic of ChinaCorrespondence: Xiaoyun Liu; Jian Lan, Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), No. 98, Fenghuang Road, Zunyi, Guizhou, 563000, People’s Republic of China, Email 656479556@qq.com; 1981551873@qq.comAbstract: Rhabdomyosarcoma, a common soft tissue malignant tumor in children and adolescents, is exceedingly rare in adults. Nevertheless, The outcome in adults is very poor, especially when compared to outcomes in children in whom significant improvements in treatment has been achieved. The first case was of a 24-year-old pregnant Chinese woman with a rare primary site of rhabdomyosarcoma in the perineal body. She presented with a perineal mass and was diagnosed during the second trimester of pregnancy, which is a very rare occurrence. The second case was a 70-year-old Chinese woman who suffered from right lower abdominal pain for 1 month and was misdiagnosed with an epithelial ovarian carcinoma. Mesenteric pleomorphic rhabdomyosarcoma was later confirmed by postoperative pathology. Both cases had undergone preoperative examination with chest and abdominal computed tomography (CT) and pelvic magnetic resonance imaging (MRI) examinations, as well as examination of complete blood count, liver panel, renal panel, and serum tumor markers. Diagnosis was based on histopathology and immunohistochemistry. The patient in the first case received chemotherapy after which the mass decreased in size; however, the patient was lost to follow-up. The second case underwent tumor resection and received chemotherapy and radiotherapy.Keywords: rhabdomyosarcoma, adult, pregnancy, diagnosis, heterogeneity, prognosis

Xin Huang,1,&ast; Yuan Liu,2,&ast; Bo Guan,1 Wenyi Yang,1 Shasha Sun,1 Jiakun Luo,1 Yukun Luo,3 Jian Cao,1 Yujiao Deng3 1Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Emergency, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Ultrasound, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yujiao Deng, Department of Ultrasound, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Email dengyujiao301@163.com Jian Cao, Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Email caojiantougao@163.comAim: To evaluate the left ventricular (LV) systolic function in elderly with non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI) using real-time three-dimensional echocardiography (RT-3DE) and two-dimensional speckle tracking imaging (STI).Methods: Forty NSTEMI and forty STEMI patients after undergoing percutaneous coronary artery intervention (PCI) were enrolled. The myocardial segments were supplied by the infarct-related artery (Myo-IRA) which were indicated by the selective coronary arteriography (SCA). The LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV) and ejection fraction (LVEF) were acquired by 4D LV Volume Tom Tec. LV longitudinal peak systolic strain (LPSS), radial peak systolic strain (RPSS), circumferential peak systolic strain (CPSS) of Myo-IRA segments, LV rotational peak degree in the base (rot-base) and in the apex (rot-apex), and twist were acquired by strain analysis software. Forty older healthy individuals were included as normal controls.Results: The LVEF of the NSTEMI and STEMI patients at 1 week after PCI were significantly lower (P< 0.05), then, this parameter was improved in both groups after 3 months, but was still significantly lower than that of the controls (P< 0.05). The LPSS, RPSS, CPSS of the Myo−IRA segments, rot−Base, rot−Apex and twist in both groups were significantly lower than those in the controls. The LPSS and CPSS of the Myo-IRA segments, rot−Base, rot−Apex and twist in NSTEMI patients were obviously higher than those in STEMI patients in 1 week and 3 months after PCI (P< 0.05). After 3 months, the RPSS of NSTEMI patients was improved notably and was obviously higher than that of STEMI patients (P< 0.05). All these values in STEMI and NSTEMI patients were improved after 3 months, apart from LPSS in STEMI patients (P> 0.05), but were still significantly lower than those in the controls (P< 0.05).Conclusion: RT-3DE and STI can sensitively assess LV systolic function with different extents of transmural damage.Keywords: echocardiography, acute myocardial infarction, left ventricular systolic function, elderly

Mengyue Lin,1,2 Mulalibieke Heizhati,1 Lin Gan,1,2 Ling Yao,1 Wenbo Yang,1 Mei Li,1 Jing Hong,1 Zihao Wu,1 Hui Wang,1,2 Nanfang Li1 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region; Xinjiang Hypertension Institute; National Health Committee Key Laboratory of Hypertension Clinical Research; Key Laboratory of Xinjiang Uygur Autonomous Region “Hypertension Research Laboratory”; Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, People’s Republic of China; 2Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of ChinaCorrespondence: Nanfang Li, Email lnanfang2016@sina.comPurpose: Patients with hypertension and glucose metabolism disorder (GMD) are at high risk of developing kidney dysfunction (KD). Therefore, we aimed to develop a nomogram for predicting individuals’ 5-year risk of KD in hypertensives with GMD.Patients and Methods: In total, 1961 hypertensives with GMD were consecutively included. Baseline data were extracted from medical electronic system, and follow-up data were obtained using annual health check-ups or hospital readmission. KD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. Subjects were randomly divided into training and validation sets with a ratio of 7 to 3. Least absolute shrinkage and selection operator method was used to identify potential predictors. Cox proportional hazard model was applied to build a nomogram for predicting KD risk. The discriminative ability, calibration and usefulness of the model were evaluated. The prediction model was verified by internal validation.Results: During the follow-up of 5351 person-years with a median follow-up of 32 (range: 3– 91) months, 130 patients developed KD. Age, sex, ethnicity, hemoglobin A1c, uric acid, and baseline eGFR were identified as significant predictors for incident KD and used for establishing nomogram. The prediction model displayed good discrimination with C-index of 0.770 (95% CI: 0.712– 0.828) and 0.763 (95% CI: 0.704– 0.823) in training and validation sets, respectively. Calibration curve indicated good agreement between the predicted and actual probabilities. The decision curve analysis demonstrated that the model was clinically useful.Conclusion: The prediction nomogram, including six common easy-to-obtain factors, shows good performance for predicting 5-year risk of KD in hypertensives with GMD. This quantitative tool could help clinicians, and even primary care providers, recognize potential KD patients early and make strategy for prevention and management.Keywords: kidney dysfunction, nomogram, hypertension, diabetes, prediction

Huaming Xu,1 Hao Tang,2 Rongrong Li,3 Zhaoxin Xia,2 Wensu Yang,2 Yi Zhu,2 Zhen Liu,2 Guoping Lu,4 Shenwang Ni,2 Jilu Shen1 1Department of Laboratory Medicine, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230012, People’s Republic of China; 2University Laboratory, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230012, People’s Republic of China; 3The First Affiliated Hospital of Anhui Medical University Laboratory Department, Hefei, Anhui, Peoples’ Republic of China; 4Laboratory Department of Fuyang Hospital Affiliated to Anhui Medical University, Fuyang, Anhui, People’s Republic of ChinaCorrespondence: Jilu Shen, Tel +86 151 5515 2963, Email shenjilu@ahmu.edu.cn; 1464675852@qq.comIntroduction: Carbapenemase-mediated antimicrobial resistance is currently a hot spot of global concern. Carbapenem-resistant organisms are highly prevalent in hospitals associated with difficult-to-treat infections, resulting in poor clinical outcome due to limited treatment options. It is urgently needed to have a rapid, efficient, and convenient molecular assay for identifying such resistant strains.Methods: For this end, we developed a new laboratory assay targeting Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) based on loop-mediated isothermal amplification, CRISPR–Cas12a, and lateral flow immunochromatographic strip (CRISPR–Cas-LAMP-lateral flow strip). The method was designed to use a guide RNA (gRNA) to recognize the target DNA and guide Cas12a to cleave the target DNA, and simultaneously cleave any single-stranded DNA within the cleavage reaction system.Results: The cleavage products are visible to the naked eye on the lateral flow strip. This method is highly sensitive in direct detection of bacteria in samples containing at least 3× 105 CFU/mL without the need for bacterial culture.Discussion: It provides shorter turnaround time and higher specificity than the conventional bacterial culture and susceptibility testing method. This new assay is applicable for extensive use in hospital infection control, as well as identification and treatment of resistant strains due to simple operation and inexpensive apparatuses.Keywords: carbapenemase, Klebsiella pneumoniae carbapenemase, New Delhi metallo-β-lactamase, loop-mediated isothermal amplification, CRISPR–Cas12a, lateral flow immunochromatographic strip, detection

We present results on simultaneous observations of Class I methanol masers at 25, 36, and 44 GHz towards 22 Galactic targets carried out with the Effelsberg 100-m telescope. The study investigates relations between the hyperfine (HF) structure of the torsion–rotation transitions in CH |$_3$| OH and maser activity. By analysing the radial velocity shifts between different maser lines together with the patterns of the HF structure based on laboratory measurements and quantum-chemical calculations, we find that in any source only one specific HF transition forms the maser emission and that this transition changes from source to source. The physical conditions leading to this selective behaviour are still unclear. Using accurate laboratory rest frequencies for the 25 GHz transitions, we have refined the centre frequencies for the HF multiplets at 36, 44, and 95 GHz: |$f_{\scriptscriptstyle 36} = (36169.2488\pm 0.0002_{\scriptscriptstyle \rm stat} \pm 0.0004_{\scriptscriptstyle \rm sys})$|  MHz. |$f_{\scriptscriptstyle 44} = (44069.4176\pm 0.0002_{\scriptscriptstyle \rm stat} \pm 0.0004_{\scriptscriptstyle \rm sys})$|  MHz, and |$f_{\scriptscriptstyle 95} = (95169.4414\pm 0.0003_{\scriptscriptstyle \rm stat} \pm 0.0004_{\scriptscriptstyle \rm sys})$|  MHz. Comparison with previous observations of 44 GHz masers performed 6–10 yr ago with a Korean 21-m Korean Very Long Baseline Interferometry Network telescope towards the same targets confirms the kinematic stability of Class I maser line profiles during this time interval and reveals a systematic radial velocity shift of |$0.013\pm 0.005$|  km s |$^{-1}$| between the two telescopes. [ABSTRACT FROM AUTHOR]

Weiwei Yang,1,&ast; Qing He,2,&ast; Zhaohui Hu,3 Xiangtao Xie2,4 1Department of Gynecology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, People’s Republic of China; 2Department of Orthopedics, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, People’s Republic of China; 3Department of Orthopedics, Liuzhou People’s Hospital, Liuzhou, Guangxi, 545005, People’s Republic of China; 4Department of Orthopedics, Liuzhou Worker’s Hospital, Liuzhou, Guangxi, 545005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaohui HuLiuzhou People’s Hospital, No. 8 Wenchang Road, Liuzhou, Guangxi, 545006, People’s Republic of China, Tel/Fax +867722662676, Email huzhaohui817@163.comXiangtao XieThe Fourth Affiliated Hospital of Guangxi Medical University, No. 156 Heping Road, Liuzhou, Guangxi, 545027, People’s Republic of China, Tel +867723832719Email xiexiangtao813@163.comPurpose: Postmenopausal osteoporosis (PMOP) is a common and debilitating chronic disease, but it has just no cure options. The objective of this study was to identify genes associated with osteoporosis and reveal potential therapeutic targets.Methods: Expression profiles from GSE13850 and GSE56815 datasets were combined for differential expression analysis. Extraction of intersecting genes from the combined datasets and the differentially expressed genes in GSE56814 were performed to construct a multi-scale embedded gene co-expression network analysis (MEGENA) to obtain module genes. Module genes with an area under the receiver operating characteristic curve (AUC) > 0.60 were chosen to construct the least absolute shrinkage and selection operator (LASSO) model to obtain feature genes. A regulated network was constructed using differentially expressed micro-RNAs (miRNAs) in GSE74209 and feature genes. Finally, key genetic pathways and pathways of the Kyoto Encyclopedia of Genes and Genomes were identified and explored.Results: The commonly identified differentially expressed genes involve oxidative phosphorylation and caffeine metabolism. We identified 66 modules with 2354 module genes based on MEGENA. CARD8, FOXO4, IL1R2, MPHOSPH6, MPRIP, MYOM1, PRR5L and YIPF4 were identified as feature genes by the LASSO model. Furthermore, predicted miRNA target genes included 8 genes associated with PMOP. The largest AUC was observed for FOXO4, which was found at the nexus of feature genes and miRNA-regulated genes and which correlated with the upregulation of dendritic cells. Moreover, FOXO4 was found to be involved in ABC transporters, as well as cocaine and nicotine addiction.Conclusion: FOXO4 may serve as potential biomarker and therapeutic target for PMOP.Keywords: postmenopausal osteoporosis, microRNAs, bioinformatics analysis, FOXO4, biomarker

Rational design of low-dimensional electronic phenomena at oxide interfaces is currently considered to be one of the most promising schemes for realizing new energy-efficient logic and memory devices. An atomically abrupt interface between paramagnetic LaNiO3 and antiferromagnetic CaMnO3 exhibits interfacial ferromagnetism, which can be tuned via a thickness-dependent metal-insulator transition in LaNiO3. Once fully understood, such emergent functionality could turn this archetypal Mott-interface system into a key building block for the above-mentioned future devices. Here, we use depth-resolved standing-wave photoemission spectroscopy in conjunction with scanning transmission electron microscopy and x-ray absorption spectroscopy, to demonstrate a depth-dependent charge reconstruction at the LaNiO3/CaMnO3 interface. Our measurements reveal an increased concentration of Mn3+ and Ni2+ cations at the interface, which create an electronic environment favorable for the emergence of interfacial ferromagnetism mediated via the Mn4+-Mn3+ ferromagnetic double exchange and Ni2+-O-Mn4+ superexchange mechanisms. Our findings suggest a strategy for designing functional Mott oxide heterostructures by tuning the interfacial cation characteristics via controlled manipulation of thickness, strain, and ionic defect states.

The combination of a microchannel heat sink with impinging jets and dimples (MHSIJD) can effectively improve the flow and heat transfer performance on the cooling surface of electronic devices with very high heat fluxes. Based on the previous work by analysing the effect of dimple radius on the overall performance of MHSIJD, the effects of dimple height and arrangement were numerically analysed. The velocity distribution, pressure drop, and thermal performance of MHSIJD under various dimple heights and arrangements were presented. The results showed that: MHSIJD with higher dimples had better overall performance with dimple radius being fixed; creating a mismatch between the impinging hole and dimple can solve the issue caused by the drift phenomenon; the mismatch between the impinging hole and dimple did not exhibit better overall performance than a well-matched design.

Voltage fade has been a major barrier to the commercialization of a series of high-energy-density battery electrodes for more than a decade. It is now re-examined with advanced characterization techniques, which find its origin is correlated to oxygen activities.

The discovery of facile Li transport in disordered, Li-excess rocksalt materials has opened a vast new chemical space for the development of high energy density, low cost Li-ion cathodes. We develop a strategy for obtaining optimized compositions within this class of materials, exhibiting high capacity and energy density as well as good reversibility, by using a combination of low-valence transition metal redox and a high-valence redox active charge compensator, as well as fluorine substitution for oxygen. Furthermore, we identify a new constraint on high-performance compositions by demonstrating the necessity of excess Li capacity as a means of counteracting high-voltage tetrahedral Li formation, Li-binding by fluorine and the associated irreversibility. Specifically, we demonstrate that 10-12% of Li capacity is lost due to tetrahedral Li formation, and 0.4-0.8 Li per F dopant is made inaccessible at moderate voltages due to Li-F binding. We demonstrate the success of this strategy by realizing a series of high-performance disordered oxyfluoride cathode materials based on Mn2+/4+ and V4+/5+ redox.

Recent advances in battery science and technology have triggered both the challenges and opportunities on studying the materials and interfaces in batteries. Here, we review the recent demonstrations of soft X-ray spectroscopy for studying the interfaces and electrode materials. The focus of this review is on the recently developed mapping of resonant inelastic X-ray scattering (mRIXS) as a powerful probe of battery chemistry with superior sensitivity. Six different channels of soft X-ray absorption spectroscopy (sXAS) are introduced for different experimental purposes. Although conventional sXAS channels remain effective tools for quantitative analysis of the transition-metal states and surface chemistry, we elaborate the limitations of sXAS in both cationic and anionic redox studies. Particularly, based on experimental findings in various electrodes, we show that sXAS is unreliable for studying oxygen redox. We then demonstrate the mRIXS as a reliable technique for fingerprinting oxygen redox and summarize several crucial observations. We conclude that mRIXS is the tool-of-choice to study both the practical issue on reversibility of oxygen redox and the fundamental nature of bulk oxygen states. We hope this review clarifies the popular misunderstanding on oxygen sXAS results of oxide electrodes, and establishes a reliable technique for detecting oxygen redox through mRIXS.

Anionic redox reaction (ARR) in lithium- and sodium-ion batteries is under hot discussion, mainly regarding how oxygen anion participates and to what extent oxygen can be reversibly oxidized and reduced. Here, a P3-type Na0.6[Li0.2Mn0.8]O2 with reversible capacity from pure ARR was studied. The interlayer O-O distance (peroxo-like O-O dimer, 2.506(3) Å), associated with oxidization of oxygen anions, was directly detected by using a neutron total scattering technique. Different from Li2RuO3 or Li2IrO3 with strong metal-oxygen (M-O) bonding, for P3-type Na0.6[Li0.2Mn0.8]O2 with relatively weak Mn-O covalent bonding, crystal structure factors might play an even more important role in stabilizing the oxidized species, as both Li and Mn ions are immobile in the structure and thus may inhibit the irreversible transformation of the oxidized species to O2 gas. Utilization of anionic redox reaction (ARR) on oxygen has been considered as an effective way to promote the charge-discharge capacity of the layered oxide cathodes for lithium- or sodium-ion batteries. The detailed mechanism of ARR, in particular how crystal structure affects and coordinates with the ARR, is not yet well understood. In the present work, a combination of X-ray and neutron total scattering measurements has been performed to study the structure of the prototype P3-type layered Na0.6[Li0.2Mn0.8]O2 with pure ARR. Unique structural characteristics, rather than prevailing knowledge of covalency of metal-oxygen, enable the stabilization of the crystal structure of Na0.6[Li0.2Mn0.8]O2 along with the ARR. This work suggests that reversible ARR can be manipulated by proper structure designs, thus to achieve high lithium or sodium storage in layered oxide cathodes. For P3-type Na0.6[Li0.2Mn0.8]O2 with relatively weak Mn-O covalent bonding, crystal structure factors play an important role in stabilizing the oxidized species, inhibiting the irreversible transformation of the oxidized species to O2 gas. The finding is important for better design of layered oxide positive materials with higher reversible capacity via the introduction of a reversible anionic redox reaction.

BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph+) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph+ B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation models for CML and BCR-ABL1+ B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia. Ptpn11 deletion impairs initiation and maintenance of CML-like myeloproliferative neoplasm, and compromises induction of BCR-ABL1+ B-ALL. SHP2, and specifically, its SH2 domains, PTP activity and C-terminal tyrosines, are essential for BCR-ABL1+, but not WT, pre-B-cell proliferation. The mitogen-activated protein kinase kinase (MEK) / extracellular signal-regulated kinase (ERK) pathway is regulated by SHP2 in WT and BCR-ABL1+ pre-B cells, but is only required for the proliferation of BCR-ABL1+ cells. SHP2 is required for SRC family kinase (SFK) activation only in BCR-ABL1+ pre-B cells. RNAseq reveals distinct SHP2-dependent transcriptional programs in BCR-ABL1+ and WT pre-B cells. Our results suggest that SHP2, via SFKs and ERK, represses MXD3/4 to facilitate a MYC-dependent proliferation program in BCR-ABL1-transformed pre-B cells.

Mingkai Gong,1 Xiangping Liu,2 Wu Yang,3 Hongming Song,1 Xian Zhao,1 Xiancheng Ai,1 Shuo Wang,1 Haibo Wang1 1Center of Diagnosis and Treatment of Breast Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 3Department of International Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of ChinaCorrespondence: Haibo WangCenter of Diagnosis and Treatment of Breast Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of ChinaEmail hbwang66@126.comBackground: Cancer metabolism and specifically lipid metabolism play an important role in breast cancer (BC) progression and metastasis. However, the role of lipid metabolism-associated genes (LMGs) in the prognosis of breast cancer remains unknown.Methods: The expression profiles and clinical follow-up information of 1053 BC were downloaded from The Cancer Genome Atlas (TCGA), and metabolic genes were downloaded from the Gene Set Enrichment Analysis (GSEA) dataset. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed on the differentially expressed metabolism-related genes. Then, the formula of the metabolism-related risk model was composed, and the risk score of each patient was calculated. The breast cancer patients were divided into high-risk and low-risk groups with a cutoff of the median expression value of the risk score, and the prognostic analysis was also used to analyze the survival time between these two groups. Finally, we analyzed the expression, interaction and correlation among the lipid metabolism-associated genes risk model.Results: The results from the prognostic analysis indicated that the survival was significantly poorer in the high-risk group than in the low-risk group in TCGA, and single-sample gene set enrichment analysis (ssGSEA) shows it is plausible that lipid metabolism is highly correlated with tumor immunity.Conclusion: Lipid metabolism-associated genes may become a new prognostic indicator predicting the survival of BC patients. The prognostic genes (n = 16) may help provide new strategies for tumor therapy.Keywords: bioinformatics, lipid metabolism-associated genes, breast cancer, lipid metabolism, TCGA

Lingling Wu, 1,* Qin Li, 2,* Junjie Deng, 3, 4 Jinglan Shen, 2 Weide Xu, 3 Wei Yang, 5 Bingyu Chen, 2 Yaoqiang Du, 2 Wei Zhang, 6 Feihang Ge, 6 Siyun Lei, 2 Kaiqiang Li, 2 Zhen Wang 2 1Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310014, People’s Republic of China; 2Department of Transfusion Medicine, Allergy Center, Ministry of Education Key Laboratory of Laboratory Medicine, Zhejiang Provincial People’s Hospital People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 3Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325000, People’s Republic of China; 4Oujiang Laboratory, Wenzhou, Zhejiang, 325000, People’s Republic of China; 5Department of Biophysics, and Department of Neurosurgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 6Hangzhou Chinese Academy of Sciences-Hangzhou Medical College Advanced Medical Technology Institute, Hangzhou, 310014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kaiqiang Li; Zhen WangZhejiang Provincial People’s Hospital, Hangzhou, People’s Republic of ChinaTel +86 0571-87666666Fax +86 0571-85131448Email likaiqiang@hmc.edu.cn; wangzhen@hmc.edu.cnPurpose: Cell membrane-camouflaged nanoparticles (NPs) are drawing increasing attention because their surfaces acquire some characteristics of the cell membranes, making them a unique class of biomimetic materials for diverse applications. Modification of cell membrane or combination of different types of membranes can enhance their functionality.Methods: We prepared platelet and tumor cell membrane camouflaged β-mangostin-loaded NPs, which were synthesized with platelet–C6 hybrid biomimetic coating, poly(lactic-co-glycolic acid), and β-mangostin (β-PCNPs). Then, we evaluated their targeting ability and anticancer activity against glioma in vitro and in vivo.Results: Biomimetic coating enhanced active drug targeting and immune escape properties of nanocarrier in C6 and THP-1 cells, respectively, which improved their cytotoxicity. β-PCNPs were characterized to study the inherent properties of both source cells. Compared with bare β-NPs, β-PCNPs exhibited high tumor-targeting capability and induced apoptosis of C6 cells in vitro. Similarly, intravenous administration of drug through β-PCNPs resulted in enhanced tumor-targeting and exhibited excellent rate of inhibition of glioma tumor growth in mice. Moreover, the blood circulation time of drug in mice in the β-PCNP group was markedly prolonged and these mice exhibited better outcome than those in the β-NP group.Conclusion: These results provide a new strategy of utilizing PCNPs as carriers for drug delivery, which improves the targeting efficiency and therapeutic efficacy of chemotherapeutic agents for glioma therapy.Keywords: glioma, hybrid membrane, biomimetic, β-mangostin, targeted delivery, anticancer

Mengyue Lin,1,2 Mulalibieke Heizhati,2 Lin Wang,2 Lin Gan,1,2 Mei Li,2 Wenbo Yang,2 Ling Yao,2 Zhongrong Wang,2 Zhikang Yang,2 Reyila Abudoyreyimu,2 Zihao Wu,2 Nanfang Li1,2 1Xinjiang Medical University, Urumqi, People’s Republic of China; 2Hypertension Center of the People’s Hospital of Xinjiang Uygur Autonomous Region; Xinjiang Hypertension Institute; National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang, People’s Republic of ChinaCorrespondence: Nanfang LiHypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region; Xinjiang Hypertension Institute; National Health Committee Key Laboratory of Hypertension Clinical Research, 91 Tianchi Road, Urumqi, Xinjiang, 830001, People’s Republic of ChinaEmail lnanfang2016@sina.comPurpose: The burden of kidney dysfunction (KD) is rapidly increasing in developing countries due to an ongoing epidemic of hypertension and diabetes. We aimed to evaluate the prevalence and associated factors of KD among population with hypertension and/or diabetes from primary care setting.Methods: This study was part of a cross-sectional study conducted in Northwest China, which aimed to investigate the epidemiological status of hypertension and other chronic noninfectious diseases. Subjects aged ≥ 18 years old with hypertension and/or diabetes were included in this study. KD was defined as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m2. Least absolute shrinkage and selection operator and multivariable logistic regression were used to identify factors associated with KD. Sensitivity analysis was performed by comparing the results of different estimated equations for GFR.Results: A total of 8899 participants with hypertension and/or diabetes were included. Prevalence of KD was 8.69% (n=144) among patients with both hypertension and DM, 3.36% (n=198) among patients with only hypertension, and 5.22% (n=70) among patients with only diabetes. Women showed higher prevalent KD than men. Modifiable factors independently associated with KD among patients with hypertension and/or diabetes included physical activity, duration of hypertension or DM, anemia, fasting plasma glucose and triglyceride. Results of different estimated equations showed similar trends of difference in the prevalence of KD among groups.Conclusion: KD is common in patients with hypertension and/or DM in Northwest China. More attention should be paid to high-risk patients, especially to those with co-existence of hypertension and DM. Control of blood glucose and triglyceride may further improve KD management in this patient population.Keywords: kidney dysfunction, hypertension, diabetes, epidemiology

Hao Tang,1 Rongrong Li,2 Huaming Xu,1 Guoping Lu,3 Zhen Liu,1 Wensu Yang,1 Zhaoxin Xia,1 Yi Zhu,1 Jilu Shen1 1The Fourth Affiliated Hospital of Anhui Medical University Laboratory Department, Hefei, People’s Republic of China; 2The First Affiliated Hospital of Anhui Medical University Laboratory Department, Hefei, People’s Republic of China; 3Laboratory Department of Fuyang Hospital Affiliated to Anhui Medical University, Fuyang, Anhui, 236000, People’s Republic of ChinaCorrespondence: Jilu ShenThe Fourth Affiliated Hospital of Anhui Medical University Laboratory, No. 100 Huaihai Avenue, Xinzhan District, Hefei, Anhui Province, 230012, People’s Republic of ChinaTel +86 151 5515 2963Email shenjilu@ahmu.edu.cnIntroduction: The recently developed DOT-MGA (direct-on-target microdroplet growth assay) has shown the desirability of direct application of this approach in positive blood cultures and its good performance in detection. This study selected 44 Enterobacteriaceae strains and implemented a DOT-MGA assay on blood cultures to detect their resistance to seven antibiotics. The results of DOT-MGA were compared with the other two antimicrobial susceptibility testing (AST) methods to analyze the detection performance of DOT-MGA.Methods: We adopted the differential centrifugation to process positive blood-culture (BC). Processed BC broth was directly used for rapid AST using DOT-MGA. Droplets of 6 μL with and without antibiotics at the EUCAST breakpoint concentration were spotted in triplicates onto the surface of a MALDI target. The plates were incubated in a wet box for 4 h before the broth was removed with filter paper. Bruker Biotyper software was used to analyze the test results compared with standard database, and the scores were used to quantify and determine the results.Results: DOT-MGA results were compared with the direct-from-BC disk-diffusion method and results were reported by broth microdilution method, respectively. The comparison demonstrated a 100% growth efficiency in DOT-MGA, a 100% classification consistency for ampicillin, ceftriaxone, and gentamicin, and > 93% classification consistency for tobramycin, aztreonam, trimethoprim-sulfamethoxazole (TMP-SMX), and ceftazidime.Discussion: These study results have shown that DOT-MGA is suitable for directly identifying bacterial resistance to positive blood cultures in clinical microbiology laboratories. Furthermore, it is conducive for early diagnosis and treatment of patients with bloodstream infection due to its convenience, time efficiency, and good performance in identifying multiple antibiotic-insensitive bacteria.Keywords: MALDI-TOF, DOT-MGA, rapid antimicrobial susceptibility testing, blood culture, antibiotic resistance, direct-from-BC disk-diffusion method

Lulu Song,1 Xiaomu Kong,2 Zhaojun Yang,1 Jinping Zhang,1 Wenying Yang,1 Bo Zhang,1 Xiaoping Chen,1 Xin Wang1 1Department of Endocrinology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Clinical Laboratory, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xin WangDepartment of Endocrinology, China-Japan Friendship Hospital, 2 Yinghua East Road, Beijing, 100029, People’s Republic of ChinaTel +86 1084205254Email xiangpian11@163.comPurpose: To assess the effect of acarbose in lowering low-grade albuminuria compared to metformin in newly diagnosed Chinese type 2 diabetes (T2DM) patients.Patients and Methods: The Metformin and AcaRbose Clinical Trial was a randomized, open-label trial in newly diagnosed T2DM patients. Participants received 48 weeks of monotherapy with acarbose (100 mg three times a day) or metformin (1500 mg once a day). As the hypoglycemic effect of acarbose and metformin has been evaluated in previous reports. This analysis studied the effect of the two antidiabetic drugs on reducing urinary albumin. The percent change in the urinary albumin/creatinine ratio (uACR) from baseline to week 48 was analyzed, and ANCOVA was employed to establish whether the effect in decreasing uACR was mediated by metabolic improvement.Results: Acarbose reduced the adjusted mean percent uACR by − 31.5% (95% confidence interval [CI] − 48.4 to − 7.5) compared with metformin. When adjusting for changes in glycated hemoglobin, body weight, systolic blood pressure and triglycerides or changes in area under the curve of glucagon-like peptide 1 (AUCGLP-1) in the standard meal test, the uACR-lowering effect was not attenuated. If stratified by eGFR, blood glucose level, sex or uACR level, the effect of acarbose versus metformin was consistent across subgroups. The proportion of patients with a reduction in uACR of at least 70% was 48.6% in the acarbose group and 34.1% in the metformin group.Conclusion: Acarbose lowered the uACR compared to metformin in newly diagnosed T2DM patients independent of improvements in hyperglycemia, blood pressure, body weight and triglycerides.Keywords: diabetes mellitus, type 2, diabetic nephropathies, hypoglycemic agents

The mechanism(s) of immune checkpoint inhibitor (ICI)-induced myasthenia gravis (MG), an immune-related adverse event (irAE) that is fatal and limits subsequent ICI use, remain unexplored. Here, through comparative genomic analysis, we identified a pathogenic p.S467C germline variant in SLC22A5 in a thymoma case with ICI-induced MG, which was found to be associated with fatty acid oxidation through its regulation on L-carnitine levels. Remarkably, ICI rechallenge with L-carnitine pretreatment led to durable response without MG-related symptoms. Thus, we provide the first clinical evidence of genetic test-directed irAE management, which integrates individualized ICI treatment into the evolving paradigm of cancer management.

Oxide heterostructures and superlattices (SLs) have attracted a great deal of attention in recent years owing to the rich exotic properties encountered at their interfaces. We focus on the potential of tunable correlated oxides by investigating the spectral function of the prototypical correlated metal SrVO3, using soft x-ray absorption spectroscopy and resonant inelastic soft x-ray scattering to access both unoccupied and occupied electronic states, respectively. We demonstrate a remarkable level of tunability in the spectral function of SrVO3 by varying its thickness within the SrVO3/SrTiO3 SL, showing that the effects of electron correlation can be tuned from dominating the energy spectrum in a strongly correlated Mott–Hubbard insulator, towards a correlated metal. We show that the effects of dimensionality on the correlated properties of SrVO3 are augmented by interlayer coupling, yielding a highly flexible correlated oxide that may be readily married with other oxide systems.

Determining the leakage rates of halogenated refrigerants from operating mobile air conditioning systems (MACs) is a challenging task. Here, we take advantage of a heavily trafficked tunnel with a traffic flow of over 40,000 motor vehicles per day in south China. We carried out measurements in 2014 on hot and humid days, and therefore, it is reasonable to assume that essentially all of the MAC units would be turned on to ensure the thermo-comfort of the occupants. Thus, we obtained the leakage rates of the three most important refrigerants from the operating MACs aboard the on-road vehicles. The emission factors (EFs) of HFC-134a, HCFC-22, and CFC-12 from the on-road operating MACs are 1.27 ± 0.11, 0.47 ± 0.04, and 0.17 ± 0.04 mg km-1 veh-1, respectively. Normalized by the percentages of vehicles using different refrigerants in their MACs, the emission rates of HFC-134a, HCFC-22, and CFC-12 are 52.2, 329, and 59.5 mg h-1 veh-1, respectively. This emission rate of HFC-134a is approximately 10 times higher than those previously reported in Europe for stationary conditions and a whole-lifetime average of fugitive losses. The unusually high leakage rates suggest that improving the leak tightness of MACs in China would help to greatly lower their emissions. The global warming potentials associated with refrigerant leakage is equal to 1.4% of the CO2 directly emitted due to fuel consumptions.