SIRT3 protects endometrial receptivity in patients with polycystic ovary syndrome.

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls (P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS (P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS: Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.

Cost-effective prognostic evaluation of breast cancer: using a STAR nomogram model based on routine blood tests.

Background: Breast cancer (BC) is the most common and prominent deadly disease among women. Predicting BC survival mainly relies on TNM staging, molecular profiling and imaging, hampered by subjectivity and expenses. This study aimed to establish an economical and reliable model using the most common preoperative routine blood tests (RT) data for survival and surveillance strategy management. Methods: We examined 2863 BC patients, dividing them into training and validation cohorts (7:3). We collected demographic features, pathomics characteristics and preoperative 24-item RT data. BC risk factors were identified through Cox regression, and a predictive nomogram was established. Its performance was assessed using C-index, area under curves (AUC), calibration curve and decision curve analysis. Kaplan-Meier curves stratified patients into different risk groups. We further compared the STAR model (utilizing HE and RT methodologies) with alternative nomograms grounded in molecular profiling (employing second-generation short-read sequencing methodologies) and imaging (utilizing PET-CT methodologies). Results: The STAR nomogram, incorporating subtype, TNM stage, age and preoperative RT data (LYM, LYM%, EOSO%, RDW-SD, P-LCR), achieved a C-index of 0.828 in the training cohort and impressive AUCs (0.847, 0.823 and 0.780) for 3-, 5- and 7-year OS rates, outperforming other nomograms. The validation cohort showed similar impressive results. The nomogram calculates a patient's total score by assigning values to each risk factor, higher scores indicating a poor prognosis. STAR promises potential cost savings by enabling less intensive surveillance in around 90% of BC patients. Compared to nomograms based on molecular profiling and imaging, STAR presents a more cost-effective, with potential savings of approximately $700-800 per breast cancer patient. Conclusion: Combining appropriate RT parameters, STAR nomogram could help in the detection of patient anemia, coagulation function, inflammation and immune status. Practical implementation of the STAR nomogram in a clinical setting is feasible, and its potential clinical impact lies in its ability to provide an early, economical and reliable tool for survival prediction and surveillance strategy management. However, our model still has limitations and requires external data validation. In subsequent studies, we plan to mitigate the potential impact on model robustness by further updating and adjusting the data and model.

The clinical impact of plasma estrogen receptor-1 mutation in patients with metastatic breast cancer: A meta-analysis.

BACKGROUND: The relevance of the discovered plasma ESR1 mutations in positive metastatic breast cancer (BC) patients who had progressing disease after aromatase inhibitor (AI)-based therapy is still being debated. OBJECTIVES: We conducted this meta-analysis to explore the prognostic and predictive role of plasma ESR1 mutations in patients with progressive BC who have previously received AI therapy. MATERIAL AND METHODS: We searched for relevant studies in the PubMed, Embase and Cochrane Library databases to be included in the meta-analysis. This study was performed to compute combined hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the progression-free survival (PFS) rate and overall survival (OS) rate. Subgroup and sensitivity analyses were also performed. The heterogeneity between studies was evaluated using the I2 statistic. RESULTS: In this meta-analysis, a total of 1,844 patients with metastatic BC and positive for estrogen receptors (ERs) were enrolled from 8 articles. The analysis revealed that patients with circulating ESR1 mutations had significantly worse PFS (HR: 1.34; 95% CI: 1.17-1.55; p < 0.001) and OS (HR: 1.59; 95% CI: 1.31-1.92; p < 0.001) compared to wild-type ESR1 patients. Subgroup analysis showed that the types of plasma ESR1 mutations were associated with differences in the prognosis of metastatic BC. The D538G mutation showed a statistically significant lower PFS (p = 0.03), while the Y537S mutation was not significantly correlated with PFS (p = 0.354). CONCLUSION: According to the findings of this meta-analysis, the assessment for plasma ESR1 mutations may provide prognostic and clinical guidance regarding subsequent endocrine therapy decisions for ER-positive, metastatic BC patients who had received prior therapy with AIs.

Direct Fabrication of PET-Based Thermotolerant Separators for Lithium-Ion Batteries with Ion Irradiation Technology.

Lithium-ion batteries (LIBs) play a pivotal role as essential components in various applications, including mobile devices, energy storage power supplies, and electric vehicles. The widespread utilization of LIBs underscores their significance in the field of energy storage. High-performance LIBs should exhibit two key characteristics that have been persistently sought: high energy density and safety. The separator, a critical part of LIBs, is of paramount importance in ensuring battery safety, thus requiring its high thermal stability and uniform nanochannels. Here, the novel ion-track etched polyethylene terephthalate (ITE PET) separator is controllably fabricated with ion irradiation technology. Unlike conventional polypropylene (PP) separators, the ITE PET separator demonstrated vertically aligned nanochannels with uniform channel size and distribution. The remarkable characteristics of the ITE PET separator include not only high electrolyte wettability but also exceptional thermal stability, capable of withstanding temperatures as high as 180 °C. Furthermore, the ITE PET separator exhibits a higher lithium-ion transfer number (0.59), which is advantageous in enhancing battery performance. The structural and inherent advantages of ITE PET separators contribute to enhance the C-rate capacity, electrochemical, and long-term cycling (300 cycles) stability observed in the corresponding batteries. The newly developed method for fabricating ITE PET separators, which possess high thermal stability and a uniform channel structure, fulfills the demand for high-temperature-resistant separators without requiring any modification procedures. Moreover, this method can be easily scaled up using simple processes, making it a competitive strategy for producing thermotolerant separators.

Natural killer cell-related prognosis signature predicts immune response in colon cancer patients.

Background: Natural killer (NK) cells are crucial components of the innate immune system that fight tumors and viral infections. Patients with colorectal cancer (CRC) have a poor prognosis, and immunotherapeutic tools play a key role in the treatment of CRC. Methods: Public data on CRC patients was collected from the TCGA and the GEO databases. Tissue data of CRC patients were collected from Guangxi Medical University Affiliated Cancer Hospital. An NK-related prognostic model was developed by the least absolute shrinkage and selection operator (LASSO) and Cox regression method. Validation data were collected from different clinical subgroups and an external independent validation cohort to verify the model's accuracy. In addition, multiple external independent immunotherapy datasets were collected to further examine the value of NK-related risk scores (NKRS) in the prediction of immunotherapy response. Potential biological functions of key genes were examined by methods of cell proliferation, apoptosis and Western blotting. Results: A novel prognostic model for CRC patients based on NK-related genes was developed and NKRS was generated. There was a significantly poorer prognosis among the high-NKRS group. Based on immune response prediction, patients with low NKRS may be more suitable for immunotherapy and they are more sensitive to immunotherapy. The proliferation rate of CRC cells was significantly reduced and apoptosis of CRC cells was increased after SLC2A3 was knocked down. SLC2A3 was also found to be associated with the TGF-ß signaling pathway. Conclusion: NKRS has potential applications for predicting prognostic status and response to immunotherapy in CRC patients. SLC2A3 has potential as a therapeutic target for CRC.

Beta2-Microglobulin as Predictive Biomarkers in the Prognosis of Hepatocellular Carcinoma and Development of a New Nomogram.

Background: Accurate prognosis is crucial for improving hepatocellular carcinoma (HCC) patients, clinical management, and outcomes post-liver resection. However, the lack of reliable prognostic indicators poses a significant challenge. This study aimed to develop a user-friendly nomogram to predict HCC patients' post-resection prognosis. Methods: We retrospectively analyzed the data from 1091 HCC patients, randomly split into training (n=767) and validation (n=324) cohorts. Receiver operating characteristic (ROC) curves determined the optimal cut-off value for alpha1-microglobulin (α1MG) and Beta2-microglobulin (ß2MG). Kaplan-Meier analysis assessed microglobulin's impact on survival, followed by Cox regression to identify prognostic factors and construct a nomogram. The predictive accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index), calibration curves, area under the ROC curve (AUC), and decision curve analysis (DCA), and were compared with the BCLC staging system, Edmondson grade, or BCLC stage plus Edmondson grade. Results: Patients with high ß2MG (≥2.395mg/L) had worse overall survival (OS). The nomogram integrated ß2MG, BCLC stage, Edmondson grade, microvascular invasion (MVI), and serum carbohydrate antigen 199 (CA199) levels. C-index for training and validation cohorts (0.712 and 0.709) outperformed the BCLC stage (0.660 and 0.657), Edmondson grade (0.579 and 0.564), and the combination of BCLC stage with Edmondson grade (0.681 and 0.668), improving prognosis prediction. Calibration curves demonstrated good agreement between predicted and observed survival. AUC values exceeded 0.700 over time, highlighting the nomogram's discriminative ability. DCA revealed superior overall net income compared to other systems, emphasizing its clinical utility. Conclusion: Our ß2MG-based nomogram accurately predicts HCC patients' post-resection prognosis, aiding intervention and follow-up planning. Significantly, our nomogram surpasses existing prognostic indicators, including BCLC stage, Edmondson grade, and the combination of BCLC stage with Edmondson grade, by demonstrating superior predictive performance.

Influence of maternal obesity on embryonic vitrification injury and subsequent pregnancy outcomes: A retrospective cohort study.

Background: We previously reported that obese mice had significantly high lipid content in embryos, and excessive lipids are detrimental to embryonic development. However, whether maternal obesity has an effect on embryonic vitrification injury and subsequent pregnancy outcomes is still controversial. This study was conducted to clarify the influence of maternal obesity on embryonic vitrification injury and subsequent pregnancy outcomes by in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods: We retrospectively collected medical record of IVF/ICSI patients from reproductive medicine centers in two tertiary hospitals. The patients were classified into a low-weight group (<18.5 kg/m2), normal-weight group (18.5-23.9 kg/m2), overweight group (24.0-27.9 kg/m2) and obese group (≥28.0 kg/m2) according to their body mass index (BMI). Multivariable logistic regression analysis was performed to compare pregnancy outcomes in fresh and frozen embryo transfer among different BMI groups to define the correlation between BMI and embryonic vitrification injury. Results: A total of 44 773 women among 20-40 years old were recruited in this study, of which 27 797 underwent their first fresh embryo transfer and 16 976 underwent their first frozen embryo transfer. For fresh embryo transfer, there was no significant difference in the clinical pregnancy rate, live birth rate, and miscarriage rate of 4 BMI groups. For frozen-thawed embryo transfer, there was a significant increase in the clinical pregnancy rate of the overweight group (AOR = 1.14, 95% CI: 1.05-1.25) and the obese group (AOR = 1.24, 95% CI: 1.03-1.50), while the miscarriage rate (AOR = 1.42, 95% CI: 1.05-1.92) also showed a significant increase in the obese group compared to the normal-weight group. Conclusion: This study provided a new understanding of the effect of maternal obesity on embryonic vitrification injury. Maternal obesity does not worsen the outcome of IVF/ICSI, particularly in the frozen-thawed group.

CCL20 is a potential therapeutic target associated with immune infiltration in breast cancer.

OBJECTIVES: CCL20 is a chemotactic factor that is involved in immune cell recruitment and cancer progression. However, the role of CCL20 in the prognosis of breast cancer remains unclear. This study analyzed correlations between CCL20 expression and immune infiltration, clinicopathological parameters, and prognosis in breast cancer patients. METHODS: Correlations between CCL20 expression and clinicopathological parameters, prognosis, and immune infiltration in breast cancer were determined using the TIMER, UALCAN, and PrognoScan databases. Furthermore, gene-gene and protein-protein interactions were determined using GeneMANIA and STING network construction, respectively. RESULTS: CCL20 expression was significantly upregulated in breast cancer and had significant associations with clinicopathological features, including race, sex, age, menopause status, cancer stage, cancer subclass, and nodal metastasis; moreover, patients with higher CCL20 expression exhibited poor prognosis. Meanwhile, CCL20 expression was significantly correlated with the infiltration of immune cells in breast cancer, including monocytes, neutrophils, tumor-associated macrophages, Th1 cells, regulatory T cells, and exhausted T cells. Moreover, the network of CCL20 expression showed the majority genes and proteins were associated with immune reactions. CONCLUSIONS: CCL20 is a prognosis-related biomarker in breast cancer on the basis of its correlation with immune infiltration levels and has potential to also be a therapeutic target.

Role of adrenal venous sampling in the differential diagnosis and treatment protocol of ACTH-independent Cushing's syndrome with bilateral adrenal lesions.

PURPOSE: The diagnosis and management of adrenocorticotropic hormone-independent Cushing's syndrome (AICS) with bilateral adrenal lesions remain challenging. Some studies have explored the value of adrenal vein sampling (AVS) in patients with AICS; however, more investigations are needed to assess its benefits for diagnosis and treatment planning in this population. METHODS: Thirteen patients with clinical, biochemical and imaging evidence of AICS with bilateral adrenal lesions underwent AVS in our department from 2017-2022 were recruited. Only the data from nine patients for whom AVS succeeded were finally included in this study and further analyzed. Blood samples were successfully collected from both adrenal veins (AV) and inferior vena cava (IVC) in these nine patients, and the levels of plasma total cortisol (PTC) and plasma aldosterone concentrations (PAC) were measured. The ratio of the PAC of the AV to the IVC was calculated, and the PTC to PAC ratios were compared between AV. The surgical strategy was chosen according to the results of AVS. Postoperative histology and immunohistochemistry of the adrenal tissues were performed. The prognosis was evaluated based on the improvement of clinical symptoms and biochemical parameters (including PTC and ACTH measurements). RESULTS: Patients with AICS were clinically diagnosed based on clinical signs, results of functional tests and the presence of bilateral adrenal lesions as observed on computed tomography imaging. An AV to IVC PAC ratio greater than 2 confirmed successful AVS. The PTC to PAC ratio (high side to low side) was greater than 2 in four patients, and less than 2 in five patients. The postoperative pathological results were consistent with clinical diagnosis and AVS. During the mean follow-up of 33 months, all nine patients achieved varying degrees of clinical improvement. CONCLUSION: Our study showed that AVS helped to distinguish unilateral and bilateral lesions, identify the laterality of the autonomous hypercortisolism, and improve therapeutic strategy selection in patients with AICS and bilateral adrenal lesions.

Role of uric acid as a biomarker of cognitive function in schizophrenia during maintenance period.

Background: Previous studies involving uric acid (UA) in some specialized disease populations have found that high UA is associated with enhanced patient function. The mechanism to explain this association may be that UA, an important antioxidant, exerts neuroprotective effects. Patients with schizophrenia (SCZ) have severe oxidative stress abnormalities, and cognitive impairment is a major obstacle to their rehabilitation. Only few studies have been conducted on UA and cognitive impairment in SCZ. This study aims to clarify the relationship between UA and cognitive impairment and explore whether UA could be used as a potential biological marker of cognition in SCZ during maintenance period. Methods: A total of 752 cases of SCZ during maintenance period from Baiyun Jingkang Hospital were included. Cognition was measured using the Mini-Mental State Examination scale. UA was measured using the Plus method. The participants were grouped on the basis of UA to evaluate the association of cognition with low-normal (3.50-5.07 mg/dL for men, 2.50-4.19 mg/dL for women), middle-normal (5.07-6.39 mg/dL for men, 4.19-5.18 mg/dL for women), high-normal (6.39-7.00 mg/dL for men, 5.18-6.00 mg/dL for women), and high (>7.00 mg/dL for men, >6.00 mg/dL for women) levels of UA. Multiple logistic regression and linear regression models and restricted cubic spline (RCS) were utilized to evaluate the relationship. Results: Uric acid was positively associated with cognitive function. Subgroup analyses showed that high UA was associated with enhanced cognition in participants with low anticholinergic cognitive burden (ACB). Conclusion: Uric acid may be used as a simple objective biological indicator to assess cognition in SCZ during maintenance period.

Construction of Clostridium tyrobutyricum strain and ionic membrane technology combination pattern for refinery final molasses recovery and butyric acid production.

Introduction: Clostridium tyrobutyricum has considerable prospect in the production of organic acids. Globally, refinery final molasses is rich in sugar and reported to have high levels of accumulation and high emission costs, recognized as an excellent substrate for C. tyrobutyricum fermentation, but there is no suitable method available at present. Methods: In this study, an acid-base treatment combined with a new green membrane treatment technology - a dynamic ion-exchange membrane -was used to pretreat refinery final molasses, so that it could be used for C. tyrobutyricum to produce butyric acid. A high-performance liquid chromatography method was established to determine the conversion of a large amount of sucrose into fermentable sugars (71.88 g/L glucose and 38.06 g/L fructose) in the treated refinery final molasses. The process of sequential filtration with 3, 1, and 0.45 µm-pore diameter dynamic ion-exchange membranes could remove impurities, pigments, and harmful substances from the refinery final molasses, and retain the fermentable sugar. Results and discussion: This means that refinery final molasses from the sugar industry could be utilized as a high-value by-product and used for the growth of C. tyrobutyricum, with industrial feasibility and economic competitiveness. Using the treated refinery final molasses as a carbon source, C. tyrobutyricum was screened by the method of adaptive evolution. The strain with butyric acid yielded 52.54 g/L, and the yield of the six carbon sugar was increased from 0.240 to 0.478 g/g. The results showed that combination of C. tyrobutyricum and ionic membrane technology broke through the bottleneck of its utilization of refinery final molasses. This study provided an innovative idea for the C. tyrobutyricum fermentation to produce butyric acid.

Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species.

The canonical transient receptor potential channel (TRPC) proteins form Ca2+-permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model. Trpc1-/- mice exhibited improved cardiac function, lower serum Troponin T and serum creatine kinase level, smaller infarct volume, less fibrotic scars, and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6-/- mice. Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury. Furthermore, Trpc1 deficiency protected adult mouse ventricular myocytes (AMVMs) and HL-1 cells from death during hypoxia/reoxygenation (H/R) injury. RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species (ROS) generation in Trpc1-/- cardiomyocytes. Among these genes, oxoglutarate dehydrogenase-like (Ogdhl) was markedly downregulated. Moreover, Trpc1 deficiency impaired the calcineurin (CaN)/nuclear factor-kappa B (NF-κB) signaling pathway in AMVMs. Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions. Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter. The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes. In conclusion, our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R, leading to increased Ca2+ influx into associated cardiomyocytes. Subsequently, this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway, ultimately exacerbating ROS production and aggravating myocardial I/R injury.

[Metabolic Outcomes of Primary Aldosteronism Patients Receiving Adrenalectomy or Spironolactone Treatments]. / æŽ¥å—è‚¾ä¸Šè ºåˆ‡é™¤æœ¯æˆ–èžºå† é ¯æ²»ç–—çš„åŽŸå‘æ€§é†›å›ºé ®å¢žå¤šç—‡æ‚£è€ ä»£è°¢è½¬å½’.

Objective: To investigate the metabolic outcomes of primary aldosteronism (PA) patients receiving adrenalectomy (ADX) or spironolactone treatment and the contributing factors to the metabolic outcomes. Methods: The clinical data of 70 patients with aldosterone-producing adenoma (APA) and 86 patients with idiopathic hyperaldosteronism (IHA) were retrospectively analyzed. All subjects received confirmatory diagnosis of APA or IHA at the Department of Endocrinology and Metabolism, West China Hospital between March 2018 and October 2020. APA patients underwent ADX, while IHA patients were given spironolactone, a mineralocorticoid receptor antagonist (MRA). After ADX or spironolactone treatment, the outcomes of the metabolic indicators and the inter-group differences between the APA patients and IHA patients were studied. Results: There was no significant difference between the baseline data of the APA group and those of the IHA group in terms of age, sex, duration of hypertension, maximum systolic blood pressure (SBP-max), maximum diastolic blood pressure (DBP-max), body mass index (BMI), fasting blood glucose (FBG), lipid parameters, and renal function. IHA patients had higher waist circumference, serum potassium, and plasma renin activity (PRA) than those of the APA patients (all P<0.05). All patients showed significant improvement in blood pressure, blood potassium, and plasma aldosterone at follow-up. However, they also showed increased triglycerides (TG) accompanied by deterioration in renal function (P≤0.001). Multiple regression showed that TG levels were associated with spironolactone treatment for IHA patients and post-treatment BMI and creatinine levels. Furthermore, APA patients showed improvement in their FBG after ADX (P=0.041), while IHA patients showed elevated levels of FBG after spironolactone treatment (P=0.037). Conclusion: After treatment, PA patients still may experience abnormal lipid metabolism and deteriorating renal function. Spironolactone therapy may give rise to worse glucolipid metabolism than ADX therapy does.

Association between lipid metabolism and cognitive function in patients with schizophrenia.

Background: The association between blood lipids and cognitive function in schizophrenia is still controversial. Thus, the present study aimed to verify the association between various lipid parameters and cognitive impairment in schizophrenic patients and potential lipid pathways. Methods: A total of 447 adult inpatients with schizophrenia were divided into cognitive normal and cognitive impairment groups based on the Mini-Mental State Examination with a cut-off of 26. The blood lipid parameters were defined as abnormal levels based on the guideline. The liquid chromatography-mass spectrometry method was used to preliminarily explore the potential lipid metabolism pathway associated with cognitive impairment. Results: There were 368 (82.3%) patients who had cognitive impairment. Herein, apolipoprotein B was positively associated with cognitive function in overall patients and age (≥45 and <45 years) and sex subgroups. After excluding patients with hypertension and diabetes, ApoB was still significantly associated with cognitive function in all the patients. The associations between other lipid parameters, including non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride, and cognitive impairment were heterogeneous in age and sex subgroups. In contrast, total cholesterol and apolipoprotein A1 were not significantly associated with cognitive impairment. Metabolomics analysis showed that metabolic pathway mainly involved sphingolipid metabolism. Meanwhile, sphinganine and 3-dehydrosphinganine were positively correlated with lipid parameters and decreased in patients with cognitive impairment as compared to those with normal cognition. Conclusions: The present study suggests a positive association between lipids and cognitive function in schizophrenic patients and needs to be further verified by a prospective study.

NF-κB inactivation attenuates the M1 macrophage polarization in experimental necrotizing enterocolitis by glutaredoxin-1 deficiency.

The pathogenesis of necrotizing enterocolitis (NEC) is severe inflammatory injury in preterm infants, which resulted from macrophage polarization. Nuclear factor-κB (NF-κB) is implicated to be involved in macrophage polarization. We here evaluated the essential role of NF-κB in macrophage polarization in NEC in human samples from neonates with NEC and the mouse experimental NEC model. Enhanced intestinal macrophage (IM) infiltration was presented in human neonates with NEC, the majority of which were M1 macrophages. Meanwhile, NF-κB was activated in the IMs in human NEC samples. NF-κB inhibition by BAY promoted the M1 to M2 macrophage polarization. Furthermore, glutaredoxin-1 (Grx1) deficiency promoted M2 polarization via NF-κB inactivation from the lipopolysaccharide-induced proinflammatory macrophages. The IMs isolated from Grx1- / - mice presented with decreases in total numbers and less macrophage differentiation. Grx1- / - derived IM were effective in the increased survival in experimental NEC through inflammation blocking. Our study provides evidence that NF-κB inactivation by Grx1 depletion contributed to the alleviation of NEC via inhibiting M1 macrophage polarization. The modulation to alternative macrophages in the intestines may provide a promising benefits for NEC treatment.

Fabrication and Characterization of Co-Doped Fe2O3 Spindles for the Enhanced Photo-Fenton Catalytic Degradation of Tetracycline.

Co-doped Fe2O3 spindles with different Co contents were successfully fabricated by a facile one-step hydrothermal method. The crystalline structure, morphology, optical properties, and chemical state of the as-prepared catalysts before and after photo-Fenton reaction were characterized. Co2+ incorporated into the Fe2O3 lattice was confirmed by the above characterizations. Also, the photocatalytic and photo-Fenton catalytic performances of the samples were evaluated by the degradation of tetracycline (TC) under visible light irradiation in the absence/presence of H2O2. The results demonstrated that Co-doped Fe2O3 spindles exhibited better catalytic degradation performance in comparison with single Fe2O3 spindles, and the sample of Co(5%)-Fe2O3 spindles displayed the highest activity and best stability. The improvement of photo-Fenton activity might be attributed to two reasons: On the one hand, Co-doped Fe2O3 spindles not only formed the Fe vacancies to reduce the band gap but also could build up an internal electric field, which inhibits electron/hole pair recombination and facilitates the transfer of photoexcited charge carriers. On the other hand, the intrinsic Co2+/Co3+ redox cycling can accelerate the circulation between Fe2+ and Fe3+ in Co(5%)-Fe2O3 spindles to facilitate H2O2 consumption and produce more ·OH radicals for TC degradation.

Evaluation of the effects of glycated hemoglobin on cardiac function in patients with short-duration type 2 diabetes mellitus: A cardiovascular magnetic resonance study.

AIMS: To investigate the association between glycated hemoglobin (HbA1c) and myocardial dysfunction and to determine whether its association is independent of myocardial perfusion. METHODS: Sixty-four patients with type 2 diabetes mellitus (T2DM) were recruited. They were divided into groups according to their HbA1c level: the controlled T2DM group (HbA1c < 7%) and uncontrolled T2DM groups (HbA1c ≥ 7%). Meanwhile, 30 age-matched healthy volunteers were included. All patients with T2DM and healthy controls underwent cardiovascular magnetic resonance imaging to evaluate the myocardial mechanics and perfusion parameters. RESULTS: The circumferential and longitudinal peak strain (PS) (p = 0.009 and 0.002 respectively) and global radial, circumferential, and longitudinal peak strain diastolic strain rates (PDSRs) (p = 0.002, 0.001, and 0.001 respectively) were lower in the uncontrolled T2DM group than in the controls without diabetes. In multivariable linear regression analysis, HbA1c was independently related to all directions of the PS and PDSR. The myocardial perfusion parameters were not independently associated with the PS or PDSR. CONCLUSIONS: Cardiac function is impaired in Chinese T2DM patients with poor glucose control (HbA1c ≥ 7%), with preserved left ventricular (LV) ejection fraction, and disease duration <10 years. Poor blood glucose control is an independent predictor of LV myocardial dysfunction for patients with short-term T2DM.

Developing a research database of primary aldosteronism: rationale and baseline characteristics.

BACKGROUND: Management of primary aldosteronism (PA) has become a research hotspot in the field of endocrinology. To obtain reliable research evidence, it is necessary to establish a high-quality PA research database. METHODS: The establishment of PA research database involved two steps. Firstly, patients with confirmation of PA diagnosis between 1 Jan 2009 to 31 Aug 2019 at West China Hospital were identified and data were extracted. Secondly, patients with confirmatory testing for PA will be enrolled into a prospective cohort. Data will be prospectively collected based on the case report forms since 1 Sep 2019. We evaluated the quality of research database through assessment of quality of key variables. RESULTS: Totally, 862 patients diagnosed as PA were identified, of which 507 patients who had positive confirmatory testing for PA were included into the retrospective database. Among 862 patients diagnosed as PA, the mean systolic blood pressure (SBP) was 156.1 (21.7) mmHg, mean diastolic blood pressure (DBP) was 97.2 (14.5) mmHg. Among included patients, the mean serum potassium level was 2.85 (IQR, (2.47-3.36) mmol/L, and the mean plasma aldosterone concentration (PAC) was 28.1 (IQR, 20.0-40.4) ng/dL. The characteristics of patients with positive confirmatory testing for PA were similar. Validation of data extracting and linking showed the accuracy were 100%. Evaluation of missing data showed that the completeness of BMI (95.9%), SBP (99.4%) and DBP (99.4%) were high. CONCLUSION: Through integrating retrospective and prospective cohort of PA, a research database of PA with high quality and comprehensive data can be established. We anticipate that the research database will provide a high level of feasibility for management of PA in China.

Ionic Transport and Sieving Properties of Sub-nanoporous Polymer Membranes with Tunable Channel Size.

Bioinspired nanoporous membranes show great potential in ionic separation and water filtration by offering high selectivity with less permeation resistance. However, complex processes always limit their applications. Here, we report a convenient approach to introduce ionic selective channels in a micron-thick polycarbonate membrane through swift heavy ion irradiation accompanied by UV sensitization and pulsed-electrical etching. The characteristic dimension of channels was tuned through regulating energy loss of the incident ion and UV sensitization time of the membrane, resulting in the sub-nanoporous membranes with mean channel diameter ranging from <2.4 to 9.7 Å. These membranes showed the voltage-activated ionic transport properties associated with the dehydration effect, and the corresponding I-V characteristics were related to ionic strength, solution pH, ionic type, and channel diameter. It was found that the transmembrane conduction of multivalent ions was severely suppressed compared to monovalent ions, until the size of the membrane channel was comparable to the hydrated diameter of multivalent ions. Ionic sieving experiments also demonstrated the excellent ionic valence selectivity of the membrane. Even for the membrane with a channel diameter close to 1 nm, the Li+/Mg2+ separation ratio was still as high as 40, and an even higher separation ratio was found for Li+/La3+ (>3000).

CD44, IL-33, and ST2 Gene Polymorphisms on Hepatocellular Carcinoma Susceptibility in the Chinese Population.

The interleukin- (IL-) 33/ST2 axis plays a pivotal role in tumorigenesis through influencing cancer stemness and other mechanisms. CD44 is one of the critical markers of hepatocellular carcinoma (HCC) among the cancer stem cells (CSCs). There is still a lack of CD44 gene single-nucleotide polymorphisms (SNPs) combined with IL-33/ST2 pathway single-nucleotide polymorphisms in HCC susceptibility analysis literature, although CD44 and IL-33/ST2 have been reported separately in human cancers. This study is aimed at investigating the relationship between CD44, IL-33, and ST2 SNPs and HCC susceptibility and clinicopathological features. We analyzed 565 HCC patients and 561 healthy controls in the Chinese population. The genes for CD44rs187115A>G, IL-33 rs1929992A>G, and ST2 rs3821204G>C were typed using the SNaPshot method. We found that the distribution frequencies of CD44 and ST2 alleles and genotypes in both the HCC case group and the control group were statistically significant (p < 0.05). The results showed that individuals carrying at least one G allele of the CD44 rs187115 gene were at a higher risk than the AA genotype carriers (p = 0.007, odds ratio (OR) = 1.429, 95% confidence interval (CI): 1.102-1.854). Similarly, individuals with at least one C allele of ST2 rs3821204 had a higher risk of HCC than those with GG genes (p ≤ 0.001, OR = 1.647, 95% CI: 1.296-2.093). Combining the haplotype analysis of the 3 loci suggested that CD44 rs187115, IL-33 rs1929992, and ST2 rs3821204 are associated with the risk of HCC and could potentially serve as useful genetic markers for HCC in some populations of China.