Effectiveness of video-based psychiatric rehabilitation for patients with early-phase schizophrenia spectrum: A randomized controlled trial.

AIM: This study aimed to establish a comprehensive set of recovery-oriented rehabilitation programs for individuals with schizophrenia, comparing the efficacy of video-based rehabilitation to traditional face-to-face interventions. The primary objective was to assess whether video-based rehabilitation could serve as a viable alternative for individuals with schizophrenia residing in remote areas. METHODS: A randomized controlled study was used to recruit 80 patients with schizophrenia in a stable post-hospitalization stage following discharge. Participants were categorized into three groups: 24 in the control group, 21 in the face-to-face group, and 35 in the remote group. Assessment parameters included psychiatric symptoms, social skills, family function and self-stigma. RESULTS: A total of 68 participants completed the program. The findings indicated significant differences (p < .05) between the control group and intervention group, particularly in the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance Scale (PSP). CONCLUSIONS: The rehabilitation program, tailored for patients in the early phase of the schizophrenia spectrum, demonstrates both effectiveness and feasibility in enhancing clinical symptoms and social functions. Notably, interventions conducted via video proved to be equally effective as those administered face-to-face.

Unrevealing the therapeutic potential of artesunate against emerging zoonotic Babesia microti infection in the murine model.

Babesiosis, a zoonotic blood protozoal disease, threatens humans and animals and is difficult to treat due to growing antimicrobial resistance. The study aimed to investigate the therapeutic efficacy of artesunate (AS), a well-known derivative of artemisinin, against Babesia microti (B. microti) using a murine infection model. Male BALB/c mice (6 weeks old; 15 per group) were chosen and randomly divided into 1) the control group, 2) the B. microti group, and 3) the B. microti + artesunate treatment groups. AS treatment at 2 mg/kg, 4 mg/kg, and 8 mg/kg of body weight significantly (p < 0.05) reduced the B. microti load in blood smears in a dose-dependent manner. Additionally, AS treatment mitigated the decrease in body weight and restored the normal state of the liver and spleen viscera index compared to the B. microti-infected group after 28 days. Hematological analysis revealed significant increases in RBC, WBC, and PLT counts post-AS treatment compared to the B. microti-infected group. Furthermore, AS administration resulted in significant reductions in total protein, bilirubin, ALT, AST, and ALP levels, along with reduced liver and spleen inflammation and lesions as observed through histopathological analysis. AS also elicited dose-dependent changes in mRNA and protein expression levels of apoptotic, proinflammatory, and anti-inflammatory cytokines in the liver compared to the control and B. microti-infected groups. Immunolabeling revealed decreased expression of apoptotic and inflammation-related proteins in AS-treated hepatic cytoplasm compared to the B. microti-infected group. AS also in dose-dependent manner decreased apoptotic protein and increased Bcl-2. Overall, these findings underscore the potential of AS as an anti-parasitic candidate in combating B. microti pathogenesis in an in vivo infection model, suggesting its promise for clinical trials as a treatment for babesiosis.

Predictive value of postprandial C-peptide for utilizing multiple daily injection therapy in type 2 diabetes.

PURPOSE: Multiple daily injection (MDI) insulin therapy is an effective method of glycemic control and appropriate assignment to MDI therapy could minimize the risks of hypoglycemia and weight gain. The aim of the present study was to identify factors associated with indication for MDI therapy in type 2 diabetes (T2DM). METHODS: We recruited 360 participants with T2DM that were admitted to the Endocrinology Department of Peking University People's Hospital between August 2017 and July 2018. They first underwent intensive insulin therapy, then were switched to an optimized, simpler insulin treatment that aimed to maintain fasting blood glucose between 4.4 and 7.2 mmol/L, without episodes of hypoglycemia. The baseline characteristics of groups administering either MDI or basal/premix insulin were compared and multivariable logistic regression analysis was used to determine the odds ratios (ORs) for factors associated with MDI therapy. Receiver operating characteristic (ROC) curves were then used to identify independent predictors of MDI insulin regimen efficacy. RESULTS: The mean age of the participants was 57.6 ± 12.9 years, and diabetes duration was 14.2 ± 8.2 years. Two hundred and sixty-seven participants administered basal/premix insulin and 93 underwent MDI therapy, of whom 61.8% and 46.2% were male, respectively (p = 0.01). The duration of diabetes was significantly longer in the MDI group (13.1 ± 7.7 years vs. 17.3 ± 8.7 years; p < 0.01). Fasting plasma glucose (FPG) was higher in the MDI group than in the basal/premix group (8.3 [6.7, 11.3] mmol/L vs. 7.2 [5.7, 9.3] mmol/L; p < 0.01), while the postprandial C-peptide concentration (PCP) was significantly lower in the MDI group (2.6 [1.8, 3.5] ng/mL) compared to the basal/premix group (3.6 [2.5, 6.2] ng/mL, p < 0.01. Multivariable logistic regression analysis suggested that diabetes duration and FPG were positively associated with MDI therapy: OR (95% confidence interval [CI]) 1.06 (1.02, 1.10) and 1.12 (1.02, 1.24), respectively. In addition, PCP was negatively associated with MDI therapy (0.72 [0.60, 0.86]). ROC analysis suggested that a PCP of < 3.1 ng/mL predicted MDI therapy with 59.6% sensitivity and 72.1% specificity. CONCLUSION: The results of our study suggest that longer diabetes duration, higher FPG, and lower PCP were associated with necessity for MDI insulin regimen. These findings should assist with the personalization of insulin treatment.

A randomized clinical trial for meal bolus decision using learning-based control in adults with type 2 diabetes.

BACKGROUND: We proposed an artificial-pancreas-like algorithm (AP-A) which could automatically determine the pre-prandial insulin dose based on intermittently scanned continuous glucose monitoring (isCGM) data trajectories in multiple dose injection (MDI) therapy. We aim to determine whether pre-prandial insulin dose adjustments guided by the AP-A is as effective and safe as physician decisions. METHODS: We performed a randomized, single-blind, clinical trial at a tertiary, referral hospital in Beijing, China. Type 2 diabetes participants were eligible if they were aged  18 years, with a glycated hemoglobin of 8.0% or higher. Eligible participants were randomly assigned (1:1) to the AP-A arm supervised by physician and the conventional physician treatment arm. The primary objective was to compare percentage time spent with sensor glucose level in 3.9-10.0 mmol/L (TIR) between the two study arms. Safety was assessed by the percentage time spent with sensor glucose level below 3.0 mmol/L (TBR). RESULTS: 140 participants were screened, of whom 119 were randomly assigned to AP-A arm (n = 59) or physician arm (n = 60). The TIR achieved by the AP-A arm was statistically non-inferior compared with the control arm (72.4% (63.3-82.1) vs. 71.2% (54.9-81.4)), with a median difference of 1.33% (95% CI, -6.00 to 10.94, non-inferiority margin -7.5%). TBR was also statistically non-inferior between the AP-A and control arms (0.0% (0.0-0.0) vs. 0.0% (0.0-0.0), respectively; median difference (95% CI, 0.00% (0.00 to 0.00), non-inferiority margin 2.0%). CONCLUSIONS: The AP-A supported physician titration of pre-prandial insulin dosage offers non-inferior glycemic control compared with optimal physician care in type 2 diabetes.

Overburden of rare ALMS1 deleterious variants in Chinese early-onset type 2 diabetes with severe insulin resistance.

AIMS: Alström syndrome (AS) is a rare recessive disorder characterised by diabetes, obesity, insulin resistance (IR), and visual and hearing impairments. Mutations in the ALMS1 gene have been identified as the causative agents of AS. This study aimed to explore the relationship between rare ALMS1 variants and clinical features in Chinese patients with early-onset type 2 diabetes (age at diagnosis ≤40 years; EOD). MATERIALS AND METHODS: ALMS1 gene sequencing was performed in 611 Chinese individuals with EOD, 36 with postprandial hyperinsulinemia, and 47 with pre-diabetes and fasting IR. In-silico prediction algorithm and the American College of Medical Genetics Guidelines (ACMG) were used to evaluate the deleteriousness and pathogenicity of the variants. RESULTS: Sixty-two rare ALMS1 variants (frequency <0.005) were identified in 82 patients with EOD. Nineteen variants were predicted to be deleterious (pD). Patients with EOD carrying pD variants had higher fasting C-peptide, postprandial C-peptide, and HOMA2-IR levels than those without variants. The frequency of ALMS1 pD variants in the subgroup with more insulin-resistant EOD was higher than that in other EOD subgroups. Two patients with EOD, obesity, and IR who carried one heterozygous pathogenic/likely pathogenic rare variant of ALMS1 according to ACMG were identified. Moreover, rare heterozygous pD variants of ALMS1 were found in participants from cohorts of postprandial hyperinsulinemia as well as in pre-diabetes with fasting IR. CONCLUSIONS: ALMS1 rare pD variants are enriched in the populations with significant IR, which is a major hallmark of diabetes pathogenesis. Accordingly, our exploratory study provides insights and hypotheses for further studies of gene function.

Tanshinone IIA Alleviates Traumatic Brain Injury by Reducing Ischemia‒Reperfusion via the miR-124-5p/FoxO1 Axis.

Background: Cerebral ischemia-reperfusion injury is a common complication of ischemic stroke that affects the prognosis of patients with ischemic stroke. The lipid-soluble diterpene Tanshinone IIA, which was isolated from Salvia miltiorrhiza, has been indicated to reduce cerebral ischemic injury. In this study, we investigated the molecular mechanism of Tanshinone IIA in alleviating reperfusion-induced brain injury. Methods: Middle cerebral artery occlusion animal models were established, and neurological scores, tetrazolium chloride staining, brain volume quantification, wet and dry brain water content measurement, Nissl staining, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription-quantitative polymerase chain reaction were performed. The viability of cells was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assays, while cell damage was measured by lactate dehydrogenase release in the in vitro oxygen glucose deprivation model. In addition, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription-quantitative polymerase chain reaction were used to evaluate the therapeutic effect of Tanshinone IIA on ischemia/reperfusion (I/R) induced brain injury, as well as its effects on the inflammatory response and neuronal apoptosis, in vivo and in vitro. Furthermore, this study validated the targeting relationship between miR-124-5p and FoxO1 using a dual luciferase assay. Finally, we examined the role of Tanshinone IIA in brain injury from a molecular perspective by inhibiting miR-124-5p or increasing FoxO1 levels. Results: After treatment with Tanshinone IIA in middle cerebral artery occlusion-reperfusion (MCAO/R) rats, the volume of cerebral infarction was reduced, the water content of the brain was decreased, the nerve function of the rats was significantly improved, and the cell damage was significantly reduced. In addition, Tanshinone IIA effectively inhibited the I/R-induced inflammatory response and neuronal apoptosis, that is, it inhibited the expression of inflammatory cytokines IL-1ß, IL-6, TNF-α, decreased the expression of apoptotic protein Bax and Cleaved-caspase-3, and promoted the expression of antiapoptotic protein Bcl-2. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, Tanshinone IIA also inhibited the expression of inflammatory factors in neuronal cells and inhibited the occurrence of neuronal apoptosis. In addition, Tanshinone IIA promoted the expression of miR-124-5p. Transfection of miR-124-5p mimic has the same therapeutic effect as Tanshinone IIA and positive therapeutic effect on OGD cells, while transfection of miR-124-5p inhibitor has the opposite effect. The targeting of miR-124-5p negatively regulates FoxO1 expression. Inhibition of miR-124-5p or overexpression of FoxO1 can weaken the inhibitory effect of Tanshinone IIA on brain injury induced by I/R, while inhibition of miR-124-5p and overexpression of FoxO1 can further weaken the effect of Tanshinone IIA. Conclusion: Tanshinone IIA alleviates ischemic-reperfusion brain injury by inhibiting neuroinflammation through the miR-124-5p/FoxO1 axis. This finding provides a theoretical basis for mechanistic research on cerebral ischemia-reperfusion injury.

[Effects of different fertilization patterns on soil improvement and vegetation restoration of desertified grassland in northwest Liaoning Province, China]. / 不同培肥模式对辽西北沙化草地土壤改良与植被恢复的影响.

Improving soil fertility is one of the key approaches for ecological restoration of the wind-sand area in northwest Liaoning Province. Taking wind-sand area in northwest Liaoning Province as test object, we conducted a fertilization experiment with treatments of inorganic fertilizer (nitrogen, phosphorus and potassium fertilizers), organic fertilizer, combined application of organic and inorganic fertilizers, and organic fertilizer combined with a biologically organic matrix (γ-polyglutamic acid), and no fertilizer as control. We measured soil organic matter content and extractable cations concentrations, vegetation coverage, and biomass under different fertilization treatments and determine the suitable fertilization mode. The results showed that compared to the control, inorganic fertilizer rapidly increased vegetation coverage and biomass, but high levels of inorganic fertilizer (150 kg N·hm-2) led to soil acidification and Ca2+ leaching. Organic fertilizer increased soil organic matter content, exchangeable K+, Ca2+, and Mg2+ contents, as well as coverage and biomass vegetation, especially combined with γ-polyglutamic acid. Overall, the combination of low levels of inorganic fertilizer (50 kg N·hm-2) and moderate levels of organic fertilizer (30000 kg·hm-2) was the best fertilization practice for the rapid and stable restoration of grassland in wind-sand area. Moreover, the extra addition of γ-polyglutamic acid (60 kg·hm-2)could effectively improve soil fertility.

Development and validation of self-screening tool for nutrition risk in patients with gastric cancer after gastrectomy: A study protocol.

AIM: This study aims to develop and validate a clinical nutrition risk screening tool to predict nutrition risk in home for the patients with gastric cancer after surgery at home so that high-risk patients can be targeted for preventive nutrition care. DESIGN: The development of self-screening tool for nutrition risk in patients with gastric cancer after gastrectomy (SNRSGC) through literature review, expert panel ratings and cognitive interview; the validation of SNRSGC is evaluated through prospective research on participants. METHODS: This research is divided into four parts: Step 1, Identification of a potential referred nutritional risk screening; Step 2, Item generation and scoring are selected through literature review methods to screen sensitive indicators which can reflect the nutritional characteristics of patients after gastric cancer surgery, establish the frame and update according to the latest guidelines; Step 3, Item reduction is determined by the rating of SNRSGC items by an expert panel and cognitive interview; Step 4, During the validation stage, we conducted research design based on the Consensus-based Standards for the selection of health Measurement Instruments checklist to evaluate the validity, reliability, interpretability and acceptability of SNRSGC. RESULTS: SNRSGC is the first screening tool specifically to predict nutrition risk for stay-at-home postoperative patients with gastric cancer, which can help patients at home detect nutritional risks at home in time and guide patients to seek medical treatment as soon as possible to improve their nutritional status.

Adrenal limb thickness is associated with metabolism profiles in patients with diabetes: A cross-sectional study.

BACKGROUND: The association between adrenal size and metabolic profiles in patients with diabetes mellitus (DM) is unclear. This study was conducted to determine whether the adrenal thickness measured by computed tomography (CT) is correlated with the metabolic profiles of patients with DM. METHODS: This was a cross-sectional study including 588 Chinese hospitalized patients with DM without comorbidities or medications known to affect adrenal morphology or hormone secretion. Adrenal limb thickness was measured on unenhanced chest CT. Participants were stratified into tertiles according to their total adrenal limb thickness. Linear and logistic regression models were used to estimate the correlations. RESULTS: After adjustment for sex and age, the adrenal thickness was positively associated with body mass index (BMI), waist circumference (WC), urinary albumin/creatinine ratio, and 24-h urinary free cortisol (UFC) and negatively correlated with high-density lipoprotein cholesterol. The sequential equation model (SEM) suggested UFC partially mediated the effect of adrenal limb thickness on WC by 12%. Adrenal thickness, but not UFC, was associated with a higher risk of existing hypertension (odds ratio [OR] = 3.78, 95% confidence interval [CI] 1.58, 9.02) and hyperlipidemia (OR = 2.76, 95% CI 1.03, 7.38), independent of age, gender, BMI, and WC. CONCLUSIONS: The adrenal thickness is independently associated with BMI, WC, cortisol levels, urinary albumin/creatinine ratio, hypertension, and dyslipidemia but not glycemic parameters in patients with diabetes. Our study encourages further studies to investigate the role of adrenal physiology in patients with diabetes.

Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes.

OBJECTIVE: CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). METHODS: We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. RESULTS: In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. CONCLUSION: CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.

Factors influencing college students' self-regulated learning in online learning environment: A systematic review.

OBJECTIVE: Drawing on the control value theory, this study aims to identify the pertinent factors of self-regulated learning in the online learning environment for college students. The analysis will inductively examine how these factors impact self-regulated learning, thereby furnishing a reference for educators and online learning platform developers to create more efficacious online learning and teaching modes. DESIGN: Systematic review. DATA SOURCES: In March 2023, electronic databases of PubMed, Web of Science, Embase, EBSCO, Cochrane and Scopus were searched, and there was no time limit for publication. REVIEW METHODS: The inclusion criteria were: (1) Includes both online learning environment and self-regulated learning variables. (2) The research object is college students. (3) The research focuses on online teaching. Assessment of risk of bias for all included studies using a mixed-methods assessment tool. RESULTS: After screening, 31 articles were finally included. Including 24 quantitative studies, 2 qualitative study and 5 mixed studies. According to the control value theory, the factors affecting self-regulated learning in online learning environment are divided into seven aspects, namely cognitive quality, motivational quality, autonomy support, goal structures and social expectations, feedback and considerations of achievement, perceived control and perceived value. CONCLUSIONS: Teachers should exercise reasonable management over the number of assignments and provide timely and supportive feedback, as well as actively create interactive learning environments to facilitate peer-to-peer communication. Developers of online learning platforms should improve the functions of the platforms according to students' needs, and provide training for teachers and students when necessary. Learners should adapt their learning status in a timely manner to realise efficient learning and improve learning outcomes.

Differential effect of interventions in patients with prediabetes stratified by a machine learning-based diabetes progression prediction model.

AIM: To investigate whether stratifying participants with prediabetes according to their diabetes progression risks (PR) could affect their responses to interventions. METHODS: We developed a machine learning-based model to predict the 1-year diabetes PR (ML-PR) with the least predictors. The model was developed and internally validated in participants with prediabetes in the Pinggu Study (a prospective population-based survey in suburban Beijing; n = 622). Patients from the Beijing Prediabetes Reversion Program cohort (a multicentre randomized control trial to evaluate the efficacy of lifestyle and/or pioglitazone on prediabetes reversion; n = 1936) were stratified to low-, medium- and high-risk groups using ML-PR. Different effect of four interventions within subgroups on prediabetes reversal and diabetes progression was assessed. RESULTS: Using least predictors including fasting plasma glucose, 2-h postprandial glucose after 75 g glucose administration, glycated haemoglobin, high-density lipoprotein cholesterol and triglycerides, and the ML algorithm XGBoost, ML-PR successfully predicted the 1-year progression of participants with prediabetes in the Pinggu study [internal area under the curve of the receiver operating characteristic curve 0.80 (0.72-0.89)] and Beijing Prediabetes Reversion Program [external area under the curve of the receiver operating characteristic curve 0.80 (0.74-0.86)]. In the high-risk group pioglitazone plus intensive lifestyle therapy significantly reduced diabetes progression by about 50% at year l and the end of the trial in the high-risk group compared with conventional lifestyle therapy with placebo. In the medium- or low-risk group, intensified lifestyle therapy, pioglitazone or their combination did not show any benefit on diabetes progression and prediabetes reversion. CONCLUSIONS: This study suggests personalized treatment for prediabetes according to their PR is necessary. ML-PR model with simple clinical variables may facilitate personal treatment strategies in participants with prediabetes.

A database of atmospheric inorganic nitrogen deposition fluxes in China from satellite monitoring.

Over the past century, atmospheric inorganic nitrogen (IN) deposition to terrestrial ecosystems has significantly increased and caused various environmental issues. China has been one of the hotspot regions for IN deposition, yet limited data exist regarding IN deposition fluxes in China at the regional scale. In this study, based on NO2 and NH3 columns acquired by satellite sensors, coupled with atmospheric chemical transport model (CTM), mixed-effects model and site observations, we constructed regional-scale IN dry and wet deposition models respectively, and finally proposed a spatially explicit database of IN deposition fluxes in China. The database includes the dry, wet and total deposition fluxes in China during 2011-2020, and the data are presented in raster form with a resolution of 0.25° × 0.25°. Overall, the database is of great importance for monitoring and simulating the trends of IN deposition over a long time series in China.

Betaxolol as a Potent Inhibitor of NDM-1-Positive E. coli That Synergistically Enhances the Anti-Inflammatory Effect in Combination with Meropenem.

With significant human and economic losses, increasing bacterial resistance is a serious global threat to human life. Due to their high efficacy, broad spectrum, and cost-effectiveness, beta-lactams are widely used in the clinical management of bacterial infection. The emergence and wide spread of New Delhi metallo-ß-lactamase (NDM-1), which can effectively inactivate ß-lactams, has posed a challenge in the design of effective new antimicrobial treatments. Medicine repurposing is now an important tool in the development of new alternative medicines. We present a known glaucoma therapeutic, betaxolol (BET), which with a 50% inhibitory concentration (IC50) of 19.3 ± 0.9 µM significantly inhibits the hydrolytic activity of the NDM-1 enzyme and may represent a potential NDM-1 enzyme inhibitor. BET combined with meropenem (MEM) showed bactericidal synergism in vitro. The efficacy of BET was further evaluated against systemic bacterial infections in BALB/c mice. The results showed that BET+MEM decreased the numbers of leukocytes and inflammatory factors in peripheral blood, as well as the organ bacterial load and pathological damage. Molecular docking and kinetic simulations showed that BET can form hydrogen bonds and hydrophobic interactions directly with key amino acid residues in the NDM-1 active site. Thus, we demonstrated that BET inhibited NDM-1 by competitively binding to it and that it can be developed in combination with MEM as a new therapy for the management of infections caused by medicine-resistant bacteria.

Safety and Effectiveness of Baricitinib in Chinese Patients with Moderate-to-Severe Rheumatoid Arthritis: 24-Week Results from a Post-Marketing Safety Study.

INTRODUCTION: Baricitinib, a JAK1/JAK2 inhibitor, is approved for treatment of moderate-to-severe rheumatoid arthritis (RA) in China. This single-arm, prospective, multi-center, post-marketing safety study (PMSS) evaluated the safety and effectiveness of baricitinib in Chinese patients. METHODS: This study included adult patients with moderate-to-severe active RA who received baricitinib over periods of approximately 12 and 24 weeks. The primary endpoint was safety, defined as week 12 adverse event (AE)/serious AE incidence. Secondary endpoints were week 24 safety and effectiveness (disease activity score with 28 joints/C-reactive protein [DAS28-CRP] and simplified/Clinical Disease Activity Index [SDAI/CDAI]). RESULTS: Safety analyses included 667 patients (female, 82.3%; mean age, 53.3 years; mean RA duration, 86.9 months); 106/667 (15.9%) were 65-74 years old and 19/667 (2.8%) were ≥ 75 years old; 87.0% received baricitinib 2 mg QD. Total exposure was 262.1 patient-years (PY). At week 12, AEs had occurred in 214 (32.1%; exposure-adjusted incidence rate [EAIR], 172.5 per 100 PY) patients (serious AEs: 22 [3.3%; EAIR, 15.0]). At week 24, AEs had occurred in 250 (37.5%; EAIR, 125.9) patients (serious AEs: 28 [4.2%; EAIR, 10.9]). Two patients (0.3%) died (of pneumonia and unknown cause); EAIR for death, 0.77. Serious infection occurred in 1.2% of patients (EAIR, 3.1). Hepatotoxicity occurred in 3.4% of patients (EAIR, 9.0). No patients met potential Hy's law laboratory criteria (alanine/aspartate aminotransferases ≥ 3 × upper limit of normal (ULN) and total bilirubin ≥ 2 × ULN). Malignancy occurred in one patient. No patients experienced venous thromboembolism (VTE) or major adverse cardiovascular events (MACE). At week 24, 52.4%, 27.5%, and 27.6% of patients achieved remission per DAS28-CRP, SDAI, and CDAI, respectively. CONCLUSIONS: This PMSS investigated the safety and effectiveness of baricitinib in clinical practice in China. No VTE/MACE or new safety signals were reported and there was promising effectiveness, supporting the use of baricitinib in Chinese patients with moderate-to-severe active RA. TRIAL REGISTRATION: EU PAS Register: EUPAS34213.

Cutting-edge regenerative therapy for Hirschsprung disease and its allied disorders.

Hirschsprung disease (HSCR) and its associated disorders (AD-HSCR) often result in severe hypoperistalsis caused by enteric neuropathy, mesenchymopathy, and myopathy. Notably, HSCR involving the small intestine, isolated hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction, and megacystis-microcolon-intestinal hypoperistalsis syndrome carry a poor prognosis. Ultimately, small-bowel transplantation (SBTx) is necessary for refractory cases, but it is highly invasive and outcomes are less than optimal, despite advances in surgical techniques and management. Thus, regenerative therapy has come to light as a potential form of treatment involving regeneration of the enteric nervous system, mesenchyme, and smooth muscle in affected areas. We review the cutting-edge regenerative therapeutic approaches for managing HSCR and AD-HSCR, including the use of enteric nervous system progenitor cells, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells as cell sources, the recipient intestine's microenvironment, and transplantation methods. Perspectives on the future of these treatments are also discussed.

PGC-1α inhibits M2 macrophage polarization and alleviates liver fibrosis following hepatic ischemia reperfusion injury.

Oxidative stress can induce inflammation, promoting macrophage polarization and liver fibrosis following hepatic ischemia-reperfusion (I/R). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) has anti-oxidant and anti-inflammatory activity. However, how PGC-1α regulates macrophage polarization following hepatic I/R remains largely unknown. Male C57BL/6 wild-type mice were pre-treated with vehicle or trichostatin A (TSA) for 2 days and subjected to surgical induction of I/R. Liver injury and fibrosis in individual mice were examined longitudinally and the expression levels of IL-6, STAT3, M2-type macrophage markers, Collagen I and α-SMA in the liver of mice were analyzed by immunohistochemistry, RT-qPCR and Western blot. The potential interaction of PGC-1α with phosphorylated NF-kBp65 was determined by immunoprecipitation. The impacts of PGC-1α deficiency in hepatocytes on their IL-6 production and macrophage polarization were tested in a Transwell co-culture system. Moreover, the M2-type macrophage polarization and liver fibrosis were examined in hepatocyte-specific PGC-1α knockout mice and AAV8-mediated PGC-1α over-expressing mice following liver I/R. The down-regulated PGC-1α expression by I/R was negatively correlated with IL-6 levels in the liver of I/R mice and PGC-1α deficiency enhanced IL-6 expression, STAT3 activation and M2-type macrophage polarization in the I/R mice, which were abrogated by TSA treatment. In addition, PGC-1α directly interacted with phosphorylated NF-kBp65 in I/R livers. Hepatocyte-specific PGC-1α deficiency increased IL-6 production and promoted macrophage polarization toward M2 type when co-culture. More importantly, administration with AAV8-PGC-1α rescued the I/R-induced liver fibrosis by inhibiting the IL-6/JAK2/STAT3 signaling and M2-type macrophage polarization in the liver. These results suggest that PGC-1α may alleviate the I/R-induced liver fibrosis by attenuating the IL-6/JAK2/STAT3 signaling to limit M2-type macrophage polarization. PGC-1α may be a therapeutic target for the treatment of liver fibrosis.

Defective Uterine Spiral Artery Remodeling and Placental Senescence in a Pregnant Rat Model of Polycystic Ovary Syndrome.

Pregnancy-related problems have been linked to impairments in maternal uterine spiral artery (SpA) remodeling. The mechanisms underlying this association are still unclear. It is also unclear whether hyperandrogenism and insulin resistance, the two common manifestations of polycystic ovary syndrome, affect uterine SpA remodeling. We verified previous work in which exposure to 5-dihydrotestosterone (DHT) and insulin (INS) in rats during pregnancy resulted in hyperandrogenism, insulin intolerance, and higher fetal mortality. Exposure to DHT and INS dysregulated the expression of angiogenesis-related genes in the uterus and placenta and also decreased expression of endothelial nitric oxide synthase and matrix metallopeptidases 2 and 9, increased fibrotic collagen deposits in the uterus, and reduced expression of marker genes for SpA-associated trophoblast giant cells. These changes were related to a greater proportion of unremodeled uterine SpAs and a smaller proportion of highly remodeled arteries in DHT + INS-exposed rats. Placentas from DHT + INS-exposed rats exhibited decreased basal and labyrinth zone regions, reduced maternal blood spaces, diminished labyrinth vascularity, and an imbalance in the abundance of vascular and smooth muscle proteins. Furthermore, placentas from DHT + INS-exposed rats showed expression of placental insufficiency markers and a significant increase in cell senescence-associated protein levels. Altogether, this work demonstrates that increased pregnancy complications in polycystic ovary syndrome may be mediated by problems with uterine SpA remodeling, placental functionality, and placental senescence.

Current Status and Health Risk Assessment of Heavy Metals Contamination in Tea across China.

Tea is a non-alcoholic beverage popular among Chinese people. However, due to the application of chemical and organic fertilizers in the tea planting process, the environment pollutionaround the tea plantation, and the instruments used in the processing, heavy metal elements will accumulate in the tea, which brings health risks for tea consumers. This study summarized heavy metal concentrations from 227 published papers and investigated the current contamination status of tea and tea plantation soils, and, finally, the risk of heavy metal exposure to tea consumers in China is assessed, in terms of both non-carcinogenic and carcinogenic risk. The average contamination of six heavy metals in tea-arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), and lead (Pb)-were 0.21, 0.14, 1.17, 14.6, 0.04, and 1.09 mg/kg, respectively. The areas with high concentrations of heavy metals in tea were concentrated primarily in southwest China, some areas in eastern China, and Shaanxi Province in northwest China. The non-carcinogenic risks of heavy metals in tea are all within safe limits. The national average HI value was 0.04, with the highest HI value of 0.18 in Tibet, which has the largest tea consumption in China. However, the carcinogenic risks of Cd in Shaanxi Province, Anhui Province, and southwest China exceed the acceptable range, and due attention should be given to these areas.

Blastic Plasmacytoid Dendritic Cell Neoplasm with Lung Involvement and Cytopenia: A Case Report and a Literature Review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hostile cutaneous malignancy with dismal prognosis and unknown etiology with rarity. Most patients received traditional chemotherapy only has one year of median survival time. This article reports an 81-year-old male patient with BPDCN who presented with skin manifestations and was diagnosed with positive CD4, CD56, and CD123 immunohistochemical results. Systematic examination revealed lung involvement and cytopenia.