Phase I PIANO trial-PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416). METHODS: Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m2 every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures. RESULTS: In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased. CONCLUSIONS: The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments.

Continuous quality improvement in a community-wide TB screening and prevention programme in Papua New Guinea.

SETTING: Daru Island in Papua New Guinea (PNG) has a high prevalence of TB and multidrug-resistant TB (MDR-TB). OBJECTIVE: To evaluate the early implementation of a community-wide project to detect and treat TB disease and infection, outline the decision-making processes, and change the model of care. DESIGN: A continuous quality improvement (CQI) initiative used a plan-do-study-act (PDSA) framework for prospective implementation. Care cascades were analysed for case detection, treatment, and TB preventive treatment (TPT) initiation. RESULTS: Of 3,263 people screened for TB between June and December 2023, 13.7% (447/3,263) screened positive (CAD4TB or symptoms), 77.9% (348/447) had Xpert Ultra testing, 6.9% (24/348) were diagnosed with TB and all initiated treatment. For 5-34-year-olds without active TB (n = 1,928), 82.0% (1,581/1,928) had tuberculin skin testing (TST), 96.1% (1,519/1,581) had TST read, 23.0% (350/1,519) were TST-positive, 95.4% (334/350) were TPT eligible, and 78.7% (263/334) initiated TPT. Three PDSA review cycles informed adjustments to the model of care, including CAD4TB threshold and TPT criteria. Key challenges identified were meeting screening targets, sputum unavailability from asymptomatic individuals with high CAD4TB scores, and consumable stock-outs. CONCLUSION: CQI improved project implementation by increasing the detection of TB disease and infection and accelerating the pace of screening needed to achieve timely community-wide coverage.

CONTEXTE: L'île de Daru en Papouasie-Nouvelle-Guinée (PNG) présente une forte prévalence de la TB et de la TB multirésistante (MDR-TB). OBJECTIF: Évaluer la mise en œuvre précoce d'un projet à l'échelle de la communauté pour détecter et traiter la TB et l'infection, décrire les processus de prise de décision et changer le modèle de soins. CONCEPTION: Une initiative d'amélioration continue de la qualité (CQI, pour l'anglais « continuous quality improvement ¼) a utilisé un cadre de planification, d'action, d'étude, d'action (PDSA, pour l'anglais «plan-do-study-act ¼) pour la mise en œuvre prospective. Les cascades de soins ont été analysées pour la détection des cas, le traitement et l'initiation du traitement préventif de la TB. RÉSULTATS: Sur 3 263 personnes dépistées pour la TB entre juin et décembre 2023, 13,7% (447/3 263) ont été dépistées positives (CAD4TB ou symptômes), 77,9% (348/447) ont subi un test Xpert Ultra, 6,9% (24/348) ont reçu un diagnostic de TB et toutes ont commencé un traitement. Chez les 5 à 34 ans sans TB active (n = 1 928), 82,0% (1 581/1 928) ont subi un test cutané à la tuberculine (TCT), 96,1% (1 519/1 581) ont eu un test de dépistage du TCT, 23,0% (350/1 519) étaient positifs au TCT, 95,4% (334/350) étaient éligibles au TPT et 78,7% (263/334) ont initié le TPT. Trois cycles d'examen PDSA ont permis d'ajuster le modèle de soins, y compris le seuil CAD4TB et les critères TPT. Les principaux défis identifiés étaient l'atteinte des objectifs de dépistage, l'indisponibilité des expectorations chez les personnes asymptomatiques avec des scores CAD4TB élevés et les ruptures de stock de consommables. CONCLUSION: L'ACQ a amélioré la mise en œuvre du projet en augmentant la détection de la TB et de l'infection et en accélérant le rythme de dépistage nécessaire pour atteindre une couverture à l'échelle de la communauté en temps opportun.

[Construction of competitive endogenous RNA regulatory network and clinical verification for repeated implantation failure].

Objective: To construct a repetitive implantation failure (RIF)-related competitive endogenous RNA (ceRNA) regulatory network and validate with clinical samples. Methods: RIF-related long non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) from the high-throughput gene expression omnibus (GEO) database Expression profile data set were obtained to construct a ceRNA regulatory network of lncRNA-miRNA-mRNA. At the same time, weighted gene co-expression network analysis (WGCNA) was used to explore hub genes in the network. This retrospective study collected RIF patients and controls (at least one pregnancy history after assisted conception) who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) for assisted pregnancy from 2020 to 2021 at the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University. In the endometrial tissue of patients with 1 pregnancy history, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to verify the mRNA expression levels of RIF-related hub genes, and Western blotting and immunohistochemistry were used to verify protein expression levels of vascular cell adhesion molecule-1 (VCAM1). Results: A RIF-related ceRNA regulatory network consisting of 32 lncRNAs, 31 miRNAs and 88 mRNAs was constructed, and 7 RIF-related hub genes were identified using WGCNA. By intersecting 88 mRNAs and hub genes in the ceRNA network, two RIF-related key genes were obtained, i.e., VCAM1 and interleukin-2 receptor α (interleukin-2 receptor α, IL-2RA). In clinical verification, the ages of the control group and RIF group [M (Q1, Q3)] were 26.50 (25.00, 34.00) and 30.50 (25.75, 35.25) years old, respectively (P>0.05). Compared with the control group, the mRNA [0.30 (0.15, 0.42) vs 0.99 (0.69, 1.34), P=0.001] and protein expression [0.44 (0.16, 1.27) vs 2.39 (1.58, 2.58), P<0.001] of VCAM1 in the endometrium of the RIF group were both reduced. Conclusions: This study uses bioinformatics analysis methods to construct a RIF-related ceRNA regulatory network, and it is confirmed through clinical samples that the expression level of VCAM1 in the endometrial tissue of RIF patients is significantly reduced.

[Screening and evaluation of clinical predictors of type 2 diabetes mellitus with cognitive impairment].

The present study aims to screen and evaluate the early clinical predictors for type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI) and dementia in Hunan province. A cross-sectional study was conducted from May 2023 to October 2023 to collect data on long-term T2DM patients who settled in Hunan province and were treated in the Department of Geriatrology at Xiangya Hospital of Central South University. The patients were grouped according to the Montreal Cognitive Assessment (MoCA) scale. Basic patient information and multiple serum markers were collected, and differences between groups were compared using one-way ANOVA or Kruskal-Wallis (KW) tests. The multivariate logistic regression analysis was utilized to assess risk factors and Nomogram models were constructed. The logistic regression analysis showed that years of education and serum levels of 1, 5-AG were related factors for the progression of T2DM to T2DM with MCI, and body weight, years of education and FPN levels affected the progression of T2DM with MCI to T2DM with dementia. Based on this, two Nomogram risk prediction models were established. The area under the curve (AUC) of the Nomogram model predicting T2DM progression to T2DM combined with MCI was 0.741, and the AUC of the Nomogram model predicting T2DM combined with MCI progression to T2DM combined with dementia was 0.734. The calibration curves (DCA) of the two models in the training and validation sets were symmetrically distributed near the diagonal line, indicating that the models in the training and validation sets could match each other. In summary, body weight, years of education, and serum HDL-3, FPN, and 1, 5-AG levels are associated with the development of MCI and dementia in T2DM patients. The Nomogram models constructed based on these factors can predict the risk of MCI and dementia in T2DM patients, providing a basis for clinical decision-making.

Raepenol™ Cream, a Complex of Natural Compounds, Promotes Wound Healing and Relieves Pruritus In Vivo.

BACKGROUND/AIM: Skin wound healing is a physiological process restoring the structural and functional integrity of injured skin. During this process, wound management preventing bacterial infection and complications is important for the regeneration of skin layers and adnexa, as well as the protective function of the skin. Therefore, the development of an effective ointment to promote wound healing without complications is beneficial. MATERIALS AND METHODS: This study developed Raepenol™ cream, comprising a base cream and natural compounds including paeonol, D-panthenol and extract of Centella asiatica, and assessed its therapeutic effect in wound healing. A rat model of skin wound healing and a mouse model of imiquimod-induced pruritus were employed. The effect of Raepenol™ cream was evaluated by wound size and histological analysis, including the integrity of skin structures and inflammatory response. RESULTS: Raepenol™ cream treatment effectively restored the structural integrity of the skin in rats, including wound closure, regeneration of skin adnexa, and reconstitution of collagen, comparable to commercial ointment. Additionally, Raepenol™ cream significantly suppressed pruritus by inhibiting mast cell infiltration or retention in the inflammatory site of mouse ears. CONCLUSION: Raepenol™ cream effectively promoted wound healing and relieved pruritus in animal models. These results suggest that it could be a promising option for wound care and pruritus relief, offering potential advantages over current ointments.

Protective Effects of Imatinib on a DSS-induced Colitis Model Through Regulation of Apoptosis and Inflammation.

BACKGROUND/AIM: Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses and a multifactorial etiology. While imatinib has demonstrated efficacy in the treatment of immune-related diseases, its potential effects in IBD treatment remain underexplored. MATERIALS AND METHODS: This study aimed to investigate the therapeutic effects of imatinib in colitis treatment. A dextran sulfate sodium (DSS)-induced colitis model was used to mimic IBD in mice. Imatinib was administered orally to mice simultaneously with DSS treatment. The effects of imatinib on DSS-induced colitis were evaluated by analyzing colitis-related pathology, including the disease activity index (DAI), histological lesions, inflammatory markers, and tight junction integrity. Additionally, western blot analysis and quantitative real-time polymerase chain reaction were used to assess inflammatory markers, tight-junction proteins, and cell death. RESULTS: In the DSS-induced colitis model, imatinib treatment exerted protective effects by attenuating weight loss, restoring colon length, reducing spleen weight, and improving the DAI score and histological lesions. Additionally, imatinib reduced the level of proinflammatory cytokines, including TNF-α, IL-6, and IL-1ß. Furthermore, imatinib treatment restored tight-junction integrity and decreased the expression of apoptosis marker proteins. CONCLUSION: Overall, imatinib treatment significantly alleviated the symptoms of DSS-induced colitis by influencing the expression of proinflammatory cytokines, tight junction proteins, and apoptotic markers in mice. These findings highlight imatinib as a potential therapeutic candidate for IBD.

Diagnostic accuracy of a real-time PCR assay for detection of Helicobacter pylori and resistance to clarithromycin and levofloxacin directly from stool.

OBJECTIVE: The non-invasive detection of Helicobacter pylori (H. pylori) and its resistance to clarithromycin and levofloxacin significantly improves the management of infected patients by enabling tailored eradication treatments without the need for endoscopic procedures. This study aimed to assess the effectiveness of real-time PCR (RT-PCR) assays in identifying H. pylori infection and antibiotic resistance in stool and gastric biopsy specimens. PATIENTS AND METHODS: Stool and gastric biopsy samples were collected from patients within three days of post-hospitalization. A total of 115 samples were analyzed for H. pylori infection, and an additional 115 samples were evaluated for resistance to clarithromycin and levofloxacin using an RT-PCR-based molecular test. Statistical analyses were performed using (SPSS 26.0 IBM Corp., Armonk, NY, USA). RESULTS: Among 115 patients (53 males, average age 50.8±13.2 years), H. pylori was detected in 93.1% of stool samples and 93.9% of gastric biopsies. The RT-PCR assay demonstrated a sensitivity of 99.1% and a specificity of 100%, with an overall diagnostic accuracy of 99.1%. Clarithromycin resistance was found in 37.3% of stool and 46.9% of gastric biopsy specimens, with the assay showing 79.6% sensitivity and 98.4% specificity. Levofloxacin resistance was identified in 32.1% of stool samples and 31.3% of gastric biopsies, with 86.3% sensitivity and 91.1% specificity of the molecular test. CONCLUSIONS: The RT-PCR-based detection of H. pylori and its resistance to clarithromycin and levofloxacin in stool samples represents a promising approach to enhance eradication therapy outcomes, potentially improving treatment efficacy. Chictr.org.cn: ChiCTR2300070267.

[Characteristics of liver volume and pathological changes with different stages of liver fibrosis in chronic liver disease].

Objective: To measure the overall and lobulated volume of the liver with different degrees of liver fibrosis and to further observe pathological changes such as liver microvasculature, hepatocyte apoptosis, and regeneration in order to understand the macroscopic volume changes of the liver during liver fibrosis and its relationship with liver tissue microscopic pathology in patients with chronic liver disease. Methods: 53 patients with chronic hepatitis B, alcoholic fatty liver disease, autoimmune liver disease, nonalcoholic fatty liver disease, and drug-induced chronic liver disease who underwent both liver biopsy tissue and abdominal magnetic resonance imaging were collected. Patients were divided into early (F1-2), middle (F3-4), and late (F5-6) in accordance with the Ishak fibrosis stage and Masson stain. The liver and spleen volumes were measured using ITK-SNAP software. CD31 immunohistochemical staining was used to reflect intrahepatic angiogenesis. Ki67 and HNF-4α multiplex immunohistochemical staining were used to reflect hepatocyte regeneration. GS staining was used to determine parenchymal extinction lesions. TUNEL staining was used to observe hepatocyte apoptosis. Spearman correlation analysis was used to analyze the relationship between liver volume changes and liver histopathological changes. Results: As liver fibrosis progressed, the total liver volume and right lobe liver volume gradually decreased (P<0.05), while the spleen volume gradually increased (P<0.05). The expression of CD31 and GS gradually increased (P<0.05), and the expression of Ki67 first increased and then decreased (P<0.05). The positivity rate of CD31 was negatively correlated with the right lobe liver volume (r=-0.609, P<0.001) and the total liver volume (r=-0.363, P=0.017). The positivity rate of Ki67 was positively correlated with the right lobe liver volume (r=0.423, P=0.018), while the positivity rate of apoptotic cells was significantly negatively correlated with the total liver volume (r=-0.860, P<0.001). The positivity rate of GS was negatively correlated with the right lobe liver volume (r=-0.440, P=0.002), and the number of PELs was negatively correlated with RV (r=-0.476, P=0.013). The CD31 positive staining area was negatively correlated with the Ki67 positive staining area(r=-0.511, P=0.009). Conclusion: As liver fibrosis progresses, patients with chronic liver disease have a depletion in total liver volume and right lobe liver volume, and this is mainly in correlation with fewer liver cells and liver tissue microvasculature disorders.

[18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography and conventional imaging modalities in the diagnosis of diabetic foot osteomyelitis: a meta-analysis.

AIM: This meta-analysis aimed to evaluate the comparative diagnostic efficacy of [18F]Fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and conventional imaging, MRI, and white blood cell (WBC) scintigraphy in detecting foot osteomyelitis among diabetic patients. MATERIALS AND METHODS: An exhaustive search was conducted within the PubMed and Embase databases to identify publications available up until February 2024. Studies were included if they evaluated the diagnostic efficacy of [18F]FDG PET or the comparative diagnostic performance between PET and (MRI or WBC scintigraphy). Two researchers independently assessed the quality of the included studies, utilizing the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. RESULTS: Nine retrospective or prospective studies involving 605 patients were included in the meta-analysis. For [18F]FDG PET, the overall sensitivity was 0.83(95% CI: 0.69-0.94), while the overall specificity was 0.92(95% CI: 0.86-0.97). In the head-to-head comparison, no significant difference of sensitivity was found between [18F]FDG PET and MRI (0.72 vs. 0.68, P=0.81), as well as between [18F]FDG PET and WBC scintigraphy (0.57 vs. 0.66, P=0.64). In addition, specificity was also found to be no significant difference between [18F]FDG PET and MRI (0.90 vs. 0.82, P=0.27), as well as [18F]FDG PET and WBC scintigraphy (0.81 vs. 0.93, P=0.09). CONCLUSION: [18F]FDG PET demonstrates similar sensitivity and specificity to MRI and WBC scintigraphy in detecting foot osteomyelitis among diabetic patients. MRI, often cited as a primary choice in guidelines, might be preferred due to its lower cost and lower dose. Further larger sample prospective studies are needed to confirm these findings.

Association between gestational cardiovascular health in the first trimester and pregnancy outcomes in the China birth cohort.

OBJECTIVES: To determine whether gestational cardiovascular health (CVH) during the first trimester is associated with a risk of adverse pregnancy outcomes. STUDY DESIGN: A multicentre prospective cohort; part of the China birth cohort study. METHODS: Pregnant women were recruited at 6-13+6 gestation weeks and followed to delivery to identify pregnancy outcomes. Gestational CVH in the first trimester was assessed using five CVH metrics: body mass index, smoking, blood pressure, glucose, and lipids. Multilevel modified Poisson regression models calculated the relative risks (RRs) and 95% confidence intervals (95% CIs) of gestational CVH for adverse pregnancy outcomes. RESULTS: Among 56,852 pregnant women, the mean score for gestational CVH during the first trimester was 9.1. Adjusting for confounding factors, each 1-point decrease in the total gestational CVH score significantly increased the risk of hypertensive disorders of pregnancy (RR = 1.682, 95% CI: 1.624-1.743), gestational diabetes mellitus (RR = 1.405, 95% CI: 1.384-1.426), preterm birth (RR = 1.184, 95% CI: 1.174-1.195), large for gestational age (RR = 1.224, 95% CI: 1.199-1.250), caesarean delivery (RR = 1.073, 95% CI: 1.049-1.097), and low Apgar score (RR = 1.131, 95% CI: 1.003-1.277) significantly increased. Meanwhile, the risk of small for gestational age decreased (SGA; RR = 0.922, 95% CI: 0.898-0.946). Worsened CVH categories significantly increased the risk of adverse pregnancy outcomes, excluding SGA. CONCLUSIONS: Poor gestational CVH in the first trimester significantly increases the risk of adverse pregnancy outcomes, emphasising the need for early improvement in gestational CVH.

Global Burden of Alzheimer's Disease and Other Dementias Attributed to High Fasting Plasma Glucose from 1990 to 2019.

BACKGROUND: Burden of Alzheimer's disease (AD) and other dementias have grown rapidly over the decades, and high fasting plasma glucose (HFPG) was one of the well-established risk factors. It is urgently needed to estimate the global burden of AD and other dementias attributable to high fasting plasma glucose between regions, countries, age groups, and sexes to inform development of effective primary disease prevention strategies and intervention policies. METHODS: The burden of AD and other dementias attributable to HFPG was estimated based on a modeling strategy using the Global Burden of Disease Study 2019 dataset. The disease burden and time trend globally and by region, country, development level, age group, and sex were evaluated. RESULTS: The number of AD and other dementias-related deaths attributable to HFPG increased from 42,998.23 (95% uncertainty interval, UI: 4459.86-163,455.78, the year of 1990) to 159,244.53 deaths (95% UI 18,385.23-583,514.15, the year of 2019). The age-standardized death rate increased from 1.69 (95% UI 0.18-6.54) in 1990 to 2.24 (95% UI 0.26-8.24) in 2019. The burden was higher in more developed regions. The burden in women was double that in men, that HFPG-attributable AD and other dementias caused 99,812.79 deaths (95% UI 9005.67-387,160.60) in women and 59,431.74 deaths (95% UI 5439.02-214,819.23) in men, with age-standardized death rate of 2.27 (95% UI 0.20-8.79) per 100,000 population in women and 2.20 (95% UI 0.20-8.00) in men. CONCLUSION: Findings from the current study emphasizes the urgent requirement for targeted interventions in high-development regions, as well as the importance of proactive measures in middle-development countries in protection of AD and other dementias. The gender disparity necessitates the integration of gender-specific considerations in targeted approaches in prevention of AD and other dementias.

Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms.

Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plausible that psilocybin could improve symptoms of AN by breaking down cognitive inflexibility. A mechanistic understanding of the actions of psilocybin is required to tailor the clinical application of psilocybin to individuals most likely to respond with positive outcomes. This can only be achieved using incisive neurobiological approaches in animal models. Here, we use the activity-based anorexia (ABA) rat model and comprehensively assess aspects of reinforcement learning to show that psilocybin (post-acutely) improves body weight maintenance in female rats and facilitates cognitive flexibility, specifically via improved adaptation to the initial reversal of reward contingencies. Further, we reveal the involvement of signalling through the serotonin (5-HT) 1 A and 5-HT2A receptor subtypes in specific aspects of learning, demonstrating that 5-HT1A antagonism negates the cognitive enhancing effects of psilocybin. Moreover, we show that psilocybin elicits a transient increase and decrease in cortical transcription of these receptors (Htr2a and Htr1a, respectively), and a further reduction in the abundance of Htr2a transcripts in rats exposed to the ABA model. Together, these findings support the hypothesis that psilocybin could ameliorate cognitive inflexibility in the context of AN and highlight a need to better understand the therapeutic mechanisms independent of 5-HT2A receptor binding.

[Annual progress on bronchial asthma diagnosis and treatment in 2023].

Bronchial asthma (referred to as asthma) is a common chronic inflammatory airway disease mediated by various immune cells, cytokines, and inflammatory mediators. This disease exhibits considerable heterogeneity in clinical symptoms, severity, and treatment outcomes, posing significant challenges to the diagnosis and treatment of asthma. This article reviews the literature on both basic and clinical research in asthma, published from October 1, 2022 to September 30, 2023. The review focuses on summarizing and elucidating four aspects of asthma: pathogenesis, diagnosis, assessment, and treatment. The aim is to provide more evidence for clinical diagnosis and treatment and offer new perspectives for future research.

A transdiagnostic and translational framework for delineating the neuronal mechanisms of compulsive exercise in anorexia nervosa.

OBJECTIVE: The development of novel treatments for anorexia nervosa (AN) requires a detailed understanding of the biological underpinnings of specific, commonly occurring symptoms, including compulsive exercise. There is considerable bio-behavioral overlap between AN and obsessive-compulsive disorder (OCD), therefore it is plausible that similar mechanisms underlie compulsive behavior in both populations. While the association between these conditions is widely acknowledged, defining the shared mechanisms for compulsive behavior in AN and OCD requires a novel approach. METHODS: We present an argument that a better understanding of the neurobiological mechanisms that underpin compulsive exercise in AN can be achieved in two critical ways. First, by applying a framework of the neuronal control of OCD to exercise behavior in AN, and second, by taking better advantage of the activity-based anorexia (ABA) rodent model to directly test this framework in the context of feeding pathology. RESULTS: A cross-disciplinary approach that spans preclinical, neuroimaging, and clinical research as well as compulsive neurocircuitry and behavior can advance our understanding of when, why, and how compulsive exercise develops in the context of AN and provide targets for novel treatment strategies. DISCUSSION: In this article, we (i) link the expression of compulsive behavior in AN and OCD via a transition between goal-directed and habitual behavior, (ii) present disrupted cortico-striatal circuitry as a key substrate for the development of compulsive behavior in both conditions, and (iii) highlight the utility of the ABA rodent model to better understand the mechanisms of compulsive behavior relevant to AN. PUBLIC SIGNIFICANCE: Individuals with AN who exercise compulsively are at risk of worse health outcomes and have poorer responses to standard treatments. However, when, why, and how compulsive exercise develops in AN remains inadequately understood. Identifying whether the neural circuitry underlying compulsive behavior in OCD also controls hyperactivity in the activity-based anorexia model will aid in the development of novel eating disorder treatment strategies for this high-risk population.

[Epidemiology of asthma based on the standard questionnaire].

Asthma is a common chronic airway disease in the world. Although the guidelines recommend the diagnostic criteria for asthma, which have been widely used in clinical practice, the standardized asthma questionnaire is often recommended for prevalence surveys in large-scale epidemiological surveys of the population, because the standardized asthma questionnaire has the characteristics of good cost-effectiveness and high response rate, and the results are also feasible for comparison between different populations or regions. There are currently four asthma epidemiological surveys in the world, including the European Community Respiratory Health Survey (ECRHS), the International Study of Asthma and Allergies in Childhood (ISAAC), the International Study of Wheezing in Infants (EISL) and World Health Survey (WHS). The above research results were also important data source for estimating the global prevalence of asthma in the Global Burden of Disease Study (GBD). In China, several national surveys were conducted on the prevalence of asthma in children and adults, but the reported prevalence of asthma was not comparable with other countries because clinical diagnostic criteria for asthma were frequently used to define asthma in these previous studies. The China Pulmonary Health (CPH) study was a national cross-sectional study that enrolled a nationally representative sample of Chinese adults aged 20 years or older, using the asthma questionnaire derived from ECRHS, we reported that the prevalence of asthma with wheezing in Chinese adults was 4.2%, representing 45.7 million adult asthmatics. However, it should be realized that these data did not include people under the age of 20 years or those with atypical asthmatic symptoms. In addition, the study shows that asthma is largely under-diagnosed and undertreated in China, and these findings call for national efforts to improve the prevention, detection and treatment of asthma in China.

[Overview of design and construction of hypertensive disorders of a pregnancy-cohort in Shenzhen].

Hypertensive disorder of pregnancy (HDP) involves two major public health issues: mother-infant safety and prevention and controlling major chronic disease. HDP poses a serious threat to maternal and neonatal safety, and it is one of the leading causes of maternal and perinatal morbidity and mortality worldwide, as well as an important risk factor for long-term cardiovascular disease (CVD). In order to explore effective strategies to prevent and control the source of CVD and reduce its risk, we have established a cohort of HDPs in Shenzhen for the primordial prevention of CVD. The construction of the HDP cohort has already achieved preliminary progress till now. A total of 2 239 HDP women have been recruited in the HDP cohort. We have established a cohort data management platform and Biobank. The follow-up and assessment of postpartum cardiovascular metabolic risk in this cohort has also been launched. Our efforts will help explore the pathophysiological mechanism of HDP, especially the pathogenesis and precision phenotyping, prediction, and prevention of pre-eclampsia, which, therefore, may reduce the risk of adverse pregnancy outcomes, and provide a bridge to linking HDP and maternal-neonatal cardiovascular, metabolic risk to promote the cardiovascular health of mothers and their infants.

Two-Year Prognostic Utility of Plasma p217+tau across the Alzheimer's Continuum.

BACKGROUND: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid-ß (Aß) and tau in Alzheimer's Disease (AD). However, its association with longitudinal cognition and comparative performance to PET Aß and tau in predicting cognitive decline are unknown. OBJECTIVES: To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on Aß (18F-NAV4694) and tau (18F-MK6240) PET. We also explored the sample size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost using p217+tau (pT+) as compared to PET Aß (A+) and tau (T+) with and without p217+tau pre-screening. DESIGN: A prospective observational cohort study. SETTING: Participants of the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and Australian Dementia Network (ADNeT). PARTICIPANTS: 153 cognitively unimpaired (CU) and 50 cognitively impaired (CI) individuals. MEASUREMENTS: Baseline p217+tau Simoa® assay, 18F-MK6240 tau-PET and 18F-NAV4694 Aß-PET with neuropsychological follow-up (MMSE, CDR-SB, AIBL-PACC) over 2.4 ± 0.8 years. RESULTS: In CI, p217+tau was a significant predictor of change in MMSE (ß = -0.55, p < 0.001) and CDR-SB (ß =0.61, p < 0.001) with an effect size similar to Aß Centiloid (MMSE ß = -0.48, p = 0.002; CDR-SB ß = 0.43, p = 0.004) and meta-temporal (MetaT) tau SUVR (MMSE: ß = -0.62, p < 0.001; CDR-SB: ß = 0.65, p < 0.001). In CU, only MetaT tau SUVR was significantly associated with change in AIBL-PACC (ß = -0.22, p = 0.008). Screening pT+ CI participants into a trial could lead to 24% reduction in sample size compared to screening with PET for A+ and 6-13% compared to screening with PET for T+ (different regions). This would translate to an 81-83% biomarker test cost-saving assuming the p217+tau test cost one-fifth of a PET scan. In a trial requiring PET A+ or T+, p217+tau pre-screening followed by PET in those who were pT+ would cost more in the CI group, compared to 26-38% biomarker test cost-saving in the CU. CONCLUSIONS: Substantial cost reduction can be achieved using p217+tau alone to select participants with MCI or mild dementia for a clinical trial designed to slow cognitive decline over two years, compared to participant selection by PET. In pre-clinical AD trials, p217+tau provides significant cost-saving if used as a pre-screening measure for PET A+ or T+ but in MCI/mild dementia trials this may add to cost both in testing and in the increased number of participants needed for testing.

Relative lateral wall thickness is an improved predictor for postoperative lateral wall fracture after trochanteric femoral fracture osteosynthesis.

Lateral wall thickness is a known predictor for postoperative stability of trochanteric femoral fractures and occurrence of secondary lateral wall fractures. Currently, the AO/OTA classification relies on the absolute lateral wall thickness (aLWT) to distinguish between stable A1.3 and unstable A2.1 fractures that does not take interpersonal patient differences into account. Thus, a more individualized and accurate measure would be favorable. Therefore, we proposed and validated a new patient-specific measure-the relative lateral wall thickness (rLWT)-to consider individualized measures and hypothesized its higher sensitivity and specificity compared with aLWT. First, in 146 pelvic radiographs of patients without a trochanteric femoral fracture, the symmetry of both caput-collum-diaphyseal angle (CCD) and total trochanteric thickness (TTT) was assessed to determine whether the contralateral side can be used for rLWT determination. Then, data of 202 patients were re-evaluated to compare rLWT versus previously published aLWT. Bilateral symmetry was found for both CCD and TTT (p ≥ 0.827), implying that bone morphology and geometry of the contralateral intact side could be used to calculate rLWT. Validation revealed increased accuracy of the rLWT compared with the gold standard aLWT, with increased specificity by 3.5% (Number Needed to Treat = 64 patients) and sensitivity by 1% (Number Needed to Treat = 75 patients). The novel rLWT is a more accurate and individualized predictor of secondary lateral wall fractures compared with the standard aLWT. This study established the threshold of 50.5% rLWT as a reference value for predicting fracture stability in trochanteric femoral fractures.

[Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis].

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.

[Predictive value of net water uptake with respect to early neurological improvement after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke].

Objective: To investigate the value of net water uptake (NWU) for predicting early neurological improvement (ENI) after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke. Methods: A case-control study. A total of 132 patients (80 men, 52 women, median age 68 years) with acute anterior circulation large vessel occlusive stroke receiving endovascular treatment were retrospectively analyzed at Jinling Hospital from October 2014 to September 2019. Patients were divided into two groups based on the occurrence of ENI, which was defined as either an improvement of NIHSS score of ≥4 points, or an NIHSS score of 0 or 1 at 24 hours after endovascular treatment. The rank sum test, Chi square test, and other methods were used to compare differences in baseline characteristics between the two groups. Logistic regression analysis was used to investigate independent predictors of postoperative ENI. Receiver operating characteristic curve analysis used to assess the capacity of NWU to predict ENI. Results: Of the 132 patients in the study, ENI occurred in 47 and did not occur in 85. In multivariate logistic regression analysis age [odds ratio (OR)=0.940, 95% confidence interval (CI) 0.903-0.979, P=0.003], time from stroke onset to puncture (OR=0.995, 95%CI 0.991-0.999, P=0.025), time from puncture to recanalization/end of operation (OR=0.985, 95%CI 0.974-0.996, P=0.007), NWU (OR=0.762, 95%CI 0.620-0.937, P=0.010), and mTICI (OR=1.644, 95%CI 1.043-2.590, P=0.032) were predictive factors for ENI. Receiver operating characteristic curve analysis indicated that NWU could effectively predict ENI (area under the curve=0.642, 95%CI 0.543-0.741, P=0.007), and prediction accuracy was improved when it was combined with other clinical parameters. Conclusion: NWU is an independent predictor of ENI in patients with acute anterior circulation large vessel occlusive stroke undergoing endovascular treatment.