[Clinical characteristics and surgical management outcomes of glaucoma secondary to congenital ectropion uveae: a preliminary analysis of penetrating Schlemm's canaloplasty].

Objective: To investigate the clinical characteristics and treatment outcomes of glaucoma secondary to congenital ectropion uveae (CEU) using penetrating Schlemm's canaloplasty. Methods: This was a retrospective case series study. Medical records of patients diagnosed with glaucoma secondary to CEU and undergoing penetrating Schlemm's canaloplasty at the Eye Hospital of Wenzhou Medical University between August 2020 and December 2021 were collected. Clinical characteristics including the extent and location of iris ectropion, type of glaucoma, were analyzed. Follow-up visits were conducted at 1, 3, 6 months, and 1 year postoperatively. Visual acuity, intraocular pressure (IOP), anterior segment and fundus condition, filtering bleb morphology, use of IOP-lowering medications, ultrasound biomicroscopy results, and other indicators were analyzed to summarize surgical outcomes. Results: Six cases (6 eyes) of glaucoma secondary to CEU were included, all unilateral, with 3 left eyes and 3 right eyes; median age was 10.0 (5.3, 28.8) years; including 3 males and 3 females. Preoperative IOP was (31.7±10.0) mmHg (1 mmHg=0.133 kPa), and the preoperative number of IOP-lowering medications used was 2.0 (2.0, 3.2). The extent of iris ectropion in the 6 cases ranged from 270 ° to 360 °, with peripheral anterior synechiae corresponding to the location of iris ectropion, and angle closure with the degree of synechiae extending beyond Schwalbe's line. No surgical complications occurred in any of the 6 cases postoperatively. At 1 month postoperatively, the IOP was (16.4±3.2) mmHg, with a median of 0.0 (0.0, 1.5) medications used. At 3 months postoperatively, the IOP was (14.8±6.0) mmHg, with a median of 0.0 (0.0, 2.2) medications used. At 6 months postoperatively, the IOP was (18.1±6.1) mmHg, with a median of 0.0 (0.0, 0.5) medications used. Among them, 5 patients had a follow-up period of 1 year postoperatively, all achieving controlled IOP without the use of IOP-lowering medications, with an average IOP of (15.5±3.1) mmHg. No obvious filtering bleb formation was observed at the surgical site in all patients. Conclusions: Glaucoma secondary to CEU manifests primarily as closed-angle glaucoma, with a correspondence between the closure range of anterior iris adhesions in the angle and the extent of iris ectropion. Penetrating Schlemm's canaloplasty demonstrates favorable and stable efficacy for its treatment.

[Advances in immunotherapy for pulmonary sarcomatoid carcinoma].

Pulmonary sarcomatoid carcinoma (PSC) is a rare, poorly differentiated non-small cell lung cancer (NSCLC) that contains sarcomatoid components or sarcomatoid differentiation, and accounts for less than 1% of all lung tumors. Compared to other types of NSCLC, PSC has more invasive biological behavior, is prone to metastasis, and has a higher recurrence rate after early surgery. Its greater resistance to traditional treatments leads to a poorer prognosis compared to other NSCLCs. Immunotherapy offers the possibility of long-term survival for PSC patients.

[Progressive necrotizing xanthogranuloma in both eyes: a case report].

A 55-year-old male patient presenting with 6 months of bilateral difficulty in eye opening was referred to the ophthalmology department. Upon examination, multiple yellowish tumor-like plaques and nodules were observed on the eyelids and chest of the patient, accompanied by keratitis and iridocyclitis. Histopathological examination of the skin lesions on the chest revealed dermal xanthomatous granulomas with progressive necrosis. Bone marrow biopsy showed mantle cell lymphoma. Based on the medical history, the diagnosis of progressive necrotizing xanthogranuloma with mantle cell lymphoma was confirmed. After 6 months of treatment with bendamustine combined with rituximab, there was partial alleviation of ocular symptoms in the patient.

Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB.

BACKGROUND: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory techniques such as liquid chromatography (LC)/mass spectrometry (MS), which are unavailable in many high-burden settings. Urine spectrophotometry could provide a low-cost alternative with simple sampling and quantification methods. METHODS: We enrolled 56 adult patients on treatment for active TB. Serum was collected at 0, 1, 2, 4, 6, and 8 h for measurement of INH concentrations using validated LC-MS/MS methods. Urine was collected at 0-4, 4-8, and 8-24 h intervals, with INH concentrations measured using colorimetric methods. RESULTS: The median peak serum concentration and total serum exposure over 24 h were 4.8 mg/L and 16.4 mg*hour/L, respectively. Area under the receiver operator characteristic curves for urine values predicting a subtherapeutic serum concentration (peak <3.0 mg/L) were as follows: 0-4 h interval (AUC 0.85, 95% CI 0.7-0.96), 0-8 h interval (AUC 0.85, 95% CI 0.71-0.96), and 0-24 h urine collection interval (AUC 0.84, 95% CI 0.68-0.96). CONCLUSION: Urine spectrophotometry may improve feasibility of personalized dosing in high TB burden regions but requires further study of target attainment following dose adjustment based on a urine threshold.

CONTEXTE: L'isoniazide (INH) est un médicament important dans de nombreux schémas thérapeutiques contre la TB, et des résultats thérapeutiques défavorables peuvent être dus à une pharmacocinétique sous-optimale. L'ajustement de la dose peut être personnalisé en mesurant les concentrations sériques maximales ; cependant, le processus implique la conservation de la chaîne du froid et des techniques de laboratoire telles que la chromatographie liquide (LC)/spectrométrie de masse (MS), qui ne sont pas disponibles dans de nombreuses régions à forte charge de morbidité. La spec-trophotométrie urinaire pourrait constituer une alternative peu coûteuse avec des méthodes d'échantillonnage et de quantification simples. MÉTHODES: Nous avons recruté 56 patients adultes sous traitement pour une TB active. Le sérum a été prélevé à 0, 1, 2, 4, 6 et 8 h pour mesurer les concentrations d'INH à l'aide de méthodes LC-MS/MS validées. L'urine a été prélevée à des intervalles de 0­4, 4­8 et 8­24 h, et les concentrations d'INH ont été mesurées à l'aide de méthodes colorimétriques. RÉSULTATS: La concentration sérique maximale médiane et l'exposition sérique totale sur 24 h étaient respectivement de 4,8 mg/L et de 16,4 mg*heure/L. L'aire sous les courbes caractéristiques de l'opérateur récepteur a été mesurée à l'aide de méthodes color-imétriques. Les aires sous les courbes caractéristiques des récepteurs pour les valeurs urinaires prédisant une concentration sérique sous-thérapeutique (pic <3,0 mg/L) étaient les suivantes : intervalle 0­4 h (AUC 0,85 ; IC 95% 0,7­0,96), intervalle 0­8 h (AUC 0,85 ; IC 95% 0,71­0,96), et intervalle de collecte d'urine 0­24 h (AUC 0,84 ; IC 95% 0,68­0,96). CONCLUSION: La spectrophotométrie urinaire peut améliorer la faisabilité d'un dosage personnalisé dans les régions à forte charge de TB, mais nécessite une étude plus approfondie de l'atteinte de la cible après l'ajustement de la dose sur la base d'un seuil urinaire.

Simplified integration of optimal self-management behaviors is associated with improved HbA1c in patients with type 1 diabetes.

PURPOSE: Living with type 1 diabetes requires burdensome and complex daily diabetes self-management behaviors. This study aimed to determine the association between integrated behavior performance and HbA1c, while identifying the behavior with the most significant impact on HbA1c. METHODS: A simple and feasible questionnaire was used to collect diabetes self-management behavior in patients with type 1 diabetes (n = 904). We assessed six dimensions of behavior performance: continuous glucose monitor (CGM) usage, frequent glucose testing, insulin pump usage, carbohydrate counting application, adjustment of insulin doses, and usage of apps for diabetes management. We evaluated the association between these behaviors and HbA1c. RESULTS: In total, 21.3% of patients performed none of the allotted behavior, while 28.5% of patients had a total behavior score of 3 or more. 63.6% of patients with a behavior score ≥ 3 achieved HbA1c goal, contrasting with only 30.4% of patients with a behavior score of 0-1. There was a mean 0.54% ± 0.05% decrease in HbA1c for each 1-unit increase in total behavior score after adjustment for age, family education and diabetes duration. Each behavior was independently correlated with a lower HbA1c level, with CGM having the most significant effect on HbA1c levels. CONCLUSIONS: Six optimal self-management behaviors, especially CGM usage, were associated with improved glycemic control, emphasizing the feasibility of implementing a simplified version of DSMES in the routine clinical care. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03610984.

Inflammatory factors mediated the effect of air pollution on ischemic stroke: a two-step, mediation Mendelian randomization study.

OBJECTIVE: Numerous investigations have indicated a correlation between air pollution (AP) and an elevated ischemic stroke (IS) likelihood. The existing literature does not provide a consensus about the possible link between AP and IS. A two-sample Mendelian randomization (MR) analysis was utilized to systematically measure the causal link between AP and ischemic stroke. Furthermore, the mediating impact of inflammatory factors was also performed by a two-step MR. MATERIALS AND METHODS: A two-sample MR analysis was utilized to examine the AP impact on the incidence of IS. Additionally, a two-step MR approach was carried out to account for possible mediating variables. The indirect impact was determined by employing the product approach, which included multiplying the AP impact on inflammatory factors by the inflammatory factors' impacts on IS. The MR effect was identified through inverse variance-weighted (IVW) meta-analysis of each Wald Ratio. Additionally, complementary studies were conducted using the weighted median and MR-egger approaches. RESULTS: The IVW method with random effects showed that the per unit increase in genetically predicted PM2.5 was linked to the 0.362-fold elevated ischemic stroke risk (OR: 1.362, 95% CI: 1.032-1.796, p=0.029). Furthermore, the IVM technique, incorporating random effects, demonstrated that the per unit increase in genetically predicted PM2.5 was related to an elevated Interleukin (IL)-1ß risk (OR: 1.529, 95% CI: 1.191-1.963, p=0.001), IL-6 (OR: 1.498, 95% CI: 1.094-2.052, p=0.012) and IL-17 (OR: 1.478, 95% CI: 1.021-2.139, p=0.038). IL-1ß, IL-6, and IL-17 modulated the PM2.5 impact on ischemic stroke, while the proportion mediated by them was 59.5%. CONCLUSIONS: A positive correlation between genetically predicted PM2.5 levels and elevated ischemic stroke risk is mediated by IL-1ß, IL-6, and IL-17.

[Pathogenic characteristics of viral diarrhea in children under five years of age in sentinel surveillance in Lulong County of Hebei Province, 2010-2020].

Objective: To analyze pathogenic characteristics of viral diarrhea in children aged <5 years in Hebei Province and provide reference for the prevention and control of viral diarrhea in children. Methods: Stool samples were collected from in-patients with diarrhea under five years old from sentinel hospitals in Lulong County of Hebei between 2010 and 2020. ELISA detected rotavirus antigen, and then positive samples were genotyped by semi nested reverse transcription PCR of two rounds. Calicivirus, genotyping astrovirus, and adenovirus were detected by real-time fluorescence quantification PCR. The data were analyzed by using software SPSS 20.0. Results: In 2 925 detected stool samples, 1 919 (65.61%) were positive. The positive rates of rotavirus, calicivirus, adenovirus, and astrovirus were 42.80% (1 252/2 925), 22.12% (647/2 925), 6.19% (181/2 925), 3.56% (104/2 925). Viral diarrhea was mainly caused by rotavirus infection, accounting for 59.30% (1 017/1 715) between 2010 and 2017, and by calicivirus infection accounting for 53.43% (109/204) between 2018 and 2020. The peak positive rate of rotavirus occurred in winter, with the highest rate in infants aged 12 to 17 months (52.96%,483/912). In the rotavirus positive samples, G9P[8] was mainly detected strains (58.31%,730/1 252), followed by G3P[8] (8.15%,102/1 252). The calicivirus-positive samples were mainly infected with norovirus GⅡ. Sequence analysis indicated that the main type was GⅡ.4 [P31] between 2011 and 2016 and GⅡ.3 [P12] in 2018. Conclusions: Rotavirus and calicivirus were the main pathogens causing infant diarrhea in children under five years old in Hebei from 2010 to 2020. Winter was the main epidemic season.

[Effect of preemptive analgesia with ibuprofen on postoperative pain after mandibular third molar extraction: a randomized controlled trial].

Objective: To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application. Methods: This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively. Results: All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] (Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] (Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] (Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively (P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] (Z=-2.81, P=0.005). Conclusions: A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

Clinical efficacy and adverse reactions analysis of PD-1/PD-L1 inhibitors in advanced esophageal squamous cell carcinoma.

OBJECTIVE: The aim of this study was to investigate the clinical efficacy and associated adverse reactions of Programmed Death Receptor-1 (PD-1)/PD-L1 inhibitors in the management of patients with advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: In this retrospective study, 54 patients with advanced ESCC treated with PD-1/PD-L1 inhibitors in our hospital from January 2021 to January 2023 were identified as the research subjects. Using propensity score matching at a 1:1 ratio, patients only receiving chemotherapy were recruited as controls. The clinical effectiveness of PD-1/PD-L1 was evaluated by comparing the objective response rate (ORR) and disease control rate (DCR). Progression-free survival (PFS) and overall survival (OS) were analyzed for treatment outcome assessments. Adverse events (AEs) between the two groups were recorded and compared. RESULTS: Patients treated with PD-1/PD-L1 inhibitors had a higher rate of ORR (33.33%) and disease control (85.19%), compared to controls with an objective response rate of 20.37% and a disease control rate of 59.26%. The two groups showed similar ORR results, while the incorporation of PD-1/PD-L1 inhibitors resulted in significantly increased DCR when compared to the controls. The median OS was 22 months (95% CI: 1,629 months) for the control group and 31 months (95% CI: 28NA) for the study group, suggesting OS benefits offered by PD-1/PD-L1 inhibitor treatment (HR=0.479, 95% CI: 0.284, 0.809). The median PFS was 15 months (95% CI: 1,223 months) for the control group and 23 months (95% CI: 1,926) for the study group, indicating more PFS benefits provided by PD-1/PD-L1 inhibitors (HR=0.662, 95% CI: 0.436, 1.005). Adverse events and their severity were recorded during patient follow-up, and no grade 5 adverse events were reported in either group. The incidence of grade 3 or higher adverse events between the two groups was similar, while PD-1/PD-L1 inhibitors appeared to significantly reduce the incidence of gastrointestinal reactions in patients. CONCLUSIONS: PD-1/PD-L1 inhibitors integrated with chemotherapy provide significant benefits in the management of patients with advanced ESCC without increasing adverse events.

Bioactivity and genome analysis of Bacillus amyloliquefaciens GL18 isolated from the rhizosphere of Kobresia myosuroides in an alpine meadow.

The unique eco-environment of the Qinghai-Tibet Plateau breeds abundant microbial resources. In this research, Bacillus amyloliquefaciens GL18, isolated from the rhizosphere of Kobresia myosuroides from an alpine meadow, and the antagonistic activity, bacteriostatic hydrolase activity, and low temperature, salt, and drought resistance of it were determined and analysed. The seedlings of Avena sativa were root-irrigated using bacteria suspensions (cell concentration 1 × 107 cfu/mL) of GL18, and the growth-promoting effect of GL18 on it was determined under cold, salt and drought stress, respectively. The whole genome of GL18 was sequenced, and its functional genes were analysed. GL18 presented significant antagonistic activity to Fusarium graminearum, Fusarium acuminatum, Fusarium oxysporum and Aspergillus niger (inhibition zone diameter > 17 mm). Transparent zones formed on four hydrolase detection media, indicating that GL18 secreted cellulase, protease, pectinase and ß-1,3-glucanase. GL18 tolerated conditions of 10 °C, 11% NaCl and 15% PEG-6000, presenting cold, salt and drought resistance. GL18 improved the cold, salt and drought tolerance of A. sativa and it showed significant growth effects under different stress. The total length of the GL18 genome was 3,915,550 bp, and the number of coding DNA sequence was 3726. Compared with the clusters of orthologous groups of proteins, gene ontology and kyoto encyclopedia of genes and genomes databases, 3088, 2869 and 2357 functional genes were annotated, respectively. GL18 contained gene clusters related to antibacterial substances, functional genes related to the synthesis of plant growth-promoting substances, and encoding genes related to stress resistance. This study identified an excellent Bacillus strain and provided a theoretical basis for improving stress resistance and promoting the growth of herbages under abiotic stress.

[Cost-effectiveness of pharmaceutical smoking cessation intervention in China primary cancer prevention].

Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

[Prevalence of frailty and related factors in middle-aged and elderly people in island and mountainous areas of Taizhou, Zhejiang Province].

Objective: To compare the prevalence of frailty and related factors in middle-aged and elderly people aged ≥45 years in island and mountainous areas of Taizhou, Zhejiang Province. Methods: Based on cross-sectional design, stratified cluster sampling and quota sampling methods were adopted. One administrative district was randomly selected from each of six coastal and three inland administrative districts in Taizhou during July to August, representing two different geographical terrains. In the island area (Jiaojiang District), all residents aged ≥45 years were included by cluster sampling. In the mountainous area (Xianju County), participants were selected through quota sampling, with same gender and age distributions. Data about their demographic characteristics, lifestyle and health-related factors were collected through questionnaire surveys and laboratory examinations. The prevalence of frailty was assessed using the Fried frailty phenotype scale. Hierarchical analysis and multivariate logistic regression analysis were used to compare the influencing factors of frailty. Results: A total of 1 011 local residents were studied, in whom island and mountainous residents accounted for 48.1% (486/1 011) and 51.9% (525/1 011) respectively; men and women accounted for 45.9% (464/1 011) and 54.1% (547/1 011) respectively. Middle-aged (45-49 years), younger elderly (60-74 years), and older elderly (≥75 years) residents accounted for 38.6% (390/1 011), 44.6% (451/1 011), and 16.8% (170/1 011) respectively. The overall prevalence rate of frailty was 3.6% (36/1 011), the prevalence rate was 3.7% (17/464) in men and 3.5% (19/547) in women. The prevalence rates in age groups 45-59,60-74 years and ≥75 years were 0.3% (1/390), 2.2% (10/451), and 14.7% (25/170), respectively. The prevalence rates of frailty and pre-frailty in island area were 6.0% (29/486) and 39.1% (190/486), respectively, which was higher than those in mountainous area (1.3%, 7/525) and (30.9%, 162/525). After adjusting for potential confounding factors, the risk for frailty in island residents was significantly higher than that in mountainous residents (aOR=1.55,95%CI: 1.07-2.25,P=0.019). In island area, older age (60-74 years:aOR=2.52,95%CI: 1.56-4.13; ≥75 years:aOR=11.65,95%CI:5.38-26.70), being women (aOR=1.94,95%CI: 1.20-3.17), suffering from depression (aOR=1.09,95%CI:1.02-1.17) were associated with frailty symptoms. In mountainous area, older age was also associated with an increased risk of frailty symptoms, but the OR value was lower than those in island area (60-74 years: aOR=1.74,95%CI:1.04-2.94;≥75 years: aOR=4.78,95%CI:2.45-9.50). Polydrug use (aOR=2.08,95%CI: 1.14-3.80) and suffering from depression (aOR=1.10,95%CI: 1.02-1.18) had significant positive association with frailty symptoms. Higher education level had significant negative association with frailty symptoms (junior high school: aOR=0.40,95%CI: 0.21-0.75; senior high school and technical secondary school: aOR=0.29,95%CI: 0.15-0.53; college or above:aOR=0.22,95%CI: 0.11-0.42). Conclusions: The prevalence of frailty in middle-aged and elderly community residents was significantly higher in island area than in mountainous area in Taizhou. The frailty-related factors varied with area. The elderly people (≥75 years) and women in island area had higher risk for frailty. Older age and suffering from depression were the independent risk factors for frailty. It is necessary to pay attention to the health risk factors and special environment in island area, and take comprehensive intervention measures to delay the process of debilitation and improve the quality of life of middle-aged and elderly people.

Association of cord plasma metabolites with birth weight: results from metabolomic and lipidomic studies of discovery and validation cohorts.

BACKGROUND: Birth weight is a good predictor of fetal intrauterine growth and long-term health. Although several studies have evaluated the relationship between metabolites and birth weight, no prior study has comprehensively investigated the metabolomic and lipidomic and further validated and quantified meaningful metabolites. METHODS: Firstly, a pseudotargeted metabolomics approach was applied to detect 2418 metabolites in 504 cord blood samples in the discovery set enrolled from the Wuhan Healthy Baby Cohort (HBC), China. Metabolome-wide association scan (MWAS) analysis and pathway enrichment were applied to discover metabolites and metabolic pathways that were significantly associated with birth weight for gestational age (BWGA) z-score. Logistic regression models were used to analyze the association of metabolites in the most significantly associated pathways with small for gestational age (SGA) and low birth weight (LBW). Subsequently, 350 cord blood samples in a validation cohort were subjected to targeted analysis to validate the metabolites screened from the discovery cohort. RESULTS: In the discovery set, 513 metabolites were significantly associated with BWGA z-score (PFDR <0.05), of which 298 KEGG-annotated metabolites were included in the pathway analysis. The primary bile acid biosynthesis pathway was the most relevant metabolic pathway associated with BWGA z-score in our study. Elevated cord plasma primary bile acids were associated with lower BWGA z-score and higher odds of SGA or LBW in the discovery and validation cohorts. In the validation set, a 2-fold increase in taurochenodeoxycholic acid (TCDCA) and taurocholic acid (TCA) was associated with 0.10 (95% CI: 0.00, 0.20) and 0.18 (95 %CI: 0.04, 0.31) decrease in BWGA z-score, respectively, after adjusting for covariates. In addition, a 2-fold increase in cord plasma TCDCA and TCA was associated with an adjusted odds ratio of 1.52 (1.00, 2.30) and 1.77 (1.05, 2.98) for SGA, respectively. The adjusted ORs for a 2-fold increase in TCDCA and TCA concentrations were 2.39 (95% CI 1.00, 5.71) and 3.21 (0.96, 10.74) for LBW, respectively. CONCLUSIONS: The results indicate a significant association between primary bile acids and lower BWGA z-score, as well as higher risk of SGA and LBW. Abnormalities of primary bile acid metabolism may play an important role in restricted fetal development. This article is protected by copyright. All rights reserved.

Novel high throughput screen reports that benzo(a)pyrene overrides mouse trophoblast stem cell multipotency, inducing SAPK activity, HAND1 and differentiated trophoblast giant cells.

INTRODUCTION: Cultured mouse trophoblast stem cells (mTSC) maintain proliferation/normal stemness (NS) under FGF4, which when removed, causes normal differentiation (ND). Hypoxic, or hyperosmotic stress forces trophoblast giant cells (TGC) differentiate. Hypoxic, hyperosmotic, and genotoxic benzo(a)pyrene (BaP), which is found in tobacco smoke, force down-regulation of inhibitor of differentiation (Id)2, enabling TGC differentiation. Hypoxic and hyperosmotic stress induce TGC by SAPK-dependent HAND1 increase. Here we test whether BaP forces mTSC-to-TGC while inducing SAPK and HAND1. METHODS: Hand1 and SAPK activity were assayed by immunoblot, mTSC-to-TGC growth and differentiation were assayed at Tfinal after 72hr exposure of BaP, NS, ND, Retinoic acid (RA), or sorbitol. Nuclear-stained cells were micrographed automatically by a live imager, and assayed by ImageJ/FIJI, Biotek Gen 5, AIVIA proprietary artificial intelligence (AI) software or open source, CellPose artificial intelligence/AI software. RESULTS: BaP (0.05-1µM) activated SAPK and HAND1 without diminishing growth. TSC-to-TGC differentiation was assayed with increasingly accuracy for 2-4 N cycling nuclei and >4 N differentiating TGC nuclei, using ImageJ/FIJI, Gen 5, AIVIA, or CellPose AI software. The AIVIA and Cellpose AI software matches human accuracy. The lowest BaP effects on SAPK activation/HAND1 increase are >10-fold more sensitive than similar effects for mESC. RA induces 44-47% 1st lineage TGC differentiation, but the same RA dose induces only 1% 1st lineage mESC differentiation. DISCUSSION: First, these pilot data suggest that mTSC can be used in high throughput screens (HTS) to predict toxicant exposures that force TGC differentiation. Second, mTSC differentiated more cells than mESC for similar stress exposures, Third, open source AI can replace human micrograph quantitation and enable a miscarriage-predicting HTS.

[Intermediate and long-term outcomes of transcatheter closure of congenital coronary cameral fistulas in 66 children].

Objective: To evaluate the intermediate and long-term outcomes and technical aspects of transcatheter closure (TCC) of coronary cameral fistulas (CCF) in pediatric patients. Methods: This was a case-control study. All pediatric patients with CCF who underwent TCC between January 2005 and December 2019 were retrospectively reviewed. Data was collected from medical records, including demographic characteristics, procedural details, intraoperative and postoperative serious adverse events, follow-up results and prognosis. Patients with serious adverse events and without serious adverse events were compared regarding their clinical features and CCF characteristics. Comparisons between groups were performed with independent sample t test, chi-square test or Fisher exact test. Results: A total of 66 CCF patients (34 boys, 32 girls, 3.9 (1.9, 6.2) years old, 15 (11, 20) kg) underwent attempted TCC. All of the CCF were all medium or large fistulas including 55 proximal fistulas (83%) and 11 distal fistulas (17%). The CCF originated more frequently from the right coronary artery (38 cases (58%)), followed by the left coronary artery (28 cases (42%)). The incidence of coronary artery aneurysms (CAA) was 61% (40/66).Procedural treatment was achieved in 64 patients and procedural success was achieved in 59 patients (92%). Six (9%) serious adverse events occurred in 5 patients during the perioperative period. Acute complications included procedure-related death in one patient and acute myocardial infarction in one patient. Periprocedural complications occurred in 3 patients at one day postoperatively including acute myocardial infarction (2 cases), occluder detachment (1 case), and tricuspid chordae tendinae rupture (1 case). Clinical follow-up data were available in 58 of the 62 patients who underwent initial successful TCC with a follow-up period of 9.3 (6.5, 13.4) years. Ten adverse events occurred in 9 patients including 5 complications consisted of aortic valve perforation (1 case), coronary thrombosis (1 case), progressive aneurysmal dilation after reintervention (1 case), and new-onset tricuspid valve prolapse with significant regurgitation (2 cases) and large residual shunts due to fistula recanalization (5 cases). Therefore, the incidence of intermediate and long-term adverse events was 17% (10/58). During the periprocedural and follow-up period, 16 adverse events occurred in 13 patients, whereas no adverse events occurred in 51 patients. Patients with seriovs adverse events presented with larger proportion of large CCF (11/13 vs. 39% (20/51), P=0.005), giant CAA (10/13 vs.14% (7/51), P=0.030), and higher mean pulmonary artery pressure ((20±9) vs.(16±6) mmHg, 1 mmHg=0.133 kPa, t=2.02, P=0.048) compared to patients without serious adverse events. Conclusions: TCC in CCF children appears to be effective with favorable intermediate and long-term outcomes. Strict indication of TCC is mandatory.

[Analysis of pre-operative factors affecting vault after posterior chamber phakic intraocular lens implantation].

Objective: To analyze the early changes in vault height and its influencing factors after implantation of posterior chamber phakic intraocular lenses (pIOL). Methods: A retrospective case series study was conducted, including patients who underwent pIOL implantation at Zhongshan Ophthalmic Center, Sun Yat-sen University, from September 2020 to August 2021, and completed a 3-month follow-up. Data were collected from myopic or myopic astigmatism patients. Preoperative ocular examinations, including Pentacam anterior segment analysis system, Sirius anterior segment analysis system, ultrasound biomicroscopy (UBM), and IOLMaster optical biometry, were performed to measure parameters such as refractive power, corneal curvature, corneal horizontal diameter, anterior chamber volume, anterior chamber depth, pupil diameter, sulcus-to-sulcus diameter (STS), and lens thickness. The degree and position of implanted pIOL, as well as vault height measured by anterior segment optical coherence tomography (AS-OCT) at 1 day, 1 week, 1 month, and 3 months postoperatively, were recorded. Statistical analyses were conducted using repeated measures analysis of variance, Pearson correlation analysis, and multiple linear regression analysis. Results: A total of 314 patients (314 eyes) were included, with 52 male (16.56%) and 262 female (83.44%) patients, and an average age of (26.44±4.60) years. The preoperative equivalent spherical power was (-8.09±2.41) D. Postoperative vault heights at 1 day, 1 week, 1 month, and 3 months were (671.88±273.02) µm, (652.26±272.21) µm, (615.08±259.69) µm, and (591.14±250.71) µm, respectively, with statistically significant differences among groups (P<0.001). Eyes with vault height>750 µm showed a greater decrease in early postoperative vault height (P<0.001). The eyes implanted with 12.1 mm pIOL had the lowest postoperative vault height, while those with 13.2 mm had the highest (P>0.05). Factors correlated with vault height at 1 day postoperatively included corneal horizontal diameter, anterior chamber depth, preoperative cylinder power, angle degree, lens thickness, and pIOL cylinder power. Factors correlated with vault height at 3 months postoperatively included corneal horizontal diameter, anterior chamber depth, preoperative cylinder power, anterior chamber volume, angle degree, lens thickness, axial length, pIOL spherical and cylinder power. Factors associated with changes in early postoperative vault height included corneal curvature K2, anterior chamber depth, anterior chamber volume, pupil diameter, horizontal STS, vertical STS, axial length, and preoperative spherical power (all P<0.05). Multiple linear regression analysis revealed that lens thickness significantly influenced vault height at 1 day postoperatively, anterior chamber volume significantly influenced vault height at 3 months postoperatively, and pupil diameter significantly influenced changes in early postoperative vault height (all P<0.05). Conclusions: Vault height after pIOL implantation is unstable in the early postoperative period and gradually decreases within 3 months. A higher baseline vault height is associated with a greater decrease. Anterior chamber volume, pupil diameter, and lens thickness are influencing factors on vault height during the first 3 months postoperatively.

Association of serum lipids and abnormal lipid score with cancer risk: a population-based prospective study.

BACKGROUND: Serum lipid levels are associated with cancer risk. However, there still have uncertainties about the single and combined effects of low lipid levels on cancer risk. METHODS: A prospective cohort study of 33,773 adults in Shanghai between 2016 and 2017 was conducted. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured. Cox proportional hazard models were used to assess the association of single and combined lipids with overall, lung, colon, rectal, thyroid gland, stomach, and female breast cancers. The effect of the combination of abnormal lipid score and lifestyle on cancer was also estimated. RESULTS: A total of 926 incident cancer cases were identified. In the RCS analysis, hazard ratios (HRs) of overall cancer for individuals with TC < 5.18 mmol/L or with LDL-C < 3.40 mmol/L were higher. Low TC was associated with higher colorectal cancer risk (HR [95% CI] = 1.76 [1.09-2.84]) and low HDL-C increased thyroid cancer risk by 90%. Abnormal lipid score was linearly and positively associated with cancer risk, and smokers with high abnormal lipid scores had a higher cancer risk, compared to non-smokers with low abnormal lipid scores (P < 0.05). CONCLUSIONS: Low TC levels were associated with an increased risk of overall and colorectal cancer. More attention should be paid to participants with high abnormal lipid scores and unhealthy lifestyles who may have a higher risk of developing cancer. Determining the specific and comprehensive lipid combinations that affect tumorigenesis remains a valuable challenge.

Diagnostic value of adenohypophyseal MRI features in female children with precocious puberty.

AIM: To evaluate the diagnostic value of adenohypophyseal magnetic resonance imaging (MRI) features for precocious puberty (PP) in female children and also to establish a non-invasive diagnostic approach in clinics. MATERIALS AND METHODS: A total of 126 female children (37, 57, and 32 female children clinically diagnosed with central PP [CPP], incomplete PP [IPP], and controls, respectively) were enrolled in this study. Data were collected and analysed using analysis of variance. Pearson correlation and stepwise multivariate linear regression analysis were used to examine the association and build prediction models. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy. RESULTS: The values of adenohypophysis volume (aPV), adenohypophysis height (aPH), and signal-intensity ratio (SIR), height, weight, and seven laboratory testing characteristics were correlated closely with the activation status of the hypothalamic-pituitary-gonad axis in the different groups (all p<0.05). Model 1 including aPV, weight, and aPH and Model 2 including SIR, aPV, and height were built to obtain predicted luteinising hormone (LH; R2 = 0.271) and LH/follicle stimulating hormone (FSH; R2 = 0.311). ROC analysis showed the predicted LH, predicted LH/FSH, and aPV were the top 3 best predictors in distinguishing CPP from controls (AUC = 0.969, 0.949, and 0.938) while predicted LH/FSH was the best predictor in distinguishing CPP from IPP and controls (AUC = 0.829 and 0.828). CONCLUSION: The adenohypophysis volume itself and the prediction models including main adenohypophyseal MRI features increased diagnostic efficiency for PP and offered a non-invasive and credible diagnostic method.

Strategies for patients with recurrent nasopharyngeal carcinoma involved internal carotid artery who are intolerant to embolization.

BACKGROUND: The surgical treatment of recurrent nasopharyngeal carcinoma (rNPC) involving the internal carotid artery (ICA) is challenging, as the massive bleeding caused by intraoperative rupture of the ICA is life-threatening. We reported that ICA embolization is an effective pretreatment to avoid fatal bleeding, but some patients cannot tolerate the procedure. We used endovascular vascular protection (ICA stents), vascular sacrifice (bypass grafting) and extravascular vascular protection (transcervical external stent placement) of the ICA to provide alternative options for these patients. METHODOLOGYy: This study enrolled patients with rNPC adjacent to or invading the ICA who were unsuitable for ICA embolization from January 2015 to June 2020. ICA pretreatment combined with endoscopic nasopharyngectomy (ENPG) was performed for the 30 patients. We report the survival outcome and incidence of complications after ICA pretreatment. RESULTS: ICA pretreatment was performed for the 30 enrolled patients, among whom 8 underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, 6 underwent bypass grafting, and 16 underwent ICA stent implantation followed by ENPG. After pretreatment, at a median follow-up of 43 months (range, 2-80 months), the 3-year locoregional overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 62.9%, 61.3%, 70.2%, and 71.4%, respectively. CONCLUSIONS: ICA pretreatment combined with salvage ENPG enables the feasible and effective resection of rNPC lesions involving the ICA in patients who cannot tolerate ICA embolization. Therefore, this treatment may be an effective method for improving outcomes. Multidisciplinary therapy is needed to reduce operation-related complications.

[Efficacy and short-term outcomes of myocardial protection using single-dose histidine-tryptophan-ketoglutarate cardioplegia during aortic root surgery with different duration of myocardial ischemia].

Objective: To explore the efficacy of myocardial protection with single-dose histidine-tryptophan-ketoglutarate (HTK) cardioplegia during aortic root operation, and the correlation between short-term clinical outcomes and duration of myocardial ischemia. Methods: The data of clinical cases undergoing myocardial protection with single-dose HTK cardioplegia during aortic root operation from January 2018 to December 2022 were retrospectively reviewed. Patients were divided into conventional HTK cardioplegia group (<3 h) and prolonged HTK cardioplegia group (≥3 h) according to duration of intraoperative myocardial ischemia. A 1∶1 propensity score matching was performed and the correlations between duration of myocardial ischemia and postoperative short-term outcomes (30-day mortality, readmission, mechanical circulation support and renal insufficiency) were analyzed. Results: A total of 282 patients were included in the final analysis, with 210 cases in the conventional HTK cardioplegia group and 72 cases inthe prolonged HTK cardioplegia group before matching. After matching, there were 64 cases (53 males and 11 females) in the conventional HTK cardioplegia group, with a mean age of (49.4±14.2) years. The prolonged HTK cardioplegia group had 64 cases (55 males and 9 females), with a mean age of (50.5±12.3) years. Higher sensitivity troponin [12 h: 10.1 (4.6, 18.7) µg/Lvs 4.1(2.2, 8.6) µg/L, P=0.002; 24 h: 7.7 (4.5, 19.0) µg/L vs 4.8 (2.2, 11.9) µg/L, P=0.025] and creatine kinase isoenzyme[12 h: 46.3 (28.1, 62.4) µg/L vs 20.7(14.1, 32.9) µg/L, P<0.001; 24 h: 26.3(13.4, 49.2) µg/L vs 14.5 (10.1, 33.5)µg/L, P=0.011] after surgery was detected in prolonged HTK cardioplegia group. Comparisons of other primary and secondary endpoint events showed no significant differences between the two groups (all P>0.05). Multivariate binary logistic regression showed that duration of myocardial ischemia had no significant effect on postoperative 30-day mortality (OR=1.255, 95%CI: 0.500-3.148, P=0.629), 30-day readmission (OR=0.378, 95%CI: 0.069-2.065, P=0.261) and mechanical circulation support (OR=0.991, 95%CI: 0.331-2.970, P=0.998). Conclusion: During aortic root surgery, single-dose HTK cardioplegia may provide satisfactory myocardial protection, and there was no significant correlation between duration of myocardial ischemia and short-term clinical outcomes.