Analysis of the total serum IgE levels in patients with acute exacerbations chronic obstructive pulmonary disease: A retrospective study.

Currently, few studies have demonstrated the relationship between total serum IgE (T-IgE) and acute exacerbation chronic obstructive pulmonary disease (AECOPD). In this study, T-IgE in AECOPD patients were investigated and jointly analyzed with the clinical characteristics. AECOPD patients hospitalized from July 2018 to July 2019 were included in this study. In this patient cohort, clinical information was investigated. Routine blood tests, C-reactive protein and T-IgE levels of patients were determined along with blood gas analysis. The length of hospital stays, mechanical ventilation during hospitalization, ICU admission, glucocorticoid related clinical information were recorded. A total of 285 AECOPD patients were included in this study, which consisted of a high proportion of males. Of all patients, 49.82% patients exhibited higher T-IgE levels. Based on the reference T-IgE value 60 kU/L, patients were divided into high T-IgE group with T-IgE > 60 kU/L, and low T-IgE group with T-IgE ≤ 60 kU/L. There was no significant difference in the dosage of glucocorticoid between the two groups. Patients in the high T-IgE group had shorter hospital stays and lower probability of mechanical ventilation compared to the low T-IgE group. After adjustment for confounding factors, T-IgE was negatively correlated with the length of hospital stays. AECOPD patients with elevated T-IgE had shorter hospital stays and lower risks of mechanical ventilation and ICU admission. Our results showed that T-IgE might play an important role on evaluating the condition and guiding for treatment decisions in AECOPD patients.

Theabrownin from Fu Brick tea ameliorates high-fat induced insulin resistance, hepatic steatosis, and inflammation in mice by altering the composition and metabolites of gut microbiota.

Fu Brick tea belongs to fermented dark tea, which is one of the six categories of tea. Fu Brick tea has been reported to reduce adiposity and has beneficial effects in the treatment of hypercholesterolemia and cardiovascular disease. Theabrownin (TB) is one of the pigments with the most abundant content in Fu Brick tea. TB has also been reported to have lipid-lowering effects, but its mechanism remains unclear. We found that TB could effectively reduce the insulin resistance and fat deposition induced by a high fat diet (HFD), decrease inflammation in the liver, improve intestinal integrity, and reduce endotoxins in circulation. Further studies showed that TB increased the abundance of Verrucomicrobiota and reduced the abundance of Firmicutes and Desulfobacterota in the intestinal tract of obese mice. The alteration of gut microbiota is closely linked to the metabolic phenotype after TB treatment through correlation analysis. Moreover, TB changed the gut microbial metabolites including L-ornithine, α-ketoglutarate, and glutamine, which have also been found to be upregulated in the liver after TB intervention. In vitro, L-ornithine, α-ketoglutarate, or glutamine significantly reduced lipopolysaccharide (LPS)-induced inflammation in macrophages. Therefore, our results suggest that TB can reduce adiposity, systemic insulin resistance, and liver inflammation induced by a HFD through altering gut microbiota and improving the intestinal tight junction integrity. The metabolites of gut microbiota might also play a role in ameliorating the HFD-induced phenotype by TB.

Serum uric acid level is associated with glomerular ischemic lesions in patients with primary membranous nephropathy: an analytical, cross-sectional study.

To investigate the relationship between serum uric acid level and glomerular ischemic lesions (GIL) in patients with primary membranous nephropathy (PMN) and identify relevant risk factors. A total of 201 patients with PMN but normal renal function confirmed by renal biopsy executed in the Liaocheng People's Hospital, China, during January 2020-January 2023 were analyzed retrospectively. The enrolled patients were divided into a hyperuricemia group and a normal serum uric acid group (control group) according to their serum uric acid levels. Then, the participants were further divided into a non-GIL group or a GIL group based on the patient's renal biopsy results. The two groups' clinical and pathological data and meaningful indicators for differences were analyzed by binary logistic regression analysis. Additionally, the serum uric acid level prediction value on GIL was investigated using receiver operating characteristic (ROC) curves. Compared with the control group, the hyperuricemia group exhibited high serum uric acid, the prevalence of GIL, serum albumin, the prevalence of hypertension, and low-density lipoprotein cholesterol (LDL) levels (P < 0.05). Compared with the non-GIL group, the GIL group exhibited were older, had enhanced serum uric acid, serum albumin, and an increased prevalence of tubular atrophy/interstitial fibrosis (TA/IF), arteriolosclerosis, and low eGFR levels (P < 0.05). The binary logistic regression analysis revealed that the serum uric acid and the TA/IF are independent risk factors of GIL (P < 0.05). The AUC of ROC of GIL of PMN patients, predicted based on the serum uric acid concentration, was 0.736 (P < 0.05), wherein the threshold = 426.5 µmol/L and the Youden's index = 0.41. Serum uric acid concentration and the TA/IF are independent risk factors of GIL in patients with PMN, and the former exhibits prediction value on GIL in patients with PMN.

Evidence for chromium crosses blood brain barrier from the hypothalamus in chromium mice model.

It has been shown that exposure to hexavalent Chromium, Cr (Ⅵ), via nasal cavity can have neurotoxicological effects and induces behavioral impairment due to the fact that blood brain barrier (BBB) does not cover olfactory bulb. But whether Cr (Ⅵ) can cross the BBB and have a toxicological effects in central nervous system (CNS) remains unclear. Therefore, we investigated the effects of Cr (Ⅵ) on mice treated with different concentrations and exposure time (14 days and 28 days) of Cr (Ⅵ) via intraperitoneal injection. Results revealed that Cr accumulated in hypothalamus (HY) in a timely dependent manner. Much more severer neuropathologies was observed in the group of mice exposed to Cr (Ⅵ) for 28 days than that for 14 days. Gliosis, neuronal morphological abnormalities, synaptic degeneration, BBB disruption and neuronal number loss were observed in HY. In terms of mechanism, the Nrf2 related antioxidant stress signaling dysfunction and activated NF-κB related inflammatory pathway were observed in HY of Cr (Ⅵ) intoxication mice. And these neuropathologies and signaling defects appeared in a timely dependent manner. Taking together, we proved that Cr (Ⅵ) can enter HY due to weaker BBB in HY and HY is the most vulnerable CNS region to Cr (Ⅵ) exposure. The concentration of Cr in HY increased along with time. The accumulated Cr in HY can cause BBB disruption, neuronal morphological abnormalities, synaptic degeneration and gliosis through Nrf2 and NF-κB signaling pathway. This finding improves our understanding of the neurological dysfunctions observed in individuals who have occupational exposure to Cr (Ⅵ), and provided potential therapeutic targets to treat neurotoxicological pathologies induced by Cr (Ⅵ).

Universal Strategy for Metal-Organic Framework Growth: From Cascading-Functional Films to MOF-on-MOFs.

Transformation of metal-organic framework (MOF) particles into thin films is urgently needed for the persistent development of well-applicable devices, and recently emerging functional-integrated hybrid frameworks. Although some flexible polymers and exclusive modification approaches have been proposed, the additive-free and widely applicable strategy has not been reported, hampering the deep investigation of the structure-performance relationship. A universal strategy for the in situ growth of large-area and continuous MOF films with controllable microstructures is introduced, through the modification of multi-scale and multi-structure substrates with poly(4-vinylpyridine) as the anchor to capture metal ions via Coulomb attraction. Based on the clarified structure-adsorption-separation mechanisms, the customized devices fabricated by in situ growth can achieve highly selective adsorption and excellently synergetic separation of various industrially relevant isomers. In addition, this strategy is also feasible for the construction of MOF-on-MOFs with varied lattice parameters. This strategy is easy to implement and will be widely applicable to the surface growth of diverse MOFs on desired substrates, and provides a new concept for developing hybrid MOFs integrating with customized functionalities.

The optimal dose of indacaterol for treatment of chronic obstructive pulmonary disease: a systematic review and Bayesian network meta-analysis.

Background: The optimal dose of indacaterol for treatment of chronic obstructive pulmonary disease (COPD) was in debate. We did this network meta-analysis to assess the efficacy and safety of three dosages (75, 150, and 300 µg) of indacaterol in patients with moderate-to-severe COPD. Methods: We searched studies from inception until January 20, 2023 on PubMed, Embase, Cochrane Library, and Web of Science database. All studies comparing different doses of indacaterol for COPD were included in this network meta-analysis. Outcomes were forced expiratory volume in 1 second (FEV1), exacerbation rate, St. George respiratory questionnaire (SGRQ), transitional dyspnea index (TDI), and adverse events. Weighted mean difference (WMD) and odds ratio (OR) with 95% credible interval (CrI) was calculated by R software with gemtc package. Results: Finally, a total of 10 studies (4,991 patients) were finally included in this network meta-analysis. Indacaterol 75 µg (WMD: 0.07; 95% CrI: 0.05-0.08), indacaterol 150 µg (WMD: 0.13; 95% CrI: 0.12-0.14), and indacaterol 300 µg (WMD: 0.22; 95% CrI: 0.22-0.23) were all more effective than the placebo, and the difference was statistically significant. Indacaterol 75 µg (OR: 0.80; 95% CrI: 0.53-1.21), indacaterol 150 µg (OR: 0.59; 95% CrI: 0.45-0.78), indacaterol 300 µg (OR: 0.35; 95% CrI: 0.26-0.46) were more effective than the placebo in terms of exacerbation rate, and the difference was statistically significant. The surface under the cumulative ranking (SUCRA) showed that indacaterol 300 µg ranked first, indacaterol 150 µg ranked second, indacaterol 75 µg ranked third, and placebo ranked the last for FEV1, SGRQ, TDI, exacerbation rate. There was no significant difference among the adverse events (P>0.05). Conclusions: Considering the network meta-analysis and rankings, 300 µg indacaterol is superior to the other two dosages in treating patients with moderate-to-severe COPD. However, the quality of available evidence limits the formation of powerful conclusions regarding the comparative efficacy or safety of different doses of indacaterol used to treat COPD. Higher-quality randomized controlled trials (RCTs) are required for further research in the future.

α-synuclein-lack expression rescues methamphetamine-induced mossy fiber degeneration in dorsal hippocampal CA3.

Methamphetamine (METH) - induced cognitive impairments may be related to synaptic degeneration at mossy fiber terminals, critical for spatial memory formation in hippocampal circuits. We have previously found METH-induced neurodegeneration in the striatum by increasing the α-synuclein (α-SYN) level. However, whether and how the METH-induced mossy fiber degeneration is also blamed for the abnormal accumulation of α-SYN remains to be elucidated. Chronic METH exposure decreased mossy fiber density but upregulatedα-SYN and phosphorylated TAU (TAU-pSer396) in hippocampal CA3, associated with glial cell overactivation, axonal neuropathies, and memory impairment. Notably, the knockout of the α-SYN gene significantly alleviated the METH-induced mossy fiber degeneration and memory impairment. Meanwhile, the TAU-pSer396 accumulation and glial activation were ameliorated by α-SYN knockout. Our findings suggest an essential role of α-SYN in mediating METH-induced mossy fiber degeneration, providing promising therapeutic and prophylactic targets for METH-related neurodegenerative diseases.

Development and validation of machine learning-augmented algorithm for insulin sensitivity assessment in the community and primary care settings: a population-based study in China.

Objective: Insulin plays a central role in the regulation of energy and glucose homeostasis, and insulin resistance (IR) is widely considered as the "common soil" of a cluster of cardiometabolic disorders. Assessment of insulin sensitivity is very important in preventing and treating IR-related disease. This study aims to develop and validate machine learning (ML)-augmented algorithms for insulin sensitivity assessment in the community and primary care settings. Methods: We analyzed the data of 9358 participants over 40 years old who participated in the population-based cohort of the Hubei center of the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals). Three non-ensemble algorithms and four ensemble algorithms were used to develop the models with 70 non-laboratory variables for the community and 87 (70 non-laboratory and 17 laboratory) variables for the primary care settings to screen the classifier of the state-of-the-art. The models with the best performance were further streamlined using top-ranked 5, 8, 10, 13, 15, and 20 features. Performances of these ML models were evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPR), and the Brier score. The Shapley additive explanation (SHAP) analysis was employed to evaluate the importance of features and interpret the models. Results: The LightGBM models developed for the community (AUROC 0.794, AUPR 0.575, Brier score 0.145) and primary care settings (AUROC 0.867, AUPR 0.705, Brier score 0.119) achieved higher performance than the models constructed by the other six algorithms. The streamlined LightGBM models for the community (AUROC 0.791, AUPR 0.563, Brier score 0.146) and primary care settings (AUROC 0.863, AUPR 0.692, Brier score 0.124) using the 20 top-ranked variables also showed excellent performance. SHAP analysis indicated that the top-ranked features included fasting plasma glucose (FPG), waist circumference (WC), body mass index (BMI), triglycerides (TG), gender, waist-to-height ratio (WHtR), the number of daughters born, resting pulse rate (RPR), etc. Conclusion: The ML models using the LightGBM algorithm are efficient to predict insulin sensitivity in the community and primary care settings accurately and might potentially become an efficient and practical tool for insulin sensitivity assessment in these settings.

Role of the In-Situ-Formed Surface (Pt-S-O)-Ti Active Structure in SO2-Promoted C3H8 Combustion over a Pt/TiO2 Catalyst.

Typically, SO2 unavoidably deactivates catalysts in most heterogeneous catalytic oxidations. However, for Pt-based catalysts, SO2 exhibits an extraordinary boosting effect in propane catalytic oxidation, but the promotive mechanism remains contentious. In this study, an in situ-formed tactful (Pt-S-O)-Ti structure was concluded to be a key factor for Pt/TiO2 catalysts with a substantial SO2 tolerance ability. The experiments and theoretical calculations confirm that the high degree of hybridization and orbital coupling between Pt 5d and S 3p orbitals enable more charge transfer from Pt to S species, thus forming the (Pt-S-O)-Ti structure with the oxygen atom dissociated from the chemisorbed O2 adsorbed on oxygen vacancies. The active oxygen atom in the (Pt-S-O)-Ti active structure is a robust site for C3H8 adsorption, leading to a better C3H8 combustion performance. This work can provide insights into the rational design of chemical bonds for high SO2 tolerance catalysts, thereby improving economic and environmental benefits.

[Research progress of stationary phase of gas chromatography based on chiral organic frameworks].

Enantiomers typically show different pharmacological, toxicological, and physiological properties. Thus, the preparation of enantiopure compounds is of great significance for human health and sustainable development. Compared with asymmetric catalysis, enantiomeric separation is simpler, faster, and more efficient; as such, it has become the preferred method for obtaining pure enantiomers. At present, enantiomeric separation methods mainly include chromatography, nanochannel membrane separation, selective adsorption, and recrystallization. In particular, gas chromatography (GC) plays an important role in enantioseparation because of its high sensitivity, excellent reproducibility, and outstanding processing capacity for various enantiomers. The stationary phase is key to the separation efficiency of GC, and more efficient, stable, and cost-effective materials that could serve as stationary phases are constantly being explored. Organic frameworks, such as covalent organic frameworks (COFs), metal-organic frameworks (MOFs), porous organic cages (POCs), metal-organic cages (MOCs), and hydrogen-bonded organic frameworks (HOFs), possess large specific surface areas, high porosities, tunable pore sizes, and easy functionalization, rendering them promising candidates for the separation of mixed analytes. Research has shown that the use of organic frameworks as stationary phases for GC results in excellent column efficiency and high resolution for various analytes, including n-alkanes, n-alcohols, polycyclic aromatic hydrocarbons, positional isomers, and organic fluorides. Furthermore, organic frameworks can be prepared as chiral stationary phases for GC by the intelligent introduction of a chiral moiety, thereby enabling the efficient separation of enantiomers. Synthetic strategies for chiral organic frameworks are primarily categorized as post-synthesis or bottom-up approaches. In general, the post-synthesis strategy can introduce various chiral sites to the framework; however, the distribution of chiral sites may not be uniform, and the ordered framework may be destroyed during the post-synthesis process. The bottom-up strategy allows for the uniform and precise distribution of chiral sites in the framework, but the synthesis of chiral monomers and the constraint between asymmetry and crystallinity limit its development. Chiral induction has been proposed as an alternative strategy for synthesizing chiral organic frameworks. The use of this strategy has led to the successful preparation of organic frameworks with abundant chiral sites and excellent crystallinity. Dynamic coating and in situ growth are the main approaches used to transform the as-prepared chiral organic frameworks into stationary phases. Notably, the in situ growth approach can yield chiral COF/MOF-coated capillary columns that provide high resolution for the separation of enantiomers with excellent repeatability and reproducibility. Nevertheless, owing to the slightly complex pretreatment process and the difficulty of synthesizing chiral organic frameworks, the in situ growth approach has not yet been widely applied. Owing to their excellent solvent processing performance, POCs, MOCs, and HOFs can be easily coated on the inner walls of columns to form membranes via dynamic or static coating. A series of enantiomers have been successfully separated and analyzed by immobilizing chiral COFs, MOFs, POCs, MOCs, and HOFs on GC capillary columns, demonstrating the great potential of chiral organic frameworks for enantiomeric separation. In general, the mechanisms by which chiral organic frameworks recognize enantiomers could be mainly categorized as van der Waals interactions, hydrogen bonding, π-π interactions, and size-exclusion effects. While molecular simulations can offer some insights into these recognition mechanisms, clarifying these mechanisms based on effective characterization remains challenging. In summary, organic frameworks show outstanding advantages for enantiomer separation. Given breakthroughs in synthetic strategies for chiral organic frameworks and the in-depth study of chiral recognition mechanisms, chiral organic frameworks may be expected to become an important aspect in the field of chiral materials, further realizing the large-scale analysis and production of chiral analytes. A total of 64 references, most of which are from the American Chemical Society, Springer Nature, Wiley Online Library, and Elsevier databases, are cited in this review.

Heterozygous variants of NOD2, IL10RA, PLA2G6 and COL7A1 correlate with Crohn's disease.

To identify candidate pathogenic genes of early-stage Crohn's disease (CD) and predict potential roles of genetic factors in CD, we performed whole exome sequencing on a child with early-stage Crohn's disease (CD) and her parents (core family), found that the patient carried heterozygous variants of 4 genes: NOD2 c. 2257 C > T, IL10RA c. 301 C > T, PLA2G6 c. 2029 C > T, COL7A1 c. 3190 G > A. Heterozygous variants of NOD2, IL10RA, PLA2G6 and COL7A1, intestinal inflammatory response is triggered, normal intestinal wall tissue damage, leading to CD phenotype.

Gut microbiota alteration and its association with immune function in post-COVID-19 patients.

To reveal the variation of gut microbiota and its association with immune function in cured patients with coronavirus 2019 (COVID-19) disease, gut microbiota of patients discharged from hospital for 20 ~ 23 months and healthy volunteers was analyzed by high throughput 16S rRNA sequencing. The diversity and abundance were compared, and the correlation with immunity factors was investigated, and changes in the content of 6 genera microorganisms with proportion higher than 0.1% were revealed in patients with COVID-19 disease: reduced content of Subdoligranulum, Haemophilus, Coprococcus, Eubacterium vertriosum group, and Lachnospiraceae ND3007 group and increased content of Hungatella. NK cells were negatively correlated to Subdoligranulum, while CD8 cells were positively correlated to Subdoligranulum but negative to Hungatella. IL-8 concentration was negatively correlated to Subdoligranulum, Haemophilus, Coprococcus, Eubacterium vertriosum group, and Lachnospiraceae ND3007 group but positively to Hungatella, while IL-1ß concentration was negatively correlated to Haemophilus and Eubacterium ventriosum group but positively to Hungatella. The variation of probiotics and potential pathogenic bacteria implies a higher risk in diseases and inflammation, and the modulation of the gut microbiota may help the healing of COVID-19 patients.

Nanoscale-controlled organicinorganic hybrid spheres for comprehensive enrichment of ultratrace chlorobenzenes in marine and fresh water.

The size of the adsorbent has the potential to influence extraction performance, but the size effect at the nanoscale is still poorly understood. In this study, organic-inorganic hybrid nanospheres (OIHNs) with controllable nanoscale sizes of 30, 50, and 100 nm were successfully prepared. These materials were further fabricated as solid phase microextraction (SPME) coatings with similar thicknesses, and coupled with gas chromatography-mass spectrometry (GC-MS) to investigate their extraction performance. The results showed that the extraction capacities of OIHNs for chlorobenzenes (CBs) and polycyclic aromatic hydrocarbons (PAHs) were much better than those of their corresponding derived carbon materials, despite the smaller specific surface areas and lower porosities of them. In addition, the enrichment performance increased significantly with decreasing particle size, and the OIHN-30 coating demonstrated the best performance, with enrichment factors ranging from 1098 to 6853 for CBs. Finally, a highly sensitive and practical analytical method was established with a wide linear range of 0.5-5000 ng·L-1, and the limits of quantification (LOQs) were 0.43-1.7 ng·L-1. The determinations of ultratrace CBs in five marine water samples and five fresh water samples were realized successfully. This study is expected to contribute to a deep understanding of the environmental effects of nanoparticles and the design of high-performance adsorbents.

Nitrogen-rich covalent organic framework as a practical coating for effective determinations of polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are high-profile organic pollutants to be poisonous, carcinogenic, and mutagenic, and widely distributed at trace levels in the environment. In order to effectively enrich PAHs, two stable covalent organic frameworks (COFs, TAPT-OMe-PDA and TPB-DMTP) were prepared by combining 2,4,6-tri(4-aminophenyl)-1,3,5-triazine (TAPT) and 1,3,5-tri(4-aminophenyl) benzene (TAPB) with 2,5-dimethoxy-phenyl-1,4-diformaldehyde (OMe-PDA), respectively. Even though the surface area of TAPT-OMe-PDA was much lower than that of TPB-DMTP, it still demonstrated much better extraction efficiencies towards PAHs as the solid phase microextraction (SPME) coating. Therefore, the TAPT-OMe-PDA coated fiber was coupled with gas chromatography-mass spectrometry (GC-MS) to establish a practical and sensitive method, after the extraction parameters (extraction time, extraction temperature, desorption temperature, desorption time, salt concentration and pH) were optimized. This developed analytical method showed wide linear ranges, low limits of detection, good repeatability and reproducibility. Finally, five PAHs in three water samples were detected and quantified precisely (2.72-38.7 ng·L-1) with satisfactory recoveries (88.3%-118%).

CXCL16 exacerbates Pseudomonas aeruginosa keratitis by promoting neutrophil activation.

Pseudomonas aeruginosa (PA) keratitis is a major cause of blindness characterized by corneal inflammation. In a murine model of PA keratitis, we assessed the detrimental effects of CXC chemokine ligand 16 (CXCL16). Quantitative PCR (qPCR), western blotting (WB) and immunofluorescence were used to measure the expression and localization of CXCL16 and its receptor, CXC chemokine receptor 6 (CXCR6). Clinical scores, plate counting, and hematoxylin-eosin staining were used to assess infection severity and its exacerbation by CXCL16. Immunofluorescence, myeloperoxidase assays, and flow cytometry were used to detect neutrophil activity and colocalization with CXCR6. WB and immunofluorescence were used to measure levels of reactive oxygen species (ROS) and matrix metalloproteinases (MMPs). These methods also were used to measure the activation of downstream NF-κB signaling and its positive feedback on CXCL16 expression. ELISA, flow cytometry, and qPCR were used to measure the expression of CXCL2 and T helper 17 (Th17) cell-related genes. CXCL16 and CXCR6 expression was increased in infected corneas. Topical application of CXCL16 exacerbated keratitis by increasing corneal bacterial load and promoting neutrophil infiltration, whereas neutralizing antibody against CXCL16 had the opposite effect. CXCL16 also increased ROS and MMP levels. This neutrophil activation may be caused by its positive feedback with the NF-κB pathway and the upregulation of CXCL2 and Th17 cell related-genes. These data suggest that CXCL16 is an attractive therapeutic target for PA keratitis.

Spontaneous unscarred uterine rupture at 13 weeks of gestation after in vitro fertilization-embryo transfer: A case report and literature review.

RATIONALE: Uterine rupture (UR) during pregnancy is a serious obstetric complication. Here we report a case of spontaneous rupture in an unscarred uterus at 13 weeks of gestation after in vitro fertilization embryo transfer, which is not common in past references. Our focus is to understand the relationship between systemic lupus erythematosus (SLE) and UR. PATIENT CONCERNS: A 33-year-old infertile woman with a history of SLE became pregnant after in vitro fertilization embryo transfer. She presented with sudden mental fatigue and dyspnea, accompanied by sweating, dizziness and lower abdominal pain at 13 weeks of gestation. DIAGNOSES: Blood analysis revealed anemia. Ultrasonography and plain computed tomography scan revealed intrauterine early pregnancy with effusion in pelvic and abdominal cavity. Laparotomy confirmed the diagnosis of UR. INTERVENTIONS: The patient underwent emergency laparotomy. Upon surgery, multiple myometrium was weak with only serosal layer visible, and there was a 2.5 cm irregular breach with exposed placenta and villous tissue in the posterior wall of the uterus. After removing intrauterine fetus and repairing the breach, there was still persistent intraperitoneal hemorrhage. The patient underwent subtotal hysterectomy finally. OUTCOMES: Postoperative recovery was uneventful. The patient was discharged on the 8th day after operation. LESSONS: Combined efforts of specialists from ultrasound, imaging and gynecologist led to the successful diagnosis and management of this patient. We should be cautious about the occurrence of unscarred uterus rupture during pregnancy of the women with the disease of SLE and long-term glucocorticoid treatment. In IVF, we had better transfer one embryo for these patients with the history of SLE. Obstetricians should strengthen labor tests to detect early signs of UR of the patients with SLE and long term glucocorticoid treatment. Once UR is suspected, prompt surgical treatment is needed as soon as possible.

Calcineurin suppresses rat H9c2 cardiomyocyteprotective autophagy under chronic intermittent hypoxia by downregulating the AMPK pathway.

Calcineurin plays a key role in cardiovascular pathogenesis by exerting pro-apoptotic effects in cardiomyocytes. However, whether calcineurin can regulate cardiomyocyte autophagy under conditions of chronic intermittent hypoxia (CIH) remains unclear. Here, we showed that CIH induced calcineurin activity in H9c2 cells, which attenuated adenosine monophosphate-activated protein kinase (AMPK) signaling and inhibited autophagy. In H9c2 cells, autophagy levels, LC3 expression, and AMPK phosphorylation were significantly elevated under conditions of CIH within 3 days. However, after 5 days of CIH, these effects were reversed and calcineurin activity and apoptosis were significantly increased. The calcineurin inhibitor 17-Allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl) -1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo- [22.3.1.04,9]octacos-18- ene-2,3,10,16-tetrone (FK506) restored AMPK activation and LC3 expression and attenuated CIH-induced H9c2 cell apoptosis. In contrast, calcineurin overexpression significantly attenuated the increase in LC3 expression and enhanced H9c2 cell apoptosis under conditions of CIH. Calcineurin inhibition failed to induce autophagy or alleviate apoptosis in H9c2 cells expressing a kinase-dead K45R AMPK mutant. Autophagy inhibition abrogated the protective effects of FK506-mediated calcineurin inhibition. These results indicate that calcineurin suppresses adaptive autophagy during CIH by downregulating AMPK activation. Our findings reveal the underlying mechanism of calcineurin and autophagy regulation during H9c2 cell survival under conditions of CIH and may provide a new strategy for preventing CIH-induced cardiomyocyte damage.

D6 high-quality expanded blastocysts and D5 expanded blastocysts have similar pregnancy and perinatal outcomes following single frozen blastocyst transfer.

Objective: We compared the pregnancy and perinatal outcomes between expanded blastocysts vitrified on D5 versus D6 following single frozen blastocyst transfer. Methods: Clinical data on 7,606 cycles of frozen-thawed blastocyst implantations were retrospectively analyzed. Depending on whether blastocysts were vitrified on D5 or D6 and the transferred blastocysts, the blastocysts were divided into 6 groups: HQB-D5, HQB-D6, 4XC-D5, 4XC-D6, 4CX-D5, and 4CX-D6 groups. The differences in clinical pregnancy rate, live birth rate, first trimester abortion rate, preterm birth rate, gestational age, birth weight, and sex ratio at birth among the groups were compared. Results: Our study showed that there was no difference in pregnancy and perinatal outcomes between the delayed formation of D6 high-quality expanded blastocysts and D5 expanded blastocysts, whether they were high-quality blastocysts or not. For low-quality blastocysts, the clinical pregnancy rate of D5 was higher than that of D6, and D5 was also better than D6 in live birth rate for those with inner cell mass rating B or above, while there was no difference between D5 and D6 for those with inner cell mass rating C. Conclusion: Based on our research, we suggest that when we are developing the implantation strategy, we give priority to the selection of high-quality expanded blastocysts, regardless of D5 and D6, whose clinical outcomes are not different. For low-quality blastocysts, D5 expanded blastocysts are preferred for transfer.

Prevalence and trends of developmental disabilities among US children and adolescents aged 3 to 17 years, 2018-2021.

Developmental disabilities prevalence seem to be high in countries around the world. It's worth understanding the most recent prevalence and trends of developmental disabilities. The objective of this study is to examine the prevalence and trends of developmental disabilities of US children and adolescents. A total of 26,422 individuals aged 3-17 years were included. Annual data were examined from the National Health Interview Survey (2018-2021). Weighted prevalence for each of the selected developmental disabilities were calculated. The prevalence of any developmental disabilities in individuals was 16.65% (95% CI 16.03-17.26%), prevalence of attention deficit/hyperactivity disorder (ADHD), learning disability (LD), autism spectrum disorder (ASD), intellectual disability (ID), and other developmental delay were 9.57% (95% CI 9.09-10.06%), 7.45% (95% CI 7.00-7.89%), 2.94% (95% CI 2.67-3.21%), 1.72% (95% CI 1.51-1.93%), and 5.24% (95% CI 4.89-5.59%), respectively. Significant increases were observed for other developmental delay (4.02-6.05%) and co-occurring LD & ID (1.03-1.82%). Findings form this study highlight a high prevalence of any developmental disabilities, although no significant increase was observed. The prevalence of other developmental delay and co-occurring LD & ID were significantly increased. Further investigation is warranted to assess potentially modifiable risk factors and causes of developmental disabilities.

Characterization and Expression Analysis of Genes from Megalobrama amblycephala Encoding Hemoglobins with Extracellular Microbicidal Activity.

Hemoglobin (Hb) usually comprises two α and two ß subunits, forming a tetramer responsible for oxygen transportation and storage. Few studies have elucidated fish hemoglobin immune functions. Megalobrama amblycephala is a freshwater-cultured fish prevalent in China. We identified two M. amblycephala hemoglobin subunits and analyzed their expression patterns and antibacterial activities. The respective full-length cDNA sequences of the M. amblycephala Hb α (MaHbα) and ß (MaHbß) subunits were 588 and 603 bp, encoding 143 and 148 amino acids. MaHbα and MaHbß were highly homologous to hemoglobins from other fish, displaying typical globin-like domains, most heme-binding sites, and tetramer interface regions highly conserved in teleosts. In phylogenetic analyses, the hemoglobin genes from M. amblycephala and other cypriniformes clustered into one branch, and those from other fishes and mammals clustered into other branches, revealing fish hemoglobin conservation. These M. amblycephala Hb subunits exhibit different expression patterns in various tissues and during development. MaHbα is mainly expressed in the blood and brain, while MaHbß gene expression is highest in the muscle. MaHbα expression was detectable and abundant post-fertilization, with levels fluctuating during the developmental stages. MaHbß expression began at 3 dph and gradually increased. Expression of both M. amblycephala Hb subunits was down-regulated in most examined tissues and time points post-Aeromonas hydrophila infection, which might be due to red blood cell (RBC) and hematopoietic organ damage. Synthetic MaHbα and MaHbß peptides showed excellent antimicrobial activities, which could inhibit survival and growth in five aquatic pathogens. Two M. amblycephala hemoglobin subunits were identified, and their expression patterns and antibacterial activities were analyzed, thereby providing a basis for the understanding of evolution and functions of fish hemoglobins.