[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

BACKGROUND:Acute lung injury is a common severe complication in sepsis patients,with a complex pathogenesis,for which there is currently no effective pharmacological treatment.The therapeutic mechanism by which human umbilical cord-derived mesenchymal stem cells improve sepsis-induced acute lung injury through the inhibition of excessive cellular pyroptosis is increasingly receiving attention.OBJECTIVE:To investigate the effects and mechanisms of human umbilical cord-derived mesenchymal stem cells on cellular pyroptosis in lung tissues of mice with sepsis-induced acute lung injury.METHODS:Totally 48 male Balb/c mice were randomly divided into sham,model,and treatment groups(n=16 per group).The model and treatment groups underwent cecum ligation and puncture to establish a sepsis-induced acute lung injury model,while the sham group underwent laparotomy without further procedures.The treatment group received a tail vein injection of 200 μL of human umbilical cord-derived mesenchymal stem cell suspension(5x105 cells)6 hours after the procedure,while the model and sham groups received 200 μL of saline 6 hours after the surgery.Twenty-eight hours post-procedure,five mice from each group were randomly selected for tail vein injection of Evans blue dye to assess pulmonary vascular permeability.The remaining mice from each group had their bronchoalveolar lavage fluid and lung tissues collected for ELISA to measure levels of interleukin-1β and interleukin-18,cell counts,and macrophage numbers in the bronchoalveolar lavage fluid.Hematoxylin and eosin staining was used to observe the pathological morphology of lung tissue.TUNEL staining was used to assess cellular pyroptosis.RT-PCR and western blot analyses were conducted to measure mRNA and protein expression levels of Toll-like receptor 4,GSDMD,and Caspase-11 in lung tissues.RESULTS AND CONCLUSION:Compared to the model group,the treatment group showed a significant decrease in pulmonary vascular permeability at 28 hours post-procedure(P＜0.05),reduced levels of interleukin-1β and interleukin-18 in bronchoalveolar lavage fluid(P＜0.05),and lower cell and macrophage counts(P＜0.05).Lung injury severity was reduced,with a decreased pyroptosis index(P＜0.05)and significantly lower levels of Toll-like receptor 4,GSDMD,GSDMD-N,and Caspase-11 mRNA and protein expression in lung tissues(P＜0.05).These results suggest that human umbilical cord-derived mesenchymal stem cells may improve the severity of sepsis-induced lung injury to some extent by inhibiting the activation of the Toll-like receptor 4/Caspase-11/GSDMD signaling pathway and reducing cellular pyroptosis in lung tissues.

BACKGROUND:Acute lung injury is a common severe complication in sepsis patients,with a complex pathogenesis,for which there is currently no effective pharmacological treatment.The therapeutic mechanism by which human umbilical cord-derived mesenchymal stem cells improve sepsis-induced acute lung injury through the inhibition of excessive cellular pyroptosis is increasingly receiving attention.OBJECTIVE:To investigate the effects and mechanisms of human umbilical cord-derived mesenchymal stem cells on cellular pyroptosis in lung tissues of mice with sepsis-induced acute lung injury.METHODS:Totally 48 male Balb/c mice were randomly divided into sham,model,and treatment groups(n=16 per group).The model and treatment groups underwent cecum ligation and puncture to establish a sepsis-induced acute lung injury model,while the sham group underwent laparotomy without further procedures.The treatment group received a tail vein injection of 200 μL of human umbilical cord-derived mesenchymal stem cell suspension(5x105 cells)6 hours after the procedure,while the model and sham groups received 200 μL of saline 6 hours after the surgery.Twenty-eight hours post-procedure,five mice from each group were randomly selected for tail vein injection of Evans blue dye to assess pulmonary vascular permeability.The remaining mice from each group had their bronchoalveolar lavage fluid and lung tissues collected for ELISA to measure levels of interleukin-1β and interleukin-18,cell counts,and macrophage numbers in the bronchoalveolar lavage fluid.Hematoxylin and eosin staining was used to observe the pathological morphology of lung tissue.TUNEL staining was used to assess cellular pyroptosis.RT-PCR and western blot analyses were conducted to measure mRNA and protein expression levels of Toll-like receptor 4,GSDMD,and Caspase-11 in lung tissues.RESULTS AND CONCLUSION:Compared to the model group,the treatment group showed a significant decrease in pulmonary vascular permeability at 28 hours post-procedure(P＜0.05),reduced levels of interleukin-1β and interleukin-18 in bronchoalveolar lavage fluid(P＜0.05),and lower cell and macrophage counts(P＜0.05).Lung injury severity was reduced,with a decreased pyroptosis index(P＜0.05)and significantly lower levels of Toll-like receptor 4,GSDMD,GSDMD-N,and Caspase-11 mRNA and protein expression in lung tissues(P＜0.05).These results suggest that human umbilical cord-derived mesenchymal stem cells may improve the severity of sepsis-induced lung injury to some extent by inhibiting the activation of the Toll-like receptor 4/Caspase-11/GSDMD signaling pathway and reducing cellular pyroptosis in lung tissues.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective : To study the best machine learning method for early prediction of hematoma expansion in hypertensive intracerebral hemorrhage based on head CT plain scan. Methods : The CT images of 130 patients with cerebral hemorrhage were retrospectively analyzed , and the texture features of the head CT plain scan were extracted. The classifier was trained by selecting the features , and the six classic machine learning methods were crossvalidated to evaluate the stability and performanceof predicting cerebral hemorrhage hematoma expansion. Results: The prediction performance of support vector machine (SVM⁃Radial) (AUC 0. 714 ± 0. 144 , accuracy 0. 723 ± 0. 109) , generalized linear model ( GLM) prediction performance ( AUC 0. 643 ± 0. 125 , accuracy 0. 587 ± 0. 136) , random forest (RF) prediction performance (AUC 0. 686 ± 0. 128 , accuracy 0. 680 ± 0. 130) , k ⁃nearest neighbor (kNN) prediction performance ( AUC 0. 657 ± 7C 15 , accuracy 0. 639 ± 39 performance 19) , gradient boosting tree algorithm (GBM) Prediction performance ( AUC 0. 718 ± 0. 141 , accuracy 0. 670 ± 0. 126) , neural network (NNet) prediction performance (AUC 0. 659 ± 0. 162 , accuracy 0. 680 ± 0. 130) , in which support vector machines showed high prediction performance , generalized linear model showed low predictive performance. Conclusion Among the six machine learning methods based on cranial CT radiomics to predict early hematoma expansion in hypertensive intracerebral hemorrhage , support vector machine (SVM⁃Radial) has the best predictive performance and has potential clinical application value.

Objective:To master the changes of Kashin-Beck disease and the examination and acceptance in Zhalantun City, and to provide scientific basis for formulating prevention and control strategies of Kashin-Beck disease.Methods:From 2016 to 2017, in each county under the jurisdiction of Zhalantun City, 5 townships affected by the disease were selected, 3 villages were selected from each township, and the prevalence of Kashin-Beck disease of all residential children aged 7 to 12 years who lived in the villages for more than 6 months were investigated. The clinical and X-ray diagnosis were performed according to the "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010) standard, and the prevalence of Kashin-Beck disease in children aged 7 to 12 years in Zhalantun City in 2016 and 2017 were compared. In accordance with the "Key Endemic Disease Control and Elimination Evaluation Measures" ([2014]79), the condition of Kashin-Beck disease and the implementation of its prevention and control measures was assessed.Results:From 2016 to 2017, 1 697 children aged 7 to 12 years were examined, there were no clinical cases of Kashin-Beck disease and 11 cases of X-ray positive changes. Among them, 844 children were examined in 2016, the positive rate of X-ray was 0.24% (2/844), the positive rate of metaphyseal was 0.24% (2/844), and no positive changes of extremities and triad were detected. A total of 853 children were examined in 2017, the positive rate of X-ray was 1.06% (9/853), the positive rate of metaphyseal was 1.06% (9/853), and no positive changes of extremities and triad were detected. The positive rate of X-ray and metaphyseal of Kashin-Beck disease in children aged 7 - 12 years in 2017 were higher than those in 2016 (χ 2 = 4.409, 4.409, P < 0.05). All surveyed villages had reached the national elimination standard (no clinical cases for children aged 7 - 12 years, X-ray positive rate ≤3% and no cases of hand bone end changes); the organization management scores of Kashin-Beck disease prevention and treatment in Zhalantun City in 2016 and 2017 were 88 points, reaching the qualified standard ( > 85 points). Conclusion:The condition of Kashin-Beck disease in Zhalantun City has reached the standard of elimination, which lays a foundation for further comprehensive elimination of Kaschin-Beck disease in Hulunbuir City.

Objective To investigate the acute stroke patients with lower respiratory tract of multi drug resistant bacteria(MDR) infection risk factors.Methods The clinical data of 170 patients with acute stroke were retrospectively analyzed from January 2013 to December 2015.The MDR infection was divided into MDR infection group and non-MDR infection group.example.Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors of MDR infection in patients with acute stroke.Results Univariate analysis: The relationship between COPD, coma, cerebral hemorrhage, cough, cough reflex, tracheal intubation, indwelling catheter, indwelling gastric tube, and combination of two or more antibiotics was more than 5 days and MDR infection(P<0.05).Multivariate logistic regression analysis: COPD, coma, tracheal intubation, cerebral hemorrhage, two or more antibiotics prophylactic use is an independent risk factor for MDR infection.Conclusion The acute stroke patients with lower respiratory tract infection in patients with MDR factors and iatrogenic factors, combined with COPD, coma, tracheal intubation, cerebral hemorrhage, irrational use of antibiotics are independent risk factors for its occurrence.