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.

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.

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.

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.

Objective To explore the relationship between the expression levels of excision repair cross complementation group 1(ERCC1), breast cancer susceptibility gene 1(BRCA1), thymidylate synthase (TS) mRNA and clinicopathological features, prognosis in advanced colorectal cancer, and the correlation between the expression levels of ERCC1 and BRCA1. Methods The expression levels of ERCC1, BRCA1 and TS mRNA of postoperative paraffin embedded tissue were tested by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) in 49 advanced colorectal cancer cases. The results were analyzed by χ2 test of the correlation between the expression levels and clinicopathological characteristics. Patients were followed up by clinic or telephone. The prognosis was analyzed by small sample Kaplan-Meier survival analysis and Log-rank time series analysis, and P<0.05 was statistically significant. Results The expression level of ERCC1 mRNA in patients with colorectal carcinoma had no obvious correlation with the clinical and pathological characteristics such as gender, age, tumor location, lymph node metastasis, distant metastasis, CEA and differentiation degree (P>0.05). The expression level of BRCA1 mRNA had no significant correlation with the above clinical and pathological features (P>0.05) except distant metastasis (P=0.030) and differentiation degree (P=0.002). The expression level of TS mRNA had no significant correlation with the above clinical and pathological features (P>0.05) except distant metastasis (P=0.003). The expression level of ERCC1 and BRCA1 mRNA obviously correlated (P=0.002). The 1 year overall survival rate was 95.92%(47/49);the 2 year overall survival rate was 83.67%(41/49);and the 3 year overall survival rate was 73.47%(36/49). Overall survival and progression-free survival time in ERCC1 mRNA low expression group (47.8, 41.0 months) was higher than that in ERCC1 mRNA low expression group (27.3, 20.0 months) respectively (P=0.001, P=0.001). Overall survival and progression-free survival time in BRCA1 mRNA low expression group (43.7, 42.7 months) was higher than that in BRCA1 mRNA high expression group (29.3, 25.1 months) respectively (P=0.009, 0.006). Overall survival time in TS mRNA low expression group (39.8 months) was higher than that in BRCA1 mRNA high expression group (25.2 months). Conclusions The expression level of ERCC1 mRNA is not correlated with its clinical and pathological characteristics, but with its biological characteristics. BRCA1 and TS levels are correlated with invasion and metastasis. Low levels of ERCC1 and BRCA1 expression have a better prognostic effect on platinum based first-line chemotherapy for advanced colorectal cancer, and they are correlated. Low level of TS also has longer disease-free survival. Three joint detection could be used as a prognostic factor for colorectal cancer chemotherapy.

Objective To explore the difference of the expression level of FK506 Binding Protein 51 (FKBP51) in colorectal adenocarcinoma and normal colorectal tissues,and the correlation between FKBP51 expression level and clinicopathological characteristics,and to clarify whether FKBP51 is involved in the occurrence and development of colorectal cancer.Methods By immunohistochemical staining [streptavidin-peroxidase (SP) method] and Western blotting methods tested 31 cases of colorectal cancer tumor tissues and normal colorectal tissues far from tumor 5 cm,and explored the expression level difference of FKBP51.Combined with clinical data of patients,results were analyzed by statistical method x2 test of four case table data.Results The high expression rate of FKBP51 in tumor tissues was 74.19％ (23/31 cases),while the high expression rate of FKBP51 in normal tissue was 9.68％ (3/31 cases).The difference was significant.The expression level of FKBP51 in patients with colorectal carcinoma had no obvious correlation with gender (P =0.771),age (P =0.474),tumor location (P =0.213),degree of differentiation (P =0.318),lymph node metastasis (P =0.124),distant metastasis (P =0.318) and clinical stage (P =0.171);and the tumor size (P =0.049),depth of invasion related (P =0.031),the difference was statistically significant.Conclusions The expression of FKBP51 in colorectal cancer was strong,while weak expression in normal colorectal tissues.With the increase of tumor infiltration and deepening,the expression of FKBP51 became stronger,which indicated that FKBP51 participated in the genesis and development of colorectal cancer,and it might become a new target for individual therapy of colorectal cancer.

Objective To investigate the effects of inhibition of adenosine monophosphate -activated protein kinase (AMPK) on expressions of cytochrome c (CytC) and caspase -3 and apoptosis in the cerebral cortex after cerebral ischemia-reperfusion injury in mice. Methods Thirty-six male C57BL/6 mice w ere randomly divided into three groups, a sham operation group, a ischemia -reperfusion group, and a AMPK inhibitor group, 12 in each group. A model of middle cerebral artery occlusion w as induced by suture method. The AMPK inhibitor compound C ( 20 mg/kg) w as injected intraperitonealy in the AMPK inhibitor group, the equal volume normal saline w as injected intraperitonealy in the sham operation group and the ischemia-reperfusion group w hen a thread w as inserted. Immunohistochemical staining w as used to detect the expression levels of CytC and caspase-3 and TUNEL method w as used to detect apoptosis at 24 h after ischemia-reperfusion. Results Compared w ith the ischemia-reperfusion group, the numbers of CytC (28.86 ±9.65/HP vs.58.86 ±9.65/HP; t = 7.615, P = 0.030 ) and caspase-3 (7.16 ±5.85/HP vs. 14.36 ±7.85/HP; t =2.548, P =0.035), and TUNEL (67.14 ±8.55/HP vs.95.00 ±13.51/HP; t = 6.891, P = 0.030) positive cels in the cerebral cortex w ere reduced significantly in the AMPK inhibitor group. Conclusion Inhibition of AMPK activity after cerebral ischemia-reperfusion may decrease apoptosis by dow nregulating the expressions of CytC and caspase -3, and play a neuroprotective effect.