Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

Aim To explore the predictive value of serum free triiodothyronine(FT3)on the long-term prognosis of patients with coronary heart disease after percutaneous coronary intervention(PCI).Methods All the subjects were from a prospective cohort study(PRACTICE study).In this study,15 250 patients with coronary heart disease after PCI in the First Affiliated Hospital of Xinjiang Medical University were selected,and the clinical data,FT3 and creatinine were collected.All the subjects were followed up regularly,and the primary follow-up endpoints were all-cause mortality and cardiogenic mortality,the secondary endpoints were major adverse cardiovascular events(MACE)and major adverse cardiovascular and cerebrovascular events(MACCE).According to the admission criteria,3 109 patients were finally in-cluded in this study.According to the baseline value of FT3,patients were divided into normal FT3 group(FT3:3.65～6.8 pmol/L,1 446 cases)and low FT3 group(FT3＜3.65 pmol/L,1 663 cases).Kaplan-Meier analysis was used for survival analysis,and Log-rank test was used for survival comparison.Multivariate Cox regression analysis was used to e-valuate the risk factors of the follow-up results of the two groups.Results Compared with the normal FT3 group,all-cause mortality and cardiogenic mortality in the low FT3 group increased significantly(P＜0.05).Kaplan-Meier analysis showed that the cumulative risk of all-cause mortality and cardiogenic mortality increased in the low FT3 group(P＜0.05).Multivariate Cox regression analysis indicated that the risk of all-cause mortality increased by 1.639 folds in the low FT3 group(HR=2.639,95％CI:1.385～5.348,P=0.007),while no statistical difference was found in cardiogenic mortality after adjusting for multiple factors(P=0.125).Conclusion The decrease in serum FT3 levels has important predictive value for all-cause mortality after PCI in patients with coronary heart disease.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Objective:To summarize the experience of diagnosis and treatment of unexplained neonatal intestinal perforation.Methods:A case summary was conducted.Intestinal perforation children who showed unclear etiology during surgical exploration in Fujian Children′s Hospital from October 2017 to October 2023 were retrospectively analyzed.The perforation characteristics, pathological characteristics, etiological analysis and surgical methods were analyzed, and the diagnosis and treatment experience was summarized.Results:There were 21 neonates with unexplained intestinal perforation, including 15 boys and 6 girls.There were more full-term infants (12 cases) than preterm ones (9 cases), and more neonates with normal birth weight (12 cases) than those with low birth weight (9 cases).Intraoperative perforation was detected in the ileum in 13 cases and colon in 8 cases.The perforation diameter ranged between 0.5-2.0 cm.Single perforation was detected in 20 cases, and 1 case had two perforations.All patients underwent full-layer multipoint biopsy and enterostomy.Pathological reports after surgery showed that Hirschsprung disease was confirmed in 10 cases, and Hirschsprung disease allied disorders were diagnosed in 8 cases.The remaining 3 cases had normal ganglion cells, and 2 cases of them had spontaneous intestinal perforation, and 1 case had meconium ileus.After operation, 3 cases gave up treatment, 1 case died, and 17 patients were discharged from hospital at the first stage.Nine cases with Hirschsprung disease received radical surgery at the age of 3-6 months.Six out of 8 patients with Hirschsprung disease allied disorders underwent fistula closure surgery after accurate evaluation.Among the 6 children who received fistula closure surgery, 1 case underwent Santulli enterostomy because of inability to defecate and abdominal distension after surgery.Two of the 6 children undergoing fistula closure surgery were still being followed up.Two cases of spontaneous intestinal perforation and 1 case of meconium ileus underwent fistula closure surgery at the age of 3 months, and postoperative defecation was normal.Conclusions:Intestinal neuronal dysplasia, meconium ileus combined with intestinal perforation and spontaneous intestinal perforation should be considered in unexplained neonatal intestinal perforation.It is recommended that enterostomy and multipoint biopsy should be performed to clarify the pathology before further treatment in children with unexplained intestinal perforation.Santulli enterostomy is a feasible staging operation.

Aim To investigate the role and mechanism of KLHL21 gene in myocardial infarction(MI)of mice.Methods KLHL21 gene knockout(KO)mice were generated using CRISPR/Cas9 technology,and C57BL/6 wild-type mice were used as controls.Sixty KLHL21 KO mice and 60 wild-type mice were randomly divided into four groups:WT+Sham group(n=30),WT+MI group(n=30),KO+Sham group(n=30)and KO+MI group(n=30).Postoperative is-chemic and infarct areas were assessed using TTC and Evans Blue staining,myocardial injury markers were measured by ELISA,cardiac function was evaluated by ultrasound,and histological changes were examined using HE and Masson stai-ning.Western blot was used to detect proteins related to the nuclear factor-κB(NF-κB)signaling pathway.Results KLHL21 protein expression in the myocardial tissue of KO mice was significantly lower than that in WT mice.The infarct area in KO+MI mice was significantly larger than that in WT+MI group.KO+MI mice showed reduced cardiac function compared with WT+MI mice.HE staining revealed myocardial cell loss,liquefactive necrosis,nuclear fragmentation,and significant neutrophil infiltration,while Masson staining showed aggravated fibrosis in KO+MI group.Serum tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),creatine kinase-MB(CK-MB),and cardiac troponin Ⅰ(cTnⅠ)lev-els were significantly increased in KO+MI mice compared with WT+MI mice.Western blot analysis showed increased lev-els of phosphorylated inhibitor of nuclear factor-κB alpha(p-IKBα),P65,and P50,and decreased nuclear factor-κB al-pha(IKBα)in KO+MI mice.Conclusion KLHL21 gene plays a preventive role in myocardial infarction in mice,possibly through inhibition of NF-κB signaling pathway activation.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Aim To explore the predictive value of serum free triiodothyronine(FT3)on the long-term prognosis of patients with coronary heart disease after percutaneous coronary intervention(PCI).Methods All the subjects were from a prospective cohort study(PRACTICE study).In this study,15 250 patients with coronary heart disease after PCI in the First Affiliated Hospital of Xinjiang Medical University were selected,and the clinical data,FT3 and creatinine were collected.All the subjects were followed up regularly,and the primary follow-up endpoints were all-cause mortality and cardiogenic mortality,the secondary endpoints were major adverse cardiovascular events(MACE)and major adverse cardiovascular and cerebrovascular events(MACCE).According to the admission criteria,3 109 patients were finally in-cluded in this study.According to the baseline value of FT3,patients were divided into normal FT3 group(FT3:3.65～6.8 pmol/L,1 446 cases)and low FT3 group(FT3＜3.65 pmol/L,1 663 cases).Kaplan-Meier analysis was used for survival analysis,and Log-rank test was used for survival comparison.Multivariate Cox regression analysis was used to e-valuate the risk factors of the follow-up results of the two groups.Results Compared with the normal FT3 group,all-cause mortality and cardiogenic mortality in the low FT3 group increased significantly(P＜0.05).Kaplan-Meier analysis showed that the cumulative risk of all-cause mortality and cardiogenic mortality increased in the low FT3 group(P＜0.05).Multivariate Cox regression analysis indicated that the risk of all-cause mortality increased by 1.639 folds in the low FT3 group(HR=2.639,95％CI:1.385～5.348,P=0.007),while no statistical difference was found in cardiogenic mortality after adjusting for multiple factors(P=0.125).Conclusion The decrease in serum FT3 levels has important predictive value for all-cause mortality after PCI in patients with coronary heart disease.

Aim To investigate the role and mechanism of KLHL21 gene in myocardial infarction(MI)of mice.Methods KLHL21 gene knockout(KO)mice were generated using CRISPR/Cas9 technology,and C57BL/6 wild-type mice were used as controls.Sixty KLHL21 KO mice and 60 wild-type mice were randomly divided into four groups:WT+Sham group(n=30),WT+MI group(n=30),KO+Sham group(n=30)and KO+MI group(n=30).Postoperative is-chemic and infarct areas were assessed using TTC and Evans Blue staining,myocardial injury markers were measured by ELISA,cardiac function was evaluated by ultrasound,and histological changes were examined using HE and Masson stai-ning.Western blot was used to detect proteins related to the nuclear factor-κB(NF-κB)signaling pathway.Results KLHL21 protein expression in the myocardial tissue of KO mice was significantly lower than that in WT mice.The infarct area in KO+MI mice was significantly larger than that in WT+MI group.KO+MI mice showed reduced cardiac function compared with WT+MI mice.HE staining revealed myocardial cell loss,liquefactive necrosis,nuclear fragmentation,and significant neutrophil infiltration,while Masson staining showed aggravated fibrosis in KO+MI group.Serum tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),creatine kinase-MB(CK-MB),and cardiac troponin Ⅰ(cTnⅠ)lev-els were significantly increased in KO+MI mice compared with WT+MI mice.Western blot analysis showed increased lev-els of phosphorylated inhibitor of nuclear factor-κB alpha(p-IKBα),P65,and P50,and decreased nuclear factor-κB al-pha(IKBα)in KO+MI mice.Conclusion KLHL21 gene plays a preventive role in myocardial infarction in mice,possibly through inhibition of NF-κB signaling pathway activation.

In recent years, cancer treatment methods and means are becoming more and more diversified, and single treatment methods often have limited efficacy, while the synergistic effect of immunity combined with chemotherapy can inhibit tumor growth more effectively. Based on this, we constructed a sodium alginate hydrogel composite system loaded with chemotherapeutic agents and tumor vaccines (named SA-DOX-NA) with a view to the combined use of chemotherapeutic agents and tumor vaccines. Firstly, the tumor vaccine (named NA) degradable under acidic conditions was constructed by in situ polymerization using chicken ovalbumin (OVA), acrylamide (AAM) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Then a hydrogel composite system SA-DOX-NA co-loaded with chemotherapeutic drug doxorubicin (DOX) and NA was prepared using sodium alginate as a matrix. The results showed that SA-DOX-NA had good in situ gel-forming ability and formed a mesh structure that could realize the co-loading of DOX and NA as well as the slow drug release. The electron microscopy results showed that SA-DOX-NA had good in situ gel-forming ability with good internal connectivity, and the three-dimensional mesh structure could realize the co-loading of DOX and NA as well as the slow drug release. The antitumor and immunomodulatory results showed that SA-DOX-NA both effectively inhibited the growth of tumor cells and efficiently promoted the proliferation and activation of DC2.4 dendritic cells without additional adjuvant. In summary, SA-DOX-NA exerts the dual efficacy of chemotherapy and immunotherapy for tumor treatment, and has a good application prospect in local tumor treatment.