ObjectiveTo explore the mechanism by which Xianglian Huazhuo prescription ameliorates chronic atrophic gastritis （CAG） through regulating the Golgi protein 73 （GP73）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway and modulating endoplasmic reticulum stress （ERS）. MethodA mouse model of CAG was induced by multiple factors， including ranitidine， N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， and irregular feeding. The CAG mice were randomized into five groups： model， Morodan （2.0 g·kg^-1）， and high-dose， medium-dose， and low-dose （7.6， 3.8， 1.9 g·kg^-1， respectively） Xianglian Huazhuo prescription， with 10 mice in each group. At the same time， 10 mice in normal group were set up. The mice in the Morodan group and the high-dose， medium-dose， and low-dose groups of Xianglian Huazhuo prescription were administrated with corresponding agents by gavage， and those in the normal group and the model group were administrated with an equal volume of normal saline. All the mice were intervened once a day for 60 consecutive days. After the last administration， the overall morphological changes of the gastric tissue were observed. Hematoxylin-eosin （HE） staining and transmission electron microscopy （TEM） were used to evaluate the pathological morphology and the endoplasmic reticulum ultrastructure in the gastric tissue. The serum levels of pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， gastrin-17 （G-17）， and GP73 were determined by enzyme-linked immunosorbent assay （ELISA）. The pepsinogen ratio （PGR， PGⅠ/PGⅡ） was calculated. The protein levels of GP73， PERK， phosphorylated （p）-PERK， glucose-regulated protein 78 （GRP78）， ATF4， CCAAT enhancer-binding protein homologous protein （CHOP）， cysteinyl aspartate-specific protease-12 （Caspase-12）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） were assessed by Western blot. The expression of GRP78 was detected by immunofluorescence （IF） assay， and the location of Bcl-2 and Bax by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed pale gastric mucosa with flattened folds and reduced and loosely arranged gastric mucosal glands， declined serum levels of PGI， PGR， G-17， and GP73 （P<0.01）. downregulated protein levels of GP73， p-PERK， ATF4， GRP78， CHOP， Caspase-12， and Bax in the gastric tissue， and upregulated protein level of Bcl-2 （P<0.01）. Compared with the model group， the Morodan group and each Xianglian Huazhuo prescription group exhibited red gastric mucosa with increased folds， alleviated pathological damage， swelling endoplasmic reticulum， elevated serum levels of PGI， G-17， and GP73 （P<0.05， P<0.01）， and upregulated protein levels of Caspase-12 and Bax and downregulated protein level of Bcl-2 in the gastric tissue （P<0.05， P<0.01）. The Morodan group and the high-dose and medium-dose Xianglian Huazhuo prescription groups exhibited increased serum level of PGR （P<0.05， P<0.01） and upregulated protein levels of GP73， p-PERK， ATF4， GRP78， and CHOP in the gastric tissue （P<0.05， P<0.01）. ConclusionXianglian Huazhuo prescription can activate the GP73/PERK/ATF4 signaling pathway and induce ERS-mediated apoptosis to alleviate the pathological damage of the gastric mucosa， thereby demonstrating a protective effect against CAG in mice.

ObjectiveTo explore the mechanism by which Xianglian Huazhuo prescription ameliorates chronic atrophic gastritis （CAG） through regulating the Golgi protein 73 （GP73）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway and modulating endoplasmic reticulum stress （ERS）. MethodA mouse model of CAG was induced by multiple factors， including ranitidine， N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， and irregular feeding. The CAG mice were randomized into five groups： model， Morodan （2.0 g·kg^-1）， and high-dose， medium-dose， and low-dose （7.6， 3.8， 1.9 g·kg^-1， respectively） Xianglian Huazhuo prescription， with 10 mice in each group. At the same time， 10 mice in normal group were set up. The mice in the Morodan group and the high-dose， medium-dose， and low-dose groups of Xianglian Huazhuo prescription were administrated with corresponding agents by gavage， and those in the normal group and the model group were administrated with an equal volume of normal saline. All the mice were intervened once a day for 60 consecutive days. After the last administration， the overall morphological changes of the gastric tissue were observed. Hematoxylin-eosin （HE） staining and transmission electron microscopy （TEM） were used to evaluate the pathological morphology and the endoplasmic reticulum ultrastructure in the gastric tissue. The serum levels of pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， gastrin-17 （G-17）， and GP73 were determined by enzyme-linked immunosorbent assay （ELISA）. The pepsinogen ratio （PGR， PGⅠ/PGⅡ） was calculated. The protein levels of GP73， PERK， phosphorylated （p）-PERK， glucose-regulated protein 78 （GRP78）， ATF4， CCAAT enhancer-binding protein homologous protein （CHOP）， cysteinyl aspartate-specific protease-12 （Caspase-12）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） were assessed by Western blot. The expression of GRP78 was detected by immunofluorescence （IF） assay， and the location of Bcl-2 and Bax by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed pale gastric mucosa with flattened folds and reduced and loosely arranged gastric mucosal glands， declined serum levels of PGI， PGR， G-17， and GP73 （P<0.01）. downregulated protein levels of GP73， p-PERK， ATF4， GRP78， CHOP， Caspase-12， and Bax in the gastric tissue， and upregulated protein level of Bcl-2 （P<0.01）. Compared with the model group， the Morodan group and each Xianglian Huazhuo prescription group exhibited red gastric mucosa with increased folds， alleviated pathological damage， swelling endoplasmic reticulum， elevated serum levels of PGI， G-17， and GP73 （P<0.05， P<0.01）， and upregulated protein levels of Caspase-12 and Bax and downregulated protein level of Bcl-2 in the gastric tissue （P<0.05， P<0.01）. The Morodan group and the high-dose and medium-dose Xianglian Huazhuo prescription groups exhibited increased serum level of PGR （P<0.05， P<0.01） and upregulated protein levels of GP73， p-PERK， ATF4， GRP78， and CHOP in the gastric tissue （P<0.05， P<0.01）. ConclusionXianglian Huazhuo prescription can activate the GP73/PERK/ATF4 signaling pathway and induce ERS-mediated apoptosis to alleviate the pathological damage of the gastric mucosa， thereby demonstrating a protective effect against CAG in mice.

Objective:To investigate the association of serum/body fluid heparin-binding protein (HBP) and blood lactate levels with disease severity and their impact on prognosis in intensive care unit (ICU) patients with sepsis.Methods:Clinical data from 100 sepsis patients admitted to Ma'anshan Shiqiye Hospital ICU (January 2023-September 2024) were retrospectively analyzed. According to Sepsis-3.0 criteria, patients were divided into: uncomplicated sepsis (general group, n=28), sepsis with organ failure/hypotension (severe group, n=61), and septic shock (shock group, n=11). Comparisons included serum/body fluid HBP, lactate, APACHE Ⅱ scores, and mortality across severity groups and laboratory parameters between survivors and non-survivors. Logistic regression was used to identify prognostic predictors. Non-normally distributed data were presented as M(Q1,Q3), comparison between groups were completed by Kruskal-Wallis H test and Mann-Whitney U tests. Spearman correlation was used to analyze relationships between biomarkers and APACHE Ⅱ scores. Categorical data were presented as n(%), and comparison between groups were completed by χ2 test or Fisher's exact tests. ROC curves was used to evaluate predictive value. Results:Shock group demonstrated significantly higher serum HBP [13.3 (12.6-16.4) μg/L], infection-site HBP [230.3 (226.3-241.1) μg/L], lactate [5.4 (4.9-5.6) mmol/L], and APACHE Ⅱ[22.0 (21.0-24.0)] than severe group [9.6 (8.9-10.5) μg/L; 208.9 (200.5-216.1) μg/L; 2.7 (2.6-2.8) mmol/L; 18.0 (17.0-19.0)] and general group [7.4 (6.3-8.1) μg/L; 190.6 (180.5-202.1) μg/L; 1.5 (1.4-1.7) mmol/L; 13.0 (12.0-14.0)] (all P<0.001). There was statistically significant difference in the mortality rate during hospita lization among three groups of patients ( χ2=30.49, P<0.001). Mortality was higher in shock group than severe group than general group [72.7% (8/11) vs. 11.5% (7/61) vs. 3.6% (1/28), all P<0.001]. Non-survivors exhibited elevated lactate [4.8 (2.7-5.5) vs. 2.6 (1.7-2.8) mmol/L, Z=-4.13, P=0.001], serum HBP [12.2 (9.2-13.3) vs. 9.3 (7.8-10.4) μg/L, Z=-3.12, P=0.002], and infection-site HBP [226.8 (209.9-237.6) vs. 203.6 (194.0-212.8) μg/L, Z=-4.32, P<0.001] vs. survivors. Serum HBP ( r=0.74), infection-site HBP ( r=0.64), and lactate ( r=0.86) were all positively correlated with APACHE Ⅱ (all P<0.001). After adjusting for age and APACHE Ⅱ, elevated serum HBP ( OR=3.743, 95% CI:1.834-7.640), infection-site HBP ( OR=3.540, 95% CI:1.932-6.486), and lactate ( OR=5.155, 95% CI:1.868-14.229) independently predicted mortality (all P<0.001). Combined biomarker detection showed superior predictive value (AUC=0.909) versus individual markers (serum HBP:0.747, infection-site HBP:0.842, lactate:0.827, all P<0.001). Conclusion:Elevated blood lactate and serum/infection-site HBP levels correlate with sepsis severity and independently predict mortality. The biomarker combination provides optimal prognostic stratification.

Objective:To explore the clinical and genetic characteristics and follow-up status of pediatric patients with hepatic glycogen storage disease in order to further improve the prognosis.Methods:The clinical data of hospitalized children diagnosed with hepatic glycogen storage disease in the Department of Gastroenterology at the Children's Hospital of Capital Institute of Pediatrics from January 2010 to April 2023 were collected and retrospectively analyzed. The results of laboratory examination and gene sequencing were analyzed, and the number of cases that exceeded three (n) were grouped according to the genetic results: Group 1 was type Ⅰ ( n=8), Group 2 was type Ⅲ ( n=5), and Group 3 was type Ⅸa ( n=8).The growth, development and prognosis of the children were followed up. The related clinical characteristics of pediatric hepatic glycogen storage disease were summarized. Results:Twenty-five pediatric patients with hepatic glycogen storage disease were enrolled in this study, with fifteen males and ten females. The mean age of diagnosis was (29.1±13.5) months. There were twelve cases (48%) accompanied with varying degrees of hypoglycemia, and two cases (8%) with severe hypoglycemia.There were nineteen cases with stature retardation (76%), four cases with anemia (16%), three cases with proteinuria (12%), and one case with cholestasis (4%).The genetic results showed that there were four cases of type Ⅰa (16%), four cases of type Ⅰb (16%), one case of type Ⅱ (4%), five cases of type Ⅲ (20%), two cases of type Ⅳ (8%), one case of type Ⅵ (4%), and eight cases of type Ⅸ (32%).The three subgroups analysis showed that there were significant statistical differences in uric acid and triglycerides among the three groups ( P<0.05), while there were no statistical significant differences in transaminase levels, fasting blood glucose, lactate, cholesterol, and low-density lipoprotein levels ( P>0.05). The height-for-age Z scores of the three groups were -2.86±1.62, -1.46±1.06, and -1.83±0.98, respectively. The growth and development of groups 2 and 3 were significantly improved compared with group 1 ( P<0.05), with Z scores of -2.28±1.07, 0.20±1.54, and 0.10±1.44 after at least one year of follow-up. All pediatric patients with type Ⅸa had discontinued using raw corn starch after more than one year of follow-up and their transaminases had returned to normal. Four pediatric patients with type Ia were orally administered raw corn starch on a regular basis, and the aminotransferases, uric acid, and lactate were normal, with hypoglycemia being monitored. Among the four cases with type Ⅰb, one had recurrent respiratory tract and intestinal infections, two were combined with Crohn's disease, and one was monitored for hypoglycemia. In four cases of type Ⅲ, raw corn starch was discontinued, and a high-protein, low-carbohydrate diet was adopted, with the exception of the presence of high creatine kinase and normal aminotransferase. Liver failure resulted in the death of one type Ⅵ case, while two were type Ⅳ cases; one died, and one case recently had slightly elevated aminotransferase. Conclusion:When pediatric patients exhibit manifestations such as hepatomegaly, elevated transaminases, fasting hypoglycemia, and delayed growth and development, it is necessary to be alert to hepatic glycogen storage disease. Clinical manifestations and biochemical indicators combined with genetic testing are helpful for the diagnosis of hepatic glycogen storage disease. Simultaneously, targeted nutritional management should be carried out according to the metabolic characteristics of different subtypes, with attention on growth and development status.

Objective:To analyze the clinical characteristics，laboratory tests，endoscopic features，treatment，and follow-up of peptic ulcers caused by eosinophilic gastrointestinal disorders（EGIDs）in children，with the aim of improving the level of understanding，diagnosis and treatment of EGIDs in children with the onset of peptic ulcers.Methods:A retrospective analysis was conducted on children admitted to the Department of Gastroenterology，Capital Center for Children's Health，Capital Medical University from January 1st，2019 to October 31st，2023，who underwent complete endoscopic examination. The first examination showed the presence of peptic ulcers（gastric or duodenal ulcers）under the endoscope，and were ultimately diagnosed with peptic ulcers caused by EGIDs through examination and follow-up. The clinical characteristics，laboratory tests，endoscopic results，and treatment follow-up were analyzed.Results:Thirty-five children were EGIDs，22 males and 13 females.Twenty-two cases（62.9%）had abdominal pain as the main symptom.Laboratory tests：17 cases（48.6%）showed a decrease in hemoglobin，15 cases（42.9%）showed an increase in eosinophil count，20 cases（57.1%）tested gastro positive for food allergen specific IgE，and 17 cases（48.6%）showed thickening of the intestinal wall on gastrointestinal ultrasound. Endoscopic features：8 cases（22.9%）showed gastric antral ulcers，including 7 cases（20.0%）with multiple gastric antral ulcers，and 25 cases（71.4%）showed duodenal bulb ulcers.There were 15 cases（42.9%）showed huge ulcers，and 14 cases（40.0%）were located in the duodenal bulb. Comparison of clinical characteristics between children with EGIDs（EGIDs group）and those with peptic ulcers caused by Helicobacter pylori infection（Hp group）：the first clinical symptom in both groups was mainly abdominal pain，but the incidence rate in the EGIDs group was lower（62.9% vs 93.5%），and the weigth for length Z score in the EGIDs group was lower［0（-1.6，0.8）vs 1.1（0，1.9）］，with statistical significance（all P<0.05）. Comparison of laboratory tests：the EGIDs group showed a statistically significant difference in hemoglobin levels［120（101，124）g/L vs 130（100，138）g/L］，eosinophil count［0.28（0.13，0.71）× 10 9/L vs 0.16（0.08，0.22）×10 9/L］，a positive rate of food allergen specific IgE detection（57.1% vs 32.3%），and a positive rate of intestinal wall thickening detected by gastrointestinal ultrasound（48.6% vs 16.1%）compared with the Hp group（all P<0.05）. Comparison of endoscopic examinations：multiple ulcers in the gastric antrum were more common in the EGIDs group than in the Hp group（20.0% vs 0），and the difference was statistically significant（ P<0.05）. Conclusion:For children with peptic ulcers with onset of abdominal pain，with anemia or malnutrition，or multiple ulcers in the gastric antrum and huge ulcers in the duodenal bulb detected by endoscopy，it is recommended to perform multi site biopsies to help diagnose EGIDs early.

Objective:To retrieve, evaluate and summarize relevant evidence on communication strategies for families with perinatal loss, and to provide an evidence-based basis for communication practice among clinical health professionals.Methods:The system searches for evidence related to the loss of family doctor-patient communication strategies during the perinatal period in computer decision support systems such as UpToDate, BMJ Best Clinical Practice, International Guidelines Network, UK National Institute for Health and Clinical Excellence, PubMed, Web of Science, CINAHL, China National Knowledge Infrastructure, Wanfang Data, as well as in Chinese and English databases and related websites.The search was conducted between January 2012 and December 2022. The literature ′s quality and extracted evidence were independently evaluated by two researchers according to professional judgement. Results:A total of 13 articles were included, including 1 clinical decision, 2 guidelines, 4 national standards, 2 expert consensus, and 4 systematic reviews. 30 pieces of evidence have been summarized across five aspects, comprising communication environment, communication skills, timing and key points of communication, communication for special populations, and system-level communication support.Conclusions:This study summarizes the relevant evidence on communication strategies for family doctor-patient communication strategies for perinatal loss. Clinical professionals should carefully select and apply relevant evidence based on available medical resources and parental preferences, Develop and implement practical standards for family doctor-patient communication strategies for perinatal loss at the system level, further harmonize communication behaviors, and improve communication quality.

ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndromes in intrahepatic cholestasis of pregnancy （ICP） and its association with perinatal outcomes， and to provide a basis for precise treatment based on TCM syndrome differentiation. MethodsA cross-sectional study was conducted among 275 patients with ICP who were admitted to The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from April 2023 to April 2025. A hierarchical cluster analysis was used to summarize TCM syndromes. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. A multivariate Logistic regression analysis was used to identify the clinical features significantly associated with TCM syndrome. ResultsThe cluster analysis identified three core TCM syndromes among the 275 patients with ICP， i.e.， liver-gallbladder damp-heat syndrome （45.8%）， syndrome of blood deficiency generating wind （30.9%）， and liver depression and spleen deficiency syndrome （23.3%）. There was a significant difference in the distribution of TCM syndromes between different groups stratified by maternal age at delivery， parity， history of ICP recurrence， gestational weeks at disease onset， total bile acid （TBA）， alanine aminotransferase （ALT）， and comorbidity with gestational diabetes mellitus （GDM） （all P<0.05）. The multivariate Logistic regression analysis showed that<34 gestational weeks at disease onset was significantly associated with all three syndromes （damp-heat： odds ratio ［OR］=3.769， P<0.001； blood deficiency： OR=4.031， P<0.001； liver stagnation： OR=3.552， P<0.001）. Liver-gallbladder damp-heat syndrome was associated with maternal age ≥35 years at disease onset （OR=2.048， P=0.014）， parity ≥2 times （OR=1.921， P=0.034）， history of ICP recurrence （OR=2.404， P=0.030）， ALT ≥200 U/L （OR=2.051， P=0.018）， comorbidity with GDM （OR=1.944， P=0.029）， and TBA ≥40 μmol/L （OR=2.542， P=0.024）. The syndrome of blood deficiency generating wind syndrome was associated with maternal age ≥35 years （OR=2.939， P=0.003）， parity ≥2 time （OR=3.222， P=0.003）， history of ICP recurrence （OR=3.809， P=0.010）， ALT ≥200 U/L （OR=2.889， P=0.006）， comorbidity with GDM （OR=3.711， P=0.001）， and comorbidity with hypertensive disorders of pregnancy （OR=4.472， P=0.011）. Liver depression and spleen deficiency syndrome was associated with TBA ≥40 μmol/L （OR=2.995， P=0.044）. The analysis of perinatal outcomes showed that there were significant differences in mode of delivery， gestational weeks at the time of delivery， postpartum blood loss， and neonatal birth weight between the three groups with different TCM syndromes （all P<0.05）. ConclusionLiver-gallbladder damp-heat syndrome， syndrome of blood deficiency generating wind， and liver depression and spleen deficiency syndrome are the main TCM syndrome types in ICP， and the distribution of TCM syndromes is closely associated with clinical factors and perinatal outcomes， which provides a basis for precise TCM syndrome differentiation and individualized treatment.

Objective:To discuss the effect of Yes-associated protein(YAP)silencing on the proliferation,migration,and invasion capabilities of the human cervical cancer(CC)SiHa cells.Methods:The human CC SiHa cells were cultured in vitro,and the lentiviral YAP shRNA was transfected into the SiHa cells to establish stably transfected YAP-shRNA experimental group(sh-YAP group)and empty plasmid control group(control group).Western blotting method was used to detect the silencing effect of YAP;immunofluorescence method was used to detect the microfilament number and morphology of actin filaments(F-actin)in the cells in both groups;CCK-8 method was used to detect the survival rates of the cells in two groups;Transwell chamber assay and wound healing assay were used to detect the numbers of migration and invasion cells and scratch healing rates of the cells in two groups;Western blotting method was used to detect the expression levels of epithelial-mesenchymal transition(EMT)markers(E-cadherin and Snail),DNA damage repair-related proteins(γ-H2AX),and apoptosis-related proteins[c-MYC and B-cell lymphoma-2(Bcl-2)]in the cells in two groups.Results:The results of lentiviral YAP shRNA transfection into SiHa cells showed that the expression level of YAP protein in the SiHa cells was significantly decreased(P＜0.05).The immunofluorescence results showed that after YAP silencing,the F-actin in SiHa cells was sparse and regularly arranged,with a reduced number of cells and a shriveled appearance.The CCK-8 results showed that compared with control group,the survival rate of the SiHa cells in sh-YAP group was significantly decreased cultured for 24 and 48 h(P＜0.01).The results of Transwell chamber assay and the wound healing assay showed that compared with control group,the numbers of migration and invasion SiHa cells in sh-YAP group were significantly decreased(P＜0.01),and the cell scratch healing rates were signifiantly decreased(P＜0.05).The Western blotting results showed that compared with control group,the expression level of E-cadherin protein in the cells in sh-YAP group was increased(P＜0.05),and the expression levels of c-MYC,Bcl-2,and γ-H2AX proteins were decreased(P＜0.05 or P＜0.01).Conclusion:YAP gene silencing leads to the depolymerization of F-actin in the human CC SiHa cells and regulates the apoptosis and DNA damage repair,potentially reversing the EMT process,thereby inhibiting the proliferation and migration of the tumor cells.

Objective To analyze the characteristics of HIV-1 pretreatment drug resistance(PDR)and molecular transmission networks in Yubei District,Chongqing,providing evidence for targeted interventions.Methods Using a cross-sectional design,plasma samples were collected from HIV/AIDS patients receiving antiretroviral therapy(ART)in Yubei District from January 2022 to December 2023.Pol gene fragments were extracted and amplified for HIV-1 genotyping and drug resistance analysis.Molecular transmission networks were constructed based on genetic distance calculations.Results Among 478 HIV-1 pol sequences,eight geno-types were identified:with CRF07_BC(60.4%,289/478),CRF08_BC(15.5%,74/478),CRF01_AE(11.7%,56/478),and CRF85_BC(5.9%,28/478).The overall PDR rate was 6.3%(30/478),with resistance to nucleoside reverse transcriptase inhibitors(NRTIs)and non-nucleoside reverse transcriptase inhibitors(NNRTIs)at 1.7%(8/478)and 5.2%(25/478),respectively.No protease inhibitor(PI)resistance was de-tected.The molecular network included 177 cases(37.0%network entry rate),forming 53 clusters with 198 connections.Cluster sizes ranged from 2 to 17 nodes,and 75.3%(149/198)of connections were associated with five subdistricts/towns:Shuanglonghu Street,Huixing Street,Luoqi Town,Gulu Town,and Baoshenghu Street.Conclusion HIV-1 genotypes in Yubei District exhibit diversity and complexity,with moderate PDR prevalence.Regional clustering of transmission networks suggests the need for enhanced molecular surveil-lance and targeted interventions based on analytical findings.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis