ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveTo investigate the mechanism by which Xianglian Huazhuo prescription （XLHZ） ameliorates chronic atrophic gastritis （CAG） through regulating glycolysis via the microRNA-34b-5p （miR-34b-5p）/6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 1 （PFKFB1） signaling pathway. MethodsBioinformatic screening was performed to identify the target genes of miR-34b-5p. In the animal experiments， a mouse model of CAG was established through a combination of N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， ranitidine， and irregular feeding. The mice were randomized into the following groups： normal， model， Morodan group （2 g·kg^-1）， and high-， medium-， and low-dose XLHZ groups（7.2，3.8，1.9 g·kg^-1）. In the cell experiments， GES-1 cells were treated with MNNG for the modeling of CAG and grouped as follows： GES-1， MNNG+GES-1， MNNG+GES-1+XLHZ（10%）， MNNG+GES-1+miR-34b-5p mimics， MNNG+GES-1+miR-34b-5p inhibitor， MNNG+GES-1+PFKFB1 inhibitor， and MNNG+GES-1+PFKFB1 mimics+XLHZ（10%）. The general conditions of mice were observed. Real-time PCR was adopted to measure the expression levels of miRNA-34b-5p and PFKFB1 mRNA in the gastric mucosa of mice in each group. Dual luciferase reporter gene was used to verify the targeting interaction between miR-34b-5p and PFKFB1 in GES-1 cells exposed to MNNG. The cell-counting kit-8 （CCK-8） was used to screen the drug-containing serum concentration. Real-time PCR was employed to verify the transfection efficiency. Fluorescent probes were used to detect the expression and nuclear translocation of hypoxia-inducible factor-1α （HIF-1α） in each group of cells. The protein levels of HIF-1α， hexokinase 2 （HK2）， PFKFB1， phosphofructokinase 1 （PFK1）， and lactate dehydrogenase （LDHA） in the gastric mucosa of mice were determined by Western blot. The levels of glucose consumption and lactate in the serum and cells were measured by biochemical methods. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the content of adenosine triphosphate （ATP） in the gastric mucosa tissue and cells. ResultsThe animal experiments showed that compared with the normal group， the model group exhibited symptoms including mental fatigue， lethargy， sparse and dull fur， a tendency to curl up， sluggish responses， reduced food and water intake， and slow body weight gain. In addition， the model group showed decreased expression of miRNA-34b-5p （P<0.01）， increased mRNA level of PFKFB1 （P<0.01）， upregulated protein levels of HIF-1α， HK2， PFKFB1， PFK1， and LDHA （P<0.01）， and increased glucose consumption， lactate content， and ATP content （P<0.01）. Compared with the model group， the XLHZ group and Morodan group showed improved mental state， gradually improved fur， increased activity， food and water intake， and body weight. HE showed that each treatment group exhibited well arranged and increased gastric mucosal glands， reduced inflammatory cells， and recovered gastric pits. Transmission electron microscopy showed that the size of mitochondria in each treatment group returned to normal， with no obvious irregular shape， complete and clear cristae， and uniform matrix. Furthermore， each treatment group showed increased expression of miRNA-34b-5p （P<0.05）， reduced mRNA level of PFKFB1 （P<0.05）， downregulated protein levels of HIF-1α， HK2， PFKFB1， PFK1， and LDHA （P<0.05）， and decreased glucose consumption， lactic acid， and ATP （P<0.05）. The cell experiments showed that the expression and nuclear translocation of HIF-1α were reduced in all groups after treatment （P<0.05）. The cell transfection efficiency was satisfactory （P<0.05）. miR-34b-5p exhibited an effect comparable to that of XLHZ， effectively inhibiting glycolysis， whereas PFKFB1 promoted glycolysis and reversed the protective effect of XLHZ in CAG mice （P<0.05）. ConclusionXLHZ could regulate the miR-34b-5p/PFKFB1 axis to inhibit glycolysis， thereby ameliorating MNNG-induced gastric mucosal atrophy.

ObjectiveTo investigate the mechanism by which Xianglian Huazhuo prescription （XLHZ） ameliorates chronic atrophic gastritis （CAG） through regulating glycolysis via the microRNA-34b-5p （miR-34b-5p）/6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 1 （PFKFB1） signaling pathway. MethodsBioinformatic screening was performed to identify the target genes of miR-34b-5p. In the animal experiments， a mouse model of CAG was established through a combination of N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， ranitidine， and irregular feeding. The mice were randomized into the following groups： normal， model， Morodan group （2 g·kg^-1）， and high-， medium-， and low-dose XLHZ groups（7.2，3.8，1.9 g·kg^-1）. In the cell experiments， GES-1 cells were treated with MNNG for the modeling of CAG and grouped as follows： GES-1， MNNG+GES-1， MNNG+GES-1+XLHZ（10%）， MNNG+GES-1+miR-34b-5p mimics， MNNG+GES-1+miR-34b-5p inhibitor， MNNG+GES-1+PFKFB1 inhibitor， and MNNG+GES-1+PFKFB1 mimics+XLHZ（10%）. The general conditions of mice were observed. Real-time PCR was adopted to measure the expression levels of miRNA-34b-5p and PFKFB1 mRNA in the gastric mucosa of mice in each group. Dual luciferase reporter gene was used to verify the targeting interaction between miR-34b-5p and PFKFB1 in GES-1 cells exposed to MNNG. The cell-counting kit-8 （CCK-8） was used to screen the drug-containing serum concentration. Real-time PCR was employed to verify the transfection efficiency. Fluorescent probes were used to detect the expression and nuclear translocation of hypoxia-inducible factor-1α （HIF-1α） in each group of cells. The protein levels of HIF-1α， hexokinase 2 （HK2）， PFKFB1， phosphofructokinase 1 （PFK1）， and lactate dehydrogenase （LDHA） in the gastric mucosa of mice were determined by Western blot. The levels of glucose consumption and lactate in the serum and cells were measured by biochemical methods. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the content of adenosine triphosphate （ATP） in the gastric mucosa tissue and cells. ResultsThe animal experiments showed that compared with the normal group， the model group exhibited symptoms including mental fatigue， lethargy， sparse and dull fur， a tendency to curl up， sluggish responses， reduced food and water intake， and slow body weight gain. In addition， the model group showed decreased expression of miRNA-34b-5p （P<0.01）， increased mRNA level of PFKFB1 （P<0.01）， upregulated protein levels of HIF-1α， HK2， PFKFB1， PFK1， and LDHA （P<0.01）， and increased glucose consumption， lactate content， and ATP content （P<0.01）. Compared with the model group， the XLHZ group and Morodan group showed improved mental state， gradually improved fur， increased activity， food and water intake， and body weight. HE showed that each treatment group exhibited well arranged and increased gastric mucosal glands， reduced inflammatory cells， and recovered gastric pits. Transmission electron microscopy showed that the size of mitochondria in each treatment group returned to normal， with no obvious irregular shape， complete and clear cristae， and uniform matrix. Furthermore， each treatment group showed increased expression of miRNA-34b-5p （P<0.05）， reduced mRNA level of PFKFB1 （P<0.05）， downregulated protein levels of HIF-1α， HK2， PFKFB1， PFK1， and LDHA （P<0.05）， and decreased glucose consumption， lactic acid， and ATP （P<0.05）. The cell experiments showed that the expression and nuclear translocation of HIF-1α were reduced in all groups after treatment （P<0.05）. The cell transfection efficiency was satisfactory （P<0.05）. miR-34b-5p exhibited an effect comparable to that of XLHZ， effectively inhibiting glycolysis， whereas PFKFB1 promoted glycolysis and reversed the protective effect of XLHZ in CAG mice （P<0.05）. ConclusionXLHZ could regulate the miR-34b-5p/PFKFB1 axis to inhibit glycolysis， thereby ameliorating MNNG-induced gastric mucosal atrophy.

Objective To explore the effects of plantamajoside on the proliferation and invasion of human gastric cancer cell line BGC823.Methods BGC823 cells were randomly separated into a control group,a plantamajoside group,an AAV-NC(transfection of empty plasmids packaged with lentivirus)group and a plantamajoside+AAV-HIF-1α(transfection of HIF-1α overexpression plasmid packaged with lentivirus)group.Cell proliferation,inva-sion,apoptosis,the numbers of vascular mimicry(VM)lumens and vascular branches,the expression of prolifera-tion,apoptosis,epithelial mesenchymal transition(EMT)related proteins,HIF-1α/VEGF pathway proteins of cells were all examined.Results Compared with control group,the BGC823 cell viability,colony formation num-ber,invasion number,VM lumen number,vascular branch number,and expression of Ki-67,PCNA,vimentin,MMP9,Snail,VEGFA,VE-cadhering,HIF-1α and VEGF protein were all lower in plantamajoside group(P＜0.05).The apoptosis rate,the cleaved Caspase-3,Bax,and E-cadherin protein expression were significantly increased(P＜0.05).Compared with plantamajoside group,the BGC823 cell viability,colony formation number,invasion number,VM lumen number,vascular branch number,and expression of Ki-67,PCNA,vimentin,MMP9,Snail,VEGFA,VE-cadherin,HIF-1α and VEGF protein were higher in the plantamajoside+AAV-HIF-1α group(P＜0.05).The apoptosis rate,the cleaved caspase-3,Bax,and E-cadherin protein expression were lower(P＜0.05).Conclusions Plantamajoside inhibits proliferation,EMT,invasion,and VM of human gastric cancer cell line and induce its apoptosis.

Objective: To investigate the hematological characteristics of the rare McLeod phenotype associated with X-linked chronic granulomatous disease, KEL and XK gene analysis, identification of unexpected antibodies, serological characteristics of high-frequency antigen antibodies, and transfusion strategies. Methods: Serological methods were employed to determine the ABO, Rh, and other blood group system antigen phenotypes of the child, along with screening and identification of unexpected antibodies. The titers of high-frequency antigen antibodies were measured using tube antihuman globulin and microcolumn gel card techniques. Kell blood group typing was performed using serological and genotyping methods, while XK gene sequencing was conducted via next-generation sequencing. Peripheral blood smears from the child's mother were examined for erythrocyte morphology. Results: The child's serological results were as follows: blood group O, ccDEE, MM, Le(a-b+), JK(a+b+), Fy(a+b-), and Kell phenotype K-k+, Kp(a-b+). Plasma analysis revealed alloantibodies anti-C、e, as well as a high-frequency antigen antibody anti-KL, with titers of 512 (tube method) and 2 048 (microcolumn gel method). Genotyping results showed KEL genotype K-k+, Kp(a-b+), Js(a-b+), while XK gene NGS identified a hemizygous deletion of exons 1-3 (XK N. 01), consistent with XK: -1 or Kx-(McLeod). The mother's peripheral blood smear exhibited prominent acanthocytes. Conclusion: The hematological features of this rare McLeod phenotype with X-CGD include weakened Kell antigen expression and a complete exon deletion in the XK gene. Early clinical attention should be given to the symptoms and laboratory diagnosis of X-linked chronic granulomatous disease in pediatric patients. XK genotyping for McLeod phenotype should be prioritized to guide cautious transfusion strategies, preventing life-threatening complications due to incompatible blood products.

Objective:To investigate the correlation between expressions of serum procalcitonin (PCT), T-cell immunogloblin domain, mucin domain 4 (TIM-4) and prognosis of patients with severe pneumonia (SP) treated with bronchoalveolar lavage (BAL).Methods:Data of 497 patients with SP in the Department of Respiratory and Critical Care Medicine of the Affiliated Hospital of Yan'an University from June 2021 to June 2024 were retrospectively analyzed. Patients were divided into good prognosis group [pneumonia severity index (PSI) score<90 points, 289 cases] and poor prognosis group (PSI score≥90 points, 208 cases) according to the prognosis status of patients at 30 days after admission. The clinical data [history of smoking, alcohol consumption, history of hypertension, history of diabetes mellitus, gender, age, body mass index, PSI score after 30 d of admission, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and clinical pulmonary infection score (CPIS) after 14 days of treatment], serum PCT and TIM-4 levels were compared between both groups. Measurement data with normal distribution were expressed as xˉ± s, and t test was used for comparison between groups. Enumeration data were represented as n (%), and the composition ratio between groups was compared by χ2 test. The influencing factors of prognosis of BAL in the treatment of SP were analyzed by multivariate Logistic regression analysis. ROC curve was applied to analyze the diagnostic efficiency of serum PCT and TIM-4 on prognosis of BAL therapy. Results:Age (56.79±11.98) years, APACHEⅡscore (9.98±3.27) and CPIS score (6.54±1.81) in the good prognosis group were younger or lower than those in the poor prognosis group [(62.74±10.57) years, (13.06±4.25), (8.12±1.97)] ( t=5.734, 9.127, 9.250, respectively, P<0.001). The PCT (0.41±0.08) μg/L and TIM-4 (61.79±15.62) ng/L after treatment were higher in the poor prognosis group than those in the good prognosis group [(0.35±0.07) μg/L, (48.76±14.58) ng/L] ( t=8.876, 9.538, respectively, P<0.001). Multivariate Logistic regression analysis suggested that after excluding the interference effects of other factors, PCT ( OR=3.615, 95% CI: 1.641-7.964) and TIM-4 ( OR=4.047, 95% CI: 1.773-9.236) were influencing factors of prognosis in patients with SP receiving BAL therapy ( P=0.002, 0.001). ROC curve analysis indicated that the AUC value of PCT, TIM-4 and the combination of both in the diagnosis of prognosis of BAL therapy of SP were 0.782, 0.828 and 0.887 respectively, all of which had efficiency on predicting prognosis (all P<0.001). The sensitivity and specificity of combined prediction were 88.00% and 72.00%. Conclusion:The expressions of serum PCT and TIM-4 are closely related to the prognosis of SP patients receiving BAL. The PCT, TIM-4 and combination of both are of important reference value for prognosis prediction.

ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective To investigate the changes of 22 bile acid sub components and 17 traditional bio-chemical indicators in serum of patients with non-alcoholic fatty liver disease(NAFLD),and the diagnostic value of detecting the above indicators alone or in combination for NAFLD.Methods A total of 168 NAFLD patients(NAFLD group)and 216 non-NAFLD apparently healthy individuals(non-NAFLD group)were se-lected,bile acid sub components were determined by liquid chromatography tandem mass spectrometry,and traditional biochemical indicators were detected by automatic biochemical analyzer.Results There were sta-tistically significant differences in the levels of 12 bile acid sub components and 12 traditional biochemical indi-cators between NAFLD group and non-NAFLD group(P<0.05).Compared to traditional biochemical indica-tors,bile acid sub components were less affected by body mass index(BMI).The area under the curve for di-agnosing NAFLD by combining three bile acid sub components[taurocholic acid(TCA),sodium taurodeoxy-cholate(TDCA),and tauroursodeoxycholic acid(UDCA)]with three traditional biochemical indicators[ala-nine aminotransferase(ALT),5'Nucleotidase(5'-NT),and small and dense low-density lipoprotein cholester-ol(sd-LDL-C)]was the largest,which was 0.810.Conclusion Twelve kinds of bile acid sub components in the blood of NAFLD patients have changed,and the combined detection of bile acid sub components and tradi-tional biochemical indicators could improve the diagnostic efficacy of NAFLD to a certain extent.