Objective:To construct an in situ pancreatic tumor model in mice and explore the mechanism of neuromedin U (NMU) remodeling the metabolic microenvironment of pancreatic tumors via the Hedgehog signaling pathway.Methods:C57BL/6 NMU -/- heterozygous mice were bred in one cage with a female-to-male ratio of 2:1. The tail tissues of offspring rats were taken, and knockout primers were designed according to the sequence structure of NMU gene. The C57BL/6 NMU -/- mouse genotypes were identified by polymerase chain reaction (PCR) and agarose gel electrophoresis. Five C57BL/6 NMU -/- homozygotes and five wild type mice aged 8 to 9 weeks were selected, and Panc02 cell suspension of pancreatic cancer in logarithmic growth phase was injected into pancreatic tail tissue to construct tumor bearing mice model of pancreatic tumor in situ. After 3 weeks of tumor loading, flow cytometry was used to detect the abundance changes of CD8 + T cells in the spleen tissues of two groups of mice. GSE102238 (data published in August 2017) and GSE62452 (data published in July 2016) datasets were download from the Gene Expression Omnibus (GEO) database, including 119 samples of pancreatic cancer tissue and 111 samples of normal pancreatic tissue adjacent to cancer, and the differential expression factors of the two groups of samples were screened. R language limma package was used to analyze the differential expression of NMU mRNA in pancreatic cancer tissues and adjacent normal tissues; the relative expression level of NMU mRNA in pancreatic cancer patients of different ages and tumor grades was analyzed by ggpubr package. The relative expression level data of NMU mRNA in pancreatic tumor patients were extracted, and the patients were divided into high expression group (>2.48) and low expression group (<2.48) based on the median value (2.48). The CIBERSORT algorithm was used to calculate the difference in the content of infiltrating immune cells in pancreatic tumors between the two groups of patients. The overall survival of patients with different relative expression levels of NMU mRNA in the OncoLnc database (59 cases in the high expression group and 59 cases in the low expression group) was compared. The data of 178 patients with pancreatic cancer in TCGA-PAAD of The Cancer Genome Atlas (TCGA) database (updated in March 2024) were download. According to the median value of relative expression of NMU mRNA (2.740), the patients were divided into the high expression group (>2.740) and the low expression group (<2.740), with 89 cases in each group. GSEA software was used to analyze the biological functions and pathways in which the genes enriched significantly. The molecules and key targets for molecular docking were explored using the large molecule protein interaction tool PDBePISA. Spearman correlation analysis was performed using R language data packets. Results:The results of C57BL/6 NMU -/- mouse genotypes analyzed by using the gel electrophoresis pattern of PCR amplification products of tail tissues showed that the wild type was one 380 bp electrophoretic band, the homozygous type was one 450 bp electrophoretic band, and the heterozygous type was 450 bp and 380 bp electrophoretic bands. After identifying and screening pure strains mouse, reproduction was carried out, and C57BL/6 NMU -/- homozygous mice were successfully obtained. The results of flow cytometry analysis showed that the proportion of CD8 + T cells in the spleen tissues of C57BL/6 NMU -/- wild-type and homozygous pancreatic tumor bearing mice was (30.38±0.37)% and (37.00±0.48)%, with a statistically significant difference between the two groups ( t = 9.79, P < 0.001). The absolute values of CD8 + T cells were (8.36±0.27)×10 4 and (10.20±0.28)×10 4, respectively, and the difference was statistically significant ( t = 3.71, P = 0.013). In the GEO database GSE102238 and GSE62452 datasets, there were differentially expressed genes in pancreatic cancer tissues compared with adjacent tissues, including 219 up-regulated genes and 325 down-regulated genes in pancreatic cancer tissues; among them, NMU was an upregulated differentially expressed gene. The relative expression of NMU mRNA in patients aged > 65 year or grade G3-G4 was higher than that in patients aged ≤ 65 years or grade G1-G2, and the differences were statistically significant (both P < 0.05). The analysis results of CIBERSORT algorithm showed that the expression abundance of CD8 + T cells, initial CD4 + T cells, activated memory CD4 + T cells, and γδ T cells in the high expression group of NMU was lower than that in the low expression group (all P < 0.05). The overall survival of the high expression group of NMU was worse than that of the low expression group in the OncoLnc database ( P = 0.010). GSEA enrichment analysis and Spearman correlation analysis revealed significant changes in the Hedgehog signaling pathway, biosynthesis of unsaturated fatty acids and pyrimidine nucleotide metabolism, which affected tumor metabolic remodeling. Conclusions:NMU may remodel the tumor microenvironment of pancreatic cancer by regulating Hedgehog signaling pathway.

Psoriasis is a chronic inflammatory skin disease with worldwide prevalence,primarily characterized by epidermal hyperplasia,abnormal keratinization,and immune cell infiltration,with a significant negative impact on patients' quality of life and mental well-being.The onset of psoriasis is closely associated with genetic susceptibility,immune dysregulation,and environmental factors.Despite research progress into the pathogenesis of psoriasis,existing treatment method still face problems including limited efficacy and obvious side effects.There is thus an urgent need for an in-depth analysis of its pathological network and the development of novel interventional strategies.The imiquimod-induced psoriasis animal model has accordingly become a crucial tool for studying psoriasis owing to its high reproducibility and excellent pathological simulation.This review systematically summarizes the core mechanism of action of the imiquimod-induced psoriasis model,expounds on the molecular basis of its action via pathways such as the cascade reaction of the core immune-inflammatory axis,the multi-regulatory network of downstream synergistic mechanisms,and the interaction between host and environmental factors.Research based on this model has successfully verified the therapeutic effects of various targeted therapies and natural products on psoriasis,demonstrating its important application value in therapeutic interventional research.We also discuss the limitations of the imiquimod-induced psoriasis model,and indicate future research directions,with the aim of providing references for further in-depth research and the treatment of psoriasis.

Psoriasis is a chronic inflammatory skin disease with worldwide prevalence,primarily characterized by epidermal hyperplasia,abnormal keratinization,and immune cell infiltration,with a significant negative impact on patients' quality of life and mental well-being.The onset of psoriasis is closely associated with genetic susceptibility,immune dysregulation,and environmental factors.Despite research progress into the pathogenesis of psoriasis,existing treatment method still face problems including limited efficacy and obvious side effects.There is thus an urgent need for an in-depth analysis of its pathological network and the development of novel interventional strategies.The imiquimod-induced psoriasis animal model has accordingly become a crucial tool for studying psoriasis owing to its high reproducibility and excellent pathological simulation.This review systematically summarizes the core mechanism of action of the imiquimod-induced psoriasis model,expounds on the molecular basis of its action via pathways such as the cascade reaction of the core immune-inflammatory axis,the multi-regulatory network of downstream synergistic mechanisms,and the interaction between host and environmental factors.Research based on this model has successfully verified the therapeutic effects of various targeted therapies and natural products on psoriasis,demonstrating its important application value in therapeutic interventional research.We also discuss the limitations of the imiquimod-induced psoriasis model,and indicate future research directions,with the aim of providing references for further in-depth research and the treatment of psoriasis.

Objective:To construct an in situ pancreatic tumor model in mice and explore the mechanism of neuromedin U (NMU) remodeling the metabolic microenvironment of pancreatic tumors via the Hedgehog signaling pathway.Methods:C57BL/6 NMU -/- heterozygous mice were bred in one cage with a female-to-male ratio of 2:1. The tail tissues of offspring rats were taken, and knockout primers were designed according to the sequence structure of NMU gene. The C57BL/6 NMU -/- mouse genotypes were identified by polymerase chain reaction (PCR) and agarose gel electrophoresis. Five C57BL/6 NMU -/- homozygotes and five wild type mice aged 8 to 9 weeks were selected, and Panc02 cell suspension of pancreatic cancer in logarithmic growth phase was injected into pancreatic tail tissue to construct tumor bearing mice model of pancreatic tumor in situ. After 3 weeks of tumor loading, flow cytometry was used to detect the abundance changes of CD8 + T cells in the spleen tissues of two groups of mice. GSE102238 (data published in August 2017) and GSE62452 (data published in July 2016) datasets were download from the Gene Expression Omnibus (GEO) database, including 119 samples of pancreatic cancer tissue and 111 samples of normal pancreatic tissue adjacent to cancer, and the differential expression factors of the two groups of samples were screened. R language limma package was used to analyze the differential expression of NMU mRNA in pancreatic cancer tissues and adjacent normal tissues; the relative expression level of NMU mRNA in pancreatic cancer patients of different ages and tumor grades was analyzed by ggpubr package. The relative expression level data of NMU mRNA in pancreatic tumor patients were extracted, and the patients were divided into high expression group (>2.48) and low expression group (<2.48) based on the median value (2.48). The CIBERSORT algorithm was used to calculate the difference in the content of infiltrating immune cells in pancreatic tumors between the two groups of patients. The overall survival of patients with different relative expression levels of NMU mRNA in the OncoLnc database (59 cases in the high expression group and 59 cases in the low expression group) was compared. The data of 178 patients with pancreatic cancer in TCGA-PAAD of The Cancer Genome Atlas (TCGA) database (updated in March 2024) were download. According to the median value of relative expression of NMU mRNA (2.740), the patients were divided into the high expression group (>2.740) and the low expression group (<2.740), with 89 cases in each group. GSEA software was used to analyze the biological functions and pathways in which the genes enriched significantly. The molecules and key targets for molecular docking were explored using the large molecule protein interaction tool PDBePISA. Spearman correlation analysis was performed using R language data packets. Results:The results of C57BL/6 NMU -/- mouse genotypes analyzed by using the gel electrophoresis pattern of PCR amplification products of tail tissues showed that the wild type was one 380 bp electrophoretic band, the homozygous type was one 450 bp electrophoretic band, and the heterozygous type was 450 bp and 380 bp electrophoretic bands. After identifying and screening pure strains mouse, reproduction was carried out, and C57BL/6 NMU -/- homozygous mice were successfully obtained. The results of flow cytometry analysis showed that the proportion of CD8 + T cells in the spleen tissues of C57BL/6 NMU -/- wild-type and homozygous pancreatic tumor bearing mice was (30.38±0.37)% and (37.00±0.48)%, with a statistically significant difference between the two groups ( t = 9.79, P < 0.001). The absolute values of CD8 + T cells were (8.36±0.27)×10 4 and (10.20±0.28)×10 4, respectively, and the difference was statistically significant ( t = 3.71, P = 0.013). In the GEO database GSE102238 and GSE62452 datasets, there were differentially expressed genes in pancreatic cancer tissues compared with adjacent tissues, including 219 up-regulated genes and 325 down-regulated genes in pancreatic cancer tissues; among them, NMU was an upregulated differentially expressed gene. The relative expression of NMU mRNA in patients aged > 65 year or grade G3-G4 was higher than that in patients aged ≤ 65 years or grade G1-G2, and the differences were statistically significant (both P < 0.05). The analysis results of CIBERSORT algorithm showed that the expression abundance of CD8 + T cells, initial CD4 + T cells, activated memory CD4 + T cells, and γδ T cells in the high expression group of NMU was lower than that in the low expression group (all P < 0.05). The overall survival of the high expression group of NMU was worse than that of the low expression group in the OncoLnc database ( P = 0.010). GSEA enrichment analysis and Spearman correlation analysis revealed significant changes in the Hedgehog signaling pathway, biosynthesis of unsaturated fatty acids and pyrimidine nucleotide metabolism, which affected tumor metabolic remodeling. Conclusions:NMU may remodel the tumor microenvironment of pancreatic cancer by regulating Hedgehog signaling pathway.

Objective To investigate the influencing factors for chronic pancreatitis(CP)complicated by pancreatogenic portal hypertension(PPH),and to establish a predictive model.Methods A retrospective analysis was performed for the clinical data of 99 patients with CP complicated by PPH who were hospitalized in The First Affiliated Hospital of Kunming Medical University,Chuxiong Yi Autonomous Prefecture People's Hospital,Wenshan People's Hospital,and Puer People's Hospital from January 2017 to December 2022,and these patients were enrolled as PPH group.The incidence density sampling method was used to select 198 CP patients from databases as control group.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.The Least Absolute Shrinkage and Selection Operator(LASSO)regression model was used to identify the potential predictive factors for CP complicated by PPH,and the predictive factors obtained were included in the multivariate Logistic regression analysis to obtain independent risk factors,which were used to establish a nomogram prediction model.The receiver operating characteristic(ROC)curve,the calibration curve,and the Hosmer-Lemeshow goodness-of-fit test were used to perform internal validation of the model,and the clinical decision curve was used to assess the clinical practicability of the model.Results There were significant differences between the two groups in sex,history of recurrent acute pancreatitis attacks,acute exacerbation of CP,bile duct stones,peripancreatic fluid accumulation,pseudocysts,pulmonary infection,elevated C-reactive protein(CRP),elevated procalcitonin,fibrinogen(FIB),neutrophil-lymphocyte ratio(NLR),gamma-glutamyl transpeptidase,total bilirubin,direct bilirubin,low-density lipoprotein(LDL),serum amylase,D-dimer,and serum albumin(all P<0.05).The predictive variables obtained by the LASSO regression analysis included sex,recurrent acute pancreatitis attacks,bile duct stones,peripancreatic fluid accumulation,pulmonary infection,pseudocysts,CRP,NLR,FIB,and LDL.The multivariate Logistic regression analysis showed that sex(odds ratio[OR]=2.716,P<0.05),recurrent acute pancreatitis attacks(OR=2.138,P<0.05),peripancreatic fluid accumulation(OR=2.297,P<0.05),pseudocysts(OR=2.805,P<0.05),and FIB(OR=1.313,P<0.05)were independent risk factors for CP complicated by PPH.The above factors were fitted into the model,and the Bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.787(95%confidence interval:0.730—0.844),and the calibration curve was close to the reference curve.The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good degree of fitting(χ2=7.469,P=0.487).The clinical decision curve analysis showed that the prediction model had good clinical practicability.Conclusion Male sex,recurrent acute pancreatitis attacks,peripancreatic fluid accumulation,pseudocysts,and FIB are independent risk factors for CP complicated by PPH,and the nomogram model established has good discriminatory ability,calibration,and clinical practicability.

Objective:To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated with pancreatogenic portal hypertension (PPH) and to establish a prediction model.Methods:From January 1, 2016 to December 31, 2022, a total of 1 095 patients diagnosed with MSAP or SAP at the First Affiliated Hospital of Kunming Medical University were enrolled and divided into PPH group (145 cases) and non-PPH group (950 cases) according to the presence or absence of concomitant PPH. The general data (gender, etiology of acute pancreatitis, days of hospitalization, etc.), complications (portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, etc.), laboratory indicators (albumin, D-dimer, etc.), and scores of modified computed tomography severity index (MCTSI) were collected in the two groups. The least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression analysis were performed to analyze the independent risk factors of MSAP and SAP complicated with PPH, and the nomogram prediction model was established. The area under the curve of the receiver operating characteristic curve was calculated to evaluate the discrimination of the calibration curve and Hosmer-Lemeshow goodness of fit test were used to assess the predictive accuracy of the model, and clinical decision curve analysis (DCA) was used to evaluate the clinical practicability of the model.Results:The results of LASSO and multivariate logistic regression analysis showed that portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin were independent risk factors of MSAP and SAP complicated with PPH ( OR=7.013, 2.085, 1.846, 1.030, 1.235 and 0.955; 95% confidence interval 4.061 to 12.112, 1.255 to 3.463, 1.066 to 3.199, 1.013 to 1.047, 1.123 to 1.357 and 0.927 to 0.983; all P<0.05). The area under the curve of the model was 0.820 (95% confidence interval 0.780 to 0.859), the calibration curve was close to the reference curve, and the Hosmer-Lemeshow goodness-fit test showed that the model had a good fit ( χ2=9.82, P=0.278). The result of DCA indicated that the model had a high net benefit in a wide range of risk threshold (threshold probability 0.1 to 0.9), and had certain clinical practicability. Conclusions:Portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin are the independent risk factors of MSAP and SAP complicated with PPH. The established nomogram model has good differentiation, calibration and clinical practicability.

Objective:To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated with pancreatogenic portal hypertension (PPH) and to establish a prediction model.Methods:From January 1, 2016 to December 31, 2022, a total of 1 095 patients diagnosed with MSAP or SAP at the First Affiliated Hospital of Kunming Medical University were enrolled and divided into PPH group (145 cases) and non-PPH group (950 cases) according to the presence or absence of concomitant PPH. The general data (gender, etiology of acute pancreatitis, days of hospitalization, etc.), complications (portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, etc.), laboratory indicators (albumin, D-dimer, etc.), and scores of modified computed tomography severity index (MCTSI) were collected in the two groups. The least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression analysis were performed to analyze the independent risk factors of MSAP and SAP complicated with PPH, and the nomogram prediction model was established. The area under the curve of the receiver operating characteristic curve was calculated to evaluate the discrimination of the calibration curve and Hosmer-Lemeshow goodness of fit test were used to assess the predictive accuracy of the model, and clinical decision curve analysis (DCA) was used to evaluate the clinical practicability of the model.Results:The results of LASSO and multivariate logistic regression analysis showed that portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin were independent risk factors of MSAP and SAP complicated with PPH ( OR=7.013, 2.085, 1.846, 1.030, 1.235 and 0.955; 95% confidence interval 4.061 to 12.112, 1.255 to 3.463, 1.066 to 3.199, 1.013 to 1.047, 1.123 to 1.357 and 0.927 to 0.983; all P<0.05). The area under the curve of the model was 0.820 (95% confidence interval 0.780 to 0.859), the calibration curve was close to the reference curve, and the Hosmer-Lemeshow goodness-fit test showed that the model had a good fit ( χ2=9.82, P=0.278). The result of DCA indicated that the model had a high net benefit in a wide range of risk threshold (threshold probability 0.1 to 0.9), and had certain clinical practicability. Conclusions:Portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin are the independent risk factors of MSAP and SAP complicated with PPH. The established nomogram model has good differentiation, calibration and clinical practicability.

To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022. Two authors independently extracted data and assessed study quality. Qualitative and quantitative analysis of data were performed. The review was registered in the PROSPERO database (CRD42022345476). Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], −1.61;95% confidence interval [95% CI], −2.44 to −0.79; p ＜ 0.001), attention deficit hyperactivity disorders (SMD, −0.39; 95% CI, −0.78 to −0.00; p = 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, −0.86; 95% CI, −1.48 to −0.24; p = 0.006) compared with control group, but showed no difference between depression group (SMD, −0.06; 95% CI, −0.15 to 0.03; p = 0.17) and the control group. Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63−0.98; p = 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69−0.99; p = 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

OBJECTIVE: To survey the residents for their understanding of Coronavirus Disease 2019 (COVID-19)-related knowledge, attitude and practices (KAP) in two hard hit provinces of China to facilitate the governmental decisions on strategies against the disease. METHODS: We invited the participants from Hubei and Henan Provinces of China for an internetbased survey starting from 12:00 on February 21, 2020 to 12:00 on February 23. The survey included the general conditions, KAP of COVID-19, psychological status and living conditions of the residents. RESULTS: The effective response rate of the questionnaire was 98.9%. The mean (P25, P75) age of the participants was 19 (16, 40) years, and 54.3% of them were students. Social media were the most important source of information concerning the pandemic of the respondents. The respondents had a high awareness of person-to-person transmission of the virus through the respiratory tract or droplets but showed a relatively low level of awareness of the population susceptible to COVID-19 and its specific symptoms. The results of multivariate analysis showed that women, undergraduate students (including college students) and higher degree holders had better knowledge of COVID-19 ( < 0.05); the proportion of respondents who expressed to have different levels of psychological stressed such as worry, anxiety and panic reached 77.2%; 16.7% of the responders considered psychological interventions necessary for their psychological conditions; 63.6% of the respondents confessed a bias against the people returning from Hubei and Henan provinces, while 22.4% worried that they might be biased because of their residence in Hubei and Henan. The rate of personal protective equipment shortage was as high as 69.4%; the rates of the responders who would "covering the mouth and nose when coughing or sneezing", "properly use masks in accordance with regulations", "maintain proper hand hygiene ", "avoid gatherings with relatives and friends" and "refrain from going to public places" were 92.4%, 95.9%, 93.5%, 88.8% and 93.1%, respectively. Women and groups with good knowledge of the disease reported better protective behaviors against the diseases ( < 0.05). CONCLUSIONS The residents in Hubei and Henan Provinces have generally good KAP related to COVID-19, and the online platforms plays a positive role to in circulating epidemic-related information. It is essential to further increase the supply of the protective materials and pay more attention to the mental health of the residents during the pandemic, and psychological counseling and psychological protection should be provided if necessary.
Attitude ; Betacoronavirus ; Coronavirus Infections ; Female ; Humans ; Pandemics ; Pneumonia, Viral