OBJECTIVE To investigate the protective effect of paeoniflorin(PF) on cardiac dysfunction and myocardial cell injury induced by cisplatin(CDDP) in rats. METHODS SD male rats were randomly divided into control group, CPPD group, and CDDP PF+low-dose, high-dose group. PowerLab multifunctional recorder was used to detect the related indexes of cardiac function: the changes of left ventricular peak pressure(LVSP), left ventricular end-diastolic pressure(LVEDP) and left ventricular pressure change rate(±dp/dt). Serum levels of inflammatory factors TNF-α, IL-1β and IL-6 were measured in each group. Myocardial tissue was stained to observe the changes of tissue structure. H9c2 cardiomyocytes were divided into control group, CDDP group, PF group and CDDP+PF group. The activity of H9c2 cardiomyocytes was measured by CCK-8. The apoptosis of cardiomyocytes in each group was detected by flow cytometry. The expressions of MAPK signaling pathway related proteins p38, ERK, JNK and their phosphorylated proteins and apoptosis-related proteins Bax, Bcl-2, Casp3, Cl-casp3 were detected in cardiomyocytes by Western blotting. RESULTS Compared with the control group, LVSP and ±dp/dt decreased, LVEDP increased in rats of CDDP group(P<0.01). Compared with CDDP group, both CDDP+low-dose and high-dose PF pretreatment increased LVSP and ±dp/dt value(P<0.05 or P<0.01), decreased LVEDP(P<0.01), and could decrease the serum inflammatory factor TNF-α, IL-1β and IL-6(P<0.01). Cell level results showed that compared with control group, in CDDP group, the cell activity decreased, the apoptosis-related protein Bax, Cl-casp3 increased(P<0.01), expression of anti-apoptotic protein Bcl-2 decreased(P<0.01), and the expression of p38 and ERK phosphorylation also increased(P<0.01). Compared with CDDP group, PF could restore cell activit, down-regulate apoptosis-related protein Bax, Cl-casp3(P<0.05 or P<0.01), and increase anti-apoptotic protein Bcl-2 expression(P<0.01), inhibit MAPK pathway p38 and ERK phosphorylation expression(P<0.01). CONCLUSION PF can restore cardiac dysfunction and myocardial cell injury induced by cisplatin in rats, which may be related to inhibiting inflammation and apoptosis by regulating ERK/p38 MAPK signal expression.

Objective:To investigate the application value of nectin-4 targeting radiotracer 68Ga-N188 in the diagnosis of pancreatic cancer. Methods:The prospective study was conducted. The clinicopathologic data of 16 patients diagnosed as pancreatic cancer on enhanced computed tomography (CT) who were admitted to the Peking University First Hospital from August to December 2022 were collected. There were 9 males and 7 females, aged (62±8)years. All patients underwent 18F-flurodeoxyglucose ( 18F-FDG) and 68Ga-N188 positron emission tomography (PET)/CT examination. Observation indicators: (1) distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients; (2) expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer; (3) comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Count data were described as absolute numbers or percentages. Results:(1) Distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients. Results of PET/CT examination showed that in 1 hour after injection, the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean) of 68Ga-N188 in fat, muscle, skin, and brain tissues of 16 patients were 0.40±0.16 and 0.25±0.09, 0.68±0.20 and 0.44±0.12, 0.39±0.14 and 0.28±0.11, 0.09±0.04 and 0.05±0.02, respectively. In the tissues of the esophagus, liver, spleen, and pancreas, the above indicators were 1.53±0.48 and 1.16±0.31, 1.49±0.45 and 0.91±0.30, 1.40±0.30 and 1.02±0.24, 1.24±0.31 and 0.96±0.25, respectively. In tumor primary lesion, the above indicators were 3.28±1.02 and 2.14±0.62, respectively, showing significant differences in SUVmax and SUVmean compared with pancreatic tissue ( t=8.03, 6.75, P<0.05). The tumor background ratio in tumor primary lesion based on SUVmax was 1.82±0.58. (2) Expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer. Results of immunohistochemical staining in 16 patients showed that there were 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression. Results of PET/CT examination showed that the SUVmax of 68Ga-N188 in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 3.77±1.10 and 2.64±0.68, showing a significant difference between them ( t=2.64, P<0.05). The SUVmax of 18F-FDG in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 6.73±3.24 and 6.43±3.45, showing no significant difference between them ( t=0.17, P>0.05). (3) Comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Of the 16 patients, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 14 and 11, respectively, for the 14 pancreatic cancer patients diagnosed by postoperative histopathology. Among them, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 3 and 1 for the 3 pancreatic cancer patients receiving evaluation for chemotherapy. The SUVmax of 18F-FDG in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 2.80±0.69 and 6.97±2.11, showing a significant difference between them ( t=3.29, P<0.05). The SUVmax of 68Ga-N188 in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 3.38±1.12 and 2.93±0.50, showing no significant difference between them ( t=0.66, P>0.05). Cases with positive results of lymph node metastases in 68Ga-N188 and 18F-FDG PET/CT were 6 and 4, respectively, for the 6 pancreatic cancer patients diagnosed with lymph node metastases by postoperative histopathology, and the SUVmax of 68Ga-N188 and 18F-FDG in lymph node metastases were 2.25±1.12 and 4.02±1.27. Conclusion:68Ga-N188 PET/CT can be used for imaging diagnosis of tumor primary lesion and lymph node metastases of pancreatic cancer.

With the improvement of surgical techniques and deeper anatomical understanding, the concept of precision surgery has gradually developed. The necessity of traditional extensive organ resection for the treatment of benign and borderline tumors is being challenged due to the high risk of long-term complications. Over the past 40 years, various modified surgical techniques have emerged, with duodenum-preserving pancreatic head resection as a representative procedure. The surgical indications have gradually transitioned from chronic pancreatitis to benign and borderline tumors of the pancreatic head. The extent of resection has evolved from major partial resection and subtotal resection to total resection of the pancreatic head. The surgical approach has also progressed from traditional open surgery to minimally invasive techniques such as laparoscopic or robot-assisted surgery, reflecting updates and optimizations in treatment concepts and surgical methods. This paper discusses the development, surgical indications, and related complications of duodenum-preserving pancreatic head resection. The aim is to provide a reference for the more standardized and rational selection of this surgical procedure in clinical practice while reducing the incidence of complications.

With the improvement of surgical techniques and deeper anatomical understanding, the concept of precision surgery has gradually developed. The necessity of traditional extensive organ resection for the treatment of benign and borderline tumors is being challenged due to the high risk of long-term complications. Over the past 40 years, various modified surgical techniques have emerged, with duodenum-preserving pancreatic head resection as a representative procedure. The surgical indications have gradually transitioned from chronic pancreatitis to benign and borderline tumors of the pancreatic head. The extent of resection has evolved from major partial resection and subtotal resection to total resection of the pancreatic head. The surgical approach has also progressed from traditional open surgery to minimally invasive techniques such as laparoscopic or robot-assisted surgery, reflecting updates and optimizations in treatment concepts and surgical methods. This paper discusses the development, surgical indications, and related complications of duodenum-preserving pancreatic head resection. The aim is to provide a reference for the more standardized and rational selection of this surgical procedure in clinical practice while reducing the incidence of complications.

Objective To investigate the status and influencing factors of pressuring feeding style a-mong caregivers in remote rural areas of Sichuan province.Methods Multistage sampling was conducted to select infants of 6-11 months old who had received complementary food and their caregivers in remote rural areas of Si-chuan province.A questionnaire was used to collect sociodemographic characteristics of infants and their caregivers,pressuring feeding behaviors,feeding environment,and caregivers'negative emotions.Quantile regression was em-ployed to analyze the factors influencing pressuring feeding among caregivers of infants.Results A total of 1358 pairs of infants and their caregivers were included,with the pressuring feeding behavior score of 11(8,14).Parity was the protective factor for caregivers'pressuring feeding(β25=-1.17,P＜0.001;β50=-1.40,P=0.002;β75=-2.18,P＜0.001).Whether infants played with toys while eating(β25=1.00,P＜0.001;β50=1.20,P=0.003;β75=1.42,P＜0.001)and whether infants watched TV/mobile phones(β25=0.50,P=0.048;β50=1.07,P=0.004)were the risk factors.At the 75th percentile,caregivers'negative emotions were the risk factor for pressuring feeding(β75=0.94,P=0.015).Caregivers'education background(β25=0.83,P=0.034;β50=0.87,P=0.021)and family income(β75=1.09,P=0.012)were also significantly associated with pressuring feeding scores at different quartile points.Conclusions Pressuring feeding behaviors of caregivers in remote rural areas of Sichuan province need to be improved.Based on the characteristics of infants and their families,guidance should be carried out to improve the feeding environment and the mental health of caregivers,thereby promoting reasonable feeding behaviors among caregivers of infants in rural areas.

OBJECTIVES: Congenital birth defects are the main source of disease burden among children under 5 years old in China. This study aims to compare the trends in disease burden of different congenital birth defects among Chinese children under 5 years old from 1990 to 2019, and to provide a scientific basis for strengthening the comprehensive prevention and control of birth defects. METHODS: Based on data from the Global Burden Disease (GBD) in 2019, the incidence mortality rate, and disability-adjusted life years (DALYs) rate of congenital birth defects among Chinese children under 5 years old from 1990 to 2019 were selected as evaluation indicators. The Joinpoint regression model was used to analyze the trends in disease burden of different types with congenital birth defects over three decades. The study also compared the differences in disease burden of congenital birth defects among children under 5 years old by gender. RESULTS: Compared to 1990, the DALYs rates of congenital heart anomalies (1 931.91/100 000), digestive congenital anomalies (364.63/100 000), neural tube defects (277.20/100 000), congenital musculoskeletal and limb anomalies (133.33/100 000), and Down syndrome (128.22/100 000) in children under 5 years old in China in 2019 were decreased 70.78%, 71.61%, 86.21%, 36.84% and 73.65%, respectively. From 1990 to 2019, the mortality rates and DALYs rates of different congenital birth defects showed an overall downward trend, but the incidence of digestive congenital anomalies and Down syndrome showed an upward trend after 2005 and 2001, respectively. Except for congenital musculoskeletal and limb anomalies, incidence of the remaining categories of birth defects were higher in boys than that in girls. CONCLUSIONS The disease burden of congenital birth defects in children under 5 years old in China is decreased substantially from 1990 to 2019, but the burden of congenital heart anomalies is still serious and the incidence of some birth defect diseases is on the rise, and it is still crucial to strengthen the prevention and treatment for birth defects in children and propose targeted measures according to their gender characteristics.
Child, Preschool ; Female ; Humans ; Male ; China/epidemiology* ; Cost of Illness ; Down Syndrome/epidemiology* ; East Asian People ; Congenital Abnormalities/epidemiology*

【Objective】 To confirm the role of Wnt signaling pathway in the occurrence and development of gastric cancer （GC）， establish a prognostic model composed of Wnt pathway related genes， and then evaluate the predictive value of the model. 【Methods】 We downloaded the gene expression data and survival data of GC in TCGA database， and used GSEA enrichment analysis to verify the enrichment of Wnt pathway in GC and para-cancer samples. In this study， univariable COX regression analysis and survival curve analysis were used to select the prognosis-related genes of GC. Then the multivariate COX proportional hazard regression model was used to obtain the prognostic model of Wnt signaling pathway related genes. Then， receiver operating characteristic （ROC） curve and forest plot were used to verify the clinical predictive value of the model. The model was then validated in GEO external database. Finally， by utilizing quantitative real-time PCR （qPCR）， we detected the expressions of Wnt signaling pathway related genes in 8 pairs of clinical GC and para-cancer samples. 【Results】 We downloaded 32 samples of normal para-cancer samples and 375 cancer samples and their corresponding clinical data. GSEA enrichment showed that compared with normal samples， Wnt pathway was significantly enriched in GC samples （P<0.05）. The results of univariate COX analysis showed that 13 Wnt pathway genes were closely related to the prognosis of GC patients. Multivariate COX determined that the model was multiplied and accumulated by ETV2， SERPINE1， CPZ， VPS35 and IGFBP1 and their corresponding coefficient β. The survival curve and ROC curve showed that the model could accurately predict the prognosis of GC patients， and the 1-year， 3-year， and 5-year areas under the curve （AUC） were 68.0%， 69.4% and 78.5%， respectively. Clinical univariate and multivariate COX analyses showed that the model could become an independent prognostic factor other than TNM system of GC. The external data set （GSE84437） validation results of GC showed that the model could better predict the prognosis of GC patients. qPCR results indicated that ETV2， SERPINE1， CPZ， VPS35 and IGFBP1 expressions were upregulated in GC samples compared with para-cancer samples. 【Conclusion】 This study further confirmed that Wnt pathway plays an important role in the progress of GC from the perspective of bioinformatics， and we have established a prognosis-related risk model， providing a new perspective for clinical genetic testing， targeted therapy and individualized therapy.

Objective By analyzing the incidence, prevalence, mortality, Disability Adjusted of Life Years (DALY) situations and trends of AIDS in China from 1990 to 2019, this paper provides scientific basis for the preventions and controls of AIDS in China. Methods The incidence, prevalence, mortality and DALY rate of AIDS from 1990 to 2019 are obtained from GBD 2019 data. The standardardized rate of four indicators are used to compare and analyze the AIDS changes in China, the United States, Japan and the global with the development of years. Results The four indicators of AIDS in China present increasing trends, with male higher than female. The incidence rate increased from 0.82/100 000 in 1990 to 2.24/100 000 in 2019, the prevalence increased from 5.63/100 000 to 38.77/100 000, and the mortality increased from 0.23/100 000 to 2.23/100 000. The DALY rate increased from 13.18/100 000 to 98.15/100 000. Compared with the global and the United States, the standardized rate of four indicators of AIDS in China in 2019 showed a trend of low level, but it was higher than that in Japan. Conclusion In recent years, some progress has been made in AIDS preventions and controls in China, but the disease burden of AIDS is still on the rise. The situation of AIDS preventions and controls is still serious and unremitting efforts should be made to reduce the burden of AIDS.

Objective:To establish a LC-MS/MS method for determination of paraquat and diquat in plasma and urine samples.Methods:Plasma is precipitated by acetonitrile then diluent with phosphate buffer (pH=7) , urine is diluent with phosphate buffer (pH=7) , then diluent samples extracted with Oasis WCX solid-phase extraction column. Samples were analyzed using LC-MS/MS in multiple reaction monitoring (MRM) mode. The analytical column was XBridge?BEH-HILIC (100 mm×2.1 mm×2.5 μm) and the mobile phase were 100 mmol ammonium formate add 0.5% formic acid and acetonitrile. Paraquat was quantified by internal standard method and diquat by external standard method.Results:The calibration curves of paraquat and diquat were linear in the concentration range of 10.0~120.0 μg/L, the correlation coefficient (r) were 0.9985~0.9994. The limit of detection of paraquat in plasma and urine were 1.98 μg/L and 1.00 μg/L, respectively, the recovery rate were 100.2%~107.3%, the RSD were 1.6%~3.3%. The limit of detection of diquat in plasma and urine were 1.80 μg/L and 2.77 μg/L, respectively, the recovery rate were 85.3%~93.1%, the RSD were 1.8%~5.5%. Conclusion:This method is sensitive and accurate, and can simultaneously determine paraquat and diquat in plasma and urine.

Objective:To establish a LC-MS/MS method for determination of paraquat and diquat in plasma and urine samples.Methods:Plasma is precipitated by acetonitrile then diluent with phosphate buffer (pH=7) , urine is diluent with phosphate buffer (pH=7) , then diluent samples extracted with Oasis WCX solid-phase extraction column. Samples were analyzed using LC-MS/MS in multiple reaction monitoring (MRM) mode. The analytical column was XBridge?BEH-HILIC (100 mm×2.1 mm×2.5 μm) and the mobile phase were 100 mmol ammonium formate add 0.5% formic acid and acetonitrile. Paraquat was quantified by internal standard method and diquat by external standard method.Results:The calibration curves of paraquat and diquat were linear in the concentration range of 10.0~120.0 μg/L, the correlation coefficient (r) were 0.9985~0.9994. The limit of detection of paraquat in plasma and urine were 1.98 μg/L and 1.00 μg/L, respectively, the recovery rate were 100.2%~107.3%, the RSD were 1.6%~3.3%. The limit of detection of diquat in plasma and urine were 1.80 μg/L and 2.77 μg/L, respectively, the recovery rate were 85.3%~93.1%, the RSD were 1.8%~5.5%. Conclusion:This method is sensitive and accurate, and can simultaneously determine paraquat and diquat in plasma and urine.