ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

Gastric cancer, a highly malignant tumor, has seen a persistent rise in global incidence in recent years. Claudin 18.2, a protein with highly specific expression in gastric cancer, has emerged as a prominent research target in therapeutic development. The overexpression of Claudin 18.2 in gastric cancer cells and its abnormal surface exposure provide novel opportunities for targeted and immunotherapeutic interventions. Therapeutic approaches targeting Claudin 18.2 have shown promising initial results in clinical trials, primarily including monoclonal antibodies and chimeric antigen receptor T-cell therapies. The authors systematically summarize the biological characteristics, mechanism of action, clinical research progress, and future treatment prospects and challenges of Claudin 18.2.

Objective:To explore the association between different feeding methods during the first six months after birth and the physical growth of children aged 3 to 5 years.Methods:Data were from the "Taicang and Wuqiang mother-child cohort study"(TAWS) in China. Children were enrolled at birth between November 2016 and September 2020 and followed up at 1, 2, 3, 6, 8, 12, 18, and 24 months, as well as at ages 3 to 5 years. Based on feeding methods within six months of age, children were categorized into an "exclusive breastfeeding group" and a "formula-feeding group". Birth-related information and feeding practices between 8 and 24 months were collected, alongside dietary habits, physical activity, and illness during preschool years. Height and weight of preschool children were measured to calculate height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), body mass index-for-age Z-score (BAZ), and the rates of stunting, underweight, wasting, overweight, and obesity. After adjusting for demographic factors, birth-related information, feeding practices between 8 to 24 months, preschool dietary habits, physical activity, and health status, multiple linear regression and logistic regression were adopted to analyze the influence of feeding methods within six months of age on the physical growth of children aged 3 to 5 years.Results:A total of 1 233 children were included, comprising 629 boys and 604 girls. The number of children aged 3, 4, and 5 years was 436, 406, and 391, respectively. About 754 children were categorized into the exclusive breastfeeding group and 479 into the formula-feeding group. Children who were introduced to formula milk within six months of age had higher HAZ (0.09±0.99), WAZ (0.24±1.07) and BAZ (0.26±1.11) scores at ages 3 to 5 compared to the exclusive breastfeeding group [HAZ, WAZ, and BAZ were (-0.04±0.92), (0.06±1.02) and (0.11±1.08), respectively]. After adjusting for confounding factors, multiple linear regression analysis showed that the β (95% CI) values for HAZ, WAZ and BAZ in the formula-feeding group were 0.16 (0.06-0.25), 0.17 (0.06-0.29) and 0.15 (0.02-0.27), respectively, compared to the exclusive breastfeeding group. After adjusting for confounding factors, the results of the multivariate logistic regression model indicated that there were no statistically significant differences in the risks of stunting, underweight, wasting, overweight, and obesity during the preschool years between the exclusive breastfeeding group and the formula-feeding group, with OR (95% CI) values of 1.04 (0.41-2.62), 0.99 (0.27-3.57), 1.63 (0.53-4.95), 1.08 (0.66-1.74), and 1.58 (0.70-3.60), respectively. Conclusion:Exclusive breastfeeding within six months of age does not increase the risk of undernutrition (including stunting, underweight or wasting) during preschool years. However, the introduction of formula feeding within six months of age significantly increases the physical growth level of the preschool stage.

Adenosine triphosphate(ATP),as a rich energy currency in cells,is released into the extracellular space through a variety of regulatory mechanisms.The role of extracellular ATP(eATP)and related purine and pyrimidine nucleotides as extracellu-lar signal molecules regulating immune cell function has been reported as evidence of purine signal transduction and has become the focus of attention as a therapeutic target for various diseases.Mast cells(MC)are distributed in tissues that come into contact with the external environment and are the first immune cells to respond to non-microbial environmental antigens.Although eATP is considered to be an activator of MC,the details remain to be further elucidated.This article describes the role of purine receptor signaling in MC degranulation.It expands the further understanding of the mechanism of allergic diseases,and further provides ideas for finding new targets for the treatment of allergic diseases and formulating new treatment strategies.

The reverse phase nystagmus is not uncommon in clinical practice.Inadequate understanding brings great confusion to clinical diagnosis and treatment,which leads to misdiagnosis frequently and also increases the eco-nomic burden on patients.The purpose of this paper is to summarize and analyze the mechanism,characteristics and clinical significance of reverse phase nystagmus,to help clinicians better understand the significance of inversion nys-tagmus in benign paroxysmal positional vertigo,in order to achieve accurate and efficient diagnosis and treatment of these patients.

Objective:To explore the association between different feeding methods during the first six months after birth and the physical growth of children aged 3 to 5 years.Methods:Data were from the "Taicang and Wuqiang mother-child cohort study"(TAWS) in China. Children were enrolled at birth between November 2016 and September 2020 and followed up at 1, 2, 3, 6, 8, 12, 18, and 24 months, as well as at ages 3 to 5 years. Based on feeding methods within six months of age, children were categorized into an "exclusive breastfeeding group" and a "formula-feeding group". Birth-related information and feeding practices between 8 and 24 months were collected, alongside dietary habits, physical activity, and illness during preschool years. Height and weight of preschool children were measured to calculate height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), body mass index-for-age Z-score (BAZ), and the rates of stunting, underweight, wasting, overweight, and obesity. After adjusting for demographic factors, birth-related information, feeding practices between 8 to 24 months, preschool dietary habits, physical activity, and health status, multiple linear regression and logistic regression were adopted to analyze the influence of feeding methods within six months of age on the physical growth of children aged 3 to 5 years.Results:A total of 1 233 children were included, comprising 629 boys and 604 girls. The number of children aged 3, 4, and 5 years was 436, 406, and 391, respectively. About 754 children were categorized into the exclusive breastfeeding group and 479 into the formula-feeding group. Children who were introduced to formula milk within six months of age had higher HAZ (0.09±0.99), WAZ (0.24±1.07) and BAZ (0.26±1.11) scores at ages 3 to 5 compared to the exclusive breastfeeding group [HAZ, WAZ, and BAZ were (-0.04±0.92), (0.06±1.02) and (0.11±1.08), respectively]. After adjusting for confounding factors, multiple linear regression analysis showed that the β (95% CI) values for HAZ, WAZ and BAZ in the formula-feeding group were 0.16 (0.06-0.25), 0.17 (0.06-0.29) and 0.15 (0.02-0.27), respectively, compared to the exclusive breastfeeding group. After adjusting for confounding factors, the results of the multivariate logistic regression model indicated that there were no statistically significant differences in the risks of stunting, underweight, wasting, overweight, and obesity during the preschool years between the exclusive breastfeeding group and the formula-feeding group, with OR (95% CI) values of 1.04 (0.41-2.62), 0.99 (0.27-3.57), 1.63 (0.53-4.95), 1.08 (0.66-1.74), and 1.58 (0.70-3.60), respectively. Conclusion:Exclusive breastfeeding within six months of age does not increase the risk of undernutrition (including stunting, underweight or wasting) during preschool years. However, the introduction of formula feeding within six months of age significantly increases the physical growth level of the preschool stage.

Objective:To examine the role of intestinal macrophages and the mechanism by which they produce reactive oxygen species (ROS) in abdominal pain induced by food antigens in mice with visceral hypersensitivity.Methods:Mouse models of visceral hypersensitivity were established by subjecting animals to acute cold restraint stress (ACRS) or acetic acid enema (AAE). Visceral sensitivity was evaluated using food antigen ovalbumin (OVA)-induced responses and rectal reflex measurements following ROS scavenging. The activity of intestinal macrophages was assessed using flow cytometry. In vitro enzyme immunoassays and in vivo imaging techniques were employed to quantify ROS levels. Furthermore, the influence of OVA on ROS levels following intestinal macrophage depletion was investigated. Cell culture experiments were conducted to investigate the effects of OVA on intestinal macrophage function and ROS production.Results:The two visceral hypersensitivity mouse models exhibited a significantly lower pain threshold compared to the control group. OVA-induced visceral hypersensitivity mice demonstrated enhanced visceral motor responses (VMRs), with an increase in abdominal ROS levels (ACRS vs. control: 62.00±7.68 vs. 19.80±2.39, P<0.001; AAE vs. control: 461.80±17.25 vs. 19.80±2.39, P<0.001). When ROS were cleared from the abdominal cavity of mice, VMRs were restored to normal levels (AAE vs. AAE+ROS: 83.50±8.72 vs. 71.66±2.67, P=0.010). In this mouse model, intestinal macrophages could be classified into CD45 Med and CD45 High subtypes based on the level of CD45 expression. In the AAE group, the expression of CD45 Med macrophages in the intestinal tract decreased (AAE vs. control: 0.121±0.026 vs. 0.194±0.021, P=0.007), whereas the expression of CD45 High macrophages increased (AAE vs. control: 0.249±0.087 vs. 0.018±0.003, P=0.027). Compared with the control group, the expression of CD11b in both types of macrophages increased significantly (CD45 Med vs. control: 39 547.00±4 422.59 vs. 4 055.67±506.05, P<0.05; CD45 High vs. control: 18 960.00±1 197.84 vs. 3 147.50±286.38, P=0.008), while the expression of F4/80 decreased (CD45 Med vs. control: 6 141.67±750.06 vs. 10 544.33±974.92, P=0.008; CD45 High vs. control: 1 291.50±119.50 vs. 4 007.50±327.39, P<0.001). These findings suggest that the activity of intestinal macrophages in visceral hypersensitivity mice is altered following OVA induction. By injecting different populations of macrophages into the peritoneal cavity of mice, it was found that compared to the AAE group, the injection of CD45 High macrophages significantly increased the VMR in mice (AAE vs. AAE CD45 High: 83.50±8.72 vs. 114.38±7.15, P<0.001), and aggravated the severity of diarrhea significantly. In vitro experiments revealed that food antigens could directly induce ROS production in macrophages. Compared with the control group, both the ACRS and AAE groups of mice exhibited significant diarrhea symptoms. In contrast, the severity of diarrhea in the Macrophages exhaust+ACRS and Macrophages exhaust+AAE groups was substantially reduced, with a significantly shortened recovery period. Additionally, compared with the AAE group, the degree of diarrhea in the AAE+ROSS group was alleviated. Conclusions:Food antigens may act on intestinal macrophages, inducing abdominal pain and diarrhea in visceral hypersensitive mice via the ROS pathway. CD45 High macrophages may play a pivotal role in this process.

Adenosine triphosphate(ATP),as a rich energy currency in cells,is released into the extracellular space through a variety of regulatory mechanisms.The role of extracellular ATP(eATP)and related purine and pyrimidine nucleotides as extracellu-lar signal molecules regulating immune cell function has been reported as evidence of purine signal transduction and has become the focus of attention as a therapeutic target for various diseases.Mast cells(MC)are distributed in tissues that come into contact with the external environment and are the first immune cells to respond to non-microbial environmental antigens.Although eATP is considered to be an activator of MC,the details remain to be further elucidated.This article describes the role of purine receptor signaling in MC degranulation.It expands the further understanding of the mechanism of allergic diseases,and further provides ideas for finding new targets for the treatment of allergic diseases and formulating new treatment strategies.

Objective:To quantitatively evaluate the effects of left bundle branch block（LBBB）on left ventricular structure，function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography（SPECT），and to investigate the relationship between myocardial work，myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy（LBBB-CM）.Methods:Fourteen male beagle dogs were selected，and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram（ECG），transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs（normal control group）matched by age and weight. The correlation between myocardial perfusion（percentage of regional tracer uptake）and myocardial work parameters，myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline，the left ventricular end-diastolic volume of 12 months after the ablation increased［（20.78 ± 5.32）ml vs（26.71 ± 7.94）ml， P = 0.003］，left ventricular ejection fraction decreased［（59.17 ± 5.67）% vs（47.69 ± 5.45）%， P<0.001］；left ventricular global/segmental longitudinal strain，global/segmental constructive work and global/segmental work efficiency decreased（all P<0.05），left ventricular global/segmental wasted work increased（all P<0.001）. Heterogenous perfusion defect was observed in LBBB dogs by SPECT，compared with lateral wall segments，the percentage of regional tracer uptake of septum was decreased（all P<0.05）. Gross anatomical and myocardial pathological changes were manifested as cardiomegaly，flaky or focal grayish thickening of endocardium，cardiomyocyte degeneration and fibrosis. Compared with normal control group，the collagen fiber volume fraction（CVF）in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased（all P<0.05）. Percentage of regional tracer uptake was positively correlated with segmental myocardial work（SMW）and segmental myocardial efficiency（SWE）（ r s = 0.49，0.31；both P<0.001），and negatively correlated with CVF and segmental wasted work（SWW）（ r s = -0.51，-0.49；both P<0.001）. Conclusions:Isolated LBBB is not benign，which can result in left ventricular remodeling，decreased cardiac constructive function，abnormal myocardial perfusion，endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion，as non-invasive examination，can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.

ObjectivesTo investigate the effect of the Bioinformatics Infrared Liver Therapeutic （BILT） instrument on portal vein blood flow， liver stiffness， and spleen stiffness in patients with liver cirrhosis， and to preliminarily explore the therapeutic effect and mechanism of the BILT instrument. MethodsA total of 78 patients with compensated liver cirrhosis who attended the outpatient service or were hospitalized in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from October 2017 to December 2021 were enrolled， among whom 68 patients completed the 12-week treatment and were randomly divided into BILT group and simulated instrument group， with 34 patients in each group. In addition to basic treatment， the patients in the BILT group received irradiation with the BILT instrument， while those in the simulated instrument group received irradiation with the simulated instrument， for 30 minutes each time， twice a day； the course of treatment was 12 weeks for both groups. The two groups were compared in terms of laboratory markers （liver function， renal function， and routine blood test results）， liver and spleen ultrasound morphology， color Doppler blood flow detection （portal vein diameter， portal vein cross-sectional area， mean portal vein velocity， peak portal vein velocity， and mean portal vein flow）， and liver/spleen stiffness measurement before and after treatment. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the non-parametric Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. The paired samples correlation test was performed for the data before and after treatment within each group， and the paired samples t-test or the non-parametric Wilcoxon signed-rank test was performed for data with significant correlations. ResultsThe paired samples correlation test showed no correlation in spleen attenuation parameter before and after treatment， suggesting that the results of spleen fat measured by FibroTouch could not be used for statistical analysis. After 12 weeks of treatment， compared with the control group， the treatment group had significantly greater increases in portal vein diameter， portal vein cross-sectional area， and mean portal vein flow and a significantly greater reduction in liver stiffness measurement （all P0.05）. At week 0 before treatment and after 12 weeks of treatment， comparison of the immediate effect after 30 minutes of BILT irradiation showed that the treatment group had significant increases in portal vein diameter， portal vein cross-sectional area， mean portal vein velocity， and mean portal vein flow （all P0.05）， while the control group showed no significant changes after irradiation （all P0.05）； compared with the control group， the treatment group had significantly greater changes in all indicators except peak portal vein flow at week 0 （all P0.05）. No adverse events were observed in either group. ConclusionThe BILT instrument can improve portal vein blood flow in the liver and alleviate liver stiffness/fibrosis in patients with liver cirrhosis.