ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

AIM: To detect the distribution and expression of vascular endothelial growth factor(VEGF)in radiation retinopathy(RR)through fluorescence targeted imaging.METHODS:Covalent binding of fluorescein FITC with VEGF antibody ranibizumab to prepare targeted fluorescent imaging probe ranibizumab-FITC. SD rats were randomly divided into three groups based on the principle of weight balance: a normal control group(Con group), a low-dose radiation group(10 Gy group), and a high-dose radiation group(30 Gy group). Medical linear accelerators and lead blocks were used to locally irradiate the rat eyeballs for modeling. Western blot and qRT-PCR were used to detect the expression levels of VEGF-A in each group and to screen for appropriate modeling dose. The inverted fluorescence microscope and the confocal microscope were used to observe the distribution of VEGF and imaging probes in the retinas of control and RR model group rats, and to verify the effectiveness of targeted probes.RESULTS:The expression level of VEGF-A in the retina of rats in the high-dose radiation group(30 Gy group)was higher than that in the normal control group(Con group). In early RR, VEGF expression was observed to be associated with microaneurysms and abnormal microvessels in the retina. VEGF accumulation was observed at the site of capillary wall damage. When retinal capillary endothelial damage occurred, targeted probes gathered on the outer surface of the vessel wall.CONCLUSION:The expression level of VEGF in the retina of RR model rats is elevated, and fluorescent targeted molecular imaging probes can detect the spatial distribution of VEGF at the microvascular lesions in the retina of RR rats.

Kidney stones are a typical model of pathological mineralization, and the association between local mineralization imbalance and systemic ectopic calcification is complex. This review systematically summarizes three major advances in the field. Firstly, at the molecular level, inflammatory/immune modulation(Th-cell activation), metabolic dysregulation(aberrant calcium-phosphate/lipid metabolism), and epigenetic control(lncRNA-driven osteogenic differentiation)act in concert to drive Randall's plaque formation. Secondly, at the systemic level, nephrolithiasis shares the Klotho pathway with vascular calcification and bone-metabolic disorders, converging on the inhibition of Wnt/β-catenin and related axes, underscoring the global impact of calcium-phosphate homeostatic disruption. Thirdly, in translational medicine, GeoBioMed technologies dissect mineral heterogeneity, AI models predict recurrence risk(AUC=0.87), CRISPR-based interventions [silencing of metastasisassociated lung adenocarcinoma transcript 1(MALAT1)], and biomimetic materials(carbonate-apatite coatings)exhibit significant therapeutic promise. Future efforts should integrate single-cell multi-omics, microbiome modulation, and cross-organ dynamic monitoring to shift the therapeutic paradigm from stone removal to the precise restoration of mineralization homeostasis.

This study constructed an inulin gel oral delivery system loaded with phycocyanin-tannic acid (PC-TA) nanoparticles (PC-TA@Inulin gel), characterized its physicochemical properties, and evaluated its therapeutic effect on dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC) in mice. PC-TA nanoparticles were prepared via pH-induced self-assembly, and spectroscopic methods were employed to verify the successful conjugation of PC and TA. The drug-loaded gel was fabricated by physical gelation, and its rheological properties were subsequently analyzed. A DSS-induced UC mouse model was established to evaluate in vivo therapeutic efficacy. The results showed that PC-TA nanoparticles had an average particle size of 262.0 nm, a polydispersity index of 0.084, and a Zeta potential of (–29.0 ± 0.5) mV, presenting a regular spherical structure. PC-TA@Inulin gel possessed favorable structural stability, self-healing capacity and typical shear thinning behavior, which satisfied the requirements for oral colon-targeted delivery. In vivo experiments confirmed that high-dose PC-TA@Inulin gel significantly alleviated body weight loss, reduced the disease activity index, restored colon length, ameliorated splenomegaly and thymic atrophy, and mitigated pathological damages including inflammatory cell infiltration and mucosal defect in the colon tissues of UC mice. In conclusion, this delivery system can effectively relieve UC symptoms in mice and repair the intestinal mucosal barrier through the synergistic anti-inflammatory and antioxidant effects of PC and TA, coupled with the colon-targeted delivery property and prebiotic effect of inulin gel, providing a novel oral formulation strategy and experimental basis for the clinical treatment of UC.

ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang （HQCFT） on rats with atherosclerosis （AS） by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D₃ injection， and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups： A blank group， a model group， a group receiving a low dose of HQCFT at 1.53 g·kg^-1 （HQCFT-L group）， a group receiving a high dose of HQCFT at 3.06 g·kg^-1 （HQCFT-H group）， and a group receiving atorvastatin calcium tablets at 1.8 mg·kg^-1 （Ato group）， with 10 rats in each group. Oral gavage administration started on the day after model establishment， once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin （HE） staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction （Real-time PCR） was used for detecting inflammatory factor levels in the aorta， high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents， targeted metabolomics for detecting short-chain fatty acid （SCFA） levels， and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group， the aortic tissue of rats in the model group showed significant AS lesions， including endothelial damage， inflammatory infiltration， and formation of fibrous plaques and calcified foci. Moreover， serum triacylglycerol （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） levels were significantly elevated （P<0.05）， while high-density lipoprotein cholesterol （HDL-C） levels were significantly reduced （P<0.05）. Significant increases were observed in whole blood viscosity， plasma viscosity， and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 （NLRP3）， Caspase-1， interleukin （IL）-β， IL-6， and tumor necrosis factor-α （TNF-α） in aortic tissue （P<0.05）. Additionally， gut microbiota composition， SCFA levels， and metabolomic profiles were significantly altered. Compared with those in the model group， serum TC， TG， and LDL-C levels， as well as the whole blood viscosity and plasma viscosity， were significantly reduced in all groups treated with HQCFT （P<0.05）. Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT， Caspase-1， IL-β， and IL-6 mRNA expression levels in the HQCFT-H group， and TNF-α mRNA expression levels in the HQCFT-L group （P<0.05）. HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid， valeric acid， and propionic acid. Non-targeted metabolomics identified 39 differential metabolites， which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition， promoting SCFA production， and regulating the levels of metabolites in intestinal contents.

ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang （HQCFT） on rats with atherosclerosis （AS） by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D₃ injection， and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups： A blank group， a model group， a group receiving a low dose of HQCFT at 1.53 g·kg^-1 （HQCFT-L group）， a group receiving a high dose of HQCFT at 3.06 g·kg^-1 （HQCFT-H group）， and a group receiving atorvastatin calcium tablets at 1.8 mg·kg^-1 （Ato group）， with 10 rats in each group. Oral gavage administration started on the day after model establishment， once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin （HE） staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction （Real-time PCR） was used for detecting inflammatory factor levels in the aorta， high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents， targeted metabolomics for detecting short-chain fatty acid （SCFA） levels， and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group， the aortic tissue of rats in the model group showed significant AS lesions， including endothelial damage， inflammatory infiltration， and formation of fibrous plaques and calcified foci. Moreover， serum triacylglycerol （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） levels were significantly elevated （P<0.05）， while high-density lipoprotein cholesterol （HDL-C） levels were significantly reduced （P<0.05）. Significant increases were observed in whole blood viscosity， plasma viscosity， and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 （NLRP3）， Caspase-1， interleukin （IL）-β， IL-6， and tumor necrosis factor-α （TNF-α） in aortic tissue （P<0.05）. Additionally， gut microbiota composition， SCFA levels， and metabolomic profiles were significantly altered. Compared with those in the model group， serum TC， TG， and LDL-C levels， as well as the whole blood viscosity and plasma viscosity， were significantly reduced in all groups treated with HQCFT （P<0.05）. Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT， Caspase-1， IL-β， and IL-6 mRNA expression levels in the HQCFT-H group， and TNF-α mRNA expression levels in the HQCFT-L group （P<0.05）. HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid， valeric acid， and propionic acid. Non-targeted metabolomics identified 39 differential metabolites， which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition， promoting SCFA production， and regulating the levels of metabolites in intestinal contents.

Objective:To analyze and identify the risk factors for preoperative hypokalemia in patients with gastrointestinal tumors and to construct a risk prediction model.Methods:A prospective research design was implemented. Patients with gastrointestinal tumors who underwent surgical treatment at the First Medical Center of the People ′s Liberation Army General Hospital between March 2023 and February 2024 were recruited as research participants through convenience sampling. These participants were randomly allocated into a modeling group or a validation group in a 7:3 ratio. Preoperative hypokalemia was defined as the outcome indicator. Multivariate Logistic regression analysis was employed to screen for risk factors, and a nomogram was subsequently constructed and validated. Results:Finally, a total of 600 patients were included in the study. In the modeling group ( n=420), 282 were male and 138 were female, 169 patients were under 60 years old, 233 patients were aged between 60 and 80 years, and 18 patients were over 80 years old. In the verification group ( n=180), there were 123 males and 57 females. Among these, 69 patients were under 60 years old, 102 patients were aged between 60 and 80 years, and 9 patients were over 80 years old. The multivariate Logistic regression analysis revealed that body mass index, occupation type, dietary habits, 6m walking speed test, grip strength relative to body mass index, and presence of digestive tract symptoms were independent risk factors for the development of preoperative hypokalemia ( χ2 values were 8.21~27.78, all P<0.05). The results of the model validation demonstrated that the areas under the receiver operating characteristic curves for the modeling and validation groups were 0.853 (95% CI 0.811-0.895) and 0.834 (95% CI 0.756-0.912), respectively, indicating a satisfactory level of predictive performance. Conclusions:The developed predictive model for preoperative hypokalemia in gastrointestinal tumors facilitates the accurate evaluation of the risk of preoperative hypokalemia and serves as a reference for effective clinical intervention.

OBJECTIVE To explore the clinical efficacy of Suyin Jiedu Prescription in the treatment of Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type and its effect on serum Klotho and inflammation levels.METHODS A total of 102 patients with Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type who met the inclu-sion criteria were randomly divided into a treatment group and a control group,51 cases in each group;a total of 84 cases were comple-ted,including 44 cases in the control group and 40 cases in the treatment group.The control group was given conventional Western medicine basic treatment,and the treatment group was given Suyin Jiedu Prescription on the basis of the control group treatment.The treatment course of both groups was 16 weeks.The levels of renal function indexes[hemoglobin(Hb),serum albumin(Alb),urea ni-trogen(BUN),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),24 h urine protein(UTP)]and TCM syndrome scores were observed in the two groups before and after treatment.The levels of serum Klotho,tumor necrosis factor α(TNF-α)and interleukin 18(IL-18)were detected by ELISA.The clinical efficacy between the two groups after treatment was compared.RE-SULTS After treatment,BUN and Scr levels of the two groups of patients were significantly decreased(P<0.05),eGFR was signifi-cantly increased(P<0.05,P<0.01),the treatment group was better than the control group(P<0.05);the TCM syndrome scores of the two groups were significantly decreased(P<0.05,P<0.01),and the treatment group was better than the control group(P<0.05,P<0.01);the serum Klotho level in the treatment group was significantly increased(P<0.05),the IL-18 level was significantly de-creased(P<0.01),and the serum Klotho,TNF-α,and IL-18 levels in the treatment group were better than those in the control group(P<0.05,P<0.01).The total clinical effective rate in the treatment group was higher than that in the control group(P<0.01).CONCLUSION Suyin Jiedu Prescription can effectively improve renal function and relieve clinical symptoms in patients with Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type,which may be related to increasing Klotho level and reducing inflammation in the body.

Objective:To investigate the expression of TSC2 in gastric cancer and its correlation with prognostic value and immune infiltration. Methods:Through Utilizing bioinformatics and experimental validation, analyzed RNA sequencing data from 624 gastric cancer patients in the TCGA-STAD dataset and the TCGA-GTEx-STAD dataset from the Cancer Genome Atlas (TCGA) database. Immunohistochemical (IHC) images of TSC2 expression in normal and gastric cancer tissues were obtained from the Human Protein Atlas (HPA). Evaluated the relationship between TSC2 expression and clinicopathological features, prognosis, immune infiltration, and immune subtypes in gastric cancer. Additionally, the expression of TSC2 in gastric cell lines was assessed by quantitative real-time PCR (qRT-PCR). Statistical analysis was conducted using SPSS 26.0 and R4.2.1 software. Results:TSC2 expression was significantly downregulated in gastric cancer tissues and cell lines compared to normal tissues. Lower expression of TSC2 correlated with worse overall survival, first progression, and progression-free survival in gastric cancer patients. TSC2 expression positively correlated with the infiltration levels of B cells, CD8 + T cells, CD4 + T cells, and macrophages, while it negatively correlated with the levels of NK cells and eosinophils. Functional enrichment analysis indicated that TSC2 was involved in pathways related to cell cycle regulation, protein transport, and immune response. TSC2 expression also associated with different immune subtypes within gastric cancer. Conclusions:TSC2 expression is downregulated in gastric cancer and is associated with poor prognosis and immune infiltration. TSC2 may act as a potential prognostic biomarker and a therapeutic target for gastric cancer.