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.

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.

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 evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for treating functional constipation, analyze the incidence of, and factors that influence, adverse events, and provide scientific evidence for optimizing FMT treatment.Methods:This retrospective, multicenter, single-arm, pre–post real-world study included 1529 patients with functional constipation from four clinical centers. Eligibility criteria comprised meeting the diagnostic criteria for functional constipation, having undergone at least one FMT treatment, complete pre- and post-treatment data available, and age ≥18 years. Patients who had received other interventions affecting gut function within 1 month before treatment and those with severe organic diseases or immune deficiencies were excluded. Applying the above criteria yielded 1529 eligible patients with functional constipation from four medical centers (1405 from the Shanghai Tenth People's Hospital Affiliated to Tongji University, 20 from the Central Hospital of Wuhan, 67 from the Shanxi Bethune Hospital and 37 from the Longgang District People's Hospital of Shenzhen). The study cohort comprised 746 male (48.8%) and 783 female patients (51.2%) of mean age (51.4 ± 17.4) years, mean body mass index (26.4 ± 4.9) kg/m2, and mean duration of disease (15.0 ± 8.3) years. The primary outcomes were the incidence, types, and severity of adverse reactions during treatment, and their impact on patients' quality of life. Secondary outcomes included: (1) the efficacy of FMT in treating constipation. This was assessed based on changes in Patient Assessment of Constipation Symptoms (PAC-SYM) scores, where higher score indicates worse symptom. (2) Subjective satisfaction, evaluated through questionnaires or rating scales, reflecting patients' acceptance of and satisfaction with the treatment, with scores ranging from 1 to 5, where higher scores indicated greater satisfaction. Paired t-tests and Wilcoxon signed-rank tests were used to evaluate changes in symptom scores and biochemical indicators before and after treatment. Logistic regression was performed to analyze factors influencing adverse events, and subgroup analyses to explored differences in efficacy between patient groups.Results:In this cohort of 1529 patients with functional constipation, adverse reactions were primarily mild to moderate (1048/1529,68.5%). They comprised fever in 54 patients (3.5%), dizziness or fatigue in 218 (14.3%), throat discomfort in 806 (52.7%), nausea and vomiting in 166 (10.9%), and abdominal distension or pain in 415 (27.1%). According to multivariate logistic regression analysis, PAC-SYM scores were associated with the rate of adverse reactions, higher scores indicating a lower risk (OR = 0.958, 95% CI: 0.923–0.993, P=0.021). Among the 1529 patients, 274 (17.9%) underwent two or more treatment courses. After one treatment course, the patients' PAC-SYM scores decreased from (37.7 ± 3.2) pre-treatment to (23.7 ± 8.6) (mean difference 14.0 ± 9.1). PAC-SYM scores decreased by (20.7 ± 7.7) after two courses of FMT, and by (19.4 ± 6.3) after three courses. After treatment, 50.7%(775/1529) of patients reported satisfaction scores of ≥4. Adverse reactions impacted satisfaction; specifically, dizziness/fatigue, throat discomfort, and abdominal distension/pain were significantly associated with satisfaction (all P < 0.05). Conclusions:FMT achieved good relief of symptoms of functional constipation and multiple treatment courses have a cumulative effect. Adverse reactions, mainly dizziness/fatigue, throat discomfort, and abdominal distension/pain, had significant negative impacts on patient satisfaction.

Objective:In this study, we aimed to investigate the short-term efficacy and safety of perioperative administration of the PD-1 inhibitor tislelizumab combined with the SOX regimen (oxaliplatin plus S-1) in patients with locally advanced gastric cancer, and to identify factors influencing therapeutic outcomes.Methods:In this retrospective cohort study, we analyzed clinical data of 166 patients who had undergone perioperative therapy and D2 radical gastrectomy in the Department of General Surgery, First Medical Center of Chinese PLA General Hospital between September 2021 and September 2023. The cohort comprised 140 men and 26 women, of median age 62 years (range: 30-75). The patients were allocated to two groups: 62 receiving tislelizumab plus SOX (combination therapy group), and 104 SOX alone (chemotherapy-only group). Primary outcomes included pathological complete response rate, treatment-related adverse events, and complications of surgery. Secondary outcomes comprised major pathological response rate, tumor regression grade (Grades 1-2 denoting favorable response, Grade 3 moderate, and Grades 4-5 poor response), R0 resection rate, and short-term survival outcomes (1-year disease-free and overall survivals). Risk factors associated with pCR in the combination group were also analyzed.Results:The combination therapy group exhibited significantly higher rates of pCR (25.8% vs. 8.7%, χ 2=8.93, P=0.003) and Grade 1 tumor regression (25.8% vs. 16.3%, χ 2=15.32, P=0.001) than the chemotherapy-only group. There were no statistically significant differences in major pathological response rates (41.9% vs. 39.4%), R0 resection rates (96.8% vs. 97.1%,), treatment- related adverse events (48.4% vs. 42.3%,), surgical complications (9.7% vs. 12.5%), 1-year disease-free survival (82.3% vs. 78.8%), or 1-year overall survival (93.5% vs. 91.3%), There were no statistically significant differences (all P>0.05). Multivariate logistic analysis identified neural invasion as an independent risk factor for reduced pCR in the combination group (OR=0.10, 95%CI:0.01-0.85, P=0.035). Conclusions:Perioperative tislelizumab combined with SOX chemotherapy improves pathological response rates in patients with locally advanced gastric cancer and has favorable short-term efficacy and safety profiles. Neural invasion may diminish the therapeutic efficacy of immunotherapy.

Alcohol abuse is a global public health problem.Excessive drinking not only damages digestive tract,cardiovascu-lar and endocrine systems,but also damages central nervous system(CNS).Recent studies have shown that alcohol interacts with neu-roimmune system to alter neuroimmune signaling and molecular expression,thereby leading to neuroinflammation and regulating a wide range of brain functions.Microglia is main cell of CNS involved in neuroimmune responses.Microglia is activated by alcohol and acts on neurons,leading to neuropsychiatric diseases,such as neuronal loss,abnormal synaptic connections,cognitive decline and motor dysfunction.Alcohol chronically stimulates digestive tract and also affects microglia along gut-brain axis.Neural properties of microglia and related immune factors and their important roles in neuroinflammation provide a new insight into neuroimmune mecha-nisms underlying alcohol-induced changes in brain function and behavior.This review discusses progress of role of microglia and their immune signaling in alcohol-induced neuroinflammation,and provides theoretical basis for further research on neurobiological mecha-nism and treatment of alcohol abuse.

The objective of this study was to investigate whether Stenotrophomonas maltophilia(S.maltophilia)induces ferroptosis,a form of iron-dependent cell death,leading to an inflamma-tory response in RAW 264.7 macrophages by elevating oxidative stress levels.RAW 264.7 cells were stimulated with varying concentrations of S.maltophilia.The concentrations of TNF-αand IL-1β were quantified using ELISA kits to assess the impact of S.maltophilia on the inflammatory response in RAW 264.7 cells.The activities of glutathione(GSH)and malondialdehyde(MDA)levels were measured using GSH and MDA assay kits to evaluate changes in oxidative stress.West-ern blot analysis was employed to detect the expression levels of COX-2,xCT,GPX4,and other proteins involved in ferroptosis signaling pathways,thereby investigating the effect of S.malto-philia on ferroptosis in RAW 264.7 cells.The results demonstrated that S.maltophilia induced concentration-dependent increases in inflammation and oxidative stress in RAW 264.7 cells,up-regulated the expression of COX-2 protein and down-regulated the expression of xCT and GPX4.Pretreatment with the ROS inhibitor N-acetylcysteine(NAC)significantly mitigated the S.malto-philia-induced oxidative stress and ferroptosis signaling activation,thereby alleviating the inflam-matory response.Furthermore,treatment with the ferroptosis inhibitor Fer-1 directly suppressed the activation of the ferroptosis signaling pathway and reversed the inflammation induced by S.maltophilia.These findings suggest that S.maltophilia triggers inflammation in RAW 264.7 cells by activating the ferroptosis signaling pathway via an increase in oxidative stress levels.

Objective To investigate the impacts of intervertebral foramen endoscopic surgery combined with silver needle hyperthermia therapy on lumbar spine function and local tenderness in patients with lumbar disc herniation(LDH).Methods From April 2020 to March 2023,100 LDH patients were randomly devided into a control group(50 cases)and an observation group(50 cases)through random number table method.The control group was treated with intervertebral foramen endoscopic surgery combined with conventional lumbar and dorsal muscle training,while observed group was treated with intervertebral foramen endoscopic surgery combined with silver needle warm therapy.The lumbar function,local tenderness,laboratory indicators,and adverse reactions were compared.Results The Japanese Orthopaedic Association(JOA)score increased in both groups after treatment,and observed group had obviously higher scores,the differences were statistically significant(P<0.05);After treatment,both groups showed a decrease in pain visual analogue scale(VAS)score,and observed group had obviously lower scores,the differences were statistically significant(P<0.05);The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),prostaglandin E2(PGE2),and 5-hydroxytryptamine(5-HT)in both groups decreased after treatment,and the observed group showed a more obvious decrease in all indicators,the differences were statistically significant(P<0.05);The incidence of adverse reactions was 4.00%(2/50)in observed group and 20.00%(10/50)in the control group,adverse reactions in observed group were obviously fewer,the difference was statistically significant(P<0.05).Conclusion The combination of intervertebral foramen endoscopic surgery and silver needle hyperthermia therapy can effectively improve lumbar spine function and alleviate local tenderness symptoms in patients with LDH.It is worthy clinical application.