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.

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: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 their inter-relationship,cognitive performance and cardio-electroencephalographic coupling in coronary heart disease(CHD)patients with heart-qi deficiency pattern were characterized.Methods Thirty CHD patients who met the diagnostic criteria for heart-qi deficiency were enrolled.Thirty healthy volunteers without heart-qi deficiency or CHD served as controls.Cognitive function was assessed with the repeatable battery for the assessment of neuropsychological status(RBANS).Simultaneous resting-state electrocardiogram and electroencephalogram were recorded,and the strength of heart-brain coupling was quantified by calculating the maximal information coefficient(MIC)between heart-rate variability(HRV)and EEG signals.Results Compared with controls,heart-qi deficiency CHD patients showed lower RBANS total scores and reduced performance in immediate memory,visuospatial/constructional ability,and attention.Significant between-group differences in HRV-EEG MIC values were observed at several channels(P<0.05).In patients,the MIC values for HRV-Beta(channel FC1)and HRV-Delta(channel F2)were positively correlated with RBANS total score(P<0.05).Conclusion CHD patients with heart-qi deficiency exhibit impaired cognition and altered cardio-electroencephalographic coupling.These findings suggest that heart-brain interactions may contribute to the pathophysiological mechanisms underlying cognitive decline in this population.

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.

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.

Objective:To evaluate the safety and oncological outcomes of robot-assisted laparoscopic inferior vena cava(IVC)segmental resection in renal tumor with IVC tumor thrombus(IVCTT).Methods:Clinical data from renal tumor patients undergoing robot-assisted laparoscopic IVC segmental resection at Peking University Third Hospital from Jan.2021 to Feb.2025 were retrospectively analyzed.Data collection included baseline demographics,tumor characteristics,perioperative parameters,and follow-up outcomes.Surgical records and pathological reports were retrieved from the electronic medical record system.Continuous variables were presented as median(P25,P75),and categorical variables as frequency(percentage).Results:Forty-four patients were enrolled.The cohort comprised 31 malesand 13 females,with a median age of 62(55,68)years.Right-sided tumors were observed in 39 cases and left-sided in 5 cases.Median tumor diameter was 8.1(6.1,10.1)cm.Mayo classifications included grade Ⅱ(n=37),Ⅲ(n=6),and Ⅳ(n=1).Neoadjuvant therapy was administered to 23 patients.Seventeen patients were complicated by IVC bland thrombus.Median operative time was 224.0(167.3,303.8)min,with intraoperative blood loss of 500.0(300.0,850.0)mL.Transfusion was administered to 19 patients,with a median blood transfusion of 800.0(400.0,1 200.0)mL.Postoperative complica-tions occurred in 25 cases(56.8％),classified as Clavien-Dindo grade Ⅰ(n=8)and grade Ⅱ(n=17).Procedure-specific complications included deep vein thrombosis(n=6),transfusion-requiring ane-mia(n=5),lower extremity edema(n=2),and pulmonary embolism(n=2),with no procedure-related mortality.Median postoperative serum creatinine was 116.0(86.5,157.5)μmnol/L.Pathological examination identified clear cell renal cell carcinoma as the predominant subtype,observed in 34 cases(77.3％).Pathological staging revealed T3b(n=12),T3c(n=29),and T4(n=3)disease,with nodal involvement(N1)in 8 cases and distant metastasis(M1)in 17.At a median follow-up of 10 months(range:1-49 months),cancer-specific mortality occurred in 3 patients,while 1 succumbed to other causes.Disease progression included pulmonary metastasis(n=5),hepatic metastasis(n=4),and local recurrence(n=4).Adjuvant therapy regimens comprised targeted-immunotherapy combina-tions(n=9)and targeted monotherapy(n=18).Conclusion:Robot-assisted laparoscopic I VC seg-mental resection achieves precise thrombus removal with confirmed short-term efficacy in renal tumor with IVCTT,though vigilance against vascular complications remains critical.

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.