Intestinal barrier damage is a prominent feature of non-alcoholic fatty liver disease （NAFLD） and serves as a critical factor driving the progression from simple fatty liver to non-alcoholic steatohepatitis （NASH）， fibrosis， and cirrhosis. The "turbid pathogenic factors entering the blood" theory integrates classical traditional Chinese medicine （TCM） principles with contemporary disease evolution trends and research findings. It posits that endogenous turbid pathogenic factors within the body infiltrate the blood vessels， leading to impure and viscous blood quality， thereby triggering various diseases. Based on this theory， this article elucidated the pathogenic mechanism of NAFLD-associated intestinal barrier damage. It argued that in NAFLD， the liver loses its dredging function， and the spleen becomes obstructed and dysfunctional. Moreover， essential nutrients fail to be properly transformed， resulting in the internal generation of turbid pathogenic factors. This subsequently initiates a series of pathological changes， namely， "infiltration of phlegm-turbidity into the blood， eroding the intestinal mucosa"， "infiltration of glucose-turbidity into the blood， macerating and eroding the intestinal mucosa"， "infiltration of heat-turbidity into the blood， scorching and eroding the intestinal mucosa"， and "infiltration of stasis-turbidity into the blood， stagnating and eroding the intestinal mucosa"， ultimately causing intestinal barrier damage. Furthermore， guided by the "turbid pathogenic factors entering the blood" theory， this article explored TCM intervention strategies： employing medicinals targeting the liver meridian to address the root cause and reduce the generation and deposition of turbid pathogenic factors in the liver， administering blood-system medicinals to clear the blood and purge turbidity， thereby intercepting the progression of the disease mechanism， and applying tonifying medicinals to bolster healthy Qi and defend against turbid invasion， allowing the damaged intestinal mucosa to gradually heal. This article presented novel theoretical and medicinal perspectives for analyzing NAFLD-associated intestinal barrier damage based on the "turbid pathogenic factors entering the blood" theory， aiming to provide new entry points and broader horizons for related research and clinical practice.

BACKGROUND:Ilizarov bone transport is very effective in the treatment of open large tibial bone defects,but there are still complications,among which the difficulty of junction healing is one of the difficult points in treatment. OBJECTIVE:To investigate the effect of Ilizarov bone transport combined with antibiotic bone cement on junction healing after operation of open large tibial bone defect. METHODS:Totally 51 patients with open large tibial bone defect(bone defect>4 cm)admitted to Binzhou Medical University Hospital from August 2010 to January 2022 were selected,of which 28 received Ilizarov bone transport alone(control group)and 23 received Ilizarov bone transport combined with antibiotic bone cement treatment(trial group).External fixation time,bone healing time,bone healing index,visual analog scale score during bone removal,bone defect limb function,junction healing and complications at the final follow-up were statistically compared between the two groups. RESULTS AND CONCLUSION:(1)All the 51 patients were followed up for a mean of(22.53±5.77)months.External fixation time,bone healing time,bone healing index,postoperative infection rate,and non-healing rate of junction were less in the trial group than those in the control group(P<0.05).There was no significant difference between the two groups in visual analog scale scores at 6 months after the second surgery and in the functional excellence and good rate of limb with bone defect at the final follow-up(P>0.05).(2)These findings indicate that compared with the Ilizarov bone transport alone,Ilizarov bone transport combined with antibiotic bone cement treatment can promote the healing of open tibial fracture junction and increase the rate of bone healing.

To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents.

The paper summarizes Professor YANG Jun's thoughts on clinical treatment with acupuncture and moxibustion. Professor YANG Jun puts forward the "refined mode for diagnosis and treatment of diseases with acupuncture and moxibustion", aiming to improve the capacity of diagnosis and treatment in clinical practice. He advocates that the diagnosis and treatment should be guided by the identification of etiologies, syndromes and meridians; in accordance with regulating the shape/form, balancing yin and yang, and harmonizing the mind; and by means of skillful techniques of acupuncture and moxibustion, simplified selection of acupoints and delicate manipulations. Besides, he stresses on the combination of multiple techniques of acupuncture (such as penetrating technique with long needle, stuck needling by lifting and pulling, and micro-acupuncture systems) with moxibustion techniques (moxibustion for resolving stasis and unblocking collaterals, pressing moxibustion, borneol moxibustion, moxibustion with medicinal plaster) in clinical practice, so as to enhance the therapeutic effects.
Moxibustion/methods* ; Acupuncture Therapy/methods* ; Humans ; China ; Acupuncture Points

OBJECTIVE: To prepare decellularized nerve grafts from alpha-1, 3-galactosyltransferase (GGTA1) gene-edited pigs and explore their biocompatibility for xenotransplantation. METHODS: The sciatic nerves from wild-type pigs and GGTA1 gene-edited pigs were obtained and underwent decellularization. The alpha-galactosidase (α-gal) content in the sciatic nerves of GGTA1 gene-edited pigs was detected by using IB4 fluorescence staining and ELISA method to verify the knockout status of the GGTA1 gene, and using human sciatic nerve as a control. HE staining and scanning electron microscopy observation were used to observe the structure of the nerve samples. Immunofluorescence staining and DNA content determination were used to evaluate the degree of decellularization of the nerve samples. Fourteen nude mice were taken, and subcutaneous capsules were prepared on both sides of the spine. Decellularized nerve samples of wild-type pigs ( n=7) and GGTA1 gene-edited pigs ( n=7) were randomly implanted in the subcutaneous capsules. Blood was drawn at 1, 3, 5, and 7 days after implantation to detect neutrophil counting. RESULTS: IB4 fluorescence staining and ELISA detection showed that GGTA1 gene was successfully knocked out in the nerves of GGTA1 gene-edited pigs. HE staining showed that the structure of the decellularized nerve from GGTA1 gene-edited pigs was well preserved; the nerve basement membrane tube structure was visible under scanning electron microscopy; no cell nuclei was observed, and the extracellular matrix components was retained in the nerve grafts by immunofluorescence staining; and the DNA content was significantly reduced when compared with the normal nerves ( P<0.05). In vivo experiments showed that the number of neutrophils in the two groups were similar at 1, 3, and 7 days after implantation, with no significant difference ( P>0.05); only at 5 days, the number of neutrophils was significantly lower in the GGTA1 gene-edited pigs than in the wild-type pigs ( P<0.05). CONCLUSION The decellularized nerve grafts from GGTA1 gene-edited pigs have well-preserved nerve structure, complete decellularization, retain the natural nerve basement membrane tube structure and components, and low immune response after xenotransplantation through in vitro experiments.
Animals ; Transplantation, Heterologous ; Galactosyltransferases/genetics* ; Sciatic Nerve/immunology* ; Swine ; Tissue Engineering/methods* ; Humans ; Graft Rejection/prevention & control* ; Gene Editing ; Mice ; Mice, Nude ; Heterografts/immunology* ; Animals, Genetically Modified ; Tissue Scaffolds ; Decellularized Extracellular Matrix

Immune checkpoint blockade therapy has demonstrated remarkable efficacy in treating various malignancies; however, its clinical application remains challenged by low response rates and immune-related adverse events. Immunoglobulin superfamily member 11 (IGSF11), an inhibitory immune checkpoint molecule, serves as a specific ligand for the V-domain immunoglobulin suppressor of T cell activation (VISTA). Through the IGSF11/VISTA axis, it suppresses T cell function and represents a promising novel target for cancer immunotherapy. IGSF11 is widely expressed across multiple tumor types, though its regulatory mechanisms vary depending on the malignancy. Studies have confirmed that blocking the IGSF11-VISTA interaction or specifically inhibiting IGSF11 exerts antitumor effects. While IGSF11 is closely associated with patient prognosis, its prognostic significance differs among cancer types. This review systematically summarizes the structural characteristics of IGSF11, its regulatory mechanisms, interaction with VISTA, and functional role within the tumor microenvironment.
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Humans ; Immunotherapy ; Neoplasms/metabolism* ; B7 Antigens/chemistry* ; Animals ; Molecular Targeted Therapy ; Tumor Microenvironment

Objective:To discuss the associations of mismatch repair(MMR)in gastric cancer with preoperative inflammatory indicators and clinicopathological features in the gastric cancer patients,and to construct a gastric cancer MMR predictive model based on preoperative inflammatory indicators and clinicopathological features of the gastric cancer patients,and to provide new ideas for evaluation of MMR status in gastric cancer.Methods:The data of 254 gastric cancer patients who underwent surgical treatment from September 2020 to October 2023 were included.According to the expression of MMR protein,the patients were divided into MMR normal(proficiout MMR,pMMR)group and MMR deficient(dMMR)group.The preoperative inflammatory indicators and clinicopathological features data of the gastric cancer patients in two groups were collected.The associations between inflammatory indicators,clinicopathological features,and MMR in dMMR group and pMMR group were analyzed using Chi-square test.The independent predictive factors for dMMR were selected to construct the nomogram.Receiver operating characteristic(ROC)curve and calibration curve were used to evaluate the predictive efficacy,and decision curve was used to evaluate the practicality of the predication model.Results:A total of 254 gastric cancer patients were included in the study,with 221 patients(87％)in pMMR group and 33 patients(13％)in dMMR group.There were statistically significant differences(P＜0.05)in age,tumor location,tumor differentiation degree,maximum tumor diameter,platelet-to-lymphocyte ratio(PLR),alkaline phosphatase(AKP),alkaline phosphatase-to-albumin ratio(AAR),fibrinogen(FB)-to-lymphocyte(FLR),FB-to-albumin(AL)(FAR),D-dimer(D-D),and FB of the gastric cancer patients between dMMR group and pMMR group.Univariate and multivariate Logistic regression analysis revealed maximum tumor diameter[odd ratio(OR)=2.958,95％confidence interval(CI):1.196-7.314,P=0.019],tumor location(OR=4.013,95％CI:1.596-10.089,P=0.003),tumor differentiation(OR=3.006,95％CI:1.250-7.230,P=0.014),FAR(OR=2.793,95％CI:1.179-6.616,P=0.020),and carbohydrate antigen 199(CA199)(OR=0.279,95％CI:0.084-0.929,P-0.038)were the independent predictors of dMMR.The area under the ROC curve(AUC)value of the gastric cancer MMR prediction model constructed based on inflammatory indicators and clinical pathological characteristics was 0.800 with the sensitivity of 0.851 and the specificity of 0.606.The calibration curve of the nomogram was found to fit the ideal curve well,and in Hosmer-Lemeshow test P=0.412,the clinical decision curve showed a better net benefit.Conclusion:The preoperative inflammatory indicators and clinicopathological features are associated with MMR in gastric cancer;maximum tumor diameter,tumor location,tumor differentiation,CA199,and FAR are the independent predictors of dMMR.The prediction model based on the above predictors could predict the MMR status of the dMMR gastric cancer patients.

Objective To investigate the effects of scoparone(Sco)on proliferation and invasion of colon cancer cell line HCT116,and its effect on the expression of epidermal growth factor receptor(EGFR).Methods 1)HCT116 cells were divided into control group,50Sco group,100Sco group and 200Sco group.The cells in con-trol group were incubated with culture medium for 48 hrs.The 50Sco group,100Sco group and 200Sco group were incubated with 50,100 and 200 μmol/L scoparone for 48 hrs respectively.2)HCT116 cells were divided into con-trol group,NC-200Sco group,NC-LV+200Sco group and EGFR-LV+200Sco group.The control group was incuba-ted with normal culture medium for 48 hrs.NC-200Sco group was incubated with 200 μmol/L scoparone for 48 hrs.NC-LV and EGFR-LV were infected into HCT116 cells in NC-LV+200Sco group and EGFR-LV+200Sco group,then incubated with 200 μmol/L scoparone for 48 hrs.Cell proliferation was detected by MTT assay and EdU stai-ning,cell apoptosis was detected by flow cytometry and cell invasion was detected by Transwell assay.EGFR mRNA was detected by RT-qPCR,the level of EGFR,Bcl-2,Bax,matrix metalloproteinase(MMP)-2 and MMP-9 protein was detected by Western blot.Results Compared to the control group,the cell viability,proportion of EdU positive cells and counting number of invasive cells in 50Sco group,100Sco group and 200Sco group all decreased(P＜0.05).Cell apoptosis rate and Bax protein expression increased(P＜0.05),the protein expression of Bcl-2,MMP-2 and MMP-9 decreased(P＜0.05).mRNA and protein expression of EGFR were de-creased(P＜0.05).Compared with NC-200 Sco group and NC-LV+200Sco group,the expression level of mRNA and protein of EGFR in EGFR-LV+200Sco group was increased(P＜0.05).Cell viability,proportion of EdU posi-tive cells and counting number of invasive cells all increased(P＜0.05).The cell apoptosis rate and Bax protein expression level were decreased(P＜0.05).The protein expression of Bcl-2,MMP-2 and MMP-9 was increased(P＜0.05).Conclusions Scoparone has anti-colon cancer cell activity and inhibits proliferation as well as invasion of colon cancer cells through inhibition of EGFR.

OBJECTIVE To establish an HPLC method for determination of the related substances in papaverine hydrochloride. METHODS NanoChrom ChromCore 120 C8 column was used; the mobile phase A consisted of 3.4 g·L−1 potassium dihydrogen phosphate aqueous solution, adjust pH to 3.5 with phosphoric acid-acetonitrile(90∶10), the mobile phase B was methanol, with gradient elution at the flow rate of 0.8 mL·min−1; the detection wavelength was 238 nm; the column temperature was 50 ℃. RESULTS The minimum separation between the main component and each impurity was >1.5; Papaverine and its thirteen impurities showed a good linear relationship in the self-concentration range(r>0.999); and the average recoveries were 93.1%−101.2% with RSDs of 2.3%−8.1%. CONCLUSION The method is accurate, sensitive and reliable, which is suitable for the determination of related substances in papaverine hydrochloride.

Approach-avoidance conflict(AAC)refers to the internal conflict that individuals experi-ence when faced with conflicting approach or avoidance thoughts.It reveals some characteristics of mental disorders,such as anxiety,depression,and addiction represented by excessive tendencies of approach or avoidance.The function of the cortico-limbic-striatal system influences behavioral choices at the neural level during the onset of AAC,and the development of related behavioral paradigms that can better represent AAC behaviors is critical to evaluating the efficacy of drugs and guiding the development of new drugs.This paper summarizes the neural mechanisms,behavioral paradigms,and applications in behavioral pharmacology related to AAC behaviors from the perspective of psychopharmacology with a view to providing new perspectives and methods for the diagnosis and treatment of related neuro-psychiatric disorders.