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.

Objective To investigate the risk factors for the occurrence of metabolic dysfunction-associated steatotic liver disease(MASLD)in lean individuals and construct a risk prediction model.Methods Based on the National Health and Nutrition Examination Survey(NHANES)database in the United States(from January 2017 to March 2020),1 123 adult individuals were included in this study.Then the participants were randomly divided into a training set(n=561)and a validation set(n=562)through simple random sampling.Data on their demographics,anthropometrics,lifestyle,underlying diseases,and laboratory test results were collected.LASSO regression analysis was used to screen potential variables in the training set,and multivariate logistic regression was employed to identify independent risk factors for lean MASLD.Based on these risk factors,a prediction model for lean MASLD was constructed(LMPM).To evaluate the clinical value of the LMPM,it was compared with two commonly used prediction models for non-alcoholic fatty liver disease,the fatty liver index(FLI)and the hepatic steatosis index(HSI).The performance of the model was evaluated and internally validated using the area under the receiver operating characteristic curve(AUC),net reclassification index(NRI),integrated discrimination improvement(IDI),calibration curve,decision curve,and clinical impact curve.Results Age,waist circumference,and triglycerides(TG)were identified as independent risk factors for the development of MASLD in lean individuals.The LMPM,constructed based on these indicators,demonstrated good discriminative ability in both the training and validation sets,with AUC values of 0.86(95%CI:0.82～0.89)and 0.81(95%CI:0.77～0.85),respectively,which were significantly better than those of FLI[training set:AUC=0.83(95%CI:0.79～0.87);validation set:AUC=0.74(95%CI:0.70～0.79)]and HSI[training set:AUC=0.71(95%CI:0.66～0.76);validation set:AUC=0.71(95%CI:0.65～0.76)].Compared with FLI and HSI,the LMPM showed improvements in NRI and IDI in both the training and validation sets.The calibration curve demonstrated its high accuracy,and both the decision curve analysis and the clinical impact curve analysis indicated that the LMPM provided greater clinical benefits.Conclusion Age,waist circumference,and TG are independent risk factors for lean MASLD.Based on these factors,a prediction model,named LMPM,is developed to assess the risk of MASLD in lean individuals,which exhibits good predictive performance and has certain guiding significance for the timely identification of high-risk populations.

Background Hexavalent chromium [Cr(VI)] exposure can cause structural disruption of intestinal flora and functional impairment. Vitamin C (VC) is one of the essential micronutrients, which plays an important role in promoting the growth of intestinal probiotics, improving the intestinal barrier, and maintaining the homeostasis of intestinal flora. However, the regulatory effect of VC on the intestinal flora disorders caused by Cr(VI) exposure remains to be investigated. Objective To investigate the effect of VC on intestinal flora disruption in mice due to Cr(VI) exposure. Methods Thirty-two SPF-grade C57BL/6 mice were acclimatized and fed for 3 d and randomly divided into control (Con), VC, potassium dichromate [K₂Cr₂O₇, Cr(VI)], and VC+K₂Cr₂O₇ [VC+Cr(VI)] groups. At 8:00 a.m. on day 4, the Con group (double-distilled water given by gavage and injected intraperitoneally), the VC group (VC given by gavage and double-distilled water injected intraperitoneally), the Cr(VI) group (double-distilled water given by gavage and K₂Cr₂O₇ solution injected intraperitoneally), and the VC+Cr(VI) group (VC given by gavage and K₂Cr₂O₇ solution injected intraperitoneally) were treated. The dose of VC was 200 mg·kg⁻¹, and the dose of K₂Cr₂O₇ was 1.25 mg·kg⁻¹. The mice were treated for 45 consecutive days and then executed, the contents of the colon were sampled in sterile freezing tubes, and three replicates were collected from each group. After labeling, the samples were immediately put into liquid nitrogen for rapid freezing. After all the samples were collected, they were transferred to a -80 ℃ ultra-low temperature refrigerator for storage. Samples of colon contents were analyzed for intestinal flora structure by high-throughput sequencing and bioinformatics software. Results The Cr(VI) exposure resulted in reduced body weight gain values in mice compared to the Con group. Pathological changes occurred in the ileal tissue of mice, with significant inflammatory cell infiltration in the Cr(VI) group and reduced inflammatory cell infiltration in the VC+Cr(VI) group. The number of operational taxonomic units (OTUs) of intestinal flora was altered in the Cr(VI) group of mice. In the α diversity analysis, the mean Sobs index in the Cr(VI) group was 240.333±67.796, the Chao index was 258.173±64.813, and the Ace index was 259.481±66.891, which were significantly lower than those in the Con group (P<0.05), the PD whole tree index in the Cr(VI) group was 27.863±2.399, which was significantly higher than that in the Con group (P<0.05), and the VC intervention significantly reversed the changes of the above indexes due to Cr(VI) exposure (P<0.05). In the β diversity analysis, the principal coordinates analysis (PCoA) results showed a significant separation between the Cr(VI) group and the Con group, and after the VC intervention, there was a retraction of the separation trend and the difference was reduced. The multi-sample similarity dendrogram results showed that the control and the VC groups clustered together first, then with the VC+Cr(VI) group, and finally with the Cr(VI) group. The abundances of Bacteroidetes, Saccharibacteria, and Tenericutes in the intestine of mice in the Cr(VI) group were decreased, and the abundance of Firmicutes was increased; the abundances of Lactobacillus, Alistipes, Bacteroides, and Ruminiclostridium were also increased. Included among these, Bacteroides showed a significantly higher abundance compared to the control mice (P<0.05). Changes in the abundances of phyla and genera of the above mentioned gut microorganisms were reversed after the VC intervention. Conclusion Cr(VI) exposure can lead to intestinal damage and disorganization of the intestinal flora structure in mice, while VC intervention can ameliorate the above changes to a certain extent and normalize the intestinal flora structure.

Bispecific antibody (BsAb) is a new type of highly effective anti-tumor drug that can specifically bind two antigens or epitopes simultaneously or successively. At present, evantuzumab targeting epidermal growth factor receptor (EGFR) and cMET has been approved for the treatment of EGFR ex20ins in locally advanced or metastatic non-small cell lung cancer (NSCLC) . Inhibitors targeting programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) , programmed death-1 (PD-1) and CTLA-4, PD-L1 and transforming growth factor-β, PD-1 and vascular endothelial growth factor are applied to NSCLC. The treatment of NSCLC is underway, showing good safety and efficacy. Further exploring the research progress of BsAbs in the treatment of NSCLC will provide a new diagnosis and treatment idea for the clinical treatment of NSCLC.