AIM: To evaluate the surgical outcomes and changes in the ocular surface microenvironment following radiofrequency minimally invasive treatment for conjunctivochalasis-induced epiphora.METHODS: Patients with epiphora primarily caused by conjunctivochalasis were enrolled. All patients had conjunctivochalasis of ≥grade II, and their symptoms showed no significant improvement after previous pharmacological treatment. All patients underwent radiofrequency minimally invasive correction of conjunctivochalasis, supplemented with artificial tears, anti-inflammatory therapy, and ocular surface repair treatment postoperatively. At 8 wk post-surgery, the ocular surface disease index(OSDI), eye redness, tear secretion, non-invasive tear break-up time, lipid layer thickness, tear ferning test, and conjunctival impression cytology were assessed to compare treatment efficacy and observe changes in the ocular surface microenvironment.RESULTS: A total of 43 cases(43 eyes)of conjunctivochalasis and with a main complaint of epiphora were included, including 23 males and 20 males, with a mean age of 64.69±3.36 years. The total effective rate of surgery was 91% at 8 wk postoperatively. Compared with preoperative values, the OSDI scores significantly decreased and the non-invasive tear break-up time was prolonged at 8 wk post-surgery(all P<0.05). No statistically significant differences were observed in lipid layer thickness or tear secretion at 8 wk postoperatively(all P>0.05). The normal rate of chloramphenicol taste test increased from 21% preoperatively to 63% postoperatively; the normal rate of eye redness increased from 40% to 70%; normal rate of tear ferning grading improved from 30% to 63%; and normal conjunctival impression cytology grading increased from 21% to 74%.CONCLUSION: Radiofrequency minimally invasive treatment is effective for conjunctivochalasis and is straightforward to perform. Patients with conjunctivochalasis often present with other ocular surface issues beyond conjunctivochalasis itself, such as insufficient tear secretion, reduced lipid layer thickness, and other dry eye-related problems. Therefore, a comprehensive approach emphasizing tear dynamics should be adopted during treatment.

ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

The brain-gut interaction theory is a multidimensional integrative concept based on the brain-gut axis， involving neural， endocrine， and immune regulatory networks as well as the gut microbiota. Zang-fu organs （脏腑） theory in traditional Chinese medicine （TCM） shows a high degree of consistency with the brain-gut interaction theory， and the core functions such as the spleen and stomach governing the ascending of the clear and descending of the turbid， the liver governing the free flow of qi， and the heart governing mental and emotional activities are closely associated with the multi-level regulatory mechanisms of the brain-gut axis. TCM therapy can modulate brain-gut interactions through multiple pathways in the treatment of spleen and stomach diseases， including the regulation of gastrointestinal hormone secretion， neurotransmitter levels， the hypothalamic-pituitary-adrenal （HPA） axis， immune homeostasis and inflammatory responses， as well as the gut microecology. However， current basic research on the brain-gut interaction theory in TCM for spleen and stomach diseases still faces several challenges， such as difficulties in integrating TCM spleen-stomach theory with modern pathophysiology， lack of innovation in research concepts， and limitations in research methodologies. It is therefore proposed that multidisciplinary collaboration， multi-omics technologies， and targeted research approaches should be adopted to provide more comprehensive methods for basic research on TCM spleen and stomach diseases， thereby promoting the in-depth development of brain-gut interaction theory.

Objective:To explore the value of a scoring system based on preoperative abdominal computed tomography (CT) for predicting the difficulty of laparoscopic cholecystectomy (LC).Methods:A retrospective analysis was conducted on 105 patients diagnosed with gallstones or cholecystitis who underwent LC at Beijing Jishuitan Hospital, Capital Medical University from January 2021 and February 2022. Based on surgical video reviews, patients were divided into the easy group ( n=58) and the difficult group ( n=47) according to the intraoperative Parkland Grading Scale (PGS), with PGS grades 1-2 assigned to the easy group, and PGS grades 3-5 assigned to the difficult group. The normally distributed measurement data were expressed as mean±standard deviation ( ± s), and compared using independent samples t-test; the non-normally distributed measurement data were expressed as median (interquartile range) [ M ( Q1, Q3)], and compared using the rank-sum test. The count data were expressed as the number of cases and percentage, and compared using the Chi-square test or Fisher exact probability method. Univariate analysis and cut-off value determination: for continuous CT variables, univariate Logistic regression and stepwise regression analyses (with surgical difficulty grouping as the dependent variable) were performed to identify the optimal combination of predictive variables and establish a scoring system. For each significantly associated continuous variable or important CT image feature from a clinical perspective, receiver operating characteristic (ROC) curve analysis was used to evaluate its predictive performance for difficult surgery. The area under the curve (AUC) was calculated, and the optimal cut-off value was determined using the Youden index to maximize the sum of sensitivity and specificity. The categorical CT image features were scored according to their original groups. The Kappa consistency test was used to assess the strength of agreement between the preoperative abdominal CT score (grouped by the optimal cut-off) and PGS grades (easy/difficult). Decision curve analysis (DCA) was employed to validate the predictive performance of the model. Results:Stepwise Logistic regression identified seven key imaging features as the optimal predictive variables for constructing the preoperative abdominal CT scoring system: maximum gallbladder cross-sectional diameter, maximum gallbladder cross-sectional width, gallbladder wall thickness, common bile duct diameter, pericholecystic fat stranding, periductal fat stranding, and impacted cystic duct stones. Each case was scored after assigning scores based on the optimal cut-off values. The total score of the preoperative abdominal CT scoring system was ≥3 points predicted difficult LC with an AUC of 0.745 (95% CI: 0.650-0.839), sensitivity of 66.0%, and specificity of 75.9%. DCA confirmed the model′s reliable predictive performance, and the preoperative abdominal CT scoring system showed good agreement with PGS grades ( Kappa value was 0.420, P<0.001). Conclusions:The preoperative abdominal CT scoring system based on pericholecystic imaging features can effectively predict the difficulty of LC with good discriminative ability. It provides a quantitative tool for preoperative assessment, surgical scheduling, and ambulatory surgery management.

Objective:To explore the molecular mechanism of TCM compound Shengxue Tongbian Granules in improving intestinal injury in septic rats through bioinformatics and experimental validation methods.Methods:The GSE131761 gene set was processed by bioinformatics to screen differential genes, then weighted gene co-expression network analysis (WGCNA) was applied to screen modular genes. The intersection of modular genes and differential genes was taken, and finally, the least absolute shrinkage and selection operator (LASSO) technique was applied to further obtain the key targets of sepsis, which was validated by experiments. Totally 72 SD rats were divided into sham-operation group, model group, dexamethasone group (0.15 mg/kg), Shengxue Tongbian Granules low- (0.3 g/kg), medium- (0.6 g/kg), and high-dosage (1.2 g/kg) groups, with 12 rats in each group. Corresponding drug interventions were administered to each treatment group before and 12 hours after modeling. The sham-operation group and the model group were gavaged daily with equal amounts of saline. Samples were collected after 24 hours. HE staining was used to detect the pathological morphology of intestinal tissues in each group of rats; ELISA was used to detect the levels of TNF-α, diamine oxidase (DAO), IL-6, IL-10, and myeloperoxidase (MPO) in rat serum. Immunohistochemistry was used to detect the protein expressions of MPO and neutrophil elastase (NE/LANE) in intestinal tissue, and Western blot was used to detect the protein expression of peptidyl arginine deaminase (PAD4) in intestinal tissue.Results:Seven final key genes related to sepsis were selected, namely ANXA3, CYP1B1, FCAR, LILRA5, PADI4, NOV, and S100A12. Experimental results showed that drug administration alleviated intestinal injury; compared with the model group, the levels of TNF-α, IL-6, MPO, and DAO decreased in the Shengxue Tongbian Granules high-dosage group ( P<0.05), the levels of ELANE and MPO were reduced in Shengxue Tongbian Granules low-, medium-, and high-dosage groups ( P<0.05), and PAD4 expression was reduced in the Shengxue Tongbian Granules high-dosage group ( P<0.05). Conclusion:Shengxue Tongbian Granules can improve the intestinal injury of septic rats, and the mechanism may be related to the inhibition of PAD4-mediated formation of NETs and the improvement of inflammatory response.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

OBJECTIVE: To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2). METHODS: Three children who were diagnosed with ILFS2 at the Children's Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). RESULTS: The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c.3596G>A and c.1181A>T in child 1, c.2617C>T and c.2T>C in child 2, and c.3596G>A and c.2817_2818insT in child 3. Among these, the c.1181A>T and c.2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+PM3+PP3) and pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION Combined with the patient's clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c.1181A>T and c.2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.
Humans ; Exome Sequencing ; Genetic Testing/methods* ; Liver Failure, Acute/etiology* ; Mutation ; Child ; Adult ; Neoplasm Proteins

[Purpose]To investigate the acceptance and willingness-to-pay(WTP)of combined can-cer screening among rural residents in Shandong Province,and to analyze its influencing factors.[Methods]A face-to-face questionnaire survey was conducted among rural residents aged 40～70 in villages setected by cluster sampling from three counties(county level city or district)in Shan-dong Province.The questionnaire was developed using the method of double-bound dichotomous choice combined with open-ended questions in contingent valuation.The factors influencing inten-sity of WTP was analyzed with using single-factor and ordinary least squares regression models.[Results]A total of 962 subjects were surveyed.89.19％of the respondents were willing to accept cancer combined screening,and 62.00％were willing to pay part of the costs.The average of WTP was 963.67 CNY,which accounted for 32.12％of the total cost.The proportion of respon-dents who were willing to pay between 0～1 500 CNY was the highest(76.49％).In the multivariate analysis,age,sex and income had significant effects on the maximum payment of multi-cancer screening.[Conclusion]The acceptance of multi-cancer screening among rural residents in the study sites is high,but the willingness-to-pay is limited.The out-of-pocket payment for multi-can-cer screening should be controlled,and a co-payment mechanism among government,enterprises,social organizations and individuals should be explored.

Objective:To investigate the characteristics of fatty acid metabolism in the hepatic steatosis (HS) population and to explore the role of inflammation in the relationship between fatty acid metabolism and HS.Methods:A total of 3 112 subjects from the 2011–2014 National Health and Nutrition Examination Survey (NHANES) database were included in this retrospective study, among whom 1 552 were in the HS group (weighted percentage: 49.87%) and 1 560 in the control group (weighted percentage: 50.13%). The differences in dietary fatty acid and serum free fatty acid (FFA) levels and metabolic characteristics were compared. Logistic and weighted quantile sum (WQS) regression models were used to evaluate the impacts of various FFA indexes on HS. Mediation analysis was conducted to examine whether inflammation served as a mediator in the relationship between FFA and HS.Results:Dietary fatty acid intake did not differ significantly between the HS and control groups. However, serum FFA metabolism characteristics differed between these two groups, with the concentrations of 28 FFAs in the HS group significantly higher than those in the control group. The risk of HS was correlated negatively with serum unsaturated fatty acids/saturated fatty acids ( OR=0.69, 95% CI: 0.64–0.75, P<0.001), polyunsaturated fatty acids/saturated fatty acids ( OR=0.63, 95% CI: 0.99–0.69, P<0.001), and Health Promotion Index ( OR=0.78, 95% CI: 0.74–0.82, P<0.001) but positively with thrombosis index ( OR=2.20, 95% CI: 1.89–2.55, P<0.001). The WQS model showed that behenic acid had the greatest contribution weight to increase the risk of HS among the 30 FFAs. After adjusting for confounding factors, the risk of HS increased by 167% (95% CI: 2.14–3.34, P<0.001) for each unit increase in the WQS index. Further mediation analysis showed that albumin/globulin ratio, white blood cell count, and neutrophil to platelet ratio significantly mediated the relationship between serum FFA and HS ( P<0.05). Conclusion:People with similar dietary fatty acid structures may present different serum FFA metabolism characteristics. Serum FFA level correlates with the risk of HS, and inflammation plays an important role in mediating the relationship between fatty acid metabolism and HS.