Recently， the American College of Gastroenterology （ACG） released the clinical guidelines on perioperative risk assessment and management of patients with cirrhosis， proposing a comprehensive approach for perioperative risk assessment and management in these patients. The guidelines mainly focus on the severity of liver diseases， extrahepatic comorbidities， and surgery-specific factors， with an emphasis on individualized risk stratification using validated risk assessment tools （such as the VOCAL-Penn score） for patients with cirrhosis. This article gives an excerpt of the key statements in the guidelines.

OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

ObjectiveTo investigate the association between serum creatinine/cystatin C ratio （CCR） and nonalcoholic fatty liver disease （NAFLD） based on the NHANES database， and to evaluate the potential significance of CCR as an indicator reflecting the metabolic status of the body. MethodsBased on the data from the NHANES database in 1999‍ ‍—‍ ‍2004， a total of 4 217 participants were enrolled and divided into NAFLD group with 1 726 participants and non-NAFLD group with 2 491 participants. CCR was compared between the two groups， and the association between CCR and NAFLD was analyzed. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression model was used to investigate the association between CCR and NAFLD； CCR was divided into 4 groups based on quartiles， and odds ratio （OR） and 95% confidence interval （CI） in the regression model was calculated with the first quartile as reference. In addition， the restricted cubic spline analysis was used to investigate whether there was a non-linear relationship between CCR and NAFLD， and interaction items were introduced into the Logistic regression model to perform an interaction analysis. Subgroup analyses were performed based on the stratification of variables to investigate the difference in the association between CCR and NAFLD in different populations. ResultsThe non-NAFLD group had a significantly higher CCR than the NAFLD group （Z=-4.76，P<0.01）. The Logistic regression analysis showed that in model 1 without adjustment of variables， CCR was negatively associated with NAFLD （OR=0.993，95%CI：0.989‍ ‍—‍ ‍0.996，P<0.01）， and in model 3 with adjustment of all variables， CCR was still negatively associated with NAFLD （OR=0.986，95%CI：0.981‍ ‍—‍ ‍0.991，P<0.01）. The analysis of CCR based on quartiles showed a significant association between the increase in CCR and the reduction in the risk of NAFLD. In model 3， compared with the individuals with the lowest quartile of CCR， the individuals with the highest quartile of CCR had a significantly lower risk of NAFLD （OR=0.426，95%CI：0.316‍ ‍—‍ ‍0.574，P<0.01）. Further interaction and subgroup analyses showed that the interaction between CCR and age/sex had a statistical significance （P_interaction<0.01 and P_interaction=0.04）. The subgroup analysis based on age showed a more significant association between CCR and NAFLD in the middle-aged population （≤60 years） （OR=0.982，95%CI：0.976‍ ‍—‍ ‍0.987）， and the subgroup analysis based on sex showed a stronger association between CCR and NAFLD in women （OR=0.979，95%CI：0.972‍ ‍—‍ ‍0.986）. ConclusionThis study shows a significant negative association between CCR and NAFLD， and such association is more significant in middle-aged individuals and women.

Epigenetic mechanisms play a crucial role in the development and progression of nonalcoholic fatty liver disease （NAFLD）， especially among lean individuals. The research on related epigenetic mechanisms has provided new clues and directions for revealing the underlying causes and treatment strategies of NAFLD. This article introduces the role of epigenetics in the development and progression of NAFLD among lean individuals in recent years， analyzes the latest research advances in the epigenetics of NAFLD in this population， and briefly describes the basic concepts of epigenetics， including DNA methylation， histone modifications， and non-coding RNA regulation. This article also discusses how epigenetic alterations impact the pathogenesis， disease progression， and treatment strategies of NAFLD in lean individuals.

ObjectiveTo investigate the association between body roundness index （BRI） and the risk of metabolic dysfunction-associated fatty liver disease （MAFLD） based on the National Health and Nutrition Examination Survey （NHANES） database， as well as the clinical value of BRI as a noninvasive tool for risk prediction. MethodsBased on the NHANES data in 2015—2020， the 4 573 individuals were divided into MAFLD group with 2 508 individuals and non-MAFLD group with 2 065 individuals， and BRI was calculated for each individual. In order to ensure data quality and reduce the impact of abnormal values on analytical results， the boxplot method was used to remove abnormal levels of BRI and improve the robustness of data. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The multivariate Logistic regression model was established to investigate the association between BRI and MAFLD. BRI was divided into four groups based on quantiles， and with the first quantile （Q1） as reference， odds ratio （OR） and 95% confidence interval （CI） were calculated for the other three models. Restricted cubic spline was used to investigate the dose-effect relationship between BRI and MAFLD. The receiver operating characteristic （ROC） curve was plotted and the area under the ROC curve （AUC） was calculated to assess the efficacy of BRI in the diagnosis of MAFLD. The decision curve analysis was used to investigate the potential clinical value of the model in clinical practice. The interaction analysis and the subgroup analysis were performed to investigate the difference in the association between BRI and MAFLD between different populations. The Lasso regression analysis was conducted for the screening and analysis of characteristic variables. ResultsCompared with the non-MAFLD group， the MAFLD group had a significantly higher BRI （Z=36.29， P<0.001）. After adjustment for the variables including age， sex， ethnicity， educational level， the proportion of individuals with poor income， marital status， smoking， hypertension， diabetes， alanine aminotransferase， aspartate aminotransferase， gamma-glutamyl transpeptidase， and high-density lipoprotein cholesterol， the fully adjusted Logistic regression model showed that BRI was significantly positively associated with the risk of MAFLD （OR=2.53， 95%CI： 2.28 — 2.80， P<0.001）. In addition， the highest BRI quartile （Q4） group had a significantly higher risk of MAFLD than the lowest quartile （Q1） group （OR=83.45， 95%CI： 51.87 — 134.26， P<0.001）. The restricted cubic spline analysis further confirmed the significant nonlinear association between BRI and MAFLD （P for nonlinear<0.001）. The interaction analysis and the subgroup analysis showed that the interaction between hypertension and BRI had statistical significance （P for interaction=0.003）， and compared with the individuals without hypertension， the individuals with hypertension had a stronger association between BRI and MAFLD （OR=1.60， 95%CI： 1.23 — 2.08， P<0.001）. The ROC curve analysis showed that the fully adjusted model based on BRI had a strong discriminatory ability in differentiating MAFLD from non-MAFLD， with an AUC of 0.887 （95%CI： 0.877 — 0.896）. The decision curve analysis showed that the fully adjusted model had good net benefits within the risk threshold of 0.10 — 0.75， which was commonly used in clinical practice. The model based on the key variables identified by the Lasso regression analysis had an AUC of 0.882 （95%CI： 0.872 — 0.892）， which confirmed the robustness of the prediction results. ConclusionThere is a significant positive correlation between BRI and the risk of MAFLD， with a stronger association observed in the hypertensive population. As a body index reflecting abdominal obesity and visceral fat accumulation， BRI shows promising application prospects in the risk assessment of MAFLD.

AIM: To compare the efficacy of intravitreal injection of ranibizumab(IVR)and intravitreal injection of conbercept(IVC)in children with retinopathy of prematurity(ROP).METHODS: Retrospective study. A total of 1 100 eyes with ROP treated with intravitreal anti-VEGF at our hospital from January 2015 to June 2023 were included. According to the different therapeutic drugs, the children were divided into two groups: IVR group and IVC group. According to the degree of ROP, the patients were divided into three groups: aggressive ROP(A-ROP), Zone Ⅰ type 1 ROP and Zone Ⅱ type 1 ROP. The reactivation and retreatment between the two groups were compared after propensity score matching(PSM)analysis, and they were followed-up for at least 3 mo after surgery.RESULTS: In Zone Ⅱ type 1 ROP, there was a statistically significant difference in the rates of reactivation and retreatment between the IVR and IVC groups(P<0.05); however, in A-ROP and Zone I type 1 ROP, there were no statistically significant differences in the rates of reactivation and retreatment between the two groups(P>0.05). The risk of reactivation and retreatment of Zone I type 1 ROP was higher than the Zone II type 1 ROP. Furthermore, the use of drugs and corrected gestational age of first treatment were influencing factors of lesion recurrence and retreatment.CONCLUSION: There is a significant difference in the initial cure effect between the two drugs in Zone II type 1 ROP, with the reactivation and retreatment rates of the IVC group being much lower than those of the IVR group.

Objective:To investigate the dosimetry effect of rotational errors of multi-channel cylinder vaginal applicator of intravaginal irradiation after surgery of endometrial cancer.Methods:A total of 18 patients who underwent surgery of endometrial cancer at Peking Union Medical College Hospital from June to December 2022 were selected.The plans of patients who adopted the treatment of multi-channel cylinder applicator of vagina were retrospectively analyzed,which maintained the same retained mode with clinical plan.The applicator was rotated clockwise by 22.5? and 45.0?,respectively,simulating the rotational errors that occurred in placing the applicator among clinical inter-fractions.And then,the changes of dosimetry of target area and organs at risk(OAR)under two kinds of rotation amplitudes were further analyzed.Results:When the applicator was rotated as 22.5?,the minimum doses to 90%volumes of CTV by 2.03%than that of clinical plan,which was significantly different(t=5.86,P<0.05),and the maximal doses to 2cc of OARs of bladder and rectum respectively increased 2.35%and 2.71%,and the differences of them were statistically significant(t=-3.49,-2.40,P<0.05),respectively.When the applicator was rotated as 45?,the D90 of the target area decreased by 5.75%than that of clinical plan,which was statistically significant(t=14.07,P<0.05).The D2cc values of the bladder and rectum increased respectively by 6.50%and 9.49%than that of clinical plan,which were statistically significant(t=-7.72,-6.9,P<0.05).The differences of the exposed doses of sigmoid colon and small intestine after the applicator was rotated by 22.5? and 45.0? between the plan and original plan were respectively less,which were not statistical significance.Conclusion:The multi-channel cylinder applicator can provide individualized dose distribution in intravaginal irradiation.However,attention should be paid to the placement of the applicator when patients undergo inter-fractional treatment,in order to avoid deviations in the angular alignment from the original plan.This can impact the dosages of the target area and OARs.

Objective:To analyze the differences in dosimetric quality and plan complexity of volumetric modulated arc therapy (VMAT) plans based on Halcyon 2.0 and Truebeam for different treatment sites of the patients.Methods:Halcyon 2.0 VMAT plans in head & neck, chest, abdomen, and pelvis treatment sites of 49 cases were retrospectively selected and the VMAT plans were re-designed based on Truebeam with the same optimization parameters. The differences in dosimetric metrics and plan complexity between the two types of plans were compared and analyzed. P<0.05 was considered as statistically significant. Results:In terms of PTV, Halcyon 2.0 plans showed better homogeneity index (HI), conformal index (CI) in the head & neck and chest. Besides, Halcyon 2.0 plans yielded better D 98% and CI in the abdomen and better D 2% in the pelvis. For organs at risk (OAR), the D 20% and D mean of bilateral lungs, and D meanof heart for Halcyon 2.0 plans in the chest were lower than those for Truebeam plans (all P<0.05). For the complexity metrics, the median average aperture area variability (AAV) of Halcyon 2.0 plans in the head & neck, abdomen and pelvis were 0.414, 0.425 and 0.432, which were better than 0.385, 0.368 and 0.361 of Truebeam plans in the corresponding sites, respectively. In the abdomen and pelvis, Halcyon 2.0 plans showed better median modulation complexity score (MCS) than Truebeam plans (0.320 vs. 0.268, 0.303 vs. 0.282; both P<0.05). The median small aperture score (SAS) for all plans of Halcyon 2.0 were better than that of Truebeam plans (all P<0.05), and the median plan average beam area (PA) of all plans of Halcyon 2.0 were larger than that of Truebeam plans (all P<0.05). Conclusions:Compared with conventional fractionated VMAT plans based on Halcyon 2.0 and Truebeam, Halcyon 2.0 plans have similar or even better dosimetric quality. However, Halcyon 2.0 plans have lower plan complexity, which makes it an advantage in clinical application.

Background Essential and non-essential elements have an important impact on the development of the central nervous system during fetal development. Due to their less developed brain, preterm infants are more sensitive to element exposure, and are high-risk groups of neurodevelopmental abnormalities. However, it is not clear whether the effects of element exposure in utero on postpartum neurodevelopment are different between full-term infants and preterm infants. Objective To evaluate the effects of element exposure levels during pregnancy on neurodevelopment of children aged 6-24 months (of corrected age), and compare the effects between preterm and full-term children. Methods A prospective study design was adopted and this study was conducted based on the Maoming Birth Cohort Study (MBCS) in Maoming City, Guangdong Province. Twenty elements in cord blood of 197 preterm infants and 297 full-term infants were measured, including 11 essential trace elements [vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), strontium (Sr), tin (Sn), and iron (Fe)], and 9 non-essential trace elements [aluminum (Al), arsenic (As), thallium (Tl), lead (Pb), uranium (U), cerium (Ce), antimony (Sb), cadmium (Cd), and yttrium (Y)]. The neurodevelopment of the children at 6, 12, and 24 months were evaluated by the Ages and Stages Questionnaires-the Third Edition (ASQ-3). A generalized estimating equation (GEE) model was adopted to evaluate the associations between elements and neurodevelopment in full-term and preterm children separately. Results The positive rates of 10 elements (Mn, Cu, Zn, Se, Sr, Fe, Sb, Tl, Pb, and As) in cord blood were greater than 80%. Among the preterm birth children, the results of GEE analysis showed that after adjusting for the covariates, for each increase of interquartile range (IQR) in ln-transformed concentration, As was associated with problems/delay in the communication and problem-solving sub-scales, with the adjusted odds ratios (OR) and 95% confidence intervals (CI) of 1.36 (1.03-1.80) and 1.55 (1.10-2.20), respectively; the adjusted OR (95%CI) of problems/delay in the fine motor and problem-solving sub-scales were 1.44 (1.00-2.07) and 1.76 (1.09-2.84) for Sb, respectively; the adjusted OR (95%CI) of problems/delay in the communication sub-scale was 1.37 (1.09-1.74) for Se. No statistically significant associations between umbilical cord blood element concentrations and neurodevelopment indicators were observed among full-term children. The results of stratified analysis by sex showed that the associations between umbilical cord blood element concentrations and neurodevelopment problems/delay were only significant among female preterm children. Conclusion Exposures to As, Se, and Sb during pregnancy may increase the risk of neurodevelopment problems/delay in preterm children aged 6-24 months, and female seem to be more vulnerable.

OBJECTIVE To optimize the extraction and separation process of chebulagic acid and chebulinic acid from Terminalia chebula. METHODS Based on single factor experiment， with particle size， liquid-solid ratio， extraction time and extraction times as factors， using the contents of chebulagic acid and chebulinic acid as indexes， orthogonal experiment was designed to optimize the extraction process of chebulagic acid and chebulinic acid. Taking sample concentration， elution solvent and the ratio of eighteen-group bonded silicone reverse phase （ODS） to the amount of raw medicine as factors， the separation processes of chebulagic acid and chebulinic acid were optimized. RESULTS The optimal extraction process of chebulagic acid and chebulinic acid included ethanol volume fraction of 70%， ultrasonic extraction， particle size of 120 mesh， liquid-solid ratio of 25∶1 （mL/g）， extraction time of 20 min， and extracting for 2 times. After 3 experiments， the average comprehensive score was 99.33 （RSD＝ 0.68%， n＝3）， and the average contents of chebulagic acid and chebulinic acid were 107.05 and 58.32 mg/g， respectively. The optimal separation process of the two components included the concentration of sample loading solution was 0.5 g/mL （1 mL was equivalent to 0.5 g of medicinal materials）， the ratio of ODS to the amount of raw medicine was 10∶1.5 （g/g）， methanol-water （1∶4， V/V） eluted chebulagic acid， methanol-water （3∶7， V/V） eluted chebulinic acid. After 3 experiments， the average total yields of the two components were 53.33%， 39.23%. After recrystallization， the purity of both components was 100%. CONCLUSIONS Established extraction and separation process of chebulagic acid and chebulinic acid is simple and feasible.