Objective To study the drug dosage and time dependency characteristics of high-fructose-high-fat-feeding plus dexamethason for inducing the mouse acute fatty liver model and to optimize the condition of drug induced fatty liver model.Methods Male KM mice were divided into the normal control group and high-fructose-high-fat-feeding plus peritoneal injection of dexamethason group.The mice were killed at 3 different time points.The mouse body mass and liver mass were detected.The liver index was calculated.The serum and liver tissue homogenate TG and serum glucose(GLU) levels were detected.The liver tissue pathological change was observed by HE staining.Total RNA reverse expression related gene was extracted from the liver tissue.The total protein was extracted from the liver tissue and the related protein expression was detected by Western Blot.Results Compared with the control group,blood and liver homogenate TG after 7 d in the dexamethason model group was increased,the liver index was increased,the pathological section displayed that the fatty liver was formed.RT-PCR showed that lipid metabolism related gene expression had obvious change.Western Blot showed that SIRT1 was significantly decreased.But with the dexamethason dosage decrease and time extending,the fatty liver related indexes were decreased,lipid metabolic gene PPAR,FOXO3 and FXR were gradually increased,while LXR was gradually decreased and protein SIRT1 was gradually increased.Conclusion High-fructose-high-fatfeeding plus peritoneal injection of dexamethason could establish the mouse acute fatty liver model,moreover the model maintenance has dependency on dexamethason dosage and medication time,which has a guidance significance for the drug interventional experiment.

Objective:To investigate the application of transverse closure of longitudinal incisions in repairing pentagonal full-thickness defects of the lower eyelid margin.Methods:A retrospective analysis was performed on clinical data collected from 26 patients with melanocytic nevi at the lower eyelid margin in Department of Dermatology, The Third People′s Hospital of Hangzhou from July 2016 to June 2019. Among the 26 patients, 10 were males, and 16 were females. After lesion resection, all the pentagonal full-thickness defects of the lower eyelid margin were repaired via transverse closure of longitudinal incisions.Results:All the pentagonal defects of the 26 cases were successfully repaired. The longitudinal incisions perpendicular to the eyelid were successfully converted into transverse incisions parallel to the eyelid margin and near the eyelash, and all incisions healed primarily. After surgery, mild congestion of the lower eyelid occurred in 3 patients, and temporary blurred vision in 1. During 1 - 2 years of postoperative follow-up, 26 patients all achieved symmetrical appearance of the skin and soft tissues around the eyes, without obvious postoperative scars or lower eyelid ectropion.Conclusions:Horizontal closure of longitudinal incisions can be used to repair the pentagonal full-thickness defects of the lower eyelid margin, because it can convert the incision closure line perpendicular to the lower eyelid margin into a horizontal transverse incision closure line parallel to the lower eyelid margin, so that the incisions and scars of the lower eyelid can be hided with a satisfactory cosmetic effect.

Objective:To explore the correlation between preoperative echocardiography indicators and surgical prognosis of children with ventricular septal defect (VSD) and conduct verification based on significant indicators and indicator ratios.Methods:A total of 1 357 children with VSD who were admitted to the Children′s Hospital, Zhejiang University School of Medicine from June 2016 to June 2021 were selected. Various measurements including the size of the VSD, left ventricular ejection fraction (LVEF), left atrial (LA) diameter, the aortic (AO) flow rate, the tricuspid regurgitation velocity and pressure gradient were extracted from preoperative echocardiography reports. This paper explored the correlation between echocardiography reports indicators, indicator ratios and postoperative auxiliary ventilation time, respectively. The patients were divided into two groups according to whether there were complications, and the differences of echocardiography reports indicators between the two groups were compared. A linear regression model was established to predict the postoperative auxiliary ventilation time using these indicators, and the least absolute shrinkage and selection operator (LASSO) regression model was used for variable selection.Results:The VSD size and AO flow velocity were weakly correlated with the postoperative auxiliary ventilation time ( r=0.32, 0.25; all P<0.01). There was no significant correlation between VSD flow velocity and postoperative auxiliary ventilation time. The AO flow velocity/VSD flow velocity and LVEF/VSD flow velocity were strongly correlated with the postoperative auxiliary ventilation time ( r=0.67, 0.51; all P<0.01). In the significance test, there were no significant differences in tricuspid regurgitation flow velocity, tricuspid regurgitation pressure gradient, LA diameter, and LVEF between the complication group and the non-complication group(all P>0.01). However, the ratio of LVEF/tricuspid regurgitation velocity in the complication group was significantly lower than that in the non-complication group, and the ratio of tricuspid regurgitation pressure gradient/LA diameter was significantly higher than that in the non-complication group (all P<0.01). The postoperative auxiliary ventilation time of VSD patients was predicted on an independent test set, with an R2 of 0.51. Conclusions:Echocardiography report indicator ratios of AO flow velocity/VSD flow velocity and LVEF/VSD flow velocity have strong correlations with postoperative auxiliary ventilation time in children with VSD, and the ratios of LVEF/tricuspid regurgitation velocity and tricuspid regurgitation pressure gradient/LA diameter are significantly different between groups with and without postoperative complications. The ratios of indicators can significantly improve this correlation and difference, which can be used to predict the prognosis of VSD operation.

Objective:To summarize and analyze the efficacy of the upper eyelid orbicularis oculi myocutaneous island flap in repairing secondary defects after resection of eyelid and periorbital skin tumors.Methods:A retrospective analysis was carried out on clinical data collected from 28 patients, whose secondary eyelid and periorbital defects were repaired with the upper eyelid orbicularis oculi myocutaneous island flaps in the Department of Dermatology, Hangzhou Third People′s Hospital from August 2019 to June 2021. The survival condition of the flaps was observed after the operation, and the appearance of the upper eyelid and periorbital skin as well as tumor recurrence were evaluated during the follow up.Results:Among the 28 cases, there were 6 males and 22 females; their ages ranged from 47 to 87 years (70.5 ± 10.9 years), 7 patients were aged 80 - 89 years, 8 aged 70 - 79 years, 8 aged 60 - 69 years, 4 aged 50 - 59 years, and 1 patient was aged 40 - 49 years. Skin defects were distributed at the upper eyelid in 1 case, at the lower eyelid in 9 cases, at the inner canthus in 1 case, at the outer canthus in 3 cases, at the upper eyebrow in 1 case, at the dorsum of the nose in 3 cases, and at the junction of the external nose, inner canthus and lower eyelid in 10 cases. The skin defects varied from 1.0 cm × 0.5 cm to 3.1 cm × 2.3 cm in size. The designed upper eyelid orbicularis oculi myocutaneous flap was 0.5 - 1.8 cm in width and 3 - 4 cm in length, and the length of the subcutaneous tunnel was 1.2 - 2.5 cm. During the follow-up of 6 months to 1.5 years, all flaps survived; scars on the upper eyelid donor sites were not obvious; there was no upper eyelid ectropion, no trichiasis, and no eyelid closure abnormality after the operation.Conclusion:The medium- or small-sized defects of the eyelid and periorbital skin can be successfully repaired by the upper eyelid orbicularis oculi myocutaneous island flap, with a favorable cosmetic effect and concealed donor areas.

Objective:To investigate the clinical efficacy of bilateral V-Y advancement island flaps on buttocks in repairing postoperative defects in patients with perianal Paget′s disease.Methods:From January 2009 to January 2021, a retrospective analysis was performed on clinical data collected from 13 patients with perianal Paget′s disease, whose perianal defects resulting from the tumor resection were reconstructed with bilateral V-Y advancement island flaps on the buttocks in the Department of Dermatology, Hangzhou Third People′s Hospital. The postoperative recovery of the buttocks and the effects on the defecation function were evaluated.Results:The areas of perianal defects in 13 cases ranged from 4.8 cm × 5.6 cm to 12.2 cm × 6.4 cm. All defects were successfully repaired by using the bilateral V-Y advancement island flaps, and all surgical wounds healed primarily. One case first received temporary ileostomy, and then received ileostomy closure 3 months later, resulting in the recovery of defecation function; in another 1 case of perianal Paget′s disease comorbid with rectal cancer, the permanent sigmoid colostomy was performed to divert feces, and the defecation function was lost. After the follow-up for 1 - 6 years, the buttocks were symmetrical in shape in all the 13 patients, and 12 with preserved anus had normal defecation function. No tumor recurrence was observed in 12 patients without other malignant tumors after the operation, while 3 patients experienced mild anal stenosis without anal mucosa eversion or wound dehiscence; 1 patient with perianal Paget′s disease complicated by anal canal adenocarcinoma developed bilateral inguinal lymph node and internal iliac lymph node metastasis 1 year after the operation, and died 6 months later.Conclusion:The bilateral V-Y advancement island flaps on the buttocks have the advantages of reliable blood supply and sufficient advancement mobility, and can be used to repair large skin defects around the anus.

ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling， 40 surviving mice were randomly divided into model group， cisplatin group ［2.5×10^-3 g·kg^-1·（3 d）^-1］， Shenqi Yiliu prescription group （27 g·kg^-1·d^-1）， and a combination group （Shenqi Yiliu prescription group + cisplatin）. The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention， the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators， including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. The TdT-mediated dUTP-biotin nick end labeling （TUNEL） assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry （IHC）， immunofluorescence （IF）， and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， and gasdermin D （GSDMD） in tumor tissues. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in tumor tissues were detected by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the mice in the blank group， those in the model group were in a poor mental state， sleepy， and lazy， and their fur color was dull， with increased levels of serum ALT and AST in liver function tests （P<0.01）. Compared with the model group， the groups with drug intervention showed improved mental state， inhibited tumor growth to varying degrees， and decreased tumor weight， and the tumor inhibition rate in the combination group was the highest （P<0.01）. HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant， while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test， the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased （P<0.05， P<0.01）. Among them， the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant （P<0.01）. TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention （P<0.05， P<0.01）， especially the cisplatin group and Shenqi Yiliu prescription group （P<0.01）. Western blot， IHC， and IF found that the protein expression levels of NLRP3， Caspase-1， and GSDMD in each group with drug intervention decreased （P<0.05， P<0.01）. Compared with the mice in the cisplatin group， those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology， and the tumor weight of the mice in the combination group decreased （P<0.05）. The levels of ALT and AST in the Shenqi Yiliu prescription group decreased （P<0.05）， and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased （P<0.05， P<0.01）， especially in the combination group （P<0.01）. The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced （P<0.01）. IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced （P<0.01）. The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the expression level of Caspase-1 protein in the combination group decreased （P<0.01）. The decrease in GSDMD protein expression was not significant， and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect， which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis， and relieve the inflammatory response in mice with liver cancer.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.