Objective To determine the time point when porcine pancreatic elastase(PPE)induced abdominal aortic aneurysm(AAA)reaches the regression phase in mice and observe the histological characteristics of AAA in regression phase.Methods AAAs were induced by transient intraluminal infusion of PPE in C57BL/6J mice.The diameters of the mouse abdominal aortas were measured before PPE infusion and sacrifice time,day 14 for AAA progression phase or day 56 for regression phase after PPE infusion,respectively.The histological characteristics of the aneurysm lesion site on day 14 and day 56 after surgery were compared and analyzed.Results The diameters of the abdominal aortas were significantly increased in both day 14 and day 56 after PPE infusion groups(diameter growth rate 147％and 155％,respectively)as compared to the baseline diameters.In the day 14 group,the infused aortas showed typical AAA characteristics,such as elastin break/degradation,medial smooth muscle cells depletion,and inflammatory cell diffused infiltration.In the day 56 group after PPE infusion,although the artery diameter did not change significantly as compared to the day 14 group,histology showed that elastin was partially repaired,new smooth muscle cells were added to the damaged aorta media,the infiltrated inflammatory cells were significantly subsided,and the adventitia neovascularization was reduced,showing a significant feature of the disease regression phase.Conclusion In the PPE-induced mouse AAA model,day 56 after surgery is an appropriate time point for observing aneurysm regression,and the histological characteristics of the regression are obvious.

ObjectiveTo observe the effect of modified Dahuang Huanglian Xiexintang on mitochondrial autophagy and browning of visceral adipose tissue in obese type 2 diabetes mellitus （T2DM） model ZDF rats. MethodForty ZDF rats were induced with a high-fat diet to establish an obese T2DM model. The rats were randomly divided into five groups： Model group， metformin group （0.18 g·kg^-1）， and high， medium， and low dose groups of modified Dahuang Huanglian Xiexintang （2.16， 1.08， 0.54 g·kg^-1）， with eight rats in each group. Additionally， eight ZDF （fa/+） rats were assigned to the normal group. All groups received an intragastric volume of 10 mL·kg^-1， with the model and normal groups receiving the same volume of purified water once daily for 12 weeks. Fasting blood glucose （FBG） was regularly measured. After 12 weeks of intervention， the body weight， epididymal fat weight， and serum levels of glucose （GLU）， glycated serum protein （GSP）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in epididymal fat tissue. Transmission electron microscopy （TEM） was employed to observe mitochondrial autophagy in adipocytes. Real-time PCR was used to detect the mRNA expression of hypoxia-inducible factor-1α （HIF-1α）， Bcl-2/adenovirus E1B 19 kDa interacting protein 3 （BNIP3）， microtubule-associated protein 1 light chain 3B （LC3B）， p62/SQSTM1， uncoupling protein 1 （UCP1）， iodothyronine deiodinase 2 （Dio2）， and PR domain containing 16 （Prdm16） in epididymal fat. Western blot was used to detect the protein expression of HIF-1α， BNIP3， LC3B， p62， and UCP1 in epididymal fat. ResultCompared with the normal group， the model group showed pathological changes in epididymal fat， with adipocyte mitochondrial condensation and numerous autophagosomes indicating mitochondrial autophagy. The model group also exhibited significantly increased body weight， epididymal fat weight， FBG， GLU， GSP， TC， TG， and LDL-C levels （P<0.01）， significantly decreased HDL-C levels （P<0.01）， significantly elevated mRNA and protein expression of HIF-1α， BNIP3， and LC3B （P<0.01）， significantly reduced mRNA and protein expression of p62 and UCP1 （P<0.01）， and significantly reduced mRNA expression of Dio2 and Prdm16 （P<0.01）. Compared with the model group， all intervention groups showed varying degrees of improvement in epididymal fat pathology. The metformin group and high-dose modified Dahuang Huanglian Xiexintang group displayed intact mitochondrial morphology， clear cristae， uniform matrix， and few autophagosomes and autophagosomes in the adipocyte cytoplasm. The metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced body weight and epididymal fat weight （P<0.01）. The epididymal fat index was reduced in all intervention groups （P<0.05）， and FBG was lowered in all intervention groups （P<0.01）.Serum GSP， GLU， TG， and LDL-C levels were reduced in the metformin group and the high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The serum TC level was significantly reduced in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.01）， and HDL-C levels were significantly increased in all intervention groups （P<0.05， P<0.01）. The mRNA and protein expression of HIF-1α， BNIP3， and LC3B were significantly reduced， and UCP1 protein expression was significantly increased in the metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The mRNA and protein expression of p62， Dio2， and Prdm16 were significantly increased in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang may inhibit mitochondrial autophagy and promote the browning of visceral adipose tissue through the HIF-1α/BNIP3/LC3B pathway， thereby improving glucose and lipid metabolism in obese T2DM rats.

Type 2 diabetes mellitus （T2DM） is based on insulin resistance （IR） and insulin secretion deficiency， with the specific mechanisms still unclear. Current research involves mechanisms such as glycolipid toxicity， inflammatory response， oxidative stress damage， and mitochondrial dysfunction. Modern traditional Chinese medicine （TCM） scholars have named it "blood glucose collateral disease" based on the clinical characteristics and natural progression of T2DM. This condition is primarily manifested as abnormal blood sugar levels in the early stages， and as the disease progresses， it gradually causes widespread damage to the body's veins and collaterals， ultimately leading to lesions in vessels and collaterals. Among these， "spleen heat" （obesity type） is the most common clinical type of T2DM. The concept of "internal heat-induced elimination" runs through both the onset and complications of T2DM， with internal heat being a key factor in its pathogenesis. The clinical application of Dahuang Huanglian Xiexintang and its modifications has achieved significant therapeutic effects. This paper reviews the origins and treatment characteristics of Dahuang Huanglian Xiexintang， along with clinical application research and experimental studies related to T2DM treatment， involving mechanisms for regulating glucose and lipid metabolism disorders， improving IR， modulating inflammatory responses， combating oxidative stress damage， regulating autophagy-related signaling pathways， modulating intestinal flora， inhibiting pyroptosis， and alleviating endoplasmic reticulum stress， with the purpose to provide direction for further research on the prevention and treatment of T2DM and its related complications， to offer reference for developing Dahuang Huanglian Xiexintang as a rapid hypoglycemic Chinese patent medicine for obese T2DM， and to better guide the clinical promotion of this drug.

Purpose To investigate the clinicopathological characteristics and genetic variations of stage Ⅰ lung adenocarci-noma with high-grade components,according to the new grading system of the WHO classification of thoracic tumors(2021).Methods A retrospective analysis was conducted on the clini-cal data of 785 patients with stage Ⅰ lung adenocarcinoma.HE,EnVision immunohistochemistry and Victoria blue staining were used,common genetic variation(EGFR/KRAS/ALK/ROS1/RET)were detected by PCR method.The correlation between different high-grade components and clinical pathological charac-teristics as well as genetic variations in stage Ⅰ lung adenocarci-noma were analyzed.Results A total of 785 cases of stage Ⅰlung adenocarcinoma were enrolled,including 332 cases with high-grade components and 453 cases without high-grade compo-nents.Among the adenocarcinomas with high-grade components,there were 7 cases of grade 1,150 cases of grade 2,and 175 ca-ses of grade 3.The positive rates of tumor cells spreading through airspace(STAS),vascular invasion,and pleural inva-sion in grade 2 adenocarcinoma with two high-grade components(61.5％,21.2％,26.9％)were significantly higher than that of the adenocarcinomas with only one high-grade component(20.4％,7.1％,5.1％),but there was no significant differ-ence in grade 3 adenocarcinoma.The positive rate(39.0％)of STAS in the micropapillary group with one high-grade component in grade 2 adenocarcinoma was significantly higher than that in the complex glandular group(9.3％)and the solid group(0),while there was no significant difference between the latter two groups.Among the three groups there were no statistically signif-icant differences in grade 3 adenocarcinoma.In 167 cases of ad-enocarcinoma with two or more high-grade components,there were 74 cases(44.3％)of complex glands combined with mi-cropapillary components,67 cases(40.1％)of complex glands combined with solid components,8 cases(4.8％)of micropap-illary combined with solid components,and 18 cases(10.8％)of three types of components.The positive rates of pleural inva-sion and KRAS gene mutation or fusion gene(ALK/ROS1/RET)in the group of complex glands combined with solid(49.3％,28.3％)were significantly higher as compared to those in the group of complex glands combined with micropapil-lary(27.0％,8.6％).The positive rate of psammoma bodies in the group with high-grade components(24.7％)was significant-ly higher than that in those without high-grade components(3.5％,P＜0.001),and the positive rate of psammoma bodies in group of gene mutation(EGFR/KRAS)(40.4％)was higher than that in the no-gene mutation group(26.7％,P＜0.05).Conclusion The clinicopathological features of different high-grade components in stage Ⅰ lung adenocarcinoma are not identi-cal,suggesting that their invasiveness may have different biologi-cal backgrounds.Characteristic morphological observations are helpful.

ObjectiveTo discuss the effect of modified Gegen Qinliantang （MGQT） on blood glucose and lipids and Takeda G protein-coupled receptor 5 （TGR5）-related pathways in pancreatic tissue of obese type 2 diabetes mellitus （T2DM） mice. MethodA total of 10 male specific pathogen free （SPF） m/m mice （7 weeks old） and 50 male SPF （7 weeks old） were adaptively fed for one week in SPF laboratory. The m/m mice were included in the blank group. T2DM was induce d in the 50 db/db mice. The model mice were randomized into the model group， metformin group （0.2 g·kg^-1）， high-dose， medium-dose， and low-dose （31.9， 19.1， 6.4 g·kg^-1） MGQT groups， with 10 in each group， and the drug dose was10 mL·kg^-1. The model group and the blank group received distilled water of the same volume. The administration lasted 12 weeks （once/day）. Fasting blood glucose （FBG） was detected regularly. After 12 weeks of administration， serum levels of glycated serum protein （GSP）， serum glucose （GLU）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected. Pathological changes in the pancreatic tissue were based on hematoxylin-eosin （HE） staining. Western blot was used to determine the protein expression of TGR5， protein kinase A （PKA）， phosphorylated （p）-PKA， cyclic-AMP response element binding protein （CREB）， p-CREB， proprotein convertase 1/3 （PC1/3）， and glucagon-like peptide-1 （GLP-1） in pancreatic tissues. The level of cyclic adenosine monophosphate （cAMP） in pancreatic tissue was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the blank group， the model group had pathological changes in pancreatic tissue， high levels of FBG， GSP， GLU， TC， TG， and LDL-C （P<0.01）， low level of HDL-C （P<0.05）， low protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in pancreatic tissue （P<0.01）， and low content of cAMP in the pancreas （P<0.01）. Pancreatic tissue lesion in the treatment groups were milder than that in the model group. Both the high-dose MGQT and metformin can reduce the levels of FBG， GSP， GLU， TC， TG， and LDL-C in db/db mice （P<0.05， P<0.01） and increase the level of HDL-C （P<0.01）. Except the GLP-1 protein in the medium-dose MGQT group， the protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in the high-dose and medium-dose MGQT groups and the metformin group increased compared with that in the model group （P<0.05， P<0.01）. The content of cAMP in the pancreatic tissue of the high-dose and medium-dose MGQT groups and the metformin group was raised compared with that in model group （P<0.05， P<0.01）. ConclusionMGQT can improve the glucose homeostasis in db/db mice with T2DM by regulating TGR5/cAMP/GLP-1 signaling pathway-related protein expression.

ObjectiveTo observe the effect of modified Gegen Qinliantang on the expression levels of proteins related to the farnesoid X receptor/small heterodimer partner/peroxisome proliferator-activated receptor α （FXR/SHP/PPARα） signaling pathway in the liver tissue of db/db model mice with type 2 diabetes mellitus （T2DM） and explore the underlying mechanism of action of modified Gegen Qinliantang. MethodThirty db/db mice were randomly divided into model group， metformin group （0.2 g·kg^-1）， and high-， medium-， and low-dose modified Gegen Qinliantang groups （31.9， 19.1， 6.4 g·kg^-1）， with 6 mice in each group. An additional six m/m mice were assigned to the blank group. Respective drugs were administered via oral gavage for 12 weeks. Mouse body weight， fasting blood glucose （FBG）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels were measured. Oil red O staining was used to observe hepatic lipid accumulation and periodic acid-schiff （PAS） staining was used to assess hepatic glycogen deposition. Ammonium ferric sulfate staining was used to observe cholesterol deposition in intestinal tissues. Western blot was employed to detect the expression of FXR， cholesterol 7α-hydroxylase （CYP7A1）， SHP， and PPARα proteins in liver tissues， and enzyme-linked immunosorbent assay （ELISA） was used to measure serum free fatty acid （FFA） levels. ResultAt the end of the treatment， compared with the blank group， the model group exhibited significant increases in mouse body weight， FBG， FFA， TC， TG， and LDL-C levels （P<0.01）， along with significant hepatic lipid droplets， reduced hepatic glycogen， noticeable cholesterol accumulation in intestinal tissues， significantly decreased expression of FXR， SHP， PPARα proteins， and significantly increased expression of CYP7A1 protein in liver tissues （P<0.01）. Compared with the model group， the metformin group and the high- and medium-dose modified Gegen Qinliantang groups demonstrated significant reductions in mouse body weight， FBG， FFA， TC， TG， LDL-C levels （P<0.05， P<0.01）， significant increases in HDL-C levels （P<0.05， P<0.01）， decreased hepatic lipid accumulation， increased hepatic glycogen， reduced intestinal cholesterol accumulation， significantly increased expression of FXR， SHP， PPARα proteins， and significantly decreased expression of CYP7A1 protein in liver tissues （P<0.01）. ConclusionModified Gegen Qinliantang may regulate the FXR/SHP/PPARα signaling pathway to suppress FFA levels and improve lipid metabolism in T2DM mice.

【Objective】 To compare the histological characteristics of porcine pancreatic elastase （PPE） induced abdominal aortic aneurysms （AAA） and angiotensin Ⅱ （AngⅡ） induced AAA in mice. 【Methods】 In the PPE group， the mouse abdominal aorta segment from the infrarenal abdominal aorta to the iliac artery was isolated and its branch arteries were ligated to avoid leakage during PPE perfusion. We perfused the isolated aorta segment with a PPE solution at a concentration of 1.5 U/mL for 5 min and then closed the abdominal cavity. The diameter of the abdominal aorta was measured before and 14 days after the surgery， and the perfusion segment of the arteries was collected at day 14 after the surgery. The histological characteristics of the aneurysm were analyzed and graded by histological and immunohistochemical methods. In the AngⅡ group， ten apolipoprotein E knockout mice were prepared， and AngⅡ [1 000 ng/(kg·min)] was infused with osmotic pumps for 28 days. The aorta was separated and the aneurysm aorta segment was analyzed. The wild type mice were used as normal health controls. 【Results】 In the PPE group， the diameter of the PPE perfused aorta segments increased and was significantly larger than the basal diameter ［（0.52±0.02） mm vs. （1.23±0.11） mm］ at day 14 after surgery. All the ten mice developed AAA after PPE application. The histological results showed typical pathological features of AAA in PPE perfused mice， such as elastic fiber breakage， smooth muscle exhaustion， and increased inflammation. Six of the ten mice developed aneurysms after AngⅡ infusion （6/10）. The aneurysms/dilatations were mostly in the suprarenal abdominal aorta， but also in the thoracic aorta and aortic arch. The histology analysis showed that the formation of arterial dissection was common after AngⅡ infusion， and the typical vascular “false lumen” was found. The breakage of elastic fibers， the exhaustion of smooth muscle damage， and the inflammatory response were not as typical as the PPE model in AngⅡ perfused animals. 【Conclusion】 The histological characteristics of PPE induced AAA are very typical and well present the inflammatory process in the development of aneurysm. The AngⅡ model is suitable for the study of aneurysms combined with aortic dissection. Both models have their own advantages and can complement each other.

Objective: To investigate the clinical efficacy of enhanced recovery after surgery(ERAS) in atrial caval shunting (ACS) for type Ⅱ Budd-Chiari syndrome(BCS). Methods: The clinical data of patients underwent ACS for type Ⅱ BCS in the Henan Province People′s Hospital from January 2014 to June 2016 were prospectively analyzed.Randomized and single-blind, controlled study was performed among the patients, and all of them underwent ACS and were divided into control group (patients underwent traditional perioperative management) and ERAS group (patients underwent ERAS perioperative management) based on a random number table.Operational and postoperative data, levels of inflammatory cytokines, stress state evaluation and postoperative complications were observed.The comparison between the two groups was evaluated with an independent sample t test.The trend analyses for variables were done using repeated measures ANOVA.The count data were analyzed using the chi-square test or Fisher exact. Results: Eighty-two patients were screened for eligibility, and allocated into the control group (40 patients) and the ERAS group (42 patients). All patients underwent ACS successfully with no death.Comparison of intraoperative status: operation time, volume of intraoperative blood and number of patients receiving blood transfusion were (211.0±12.9) minutes vs. (207.7±10.7) minutes, (167.5±28.3) ml vs. (165.0±28.4) ml and 3 cases vs. 1 case between the control group and the ERAS group, respectively, showing no difference between the two groups (t=0.90, 0.29, χ²=0.32, all P>0.05). Comparison of postoperative status: time of gastric tube removal, time of catheter removal, time of chest tube, time to flatus, time of food intake, duration of postoperative infusion, duration of postoperative hospital stay and numeric rating scale were (3.7±0.5)days vs. (0.0±0.0)days, (2.3±0.7)days vs. (1.4±0.5)days, (3.7±0.7)days vs. (2.3±0.5)days, (75.2±3.8)hours vs. (46.6±4.2)hours, (75.7±4.7)hours vs. (21.4±2.1)hours, (10.0±1.0)days vs. (5.8±0.9)days, (11.4±1.0)days vs. (7.8±0.6)days, 2.9±0.4 vs. 1.9±0.6 between the control group and the ERAS group, respectively, with statistically differences (t=35.03, 4.36, 8.10, 22.89, 47.78, 14.75, 14.22, 6.13, all P<0.05). Stress state evaluation: the levels of IR were (2.7±0.1) vs.(2.7±0.1), (8.8±0.7) vs. (5.2±0.3), (11.0±0.5) vs. (7.3±0.5), (4.9±0.2) vs. (3.9±0.1), and the levels of C-reaction protein were (14.6±1.3)mg/L vs.(14.6±1.1) mg/L, (101.2±13.6) mg/L vs. (89.5±6.9) mg/L, (62.7±8.6) mg/L vs. (56.4±8.4) mg/L, (46.4±6.7) mg/L vs. (40.0±5.6) mg/L from pre-operation to postoperative day 1, 3 and 5 between the control group and the ERAS group, respectively, with statistically significant differences in changing trends(F=136.61, 4.97, both P<0.05). Comparisons of levels of inflammatory cytokines: the levels of IL-6 were (43.1±2.7) ng/L vs. (43.6±3.6) ng/L, (135.1±6.4) ng/L vs. (117.4±5.7) ng/L, (145.4±6.7) ng/L vs. (128.5±5.5) ng/L, (93.3±3.7) ng/L vs. (88.0±3.9) ng/L, and the levels of TNF-α were (10.4±0.3)mmol/L vs. (10.4±0.3) mmol/L, (14.4±0.4) mmol/L vs. (12.6±0.4) mmol/L, (15.6±0.4) mmol/L vs. (13.8±0.4) mmol/L, (12.3±0.7) mmol/L vs. (11.4±0.6) mmol/L from pre-operation to postoperative day 1, 3 and 5 between the control group and the ERAS group, respectively, with statistically significant differences in changing trends (F=15.15, 21.45, both P<0.05). Comparison of postoperative complications: incidence of complications was 30.0%(12/40) in the control group and 11.9%(5/42) in the ERAS group, and the numbers of patients with nausea and vomiting, respiratory complications and cardiovascular complications were 4, 3, 5 cases in the control group and 3, 1, 1 case in the ERAS group, respectively, showing statistically differences in the incidence of complications(χ²=4.08, P<0.05). All the 82 patients were followed up for 2 to 22 months (median time, 12 months), no patients received reoperation or re-admitted to the hospital duo to complications. Conclusion ERAS management in the perioperative period of ACS for BCS is beneficial to postoperative recovery of patients, and can relieve postoperative stress state and inflammatory response, reduce the duration of hospital stay, and incidence of postoperative complications.

Objective To explore the value of peripheral blood samples in KRAS mutation testing of colorectal cancer patients and the correlation between the number of circulating tumor cells and KRAS mutation testing.Methods We detected KRAS mutation using amplification refractory mutation system PCR method in paraffin embedded tissues and matched peripheral blood samples obtained from 112 colorectal cancer patients and 10 proctitic peripheral blood samples in Affiliated Hospital of Jiangnan University between 2013 and 2014.Meanwhile,immunofluorescence in situ hybridization method was used to count the circulating tumor cells in peripheral blood samples and proctitic control samples.Results Among the 112 colorectal cancer samples tested,25 cases of peripheral blood samples found KRAS mutation (41.1％) and which was 46 in formalin fixed paraffin embedded tissues testing (22.3 ％),with a significant difference (x2 =40.12,P ＜ 0.001).One case with KRAS wild type in formalin fixed paraffin embedded tissues was mutation type in peripheral samples.In another case,mutation site was different in different kinds of samples.The sensibility of KRAS mutation testing was 73.3％,41.9％ and 16.7％ when the number of circulating tumor cells was more than 15,5 to 15,and 1 to 5,respectively,with significant differences (x2 =23.70,P ＜ 0.001).No KRAS mutation and no circulating tumor cells were found in 10 proctitic control samples.Conclusion We find high specificity in KRAS mutation testing of peripheral blood samples.but the accurate rate is not satisfying.KRAS mutation testing in peripheral blood samples may be an optional choice to test KRAS mutations for colorectal cancer patients who were not subjected to surgery.The sensibility of KRAS mutation testing in peripheral blood samples has a corretion with the number of circulating tumor cells.

Objective Comparison of the modified Weaver-Dunn method with AO clavicular hook plate for acromioclavicular joint dislocation efficacy.Methods Surgical treatment of Rockwood Ⅲ to the V Type acromioelavicular joint dislocation 35 cases,depending on the surgical approach,were divided into 2 groups of the modified Weaver-Dunn method and AO clavicular hook plate.Operation time,blood loss,hospitalization costs,postoperative Xray film results,the clinical efficacy results and complications were compared between two groups.Results Modified Weaver-Dunn method Section of the longer operative time,mean intraoperative blood loss more.Shoulder pain,the incidence of postoperative modified Weaver-Dunn method group is significantly lower than the AO clavicular hook plate group,abduction activity was better than AO clavicular hook plate group.AO clavicular hook plate group prone to shoulder mobility and shoulder pain.Postoperative Karlsson assessment standard,modified Weaver-Dunn method were excellent in 10,good in 4 cases and poor in 1,excellent rate was 93％ ;AO clavicular hook plate group were excellent in 8 cases,good in 7 cases and poor in 5 cases,excellent rate of 75 ％.Conclusion Modified Weaver-Dunn method is used to treat complete acromioclavicular joint dislocation.Postoperative shoulder pain and shoulder mobility are in low incidence of shoulder function recovery effect.