1.Effects of laminarin on non-proliferative diabetic retinopathy in C57BL/6 mice based on transcriptomics analysis
Lei Zhang ; Sumei Zhang ; Zhen Yang ; Weikang Hu ; Hongmei Bai ; Wenjing Zhou ; Zihan Wang ; Mingcong Li ; Shengquan Zhang ; Rongfeng Liao
Acta Universitatis Medicinalis Anhui 2025;60(3):392-398
Objective :
To investigate the effect of laminarin(LAM) on nonproliferative diabetes retinopathy by high throughput sequencing(RNA-seq).
Methods :
The diabetes model was established by intraperitoneal injection of streptozotocin(STZ), and the effect of LAM on diabetic mice was observed.C57BL/6 mice were randomly divided into three groups: Control group, Model group, and LAM group, with 8 mice in each group. After 8 weeks of modeling, the LAM group received a 4-week intraperitoneal injection of LAM treatment. Changes in blood glucose and body weight of the three groups of mice were recorded, HE staining was performed to examine retinal lesions, and RNA-seq was used to identify differentially expressed genes(DEGs) in diabetic retinopathy(DR) under the action of STZ and LAM.
Results :
STZ successfully established the model of DR, and LAM reduced the blood sugar in diabetic mice to a certain extent and improved the pathological morphology of retinal structural looseness in diabetic mice. After RNA-seq analysis of DEGs, it was found that there were a total of 214 DEGs in the retina of the Model group mice compared to the Control group. Enrichment analysis revealed that DR could exacerbate the lesions through the PI3K Akt signaling pathway. There were a total of 42 DEGs in the retina of the Model group and LAM group mice, and enrichment showed that LAM improved the lesions through the neutrophil extracellular trap pathway. Early growth response factor 1(Egr1), FBJ osteosarcoma oncogene(Fos), nuclear receptor subfamily 4A member 1(Nr4a1), and salt-induced kinase 1(Sik1) were regulated by STZ, and LAM significantly regulated their expression, which might be closely related to LAM′s treatment of diabetic retinopathy.
Conclusion
DEGs can exacerbate the severity of diabetic retinopathyviathe PI3K-Akt signaling pathway. LAM can mitigate diabetic retinopathyviathe neutrophil extracellular trap pathway. Egr1, Fos, Nr4a1, and Sik1 are key genes involved in LAM treatment of STZ-induced DR.
2.Endoplasmic reticulum stress involved in high-fat induced metabolic dysfunction-associated steatotic liver disease
Weikang Hu ; Wenjing Zhou ; Jun Zhang ; Zhen Yang ; Hongmei Bai ; Zihan Wang ; Yinliang Qi ; Shengquan Zhang ; Sumei Zhang
Acta Universitatis Medicinalis Anhui 2025;60(6):1086-1090
Objective :
To investigate the role of endoplasmic reticulum stress in the occurrence and development of fatty liver induced by high fat.
Methods :
In the high-fat Drosophila model, the high-fat group was fed with high-fat medium, while the control group was fed with normal medium; in the mouse fatty liver model, the high-fat group was fed with high-fat diet, and the control group was fed with normal diet; in the HepG2 cell steatosis model, the high-fat group was induced by palmitic acid(PA), and the control group was cultured with DMEM. The fat body size of the third instar larvae of Drosophila melanogaster was photographed. Steatosis in mice liver and HepG2 cells was observed by H&E and Oil Red staining. The expression levels of ATF6, Bip and CHOP in the third instar larvae, liver tissues of mice and HepG2 cells were analyzed by quantitative real-time polymerase chain reaction(qPCR) and Western blot.
Results :
In Drosophila model, fat body and fat storage were obviously increased in high fat fed flies when compared with control group. The formation of liver fat droplets and cells vacuolation were confirmed by H&E and Oil Red staining in mice livers fed with high fat and HepG2 cells with palmitic acid treatment. The expression levels of ATF6, Bip and CHOP were significantly increased in third instar larvae and mice livers fed with high fat and palmitic acid treated HepG2 cells with palmitic acid treatment.
Conclusion
High fat may induce the occurrence and development of hepatic steatosis by activating endoplasmic reticulum stress.
3.Effects of LSS function deficiency on intestinal function in NAFLD model mice
Hongmei Bai ; Zhen Yang ; Weikang Hu ; Zihan Wang ; Wenjing Zhou ; Qingya He ; Jian Zhong ; Mingcong Li ; Li Liu ; Chaoyang Zhang ; Sumei Zhang ; Shengquan Zhang
Acta Universitatis Medicinalis Anhui 2025;60(9):1653-1660
Objective:
To investigate the effect of loss of function of lanosterol synthase( LSS) gene on intestinal function in a mouse model of non-alcoholic fatty liver disease( NAFLD) induced by a high-fat diet.
Methods:
LSS gene heterozygous knockout C57 mice ( LSS + / -) were established using the CRISRP / Cas9 system.After being fed a high-fat diet with 60% fat content for 6 months,the fat deposition in liver tissues was detected by HE and Oil red O staining,the morphological changes of small intestine tissue were detected by HE staining.The changes in total cholesterol content in intestinal tissue were detected by kits.The gastrointestinal motility function of mice was detected by phenol red paste.The intestinal permeability was detected by Evans blue staining,and the expression of LSS,tight junction protein ( Claudin) -1,Claudin-5,cluster of differentiation 36 ( CD36) ,and Niemann-Pick type C1-like 1 protein ( NPC1L1) proteins in small intestinal tissues were detected by Western blot.
Results :
The results of HE and Oil red O staining of liver tissues showed that liver fat deposition in LSS gene heterozygous knockout mice was lower than that in wild-type mice in the high-fat diet group.The total cholesterol content in intestinal tis- sue of LSS gene heterozygous knockout mice decreased ( P <0. 01) ,but no morphological differences were ob- served between the two groups of mice by HE staining of intestinal tissues.The gastrointestinal motility function of LSS gene heterozygous knockout mice did not show significant changes.The intestinal permeability of LSS gene het- erozygous knockout mice in the high-fat diet group decreased as detected by Evans blue ( P<0. 05) .The expres- sion levels of Claudin-5 protein in the intestinal tissue of LSS gene heterozygous knockout mice in the high-fat diet group increased ( P <0. 05 ) ,while the expression of LSS protein in the intestinal tissues of LSS heterozygous knockout mice decreased ( P <0. 05) .
Conclusion
In the NAFLD model induced by a high-fat diet,LSS gene heterozygous knockout reduces liver fat deposition induced by a high-fat diet and improves intestinal barrier function by regulating cholesterol metabolism in intestinal tissues and up-regulating the expression of Claudin-5.
4.Changes in behavior and spatial memory of C57BL/6J mice of different ages
Zhen Yang ; Hongmei Bai ; Weikang Hu ; Mingcong Li ; Xiaoli Jiang ; Chaoyang Zhang ; Zihan Wang ; Wenjing Zhou ; Qingya He ; Jian Zhong ; Shengquan Zhang
Acta Universitatis Medicinalis Anhui 2025;60(8):1410-1417
Objective :
To explore the changes in behavior and spatial memory of C57BL/6J female mice of different ages (youth , middle-aged , and elderly) .
Methods:
C57BL/6J female mice were divided into female youth group (YG group) , female middle-aged group ( MG group) and female elderly group ( OG group) according to age. The Morris water maze test measured spatial memory ability , and the open field and elevated cross maze test observed activity level and anxiety level. Western blot was used to determine the protein expressions of CREB , CaMKⅡ(pan) and CaMKⅡ(p) in the hippocampus of the brain tissues of female mice in each group.
Results:
Compared with the YG group , the weight of the MG group and the OG group significantly increased (P < 0. 01 , P < 0. 001) . Compared with the OG group , the third quadrant escape latency and the number of crossings in the YG group and MG group were shortened , and the difference was not statistically significant. Compared with the OG group , there was a statistically significant difference in the exercise speed in the open field of the YG group (P < 0. 01) , there was no significant difference in the movement speed in the open field of the MG group , the number of entries into the central zone significantly increased in the MG group ( P < 0. 05 ) , and there was no significant difference in the number of entries in the YG group (P > 0. 05) . Compared with the OG group , the YG group had a statistically significant difference in the elevated cross maze (P < 0. 05) , the MG group had no statistically signif- icant difference in the elevated cross maze , and the number of closed arm entries in the YG group and MG group significantly increased (P < 0. 001 , P < 0. 01) . Compared with the YG group , the relative expression level of CaMKⅡ(pan) in the OG group was statistically significant ( P < 0. 05 ) , while the relative expression level of CaMKⅡ(pan) in the MG group was not statistically significant ( P > 0. 05) .
Conclusion
With the increase of age , the weight of C57BL/6J female mice gradually increased , the activity level and desire to explore gradually de- creased , the spatial memory ability also declined , and the anxiety level and anxiety-like behavior increased. This study helps to reveal the effect of age on the activity level and cognitive function of females , and provides a refer- ence for studying cognitive and memory decline in older females.
5.Health promotion measures for common allergic diseases
Shunan LIU ; Hongxiang CHEN ; Ying XIONG ; Guanghui LIU ; Weikang ZHOU
Chongqing Medicine 2024;53(1):149-154
Allergic diseases seriously affect people's health,throughout the whole life cycle,from chil-dren to adults and then to the elderly allergy,can be lifelong onset,and need comprehensive prevention and treatment of the whole life cycle.Its occurrence and development have certain rules,it is usually first manifes-ted as atopic dermatitis in infants and young children,and then gradually develops into food allergy,allergic rhinitis(AR),and allergic asthma.Intervention in atopic dermatitis and or reducing the sensitization of food allergens can inhibit the allergic process and reduce the occurrence of AR and allergic asthma.Therefore,inter-vening and blocking the allergic processes is the key to the prevention and treatment of allergic diseases.This article focuses on the comprehensive intervention measures of allergic diseases(including health education,al-lergen intervention,nutrition intervention,daily nursing,psychological intervention)and disease monitoring,in order to promote the development of the prevention and treatment of allergic diseases.
6.Role of Ghrelin in gastric cancer
Weikang LI ; Dongbao LI ; Jiayu REN ; Xiaotong SUN ; Kaipeng DUAN ; Jin ZHOU
Basic & Clinical Medicine 2024;44(10):1460-1464
Ghrelin is a newly discovered gastrointestinal peptide that is involved in regulating the body's growth,development and energy balance,and plays a key role in the occurrence and progression of malignant tumors,such as cell proliferation,migration,invasion,apoptosis,inflammatory response and vascular disease.Generate immune cell infiltration and so on.Ghrelin affects the progression of gastric cancer by activa-ting NF-κB/p65 and AMPK and other signaling pathways.Ghrelin not only assist in early screening of gastric cancer,but also function a new marker for predicting the prognosis and survival of gastric cancer patients.Ghrelin and its analogs have clinical application value in the treatment of gastric cancer-related syndromes such as cachexia or sarcopenia.
7.Multi-Parameters Derived from Dual-Layer Spectral-Detector CT in Evaluating the Pathological Tumor Staging of Rectal Adenocarcinoma
Weicui CHEN ; Sifan ZHOU ; Wuxi ZHENG ; Hanliang ZHANG ; Jianye LU ; Yunying LIN ; Weikang HUANG ; Jialiang CHEN
Chinese Journal of Medical Imaging 2024;32(1):81-86
Purpose To explore the value of dual-layer spectral detector CT(DLSCT)in evaluating preoperative tumor staging in rectal adenocarcinoma(RA).Materials and Methods A total of 78 patients with pathologically confirmed RA in Guangdong Provincial Hospital of Chinese Medicine from May 2021 to March 2022 were involved in this retrospective study.All the patients underwent plain and dual-phase contrast-enhanced scans by DLSCT within one week before surgery.Taking pathological results as the golden standard,the accuracy rates of tumor staging were calculated and compared between the multiple-parameter maps derived from DLSCT and 120 kVp polyenergetic image.The effective atomic number(Z-eff)from plain scan,iodine concentration(IC)from arterial phase(AP)and venous phase(VP)were measured.The normalized iodine concentration(NIC)in AP and VP were calculated.The differences of Z-eff,NICAP and NICVP were compared among the pT1-2,pT3 and pT4 groups.The correlation between the pT stages and above values was assessed and the diagnostic efficiencies were analyzed.Results The overall accuracy rate(88.46%vs.67.95%;χ2=9.628,P=0.002),the pT1-2 staging accuracy rate(80.00%vs.40.00%;χ2=6.667,P=0.01),and the pT3 staging accuracy rate(88.10%vs.69.05%;χ2=4.525,P=0.033)of multiple-parameter maps derived from DLSCT were significantly higher than those of 120 kVp polyenergetic image,respectively.The Z-eff,NICAP and NICVP were significantly different among pT stage groups(F=6.456,11.029,12.698,all P<0.05)and exhibited a positive correlation with pT stages(r=0.371,0.367,0.363,all P<0.01).The areas under the curve of Z-eff,NICAP and NICVP to assess pT3-4 staging RA were 0.77,0.71 and 0.74,respectively.Conclusion The multiple-parameter maps derived from DLSCT can significantly improve the diagnostic accuracy of preoperative tumor staging of RA.Z-eff from plain scan and NIC from dual-phase helps differentiate pT1-2 from pT3-4 staging RA.
8.Efficacy analysis of laparoscopic proximal gastrectomy with single-flap esophagogastrostomy in 7 cases of early gastric cancer
Kaipeng DUAN ; Dongbao LI ; Weikang LI ; Xiaotong SUN ; Lixing GU ; Pengbo WANG ; Jin ZHOU
Chinese Journal of General Surgery 2024;33(10):1633-1641
Background and Aims:In recent years,function-preserving proximal gastrectomy with reconstruction has become an important approach for the treatment of early gastric cancer.However,there is no standardized surgical technique,and the short-and long-term outcomes of various new procedures remain unclear.This study was performed to evaluate the safety and short-term efficacy of laparoscopic proximal gastrectomy plus esophagogastrostomy with single-flap technique for early gastric cancer. Methods:The clinical data and follow-up records of 7 patients who underwent laparoscopic proximal gastrectomy with single-flap esophagogastrostomy in the First Affiliated Hospital of Soochow University between December 2021 and December 2022 were retrospectively analyzed.Perioperative safety,postoperative reflux,anastomotic stricture at 6 months,and related nutritional parameters were assessed.The nutrition-related indicators of this group of patients were compared with those of 11 patients who underwent total gastrectomy with Roux-en-Y anastomosis for early gastric cancer during the same period. Results:All 7 patients successfully underwent laparoscopic proximal gastrectomy with single-flap esophagogastrostomy.The average operative time was(212.9±20.6)min,with anastomosis taking(54.7±10.5)min;the mean intraoperative blood loss was(28.6±9.0)mL.No Clavien-Dindo grade Ⅲ or higher complications were observed during hospitalization.None of the patients experienced significant reflux symptoms,although 1 patient developed anastomotic stricture 3 months after operation.There were no statistically significant differences in hemoglobin concentration,albumin level,prealbumin level,total protein concentration,and lymphocyte count between preoperative and 6-month postoperative measurements(all P>0.05).Compared to patients who underwent total gastrectomy with Roux-en-Y anastomosis,those who had the proximal gastrectomy with single-flap esophagogastrostomy showed a lower percentage decrease in body weight,skeletal muscle area at the third lumbar vertebra(L3),visceral fat area at L3,and hemoglobin concentration at 1 year after operation(all P<0.05). Conclusion:Laparoscopic proximal gastrectomy with single-flap esophagogastrostomy is a safe and feasible surgical option for early gastric cancer,offering effective anti-reflux outcomes while minimizing the risk of anastomotic stricture.This procedure has a lower impact on postoperative nutritional status compared to total gastrectomy.
9.Plasma ghrelin concentration on postoperative complications and nutritional status in patients with gastric cancer
Weikang LI ; Kaipeng DUAN ; Dongbao LI ; Jiayu REN ; Xiaotong SUN ; Lixing GU ; Jin ZHOU
Chinese Journal of General Surgery 2024;39(8):615-619
Objective:To investigate the impact of neuroendocrine function on postoperative complications and nutritional status in gastric cancer patients.Methods:Clinical data of 102 gastric cancer patients who underwent radical gastrectomy at the Department of General Surgery, First Affiliated Hospital of Soochow University, from Aug 2021 to Jun 2022 were retrospectively analyzed.Results:Among the 102 gastric cancer patients, 18 (17.6%) suffered from postoperative complications. Univariate analysis indicated that age, BMI, preoperative plasma ghrelin concentration, and preoperative hemoglobin levels were associated with early postoperative complications following radical gastrectomy. Multivariate analysis revealed that age, BMI, and preoperative plasma ghrelin concentration ( P<0.05) were independent risk factors for postoperative complications in gastric cancer patients. Differential analysis of ghrelin concentration demonstrated correlations with hemoglobin levels, skeletal muscle index, albumin, and creatinine, and a positive correlation with the skeletal muscle index. Conclusions:Reduced preoperative neuroendocrine hormone ghrelin concentration is an independent risk factor for postoperative complications in gastric cancer patients. Ghrelin concentration is correlated with the skeletal muscle index in these patients.
10.Clinical imaging features and prognosis of von Hippel-Lindau syndrome associated with pancreatic lesions
Qiuzheng CHEN ; Jingcheng ZHOU ; Zonghao LIU ; Xiaochao GUO ; Weikang LIU ; Xiaodong TIAN ; Kan GONG ; Yinmo YANG
Chinese Journal of Digestive Surgery 2023;22(5):650-656
Objective:To investigate the clinical imaging features and prognosis of von Hippel-Lindau (VHL) syndrome associated with pancreatic lesions.Method:The retrospective case-control study was conducted. The clinicopathological data of 161 patients with VHL syndrome who were admitted to Peking University First Hospital from September 2010 to August 2022 were collected. There were 83 males and 78 females, with age of onset as 27.0(range, 8.0-66.0)years. Observation indicators: (1) imaging results of VHL syndrome associated with pancreatic lesions; (2) clinical characteristics of VHL syndrome associated with pancreatic lesions; (3) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions; (4) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic neuroendocrine neoplasms (pNENs). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Results:(1) Imaging results of VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, there were 151 patients associated with pancreatic lesions and 10 patients not associated with pancreatic lesions. Of the 151 patients with VHL syndrome associated with pancreatic lesions, there were 136 patient with pancreatic cystic lesions and 34 patients with pNENs, 22 patients with both pNENs and pancreatic cystic lesions, and the type of pancreatic lesions could not be accurately determined in 3 cases. (2) Clinical characteristics of VHL syndrome associated with pancreatic lesions. The age of onset in 151 patients with VHL syndrome associated with pancreatic lesions was 33.0(range, 14.0-68.0)years. Cases with gene site mutation of exon 1, exon 2, exon 3 and other types of gene site was 51, 16, 43 and 41, respectively. There were 116 patients of VHL type 1 and 35 patients of VHL type 2. There were 92 patients with family history of VHL syndrome and 59 patients without family history of VHL syndrome. There were 127 patients combined with renal cell carcinoma, 112 patients combined with central nervous system lesions, 46 patients combined with retinal hemangioblastoma. Patients may combined with multiple lesions. (3) Comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions. The age of onset, VHL syndrome type (VHL1 type, VHL2 type) and cases combined with renal cell carcinoma were 32.5(range, 14.0-68.0)years, 110, 26 and 115 in 136 patients with VHL syndrome associated with pancreatic cystic lesions, versus 22.0(range, 8.0-64.0)years, 13, 12 and 14 in 25 patients with VHL syndrome not associated with pancreatic cystic lesions, showing significant differences in the above indicators between them ( Z=-3.384, χ2=9.770, 10.815, P<0.05). (4) Comparison of clinicopathological factors in patients with VHL syndrome associated with pNENs. The age of onset, gene mutation sites (exon 1, exon 2, exon 3, other types of gene site) and VHL syndrome type (VHL1 type, VHL2 type) were 33.5(range, 14.0-64.0)years, 12, 5, 14, 3 and 18, 16 in 34 patients with VHL syndrome associated with pNENs, versus 27.0(range, 9.0-66.0)years, 41, 12, 32, 42 and 105, 22 in 127 patients with VHL syndrome not associated with pNENs, showing significant differences in the above indicators between them ( Z=-4.030, χ2=8.814, 13.152, P<0.05). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, 3 patients underwent surgical treatment, and the remaining patients were followed up. All 161 patients with VHL syndrome were followed up for 6 (range, 1-12)years, in which 15 patients died and 146 patients alive during the follow-up. The follow-up time of 3 patients undergoing surgical treatment was 4, 14, 9 years, respectively, and all of them were alive. Conclusions:The clinical imaging features of pancreatic lesions related to VHL syndrome are cystic lesions and pNENs, which with the characteristics of multiple lesions and benign tumors. Such patients usually do not requiring surgical treatment and have good prognosis.


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