1.Palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis: A new target for anti-myocardial fibrosis.
Xuewen YANG ; Yanwei ZHANG ; Xiaoping LENG ; Yanying WANG ; Manyu GONG ; Dongping LIU ; Haodong LI ; Zhiyuan DU ; Zhuo WANG ; Lina XUAN ; Ting ZHANG ; Han SUN ; Xiyang ZHANG ; Jie LIU ; Tong LIU ; Tiantian GONG ; Zhengyang LI ; Shengqi LIANG ; Lihua SUN ; Lei JIAO ; Baofeng YANG ; Ying ZHANG
Acta Pharmaceutica Sinica B 2025;15(9):4789-4806
Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.
2.Analysis of Gut Microbiota Diversity in Osteoporosis Patients with Various Traditional Chinese Medicine Syndrome Types in the Lingnan Region
Huan LI ; Wending YAN ; Tianzhao TIAN ; Jinyuan WANG ; Haodong LIANG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(7):1574-1582
Objective To investigate the diversity of gut microbiota in osteoporosis(OP)patients with various traditional Chinese medicine(TCM)syndrome types in the Lingnan region.Methods The analysis was carried out in 13 OP patients with blood stasis and qi stagnation syndrome(Group 1)and 13 OP patients with liver-kidney deficiency syndrome(Group 2)who were treated at Guangzhou Hospital of Chinese Medicine,the Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2023 to December 2023.Fecal samples of both groups were collected,and baseline comparisons between the two groups were performed before testing.After DNA extraction,valid sequencing data were processed by operational taxonomic unit(OTU)clustering,species annotation,and microbial community composition analysis.Alpha and Beta diversity indices were employed to assess species diversity,and LEfSe was used to identify key microbial taxa.Results No significant differences in baseline characteristics such as gender and age were presented between the two groups(P>0.05).Microbial community composition analysis revealed no significant differences in the top 15 abundant taxa at various taxonomic levels between the two groups,but structural variations were noted.Alpha diversity analysis showed that the Simpson index in Group 1 differed from that in Group 2(P<0.05),while chao 1,ACE,richness,and coverage indices exhibited no significant differences between the two groups(P>0.05).In Beta diversity analysis,multi-response permutation analysis(MRPP)indicated no significant intergroup differences in community structure(P>0.05),whereas principal coordinate analysis(PCoA)suggested distinct differences in the distribution of species composition.LEfSe identified 14 taxa(e.g.,Lachnospiraceae and Lachnospirales)with significantly higher abundance and 5 taxa(e.g.,Anaeromassilibacillus and Desulfovibrio)with significantly lower abundance in Group 1.Conclusion OP patients with various TCM syndrome types in the Lingnan region exhibit distinct gut microbiota diversity and dominant microbial taxa,which will provide an objective basis for TCM syndrome differentiation of OP.
3.Porphyromonas gingivalis promotes autophagy in esophageal squamous cell carcinoma via the miR-21-5p/RASA1/ERK axis
Yubo DU ; Yelin JIAO ; Yueyue CHENG ; Haodong CHENG ; Yi RU ; Gaofeng LIANG ; Shegan GAO ; Yijun QI
Acta Universitatis Medicinalis Anhui 2024;59(9):1621-1628
Objective To investigate the molecular mechanism underlying Porphyromonas gingivalis(Pg)-induced autophagy in esophageal squamous cell carcinoma(ESCC).Methods After Pg infected KYSE70 cells and KYSE140 cells pretreated with siAtg7 or Chloroquin(CQ),Western blot was used to measure protein levels of Atg7,LC3-Ⅱ/LC3-Ⅰ,and p62;Immunofluorescent confocal imaging analysis was used to detect autophagosome and autolysosome;CCK-8 assay was used to test cell viability;Transwell assay was used for ESCC cell migration and invasion potentials.Likewise,miR-21-5p inhibitor,RASA1 overexpression plasmid,or U0126 were used to block miR-21-5p/RASA1/ERK signaling pathway prior to Pg infection,followed by the aforementioned methods.In addition,immunohistochemistry was used to examine Pg abundance and LC3 protein levels,and RT-PCR was used to evaluate miR-21-5p expression in ESCC and adjacent tissue samples,followed by correlation analyses be-tween Pg and LC3,and Pg and miR-21-5p.Results Pg infected KYSE70 cells and KYSE140 cells showed upreg-ulation Atg7 protein and LC3-Ⅱ/LC3-Ⅰ protein but downregulation of RASA1 protein and p62 protein,enhanced cell proliferation,migration,and invasion as well as immunofluorescent spots of red,green,and yellow in mRFP-GFP-LC3-labeled ESCC cells.Pretreatment with CQ or siAtg7 abolished the above alterations induced by Pg.Con-sistently,pretreatment with miR-21-5p inhibitor,U0126,or RASA1 overexpression plasmid also blocked Pg-stimu-lated autophagy.In ESCC samples,Pg abundance was correlated with upregulation of miR-21-5p and LC3.Con-clusion Pg promotes autophagy in esophageal squamous cell carcinoma via miR-21-5p/RASA1/ERK signaling pathway.
4.Current research progress of diagnosis of iliac vein stenosis based on multi-modal imaging
Qi ZHANG ; Xinyue SONG ; Yichen DONG ; Haodong SHI ; Xiaoyan LIANG ; Hongyong DUAN
International Journal of Surgery 2023;50(3):203-208
Iliac vein stenosis (IVS), known as iliac vein compression syndrome, refers to a series of diseases caused by iliac vein compression or intraluminal adhesions leading to lower extremity vein or pelvic vein drainage disturbance and other clinical manifestations which is quite common in vascular surgery. The vast majority of patients with symptoms of chronic venous insufficiency (CVI) have IVS. In clinical work, IVS does not typically appear as a single symptom, while often combining with other lesions, such as varicose veins of the lower extremities, skin pigmentation, ulcer formation. Studies on its aetiology and epidemiology have found a mean age of onset of 40 years, the age of onset in females is lower than that in males, and the average of stress in females is significantly higher than that in males. Typical IVS occurs mainly in the left lower extremity in young women of reproductive age, but exceptions remain. In summary, the importance of the diagnosis of IVS in clinical practical work can be seen. CVI is a general term for all diseases that affect the morphology and function of the venous system. Compared with chronic venous disease (CVD), CVI include venous system abnormalities without symptoms or signs. Thus, it more accurately describes the diagnosis and treatment of IVS that requires clinical guidance, so its concept is quoted. With the development and advancement of medical imaging, more and more techniques provide help in the diagnosis and treatment of IVS. Therefore, professionals in various specialties have made relevant studies about the benefits and drawbacks of imaging techniques for diagnosis, treatment modalities, and prognostic management of this disease, in order to improve the diagnostic efficacy. Consequently, this review is focused on the current situation of the diagnosis and treatment of IVS under multi-modal imaging, hoping to provide choices of medical imaging technologies for the different states, and to find a better and personalized plan for patients.
5.Significance of white blood cells count, C-reactive protein and procalcitonin for the detection of infectious complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
Haodong SHI ; Qi ZHANG ; Xiaoyan LIANG ; Bo HUANG
International Journal of Surgery 2023;50(9):596-604,F4
Objective:To investigate the risk factors for infection after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+ HIPEC), and observe the infection in patients who underwent this combined procedure, to explore the predictive value of postoperative white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT) and systemic immune inflammation index (SII) for postoperative infection.Methods:Clinical data of 106 patients who underwent CRS + HIPEC in the Fifth Medical Clinical College of Shanxi Medical University between July 2019 and July 2022 were retrospectively analyzed. These patients, including 61 males and 45 females, (58.93±10.65) years old, were divided into the infection group ( n=19) and the non-infection group ( n=87) according to the presence of postoperative infection. Risk factors were analyzed for patients in the infection group, and postoperative WBC, CRP, PCT and SII were determined for patients in both groups to determine their prognostic values. Risk factors for postoperative secondary infection in patients with CRS+ HIPEC were analyzed using univariate and multivariate logistic regression. Predictive values of WBC, PCT, CRP and SII for postoperative infection were evaluated by receiver operating characteristic (ROC) curve, and the optimal cutoff values of these variables were determined by Youden index and evaluated using sensitivity, specificity, positive predictive value, and negative predictive value as evaluation indexes. Nomogram prediction model was constructed using R software and samples were included in this model to calculate the total score of these patients. ROC curve analysis and calibration curve verification were then performed. Results:Univariate analysis showed significant differences in age, body mass index (BMI), postoperative fistulization, preoperative serum albumin, combined multiple organ resection, and operation duration between the infection and non-infection groups ( P<0.05). WBC, CRP, PCT and SII were compared between the infection group and the non-infection group on were compared on postoperative days 1, 3, 5 and 7, and the ROC curves were plotted accordingly. The area under the ROC curve (AUC) of the WBC, CRP, PCT and SII on postoperative Days 1, 3, 5 and 7, and their 95% CI, sensitivities and specificities were compared. It was found that the predictive values of the 5th postoperative day WBC and PCT, and the 7th postoperative day CRP were superior to those determined on other postoperative days, and SII was not significant in predicting postoperative secondary infection in patients who underwent CRS+ HIPEC. The cut-off values of the 5th postoperative day WBC and PCT and the 7th postoperative day CRP were 7.7×10 9/L, 2.068 ng/mL and 76.43 mg/L, respectively, and AUCs and their 95% CI were 0.754 and (0.625, 0.883), 0.830 and (0.717, 0.943), 0.715 and (0.584, 0.846), respectively, with sensitivities of 78.9%, 68.4% and 63.2%, respectively, and specificities of 70.1%, 96.5% and 75.9%, respectively. The predictive values of PCT on postoperative days 1, 3, 5 and 7 were superior to those of WBC, CRP and SII determined on each corresponding day. The cut-off values of the 5th postoperative day WBC and PCT and the 7th postoperative day CRP were used as the classification thresholds, and the results after classification as well as significant variables in univariate analysis, including age, BMI≥25 kg/m 2, postoperative fistulization, preoperative serum albumin≥35 g/L, number of organs resected and operation duration were included in multivariate logistic regression analysis. The results showed that BMI≥25 kg/m 2, combined multiple organ resection, WBC and PCT on the 5th postoperative day and, CRP on the 7th postoperative day were independent risk factors for secondary infection ( P<0.05). A Nomogram prediction model was then constructed. Points indicated the scores for each variable, and the corresponding scores were 70 when BMI was ≥25 kg/m 2, 80 when multiple organ resection was combined, 100 when the 5th postoperative day WBC was ≥7.7×10 9/L, and 79 when the 7th postoperative day CRP was ≥76.3. The sum of the scores for all variable was calculated and used as total score for the patient. The total score obtained from the Nomogram prediction model was used for ROC curve analysis and calibration curve verification. The ROC curve analysis showed that the AUC was 0.966, with a sensitivity of 0.895 and specificity of 0.966, indicating an excellent discriminative power of the model. The significance level of the calibration curve was 0.05, and the absolute error between the predicted and actual incidences of postoperative infection after CRS+ HIPEC was 0.038. Conclusions:The incidence of secondary infection after CRS+ HIPEC is related to factors such as BMI and combined multiple organ resection. Inflammation markers in peripheral blood, including PCT, CRP and WBC, can serve as predictors for postoperative secondary infection in patients with CRS+ HIPEC, and the fifth postoperative day WBC and PCT and the seventh postoperative day CRP among others have the highest diagnostic values for postoperative infections. In addition, the predictive value of combined diagnosis is superior to that of individual testing.
6.Epidemiological characteristics of traumatic spinal cord injury in China in 2018
Dingjun HAO ; Baorong HE ; Liang YAN ; Jinpeng DU ; Xiao QI ; Shicheng YU ; Jiaojiao ZHANG ; Wenjing ZHENG ; Rongqiang ZHANG ; Dageng HUANG ; Junsong YANG ; Ming ZHU ; Jiawei OUYANG ; He ZHAO ; Keyuan DING ; Haodong SHI ; Yang CAO ; Ying ZHANG ; Qinghua TANG ; Yuan LIU ; Zilong ZHANG ; Yuhang WANG ; Ye TIAN ; Hao CHEN ; Lulu BAI ; Heng LI ; Chenchen MU ; Youhan WANG ; Xiaohui WANG ; Chao JIANG ; Jianhua LIN ; Bin LIN ; Shunwu FAN ; Lin NIE ; Jiefu SONG ; Xun MA ; Zengwu SHAO ; Yanzheng GAO ; Zhong GUAN ; Yueming SONG ; Weihu MA ; Qixin CHEN
Chinese Journal of Trauma 2021;37(7):618-627
Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions,9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury,injury level,severity of injury,segment and type of fracture,complications,death and other data were collected by medical record questionnaire,and analyzed according to geographical region,age and gender.Results:Medical records of 4,134 patients were included in this study,with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million (95% CI 50.122-50.846). The highest incidence in the Eastern region was 53.791 / 1 million (95% CI 53.217-54.365). In the whole country,the main causes of injury were high falls (29.58%),as well as in the Western region (40.68%),while the main causes of injury in the Eastern and Central regions were traffic injuries (31.22%,30.10%). The main injury level was cervical spinal cord in the whole country (64.49%),and the proportion of cervical spinal cord injury in the Central region was the highest (74.68%),and the proportion of lumbosacral spinal cord injury in the Western region was the highest (32.30%). The highest proportion of degree of injury was incomplete quadriplegia (55.20%),and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation,77.95% in the Western region and only 54.77% in the Central region. In the whole country,the head was the main combined injury (37.87%),as well as in the Eastern and Central regions,while the proportion of chest combined injury in the Western region was the highest (38.57%). A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients (0.56%) died in hospital,of which 17(73.91%) died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level,incomplete quadriplegia as the main degree of injury,head as the main combined injury,and respiratory complications as the main complication.
7.Osteoinduction of calcium phosphate and its application
Haodong CHEN ; Jinfeng YAO ; Zhigang LIANG
Chinese Journal of Tissue Engineering Research 2016;20(25):3785-3792
BACKGROUND: With good biocompatibility, osteoconduction and biodegradability, calcium phosphate ceramics is considered as a substitute of autologous bone; furthermore, it also has the potentiel of osteoinduction after structure optimization. OBJECTIVE: To review the physicochemical properties of calcium phosphate ceramic and its osteoinduction. METHODS: A computer-based search of databases such as PubMed, Springer, ResearchGate and Baidu Academic was performed for articles relevant to calcium phosphate ceramics published from January 2000 to October 2015. And the keywords were “calcium phosphate, osteoinduction, tissue engineering, scaffolds” in English. RESULTS AND CONCLUSION: To date, there are four ideal kinds of calcium phosphate materials including hydroxyapatite, tricalcium phosphate, amorphous calcium phosphate and hydroxyapatite/tricalcium phosphate biphasic ceramic material. Hydroxyapatite has better strength and cel adsorption capacity, but has poor biodegradation. Tricalcium phosphate has good abilities of osteogenesis and degradation, but its degradation rate is hard to match the new bone formation,and its strength is also relatively poor. Amorphous calcium phosphate has neither strength nor solubility. In contrast, biphasic calcium phosphate ceramics has moderate degradation rate between hydroxyapatite and tricalcium phosphate, and therefore, it either can be replaced by autologous bone after degradation or exhibits proper strength. While how to further improve the physical properties and promote osteogenesis stil need much deeper research.
8.Clinical and histopathological features of colorectal sessile serrated adenoma/polyp and its differential diagnosis.
Yunjin WU ; Haodong XU ; Hailong ZHU ; Xuyou ZHU ; Jun LIANG ; Yu ZENG ; Suxia ZHANG ; Xianghua YI
Chinese Journal of Pathology 2014;43(9):588-592
OBJECTIVETo investigate clinicopathological characteristics of colorectal sessile serrated adenoma/polyp (SSA/P) and its differential diagnosis from other serrated lesions.
METHODSClinicopathological features of all cases of colorectal serrated lesions from 5 209 colorectal biopsy samples at Shanghai Tongji Hospital from 2008 to 2013 were reviewed. Three hundred and fifty-three cases of serrated lesions were erolled in the study. Morphological features of SSA/P were investigated with an emphasis on histologic criteria for diagnosis and a literature review was performed.
RESULTSThree hundred and fifty-three cases of serrated lesions were identified, including 25 SSA/P (7.1%), 278 hyperplastic polyp (HP, 78.8%), and 44 traditional serrated adenoma (TSA, 12.5%). Twenty-five patients with SSA/P consisted of 16 males and 9 females with a mean age of 62.2 years (aged 34-84 years) and the lesions involved sigmoid colon (14 cases), ascending colon (9 cases), rectum (1 case) and transverse colon (1 case). Grossly, the majority of SSA/P was sessile with an averaged size of 0.73 cm. Histologically, typical SSA/P had elongated crypts with prominent serration and distorted crypts architecture. The detection rates of crypts dilatation and branching in SSA/P and HP were 100% (25/25) and 24% (12/50, P < 0.01), 72% (18/25) and 4% (2/50, P < 0.01), respectively. Morphological features observed only in SSA/P included L-shaped crypts (48%, 12/25), pseudo infiltration of mucosa muscle (16%, 4/25), atypical nuclei (32%, 8/25), and increased mucus secretion (24%, 6/25).
CONCLUSIONSSSA/P microscopically shows prominent serration and abnormal architectures of crypts. Complete tissue sectioning and correct embedding are helpful for the diagnosis. SSA/P without cytological dysplasia should be distinguished from HP, especially those with only a few distorted crypts.
Adenoma ; pathology ; China ; Colonic Polyps ; pathology ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia ; Intestinal Polyps ; pathology ; Male ; Polyps ; pathology ; Rectal Neoplasms ; pathology
9.Clinical and histopathological features of colorectal sessile serrated adenoma/polyp and its differential diagnosis
Yunjin WU ; Haodong XU ; Hailong ZHU ; Xuyou ZHU ; Jun LIANG ; Yu ZENG ; Suxia ZHANG ; Xianghua YI
Chinese Journal of Pathology 2014;(9):588-592
Objective To investigate clinicopathological characteristics of colorectal sessile serrated adenoma/polyp ( SSA/P) and its differential diagnosis from other serrated lesions. Methods Clinicopathological features of all cases of colorectal serrated lesions from 5 209 colorectal biopsy samples at Shanghai Tongji Hospital from 2008 to 2013 were reviewed.Three hundred and fifty-three cases of serrated lesions were erolled in the study .Morphological features of SSA/P were investigated with an emphasis on histologic criteria for diagnosis and a literature review was performed.Results Three hundred and fifty-three cases of serrated lesions were identified , including 25 SSA/P ( 7.1%) , 278 hyperplastic polyp ( HP, 78.8%) , and 44 traditional serrated adenoma ( TSA, 12.5%).Twenty-five patients with SSA/P consisted of 16 males and 9 females with a mean age of 62.2 years ( aged 34-84 years ) and the lesions involved sigmoid colon (14 cases), ascending colon (9 cases), rectum (1 case) and transverse colon (1 case).Grossly, the majority of SSA/P was sessile with an averaged size of 0.73 cm.Histologically, typical SSA/P had elongated crypts with prominent serration and distorted crypts architecture.The detection rates of crypts dilatation and branching in SSA/P and HP were 100% ( 25/25 ) and 24% ( 12/50, P <0.01 ) , 72%(18/25) and 4%(2/50, P<0.01), respectively.Morphological features observed only in SSA/P included L-shaped crypts ( 48%, 12/25 ) , pseudo infiltration of mucosa muscle ( 16%, 4/25 ) , atypical nuclei (32%, 8/25), and increased mucus secretion (24%, 6/25).Conclusions SSA/P microscopically shows prominent serration and abnormal architectures of crypts.Complete tissue sectioning and correct embedding are helpful for the diagnosis.SSA/P without cytological dysplasia should be distinguished from HP, especially those with only a few distorted crypts .


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