1.Astragalin Regulates Autophagy and Apoptosis of Astrocytes in L4-5 Spinal Dorsal Horn of Mouse Inflammatory Pain Model
Weishan ZHANG ; Jiahong LIN ; Can WANG ; Runheng ZHANG ; Junhua YANG ; Jing LIU ; Guoying LI ; Yuxin MA
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):186-196
ObjectiveTo explore the effects of astragalin (AST) on autophagy and apoptosis of astrocytes in the L4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant (CFA). MethodsTwenty-four male C57BL/6 mice, aged six months, were randomly assigned to four groups: control group, saline group, CFA model group, and CFA+AST group, six mice in each group. The inflammatory pain model was established by injection of 10 µL CFA into the right lateral malleolus fossa. The saline group were injected with an equal amount of normal saline at the same site. The inflammatory pain mice in CFA+AST group were further treated with AST (60 mg/kg) intraperitoneally once a day for 21 consecutive days. Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1, apoptosis-related factors including Cleaved-Caspase3 and Caspase9, and the astrocyte marker such as GFAP in the L4-5 spinal dorsal horn of the mice in each group. Western blot was used to examine the protein expression levels of autophagy-related proteins(ATG12, Beclin-1) and apoptosis-related proteins(Caspase 3, Caspase 9) in the L4-5 spinal dorsal horn of mice. ResultsImmunofluorescent staining showed that in the L4-5 dorsal horn of the spinal cord, the fluorescence intensity of ATG12 (P<0.000 1) and Beclin-1 (P<0.000 1) was significantly increased, while that of Cleaved-Caspase 3 (P<0.001) and Caspase 9 (P<0.000 1) was decreased in the CFA+AST group when compared to the CFA model group. Furthermore, AST could inhibit the activation of astrocytes. Western blot further confirmed that AST significantly upregulated the expression of ATG12 (P<0.000 1) and Beclin-1 (P<0.000 1) in the L4-5 spinal cord of CFA mice, and downregulated the expression of Caspase 3 (P<0.01) and Caspase 9 (P<0.001). ConclusionsAST promotes autophagy of astrocytes and inhibits their apoptosis in the L4-5 spinal dorsal horn of CFA mice.
2.Application progresses of new ultrasonic technologies for assisting diagnosis of BI-RADS 4 lesions
Jiahong LI ; Pengji LIN ; Tianqi WU ; Mingsong XUE ; Tingwei CHEN ; Weixiang LIANG ; Tao LIU
Chinese Journal of Interventional Imaging and Therapy 2024;21(1):52-55
The ultrasonic manifestations of benign and malignant breast imaging-reporting and data system(BI-RADS)4 lesions overlap in some degrees,is able to result in unnecessary biopsy or untimely therapy.Accurate classifying the nature of BI-RADS 4 breast lesions can provide reliable references for clinical decision-making.The progresses of application of new ultrasonic technologies,including automated breast volume scanner,superb micro-vascular imaging,elastography,contrast-enhanced ultrasound and artificial intelligence for assisting diagnosis of BI-RADS 4 lesions were reviewed in this article.
3.Value of nomogram based on preoperative ultrasound and inflammatory indexes in predicting axillary high nodal burden in early breast cancer
Wenhua LIN ; Wenwen WANG ; Shaoling YANG ; Junjia TAO ; Kun ZHAO ; Lan HE ; Hongzhen ZHANG ; Jiahong GU ; Ziwei ZHENG
Chinese Journal of Ultrasonography 2023;32(4):339-347
Objective:To explore the values of ultrasound, pathology combined with inflammatory indicators in predicting high nodal burden (HNB) in patients with early breast cancer and to construct a nomogram to provide reference for individualized diagnosis and treatment.Methods:The ultrasonographic, pathological features and preoperative inflammatory indicators of 378 female patients diagnosed with early breast cancer confirmed by pathology in the South Hospital of the Sixth People′s Hospital Affiliated to Shanghai Jiaotong University from January 2014 to July 2022 were retrospectively analyzed. They were randomly divided into training set ( n=302) and test set ( n=76) in a ratio of 8∶2, and the baseline data of the two groups were compared. The optimal cutoff values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were obtained by ROC curve. In the training set, with axillary high lymph node load (≥3 metastatic lymph nodes) as the dependent variable, independent influencing factors of HNB were identified by univariate and multivariate Logistic regression analyses, and the nomogram was established. The test set data were used to verify the model. The discrimination, calibration and clinical applicability of the model were assessed by the area under the ROC curve (AUC), C-index, the calibration curve, Brier score and the decision curve analysis, respectively. Results:There were no significant differences in all variables between the training set and the test set (all P>0.05). ROC curve analysis results showed that AUCs of NLR, PLR and LMR were 0.578, 0.547 and 0.516, respectively, and the optimal cut-off values were 2.184, 150 and 3.042, respectively. Univariate Logistic regression analysis showed that age, pathological type, histological grade, Ki-67, lymphovascular invasion, NLR, PLR, ultrasonic characteristics (maximum diameter of primary tumor, shape, long/short diameter of lymph node, cortical thickness, cortical and medullary boundary, lymph node hilum, lymph node blood flow pattern) were correlated with HNB of early breast cancer (all P<0.05). Multivariate Logistic regression analysis showed that ultrasonic characteristics (maximum diameter of primary tumor >2 cm, effacement of lymph node hilum, non-lymphatic portal blood flow), lymphovascular invasion, Ki-67>14% and NLR>2.184 were independent risk factors for HNB in early breast cancer ( OR=7.258, 8.784, 6.120, 8.031, 3.394 and 3.767, respectively; all P<0.05) and were used to construct the nomogram model. The AUC of the training set was 0.914 (95% CI=0.878-0.949), C-index was 0.914; The AUC of the test set was 0.871 (95% CI=0.769-0.973), C-index was 0.871, indicating good discrimination. Calibration curve and Brier score were 0.090, indicating high calibration degree of the model. The clinical decision curve indicated good clinical benefit. Conclusions:The nomogram based on ultrasonic characteristics (maximum diameter of primary tumor, lymph node hilum, lymph node blood flow pattern), lymphovascular invasion, Ki-67 and NLR can effectively predict the risk of HNB in patients with early breast cancer, and provide a reference for precision diagnosis and treatment to avoid excessive or insufficient treatment.
4.Hotspots and difficulties of biliary surgery in older patients.
Zongming ZHANG ; Jiahong DONG ; Fangcai LIN ; Qiusheng WANG ; Zhi XU ; Xiaodong HE ; Shizhong YANG ; Youwei LI ; Limin LIU ; Chong ZHANG ; Zhuo LIU ; Yue ZHAO ; Haiyan YANG ; Shuyou PENG
Chinese Medical Journal 2023;136(9):1037-1046
With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.
Humans
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Aged
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Aged, 80 and over
;
Biliary Tract Surgical Procedures
;
Gallstones
;
Laparoscopy
;
Treatment Outcome
;
Aging
;
Retrospective Studies
5.Astragalin induces autophagy of astrocytes in anterior cingulate cortex of inflammatory pain mice
Jiahong LIN ; Shuhan WANG ; Runheng ZHANG ; Cuizhu YANG ; Yaqi YANG ; Chang ZHOU ; Pei TANG ; Jing LIU ; Yuxin MA
Chinese Journal of Pathophysiology 2023;39(12):2158-2164
AIM:To investigate the effects of astragalin(AST)on activation status of astrocytes and the ex-pression level of autophagy-related proteins in the cortex of the anterior cingulate cortex of mice with a complete Freund's adjuvant(CFA)-induced inflammatory pain model.METHODS:Twenty-four 6-month-old male C57BL/6 mice were ran-domly divided into four groups:control group,saline group,CFA model group and CFA+60 mg/kg AST administration group,and six mice in each group.Mice in the AST administration group received 60 mg/kg AST by intraperitoneal injec-tion on a body weight basis for 21 d.The paw withdrawal threshold in each group of mice was evaluated by the von Frey test.The expression levels of autophagy-related factors LC3,p62,ATG12 and beclin-1,and astrocyte activation were de-tected by multiplex immunofluorescence staining in the anterior cingulate cortex of mice in each group.Western blot was used to measure the levels of autophagy-related proteins LC3,p62,ATG12 and beclin-1 in the anterior cingulate cortex of mice in each group.RESULTS:Behavioural tests showed that AST significantly increased mechanical pain thresholds in CFA mice(P<0.05).The results from multiple immunofluorescent staining showed that AST significantly increased the fluorescence intensity of LC3(P<0.01),ATG12(P<0.01)and beclin-1(P<0.05),attenuated the fluorescence intensi-ty of p62(P<0.05),and inhibited the activation of astrocytes in the anterior cingulate cortex of CFA mice.Western blot results further confirmed that AST significantly increased the expressions of LC3(P<0.01),ATG12(P<0.01),beclin-1(P<0.01),and decreased the expression of p62(P<0.05)in the anterior cingulate cortex of CFA mice.CONCLU-SION:AST relieves CFA-induced inflammatory pain of mice,and its analgesic mechanism may be related to the inhibi-tion of activation of cortical astrocytes in the anterior cingulate cortex and the promotion of autophagy in CFA mice.
6.Effectiveness of robot-guided percutaneous fixation and decompression via small incision for advanced thoracolumbar metastases.
Jiahong LI ; Shu LIN ; Liuyi TANG ; Jiang HU ; Lun WAN ; Kun ZHANG ; Weimin LIANG ; Shan WANG
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(9):1113-1118
OBJECTIVE:
To evaluate the effectiveness of robot-guided percutaneous fixation and decompression via small incision in treatment of advanced thoracolumbar metastases.
METHODS:
A clinical data of 57 patients with advanced thoracolumbar metastases admitted between June 2017 and January 2021 and met the selection criteria was retrospectively analyzed. Among them, 26 cases were treated with robot-guided percutaneous fixation and decompression via small incision (robot-guided group) and 31 cases with traditional open surgery (traditional group). There was no significant difference in gender, age, body mass index, lesion segment, primary tumor site, and preoperative Tokuhashi score, Tomita score, Spinal Instability Neoplastic Score (SINS), visual analogue scale (VAS) score, Oswestry disability index (ODI), Karnofsky score, and Frankel grading between groups ( P>0.05). The operation time, hospital stays, hospital expenses, intraoperative blood loss, postoperative drainage volume, duration of intensive care unit (ICU) stay, blood transfusion, complications, and survival time were compared. The pedicle screw placement accuracy was evaluated according to the Gertzbein-Robbins grading by CT within 4 days after operation. The pain, function, and quality of life were evaluated by VAS score, ODI, Karnofsky score, and Frankel grading.
RESULTS:
During operation, 257 and 316 screws were implanted in the robot-guided group and the traditional group, respectively; and there was no significant difference in pedicle screw placement accuracy between groups ( P>0.05). Compared with the traditional group, the operation time, hospital stays, duration of ICU stay were significantly shorter, and intraoperative blood loss and postoperative drainage volume were significantly lesser in the robot-guided group ( P<0.05). There was no significant difference in hospital expenses, blood transfusion rate, and complications between groups ( P>0.05). All patients were followed up 8-32 months (mean, 14 months). There was no significant difference in VAS scores between groups at 7 days after operation ( P>0.05), but the robot-guided group was superior to the traditional group at 1 and 3 months after operation ( P<0.05). The postoperative ODI change was significantly better in the robot-guided group than in the traditional group ( P<0.05), and there was no significant difference in the postoperative Karnofsky score change and Frankel grading change when compared to the traditional group ( P>0.05). Median overall survival time was 13 months [95% CI (10.858, 15.142) months] in the robot-guided group and 15 months [95% CI (13.349, 16.651) months] in the traditional group, with no significant difference between groups ( χ 2=0.561, P=0.454) .
CONCLUSION
Compared with traditional open surgery, the robot-guided percutaneous fixation and decompression via small incision can reduce operation time, hospital stays, intraoperative blood loss, blood transfusion, and complications in treatment of advanced thoracolumbar metastases.
Humans
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Blood Loss, Surgical
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Quality of Life
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Retrospective Studies
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Robotics
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Surgical Wound
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Decompression
7.Correlation of prolongation of PR interval with carotid atherosclerosis in middle-aged and elderly patients with type 2 diabetes mellitus
Kun ZHAO ; Lingling WU ; Shaoling YANG ; Jing HU ; Fengling WANG ; Linyan FAN ; Hongzhen ZHANG ; Wenhua LIN ; Jiahong GU ; Meixiang GUO
Chinese Journal of Endocrinology and Metabolism 2022;38(7):577-582
Objective:To investigate the relationship between prolonged PR interval and carotid atherosclerosis(CAS)in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 537 middle-aged and elderly inpatients with T2DM in the Southern Branch of the Sixth People′s Hospital of Shanghai Jiaotong University from January 2019 to January 2021 were selected as the research objects. Color Doppler ultrasound was used to detect bilateral carotid artery intima-media thickness(CIMT). The subjects were divided into carotid atherosclerosis group(CAS group, n=352)and non-carotid atherosclerosis group(NCAS group, n=185). The difference in the PR interval of ECG between the two groups was compared. Pearson or Spearman rank correlation analysis was used for evaluating the correlation of PR interval and CAS lesions with various clinical index. The relationship between PR interval and CAS lesions was adopted by multivariate logistic regression analysis. Results:The average PR interval of middle-aged and elderly patients with T2DM was(164.57±23.02)ms. The average PR interval in CAS group was significantly higher than that in NCAS group [(169.76±24.28) vs (154.70±16.42)ms, P<0.01]. The results of multifactorial logistic regression analysis showed that age, low density lipoprotein-cholesterol, serum osteocalcin, and PR interval were independent factors influencing the development of CAS lesions in middle-aged and elderly patients with T2DM( OR=1.079, 1.936, 0.879, 1.039, respectively, P<0.05 or P<0.01)where each 1 ms increase in PR interval was associated with a 3.9% increase in the risk of CAS in middle-aged and elderly patients with T2DM( OR=1.039, 95% CI 1.006-1.073, P=0.020). Multivariate logistic regression analysis showed that middle-aged and elderly type 2 diabetic patients with PR interval≥158 ms were 4.072 times more likely to have CAS lesions than those with PR interval<158 ms( OR=4.072, 95% CI 1.417-11.702, P<0.01). Conclusion:The PR interval of electrocardiogram is correlated with CAS lesions in middle-aged and elderly patients with T2DM. Middle-aged and elderly type 2 diabetic patients with significantly prolonged PR interval should be reminded to screen for CAS lesions early.
8.A case of overlap myoclonic epilepsy with ragged-red fibers-Leigh syndrome associated with mitochondrial DNA 8344A>G mutation
Chong SUN ; Jun LU ; Jianying XI ; Jie LIN ; Jiahong LU
Chinese Journal of Neurology 2021;54(10):1059-1063
Overlap myoclonic epilepsy with ragged-red fibers (MERRF)-Leigh syndrome is a rare mitochondrial encephalomyopathy. A case of MERRF-Leigh syndrome associated with mitochondrial DNA 8344A>G (m.8344A>G) mutation was reported in this article. The patient has suffered from the disease since 15-year old with myoclonus, exercise intolerance, ataxia, limb weakness, dysphasia, dyspnea, blurred vision and hearing loss. Magnetic resonance imaging revealed lesions on right thalamus, bilateral medulla and lumbar spinal cord and atrophy of cervical spinal cord. Electromyography showed predominantly axonal damage of both sensory nerve and motor nerve. Histochemical analyses revealed ragged red fibers, ragged blue fibers, succinate dehydrogenase-stronghly reactive vessels and decreased cytochrome oxidase activity. Gene tests demonstrated a high level of m.8344A>G mutation and m. 14484T>C mutation. MERRF-Leigh overlap syndrome with m.8344A>G mutation was rare. Bulbar paralysis following myoclonus is the main clinical symptom.
9.Risk factors of post traumatic cerebral infarction after craniotomy for severe traumatic brain injury
Cheng WANG ; Jixin DUAN ; Zhijun ZHONG ; Lin HAN ; Hanchang YU ; Yuan LIU ; Hui TANG ; Jiahong HE ; Hongmiao XU
Chinese Journal of Trauma 2019;35(1):57-61
Objective To investigate the risk factors associated with post traumatic cerebral infarction (PTCI) after craniotomy hematoma evacuation for severe traumatic brain injury (sTBI) so as to provide clinical reference for the early prevention of postoperative PTCI.Methods A retrospective case control study was conducted to analyze the clinical data of 558 sTBI patients who received craniotomy hematoma evacuation admitted to Changsha Hospital of Traditional Chinese Medicine from October 2006 to June 2016.There were 340 males and 218 females,aged 15-71 years,with an average of 47.8 years.Among them,75 patients were at the age of less than 30 years,315 were at 30-50 years,and 168 were above 50 years.According to the Glasgow coma score (GCS),there were 127 patients with 3-4 points,124 with 5-6 points,and 307 with 7-8 points.The patients were divided into PTCI group (51 patients)and non-PTCI group (507 patients).The related indicators of the two groups of patients after admission were collected,including gender,age,injury cause,GCS,skull base fracture,traumatic subarachnoid hemorrhage (tSAH),cerebral hernia,hypotension,the time from injury to craniotomy,and whether decompressive craniectomy was performed.Univariate analysis was first performed for these factors,followed by multivariate logistic regression analysis.Results There were no significant differences in gender,age,injury cause,skull base fracture,and decompressive craniectomy between PTCI group and control group (P > 0.05).In the PTCI group,there were 29 patients with GCS of 3-4 points,17 with 5-6 points,and five with 7-8 points;there were 48 patients with tSAH,37 patients with cerebral hernia,and 18 patients with hypotension.In terms of the time from injury to craniotomy,it took < 3 hours in 30 patients,3-6 hours in 12,6-12 hours in five,and > 12 hours in four.In the non-PTCI group,there were 98 patients with GCS of 3-4 points,107 with 5-6 points,and 302 with 7-8 points.There were 34 patients with tSAH,117 with cerebral hernia,and 35 with hypotension.In terms of the time from injury to craniotomy,it took <3 hours in 294 patients,3-6 hours in 130,6-12 hours in 68,and > 12 hours in 15.The differences between the two groups were statistically significant (P < 0.05).Multivariate logistic regression analysis indicated that GCS of 3-6 points,tSAH,cerebral hernia,time from injury to craniotomy,and hypotension were significantly associated with PTCI after operation for sTBI (P < 0.01).Conclusions GCS of 3-6 points,tSAH,cerebral hernia,duration from injury to craniotomy,and hypotension time > 3 hours are the high risk factors of PTCI in sTBI patients after craniotomy.For patients with these high risk factors,craniotomy should be performed in time,and the perioperative blood pressure and intracranial pressure stability should be maintained so as to relieve vasospasm.
10.A clinical and natural history research on mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
Chong SUN ; Jie LIN ; Shuang CAI ; Wenhua ZHU ; Sushan LUO ; Jianying XI ; Jun LU ; Kai QIAO ; Mingshi GAO ; Chongbo ZHAO ; Jiahong LU
Chinese Journal of Neurology 2018;51(2):118-123
Objective To summarize the clinical features,natural history and causes of death of mitochondrial encephalomyopathy,lactic acidosis and stroke-like episodes (MELAS).Methods We retrospectively evaluated the clinical findings of 64 patients diagnosed as MELAS more than 3 years (death cases excluded) in Huashan Hospital from January 2005 to March 2017 and analyzed the natural course and the causes of death of the disease.Results Among 64 patients,the male-to-female ratio was 1.3 ∶ 1.Median onset age was 20.5 (16.8) years.The peak of incidence age was from 14 to 22 years.The most common features of MELAS in acute phase were seizures (48/64,75.0%),headache (41/64,64.1%),blurred vision (37/64,57.8%),nausea and vomiting (27/64,42.1%),fever (25/64,39.1%),mental and behavioral disorder (24/64,37.5%).Lactate dehydrogenase (31/60,51.6%),resting blood lactic acid (43/58,74.1%) and cerebral spinal fluid lactic acid (9/9) were elevated.Abnormal findings in electroencephalogram (36/40,90.0%),electrocardiogram (37/47,78.7%),electromyography (25/41,61.0%) were detected.In this cohort,20 patients (20/64,31.3%) with MELAS were dead.A Kaplan-Meier survival curve showed the estimated overall median survival time was 12 years.The median survival time of the group onset before sex maturity (≤ 14 years) was 8 years and that in the group onset after sex maturity (> 14 years) was 21 years.The causes of death were cardiogenic incidence (4/20,20.0%),pulmonary infection (4/20,20.0%),lactic acidosis (2/20,10.0%) and status epilepticus (2/20,10.0%).Conclusions MELAS is usually presented in young people associated with high mortality rate.The leading causes of death are cardiogenic,pulmonary infection and lactic acidosis.

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