1.Mechanism of Huanglian Jiedutang in Improving Pyroptosis, Neuroinflammation, and Learning and Cognitive Functions in APP/PS1 Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Wei CHENG ; Shuo YANG ; Zhangxin HE ; Wei CHEN ; Aihua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):11-19
ObjectiveTo investigate the mechanism by which Huanglian Jiedutang (HLJDT) inhibits pyroptosis and neuroinflammation in Alzheimer's disease (AD) mice via the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase)-1/gasdermin D (GSDMD) pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group (model group), the positive control group (Donepezil group, 0.65 mg·kg-1), and the HLJDT treatment group (HLJDT group, 5.2 g·kg-1). Ten C57BL/6 mice were assigned to the blank control group (control group). The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology, quantity, and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 (PSD95), amyloid precursor protein (APP), inflammatory factors including nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), as well as pyroptosis pathway-related proteins including NLRP3, Caspase-1, GSDMD, and GSDMD-N. ResultsCompared with the control group, the model group exhibited significantly decreased learning and memory abilities (P<0.01), reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly increased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.01). Protein levels of PSD95 were markedly decreased, while the expression levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly elevated (P<0.01). Compared with the model group, both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities (P<0.05, P<0.01), increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly decreased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.05, P<0.01). Protein levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly downregulated, while PSD95 expression was significantly upregulated (P<0.05, P<0.01). There was no statistically significant difference in GSDMD-N levels in the Donepezil group, while GSDMD-N expression was significantly decreased in the HLJDT group (P<0.05). ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice, and attenuate neuronal loss and synaptic damage, possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.
2.Mechanism of Huanglian Jiedutang in Improving Pyroptosis, Neuroinflammation, and Learning and Cognitive Functions in APP/PS1 Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Wei CHENG ; Shuo YANG ; Zhangxin HE ; Wei CHEN ; Aihua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):11-19
ObjectiveTo investigate the mechanism by which Huanglian Jiedutang (HLJDT) inhibits pyroptosis and neuroinflammation in Alzheimer's disease (AD) mice via the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase)-1/gasdermin D (GSDMD) pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group (model group), the positive control group (Donepezil group, 0.65 mg·kg-1), and the HLJDT treatment group (HLJDT group, 5.2 g·kg-1). Ten C57BL/6 mice were assigned to the blank control group (control group). The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology, quantity, and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 (PSD95), amyloid precursor protein (APP), inflammatory factors including nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), as well as pyroptosis pathway-related proteins including NLRP3, Caspase-1, GSDMD, and GSDMD-N. ResultsCompared with the control group, the model group exhibited significantly decreased learning and memory abilities (P<0.01), reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly increased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.01). Protein levels of PSD95 were markedly decreased, while the expression levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly elevated (P<0.01). Compared with the model group, both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities (P<0.05, P<0.01), increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region (P<0.01), and significantly decreased hippocampal mRNA expression levels of NLRP3, Caspase-1, GSDMD, NF-κB, TNF-α, IL-1β, and IL-18 (P<0.05, P<0.01). Protein levels of NLRP3, Caspase-1, GSDMD, p-NF-κB/NF-κB, TNF-α, IL-1β, and APP were significantly downregulated, while PSD95 expression was significantly upregulated (P<0.05, P<0.01). There was no statistically significant difference in GSDMD-N levels in the Donepezil group, while GSDMD-N expression was significantly decreased in the HLJDT group (P<0.05). ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice, and attenuate neuronal loss and synaptic damage, possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.
3.Analysis of the comparison results of dental CBCT phantoms in radiological health technical service institutions in Guangdong Province, China
Xuan LONG ; Hongwei YU ; Zhan TAN ; Lei CAO ; Weixu HUANG ; Huifeng CHEN ; Aihua LIN
Chinese Journal of Radiological Health 2025;34(2):219-224
Objective To understand the situation of dental cone beam computed tomography (CBCT) quality control testing phantoms in radiation health technical service institutions in Guangdong province, analyze the differences among different phantoms, and provide a reference for dental CBCT quality control testing. Methods The testing phantoms of 49 radiation health technical service institutions were used as the research objects. The designated CBCT equipment was used for scanning and imaging. The Z-score method was used to evaluate the high-contrast resolution, low-contrast resolution, and distance measurement deviation of each phantom. Results The satisfaction rates of various items for the phantoms in 49 institutions ranged from 85.7% to 100%. The distance measurement deviations of four institutions were “suspicious”, and the high-contrast resolution of four institutions and the distance measurement deviation of one institution were “unsatisfactory”. Conclusion The overall performance of dental CBCT quality control testing phantoms in radiological health technical service institutions in Guangdong province is satisfactory. However, there are still some phantoms with poor results in items such as distance measurement deviation and high-contrast resolution. The structural design, material selection, and manufacturing process of the phantom may all affect the results of quality control testing. Therefore, appropriate phantoms, optimized exposure conditions, and suitable reconstruction algorithms should be used in CBCT quality control testing to ensure accurate and reliable measurements.
4.Surgical treatment and prognosis analysis of hilar cholangiocarcinoma
Xiangcheng LI ; Changxian LI ; Hui ZHANG ; Feng CHENG ; Feng ZHANG ; Liyong PU ; Chuanyong ZHANG ; Ke WANG ; Lianbao KONG ; Xiaofeng QIAN ; Donghua LI ; Wenxiong LU ; Ping WANG ; Aihua YAO ; Jianfeng BAI ; Xiaofeng WU ; Ruixiang CHEN ; Xuehao WANG
Chinese Journal of Surgery 2024;62(4):290-301
Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.
5.Effect of remazolam on sleep rhythm and postoperative delirium in elderly patients undergoing spinal surgery
Jianzhong WANG ; Tingting LI ; Hongying JIANG ; Wei ZHOU ; Aihua SHU ; Xiaobo CHEN ; Mi ZHOU
The Journal of Clinical Anesthesiology 2024;40(7):693-698
Objective To investigate the effects of remazolam on melatonin secretion,sleep rhythm and postoperative delirium(POD)in elderly patients undergoing spinal surgery.Methods A total of 160 elderly patients,76 males and 84 females,aged 65-80 years,BMI 18.5-24.0 kg/m2,ASA physical status Ⅱ or Ⅲ,from November 2023 to January 2024 undergoing spinal surgery(lumbar interbody fusion,posterior approach)under general anesthesia were selected.The patients were divided into two groups by random number table method:the remazolam group(group R)and the propofol group(group P),80 pa-tients in each group.Group R was given remazolam 0.3 mg/kg for anesthesia induction,and then continued to pump remazolam 0.3-0.8 mg·kg-1·h-1 for anesthesia maintenance.Group P was given propofol 2.0 mg/kg for anesthesia induction,and then continued to pump propofol 4-6 mg·kg-1·h-1 for anesthesia maintenance.The levels of melatonin and cortisol were recorded at 04:00 a.m.on the day of surgery,1 day,2 and 3 days after surgery.Pittsburgh sleep quality index(PSQI)and VAS pain scores at rest were recorded 1 day before surgery,1 day and 2 days after surgery and before discharge.The occurrence of POD and post-operative sleep disorder(POSD)were recorded.The duration of extubation,PACU stay time,total analgesia pump compressions,effective analgesia pump compressions,number of remedial analgesia cases,intraoperative hypotension,postoperative nausea and vomiting,dizziness,respiratory depression and other adverse events were recorded.Results Compared with group P,the extubation time and PACU residence time in group R were significantly shortened(P<0.05),the level of melatonin was significantly increased while the level of cortisol was significantly decreased at 4:00 a.m.,and the PSQI was significantly decreased 1 day after surgery(P<0.05),the incidence of POD,POSD,and intraoperative hypotension were signifi-cantly decreased(P<0.05).There were no significant differences in extubation time,total and effective times of analgesic pump,rate of remedial analgesia,intraoperative hypotension,postoperative nausea,vom-iting,dizziness and respiratory depression between the two groups.Conclusion Remazolam has little effect on the secretion rhythm of melatonin and cortisol and the sleep rhythm after spinal surgery in elderly pa-tients,and the recovery is faster,which can reduce the incidence of POD and alleviate the sleep disorder af-ter spinal surgery.
6.Effect of opioid-free anesthesia combined with quadratus lumborum block in laparoscopic radical colorectal cancer resection
Wei ZHOU ; Kai WANG ; Aihua SHU ; Chuanxi CHENG ; Xiaobo CHEN
The Journal of Clinical Anesthesiology 2024;40(9):938-943
Objective To explore the effect of opioid-free anesthesia(OFA)combined with quad-ratus lumborum block(QLB)in laparoscopic radical colorectal cancer resection.Methods Sventy patients were selected for undergoing laparoscopic radical colorectal cancer resection from March to December 2023,49 males and 21 females,aged 18-75 years,BM1 18.5-28.0 kg/m2,ASA physical status Ⅱ or Ⅲ.The patients were divided into two groups using random number table method:the OFA group(group OFA)and the conventional opioid anesthesia group(group OA),35 patients in each group.Group OFA underwent bi-lateral posterior QLB under ultrasound guidance before anesthesia induction(0.25%ropivacaine 30 ml on each side),and anesthesia induction and maintenance were performed using opioid-free anesthesia regimen.And group OA cannot undergo QLB,and anesthesia induction and maintenance were carried out using opioid containing regimen.The patient's HR and MAP were recorded before anesthesia induction(T0),1 minute after endotracheal intubation(T1),before pneumoperitoneum establishment(T2),1 minute after pneumo-peritoneum establishment(T3),1 hour after surgery(T4),the end of surgery(T5),and leaving the oper-ating room(T6).The time from the patient's anesthetic discontinuation to extubation,the length of stay in the PACU,and the Steward and VAS pain scores when the patient leaves the operating room,which were recorded.NRS scores at rest and in the motor state 6,12,24,and 48 hours after surgery,time to first ex-haust,time to first ambulation,and length of postoperative hospital stay,effective PCIA pressing times and use of additional analgesic drugs within 48 hours after the operation,and postoperative adverse reactions(nausea,vomiting,hallucinations)were also recorded.Results Compared with T0,the MAP of the two groups decreased significantly at T1,T2,T4,and T5(P<0.05),the HR in group OFA increased signifi-cantly at T1 and slowed down at T4 and T5(P<0.05),and the HR in group OA decreased significantly at T1-T5(P<0.05).Compared with group OA,the HR in group OFA increased significantly at T1-T3,and the MAP increased significantly at T1(P<0.05).Compared with group OA,the extubation time and PACU residence time were significantly delayed(P<0.05),and the Steward score when leaving the oper-ating room was significantly lower in group OFA(P<0.05).Compared with group OA,NRS score was sig-nificantly deceased 6,12,24,and 48 hours after the surgery(P<0.05),time to first exhaust,time to first ambulation,and length of postoperative hospital stay were significantly shartened(P<0.05),and ef-fective PCIA pressing times and additional analgesia times were significantly decreased(P<0.05),inci-dence of intraoperative hypotensionand postoperative nausea and vomiting(P<0.05).Conclusion OFA combined with QLB can safely and effectively complete laparoscopic radical colorectal cancer surgery.Pa-tients with such anesthetic methods are hemodynamically more stable during anesthesia induction and intrao-peratively.These patients have better postoperative analgesia and less need for additional analgesics,and less incidence of postoperative nausea and vomiting.This approach is more beneficial for the recovery of the patient's gastrointestinal function.
7.Animal Model of Ankylosing Spondylitis Based on Its Clinical Symptoms of Traditional Chinese and Western Medicine
Juanjuan YANG ; Haidong WANG ; Jinhai WANG ; Haolin LI ; Zhendong WANG ; Fangmei JIN ; Weiqing LI ; Aihua WANG ; Ping CHEN
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(4):944-950
Ankylosing spondylitis(AS)is a typical spinal arthritis characterised by inflammatory back pain,which seriously affects the health and quality of life of patients.The clinical efficacy of Chinese medicine in the treatment of ankylosing spondylitis is clear,but the mechanism is not clear,and the existing animal models cannot be well applied to the evaluation of Chinese medicine in the treatment of ankylosing spondylitis.Therefore,this paper summarizes the existing animal models based on Chinese and Western medicine clinical diagnosis,disease characteristics,etiology and Chinese medicine evidence,and finds that among the existing animal models,the proteoglycan-induced arthritis mouse model has a higher Chinese and Western medicine clinical fit than the other models,but lacks the corresponding Chinese medicine evidence model evaluation.The other animal models had a higher Western clinical match,but lacked the characteristics of the Traditional Chinee Medicine(TCM)syndrome.As ankylosing spondylitis is a chronic inflammatory autoimmune disease with complex pathogenic factors,the existing animal models cannot better simulate the clinical symptoms.Therefore,the establishment of animal models of ankylosing spondylitis with the characteristics of Chinese and Western clinical evidence is a future research priority for AS TCM.
8.Analysis of factors affecting postnatal glucose metabolism in pregnant women with gestational diabetes and construction of a nomogram prediction model
Juan SHI ; Yunhua YAN ; Aihua ZHANG ; Peixin LI ; Ning LI ; Wei CHEN
Chinese Journal of Postgraduates of Medicine 2024;47(6):487-492
Objective:To analyze the relevant factors affecting postnatal glucose metabolism in pregnant women with gestational diabetes and construct a nomogram prediction model.Methods:Using a retrospective study method, 210 cases of gestational diabetes patients admitted to Danyang People′s Hospital from March 2019 to November 2021 were selected as the study subjects, and they were divided into 125 cases of normal group and 85 cases of abnormal group according to the postnatal glucose metabolism. The predictive value was analyzed using the subject work characteristics (ROC) curve experiment; the risk factors affecting abnormal postpartum glucose metabolism in pregnant women with gestational diabetes mellitus were analyzed using Logistic regression experiment; and the clinical efficacy of the column-line diagram model was verified using internal data.Results:There was no statistically significant difference between the two groups when comparing the general information such as age ( P>0.05); compared with the normal group, the abnormal group had higher values of total cholesterol (TG), postprandial 2 h blood glucose (OGTT 2 h), glycosylated hemoglobin, and pre-pregnancy body mass index (BMI): (4.23 ± 1.35) mmol/L vs. (3.65 ± 1.50) mmol/L, (9.36 ± 1.25) mmol/L vs. (8.20 ± 1.51) mmol/L, (8.31 ± 2.96)% vs. (6.73 ± 2.23)%, (24.96 ± 4.21) kg/m 2 vs. (23.20 ± 3.25) kg/m 2, and those with a family history of diabetes mellitus were higher: 47.06%(40/85) vs. 20.80%(26/125), there were statistical differences ( P<0.05); the area under the curve (AUC) of TG, OGTT 2 h, glycated hemoglobin, and pre-pregnancy BMI were 0.605, 0.720, 0.670, and 0.616, with optimal cut off values of 4.65 mmol/L, 8.33 mmol/L, 8.06%, and 25.27 kg/m 2; TG (>4.65 mmol/L), OGTT 2 h (>8.33 mmol/L), glycated hemoglobin (>8.06%), and preconception BMI (>25.27 kg/m 2), and family history of diabetes mellitus (yes) were risk factors for abnormal glucose metabolism in pregnant women ( P<0.05); the C-index of the risk of postpartum glucose metabolism in pregnant women with gestational diabetes mellitus predicted by the column chart model was 0.750 (95% CI 0.672 - 0.864). The model predicted that the threshold of the risk of postnatal glucose metabolism in pregnant women with gestational diabetes mellitus was >0.07. Conclusions:TG (>4.65 mmol/L ), OGTT 2 h (>8.33 mmol/L ), glycated haemoglobin (>8.06%), pre-pregnancy BMI (>25.27 kg/m 2), and family history of diabetes (yes) are risk factors for abnormal glucose metabolism in pregnant women, and the model constructed based on the variables have good predictive power.
9.Construction of a Nomogram model for personalized prediction of the risk of delayed postoperative bleeding after endoscopic submucosal dissection for early gastric cancer
Tingting GONG ; Aihua QIAN ; Xi CHEN
Journal of Surgery Concepts & Practice 2024;29(3):236-242
Objective To analyze the influencing factors of delayed postoperative bleeding(DPPB)after endoscopic submucosal dissection(ESD)for early gastric cancer and construct a Nomogram model.Methods The clinical information of 234 patients who underwent ESD treatment at our hospital and pathologically diagnosed with early gastric cancer from April 2021 to April 2023 were collected.The patients were grouped based on the presence or absence of DPPB.Logistic regression analysis was applied to screen for risk factors affecting DPPB after ESD in early gastric cancer patients.R software was applied to construct a Nomogram model for predicting the risk of DPPB in early gastric cancer patients after ESD.Receiver operator characteristic(ROC)curve,calibration curve,and Hosmer-Lemeshow goodness of fit test were plotted to evaluate the Nomogram model.Results A total of 23(9.8%)of 234 early gastric cancer patients who underwent ESD treatment developed DPPB.Multivariate Logistic regression analysis showed that the number of biopsies≥3(95%CI:2.482-20.424,P=0.000),the maximum diameter of lesions≥3 cm(95%CI:1.620-13.244,P=0.004),the depth of invasion to submucosa(95%CI:1.421-10.536,P=0.008),and intraoperative bleeding(95%CI:1.160-11.300,P=0.027)were independent risk factors for DPPB after ESD in early gastric cancer patients.The area under ROC curve(AUC)was 0.838(95%CI:0.743-0.932).The slope of the calibration curve was close to 1.Hosmer-Lemeshow goodness of fit test showed χ2=3.328,P=0.505.Conclusions The number of biopsies≥3,the maximum diameter of lesion≥3 cm,the depth of invasion to submucosa,and intraoperative bleeding are independent risk factors for DPPB after ESD in early gastric cancer patients.The Nomogram model based on these four independent risk factors can effectively predict the risk of DPPB after ESD in early gastric cancer patients.
10.Surgical treatment and prognosis analysis of hilar cholangiocarcinoma
Xiangcheng LI ; Changxian LI ; Hui ZHANG ; Feng CHENG ; Feng ZHANG ; Liyong PU ; Chuanyong ZHANG ; Ke WANG ; Lianbao KONG ; Xiaofeng QIAN ; Donghua LI ; Wenxiong LU ; Ping WANG ; Aihua YAO ; Jianfeng BAI ; Xiaofeng WU ; Ruixiang CHEN ; Xuehao WANG
Chinese Journal of Surgery 2024;62(4):290-301
Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

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