1.Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.
Junyu LU ; Yunxin SHI ; Yongkang LI ; Ziyi NIU ; Shengxi WU ; Ceng LUO ; Rou-Gang XIE
Neuroscience Bulletin 2025;41(12):2296-2321
Chronic pain, frequently comorbid with neuropsychiatric disorders, significantly impairs patients' quality of life and functional capacity. Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis. This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels: (1) Peripheral Sensitization: CCL2/CCR2 modulates TRPV1, Nav1.8, and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain. (2) Spinal Cord Central Sensitization: CCL2/CCR2 contributes to NMDAR-dependent plasticity, glial activation, GABAergic disinhibition, and opioid receptor desensitization. (3) Supraspinal Central Networks: CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions, including the ACC, CeA, NAc, and hippocampus, and it also increases pain sensitization through the descending facilitation system. Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed, highlighting novel avenues for chronic pain management.
Humans
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Chronic Pain/physiopathology*
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Animals
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Neuroglia/metabolism*
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Chemokine CCL2/metabolism*
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Receptors, CCR2/metabolism*
2.Clinical application of intraperitoneal chemotherapy ports in patients with gastric cancer and peritoneal metastases
Zhong ZHANG ; Sheng LU ; Yaping GUO ; Feng BIAN ; Yongkang XU ; Xiaodong MO ; Hexia LUO ; Xinyu TANG ; Min SHI ; Jun ZHANG ; Chao YAN ; Yu CHEN ; Zhenggang ZHU
Chinese Journal of Gastrointestinal Surgery 2025;28(5):521-527
Objective:To evaluate the clinical value and safety of an intraperitoneal chemotherapy port technique in patients with gastric cancer and peritoneal metastases undergoing intraperitoneal chemotherapy.Methods:This was a retrospective, descriptive case analysis. From November 2022 to October 2024, patients diagnosed with gastric cancer and peritoneal metastases at Wuxi Branch of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine with an expected survival >3 months, underwent laparoscopic exploration combined with implantation of an intraperitoneal chemotherapy port [PORT-A-CATH II system (Model 21-4055-24)] implantation. The procedure was as follows: (1) after laparoscopic exploration, a 4-cm skin incision was made at a predetermined site and a subcutaneous pocket created by dissecting to the muscle fascia and removing subcutaneous fat as needed to position the port septum 0.5-1.0 cm from the skin surface; (2) under direct laparoscopic visualization, the abdominal cavity was punctured and a guidewire inserted, followed by an 8.5 Fr sheath, through which a catheter with three trimmed side holes was placed after removal of the sheath; (3) the catheter length in the abdominal cavity was adjusted to 25–30 cm and the catheter trimmed, and connected to the port base, ensuring it extended beyond the connector's visible hole; (4) the whole port was placed within the subcutaneous pocket, and non-absorbable sutures used to create a double purse-string suture at the catheter's abdominal entry, forming an anti-reflux ring; (5) non-absorbable sutures were used to securely fix the port to the fascia through its four base holes and the exposed catheter segments on the fascia sutured and buried; (6) patency was confirmed by injecting saline and followed by intermittent skin closure provided there was no bleeding; and (7) the catheter tip was positioned in the pelvic cavity under laparoscopic guidance. Postoperatively, the patients underwent normothermic intraperitoneal and systemic treatment. The port infusion protocol involved disinfecting the skin (>10 cm diameter) around the port, confirming the puncture site, inserting a Huber needle vertically at 90° to the port base, infusing 100 mL saline to ensure patency, followed by continuous infusion of 1000 mL paclitaxel solution, and sealing with 20 mL saline before removing the needle. No saline flushing was required between chemotherapy infusions. The primary outcomes were the incidence and management of complications post-port implantation.Results:The study cohort comprised 225 patients with gastric cancer and peritoneal metastases. Using standardized port implantation and postoperative puncture procedures, the complication rate during follow-up was 14.2% (32/225), including effusion in 14 patients (6.2%), port infection in 10 (4.4%), incision dehiscence in four (1.8%), port inversion in two (0.9%), hematoma in one (0.4%), and catheter rupture in one (0.4%). Seventy-five percent (24/32) of patients with complications recovered and continued using the port after conservative treatments (e. g., aspiration of effusions, antibiotic therapy, incision management), whereas the remaining 25.0% (8/32) with complications required surgical removal of the port because the treatment was ineffective. The presence of preoperative ascites ( P=0.019) and peritoneal cancer index score>15 ( P=0.038) were significantly associated with development of complications. Conclusions:Our standardized procedure for intraperitoneal chemotherapy port implantation is safe and feasible for patients with gastric cancer and peritoneal metastases, having a low overall complication rate. Most complications can be successfully managed with conservative treatment, the device thus providing reliable support for intraperitoneal chemotherapy.
3.Clinical application of intraperitoneal chemotherapy ports in patients with gastric cancer and peritoneal metastases
Zhong ZHANG ; Sheng LU ; Yaping GUO ; Feng BIAN ; Yongkang XU ; Xiaodong MO ; Hexia LUO ; Xinyu TANG ; Min SHI ; Jun ZHANG ; Chao YAN ; Yu CHEN ; Zhenggang ZHU
Chinese Journal of Gastrointestinal Surgery 2025;28(5):521-527
Objective:To evaluate the clinical value and safety of an intraperitoneal chemotherapy port technique in patients with gastric cancer and peritoneal metastases undergoing intraperitoneal chemotherapy.Methods:This was a retrospective, descriptive case analysis. From November 2022 to October 2024, patients diagnosed with gastric cancer and peritoneal metastases at Wuxi Branch of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine with an expected survival >3 months, underwent laparoscopic exploration combined with implantation of an intraperitoneal chemotherapy port [PORT-A-CATH II system (Model 21-4055-24)] implantation. The procedure was as follows: (1) after laparoscopic exploration, a 4-cm skin incision was made at a predetermined site and a subcutaneous pocket created by dissecting to the muscle fascia and removing subcutaneous fat as needed to position the port septum 0.5-1.0 cm from the skin surface; (2) under direct laparoscopic visualization, the abdominal cavity was punctured and a guidewire inserted, followed by an 8.5 Fr sheath, through which a catheter with three trimmed side holes was placed after removal of the sheath; (3) the catheter length in the abdominal cavity was adjusted to 25–30 cm and the catheter trimmed, and connected to the port base, ensuring it extended beyond the connector's visible hole; (4) the whole port was placed within the subcutaneous pocket, and non-absorbable sutures used to create a double purse-string suture at the catheter's abdominal entry, forming an anti-reflux ring; (5) non-absorbable sutures were used to securely fix the port to the fascia through its four base holes and the exposed catheter segments on the fascia sutured and buried; (6) patency was confirmed by injecting saline and followed by intermittent skin closure provided there was no bleeding; and (7) the catheter tip was positioned in the pelvic cavity under laparoscopic guidance. Postoperatively, the patients underwent normothermic intraperitoneal and systemic treatment. The port infusion protocol involved disinfecting the skin (>10 cm diameter) around the port, confirming the puncture site, inserting a Huber needle vertically at 90° to the port base, infusing 100 mL saline to ensure patency, followed by continuous infusion of 1000 mL paclitaxel solution, and sealing with 20 mL saline before removing the needle. No saline flushing was required between chemotherapy infusions. The primary outcomes were the incidence and management of complications post-port implantation.Results:The study cohort comprised 225 patients with gastric cancer and peritoneal metastases. Using standardized port implantation and postoperative puncture procedures, the complication rate during follow-up was 14.2% (32/225), including effusion in 14 patients (6.2%), port infection in 10 (4.4%), incision dehiscence in four (1.8%), port inversion in two (0.9%), hematoma in one (0.4%), and catheter rupture in one (0.4%). Seventy-five percent (24/32) of patients with complications recovered and continued using the port after conservative treatments (e. g., aspiration of effusions, antibiotic therapy, incision management), whereas the remaining 25.0% (8/32) with complications required surgical removal of the port because the treatment was ineffective. The presence of preoperative ascites ( P=0.019) and peritoneal cancer index score>15 ( P=0.038) were significantly associated with development of complications. Conclusions:Our standardized procedure for intraperitoneal chemotherapy port implantation is safe and feasible for patients with gastric cancer and peritoneal metastases, having a low overall complication rate. Most complications can be successfully managed with conservative treatment, the device thus providing reliable support for intraperitoneal chemotherapy.
4.Evaluation of the Application Potential and Challenges of Large Language Models in the Field of Laboratory Medicine
Xiaoqin LU ; Wei JIA ; Yuxiang WU ; Yongkang WU
Chinese Journal of Clinical Laboratory Science 2024;42(8):619-623
Objective To evaluate the performance of ChatGPT-4.0 and ERNIE Bot-4.0 in the field of laboratory medicine,and ex-plore their application potential and challenges in this professional domain.Methods Using the national clinical medical laboratory technology(intermediate)examination questions as a benchmark,we compared the performance of the two models in mastering labora-tory medicine knowledge and answering consistency.We also and assessed the models'ability in interpreting test results and assisting diagnosis through 30 laboratory medicine cases.Results In the clinical medical examination technology test,both models passed the 60%qualification threshold.ChatGPT-4.0 was superior to ERNIE Bot-4.0 in terms of answering speed and consistency,but its answer-ing accuracy was significantly lower than that of ERNIE Bot-4.0(73.25%vs 80.75%).ERNIE Bot-4.0's accuracy rate was higher than the average accuracy rate of clinical aboratory personnel in this examination(78.03%).In the accuracy analysis of different question types,both performed worst in experimental technology questions(ERNIE Bot-4.0:66.32%,ChatGPT-4.0:60.53%)and best in bas-ic medical knowledge questions(both scoring 86.00%).In the case analysis test,ERNIE Bot-4.0 outperformed ChatGPT-4.0 in all cat-egories.Both models performed well in routine case analysis but made errors in complex case analysis.Conclusion In the field of la-boratory medicine,both large language models have shown certain application potential,especially in a Chinese context,where ERNIE Bot-4.0 significantly outperforms ChatGPT-4.0 in terms of answering accuracy and case analysis ability,indicating its relative advantage in domestic applications.However,both models still need improvement in experimental technical knowledge,complex case analysis ca-pabilities,and the accuracy and consistency of result output.At the current stage,there are still certain risks in directly applying such general large language models to clinical test result interpretation and assisted diagnosis,which provides a new research direction for the interpretation of test reports.
5.Factors influencing the severity of alcohol use disorder and the construction of risk prediction model
Xuezhi YANG ; Bing LU ; Wan WEI ; Zhen ZENG ; Sigui HU ; Yongkang CAO ; Zhenyu MA
Sichuan Mental Health 2024;37(2):131-136
BackgroundAlcohol use disorder (AUD) is a common chronic and relapsing psychiatric disorders. Identifying severe AUD early and intervening promptly is crucial to prevent irreversible harm. Currently, the assessment of AUD severity primarily relies on psychiatric examination by clinicians, and there is limited research on the factors influencing AUD severity and the development of prediction models. ObjectiveTo analyze the factors influencing AUD severity, and construct a risk prediction model to aid in the assessment of disease progression in AUD patients. MethodsA retrospective analysis was conducted on 1 358 first-time hospitalized patients admitted to Nanning Fifth People's Hospital from January 1, 2017 to December 31, 2022. These patients met the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria for AUD. Basic patient data was collected, and the patients were divided into two groups based on disease severity: mild-moderate group (n=330) and severe group (n=1 028). The patients were randomly divided into training and test sets in a 7∶3 ratio. A Logistic regression model was constructed in the training set, and the predictive ability of the model for disease severity was evaluated using the receiver operating characteristic (ROC) curve in the test set. ResultsCompared with the mild-moderate group, the severe group had a higher proportion of patients living in urban areas (χ2=7.804), were farmers (χ2=17.991), had a higher frequency of alcohol consumption (more than 1 to 2 drinks/day) (χ2=35.267), had a higher age at first drinking (t=-3.858), had a greater number of comorbid somatic disorders (Z=-22.782), and had higher proportions of γ-Glutamyl transpeptidase (χ2=259.940) and total bilirubin abnormalities (χ2=148.552) (P<0.01). Logistic analysis conducted in the training set showed that being a farmer (OR=2.024, 95% CI: 1.352~3.029), having an older age at first drinking (OR=1.075, 95% CI: 1.025~1.129), drinking outside of mealtimes (OR=3.988, 95% CI: 2.408~6.606), having total bilirubin abnormalities (OR=1.034, 95% CI: 1.000~1.069), and having more comorbid somatic diseases (OR=4.386, 95% CI: 2.636~7.298) were identified as risk factors for disease severity in AUD patients. The area under curve (AUC) for this model in the test set was 0.906. ConclusionIn psychiatric hospitals, being a farmer, having an older age at first drinking, drinking outside of mealtimes, having abnormal total bilirubin levels, and having comorbidities with somatic illnesses may be risk factors for severe AUD.
6.Application value of adjustable closed loop in SBS with ostomy in continuity
Qi GAO ; Zhaoping LAN ; Weike XIE ; Qi WANG ; Yongkang PAN ; Chaoxiang LU ; Zhongwen LI ; Lei WANG
Chinese Journal of Primary Medicine and Pharmacy 2020;27(17):2107-2111
Objective:To evaluate the effect and safety of adjustable closed loop(ACL) in the treatment of short bowel syndrome (SBS).Methods:From January 2017 to December 2017, the clinical data of 2 cases with ostomy in continuity after surgery in Children's Hospital Affiliated to Xi'an Jiaotong University were analyzed.The age was 1 and 3 months, both were females, and preservation of intestinal tube length were 65 cm and 60 cm respectively.They were all diagnosed SBS with a lot of stool like water.Self-made ACL was installed to maintain SBS.The blood circulation of stoma, weight, BMI, defecating, abdomen, nutrition status changes, nursing convenience, intestinal infection susceptibility were observed.Results:There was no necrosis in stoma, and the overall condition was improved, and no significant increase in abdominal distension.ACL used in babies with ostomy in continuity could improve the anus stool, weight, nursing convenience.Conclusion:ACL installed in baby with SBS could contribute to intestinal management, and is easy to install.
7.Efficacy of microbubble-enhanced sonothrombolysis on platelet-rich thrombi and erythrocyte-rich thrombi of different ages
Shifei WANG ; Yuanwen JING ; Hairui LI ; Chixiong HUANG ; Yongkang LU ; Jianping BIN
Chinese Journal of Medical Imaging Technology 2017;33(6):832-837
Objective To investigate the efficacy of microbubble-enhanced sonothrombolysis on platelet-rich thrombi (PRT) and erythrocyte-rich thrombi (ERT) in different ages.Methods PRT and ERT in different ages were prepared both in vitro and in vivo of common carotid artery in rats.All the participants were divided into 8 groups with 4 in vitro and another 4 in vivo experiment,including PRT 3 h,PRT 24 h,ERT 3 h,ERT 24h in vitro groups and PRT 3 h,PRT 24 h,ERT 3 h,ERT 24 h in vivo groups.Microbubble-enhanced sonothrombolysis was carried out in both in vitro and in vivo experiments,and the ultrasonic images were collected.The components of PRT and ERT were identified by histopathological examination.The percentage increase of luminal cross sectional area and lytic ratio in vitro,and the recanalization rate and mean blood flow velocity of common carotid artery in vivo were mainly analyzed.Results After sonothrombolysis,both in vitro and in vivo experiment showed there was no statistically significant difference of the percentage increase of luminal cross sectional area ([121.12 ± 13.21]% vs [130.09 ± 15.34]%),lytic ratio ([39.83± 7.09]% vs [42.14±5.17]%),recanalization rate (83.33% vs 91.67%) and blood flow velocity of common carotid artery ([0.21±0.02]m/s vs [0.22±0.01]m/s) between PRT 3 h group and ERT 3 h group (both P>0.05).PRT 24 h group compared with EPR 24 h group,PRT 24 h group compared with PRT 3 h group,as well as ERT 24 h group compared with ERT 3 h group,the percent increase of luminal cross sectional area,lytic ratio,recanalization rate and blood flow velocity of common carotid artery reduced (all P<0.05).Conclusion The efficacy of microbubble-enhanced sonothrombolysis on PRT and ERT in vitro and in vivo of of rat common carotid artery model decrease with the increase of thrombus age,especially for the PRT.
8.Impact of Insulin Resistance and Adiponectin Lacking on Myocardial Remodeling in Experimental Mice
Lu XU ; Yajuan LIU ; Qing ZHANG ; Yi QIN ; Na ZHANG ; Yongkang REN ; Ruiying YANG
Chinese Circulation Journal 2017;32(8):808-812
Objective: To explore the impact of insulin resistance (IR) and adiponectin (APN) lacking on myocardial remodeling in experimental mice. Methods:16 normal C57 mice were divided into 2 groups: Control group and IR group; in addition, 16 APN gene knockout(APNKO) mice were divided into another 2 groups: APNKO group and APNKO+IR group.n=8 in each group. The mice in Control group and APNKO group were fed with normal diet, in IR group and APNKO+IR group were fed with high fat diet to create the IR model. All animals were treated for 12 weeks. Blood levels of total cholesterol(TC), triglycerides(TG),fasting plasma glucose(FPG) and fasting insulin(FINS) were examined; heart weight and left ventricular weight were measured; left ventricular myocardial morphological changes and the degree of ifbrosis were assessed by HE staining and Masson staining; protein expressions of myocardial matrix metalloproteinase-9 (MMP-9) and APN were detected by immunehistochemistry and Western blot analysis. Results: Compared with Control group, IR group, APNKO group and APNKO+IR group showed elevated blood levels of TC, TG, FPG and FINS; increased heart weight and left ventricular weight, allP<0.05; IR group, APNKO group and APNKO+IR group presented more myocardial hypertrophy, decreased protein expression of APN and increased protein expression of MMP-9, allP<0.05.Conclusion: IR and APN lacking could incur myocardial remodeling in experimental mice and they had synergistically facilitated effect.
9.Insulin resistance and low leveladiponectin co-promote cardiac remodeling in mice
Lu XU ; Yajuan LIU ; Qing ZHANG ; Na ZHANG ; Yongkang REN ; Ruiying YANG
Basic & Clinical Medicine 2017;37(5):625-629
Objective The study the effect on cardiac remodeling induced by low level adiponectin(APN)and insulin resistance(IR).Methods 16 wild-type C57 mice were randomly divided into control and IR groups.16 APN gene knockout mice were randomly divided into APNKO and APNKO+IR groups.The IR and APNKO+IR groups were a high-fat feed to induce insulin resistance.After 12 weeks,cholesterol(TC),triglycerides(TG),fasting plasma glucose(FPG), fasting insulin(FINS) were measured.HOMA-IR,HWI and LVWI were calculated.The left ventricular myocardial were examined by microscopy to observe the degree of myocardial fibrosis,and the protein expression of matrix metalloproteinase-9(MMP-9) and APN in myocardial were detected with western blot.ResultsLow level APN and IR increased heart weight, left ventricular weight, HWI, LVWI(P<0.05).There were interaction between IR and low level APN on the TC,TG, FPG, FINS, and the index related myocardial fibrosis(P<0.05), and they were positive effect.There was also interaction effect between IR and low level APN on myocardial APN expression, but it was the negative effects (P<0.05).Conclusions Both low level adiponectin and insulin resistance could lead to cardiac remodeling synergistically.
10.Comparative Study for the Patients of Hypertensive Hypertrophic Cardiomyopathy in Elder age and the Patients of Hypertensive Left Ventricular Hypertrophy
Lu HUA ; Haiyan DU ; Yunfeng NIU ; Zhimin WANG ; Yongkang TAO ; Lirong YAN ; Chaomei FAN ; Yishi LI
Chinese Circulation Journal 2014;(6):432-435
Objective: To compare the clinical characteristics and plasma level of N-terminal pro-brain natriuretic peptide (NT-proBNP) between the patients with hypertensive hypertrophic cardiomyopathy in elder age (HHCME) and the patients with hypertensive left ventricular hypertrophy (HTN-LVH).
Methods: Our work included 2 groups, HHCME group,n=47 and HTN-LVH group,n=44. Duplex Doppler echocardiography was performed to determine left atrial diameter (LAd), left ventricular end-diastolic dimension (LVEDd), interventricular septal thickness (IVST), left ventricular ejection fraction (LVEF), velocity of early diastolic period (VE) and velocity of end-diastolic period (VA) in mitral valve oriifce. Plasma level of NT-proBNP was measured by ELISA. The above indexes were compared between 2 groups.
Results:①Compared with HTN-LVH group, HHCME group presented decreased LVEDd and increased IVST, LVEF, allP<0.001. There were no signiifcant differences in VE/VA ratio and LAd between 2 groups, allP>0.05.②Plasma level of NT-proBNP was higher in HHCME group,P<0.01. With the adjusted age, gender, history of hypertension, LAd, IVST, left ventricular systolic and diastolic function, the level of NT-proBNP in HHCME group (1317.19 fmol/ml) was still signiifcantly higher than that in HTN-LVH group (526.19fmol/ml),P<0.01.
Conclusion: The plasma NT-proBNP level was higher in HHCME patients than that in HTN-LVH patients which indicated that HHCME patients may have worse prognosis. NT-proBNP might be helpful for differencing HHCME.

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