This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective:To compare the safety and efficacy of novel en-bloc Holmium laser enucleation of the prostate（HoLEP）with complete membranous urethral mucosa sparing technique with traditional 2-lobe technique HoLEP in benign prostatic hyperplasia（BPH）treatment.Methods:The data of BPH patients treated with HoLEP from January 2023 to May 2024 in Xinhua Hospital，School of Medicine，Shanghai Jiaotong University were retrospectively reviewed. Seventy-two patients received novel en-bloc HoLEP with complete membranous urethral mucosa sparing technique（novel en-bloc group），while 79 patients received traditional 2-lobe technique HoLEP（traditional 2-lobe technique group）.There was no significant difference between novel en-bloc group and traditional 2-lobe technique group in the age［（71.0 ± 7.1）years vs.（69.8 ± 6.5）years］，body mass index［（24.5 ± 2.8）kg/m 2 vs.（23.9 ± 3.5）kg/m 2］，international prostate symptom score（IPSS）［26.0（22.0，28.0）vs. 25.0（22.0，28.0）］，quality of life（QOL）score［5.0（5.0，6.0）vs. 5.0（5.0，6.0）］，prostate sepcific antigen（PSA）［4.98（2.40，11.11）ng/ml vs. 4.38（1.62，7.54）ng/ml］and prostate volume［（74.06 ± 42.67）ml vs.（70.10 ± 33.94）ml］（all P > 0.05）. The incidence of acute urinary retention in novel en-bloc group was significantly higher than that in traditional 2-lobe technique group［31.94%（23/72）vs. 17.72%（14/79）， P = 0.042］.The procedure of novel en-bloc was shown as followed：expose the prostatic capsule near the verumontanum and expand the initial capsule plane on both sides. The prostatic urethral mucosa was cut off in a circular pattern medial to the external urethral sphincter，which could form a complete “circular mucosal pad”. Seperate the apical gland along the capsule plane at 12 o’clock and expand the capsule plane until the bladder neck was reached.The bladder neck was then used as a marker so as to separate the glands on both sides along the capsule plane and merge with the initial plane. The entire lobe of the prostate was finally removed along the surgical capsule of the prostate. The procedure of traditional two lobe method was shown as followed：expose the prostatic capsule near the verumontanum and then divide the prostate into two lobes by longitudinal incision at 6 and 12 o’clock. The mucosa was horizontally cut at 12 o’clock，medial to the external urethral sphincter in order to preserve the apical urethral mucosal flap. The twp lobes were then removedd respectively along the capsule layer. The surgery-related indicators，perioperative complications and other data were compared between the two groups，as well as IPSS，QOL score，lower urinary tract symptoms，and the incidence of stress urinary incontinence in the two groups 1 month after surgery. Results:Compared with the patients underwent 2-lobe technique HoLEP，the patients underwent novel en-bloc HoLEP had lower hemoglobin loss［0.50（-5.50，7.50）g/L vs. 7.00（1.00，13.25）g/L， P = 0.003］，lower operation time［（72.06 ± 34.37）min vs.（85.42 ± 40.35）min， P = 0.030］，higher surgical efficacy［（0.72 ± 0.31）g/min vs.（0.55 ± 0.29）g/min， P = 0.002］and lower incidence of stress urinary incontinence one month after operation［2.78%（2/72）vs. 10.13%（8/79）， P = 0.070］. There was no significant difference in the incidence of postoperative gross hematuria［0 vs. 2.53%（2/79）］，postoperative sepsis［1.39%（1/72）vs. 1.27%（1/79）］，postoperative dysuria［4.17%（3/72）vs. 5.06%（4/79）］，postoperative IPSS improvement［12.0（11.0，13.0）vs. 12.0（10.0，14.0）］and postoperative QOL improvement［3.0（2.0，3.0）vs. 3.0（2.0，3.0）］between the two groups（ P > 0.05）. The patients were further divided into 2 sub-groups according to whether prostate volume ≥ 60 ml or not. In the patients of prostate volume < 60 ml，surgical efficacy was significantly higher in novel en-bloc HoLEP group than that in traditional 2-lobe technique group［（0.55 ± 0.25）g/min vs.（0.41 ± 0.19）g/min， P = 0.028］. In the patients of prostate volume ≥ 60 ml，the surgical efficacy of novel en-bloc HoLEP was also higher［（0.88 ± 0.28）g/min vs.（0.66 ± 0.31）g/min， P = 0.006］. Conclusions:Novel en-bloc HoLEP with complete membranous urethral mucosa sparing technique was demonstrated to has lower blood loss，shorter operation time，higher surgical efficacy and lower incidence of stress urinary incontinence，which is suitable of all sizes of prostate.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective:To compare the safety and efficacy of novel en-bloc Holmium laser enucleation of the prostate（HoLEP）with complete membranous urethral mucosa sparing technique with traditional 2-lobe technique HoLEP in benign prostatic hyperplasia（BPH）treatment.Methods:The data of BPH patients treated with HoLEP from January 2023 to May 2024 in Xinhua Hospital，School of Medicine，Shanghai Jiaotong University were retrospectively reviewed. Seventy-two patients received novel en-bloc HoLEP with complete membranous urethral mucosa sparing technique（novel en-bloc group），while 79 patients received traditional 2-lobe technique HoLEP（traditional 2-lobe technique group）.There was no significant difference between novel en-bloc group and traditional 2-lobe technique group in the age［（71.0 ± 7.1）years vs.（69.8 ± 6.5）years］，body mass index［（24.5 ± 2.8）kg/m 2 vs.（23.9 ± 3.5）kg/m 2］，international prostate symptom score（IPSS）［26.0（22.0，28.0）vs. 25.0（22.0，28.0）］，quality of life（QOL）score［5.0（5.0，6.0）vs. 5.0（5.0，6.0）］，prostate sepcific antigen（PSA）［4.98（2.40，11.11）ng/ml vs. 4.38（1.62，7.54）ng/ml］and prostate volume［（74.06 ± 42.67）ml vs.（70.10 ± 33.94）ml］（all P > 0.05）. The incidence of acute urinary retention in novel en-bloc group was significantly higher than that in traditional 2-lobe technique group［31.94%（23/72）vs. 17.72%（14/79）， P = 0.042］.The procedure of novel en-bloc was shown as followed：expose the prostatic capsule near the verumontanum and expand the initial capsule plane on both sides. The prostatic urethral mucosa was cut off in a circular pattern medial to the external urethral sphincter，which could form a complete “circular mucosal pad”. Seperate the apical gland along the capsule plane at 12 o’clock and expand the capsule plane until the bladder neck was reached.The bladder neck was then used as a marker so as to separate the glands on both sides along the capsule plane and merge with the initial plane. The entire lobe of the prostate was finally removed along the surgical capsule of the prostate. The procedure of traditional two lobe method was shown as followed：expose the prostatic capsule near the verumontanum and then divide the prostate into two lobes by longitudinal incision at 6 and 12 o’clock. The mucosa was horizontally cut at 12 o’clock，medial to the external urethral sphincter in order to preserve the apical urethral mucosal flap. The twp lobes were then removedd respectively along the capsule layer. The surgery-related indicators，perioperative complications and other data were compared between the two groups，as well as IPSS，QOL score，lower urinary tract symptoms，and the incidence of stress urinary incontinence in the two groups 1 month after surgery. Results:Compared with the patients underwent 2-lobe technique HoLEP，the patients underwent novel en-bloc HoLEP had lower hemoglobin loss［0.50（-5.50，7.50）g/L vs. 7.00（1.00，13.25）g/L， P = 0.003］，lower operation time［（72.06 ± 34.37）min vs.（85.42 ± 40.35）min， P = 0.030］，higher surgical efficacy［（0.72 ± 0.31）g/min vs.（0.55 ± 0.29）g/min， P = 0.002］and lower incidence of stress urinary incontinence one month after operation［2.78%（2/72）vs. 10.13%（8/79）， P = 0.070］. There was no significant difference in the incidence of postoperative gross hematuria［0 vs. 2.53%（2/79）］，postoperative sepsis［1.39%（1/72）vs. 1.27%（1/79）］，postoperative dysuria［4.17%（3/72）vs. 5.06%（4/79）］，postoperative IPSS improvement［12.0（11.0，13.0）vs. 12.0（10.0，14.0）］and postoperative QOL improvement［3.0（2.0，3.0）vs. 3.0（2.0，3.0）］between the two groups（ P > 0.05）. The patients were further divided into 2 sub-groups according to whether prostate volume ≥ 60 ml or not. In the patients of prostate volume < 60 ml，surgical efficacy was significantly higher in novel en-bloc HoLEP group than that in traditional 2-lobe technique group［（0.55 ± 0.25）g/min vs.（0.41 ± 0.19）g/min， P = 0.028］. In the patients of prostate volume ≥ 60 ml，the surgical efficacy of novel en-bloc HoLEP was also higher［（0.88 ± 0.28）g/min vs.（0.66 ± 0.31）g/min， P = 0.006］. Conclusions:Novel en-bloc HoLEP with complete membranous urethral mucosa sparing technique was demonstrated to has lower blood loss，shorter operation time，higher surgical efficacy and lower incidence of stress urinary incontinence，which is suitable of all sizes of prostate.

Objective:To compare the efficacy of robot assisted laparoscopic partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) in the treatment of pediatric renal tumors.Methods:A retrospective analysis was conducted on the clinical data of 29 children with renal tumors admitted to Xinhua Hospital from March 2019 to March 2024. Among them, there were 10 cases in the RAPN group, including 6 males and 4 females; The median age is 7.5 (4, 12) years old, with a tumor diameter of (4.3±1.6) cm, a median R. E. N. A.L. score of 9 (8, 11), and relative tumor size (tumor volume/contralateral kidney volume) of (34.0%±19.3%). There were 19 cases in the LPN group, 8 males and 11 females; the median age is 5.0(4, 11) years old, with a tumor diameter of (4.4±1.6) cm, a median R. E. N. A.L. score of 9 (8, 11), and relative tumor size(37.7%±18.1%). There was no statistically significant difference in preoperative characteristics between the two groups ( P>0.05). Both groups underwent partial nephrectomy, with renal artery occlusion and then warm ischemia. Clinical data from both groups during and postoperatively were compared, and a simple linear regression analysis was utilized to assess the correlation between the relative size of the tumor and the duration of intraoperative warm ischemia. Results:All 29 cases underwent a successful surgery. Compared with the LPN group, the total surgery time in the RAPN group was (115.0±28.4) minutes versus (127.9±28.2) min( P=0.25); the warm ischemia time was (20.9±3.0) min versus (27.0±4.5) min, respectively( P<0.01); the intraoperative bleeding was (50.0±24.5) ml and (80.0±21.2) ml( P<0.01); the difference in hemoglobin level before and after surgery was (10.3±3.5) g/L versus (12.9±2.7) g/L( P<0.05), respectively; the median postoperative drainage time was 3.5 (3, 4) days versus 4.0(3, 6) days( P=0.17); the median postoperative hospital stay was 4.5 (4, 8) days versus 6.0(5, 10) days( P<0.05). There were 3 cases of renal cell carcinoma associated with the MiT family translocation, 2 cases of mixed epithelial and stromal tumors, and 2 cases of cystic nephroma by postoperative pathological examination in the RAPN group. There were 10 cases of nephroblastoma, 3 cases of teratoma, 2 cases of renal cell carcinoma associated with the MiT family translocation, 2 cases of metanephric adenoma, 1 case of unclassified renal cell carcinoma, and 1 case of cystic nephroma in the LPN group. Apart from one child in the LPN group who developed a postoperative fever over 39℃, no other severe complications occurred during or after the surgery in the remaining patients. Compared with preoperative parameters, eGFR decreased (8.9±18.9) ml/(min·1.73m 2) and (21.4±34.8) ml/(min·1.73m 2) in the RAPN group and LPN group, respectively, 1 month postoperatively( P=0.36); three months after surgery, eGFR was followed up, and the RAPN group and LPN group showed a decrease of (5.9±23.4) ml/(min·1.73m 2) and (13.9±20.1) ml/(min·1.73m 2) compared with preoperative levels, respectively( P=0.42). Linear regression analysis indicated that in the LPN group, intraoperative warm ischemia time exhibited a progressively increasing trend with the augmentation of the tumor's relative size, and warm ischemia time = 0.1688×tumor relative size+ 20.64, ( R2=0.46, P<0.01). Based on this, it is estimated that when the tumor's relative size exceeds 55.5%, the intraoperative warm ischemia time often surpassed 30 minutes. However, in the RAPN group, this trend is not statistically significant (P>0.05). Conclusions:Both LPN and RAPN are safe and feasible for the treatment of pediatric renal tumors. Compared with LPN, RAPN surgery has advantages of shortening warm ischemia time and reducing intraoperative bleeding, which helps patients recover early. RAPN is a better choice for children with a relative renal tumors size over 55.5%.

Objective:To compare the efficacy of robot assisted laparoscopic partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) in the treatment of pediatric renal tumors.Methods:A retrospective analysis was conducted on the clinical data of 29 children with renal tumors admitted to Xinhua Hospital from March 2019 to March 2024. Among them, there were 10 cases in the RAPN group, including 6 males and 4 females; The median age is 7.5 (4, 12) years old, with a tumor diameter of (4.3±1.6) cm, a median R. E. N. A.L. score of 9 (8, 11), and relative tumor size (tumor volume/contralateral kidney volume) of (34.0%±19.3%). There were 19 cases in the LPN group, 8 males and 11 females; the median age is 5.0(4, 11) years old, with a tumor diameter of (4.4±1.6) cm, a median R. E. N. A.L. score of 9 (8, 11), and relative tumor size(37.7%±18.1%). There was no statistically significant difference in preoperative characteristics between the two groups ( P>0.05). Both groups underwent partial nephrectomy, with renal artery occlusion and then warm ischemia. Clinical data from both groups during and postoperatively were compared, and a simple linear regression analysis was utilized to assess the correlation between the relative size of the tumor and the duration of intraoperative warm ischemia. Results:All 29 cases underwent a successful surgery. Compared with the LPN group, the total surgery time in the RAPN group was (115.0±28.4) minutes versus (127.9±28.2) min( P=0.25); the warm ischemia time was (20.9±3.0) min versus (27.0±4.5) min, respectively( P<0.01); the intraoperative bleeding was (50.0±24.5) ml and (80.0±21.2) ml( P<0.01); the difference in hemoglobin level before and after surgery was (10.3±3.5) g/L versus (12.9±2.7) g/L( P<0.05), respectively; the median postoperative drainage time was 3.5 (3, 4) days versus 4.0(3, 6) days( P=0.17); the median postoperative hospital stay was 4.5 (4, 8) days versus 6.0(5, 10) days( P<0.05). There were 3 cases of renal cell carcinoma associated with the MiT family translocation, 2 cases of mixed epithelial and stromal tumors, and 2 cases of cystic nephroma by postoperative pathological examination in the RAPN group. There were 10 cases of nephroblastoma, 3 cases of teratoma, 2 cases of renal cell carcinoma associated with the MiT family translocation, 2 cases of metanephric adenoma, 1 case of unclassified renal cell carcinoma, and 1 case of cystic nephroma in the LPN group. Apart from one child in the LPN group who developed a postoperative fever over 39℃, no other severe complications occurred during or after the surgery in the remaining patients. Compared with preoperative parameters, eGFR decreased (8.9±18.9) ml/(min·1.73m 2) and (21.4±34.8) ml/(min·1.73m 2) in the RAPN group and LPN group, respectively, 1 month postoperatively( P=0.36); three months after surgery, eGFR was followed up, and the RAPN group and LPN group showed a decrease of (5.9±23.4) ml/(min·1.73m 2) and (13.9±20.1) ml/(min·1.73m 2) compared with preoperative levels, respectively( P=0.42). Linear regression analysis indicated that in the LPN group, intraoperative warm ischemia time exhibited a progressively increasing trend with the augmentation of the tumor's relative size, and warm ischemia time = 0.1688×tumor relative size+ 20.64, ( R2=0.46, P<0.01). Based on this, it is estimated that when the tumor's relative size exceeds 55.5%, the intraoperative warm ischemia time often surpassed 30 minutes. However, in the RAPN group, this trend is not statistically significant (P>0.05). Conclusions:Both LPN and RAPN are safe and feasible for the treatment of pediatric renal tumors. Compared with LPN, RAPN surgery has advantages of shortening warm ischemia time and reducing intraoperative bleeding, which helps patients recover early. RAPN is a better choice for children with a relative renal tumors size over 55.5%.

Objective:To explore the application selection of preputial circular flap pedicle in the treatment of complex long segment urethral stricture.Methods:The data of 11 patients who underwent surgical reconstruction of the urethra for complex long segment urethral stricture between October 2019 and November 2022 in Xinhua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine were retrospectively analyzed. The patients’ average age was 46(range 40-66) years old, with average urethral stricture length of 7 (range 6-13) cm and average maximum preoperative urinary flow rate of 5 (range 3-7) ml/s. They had a history of recurrent urinary tract infections and endoscopic treatment for urinary tract stones. Among the 11 cases, one patient had necrotizing fasciitis of the scrotum with complete destruction and loss of the scrotal urethra. This patient received acute bladder diversion, surgical debridement, vacuum sealing drainage, and negative pressure suction during the acute phase. And six months later, a circular preputial pedicle flap was used to reconstruct a 12 cm urethral defect in the scrotal region. The remaining 10 patients underwent preputial circular flap pedicle onlay urethral reconstruction. The changes in the patient's maximum urinary flow rate, and the signs of restenosis, urinary fistula, or urethral diverticulum were analyzed.Results:All 11 patients who underwent preputial circular flap pedicle urethral reconstruction had unobstructed urination after surgery. Surgical time ranged from 96 to 246 min, with an average of 121 min. The intraoperative blood loss ranged from 10 to 200 ml, with an average of 46 ml. The hospital stay ranged from 6 to 13 d, with an average of 9 d. The indwelling catheterisation time ranged from 18 to 28 d, with an average of 20 d. The patients were followed-up for 9 to 32 months, with an average of 24 months. All 11 cases had smooth urinary flow after surgery, and the maximum urinary flow rate ranged from 16.1 to 24.2 ml/s, with an average of 17.6 ml/s, which was significantly higher than that before surgery. Two patients had post-void dribbling after four weeks, and imaging showed the formation of a diverticulum in the reconstructed segment of the urethra.Conclusions:Urethral reconstruction with preputial circular flap pedicle is a viable treatment option for complex long segment urethral stricture. The surgical outcomes are satisfactory, and the choice of treatment should be based on the patient's own conditions and the surgeon's technical expertise.

Adenosine triphosphate(ATP)is the most common energy supplier in living organisms and also an important signaling molecule.The expression level of ATP is significantly upregulated in the tumor microenvironment.The purinergic receptor ion channel P2X is widely distributed in various tissues.ATP can specifically activate the P2X receptor to induce the opening of gated ion channels in the microenvironment,thereby affecting the downstream signal transduction in regulating the physiological activities.Notably,abnormal purinergic signal plays an important role in tumor progression.This review focuses on the expression,structure,and function of the P2X receptor protein family.It also elucidates the mechanisms by which the P2X receptor family participates in the progression of various solid tumors,as well as research on targeted P2X family for tumor therapy.These studies will enrich the basic research theory related to purinergic signaling and provide the new targets and strategies for clinical therapy of solid tumors by targeting P2X family.

Objective To investigate the efficacy and safety of using the fourth arm in retroperitoneal robot-assisted partial nephrectomy(PN)for cT1b stage renal tumors.Methods Clinical data of 49 patients with cT1b stage renal tumors who underwent retroperitoneal robot-assisted PN performed by the same surgeon in our hospital during Jan.2022 and Dec.2023 were retrospectively analyzed.The patients were divided into two groups based on whether the fourth arm was used or not:application group(n=21)and non-application group(n=28).The basic information,operation time,warm ischemia time,intraoperative blood loss,postoperative complications and other data were compared between the two groups.Results All operations were successful,with no conversion to open surgery or radical nephrectomy.The application group had significantly shorter operation time[(128.76±31.58)min vs.(151.11±33.21)min,P=0.021],shorter warm ischemia time[(24.67±4.80)min vs.(27.61±3.54)min,P=0.017],and less intraoperative blood loss[(109.05±39.99)mL vs.(139.29±54.43)mL,P=0.037]compared with the non-application group.The increase of postoperative creatinine was(18.64±16.05)μmol/L in the application group and(20.30±13.49)μmol/L in the non-application group respectively.Complications occurred in 3 cases in the application group and 5 cases in the non-application group,with no significant difference(P＞0.05).Conclusion When we perform the retroperitoneal robot-assisted partial nephrectomy for cT1b stage renal tumors,using the fourth arm can shorten the operation time and warm ischemia time,and reduce the intraoperative blood loss,which should be applied more in clinic.

OBJECTIVE To investigate the impacts of andrographolide on sciatic nerve function injury in diabetic peripheral neuropathy （DPN） rats by regulating high-mobility group protein box 1 （HMGB1）/receptor for advanced glycation end products （RAGE） signal pathway. METHODS A total of 84 rats were randomly divided into the control group （normal saline）， DPN group （normal saline）， low-dose andrographolide group （0.833 mg/kg）， high-dose andrographolide group （3.332 mg/kg）， lipoic acid group （positive control， 0.1 g/kg）， recombinant rat HMGB1 protein （rHMGB1） group （8 μg/kg）， and high-dose andrographolide+ rHMGB1 group， with 12 rats in each group. All rats except those in the control group were fed with high glucose and high fat diet combined with intraperitoneal injections of streptozotocin to establish the DPN rat model. After 24 hours of successful modeling， medication was administered daily for 8 weeks. The changes in fasting blood glucose， mechanical pain threshold， heat pain threshold and sciatic nerve conduction velocity were detected. Pathological changes in the sciatic nerve of rats and the activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） in the sciatic nerve of rats were also detected. Besides， the expressions of HMGB1， RAGE proteins and phosphorylation level of nuclear factor κB p65（NF-κB p65） protein in rat sciatic nerves were found. RESULTS Compared with the control group， the pathological damage of the sciatic nerve of rats in the DPN group was strengthened， the fasting blood glucose， heat pain threshold， MDA content and the 诊治。E-mail：dqiaur@163.com expressions of HMGB1， RAGE proteins and phosphorylation level of NF-κB p65 protein were increased （P＜0.05）， while the mechanical pain threshold， sensory nerve conduction velocity， motor nerve conduction velocity， and SOD activity were decreased/slowed down （P＜0.05）. Compared with the DPN group， the above indexes were significantly potentiated in the andrographolide low- and high-dose groups and lipoic acid group （P＜0.05）， and the corresponding trends in the rHMGB1 group were opposite to those in the above three administration groups （P＜0.05）. Moreover， rHMGB1 attenuated the hypoglycemic effect of high-dose andrographolide on blood glucose and the improvement of oxidative stress injury in the sciatic nerve of DPN rats （P＜0.05）. CONCLUSIONS Andrographolide may reduce blood glucose by inhibiting the HMGB1/RAGE pathway and oxidative stress， thus ameliorating sciatic nerve injury in DPN rats.