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.

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 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 study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

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.

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 explore the application and research progress of lasers in the treatment of kidney neoplasms through an integrated bibliometric and Meta-analysis study.Methods:On June 7th, 2024, an online search of the Web of Science Core Collection (WoSCC) and China National Knowledge Infrastructure (CNKI) databases for all relevant literature on lasers in kidney neoplasms was conducted. The retrieved results were subjected to a comprehensive bibliometric analysis. The high-quality studies were then screened to further describe the clinical characteristics of patients who underwent laser-assisted laparoscopic partial nephrectomy (LLPN). Subsequently, a Meta-analysis was performed using RevMan 5.4.1 software on further selected high-quality studies to compare the changes in renal function before and after LLPN treatment, and the differences in efficacy between LLPN and traditional laparoscopic partial nephrectomy (LPN).Results:Our study obtained a total of 549 publications on lasers in kidney neoplasms, including 513 in English and 36 in Chinese. Bibliometric analysis revealed an overall upward trend in the annual publications and citations in this field. China was found to be a leading contributor ranking second in total publications ( n=100, 18.2%). The primary application of laser treatment was in nephron-sparing surgery for kidney neoplasms, especially in LPN. We further screened 11 high-quality studies comprising 284 patients who underwent LLPN for kidney neoplasms. Comprehensive descriptive statistical analysis was performed on clinical characteristics of the 284 patients. All patients had T 1a stage tumors with a mean tumor length of 2.6 cm (range: 0.8-4.0 cm), all being local, solitary, and exophytic tumors. Further Meta-analysis indicated that there were no significant differences in renal function indicators including both serum creatinine levels ( MD=4.52, 95% CI-9.73-0.69, P = 0.09) and estimated glomerular filtration rate ( MD=3.05, 95% CI-1.03-7.13, P= 0.14) before and after LLPN. Additionally, compared to traditional LPN, LLPN showed significantly reduced operative time ( MD=-10.58, 95% CI= -13.11-8.06, P<0.001), but no significant differences in estimated blood loss ( MD= -27.09, 95% CI-67.38-13.21, P=0.19) and hospital stay ( MD=-1.59, 95% CI-3.42-0.25, P=0.09). Conclusions:The application of lasers in managing of kidney neoplasms is arousing increasing attention among urologists. LLPN offers several advantages, including precise cutting and effective hemostasis. This technique demonstrates considerable clinical value for patients with exophytic T 1a kidney neoplasms undergoing "zero-ischemia" nephron-sparing surgery.

Clinical cases of necrotizing fasciitis and complete urethral defects in the scrotal region are rare. The diagnosis and treatment are very challenging. This article reports one case. The patient was admitted to the hospital after 1 week of poor urination and 2 days of scrotal swelling, and then underwent bladder diversion, surgical debridement, vacuum-sealing drainage, and wound closure. After four weeks, the wound healed and the patient was discharged. Six months later after surgery, scrotal urethral reconstruction was performed using a circular phimosis pedicled skin flap graft to repair the 12 cm urethral defect. The urethral catheter was removed after three weeks. The bladder fistula tube was removed after 5 weeks. During the follow-up of one year, there was no occurrence of urinary fistula and urinary obstruction.