Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Objective To construct an accurate clinical model of lower limb varicose veins in rats through surgery that provides theoretical support for evaluating drug therapy.Methods 30 SD rats,15 males and 15 females,were randomly divided into a control group and surgical group.In the surgical group,the rats lower limb veins(including the small saphenous vein and femoral vein)were ligated via improved lower limb vein ligation,i.e.,the small saphenous vein was completely ligated with the femoral vein,and the thrombosis result ed in a lasting increase in the internal pressure of the deep veins of the lower limb,causing varicose symptoms.On the 6th week after surgery,the varicose veins of the rats in the surgical group were scored to select those that were successfully modeled.Then,the successfully modeled rats were randomly divided into a model group and Maizhiling group.Maizhiling 62.5 mg/kg was orally administered to the treatment group once a day,while the control and model group received an equal volume of physiological saline orally every day for 20 consecutive days.On the day before administration and 7 d,14 d and 20 d after administration,macro photography and scoring were performed on the lower limbs of the rats.After completion,an approximately 1 cm long saphenous vein above the ankle joint of the lower limb on the surgical side was removed from the model group and Maizhiling group rats,while from the control group,the corresponding saphenous vein of the lower limb on the same side was removed.Pathological tissue observation was performed using HE staining,Masson staining,and immunohistochemical examination for interleukin-2(IL-2)and tissue inhibitor of metalloproteinases(TIMP-1).Results Of the 22 rats in the surgical group,20 were successfully modeled,with a success rate of 91％.According to the manifestations of venous dilation,varicose veins,and redness in the lower limbs of rats,the varicose vein score of the model group increased significantly compared with that of the control group(P＜0.01).After the therapeutic dose of Maizhiling was administered,the varicose vein score in the Maizhiling group decreased significantly compared with that of the model group(P＜0.01).Pathological examination showed significant varicose-vein-like changes and mild inflammation in the model group.The Maizhiling group showed reduced varicose veins and inflammation.Conclusions A rat model of lower limb varicose veins was successfully established,providing a new research method for the study of drugs and treatment method related to lower limb varicose diseases.

Objective To construct an accurate clinical model of lower limb varicose veins in rats through surgery that provides theoretical support for evaluating drug therapy.Methods 30 SD rats,15 males and 15 females,were randomly divided into a control group and surgical group.In the surgical group,the rats lower limb veins(including the small saphenous vein and femoral vein)were ligated via improved lower limb vein ligation,i.e.,the small saphenous vein was completely ligated with the femoral vein,and the thrombosis result ed in a lasting increase in the internal pressure of the deep veins of the lower limb,causing varicose symptoms.On the 6th week after surgery,the varicose veins of the rats in the surgical group were scored to select those that were successfully modeled.Then,the successfully modeled rats were randomly divided into a model group and Maizhiling group.Maizhiling 62.5 mg/kg was orally administered to the treatment group once a day,while the control and model group received an equal volume of physiological saline orally every day for 20 consecutive days.On the day before administration and 7 d,14 d and 20 d after administration,macro photography and scoring were performed on the lower limbs of the rats.After completion,an approximately 1 cm long saphenous vein above the ankle joint of the lower limb on the surgical side was removed from the model group and Maizhiling group rats,while from the control group,the corresponding saphenous vein of the lower limb on the same side was removed.Pathological tissue observation was performed using HE staining,Masson staining,and immunohistochemical examination for interleukin-2(IL-2)and tissue inhibitor of metalloproteinases(TIMP-1).Results Of the 22 rats in the surgical group,20 were successfully modeled,with a success rate of 91％.According to the manifestations of venous dilation,varicose veins,and redness in the lower limbs of rats,the varicose vein score of the model group increased significantly compared with that of the control group(P＜0.01).After the therapeutic dose of Maizhiling was administered,the varicose vein score in the Maizhiling group decreased significantly compared with that of the model group(P＜0.01).Pathological examination showed significant varicose-vein-like changes and mild inflammation in the model group.The Maizhiling group showed reduced varicose veins and inflammation.Conclusions A rat model of lower limb varicose veins was successfully established,providing a new research method for the study of drugs and treatment method related to lower limb varicose diseases.

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses

OBJECTIVETo compare the surgical effect of three-dimensional (3D) versus 2D laparoscopic surgery in ureter lithotomy.

METHODSFrom January 2014 to 2015 May, 45 patients with ureteral calculi were randomly allocated into 2 groups to undergo ureter lithotomy under 3D laparoscopy (25 cases) and 2D laparoscopy (20 cases). The time used for each surgical process (including the exposure, D-J tube discharge, suture and other surgical procedures) was recorded and compared between the two groups.

RESULTSThe operation was completed smoothly in all the 45 patients. In this cohort, the wound drainage tube was removed in a mean of 3.0mnplus;0.8 days after the operation, the catheter was removed after a week, and the double J tube was removed at 1 month. Follow-up intravenous pyelography at 3 months after the operation reveal ureteral stricture in none of the cases. Comparison of the surgical data showed that the time used in each surgical process was significantly shorter in the 3D group than in the 2D group (P<0.05). 3D laparoscopic surgery allowed more precise operation by providing a good sense of depth as in an open surgery to reduce the operation time.

CONCLUSIONSAs a minimally invasive surgical technique, 3D laparoscopic surgery facilitates more precise and easier operation compared with 2D laparoscopy in ureter lithotomy.

Humans ; Imaging, Three-Dimensional ; Kidney Pelvis ; Laparoscopy ; methods ; Operative Time ; Retroperitoneal Space ; Ureter ; Ureteral Calculi ; surgery

OBJECTIVETo compare the safety, feasibility and efficacy of transperitoneal and retroperitoneal laparoscopic partial nephrectomy (LPN) in the treatment of renal tumors with R. E. N. A. L score more than 7.

METHODSThe clinical data were collected from 62 patients undergoing transperitoneal LPN (32 cases) and retroperitoneal LPN (30 cases) for a complex renal mass (R.E.N.A.L. score≥7) between January 2012 and March 2014. The surgical and early postoperative outcomes and complications were analyzed to evaluate the efficacy of the treatments. The mean operative time, estimated blood loss, warm ischemia time, surgical complications, blood transfusion rate, tolerating regular diet time, postoperative hospital stay and surgical margin were compared between the two groups.

RESULTSThe operations were completed successfully in all cases except for 1 case in transperitoneal group and 3 in retroperitoneal group that required conversion to open surgery. No significant differences were found in age, body mass index, ASA score, Charlson comorbidity index, tumor size or R.E.N.A.L. nephrometry score (P>0.05), nor in estimated blood loss, warm ischemia time, intraoperative complication, blood transfusion rate or surgical margin between the two groups (P>0.05, respectively). The transperitoneal LPN group had a shorter mean operative time than retroperitoneal LPN group (210.4∓59.2 vs 252∓58.3 min, P<0.05) but showed longer tolerating regular diet time (47∓10 h vs 23∓6 h, P<0.05) and postoperative hospital stay time (8.4∓1.9 days vs 6.5∓1.6 days, P<0.05).

CONCLUSIONBoth transperitoneal LPN and retroperitoneal LPN are safe, feasible and effective for surgical management of complex localized tumors, but the transperitoneal procedure offers larger operative space with better exposure; the retroperitoneal procedure better promotes postoperative recovery of the patients.

Humans ; Kidney Neoplasms ; diagnosis ; surgery ; Laparoscopy ; Length of Stay ; Nephrectomy ; Operative Time ; Retroperitoneal Space ; Retrospective Studies ; Treatment Outcome

Objective To compare the safety, feasibility and efficacy of transperitoneal and retroperitoneal laparoscopic partial nephrectomy (LPN) in the treatment of renal tumors with R. E. N. A. L score more than 7. Methods The clinical data were collected from 62 patients undergoing transperitoneal LPN (32 cases) and retroperitoneal LPN (30 cases) for a complex renal mass (R.E.N.A.L. score≥7) between January 2012 and March 2014. The surgical and early postoperative outcomes and complications were analyzed to evaluate the efficacy of the treatments. The mean operative time, estimated blood loss, warm ischemia time, surgical complications, blood transfusion rate, tolerating regular diet time, postoperative hospital stay and surgical margin were compared between the two groups. Results The operations were completed successfully in all cases except for 1 case in transperitoneal group and 3 in retroperitoneal group that required conversion to open surgery. No significant differences were found in age, body mass index, ASA score, Charlson comorbidity index, tumor size or R.E.N.A.L. nephrometry score (P>0.05), nor in estimated blood loss, warm ischemia time, intraoperative complication, blood transfusion rate or surgical margin between the two groups (P>0.05, respectively). The transperitoneal LPN group had a shorter mean operative time than retroperitoneal LPN group (210.4±59.2 vs 252±58.3 min, P<0.05) but showed longer tolerating regular diet time (47 ± 10 h vs 23 ± 6 h, P<0.05) and postoperative hospital stay time (8.4 ± 1.9 days vs 6.5 ± 1.6 days, P<0.05). Conclusion Both transperitoneal LPN and retroperitoneal LPN are safe, feasible and effective for surgical management of complex localized tumors, but the transperitoneal procedure offers larger operative space with better exposure; the retroperitoneal procedure better promotes postoperative recovery of the patients.

Objective To compare the safety, feasibility and efficacy of transperitoneal and retroperitoneal laparoscopic partial nephrectomy (LPN) in the treatment of renal tumors with R. E. N. A. L score more than 7. Methods The clinical data were collected from 62 patients undergoing transperitoneal LPN (32 cases) and retroperitoneal LPN (30 cases) for a complex renal mass (R.E.N.A.L. score≥7) between January 2012 and March 2014. The surgical and early postoperative outcomes and complications were analyzed to evaluate the efficacy of the treatments. The mean operative time, estimated blood loss, warm ischemia time, surgical complications, blood transfusion rate, tolerating regular diet time, postoperative hospital stay and surgical margin were compared between the two groups. Results The operations were completed successfully in all cases except for 1 case in transperitoneal group and 3 in retroperitoneal group that required conversion to open surgery. No significant differences were found in age, body mass index, ASA score, Charlson comorbidity index, tumor size or R.E.N.A.L. nephrometry score (P>0.05), nor in estimated blood loss, warm ischemia time, intraoperative complication, blood transfusion rate or surgical margin between the two groups (P>0.05, respectively). The transperitoneal LPN group had a shorter mean operative time than retroperitoneal LPN group (210.4±59.2 vs 252±58.3 min, P<0.05) but showed longer tolerating regular diet time (47 ± 10 h vs 23 ± 6 h, P<0.05) and postoperative hospital stay time (8.4 ± 1.9 days vs 6.5 ± 1.6 days, P<0.05). Conclusion Both transperitoneal LPN and retroperitoneal LPN are safe, feasible and effective for surgical management of complex localized tumors, but the transperitoneal procedure offers larger operative space with better exposure; the retroperitoneal procedure better promotes postoperative recovery of the patients.

Objective To summarize the safety and efficacy of Sunitinib in the treatment of metastatic renal clear cell carcinoma. Methods Fifteen patients with clear cell metastatic RCC were treated with Sunitinib,with 11 males and 4 females,aged from 26 to 74 years with median age of 55 years.Thirteen cases of 15 were T3 to T4 stage,and 8 cases underwent radical nephrectomy,while 5 other cases underwent renal biopsy with the pathological diagnosis of renal cancer.The other two cases (one man and one woman)with the solitary kidney renal cell carcinoma ( stage T1a) and renal insufficiency,were diagnosed as metastatic renal cell carcinoma by biopsy.Sunitinib monotherapy was administered by the regimen of 6 weeks per cycle with daily oral Sunitinib 4 weeks,followed by 2 weeks off ( from 1 - 10 cycles).Response was evaluated by RECIST.Renal tumor was 9.52 ± 3.3 cm in diameter at baseline,and the assessment of metastases included retroperitoneal lymph nodes (6 cases),mediastinal lymph nodes (3 cases),brain (2 cases),lung (6 cases),bone (2 cases) and liver (2 cases).Karnofsky score,tumor changes,adverse events and the survival of each patient was assessed and recorded. Results The follow-up duration was from 1.5 - 15months,with median follow-up of 6 months,and tumor response was evaluated by RECIST.Seven of 15 patients (46.7％) treated with Sunitinib achieved partial responses (PR),7 patients (46.7％) demonstrated stable disease (SD),and 1 patient (6.7％) developed progressive disease (PD) during the follow-up.Objective Response Rate (ORR) was 46.7％,PR + SD was 93.3％,6 months PFS was 93.3％,and median PFS was 12 months,respectively.Renal tumor was 8.7 ± 4.0 cm in diameter after therapy.Two PR patients with the obvious effectiveness had experienced progressed hypertension,and one cases with hypertension that could be controlled below 140/90 mm Hg ( 1 mm Hg =0.133 kPa) by a single drug before treatment,showed increased blood pressure ( ＞ 160/105 mm Hg) following the second cycles treatment,who were administered increased dosage and combination therapy.The other case without history of hypertension,showed high blood pressure ( ＞ 150/100 mm Hg) in the third cycle,and could be controlled well by antihypertensive drugs.Fortunately,the tumor of these two cases reduced obviously by more than 50％. 1/2 adverse reactions of 12 cases:yellowing of the skin and yellow sweat ( 12 cases,80％ ),fatigue ( 12 cases,80％ ),4 cases of hypothyroidism (26.7％),bilirubin and triglyceride levels elevated in 7case (46.7％); Four cases showed 3/4 degree adverse events with the emergence of gastrointestinal bleeding in one case secondary to platelets reduction (6.7％).Three cases (20％) showed serious fatigue,nausea,vomiting and severe hand-foot skin reaction. Conclusions Sunitinib is recommended for the treatment of metastatic renal clear cell carcinoma with good efficacy and safety.

Objective To investigate the changes of esophageal visceral sence stimulated by esophageal distention in rabbits and the protein expressions of calcitonin gene related peptide(CGRP),P substance(SP),5-hydroxytryptamine(5-HT),Fos protein in central nervous system(CNS).Methods Twenty New Zealand rabbits were randomly divided into experimental group(n=8,received esophageal distention with 0.9 cm balloon for 30 s twice a day for 14 days),control group(n=6,received esophageal stimulation without balloon for 30 s twice a day for 14 days)and blank control grouop(n=6).The esophageal visceral sense was evaluated by animal behavior scores.The expressions of SP,CGRP,5-HT and Fos protein esophagus mucosa,spine,nucleus tractus solitari (NTS),periaqueductal gray(PAG)and thalamus were measured by immunochistochemistry.Results At the same behavior scores,the tube diameter of experimental group was significant lower than those of control group(P＜0.05).The expression of SP in esophagus mucosa,spine and NTS was significant increased in experimental group compared to two control groups(P＜0.05).The expression of CGRP and Fos in esophagus mucosa.spine,NTS,PAG and thalamus was increased in experimental group compared to two control groups(P＜0.05).The expression of 5-HT in esophagus mucosa and spine was higher in experimental group than that in control and blank control groups (esophagus: 27.67±3.27 vs 11.00±1.79 or 11. 17±1.33;spine:24.00±5.22 vs 11.33±2.94 or 11. 83±2. 48, P＜0. 01). But the expression of 5-HT in PAG was lower in experimental group( 13. 17±2.04) than that in control 17.67±2.07)and blank control (16.83±2.32) groups (P＜0. 05). There was significant correlation between CGRP and Fos, SP and Fos, CGRP and SP in spine (r=0. 813,0. 779,0. 772,P=0. 025,0.034, 0. 036, respectively). Conclusions Esophageal hypersensitivity may be induced by esophageal distention. The expresstion of SP, CGRP, 5-HT was increased in the esophageal mueosa and CNS, which indicate that these neurotransmitters and CNS may play an important role in the increase of esophageal visceral sense.