Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Objective To investigate the effect of 3-bromopyruvate (3-BrPA) on transplanted rectal tumors in experimental rabbit models. Methods A total of 60 New Zealand white rabbits with transplanted rectal tumor were randomly and equally divided into low-dose (0.5 mmol/L), medium-dose (1.0 mmol/L), high-dose (2.0 mmol/L) treatment groups and saline control group with 15 rabbits in each group. Arterial perfusion of 10 ml 3-BrPA with concentration of 0.5 mmol/L, 1.0 mmol/L and 2.0 mmol/L via caudal mesenteric artery was respectively employed for the rabbits of the corresponding treatment group; the control group was perfused with equal amounts of saline. Four days later, rectal tumors were removed by vivisection. The necrosis degree of tumor cells was determined by microscopic examination, and the necrosis rate was calculated. The effect of different 3-BrPA concentrations on the rectal tumor was evaluated. Results The rectal tumor transplantation and transcatheter 3-BrPA or saline perfusion was successfully completed in all 60 experimental rabbits. Microscopically, tumor cells showed different degrees of damage in experimental rabbits. In low-dose (0.5 mmol/L) treatment group, gradeⅠnecrosis was observed in 3 rabbits, gradeⅡin 11 rabbits, and gradeⅢin one rabbit;the effective rate was 6.7%. In medium-dose (1.0 mmol/L) treatment group, gradeⅡnecrosis was seen in 2 rabbits, grade Ⅲ in 10 rabbits, and grade Ⅳ in 3 rabbits; the effective rate was 86.6%. In high-dose (2.0 mmol/L) treatment group, gradeⅢnecrosis was detected in 2 rabbits and gradeⅣin 13 rabbits;the effective rate was 100.0%. In the saline control group, grade I necrosis was observed in 15 rabbits. Statistically significant differences in tumor necrosis rate and effective rate existed between medium-dose (1.0 mmol/L) treatment group and high-dose (2.0 mmol/L) treatment group (P<0.05). Statistically significant differences in tumor necrosis rate also existed between each other among the four groups with necrosis of gradeⅠto gradeⅣ(P<0.05). 3-BrPA had obvious therapeutic effect, while it showed no damage to the normal intestinal tissue. Conclusion For the treatment of transplanted rectal tumor in rabbit models, arterial infusion of 3-BrPA has certain therapeutic effect. In the high-dose group, the necrosis rate and effective rate are the highest, and the therapeutic results are the most significant.

Objective To study the efficacy and safety of entacapone as an adjunct to levodopa treatment in pakinsonian patients with wearing-off motor fluctuations. Methods A total 209 pakinsonian patients with end-of-dose deterioration participated in a multi-center,12-weeks randomized,placebo-controlled,double blind,parallel-group trial.The efficacy of entacapone was assessed using the patient’s diary card,the Unified Parkinson’s Disease Rating Scale (UODRS) score,the daily levodopa dosage,and the global assessment of changes.Results 96.2% of the entacapone and 92.4% of the placebo-treated patients completed the study.In 209 cases of the ITT population,in comparison to the placebo-treated patients,entacapone had increased the mean “on” time (h/d) from 7.4?1.8 in base-line to 9.1?2.5 in week 12,decreased the “fof” time (from 6.8?2.2 in base-line to 5.2?2.8 in week 12),improved the motor scores (from 36.7?11.3 in base-line to 30.0?14.4 in week 12),and reduced the levodopa dose (from 589.2?264.3 in base-line to 561.5?248.1 in week 4). The improvement was also evident on impression of successful treatment for 69.9% of neurologists through global change assessment.There was no significant difference in the frequency of dopaminergic adverse events and serious laboratory abnormalities between entacapone and placebo groups.Conclusion The results of this study demonstrate that entacapone,the COMT inhibitor is a safe and effective extender of levodopa treatment for Parkinson’s disease patients with motor flucturations.

AIM To investigate the protective effect of daidzeid (DZ) on cerebral ischemia and it mechanism in mice METHODS Cerebral ischemia was induced by cutting heads and bilateral carotid arteries were completely or incompletely ligated RESULTS The stroke index score in ischemic mice was reduced by DZ, an the persistent time of gasping of mice by decapitation and survival time of mice by bilateral carotid arteries ligation were prolonged by DZ DZ could reduce the content of brain lactic acid while improve the brain superoxide dismutase activity CONCLUSIONS The results indicate that DZ has the protectiveeffect on cerebral ischemia injury Its mechanism may be related with its effect of decreasing of lactic acid content and reducing of free radicals production