ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

Objective To utilize the magnetic resonance neurography (MRN) as a feasible tool for measuring the anatomical parameters of lumbar spinal nerves, and further to evaluate the neuro-safety of interlaminar percutaneous endoscopic lumbar discectomy.Methods Thirty healthy adult volunteers without significant history of low back pain or lumbar deformity were selected in our hospital from September 2016 to December 2016. All subjects accepted MRN. The nerve roots of L2-S1 were measured at the starting point of dural sac, and the angles between nerve roots and dural sac were measured. The distances between L2-L5 nerve roots and the edge of ipsilateral dural sac were measured and analyzed statistically.Results All MRN showed a gradual increase in the origin of the nerve roots from L2 to S1. The origin of the root was found to be below the corresponding disc for the L2 to L4 roots. There were 70％ of the L5 roots originated below the L4/5 disc, 26.7％ at the L4/5 disc, and 3.3％ above the L4/5 disc; about 70％ of the S1 roots originated above the L5/S1 disc. There were no statistically significant differences in the angles between dural sac and both left and right nerve roots (P>0.05). The angels between the nerve root and the dural sac from L5 and S1 was smaller than those from L2, L3, and L4 (P<0.05); that from S1 was significantly smaller than that from L5 (P<0.05). The distance of the nerve root and the ipsilateral dural sac was significantly increased in each side from L2 to L5 (P<0.05). There was no statistically significant difference in the distances between the left and right nerve roots and the edge of the ipsilateral dural sac in the same segment (P>0.05).Conclusion MRN is a feasible tool to measure the anatomical parameters of the lumbar spinal nerve, and there is a safe neurological area of the percutaneous endoscopic lumbar discectomy through the interlaminar approach.

Objective To evaluate the efficacy of facial acupoint injection combined with nerve block in treating hemifacial spasm. Methods Fifty?four patients of both sexes, aged 26-73 yr, with the course of disease 6 months-17 yr from February 2015 to January 2016, were included in this study accord?ing to diagnostic criteria for hemifacial spasm based on expert consensus in 2014. Patients were divided into 2 groups(n=27 each)using a random number table: facial acupoint injection combined with nerve block group(group A)and nerve block group(group B). In group A, the mixed injection 2 ml(2% lidocaine hydrochloride 5 ml, compound betamethasone 1 ml, mecobalamin 1 mg, diluted to 18 ml in normal sa?line)was given at facial Sibai, Jiachengjiang, Xiaguan and Yifeng acupoints once every 5 days, 3 times in total;facial nerve block was performed via the stylomastoid foramen with the mixed injection(5 ml) previously described once every 5 days, 3 times in total;stellate ganglion block was performed on the right and left side alternately once a day, 5 times on each side. In group B, patients received facial nerve block and stellate ganglion block, and no facial acupoint injection was applied. The Cohen rating and Shorr out?come were recorded before treatment and at 10th day, 3rd month and 1 yr after treatment, and the recur?rence was recorded at 3 months and 1 yr after treatment. Results Compared with group B, Cohen classifi?cation was significantly decreased, and the effective rate was increased at 10th day, 3rd month and 1 yr af?ter treatment, and the recurrence rate was decreased at 3 months and 1 yr after treatment in group A(P<0.05). Conclusion The facial acupoint injection combined with nerve block produces better long?term ef?ficacy in treating hemifacial spasm than nerve block alone.

Objective To evaluate the effect of exogenous resolvin D2 on radicular pain in a rat model of non-compressive lumbar intervertebral disc herniation.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 230-270 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),radicular pain induced by non-compressive lumbar intervertebral disc herniation group (group P) and exogenous resolvin D2 group (group R).The right L5 dorsal root ganglions were covered by autologous nucleus pulposus tissues to establish the model of non-compressive lumbar disc herniation in P and R groups.The corresponding surgical site was only exposed in group S.The corresponding drugs were intrathecally injected within 3 days after establishing the model,phosphate buffer solution 10 μl was injected in group P,1 ng/μl resolvin D2 solution 10 μl was injected in group R,and normal saline 10 μl was given for pipe washing after administration in the three groups.The mechanical paw withdrawal threshold (MWT) was measured on 1 day before establishing the model and 1-7 days after establishing the model.The spinal dorsal horns of lumbar enlargement segments were removed on day 7 after establishing the model for determination of the expression of glial fibrillary acidic protein (GFAP) (by Western blot) and co-expression of G-protein-coupled receptor 18 with GFAP (by double-label immunofluorescence).Results Compared with group S,the MWT was significantly decreased at 1-7 days after establishing the model,and the expression of GFAP was up-regulated in group P (P＜0.05).Compared with group P,the MWT was significantly increased at 3-7 days after establishing the model,and the expression of GFAP was down-regulated in group R (P＜0.05).G-protein-coupled receptor 18 was co-expressed with GFAP.Conclusion Exogenous resolvin D2 can reduce radicular pain in a rat model of non-compressive lumbar intervertebral disc herniation,and the mechanism is related to inhibiting activation of astrocytes in the spinal dorsal horns.

Objective To explore the effect of resolvin D2 ( RvD2) on radicular pain induced by interver-tebral disc herniation. Methods Thirty-six male Sprague-Dawley rats were randomly divided into a sham opera-tion group, a model group and an RvD2 group, each of 12. Non-compressive lumbar disc herniation was induced in the rats in the model and RvD2 groups using the autologous nucleus pulposus filling method. Those in the sham group had the surgical site exposed without any other treatment. After the modeling, 10μl of phosphate-buffered sa-line solution was administered intrathecally to the rats in the sham and model groups for 3 days, while the rats in the RvD2 group received 10 ng/10 μl of RvD2 intrathecally as well. Paw withdrawal thresholds (50％PWT) were ob-served 1 day before modeling and 7 days afterward for the rats of all three groups. On the 7th day after modeling, the L4 to L6 spinal dorsal horns on the surgery side were resected to detect the protein expression of phosphorylated protein kinase B ( p-AKT) , protein kinase B ( t-AKT) , phosphorylated glycogen synthase kinase 3β( p-GSK-3β) and glycogen synthase kinase 3β( GSK-3β) using western blotting. The protein levels of tumor necrosis factor alpha ( TNF-α) , interleukin-6 ( IL-6) , transforming growth factor-β1 ( TGF-β1) and interleukin-10 ( IL-10) were de-termined using enzyme-linked immunosorbent assays. Results On the 1st and 7th day after modeling, significant differences were observed between the model and sham groups in terms of the 50％PWT. From the 3rd day the aver-age 50％PWT in the RvD2 group was significantly higher than that of the model group at the same time points. On the 7th day after the modeling the average p-AKT and p-GSK-3βprotein levels of the model and RvD2 groups were significantly different from that of the sham group, and the model group′s average was also of significantly different from that of the RvD2 group. The average protein levels of the pro-inflammatory cytokines TNF-αand IL-6, as well as of the anti-inflammatory factors TGF-β1 and IL-10 in the dorsal horns of the model group and the RvD2 group were also significantly different on the 7th day, and both were significantly different from the sham group′s average. Conclusion RvD2 can alleviate radicular pain in rats with non-compressive disc herniation. The mechanisms might involve inhibition of GSK-3β activity, down-regulation of pro-inflammatory factors and up-regulation of anti-inflammatory factors.

Objective To investigate the analgesic effect of Resolvin D1 (RvD1) on radicular pain induced by herniated nucleus pulposusand its underlying mechanism.Methods Fifty-six male rats were randomly divided intoa sham group,a model group,a 10 ng group anda 100 ng group,each of 14.The rat model of non-compressive lumber disc herniation was established in all except the sham group.The former two groups were then injected with 10 μl of phosphate buffer solution (PBS) while the latter 2 groups were injected with 10 μl of PBS containing 10 and 100 ng of RvD1 respectively daily for three successive days.The rats' 50％ paw withdrawal threshold (PWT) was evaluated 1 day before and on 7 successive days after surgery.On day 7 the rats' spinal cords were removed to assess the expression of tumor necrosis factor-or (TNF-α),interlukin-1β (IL-1β) and interlukin-10 (IL-10) using ELISA methods.The levels of ERK and NF-κB/p65 were measured using Western blotting.Results Theaverage 50％PWT of the model group decreased significantly from day 1 to day 7 compared with the sham group,but was significantly lower thanthe RvD1 10 ng group from day 3 to day 7.Moreover the 50％PWT in the RvD1 100 ng group increased significantlyfrom day 2 to day 7 compared with the model group (P＜0.05).The average expression of both TNF-α and IL-1β of the model group was upregulated significantly and that of IL-10 decreased significantly compared with the sham group.Compared with the model group,the expression of TNF-α and IL-1β decreased significantly (P＜0.05)and the level of IL-10 was significantlyup-regulated (P＜0.05) both in the RvD1 10 ng group and 100 ng group.Moreover,the changes were larger in the RvD1 100 ng group (P＜0.05).Compared with the sham group,the levels of p-ERK and NF-κB/p65 in the model group were significantly up-regulated (P＜0.05).Compared with the model group,intrathecal injection of RvD1 (10 ng or 100 ng) significantly decreased the expressions of p-ERK and NF-κB/p65 (P＜0.05).Moreover,the decrease wasgreater in the RvD1 100 ng group (P＜0.05).Conclusions RvD1 might alleviate the radicular inflammation and pain byregulating the balance of inflammatory mediators and activation of p-ERK and NF-κB/p65 pathways.It may offer novel therapeutic approaches for the management of lumbar disc herniation.

Objective To investigate the effect of lipoxin A4 LXA4) on radicular pain caused by intervertebral disc herniation.Methods Non-compressive intervertebral disc herniation was induced into forty-eight adult male Sprague-Dawley rats,and they were divided into a sham group (sham operation + 10 μl normal saline),a control group (modeled + 10 μl normal saline),an LXA4 10 ng group (modeled + 10 ng LXA4) and an LXA4 100 ng group (modeled + 100 ng LXA4),with 12 rats in each group.The normal saline (10 μl) or LXA4 (10 μl) was administered intrathecally right after the operation and on each of the three succeeding days.General behavior was observed and the 50％ paw withdrawal threshold (50％ PWT) was measured.On postoperative day 7 all the rats were killed and the ipsilateral lumbar (L4~) segments of their spinal dorsal horns were removed for determination of the expression of p-JNK,t-JNK,p-ERK and t-ERK proteins using western blotting.TNF-α,IL-1β and TGF-β1 expression were determined using ELISA.Results There was no significant difference in the 50％PWT of the sham group before and after surgery,but the 50％ PWTs of the control group and the LXA4 10 ng group were significantly decreased after the operation compared with their values beforehand and significantly lower than the value of the sham group at all time points.Moreover,the 50％ PWT of the LXA4 10 ng group on postoperative days 3 and 5 was significantly higher than the control group;as was the value of the LXA4 100 ng group on postoperative days 2,3,4,5,6 and 7.The p-JNK and p-ERK expression in the control group,the LXA4 10 ng group and the LXA4 100 ng group were all increased significantly more than in the sham group,but their expression in the LXA4 10 ng group and LXA4 100 ng group were decreased significantly more in a dose-dependent manner compared with the control group,with the LXA4 100 ng group showing the greatest decrease.There were no significant differences in t-JNK or t-ERK expression within each group.Conclusion LXA4 can alleviate radicular pain caused by non-compressive lumbar intervertebral disc herniation.The underlying mechanism involves inhibiting the activation of the ERK and JNK pathways,reducing the expression of pro-inflammatory cytokines and increasing the expression of anti-inflammatory cytokines.