Objective To evaluate the efficacy of lidocaine solid lipid nanoparticles (L-SLNs) for sciatic nerve blockade in rats.Methods Lidocaine-loaded SLNs were prepared using high pressure homogenization.Ninety SPF male Wistar rats,weighing 220-280 g,were randomized into 6 groups (n =15 each) using a random number table:control group (group C),1％ L-SLN group (group L1-SLN),1％ lidocaine group (group L1),2％ L-SLN group (group L2-SLN),2％ lidocaine group (group L2),and blank SLN group (group SLN).In C,L1-SLN,L1,L2-SLN,L2 and SLN groups,normal saline,1％ lidocaine SLN,1％ lidocaine,2％ lidocaine SLN,2％ lidocaine and blank SLN (200 μl) were injected,respectively,around the sciatic nerve.Before sciatic nerve blockade (baseline) and at 10,20,30,60,120,180,240,300,360,420,480,540 and 600 min after blockade,the paw withdraw latency to a thermal stimulus was measured,and maximum possible effect (MPE) was calculated to reflect the degree of sensory block.Before sciatic nerve blockade and at 10,20,30,60,120 and 150 min after blockade,extensor postural thrust (EPT) of the hind limbs was detected to reflect the degree of motor block.The sciatic nerve at the injection site and the tissues around the site were obtained for observation of the pathological changes at 2 days and 1 and 4 weeks after blockade.Results Compared with the baseline value before blockade and group C,the MPE was significantly increased in at 10-30 min after blockade group L1,at 10-60 min after blockade in group L2,at 10-360 min after blockade in group L1-SLN,and at 10-540 min after blockade in group L2-SLN,and the EPT was decreased at 10-30 min after blockade in group L1,at 10-60 min after blockade in group L2 and group L1-SLN,and at 10-90 min after blockade in group L2-SLN.Compared with group L1,the MPE was significantly decreased at 10 min after blockade,no significant change was found at 20-30 min after blockade,and the MPE was increased at 60-360 min after blockade,and the EPT was increased at 10-30 min after blockade,and no significant change was found at the other time points in group L1-SLN.Compared with group L2,no significant change was found in the MPE at 10-30 min after blockade,the MPE was significantly increased at 60-540 minafter blockade,and the EPT was increased at 10-60 min after blockade,and no significant change was found at the other time points in L2-SLN group.In SLN,L1-SLN and L2-SLN groups,no pathological changes were found in the sciatic nerve at the injection site and the tissues around the site,and only mild inflammatory responses were observed.Conclusion L-SLNs can prolong the duration of block when applied for sciatic nerve blockade in rats and biocompatibility is good.

Objective To investigate the toxicity of lidocaine solid lipid nanoparticles (SLNs) in human neurons.Methods Lidocaine-loaded SLNs were prepared using high pressure homogenization.SHSY5Y cells were cultured in vitro and inoculated on 96-well plates (100 μl/well) at a density of 5× 105 cells/ml.SH-SY5Y cells were randomized into 10 groups (n =30 each) using a random number table:control group (group C), different concentrations of lidocaine groups (L1-4 groups), different concentrations of lidocaine SLN groups (L-SLN1-4 groups), and blank SLN group (group SLN).The cells were cultured routinely in group C.The cells were incubated with the culture medium containing lidocaine with the final concentrations of 1.000％, 0.500％, 0.250％ and 0.125％ in L1-4 groups, respectively.In LSLN1-4 groups, the cells were incubated with the culture medium containing lidocaine SLNs with the final concentrations of 1.000％, 0.500％, 0.250％ and 0.125％ in L1-4 groups, respectively.Before incubation (at the corresponding time points in group C), and at 1, 12 and 24 h of culture or incubation (T0-3) , 6 wells in each group were selected for measurement of the cell survival rate (using methyl thiazolyl tetrazolium assay).The cell morphology was examined with optical microscope at T3.Results Compared with that at T0, the cell survival rate was significantly decreased at each time point in L1-4 and L-SLN1,2 groups, at T2,3 in L-SLN3 group, and at T3 in L-SLN4 group (P＜0.05) , and no significant change was found in SLN and C groups (P＞0.05).The cell survival rate was significantly lower at T2,3 in L1-4 and L-SLN1-3 groups, and at T3 in group L-SLN4 than that at T1, and at T3 in L1-4 and L-SLN1-4 groups than that at T2 (P＜0.05).Compared with group C, the cell survival rate was significantly decreased at each time point in L1-4 and L-SLN1,2 groups, at T2,3 in group L-SLN3, and at T3 in group L-SLN4 (P＜0.05) , and no significant change was found in group SLN (P＞0.05).Compared with group L-SLN at the corresponding concentration, the cell survival rate was significantly decreased at each time point in group L1-4 (P＜0.05).Conclusion Lidocaine SLNs have toxic effect on human neurons, but the effect is weaker than that caused by Iidocaine solution.

Personalized medicine emphasizes individualized and dynamic treatment decisions. There is an urgent need for a new efficacy evaluation system that can adapt to this approach. By reviewing past clinical research practices， this article pointed out the innovative needs of traditional Chinese medicine （TCM） efficacy evaluation from the perspective of personalized medicine in terms of ethical review， trial design， data management， and statistical analysis. Focusing on these needs， the article has proposed a strategic framework using syndrome differentiation and treatment in TCM as an example. The framework includes a method based on subgroup dynamic-static parallel group design and analysis， a safeguard mechanism of continuous review， dynamic informed consent， and multicenter ethical review， a technological support platform for personalized clinical efficacy evaluation and evidence support， and a statistical strategy integrating Bayesian and traditional analysis methods， aiming to promote the development of personalized TCM diagnosis and treatment.

To explore the positioning of acupoints, a research was done with PubMed for system reviews and clinical trials on treatment of low-back pain with sham-acupuncture controlled design from January 1, 2010 to October 27, 2017. Six system reviews and 12 sham-controlled acupuncture random trials were found. The statistical difference was not found in all the 6 trials with standard acupoint compared with the sham-acupuncture among the 8 penetrating skin sham-control trials. The statistical difference was found in the two trials with penetrating skin sham control, who was used individualized treatment, twirling for arrival or palpation for point. It is considered that sham-acupuncture penetrating skin is not a placebo, and needling with standard or dynamic acupoint may reduce low-back pain, and dynamic acupoint positioning may be better than standard acupoint positioning.
Acupuncture Therapy ; Evidence-Based Medicine ; Humans ; Low Back Pain ; therapy ; Research

ObjectiveTo observe the effect of bilateral sequential repetitive transcranial magnetic stimulation on the motor function of upper limbs in stroke patients. MethodsFrom December, 2020 to December, 2022, 62 stroke inpatients in the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine were included. They were randomly divided into control group (n = 31) and observation group (n = 31). Both groups accepted conventional medicine and rehabilitation, as well as electroacupuncture antagonistic muscle therapy. Before electroacupuncture, the observation group acceped low-frequency repetitive transcranial magnetic stimulation at primary motor cortex (M1) on the healthy side, followed by intermittent theta burst stimulation at M1 on the affected side, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), modified Barthel Index (MBI) and modified Ashworth Scale (MAS), and motor evoked potential (MEP) latency was compared before and after treatment. ResultsOne patient dropped down in the observation group, and no adverse event happened. After treatment, the scores of FMA-UE and MBI significantly increased (|t| > 9.953, P < 0.001), and the score of MAS and the latency of MEP significantly decreased (|t| > 5.043, P < 0.001) in both groups; while all of them were better in the observation group than in the control group (|t| > 2.237, P < 0.05). ConclusionBilateral sequential repetitive transcranial magnetic stimulation can effectively promote the recovery of upper limb motor function in stroke patients.

Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.