Tourette syndrome （TS） is a highly prevalent neurodevelopmental disorder in children， clinically characterized primarily by motor and/or vocal tics. Its pathogenesis is associated with hyperactivity of the dopaminergic system in the basal ganglia， and current medical treatments are limited by adverse reactions and unsatisfactory efficacy. In traditional Chinese medicine （TCM）， TS is classified under categories such as "liver wind" and "convulsions"， and is considered to be closely related to liver dysregulation. Uncariae Ramulus Cum Uncis （URCU） is a commonly used wind-dispelling herb. URCU has a clearly defined origin and a rich chemical composition， with alkaloids as its major active constituents， including rhynchophylline and isorhynchophylline. Its plasma components include multiple prototype alkaloids， which exhibit metabolic differences and phenomena such as enterohepatic circulation. Its brain-entering components possess blood-brain barrier permeability， and their distribution is associated with pharmacological effects. In recent years， increasing numbers of studies have focused on the pharmacological effects and mechanisms of the active components of URCU in the treatment of TS. This article systematically reviews the mechanisms by which URCU and its main active constituents exert therapeutic effects on TS from the following aspects： regulation of monoamine and amino acid neurotransmitters to improve neurotransmitter system imbalance， neuroprotection and intervention in neuroinflammation-related pathways； antioxidant effects through activation of antioxidant signaling pathways， and immunomodulatory functions influencing immune cells and the gut microbiota. In addition， the clinical application of compound formulas containing URCU in the treatment of TS is summarized， with the aim of providing new perspectives for further research on the pharmacological mechanisms of URCU and the treatment of TS.

Tourette syndrome （TS） is a highly prevalent neurodevelopmental disorder in children， clinically characterized primarily by motor and/or vocal tics. Its pathogenesis is associated with hyperactivity of the dopaminergic system in the basal ganglia， and current medical treatments are limited by adverse reactions and unsatisfactory efficacy. In traditional Chinese medicine （TCM）， TS is classified under categories such as "liver wind" and "convulsions"， and is considered to be closely related to liver dysregulation. Uncariae Ramulus Cum Uncis （URCU） is a commonly used wind-dispelling herb. URCU has a clearly defined origin and a rich chemical composition， with alkaloids as its major active constituents， including rhynchophylline and isorhynchophylline. Its plasma components include multiple prototype alkaloids， which exhibit metabolic differences and phenomena such as enterohepatic circulation. Its brain-entering components possess blood-brain barrier permeability， and their distribution is associated with pharmacological effects. In recent years， increasing numbers of studies have focused on the pharmacological effects and mechanisms of the active components of URCU in the treatment of TS. This article systematically reviews the mechanisms by which URCU and its main active constituents exert therapeutic effects on TS from the following aspects： regulation of monoamine and amino acid neurotransmitters to improve neurotransmitter system imbalance， neuroprotection and intervention in neuroinflammation-related pathways； antioxidant effects through activation of antioxidant signaling pathways， and immunomodulatory functions influencing immune cells and the gut microbiota. In addition， the clinical application of compound formulas containing URCU in the treatment of TS is summarized， with the aim of providing new perspectives for further research on the pharmacological mechanisms of URCU and the treatment of TS.

BACKGROUND:Polycaprolactone has been widely used in bone tissue engineering due to its excellent processing and degradation performance,but its poor hydrophilicity and mechanical strength cannot provide a good growth environment for osteoblasts.OBJECTIVE:To prepare polycaprolactone/nanodiamond-phospholipid composite materials,evaluate its biocompatibility and in vitro ability to promote bone differentiation.METHODS:Nanodiamond was modified using phospholipids,and polycaprolactone was used as the raw material.Polycaprolactone/nanodiamond-phospholipid composite materials with different mass ratios(0%,2.5%,7.5%,and 10%)were prepared by solution casting method.Polycaprolactone/nanodiamonds were used for comparison.The surface morphology,elemental composition,mechanical properties,and water contact angle of each group of materials were observed to select composite materials with better physical and chemical properties.MC3T3-E1 cells were inoculated onto pure polycaprolactone membrane,polycaprolactone/7.5%nanodiamond-phospholipid membrane,and polycaprolactone/7.5%polycaprolactone/nanodiamond membrane,respectively,to detect cell proliferation,adhesion,and osteogenic differentiation ability.RESULTS AND CONCLUSION:(1)The successful preparation of the polycaprolactone/nanodiamond-phospholipid composite material was confirmed by scanning electron microscopy and surface element composition.Compared with pure polycaprolactone membrane,the tensile strength of the polycaprolactone/7.5%nanodiamond-phospholipids membrane increased by 86.06%,the elastic modulus increased by 54.76%,and the water contact angle decreased to 70.0°,showing good physical and chemical properties.(2)The CCK-8 assay results showed that compared with pure polycaprolactone membrane and polycaprolactone/7.5%nanodiamond membrane,polycaprolactone/7.5%nanodiamond-phospholipid membrane could promote the proliferation of MC3T3-E1 cells.Phalloidine staining exhibited that compared with the polycaprolactone/7.5%nanodiamond membrane,the MC3T3-E1 cells on pure polycaprolactone and polycaprolactone/7.5%nanodiamond-phospholipid membrane were mostly rhomboid or spindle-shaped fibers,and the cells were more closely connected.Alkaline phosphatase staining showed that MC3T3-E1 cells on polycaprolactone/7.5%nanodiamond-phospholipid membrane exhibited stronger osteogenic differentiation ability compared with pure polycaprolactone membrane and polycaprolactone/7.5%nanodiamond membrane.(3)The results indicate that the polycaprolactone/nanodiamond-phospholipid composite material has good mechanical properties,hydrophilicity,biocompatibility,and the ability to promote osteogenic differentiation in vitro.

Objective:To investigate therapeutic effect and mechanism of sanguinarine on postherpetic neuralgia(PHN)rats by modulating C-X-C chemokine ligand 12(CXCL12)/C-X-C chemokine receptor 4(CXCR4)signaling pathway.Methods:SD rats were randomly grouped into control group,model group,low-dose(50 mg/kg)sanguinarine group,high-dose(100 mg/kg)sanguina-rine group,NUCC-390(CXCL12/CXCR4 signal activator,2.2 mg/kg)group,high-dose(100 mg/kg)sanguinarine+NUCC-390(2.2 mg/kg)group,with 10 rats in each group.Rats in model group and drug-treated groups were injected with resin toxin(RTX)by intraperitoneal injection to induce PHN model,rats in control group were intraperitoneally injected with an equal dose of normal saline containing 10%Tween 80 and 10%ethanol.After treatment of sanguinarine and NUCC-390,symptoms of long-term spontaneous pain,mechanical hyperalgesia and thermal hyperalgesia were detected,number of spontaneous paw withdrawal reflexes,paw with-drawal threshold to mechanical stimulation(PWMT),and response latency to thermal stimulation(PWTL)were compared;spinal cord nerve cell apoptosis was detected by TUNEL staining;ELISA was used to detect levels of inflammatory factors TNF-α,IL-1β,cyclooxygenase-2(COX-2)in rat spinal cord tissue and serum;Western blot was used to detect expressions of CXCL12/CXCR4 path-way-related proteins in spinal cord tissues of rats in each group.Results:Compared with control group,PWMT of model group was obviously decreased(P<0.05),number of spontaneous foot withdrawal reflexes,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were obviously increased(P<0.05).Compared with model group,PWMT of rats in low-dose sanguinarine group and high-dose sanguinarine group was increased(P<0.05),number of spontaneous foot withdrawal reflexes,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were all decreased(P<0.05);PWMT of rats in NUCC-390 group was decreased(P<0.05),number of spontaneous foot withdrawal reflex,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were increased(P<0.05).Compared with high-dose sanguinarine group,PWMT of rats in high-dose sanguinarine+NUCC-390 group was decreased(P<0.05),number of spontaneous foot withdrawal reflex,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were increased(P<0.05).Conclusion:Sanguinarine can reduce expression of inflammatory factors by down-regulating CXCL12/CXCR4 signaling pathway,thereby preventing occurrence of inflammatory response in PHN rats,inhibiting apoptosis of spinal nerve cells,and finally reducing long-term spontaneous pain,mechanical allodynia and thermal hypoalgesia in rats.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Background and purpose:There are few studies on the quality of life after transanal total mesorectal excision(TaTME)for rectal cancer,and there is a lack of evidence-based research.This study aimed to evaluate the impact of TaTME in comparison to laparoscopic total mesorectal excision(LaTME)on postoperative quality of life in patients.Methods:A retrospective analysis was conducted on clinical and pathological data from rectal cancer patients who underwent LaTME and TaTME between September 2019 and September 2022 at Renhe Hospital,Baoshan District,Shanghai,and Fudan University Shanghai Cancer Center.All the patients completed a set of validated questionnaires one year postoperatively,including the EORCT QLQ-C30,Low Anterior Resection Syndrome(LARS)score,International Prostate Symptom Score(IPSS),Generalized Anxiety Disorder-7(GAD-7),and Patient Health Questionnaire-9(PHQ-9).Comparative analysis of these survey results was performed.The study was approved by the Ethics Committee of Renhe Hospital,Baoshan District,Shanghai.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:A total of 39 patients in the TaTME group and 38 patients in the LaTME group were included.There were no statistically significant differences between two groups regarding demographic variables such as gender and age,as well as clinical factors including tumor distance from the anal verge,tumor stage,and preoperative neoadjuvant treatment protocols.Analysis of EORCT QLQ-C30 results indicated equivalent overall quality of life between the two groups;however,the TaTME group reported significantly more severe insomnia(P=0.020).No significant differences were observed in LARS severity or total scores between the groups,though the TaTME group demonstrated superior functional outcomes in terms of incontinence for liquid stools and clustering of stools(P=0.007,P=0.004).Additionally,both groups exhibited comparable results in IPSS,and levels of depression and anxiety.Conclusion:The findings suggest that TaTME and LaTME yield similar outcomes in terms of anal and urinary function,overall quality of life,and psychological health,indicating that it is a viable and safe alternative to LaTME in terms of postoperative quality of life.

[Purpose]To investigate the potential causal relationships between serum levels of trace elements and head and neck cancers.[Methods]Single nucleotide polymorphism(SNP)of oral cancer,oropharyngeal cancer,laryngeal cancer and thyroid cancer,associated with calcium,copper,iron,magnesium,zinc,were obtained from genome-wide association studies(GWAS).A two-sample bidirectional Mendelian randomization(MR)analysis was performed using the inverse variance weighting(IVW)method by calculating odds ratio(OR)and 95％confidence interval(CI).Pleiotropy was assessed using MR-PRESSO and MR-Egger regression,and sensitivity analysis was conducted via the"leave-one-out"method.[Results]IVW analysis revealed a causal association between serum magnesium levels and the incidence of oral cancer(OR=0.976,95％CI:0.956～0.997,P=0.025),also between thyroid cancer and serum calcium levels(OR=1.008,95％CI:1.001～1.015,P=0.023).No significant causal associations were observed between other trace ele-ments and head and neck cancers(all P＞0.05).[Conclusion]This MR study suggests that serum magnesium levels serve as a protective factor against oral cancer,while thyroid cancer leads to el-evated serum calcium levels.

ObjectiveTo investigate the effect of video-based educational intervention combined with maternal presence on perioperative adverse outcomes in preschool children undergoing general anesthesia， including cooperation in anesthesia induction， perioperative anxiety， pain and agitation during recovery. MethodsA total of 300 preschool children scheduled for general anesthesia in our hospital from June to December 2023 were randomly assigned to control group （n=150） and intervention group （n=150）. The control group received routine recovery care. For the intervention group， in addition to routine recovery care， a preoperative visit was scheduled one day before surgery. During this visit， mothers were guided to watch anesthesia videos with their children. During the waiting period in the operating room and 30 minutes after awakening， the mothers were guided to accompany the children for more than 30 minutes. Recovery conditions were recorded using the surgical anesthesia information system， and the children’s anesthetic induction compliance， perioperative anxiety， pain， and agitation were evaluated and recorded using the modified Yale Preoperative Anxiety Scale （m-YPAS）， the Induction Compliance Scale （ICC）， the Children’s Pain Behavior Scale （FLACC）， and the Pediatric Agitation and Emergence Delirium Scale （PAED）. ResultsOn the preoperative visit day， there were no statistically significant differences in baseline data between the two groups （P > 0.05）. For perioperative anxiety， the m-YPAS scores of the intervention group were significantly lower than those of the control group， both when entering the operating room waiting area （35.27±6.48 vs. 41.79±6.68， P < 0.05） and 30 minutes after postoperative recovery （20.13±7.05 vs. 35.75±9.51， P < 0.05）. In terms of anesthesia induction cooperation， the ICC scores of the intervention group were significantly lower than those of the control group （1.84±0.95 vs. 3.17±0.62， P < 0.05）， and the proportion of good induction cooperation was significantly higher than that of the control group （24.00% vs. 12.67%， P < 0.05）. There was no significant difference in awakening duration between the two groups， but the intervention group had a significantly shorter length of stay in the post-anesthesia care unit than the control group （0.90±0.29 hours vs. 1.29±0.42 hours， P < 0.001）. For perioperative agitation， the PAED scores of the intervention group were significantly lower than those of the control group （entering in the operating room waiting area： 8.5 vs. 9.2， P < 0.05； 30 minutes after postoperative recovery： 4.2 vs. 7.8， P < 0.05）. In terms of pain scores， the FLACC scores of the intervention group were also significantly lower than those of the control group， both when entering the operating room waiting area （ 5.3 vs. 6.7， P < 0.05； 30 minutes after postoperative recovery： 2.1 vs. 4.9， P < 0.05）. ConclusionsVideo-based educational intervention combined with maternal presence reduces the perioperative anxiety， pain and agitation of preschool children undergoing general anesthesia， and improved the compliance of anesthesia induction. It is recommended to promote this intervention measure in clinical practice.

Objective:To investigate therapeutic effect and mechanism of sanguinarine on postherpetic neuralgia(PHN)rats by modulating C-X-C chemokine ligand 12(CXCL12)/C-X-C chemokine receptor 4(CXCR4)signaling pathway.Methods:SD rats were randomly grouped into control group,model group,low-dose(50 mg/kg)sanguinarine group,high-dose(100 mg/kg)sanguina-rine group,NUCC-390(CXCL12/CXCR4 signal activator,2.2 mg/kg)group,high-dose(100 mg/kg)sanguinarine+NUCC-390(2.2 mg/kg)group,with 10 rats in each group.Rats in model group and drug-treated groups were injected with resin toxin(RTX)by intraperitoneal injection to induce PHN model,rats in control group were intraperitoneally injected with an equal dose of normal saline containing 10%Tween 80 and 10%ethanol.After treatment of sanguinarine and NUCC-390,symptoms of long-term spontaneous pain,mechanical hyperalgesia and thermal hyperalgesia were detected,number of spontaneous paw withdrawal reflexes,paw with-drawal threshold to mechanical stimulation(PWMT),and response latency to thermal stimulation(PWTL)were compared;spinal cord nerve cell apoptosis was detected by TUNEL staining;ELISA was used to detect levels of inflammatory factors TNF-α,IL-1β,cyclooxygenase-2(COX-2)in rat spinal cord tissue and serum;Western blot was used to detect expressions of CXCL12/CXCR4 path-way-related proteins in spinal cord tissues of rats in each group.Results:Compared with control group,PWMT of model group was obviously decreased(P<0.05),number of spontaneous foot withdrawal reflexes,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were obviously increased(P<0.05).Compared with model group,PWMT of rats in low-dose sanguinarine group and high-dose sanguinarine group was increased(P<0.05),number of spontaneous foot withdrawal reflexes,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were all decreased(P<0.05);PWMT of rats in NUCC-390 group was decreased(P<0.05),number of spontaneous foot withdrawal reflex,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were increased(P<0.05).Compared with high-dose sanguinarine group,PWMT of rats in high-dose sanguinarine+NUCC-390 group was decreased(P<0.05),number of spontaneous foot withdrawal reflex,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were increased(P<0.05).Conclusion:Sanguinarine can reduce expression of inflammatory factors by down-regulating CXCL12/CXCR4 signaling pathway,thereby preventing occurrence of inflammatory response in PHN rats,inhibiting apoptosis of spinal nerve cells,and finally reducing long-term spontaneous pain,mechanical allodynia and thermal hypoalgesia in rats.

Objective To examine the expression pattern of apoptosis signal-regulating kinase 1(ASK1)in the intestinal tissues of patients with Crohn's disease(CD),and analyze its mechanistic impact on intestinal epithelial barrier function and inflammatory responses.Methods Ileal tissue samples from Crohn's disease patients and healthy controls were collected.ASK1 protein level was assessed by immunohistochemistry,and its relationship with the Crohn's disease activity index(CDAI)was analyzed.A mouse model of acute colitis was constructed using TNBS,and subjected to qRT-PCR,Western blotting and immunohistochemistry for ASK1 expression,and the association between ASK1 expression and the disease activity index was examined.Lentivirus transfection was employed to create stable Caco-2 cell lines with altered ASK1 expression,and the intestinal barrier integrity and inflammation were assessed by measuring transepithelial electrical resistance(TEER),FITC-dextran leakage,and IL-6,IL-1β levels.Furthermore,the effects of ASK1 expression on Krüppel-like factor 4(KLF4)levels was examined using qRT-PCR and Western blotting.Results ASK1 was highly expressed in the ileum of CD patients and positively correlated with CDAI.In a TNBS-induced mouse model of acute colitis,ASK1 expression was up-regulated and positively correlated with DAI.Inflammation-induced ASK1 overexpression weakened the Caco-2 cell intestinal barrier,whereas ASK1 knockdown strengthened it.Moreover,ASK1 had the capability to enhance the expression of inflammatory factors.Additionally,ASK1 knockdown increased KLF4 expression,while overexpression decreased it,indicating a negative correlation between ASK1 and KLF4.Conclusion ASK1 expression is notably higher in CD and positively correlates with disease activity.ASK1 can influence intestinal barrier integrity and inflammatory factor expression,possibly through its impact on KLF4 expression.