Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology* ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Humans ; Anticonvulsants/pharmacology* ; Epilepsy/drug therapy* ; Mutation ; Cerebral Cortex/drug effects* ; Action Potentials/drug effects* ; Carbamazepine/pharmacology*

Objective To analyze the consistency between computer tomography angiography(CTA)and digital subtraction angiography(DSA)in evaluating the global limb anatomic staging system(GLASS)stage of patients with chronic limb-threatening ischemia(CLTI).Methods The clinical data of patients with CLTI,who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University of China to receive treatment between January 2017 and December 2020,were retrospectively analyzed.Taking the DSA assessment as the gold standard,the consistency of CTA and DSA in evaluating the GLASS stage of patients with CLTI was analyzed.Results In the assessment of GLASS stage of CLTI,CTA showed strong agreement with DSA.The weighted Kappa coefficient of CTA and DSA for the staging of femoropopliteal segment was 0.798(95％CI=0.722-0.873,P＜0.01),and the weighted Kappa coefficient of CTA and DSA for the staging of infrapopliteal artery segment was 0.785(95％ CI=0.725-0.845,P＜0.0l).For the overall staging of GLASS,the weighted Kappa coefficient of CTA and DSA was 0.832(95％ CI=0.752-0.91 1,P＜0.01).All the above results indicated that a very strong consistency existed between CTA and DSA in evaluating the GLASS stage of patients with CLTI.Conclusion CTA examination of lower limb can accurately evaluate GLASS score and stage of CLTI patient's target lesions,which is helpful in diagnosing lower extremity arteriosclerosis occlusion disease as well as in assessing the technical difficulty degree of its revascularization operation.(J Intervent Radiol,2024,33:300-303)

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

15q11-q13 Duplication syndrome is a rare genetic disease of the nervous system, characterized by developmental retardation, intellectual impairments, hypotonia, autism, epilepsy and so on. This article reports a 33-year-old male patient, with the clinical manifestation of early-onset intractable epilepsy and mental retardation. The high-throughout whole exome sequencing showed a 10.53 Mb repeat sequence in the 15q11.2-q13.3 region, further confirming the diagnosis of 15q11-q13 duplication syndrome. The literature reports of the pathogenic mechanism, classification, typical clinical manifestation, seizure features,accessory examination and therapy of the 15q11-q13 duplication syndrome are summarized and reviewed, so as to enhance the understanding of the disease, as well as to improve the diagnosis and treatment level of the clinicians.

[摘 要] 目的：探究益气活血汤对恶性肿瘤患者癌痛及癌因性疲乏（CRF）的疗效。方法: 选取2020年1月至2022年12月间安徽省中医药大学第二附属医院收治的82例确诊发生CRF的恶性肿瘤患者（气血亏虚证），采用随机数字表余数分组法将其分为对照组与观察组，每组各41例。对照组患者采用常规止痛、止吐、化痰等对症治疗及健康、心理指导，观察组患者在对照组干预的基础上联合益气活血汤治疗，4周为1个疗程。治疗前及治疗4周后，对两组患者进行中医证候积分评估，以积分变化评估中医临床疗效；采用修订版Piper疲乏量表（RPFS）评估CRF的改善情况；采用数字疼痛分级法（NRS）评分比较癌痛情况；检测患者外周血纤维蛋白原（FIB）、D-二聚体（D-D）评价凝血功能差异，检测患者肝、肾功能指标以评估益气活血汤治疗的安全性。结果：治疗前，两组患者在中医证候积分、RPFS评分、NRS评分及外周血FIB、D-D方面的差异均无显著统计学意义（均P>0.05）。治疗4周后，两组患者在神疲乏力、面色淡白或萎黄、自汗、失眠健忘、手足麻木的证候评分及总积分均较治疗前明显降低（均P<0.05），且观察组各项评分均低于对照组（均P<0.05），中医临床疗效明显高于对照组（P<0.05）；两组患者RPFS各维度评分及总分均较治疗前降低（均P<0.05），观察组行为、情感、感觉维度RPFS评分及总分均低于对照组（均P<0.05），观察组CRF的改善明显优于对照组（P<0.05）；两组患者NRS评分及外周血FIB、D-D指标均较治疗前降低（均P<0.05），且观察组均低于对照组（均P<0.05）。两组患者治疗期间均未发生肝功能、肾功能等明显异常，说明益气活血汤安全性良好。结论：益气活血汤可纠正气血亏虚之证，改善机体凝血功能，促进恶性肿瘤患者CRF及癌痛的减轻，临床应用价值较高。

Clear cell renal cell carcinoma(ccRCC)is a frequently occurring renal cancer.The Von Hippel-Lindau disease tumor suppressor VHL,a known tumor suppressor gene,is frequently mutated in about 50％of patients with ccRCC.However,it is unclear whether VHL influences the progression of ccRCC tumors expressing wild-type VHL.In the present study,we found that higher expression of VHL was correlated with the better disease-free survival(DFS)in ccRCC patients using The Cancer Genome Atlas(TCGA)datasets.We revealed that VHL overexpression in ccRCC cells inhibited epithelial-mesenchymal transition(EMT),sterol regulatory element-binding protein 1(SREBP1)-regulated triglyceride synthesis,and cell proliferation.Proteomic anal-ysis provided us a global view that VHL regulated four biological processes,including metabolism,immune regulation,apoptosis,and cell movement.Importantly,we found that VHL overexpression led to up-regulated expression of proteins associated with antigen processing and interferon-responsive proteins,thus rendering ccRCC cells more sensitive to interferon treatment.We defined an interferon-responsive signature(IRS)composed of ten interferon-responsive proteins,whose mRNA expression levels were positively correlated with DFS in ccRCC patients.Taken together,our results propose that the subset of ccRCC patients with high VHL expression benefit from immunotherapy.

Objective:To evaluate the feasibility and clinical results of micro-dissected chimeric (II-MCh) perforator flap based on the descending branch of lateral circumflex femoral artery(d-LCFA) for repairing composite soft tissue defects of limbs.Methods:From April, 2011 to December, 2019, a total of 19 cases of composite soft tissue defects of limbs combined with deep cavity were repaired with II-MCh perforator flap or micro-dissected thin lobulated (III-MPCh) perforator flap based on d-LCFA. The flap was micro-dissected before cut off the perforator. The deep dead cavity was filled with muscle flap, and the superficial wound was repaired with micro-dissected thin perforator flap. The sizes of flaps were 6.0 cm×3.0 cm-33.0 cm×8.0 cm. The muscle flaps were cut with volumes of 5.0 cm×3.0 cm×1.0 cm-13.0 cm×10.0 cm×1.5 cm. Donor sites of the flap were closed directly. Postoperative reviews were assigned at 1, 3, 6, 9 and 12 months. The appearance, colour, texture and recurrence of infection of the flap were checked and recorded.Results:Sixteen flaps survived successfully without necrosis and with primary healing at the donor sites. Two flaps had venous occlusion within 24 hours after surgery and healed after surgical exploration and venous anastomosis. One flap had arterial crisis within 24 hours after surgery and healed after surgical exploration and arterial anastomosis. All patients entered follow-up for 8-36 months with an average of 16 months. All recipient sites achieved satisfactory appearance and function, and only linear scars left at the donor sites.Conclusion:The II-MCh perforator flap based on d-LCFA is a special modality of anterolateral thigh perforator flap, which achieves a satisfying appearance at the recipient site by micro-dissecting the flap within one procedure. This emerging technique can effectively fill the dead cavity, and is an effective method to repair complex soft tissue defects of limbs combined with deep cavity.

Objective:To investigate the efficacy and safety of infliximab in the treatment of severe plaque psoriasis and its effect on the expression of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) in psoriatic lesions.Methods:A total of 17 patients with severe plaque psoriasis were enrolled from Shanghai Skin Disease Hospital from February 2019 to April 2019, and were treated with intravenous drips of infliximab at a dose of 5 mg/kg at weeks 0, 2, 6, 14, 22, 30, 38 and 46. Efficacy was evaluated by using the psoriasis area and severity index (PASI) score at weeks 2, 6, 10, 14, 22, 30, 38, 46 and 52, and adverse events were recorded during the trial. Real-time PCR was performed to determine the expression of PD-1 and PD-L1 in skin tissues of 8 volunteer controls, as well as in skin lesions of 14 patients with plaque psoriasis before treatment and 5 patients with plaque psoriasis after 10-week treatment, and immunofluorescence assay to measure the expression of PD-1 and PD-L1 in skin tissues of 5 volunteers and 5 patients with psoriasis. The independent sample t-test was used to compare the expression of PD-1 and PD-L1 in skin tissues between the patients with plaque psoriasis and controls, and paired t-test to compare the expression of PD-1 and PD-L1 in the skin lesions of patients before and after infliximab treatment. Results:After 2, 6, 10, 14, 22, 30, 38, 46 and 52 weeks of infliximab treatment, the proportion of patients with plaque psoriasis achieving PASI75 was 1/17, 6/16, 9/16, 10/16, 15/15, 14/15, 13/14, 11/13 and 10/11, respectively. Antinuclear antibody staining turned positive in 12 patients, which was the most common adverse reaction, and 1 patient experienced an infusion reaction, which was the most severe adverse reaction. Before the treatment, the expression of PD-1 and PD-L1 (1.111 ± 0.391, 0.902 ± 0.169, respectively) was significantly higher in the skin lesions of patients with psoriasis than in the skin tissues of controls (0.620 ± 0.225, t=3.116, P=0.007; 0.474 ± 0.360, t=3.208, P=0.006, respectively) ; after infliximab treatment, the expression of PD-1 and PD-L1 (0.570 ± 0.230, 0.150 ± 0.050, respectively) in the improved skin lesions was significantly lower than that in the corresponding lesions before the treatment (1.238 ± 0.414, t=3.107, P=0.036; 0.966 ± 0.184, t=8.423, P=0.001, respectively) . Conclusions:Infliximab is effective and safe for the treatment of plaque psoriasis, but monitoring is necessary during treatment. The expression of PD-1 and PD-L1 is aberrantly upregulated in plaque psoriasis lesions, and decreased after infliximab treatment, suggesting that PD-1/PD-L1 may be involved in inflammation regulation in psoriasis.

Psoriasis is an immune-mediated chronic inflammatory disease,whose occurrence is closely associated with genes,immunity,environment and other factors.Classic comorbidities associated with psoriasis mainly include cardiovascular diseases,obesity and inflammatory bowel diseases.Emerging data have shown some other diseases closely associated with psoriasis,including metabolic syndrome,chronic renal diseases,tumors,infections,and so on.This review summarizes psoriasis-associated comorbidities that have been reported in studies,and analyzes the possible co-pathogenesis of these diseases and psoriasis.

To investigate the antioxidant and anti-melanogenesis activities of an ultrasonic extract of red sea cucumber, Stichopus japonicus, collected from Jeju Island. Methods: Antioxidant activity experiments were assessed by an electron spin resonance system and a cellular model of immortalized human keratinocytes (HaCaT) to determine its radical scavenging activity and protective effects against 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress. Antimelanogenic activity of the ultrasonic extract of red sea cucumber was also examined using the melanoma cell model B16F10 and mushroom tyrosinase. Following the induction by ?-melanocytestimulating hormone, the effects of the ultrasonic extract of red sea cucumber on intracellular tyrosinase activity, melanin content and the melanogenic protein expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related proteins (TRP-1, and TRP-2) were examined. Results: The ultrasonic extract of red sea cucumber significantly scavenged 2,2-diphenyl-1-picrylhydrazyl and alkyl radicals [IC50: (0.9240.035) and (0.3270.006) mg/mL, respectively], as well as showed a protective effect against oxidative stress and attenuated generation of intracellular reactive oxygen species on AAPHinduced HaCaT cells, with no cytotoxicity (12.5-400 ug/mL). The ultrasonic extract of red sea cucumber also exhibited a tyrosinase inhibitory effect [IC50: (2.7500.006) mg/mL]. On ?-melanocytestimulating hormone-stimulated B16F10 melanoma cells, the ultrasonic extract of red sea cucumber (25-200 ug/mL) significantly inhibited not only melanin synthesis and tyrosinase activity, but also protein expressions of microphthalmia-associated transcriptional factor, tyrosinase, TRP-1, and TRP-2. Conclusions: The ultrasonic extract of red sea cucumber shows antioxidant and anti-melanogenic potential and may be a natural candidate for anti-aging as well as a whitening agent in the cosmeceuticals industry.