FSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms.

FSD-C10, a Fasudil derivative, was shown to reduce severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through the modulation of the immune response and induction of neuroprotective molecules in the central nervous system (CNS). However, whether FSD-C10 can promote neuroregeneration remains unknown. In this study, we further analyzed the effect of FSD-C10 on neuroprotection and remyelination. FSD-C10-treated mice showed a longer, thicker and more intense MAP2 and synaptophysin positive signal in the CNS, with significantly fewer CD4(+) T cells, macrophages and microglia. Importantly, the CNS of FSD-C10-treated mice showed a shift of activated macrophages/microglia from the type 1 to type 2 status, elevated numbers of oligodendrocyte precursor cells (OPCs) and oligodendrocytes, and increased levels of neurotrophic factors NT-3, GDNF and BDNF. FSD-C10-treated microglia significantly inhibited Th1/Th17 cell differentiation and increased the number of IL-10(+) CD4(+) T cells, and the conditioned medium from FSD-C10-treated microglia promoted OPC survival and oligodendrocyte maturation. Addition of FSD-C10 directly promoted remyelination in a chemical-induced demyelination model on organotypic slice culture, in a BDNF-dependent manner. Together, these findings demonstrate that FSD-C10 promotes neural repair through mechanisms that involved both immunomodulation and induction of neurotrophic factors

EcomGPT: Instruction-tuning Large Language Model with Chain-of-Task Tasks for E-commerce

Recently, instruction-following Large Language Models (LLMs) , represented by ChatGPT, have exhibited exceptional performance in general Natural Language Processing (NLP) tasks. However, the unique characteristics of E-commerce data pose significant challenges to general LLMs. An LLM tailored specifically for E-commerce scenarios, possessing robust cross-dataset/task generalization capabilities, is a pressing necessity. To solve this issue, in this work, we proposed the first e-commerce instruction dataset EcomInstruct, with a total of 2.5 million instruction data. EcomInstruct scales up the data size and task diversity by constructing atomic tasks with E-commerce basic data types, such as product information, user reviews. Atomic tasks are defined as intermediate tasks implicitly involved in solving a final task, which we also call Chain-of-Task tasks. We developed EcomGPT with different parameter scales by training the backbone model BLOOMZ with the EcomInstruct. Benefiting from the fundamental semantic understanding capabilities acquired from the Chain-of-Task tasks, EcomGPT exhibits excellent zero-shot generalization capabilities. Extensive experiments and human evaluations demonstrate that EcomGPT outperforms ChatGPT in term of cross-dataset/task generalization on E-commerce tasks.Comment: Initial version of EcomGP

Comparison of the clinical features and long-term prognosis of gallbladder neuroendocrine carcinoma versus gallbladder adenocarcinoma: A propensity score-matched analysis

Gallbladder neuroendocrine carcinoma (GBNEC) is rare and characterized by a low degree of tumor differentiation. The clinical features of GBNEC versus gallbladder adenocarcinoma (GBADC) remain a subject of debate. A total of 201 GBADC and 36 GBNEC cases that underwent surgery resection between January 2010 and 2022 at the Department of Biliary Surgery, West China Hospital, Sichuan University were included. A 1:1 propensity score matching (PSM) was performed based on seven predefined variables: age, sex, the American Joint Committee on Cancer (AJCC) stage, resection status, perineural invasion (PNI), lymphovascular invasion (LVI), and degree of tumor differentiation. Compared with GBADC, GBNEC patients were younger (median age 56.0 vs 64.0 years; P = 0.001), and more patients presented with advanced stages of tumor (P = 0.003). Patients with GBNEC also had a higher rate of PNI (55.6% vs 22.4%; P < 0.001), and LVI (63.9% vs 45.80%; P = 0.658). Before PSM, GBNEC patients had inferior prognoses compared with GBADC patients with a shorter median overall survival (mOS) (15.02 vs 20.11 months; P = 0.0028) and a shorter median recurrence-free survival (mRFS) (10.30 vs 15.17 months; P = 0.0028). However, after PSM analyses, there were no differences in OS (mOS 18.6 vs 18.0 months; P=0.24) or RFS (mRFS 10.98 vs 12.02 months; P = 0.39) between the GBNEC and GBADC cases. After multivariate analysis, tumor diagnosis (GBNEC vs GBADC) was not identified as an independent risk factor for shorter RFS (P = 0.506) or OS (P = 0.731). Unfavorable pathological features, including advanced AJCC tumor stages, poor differentiation, presence of LVI, and positive resection margins (all P < 0.05), were independent risk factors for inferior OS and RFS. GBNEC is difficult to diagnose early and has a prognosis comparable to stage-matched poorly differentiated GBADC. Tumor diagnosis (either GBADC or GBNEC) was not an independent risk factor for the patient’s OS. Unfavorable pathological features of the neoplasm are the main determinants

帕金森病认知功能损害的中医药治疗

Parkinson’s disease (PD) is a degenerative disease of the central nervous system that involves many other systems. Cognitive impairment is one of the major presentations of non-motor symptoms of PD. Mild cognitive impairment in Parkinson’s disease (PD-MCI), a predictive factor of the transformation of PD to dementia is a common cognitive defect in PD patients. The effects of traditional Chinese Medicine on cognitive impairment in Parkinson’s disease were valued at home and abroad. Traditional Chinese Medicine has less toxic and side effects, treatment based on syndrome differentiation, and adjustment the balance of Yin and Yang for patients. Combination of Chinese and western medicine treatment could not only reduce the amount of dopamine agents but also counteract the toxic and side effects induced by dopamine agents. Meanwhile, combination of Chinese and western medicine treatment could delay the occurrence and development of cognitive impairment, and has broad application prospect.帕金森病（PD）是一种累及多系统的中枢神经系统变性病。认知功能障碍是PD非运动症状的重要表现形式，大多数PD患者均伴有认知功能损害并最终发展成为痴呆。中医药在帕金森病治疗中的作用越来越受到国内外的重视。中药具有毒副作用小且通过辨证论治、从整体调节患者阴阳平衡的特点，中西医结合治疗既能减少多巴胺制剂用量，又能有效拮抗和治疗西药所引起的毒副作用，延缓认知障碍的发生和发展，具有广阔应用前景

Mechanical antihypersensitivity effect induced by repeated spinal administrations of a TRPA1 antagonist or a gap junction decoupler in peripheral neuropathy

Spinal transient receptor potential ankyrin 1 (TRPA1) channel is associated with various pain hypersensitivity conditions. Spinally, TRPA1 is expressed by central terminals of nociceptive nerve fibers and astrocytes. Among potential endogenous agonists of TRPA1 is H2O2 generated by D-amino acid oxidase (DAAO) in astrocytes. Here we studied whether prolonged block of the spinal TRPA1 or astrocytes starting at time of injury attenuates development and/or maintenance of neuropathic hypersensitivity. Additionally, TRPA1 and DAAO mRNA were determined in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH). Experiments were performed in rats with spared nerve injury (SNI) and chronic intrathecal catheter. Drugs were administered twice daily for the first seven injury days or only once seven days after injury. Mechanical hypersensitivity was assessed with monofilaments. Acute and prolonged treatment with Chembridge-5861528 (a TRPA1 antagonist), carbenoxolone (an inhibitor of activated astrocytes), or gabapentin (a comparison drug) attenuated tactile allodynia-like responses evoked by low (2 g) stimulus. However, antihypersensitivity effect of these compounds was short of significance at a high (15 g) stimulus intensity. No preemptive effects were observed. In healthy controls, carbenoxolone failed to prevent hypersensitivity induced by spinal cinnamaldehyde, a TRPA1 agonist TRPA1 and DAAO mRNA in the DRG but not SDH were slightly increased in SNI, independent of drug treatment The results indicate that prolonged peri-injury block of spinal TRPA1 or inhibition of spinal astrocyte activation attenuates maintenance but not development of mechanical (tactile allodynia-like) hypersensitivity after nerve injury. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

2-Chloro-N′-(2-hy­droxy-3,5-diiodo­benzyl­idene)benzohydrazide

In the title compound, C14H9ClI2N2O2, the dihedral angle between the benzene rings is 65.9 (2)° and an intra­molecular O—H⋯N hydrogen bond generates an S(6) ring. The mol­ecule has an E conformation about the C=N bond. In the crystal, mol­ecules are linked into C(4) chains propagating in [001] by N—H⋯O hydrogen bonds