Enrichment and detection of polycyclic aromatic hydrocarbon in tea and coffee using phenyl-functionalized NiFe2O4@Ti3C2TX based magnetic solid-phase extraction.

Polycyclic aromatic hydrocarbons (PAHs) are commonly found in various environmental matrices and have received significant attention due to their toxic effects on ecosystems and environmental health. In this study, a specific magnetic composite material derived from MXene, known as phenyl-functionalized NiFe2O4@Ti3C2TX, was designed and synthesized using a simple method. This composite material was used to develop an effective magnetic solid-phase extraction (MSPE) method for enriching trace polycyclic aromatic hydrocarbons (PAHs) in tea and coffee samples. The eluted PAHs were analyzed via gas chromatography-tandem mass spectrometry. Under optimal conditions, this method exhibited excellent linear relationships for 16 PAHs within the ranges of 0.001-25 and 0.0005-25 µg/L, with correlation coefficients exceeding 0.9979. The limits of detection for the target PAHs ranged from 0.1 to 0.3 ng/L. The effectiveness of the proposed method was evaluated by analyzing tea and coffee samples, and the satisfactory spiked recoveries of PAHs ranged from 84.5% to 112.6%.

Construction of nitrogen-doped carbon dots-based fluorescence probe for rapid, efficient and sensitive detection of chlortetracycline.

Antibiotics are widely used in clinical medicine due to their excellent antibacterial abilities. As typical emerging pollutants, their misuse can lead to excess antibiotics entering the environment, causing antimicrobial resistance and leading to serious health problems via food chain. Herein, a nano-fluorescent probe based on nitrogen-doped carbon dots (N-CDs) was constructed for the sensitive detection of chlortetracycline (CTC). N-CDs with stable fluorescence were synthesized by hydrothermal method using alizarin red and melamine as raw materials. The N-CDs exhibited significant independence to excitation wavelength. The fluorescence of N-CDs was significantly quenched by CTC ascribing to the fluorescence resonance energy transfer mechanism. The concentration of N-CDs, solution pH and incubation time were optimized to obtain the optimal detection parameters. Under optimal conditions, CTC exhibited excellent linearity over the range of 20-1200 µg/L, and the detection limit was 8.74 µg/L. The method was validated with actual water samples and achieved satisfied spiked recoveries of 97.6-102.6%. Therefore, the proposed method has significant application value in the detection of CTC in waters.

Novel inhibitors of acute, axonal DLK palmitoylation are neuroprotective and avoid the deleterious side effects of cell-wide DLK inhibition.

Dual leucine-zipper kinase (DLK) drives acute and chronic forms of neurodegeneration, suggesting that inhibiting DLK signaling could ameliorate diverse neuropathological conditions. However, direct inhibition of DLK's kinase domain in human patients and conditional knockout of DLK in mice both cause unintended side effects, including elevated plasma neurofilament levels, indicative of neuronal cytoskeletal disruption. Indeed, we found that a DLK kinase domain inhibitor acutely disrupted the axonal cytoskeleton and caused vesicle aggregation in cultured dorsal root ganglion (DRG) neurons, further cautioning against this therapeutic strategy. In seeking a more precise intervention, we found that retrograde (axon-to-soma) pro-degenerative signaling requires acute, axonal palmitoylation of DLK and hypothesized that modulating this post-translational modification might be more specifically neuroprotective than cell-wide DLK inhibition. To address this possibility, we screened >28,000 compounds using a high-content imaging assay that quantitatively evaluates DLK's palmitoylation-dependent subcellular localization. Of the 33 hits that significantly altered DLK localization in non-neuronal cells, several reduced DLK retrograde signaling and protected cultured DRG neurons from DLK-dependent neurodegeneration. Mechanistically, the two most neuroprotective compounds selectively prevent stimulus-dependent palmitoylation of axonal pools of DLK, a process crucial for DLK's recruitment to axonal vesicles. In contrast, these compounds minimally impact DLK localization and signaling in healthy neurons and avoid the cytoskeletal disruption associated with direct DLK inhibition. Importantly, our hit compounds also reduce pro-degenerative retrograde signaling in vivo, suggesting that modulating DLK's palmitoylation-dependent localization could be a novel neuroprotective strategy.

Long-term follow-up of relapse and remission of CIDP in a Chinese cohort.

Objective: We aim to describe the long-term outcome of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) after immune treatment in a Chinese cohort. Methods: Between March 2015 and March 2023, 89 patients fulfilling the criteria for CIDP were followed up for a median of 22 months after treatment. Nine had positive antibodies against nodal-paranodal cell-adhesion molecules. Patients were treated according to clinical requirements with prednisone, intravenous immunoglobulin (IVIg) and/or immunosuppressant. Results: A total of 78/89 patients had decreased inflammatory neuropathy cause and treatment (INCAT) scores at the last follow-up. For CIDP patients treated with steroids, 35 were stable without relapse after cessation or with a small maintenance dose; 2 relapsed at a high dose (20 mg/day); 15 relapsed at a low dosage (<20 mg/day) and 11 did not respond. The INCAT before treatment was significantly lower in those without relapse (median INCAT 2 vs 3, p=0.030). IVIg was effective in 37/52 CIDP patients. 28 CIDP patients and 4 autoimmune nodopathy patients were treated with immunosuppressants. The average INCAT was 3.3±1.9 before and 1.9±1.3 after immunosuppressant treatment (p=0.001) in CIDP. Conclusion: The long-term prognosis of CIDP patients was generally favourable. Nearly half of our patients treated with steroid were stable without relapse after cessation or with a small maintenance dose. The risk of relapse was higher in those with high INCAT. We recommend slowly tapering prednisone based on clinical judgement.

High enrichment and sensitive measurement of oxytetracycline in tea drinks by thermosensitive magnetic molecular imprinting based magnetic solid phase extraction coupled with boron doped carbon dots.

As a typical kind of new pollutants, there are still some challenges in the rapid detection of antibiotics. In this work, a sensitive fluorescent probe based on boron-doped carbon dots (B-CDs) in combination with thermo-responsive magnetic molecularly imprinted polymers (T-MMIPs) was constructed for the detection of oxytetracycline (OTC) in tea drinks. T-MMIPs were designed, fabricated and employed to enrich OTC at trace level from tea drinks, and B-CDs were utilized as the fluorescent probe to detect the concentration of OTC. The proposed method exhibited good linear relationship with OTC concentration from 0.2 to 60 µg L-1 and the limit of detection was 0.1 µg L-1. The established method has been successfully validated with tea beverages. Present work was the first attempt application of T-MMIPs in combination with CDs in detection of OTC, and demonstrated that the proposed method endowed the detection of OTC with high selectivity, sensitivity, reliability and wide application prospect, meanwhile offered a new strategy for the method establishment of rapid and sensitive detection of trace antibiotics in food and other matrices.

Neuromuscular ultrasound in combination with nerve conduction studies helps identify inflammatory motor neuropathies from lower motor neuron syndromes.

BACKGROUND AND PURPOSE: Identifying patients with inflammatory motor neuropathies (IMNs) is warranted since effective treatments are available and the prognosis of these patients differs from that of amyotrophic lateral sclerosis patients. METHODS: Between January 2019 and May 2022, 102 consecutive treatment-naïve lower motor neuron syndrome (LMNS) patients were recruited; these patients were suspected of having multifocal motor neuropathy, pure motor chronic inflammatory demyelinating polyneuropathy or amyotrophic lateral sclerosis with initial lower motor neuron presentation. Neuromuscular ultrasound (US) and nerve conduction studies (NCSs) were conducted at baseline. Relevant diagnostic investigations were performed if clinically warranted. The proposed US evidence of IMN was as follows: (i) nerve enlargement at ≥1 of the predetermined sites or (ii) absence of high intensity fasciculations in predefined muscle groups. Final diagnoses were made by experienced physicians after a prolonged follow-up period (≥12 months). IMN patients were defined as LMNS patients who experienced convincing improvements in response to immunotherapies. IMN patients without electrodiagnostic demyelinating features were diagnosed with treatment-responsive LMNS (TR-LMNS). RESULTS: In total, 16 patients were classified as IMN, including nine chronic inflammatory demyelinating polyneuropathy/multifocal motor neuropathy patients and seven TR-LMNS patients. Six TR-LMNS patients were identified by neuromuscular US. The sensitivity and specificity of NCSs, nerve US and muscle US were 56.3% and 100%, 43.8% and 90.7% and 68.8% and 97.7%, respectively. When these three modalities were combined, the sensitivity and specificity were 93.8% and 88.4%, respectively. CONCLUSION: Neuromuscular US studies are supplementary modalities to NCSs, and the combined use of these techniques might improve the identification of IMNs in LMNS patients.

The distribution pattern of nerve enlargement in clinical subtypes of chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: We aim to investigate nerve enlargement patterns and their correlation with clinical subtypes and treatment response using nerve ultrasound in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Between March 2015 and December 2021, 135 CIDP patients were recruited. Nerve ultrasound and electrophysiological studies were performed on the median and ulnar nerves. The responses to intravenous immunoglobulin (IVIg) or prednisone were evaluated with the disability score. RESULTS: There were 99 typical CIDP cases, 10 Lewis-Sumner syndrome (LSS) cases, 15 distal acquired demyelinating symmetric neuropathy (DADS) cases, nine pure motor CIDP cases, and two pure sensory CIDP cases. Sixty (61%) typical CIDP and seven (78%) pure motor CIDP patients had moderately increased or normal cross-sectional area (CSA), and 10 (67%) DADS and seven (70%) LSS patients had significantly increased CSA. The peripheral nerve showed a diffuse enlargement pattern in 46 (51%) typical CIDP, five (50%) LSS, three (25%) DADS, and three (33%) pure motor CIDP patients and a proximal regional enlargement pattern in 11 (12%) typical CIDP, one (10%) LSS, six (50%) DADS, and four (44%) pure motor CIDP patients. Patients with diffusely moderate enlargement patterns and those with proximal regional enlargement showed a higher response rate to glucocorticoids than to IVIg. CONCLUSIONS: Various distribution patterns of nerve enlargement existed in CIDP. Although almost all patterns could be detected in each CIDP subtype, diffusely moderate enlargement was more common in typical CIDP and LSS, while proximal regional enlargement was more common in DADS and pure motor CIDP. Different enlargement patterns might indicate different treatment responses.

Comorbidity of Myasthenia gravis and Graves' disease as immune reconstitution-associated autoimmune disease in HIV infection: A case report and literature review.

BACKGROUND: Comorbidity of Myasthenia gravis (MG) and Graves' disease (GD) in treated HIV-infected individuals has rarely been described and little study has been done on the link between HIV-related immune reconstitution and autoimmune diseases occurring post antiretroviral therapy. CASE PRESENTATION: Here we report on a 33-year-old Chinese man with HIV infection who had been virologically suppressed since 2018. The patient was diagnosed with GD and was treated in 2020. Early in 2022, he developed fluctuating weakness and fatigue involving the bilateral extraocular muscles and limbs. With a positive neostigmine test, he was considered to have MG, but showed a poor response to oral medication. After multiple failed medication attempts, a thymectomy was finally performed to resolve his symptoms. The consecutive onset of immunological events may have partially resulted from immune reconstitution after viral control. CONCLUSIONS: This is a rare case of HIV-related immune reconstitution-associated autoimmune disease (IRAD) with comorbidity of MG and GD which was reported initially. Cooperation with multidisciplinary teams is essential to avoid misdiagnosis and to promote the overall health of HIV-infected patients.

Case report: Mononeuropathy multiplex of extranodal natural killer/T-cell lymphoma misdiagnosed as systemic vasculitis.

Background: Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma that typically develops in the upper aerodigestive tract. Case presentation: We encountered an ENKTL patient who presented with purpura-like rashes and foot drops as initial symptoms and later developed other peripheral nerve involvement. The nerve conduction study of both the motor nerve and the sensory nerve showed axonal damage resembling mononeuropathy multiplex. Although the initial response to steroids was encouraging, the patient's symptoms reappeared and aggravated. A biopsy of the abdominal subcutaneous fat tissue with additional immunohistochemistry revealed neoplastic NK/T lymphocytes. Conclusion: We reported the first case presented as mononeuropathy multiplex as the initial clinical manifestation in ENKTL patients. Lymphoma should be considered in the diagnosis of atypical mononeuropathy in multiplex patients.

Pembrolizumab for the treatment of progressive multifocal leukoencephalopathy in China.

The aim of this study is to analyze the clinical characteristics and outcomes of Chinese patients with progressive multifocal leukoencephalopathy (PML) who were treated with programmed cell death protein 1 (PD1) blockade therapies. We retrospectively analyzed patients who were admitted to our hospital between October 1, 2020, and October 1, 2022, diagnosed with PML and treated with PD1 blockade therapies. Four patients with PML who were treated with PD1 blockade therapies were identified. All patients were male, and their ages ranged from 19 to 54 years old. One patient (Case 2) exhibited mild pleocytosis, while three patients (Cases 2-4) had markedly reduced T lymphocyte cell counts prior to treatment. The time interval between symptom onset and treatment initiation ranged from six to 54 weeks. All patients received pembrolizumab treatment, with a total of two to four doses administered. Three patients who responded to pembrolizumab treatment showed clinical improvement starting around 8 weeks after the initiation of therapy. Although one patient did not show clinical improvement, they ultimately survived until the last follow-up. None of the patients in this study exhibited immune-related adverse events or immune reconstitution inflammatory syndrome. PD1 blockade appears to be a promising novel therapeutic option for PML; additional prospective studies are necessary to confirm its efficacy.

A large pedigree study confirmed the CGG repeat expansion of RILPL1 Is associated with oculopharyngodistal myopathy.

BACKGROUND: Oculopharyngodistal myopathy (OPDM) is an autosomal dominant adult-onset degenerative muscle disorder characterized by ptosis, ophthalmoplegia and weakness of the facial, pharyngeal and limb muscles. Trinucleotide repeat expansions in non-coding regions of LRP12, G1PC1, NOTCH2NLC and RILPL1 were reported to be the etiologies for OPDM. RESULTS: In this study, we performed long-read whole-genome sequencing in a large five-generation family of 156 individuals, including 21 patients diagnosed with typical OPDM. We identified CGG repeat expansions in 5'UTR of RILPL1 gene in all patients we tested while no CGG expansion in unaffected family members. Repeat-primed PCR and fluorescence amplicon length analysis PCR were further confirmed the segregation of CGG expansions in other family members and 1000 normal Chinese controls. Methylation analysis indicated that methylation levels of the RILPL1 gene were unaltered in OPDM patients, which was consistent with previous studies. Our findings provide evidence that RILPL1 is associated OPDM in this large pedigree. CONCLUSIONS: Our results identified RILPL1 is the associated the disease in this large pedigree.

Differentiation Between Amyotrophic Lateral Sclerosis and Mimics Using Quantitative Analysis of Fsciculation with Muscle Ultrasound.

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ2 = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.

Rheumatoid meningitis: a rare neurological complication of rheumatoid arthritis.

Objective: To describe the clinical and neuroimaging characteristics of rheumatoid meningitis (RM) in Chinese patients. Methods: The patients admitted to our hospital with the diagnosis of RM in the past 8 years were retrospectively analyzed. Results: Six patients with RM were identified among 933 patients admitted with rheumatoid arthritis (RA). The symptoms of meningitis occurred after onset of arthritis in five patients and before onset in one. Headache (n=6), hyperacute focal neurological deficits (n=4) and seizures (n=3) were the most prevalent symptoms. The nadir modified Rankin Scale score was ≥3 in five patients. Rheumatoid factor was elevated in all patients, and interleukin-6 levels in cerebrospinal fluid were dramatically elevated in three of four tested patients. Magnetic resonance imaging of the brain revealed that the meninges were affected in all patients and the cerebral parenchyma was affected in one patient. The lesions were generally located in the frontoparietal region and showed restricted diffusion along the adjacent subarachnoid space. RM occurred during disease-modifying therapy in four patients. In the acute episode, three patients improved on tocilizumab and the other three improved on pulse corticosteroids. For maintenance therapy, two patients received combined therapy of tocilizumab and other immunosuppressive agents, one received adalimumab and methotrexate, and two received low-dose oral corticosteroids with an immunosuppressive agent. Five patients had a good outcome, and one died of Pneumocystis jirovecii pneumonia after stabilization of his neurologic conditions. No relapse of RM occurred on immunotherapy during follow-up. Conclusions: Chinese patients with RM share some remarkable clinical and neuroimaging features and respond well to appropriate immunotherapy. Tocilizumab could be a treatment option for this severe complication of RA.

The cross-sectional area of peripheral nerve in amyotrophic lateral sclerosis: A case-control study.

OBJECTIVE: A growing body of literature recognises the importance of peripheral nerve ultrasound in neuromuscular disorders. Several attempts have been made to differentiate amyotrophic lateral sclerosis (ALS) from multifocal motor neuropathy (MMN) using peripheral nerve ultrasound. A much-debated question is whether the cross-sectional area (CSA) of peripheral nerve in ALS patients is significantly smaller compared to healthy controls. This study aims to determine the CSA of peripheral nerves in patients with ALS. METHODS: One hundred and thirty-nine patients with ALS and 75 healthy controls were recruited. Ultrasound of the median, ulnar, and trunks of the brachial plexus and cervical nerve roots was undertaken in ALS patients and controls. RESULTS: Compared to controls, ALS patients had mild reductions of the median nerve, most sites of the ulnar nerve, trunks of the brachial plexus and cervical nerve roots. Another important finding of this study is that the median nerve tends to have a more significant reduction than the ulnar nerve in ALS patients, especially at the proximal. CONCLUSIONS: Ultrasound could be sensitive to nerve motor fibre loss in patients with ALS. CSA at the proximal Median nerve may be a promising biomarker in patients with ALS.

Palmitoylation-dependent control of JAK1 kinase signaling governs responses to neuropoietic cytokines and survival in DRG neurons.

Janus Kinase-1 (JAK1) plays key roles during neurodevelopment and following neuronal injury, while activatory JAK1 mutations are linked to leukemia. In mice, Jak1 genetic deletion results in perinatal lethality, suggesting non-redundant roles and/or regulation of JAK1 for which other JAKs cannot compensate. Proteomic studies reveal that JAK1 is more likely palmitoylated compared to other JAKs, implicating palmitoylation as a possible JAK1-specific regulatory mechanism. However, the importance of palmitoylation for JAK1 signaling has not been addressed. Here, we report that JAK1 is palmitoylated in transfected HEK293T cells and endogenously in cultured Dorsal Root Ganglion (DRG) neurons. We further use comprehensive screening in transfected non-neuronal cells and shRNA-mediated knockdown in DRG neurons to identify the related enzymes ZDHHC3 and ZDHHC7 as dominant protein acyltransferases (PATs) for JAK1. Surprisingly, we found palmitoylation minimally affects JAK1 localization in neurons, but is critical for JAK1's kinase activity in cells and even in vitro. We propose this requirement is likely because palmitoylation facilitates transphosphorylation of key sites in JAK1's activation loop, a possibility consistent with structural models of JAK1. Importantly, we demonstrate a leukemia-associated JAK1 mutation overrides the palmitoylation-dependence of JAK1 activity, potentially explaining why this mutation is oncogenic. Finally, we show that JAK1 palmitoylation is important for neuropoietic cytokine-dependent signaling and neuronal survival and that combined Zdhhc3/7 loss phenocopies loss of palmitoyl-JAK1. These findings provide new insights into the control of JAK signaling in both physiological and pathological contexts.

Efficacy and safety of oliceridine treatment in patients with postoperative pain: a systematic review and meta-analysis of randomized controlled trials.

AIM: Our aim was to conduct a systematic review and meta-analysis to examine the efficacy and safety of oliceridine in patients with postoperative pain. METHODS: Four databases were searched from the beginning of the database to the present. We included all randomized controlled trials (RCT) that evaluated the efficacy and safety of oliceridine in patients with postoperative pain. Our endpoints were the proportion of treatment responders to the oliceridine regimen and the incidence of adverse effects such as nausea and vomiting. RESULTS: The analysis showed that more patients responded significantly with oliceridine compared to placebo. The proportion of treatment responders to oliceridine was comparable to that of morphine. Oliceridine had analgesia effects similar to morphine compared to placebo. The incidence of respiratory safety events was significantly lower with oliceridine compared to morphine. Oliceridine was significantly associated with more adverse events such as nausea and vomiting compared to placebo. The safety profile of oliceridine was superior to morphine compared to morphine. CONCLUSIONS: Our systematic review and meta-analysis showed that oliceridine is an effective and safe intravenous analgesic in patients with postoperative pain, producing rapid postoperative analgesic and usually well tolerated, and reducing incidence of adverse events compared to morphine. PROSPERO REGISTRATION: CRD42023391581.

Selective fluorescent probe for sensitive determination of bisphenol A based on molecularly imprinted polymers decorated carbon dots derived from citric acid and ethylenediamine.

Bisphenol A (BPA) is an endocrine disrupting chemical and poses a grave threat to the human health. Herein, a fluorescent probe constructed with molecularly imprinted polymers decorated carbon dots (CDs@MIPs) was proposed for determination of BPA with high selectivity. The CDs@MIPs were constructed using BPA, 4-vinylpyridine and ethylene glycol dimethacrylate as template, functional monomer and cross linker, respectively. The obtained fluorescent probe not only owned a highly selective recognition function derived from MIPs but also displayed an excellent sensitivity for sensing BPA stemmed from CDs. The fluorescence intensity of CDs@MIPs was varied before and after the removal of BPA templates. The fluorescent decrease fraction of the fluorescent probe demonstrates a nice linearity in BPA concentration range of 10-2000 nM (r2 = 0.9998) and the detection limit is as low as 1.5 nM. The fluorescent probe was triumphantly utilized to sense the level of BPA in real aqueous and plastic samples with good results. Moreover, the fluorescent probe offered a wonderful means for fast identification and sensitive detection of BPA from environmental aqueous samples.

The influence of intrathecal injection of methotrexate and dexamethasone on neuropsychiatric systemic lupus erythematosus (NPSLE): a retrospective cohort study of 386 patients with NPSLE.

BACKGROUND: Neuropsychiatric involvement is one of the major concerns in systemic lupus erythematosus (SLE). The therapeutic effect of intrathecal treatment of methotrexate and dexamethasone has been investigated in some exploratory studies, but its influence on the long-term prognosis of neuropsychiatric SLE (NPSLE) remains unknown. METHODS: This was a propensity score-matched retrospective study. Outcomes at discharge and time free from NPSLE relapse or death were evaluated by multivariate logistic regression, survival analysis, and Cox regression as appropriate. RESULTS: Among 386 hospitalized patients with NPSLE, the median [IQR] age was 30.0 [23.0-40.0] years, and 342 patients (88.4%) were female. Of those, 194 patients received intrathecal treatment. Patients in the intrathecal treatment group had higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores (median 17 vs. 14 points, IQR 12-22 vs. 10-19 points, P <0 .001) and were more likely to receive methylprednisolone pulse therapy (71.6% vs. 49.5%, P < 0.001) than those who did not receive intrathecal therapy. Intrathecal treatment was associated with a higher probability of survival and being free from NPSLE relapse than control treatment among the 386 unmatched patients (P =0.042 by log-rank test) and within 147 propensity score-matched pairs (P =0.032 by log-rank test). In the subgroup of NPSLE patients with increased levels of protein in cerebrospinal fluid, intrathecal treatment had a positive influence on their prognosis (P < 0.001). CONCLUSIONS: Intrathecal treatment of methotrexate and dexamethasone was associated with a more favorable prognosis of NPSLE and may serve as a valuable additional therapy for NPSLE patients, especially for those with elevated levels of protein in cerebrospinal fluid.

The chemical structures and biological activities of indole diterpenoids.

Indole diterpenoids (IDTs) are an essential class of structurally diverse fungal secondary metabolites, that generally appear to be restricted to a limited number of fungi, such as Penicillium, Aspergillus, Claviceps, and Epichloe species, etc. These compounds share a typical core structure consisting of a cyclic diterpene skeleton of geranylgeranyl diphosphate (GGPP) and an indole ring moiety derived from indole-3-glycerol phosphate (IGP). 3-geranylgeranylindole (3-GGI) is the common precursor of all IDTs. On this basis, it is modified by cyclization, oxidation, and prenylation to generate a large class of compounds with complex structures. These compounds exhibit antibacterial, anti-insect, and ion channel inhibitory activities. We summarized 204 compounds of IDTs discovered from various fungi over the past 50 years, these compounds were reclassified, and their biological activities were summarized. This review will help to understand the structural diversity of IDTs and provide help for their physiological activities.