Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

Phytochemical constituents, in-vitro anticancer activity and computational studies of Cymbopogon schoenanthus.

The cytotoxic effects of Cymbopogon schoenanthus L. aerial part ethanol extract were examined against some cancer cell lines, and HUVEC normal cell lines using MTT assay. The ethanolic extract was prepared by ultrasonic-assisted extraction and analyzed by GC-MS and HPLC. The extract was found to be rich in terpene compounds. The extract proved to be highly selective and effective against breast and prostate cancer cell lines (MDA-MB-435, MCF-7, and DU 145) with IC50 as low as 0.7913 ± 0.14, 12.841 ± 0.21, and 30.51 ± 0.18 µg/ml, respectively. In silico modeling was performed to investigate the binding orientation and affinity of the major identified compounds against Polo-like kinase (PLK1 protein) a cancer molecular target using molecular docking and molecular dynamic whereas eudesm-5-en-11-ol, piperitone, and 2,3-dihydrobenzofuran displayed better binding affinity and stability against PLK1 compared to the reference drug. These findings encourage further in vivo studies to assess the anti-cancer effects of C. schoenanthus extract and its components.

Progress in Understanding the Role and Therapeutic Targets of Polarized Subtypes of Macrophages in Pulmonary Fibrosis.

Pulmonary fibrosis represents the advanced phase of diverse pulmonary ailments, and at present, a definitive cure for these ailments is lacking. Furthermore, underlying mechanisms causative of these ailments remain elusive. Macrophages are immune cells that resist external stimuli in the early stages after birth. These cells can polarize into the classically (M1) and alternatively (M2) activated macrophages. When stimulated owing to the presence of toxic factors, M1 macrophages produce several pro-inflammatory factors, which mediate the inflammatory injury response of the alveolar tissue. The secretion of diverse growth factors by M2 macrophages contributes to the pathogenesis of aberrant alveolar structural fibrosis and remodeling. The abnormal activity of M2 macrophages is considered a critical factor in the formation of pulmonary fibrosis. In this mini-review, to highlight the clinical implications of research studies, we summarize the role and therapeutic targets of polarized subtypes of macrophages in pulmonary fibrosis and the role of targeting macrophages for the treatment of pulmonary fibrosis.

Artificial intelligence in psychiatry research, diagnosis, and therapy.

Psychiatric disorders are now responsible for the largest proportion of the global burden of disease, and even more challenges have been seen during the COVID-19 pandemic. Artificial intelligence (AI) is commonly used to facilitate the early detection of disease, understand disease progression, and discover new treatments in the fields of both physical and mental health. The present review provides a broad overview of AI methodology and its applications in data acquisition and processing, feature extraction and characterization, psychiatric disorder classification, potential biomarker detection, real-time monitoring, and interventions in psychiatric disorders. We also comprehensively summarize AI applications with regard to the early warning, diagnosis, prognosis, and treatment of specific psychiatric disorders, including depression, schizophrenia, autism spectrum disorder, attention-deficit/hyperactivity disorder, addiction, sleep disorders, and Alzheimer's disease. The advantages and disadvantages of AI in psychiatry are clarified. We foresee a new wave of research opportunities to facilitate and improve AI technology and its long-term implications in psychiatry during and after the COVID-19 era.

Supplementingand activating blood circulation method to treat vertebrobasilar dolichoectasia with posterior circulatory watershed infarction: a case report of two patients.

Vertebrobasilar dolichoectasia (VBD), a rare posterior circulation vascular variant disease, is an important risk factor for many acute cerebrovascular diseases. An insufficient understanding of VBD often leads to misdiagnose. Two cases of VBD that were initially diagnosed as posterior circulation watershed infarction are reported here. Absence of common causes of stroke including hypoperfusion, blood system diseases, carotid and aortic dissection, and eosinophil elevation, the symptoms of the 2 patients met the diagnostic criteria of VBD. Both patients displayed symptoms that were in line with the Traditional Chinese Medicine (TCM) syndrome pattern of "deficiency and blood stasis". Accordingly, they were comprehensively treated with Supplementingand activating blood circulation method. The clinical manifestations of the 2 patients were remarkably improved and no recurrence of watershed infarction was found in a 1-year follow-up. A detailed medical history and laboratory examination are capable of improving diagnostic accuracy of VBD. TCM treatment based on syndrome identification might be a promising candidate for VBD management.

Source apportionment and quantitative risk assessment of heavy metals at an abandoned zinc smelting site based on GIS and PMF models.

The abandoned smelters have caused serious hazards to the surrounding environment and residents. Taking an abandoned zinc smelter in southern China as an example, a total of 245 soil samples were collected to study spatial heterogeneity, source apportionment, and source-derived risk assessment of heavy metal(loid)s (HMs) in the region. The results showed that the mean values of all HMs concentrations were higher than the local background values, with Zn, Cd, Pb, and As contamination being the most serious and their plume penetrating to the bottom layer. Four sources were identified by principal component analysis and positive matrix factorization, with their contributions to the HMs contents ranked as: surface runoff (F2, 63.2%) > surface solid waste (F1, 22.2%) > atmospheric deposition (F3, 8.5%) > parent material (F4, 6.1%). Among these, F1 was a determinant source of human health risk with a contribution rate of 60%. Therefore, F1 was considered to be the priority control factor, but it only accounted for 22.2% of HMs contents contribution. Hg dominated the ecological risk with a contribution of 91.1%. Pb (25.7%) and As (32.9%) accounted for the non-carcinogenic risk, while As (95%) dominated the carcinogenic effect. The spatial characteristics of human health risk values derived from F1 indicated that high-risk areas were mainly distributed in the casting finished products area, electrolysis area, leaching-concentration area, and fluidization roasting area. The findings highlight the significance of priority control factors (including HMs, pollution sources and functional areas) for consideration in the integrated management of this region, thus saving costs for effective soil remediation.

DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice / 生物医学与环境科学（英文）

OBJECTIVE@#To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD.@*METHODS@#Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 +), and DJ1-knockdown group (DJ1 -). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice.@*RESULTS@#DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA).@*CONCLUSION@#DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.

Clinical analysis of monochorionic-diamniotic twins with genetic discordance / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of 5 cases of monochorionic-diamniotic (MCDA) with genetic discordance.@*METHODS@#148 cases of MCDA twins who were diagnosed by amniocentesis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 2016 to June 2020 were selected as the study subjects. Relevant clinical data of the pregnant women were collected, and amniotic fluid samples of the twins were collected separately. Chromosomal karyotyping analysis and single nucleotide polymorphism array (SNP array) assay were carried out.@*RESULTS@#The results of chromosomal karyotyping analysis showed that 5 of the MCDA twins had inconsistent chromosome karyotypes, with an incidence of 3.4% (5/148). SNP array assay showed that 3 fetuses were mosaics.@*CONCLUSION@#Genetic discordance occurs among MCDA twins, and prenatal counseling for such cases should be given by doctors with experience in medical genetics and fetal medicine, and personalized clinical management should be recommended.

Polysaccharide of Balanophora involucrata Hook. f. attenuates cell ferroptosis in rats with experimental liver injury through SLC7A11/GPX4 pathway / 药学学报

Polysaccharide of Balanophora involucrata Hook. f. (BPS), the major component of Balanophora involucrata Hook. f., was confirmed the protective effect on liver injury in our previous study. This research aimed to investigate the protective mechanism of BPS on experimental liver injury by attenuating cell ferroptosis through modulating solute carrier family 7 member 11/glutathione peroxidase 4 (SLC7A11/GPX4) pathway. The animal experiment was approved by the Experimental Animal Ethical Committee of Hubei Minzu University and all rats had received human care in compliance with the institutional animal care guidelines. Rats were given intraperitoneal injection of (D-galactosamine, D-GalN) solution (800 mg·kg-1) one time to establish the acute liver injury model. The results showed aspartate amino transferase (AST), alanine aminotransferase (ALT) and 4-hydroxynonenal (4-HNE) levels in serum were decreased, and the contents of reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA) and lipid peroxide (LPO) in liver tissues also decreased and glutathione (GSH) level increased after BPS administration with 200 mg·kg-1. Besides, BPS reduced iron deposition and increased the expression of SLC7A11 and GPX4 proteins in liver tissue. In conclusion, BPS ameliorated experimental liver injury by alleviating cell ferroptosis through SLC7A11/GPX4 pathway. The present study pointed to the possibility of utilizing BPS for protection against liver injury in clinic.

Novel role of AMPK in cocaine reinforcement via regulating CRTC1.

Repeated cocaine exposure causes compensatory neuroadaptations in neurons in the nucleus accumbens (NAc), a region that mediates reinforcing effects of drugs. Previous studies suggested a role for adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor, in modulating neuronal morphology and membrane excitability. However, the potential involvement of AMPK in cocaine use disorder is still unclear. The present study employed a cocaine self-administration model in rats to investigate the effect of AMPK and its target cyclic adenosine monophosphate response element binding protein-regulated transcriptional co-activator 1 (CRTC1) on cocaine reinforcement and the motivation for cocaine. We found that intravenous cocaine self-administration significantly decreased AMPK activity in the NAc shell (NAcsh), which persisted for at least 7 days of withdrawal. Cocaine reinforcement, reflected by self-administration behavior, was significantly prevented or enhanced by augmenting or suppressing AMPK activity pharmacologically and genetically, respectively. No difference in sucrose self-administration behavior was found after the same manipulations. The inhibition of AMPK activity in the NAcsh also increased the motivation for cocaine in progressive-ratio schedules of reinforcement, whereas the activation of AMPK had no effect. The knockdown of CRTC1 in the NAcsh significantly impaired cocaine reinforcement, which was rescued by pharmacologically increasing AMPK activity. Altogether, these results indicate that AMPK in the NAcsh is critical for cocaine reinforcement, possibly via the regulation of CRTC1 signaling. These findings may help reveal potential therapeutic targets and have important implications for the treatment of cocaine use disorder and relapse.

The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study.

BACKGROUND: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder. An unconditioned stimulus (US)-triggers a memory reconsolidation updating procedure (MRUP) that has been developed and demonstrated its effectiveness in decreasing relapse to cocaine and heroin in preclinical models. However, utilizations of abused drugs as the US to initiate MRUP can be problematic. We therefore designed a translational rat study and human study to evaluate the efficacy of a novel methadone-initiated MRUP. METHODS: In the rodent study, male rats underwent heroin self-administration training for 10 consecutive days, and were randomly assigned to receive saline or methadone at 10 min, 1 h or 6 h before extinction training after 28-day withdrawal. The primary outcome was operant heroin seeking after reinstatement. In the human experimental study, male OUD patients were randomly assigned to get MRUP at 10 min or 6 h after methadone or methadone alone. The primary outcomes included experimental cue-induced heroin craving change, sustained abstinence and retention in the study at post intervention and the 5 monthly follow-up assessments. The secondary outcomes were changes in physiological responses including experimental cue-induced blood pressure and heart rate. FINDINGS: Methadone exposure but not saline exposure at 10 min or 1 h before extinction decreased heroin-induced reinstatement of heroin seeking after 28-day of withdrawal in rats (F (8,80) = 8.26, p < 0.001). In the human study, when the MRUP was performed 10 min, but not 6 h after methadone dosing, the MRUP promoted sustained abstinence from heroin throughout 5 monthly follow-up assessments compared to giving methadone alone without MRUP (Hazard Ratio [95%CI] of 0.43 [0.22, 0.83], p = 0.01). The MRUP at 10 min, but not at 6 h after dosing also decreased experimental cue-induced heroin craving and blood pressure increases during the 6-month study duration (group × months × cue types, F (12, 63·3) = 2.41, p = 0.01). INTERPRETATION: The approach of MRUP within about 1 to 6 h after a methadone dose potently improved several key outcomes of OUD patients during methadone maintenance treatment, and could be a potentially novel treatment to prevent opioid relapse. FUNDING: National Natural Science Foundation of China (NO. U1802283, 81761128036, 82001400, 82001404 and 31671143) and Chinese National Programs for Brain Science and Brain-like Intelligence Technology (NO. 2021ZD0200800).

Exposure to polystyrene microplastics impairs hippocampus-dependent learning and memory in mice.

Microplastics (MPs) pollution has become a serious environmental issue worldwide, but its potential effects on health remain unknown. The administration of polystyrene MPs (PS-MPs) to mice for eight weeks impaired learning and memory behavior. PS-MPs were detected in the brain especially in the hippocampus of these mice. Concurrently, the hippocampus had decreased levels of immediate-early genes, aberrantly enhanced synaptic glutamate AMPA receptors, and elevated neuroinflammation, all of which are critical for synaptic plasticity and memory. Interestingly, ablation of the vagus nerve, a modulator of the gut-brain axis, improved the memory function of PS-MPs mice. These results indicate that exposure to PS-MPs in mice alters the expression of neuronal activity-dependent genes and synaptic proteins, and increases neuroinflammation in the hippocampus, subsequently causing behavioral changes through the vagus nerve-dependent pathway. Our findings shed light on the adverse impacts of PS-MPs on the brain and hippocampal learning and memory.

Clinical Efficacy of Gandou Fumu Granules on Wilson Disease with Liver-kidney Deficiency and Phlegm-blood Stasis / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Gandou Fumu granules （GDFM） in the treatment of Wilson disease （WD） with liver-kidney deficiency and phlegm-blood stasis. MethodNinety WD patients in The First Affiliated Hospital of Anhui University of Chinese Medicine were randomly divided into a control group （45 cases） and a treatment group （45 cases）. All patients were treated with sodium 2，3-dimercaptopropane-1-sulfonate （DMPS）， while those in the treatment group received additional GDFM. All patients were treated for four courses （32 days）. The traditional Chinese medicine （TCM） syndrome scores，clinical effective rate，24 h urinary copper，ceruloplasmin （CER），tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β），interleukin-6 （IL-6），superoxide dismutase （SOD），glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） levels of the two groups before and after treatment were observed. ResultAfter treatment， the TCM syndrome scores of the two groups decreased （P<0.01），and the score of TCM syndrome in the treatment group was lower than that of the control group （P<0.01）. The total effective rate of the treatment group was 82.22% （37/45）， higher than 57.78% （26/45） of the control group （χ2=6.402，P<0.05）. There was no significant difference in CER before and after treatment in both groups. The post-treatment 24 hour urinary copper increased （P<0.01）， which was higher in the treatment group than that in the control group （P<0.05）. The TNF-α，IL-1β， and IL-6 levels were significantly reduced in both groups after treatment（P<0.01），and the above indicators in the treatment group were significantly lower than those in the control group （P<0.01）. After treatment，the SOD level increased and the MDA level decreased in the control group （P<0.01）， while no significant difference in GSH-Px level was observed. The SOD and GSH-Px levels increased and the MDA level decreased in the treatment group （P<0.01）. After treatment， SOD and GSH-Px levels of the treatment group were higher than those in the control group， while the MDA level was lower than that in the control group（P<0.05，P<0.01）. ConclusionGDFM can improve the TCM syndrome score and clinical efficacy，enhance the copper removing effect，and inhibit the inflammatory response and antioxidative stress in the treatment of WD with liver and kidney deficiency and phlegm-blood stasis.

Intervention of Gandou Fumu Decoction on Liver Fibrosis in Mice with Wilson's Disease Through JNK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo identify the protective effect and possible mechanism of Gandou Fumu decoction （GDFMD） on liver fibrosis in mice with Wilson's disease. MethodA total of 50 homozygous TXJ mice were randomly divided into five groups， with 10 mice in each group. Ten wild-type mice were selected as a normal group. The GDFMD high， medium， and low-dose groups were given 13.92， 6.96， 3.48 g·kg-1 of GDFMD， respectively. The penicillamine group were given 0.1 g·kg-1 of penicillamine. The model group and the normal group were given the same volume of 0.9% sodium chloride solution once a day for 4 consecutive weeks. The enzyme-linked immunosorbent assay （ELISA） method was performed to detect serum superoxide dismutase （SOD） activity and malondialdehyde （MDA） content. Corresponding kits were used to detect the mitochondrial adenine triphosphate （ATP） content and Na+-K+-ATPase activity in liver tissues. Hematoxylin-eosin （HE） and Masson staining were used to observe the pathological morphology of liver tissue， and transmission electron microscope was used to observe ultrastructural changes of liver tissues in mice. Western blot was used to detect the c-Jun N-terminal kinase， the phosphorylated protein， and the expressions of Caspase-3， B cell lymphoma-2 （Bcl-2）， and Bcl-2 associated X protein （Bax） in c-Jun N-terminal kinase （JNK） signaling pathway. ResultCompared with the normal group， MDA content increased and SOD activity decreased in the model group （P<0.05）. Compared with the model group， SOD activities in the GDFMD high-， medium-， and low-dose groups and the penicillamine group significantly increased （P<0.01）， and MDA content significantly decreased （P<0.05， P<0.01）. Compared with the normal group， ATP content and Na+-K+-ATPase activity significantly decrease in the model group （P<0.05）. Compared with the model group， ATP content and Na+-K+-ATPase activity in the GDFMD medium and high-dose groups and the penicillamine group significantly increased （P<0.05， P<0.01）. The results of the pathological morphology of liver tissue showed that a large number of liver cells degeneration and necrosis， inflammatory cell infiltration， unclear liver lobule structure， and collagen fiber deposition were observed in the model group. Transmission electron microscopy showed that the number of mitochondria in liver tissues significantly reduced， the mitochondria were locally damaged， and the cristae of mitochondria were broken even disappear in the model group. The pathological morphology of liver tissue and mitochondrial structure recovered to varying degrees after medicinal intervention. The results of Western blot suggested that， compared with the normal group， the expression levels of phosphorylation-JNK （p-JNK）， p-JNK/JNK， Caspase-3， and Bax in the liver tissues were up-regulated， while the expression of Bcl-2 was down-regulated in the model group （P<0.05）. The expression levels of p-JNK， p-JNK/JNK， Caspase-3 and Bax were down-regulated and the expression of Bcl-2 was up-regulated in the GDFMD high and medium-dose groups and the penicillamine group （P<0.01）. ConclusionGDFMD can alleviate oxidative stress damage and recover mitochondrial function of TXJ mice with liver fibrosis. The mechanism of GDFMD may be related to regulating the JNK signaling pathway and downstream factors and inhibiting cell apoptosis.

Effect of Gandou Decoction on Mitophagy in Toxic Milk （TX） Mouse Model of Wilson Disease Based on Pink1/Parkin Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Gandou decoction （GDD） on the mitophagy of hippocampal neurons in toxic milk （TX） mouse model of Wilson disease and explore the protective mechanism of GDD against neuron injury through the PTEN induced kinase 1 （Pink1） /E3 ubiquitin ligase （Parkin） pathway. MethodSixty mice were randomly divided into a blank group， a model group， a penicillamine group （0.09 g·kg-1）， and low- （5.5 g·kg-1）， medium- （11 g·kg-1）， and high-dose （22 g·kg-1） GDD groups， and treated correspondingly by gavage for 8 weeks. Morris water maze， traction test， and pole test were used for the evaluation of animal behaviors. Hematoxylin-eosin （HE） staining and transmission electron microscopy were used to observe cell apoptosis， ultrastructure， autophagy， and mitochondrial structure. The levels of superoxide dismutase （SOD）， reactive oxygen species （ROS）， and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Pink1， Parkin， autophagy-associated protein Beclin-1， microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ）， and p62. Western blot was conducted to detect the protein expression of Pink1， Parkin， Beclin-1， LC3Ⅱ/Ⅰ， and p62. ResultCompared with the blank group， the model group showed prolonged escape latency， decreased times of platform crossing， lower score in the traction test， and longer pole climbing time （P<0.01）. Compared with the model group， the medium- and high-dose GDD groups and the penicillamine group showed shortened escape latencies， increased times of platform crossing， higher scores in the traction test， and shortened pole climbing time （P<0.01）. Compared with the blank group， the model group displayed severely damaged neurons and increased autophagosomes. Compared with the model group， the medium- and high-dose GDD groups and the penicillamine group showed improved neuron damage and reduced autophagosomes. The levels of ROS and MDA were higher and SOD was lower in the model group than those in the blank group （P<0.01）， while the levels of the above indicators were reversed by GDD intervention as compared with the model group （P<0.01）. Compared with the blank group， the model group exhibited up-regulated mRNA and protein expression of Pink1， Parkin， LC3Ⅱ， and Beclin-1 and down-regulated p62 （P<0.05）. Compared with the model group， the medium- and high-dose GDD groups showed reduced mRNA and protein expression of Pink1， Parkin， LC3Ⅱ， and Beclin-1 and increased p62 （P<0.05， P<0.01）. ConclusionGDD can significantly inhibit the excessive mitophagy in neurons of TX mice and protect neurons from damage. The mechanism may be related to the regulation of the Pink1/Parkin pathway.

Expert consensus on clinical application of GBE50 Dispersible Tablets for ischemic cardiovascular and cerebrovascular diseases / 中国中药杂志

Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.

Bone marrow mesenchymal stem cells attenuate pyroptosis lipopolysaccharide-induced renal injury rats / 中华危重病急救医学

Objective:To investigate the effect and mechanism of bone marrow mesenchymal stem cell (BMSC) on pyroptosis of rats with kidney injury.Methods:Bone marrow of 4-5 week-old female Sprague-Dawley (SD) rats was isolated in vitro and BMSC was obtained. The third generations of BMSC were used to further experiments. Fifteen 6 week-old SD rats were cluster-randomized divided into control group, kidney injury group and BMSC group (5 rats in each group). Rats in kidney injury group were injected with lipopolysaccharide (LPS) 1 mg/kg via tail vein; the control group was given the same amount of normal saline. BMSC group was injected with 0.5 mL BMSC (including 2×10 6 BMSC) via tail vein after modeling; the kidney injury group received the same amount of normal saline. On day 3 after these injections, serum creatinine (SCr) was detected by picric acid method, and blood urea nitrogen (BUN) was detected by diacetyl monoxime. The levels of cystatin C (Cys C), interleukins (IL-1β and IL-18) in blood were detected by enzyme-linked immunosorbent assay (ELISA). The rats were then sacrificed and their kidneys were removed for subsequent detection. The mRNA expression levels of NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate-specific protease-1 (caspase-1) of kidney were detected by quantificational real-time quantitative polymerase chain reaction (qRT-PCR). The protein expression levels of NLRP3 and caspase-1 of kidney were detected by Western blotting. Results:In vitro, after bone marrow cell suspension was cultured for 24 hours, a large number of round adherent cells and suspended cells appeared in each culture flask. After 4-5 days of culture, a large number of long spindle cells adhered to the wall, and there were still obvious impurity cells. After trypsin digestion and passage to the third generation, the long spindle adherent cells grew mainly in the culture flask and were basically purified as BMSC. In vivo, compared with the control group, the levels of SCr, BUN, Cys C, IL-1β and IL-18 in kidney injury group were increased [SCr (μmol/L): 85.22±2.29 vs. 21.80±0.59, BUN (mmol/L): 11.50±0.64 vs. 5.86±0.83, Cys C (mg/L): 0.13±0.01 vs. 0.11±0.02, IL-1β (ng/L): 31.49±1.42 vs. 4.74±0.49, IL-18 (ng/L): 29.01±1.95 vs. 1.52±0.03, all P < 0.05]. The mRNA and protein expression levels of NLRP3, caspase-1 were significantly increased [NLRP3 mRNA (2 -ΔΔCt): 3.635±0.296 vs. 1.000±0.002, caspase-1 mRNA (2 -ΔΔCt): 4.020±0.228 vs. 1.001±0.003; NLRP3 protein (NLRP3/β-actin): 1.560±0.868 vs. 0.902±0.036, caspase-1 protein (caspase-1/β-actin): 1.392±0.097 vs. 0.895±0.046, all P < 0.05]. Compared with kidney injury group, the levels of SCr, BUN, IL-1β and IL-18 in BMSC group were significantly decreased [SCr (μmol/L): 51.64±3.84 vs. 85.22±2.29, BUN (mmol/L): 9.90±0.46 vs. 11.50±0.64, IL-1β (ng/L): 24.20±1.45 vs. 31.49±1.42, IL-18 (ng/L): 12.97±1.25 vs. 29.01±1.95, all P < 0.05]. The mRNA and protein expression levels of NLRP3, caspase-1 were significantly decreased [NLRP3 mRNA (2 -ΔΔCt): 1.488±0.136 vs. 3.635±0.296, caspase-1 mRNA (2 -ΔΔCt): 1.643±0.143 vs. 4.020±0.228; NLRP3 protein (NLRP3/β-actin): 1.227±0.053 vs. 1.560±0.868, caspase-1 protein (caspase-1/β-actin): 1.159±0.107 vs. 1.392±0.097, all P < 0.05]. Conclusion:In vivo, BMSC may attenuate pyroptosis in LPS-induced kidney injury rats.

Progress of chimeric antigen receptor T-cell therapy for drug resistance and relapse of hematologic malignancies / 白血病·淋巴瘤

Chimeric antigen receptor T-cell (CAR-T) has made a breakthrough in the treatment of hematologic malignancies, but drug resistance and recurrence have limited its wide application. And at the 63rd annual meeting of the American Society of Hematology, a series of related reports on the mechanism and prevention strategies of drug resistance and recurrence after CAR-T therapy were carried out. These reports provide important indications for improving the clinical efficacy of CAR-T therapy and reducing relapse.

Distribution of mesencephalic astrocyte derived neurotrophic factor in human, mouse and rat brain / 解剖学报

Objective To observe the distribution of mesencephalic astrocyte derived neurotrophic factor (MANF) within the brain in human, mice and rats and the comparison across the species. Methods An immunohistochemical method was applied to investigate the expression of MANF and to compare the differences among species in the brain of human specimens ( n = 5) , mice ( n = 6) , and rats ( n = 6). Results The expression of MANF varied in different brain regions in human, mice and rats. In human, in the cortex, the expression of MANF was the highest among all brain regions. In the subcortical areas or the nucleus, brainstem and cerebellum expression level of MANF were relatively lower. The distribution of MANF in mouse and rat brain were slightly different from that in human brain, but generally consistent. Conclusion The distribution pattern of MANF is similar across the species, however, within a species, MANF expression levels varies in different brain regions.