Safe Optimal Tear Drop View for Spinopelvic Fixation Using a Three-Dimensional Reconstruction Model of the Pelvis

Background@#Spinopelvic fixation (SPF) has been a challenge for surgeons despite the advancements in instruments and surgical techniques. C-arm fluoroscopy-guided SPF is a widely used safe technique that utilizes the tear drop view. The tear drop view is an image of the corridor from the posterior superior iliac spine to the anterior inferior iliac spine (AIIS) of the pelvis. This study aimed to define the safe optimal tear drop view using three-dimensional reconstruction of computed tomography images. @*Methods@#Three-dimensional reconstructions of the pelvises of 20 individuals were carried out. By rotating the reconstructed model, we simulated SPF with a cylinder representing imaginary screw. The safe optimal tear drop view was defined as the one embracing a corridor with the largest diameter with the inferior tear drop line not below the acetabular line and the lateral tear drop line medial to the AIIS. The distance between the lateral border of the tear drop and AIIS was defined as tear drop index (TDI) to estimate the degree of rotation on the plane image. Tear drop ratio (TDR), the ratio of the distance between the tear drop center and the AIIS to TDI, was also devised for more intuitive application of our simulation in a real operation. @*Results@#All the maximum diameters and lengths were greater than 9 mm and 80 mm, respectively, which are the values of generally used screws for SPF at a TDI of 5 mm and 10 mm in both sexes. The TDRs were 3.40 ± 0.41 and 3.35 ± 0.26 in men and women, respectively, at a TDI of 5 mm. The TDRs were 2.26 ± 0.17 and 2.14 ± 0.12 in men and women, respectively, at a TDI of 10 mm. @*Conclusions@#The safe optimal tear drop view can be obtained with a TDR of 2.5 to 3 by rounding off the measured values for intuitive application in the actual surgical field.

Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy / 中华儿科杂志

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

Clinical features of 6 children with uridine-responsive developmental epileptic encephalopathy 50 caused by CAD gene variants / 中华儿科杂志

Objective: To analyze the clinical features of children with uridine responsive developmental epileptic encephalopathy 50 (DEE50) caused by CAD gene variants. Methods: A retrospective study was conducted on 6 patients diagnosed with uridine-responsive DEE50 caused by CAD gene variants at Beijing Children's Hospital and Peking University First Hospital from 2018 to 2022. The epileptic seizures, anemia, peripheral blood smear, cranial magnetic resonance imaging (MRI), visual evoked potential (VEP), genotype features and the therapeutic effect of uridine were descriptively analyzed. Results: A total of 6 patients, including 3 boys and 3 girls, aged 3.5(3.2,5.8) years, were enrolled in this study. All patients presented with refractory epilepsy, anemia with anisopoikilocytosis and global developmental delay with regression. The age of epilepsy onset was 8.5 (7.5, 11.0) months, and focal seizures were the most common seizure type (6 cases). Anemia ranged from mild to severe. Four patients had peripheral blood smears prior to uridine administration, showing erythrocytes of variable size and abnormal morphology, and normalized at 6 (2, 8) months after uridine supplementation. Two patients suffered from strabismus, 3 patients had VEP examinations, indicating of suspicious optic nerve involvement, and normal fundus examinations. VEP was re-examined at 1 and 3 months after uridine supplementation, suggesting significant improvement or normalization. Cranial MRI were performed at 5 patients, demonstrating cerebral and cerebellar atrophy. They had cranial MRI re-examined after uridine treatment with a duration of 1.1 (1.0, 1.8) years, indicating significant improvement in brain atrophy. All patients received uridine orally at a dose of 100 mg/(kg·d), the age at initiation of uridine treatment was 1.0 (0.8, 2.5) years, and the duration of treatment was 2.4 (2.2, 3.0) years. Immediate cession of seizures was observed within days to a week after uridine supplementation. Four patients received uridine monotherapy and were seizure free for 7 months, 2.4 years, 2.4 years and 3.0 years respectively. One patient achieved seizure free for 3.0 years after uridine supplementation and had discontinued uridine for 1.5 years. Two patients were supplemented with uridine combined with 1 to 2 anti-seizure medications and had a reduced seizure frequency of 1 to 3 times per year, and they had achieved seizure free for 8 months and 1.4 years respectively. Conclusions: The clinical manifestations of DEE50 caused by CAD gene variants present a triad of refractory epilepsy, anemia with anisopoikilocytosis, and psychomotor retardation with regression, accompanied by suspected optic nerve involvement, all of which respond to uridine treatment. Prompt diagnosis and immediate uridine supplementation could lead to significant clinical improvement.

Effects of N-butanol extract of Amygdalus mongolica on rats with bleomycin‐induced pulmonary fibrosis based on metabolomics

Pulmonary fibrosis (PF) is a major public health issue with limited treatment options. As the active ingredient of the n-butanol extract of Amygdalus mongolica (BUT), amygdalin inhibits PF. However, its mechanisms of action are unclear and need further verification. Therefore, the purpose of the present studies was to investigate the anti-fibrotic effects of BUT on PF by serum metabolomics and the transforming growth factor β (TGF-β) pathway. Sixty male Sprague-Dawley rats were randomly divided into control, untreated PF, prednisone-treated (5 mg/kg), and BUT-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. The serum metabolomics profiles were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and metabolism network analysis. The expression of TGF-β1, Smad-3, Smad-7, and α-smooth muscle actin (α-SMA) was measured using a real-time polymerase chain reaction in the lung tissue. BUT significantly alleviated fibrosis by reducing the mRNA expressions of TGF-β1 (from 1.73 to 1.13), Smad-3 (from 2.01 to 1.19), and α-SMA (from 2.14 to 1.19) and increasing that of Smad7 (from 0.17 to 0.62). Twenty-eight potential biomarkers associated with PF were identified. In addition, four key biomarkers were restored to baseline levels following BUT treatment, with the lowest dose showing optimal effect. Furthermore, A. mongolica BUT was found to improve PF by the pentose phosphate pathway and by taurine, hypotaurine, and arachidonic acid metabolism. These findings revealed the mechanism of A. mongolica BUT antifibrotic effects and metabolic activity in PF rats and provided the experimental basis for its clinical application.

Heme peroxidases are responsible for the dehydrogenation and oxidation metabolism of harmaline into harmine / 中国天然药物

Harmaline and harmine are β-carboline alkaloids with effective pharmacological effects. Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H2O2. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-β-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.

Impact of nonsteroidal anti-inflammatory drugs on efficacy of anti-PD-1 therapy for primary liver cancer / 南方医科大学学报

OBJECTIVE@#To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma.@*METHODS@#We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups.@*RESULTS@#There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729).@*CONCLUSION@#Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.

Clinical characteristics and gene analysis of GRIN2B gene related neurological developmental disorders in children / 中华儿科杂志

Objective: To analyse the clinical and gene characteristics of GRIN2B gene related neurological developmental disorders in children. Methods: The data of 11 children with GRIN2B gene related neurological developmental disorders from November 2016 to February 2021 were collected from Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health and analyzed retrospectively. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Results: Among 11 children 6 were boys and 5 were girls. Two of them were diagnosed with developmental and epileptic encephalopathy. The ages of seizures onset were 3 months and 9 months, respectively. Seizure types included epileptic spasm, tonic seizures, tonic spasm and focal seizures, and 1 patient also had startle attacks. EEG showed interictal multifocal epileptiform discharges. Both of them were added with more than 2 anti-seizure drugs, which were partially effective but could not control. They had moderate to severe mental and motor retardation. The phenotype of 9 cases was developmental delay or intellectual disability without epilepsy, age of visit 1 year to 6 year and 4 months of whom 5 cases had severe developmental delay, 2 cases had moderate and 2 cases had mild delay. Multi-focal epileptiform discharges were observed in 3 cases, no abnormality was found in 3 cases, and the remaining 3 cases did not undergo EEG examination. Ten cases underwent brain magnetic resonance imaging (MRI), 6 cases had nonspecific abnormalities and 4 cases were normal. Nine GRIN2B gene heterozygous variants were detected by next-generation sequencing in these 11 patients, 8 cases had missense variants and 1 case had nonsense variant, all of which were de novo and 3 of which were novel. Missense variants were found in 10 patients, among them 6 cases had severe developmental delay, 3 cases had moderate and 1 case had mild developmental delay, but the patient with nonsense variant showed mild developmental delay without epilepsy. Conclusions: The phenotypes of GRIN2B gene related neurological developmental disorders in children are diverse, ranging from mild intellectual impairment without epilepsy to severe epileptic encephalopathy. Patients with epileptic phenotype usually have an onset age of infancy, and spasm and focal seizures are the most common seizure types. And the epiletice episodes are refractory. Most of the patients with missense variants had severe developmental delay.

The protective effect of ritonavir against Gynura japonica-induced liver injury in rats / 药学学报

Numerous in vitro studies have shown that most pyrrolizidine alkaloids (PAs) are hepatotoxic after being metabolically activated by cytochrome P450 (CYP) 3A4. However, the key role of CYP3A4 has not been confirmed in vivo. Therefore, the CYP3A4 chemical inhibitor ritonavir was employed in this work and the effect of ritonavir on Gynura japonica-induced liver injury in rats was investigated. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Acute liver injury was induced by a single gavage of Gynura japonica extracts (GJE, 8 g·kg-1); rats in the protection group were gavaged with ritonavir (RIT, 30 mg·kg-1) 1 h before GJE treatment. The results show that RIT could significantly attenuate GJE-induced liver injury in rats. Rats in the protection group showed decreased serum activities for alanine aminotransferase and aspartate aminotransferase, as well as lower total bile acids. In addition, the infiltration of inflammatory cells, sinusoidal hemorrhage, and hepatic necrosis in GJE-treated rats were markedly attenuated in the protection group. The content of pyrrole-protein adducts (PPAs), a recommended biomarker for PA-induced hepatotoxicity in clinics, was determined at 10 min to 24 h after GJE treatment. The content of 13 bile acids was also quantified. RIT treatment reduced the content of PPAs in serum dramatically and restored the impaired bile acid homeostasis caused by GJE. These studies indicate that RIT attenuated Gynura japonica-induced liver injury in rats, which was closely related to the inhibition of the metabolic activation of PAs and the regulation of bile acid metabolism. These results provide a better understanding of the relationship between CYP3A4 and PA-induced toxicity. This work will also be helpful in developing effective treatments for PA-induced liver injury and making a reasonable evaluation of the safety of drugs containing PAs in clinic.

The protective effect of schisandrol A against senecionine-induced hepatotoxicity in mice / 药学学报

Hepatotoxicity induced by herbal medicines such as Gynura japonica, which contains large amount of pyrrolizidine alkaloids (PAs) such as senecionine (SEN), is among the most serious problems of herbal drug-induced liver injury, yet there is no effective treatment in clinic. We have previously reported that ritonavir (the well-known CYP3A4 inhibitor) protected rats against Gynura japonica-induced liver injury in rats, which was closely related to the inhibition of the metabolic activation of PAs. A large number of lignans have been identified in Schisandrae Chinensis Fructis and are reported to attenuate drug-induced liver injuries by modulating the drug metabolism enzymes. Therefore, the present study investigated the protective effect and potential mechanism of schisandrol A (SoA, a representative lignan identified in Schisandrae Chinensis Fructis) against SEN-induced hepatotoxicity in mice. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine (PZSHUTCM210604002). Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Liver injury was induced by a single gavage of SEN (150 μmol·kg-1); mice in the protection group were gavaged with SoA (116 μmol·kg-1) 7 days before SEN treatment. The results show that SoA dramatically alleviated SEN-induced liver injury in mice. Mice in the protection group showed decreased serum activities for alanine aminotransferase and aspartate aminotransferase; in addition, the hepatic necrosis and sinusoidal hemorrhage in SEN-treated mice were markedly attenuated in the protection group. The serum contents of SEN metabolites in mice were decreased. In vitro studies were performed by using human liver microsomes and proved that SoA inhibits CYP3A4 to decrease the metabolism of SEN. These studies indicate that SoA attenuated SEN-induced liver injury in mice, which was closely related to the inhibition of the metabolic activation of SEN. These results provide a better understanding of the relationship between CYP3A4 and PA-induced toxicity. This work also will be helpful in developing effective treatments for SEN-induced liver injury based on inhibition of its metabolic activation, and in making reasonable evaluations of the safety of herbal medicines containing PAs such as G. japonica.

Expert Consensus on Rheumatic Immune Diseases Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

In the clinical practice of rheumatic immune diseases in traditional Chinese medicine （TCM），it`s still unclear about the dominant diseases and breakthrough points. It`s urgent missions to formulate TCM diagnosis and treatment guidelines widely recognized and integrated by traditional Chinese medicine and Western medicine. In order to clarify the dominant diseases and breakthrough points in rheumatism，China association of Chinese medicine initiated a research group covering experts in the field of rheumatism of traditional Chinese medicine and Western medicine. Based on questionnaire survey and on-site discussion，experts had reached the following consensus. Evidence-based medicine research using modern medical methods and scientific methods should be carried out to provide objective clinical evidences. "Four mutuality" were put forward as the basis for the work of integrated traditional Chinese and Western medicine，that is the mutual communication using the exchangeable context，the mutual explanation using common theories，the mutual certification using common standards，and the mutual integration using common means. Key works should focus on solving refractory rheumatism in the future. In terms of dominant diseases and breakthrough points，this paper introduces 21 breakthrough points in 6 dominant diseases，including rheumatoid arthritis，ankylosing spondylitis，Sjogren's syndrome，hyperuricemia and gout，systemic lupus erythematosus and fibromyalgia syndrome. Advice on this discussion can provide valuable references for developing the treatment scheme of rheumatism with TCM and integrated Chinese and Western medicine and clinical practice and scientific research.

Progress on Molecular Mechanism of Curcumin and Its Nano-preparation Against Liver Cancer / 中国实验方剂学杂志

There are certain limitations in the application of liver transplantation， resection and radiofrequency ablation for liver cancer. Therefore，specific and selective new drugs are needed to provide better treatment. Curcumin is a hydrophobic polyphenol with a wide range of activities，such as anti-inflammatory，antibacterial，anti-oxidant and anti-tumor properties. Its nano-preparation has stronger growth inhibition and pro-apoptosis effects on tumor cells. Literature retrieval found that curcumin's anti-liver cancer molecular mechanisms include inhibiting cell proliferation by regulating the expressions of relevant miR，glyoxalase 1（GLO1），CD133 and vascular endothelial growth factor （VEGF），inhibiting signal transducer and activator of transcription （STAT3） and YAP expression to induce cell apoptosis，regulating the heat shock protein 70 （HSP70）-Toll-like receptor 4 （TLR4） signaling pathway，Wnt/β-catenin and transforming growth factor（TGF）/epithelial-mesenchymal transition（EMT） pathways，nuclear factor-κB （NF-κB） signaling pathway and nuclear factor E2-related factor 2（Nrf2）/ Kelch-like ECH-related protein 1（Keap1） signaling pathway，inhibiting p38 mitogen-activated protein kinase （MAPK） phosphorylation，to reduce Lin28B expression，regulating phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and inhibiting G protein-coupled receptors （GPR81）/hydroxycarboxylic acid receptor-1 （HCAR-1） expression to reverse transformation therapy resistance. Curcumin nano-preparation mainly includes polymer micelles，liposomes，loaded microbubbles，nanocapsules and nanoparticles. Curcumin is mainly delivered to liver cancer cells to rapidly release the drug，enhance the anti-liver cancer effect and reduce toxic and side effects in normal liver cells. The mechanisms include activation of DR5/Caspase-mediated exogenous apoptosis pathway and VEGF/VEGF receptors （VEGFRs） signaling pathway，loss of mitochondrial membrane potential and increase of intracellular reactive oxygen species （ROS）. This paper summarizes the molecular mechanism of curcumin and its nano-preparation against liver cancer，in order to further define the molecular mechanism of liver cancer and provide a new reference for its clinical diagnosis and treatment.

Prescription Research and Clinical Application of Yiguanjian / 中国实验方剂学杂志

By systematically sorting out the ancient medical books and modern clinical literature of Yiguanjian， the historical evolution of this formula， including its source， composition， origin， processing， dosage， preparation and usage， functions and indications， evolution of prescription meaning， is textual so as to clarify the historical evolution and clinical application of Yiguanjian. On the basis of fully considering the actual demand of development of famous classical formula preparation and the usage habit of modern clinical practice， the feasible development suggestions were put forward. Yiguanjian is composed of six herbs， which is derived from Yifang Jiedu (《医方絜度》) . It is an ancient book of traditional Chinese medicine edited by QIAN Min-jie in Qing dynasty. The original medicinal plants and medicinal parts of the formula were basically the same as those recorded in the 2020 edition of Chinese Pharmacopoeia. The raw products should be selected for decoction pieces and processed according to the methods recorded in the 2020 edition of Chinese Pharmacopoeia. The reference dose of the medicine in this formula is set out in Yifang Jiedu. According to dosage of one Qian（钱）=3.73 g， the dosages of Glehniae Radix， Ophiopogonis Radix and Angelicae Sinensis Radix were 5.60 g， the dosages of Lycii Fructus and Rehmanniae Radix were 11.19 g， the dosage of Toosendan Fructus was 7.46 g. These decoction pieces were boiled and warm decoction was taken. According to ancient medical records， the formula always has the effect of nourishing Yin and relieving Qi of liver. It is used to treat syndrome of stagnation of liver-Qi and deficiency of liver-Yin and kidney-Yin， which can be seen with pain in chest， stomach and flank， acerbity and vomiting， dry throat and mouth， red tongue， weak pulse or deficiency of string and hernia. Here， the source， processing and others of Yiguanjian were clarified， providing a literature reference for the development and application of this famous classical formula.

Strictosidine synthase, an indispensable enzyme involved in the biosynthesis of terpenoid indole and β-carboline alkaloids / 中国天然药物

Terpenoid indole (TIAs) and β-carboline alkaloids (BCAs), such as suppressant reserpine, vasodilatory yohimbine, and antimalarial quinine, are natural compounds derived from strictosidine. These compounds can exert powerful pharmacological effects but be obtained from limited source in nature. the whole biosynthetic pathway of TIAs and BCAs, The Pictet-Spengler reaction catalyzed by strictosidine synthase (STR; EC: 4.3.3.2) is the rate-limiting step. Therefore, it is necessary to investigate their biosynthesis pathways, especially the role of STR, and related findings will support the biosynthetic generation of natural and unnatural compounds. This review summarizes the latest studies concerning the function of STR in TIA and BCA biosynthesis, and illustrates the compounds derived from strictosidine. The substrate specificity of STR based on its structure is also summarized. Proteins that contain six-bladed four-stranded β-propeller folds in many organisms, other than plants, are listed. The presence of these folds may lead to similar functions among organisms. The expression of STR gene can greatly influence the production of many compounds. STR is mainly applied to product various valuable drugs in plant cell suspension culture and biosynthesis in other carriers.

Clinical characteristics of hypertrophic cardiomyopathy and restricted cardiomyopathy patients complicating with intracardiac thrombosis / 中华心血管病杂志

Objective: To investigate the clinical characteristics of patients with hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) complicating with intracardiac thrombosis. Methods: This is a retrospective observational study. Consecutive patients diagnosed with HCM or RCM and complicated with intracardiac thrombosis (including left and right atrium or ventricular thrombosis), who were admitted to the Heart Failure Care Unit of Fuwai Hospital, Chinese Academy of Medical Sciences, from September 2008 to September 2018, were enrolled in this study. Patients with myocardial infarction were excluded. The general clinical data of the enrolled patients, including demographic data, major complications, laboratory indicators, echocardiographic indicators, drug application and distribution of intracardiac thrombosis, were collected from electronic medical record system and analyzed. Results: A total of 98 patients were enrolled in this study, including 52 patients (53.1%) with HCM and 46 patients (46.9%) with RCM. The most common comorbidity was atrial fibrillation/flutter: 40 patients (76.9%) in HCM group and 36 patients (78.3%) in RCM group. Majority of patients received oral anticoagulants treatment: 43 patients (82.7%) in HCM group and 35 patients (76.1%) in RCM group. Intracardiac thrombosis was mainly located in the left atrium in both HCM group (39 cases (75.0%)) and RCM group (32 cases (69.6%)). Thrombosis was found in ≥ 2 chambers in 7 patients (7.1%). Rate of left atrial thrombosis was the highest (81.6% (62/76)) in HCM and RCM patients complicating with atrial fibrillation/flutter. Intra-aneurysmal thrombosis occurred in 4 out of 5 patients complicated with apical left ventricular aneurysm. The rate of left ventricular thrombosis in patients with left ventricular ejection fraction≥50% was 7.4% (4/54), which was significantly lower than that in patients with left ventricular ejection fraction<50% (34.5%(10/29)) (P<0.01). Conclusion: There are certain distribution characteristics of HCM and RCM patients with intracardiac thrombosis, and the left atrium is the most common site of thrombosis, more attention should be paid in HCM and RCM patients on the diagnosis and treatment of intracardiac thrombosis.

Clinical effect of tacrolimus in the treatment of myasthenia gravis in children / 中国当代儿科杂志

OBJECTIVE@#To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG).@*METHODS@#A total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment.@*RESULTS@#After tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05).@*CONCLUSIONS@#Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.

Gray matter atrophy in parkinsons disease and the parkinsonian variant of multiple system atrophy: a combined roi- and voxel-based morphometric study

OBJECTIVES: Parkinson's disease (PD) and the parkinsonian variant of multiple system atrophy (MSA-P) are distinct neurodegenerative disorders that share similar clinical features of parkinsonism. The morphological alterations of these diseases have yet to be understood. The purpose of this study was to evaluate gray matter atrophy in PD and MSA-P using regions of interest (ROI)-based measurements and voxel-based morphometry (VBM). METHODS: We studied 41 patients with PD, 20 patients with MSA-P, and 39 controls matched for age, sex, and handedness using an improved T1-weighted sequence that eased gray matter segmentation. The gray matter volumes were measured using ROI and VBM. RESULTS: ROI volumetric measurements showed significantly reduced bilateral putamen volumes in MSA-P patients compared with those in PD patients and controls (p<0.05), and the volumes of the bilateral caudate nucleus were significantly reduced in both MSA-P and PD patients compared with those in the controls (p<0.05). VBM analysis revealed multifocal cortical and subcortical atrophy in both MSA-P and PD patients, and the volumes of the cerebellum and temporal lobes were remarkably reduced in MSA-P patients compared with the volumes in PD patients (p<0.05). CONCLUSIONS: Both PD and MSA-P are associated with gray matter atrophy, which mainly involves the bilateral putamen, caudate nucleus, cerebellum, and temporal lobes. ROI and VBM can be used to identify these morphological alterations, and VBM is more sensitive and repeatable and less time-consuming, which may have potential diagnostic value.

Kinetic study of pyrrolizidine alkaloid-derived pyrrole-protein adducts in rats after intragastric administration of Gynura japonica / 药学学报

Recently, hepatic sinusoidal obstruction syndrome (HSOS) induced by misuse of Gynura japonica has increased and gained global attention. Large amounts of pyrrolizidine alkaloids (PAs) are present in G. japonica; these PAs are metabolically activated to generate pyrrole-protein adducts (PPAs). In this study, male SD rats were treated orally with a single dose of G. japonica extract (GJE) at 0.062 5, 0.25, 0.5, 1, and 2 g·kg-1. Blood was collected from the orbital venous plexus at 2, 12, 24 and 48 h, and at 48 h after treatment the rats were anesthetized with isoflurane and livers were collected for hematoxylin & eosin staining. The kinetics of PPAs at different doses were studied at 10, 20, 30 min, 1, 2, 4, 6, 12, 24 h, and 48 h, after a single gavage of GJE. The experimental scheme was approved by the ethics committee of animal experiments of Shanghai University of Traditional Chinese Medicine (PZSHUTCM190912019). The concentration of PPAs in serum was determined by liquid chromatography-mass spectrometry (LC-MS). Kinetic data were processed by using the non-compartmental pharmacokinetics data analysis software program PK solutions 2™. The results demonstrate that the concentration of PPAs increased with the dose of GJE and positively correlated with the severity of liver injury. The elimination rate of PPAs in rats was significantly prolonged at higher doses. The level of PPAs and their clearance rate may serve as useful references for the detoxification of PAs-induced injuries.

Influence of Rho kinase inhibitor combined furosemide and spironolactone on cardiac function , serum levels of AST , LDH and CK‐MB in patients with acute left heart failure／ / 心血管康复医学杂志

To explore application value of Rho kinase inhibitor (RKI) combined furosemide and spironolactone in patients with acute left heart failure (ALHF).Methods : A total of 94 ALHF patients were randomly and equally divided into diuretic group (received furosemide and spironolactone based on routine treatment ) and triple therapy group (received RKI‐‐fasudil hydrochloride based on diuretic group ) , both groups were continuously treated for 7d.LVESV , LVEDV , LVEF ,serum levels of aspartate transaminase (AST) , lactate dehydrogenase (LDH) and creatine kinase isoenzyme MB (CK‐MB) before and after treatment , therapeutic effects were observed and compared between two groups .Results : Total effective rate of triple therapy group was significantly higher than that of diuretic group (95.75% vs.82.98%) , P＝0.045. Compared with before treatment , there was significant rise in LVEF , and significant reductions in LVESV , LV‐EDV ,serum levels of AST , LDH and CK‐MB in two groups after treatment , P＝0.001 all ;compared with diuretic group after treatment , there was significant rise in LVEF [ (48.27 ± 5.95)% vs.(55.14 ± 6.74)%] , and significant reductions in LVESV [ (86.29 ± 10.41) ml vs.(65.96 ± 9.84) ml] , LVEDV [ (133.71 ± 13.42) ml vs.(120.35 ± 11.25) ml] , serum levels of AST [ (81.23 ± 10.44) U／L vs.(57.58 ± 8.42) U／L] , LDH [ (184.24 ± 13.51) U／Lvs.(124.65 ± 12.42) U／L] and CK‐MB [ (187.84 ± 13.45) U／L vs.(132.54 ± 11.69) U／L] in triple therapy group , P＝0.001 all. There was no significant difference in adverse reactions during treatment between two groups , P＞0.05 both .Conclusion :Rho kinase inhibitor combined furosemide and spironolactone can significantly improve cardiac function and reduce myocar ‐dial damage , and it＇s safe and reliable , which is worth extending .

The improvement of bioactive secondary metabolites accumulation in Rumex gmelini Turcz through co-culture with endophytic fungi

Abstract Aspergillus sp., Fusarium sp., and Ramularia sp. were endophytic fungi isolated from Rumex gmelini Turcz (RGT), all of these three strains could produce some similar bioactive secondary metabolites of their host. However the ability to produce active components degraded significantly after cultured these fungi alone for a long time, and were difficult to recover. In order to obtain more bioactive secondary metabolites, the co-culture of tissue culture seedlings of RGT and its endophytic fungi were established respectively, and RGT seedling was selected as producer. Among these fungi, Aspergillus sp. showed the most significant enhancement on bioactive components accumulation in RGT seedlings. When inoculated Aspergillus sp. spores into media of RGT seedlings that had taken root for 20 d, and made spore concentration in co-culture medium was 1 × 104 mL-1, after co-cultured for 12 d, the yield of chrysophaein, resveratrol, chrysophanol, emodin and physcion were 3.52-, 3.70-, 3.60-, 4.25-, 3.85-fold of the control group. The extreme value of musizin yield was 0.289 mg, which was not detected in the control groups. The results indicated that co-culture with endophytic fungi could significantly enhance bioactive secondary metabolites production of RGT seedlings.

Protective Effect of Norcantharidin on Collagen-Induced Arthritis Rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of norcantharidin (NCTD) on collagen-induced arthritis (CIA) rats.</p><p><b>METHODS</b>Sixty Sprague-Dawley(SD) rats were randomly divided into 6 groups (n=10): normal group, CIA model group(model group), NCTD low-dose group [1.35 mg/(kg•d)], NCTD middle-dose group [2.7 mg/(kg•d)], NCTD high-dose group [5.4 mg/(kg•d)] and methotrexate (MTX) group [1.8 mg/(kg/w)]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin (H&E) staining. The serum levels of interleukin (IL) 1β, IL-6, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), IL-17 and transform growth factor (TGF) β were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression of retinoid-related orphan nuclear receptorγt (RORγt) and forkhead box P3 (Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction.</p><p><b>RESULTS</b>MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats' ankle joints compared with the model group (P<0.05 or P<0.01). All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats (P<0.05). Only middle- and high-dose of NCTD prominently decreased serum IL-1β and TGF-β levels of CIA rats (P<0.05). However, NCTD has no effect on vascular endothelial growth factor (VEGF) level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group (P<0.05). The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group (P<0.05).</p><p><b>CONCLUSIONS</b>NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.</p>