Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations / 中华儿科杂志

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism.@*METHODS@#THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot.@*RESULTS@#1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway.@*CONCLUSION@#Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

Clinical Characteristics and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively.@*RESULTS@#4 patients had bone marrow， spleen and lymph nodes involvement， 2 patients had skin lesions， and 3 patients had central nervous system infiltration． Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients， and CD304 in 3 patients． One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again． One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine.@*CONCLUSION@#The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.

Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome / 生物医学与环境科学（英文）

OBJECTIVE@#Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).@*METHODS@#We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.@*RESULTS@#Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.@*CONCLUSION@#Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.

Predictive value of left ventricular ejection fraction reserve assessed by SPECT G-MPI for major adverse cardiovascular event in patients with coronary artery disease / 中华心血管病杂志

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.

Predictive value of the proportion of hibernating myocardium in total perfusion defect on reverse remodeling in patients with HFrEF underwent coronary artery bypass graft / 中华心血管病杂志

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with 18F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with 18F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and 18F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and 18F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.

Clinical and genetic spectrum of SCN2A gene associated epilepsy and episodic ataxia / 中华儿科杂志

Objective: To explore the clinical manifestations and genetic characteristics of patients with epilepsy and episodic ataxia caused by SCN2A gene variation. Methods: The clinical data of seizure manifestation, imaging examination and genetic results of 5 patients with epilepsy and (or) episodic ataxia because of SCN2A gene variation admitted to the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University from July 2017 to January 2021 were analyzed retrospectively. Results: Among 5 patients, 4 were female and 1 was male. The onset age of epilepsy ranged from 4 days to 8 months. There were 2 cases of benign neonatal or infantile epilepsy and 3 cases of epileptic encephalopathy, in whom 1 case had development retardation,1 case transformed from West syndrome to infantile spasm and another one transformed from infantile spasm to Lennox-Gastaut syndrome. One case of benign neonatal-infantile epilepsy was characterized by neonatal onset seizures and episodic ataxia developed at the age of 78 months. Electroencephalograms at first visit of 5 cases showed that 2 cases were normal, 1 case had focal epileptic discharge, and 2 cases had multi-focal abnormal discharge with peak arrhythmia. The brain magnetic resonance imaging (MRI) of 3 cases were nomal, 1 case was abnormal (brain atrophy with decreased white matter) and the results of 1 case was unknown. The follow-up time ranged from 17 months to 89 months. Four cases of epilepsy were controlled and 1 case died at 2 years of age. Two cases had normal intelligence and motor development, 2 had moderate to severe intelligence retardation and motor critical state, and 1 had moderate to severe intelligence and motor development retardation. SCN2A gene variations were identified in all cases. There were 4 missense variations and 1 frameshift variation. Three variations had not been reported so far, including c.4906A>G,c.3643G>T,c.638delT. Conclusions: Variations in SCN2A gene can cause benign neonatal or infantile epilepsy and epileptic encephalopathy. Some children develop episodic ataxia with growing age. The variation of SCN2A gene is mainly missense variation.

Chronic Toxicity of Tanreqing Injection in Beagle Dogs / 中国实验方剂学杂志

Objective:To observe the possible toxicity of long-term intravenous injection of Tanreqing injection in Beagle dogs， so as to provide experimental data for its clinical safe medication. Method:A total of 32 Beagle dogs （16 males and 16 females） were randomly divided into the low- （2.5 mL·kg^-1）， medium- （5.0 mL·kg^-1）， and high-dose （10.0 mL·kg^-1） Tanreqing injection groups and control group according to their body mass indices， with eight dogs in each group. In the waking state， the dogs were treated with intravenous injection of corresponding drugs into the medial cephalic vein of forelimb for 13 weeks， followed by four-week drug withdrawal. After the observation of general condition， body mass， and food consumption， the Beagle dogs were subjected to electrocardiography， ophthalmoscopy， hematological examination， serum biochemistry， and blood coagulation test in the middle of medication （week 6）， at the end of medication （week 13）， and during recovery （week 17）. Then the gross anatomy was conducted for calculating the major organ coefficients and observing the histopathological changes. Result:No obvious toxic reaction was found in each group， but the decreased fibrinogen and increased Kupffer's cells phagocytizing yellow-brown pigment in hepatic sinusoids were observed in the high-dose Tanreqing injection group following three months of medication. Reduction of fibrinogen was not observed in recovery period， but Kupffer's cells that phagocytized yellow-brown pigment still existed. Conclusion:The intravenous injection of Tanreqing injection at 2.50 mL·kg^-1（low dose）， 5.00 mL·kg^-1 （medium dose） or 10.00 mL·kg^-1（high dose） for three months in Beagle dogs resulted in no obvious toxic reaction. However， it is still suggested to test the liver function and blood coagulation after long-term administration of high-dose Tanreqing injection.

Plant metabolomics for studying the effect of two insecticides on comprehensive constituents of Lonicerae Japonicae Flos / 中国天然药物

Pesticides' overuse and misuse have been reported to induce ingredient variations in herbal medicine, which is now gaining attention in the medicinal field as a form of alternative medicine. To date, available studies on pesticide-induced ingredient variations of herbal medicine are limited only on a few compounds and remain most others unexamined. In this study, a plant metabolomics-based strategy was performed to systematically explore the effects of two frequently used insecticides on the comprehensive constituents of Lonicerae Japonicae Flos (LJF), the flower buds of Lonicera japonica Thunb. Field trials were designed on a cultivating plot of L. japonica with controls and treatments of imidacloprid (IMI) and compound flonicamid and acetamiprid (CFA). Unbiased metabolite profiling was conducted by ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometer. After data pretreatment by automatic extraction and screening, a data matrix of metabolite features was submitted for statistical analyses. Consequently, 29 metabolic markers, including chlorogenic acids, iridoids and organic acid-glucosides were obtained and characterized. The relative quantitative assay was subsequently performed to monitor their variations across flowering developments. This is the first study that systematically explored the insecticide-induced metabolite variations of LJF while taking into account the inherent variability of flowering development. The results were beneficial for holistic quality assessment of LJF and significant for guiding scientific use of pesticides in the large-scale cultivation.

Advances on metabolizing enzyme and transporter mediated potential interactions between ciprofloxacin and Chinese materia medica / 中草药

The combination of Chinese and Western medicine is common in clinical practice. Ciprofloxacin is one of the most commonly used fluoroquinolones for the treatment of infectious diseases. In order to improve the therapeutic effect of infectious diseases or cope with patients with multiple diseases at the same time, the combination of ciprofloxacin with one or more traditional Chinese medicines is more common. The herb-drug interactions produced by the combination of Chinese materia medica and ciprofloxacin may play an active role in increasing efficacy and reducing toxicity, and may also lead to treatment failure or adverse reactions. The herb-drug interaction mechanisms will occur in the course of absorption (A), distribution (D), metabolism (M), and excretion (E). The effects of drug-metabolizing enzymes and transporters on the ADME process of ciprofloxacin have received much attention in recent years. Therefore, this paper reviews the potential interaction between common Chinese medicine and ciprofloxacin from the perspective of drug-metabolizing enzymes and transporters. It is expected to provide the basis on the rational use of ciprofloxacin and Chinese materia medica.

Thromboxane A2 receptor contributes to the activation of rat pancreatic stellate cells induced by 8-epi-prostaglandin F2α / 中华医学杂志(英文版)

BACKGROUND@#Pancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA2r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA2r in the activation of PSCs induced by 8-epi-prostaglandin F2α (8-epi-PGF2α).@*METHODS@#TxA2r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF2α (10, 10, 10 mol/L) for 48 h, and SQ29548 (10, 10, and 10 mol/L), a TxA2r-specific antagonist for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10 mol/L) for 2 h, followed by 10 mol/L 8-epi-PGF2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student's t test.@*RESULTS@#TxA2r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF2α significantly increased mRNA levels of α-SMA (10 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t = 10.70, P < 0.001; 10 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t = 10.83, P < 0.001; 10 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t = 11.40, P < 0.001) and collagen I (10 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t = 15.41, P < 0.001) and α-SMA (10 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t = 15.17, P < 0.001; 10 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t = 11.29, P < 0.001; 10 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t = 12.86, P < 0.001). After being treated with SQ29548 (10 mol/L) and then 8-epi-PGF2α (10 mol/L), the mRNA levels of α-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t = 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group.@*CONCLUSIONS@#The results show that 8-epi-PGF2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF2α. The result indicated that TxA2r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.

Comparison of epidemiological and clinical characteristics of COVID-19 patients with and without Wuhan exposure history in Zhejiang Province, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

BACKGROUND@#A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure.@*METHODS@#We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan.@*RESULTS@#Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups.@*CONCLUSIONS@#From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.

Atomization Characteristics of Baicalin， Ursodeoxycholic Acid and Caffeic Acid in Tanreqing Inhalation Solution / 中国实验方剂学杂志

Objective:To investigate the effect of different angles of atomizer on the delivery rates and total delivery quantities of Tanreqing inhalation solution， so as to provide reference for the clinical use of this preparation. Method:Taking baicalin， ursodeoxycholic acid， caffeic acid as indexes， PARI Boy SX compression atomization inhaler （equipped with red core atomizing cup） and BRS2000 respiratory simulator were used， the effects of different angles of the atomizer （upper 15 degree， lower 15 degree， upper 30 degree， lower 30 degree， partial 15 degree， partial 30 degree， vertical） on the delivery rates and total delivery quantities of Tanreqing inhalation solution were investigated. The respiratory patterns of adults， children， infants and young children were selected to determine the delivery rates and total delivery quantities of three components in Tanreqing inhalation solution. Result:In the same atomization time， the delivery rates and the total delivery quantities of caffeic acid and ursodeoxycholic acid in Tanreqing inhalation solution were not significantly affected by the atomizer from different angles， but significantly affected baicalin. At the vertical angle， the delivery rate and total delivery quantity of baicalin were higher than the other angles. Under different respiratory modes， there were significant differences in the delivery rates and total delivery quantities of these three components in the inhalation solution. Compared with other respiratory modes， the delivery rates and total delivery quantities of baicalin， ursodeoxycholic acid and caffeic acid were the highest in the adult respiratory mode， with delivery rates of （555.5±16.61）， （226.3±6.54）， （26.1±0.32） μg·min-1 and total delivery quantities of （4 001.1±82.97）， （1 754.9±63.73）， （167.6±1.42） μg， respectively. Conclusion:The use angle of atomizer has a certain effect on the delivery rate and total delivery quantity of Tanreqing inhalation solution， so it is suggested that the vertical angle should be kept as far as possible in clinical use. Under the four respiratory patterns， the delivery rate and total delivery quantity of Tanreqing inhalation solution are different， suggesting that the atomization dose or atomization time should be adjusted according to the respiratory characteristics of the patients to ensure the safety and effectiveness of clinical medication.

Association between brain glucose metabolism and cardiac dysfunction in patients with ischemic heart disease undergoing (18)F-FDG PET/CT imaging / 中华心血管病杂志

Objective: To evaluate the relationship between the brain glucose metabolism and left ventricular function parameters, and to explore the cerebral glucose metabolism reduction regions in patients with ischemic heart disease (IHD). Methods: A total of 110 consecutive IHD patients who underwent gated (99)Tc(m)-sestamibi (MIBI) SPECT/CT myocardial perfusion imaging, gated (18)F-fluorodeoxyglucose (FDG) PET/CT myocardial and brain glucose metabolic imaging within three days in Beijing Anzhen Hospital from April 2016 to October 2017, were enrolled in this study. Left ventricular functional parameters of SPECT/CT and PET/CT including end-diastolic volume (EDV), end-systolic volume (ESV) and left ventricular ejection fraction (LVEF) were analyzed by QGS software. Viable myocardium and myocardial infarction region were determined by 17-segment and 5 score system, and the ratio of viable myocardium and scar myocardium was calculated. According to the range of viable myocardium, the patients were divided into viable myocardium<10% group (n=44), viable myocardium 10%-<20% group (n=36) and viable myocardium≥20% group (n=30). Pearson correlation analysis was used to analyze the correlation between the range of viable myocardium and scar myocardium and the level of cerebral glucose metabolism. Brain glucose metabolism determined by the mean of standardized uptake value (SUV(mean)) was analyzed by SPM. The ratio of SUV(mean) in whole brain and SUV(mean) in cerebellum were calculated, namely taget/background ratio (TBR). Differences in cerebral glucose metabolism among various groups were analyzed by SPM. Results: There were 101 males, and age was (57±10) years in this cohort. The extent of viable myocardium and the extent of scar, LVEF evaluated by SPECT/CT and PET/CT were significantly correlated with TBR (r=0.280, r=-0.329, r=0.188, r=0.215 respectively,all P<0.05). TBR value was significantly lower in viable myocardium<10% group, compared with viable myocardium 10%-<20% group (1.25±0.97 vs. 1.32±0.17, P<0.05) and viable myocardium≥20% group (1.25±0.97 vs. 1.34±0.16, P<0.05). Furthermore, in comparison with viable myocardium≥20% group, the hypo-metabolic regions of viable myocardium<10% group were located in the precuneus, frontal lobe, postcentral gyrus, parietal lobe, temporal lobe, and so on. Conclusions: There is a correlation between impaired left ventricular function and brain glucose metabolism in IHD patients. In IHD patients with low myocardial viability, the level of glucose metabolism in the whole brain is decreased, especially in the brain functional areas related to cognitive function.

Effect of Tanreqing Injection Combined with Imipenem-cilastatin in Inhibiting Extensively-drug Resistant Pseudomonas aeruginosa / 中国实验方剂学杂志

Objective:To observe the effect of combination of Tanreqing injection(Tanreqing) and imipenem-cilastatin on extensively-drug resistant Pseudomonas aeruginosa (XDPA), and study the mechanism of the combination. Method:The minimum inhibitory concentrations (MICs) of Tanreqing and imipenem-cilastatin against planktonic XDPA strain isolated in clinic were determined by the broth microdilution method. The checkerboard method was used to evaluate the combination effect. The bacterial metabolic activity in mature biofilm was studied by microtiter-plate test. The destructive effect of combination drugs on dynamic biofilm was observed by using BioFlux system, and viable cells were examined by confocal laser scanning microscope (CLSM) after treatment. The scanning electron microscopy (SEM) was used for observing Pseudomonas aeruginosa and length measurement. Result:The MIC values of imipenem-cilastatin and Tanreqing were 512 mg·L-1 and more than 16 500 mg·L-1. The checkerboard analysis showed that Tanreqing could enhance the sensitivity of imipenem-cilastatin, while the combination drugs synergistically inhibited the growth of bacteria. Compared with the control group or the imipenem-cilastatin individual group, the combined drugs significantly reduced the amount of living bacteria in the biofilm (PPPConclusion:Tanreqing and imipenem-cilastatin synergistically inhibit the bacterial growth in planktonic and biofilm states, and destruct biofilms.

Effect of Gancao Xiexintang Combined with Vitamin B12 on T Lymphocyte Subset, Ulcer Area, Oral Flora in Children with Recurrent Oral Ulcer / 中国实验方剂学杂志

Objective:To investigate the clinical efficacy of Gancao Xiexintang combined with vitamin B12 on recurrent oral ulcer (ROU) in children. Method:Totally 116 children with ROU admitted in Jiangxi Provincial Children's Hospital from June 2016 to June 2018 were divided into observation group and control group on the basis of random number table,with 58 cases in each group. The control group was orally treated with vitamin B12, while the observation group was orally treated with Gancao Xiexintang in addition to the therapy of the control group. All of the children were treated for 14 days. Clinical efficacy, changes of T lymphocyte subset (CD3+, CD4+, CD8+, CD4+/CD8+), ulcer area, content of oral flora (veillonella, streptococcus) before and after treatment, and side effect were compared between the two groups. Result:The overall effective rate of the observation group was 96.6%(56/58), which was much higher than 84.5%(49/58) of the control group (P+, CD4+, CD4+/CD8+in peripheral blood, but lower CD8+compared with those before treatment (P+, CD4+, CD8+, CD4+/CD8+) indexes in observation group was improved more significantly (PPPPPConclusion:In treating ROU in children, the combination of Gancao Xiexintang and vitamin B12 can significantly correct imbalance of T lymphocyte subset, promote the recovery of oral ulcer, and positively regulate oral micro-ecological environment, with an exact curative effect and high patient tolerance.

Mechanisms of quinolone resistance of carbapenem-resistant Enterobacteriaceae / 中国感染控制杂志

Objective To study the prevalence of plasmid-mediated quinolone resistance (PMQR) genes in carbapenem-resistant Enterobacteriaceae (CRE) and its resistance mechanism.Methods Clinically isolated CRE strains in a hospital from March 2015 to March 2018 were collected, then identified and performed antimicrobial susceptibility test by VITEK2 Compact analyzer, carriage of PMQR genes qnrA, qnrB, qnrS, qepA and acc (6') Ib-cr were determined by polymerase chain reaction (PCR) and sequencing, the horizontal transfer of PMQR genes were verified by plasmid conjugation test.Results Resistance rates of carbapenem-resistant Escherichia coli and carbapenem-resistant Klebsiella pneumoniae to quinolones were 100％ and 15.56％-33.33％ respectively.Detection rate of acc (6') Ib-cr gene was the highest (87.72％), followed by qnrB (77.19％) and qnrS (17.54％), 2 strains (3.51％) carried qnrA gene, qepA gene was not isolated, 84.21％ of strains harbored 2 or 3 PMQR genes.PMQR gene was transfected into all the 8 conjugated strains, but minimum inhibitory concentration value of quinolones didn't change significantly.Conclusion The detection rate of PMQR genes in CRE in this hospital is high, but there is a certain sensitivity to quinolones.

Two new phenolic glycosides isolated from the fruits of Citrus aurantium / 中国天然药物

The present study was designed to investigate the chemical constituents of the fruit of Citrus aurantium L.. The compounds were isolated and purified by various chromatographic techniques, and their structures were elucidated on the basis of physicochemical properties and spectral data. Two new phenolic glycosides (compounds 1 and 2) were obtained and identified as 1-O-3, 5-dihydroxyphenyl-(6-O-4-hydroxybenzoyl)-β-D-glucopyranoside (1) and 1-O-3, 5-dihydroxyphenyl-(6-O-3-methoxy-4-hydroxy benzoyl)-β-D-glucopyranoside (2), respectively.

Transrectal ultrasound conductance-guided administration of traditional Chinese medicine for histological prostatitis in men with small-size BPH and LUTS after TURP / 中华男科学杂志

Objective@#To investigate the effects of transrectal ultrasound conductance (TRUSC)-guided administration of traditional Chinese medicine on histological prostatitis in men with small-size BPH and low urinary tract symptoms (LUTS) after transurethral resection of the prostate (TURP).@*METHODS@#This study included 167 BPH patients without surgical contraindications. We randomized the patients into an experimental group (n = 84) and a control group (n = 83), with no statistically significant differences between the two groups in age, prostate volume, International Prostate Symptom Score (IPSS), and quality of life (QoL) (P >0.05). The patients of the experimental group received TRUSC-guided administration of traditional Chinese medicine, qd, for 7 days before TURP, while those of the control group underwent TURP only. After treatment, we compared the results of postoperative pathological examination of the prostate tissue, the histological grade of inflammation, IPSS, and QoL scores between the two groups of patients.@*RESULTS@#In the experimental group, there were 12 cases of non-inflammation (14.3%), 43 cases of mild inflammation (51.2%), 28 cases of moderate inflammation (33.3%), and 1 case of severe inflammation (1.2%), as compared with 8 cases of non-inflammation (9.6%), 28 cases of mild inflammation (33.7%), 45 cases of moderate inflammation (51.8%), and 2 cases of severe inflammation (2.4%) in the control group (P <0.05). Compared with the baseline, both the experimental and control groups showed significant improvement at 4 weeks after surgery in IPSS (22.20±4.14 vs 4.26±2.64 and 23.05±4.11 vs 7.02±4.15, P <0.05) and QoL scores (4.33±0.83 vs 1.25±1.64 and 4.25±0.91 vs 2.05±1.95, P <0.05).@*CONCLUSIONS@#TRUSC-guided administration of traditional Chinese medicine can significantly alleviate histological inflammation and improve QoL in men with small-size BPH and LUTS after TURP.

Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-γ and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats.</p><p><b>METHODS</b>Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups: ControlTAK242, IgANTAK242, toll-like receptor 4 inhibitor (TAK242) groups (rats were administrated with TLR4 inhibitor, TAK242) and ControlPio, IgANPio, Pio groups (rats were administrated with PPAR-γ agonist, pioglitazone). Urinary albumin-to-creatinine ratio (ACR), serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin-1 beta (IL-1β) message ribonucleic acid (mRNA) and protein expression in renal tissues. Results were presented as mean ± standard deviation. Differences between groups were analyzed by one-way analysis of variance.</p><p><b>RESULTS</b>Compared to normal rats, experimental rats showed higher ACR (4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P < 0.05), obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-1β (48.28 ± 13.49 pg/ml vs. 35.56 ± 7.41pg/ml, P < 0.05), and renal expression of IL-1β and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-1β, and serum IL-1β were decreased in rats treated with TAK242, and the expression of TLR4 mRNA and protein was significantly reduced in Pio group compared to IgANPiogroup (1.22 ± 0.28 vs. 1.72 ± 0.45, P < 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P < 0.01).</p><p><b>CONCLUSIONS</b>Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.</p>