Abnormal liver biochemical parameters in pregnancy during the epidemic of coronavirus disease 2019 / 临床肝胆病杂志

ObjectiveTo investigate the differences in abnormal liver biochemical parameters in pregnant patients during the epidemic or non-epidemic period of coronavirus disease 2019 （COVID-19）. MethodsA retrospective analysis was performed for 539 pregnant women who were discharged from Department of Obstetrics， Peking University First Hospital， from October 2017 to March 2022 and had at least one abnormal liver biochemical parameter among alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBil）， and total bile acid. The patients in the epidemic period of COVID-19 and those in the non-epidemic period of COVID-19 were compared in terms of etiology， coagulation parameters， aminotransferases， bile acid， and renal function. The independent samples t-test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. ResultsAmong the patients discharged from Department of Obstetrics during the non-epidemic period of COVID-19， 262 had abnormal liver biochemical parameters， accounting for 1.46%， while 277 patients had abnormal liver biochemical parameters during the epidemic period of COVID-19， accounting for 1.73% among the patients discharged from Department of Obstetrics during the same period of time， and there was a significant difference between these two groups （χ2=3.947， P=0.047）. The etiological analysis of the patients with abnormal liver biochemical parameters during the two periods showed that there was no difference in the proportion of patients with four pregnancy-specific liver diseases （hyperemesis gravidarum， preeclampsia and eclampsia， intrahepatic cholestasis of pregnancy， and acute fatty liver of pregnancy）. As for the patients with abnormal liver biochemical parameters in pregnancy， there was no significant difference in the proportion of patients with normal creatinine and stimated glomerular filtration rate （eGFR） between the epidemic period and the non-epidemic period （86.78% vs 87.90%， χ2=0.141， P=0.708）. The patients with ALT≥5×upper limit of normal accounted for 7.94% in the epidemic period of COVID-19 and 9.54% in the non-epidemic period （χ2=0.433， P=0.511）， and the patients with severe cholestasis accounted for 7.75% in the epidemic period of COVID-19 and 9.27% in the non-epidemic period （χ2=0.392， P=0.531）. The proportion of patients with obstetric bleeding during the epidemic period of COVID-19 was significantly lower than that during the non-epidemic period （14.61% vs 24.19%， χ2=489.334， P<0.001）. ConclusionThere is no difference in the proportion of patients with pregnancy-specific liver diseases among the patients with abnormal liver biochemical parameters in pregnancy between the epidemic period and the non-epidemic period of COVID-19， and there is no change in the proportion of patients with normal creatinine and eGFR among these patients in the epidemic period of COVID-19.

Association between Helicobacter pylori infection and albuminuria among physical examination population / 中华健康管理学杂志

Objective:To investigate the correlation between Helicobacter pylori ( H.pylori) infection and albuminuria inphysical examination population. Methods:It was a cross-sectional study. All the adults who received physical examination and underwent 13C-urea breath test at the Physical Examination Center in Tongji Hospital in 2021 were selected as the study subjects. General data (such as demographic information and past medical history) were documented. The physical measurement and blood biochemical indicators were checked too. Multivariate analysis was used to analyze the relationship between H. pylori infection and albuminuria. Results:A total of 30 311 subjects were included in this analysis. There were 17 123 males and 13 188 females with an age of (44.51±12.17) years. The positive rate of H. pylori infection was 27.3%. The incidence of albuminuria in subjects with H. pylori infection was 6.7%, and it was 6.1% in the subjects without H. pylori infection ( P=0.031). After adjusting for the confounding factors such as gender, age, diabetes and hypertension, H. pylori infection was independently associated with the risk of albuminuria (odds ratio ( OR)=1.133, 95% CI: 1.018-1.261, P=0.022). Conclusion:H. pylori infection is positively correlated with the occurrence of albuminuria in the physical examination population.

Advances in Phytochemistry and Modern Pharmacology of Saposhnikovia Divaricata (Turcz.) Schischk / 中国结合医学杂志

Saposhnikovia divaricata (Turcz.) Schischk (S. divaricata, Fangfeng) is a herb in the Apiaceae family, and its root has been used since the Western Han Dynasty (202 B.C.). Chromones and coumarins are the pharmacologically active substances in S. divaricata. Modern phytochemical and pharmacological studies have demonstrated their antipyretic, analgesic, anti-inflammatory, antioxidant, anti-tumor, and anticoagulant activities. Technological and analytical strategy theory advancements have yielded novel results; however, most investigations have been limited to the main active substances-chromones and coumarins. Hence, we reviewed studies related to the chemical composition and pharmacological activity of S. divaricata, analyzed the developing trends and challenges, and proposed that research should focus on components' synergistic effects. We also suggested that, the structure-effect relationship should be prioritized in advanced research.

Functional annotation map of natural compounds in traditional Chinese medicines library: TCMs with myocardial protection as a case

The chemical complexity of traditional Chinese medicines (TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform (TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included: (1) selection of herbal drugs of target based on TCMs knowledge base; (2) chemome profiling of TCMs extract library by LC‒MS; (3) cytological profiling of TCMs extract library by high-content cell-based imaging; (4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes; (5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs (Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089 mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.

Effects of occupational therapy on upper extremity for patients with stroke: a systematic review using WHO-FICs / 中国康复理论与实践

ObjectiveTo construct a framework of PICO for occupational therapy to improve upper extremity function in stroke patients based on World Health Organization Family of International Classifications (WHO-FICs), and to analyze the functional outcome of major occupational therapies to improve upper extremity in stroke. MethodsUsing the WHO-FICs framework, the databases such as Web of Science, PubMed, CNKI and SinoMed were searched for literature related to occupational therapy interventions for upper extremity function in stroke patients from the date of establishment to October, 2022, and the contents of the literature were extracted for a systematic review. ResultsTen randomized controlled trials from six countries were finally included, involving 382 participants (≥ 18 years old). The literatures were mainly from the fields of rehabilitation medicine, physics and rehabilitation medicine, neuroscience, bioengineering medicine, occupational therapy and other research fields, and were published mainly after 2013. The quality of the included literatures was evaluated using Physiotherapy Evidence Database (PEDro) scale with a mean score of 7.5. Based on the WHO-FICs framework, the types of diseases included intracerebral haemorrhage (8B00), cerebral ischemic stroke (8B11), subarachnoid hemorrhage (8B01), abnormality of tonus and reflex (MB47), and hemiplegia (MB53). The main dysfunctions of the upper extremity after stroke included mobility of joint functions (b710), stability of joint functions (b715), muscle power functions (b730), muscle tone functions (b735), motor reflex functions (b750), control of voluntary movement functions (b760), involuntary movement functions (b765). Activity and participation included activity of upper limb, such as lifting and carrying objects (d430), hand and arm use (d445), and fine hand use (d440); and the daily life activities and social participation, such as self-care (d510-d570), domestic life (d610-d660), major life areas (d810-d879), community, social and civic life (d910-d950). Therapeutic interventions on body functions included electrical stimulation of muscle functions (MU2.SC.BP), assistance and guidance of exercise for involuntary movement reaction (MV2.PG.ZZ); therapeutic interventions involving activity and participation were training in lifting and carrying (SIA.PH.ZZ), training in fine hand use (SIG.PH.ZZ), exercises of arm and hand use (SIJ.PH.ZZ), self care (SM1-SMH), household tasks (SO2-SOD), and playing games (SXD.PH.ZZ); 15 to 60 minutes a time, three to ten times a week, for three to eight weeks, in hospital or at home. The outcomes of the intervention were divided into three levels. At the body function level, patients had improved neuromotor conduction function, reflex function, casual motor control, coordination and speed, joint mobility, and grip strength. At the activity and participation level, there were enhancements in upper limb mobility and speed, fine hand function and speed, frequency and quality of upper limb activity participation, and the capacities of daily living and reduced difficulty in daily activity tasks. In terms of whole functioning, patients had acquired quality of life and well-being and acquainted a feeling of pleasure and accomplishment. ConclusionA PICO framework was constructed for occupational therapy based on WHO-FICs. The health conditions included intracerebral haemorrhage, cerebral ischemic stroke, subarachnoid hemorrhage, abnormality of tonus and reflex, and hemiplegia. Upper extremity motor dysfunction mainly included dysfunction of voluntary motor control, low or hyperactive motor reflexes, abnormalities in muscle tone, impaired muscle coordination, poor stability of joint activities, and reduced muscle strength, etc. Activity limitation and participation restriction were manifested as functioning in the fields of arm and hand activity participation, fine manual activity, and activities of daily living and social participation. Therapeutic interventions at body function level included brain-computer interface-based functional electrical stimulation and unimanual mirror therapy; therapeutic interventions at activity and participation level included action observation training, bimanual mirror therapy, task-oriented training, bilateral arm training and upper extremity robotics training. The health and functional benefits included the improvements in upper extremity motor function, upper extremity mobility and participation levels, activities of daily living and social participation, and quality of life and well-being.

Characterization and identification of alkaloids in Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex based on UHPLC-IM-Q-TOF-MS / 中国中药杂志

A strategy combining collision cross section(CCS) prediction and quantitative structure-retention relationship(QSRR) model for quinoline and isoquinoline alkaloids was established based on UHPLC-IM-Q-TOF-MS and applied to Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex. The strategy included the following three steps.(1) The molecular features were extracted by the "find features" algorithm.(2) The potential quinoline and isoquinoline alkaloids were screened by filtering the original characteristic ions extracted from Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex by the established CCS vs m/z prediction interval.(3) According to the retention time of candidate compounds predicted by QSRR model, the chemical constituents were identified in combination with the characteristic fragment ions and pyrolysis law of secondary mass spectrometry. With the strategy, a total of 80 compounds were predicted, and 15 were identified accurately. The strategy is effective for the identification of small analogs of traditional Chinese medicine.

Cloning, expression analysis and enzyme activity verification of dihydroflavonol 4-reductase from Cistanche tubulosa (Schenk) Wight flower / 药学学报

Dihydroflavonol 4-reductase (DFR) plays an essential role in the biosynthesis of anthocyanin and regulation of plant flower color. Based on the transcriptome data of Cistanche tubulosa (Schenk) Wight, a full-length cDNA sequence of CtDFR gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR). CtDFR contains an open reading frame (ORF) of 1 263 bp which encodes 420 amino acids with a predicted molecular weight of 47.5 kDa. The sequence analysis showed that CtDFR contains a nicotinamide adenine dinucleotide phosphate (NADPH) binding domain and a specific substrate binding domain. The expression analysis indicated that CtDFR was highly expressed in red and purple flowers, and the relative expression levels were 4.04 and 19.37 times higher than those of white flowers, respectively. The recombinant CtDFR protein was expressed in E.coli BL21 (DE3) using vector pET-28a-CtDFR and was purified. In vitro enzyme activity analysis, CtDFR could reduce three types of dihydroflavonols including dihydrokaempferol, dihydroquercetin, and dihydromyricetin to leucopelargonidin, leucocyanidin and leucodelphinidin. Subcellular localization analysis showed that CtDFR was mainly localized in the cytoplasm. These results demonstrate that CtDFR plays an important role in regulation of flower color in C. tubulosa and make a valuable contribution for the further investigation on the regulation mechanism of C. tubulosa (Schenk) Wight flower color.

Comparison of curative effect between Tianji robot assisted screw placement and traditional cannulated screw internal fixation for femoral neck fracture / 中国骨伤

OBJECTIVE@#To investigate the clinical efficacy and advantages of Tianji orthopedic robot assisted cannulated screw internal fixation for femoral neck fracture.@*METHODS@#The clinical data of 41 patients with femoral neck fracture who underwent internal fixation with cannulated screws from January 2019 to January 2022 were retrospectively analyzed. According to different surgical methods, they were divided into Tianji robot group and traditional cannulated screw fixation group (traditional operation group). Among them, there were 18 patients in Tianji robot group including 8 males and 10 females with age of (56.00±4.22) years old, Garden typeⅠ (4 cases), type Ⅱ (11 cases), type Ⅲ (2 cases), and type Ⅳ (1 case). There were 23 patients in the traditional operation group, including 10 males and 13 females, aged (54.87±4.81) years old;there were 5 cases of Garden typeⅠ, 14 cases of type Ⅱ, 3 cases of type Ⅲ and 1 case of type Ⅳ. The operation time, intraoperative blood loss, fluoroscopy times, guide needle placement times, operation costs and other indicators were observed and compared between two groups. Harris score was used to evaluate hip joint function 12 months after operation.@*RESULTS@#The wounds of all patients healed in Grade A without complications. There were significant differences between two groups in terms of operation time, times of intraoperative fluoroscopy, times of guide needle placement, amount of intraoperative bleeding, and operation cost (P<0.05). All 41 patients were followed up for at least 12 months. The fractures of both groups were healed. There was no infection, screw loosening, fracture displacement and femoral head necrosis in Tianji robot group during follow-up;Screw loosening occurred in 2 patients in the traditional operation group during follow-up. At 12 months after operation, Harris hip joint function score of Tianji robot group was higher than that of traditional operation group in daily activity, lameness, joint activity score and total score (P<0.05).@*CONCLUSION@#Tianji robot assisted nail placement is a better method for the treatment of femoral neck fracture, which improves the surgical efficiency, is more accurate, has higher success rate of one-time nail placement, shorter operation time, less radiation, and has better hip joint function recovery after surgery.

Evaluation of CLIA plus NAT for detecting HBsAg single-ELISA-reactive samples of blood donors / 中国输血杂志

【Objective】 To study the detection performance of HBsAg single-ELISA-reactive samples of blood donors. 【Methods】 Two kinds of ELISA reagents from different manufacturers (named as reagents A and B) were used for HBsAg screening. A total of 276 samples, from January 2017 to May 2021, with HBsAg single-ELISA-reactive results were collected for further nucleic acid detection technology (NAT) and chemiluminescence immunoassay (CLIA) testing, to undergo HBV-DNA and five hepatitis B tests, respectively. The relationship between HBsAg single-ELISA-reactivity, NAT and CLIA was statistically analyzed. 【Results】 Among the 276 HBsAg single-ELISA-reactive samples, 14 were NAT reactive, with the positive rate of 5.07% (14/276). Fisher′s exact test was used to compare the compliance of reagents A and B with NAT reactivity, and the difference was not statistically significant (P<0.05). Among 14 HBsAg+ /NAT+ samples retested by CLIA, 2 were HBsAg reactive(14.29%, 2/14), 13 were anti-HBc reactive (92.86%, 13/14), 9 had the quantitative value of anti-HBs <10 mIU/mL, 5 had the quantitative value of anti-HBs between 10 to 100mIU/ mL. A total of 5 serological patterns were detected, and anti-HBe+ /anti-HBc+ pattern was the dominant. There were 262 cases of HBsAg+ /NAT- samples, but only 1 (0.38%, , 1/262) case was HBsAg reactive by CLIA, 100 were anti-HBc reactive (38.17%, 100/262), 144 (54.96%, 144/262) were anti-HBs reactive, and 1 was HBeAg reactive. A total of 8 serological patterns were detected. 【Conclusion】 Most of HBsAg single-ELISA-reactive results are false, and NAT could effectively reduce the residual risk of transfusion transmitted diseases.

IL-6 exacerbates potential arrhythmia of Chan Su intravenous injection / 中国药理学通报

Aim To explore the arrhythmic risk of Chan Su intravenous injection(CS)and its underlying mechanismin in the absent or presence of IL-6.Methods The recording techniques of guinea pig in vivo ECG, the action potential, L-type Ca2+ and Na+ currents from left ventricular myocytes were used to analyze heart rate(HR), P-R, QRS and QTc intervals and the underlying mechanism.Results① CS at one time CRD(clinically relevant dose)insignificantly changed the guinea pig in vivo ECG.However, the IL-6(18.4 μg·kg-1)only and the combinational use of IL-6(18.4 μg·kg-1)plus CS(one time CRD)remarkably prolonged the P-R and QTc intervals.② The CS at one time CRC(clinically relevant concentration)had no significant change in the action potential duration at 90% repolarization level(APD90).The IL-6(20 μg·L-1)only and the combination of CS at one time CRC plus IL-6(20 μg·L-1)significantly prolonged APD90.③ Moreover, the IL-6(20 μg·L-1)combined with CS at one time CRC significantly inhibited the L-type Ca2+ current. CS at one, five, ten time CRC, IL-6(20 μg·L-1)alone and IL-6(20 μg·L-1)combined with CS had no significant effects on Na+current.Conclusions CS intravenous injection has low risk of arrhythmia in the clinical settings.However, in presence of high titer of IL-6 characterized by inflammation, CS may induce the atrioventricular conduction block due to the blockade effect on Ca2+ current by both of CS and IL-6.

Cloning, expression and functional identification of cytochrome P450 reductase gene in Aquilaria sinensis / 药学学报

Cytochrome P450 reductase (CPR) is essential for the electron transport chain of cytochrome P450s, playing an indispensable role in electron transfer in vivo. In this study, one cDNA encoding cytochrome P450 reductase (Ascpr1) was identified from the callus of Aquilaria sinensis. Ascpr1 contains an open reading frame of 2 124 bp. The deduced protein is composed of 707 amino acids, with a predicted molecular weight of 78.82 kD. Phylogenetic analysis revealed that AsCPR1 is a type Ⅱ CPR protein closely related to the CPR from Theobroma cacao. Transmembrane prediction using TMHMM 2.0 indicated that the amino acids 52-71 of AsCPR1 comprise a transmembrane region. After truncating of 67 amino acid residues from N-terminal, the truncated AsCPR1 was successfully expressed in E. coli Transetta (DE3). Further purification of the recombinant AsCPR1 by affinity chromatography and determination of the enzymatic activity allowed the reducing ability of AsCPR1 to cytochrome C in vitro. The results pave the way for further study on the synthesis of defensive chemicals involved in P450s and the functions of CPR in self-defense of A. sinensis.

Review of research progresses in genetics related to myopia / 国际眼科杂志(Guoji Yanke Zazhi)

@# Myopia is an extremely common state of refractive error, and the incidence of myopia is increasing year by year and the age of onset is usually earlier. It has grown up to be a major public health problem that endangers people's visual health. Studies have demonstrated that myopia is a multi-factor complex disease which affected by genetic factors, environmental factors and gene-environment interaction. Genetics includes classical genetics and epigenetics. The emergence of epigenetic research has opened a new perspective of basic research on myopia. In recent years, the researchers have proposed that the occurrence of myopia may be related to epigenetics, and more and more experimental studies have also proved this view. The genetic study of myopia has identified several myopia genes and candidate genes for high myopia and myopia by using linkage and genome-wide association methods, which greatly deepened the understanding of the genetic basis of myopia. This article reviews the research on classical genetics and epigenetics of myopia in recent years.

Effects of mesenchymal stem cells on primary culture and secretion function of parathyroid cells in vitro / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the effects of adipose-derived mesenchymal stem cells (ADMSCs) on proliferation and hormone secretion of parathyroid cells in votro. Methods: The parathyroid cells and ADMSCs were obtained from 10 SD rats by cell separation and culture. The phenotype of P3 generation for ADMSCs was detected by flow cytometry. The co-culture of parathyroid cells and ADMSCs was conducted in the ratios of 2∶1, 1∶1, 1∶2 and 1∶5, respectively. The level of parathyroid hormone in cell supernatant was determined. The results were compared with the parathyroid hormone in the supernatant of parathyroid cells cultured separately in the corresponding number. The effects of ADMSCs on the hormone secretion of parathyroid cells were evaluated. SPSS 11.0 software was used for statistical analysis. Results: The primary culture of either parathyroid cells or ADMSCs and the co-culture of these cells in vitro were performed successfully, and the in vitro culture of different proportions of the two cells showed different effects on parathyroid hormone secretion. The co-culture of parathyroid cells and ADMSCs, especially in the ratio of 1∶5, facilitated the secretion of parathyroid hormone ((1.3±0.0) vs. (0.8±0.1), (1.3±0.0) vs. (0.9±0.0), (1.7±0.5) vs. (0.9±0.0), (1.7±0.0) vs. (1.2±0.2))ng/L with t value of 25.46, 64.30, 3.32, 7.16, P<0.05 on the 2nd, 4th, 6th and 8th days respectively. Secondly, when the ratio was 1∶2, the PTH level showed an upward trend. Conclusion: Parathyroid cells and ADMSCs can be co-cultured in vitro, facilitating the secretion of parathyroid hormone under the appropriate cell proportion such as the ratio of by parathyroid cells to ADMSCs at 1∶5.

Risk stratification and treatment progress of smoldering multiple myeloma / 白血病·淋巴瘤

Smoldering multiple myeloma is a kind of heterogeneous asymptomatic plasma cell disease. Some patients have a high risk of developing symptomatic multiple myeloma. However, the starting point and options of treatment for smoldering multiple myeloma patients are still unclear. This article reviews the risk stratification and treatment progress of smoldering multiple myeloma.

Interference of CD38 monoclonal antibody in blood compatibility testing and its countermeasures: A general consensus among experts / 中国输血杂志

With continuous discovery of tumor immune targets and continuous changes in antibody research and development technology, antibody drugs are becoming more and more widely used in clinical practice. However, some targets are not only expressed on tumor cells, but also on red blood cells. Therefore, the clinical application of antibodies against the corresponding targets may interfere with the detection of blood transfusion compatibility, resulting in difficulty in blood matching or delay of blood transfusion. This consensus summarizes the current solutions for the interference of CD38 monoclonal antibody (CD38 mAb) in transfusion compatibility testing. After analyzing the advantages and disadvantages of different methods, polybrene and sulfhydryl reducing agents [dithiothreitol (DTT) or 2-mercaptoethanol (2-Me)], as a solution for CD38 mAb interference in blood compatibility testing, are recommended for Chinese patients, so as to eliminate blood transfusion interference produce by CD38 mAb and further provide a pre-transfusion workflow for clinicians and technicians in Department of Blood Transfusion.

Mechanism of RNA Binding Protein Sam68 Regulating Biological Behavior of Gastric Cancer Cells and Prognosis of Patients / 胃肠病学

Background: The dysregulation of expression of Sam68 gene can induce cell cycle progression, cell proliferation, transformation, tumorigenesis, and metastasis of multiple types of cancer cells. However, the specific role and molecular mechanism of Sam68 in gastric cancer cells are still uncertain. Aims: To investigate the correlation of expression of Sam68 with prognosis of gastric cancer patients and biological behavior of gastric cancer cells. Methods: A total of 161 gastric cancer tissue and paracancerous normal tissue specimens were collected. Western blotting and immunohistochemical staining were used to detect the expression of Sam68, and its correlations with clinicopathological features were analyzed. Gastric cancer AGS cells were transfected by siRNA Sam68. Cell proliferation was evaluated by CCK-8 assay, cell migration ability was evaluated by scratch test, and cell invasion ability was evaluated by Transwell test. Results: Expression of Sam68 was increased in gastric cancer tissue, and was correlated with depth of infiltration, TNM staging and lymph node metastasis. The high expression of Sam68 was correlated with poor prognosis of gastric cancer patients. After transfection with Sam68 siRNA, cell proliferation, cell cycle progression, migration and invasion ability were decreased. Conclusions: Sam68 may be a new factor for the growth, migration and invasion of gastric cancer cells, and has significant value in predicting the prognosis of gastric cancer patients.

The positive inotropic effect of phosphodiesterase type 8 inhibitor of PF-04957325 in rats and its underlying mechanism / 中国药理学通报

Aim To investigate the inotropic effect of PF-04957325, a phosphodiesterase type 8 inhibitor, in normal rats and its underlying molecular mechanism. Methods The techniques of in vivo rat left ventricular pressure-volume loop (P-V loop) and isolated perfusion rat heart were used to analyze the hemodynamics and positive inotropic effect of rat hearts. The Ca transient induced by field stimulation was used to analyze the hemodynamics of sarcoplasmic reticulum (SR) Ca + uptaking. Western blot was used to analyze the phosphorylation levels of SR phospolamban (PLB) and ryanodine receptor type 2 (RyR2). Results The P-V loop experiment indicated that PF-04957325 (0.5 mg · kg

Cloning and expression analysis of chalcone isomerase from Aquilaria sinensis / 药学学报

Chalcone isomerases (CHIs) play an essential role in the biosynthesis of flavonoids important in plant self-defense. Based on the transcriptome data of Aquilaria sinensis Calli, a full-length cDNA sequence of CHI1 (termed as AsCHI1) was cloned by reverse transcription PCR. AsCHI1 contains a complete open frame (ORF) of 654 bp. The deduced protein is composed of 217 amino acids, with a predicted molecular weight of 23.11 kDa. The sequence alignment and phylogenetic analysis revealed that AsCHI1 has conserved most of the active site residues in type I CHIs, indicating a close relationship with the CHI from Gossypium hirsutum. The recombinant AsCHI1 protein was obtained by heterologous expression of AsCHI1 in E. coli BL21(DE3). The purified AsCHI1 protein exhibited CHI activity by catalyzing the production of naringenin from naringenin chalcone. Remarkably, AsCHI1 expression in A. sinensis Calli treated with various abiotic stresses including salt, mannitol, cold, and heavy metals could be markedly increased, and plant hormones such as abscisic acid (ABA), gibberellin (GA3), and salicylic acid (SA) could also increase the expression of AsCHI1, suggesting that AsCHI1 might play an important role in plant self-defense. The results expand our understanding of the biosynthesis of flavonoids in A. sinensis and give further insight into the defensive responses of A. sinensis to abiotic and biotic stresses.

Poor outcomes of delirium in the intensive care units are amplified by increasing age: A retrospective cohort study / 世界急诊医学杂志（英文）

@#BACKGROUND: Delirium in patients in intensive care units (ICUs) is an acute disturbance and fluctuation of cognition and consciousness. Though increasing age has been found to be related to ICU delirium, there is limited evidence of the effect of age on delirium outcomes. The aim of this study is to investigate the relationship between age categories and outcomes among ICU delirium patients. METHODS: Data were extracted from the electronic ICU (eICU) Collaborative Research Database with records from 3,931 patients with delirium. Patients were classified into non-aged (<65 years), young-old (65-74 years), middle-old (75-84 years), and very-old (≥85 years) groups. A Cox regression model was built to examine the role of age in death in ICU and in hospital after controlling covariates. RESULTS: The sample included 1,667 (42.4%) non-aged, 891 (22.7%) young-old, 848 (21.6%) middle-old, and 525 (13.3%) very-old patients. The ICU mortality rate was 8.3% and the hospital mortality rate was 15.4%. Compared with the non-aged group, the elderly patients (≥65 yeras) had higher mortality at ICU discharge (χ 2=13.726, P=0.001) and hospital discharge (χ 2=56.347, P<0.001). The Cox regression analysis showed that age was an independent risk factor for death at ICU discharge (hazard ratio [HR]=1.502, 1.675, 1.840, 95% confidence interval [CI] 1.138-1.983, 1.250-2.244, 1.260-2.687; P=0.004, 0.001, 0.002 for the young-, middle- and very-old group, respectively) as well as death at hospital discharge (HR=1.801, 2.036, 2.642, 95% CI 1.454-2.230, 1.638-2.530, 2.047-3.409; all P<0.001). CONCLUSIONS: The risks of death in the ICU and hospital increase with age among delirious patients.

Progress of autophagy in the pathogenesis of dry age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

@#Age-related macular degeneration(ARMD)is a major clinical blind-inducing eye disease, and its pathogenesis is closely related to the autophagy of RPE cells and the signaling pathway of nuclear factor erythroid-2 related factor 2(Nrf2). Autophagy is one of the common and important physiological phenomena in human body, which is of vital significance for maintaining the stability and metabolism of cells. Nrf2 is a key transcription factor regulating cells to fight against foreign bodies and oxidative damage, and Nrf2 signaling pathway plays a wide range of cell protective functions in anti-tumor, anti-stress and other aspects. With the development of research, it is found that there are extensive interaction mechanisms between autophagy and Nrf2 signaling pathway. Inhibition of autophagy leads to accumulation of p62, which activates the Nrf2 signaling pathway by binding with Keap1(kelch-like ech-associated protein1). At the same time, studies have also found that reactive oxygen species(ROS)and other factors also participate in the mutual regulation between autophagy and Nrf2.This paper will review the recent research progress on the interaction between Nrf2 signaling pathway and autophagy in the development of ARMD. Hope to provide a new perspective for the treatment of ARMD.