A nomogram for predicting the risk of preeclampsia in women with intrahepatic cholestasis of pregnancy based on prenatal monitoring time: a multicenter retrospective cohort study.

BACKGROUND AND AIMS: Intrahepatic cholestasis of pregnancy (ICP) is a special liver disease during pregnancy, characterized by abnormal bile acid metabolism. However, there is no consensus on how to group women with ICP based on the time of diagnosis worldwide. This study aimed to adopt a new grouping model of women with ICP, and the time from diagnosis to delivery was defined as the monitoring period. METHODS: This retrospective real-world data study was conducted across multiple centers and included 3172 women with ICP. The study first evaluated the significant difference in medication and nonmedication during different monitoring times. The least absolute shrinkage and selection operator (LASSO) model was then used to screen nine risk factors based on the predictors. The model's discrimination, clinical usefulness, and calibration were assessed using the area under the receiver operating characteristic (ROC) curve, decision curve, and calibration analysis. RESULTS: The incidence of preeclampsia risk in ICP patients without drug intervention increased with the extension of the monitoring period. However, the risk of preeclampsia decreased in ICP patients treated with ursodeoxycholic acid. A predictive nomogram and risk score model was developed based on nine risk factors. The area under the ROC curve of the nomogram was 0.765 [95% confidence interval (CI): 0.724-0.807] and 0.812 (95% CI: 0.736-0.889) for the validation cohort. CONCLUSIONS: This study found that a longer ICP monitoring period could lead to adverse pregnancy outcomes in the absence of drug intervention, especially preeclampsia. A predictive nomogram and risk score model was developed to better manage ICP patients, maintain pregnancy to term delivery, and minimize the risk of severe adverse maternal and fetal outcomes.

Burden and trends of mental disorders in China from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

PURPOSE: Mental disorders remain the leading causes of disability worldwide. We aimed to determine the burden and trends of mental disorders in China from 1990 to 2019. METHODS: The incidence, prevalence, and disability-adjusted life years (DALYs) of mental disorders at national level of China were examined by age, sex, and subcategories. Temporal trends in the age-standardized rates for incidence, prevalence, and DALYs were assessed by the average annual percentage change (AAPC). All estimates are presented as numbers and age-standardized rates, with 95% uncertainty intervals (UIs). RESULTS: The number of incident cases due to mental disorders increased from 42.90 million to 52.72 million, the number of prevalent cases increased from 132.63 million to 160.16 million, and the number of DALYs increased from 15.64 million to 20.29 million during 1990-2019. Decreasing trends were observed in the age-standardized rates for incidence, prevalence and DALYs. Anxiety and depressive disorders were more frequent in women, while ADHD, conduct disorder, and autism spectrum disorders were more common in men. Compared with 1990, the age-specific incidence rates were higher in individuals under 14 years and over 55 years, whereas rates were lower in those aged 15-49 years in 2019. CONCLUSION: The number of incident cases, prevalent cases, and DALYs due to mental disorders gradually increased in China from 1990 to 2019. Anxiety and depressive disorders were the leading causes of burden due to mental disorders, which affected women more than men. Mental disorders deserve greater attention in health policy decision making.

Ruthenium(II)-Catalyzed [4 + 2] Electro-Oxidative Annulation of C6-Arylpurines/Purine Nucleosides.

A sustainable pathway for the synthesis of tetracyclic purinium salts via ruthenium-catalyzed electro-oxidative annulation of C6-arylpurine nucleosides with alkynes without a stoichiometric metal oxidant has been developed. The protocol described herein exhibits high regioselectivity, broad scope, and wide functional group tolerance, allowing efficient coupling of various biologically important molecules including acyclic, ribosyl, arabinosyl, and deoxyribosyl purine nucleoside derivatives. A novel purinoisoquinolinium-coordinated ruthenium(0) sandwich intermediate has been isolated, crystallographically characterized, and electrochemically analyzed, offering direct mechanistic insight.

Thirty-day outcomes of in-hospital multi-vessel versus culprit-only revascularization strategy for ST-segment elevation myocardial infarction with multivessel coronary disease.

BACKGROUND: Many studies have demonstrated the benefit of complete multivessel revascularization versus culprit-only intervention in patients of ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, only a few single-center retrospective studies were performed on small Chinese cohorts. Our study aims to demonstrate the advantage of multivessel percutaneous intervention (PCI) strategy on 30-day in-hospital outcomes to patients with STEMI and multivessel disease in larger Chinese population. METHODS: From the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, 5935 patients with STEMI and multivessel disease undergoing PCI and hospitalized for fewer than 30 days were analyzed. After 5: 1 propensity score matching, 3577 patients with culprit-only PCI and 877 with in-hospital multivessel PCI were included. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of myocardial infarction, all-cause death, stent thrombosis, heart failure, and stroke. RESULTS: Multivariable logistic regression analysis revealed that in-hospital multivessel PCI was associated with lower risk of 30-day MACCE (adjusted OR = 0.75, 95% CI: 0.57-0.98, P = 0.032) than culprit-only PCI and conferred no increased risk of all-cause death, myocardial infarction, stent thrombosis, stroke, or bleeding. Subgroup analysis showed that MACCE reduction was observed more often from patients with trans-femoral access (OR = 0.34, 95% CI: 0.15-0.74) than with trans-radial access (OR = 0.87, 95% CI: 0.66-1.16, P for interaction = 0.017). CONCLUSIONS: The in-hospital multivessel PCI strategy was associated with a lower risk of 30-day MACCE than culprit-only PCI in patients with STEMI and multivessel coronary artery disease.

Effect of Water Exercise Therapy on Lower Limb Function Rehabilitation in Hemiplegic Patients with the First Stroke.

Objective: To investigate water exercise therapy's effect on lower limb function rehabilitation in patients with the first stroke. Method: 160 patients with the first stroke and lower limb dysfunction who received rehabilitation treatment in the Geriatric Hospital of Hainan, China, from May 2020 to June 2021 were randomly divided into two groups, the control group, and the hydrotherapy group. Each group comprises 80 cases in each group. The control group received conventional drug therapy and traditional rehabilitation training, while the hydrotherapy group received underwater exercise training in combination with the routine group treatment plan. The National Health Center Stroke Scale (NIHSS), the modified Rankin scale (MRS), the limb motor function score table (Fugl-Meyer assessment, FMA), Functional Walking Scale (functional ambulation category scale, FAC), Berg Balance Scale (BBS) and the modified Barthel index (MBI) were respectively used to evaluate the neurological function, lower limb motor function, walking function, balance function and daily living ability before and after treatment. Result: There was no significant difference in NIHSS, MRS, FMA, FAC, BBS, and MBI scores between the two groups before treatment (P > .05). However, after 8 weeks of treatment, there was a significant difference in FMA, FAC, BBS, and MBI scores between the two groups (P = .00035). The FMA scores in control group was 16.60 ± 4.49, while 21.45 ± 2.96 after treatment. The FAC scores in control group was 1.45 ± 0.68, while 1.95 ± 0.783 after treatment. Conclusion: Early water exercise training in hemiplegic patients with the first stroke can significantly enhance the balance ability, walking ability as well as limb coordination of patients.

GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol.

The mechanism underlying the hypnosis effect of propofol is still not fully understood. In essence, the nucleus accumbens (NAc) is crucial for regulating wakefulness and may be directly engaged in the principle of general anesthesia. However, the role of NAc in the process of propofol-induced anesthesia is still unknown. We used immunofluorescence, western blotting, and patch-clamp to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to explore the role of NAc GABAergic neurons in regulating propofol-induced general anesthesia states. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. We found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. Meanwhile, patch-clamp recording of brain slices showed that firing frequency induced by step currents in NAc GABAergic neurons significantly decreased after propofol perfusion. Notably, chemically selective stimulation of NAc GABAergic neurons during propofol anesthesia lowered propofol sensitivity, prolonged the induction of propofol anesthesia, and facilitated recovery; the inhibition of NAc GABAergic neurons exerted opposite effects. Furthermore, optogenetic activation of NAc GABAergic neurons promoted emergence whereas the result of optogenetic inhibition was the opposite. Our results demonstrate that NAc GABAergic neurons modulate propofol anesthesia induction and emergence.

Target Recognition in SAR Images by Deep Learning with Training Data Augmentation.

Mass production of high-quality synthetic SAR training imagery is essential for boosting the performance of deep-learning (DL)-based SAR automatic target recognition (ATR) algorithms in an open-world environment. To address this problem, we exploit both the widely used Moving and Stationary Target Acquisition and Recognition (MSTAR) SAR dataset and the Synthetic and Measured Paired Labeled Experiment (SAMPLE) dataset, which consists of selected samples from the MSTAR dataset and their computer-generated synthetic counterparts. A series of data augmentation experiments are carried out. First, the sparsity of the scattering centers of the targets is exploited for new target pose synthesis. Additionally, training data with various clutter backgrounds are synthesized via clutter transfer, so that the neural networks are better prepared to cope with background changes in the test samples. To effectively augment the synthetic SAR imagery in the SAMPLE dataset, a novel contrast-based data augmentation technique is proposed. To improve the robustness of neural networks against out-of-distribution (OOD) samples, the SAR images of ground military vehicles collected by the self-developed MiniSAR system are used as the training data for the adversarial outlier exposure procedure. Simulation results show that the proposed data augmentation methods are effective in improving both the target classification accuracy and the OOD detection performance. The purpose of this work is to establish the foundation for large-scale, open-field implementation of DL-based SAR-ATR systems, which is not only of great value in the sense of theoretical research, but is also potentially meaningful in the aspect of military application.

Insight into microvascular adaptive alterations in the Glisson system of biliary atresia after Kasai portoenterostomy using X-ray phase-contrast CT.

OBJECTIVES: To investigate microvascular alterations in the Glisson system of biliary atresia (BA) patients after Kasai portoenterostomy (KP) using three-dimensional (3D) virtual histopathology based on X-ray phase-contrast CT (PCCT). METHODS: Liver explants from BA patients were imaged using PCCT, and 32 subjects were included and divided into two groups: KP (n = 16) and non-KP (n = 16). Combined with histological analysis and 3D visualization technology, 3D virtual histopathological assessment of the biliary, arterial, and portal venous systems was performed. According to loop volume ratio, 3D spatial density, relative surface area, tortuosity, and other parameters, pathological changes of microvasculature in the Glisson system were investigated. RESULTS: In the non-KP group, bile ducts mostly manifested as radial multifurcated hyperplasia and twisted into loops. In the KP group, the bile duct hyperplasia was less, and the loop volume ratio of bile ducts decreased by 13.89%. Simultaneously, the arterial and portal venous systems presented adaptive alterations in response to degrees of bile duct hyperplasia. Compared with the non-KP group, the 3D spatial density of arteries in the KP group decreased by 3.53%, and the relative surface area decreased from 0.088 ± 0.035 to 0.039 ± 0.015 (p < .01). Deformed portal branches gradually recovered after KP, with a 2.93% increase in 3D spatial density and a decrease in tortuosity from 1.17 ± 0.06 to 1.14 ± 0.04 (p < .01) compared to the non-KP group. CONCLUSION: 3D virtual histopathology via PCCT clearly reveals the microvascular structures in the Glisson system of BA patients and provides key insights into the morphological mechanism of microvascular adaptation induced by biliary tract dredging after KP in BA disease. KEY POINTS: • 3D virtual histopathology via X-ray phase-contrast computed tomography clearly presented the morphological structures and pathological changes of microvasculature in the Glisson system of biliary atresia patients. • The morphological alterations of microvasculature in the Glisson system followed the competitive occupancy mechanism in the process of biliary atresia.

Thirty-day outcomes of in-hospital multi-vessel versus culprit-only revascularization strategy for ST-segment elevation myocardial infarction with multivessel coronary disease / 老年心脏病学杂志（英文版）

BACKGROUND@#Many studies have demonstrated the benefit of complete multivessel revascularization versus culprit-only intervention in patients of ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, only a few single-center retrospective studies were performed on small Chinese cohorts. Our study aims to demonstrate the advantage of multivessel percutaneous intervention (PCI) strategy on 30-day in-hospital outcomes to patients with STEMI and multivessel disease in larger Chinese population.@*METHODS@#From the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, 5935 patients with STEMI and multivessel disease undergoing PCI and hospitalized for fewer than 30 days were analyzed. After 5: 1 propensity score matching, 3577 patients with culprit-only PCI and 877 with in-hospital multivessel PCI were included. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of myocardial infarction, all-cause death, stent thrombosis, heart failure, and stroke.@*RESULTS@#Multivariable logistic regression analysis revealed that in-hospital multivessel PCI was associated with lower risk of 30-day MACCE (adjusted OR = 0.75, 95% CI: 0.57-0.98, P = 0.032) than culprit-only PCI and conferred no increased risk of all-cause death, myocardial infarction, stent thrombosis, stroke, or bleeding. Subgroup analysis showed that MACCE reduction was observed more often from patients with trans-femoral access (OR = 0.34, 95% CI: 0.15-0.74) than with trans-radial access (OR = 0.87, 95% CI: 0.66-1.16, P for interaction = 0.017).@*CONCLUSIONS@#The in-hospital multivessel PCI strategy was associated with a lower risk of 30-day MACCE than culprit-only PCI in patients with STEMI and multivessel coronary artery disease.

Sequence Type 5 (ST5) as a Possible Predictor of Bacterial Persistence in Adult Patients with Methicillin-Resistant Staphylococcus aureus Pneumonia Treated with Vancomycin.

Vancomycin remains the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This study assessed risk factors for vancomycin failure in 63 patients with MRSA pneumonia through detailed clinical, microbiological, pharmacokinetic/pharmacodynamic, and genetic analyses of prospective multicenter studies conducted from February 2012 to July 2018. Therapeutic drug monitoring was performed during vancomycin treatment, and the 24-h area under the curve (AUC0-24) was calculated. All baseline strains were collected for MIC determination, heterogeneous vancomycin-intermediate S. aureus (hVISA) screening, and biofilm determination. Whole-genome sequencing was performed on the isolates to analyze their molecular typing and virulence and adhesion genes. Clinical signs and symptoms improved in 44 patients (44/63, 69.8%), with vancomycin daily dose (P = 0.045), peak concentration (P = 0.020), and sdrC (P = 0.047) being significant factors. Isolates were eradicated in 51 patients (51/63, 81.0%), with vancomycin daily dose (P = 0.009), cardiovascular disease (P = 0.043), sequence type 5 (ST5; P = 0.017), tst (P = 0.050), and sec gene (P = 0.044) associated with bacteriological failure. Although the AUC0-24/MIC was higher in the groups with bacterial eradication, the difference was not statistically significant (P = 0.108). Multivariate analysis showed that no variables were associated with clinical efficacy; ST5 was a risk factor for bacterial persistence (adjusted odds ratio, 4.449; 95% confidence interval, 1.103 to 17.943; P = 0.036). ST5 strains had higher frequencies of the hVISA phenotype, biofilm expression, and presence of some adhesion and virulence genes such as fnbB, tst, and sec than non-ST5 strains. Our study suggests that ST5 is a possible predictor of bacterial persistence in MRSA pneumonia treated with vancomycin. IMPORTANCE Few studies have simultaneously examined the influence of clinical characteristics of patients with pneumonia, the vancomycin pharmacokinetic/pharmacodynamic (PK/PD) index, and the phenotypic and genetic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains. We assessed risk factors for vancomycin failure in patients with MRSA pneumonia by analyzing these influences in a prospective multicenter study. Sequence type 5 (ST5) was a possible predictor of bacterial persistence in adult patients with MRSA pneumonia (adjusted odds ratio, 4.449). We found that this may be related to ST5 strains having higher levels of vancomycin heterogeneous resistance, biofilms, and the presence of adhesion and virulence genes such as fnbB, tst, and sec.

Comparative genomic analysis of the genus Marinomonas and taxonomic study of Marinomonas algarum sp. nov., isolated from red algae Gelidium amansii.

Members of the genus Marinomonas are known for their environmental adaptation and metabolically versatility, with abundant proteins associated with antifreeze, osmotic pressure resistance, carbohydrase and multiple secondary metabolites. Comparative genomic analysis focusing on secondary metabolites and orthologue proteins was conducted with 30 reference genome sequences in the genus Marinomonas. In this study, a Gram-stain-negative, rod-shaped, non-flagellated and strictly aerobic bacterium, designated as strain E8T, was isolated from the red algae (Gelidium amansii) in the coastal of Weihai, China. Optimal growth of the strain E8T was observed at temperatures 25-30 °C, pH 6.5-8.0 and 1-3% (w/v) NaCl. The DNA G + C content was 42.8 mol%. The predominant isoprenoid quinone was Q-8 and the major fatty acids were C16:0, summed feature 3 and summed feature 8. The major polar lipids were phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). Based on data obtained from this polyphasic taxonomic study, strain E8T should be considered as a novel species of the genus Marinomonas, for which the name Marinomonas algarum is proposed. The type strain is E8T (= KCTC 92201T = MCCC 1K07070T).

Oceanisphaera pacifica sp. nov., isolated from the intestine of Trichiurus japonicus.

A Gram-stain-negative, strictly aerobic, non-flagellated, oxidase- and catalase-positive, rod-shaped marine bacterium, designated strain DM8T, was isolated from the intestine of Trichiurus japonicus in Weihai, China. The strain optimally grew at 25-35℃, with 1.0-4.0% (w/v) NaCl and at pH 7.0-8.0. Its colonies were circular, slightly yellow, non-transparent, smooth, and approximately 0.8-1.5 mm in diameter, after being cultured for 48 h on marine agar 2216. Based on the result of phylogenetic analysis of 16S rRNA gene sequence, strain DM8T had close relationship with Oceanisphaera profunda SM1222T (96.9%) and the type strain DSM 15406 T of the type species Oceanisphaera litoralis (94.7%), respectively. Genome sequencing revealed a genome size of 3,109,059 bp and a G + C content of 46.9 mol%. It had Q-8 as the sole respiratory quinone and possessed C16:0, summed features 3 (C16:1ω7c/C16:1ω6c) and summed features 8 (C18:1ω7c/C18:1ω6c) as major fatty acids. The major polar lipid profile was composed of phosphatidylglycerol and phosphatidylethanolamine. Based on the phenotypic, chemotaxonomic characterizations, phylogenetic properties and genome analysis, strain DM8T should represent a novel species of the genus Oceanisphaera, for which the name Oceanisphaera pacifica sp. nov. is proposed. The type strain is DM8T (= KCTC 82764 T = MCCC 1K06133T).

Corosolic acid and its structural analogs: A systematic review of their biological activities and underlying mechanism of action.

BACKGROUND: The corosolic acid (CA), also known as plant insulin, is a pentacyclic triterpenoid extracted from plants such as Lagerstroemia speciosa. It has been shown to have anti-diabetic, anti-inflammatory and anti-tumor effects. Its structural analogs ursolic acid (UA), oleanolic acid (OA), maslinic acid (MA), asiatic acid (AA) and betulinic acid (BA) display similar individual pharmacological activities to those of CA. However, there is no systematic review documenting pharmacological activities of CA and its structural analogues. This study aims to fill this gap in literature. PURPOSE: This systematic review aims to summarize the medical applications of CA and its analogues. METHODS: A systematic review summarizes and compares the extraction techniques, pharmacokinetic parameters, and pharmacological effects of CA and its structural analogs. Hypoglycemic effect is one of the key inclusion criteria for searching Web of Science, PubMed, Embase and Cochrane databases up to October 2020 without language restrictions. 'corosolic acid', 'ursolic acid', 'oleanolic acid', 'maslinic acid', 'asiatic acid', 'betulinic acid', 'extraction', 'pharmacokinetic', 'pharmacological' were used to extract relevant literature. The PRISMA guidelines were followed. RESULTS: At the end of the searching process, 140 articles were selected for the systematic review. Information of CA and five of its structural analogs including UA, OA, MA, AA and BA were included in this review. CA and its structural analogs are pentacyclic triterpenes extracted from plants and they have low solubilities in water due to their rigid scaffold and hydrophobic properties. The introduction of water-soluble groups such as sugar or amino groups could increase the solubility of CA and its structural analogs. Their biological activities and underlying mechanism of action are reviewed and compared. CONCLUSION: CA and its structural analogs UA, OA, MA, AA and BA are demonstrated to show activities in lowering blood sugar, anti-inflammation and anti-tumor. Their oral absorption and bioavailability can be improved through structural modification and formulation design. CA and its structural analogs are promising natural product-based lead compounds for further development and mechanistic studies.

Pharmacokinetics, pharmacodynamics, and safety of single- and multiple-dose intravenous ceftobiprole in healthy Chinese participants.

BACKGROUND: Ceftobiprole is a novel ß-lactam cephalosporin with activity against Gram-positive and -negative bacteria. The aim of the present study was to investigate the pharmacokinetics (PK), pharmacokinetics/pharmacodynamics (PK/PD), safety and tolerance of ceftobiprole in Chinese participants, to evaluate this dosage regimen for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) in China. METHODS: The use of ceftobiprole was investigated in a single-center, open-label, single- and multiple-dose study using 12 healthy Chinese participants (6 males and 6 females). Ceftobiprole plasma and urine concentrations were analyzed using a validated liquid chromatography-tandem mass spectrometry assay. The PK/PD characteristics of 500 mg ceftobiprole every 8 h at 1.5-, 2-, 3-, or 4-h infusion time were analyzed by Monte Carlo simulations (MCS). RESULTS: The maximum plasma concentration of ceftobiprole was observed 2 h after dosage; its terminal half-life was about 3 h. Ceftobiprole was predominantly eliminated in urine, and the cumulative excretion in 24 h was >90%. There was no accumulation after multiple dosing. Both single and multiple doses were well tolerated, with no severe or serious adverse events (AEs). PK/PD analysis indicated that Staphylococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus) were sensitive to ceftobiprole. About half of extended-spectrum ß-lactamase (ESBL) non-producing Enterobacteriaceae are sensitive to ceftobiprole, according to PK/PD results of ceftobiprole. For Pseudomonas aeruginosa (P. aeruginosa), no regimen was found to be effective against strains. CONCLUSIONS: The PK/PD results indicated that 500 mg ceftobiprole every 8 h at 2-h infusion time is expected to achieve good microbiological efficacy in the treatment of CAP and HAP in China.

Use of Head and Neck Magnetic Resonance Angiography to Explore Neurological Function Recovery and Impact of Rehabilitation Nursing on Patients with Acute Stroke.

OBJECTIVE: To analyze neurological function recovery and the impact of rehabilitation nursing in patients with cerebral stroke after treatment to aid clinical diagnosis and treatment of cerebral stroke. METHODS: The study comprised 140 patients who were hospitalized in the neurology department for magnetic resonance angiography examination. Patients were divided into a treatment group (70 patients) and a control group (70 patients) based on treatment plan. Digital subtraction angiography was regarded as the gold standard diagnostic examination. In patients in both groups, magnetic resonance angiography features of the M1 segment of the middle cerebral artery and diagnostic specificity and sensitivity were recorded. An activities of daily living score was used to assess neurological function of patients before and after rehabilitation. RESULTS: The activities of daily living scores of patients in both groups increased significantly after treatment (P < 0.05); the scores of patients in the treatment group increased more significantly (P < 0.05). The total effective rate was 89% in the treatment group and 60% in the control group. The difference between the 2 groups was statistically significant (P < 0.05). After treatment, the degree of M1 segment stenosis in both groups was better than before treatment, and the number of collateral circulation branches was increased; the improvements in the treatment group were more significant (P < 0.05). CONCLUSIONS: Rehabilitation nursing could greatly improve the stenosis of blood vessels in patients with acute cerebral stroke and promote the establishment of collateral circulation, thereby effectively enhancing the recovery of neurological function and strengthening the ability of patients to perform activities of daily living.

Effects of Different Component Contents of Colistin Methanesulfonate on the Pharmacokinetics of Prodrug and Formed Colistin in Human.

PURPOSES: To evaluate the effects of component contents in different colistin methanesulfonate (CMS) formulas on their clinical pharmacokinetics of the prodrug CMS and the formed colistin. METHODS: Two CMS formulas (CTTQ and Parkedale) were investigated in a single dose, randomized, open-label, crossover study conducted in 18 healthy Chinese subjects. Both CMS formulas met the requirements of European Pharmacopoeia 9.2 with 12.1% difference in the two major active components (CMS A and CMS B). The PK parameters after a single intravenous infusion of CMS at 2.5 mg/kg were calculated and the steady-state plasma colistin concentrations (Css,avg) following multiple dosing, once every 12 h for 7 days, were simulated with the non-compartment model. RESULTS: The systemic exposure (AUC0-inf) of CMS were 59.49 ± 5.90 h·µg/mL and 51.09 ± 4.70 h·µg/mL, and the AUC0-inf of colistin were 15.39 ± 2.63 h·µg/mL and 12.36 ± 2.10 h·µg/mL for CTTQ and Parkedale, respectively. The ratios (90% CI) of geometric mean of AUC0-inf of CTTQ to Parkedale were 116.38% (112.95%, 119.91%) and 124.49% (120.76%, 128.35%) for CMS and colistin, respectively. The predicted Css,avg (95% CI) were 0.92 (0.85, 0.99) µg/mL and 0.74 (0.69, 0.79) µg/mL for CTTQ and Parkedale, respectively. CONCLUSION: The difference in component content in the two CMS formulas had a significant (P < 0.001) impact on the systemic exposure of colistin in human, thus, warranted essential considerations in clinical applications.

The multiple effects of hydrogen sulfide on cadmium toxicity in tobacco may be interacted with CaM signal transduction.

Soilless culture experiments with tobacco were conducted to explore how the signal molecule H2S (0.3, 0.6, 0.9, and 1.2 µM) alleviated the toxicity of Cd2+ (50 mg/L). The results suggested that photosynthesis was enhanced as H2S improved the tobacco ΦPSII, ETR, Photo, Cond, and Tr, and that by increasing the NPQ, it consumed considerable amount of energy to enhance plant resistances during Cd2+ exposure. Furthermore, H2S increased the gene transcription of NtSOD3, NtPOD1, and CAT1, to enhance antioxidant enzyme activity, which reduces the generation of the reactive oxygen protective membrane integrity. Additionally, H2S increased the gene expression of the tobacco PC genes, Pr2 and Pr8 promoted the formation of the Cd2+ complexes and transportation to the vacuole, resulting in improved Cd-ATPase gene expression, away from organelles, to alleviate the Cd2+ poison. Furthermore, H2S regulated the relative absorption of K+ and Ca2+, which antagonized the Cd2+, and reduced its transportation to the aboveground plant material. Finally, the expression level of CaM increased with the application of H2S, and was highly correlated with the fitted results of a variety of resistance indicators, thereby indicating that H2S regulatory resistance mechanisms might be associated with Ca2+ signal transduction.

Doppler grading for decompression bubbles / 中国职业医学

Ultrasonic bubble detection has been widely used in predicting the risk of decompression sickness and evaluating the efficiency and safety of decompression procedures. Currently, the widely used SPENCER scale is conducted by using Doppler ultrasound to monitor the bubble signal in the precordial region of subjects. KM grading system is a computerized system based on Doppler ultrasound. The grading score can be converted into SPENCER bubble grading scale score and the bubble grading is precise and suitable for the motion status. On the basis of the above two methods, the KISMAN integrated severity score, extended SPENCER bubble grading and simplified Doppler bubble grading system were established. They not only coordinated analysis of Doppler ultrasound bubble detection results with other risk factors of decompression disease, but also convenient to use computer for processing detection results. With the in-depth application of Fourier technique and empirical mode decomposition in Doppler audio bubble signal detection, methods such as three-parameter fuzzy analysis and energy operator method are playing an important role in automatic bubble analysis. Optimization of detection technology and improvement of sensitivity and accuracy of automatic analysis are important development directions in the field of decompression bubble Doppler grating technology.

Molecular Mechanism of Salvia miltiorrhiza Quality Formation Based on Single Nucleotide Polymorphism of Functional Genes / 中国实验方剂学杂志

Objective:To investigate the relationship between the single nucleotide polymorphism（SNP）of function genes and effective components of <italic>Salvia miltiorrhiza</italic> and the molecular mechanism of specific quality formation of <italic>S. miltiorrhiza</italic>. Method:The fingerprints of components in <italic>S. miltiorrhiza</italic> from eight different habitats and varieties were obtained by high-performance liquid chromatography （HPLC）. The full-length cDNA of three functional genes<italic> </italic>acetyl-CoA C-acetyltransferase（<italic>SmAACT</italic>），4-diphosphocytidyl-2-C-methyl-<italic>D</italic>-erythritol kinase（<italic>SmCMK</italic>） and isopentenyl diphosphate isomerase（<italic>SmIPPI</italic>） in tanshinone metabolic pathway were amplified by polymerase chain reaction（PCR），cloned， and sequenced，followed by bioinformatics analysis. Result:The full-length cDNA sequences of three functional genes <italic>SmAACT</italic>，<italic>SmCMK</italic>， and <italic>SmIPPI</italic> in tanshinone metabolic pathway were obtained from 23 strains of <italic>S. miltiorrhiza</italic> from eight different habitats and varieties. As revealed by the analysis of SNP and amino acid polymorphisms of three functional genes，18，16， and 14 SNP sites were found respectively. HPLC results showed the samples from Beijing，Hubei，Shandong （No. SDB），Shanxi，Henan， and Shandong （No. SDZ） were clustered into one branch，and those from Hebei and Inner Mongolia were clustered into another branch， which suggested that the variation trend of <italic>S. miltiorrhiza</italic> components had little correlation with geographical distance，but the variety was a critical factor for the quality. Conclusion:There was an obvious genetic differentiation trend in <italic>S. miltiorrhiza</italic> from different habitats，and different origin-specific genotypes were formed. The molecular mechanism of the formation of the specific quality of <italic>S. miltiorrhiza</italic> from different habitats was discussed，which laid a foundation for the stability and effectiveness of clinical medication，and guided the breeding of excellent varieties of <italic>S. miltiorrhiza</italic>.