The relationship between fine motor skills and executive function in boys with attention deficit hyperactivity disorder / 中国学校卫生

Objective@#To investigate the relationship between fine motor skills and executive function in school aged boys with attention deficit hyperactivity disorder (ADHD) aged 6-10 years, so as to provide a reference for promoting executive function.@*Methods@#From November 2022 to May 2021,65 boys with ADHD were recruited from a tertiary hospital in Beijing and a public elementary school in Beijing, and 65 boys with typical development according to age and sex were recruited as controls. Children s fine motor skills were assessed using the movement assessment battery for children, second version (MABC-2), and children s inhibitory control, working memory, and cognitive flexibility were assessed using the Stroop color word test (SCWT), Rey osterrich complex figure test (ROCFT) and trail making test (TMT), respectively. Independent samples t-tests were used to analyze the differences between the two groups, and Pearson correlation analysis and stratified regression analysis were used to explore the relationship between fine motor skills and executive functioning in boys with ADHD.@*Results@#In the fine motor skills test, boys with ADHD scored significantly lower (8.68±3.62) than control boys (11.22±2.27)( t =4.80, P <0.05); in the executive function test, the results of SCWT, ROCFT, and TMT tests were significantly worse in boys with ADHD than in normal boys ( t =-4.53-4.42, P < 0.05). Correlation analysis showed that the fine motor skill scores of boys with ADHD were negatively correlated with the number of word sense errors ( r =-0.35) and color errors ( r =-0.42), and positively correlated with memory scores for delayed structure ( r =0.30) and detail ( r =0.25), which were negatively correlated with TMT-A ( r =-0.34),TMT-B reaction time ( r =-0.26), number of errors ( r =-0.43) ( P <0.05). Stratified regression analysis showed that fine motor skill scores of boys with ADHD were predictive of test results for inhibitory control, working memory and cognitive flexibility, with explanatory rates of 15%, 7%, and 19%, respectively.@*Conclusion@#Fine motor skills in boys with ADHD are correlated with executive functions, and fine motor skills could predict inhibitory control, working memory and cognitive flexibility to some extent. The development of fine motor skills in boy with ADHD could promote their executive functions.

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study / 대한뇌졸중학회지

Background@#and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. @*Methods@#In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). @*Results@#Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. @*Conclusion@#This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Research progress of metabolomics in acute kidney injury / 中华危重病急救医学

Acute kidney injury (AKI) is caused by a variety of diseases, which leads to acute renal function decline, azotemia, water and electrolyte disorders and acid-base balance disorders. Metabolomics is a research method that can quantitatively analyze all metabolites in an organism and find the relative relationship between metabolites and physiological and pathological changes. In recent years, several metabolites screened based on metabolomics have been proposed as potential biomarkers to assess the early development and prognosis of AKI and for the discovery of unknown potential therapeutic targets. Based on metabolomics, this paper reviews the risk prediction, early diagnosis, disease monitoring, prognosis assessment and the application of corresponding drugs for AKI, so as to provide reference for precision medicine.

Two new 2,3-seco triterpenoids from Rubus pirifolius Smith / 药学学报

Eight compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Rubus pirifolius Smith by AB-8 macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as 1D/2D NMR, MS, UV, IR and by comparison with literature information as rubussecotriterpene A (1), rubussecotriterpene B (2), cecropiacic acid (3), cecropiacic acid 3-methyl ester (4), alphitolic acid (5), betulinic acid (6), betulin (7), and obtusalin (8). Compounds 1 and 2 are new compounds, and compounds 3-8 were isolated from this plant for the first time.

Preparation and characterization of linolenic acid-chitosan micelle for doxorubicin oral delivery and its in situ intestinal absorption in rats / 药学学报

In this study, a novel oral drug delivery system based on linolenic acid-modified chitosan (CS-LA) micelle was developed to improve the oral bioavailability of doxorubicin (DOX), which was proven by its in vivo intestinal absorption in rats. The DOX-loaded CS-LA micelles (CS-LA@DOX) were prepared by the dialysis method. The synthesized micelle material was identified by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR). A series of the micelle properties, including particle size distribution, zeta potential, encapsulation efficiency (EE), drug loading (DL), micromorphology, polymorphy, and critical micelle concentration (CMC) were characterized or tested. The in vitro release of micelles was observed by the dialysis method, and the absorption-promoting effect of micelles was investigated by intestinal circulation experiments in rats. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guilin Medical University. The results of 1H-NMR and FT-IR showed that CS and LA were covalently bound via an amide linkage. The DOX encapsulated in the micelle core was in an amorphous state. The as-prepared micelles in the transmission electron microscope (TEM) image showed regular spherical shapes and uniform sizes with a series of excellent characteristics including (119.2 ± 2.1) nm of mean particle size [polymer dispersity index (PDI), 0.190 ± 0.08], +12.1 mV of zeta potential, (70.23 ± 0.74) % of EE, (8.77 ± 0.02) % of DL and 51.75 μg·mL-1 of CMC. Compared with the reference, DOX hydrochloride, the proposed micelle drug delivery system showed an obvious sustained-release effect in vitro release; and enhanced drug absorption in the small intestine of rats.

Effect of fire needling on imiquimod induced psoriasis-like lesion and STAT3 pathway in mice / 中国针灸

OBJECTIVE@#To observe the effect of fire needling on psoriasis-like lesion and the signal transducer and activator of transcription 3 (STAT3) pathway in mice and compare the therapeutic effect between different interventions of fire needling therapy (surrounding technique of fire needling, fire needling at "Dazhui" [GV 14] and "Zusanli" [ST 36]).@*METHODS@#Thirty male BALB/c mice were randomized into a blank group, a model group, a dexamthasone group, a surrounding technique group and an acupoint group, 6 mice in each one. Except the blank group, the mice in the rest groups were established as psoriasis-like lesion model by topical application with imiquimod cream, once daily, consecutively for 8 days. From day 4 to day 8, in the dexamthasone group, gastric infusion with 0.2 mL dexamthasone was administered, once daily. On day 4, 6 and 8, in the surrounding technique group, fire needling was exerted around the skin lesion; and fire needling was applied to "Dazhui" (GV 14) and "Zusanli" (ST 36) in the acupoint group, once a day. The changes in skin lesion on the dorsal parts of mice were observed in each group to score the psoriasis area and severity index (PASI). Using HE staining, the dermal morphological changes and epidermal thickness were observed in the mice of each group. The positive expression of proliferating cell-associated antigen Ki-67 was determined by immunofluorescence. Immunohistochemistry method was used to determine the expressions of , and T cells of skin tissue in each group. Using real-time PCR, the expressions of interleukin (IL)-17, IL-22, tumor necrosis factor α(TNF-α) mRNA were determined. Western blot method was adopted to determine the protein expressions of STAT3 and p-STAT3 in skin tissue in each group.@*RESULTS@#Compared with the blank group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all increased in the mice of the model group (P<0.01). Except for the erythema scores of the dexamethasone group and the surrounding technique group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all decreased in each intervention group as compared with the model group (P<0.01). The infiltration scores and the total scores in the dexamethasone group and the acupoint group were lower than those in the surrounding technique group respectively (P<0.01, P<0.05). In comparison with the blank group, Ki-67 positive cell numbers and the numbers of , and T cells in skin tissue were increased in the mice of the model group (P<0.01). Ki-67 positive cell numbers and the numbers of , and T cells were reduced in each intervention group as compared with the model group (P<0.01), and the numbers of and T cells in the acupoint group were less than the surrounding technique group (P<0.01). Compared with the blank group, the mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all increased in the model group (P<0.01). The mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all decreased in each intervention group as compared with the model group (P<0.01, P<0.05). The mRNA expressions of IL-17, IL-22 and TNF-α in the acupoint group, as well as mRNA expression of IL-17 in the surrounding technique group were all lower than the dexamethasone group (P<0.01), while, the mRNA expression of IL-22 in the acupoint group was lower than the surrounding technique group (P<0.01).@*CONCLUSION@#Fire needling therapy improves skin lesion severity in imiquimod induced psoriasis-like lesion of the mice, which is probably related to the inhibition of STAT3 pathway activation and the decrease of Th17 inflammatory factors expression. The systemic regulation of fire needling at "Dazhui" (GV 14) and "Zusanli" (ST 36) is superior to the local treatment.

Evaluation on the efficacy of moxifloxacin hydrochloride based on physiological pharmacokinetic models / 药学学报

This study is to establish and validation in vivo models of moxifloxacin based on the theory of physiologically based pharmacokinetics (PBPK), and then to predict the distribution of moxifloxacin in human venous return and organ such as lung, spleen and so on. The efficacy of moxifloxacin and its pharmaceutical preparations were quantified by comparing the pharmacokinetic parameters with the minimum inhibitory concentration of related pathogenic bacterium. The results showed that the anti-infection efficacy of pharmaceutical moxifloxacin preparation in the corresponding organs was basically the same. The PBPK model of moxifloxacin preparations can be more accurately described the pharmacokinetic of anti-infective drugs in human, it is suitable for the efficacy evaluation of anti-infective drugs and provides a strong basis for the corresponding scientific research and scientific supervision.

Application Advantages of Nanoemulsion in Field of Traditional Chinese Medicine Preparation：A Review / 中国实验方剂学杂志

As a new technology with unique drug delivery advantages， nanoemulsion has been widely used in the field of traditional Chinese medicine （TCM） preparations. By searching， classifying and sorting out the literature reports at home and abroad in recent years， this paper systematically expounded the application advantages and production mechanism of nanoemulsion in delivering effective components of TCM from three aspects of improving oral bioavailability， enhancing targeting effect and delaying drug release. The current formulation optimization strategies， preparation processes and quality evaluation indicators commonly used in TCM nanoemulsion were summarized. Based on the research status of TCM nanoemulsion with different active components， the common problems and possible solutions in the development of TCM nanoemulsion were discussed， and the future research hotspots and directions of TCM nanoemulsion were prospected. This article clarifies the feasibility of nanoemulsion for enriching the selection of TCM dosage forms， which can provide reference for the subsequent rational design and improvement of TCM preparations. At the same time， it is revealed that the research focus of TCM nanoemulsion in the future lies in the integrated research of TCM compounds， and shows a trend of multi-disciplinary joint and targeted research.

Pharmacokinetic study on five components in phthalide target areas of Chaxiong and its β-CD inclusion compounds based on UPLC-MS/MS / 中国中药杂志

This study aims to establish a method for the determination of the concentration of five main components of phthalide target areas of Chaxiong(CPTA) and its inclusion of β-CD in the plasma of rats, and determine the pharmacokinetic parameters, absolute bioavailability and relative bioavailability of CPTA/β-CD inclusion compound in vivo. The plasma concentrations of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide were determined with UPLC-MS/MS. The content determination was conducted at the chromatographic conditions as follows: Shim-pack GIST C_(18)-AQ HP column(2.1 mm×100 mm, 3 μm), mobile phase of 0.1% formic acid solution(A)-acetonitrile(B), gradient elution, flow rate of 0.3 mL·min~(-1), column temperature of 35 ℃ and injection volume of 2 μL. The mass spectra were obtained with electrospray ion source(ESI), positive ion mode and multi reaction monitoring. CPTA/β-CD inclusion compound was prepared by grinding method, DAS 2.0 software was used to model the data, and the absolute bioavailability of CPTA and relative bioavailability of inclusion compound were calculated. Finally, the methods for the determination of five components of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide in CPTA, were successfully established. The linear relationship among the five components was good within their respective ranges, r>0.99. The absolute bioavailability of the five components in rats was 22.30%, 16.32%, 21.90%, 10.16% and 12.43%, respectively. After CPTA/β-CD inclusion was prepared, the relative bioavailability of the five components was 138.69%, 198.39%, 218.01%, 224.54% and 363.55%, respectively, significantly improved. This method is rapid, accurate and sensitive, so it is suitable for the pharmacokinetic study of extracts in traditional Chinese medicine and their preparations.

Safety of administration of norepinephrine through peripheral vein line in patients with septic shock / 中华危重病急救医学

Objective:To analysis the risk factors and safety of administration of norepinephrine (NE) via peripheral vein line (PVL) in patients with septic shock.Methods:A single-center retrospective study was conducted. According to the Lanzhou University Second Hospital information system (HIS) and nursing adverse events report cards, patients with septic shock administrated with NE via PVL to correct the hypotension from January 1st 2015 to December 31st, 2019 were enrolled. The patients' general information, placement location of peripheral venous catheter and venousneedle type, characteristics of NE usage and patient general condition when extravasation occurred were collected. The univariate analysis and Logistic regression were used to analyze risk factors associated with extravasation. Also, the receiver operator characteristic curve (ROC curve) was drawn, and the predictive value of risk factors for extravasation was analyzed.Results:A total of 1 022 cases with NE were enrolled. After a preliminary screening, a total of 910 cases with NE were used to correct low blood pressure, including 116 cases of peripheral venous infusion. The average age was (52.91±18.69) years old, with majority of female (77 cases, 66.4%). Basic diseases were mainly chronic obstructive pulmonary disease (COPD, 100 cases, 86.2%), followed by hypertension(91 cases, 78.4%), coronary heart disease (87 cases, 75.0%), type 2 diabetes (74 cases, 63.8%) respectively, the primary disease was septic shock in 109 cases (94.0%). A total of 147 peripheral venous catheters were inserted, and the most common site of puncture was the forearm [78.9% (116/147)], followed by the hand [12.2% (18/147)] and the median cubital vein [8.8% (13/147)]. 89.9% of the needles were 20 G in diameter, and 75 cases (64.7%) were converted to central venous catheters (CVC) during subsequent treatment due to continuous infusion of NE. Six patients (5.2%) had extravasation, the median time of extravasation was 29 (23-39) hours, and the median time of NE was 23 (11-53) hours, including 2 patients with an infusion concentration of 60 mg/L and 4 patients with an infusion concentration of 120 mg/L.The infusion speed was 0.5-1.0 μg·kg -1·min -1, and the average speed of infusion was (0.75±0.04) μg·kg -1·min -1 when extravasation. Univariate and binary Logistic regression analysis showed that the risk factors related to the occurrence of extravasation included: ① patient factors: the presence of basic diseases, hypertension [odds ratio ( OR) = 3.11, 95% confidence interval (95% CI) was 3.09-3.12, P = 0.001] and edema ( OR = 1.79, 95% CI was 1.32-2.99, P = 0.032). ② Factors of infusion fluid itself: long-term (> 24 hours) infusion ( OR = 2.91, 95% CI was 1.04-5.96, P = 0.040), infusion concentration > 60 mg/L ( OR = 1.88, 95% CI was 1.32-3.99, P = 0.024), infusion speed > 0.3 μg·kg -1·min -1 ( OR = 2.43, 95% CI was 2.38-2.51, P = 0.029) and diameter of needles < 20 G ( OR = 3.11, 95% CI was 3.09-3.22, P = 0.033).③ Medical personnel factors: lack of observation and assessment ( OR = 1.09, 95% CI was 1.03-6.77, P = 0.043). The ROC curve analysis showed that: edema, long-term infusion (> 24 hours), infusion rate > 0.3 μg·kg -1·min -1and diameter of needles < 20 G had a certain predictive value for extravasation of NE through peripheral venous infusion in patients with septic shock, the area under ROC curve (AUC) was 0.610, 0.762, 0.672, 0.629, 95% CI was 0.508-0.713, 0.675-0.849, 0.571-0.772, 0.525-0.732, and P values were 0.044, 0.000, 0.002, 0.019, respectively. Conclusions:Hypertension, edema, long-term infusion (> 24 hours), infusion concentration > 60 mg/L, infusion speed > 0.3 μg·kg -1·min -1, diameter of needle < 20 G, and lack of observation and evaluation by medical staff regularly were risk factors affecting the safety of peripheral intravenous NE in patients with septic shock. Peripheral NE should be avoided in the presence of the above risk factors.

Active fraction combination from Liuwei Dihuang decoction improves adult hippocampal neurogenesis and neurogenic microenvironmentin cranially irradiated mice / 中国药理学与毒理学杂志

OBJECTIVE Cranial radiotherapy is clinically used in the treatment of brain tumors;however, the conse?quent cognitive and emotional dysfunctions seriously impair the life quality of patients. LW-AFC, an active fraction combi?nation extracted from classical traditional Chinese medicine prescription Liuwei Dihuang decoction, can improve cogni?tive and emotional dysfunctions in many animal models;however, the protective effect of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions has not been reported. Recent studies indicate that impairment of adult hippocampal neurogenesis (AHN) and alterations of the neurogenic microenvironment in the hippocampus constitute crit?ical factors in cognitive and emotional dysfunctions following cranial irradiation. Here, our research further investigated the potential protective effects and mechanisms of LW-AFC on cranial irradiation-induced cognitive and emotional dys?functions in mice. METHODS LW-AFC (1.6 g·kg-1) was intragastrically administered to mice for 14 d before cranial irra?diation (7 Gyγ-ray). AHN was examined by quantifying the number of proliferative neural stem cells and immature neu?rons in the dorsal and ventral hippocampus. The contextual fear conditioning test, open field test, and tail suspension test were used to assess cognitive and emotional functions in mice. To detect the change of the neurogenic microenvi?ronment, colorimetry and multiplex bead analysis were performed to measure the level of oxidative stress, neurotrophic and growth factors, and inflammation in the hippocampus. RESULTS LW-AFC exerted beneficial effects on the contex?tual fear memory, anxiety behavior, and depression behavior in irradiated mice. Moreover, LW-AFC increased the num?ber of proliferative neural stem cells and immature neurons in the dorsal hippocampus, displaying a regional specificity of neurogenic response. For the neurogenic microenvironment, LW-AFC significantly increased the contents of superox?ide dismutase, glutathione peroxidase, glutathione, and catalase and decreased the content of malondialdehyde in the hippocampus of irradiated mice, accompanied by the increase in brain-derived neurotrophic factor, insulin-like growth factor-1, and interleukin-4 content. Together, LW-AFC improved cognitive and emotional dysfunctions, promoted AHN preferentially in the dorsal hippocampus, and ameliorated disturbance in the neurogenic microenvironment in irradiated mice. CONCLUSION LW-AFC ameliorates cranial irradiation-induced cognitive and emotional dysfunctions, and the underlying mechanisms are mediated by promoting AHN in the dorsal hippocampus and improving the neurogenic micro?environment. LW-AFC might be a promising therapeutic agent to treat cognitive and emotional dysfunctions in patients receiving cranial radiotherapy.

Cognitive impairment in children with benign childhood epilepsy with centrotemporal spikes and attention deficit hyperactivity disorder: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the difference in cognitive impairment between the children with benign childhood epilepsy with centrotemporal spikes (BECT) and attention deficit hyperactivity disorder (ADHD) and those with BECT or ADHD alone.@*METHODS@#A prospective study was performed on 80 children with BECT and ADHD, 91 children with BECT, and 70 children with ADHD , who were diagnosed with the diseases for the first time. Seventy children of the same age who underwent physical examination were enrolled as the healthy control group. Event-related potential P300, Wechsler Intelligence Scale for Children, and integrated visual and auditory continuous performance test were used to measure and compare each index between groups.@*RESULTS@#Compared with the healthy control group, the BECT+ADHD group, the BECT group, and the ADHD group had a significantly prolonged P300 latency, a significant reduction in the amplitude of P300, and significant reductions in the scores of verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ), auditory response control quotient (ARCQ), visual response control quotient, full response control quotient (FRCQ), auditory attention quotient (AAQ), visual attention quotient, and full attention quotient (@*CONCLUSIONS@#Compared with the children with BECT or ADHD alone, the children with both BECT and ADHD have basically the same fields of cognitive impairment but a higher degree of cognitive impairment in some fields.

Moxibustion on plaque psoriasis of blood stasis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the short-term and long-term effects of moxibustion on plaque psoriasis of blood stasis, and to compare the curative effect between moxibustion and calcipotriol ointment.@*METHODS@#A total of 80 patients with plaque psoriasis of blood stasis were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 4 cases dropped off). Both groups were given routine medical vaseline topical emollient basic treatment. In the observation group, moxibustion was applied to @*RESULTS@#After treatment, the PASI scores in the both groups were lower than before treatment (@*CONCLUSION@#Both moxibustion and calcipotriol ointment have good short-term effects on plaque psoriasis of blood stasis. Moxibustion has more advantages in reducing the recurrence rate of psoriasis, improving the main clinical symptoms of TCM and quality of life.

Application of a risk stratification-based model for prediction of acute kidney injury combined with hemoperfusion in patients with sepsis: a prospective, observational, pilot study / 中华危重病急救医学

Objective:To evaluate the efficacy and safety of a risk stratification-based model for prediction of acute kidney injury (AKI) combined with hemoperfusion (HP) in the treatment of patients with sepsis.Methods:A prospective, observational, pilot trial was conducted. The patients who met the Sepsis-3 diagnostic criteria admitted to intensive care unit of Lanzhou University Second Hospital from May to December in 2019 were enrolled as the research objects. Through the AKI early warning model established by the research group in the early stage, AKI risk > 30% was defined as AKI high risk. Patients with AKI high risk were enrolled in the observation group, and the remaining patients were enrolled in the control group. All patients were given conventional treatment, including the search and treatment of original infection sites, the use of antibiotics and main organ function support. Patients in the observation group were combined with HP treatment on the basis of conventional treatment, 2.5 hours per day for 3 days. The baseline data of gender, age, infection site, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, mean arterial pressure (MAP) and serum creatinine (SCr) were recorded. The inflammatory indexes such as interleukin-6 (IL-6), lipopolysaccharide (LPS) and procalcitonin (PCT) were detected at ICU admission, 24 hours and 72 hours after ICU admission, and the length of ICU stay, ICU mortality and bleeding were recorded.Results:Among the 49 patients with sepsis enrolled in this study, the main diagnosis was pneumonia, and Gram-negative (G -) bacilli were the main pathogenic bacteria [61.2% (30/49)]. Among them, 30 patients with AKI risk > 30% were in the observation group, and the remaining 19 patients were in the control group. There was no significant difference in gender, age, infection site, APACHE Ⅱ score, SOFA score, MAP or other baseline data between the two groups, but the baseline value of SCr in the observation group was significantly higher than that in the control group (μmol/L: 112.2±34.4 vs. 93.4±13.0, P < 0.05). At ICU admission, there was no significant difference in IL-6, LPS or PCT between the two groups. However, with the extension of ICU time, the inflammatory indexes of the two groups showed a downward trend. At 24 hours after ICU admission, there was no significant difference in IL-6, LPS or PCT between the two groups. At 72 hours after ICU admission, IL-6 in the experimental group decreased significantly as compared with the control group (ng/L: 90.9±38.1 vs. 119.1±41.9, P < 0.05), but there was no significant difference in LPS or PCT between the two groups. The length of ICU stay in the experimental group was significantly shorter than that in the control group (days: 9.77±2.76 vs. 12.47±3.85, P < 0.01), but there was no significant difference in the ICU mortality between the experimental group and control group (20.0% vs. 21.1%, P > 0.05). None of the 49 patients had severe bleeding events. Conclusions:The application of a risk stratification-based model for prediction of AKI combined with HP in septic patients is feasible both in theory and in clinical practice, and shortens the length of ICU stay, but fails to effectively remove inflammatory mediators or reduce sepsis mortality. A large sample, multicenter, randomized controlled study is still needed for further verification.

Effect of bortezomib on the proliferation and apoptosis of acute T lymphocyte leukemia cell line Jurkat and its related mechanism / 中国基层医药

Objective:To explore the effects and mechanisms of bortezomib on the proliferation and apoptosis of acute T lymphocyte leukemia cell line Jurkat.Methods:MTT assay was used to test the influence of bortezomib on the proliferation of Jurkat cells.Flow cytometry was used to detect the influence of bortezomib on apoptosis of Jurkat cells.Real-time quantitative polymerase reaction(RT-PCR) was used to detect the effects of bortezomib on the expression of Bax, Bcl-2 and Cox-2 genes in Jurkat cells.Results:The inhibition rates of 5ng/mL, 10ng/mL, 20ng/mL and 40ng/mL bortezomib on Jurkat cells at 24h were (13.23±0.71)%, (39.53±0.95)%, (53.07±1.12)%, (60.43±0.75)%, respectively, and the inhibition rates at 48h were (25.20±0.96)%, (52.80±1.30)%, (60.67±0.64)%, (75.10±1.35)%, respectively.The inhibitory rates of proliferation of Jurkat cells at 72h were (38.37±0.93)%, (60.94±0.85)%, (73.83±5.08)%, (88.37±1.55)%, respectively.The inhibitory rates of proliferation of Jurkat cells increased with the increase of drug concentration and the prolongation of action time, and the differences were statistically significant( F=1 602.202, 1 085.089, 181.034, all P<0.05). Bortezomib (5ng/mL, 10ng/mL, 20ng/mL and 40ng/mL) treatment for 24h, 48h and 72h, the apoptosis rate of Jurkat cells increased with the increase of drug concentration and the prolongation of action time, the differences were statistically significant( F=1 288.571, 223.378, 251.175, all P<0.05). The expression of Bax mRNA in Jurkat cells increased with the increase of drug concentration and time( F=258.446, 518.929, 276.764, all P<0.05). The Bcl-2 mRNA and Cox-2 mRNA expression levels decreased with the increase of drug concentration and the prolongation of action time( FBcl-2 mRNA=236.848, 264.849, 343.968, FCox-2 mRNA=679.404, 1288.681, 1541.850, all P<0.05). Conclusion:Bortezomib can inhibit the proliferation and induce apoptosis of Jurkat cells.Bortezomib can increase the expression of Bax mRNA and decrease the expression of Bcl-2 and Cox-2 mRNA, which may be the molecular mechanism of bortezomib to promote apoptosis.

Awareness, treatment and control of hypertension in 640 000 adults in eastern China / 中华流行病学杂志

Objective@#To understand the awareness, treatment, and control of hypertension in residents aged 35-75 years in eastern China, analyze the treatment mode for antihypertensive agents while identifying those factors affecting awareness, treatment and control.@*Methods@#The data collected in eastern China from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project were used to obtain the information about the awareness, treatment and control of hypertension in the residents and the antihypertensive medication treatment mode in this area. Multilevel mixed-effects model was used to explore the association of the demographic characteristics of hypertension patients with the rates of awareness, treatment and control of hypertension.@*Results@#A total of 640 539 participants aged 35-75 years, mean age (56.9±9.6) years, were included in the analysis, women accounted for 59.7% and 318 741 (49.8%) of the participants suffered from hypertension. Among those hypertensive patients, 46.5% were aware of their condition, 38.1% were taking prescribed antihypertensive medications, and 11.1% had achieved the control of hypertension, the differences were significant among provinces, between urban area and rural area and among different demographical groups. Calcium-channel blockers was the most commonly used medication (45.1%), and 78 735 hypertension patients (86.2%) took only one type of medication. Older age, higher household income, higher level of education, and histories of myocardial infarction, stroke and diabetes were associated with higher awareness, treatment and control of hypertension (P<0.05).@*Conclusions@#The rates of awareness, treatment and control of hypertension were low in residents in eastern China. The differences in hypertension management were significant among provinces and between urban area and rural area. Further efforts are needed to enhance the system of hypertension prevention, screening, diagnosis and treatment.

Effect and mechanism of total flavonoids of Lichi Semen on CCl_4-induced liver fibrosis in rats, and prediction of Q-marker / 中国中药杂志

This paper was to investigate the effect of total flavonoids of Lichi Semen(TFL) on carbon tetrachloride(CCl_4)-induced liver fibrosis in rats, analyze and predict its mechanism of action and potential quality markers(Q-marker). Firstly, male SD rats were taken and injected subcutaneously with a 40% CCl_4-vegetable oil solution twice a week for 8 consecutive weeks to establish a rat model of liver fibrosis. The rats with liver fibrosis were randomly divided into model group, silybin group(43.19 mg·kg~(-1)), Fuzheng Huayu Capsules group(462.75 mg·kg~(-1)), and TFL groups(100 mg·kg~(-1) and 25 mg·kg~(-1)), with normal rats as a blank group, 10 rats in each group. Except for the blank group, the rats in the other groups were subcutaneously injected with 40% CCl_4-vegetable oil solution of a maintenance dose, once a week. The rats in various treatment groups received corresponding doses of drugs, while the rats in the blank group and model group received the same volume of normal saline once a day for 4 weeks. At the end of the experiment, blood was collected from the abdominal aorta and the liver tissues were collected. The levels of total bilirubin(TBiL), direct bilirubin(DBiL), indirect bilirubin(IBiL), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum were detected by using an automatic biochemical detector. Masson staining was used to observe the histopathological changes of rat liver. Then, the chemical compositions of TFL were collected, and the action targets of these chemical compositions were predicted through SWISS database and reverse molecular docking server(DRAR-CPI). After screening of disease targets of liver fibrosis by Gene Cards database, the protein-protein interaction was analyzed with use of STRING database, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) enrich analysis were also carried out. Moreover, an iTRAQ proteomics technology was used to determine protein expression in liver tissues of rats in TFL, model and blank groups to verify the targets. Furthermore, Cytoscape software was used to establish and visualize the network of chemical components, targets and pathways, and predict the potential Q-marker of TFL. The results showed that the levels of TBiL, DBiL, IBiL, ALT, and AST in the model group were significantly higher than those in the blank normal group(P<0.05), and the above levels in the treatment groups were lower than those in the model group, but with no significant differences. Masson staining showed that the liver damage and the degree of fibrosis were severe in the model group, and were relieved to different degrees in the treatment groups. Then, 74 chemical components were screened, which could act on 865 targets such as EGFR and SRC, participating in the regulation of cancer pathways, PI3 K-Akt signaling pathway, HIF-1 signaling pathway and other signaling pathways closely related to liver fibrosis. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin showed the highest correlation with liver fibrosis-related targets and pathways. Proteomics results showed that a total of 18 proteins among the 45 proteins predicted by internet pharmacology were identified, among which 6 proteins were significantly expressed, including 5 up-regulated proteins and 1 down-regulated protein. The protein expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1 was significantly returned to a normal state in the TFL treatment groups. In conclusion, TFL may demonstrate the anti-hepatic fibrosis and potential hepatoprotective effects by regulating the expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1, which may be associated with the regulation of multiple signaling pathways related to liver fibrosis such as PI3 K-Akt pathway. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin could be regarded as potential Q-markers of TFL for quality control.

Determination of genotoxic impurities of alkyl methanesulfonates in methanesulfonic acid by gas chromatography–mass spectrometry / 中国药科大学学报

@#An analytical liquid-liquid extraction-gas chromatography–mass spectrometry (LLE-GC-MS) method was established for the determination of genotoxic impurities including methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS) and isopropyl methanesulfonate (IMS) in methanesulfonic acid. An Agilent HP-1MS capillary column (30 m × 0.32 m, 1 μm) was used for separating the analytes by programmed heating with the inlet temperature of 220 °C. Mass spectrometry was operated in positive ion mode, and selective ion monitors were set at m/z 80 for MMS, m/z 79 for EMS, m/z 123 for IMS and m/z 56 for internal standard butyl methanesulfonate (BMS). Results showed that the baseline separation of MMS, EMS and IMS was achieved, and the blank extraction solution had no interference; good linearity was achieved in the range of 37-1 480 ng/mL for three alkyl methanesulfonates; The mean recoveries of MMS, EMS, IMS were 104.99%, 107.26%,108.85%, respectively, with RSD ≤ 4.54%. The established method has the characteristics of specific, sensitive, accurate, stable and good versatility, and has been used for the detection and control of alkyl methanesulfonate impurities in methanesulfonic acid from a variety of manufacturers.

Awareness, treatment and control of hypertension in 640 000 adults in eastern China / 中华流行病学杂志

To understand the awareness, treatment, and control of hypertension in residents aged 35-75 years in eastern China, analyze the treatment mode for antihypertensive agents while identifying those factors affecting awareness, treatment and control. The data collected in eastern China from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project were used to obtain the information about the awareness, treatment and control of hypertension in the residents and the antihypertensive medication treatment mode in this area. Multilevel mixed-effects model was used to explore the association of the demographic characteristics of hypertension patients with the rates of awareness, treatment and control of hypertension. A total of 640 539 participants aged 35-75 years, mean age (56.9±9.6) years, were included in the analysis, women accounted for 59.7 and 318 741 (49.8) of the participants suffered from hypertension. Among those hypertensive patients, 46.5 were aware of their condition, 38.1 were taking prescribed antihypertensive medications, and 11.1 had achieved the control of hypertension, the differences were significant among provinces, between urban area and rural area and among different demographical groups. Calcium-channel blockers was the most commonly used medication (45.1), and 78 735 hypertension patients (86.2) took only one type of medication. Older age, higher household income, higher level of education, and histories of myocardial infarction, stroke and diabetes were associated with higher awareness, treatment and control of hypertension (<0.05). The rates of awareness, treatment and control of hypertension were low in residents in eastern China. The differences in hypertension management were significant among provinces and between urban area and rural area. Further efforts are needed to enhance the system of hypertension prevention, screening, diagnosis and treatment.