Dihydroartemisinin inhibits plasmid transfer in drug-resistant Escherichia coli via limiting energy supply.

Conjugative transfer of antibiotic resistance genes (ARGs) by plasmids is an important route for ARG dissemination. An increasing number of antibiotic and nonantibiotic compounds have been reported to aid the spread of ARGs, highlighting potential challenges for controlling this type of horizontal transfer. Development of conjugation inhibitors that block or delay the transfer of ARG-bearing plasmids is a promising strategy to control the propagation of antibiotic resistance. Although such inhibitors are rare, they typically exhibit relatively high toxicity and low efficacy in vivo and their mechanisms of action are inadequately understood. Here, we studied the effects of dihydroartemisinin (DHA), an artemisinin derivative used to treat malaria, on conjugation. DHA inhibited the conjugation of the IncI2 and IncX4 plasmids carrying the mobile colistin resistance gene ( mcr-1) by more than 160-fold in vitro in Escherichia coli, and more than two-fold (IncI2 plasmid) in vivo in a mouse model. It also suppressed the transfer of the IncX3 plasmid carrying the carbapenem resistance gene bla NDM-5 by more than two-fold in vitro. Detection of intracellular adenosine triphosphate (ATP) and proton motive force (PMF), in combination with transcriptomic and metabolomic analyses, revealed that DHA impaired the function of the electron transport chain (ETC) by inhibiting the tricarboxylic acid (TCA) cycle pathway, thereby disrupting PMF and limiting the availability of intracellular ATP for plasmid conjugative transfer. Furthermore, expression levels of genes related to conjugation and pilus generation were significantly down-regulated during DHA exposure, indicating that the transfer apparatus for conjugation may be inhibited. Our findings provide new insights into the control of antibiotic resistance and the potential use of DHA.

CD168+ macrophages promote hepatocellular carcinoma tumor stemness and progression through TOP2A/ß-catenin/YAP1 axis.

Liver cancer stem-like cells (LCSCs) are the main cause of heterogeneity and poor prognosis in hepatocellular carcinoma (HCC). In this study, we aimed to explore the origin of LCSCs and the role of the TOP2A/ß-catenin/YAP1 axis in tumor stemness and progression. Using single-cell RNA-seq analysis, we identified TOP2A+CENPF+ LCSCs, which were mainly regulated by CD168+ M2-like macrophages. Furthermore, spatial location analysis and fluorescent staining confirmed that LCSCs were enriched at tumor margins, constituting the spatial heterogeneity of HCC. Mechanistically, TOP2A competitively binds to ß-catenin, leading to disassociation of ß-catenin from YAP1, promoting HCC stemness and overgrowth. Our study provides valuable insights into the spatial transcriptome heterogeneity of the HCC microenvironment and the critical role of TOP2A/ß-catenin/YAP1 axis in HCC stemness and progression.

Development and Validation of a Predictive Risk Model for Vision-threatening Diabetic Retinopathy in Patients with Type 2 Diabetes / 中山大学学报(医学科学版)

ObjectiveTo develop and validate a predictive risk model for vision-threatening diabetic retinopathy in patients with type 2 diabetes using readily accessible clinical data， which may provide a convenient and effective prediction tool for early identification and referral of at-risk populations. MethodsA nomogram model was developed using a dataset obtained from patients with T2DM who participated in the Guangzhou Diabetic Eye Study from November 2017 to December 2020. Logistic regression was used to construct the model， and model performance was evaluated using receiver operating characteristic curve， Hosmer-Lemeshow test， calibration curve and decision curve analysis. The model underwent internal validation through the mean AUC of k-fold cross-validation method， and further external validation was conducted in the Dongguan Eye Study. ResultsA total of 2 161 individuals were included in the model development dataset， of whom 135 （6.25%） people were diagnosed with VTDR. Age （P＜0.001，OR=0.927，95%CI：0.898~0.957） and body mass index （P＜0.001，OR =0.845，95%CI：0.821~0.932） were found to be negatively correlated with VTDR， whereas diabetes duration （P＜0.001，OR=1.064，95%CI：1.035~1.094）， insulin use （P =0.045，OR =1.534，95%CI：1.010~2.332）， systolic blood pressure （P＜0.001，OR =1.019，95%CI：1.008~1.029）， glycated hemoglobin （P＜0.001，OR =1.484，95%CI：1.341~1.643）， and serum creatinine （P＜0.001，OR =1.017，95%CI：1.010~1.023） were positively correlated with VTDR. All these variables were included in the model as predictors. The model showed strong discrimination in the development dataset with an area under the receiver operating characteristic curve （AUC） of 0.797 and in the external validation dataset （AUC 0.762）. The Hosmer-Lemeshow test（P＞0.05）and the calibration curve displayed good agreement. Decision curve analysis showed that the nomogram produced net benefit in the two datasets. ConclusionsIndependent factors influencing VTDR include age， duration of diabetes mellitus， insulin use， body mass index， systolic blood pressure， glycosylated hemoglobin， and serum creatinine. The nomogram constructed using these variables demonstrates a high degree of predictive validity. The model can serve as a valuable tool for early detection and referral of VTDR in primary care clinics. Therefore， its application and promotion are highly recommended.

Single-cell RNA Sequencing Analysis Reveals New Immune Disorder Complexities in Hypersplenism.

Hypersplenism (HS) is a concomitant symptom of liver or blood disease. Not only does the treatment of HS face challenges, but the transcriptome of individual cells is also unknown. Here, the transcriptional profiles of 43,037 cells from four HS tissues and one control tissue were generated by the single-cell RNA sequencing and nine major cell types, including T-cells, B-cells, NK cells, hematopoietic stem cells, neutrophil cells, mast cells, endothelial cells, erythrocytes, and dendritic cells were identified. Strikingly, the main features were the lack of CCL5+ B-cells in HS and the presence of SESN1+ B cells in HS with hepatocellular carcinoma (HS-HCC). In cell-cell interaction analysis, CD74-COPA and CD94-HLA-E in HS were found to be up-regulated. We further explored HS-specifically enriched genes (such as FKBP5, ADAR, and RPS4Y1) and found that FKBP5 was highly expressed in HCC-HS, leading to immunosuppression. Taken together, this research provides new insights into the genetic characteristics of HS via comprehensive single-cell transcriptome analysis.

Molnupiravir combined with different repurposed drugs further inhibits SARS-CoV-2 infection in human nasal epithelium in vitro

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in late 2019, has caused a worldwide pandemic with unprecedented economic and societal impact. Currently, several vaccines are available, and multitudes of antiviral treatments have been proposed and tested. Although many of the vaccines show high clinical efficacy, they are not equally accessible worldwide. Additionally, due to the continuous emergence of new virus variants, and generally short duration of immunity, the development of safe and effective antiviral treatments remains of the utmost importance. Since the emergence of SARS-CoV-2, substantial efforts have been undertaken to repurpose existing and approved drugs for accelerated clinical testing and potential emergency use authorizations. However, drug-repurposing using high throughput screenings in cellular assays, often identify hits that later prove ineffective in clinical studies. Our approach was to evaluate the activity of compounds that have either been tested clinically or already undergone extensive preclinical profiling, using a standardized in vitro model of human nasal epithelium. Secondly, we evaluated drug combinations using sub-maximal doses of each active single compound. Here, we report the antiviral effects of 95 single compounds and 30 combinations. The data show that selected drug combinations including 10 M of molnupiravir, a viral RNA-dependent RNA polymerase (RdRp) inhibitor, effectively inhibit SARS-CoV-2 replication. This indicates that such combinations are worthy of further evaluation as potential treatment strategies against coronavirus disease 2019 (COVID-19).

Dexmedetomidine alleviates LPS/D-Gal-induced acute liver injury via up-regulation of LC3-II expression in mice / 生理学报

The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels were determined by ELISA. The protein expression levels of LC3-II and P62 in liver tissue were determined by Western blot. Liver histopathological changes were detected by HE staining. The results showed that, compared with control group, LPS/D-Gal enhanced ALT and AST activity, increased TNF-α and IL-6 levels, as well as MPO activity, up-regulated LC3-II and P62 protein expression levels, and significantly induced pathological damage in liver tissue. DEX reversed the above changes in the LPS/D-Gal group, whereas these protective effects of DEX were blocked by 3-MA. The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy.

miR-205-5p/E2F1 signal axis is involved in the regulation of radiosensitivity of glioma cells through suppressing the classical Wnt/β-catenin signaling pathway / 中华放射肿瘤学杂志

Objective:To explore the mechanism of miR-205-5p/E2F1 signal axis in regulating the glioma U251, U87 radiotherapy resistance.Methods:X-ray gradual ascending and intermittent induction method was used to irradiate the glioma U251 cells to establish U251/TR, U87/TR radiation-resistant cell lines. Then, the morphology, migration, invasion and proliferation abilities of cells (U251/TR, U87/TR radiation-resistant cells and U251, U87 radiation-sensitive cells) were analyzed. Luciferase gene detection system and point mutation technique were employed to analyze the mechanism of miR-205-5p and E2F1 gene activity on U251 and U87 radiation-resistant cell lines.Results:Compared with the radiation-sensitive U251 cells, the radiation-resistant cells U251/TR, U87/TR showed increased proliferation activity, enhanced migration and invasion abilities and decreased apoptosis under X-ray irradiation. miR-205-5p mimics transfection could down-regulate the expression of E2F1 factor in U251/TR cells, inhibit cell proliferation, invasion and migration and increase the radiosensitivity of U251/TR cells. miR-205-5p mimics transfection combined with with E2F1 down-regulation exerted anti-tumor effect and decreased cell tolerance by suppressing the Wnt/β-catenin signaling pathway activity.Conclusions:The glioma radiation-resistant cell line U251/TR, U87/TR can be established by X-ray gradual ascending and intermittent induction method. The miR-205-5p/E2F1 signal axis exerts tumor-suppressing effect through the classical Wnt/β-catenin signaling pathway, which can be used as an therapeutic target to increase the radiosensitivity of glioma.

Emodin reactivated autophagy and alleviated D-galactosamine/lipopolysaccharide-induced acute liver injury / 中华急诊医学杂志

Objective:To explore the protective effect of emodin on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury and its mechanism.Methods:A total of 40 male BALB/c mice were randomly (random number) divided into 5 groups ( n=8 in each group): the control group, the emodin group, the D-GalN/LPS group, the emodin+D-GalN/LPS group and the 3-MA+emodin+D-GalN/LPS group. D-GalN (700 mg/kg) and LPS (10 μg/kg) were intraperitoneally injected to induce acute liver injury in mice. Autophagy inhibitor 3-MA (15 mg/kg) and/or emodin (20 mg/kg) were intraperitoneally injected 30 min before the liver injury model. The animals were sacrificed under anaesthesia 6 h after D-GalN/LPS challenge, blood samples and liver tissues were collected. The levels of alanineaminotransferase (ALT) and aspartateaminotransferase (AST) in serum, and myeloperoxidase (MPO) activity of liver tissues were determined by colorimetric quantitative method; the levels of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured by ELISA; the expression of LC3-II and Beclin 1 in the liver tissues were evaluated by Western blot; the pathological changes of liver was evaluated by HE staining. Animal survival rate was also analyzed. The one-way ANOVA was use to compare quantitative data, SNK- q test was used for pairwise comparison between two groups, and Games-Howell test was used when homogeneity of variance were not met. Results:Compared with the control group, the levels of ALT, AST, TNF-α, IL-6 and MPO activity [(2 476.80 ± 263.14) U/L, (271.71 ± 47.15) U/L, (537.92 ± 89.35) pg/mL, (169.74 ± 25.52) pg/mL, and (1.37 ± 0.22) U/mg] were obviously increased in the D-GalN/LPS group ( P<0.05). Compared with the D-GalN/LPS group, the levels of ALT, AST, TNF-α, IL-6 and MPO activity [(1 248.01 ± 380.70) U/L, (142.59 ± 34.63) U/L, (288.91 ± 67.21) pg/mL, (61.83 ± 13.64) pg/mL, and (0.80 ± 0.21) U/mg] were obviously decreased in the emodin+ D-GalN/LPS group ( P<0.05). Compared with the D-GalN/LPS group, the histopathological abnormalities in liver tissue were significantly alleviated and the survival rate of mice was improved in the emodin+ D-GalN/LPS group. Compared with the control group, the expression of LC3-II and Beclin1 was decreased in the liver tissue in the D-GalN/LPS group, while compared with the D-GalN/LPS group, the expression of LC3-II and Beclin1 was increased in the emodin+ D-GalN/LPS group. With co-administration of 3-MA, the protective effects of emodin in acute liver injury were reversed, the levels of AST, ALT, TNF-α, IL-6, and MPO [(2 398.78 ± 233.57) U/L, (242.79 ± 43.46) U/L, (505.07 ± 67.89) pg/mL, (151.46 ± 14.11) pg/mL, and (1.27 ± 0.15) U/mg] were increased, and the pathological damage of liver tissue was aggravated. Conclusions:Emodin alleviates D-GalN/LPS-induced acute liver injury in mice, which may be related to the activation of protein LC3-II, Beclin1 and restored autophagy.

Glycyrrhizic acid: a potential drug against COVID-19 / 药学学报

Pneumonia caused by SARS-CoV-2 has seriously threatened human life and health worldwide and caused a large number of deaths. Viral infection and acute inflammation are important causes of death, so it is particularly important to combine antiviral therapy with anti-inflammatory therapy. Glycyrrhizic acid, the main component of the glycyrrhizic root extract, has a wide range of pharmacological effects as well as high efficiency and low toxicity, its preparation has been widely used in the treatment of chronic hepatitis and other diseases. Glycyrrhizic acid can regulate the expression and release of a variety of cytokines and play a significant anti-inflammatory effect. At the same time, glycyrrhizic acid also showed significant inhibition towards a variety types of viruses. Therefore, the potential application of glycyrrhizic acid as COVID-19 treatment should be explored.

PGC-1α regulate critical period plasticity via gene × environment interaction in the developmental trajectory to schizophrenia.

Genes and environmental conditions are thought to interact in the development of postnatal brain in schizophrenia (SZ). Genome wide association studies have identified that PPARGC1A being one of the top candidate genes for SZ. We previously reported GABAergic neuron-specific PGC-1α knockout mice (Dlx5/6-Cre:PGC-1αfl/fl) presented some characteristic features of SZ. However, there is a fundamental gap of the molecular mechanism by which PGC-1α gene involved in the developmental trajectory to SZ. To explore whether PGC-1α regulates environmental factors interacting with genetic susceptibility to trigger symptom onset and disease progression, PGC-1α deficient mice were utilized to model genetic effect and an additional oxidative stress was induced by GBR injection. We confirm that PGC-1α gene deletion prolongs critical period (CP) timing, as revealed by delaying maturation of PV interneurons (PVIs), including their perineuronal nets (PNNs). Further, we confirm that gene × environment (G × E) influences CP plasticity synergistically and the interaction varies as a function of age, with the most sensitive period being at preweaning stage, and the least sensitive one at early adult age in PGC-1α deficient mice. Along this line, we find that the synergic action of G × E is available in ChABC-infusion PGC-1α KO mice, even though during the adulthood, and the neuroplasticity seems to remain open to fluctuate. Altogether, these results refine the observations made in the PGC-1α deficient mice, a potential mouse model of SZ, and illustrate how PGC-1α regulates CP plasticity via G × E interaction in the developmental trajectory to SZ.

Adult conditional knockout of PGC-1α in GABAergic neurons causes exaggerated startle reactivity, impaired short-term habituation and hyperactivity.

Interneurons not only contribute to the global balance of activity in cortical networks but also mediate the precise gating of information through specific proteins. Accumulating evidence demonstrates that peroxisome-proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1α) is concentrated in inhibitory interneurons and that it plays an important role in neuropsychiatric diseases. However, the functions of the transcriptional coactivator PGC-1α in sensorimotor gating, short-term habituation and spatial reference memory are still not entirely clear. To investigate the precise involvement of PGC-1α in the progression of psychiatric disorders, we first generated PGC-1α conditional knockout mice through transgenic expression of Cre recombinase under the control of dlx5/6 promoter, Cre-mediated excision events occurred specifically in γ-amino-butyric-acid-(GABA)ergic neurons. Short-term habituation and spatial reference memory in Dlx5/6-Cre::PGC-1αfl/fl mice were evaluated using the novel object recognition test and the Morris water maze test, and sensorimotor gating was measured by prepulse inhibition of the acoustic startle reflex. Protein expression of parvalbumin (PV) in specific brain regions was studied by western blotting, immunofluorescence and immunohistochemistry. Here, we show that mice lacking the PGC-1α gene in GABAergic neurons exhibit deficits in short-term habituation, hyperactivity, reduced prepulse inhibition and exaggerated startle reactivity but normal associative spatial reference memory. In particular, these mice display aberrant salience, whereby more attention is paid to a further copy of the original object (now familiar) (relative to the first presentation of the original object, and relative to the presentation of the novel object). These behavioral dysfunctions were associated with decreased PV expression in the cortex (including somatosensory and motor cortex) as well as in the hippocampus, especially in its CA1 and CA3 regions. Together, these findings draw attention to a hyper-response phenotype of PGC-1α conditional knockout mice and indicate that PGC-1α is a novel regulator of gene expression and function in PV-positive interneurons and a potential therapeutic target for psychiatric disorders associated with PGC-1α dysregulation.

Inhibition of expression of glucocorticoids receptors may contribute to postpartum depression.

Although postpartum depression (PPD) is the leading cause of disability worldwide, its molecular mechanisms are poorly understood. Recent evidence has suggested that impaired glucocorticoid receptor (GR), the signaling of key molecules of the HPA axis, plays a key role in the behavioral and neuroendorcrine alterations of major depression. However, the role of GR in postpartum period, which following with the abrupt withdrawal of placental corticotropin releasing hormone (CRH) and resulting in a re-equilibration of the maternal HPA axis in the days of post-delivery, is still not entirely clear. Previously, a hormone-simulated pregnancy (HSP), and the subsequent 'postpartum' withdrawal in estrogen has been employed to mimic the fluctuations in estradiol associated with pregnancy and postpartum. Using the HSP model, we investigated here the effect of 'postpartum' withdrawal in estrogen as well as depression- and anxiety-like behavior by intra-hippocampal infusion with GR inhibitor-RU486. Following the successful acquisition of PPD model by withdrawal in estrogen, reduced GR expression was observed in hippocampus. Further, HSP-rats suffered intra-hippocampal RU486 infusion presented depression- and anxiety-like behavior as postpartum depression. Together, these results suggest an important, though complex, role for GR in the behavioral regulation of postpartum depression.

Effect of moxibustion on clinical symptoms, peripheral inflammatory indexes and T lymphocyte subsets in COVID-19 patients / 中国针灸

OBJECTIVE@#To explore the therapeutic effect and the mechanism of the adjuvant treatment with moxibustion on coronavirus disease 2019 (COVID-19).@*METHODS@#A total of 95 patients with COVID-19 were randomly divided into a moxibustion group (45 cases) and a basic treatment group (50 cases). The routine treatment of western medicine was applied in the patients of both groups. In the moxibustion group, on the base of the treatment of western medicine, moxibustion was applied to Dazhui (GV 14), Feishu (BL 13), Qihai (CV 6) and Zusanli (ST 36), once daily and consecutively for 14 days. At the end of treatment courses, clinical symptom scores for cough, asthmatic breathing, chest oppression and short breath, as well as their remission rates were compared between the two groups before and after treatment. Before and after treatment, the white blood cell (WBC) count, the levels of c-reactive protein (CRP) and interleukin-6 (IL-6) and the absolute number of T lymphocyte subsets, i.e. , and of the peripheral blood were compared in the patients between the two groups. The principal component analysis was adopted to analyze the common data extracted from the above 10 clinical indexes variables and comprehensively evaluate the differences in the therapeutic effect of two regimens.@*RESULTS@#The clinical symptom scores were all decreased after treatment in both of the moxibustion group and the basic treatment group as compared with those before treatment (@*CONCLUSION@#On the base of the routine treatment with western medicine, moxibustion therapy supplemented relieves the clinical symptoms, reduces the levels of inflammatory indexes, i.e. IL-6 and CRP as well as improves the absolute number of peripheral T lymphocyte subsets. The clinical therapeutic effect of such regimen with moxibustion supplemented is significantly better than the simple routine treatment of western medicine.

Fixation of os acromiale using polyester sutures: a novel surgical treatment.

BACKGROUND: Patients with unstable os acromiale often complain of shoulder pain. Numerous surgical treatment options have been introduced with inconsistent clinical results. In this study, a novel surgical treatment using polyester sutures to fix unstable os acromiale was introduced, and clinical results were reported. METHODS: We retrospectively studied 10 shoulders that were diagnosed with os acromiale from January 2014 to January 2016. All 10 cases were of the meso-acromion type. Except for the first case in our series, cases of os acromiale were fixed using polyester sutures arthroscopically. The standardized scores and visual analog scale (VAS) were recorded preoperatively and at each follow-up. A computed tomography (CT) scan was ordered at the follow-up of 12 months. RESULTS: The average follow-up length was 28.7 months, ranging from 26 to 33 months. The average Constant score before surgery was 40.50±4.53 points, which significantly improved to 75.60±5.17 points after surgery. The average VAS score was reduced from 5.20±1.14 points to 1.60±0.84. At the follow-up of 12 months, a CT scan was ordered. All the patients showed a bony union of the os acromiale. On the CT scan, two small pits could be seen on the medial and lateral side of the acromion, which indicated the level of the os acromiale. The position of the os acromiale was good, and no evident sclerosis was found on the edges of the fragments. CONCLUSIONS: Polyester sutures could provide reliable strength for the fixation of os acromiale without any irritation from hardware.

Clinical outcomes after absorbable suture fixation of patellar osteochondral fracture following patellar dislocation.

BACKGROUND: Osteochondral fracture (OCF) is one of the severe complications following a patellar dislocation. The appropriate fixation method for patients with OCF remains controversial. METHODS: Eighteen patients who had undergone surgery after a patellar dislocation were recruited retrospectively. Patellar OCF was fixed with an absorbable suture in an unreported method. The medial patellofemoral ligament (MPFL) was repaired or reconstructed if necessary. The Lysholm and Kujala knee scoring systems were used to evaluate the knee function. Imaging examinations were used to confirm the fracture healing. RESULTS: The mean period of follow-up was 36 months. All patients recovered well postoperatively without symptomatic complications. The Lysholm score and the Kujala score improved significantly from 37.6 (SD =6.8) and 45.9 (SD =6.4) preoperatively to 80.9 (SD =7.4) and 89.4 (SD =6.8) postoperatively at the latest follow-up, respectively. Imaging evidence including X-ray and MRI revealed good healing of the OCFs. CONCLUSIONS: This study showed satisfactory mid-term outcomes of OCF fixation using absorbable suture, which supports this method's potential to be a novel surgical method in the treatment of patellar OCF caused by a patellar dislocation.

Injury effect of navy new concept weaponry on combatants and its medical prevention / 第二军医大学学报

New concept weaponry have much greater damage effects than traditional weaponry, not only destroying military equipment and communication systems, but also severely injurying combatants. Typical new concept weaponry, including shipborne laser weapons, electromagnetic pulse weapons and infrasonic weapons, holds destructive power by special light, sound, or electromagnetic wave. This paper expounds the injury effects of new concept weapons on combatants and its medical protection measures, so as to provide reference for the health service support under the condition of new concept weapons.

Islet β-cell function in patients with gout and hyperuricemia accompanied by increased 1h postload plasma glucose / 中华内分泌代谢杂志

All of 143 patients with gout or hyperuricemia were divided into type 2 diabetes(n=43), impaired glucose regulation(n=45),and normal glucose tolerance(n=55)groups. Moreover,a cut point of 8.6 mmol/L in one hour postload plasma glucose(1hPG)of oral glucose tolerance test was used to sub-divide the normal glucose tolerance group into 1hPG≥8.6 mmol/L(n=30)and 1hPG<8.6 mmol/L(n=25)groups. The first-and second-phase insulin secretion indexes were compared among four groups. The results showed that there was no statistical difference in the second-phase insulin secretion index among impaired glucose regulation,1hPG≥8.6 mmol/L,and 1hPG<8.6 mmol/L groups(P>0.05). The first-phase insulin secretion index revealed no significant difference between impaired glucose regulation and 1hPG≥8.6 mmol/L groups(P>0.05),but obviously decreased in these two groups compared with 1hPG<8.6 mmol/L group(P<0.05). The modified β cell function indexes were gradually decreased in 1hPG<8.6 mmol/L,1hPG≥8.6 mmol/L, and impaired glucose regulation groups(P<0.05). These results suggest that when 1hPG of the patients with gout and hyperuricemia is over 8.6 mmol/L,the first-phase insulin secretion will be impaired.

Effect of precision anesthesia strategy on postoperative cognitive function in elderly patients undergoing hip replacement / 中华麻醉学杂志

Objective To evaluate the effect of precision anesthesia strategy on postoperative cognitive function in elderly patients undergoing hip replacement.Methods Seventy elderly patients of both sexes,aged 65-85 yr,weighing 50-75 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective unilateral hip replacement under general anesthesia,with years of education＞6 yr,were divided into 2 groups (n =35 each) using a random number table:precision anesthesia group (group P) and routine anesthesia group (group R).Anesthetic protocol and perioperative management were optimized using precision anesthesia strategy in group P.Routine anesthetic protocol and perioperative management were performed in group R.Peripheral venous blood samples were collected at 1 day before operation (T0) and 1,6,12 and 24 h after operation (T1-4) for determination of serum S100β protein,neuronspecific enolase (NSE),interleukin-1beta (IL-1β),IL-6,tumor necrosis factor-alpha (TNF-α) and Creactive protein (CRP) concentrations by enzyme-linked immunosorbent assay.The patient's cognitive function was assessed using Mini-Mental State Examination (MMSE) at T0 and 3 and 7 days after operation (T5,6).Results Compared with the baseline at T0,the serum S100β protein and NSE concentrations were significantly increased at T1-3,the serum IL-1β,IL-6 and TNF-α concentrations were increased at T1-4,the CRP concentrations were increased at T2,3,MMSE scores were decreased at T5 in group R,and the serum S100β protein,IL-1β and IL-6 concentrations were significantly increased at T1-3,the serum NSE and CRP concentrations were increased at T2,the serum TNF-α concentrations were increased at T1-4,and MMSE cores were decreased at T5 in group P (P＜0.05).Compared with group R,the serum S100β protein and IL-1β concentrations were significantly decreased at T1,2,the serum NSE and TNF-α concentrations were decreased at T1-3,the serum IL-6 concentrations were decreased at T2,3,and MMSE scores were increased at T5 in group P (P＜ 0.05).Conclusion Precision anesthesia strategy can improve postoperative cognitive function in elderly patients undergoing hip replacement,which is related to inhibiting inflammatory responses.

Protective Effect of Water-soluble Total Flavonoids from Isodon Lophanthoides var.gerardianus ( Benth.) H.Hara on H2 O2-induced LO2 Cells Damage / 中国药师

Objective:To explore the protective effect of the water-soluble total flavonoids from Isodon lophanthoides var.gerardia-nus (Benth.) H.Hara on LO2 cells damage.Methods:The cytotoxicity was evaluated by MTT cell viability determination to confirm the concentration range .Hepatocyte damage model was established by H 2 O2 treatment.After the oxidative stress hepatocyte was coin-cubated with WSTF at different concentrations for various times , the protective effect of WSTF on H 2 O2-induced hepatocyte damage was evaluated by MTT cell viability determination and the content determination of ALT , AST and MDA in cell supernatant .The inhibition of WSTF against H 2 O2-induced LO2 cells apoptosis was evaluated by the quantitative determination of Rhodamine 123 fluorescence and intracellular ROS.Results:The LO2 cells injured by 0.3 mmol· L-1 H2 O2 treatment for 4 h were used as the hepatocyte damage model.The concentration range of WSTF was 0.0312-0.125 mg· ml-1.WSTF could inhibit H2O2-induced injury in LO2 cells and obviously reduce ALT, AST and MDA.Moreover, WSTF could reverse mitochondrial membrane potential depolarization and decrease the amount of intracellular ROS .Conclusion:WSTF exhibits notable protective and curative effects on hepatocyte damage in vitro.

Study on Qualitative and Quantitative Analysis of Monotropein in Liquidambaris Radix / 中国中医药信息杂志

Objective To establish qualitative and quantitative methods for analyzing monotropein in Liquidambaris Radix. Methods Monotropein in Liquidambaris Radix was identified by using TLC. The contents of monotropein in the samples were determined by HPLC on an Sino Chrom ODS-BP column (4.6 mm × 250 mm, 5 μm) with methanol-0.1％ phosphoric acid solution (1:99) as the mobile phase at the flow rate of 1.0 m L/min; the detection wavelength was 235 nm; the column temperature was 25 ℃; the injection volume was 10 μL. Results Monotropein in Liquidambaris Radix could be identified by TLC. Monotropein showed good linear relation in the range of 0.150 1– 1.501 0 μg (r=0.999 8), and the average recovery rate was 95.93％ (RSD=0.60％). The contents of monotropein in Liquidambaris Radix from 10 different producing areas were among the range of 0.20％–1.15％. Conclusion The method is simple, stable, reliable and reproducible, which can be used for the quality control of Liquidambaris Radix.