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The aqueous two-phase system (ATPS) is an all-aqueous system fabricated from two immiscible aqueous phases. It is spontaneously assembled through physical liquid-liquid phase separation (LLPS) and can create suitable templates like the multicompartment of the intracellular environment. Delicate structures containing multiple compartments make it possible to endow materials with advanced functions. Due to the properties of ATPSs, ATPS-based drug delivery systems exhibit excellent biocompatibility, extraordinary loading efficiency, and intelligently controlled content release, which are particularly advantageous for delivering drugs in vivo. Therefore, we will systematically review and evaluate ATPSs as an ideal drug delivery system. Based on the basic mechanisms and influencing factors in forming ATPSs, the transformation of ATPSs into valuable biomaterials is described. Afterward, we concentrate on the most recent cutting-edge research on ATPS-based delivery systems. Finally, the potential for further collaborations between ATPS-based drug-carrying biomaterials and disease diagnosis and treatment is also explored.

Research progress on chemical structures and pharmacological effects of natural cytisine and its derivatives / 中国中药杂志

Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type. This study reviewed the research progress on the structures, plant sources, biosynthesis, and pharmacological activities of alkaloids of various types.

The effects of nucleotide-binding oligomerization domain-like receptor 3 inflammasome on obstructive sleep apnea and its complications / 中华预防医学杂志

Obstructive sleep apnea (OSA) is a sleep disorder with a high incidence and severe impact on the human body, which can induce systemic chronic inflammatory responses. Chronic inflammation is an important cause of exacerbation of OSA and its associated complications. Nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) is an inflammasome that is widely found in epithelial cells and immune cells and plays an important role in inflammatory diseases as an important component of innate immunity. Research evidence suggests that the activation of NLRP3 inflammasomes can exacerbate the damage to neurons, endothelial cells, lung and kidney caused by OSA, and these effects can be eliminated by genetic or pharmacological deletion of NLRP3. Targeting inhibition of NLRP3 inflammasome may serve as a co-therapeutic strategy for OSA-induced related complications. This article reviews NLRP3 inflammasome and its mechanism in OSA-related concurrent diseases, which can provide scientific basis for prevention and intervention of OSA and its related complications.

The effects of nucleotide-binding oligomerization domain-like receptor 3 inflammasome on obstructive sleep apnea and its complications / 中华预防医学杂志

Obstructive sleep apnea (OSA) is a sleep disorder with a high incidence and severe impact on the human body, which can induce systemic chronic inflammatory responses. Chronic inflammation is an important cause of exacerbation of OSA and its associated complications. Nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) is an inflammasome that is widely found in epithelial cells and immune cells and plays an important role in inflammatory diseases as an important component of innate immunity. Research evidence suggests that the activation of NLRP3 inflammasomes can exacerbate the damage to neurons, endothelial cells, lung and kidney caused by OSA, and these effects can be eliminated by genetic or pharmacological deletion of NLRP3. Targeting inhibition of NLRP3 inflammasome may serve as a co-therapeutic strategy for OSA-induced related complications. This article reviews NLRP3 inflammasome and its mechanism in OSA-related concurrent diseases, which can provide scientific basis for prevention and intervention of OSA and its related complications.

FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression / 医学前沿

FRMD6, a member of the 4.1 ezrin-radixin-moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6-/- gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

Dnmt1 overexpression causes genomic hypermethylation, loss of imprinting, and embryonic lethality.

Biallelic expression of Igf2 is frequently seen in cancers because Igf2 functions as a survival factor. In many tumors the activation of Igf2 expression has been correlated with de novo methylation of the imprinted region. We have compared the intrinsic susceptibilities of the imprinted region of Igf2 and H19, other imprinted genes, bulk genomic DNA, and repetitive retroviral sequences to Dnmt1 overexpression. At low Dnmt1 methyltransferase levels repetitive retroviral elements were methylated and silenced. The nonmethylated imprinted region of Igf2 and H19 was resistant to methylation at low Dnmt1 levels but became fully methylated when Dnmt1 was overexpressed from a bacterial artificial chromosome transgene. Methylation caused the activation of the silent Igf2 allele in wild-type and Dnmt1 knockout cells, leading to biallelic Igf2 expression. In contrast, the imprinted genes Igf2r, Peg3, Snrpn, and Grf1 were completely resistant to de novo methylation, even when Dnmt1 was overexpressed. Therefore, the intrinsic difference between the imprinted region of Igf2 and H19 and of other imprinted genes to postzygotic de novo methylation may be the molecular basis for the frequently observed de novo methylation and upregulation of Igf2 in neoplastic cells and tumors. Injection of Dnmt1-overexpressing embryonic stem cells in diploid or tetraploid blastocysts resulted in lethality of the embryo, which resembled embryonic lethality caused by Dnmt1 deficiency.

Electroacupuncture at Siguan points for migraine of liver yang hyperactivity: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of electroacupuncture at Siguan points and flunarizine hydrochloride capsule on migraine of liver yang hyperactivity.@*METHODS@#A total of 110 patients with migraine of liver yang hyperactivity were randomly divided into an electroacupuncture group (55 cases, 2 cases dropped off) and a western medication group (55 cases, 2 cases dropped off). In the electroacupuncture group, electroacupuncture was applied at Siguan points (Hegu [LI 4] and Taichong [LR 3]), with disperse-dense wave of 2 Hz/100 Hz in frequency and current intensity of 0.1-1 mA, 30 min each time, once a day, 5 times per week for 4 weeks. Flunarizine hydrochloride capsule was given orally in the western medication group, 10 mg a day for 4 weeks. The visual analogue scale (VAS) score and the migraine attack days were observed before and after treatment, during follow-up of 1, 3 and 6 months, and the migraine symptom score was observed before and after treatment in the two groups.@*RESULTS@#After treatment, during follow-up of 1, 3 and 6 months, the VAS scores and the migraine attack days in the two groups were decreased compared with before treatment (Ｐ<0.05), and above indexes in the electroacupuncture group were lower than the western medication group (Ｐ<0.05). After treatment, the migraine symptom scores in the two groups were decreased (Ｐ<0.05), the change in the electroacupuncture group was greater than the western medication group (Ｐ<0.05).@*CONCLUSION@#Electroacupuncture at Siguan points could effectively reduce headache intensity and migraine attack days, relieve migraine symptoms in patients with migraine of liver yang hyperactivity, and the efficacy is superior to oral flunarizine hydrochloride capsules.

Establishment of an Iron-overloaded Mouse Model with Tuberculosis and Analysis of the Iron Metabolism Index / 中国医学科学院学报

Objective To establish a mouse model of exogenous iron overload combined with tuberculosis(TB). Methods C57BL/6N mice were divided into negative control, low-, medium-, and high-dose iron groups and received intraperitoneal injection of iron dextran at 0, 3.75, 7.50, and 15.00 mg/dose(3 times/week for 4 weeks), respectively.After 4 weeks, the organ morphology and body weight of the mice were evaluated.The content of serum iron, ferritin, transferrin, and transferrin receptor was determined by ELISA.Heart, liver, spleen, lung, kidney, and small intestine were analyzed for tissue iron content and iron deposition pathology.

Adult Age Estimation of CT Image Reconstruction of the Laryngeal Cartilages and Hyoid Bone Based on Data Mining / 法医学杂志

Objective To explore the feasibility of the CT image reconstruction of laryngeal cartilage and hyoid bone in adult age estimation using data mining methods. Methods The neck thin slice CT scans of 413 individuals aged 18 to <80 years were collected and divided into test set and train set, randomly. According to grading methods such as TURK et al., all samples were graded comprehensively. The process of thyroid cartilage ossification was divided into 6 stages, the process of cricoid cartilage ossification was divided into 5 stages, and the synosteosis between the greater horn of hyoid and hyoid body was divided into 3 stages. Multiple linear regression model, support vector regression model, and Bayesian ridge regression model were developed for adult age estimation by scikit-learn 0.17 machine learning kit （Python language）. Leave-one-out cross-validation and the test set were used to further evaluate performance of the models. Results All indicators were moderately or poorly associated with age. The model with the highest accuracy in male age estimation was the support vector regression model, with a mean absolute error of 8.67 years, much higher than the other two models. The model with the highest accuracy in female adult age estimation was the support vector regression model, with a mean absolute error of 12.69 years, but its accuracy differences with the other two models had no statistical significance. Conclusion Data mining technology can improve the accuracy of adult age estimation, but the accuracy of adult age estimation based on laryngeal cartilage and hyoid bone is still not satisfactory, so it should be combined with other indicators in practice.

Research Progress on Automatic Assessment of Bone Age / 法医学杂志

Bone age is an important indicator of human growth and development, which can objectively reflect the growth level and maturity of individuals. Traditional manual bone age assessment usually compares the X-ray of the left wrist with the reference standard to obtain the corresponding bone age. This method is time-consuming and its results vary with different observers. In recent years, with the continuous development of computer science, bone age assessment has began to change from traditional manual assessment to automatic assessment. Although there has already been numerous researches on automatic bone age assessment, most of them are still in the experimental stage. This paper reviews related research and progress on automatic bone age assessment at home and abroad in recent years, in order to provide reference and research ideas for relevant researchers.

Estimation of Sex from Patella Measurements in Sichuan Han Population Based on CT-Three-Dimensional Volume Reconstruction Technique / 法医学杂志

Objective To estimate sex based on patella measurements of Sichuan Han population by computed tomography three-dimensional volume reconstruction technique, and to explore the application value of patella in sex estimation. Methods CT three-dimensional volume reconstruction images of patella of 250 individuals were collected, the four measurement indicators including patellar length, patellar width, patellar thickness, and patellar volume were measured. The t-test was used to determine measurement indicators with sex differences. Fisher discriminant analysis was used to establish the sex discriminant function and the prediction accuracy was calculated by leave-one-out cross validation. Results The sex differences of the four measurement indicators had a statistical significance （P<0.05）. The accuracy rate of the univariate discriminant function established by the patellar length was the highest （82.0%）. The accuracy rates of the all indicators discriminant function and the stepwise discriminant function were 80.4% and 81.6%, respectively. Conclusion It is feasible and accurate to estimate sex of Sichuan Han population by patella measurements with CT three-dimensional volume reconstruction technique. The method may be used as an alternative for sex estimation of Sichuan Han population when other bones with higher accuracy are not available.

Age Estimation in Han Adults by Thin-Layer CT Scan of Cranial Sutures / 法医学杂志

Objective To explore the value of degree of cranial suture closure in forensic adult age estimation by thin-layer CT scan and establish an adult age estimation model of the Han nationality. Methods Thin-layer CT scan samples of the heads of 220 healthy Sichuan Han adults （110 males, 110 females） aged 20 to 70 were collected, of which 20 samples （10 males, 10 females） were randomly selected as test samples. The sagittal suture, coronal suture （both left and right） and lambdoid suture （both left and right） were respectively and equally divided into 2 segments, and every segment was equally divided into 10 layers and the corresponding multiplanar reformation （MPR） images were selected. The closure of cranial sutures on MPR images was classified into the grades 1-7. The correlations between cranial sutures and age were analyzed to build regression equation for age estimation. Results The degree of closure of sagittal suture, coronal suture （both left and right） and lambdoid suture （both left and right） was positively correlated with age. The coefficient of determination （R2） of regression equation was 0.419 in males, 0.589 in females, and 0.522 in all samples. The results of the verification test showed that the mean absolute error （MAE） was 6.39 years in males, 6.16 years in females, and 6.29 years in all samples. Conclusion There was a higher accuracy in adult age estimation by thin-layer CT scan of cranial sutures. The age of Han nationality adults can be estimated by the degree of cranial sutures closure.

Research Progress of Adult Age Determination with Imaging Methods / 法医学杂志

Adult age determination plays an important role in individual identification, criminal investigation and social welfare. The most popular adult age determination indicators are pubic symphysis, iliac auricular surface, costal cartilage, cranial sutures, teeth, laryngeal cartilage, etc. In recent years, with the progress of CT imaging and 3D reconstruction technology, the adult age determination study gradually has transferred from a time-consuming general observation of bones with complex pre-processing in the past to the non-destructive, convenient, time-saving and easy to store image analysis technology. To explore more accurate, rapid and convenient adult age determination methods, multiple imaging methods and artificial intelligence have been applied in adult age determination. This paper reviews the common methods and research progress of adult age determination at home and abroad, infers the development direction of adult age determination, in order to provide reference for the improvement and optimization of forensic adult age determination.

Minimally invasive treatment of clavicular fractures with cannulated screw.

OBJECTIVE: To evaluate minimally invasive treatment of clavicular fractures with cannulated screw. METHODS: Data of 65 patients who had undergone minimally invasive treatment with cannulated screws for clavicular fractures from April 2009 to October 2010 were retrospectively analyzed and compared with those of 65 patients with clavicular fractures who had been treated by the same surgeons with plates. In the study group, there were 41 males and 24 females, aged from 19-67 years (mean, 35.8 years). According to Craig's classification, there were 29 group 1 and 36 of group 2-II. Neer scores were used to evaluate shoulder function and radiographs to assess fracture union. RESULTS: The incision length was 4-5 cm in the cannulated screw group (CSG) and 10-11 cm in the reconstructive plate group (RPG). Radiographs showed bone union was achieved in both groups, the bone healing time being 13.2 ± 6.9 weeks in the CSG and 16.3 ± 8.7 weeks in the RPG. All patients were followed up for 6 to 20 months (average, 10.6 months). The average Neer score was 96.6 ± 3.4 in the CSG and 94.2 ± 5.8 in the RPG. In the CSG, screw loosening occurred in five, and fracture displacement in three. There was a significant difference in fracture healing time between two groups but not in Neer score. CONCLUSION: Minimally invasive treatment of clavicular fractures with cannulated screws has the advantages of minimal invasion, short bone healing time, good clinical outcomes, and being relatively inexpensive.

Increased Na+/Ca2+ exchanger activity promotes resistance to excitotoxicity in cortical neurons of the ground squirrel (a Hibernator).

Ground squirrel, a hibernating mammalian species, is more resistant to ischemic brain stress than rat. Gaining insight into the adaptive mechanisms of ground squirrels may help us design treatment strategies to reduce brain damage in patients suffering ischemic stroke. To understand the anti-stress mechanisms in ground squirrel neurons, we studied glutamate toxicity in primary cultured neurons of the Daurian ground squirrel (Spermophilus dauricus). At the neuronal level, for the first time, we found that ground squirrel was more resistant to glutamate excitotoxicity than rat. Mechanistically, ground squirrel neurons displayed a similar calcium influx to the rat neurons in response to glutamate or N-methyl-D-aspartate (NMDA) perfusion. However, the rate of calcium removal in ground squirrel neurons was markedly faster than in rat neurons. This allows ground squirrel neurons to maintain lower level of intracellular calcium concentration ([Ca2+]i) upon glutamate insult. Moreover, we found that Na+/Ca2+ exchanger (NCX) activity was higher in ground squirrel neurons than in rat neurons. We also proved that overexpression of ground squirrel NCX2, rather than NCX1 or NCX3, in rat neurons promoted neuron survival against glutamate toxicity. Taken together, our results indicate that ground squirrel neurons are better at maintaining calcium homeostasis than rat neurons and this is likely achieved through the activity of ground squirrel NCX2. Our findings not only reveal an adaptive mechanism of mammalian hibernators at the cellular level, but also suggest that NCX2 of ground squirrel may have therapeutic value for suppressing brain ischemic damage.

G protein-coupled receptor LGR6 is an independent risk factor for colon adenocarcinoma / 医学前沿

LGR6 is a member of the G protein-coupled receptor family that plays a tumor-suppressive role in colon cancer. However, the relationship between LGR6 expression in patients and clinicopathological factors remains unclear. This study aimed to clarify whether the expression level of LGR6 is correlated with colon adenocarcinoma progression. Immunohistochemistry was used to detect LGR6 expression in colon adenoma tissues (n = 21), colon adenocarcinoma tissues (n = 156), and adjacent normal tissues (n = 124). The expression levels of LGR6 in colon adenoma and adenocarcinoma were significantly higher than those in normal colon epithelial tissues (P < 0.001). Low LGR6 expression predicted a short overall survival in patients with colon adenocarcinoma (log-rank test, P = 0.016). Univariate and multivariate survival analyses showed that, in addition to N and M classification, LGR6 expression served as an independent prognostic factor. Thus, low expression of LGR6 can be used as an independent prognostic parameter in patients with colon adenocarcinoma.

Analysis of infection status and recombination types of norovirus in patients with acute gastroenteritis in the Ningxia Hui Autonomous Region from 2016 to 2017 / 中华预防医学杂志

Objective@#To analyze the infection status and recombination of Norovirus in patients with acute gastroenteritis in Ningxia.@*Methods@#The specimens of 10 sentinel hospitals in Ningxia were collected from 2016 to 2017. Real-time quantitative PCR was used for nucleic acid detection. GⅡ-positive samples were amplified by RT-PCR for the RdRp and Capsid regions, then sequenced and genotyped. Evolution analysis was performed using software such as MEGA-X, and recombination analysis was performed using Simplot 3.5.1 and RDP4.@*Results@#The age of the 2 334 cases was 1.42 (0.68, 7.69) years old, 1 133 cases in 2016 and 1 201 cases in 2017, 1 343 and 991 cases for males and females respectively. The positive rate of Norovirus GⅠ genogroup was 0.86% (20/2 334), and GⅡ genogroup was 14.82% (346/2 334). A total of 78 recombinant strains were sequenced and 12 recombinant types were found. GⅡ.Pe/GⅡ.4Sydney_2012 and GⅡ.P12/GⅡ.3 were the main epidemic strains, accounting for 35.90% (28 strains) and 32.05% (25 strain) respectively, followed by GⅡ.P16/GⅡ.2 accounting for 12.82% (10 strains). Among them,GⅡ.P7/GⅡ.6 (2 strains), GⅡ.P12/GⅡ.3 (6 strains), GⅡ.P16/GⅡ.1 (2 strains), GⅡ.P16/GⅡ.2 (5 strains), GⅡ.Pe/GⅡ.4 (7 strains) were detected for the first time in Ningxia. Recombinant strains were all intergenotype recombination, and the recombination breakpionts were all located within ORF1.@*Conclusion@#Norovirus infection in Ningxia area was mainly in GⅡ genogroup from 2016 to 2017, and most of them were recombinant strains. GⅡ.Pe/GⅡ.4Sydney_2012 and GⅡ.P12/GⅡ.3 were the main epidemic strains, followed by GⅡ.P16/GⅡ. 2.

Effects of ginkgo biloba extract combined with glucocorticoid on olfactory function and inflammatory cytokines in mice with allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

To determine whether ginkgo biloba extract(GBE)combined with dexamethasone(DEX)plays a role in the treatment of allergic rhinitis-related olfactory dysfunction using an animal model.Six week old BALB/C mice were sensitized and challenged with ovalbumin.30 sensitized mice were divided into three groups:Group 1 was given high-dose GBE and DEX(n=10);Group 2 was given low dose GBE and DEX(n=10);Group 3 was given DEX alone(n=10).We assessed the histology of the olfactory mucosa and serum IL-4,IFN-γ,and caspase 1.A significant higher fraction of mice in group 1 could find the food pellet within300 scompared to group 3(<0.05).Caspase-1 levels improved during the second week compared with the first week in each group.IFN-γlevels were significantly lower during the second week compared with the first week(<0.05,all).IL-4 levels also were significantly lower during the second week compared with the first week in all groups except those receiving DEX alone.IFN-γ/IL-4 levels in each group were significantly lower during the second week compared with the first week(<0.05,all).In this animal model of allergic rhinitis-related olfactory dysfunction,the addition of ginkgo biloba extract to dexamethasone have a better anti-inflammatory effect,which can partly improve the therapeutic effect on olfactory dysfunction caused by allergic rhinitis.

Preliminary study of DTI on cerebral white matter micro-structure of patients with idiopathic olfactory loss / 临床耳鼻咽喉头颈外科杂志

OBJECTIVES@#To investigate the cerebral white matter micro-structure in patients with idiopathic olfactory loss using diffusion tensor imaging (DTI).@*METHODS@#Sixteen patients with idiopathic olfactory loss and sixteen normal subjects matched by age and sex were recruited in this study. Sniffin'Stick olfactory test was performed to evaluate the olfactory function of all subjects. We acquired diffusion tensor images with an echo planar imaging (EPI) sequence from all subject on a 3T scanner. The fractional anisotropy (FA) images were performed using DTI-studio, and bilateral Piriform cortex, Orbitofrontal cortex, Hippocampus and Insula cortex adjacent white matter and Capsula interna were delineated as the region of interesting (ROI), the FA for each ROI was calculated. Independent sample t test analysis was used to compare the FA value of all ROIs between the controls and patients. In addition, correlation analysis between FA value and MMSE score in patients were conducted.@*RESULTS@#Compared with the controls, patients showed significantly decreased FA value in the adjacent white matter of bilateral Piriform cortex, Orbitofrontal cortex, Hippocampus and Insula cortex (0.05).@*CONCLUSIONS@#The patients with idiopathic olfactory loss show the damage of white matter micro-structure in the olfactory center, which could be important for the pathogenesis study and early intervention of idiopathic olfactory loss.

Pharmacokinetics of α-asarone after intranasal and intravenous administration with PLA-α-asarone nanoparticles / 中国中药杂志

PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respectively. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74.2%, 142.24 and 29.83%, respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration, indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition, the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asarone dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration.