Retrospective Analysis of Steady-State Sodium Valproate Plasma Concentrations in Chinese Patients With Bipolar Disorder: Impact of Demographic and Clinical Characteristics.

BACKGROUND: This study comprehensively examined the demographic and clinical characteristics of patients undergoing valproic acid therapy and explored their potential impact on plasma valproic acid concentrations. All enrolled patients were administered the extended-release formulation. An in-depth investigation of factors, including dose, age, sex, body mass index, co-administered medications, and laboratory test findings, was conducted to evaluate their potential influence on study outcomes. METHODS: In total, 164 patients met the inclusion criteria and were included in the analysis. The patient age ranged from 13 to 60 years, with a median age of 25.71 years. Most patients (89%) received a daily dose of 1 g valproic acid. Co-administered psychiatric medications included aripiprazole, quetiapine, and lorazepam. Laboratory test results, such as hemoglobin and transaminase levels, were also collected as part of the study. RESULTS: The average plasma valproic acid plasma concentration was 79.8 mg/L. The dose significantly affected valproic acid concentrations, as a higher percentage of measurements exceeded the therapeutic range at a daily dose of 1 g. Furthermore, females exhibited significantly higher valproic acid concentrations compared with males at the same dose (P < 0.05). However, different age groups showed no statistically significant differences in valproic acid concentrations (P > 0.05). The co-administered antipsychotic and antidepressant medications significantly affected valproate concentrations, as reflected in the multiple regression model (P < 0.01). CONCLUSIONS: This study offers valuable insights into the demographic and clinical characteristics of patients undergoing valproic acid therapy. It highlights the influence of dose, sex, and concomitant medications on plasma valproic acid concentrations. Overall, these findings can help guide dose adjustments and implement personalized treatment strategies in valproic acid therapy.

Cuproptosis-related genes are involved in immunodeficiency following ischemic stroke.

Introduction: Accumulating studies have shown that copper has a detrimental effect in cells, and the cuproptosis-related gene signatures have been constructed as clinical tools to predict prognosis in tumors. However, the heterogeneity of cuproptosis has not been fully investigated in ischemic stroke.Methods: Here, we combined the bulk RNA-seq and single cell-RNA-seq data for stroke to investigate the role of cuproptosis in stroke. Results: We identified the cuproptosis-related differentially expressed genes (CuDEGs) in ischemic stroke. Then, we tried to find the hub genes with the machine learning method and WGCNA. We highlighted four genes identified by these methods and proposed a potential diagnostic model in ischemic stroke. Conclusions: Our findings revealed cuproptosis-related hub genes, which could provide useful biomarkers in ischemic stroke.

Artificial LiF-Rich Interface Enabled by In situ Electrochemical Fluorination for Stable Lithium-Metal Batteries.

Lithium (Li)-metal batteries are promising next-generation energy storage systems. One drawback of uncontrollable electrolyte degradation is the ability to form a fragile and nonuniform solid electrolyte interface (SEI). In this study, we propose the use of a fluorinated carbon nanotube (CNT) macrofilm (CMF) on Li metal as a hybrid anode, which can regulate the redox state at the anode/electrolyte interface. Due to the favorable reaction energy between the plated Li and fluorinated CNTs, the metal can be fluorinated directly to a LiF-rich SEI during the charging process, leading to a high Young's modulus (~2.0 GPa) and fast ionic transfer (~2.59×10-7  S cm-1 ). The obtained SEI can guide the homogeneous plating/stripping of Li during electrochemical processes while suppressing dendrite growth. In particular, the hybrid of endowed full cells with substantially enhanced cyclability allows for high capacity retention (~99.3 %) and remarkable rate capacity. This work can extend fluorination technology into a platform to control artificial SEI formation in Li-metal batteries, increasing the stability and long-term performance of the resulting material.

Clinicopathologic features of stomach oxyntic gland neo-plasms on 49 patients / 中国现代普通外科进展

Objective:To analyze the clinicopathological features of gastric oxyntic gland neo-plasms.Methods:Forty-nine cases of stomach oxyntic gland neoplasms including oxyntic gland adenoma(OGA)and gastric adenocarcinoma of the fundic gland type(GA-FG)diagnosed in the Sec-ond Hospital of Shandong University from January 2016 to December 2020 were selected.The clini cal information,endoscopic appearance,histological features and immunophenotype were analyzed retrospectively,and followed up.Results:Age of the gastric oxyntic gland neoplasm patients ranged from 19 to 83 years old,with an average age of(57.3±2.4)years old.The male-to-female ratio was 24:25.Most of the lesions were located in the gastric body(27/49)and fundus(15/49).There were four endoscopic phenotypes:flat bulging,polypoid,flat and depression.In some lesions,there were dilated dendritic vessels.48 cases were single onset.The mean maximum diameter of lesions was(3.9±0.5)mm(1.0～7.0 mm).Seven cases showed submucosal invasion,and the inva-sion depth was less than 500 μm.The tumor consists of the dense glandular and the glandular con-nects to form a strip shape,which is irregularly branched and labyrinthlike under the microscope.These tumor cells were well differentiated and the morphology was similar to oxyntic gland cells.The chief cells were the predominant cells.The nucleus was mildly enlarged with slight pleomorphism and the mitosis was uncommon.The oxyntic gland neoplasms of the stomach were diffusely posi-tive for Mucin-6(MUC6)(100％)and Pepsinogen Ⅰ(83％),focally positive for H+/K+-ATPase(58％).Conclusions:The stomach oxyntic gland neoplasm is a new histology type with unique clinico-pathological features.The incidence of this neoplasm is low and the prognosis is good but it still needs long-term follow-up.

Analysis of the current status and regulatory effectiveness of daylighting and artificial lighting in primary and secondary school classrooms in Shanghai / 中国学校卫生

Objective@#To understand the current situation and regulatory effectiveness of daylighting and artificial lighting in primary and secondary school classrooms in Shanghai, so as to provide a basis for enhancing the visual environment of school classrooms.@*Methods@#From April 2021 to December 2023, the daylighting and artificial lighting conditions of classrooms in 1 735 regular primary and secondary schools currently in operation in Shanghai were monitored, and the qualified rate of each indicator was calculated. The Chisquare test or Fisher exact probability method were used to compare the differences in qualification rates across different educational stages, regions, school type, both before and after the implementation of regulatory measures. The regulatory measures included convene interview, propaganda and education, supervision order, supervisory opinion paper, rectification requests and offenses and punishment.@*Results@#The qualified rate of daylighting and artificial lighting in primary and secondary school classrooms was 30.1%, with a qualified daylighting rate of 85.6% and a qualified artificial lighting rate of 32.9%. There was no statistically significant differences in the qualified rate of daylighting and artificial lighting in primary and secondary schools (32.4%，28.1%；χ2=3.76，P＞0.05). However, statistically significant differences were found in the qualified rate of daylighting and artificial lighting in urban and rural school classrooms (32.6%，26.7%), as well as in public and private schools (31.4%, 20.6%) (χ2=6.99，9.92，P＜0.05). Following the implementation of regulatory measures, the qualified rate of classroom daylighting and artificial lighting improved from 30.1% to 83.2%, while the respective qualified rates of daylighting and artificial lighting increased from 85.6% to 91.1% and 32.9% to 90.5%. Compared to the preimplementation period, the qualified rate of classroom daylighting and artificial lighting, as well as the respective rates of daylighting and artificial lighting, all showed statistically significant differences after the implementation of regulatory measures (χ2=995.29，25.34，1 219.87，P<0.01).@*Conclusions@#Effective regulatory measures can promote enhanced classroom daylighting and artificial lighting. Attention should be paid to improving classroom artificial lighting, in order to provide students with enhanced visual environment.

Expression and distribution of brain⁃derived neurotrophic factor in different cerebrum regions of yak and cattle / 解剖学报

Objective To clarify the expression and distribution of brain⁃derived neurotrophic factor (BDNF) in the cerebrum of plateau yaks and cattle, and to explore the relationship between BDNF function and the adaptability of altitude hypoxia. Methods Five yaks and five cattles were selected.The content and distribution of BDNF in frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebrum white matter and hippocampus of yak and cattle were analyzed by Real⁃time PCR, Western blotting and Immunohistochemistry. Results Real⁃time PCR result showed that BDNF mRNA expression in the cerebrum of yaks and cattles was highest in temporal cortex, followed by hippocampus, parietal cortex, occipital cortex and frontal cortex, and lowest in white matter. Western blotting results showed that the content of BDNF protein in the cerebrum of yaks was the highest in temporal cortex,followed by hippocampus. The content of BDNF protein in other tissues was parietal cortex, frontal cortex and cerebrum white matter, and the content of BDNF protein was the lowest in occipital cortex. The content of BDNF protein intlecerebrum of cattles was the highest in the temporal cortex, followed by the hippocampus. The content of BDNF protein in other tissues was parietal cortex, occipital cortex and frontal cortex in descending order, and the protein content in cerebrum white matter was the lowest. Immunohistochemical results showed that the positive expression of BDNF protein in the cerebrum of yaks and cattles was basically similar, mainly distributed in the granulosa cells and glial cells in the frontal cortex, temporal cortex, parietal cortex and occipital cortex, glial cells in cerebrum white matter, pyramidal cell layer and polyform cell layer in the hippocampus. There was the small amount of distribution in Martinotti cells and the molecular layer of hippocampus in the cerebral cortex. Conclusion BDNF mRNA and protein are distributed and expressed in different brain regions of yaks and cattles, but the expression level different, which is speculated to be closely related to the specific functions of different cerebrum regions. The expression level of the cerebrum of yak is higher than that of cattle except occipital cortex, suggesting that it is related to the altitude hypoxic environment. BDNF may play an important role in enhancing hypoxic tolerance and protecting internal environmental homeostasis in the process of animal adaptation to hypoxic environment.

Characterization and phylogenetic analysis of chloroplast genome of Cynanchum wallichii and Cynanchum otophyllum / 药学学报

italic>Cynanchum wallichii and Cynanchum otophyllum belong to the genus Cynanchum in the family Apocynaceae, and are important medicinal plants. In this study, we sequenced and assembled the chloroplast genomes of C. wallichii and C. otophyllum, and performed a phylogenetic analysis of the structural characteristics of their chloroplast genomes and their phylogenetic positions. The results showed that the chloroplast genomes of both C. wallichii and C. otophyllum had a typical tetrad structure, with 133 genes annotated, and the total GC contents of both were similar. Codon preference analysis showed that the relative synonymous codon usage in the chloroplast genomes of C. wallichii and C. otophyllum differed slightly, but the differences were not significant, and there was a strong A or U preference at the third codon position. In both chloroplast genomes, 91 and 103 simple sequence repeats were detected respectively, and the largest proportion of A/T type repeats. Nucleotide polymorphism analysis showed that the nucleotide diversity of the intergenic sequences in the chloroplast genome of genus Cynanchum were generally higher than those of the common gene sequences. A pair of primers was designed based on the high variation region of the chloroplast genome to identify C. wallichii and C. otophyllum. The phylogenetic analysis showed that the C. wallichii and Cynanchum thesioides were the closest relatives, while the C. otophyllum, Cynanchum bungei and Cynanchum wilfordii formed a stable monophyletic clade within the genus Cynanchum, and the three species were closely related. The comparative analysis of the chloroplast genomic characteristics and phylogeny of C. wallichii and C. otophyllum will provide a theoretical basis for the species identification of the two plants and for the study of genetic diversity and phylogeny of the genus Cynanchum.

Effect of type of carrier material on the in vitro properties of solid dispersions of progesterone / 药学学报

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

Research progress of needle-free injection technology / 药学学报

Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.

Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy / 中国药房

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

The effect of long-term moderate exercise on myocardial metabolome in rats.

Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0% V̇O2max treadmill running) is optimal in protecting from exhaustive exercise-induced cardiac ischemic injury. This study is aimed to investigate the effect of long-term moderate exercise on myocardial metabolome in rats. Thirteen male Sprague-Dawley rats were randomly assigned into the control group (C) and the long-term moderate exercise group (E). The targeted metabolomics of the myocardium was analyzed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. Results showed that the metabolites categories of bile acids (BAs), fatty acids (FAs), and phenylpropanoic acids were significantly decreased. The biosynthesis of unsaturated FAs pathway was significantly downregulated. The altered metabolites in the E Group included decreased FAs (pentadecanoic acid, 10Z-heptadecenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, docosapentaenoic acid, and 10Z-nonadecenoic acid), decreased BAs (chenodeoxycholic acid and beta-muricholic acid), decreased organic acids (glycolic acid and 2-hydroxyglutaric acid), decreased carbohydrate (N-acetylneuraminic acid, Neu5Ac), decreased amino acids (α-aminobutyric acid and norvaline), decreased phenylpropanoic acids (hydroxyphenyllactic acid), and benzoic acids (4-hydroxybenzoic acid and phthalic acid). The results indicated that long-term moderate exercise has promoted lipids utilization in myocardium while exerted little influence on carbohydrate metabolism and diminished many detrimental metabolites. Notably, decrease of myocardial carbohydrate Neu5Ac after long-term moderate exercise might predict a prospective metabolomics biomarker for cardioprotection. This research has displayed the effect of long-term moderate exercise on myocardial metabolomic profiling in rats and indicated some promising metabolites which can be applied for exercise benefits in future.

Explainable machine learning for long-term outcome prediction in two-center stroke patients after intravenous thrombolysis.

Objective: Neurological outcome prediction in patients with ischemic stroke is very critical in treatment strategy and post-stroke management. Machine learning techniques with high accuracy are increasingly being developed in the medical field. We studied the application of machine learning models to predict long-term neurological outcomes in patients with after intravenous thrombolysis. Methods: A retrospective cohort study was performed to review all stroke patients with intravenous thrombolysis. Patients with modified Rankin Score (mRs) less than two at three months post-thrombolysis were considered as good outcome. The clinical features between stroke patients with good and with poor outcomes were compared using three different machine learning models (Random Forest, Support Vector Machine and Logistic Regression) to identify which performed best. Two datasets from the other stroke center were included accordingly for external verification and performed with explainable AI models. Results: Of the 488 patients enrolled in this study, and 374 (76.6%) patients had favorable outcomes. Patients with higher mRs at 3 months had increased systolic pressure, blood glucose, cholesterol (TC), and 7-day National Institute of Health Stroke Scale (NIHSS) score compared to those with lower mRs. The predictability and the areas under the curves (AUC) for the random forest model was relatively higher than support vector machine and LR models. These findings were further validated in the external dataset and similar results were obtained. The explainable AI model identified the risk factors as well. Conclusion: Explainable AI model is able to identify NIHSS_Day7 is independently efficient in predicting neurological outcomes in patients with ischemic stroke after intravenous thrombolysis.

TRPV4 channel is involved in HSV-2 infection in human vaginal epithelial cells through triggering Ca2+ oscillation.

Herpes simplex virus (HSV) infection induces a rapid and transient increase in intracellular calcium concentration ([Ca2+]i), which plays a critical role in facilitating viral entry. T-type calcium channel blockers and EGTA, a chelate of extracellular Ca2+, suppress HSV-2 infection. But the cellular mechanisms mediating HSV infection-activated Ca2+ signaling have not been completely defined. In this study we investigated whether the TRPV4 channel was involved in HSV-2 infection in human vaginal epithelial cells. We showed that the TRPV4 channel was expressed in human vaginal epithelial cells (VK2/E6E7). Using distinct pharmacological tools, we demonstrated that activation of the TRPV4 channel induced Ca2+ influx, and the TRPV4 channel worked as a Ca2+-permeable channel in VK2/E6E7 cells. We detected a direct interaction between the TRPV4 channel protein and HSV-2 glycoprotein D in the plasma membrane of VK2/E6E7 cells and the vaginal tissues of HSV-2-infected mice as well as in phallic biopsies from genital herpes patients. Pretreatment with specific TRPV4 channel inhibitors, GSK2193874 (1-4 µM) and HC067047 (100 nM), or gene silence of the TRPV4 channel not only suppressed HSV-2 infectivity but also reduced HSV-2-induced cytokine and chemokine generation in VK2/E6E7 cells by blocking Ca2+ influx through TRPV4 channel. These results reveal that the TRPV4 channel works as a Ca2+-permeable channel to facilitate HSV-2 infection in host epithelial cells and suggest that the design and development of novel TRPV4 channel inhibitors may help to treat HSV-2 infections.

Effects of breast cancer mesenchymal stem cells on proliferation and migration of breast cancer MCF-7 cells via IL-6-STAT3 signaling pathway / 肿瘤研究与临床

Objective:To explore the effects of breast cancer mesenchymal stem cells (BC-MSC) on the proliferation and migration of breast cancer MCF-7 cells and the related mechanisms.Methods:The resected cancer tissues and paracancerous tissues were taken from breast cancer patients after surgery, and the bone marrow samples of healthy people were selected. BC-MSC, breast cancer paracancerous mesenchymal stem cells (BCN-MSC) and bone marrow mesenchymal stem cells (BM-MSC) of healthy people were isolated and cultured by tissue adhesion method, and their differentiation ability was induced by the addition of osteogenic and lipogenic induction, and their surface markers were detected by flow cytometry. The supernatants of BC-MSC, BCN-MSC and BM-MSC of healthy people cultured for 48 h were collected and used for the culture of MCF-7 cells as BC-MSC group, BCN-MSC group and BM-MSC group, respectively, and the control group was the conventional cultured MCF-7 cells. The proliferation ability of MCF-7 cells in each group was detected by methyl thiazol tetrazolium (MTT) assay, the clone formation ability of MCF-7 cells was detected by plate cloning assay, the migration ability of MCF-7 cells was detected by Transwell assay, and the mRNA relative expressions of interleukin (IL)-6 and epithelial mesenchymal transition (EMT)-related genes (E-cadherin, vimentin, snail) were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) in MCF-7 cells. Western blotting was used to detect expressions of p-STAT3, E-cadherin, vimentin and snail proteins in MCF-7 cells. Luminex liquid microarray technology was used to detect cytokine levels in culture supernatants of different mesenchymal stem cells (MSC). IL-6 neutralizing antibody was added into the supernatant of BC-MSC, MCF-7 cells were cultured with the supernatant (BC-MSC+IL-6 neutralizing antibody group), and then the proliferation and migration abilities of MCF-7 cells were tested, as well as the expression changes of related genes and proteins.Results:BC-MSC, BCN-MSC and BM-MSC were successfully isolated; BC-MSC had positive expressions of CD29, CD44 and CD90 and negative expressions of CD14, CD34 and CD45, which were in line with the characteristics of MSC. MTT assay showed that the absorbance values of MCF-7 cells cultured for 48 h in the control group, BC-MSC group, BCN-MSC group and BM-MSC group were 0.31±0.02, 0.54±0.03, 0.43±0.02 and 0.42±0.02, respectively, and the difference was statistically significant ( F = 56.52, P < 0.05); the results of plate cloning experiments showed that the number of clones in each petri dish of the four groups were 180±9, 439±17, 319±16 and 306±19, respectively, and the difference was statistically significant ( F = 222.70, P < 0.05); Transwell assay showed that the numbers of membrane-penetrating cells in the four groups were 6.5±1.0, 23.2±2.4, 16.0±1.3 and 14.8±2.0, respectively, with the statistically significant difference ( F = 49.44, P < 0.05); qRT-PCR assay showed that the relative expressions of IL-6 mRNA in the control group, BC-MSC group, BCN-MSC group and BM-MSC group were 1.07±0.11, 13.79±3.80, 6.68±1.66 and 6.12±1.52, respectively, and the difference was statistically significant ( F = 107.60, P < 0.05), and the relative expression of E-cadherin mRNA in MCF-7 cells of BC-MSC, BCN-MSC and BM-MSC groups was lower than that of the control group, while the relative expressions of vimentin and snail mRNA were higher than those of the control group, and the differences were statistically significant (all P < 0.05). Western blotting assay showed that the relative expression of E-cadherin mRNA in MCF-7 cells of BC-MSC, BCN-MSC and BM-MSC groups was lower than that of the control group. Western blotting showed that the level of E-cadherin protein in BC-MSC, BCN-MSC and BM-MSC groups was lower than that in the control group, and the levels of vimentin and snail proteins were higher than those in the control group; Luminex liquid microarray technology showed that the content of IL-6 cytokine in the supernatants of BC-MSC, BCN-MSC and BM -MSC cultures were higher, and the relative expressions were 1.75±0.21, 1.00±0.10 and 0.96±0.08, respectively, and the difference was statistically significant ( F = 43.22, P < 0.05). The results of MTT assay showed that the absorbance values of MCF-7 cells in BC-MSC group and BC-MSC+IL-6 neutralizing antibody group were 0.56±0.05 and 0.42±0.04, respectively, and the difference was statistically significant ( t = -3.11, P < 0.05); the results of Transwell assay showed that the numbers of membrane-penetrating cells in the two groups were 30.3±1.5 and 17.3±2.1, respectively, and the difference was statistically significant ( t = -7.12, P < 0.05); qRT-PCR assay showed that the relative expressions of E-cadherin mRNA were 0.44±0.05 and 0.76±0.05 ( t = 6.40, P < 0.01), the relative expressions of vimentin mRNA were 2.90±0.21 and 1.79±0.21 ( t = 5.29, P < 0.01), and the relative expressions of snail mRNA were 3.20±0.20 and 1.91±0.30 ( t = 2.16, P < 0.01); Western blotting assay showed that the degrees to down-regulate the expression of E-cadherin protein and up-regulate the expressions of vimentin and snail proteins in the BC-MSC+IL-6 neutralizing antibody group were weakened compared with the BC-MSC group. Conclusions:BC-MSC can promote the proliferation and migration of breast cancer MCF-7 cells probably through activating IL-6-STAT3 signaling pathway-induced EMT by its secretion of IL-6.

Expression and localization of neuroglobin in the brain tissue of Saiga antelope / 解剖学报

Objective Saiga antelope is a small population inhabiting in desert and semi desert areas of national and world endangered protected animals, its wild population is extremely rare. In order to explore the correlation between hypoxic tolerance and neuroglobin (NGB) in Saiga antelope. A female Saiga antelope died of dystocia was used as the experimental animal, and the tissue samples were sampled repeatedly for 3 times to study the distribution and expression of NGB in brain of Saiga antelope in the process of adapting to hypoxia. Methods The distribution and expression of NGB in the parietal lobe, frontal lobe, temporal lobe, occipital lobe, hypothalamus, hippocampus, pear like leaf, cingulate gyrus, striatum and thalamus of Saiga antelope were detected by immunohistochemistry(IHC) and Real-time PCR. Results The result of IHC showed that NGB was positive in all parts of Saiga antelope brain, and the cells that had positive reactions in the parietal, frontal, temporal and occipital lobes of the cerebral cortex were mostly granular cells and martinotti cells. NGB was found in the granular cell layer, pyramidal cell layer and molecular cell layer in hippocampus, and the positive staining of pyramidal cell layer was the strongest. NGB positive expression in Pear like leaves and hypothalamus mainly occured in multi-type cells. NGB was expressed in the granulocytes and glial cells of cingulate gyrus, mainly in the granular cells. The positive expression of NGB in striatum was mainly located in granular cells, the positive expression of NGB in thalamus could be seen in the polymorphosis and glial cells, and the positive substance of the multi-type cells was obviously colored. The result of Real-time PCR showed that NGB was expressed in different regions of Saiga antelope brain, the highest expression in the frontal lobe of the cerebral cortex, the second in the parietal lobe, and the expression was significantly higher than that in the rest of the brain tissue (P0.05). Conclusion The expression of NGB in different regions of Saiga antelope has some selective differences in the long-term adaptation to hypoxia environment. The frontal and parietal lobes have the highest tolerance to hypoxia, followed by hippocampus, and the striatum is the weakest, which may be related to the specific functions of different regions of brain tissue, but the specific mechanism remains to be further explored.

Research progress of artificial intelligence in 3D printed drugs / 药学学报

In 2015, the United States put forward the concept of precision medicine, which changed medical treatment from "one size fits all" to personalization, and paid more attention to personalization and drug customization. In the same year, Spritam®, the world's first 3D printed tablet, was in the market, marking the emerging pharmaceutical 3D printing technology was recognized by regulatory authorities, and it also provided a new way for drug customization. 3D printing technology has strong interdisciplinary and high flexibility, which puts forward higher requirements for pharmaceutical staffs. With the development of artificial intelligence (AI), modern society can perform various tasks, such as disease diagnosis and robotic surgery, with superhuman speed and intelligence. As a major AI technology, machine learning (ML) has been widely used in many aspects of 3D printing drug, accelerating the research and development, production, and clinical application, and promoting the new process of global personalized medicine and industry 4.0. This paper introduces the basic concepts and main classifications of 3D printing drug, non-AI drug optimization technology and ML. It focuses on the analysis of the research progress of ML in 3D printing drug, and elucidates how AI can empower the intelligent level of 3D printing drug in pre-processing, printing, and post-processing process. It provides a new idea for accelerating the development of 3D printed drug.

Preparation and preliminary evaluation of SARS-CoV-2 DNA vaccine based on PLGA nanoparticles / 药学学报

We constructed and optimized the plasmid DNA (pDNA) Opt-S encoding the gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, using poly (lactic-co-glycolic acid) copolymer (PLGA) as a delivery carrier for pDNA. PLGA-pDNA NPs were loaded by nanoprecipitation and its properties in vitro were preliminary evaluated. The results showed that the prepared PLGA-pDNA NPs were regular morphology, clear edges, with an average particle size of (184.2 ± 2.4) nm, polydisperse index (PDI) of 0.093 ± 0.013, zeta potential of (-68.10 ± 0.36) mV, and encapsulation rate of (98.92 ± 0.22)%. The PLGA-pDNA NPs were stable at -20 ℃ for 7 months and could protect pDNA against nuclease degradation. And they also exhibited sustained release of pDNA in vitro. The PLGA-pDNA NPs have low cytotoxicity and high safety. In addition, in vitro transfection experiments showed that the SARS-CoV-2 S gene could enter cells and be expressed. These results indicate that PLGA-pDNA NPs non-viral gene vector have simple preparation process and good performance, which are expected to provide a new idea for the research and development of SARS-CoV-2 vaccine.

Mammalian DMRTs: Structure, function and relationship with cancer / 生理学报

DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.

Effects of post-traumatic stress disorder on the excitability of glutamatergic and GABAergic neurons in dorsal and ventral hippocampus in mice / 生理学报

The purpose of this study was to investigate the effects of post-traumatic stress disorder (PTSD) on electrophysiological characteristics of glutamatergic and GABAergic neurons in dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) in mice, and to elucidate the mechanisms underlying the plasticity of hippocampal neurons and memory regulation after PTSD. Male C57Thy1-YFP/GAD67-GFP mice were randomly divided into PTSD group and control group. Unavoidable foot shock (FS) was applied to establish PTSD model. The spatial learning ability was explored by water maze test, and the changes in electrophysiological characteristics of glutamatergic and GABAergic neurons in dHPC and vHPC were examined using whole-cell recording method. The results showed that FS significantly reduced the movement speed, and enhanced the number and percentage of freezing. PTSD significantly prolonged the escape latency in localization avoidance training, shortened the swimming time in the original quadrant, extended the swimming time in the contralateral quadrant, and increased absolute refractory period, energy barrier and inter-spike interval of glutamatergic neurons in dHPC and GABAergic neurons in vHPC, while decreased absolute refractory period, energy barrier and inter-spike interval of GABAergic neurons in dHPC and glutamatergic neurons in vHPC. These results suggest that PTSD can damage spatial perception of mice, down-regulate the excitability of dHPC and up-regulate the excitability of vHPC, and the underlying mechanism may involve the regulation of spatial memory by the plasticity of neurons in dHPC and vHPC.