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.

A nested case-control study on the association of neonatal cord blood selenium, iron and copper with congenital heart disease / 中华预防医学杂志

Objective: To investigate the relationship between the levels of selenium, iron and copper in cord blood of neonates and the risk of congenital heart disease (CHD), and analyze their interaction effects. Methods: The subjects were obtained from the birth cohort in Lanzhou area established from 2010 to 2012. A baseline survey was conducted in the first trimester, and the follow-up was conducted in the second trimester, third trimester and 42 days after delivery. The umbilical vein blood was collected from newborns at delivery, and information on their birth outcomes was extracted from medical records. A nested case-control study was used to select 97 neonates with CHD newly diagnosed by echocardiography as the case group, and 194 neonates were selected as the control group by 1∶2 matching according to their mother's age, block and CHD onset time. Inductively coupled ion mass spectrometry was used to detect the concentrations of selenium, iron and copper in neonatal cord blood. The element exposure was categorized into three groups, the low, medium and high concentrations, according to the quartiles Q1 and Q3 of selenium, iron and copper concentrations in the control group. The association between cord blood selenium, iron and copper concentrations and CHD was analyzed by conditional logistic regression model using medium concentration as the reference standard. The association of their interactions with CHD was analyzed by a phase multiplication model. Results: The M (Q1, Q3) concentration of neonatal cord blood copper was 746.12 (467.48, 759.74) μg/L in the case group and 535.69 (425.21, 587.79) μg/L in the control group, with a statistically significant difference between the two groups (P<0.05). After adjustment for confounders, logistic regression models showed that the risk of CHD development was increased in neonates with either high copper in cord blood (OR=4.062, 95%CI: 2.013-8.199) or high copper combined with high iron (OR=3.226, 95%CI: 1.343-7.750). No correlation was observed between selenium and iron concentrations and the development of CHD in neonates. There was a multiplicative interaction between copper and iron in cord blood on the risk of developing CHD (OR=1.303, 95%CI: 1.056-1.608). Conclusion: There is a multiplicative interaction between iron and copper elements. The high copper and the high copper combined with high iron in umbilical cord blood are risk factors for neonatal CHD.

Research progress in drugs targeting tumor associated macrophage / 药学学报

Tumor brings great threat to human public health. In recent years, incidence rate and mortality of tumor were rapidly increased in the world. Anti-tumor therapies have undergone the development of cytotoxic therapy, targeted therapy, and immunotherapy. Among them, tumor immunotherapy is rapidly developed and becomes an important anti-tumor therapy in recent years, although it also brings some related side effects. Tumor microenvironment (TME) is composed of immune cells, vascular vessels, fibroblasts, the extracellular matrix, etc. TME significantly affects the efficacy of immunotherapy. Macrophages in the TME are named as tumor associated macrophages (TAMs). Recently, increasing studies have shown that TAMs play an important role in the regulation of tumor immunity, especially in tumor immune surveillance and immune escape. Currently, more and more anti-tumor immunotherapy strategies targeting TAMs are at the development stage. Based on the important role of TAMs in the TME and their potential as therapeutic targets in tumor immunotherapy, we first reviewed the subtypes and functions of TAMs, as well as the roles of TAMs in tumors. Furthermore, we summarized the research progress on anti-tumor strategies targeting TAMs and the current status of drug targeting TAMs. The current review will provide new ideas and novel insights for tumor immunotherapy.

Expression and localization of vascular endothelial growth factor-B in diencephalon and brainstem related tissues of the Yak’s brain / 解剖学报

Objective To explore the expression and distribution characteristics of vascular endothelial growth factor-B(VEGF-B) in diencephalon and brainstem of Yak’s brain tissues, and to investigate the associations between its expression and hypoxia adaptation. Methods Five healthy yaks were selected, and the brain tissues were divided and collected according to the gross anatomical structure of the brain, including pituitary, thalamus, hypothalamus, oblongata and pons. The characteristics of expression and location of VEGF-B in different regions of Yak’s brain tissues were detected by Real-time PCR, Western blotting and immunohistochemical techniques. Results The results showed that the highest expression level of VEGF-B mRNA of yak brain tissue was in the pituitary, and the content was significantly higher than that found in other parts of the brain(P<0. 05). Following the expressions were in the hypothalamus, thalamus and medulla oblongata, while the lowest expression level was in pons. The expression level of VEGF-B protein in Yak’s brain tissue was similar to the mRNA expression level except that the thalamus was higher than that of hypothalamus. The result of immunohistochemistry showed that VEGF-B protein-positive substances were mainly distributed in the cytoplasm of various types of cells. Among them, the positive staining of VEGF-B was mainly concentrated in eosinophils of pituitary. The positive staining of VEGF-B was mainly concentrated in pleomorphic cells of thalamus and hypothalamus. The distribution of VEGF-B protein-positive substances were mainly focused in nerve cell body of medulla oblongata and pons. Conclusion VEGF-B protein is expressed in both diencephalon and brainstem of yak, which may be closely related to its functions of anti-apoptosis, "survival factor" and angiogenesis. However, the specific mechanism of its neuroprotective effect on Yak brain under hypoxic environment needs to be further studied. The difference of expression in different regions may be related to the tissue specificity and function in different regions of the brain.

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 on experimental animal models of hyperuricemia / 中国药理学通报

Hyperuricemia is a chronic metabolic disease caused by purine metabolism disorder or uric acid excretion disorder. The experimental animal model of hyperuricemia is the basis for studying the pathological mechanism and drug treatment of hyperuricemia. This paper reviews the experimental animal models of hyperuricemia commonly used in drug research, and introduces the modeling principle, preparation methods, species selection and related detection techniques of the models, so as to provide reference for the application of such models in research.

Exploring the mechanism of anti-hereditary Parkinson's disease of baicalein based on PINK1 RNAi Drosophila model / 药学学报

The aim of this study was to investigate the effect of baicalein on a Drosophila model of hereditary Parkinson's disease caused by gene mutations and to preliminarily elucidate the mechanism of baicalein in delaying hereditary Parkinson's disease. In this paper, PTEN-induced putative kinase 1 (PINK1)-RNAi Parkinson's Drosophila were used as the model group and wild-type Drosophila w1118 were used as the control group. Different doses of baicalein and Madopa were administered to the model group to observe their effects on the life span, motor ability, the abnormal rate of wings, dopamine content and dopaminergic neurons of PINK1-RNAi Parkinson's Drosophila and their effects on mitochondrial dysfunction including adenosine triphosphate (ATP), mitochondrial DNA (mtDNA) and reactive oxygen species (ROS) content. The results showed that the effective administration doses of baicalein were 0.8 mg·mL-1 for low concentration, 1.6 mg·mL-1 for medium concentration and 3.2 mg·mL-1 for high concentration, and the optimal administration dose of the positive drug Madopa was 0.1 μg·mL-1. Baicalein and Madopa could significantly improve the life span, exercise ability and reduce the abnormal rate of wings of PINK1-RNAi male Drosophila (P < 0.05), and low dose baicalein showed the best effect; baicalein could improve the loss of dopaminergic neurons, and the effects of low dose and high dose were the best, but Madopa showed no significant effect; baicalein and Madopa had no significant effect on dopamine content (P > 0.05). Baicalein and Madopa could increase the ATP content of PINK1-RNAi male Drosophila (P < 0.05), and low dose baicalein showed the best effect; middle dose baicalein could significantly increase the mtDNA content of PINK1-RNAi male Drosophila (P < 0.05), but Madopa had no significant effect; baicalein and Madopa had no significant effect on ROS content (P > 0.05).

Progress on targets and therapeutic drugs for pancreatic cancer / 药学学报

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

Advances in research of heart organoid and its application in drug discovery / 药学学报

Cardiovascular diseases are fatal threats to human health and also important fields in drug discovery. Organoid is a miniature with the structure and function similar to the organ, which is formed by the self-updating and specific differentiation of stem cells during the in vitro culture. Considering its characteristics of human origin, physical features, self-assembling and genetic stability, heart organoid has attracted much attention in the study of cardiogenesis, cardiovascular diseases modeling and related drug research. Hence, this article will review the development of heart organoids and its construction strategies, highlighting its application and prospects in drug discovery.

The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-κB signaling pathway / 药学学报

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg·kg-1), and positive control sildenafil group (100 mg·kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% ± 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF-κB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) by DYY.

Study on the differences in chemical composition of Scutellaria baicalensis leaves from different origins in Shanxi Province based on plant metabolomics and targeted quantitative analysis / 药学学报

By integrating plant metabonomics and target quantitative analysis methods, this study systematically analyzed the differences of chemical constituents in Scutellaria baicalensis leaves from different producing areas in Shanxi, so as to provide theoretical basis for rational and effective utilization of Scutellaria baicalensis leaves. Based on the idea of plant metabonomics, the liquid quality of 53 batches of Scutellaria baicalensis leaves from 8 different producing areas in Shanxi was analyzed by UPLC-QTOF-MS, and the collected data were imported into SIMCA 14.1 software for multivariate statistical analysis to screen the different chemical constituents among different habitats in Shanxi. Meanwhile, a method for simultaneous determination of 7 flavonoids and 3 organic acids in Scutellaria baicalensis leaves was optimized and established to quantitatively analyze the differences of chemical components in Scutellaria baicalensis leaves from different producing areas in Shanxi. The results of plant metabonomics showed that there were differences in the chemical composition of Scutellaria baicalensis leaves in northern Shanxi (Datong, Xinzhou), Jinzhong (Yangquan, Luliang) and southern Shanxi (Changzhi, Yuncheng, Jincheng, Linfen): there were 14 significant differences in chemical composition between northern Shanxi and Jinzhong; there were 18 significant differences in chemical constituents between southern Shanxi and central Shanxi. There were 15 significant differences in chemical constituents between northern Shanxi and southern Shanxi. Among them, scutellarin and isocarthamidin-7-O-glucuronide were the common differences among the three regions, and the content of scutellarin was the highest in southern Shanxi and the lowest in northern Shanxi. The content of isocarthamidin-7-O-glucuronide was the highest in Jinzhong area and the lowest in northern Shanxi area. Quantitative analysis further confirmed that the average contents of apigenin, naringenin and citric acid were the highest in northern Shanxi, scutellarin, caffeic acid, apigenin-7-O-glucuronide, malic acid and wogonoside were the highest in southern Shanxi, and wogonoside and baicalin were the highest in central Shanxi. This study is of great significance to the quality control of Scutellaria baicalensis leaf resources, and provides theoretical basis for rational and effective utilization of Scutellaria baicalensis leaf resources.

Relationship between pesticide exposure and lipid metabolism in population / 中华劳动卫生职业病杂志

Objective: To investigate the effect of pesticides and herbicides on lipid metabolism. Methods: In November 2020, Based on the data of the national health and Nutrition Survey (NHANES) (2011-2014) , select the population aged 20~65 who have demographic information, pesticide use and data of four lipid metabolism indicators [total cholesterol (TC) , triglyceride (TG) , high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) ] (n=3039) . The subjects were divided into insecticide group (320 people) and non insecticide group (2719) according to the use of insecticides, and herbicide group (156 people) and non herbicide group according to the use of herbicides. Results: Among the 3039 subjects, the males and female were 1509 (49.7%) and 1530 (50.3%) respectively. The males age was (39.7±12.0) years and the females age was (40.2±12.0) years The concentration of HDLC in the NHANES (55.4±15.0) mg/dl was lower than that of (58.2±14.2) mg/dL in the non herbicide group (P<0.05) (b=-0.044, P<0.05) . The results showed that the use of herbicides was related to the decrease of HDLC and the increase of LDLC and LDLC/HDLC in female population (b=-0.050, 0.062, 0.067, all P<0.05) . Conclusion: Herbicide exposure can cause the change of lipid metabolism, and the effect on female population is more obvious.

Changes in the morphology and function of the meibomian glands in patients with type 2 diabetes mellitus and their effects on the function of tear film / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes of morphology and function of meibomian glands in patients with type 2 diabetes mellitus and its influence on the tear film. METHODS: A total of 52 patients(104 eyes)with type 2 diabetes mellitus who came to our hospital from January 2018 to January 2020 were selected. Then they were divided into non-diabetic retinopathy group(NDR group, 31 cases with 62 eyes)and diabetic retinopathy group(DR group, 21 cases with 42 eyes)according to the fundus changes. While 38 cases(76 eyes)of diabetic-free cataract patients who treated at the same time were selected as the control group. The differences of three groups were compared with the morphology and the scores of the function of lid edge and meibomian glands, the scores of fluorescence staining of cornea, break-up time(BUT)of tear film, lipid layer thickness(LLT), blink times(BT)and partial blink rate(PBR).RESULTS: The morphology and the scores of function of lid edge and meibomian glands, the scores of fluorescence staining of cornea were significantly higher than the control group, and the DR group was significantly higher than the NDR group(all P<0.05). The BUT in the DR group and NDR group was significantly lower than that in the control group, and the DR group was significantly lower than that in the NDR group(all P<0.05). There were differences in LLT, BT and PBR among the three groups(P<0.05). The LLT and BT in the DR group and NDR group were significantly lower than those in the control group, and PBR was significantly higher than that in control group(all P<0.05), but there was no significant difference between the DR group and the NDR group(all P>0.05). Type 2 diabetes mellitus patients with morphology abnormalities of meibomian gland have a higher incidence of abnormal tear film function.CONCLUSION: Patients with type 2 diabetes mellitus are prone to shortening and loss of meibomian glands, which is easy to cause the dysfunction of the meibomian gland and decrease the stability of the tear film. While the patients with DR, the morphology abnormalities and dysfunction of the meibomian glands are more pronounced, and the stability of the tear film is worse.

Effect of neoadjuvant chemotherapy on breast invasive ductal carcinoma and changes of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki67 in tissues / 中国综合临床

Objective:To observe the clinical effect on patients of invasive ductal carcinoma of the breast by neoadjuvant chemotherapy, and to analyze the changes of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and Ki67 in neoplasm.Methods:A total of 83 patients which were treated by neoadjuvant chemotherapy in breast invasive ductal carcinoma diagnosed were selected in North China University of Science and Technology Affiliated Hopital from January 2014 to December 2020. There were 30 cases of Luminal type A, 31 cases of Luminal type B, 10 cases of HER-2 positive type and 12 cases of triple negative type. To observe the clinical effect of different molecular subtypes, detect the expression of Er, PR, HER-2 and Ki67 in pathological tissues before and after neoadjuvant chemotherapy, and conduct a retrospective case-control study. Comparison between the two groups use χ2 test, matched χ2 and accurate probability method. Results:Fifty-eight cases were clinically effective, the total effective rate was 69.8% (58/83), and 9 cases were pathological complete response (pCR), accounting for 10.8% (9/83). After neoadjuvant chemotherapy, the highest clinical efficacy was luminal type B in 26 cases, and the highest PCR was triple negative type in 3 cases. The pathological results showed that the expression of ER (6 cases of positive expression were increased, χ2=1.03, P=0.310), PR (8 cases of positive expression were increased, χ2=1.56, P=0.210) and HER-2 (2 cases of positive expression were decreased, χ2=0.10, P=0.748) was not different before and after neoadjuvant chemotherapy. The expression of Ki67 was decreased in 25 cases (30.1%) after chemotherapy compared with 59 cases (71.1%) before chemotherapy (34 cases of positive expression were decreased, χ2=27.85, P<0.001). Five cases were added among Luminal type A after chemotherapy, all of which were transformed from Luminal type B, but the kappa value was 0.919 (>0.75), the consistency rate was 91.9%. The consistency was idea before and after chemotherapy. Five cases were added after Luminal type A chemotherapy, all of which were transformed from Luminal type B, but the kappa value was 0.919 ( P>0.75), and the consistency rate was 91.9%,The consistency before and after chemotherapy was good. After chemotherapy, HER-2 expression remained unchanged in 59 cases (clinically effective in 48 cases), up-regulated in 9 cases (clinically effective in 4 cases) and down regulated in 15 cases (clinically effective in 6 cases)( χ2=12.82, P=0.002). Ki67 expression remained unchanged in 35 cases (20 cases were clinically effective), up-regulated in 7 cases (2 cases were clinically effective) and down regulated in 41 cases (36 cases were clinically effective)( χ2=14.63, P=0.001). Conclusion:The clinical effect of neoadjuvant chemotherapy in the treatment of breast invasive ductal carcinoma is ideal. The clinical effective rate of Luminal B type is the highest, and the pCR rate of triple negative type is the highest.And it can significantly reduce the expression of Ki67. The down-regulation of HER-2 and Ki67 is significant for clinical efficiency.

Progress in RIPK3-mediated necroptosis involved in myocardial ischemia-reperfusion injury / 中国药理学通报

Aim Timely re establishment of coronary blood How in patients with myocardial infarction is the cornerstone of their treatment; however, substantial amount of damage can oecur as a consequence of reperfusion.In recent years it has been found that receptor interacting protein kinase 3 ( RIPK3 ) contributes remarkably to myocardial ischemia-reperfusion injury (MIRI).RIPK3 can regulate necroptosis through RIPK1/RIPK3/MLKL and CaMKII, respectively, and participate in the MIRI process.This artiele reviews the researeh progress of RIPK3-mediated ne¬ croptosis involved in MIRI from endoplasmic reticulum stress, mitochondrial fragmentation disturbanee, cardiac microvascular dysfunction and inflammation, and focuses on whether RIPK3 can be used as a new target for anti-MIRI, so as to provide a new strategy and choice for improving the clinical treatment effect and prognosis of ischemic heart disease.

Research progress and application of animal models for drug development in multiple sclerosis / 中国药理学通报

Multiple sclerosis ( MS) is an immune-mediated chro¬nic inflammatory disease of the central nervous system (CNS) , which is regulated by multiple pathophysiological mechanisms.There are four clinical phenotypes of MS, including relapsing-re- mitting MS ( RRMS) , primary progressive MS ( PPMS) , sec- ondary-pmgressive MS ( SPMS) , and progressive relapsing MS ( PRMS) , among which RRMS is the main type.'Hie pathogen¬esis of MS is not clear and it could not he cured, so long-term drug treatment is needed for the MS patients.Nowadays, animal models play an important role in the preclinical research of MS drugs.'Hie MS animal models are mainly divided into experi¬mental autoimmune encephalomyelitis (EAE) model, toxin in¬ duced demyelination model, and vims induced demyelination model, among which EAE model is most widely used.'Hie three types of MS animal models demonstrate specific characteristics due to the different induction methods and animal species, and they correspond to specific clinical types of MS.According to the different clinical types of MS, the use of appropriate animal models for drug research and development will help us develop more targeted and potential therapeutic dnrgs, making it possible to cure MS.

Preparation and evaluation of experimental animal models of ischemic brain injury / 中国药理学通报

Aim Ischemic brain injury ( IBI) is one of the main causes of death and disability worldwide.Faced with this serious disease, human beings still laek effective treatment methods.With the advancement of science and the improvement of medi¬cal standards, the basic and clinieal research of cerebrovaseular diseases continues to develop to a higher and more in-depth lev¬el.Due to the limitations of clinical researeh, animal models of eerebral ischemia have beeome an indispensable tool for studying the mechanism of cerebrovascular disease damage and prevention and treatment measures.It is necessary to construct scientific, standard and standardized experimental methods and proee- dures..Methods This artiele combines our laboratory s long-tenn praetieal experienee in preparing animal models of cerebral is¬chemia.comprehensive literature data, comparison and evalua¬tion of the characteristics of commonly used animal models.Re¬sults Standardized preparation methods and discusses the com¬mon criteria for preparing experimental animal models of cerebral Ischemia, which is the occurrence of cerebral ischemia injury.Conclusions 'Hie researeh of mechanism and the researeh and de¬velopment of prevention and treatment drugs provide reliable ex¬perimental animal models.

Research progress on mechanisms and therapeutic drugs of hypoxic pulmonary hypertension / 中国药理学通报

Hypoxic pulmonary hypertension ( HPH) is a complex mechanism of HPH is complex, and it has a high mortality rate cardiopulmonary disease eaused by hypoxia.The pathological of disability.Clinically the diug of treatment for HPH is unspe-cialized, mainly relying on traditional vasomotor dnrgs, inclu¬ding prostaglandin 12 receptor agonists, endothelin receptor an¬tagonists and phosphodiesterase-5 inhibitors, but their efficacy cannot be achieved.To meet the clinical need, it is of great sig¬nificance to develop targeted anti-HPH dnigs.To provide ideas for the discovery of HPH treatment drugs, the pathophysiological mechanism of HPH and the current status of dmg development are reviewed in the paper.

Research progress in regulating cAMP pathway to prevent and treat chronic obstructive pulmonary disease / 中国药理学通报

Cyclic adenosine monophosphate(cAMP)is a “second messenger” that regulates cell signal transduction. Adenylyl cyclases(ACs)and phosphodiesterases(PDEs)can directly regulate cAMP level in cells and then regulate the downstream signaling pathways. Increasing intracellular cAMP level can inhibit inflammation and enhance smooth muscle relaxation, which is an effective strategy for the prevention and treatment of chronic obstructive pulmonary disease(COPD). This paper briefly summarizes the signaling pathways regulating cAMP and their mechanisms and related drugs in COPD therapy, hoping to provide references for further research and development of new target drugs which regulate cAMP for the prevention and treatment of COPD.

The research advance on subtypes and relevant therapy of Parkinson's disease / 药学学报

Parkinson's disease (PD) is a progressive neurodegenerative disease with a high clinical heterogeneity. According to its motor symptoms, PD patients are divided into predominant tremor-dominant, postural instability and gait difficulty-dominant/akinetic-rigid and mixed subtypes. Different subtypes show different prognostic characteristics and different sensitivities to drugs. Therefore, the early classification of PD is of great significance for the treatment and prognosis of the disease. This paper reviews the clinical classification methods of different subtypes of PD, summarizes the latest biochemical markers and imaging features, and analyzed the differences in incidence, prognosis and pathological mechanism. The current clinical treatment drugs and methods have been preliminarily targeted for treatment based on PD classification, and there are many animal models of PD subtypes have been studied, providing new methods and strategies for mechanism research and preclinical pharmacodynamics evaluation of PD subtypes.