OBJECTIVES: To investigate the effect of Ching Shum Pills (CSP) for alleviating non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism. METHODS: In a mouse model of NAFLD, the therapeutic effect of CSP was evaluated by measuring serum glucose, lipid profiles (TC, TG, LDL-C, HDL-C), and hepatic function markers. Network pharmacology was employed to identify active compounds in CSP and their targets using TCMSP, HERB, SwissTargetPrediction, GeneCards, OMIM, and DisGeNET. Protein-protein interaction (PPI) networks, Gene Ontology (GO), and KEGG pathway analyses were conducted. Molecular docking (AutoDock Vina) was used to assess the compound-target binding affinities. Quantitative real-time PCR (qRT-PCR) was used to validate the mRNA expressions of the core genes in the liver tissue of the mouse models. RESULTS: In the mouse model of NAFLD, treatment with CSP significantly reduced body weight gain and serum TG levels of the mice, and high-dose CSP treatment resulted in obvious reduction of ALT levels and hepatic fat accumulation. Network pharmacology analysis identified quercetin and 2-monolinolenin as the key bioactives in CSP, which target TNF, AKT1, IL6, TP53, and ALB. Docking simulations suggested strong binding between the two core compounds and their target proteins. The results of qRT-PCR showed that high-fat diet induced significant downregulation of Tp53, Cpt1, and Ppara expressions in mice, which was effectively reversed by CSP treatment. CONCLUSIONS CSP can improve lipid metabolism disorders in NAFLD mice through a regulatory mechanism involving multiple targets and pathways to reduce liver fat accumulation and protect liver function. The key components in CSP such as quercetin and linolenic acid monoacylglycerol may participate in the regulation of such metabolic processes as fatty acid oxidation by targeting TP53.
Animals ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Lipid Metabolism/drug effects* ; Molecular Docking Simulation ; Disease Models, Animal ; Liver/metabolism* ; Male ; Lipid Metabolism Disorders/drug therapy* ; PPAR alpha/metabolism* ; Mice, Inbred C57BL ; Network Pharmacology

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Different sagittal and vertical malocclusions exhibit different characteristics in the growth,development,and final morphol-ogy of the temporomandibular joint.Different skeletal malocclusions affect the spatial and morphological characteristics of the final tem-poromandibular joint through different growth and development mechanisms.These mechanisms have important guiding significance for determining the etiology and guiding treatment plans of maxillofacial malocclusion in children and adolescents in clinical practice.This article summarized and analyzed morphological differences of the temporomandibular joint fossa and condyle in different sagittal and ver-tical malocclusions,as well as the relative position of the condyle in the fossa.It is found that there is a connection between different maxillofacial malocclusions and the characteristics of the temporomandibular joint,with the vertical direction having a more significant impact on the temporomandibular joint than the sagittal direction;the impact of vertical malocclusion on the temporomandibular joint is mainly reflected in the shape of the joint fossa and the position of the condyle in the fossa.The joint fossa of hyperdivergent malocclu-sion is often relatively low and flat,with the condyle located in the anterior upper position of the fossa.The joint fossa of hypodivergent is relatively narrow and deep,and the condyle is relatively backward and lower in the joint fossa.The possible mechanisms were also elaborated,providing reference for clinicians'comprehensive diagnosis and treatment.

Objective:To establish a polymerase chain reaction(PCR)method to accurately discriminate the crude materials and aqueous extract of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorff and Ptyas korros.Methods:Specific primers were designed using mitochondrial Cytb gene(CO1)as a target gene,and annealing temperature,number of cycles and the type of DNA polymerases were optimized.The mixed samples were detected by this method.Results:By this multiplex allele-specific PCR identification method,135,182,246 and 197 bp of specific fragments were amplified from DNA templates of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorffi and Ptyas korros,respectively,following the conditions:cycle number of 35,annealing temperature of 62 ℃.The adulterants and the blank control showed no bands.The method could simultaneously and accurately identify the snake-derived components in the mixed samples.Conclusion:The method can be used to identify the samples of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorffi and Ptyas korros simultaneously,accurately and rapidly,and is suitable for the identification of standard decoctiond and formula granules samples.

【Objective】 To investigate the correlation between the titer of anti-A or anti-B antibodies before and after the absorption of IgG anti-AB antibodies in the serum of type O mothers with ABO hemolytic disease of fetus and newborn (ABO-HDFN) and the total bilirubin in the serum of the children. 【Methods】 Serum samples from 119 children diagnosed with ABO-HDFN and their mothers sent to the Beijing Red Cross Blood Center from January to December 2020 were selected, and clinical data of the children were collected. Three hemolysis tests and serum total bilirubin (TBIL) determination were conducted on the children. IgG anti-A or anti-B antibody titers were tested before and after the mother′s serum absorbed IgG anti-AB antibodies. Statistical analysis was conducted on the IgG antibody titers and the TBIL results of the children. The differences in TBIL results corresponding to different IgG antibody titers were compared. The Spearman test was used to analyze the correlation between the IgG anti-A or -B antibody titers and TBIL results before and after the absorption of IgG anti-AB antibodies. 【Results】 There were differences in the TBIL results corresponding to IgG anti-A or anti-B titers at different levels in the serum of type O mothers after absorption by IgG anti-AB antibodies (F=8.401, 19.622, P<0.05). There was no significant correlation between the IgG anti-A or anti-B titers of maternal serum before absorption by IgG anti-AB antibodies and neonatal TBIL results (r=0.181, 0.248, P>0.05). The IgG anti-A or anti-B titers of maternal serum absorbed by IgG anti-AB antibodies were positively correlated with neonatal TBIL results (r=0.487, 0.629, P<0.05). 【Conclusion】 There is a positive correlation between the titer of IgG anti-A or anti-B antibodies in the serum of type O mothers after absorbing IgG anti-AB antibodies and the TBIL results of ABO-HDFN children. The trend of increased total bilirubin in newborn serum ban be accurately predicted by detecting the titer level of IgG anti-A or anti-B antibodies in the serum of mothers after absorbing IgG anti-AB antibodies.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

【Objective】 To investigate the inactivation function of 25Gy X-ray irradiation on apheresis platelets’ lymphocytes and its effect on the quantity of apheresis platelets(AP). 【Methods】 Twenty healthy voluntary AP donors from January to May 2021 in our center were selected, and 2 bags of AP were donated by each of them. The APs were divided into two groups to undergo X-ray and γ-ray irradiation for 10 min. Lymphocytes were separated from AP samples, before and after irradiation, by lymphocyte separation solution to analyze and compare the effect of X-ray and γ-ray on lymphocyte proliferation. The CD41b, CD62p, blood routine and pH of APs before and 1-day/3-day after irradiation were detected. SPSS statistical software was used to analyze and compare the differences between groups by independent sample t-test. 【Results】 After 25Gy X-ray and γ-ray irradiation, the inhibition rates of lymphocytes were (98.034±1.778)% and (97.882±1.915)%, respectively.Compared with the γ irradiation group, the difference of Plt, PDW, MPV, P-LCR, PCT, pH, CD41b and CD62p between 1-day and 3-day group after 25Gy X-ray irradiation showed not statistically significance (P>0.05). 【Conclusion】 25Gy X-ray irradiation can effectively inactivate lymphocytes in APs, and the radiation effect was equivalent with γ-ray; at the same time, there was no significant influence on the quantity of APs.

OBJECTIVE：To study the improvement effects of Weijing deco ction on AECOPD model rats and its possibile mechanism. METHODS ：Totally 55 male SD rats were randomly divided into normal group ，model group ，Weijing decoction low-dose and high-dose groups （8.37，16.74 g/kg，by crude drug ），dexamethasone group （positive control group ，0.09 mg/kg），with 11 rats in each group. Except for normal group ，AECOPD model was induced by cigarettes combined with lipopolysaccharide in other groups. After modeling ，normal group and model group were given constant volume of water intragastrically ，and other groups were given relevant medicine intragastrocally ，twice a day ，for 14 days. After last intragastric administration ，the serum level of IL- 1 β was determined，and pathological changes of lung tissue and bronchus were observed in each group ；mRNA expression of MMP-9 and TIMP- 1 genes in lung tissue were detected ；protein expression of Ras homologous gene family member （RhoA）， dishevelled associated activator of morphogenesis- 1（DAAM1）and hyperplasic suppress gene （HSG）in lung tissue were also determined. RESULTS ：Compared with normal group ，the levels of IL- 1β in serum，mRNA expression of MMP- 9 and TIMP-1 as well as protein expression of RhoA and DAAM 1 in lung tissue were increased significantly in the model group（P＜0.05），while protein expression of HSG in lung tissue was decreased significantly （P＜0.05）；there were many chronic inflammatory cells infiltrating around the bronchus ，some airway mucosa epithelium exfoliating ，alveolar compensatory dilation，pulmonary septal capillary dilation and hyperemia. Compared with model group ，the levels of IL- 1β in serum，mRNA expression of MMP- 9 and TIMP- 1 in lung tissue were decreased significantly in Weijing decoction high-dose group （P＜0.05）；the protein expression of RhoA and DAAM 1 in lung tissue were decreased significantly in Weijing decoction low-dose and high-dose groups（P＜0.05），while the protein expression of HSG in lung tissue was increased （P＜0.05）；the pathological changes of Weijing decoction high-dose group ，such as inflammatory cells infiltrating around the bronchus and shedding of airway mucosa ， were improved significantly ， and there was complete alveolar epithelium structure but no obvious pulmonary dilation. CONCLUSIONS：Weijing decoction can improve AECOPD model rats to certain extent ；its mechanism may be associated with down-regulating mRNA expression of MMP- 9 and TIMP -1 as well as protein expression of RhoA and DAAM 1 in lung tissue ， up-regulating protein expression of HSG in lung tissue so as to inhibit the airway remodeling.

OBJECTIVE：To establish the quality standards of Mongolian medicine Cynanchum thesioides. METHODS ：TLC was used for the qualitative identification of C. thesioides . According to 2015 edition of Chinese Pharmacopeia （part Ⅳ），the moisture，total ash and ethanol-soluble extract were determined. HPLC method was used to determine the content of thesioideoside in C. thesioides . RESULTS ：TLC spots were clear ，there were same yellow green fluorescent spots on the corresponding position of the sample （C. thesioides ）and control （thesioideoside）. In 22 batches of samples ，contents of moisture were 6.18％-12.97％，total ash were 4.64％-7.95％，ethanol-soluble extract were 12.46％-32.70％. The linear range of thesioideoside were 0.048-3.050 μg（R2＝ 0.999 9）. RSDs of precision ， stability， repeatability and durability tests were all less than 1％ . The recoveries were 104.03％-106.36％（RSD＝0.96％，n＝6）. The contents of thesioideoside in 22 batches of C. thesioides were 0.006 2％-0.130 5％. CONCLUSIONS：It is suggested that the moisture and total ash should not exceed 11.50％ and 7.50％，respectively；the contents of ethanol-soluble extract and the sioideoside are no less than 17.00％ and 0.05％，respectively. The established quality standards can be used for quality control of Mongolian medicine C. thesioides .

To investigate the relationship between single nucleotide polymorphisms (SNPs) of CACNA1C (SNPs rs58619945, rs7316246 and rs216008) and susceptibility of chronic spontaneous urticaria (CSU) as well as the curative effect of non-sedating antihistamine drugs.
 Methods: Peripheral blood were extracted from 191 CSU patients to collect DNA. Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI) changes were collected from these patients with different non-sedating antihistamine drugs. PubMed retrieval system was used to select the 3 SNPs (rs58619945, rs7316246 and rs216008) of CACNA1C. Susceptibility of CSU and curative effect of non-sedating antihistamine drugs (desloratadine, mizolastine, fisofenadine) in 189 CSU patients and 105 controls with different SNPs were compared with Chi-squared test. Data of 105 southern Chinese controls were extracted from the 1 000 genome database.
 Results: Frequency of rs58619945 G allele in the CSU patients was significantly higher than that in the controls [OR(95%CI)=0.660(0.470-0.925), P=0.016]. However, there was no significant differences in rs7316246 and rs216008 between the CSU patients and the controls. Meanwhile there was no significant difference in general curative effect of the 3 drugs in the 3 SNPs (rs58619945: OR=0.843, P=0.454; rs7316246: OR=2.103, P=0.102; rs216008: OR=0.237, P=0.363). There was significant difference in different alleles of rs216008 in the patients administered by desloratadine [OR(95%CI)=0.480(0.247-0.933), P=0.029]. No difference was shown in the 3 SNPs in patients administered by mizolastine.
 Conclusion: The rs58619945 A/G might be related to susceptibility of CSU, and the rs216008 mutation might affect drug response of desloratadine.
Calcium Channels, L-Type ; genetics ; Chronic Disease ; Genetic Predisposition to Disease ; Histamine H1 Antagonists, Non-Sedating ; therapeutic use ; Humans ; Loratadine ; analogs & derivatives ; therapeutic use ; Polymorphism, Single Nucleotide ; Prognosis ; Retrospective Studies ; Urticaria ; drug therapy ; genetics