OBJECTIVETo study the analgesic effects and mechanism of Yuanhuzhentong capsule.

METHODThe rats trigeminal nerve headache model, the migraine model caused by nitroglycerim, and the mice hot plate test. The rat formalin test were used to evaluate the analgesic effects. The effects on mice automative activities, the content of monoamine neurotansmitters in rats trigeminal nerve headache model and the hemorrheology in model of blood stasis were investigated to analyze the analgesic effects.

RESULTYuanhuzhentong capsule can prolong the latency of the rats trigeminal nerve headache model and reduce the durante dolors. It can relieve the reaction caused by nitroglycerim in different times and increase the threshold in mice hot plate test. It can decrease obviously the response time of the chronicity pain model rat caused by formalin in second phase and also decrease the counts of automative activities in 5 min. It can increase the content of 5-HT and decrease blood viscosity in blood stasis model rats.

CONCLUSIONThe results indicated that Yuanhuzhentong capsule has obvious analgesic effects, and the mechanism concernes with the sedation, adjusting the secretion of NT in brain and improving the blood circulation.

Analgesics ; administration & dosage ; Animals ; Capsules ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Headache ; drug therapy ; physiopathology ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Pain ; drug therapy ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective To understand with greater clearness the genetic polymorphism of (GCT)n repeat of MHC class I chain-related gene A (MICA)in some Chinese populations and provide preliminary genetic evidence for the independent origin of Chinese Baima Tibetan (BMT). Methods ACD-blood or saliva specimens of 411 unrelated individuals from four Chinese populations were collected. A primer pair spanning exon 5 of MICA gene was used to amplify the GCT region. Alleles were detected by PCR and denaturing PAGE. Comparison of the allelic distributions among the four populations was carried out. Results Five previously reported alleles have been observed in all the four populations, but the allelic distributions are different from one another. The most frequent allele is the A5 in all the four populations (0.325 in BMT, 0.345 in Tibetans, 0.390 in Chengdu Hans and 0.319 in Qiangs). A5.1 allele is the second most frequent allele in Chengdu Hans (0.230) and in Qiangs (0.293), while the second most frequent alleles for BMT and Tibetans are A4 (0.254) and A9 (0.272) respectively. The distribution of alleles in BMT is significantly different from that in the other three populations. Conclusion Alleles of MICA gene exon 5 are conservative in all populations studied so far. The results suggest that genetically BMT might be an independent ethnic population.

Objective To investigate the expression levels of serum microRNA-33a-5p(miR-33a-5p)and Sirtuin6(SIRT6)in patients with esophageal cancer,and their relationship with clinical pathological characteristics and prognosis.Methods From March 2018 to March 2020,123 newly diagnosed patients with esophageal cancer(esophageal cancer group)and 94 patients with esophagitis(benign lesion group)admitted to our hospital were collected as the research subjects,another 72 healthy individuals who underwent physical examination were regarded as the health control group;the clinical and pathological characteristics of esophageal cancer patients were collected.Real-time fluorescence quantitative PCR method was applied to detect the expression of miR-33a-5p and SIRT6 mRNA in three groups of serum,the relationship between the expression levels of serum miR-33a-5p and SIRT6 mRNA in esophageal cancer patients and clinical pathological characteristics was analyzed;TargetScanHuman website was applied to predict the targeting relationship between miR-33a-5p and SIRT6;Pearson method was applied to analyze the correlation between serum miR-33a-5p and SIRT6 mRNA expression levels in esophageal cancer patients;Kaplan-Meier method was applied to analyze the relationship between the expression levels of serum miR-33a-5p and SIRT6 mRNA in esophageal cancer patients and their prognosis;Cox regression was applied to analyze the prognostic factors of esophageal cancer patients.Results The expression level of serum miR-33a-5p in the esophageal cancer group was greatly higher than that in the benign lesion group and healthy control group(P＜0.05),the expression level of serum SIRT6 mRNA was greatly lower than that of the benign lesion group and healthy control group(P＜0.05);TargetScanHuman website predicts that there was a targeted binding site between miR-33a-5p and SIRT6,and there was a negative correlation between serum miR-33a-5p and SIRT6 mRNA expression levels in esophageal cancer patients(r=-0.468,P＜0.05);the expression levels of serum miR-33a-5p and SIRT6 mRNA in esophageal cancer patients were related to TNM staging,lymph node metastasis,and degree of differentiation;the 3-year survival rate of esophageal cancer patients with low expression of serum miR-33a-5p and high expression of SIRT6 mRNA was greatly higher than that of esophageal cancer patients with high expression of miR-33a-5p and low expression of SIRT6 mRNA(P＜0.05);Cox regression analysis showed that high expression of miR-33a-5p and low expression of SIRT6 mRNA were independent risk factors for death in esophageal cancer patients(P＜0.05).Conclusion The expression level of serum miR-33a-5p in esophageal cancer patients is greatly increased,while the expression level of SIRT6 mRNA is greatly reduced;the expression levels of both are closely related to the clinical pathological characteristics and prognosis of esophageal cancer patients.

OBJECTIVES: Fluorouracil chemotherapeutic drugs are the classic treatment drugs of gastric cancer. But the problem of drug resistance severely limits their clinical application. This study aims to investigate whether hypoxia microenvironment affects gastric cancer resistance to 5-fluorouracil (5-FU) and discuss the changes of gene and proteins directly related to drug resistance under hypoxia condition. METHODS: Gastric cancer cells were treated with 5-FU in hypoxia/normoxic environment, and were divided into a Normoxic+5-FU group and a Hypoxia+5-FU group. The apoptosis assay was conducted by flow cytometry Annexin V/PI double staining. The real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression level of hypoxia inducible factor-1α (HIF-1α), multidrug resistance (MDR1) gene, P-glycoprotein (P-gp), and vascular endothelial growth factor (VEGF) which were related to 5-FU drug-resistance. We analyzed the effect of hypoxia on the treatment of gastric cancer with 5-FU. RESULTS: Compared with the Normoxic+5-FU group, the apoptosis of gastric cancer cells treated with 5-FU in the Hypoxia+5-FU group was significantly reduced (P<0.05), and the expression of apoptosis promoter protein caspase 8 was also decreased. Compared with the the Normoxic+5-FU group, HIF-1α mRNA expression in the Hypoxia+5-FU group was significantly increased (P<0.05), and the mRNA and protein expression levels of MDR1, P-gp and VEGF were also significantly increased (all P<0.05). The increased expression of MDR1, P-gp and VEGF had the same trend with the expression of HIF-1α. CONCLUSIONS Hypoxia is a direct influencing factor in gastric cancer resistance to 5-FU chemotherapy. Improvement of the local hypoxia microenvironment of gastric cancer may be a new idea for overcoming the resistance to 5-FU in gastric cancer.
Humans ; Fluorouracil/therapeutic use* ; Vascular Endothelial Growth Factor A/metabolism* ; Stomach Neoplasms/drug therapy* ; Drug Resistance, Multiple ; Vascular Endothelial Growth Factors/metabolism* ; Hypoxia ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics* ; Cell Line, Tumor ; Cell Hypoxia ; RNA, Messenger/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Tumor Microenvironment

Objective To investigate the effects of chronic intermittent hypoxia(CIH)and reoxygenation on insulin resistance(IR)and expressions of miR-27a-3p/PPARγ/IRS1/PI3K/AKT in rat skeletal muscle.Methods GEO database was used for screening the differentially expressed miRNAs in CIH,and their target genes were subjected to GO and KEGG enrichment analysis followed by construction of the miRNA-mRNA-pathway regulatory network using Cytoscape.In the animal experiment,48 male SD rats were randomly divided into normoxia group and CIH group(8 weeks of CIH followed by 4 weeks of normoxic recovery).Blood and skeletal muscle samples were collected at baseline,8 weeks,and 12 weeks to evaluate the changes in fasting blood glucose(FBG)and fasting insulin(FINS)levels and muscular pathology.RT-qPCR and Western blotting were used to detect the changes in the expressions of miR-27a-3p,PPARγ,GLUT4,IRS1,p-IRS1,PI3K,p-AKT and AKT in the muscular tissues.Results No muscular miRNA datasets for CIH were available in GEO database,from which only a kidney-related dataset(GSE202480)was obtained,based on which a total of 165 differentially expressed miRNAs were identified.GO/KEGG analysis suggested that these miRNAs were involved in muscular regulation and insulin signaling.The miRNA-mRNA-pathway network highlighted miR-27a-3p as a crucial regulator in the PPAR and PI3K/AKT pathway.In the animal experiment,the rats subjected to CIH for 8 weeks showed significantly increased FBG,FINS,HOMA-IR,and PPARγ levels,loose muscle fiber arrangement,decreased cross-sectional area of the muscle fibers,and lowered expressions of miR-27a-3p,p-IRS1/IRS1,PI3K,and p-AKT/AKT in the skeletal muscles.Conclusion CIH increases IR,causes skeletal muscle pathology,downregulates miR-27a-3p expression,upregulates PPARγ expression,and inhibits IRS1/PI3K/AKT insulin signaling in the skeletal muscles of rats,and these changes can be reversed by reoxygenation.MiR-27a-3p may participate in CIH-induced IR by modulating the PPAR γ/IRS1/PI3K/AKT signaling pathway.

Objective To investigate the effects of chronic intermittent hypoxia(CIH)and reoxygenation on insulin resistance(IR)and expressions of miR-27a-3p/PPARγ/IRS1/PI3K/AKT in rat skeletal muscle.Methods GEO database was used for screening the differentially expressed miRNAs in CIH,and their target genes were subjected to GO and KEGG enrichment analysis followed by construction of the miRNA-mRNA-pathway regulatory network using Cytoscape.In the animal experiment,48 male SD rats were randomly divided into normoxia group and CIH group(8 weeks of CIH followed by 4 weeks of normoxic recovery).Blood and skeletal muscle samples were collected at baseline,8 weeks,and 12 weeks to evaluate the changes in fasting blood glucose(FBG)and fasting insulin(FINS)levels and muscular pathology.RT-qPCR and Western blotting were used to detect the changes in the expressions of miR-27a-3p,PPARγ,GLUT4,IRS1,p-IRS1,PI3K,p-AKT and AKT in the muscular tissues.Results No muscular miRNA datasets for CIH were available in GEO database,from which only a kidney-related dataset(GSE202480)was obtained,based on which a total of 165 differentially expressed miRNAs were identified.GO/KEGG analysis suggested that these miRNAs were involved in muscular regulation and insulin signaling.The miRNA-mRNA-pathway network highlighted miR-27a-3p as a crucial regulator in the PPAR and PI3K/AKT pathway.In the animal experiment,the rats subjected to CIH for 8 weeks showed significantly increased FBG,FINS,HOMA-IR,and PPARγ levels,loose muscle fiber arrangement,decreased cross-sectional area of the muscle fibers,and lowered expressions of miR-27a-3p,p-IRS1/IRS1,PI3K,and p-AKT/AKT in the skeletal muscles.Conclusion CIH increases IR,causes skeletal muscle pathology,downregulates miR-27a-3p expression,upregulates PPARγ expression,and inhibits IRS1/PI3K/AKT insulin signaling in the skeletal muscles of rats,and these changes can be reversed by reoxygenation.MiR-27a-3p may participate in CIH-induced IR by modulating the PPAR γ/IRS1/PI3K/AKT signaling pathway.

Objective : To investigate the role of endoplasmic reticulum stress in hepatic insulin resistance induced by intermittent hypoxia in rats． Methods : Twenty-four SD rats were randomly divided into control group ( NC group) and intermittent hypoxia group ( CIH group) ．The NC group was placed in a normoxia environment for 12 weeks，and the CIH group was given intermittent hypoxia for 8 weeks，and then returned to normoxia until the 12th week．In both groups，fasting blood glucose (FBG) ，fasting insulin (FINS) ，and liver inositol-requiring enzyme- 1 α(IRE1 α) ，X-box binding protein 1s(XBP1s) ，forkhead box transcription factor O1 (FoxO1) ，activating transcription factor-6(ATF6) ，cAMP-response element binding protein( CREB) ，CREB-regulated transcription coacti- vator-2( CRTC2) ，double-stranded RNA-dependent protein kinase-like ER kinase ( PERK) ，eukaryotic initiation factor 2 α(eIF2 α) ，protein kinase B ( AKT) ，phosphoenolpyruvate carboxykinase ( PEPCK) ，glucose-6-phosphat- ase( G6Pase) mRNA were measured at baseline，week 8，and week 12 . Results : There was no significant differ- ence in each observation index between the two groups at baseline ; at 8 weeks，the levels of FBG，FINS and the mRNA levels of IRE1α , XBP1s，ATF6，PERK，eIF2 α , PEPCK and G6Pase in the CIH group were higher than those in the NC group (P＜0. 05) ，while the mRNA levels of CREB，CRTC2 and AKT were lower than those in the NC group (P＜0. 05) ; at 12 weeks，there was no significant difference in each observation index between the two groups．Pearson correlation analysis showed(8th week of intermittent hypoxia group) : homeostasis model as- sessment-insulin resistance(HOMA-IR) was positively correlated with FoxO1，CREB，CRTC2 and PERK，eIF2 α mRNA levels (r = 0. 172，0. 595，0. 183，0. 702，0. 608 ; P＜0. 05) while it was negatively correlated with IRE1α , XBP1s，ATF6，AKT mRNA levels (r = －0. 422 ，－0. 327 ，－0. 309 ，－0. 399 ; P＜0. 05) ． Conclusion Intermittent hypoxia can lead to insulin resistance，and endoplasmic reticulum stress may mediate this effect.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.