Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P＞0.05).The highest thrombotic rate was 26.09％(12/46)in JAK2 group,then 12.5％(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78％),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P＜0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)％,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)％in triple-negative group(P＜0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P＜0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P＜0.05,P＜0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P＜0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.

Objective:To analyze the genes related to platelet activation in essential thrombocythemia (ET)based on transcriptome sequencing technology (RNA-seq ),and to explore the potential targets related to ET thrombosis. Methods:Blood samples from ET patients and healthy individuals were collected for RNA-seq,and differentially expressed lncRNAs,miRNAs,and mRNAs were selected to construct a lncRNA-miRNA-mRNA regulatory network. Differential mRNAs in the regulatory network were enriched and analyzed using Gene Ontology (GO ) and Kyoto Encyclopedia of Genes and Genomes (KEGG).The real-time PCR method was applied to validate differential mRNAs on crucial signaling pathways.Results:A total of 32 lncRNAs (3 up-regulated,29 down-regulated),16 miRNAs (8 up-regulated,8 down-regulated),and 35 mRNAs (27 up-regulated,8 down-regulated)were identified as differentially expressed.Among them,5 lncRNAs,12 miRNAs,and 19 mRNAs constituted the regulatory network.KEGG enrichment analysis showed that the differential mRNAs were related to the platelet activation signaling pathway,and there were 6 differential mRNAs related to platelet activation,namely F2R,ITGA2B,ITGB1,ITGB3,PTGS1,and GP1 BB,which were all up-regulated in their expression.RT-PCR results showed that the expression of five mRNAs including F2R,ITGA2B,ITGB1,ITGB3,and GP1BB were upregulated in ET patients compared with healthy subjects,and consistent with RNA-seq results,while PTGS1 expression was not significantly different.Conclusion:Differential mRNAs in ET patients are related to the platelet activation pathway,and F2R,ITGA2B,ITGB1,ITGB3,and GP1BB mRNAs may serve as novel targets associated with platelet activation in ET.

The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α₂β₂ and fetal α₂ε₂ hemoglobins were identified, while erythrocytes of plateau zokors only had adult α₂β₂ hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.
Animals ; Altitude ; Amino Acids ; Hemoglobins ; Hypoxia ; Lagomorpha

OBJECTIVE: To understand the biological characteristics of polycythemia vera (PV) patients with myeloid fibroplasia, and further analyze the risk factors affecting myeloid fibroplasia in PV patients, so as to provide ideas for predicting the occurrence of myeloid fibroplasia in PV patients. METHODS: Forty patients with PV in the Department of Hematology, Xiyuan Hospital of China Academy of Chinese Medical Sciences were collected and divided into two groups, with (hyperplasia group) and without (Non-proliferative group) hyperplasia of bone marrow fibers. The differences of basic clinical characteristics, blood routine, biochemistry, bone marrow cells, coagulation function and other indicators between the two groups were compared, and the independent risk factors affecting the proliferation of bone marrow fibrous tissue in PV patients were further analyzed by multivariate regression. RESULTS: Compared with Non-proliferative group, the JAK2 mutation rate (95% vs 70%，P=0.037), eosinophilic cell count (0.19 vs 0.11, P=0.047) and eosinophilic percentage (1.84 vs 1.27, P=0.001) in PV patients with hyperplasia were significantly increased, triglycerides (1.55 vs 1.91, P=0.038) and low-density lipoprotein (1.50 vs 3.08, P=0.000) were significantly reduced, bone marrow hematopoietic volume (0.85 vs 0.6, P=0.001), granulocyte/erythrocyte ratio (3.40 vs 1.89, P=0.033), lymphocyte/erythrocyte ratio (0.60 vs 0.42, P=0.033), and granulocyte+lymphocyte/erythrocyte ratio (3.72 vs 2.37, P=0.026) were significantly increased, thrombin time (18.84 vs 18.12, P=0.043) was significantly prolonged. Multivariate regression analysis results showed that peripheral blood eosinophil ≥2% and low-density lipoprotein ≤2 mmol/L were independent risk factors for bone marrow fibrous tissue hyperplasia in PV patients (P<0.05). CONCLUSION Increased proportion of peripheral blood eosinophils and decreased low density lipoprotein are risk factors for bone marrow fibrous tissue hyperplasia in PV patients.
Humans ; Bone Marrow/pathology* ; Polycythemia Vera ; Hyperplasia/pathology* ; Granulocytes/pathology* ; Janus Kinase 2/genetics* ; Risk Factors ; Lipoproteins, LDL ; Polycythemia/pathology*

Objective: This study aimed to identify the risk factors for genitourinary fistulas and delayed fistula recognition after radical hysterectomy for cervical cancer. Methods: This study was a retrospective analysis of data collected in the Major Surgical complications of Cervical Cancer in China (MSCCCC) database from 2004–2016. Data on sociodemographic characteristics, clinical characteristics, and hospital characteristics were extracted. Differences in the odds of genitourinary fistula development were investigated with multivariate logistic regression analyses, and differences in the time to recognition of genitourinary fistula were assessed by Kruskal–Wallis test. Results: In this study, 23,404 patients met the inclusion criteria. Surgery in a cancer center, a women’s and children’s hospital, a facility in a first-tier city, or southwest region, stage IIA, type C1 hysterectomy, laparoscopic surgery and ureteral injury were associated with a higher risk of ureterovaginal fistula (UVF) (p<0.050). Surgery in southwest region, bladder injury and laparoscopic surgery were associated with greater odds of vesicovaginal fistula (VVF) (p<0.050). Surgery at cancer centers and high-volume hospitals was associated with an increase in the median time to UVF recognition (p=0.016; p=0.005). International Federation of Gynecology and Obstetrics (FIGO) stage IIA1-IIB was associated with delayed recognition of VVF (p=0.040). Conclusion Intraoperative urinary tract injury and surgical approach were associated with differences in the development of UVFs and VVFs. Patients who underwent surgery in cancer centers and high-volume hospitals were more likely to experience delayed recognition of UVF. Patients with FIGO stage IIA1-IIB disease were more likely to experience delayed recognition of VVF.

Calreticulin/genetics* ; DNA Methylation ; Female ; Humans ; Janus Kinase 2/genetics* ; Mutation ; Myeloproliferative Disorders/genetics* ; Polycythemia Vera/genetics*

OBJECTIVE: To analysis the specific protein markers of essential thrombocythemia (ET) based on proteomics technology, to explore and verify the differential protein related to platelet activation. METHODS: Blood samples were obtained from ET patients and healthy people and a certain protein mass spectrometry was detected using label-free quantitative technology. The proteins relative abundance increased or down-regulated by 1.3 times in the disease group compared with the control group, and the protein abundance in the two groups t test P＜0.05 were defined as differential proteins. Bioinformatics analysis of the differential proteins was performed using GO and KEGG. The difference in the average protein abundance between the two groups was analyzed by t test and P＜0.05 was considered statistically significant. Differential proteins were selected for verification by parallel reaction monitoring (PRM) technology. RESULTS: A total of 140 differential proteins were found, of which 72 were up-regulated and 68 were down-regulated. KEGG enrichment showed that the differential protein expression was related to the platelet activation pathway. The differential proteins related to platelet activation were GPV, COL1A2, GP1bα, COL1A1 and GPVI. Among them, the expressions of GPV, GP1bα and GPVI were up-regulated, and the expressions of COL1A2 and COL1A1 were down-regulated. PRM verification of COL1A1, GP1bα, GPVI and GPV was consistent with LFP proteomics testing. CONCLUSION Differential proteins in ET patients are related to platelet activation pathway activation.Differential proteins such as GPV, GPVI, COL1A1 and GP1bα can be used as new targets related to ET platelet activation.
Blood Platelets/metabolism* ; Humans ; Platelet Activation ; Platelet Membrane Glycoproteins/metabolism* ; Technology ; Thrombocythemia, Essential

In the present study, the composition and content of pulmonary surfactant (PS) were analyzed to explore the hypoxia adaptation mechanism in plateau zokors (Myospalax baileyi) and plateau pikas (Ochotona curzoniae). 36 plateau zokors and plateau pikas were trapped alive at the Laji Mountain in Guide County, Qinghai Province (at the altitude of about 3 600 m), and 36 Sprague-Dawley (SD) rats were purchased from the experimental animal center of Lanzhou University (at the altitude of about 1 500 m). All animals were lavaged after laboratory anesthesia, the blood in lung tissues was fully washed out and the lung tissues were then taken out to obtain the bronchoalveolar lavage fluid by bronchoalveolar lavage. The composition and content of phospholipids in the PS of three different kinds of animals were analyzed by using high performance liquid chromatography; the protein composition, content and types in the PS were analyzed by G-250 Coomassie brilliant blue method, polyacrylamide gel electrophoresis (PAGE) and mass spectrometry; the dissolved oxygen in the PS solutions were determined by using dissolved oxygen electrode. The results showed that the total contents of phospholipids in the PS were successively increased among plateau zokors, plateau pikas and SD rats (P < 0.05), while the total content of proteins successively decreased (P < 0.05). There were five phospholipids identified in the PS, including linoleic palmitoylphosphatidylcholine (LPPC), dipalmitoylphosphatidylcholine (DPPC), phosphatidylglyerol (PG), phosphatidylinositol (PI) and phosphatidylserine (PSe), but the relative contents of these phospholipids were different. The relative content of LPPC was successively increased among plateau zokors, plateau pikas and SD rats (P < 0.01). The relative contents of DPPC, PG and PI in the PS of plateau zokors were significantly higher than those of plateau pikas (P < 0.01), while insignificant differences between plateau pikas and SD rats (P > 0.05). The relative content of PSe had no significant differences between plateau zokors and plateau pikas (P > 0.05), but both were significantly higher than that of SD rats (P < 0.01). The serum albumin (SA) was identified in the PS of three kinds of animals, including homologous tetramer protein containing heme, which is composed of hemoglobin β subunit, in plateau zokors and plateau pikas. Immunoglobulin (Ig) heavy chain was found in PS of plateau zokors and SD rats. The content of Ig heavy chain in plateau zokor was significantly higher than that in SD rats (P < 0.01), and the content of protein containing heme was significantly higher than that in plateau pikas (P < 0.05). The amount of dissolved oxygen was successively decreased in the PS among plateau zokors, plateau pikas and SD rats (P < 0.01), but it was significantly higher than that in saline (P < 0.01). These results suggest that the total content of proteins in the PS of plateau zokors and plateau pikas was significantly higher, while the total content of phospholipids was significantly decreased. There were high content of homologous tetramer protein containing heme in the PS of plateau zokors and plateau pikas. The relative content of DPPC, the main component of phospholipids, was significantly increased in plateau zokors. The changes of PS component and content improve the adaptability of the two plateau animals in hypoxia environment.
Altitude ; Animals ; Hypoxia ; Lagomorpha ; Pulmonary Surfactants ; Rats ; Rats, Sprague-Dawley

Aim To investigate the effects of YL- IPA08 on the endogenous metabolites of PTSD model rats by metabolomics methods, and to explore the metabolic pathways and possible mechanisms of YL-IPA08 against PTSD. Methods The rats were randomly divided into control group, PTSD model group, and administration group of PTSD rats induced by forced swimming test, and the treatment group was given YL- IPA08 (2 mg • kg"1) by intragastric gavage for 15 consecutive days. High-performance liquid chromatog- raphy-mass spectrometry (HPLC-MS/MS) technology was used to detect the endogenous differential metabolites and the associated metabolic pathways in rat plasma samples. Targeted quantitative technology was simultaneously applied to detect the concentrations of 18 bile acids in rat plasma. Results Compared with control group, 40 kinds of endogenous metabolites including glutamic acid, proline, valine, arginine, leucine , cholic acid, and creatine showed significant difference, and the concentrations of 11 bile acids significantly increased in plasma of model group as well. Compared with model group, after YL-IPA08 intervention , the above-mentioned potential metabolites ap-peared to return to normal levels. Conclusions Metabolomics analysis reveals that YL-IPA08 has intervention effect on PTSD model rats. The mechanism may be related to the regulation of amino acid metabolism and bile acid metabolism.

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.
Amphetamine-Related Disorders/epidemiology* ; Heroin ; Humans ; Illicit Drugs ; Methamphetamine/adverse effects* ; Substance Abuse Detection