OBJECTIVE: To investigate the whole-genome differential methylation profile of patients with high-altitude polycythemia (HAPC). METHODS: In this study, a total of 20 adult male patients with HAPC were included, including 10 Tibetan and 10 Han patients. The control group consisted of 20 healthy adult males, including 10 Tibetan and 10 Han patients. Peripheral blood was collected from each group for DNA extraction and quality inspection, and DNA libraries were constructed. The differential methylation regions (DMRs) between groups were detected using reduced representation bisulfite sequencing, with enriched regions compared to those of the control group. The differential enrichment regions were selected, and the intersection of the enriched regions was associated with genes. The methylation enrichment regions that differed significantly between groups were filtered based on the number of enriched samples in the enriched regions between the groups. GO, KEGG functional, and pathway analysis were performed on the differentially associated gene sets to reveal significant differences between the patients and control groups at the functional and pathway levels. RESULTS: In comparison with the control group, 17 152 sites with more than 25% difference and 15 558 sites with less than -25% difference were identified in Tibetan patients. The top 5 genes with the largest methylation differences between the two groups were MCCC2, RP3-399L15.3, ZNF621, RP11-394A14.2 and SLC39A10. The top significantly different pathways annotated in the differentially expressed genes pathway was serotonergic synapse. In comparison with the control group, 2 687 CpG sites with a greater than 25% difference and 2 602 CpG sites with a less than -25% difference were identified in Han patients. The top 5 genes with the largest methylation differences between the two groups were NAA25, CORO2B, PDC, ZNF853, and MLLT10. The top significantly different pathways annotated in the differentially expressed genes pathway were glutamatergic synapse, retrograde endocannabinoid signaling, Rap1 signaling pathway and cholinergic synapse. In comparison with the control group, 3 895 CpG sites with a greater than 25% difference and 3 969 CpG sites with a less than -25% difference were identified in HAPC patients. The maximum methylation difference between the two groups could reach 78.1%, while the minimum was -42.6%. The top 5 genes with the largest methylation differences between the two groups were MCCC2, ARSJ, CTNNA3, SLC39A10, and SWAP70. The top significantly different pathways annotated in the differentially expressed genes pathway was signaling pathways regulating pluripotency of stem cells. CONCLUSION The occurrence of HAPC may be related to abnormal changes in DNA methylation, and methylation sites may be helpful for the early diagnosis of HAPC.
Humans ; DNA Methylation ; Altitude ; Polycythemia/genetics* ; Male ; Adult ; CpG Islands

Objective To study the chemical constituents of Fallopia aubertii L.Henry Holub. Methods The chemical constituents of Fallopia aubertii L.Henry Holub. were separated and purified by online two-dimensional preparative liquid chromatography and identified by physical and chemical constants and spectral analysis. The inhibitory activities on xanthine oxidase were determined by ultraviolet spectrophotometry. Results Ten compounds were isolated from the extract of Fallopia aubertii L.Henry Holub, including isotachioside（1）, 3,4,5-trimethoxyphenyl-（6'-O-galloyl）-O-β-D-Glucopyranoside（2）, 1-hydroxy-,4,5-1-O-[6'-O-（4''-carboxy-1'',3'',5'trihydrotrimethoxyphenylxy）-phenyl]-β-D-glucopyranoside（3）, myricetrin（4）, myricetin（5）, rutin（6）, quercetin-3-O-β-D-galactoside（7）, quercetin-3-O-β-D-glucopyranoside（8）, lyciumideA（9）, and N-trans-Feruloyltyramine（10）. The inhibitory activity test results showed that the IC₅₀ of compound 5 was 15.92 μmol/L, and the IC₅₀ of compound 6 was 87.36 μmol/L. Conclusion Compounds 1,2,3,4 and 8 were isolated from Medicago polymorpha for the first time. Compounds 5 and 6 had xanthine oxidase inhibitory activity.

Objective: To analyze the demographic characteristics of patients with red blood cell transfusion reactions, the usage of red blood cell preparations, and the differences in the composition ratio of adverse reactions based on multi-center data from the Haemovigilance Network, in order to reveal the clinical characteristics of red blood cell transfusion and its underlying issues. Methods: Clinical data of patients who experienced transfusion reactions after red blood cell transfusion in the Haemovigilance Network from 2018 to 2023 were collected. The demographic characteristics of patients who experienced transfusion reactions with different types of red blood cell preparations, the utilization of these preparations, and the differences of the composition ratios of transfusion reactions were analyzed. Count data were expressed as numbers (n) or percentages (%), and comparisons between groups were performed using the Chi-square test. Results: Red blood cell transfusion reactions were more common in females (53.56%), with the majority of patients aged 50-69 years (35.54%). The Han polulation accounted for the vast majority of patients (92.77%), and patients in the hematology and obstetrics/gynecology departments had a relatively high proportion of transfusion reactions (13.26% and 14.26%, respectively). Leukocyte-reduced red blood cells and suspended red blood cells were the most common types of transfusion reactions reported among red blood cell preparations. Allergic reactions and non-hemolytic febrile reactions were the most common transfusion reactions, and there were significant differences in the composition ratios of allergic reactions (χ =869.89, P<0.05) and non-hemolytic febrile reactions (χ =812.75, P<0.05) across various types of red blood cell preparations. Conclusion: There are differences in the demographic characteristics and composition ratio of transfusion reactions among different red blood cell preparations. The management of red blood cell transfusion reactions should be tailored to patient characteristics and conditions, and the selection and use of blood products should be optimized to reduce or avoid the occurrence of transfusion reactions, such as considering the use of washed red blood cells for patients with a history of transfusion allergies or those prone to allergies.

Background and purpose:Thyroid cancer is the most common malignant endocrine tumor,particularly prevalent among the Asian population.The overall survival for thyroid cancer patients is relatively high,but there are significant survival differences among patients.Based on long-term hospital-based cancer registry database,this study analyzed the 10-year observed overall survival(OS)rate of thyroid cancer cases and the distribution of causes of death,providing real-world evidences to further survival management of thyroid cancer in China.Methods:A total of 55343 thyroid cancer patients who underwent treatment at Fudan University Shanghai Cancer center from 2005 to 2021 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was October 31,2024.Kaplan-Meier method was applied in evaluating the OS rate,and survival data were described by different subgroups as age group,gender,treatment period,tumor staging and pathological characteristics.The standardized mortality ratio(SMR)and absolute excess risk(AER)were calculated using general Shanghai population as the reference,and the mortality risk was described by gender,age at diagnosis and histological subtype.Results:With a median follow-up time of 63.01 months,the overall 1-,3-,5-and 10-year OS rates of thyroid cancer patients were 99.67%(95%CI:99.62%-99.72%),99.11%(95%CI:99.03%-99.19%),98.48%(95%CI:98.36%-98.60%)and 95.81%(95%CI:95.50%-96.11%),respectively.The 10-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 97.99%(95%CI:97.70%-98.28%),89.80%(95%CI:87.24%-92.37%),77.84%(95%CI:70.76%-84.92%)and 62.95%(95%CI:55.37%-70.54%),respectively.The differences in OS among patients with different age,gender and histological classification were significant.1256(2.27%)deaths occurred,of which 18.63%,50.88%and 7.32%were attributable to thyroid cancer,other cancers and cardiovascular disease(CVD),respectively.Compared with the general population,patients with different subtypes of thyroid cancer had higher all-cause mortality rates,progressively increasing with papillary,follicular,medullary and anaplastic thyroid carcinoma/poorly differentiated carcinoma.Compared with general population,the death risk was 2.24 times higher in papillary thyroid cancer patients(95%CI:2.06-2.44),9.94 times higher in follicular thyroid cancer patients(95%CI:6.79-14.09),12.16 times higher in medullary thyroid cancer patients(95%CI:8.05-17.69),and the highest risk was observed in patients with anaplastic thyroid carcinoma/poorly differentiated carcinoma[SMR=79.67(95%CI:58.38-106.31),AER=766.01/1 000 person-years].Conclusion:The 10-year long survival data and cause of death for thyroid cancer patients with different histological types were reported in China based on a large single institution hospital-based cancer registry database.Staging and histological characteristics were the most important factors directly affected the survival.Early diagnosis and individualized treatment are crucial for improving prognosis.

Background and purpose:Thyroid cancer is the most common malignant endocrine tumor,particularly prevalent among the Asian population.The overall survival for thyroid cancer patients is relatively high,but there are significant survival differences among patients.Based on long-term hospital-based cancer registry database,this study analyzed the 10-year observed overall survival(OS)rate of thyroid cancer cases and the distribution of causes of death,providing real-world evidences to further survival management of thyroid cancer in China.Methods:A total of 55343 thyroid cancer patients who underwent treatment at Fudan University Shanghai Cancer center from 2005 to 2021 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was October 31,2024.Kaplan-Meier method was applied in evaluating the OS rate,and survival data were described by different subgroups as age group,gender,treatment period,tumor staging and pathological characteristics.The standardized mortality ratio(SMR)and absolute excess risk(AER)were calculated using general Shanghai population as the reference,and the mortality risk was described by gender,age at diagnosis and histological subtype.Results:With a median follow-up time of 63.01 months,the overall 1-,3-,5-and 10-year OS rates of thyroid cancer patients were 99.67%(95%CI:99.62%-99.72%),99.11%(95%CI:99.03%-99.19%),98.48%(95%CI:98.36%-98.60%)and 95.81%(95%CI:95.50%-96.11%),respectively.The 10-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 97.99%(95%CI:97.70%-98.28%),89.80%(95%CI:87.24%-92.37%),77.84%(95%CI:70.76%-84.92%)and 62.95%(95%CI:55.37%-70.54%),respectively.The differences in OS among patients with different age,gender and histological classification were significant.1256(2.27%)deaths occurred,of which 18.63%,50.88%and 7.32%were attributable to thyroid cancer,other cancers and cardiovascular disease(CVD),respectively.Compared with the general population,patients with different subtypes of thyroid cancer had higher all-cause mortality rates,progressively increasing with papillary,follicular,medullary and anaplastic thyroid carcinoma/poorly differentiated carcinoma.Compared with general population,the death risk was 2.24 times higher in papillary thyroid cancer patients(95%CI:2.06-2.44),9.94 times higher in follicular thyroid cancer patients(95%CI:6.79-14.09),12.16 times higher in medullary thyroid cancer patients(95%CI:8.05-17.69),and the highest risk was observed in patients with anaplastic thyroid carcinoma/poorly differentiated carcinoma[SMR=79.67(95%CI:58.38-106.31),AER=766.01/1 000 person-years].Conclusion:The 10-year long survival data and cause of death for thyroid cancer patients with different histological types were reported in China based on a large single institution hospital-based cancer registry database.Staging and histological characteristics were the most important factors directly affected the survival.Early diagnosis and individualized treatment are crucial for improving prognosis.

Objective: To explore the drug resistance of Isolated From Blood Culture Escherichia coli (E. coli) in a hospital in Qinghai over the past seven years, to evaluate the ability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze the homologous origin of E. coli, and to establish a protein fingerprint library to match with it, adjuvant clinical experience medication so as to provide the basis for the prevention and control of hospital-acquired infections. Methods: Retrospective analysis of blood cultures sent to hospitals from January 2016 to December 2022. Drug resistance and resistance changes in E. coli.A total of 1 841 E. coli strains were isolated from Qinghai Provincial People's Hospital from January 2016 to December 2022; all strains were identified by MALDI-TOF MS, and the VITEK2.0 drug sensitivity analyzer was applied for drug sensitivity analysis of the strains, and the mass spectrometry homology analysis and self-constructed protein fingerprint library were carried out by MALDI-Biotyper software; the protein fingerprint library was built by using WHONET5.6 software was used to statistically analyze the drug sensitivity results, SPSS23.0 software was used to analyze the relationship between fingerprint typing and drug sensitivity, and the χ² test was used for intergroup comparisons. Results: A total of 1 841 strains of E. coli were detected in 4 582 positive blood culture specimens from January 2016 to December 2022, with a detection rate of 40.17%; the resistance rate of E. coli from blood sources to piperacillin/tazobactam and ceftriaxone was on the rise, and it was slightly decreased to cefepime, amikacin, levofloxacin, and sulfamethoxazole, and there was not much change to the rest of the drugs; After MALDI-Biotyper clustering analysis, the 1841 E. coli strains from Isolated From Blood Culture were classified into two major clusters and five subtypes, of which type Ⅰa1 accounted for about 40%, type Ⅰa2 accounted for about 2.7%, type Ⅰb accounted for about 3.8, type Ⅱa accounted for about 46%, and type Ⅱb accounted for about 7.5%. The detection rate of type Ⅰa1 E. coli was higher in general surgery (50.45%) and emergency surgery (50.92%), and the detection rate of type Ⅰb E. coli was higher in emergency medicine(10.05%)than in other departments. The drug sensitivity results of different subtypes were compared with each other, the resistance rate of type Ⅰa1 E. coli to cefepime was 21.3% higher than that of the remaining four types, and the difference was statistically significant (χ²=37.74,P=0.000); the resistance rate of type Ⅱ E. coli(>60%) to sulfamethoxazole was higher than that of type Ⅰ (<60%) as a whole, and the difference was statistically significant (χ²=15.248,P=0.004); and a preliminary database of homologous protein fingerprints of E. coli has been established E. coli homologous protein fingerprint library and validated. The drug susceptibility results of 1 288 E. coli strains in the validation set were statistically analyzed and compared with those in the training set. There was no significant difference(P>0.05). Conclusion: In recent years, the resistance rate of E. coli isolated from a hospital in Qinghai province to piperacillin/Tazobactam, cefepime, amicacin and other antibiotics has changed greatly. A fingerprint database of E. coli homologous protein was established, and it was found that the drug sensitivity data of E. coli were different among different fingerprint types. According to drug sensitivity, drug use could assist clinical experience and provide evidence for prevention and control of hospital illness.
Humans ; Blood Culture ; Escherichia coli ; Cefepime ; Retrospective Studies ; Drug Resistance ; Sulfamethoxazole ; Piperacillin ; Tazobactam

Humans ; Female ; Tibet ; Kashin-Beck Disease/epidemiology* ; China ; Metabolomics

Objective : To investigate the effects of hypoxia , high glucose single factor and hypoxia high glucose compound factors on the pyroptosis of rat glomerular podocytes . Methods : Rat glomerular podocytes were cultured in vitro and randomly divided into control group , high glucose group , hypoxia group and hypoxia high glucose group , EdU method was used to detect the cell proliferation , transmission electron microscope was used to observe the morphology and size changes of nucleus and mitochondria , and Western blot was used to detect pyroptosis related proteins nucleotide⁃binding oligomerization domain⁃like receptor protein 3(NLRP3) , Cysteinyl aspartate specific proteinase⁃1(Caspase⁃1) , gasdermin( GSDMD) and inflammatory factor pro⁃interleukin⁃1β( Pro⁃IL⁃1β) , interleukin(IL) Ⅳ1β , IL⁃18 . The effect of hypoxia and high glucose on the pyroptosis of rat glomerular podocytes was analyzed . Results : EdU results showed that hypoxia and high glucose inhibited the proliferation ability of rat glomerlar podocytes (P < 0. 05) . The results of transmission electron microscopy suggested that hypoxia and high glucose promoted the occurrence of pyroptosis of rat glomerular podocytes . Western blot showed that hypoxia and high glucose promoted pyroptosis of rat glomerular podocytes , and increased the expression of pyroptosis related proteins NLRP3 , Caspase⁃1 and GSDMD , among which the expression of pyroptosis protein increased most significantly in hypoxia and high glucose group (P < 0. 05) . At the same time , it also increased the expression of pro⁃inflammatory factor Pro⁃IL⁃1β , IL⁃1β and IL⁃18 (P < 0. 05) . Conclusion hypoxia and high glucose can induce pyroptosis of rat glomerular podocytes , one of the mechanisms may be through affecting NLRP3 ⁃Caspase⁃1 ⁃GSDMD and its down⁃ stream inflammatory factors .