Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

A young female patient with acne and elevated testosterone level underwent plasma steroid hormones testing and found a significant increase in aldosterone. We excluded testing interference and verified the absence of hypertension, hypokalemia, and adrenal occupancy, as well as primary and secondary hyperaldosteronism. During follow-up, a temporal correlation was found between aldosterone levels and the use of drospirenone and ethinylestradiol tablets. It was observed that the combination of drospirenone and ethinylestradiol could lead to the increase of aldosterone level and the concentration ratio of aldosterone to direct renin through different mechanisms. Drospirenone exerts an antagonistic effect on mineralocorticoid receptor to prevent the development of hypertension or hypokalemia. In clinical practice, it is necessary to pay attention to the effect of this drug on screening markers for primary aldosteronism. In the laboratory examination, when female patients with no symptoms of hypertension and hypokalemia but with elevated aldosterone levels are encountered, it can be verified whether they have a history of use of compound estrogen-progestin such as drospirenone and ethinylestradiol tablets, and appropriate tips are provided in the report.

Objective:To establish and validate an LC-MS/MS method for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in cerebrospinal fluid. Additionally, the consistency between this method and three mainstream detection methods was evaluated.Methods:This study involved method establishment, validation, and consistency evaluation. The N15 labeled β-amyloid protein was used as the internal standard. Extraction was performed using Waters MCX 96-wells solid phase extraction plate, and the eluent was collected to QuanRecovery MaxPeak 700 μl plate. At the positive ion mode, the multi-reaction ion monitoring mode based on electric spray ionization is chosen for the determination of CSF Aβ 1-42, Aβ 1-40, and Aβ 1-38. Referring to the CLSI C62-A and EP-15A3 guidelines, the method is evaluated and verified, including quantitation of limit (LOQ), linearity, recovery, precision, and accuracy. In addition, a total of 57 clinical residual CSF samples were collected and the concentrations of Aβ 1-42 and Aβ 1-40 were determined based on manual INNOTEST ELISA assay and Lumipulse G and Roche Elecsys fully automated biochemical analyzers. The comparison analysis and deviation evaluation were conducted by passing-bablok and Bland Altman methods.Results:The analysis time of this method is 8 min, and the LOQ of Aβ 1-42, Aβ1-40 and Aβ1-38 is 0.1 ng/ml, 0.5 ng/ml, and 0.1 ng/ml, respectively, and the linear range can meet the needs of clinical detection. Respectively, the recovery is 86.2%-93.8%, 100.9%-103.9% and 103.3%-107.1%; the total imprecision is 4.7%-7.4%, 3.5%-4.6% and 5.2%-10.9%. The measured values of Aβ 1-42 certified reference materials are all within the allowable uncertainty requirements. Moreover, the carryover rate of three analytes was all≤0.11%. In addition, the correlations of Aβ 1-42 and Aβ1-40 in CSF between this LC-MS/MS method and the INNOTEST ELISA method, Lumipulse G and Roche Elecsys fully automated biochemical analyzers were all deemed good, with correlation coefficient (r) ranging from 0.920 to 0.970. However, the measured values between the four methods were remarkably different.Conclusion:We established and validated a robust method based on LC-MS/MS technology for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in CSF. The method is accurate, simple, and suitable for clinical measurements. However, despite good correlations, there were substantial differences in the measurement results of Aβ 1-42 and Aβ 1-40 among different analytical platforms, indicating the need for further promotion of harmonization and standardization processes for AD classic biomarkers.

Objective To investigate and analyze the level of homocysteine(Hcy)in Tibet and to analyze the differences of Hcy level in different altitude regions,genders and ages,and thus to provide the prevalence profile of hyperhomocysteine and the differences in relevant tests between HHcy(hyperhomocysteinemia)and non-HHcy pop-ulations.Methods Totally 1 615(male n＝585)subjects were selected from Ngari,Lhasa,Shigatse and Nyingchi plat-eau areas of Tibet by stratified cluster sampling.Serum Hcy level was analyzed and the difference of Hcy level in pop-ulations located at different altitude plateau areas,gender groups were found.The prevalence of hyperhomocysteine and related test were analyzed.Kruskal Wallis test was used to compare Hcy levels in different altitudes,genders and age groups,and Pearson Chi-square test was used to compare HHcy prevalence.Variance analysis was used for the differences of different test indicators between non-HHcy and HHcy populations.Results The level of Hcy in differ-ent regions and different genders were statistically significant,which was higher in males than that in females,and higher in Lhasa and Shigatse than in Nyingchi and Ngari.There was difference in serum HHcy prevalence among dif-ferent genders,regions and age groups.Males showed a higher level than females,people from Lhasa and Shigatse showed a higher level than those from Nyingchi and Ngari.Conclusions The incidence of hyperhomocysteinemia in Tibet is statistically significant in different areas,different genders and different age groups.So this study provides a scientific basis for the rational use of Hcy as an indicator in clinical practice of prevention and treatment of related diseases in plateau areas.

Objective:To investigate the clinical efficacy of pancreaticoduodenectomy with TRIANGLE operation in the treatment of pancreatic head cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 51 patients with pancreatic head cancer who were admitted to the Sichuan Provincial People′s Hospital, Affiliated Hospital of School of Medicine of University of Electronic Science and Technology of China from January 2017 to July 2018 were collected. There were 33 males and 18 females, aged from 42 to 74 years, with a median age of 56 years. Of the 51 patients, 24 cases undergoing standard pancreaticoduodenectomy, in which No.12, 13 and 17 lymph nodes were dissected, combined with transcatheter arterial infusion chemo-therapy (TAI) were allocated into the standard group, and 27 cases undergoing pancreaticoduo-denectomy with TRIANGLE operation, in which No.7, 8, 9, 12, 13, 16, 17 lymph nodes were dissected, combined with TAI were allocated into the TRIANGLE group, respectively. Observation indicators: (1) intraoperative conditions of the two groups; (2) postoperative conditions of the two groups; (3) follow-up and survival. Follow-up was conducted using outpatient examination and telephone interview once three months to detect tumor recurrence and metastasis and survival of patients up to July 2021 or the death of patient. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the chi-square test or the Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Kaplan‐Meier method was used to calculate the survival rate and median survival time and draw survival curve. Log‐Rank test was used for survival analysis. Results:(1) Comparison of intraoperative conditions between the two groups. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion were (501±61)minutes, (563±278)mL, 4 in the standard group, versus (556±46)minutes, (489±234)mL, 6 in the TRIANGLE group, respectively. There was a significant difference in the operation time between the two groups ( t=3.62, P<0.05) but there was no significant difference in the volume of intraoperative blood loss or cases with intraoperative blood transfusion between the two groups ( t=1.03, χ2=0.25, P>0.05). (2) Comparison of postoperative conditions between the two groups. Of the 51 patients, 30 had 50 times of postoperative complications, including 18 times of grade Ⅰ complications of Clavien-Dindo classification, 29 times of grade Ⅱ complications of Clavien-Dindo classification, 2 times of grade Ⅲa complications of Clavien-Dindo classification, 1 time of grade Ⅲb complications of Clavien-Dindo classification, respectively. Cases with postoperative complications, cases with delayed gastric emptying, cases without or with pancreatic fistula as class A or class B, cases with biliary fistula, cases with bleeding, cases with diarrhea were 15, 4, 13, 7, 4, 4, 2, 2 in the standard group, versus 15, 6, 14, 10, 3, 4, 1, 3 in the TRIANGLE group, respectively. There was no significant difference in cases with postoperative complications, cases with delayed gastric emptying, cases with pancreatic fistula between the two groups ( χ2=0.16, 0.02, Z=-0.04, P>0.05) and there was no significant difference in cases with biliary fistula, cases with bleeding, cases with diarrhea between the two groups ( P>0.05). Cases with complications as Clavien-Dindo grade Ⅰ, grade Ⅱ, grade Ⅲ were 10, 11, 2 in the standard group, versus 8, 18, 1 in the TRIANGLE group, showing no significant difference between the two groups ( Z=-0.67, P>0.05). The duration of postoperative hospital stay was (23±8)days in both of the standard group and the TRIANGLE group, showing no significant difference between the two groups ( t=0.31, P>0.05). (3) Follow-up and survival. All the 51 patients were followed-up for 6 to 54 months, with a median follow-up time of 17 months. The postoperative 1-year overall survival rate was 75.0% and 81.5% in the standard group and the TRIANGLE group, respectively. The postoperative 3-year overall survival rate was 12.5% and 22.2% in the standard group and the TRIANGLE group, respectively. The median postoperative survival time was 15.00 months (95% confidence interval as 12.63 to 17.37 months) and 21.00 months (95% confidence interval as 15.91 to 19.62 months) in the standard group and the TRIANGLE group, respectively. There was a significant difference in survival of patients between the two groups ( χ2=4.30, P<0.05). Cases with tumor recurrence during post-operative 1 year and 3 year were 9 and 20 in the standard group, versus 6 and 15 in the TRIANGLE group, respectively. There was no significant difference in cases with tumor recurrence during postoperative 1 year between the two groups ( P>0.05) and there was a significant difference in cases with tumor recurrence during postoperative 3 year between the two groups ( P<0.05). Conclusion:Compared with standard pancreaticoduodenectomy, pancreaticoduodenectomy with TRIANGLE operation can prolong the median survival time of patients with pancreatic head cancer without increasing surgical related complications.

Objective:To evaluate the performance of magnetic beads extraction method (MGE) for the measurement of catecholamine metabolites by liquid chromatography tandem mass spectrometry.Methods:This is a methodological evaluation study. The linearity, limit of quantitation, recovery, precision, and matrix effect of catecholamine metabolites 3-methoxyepinephrine (MN), 3-methoxynorepinephrine (NMN) and 3-methoxytyramine (3-MT) extracted by MGE method were evaluated according to CLSI C62-A. Consensus of method development and validation of liquid chromatography-tandem mass spectrometry in clinical laboratories and other guidelines, 132 clinical residual plasma samples were collected and extracted by automated MGE and traditional solid phase extraction (SPE) method to compare the harmonization of the two extraction methods.Results:The linearity of MN, NMN and 3-MT extracted by automated MGE was>0.99, and the LOQ for MN, NMN and 3-MT were 0.033 5 nmol/L, 0.054 7 nmol/L and 0.011 0 nmol/L, respectively. The repeatability of MN, NMN and 3-MT were 1.3%-5.1%, 2.2%-5.6% and 1.7%-7.1%, respectively. The total imprecision in the laboratory were 1.5%-8.2%, 2.2%-7.7%, 2.1%-11.2%. Although the absolute recovery is low, the average relative recoveries of MN, NMN and 3-MT were 91.5%-108.5%, 92.0%-108.6%, and 89.3%-104.1%, respectively, and the percentage deviation from the expected concentration was within 15%. After isotope internal standard correction, the relative matrix effect is close to 100%, which can compensate for the potential matrix effect. The results of MGE and SPE of MN, NMN and 3-MT showeda good correlation (correlation coefficient r>0.99). The average relative deviations of MN, NMN and 3-MT were 0.2%, -1.4% and 1.0%, respectively. Conclusion:The automatic MGE method hasa good performance in extracting catecholamine metabolites, and is expected to be used in high-throughput analysis of samples in clinical in the future.

Objective:To explore the prognostic value of survival after veno-arterial ECMO (SAVE) score combined with 24-h lactate on the machine in patients with extracorporeal cardiopulmonary resuscitation (ECPR).Methods:Totally 59 patients treated with ECPR in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University from April 2017 to June 2021 were retrospectively analyzed. According to the 28-day prognosis, the patients were divided into the death group ( n=36) and the survival group ( n=23). The differences in baseline data were analyzed, and multivariate logistic regression was performed to identify the influencing factors of 28-day mortality in patients with ECPR. The receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of SAVE score, 24-h lactate and their combined detection for predicting 28-day mortality risk in patients with ECPR. Results:The 28-day survival rate of patients with ECPR was 39% (23/59). SAVE score of the death group was significantly lower than that of the survival group (-11.67±4.60 vs. -2.43±4.77, P<0.001), and the 24-h lactate in the death group was significantly higher than that in the survival group [5.94 (3.37, 12.40) mmol/L vs. 1.65 (1.07, 3.15) mmol/L, P<0.001]. Multivariate logistic regression analysis showed that SAVE score ( OR=0.703, 95% CI: 0.566-0.873, P=0.001) and 24-h lactate ( OR=1.608, 95% CI: 1.025-2.523, P=0.039) were independent influencing factors of 28-day mortality in ECPR patients. ROC curve analysis showed that the best cut-off value of SAVE score was -6, the sensitivity was 78.30% and specificity was 91.70%. The best cutoff value of 24-h lactate was 4.7 mmol/L, the sensitivity was 63.90% and specificity was 100.00%. The sensitivity and specificity of the combined detection of SAVE score and 24-h lactate were 82.60% and 100.00%, respectively. The area under the curve (AUC) of SAVE score combined with 24-h lactate for predicting the 28-day mortality risk in patients with ECPR was larger than that of SAVE score and 24-h lactate alone (0.952 vs. 0.917; 0.952 vs. 0.847). Conclusions:Lower SAVE score and higher 24-h lactate are independently risk factors of 28-day mortality in patients with ECPR, and SAVE score combined with 24-h lactate on the machine has a good predictive value for the prognosis of patients with ECPR.

Chest trauma is one of the most common injuries. Venous thromboembolism (VTE) as a common complication of chest trauma seriously affects the quality of patients′ life and even leads to death. Although there are some consensus and guidelines on the prevention and treatment of VTE at home and abroad, the current literatures lack specificity considering the diagnosis, treatment and prevention of VTE in patients with chest trauma have their own characteristics, especially for those with blunt trauma. Accordingly, China Chest Injury Research Society and editorial board of Chinese Journal of Traumatology organized relevant domestic experts to jointly formulate the Chinese expert consensus on the diagnosis, treatment and prevention of chest trauma venous thromboembolism associated with chest trauma (2022 version). This consensus provides expert recommendations of different levels as academic guidance in terms of the characteristics, clinical manifestations, risk assessment, diagnosis, treatment, and prevention of chest trauma-related VTE, so as to offer a reference for clinical application.

Background: Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China. Methods: After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test. Results: The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71–4.92 mIU/L, 12.2–20.1 pmol/L, 3.9–6.0 pmol/L, 65.6–135.1 nmol/L, and 1.2–2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens. Conclusions Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.

Extrachromosomal DNA (ecDNA) is a small segment of circular DNA located outside the chromosome, which has the function of self-replication. Recently, amplification of oncogenes on ecDNA has been proved to be a common phenomenon in tumor cells, and has some characteristics worth studying, such as correlation with patients' poor prognosis. Multiple chromosomal events are involved in the formation of ecDNA, and its amplification can directly increase the number of DNA copies of extra-chromosomal oncogenes and accelerate the generation and development of tumors. Moreover, the segregation pattern of unequal transmission of parental ecDNA cells to offspring not only increases tumor heterogeneity, but also enhances tumor adaptation to environment and response to therapy. This article reviews the current status and potential significance of ecDNA in tumor cells.
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