Although alterations in lipid metabolism were associated with neurodegenerative diseases, the association between lipids in cord blood and infants’ neurodevelopment remains poorly characterized. Neonates’ cord blood lipids were detected, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), Non-high-density lipoprotein cholesterol (Non-HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). At one year of age, neurodevelopmental performance was assessed among infants in a birth cohort from Yunnan, China. Multivariable linear and logistic regression analyses were conducted to evaluate whether lipid concentrations measured in cord blood were related to neurodevelopmental performance during infancy. This study included 315 infants. The prevalence of neurodevelopmental delay was 13.7

ObjectiveTo explore the correlation between MTHFR C677T gene polymorphism and hypertension, hyperhomocysteinemia(Hcy), and hyperlipidemia in the Tibetan population of Tibet.MethodsUsing a cluster sampling method, participants from high-altitude regions including Ngari Prefecture, Lhasa City, and Nyingchi City in Tibet were enrolled. Differences in MTHFR C677T genotype distribution among individuals with hypertension, HHcy, and hyperlipidemia were analyzed, and multivariate logistic regression was performed to assess the association between these conditions and the TT genotype.ResultsA total of 574 eligible subjects were included, with a mean age of 40.64±12.67 years. Males accounted for 46.7%(268/574) and females 53.3%(306/574). Regional distribution was 34.8%(200/574) from Nyingchi City, 33.1%(190/574) from Lhasa City, and 32.1%(184/574) from Ngari Prefecture. Mean systolic and diastolic blood pressures were 117.89±18.98 mm Hg and 79.74±14.88 mm Hg, respectively. The frequency of the TT genotype was significantly higher in the hypertension group than in the non-hypertension group(12.32% vs. 5.96%, P=0.013), and higher in the hyperhomocysteinemia group than in the non-hyperhomocysteinemia group(9.41% vs. 3.31%, P=0.010). No significant difference in TT genotype frequency was observed between the hyperlipidemia and non-hyperlipidemia groups(P > 0.05). Compared with the CC/CT genotypes, the TT genotype was associated with hypertension(OR=2.855, 95% CI: 1.393-5.990) and hyperhomocysteinemia(OR=4.788, 95% CI: 1.617-14.180), but not with hyperlipidemia.ConclusionsThe MTHFR C677T TT genotype is significantly associated with hypertension and hyperhomocysteinemia in the Tibetan population, suggesting that this polymorphism may be a genetic risk factor for these diseases in high-altitude regions.

Background and Aims This study explored the link between the Chinese visceral adiposity index (CVAI) and hypertension/prehypertension in middle-aged and elderly Chinese adults, comparing its predictive accuracy with other adiposity indices. Methods and Results Data from Nanjing's 2017-2018 chronic disease surveillance was analyzed for individuals over 45, using a generalized linear mixed model and ROC curves to assess the impact of CVAI and other indices. After adjusting for selected covariates, the results showed that, with the lowest group as the reference, the ORs of risk of hypertension were 1.536, 2.088 and 3.391 for CVAI; 1.338, 1.845 and 2.489 for the lipid accumulation product index (LAP); 1.277, 1.465 and 1.935 for the triglyceride glucose index (TyG); 1.396, 2.287, and 3.617 for body mass index (BMI); 1.961 for waist circumference (WC); 1.915 for the waist-to-height ratio (WHtR); and 1.299 for the waist-to-hip ratio (WHR), respectively. Similar results were also found in the impact of various obesity variables on prehypertension, respectively. ROC analyses indicated CVAI as the strongest predictor of hypertension and prehypertension compared to other adiposity indices. Conclusions CVAI is significantly associated with hypertension and prehypertension, surpassing conventional indices in predictive power for these conditions in the studied demographic.

e16116 Background: Neoajuvant chemoradiation is the standard treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors (ICIs) have shown a survival benefit for advanced ESCC and showed promising efficacy in neoadjuvant treatment for several cancers. This study aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab followed by surgery for resectable ESCC. Methods: This is a single-arm, phase Ib study. Eligibility criteria include histologically confirmed ESCC and clinical T3-4aN0M0 or T2-4aN+M0 (AJCC/UICC 8th). Patients received neoadjuvant radiotherapy (41.4Gy in 23 fractions) with concurrent chemotherapy (paclitaxel, 50 mg/m2, carboplatin area under the curve of 2mg/mL/min, QW*5). Then followed by two cycles of tislelizumab (200mg, Q3W). The primary endpoint was the pathological complete response (pCR) rate and safety. Results: From Feb 2022 to Jan 2024, 35 patients had been enrolled, of whom the median age was (65.5 (95%CI, 59-67), including 31 (88.6%) males. 12 patients were still undergoing chemoradiotherapy and 2 patients did not receive immunotherapy due to pneumonia and myocarditis after chemoradiotherapy. 16 patients completed all 2 cycles tislelizumab preoperatively and 5 patients completed 1 cycle tislelizumab because of AEs. Two patients refused surgery after achieved complete clinical response under radiology and were still alive, the other 19 patients underwent resection. The R0 resection rate was 94.7% (18/19). The pCR rate was 63.2% (12/19) and the MPR rate was 78.9% (15/19). During neoadjuvant treatment, 8 patients had a grade 3 or worse adverse event including leukopenia (33.3%, 7/21, Grade 3), esophagitis (4.8%, 1/21, Grade 3) and anemia (4.8%, 1/20, Grade 4). One patient developed grade 4 postoperative complication (5.3%, 1/19, pneumonia) and died within 90 days of surgery due to COVID-19. Grade 1-2 postoperative complications occurred in 21.1% (4/19) patients, including anastomotic fistula (21.1%, 4/19), chylothorax (5.3%, 1/19) and pneumonia (10.5%, 2/19). Conclusions: Preliminary results showed that neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab showed promising outcomes and well tolerated for resectable ESCC patients. Further larger prospective studies are needed to confirm such findings.

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.

PurposeNewly diagnosed T1-2N0 esophageal cancer (EC) is generally deemed as early local disease, with distant metastases (DM) easily overlooked. This retrospective study aimed to describe the metastatic patterns, identify risk factors and established a risk prediction model for DM in T1-2N0 EC patients. MethodsA total of 4623 T1-2N0 EC patients were identified in the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2018. Multivariable logistic regression was used to identify risk factors for DM. A nomogram was developed for presentation of the final model. ResultsOf 4623 T1-2N0 patients, 4062 (87.9%) had M0 disease and 561 (12.1%) had M1 disease. The most common metastatic site was liver (n = 156, 47.3%), followed by lung (n = 89, 27.0%), bone (n = 70, 21.2%) and brain (n = 15, 4.5%). Variables independently associated with DM included age at diagnosis, gender, tumor grade, primary site, tumor size and T stage. A nomogram based on the variables had a good predictive accuracy (area under the curve: 0.750). Independent risk factors for bone metastases (BoM), brain metastases (BrM), liver metastases (LiM) and lung metastases (LuM) were identified, respectively. ConclusionsWe identified independent predictive factors for DM, as well as for BoM, BrM, LiM and LuM. Above all, a practical and convenient nomogram with a great accuracy to predict DM probability for T1-2N0 EC patients was established.

Pregnant women have been ubiquitously exposed to pyrethroid pesticides. Previous studies, mainly based on third trimester measurements of maternal urinary pyrethroid metabolites, have reported inconsistent findings in the effects of prenatal pyrethroid exposure on children's neurodevelopmental outcomes. The purpose of this study was to clarify if pyrethroid exposure during the entire three trimesters of pregnancy may be associated with deleterious effects on infant neurodevelopmental status, particularly at a high dosage of exposure. We measured maternal urinary concentrations of pyrethroid metabolites in all trimesters of pregnancy and assessed children's neurodevelopment at one year of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multiple linear regression models were used to estimate the effects of metabolites (3-PBA, 4 F-3-PBA, cis-DBCA) in each trimester on BSID-III composite scores. Logistic regression analyses were applied to predict developmental delay vs non-delayed status (cut-off composite score of below 80 for developmental delay) based on the maternal levels of pyrethroid metabolites. In the first, second and third trimesters of pregnancy, the detection rates of pyrethroid metabolites were 94.7%, 90.7%, and 89.0%; the 50th percentiles of exposure level were 0.24 g/g, 0.24 ug/g and 0.21 ug/g for 3-PBA, -0.14 g/g, -0.17 ug/g and 0.15 ug/g for 4 F-3PBA, 0.21 g/g, 0.25 ug/g and 0.19 ug/g for cis-DBCA respectively. In the second trimester, 3-PBA was inversely associated with Cognition and Language scores [beta = -3.34 (95% CI = -6.11, -0.57) and beta = 2.90 (95% CI = -5.20, -0.61), respectively], and significantly increased the risk of Cognition and Language developmental delay [OR= 1.64 (95% CI = 1.03, 2.62) and OR = 1.52 (95% CI = 1.06, 2.19), respectively]; cis-DBCA was inversely associated with Adaptive Behavior scores [13 = 0.73 (95% CI = 1.27, 0.19)], and significantly increased the risk of Adaptive Behavior developmental delay [OR= 1.11 (95% CI = 1.02, 1.21)]. When the maternal levels of pyrethroid metabolites were stratified into the regression models according to the 90th percentile of exposure, in the first trimester, Cognition and Motor scores were inversely associated with higher cis-DBCA [beta = -7.19 (95% CI = -12.97, -1.41) and beta = -8.20 (95% CI = -13.35, -3.05), respectively], Language scores were inversely associated with higher 3-PBA [beta = 6.01 (95% CI = 10.96, 1.06)]; in the second trimester, Cognition scores were inversely associated with higher cis-DBCA [beta = -6.64 (95% CI = -12.51, -0.76)], Language scores were inversely associated with higher 3-PBA [beta = -5.17 (95% CI = -10.07, -0.27)] and cis-DBCA [beta = -5.40 (95% CI = -10.28, -0.52)]. We concluded that pyrethroid exposure in the first and second trimesters was associated with poorer infants neurodevelopmental outcomes at one year of age, and these effects were particularly pronounced at high levels of pyrethroid exposure.

Background The gut microbiome is associated with the response to immunotherapy in a variety of advanced cancers. However, the influence of the gut microbiome on locally advanced esophageal squamous cell carcinoma (ESCC) during programmed cell death protein 1 (PD-1) antibody immunotherapy plus chemotherapy is not clearly demonstrated. To explore the crosstalk between the gut microbiome and clinical response in locally advanced thoracic ESCC during neoadjuvant camrelizumab and chemotherapy Methods Patients who were diagnosed with locally advanced thoracic ESCC and had not received treatment were enrolled. The treatment regimen was two cycles of camrelizumab combined with carboplatin and albumin paclitaxel before surgery. The research endpoints were pathological complete response (pCR) and major pathological response (MPR). Fecal samples were collected at three time points: before neoadjuvant therapy, after two cycles of neoadjuvant therapy, and after surgery. We performed 16S ribosomal ribonucleic acid (rRNA) V3–V4 sequencing of the gene amplicons of fecal samples, as well as bacterial diversity and differential abundance analyses. Results A total of 46 patients were recruited, and 44, 42, and 35 fecal samples were collected at the three time points, respectively. Statistically significant differences were observed in the amplicon sequence variant (ASV)-level alpha diversity indices, including Chao1, Shannon, and Good’s coverage, between the three time points. The non-pCR-enriched gut microbiota included Proteobacteria, Dialister, Aeromonadales, Pseudomonadales, Thermi, Deinococci, Moraxellaceae, Rhodocyclales, Rhodocyclaceae, and Acinetobacter. The non-MPR-enriched gut microbiota included Pseudomonadales and the mitochondria family. The MPR-enriched gut microbiota included the Barnesiellaceae, Pyramidobacter, Dethiosulfovibrionaceae, Odoribacteraceae, Butyricimonas, Prevotella, Barnesiella, and Odoribacter. Patients with ≥3 grade adverse events (AEs) exhibited enrichment in the Succiniclasticum, Nakamurella, Rhizobium, Granulicella, Phyllobacteriaceae, Pelagibacteraceae, Actinosynnemataceae, Aquirestis, Flavisolibacter, Chelativorans, Coxiellaceae Acidicapsa, Acidobacteriaceae, Lentzea, Staphylococcus, Plesiomonas, Dysgonomonas, Pseudonocardia, and Ellin6075. Conclusions We found that the diversity of the gut microbiome declined after neoadjuvant PD-1 antibody immunotherapy plus chemotherapy and surgery. Patients with pCR had different types and proportions of gut microbiota before treatment compared to those without pCR. We also observed the difference between patients with or without ≥ grade 3 AEs. The taxonomic features of the gut microbiome are potential biomarkers that could predict the pathological response and AEs.

Background Neoadjuvant therapy followed by esophagectomy has been recognized as an effective treatment for locally advanced esophageal cancer, though still has a dismal prognosis. Antibodies against programmed death 1 (PD-1) protein improve survival in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) compared with chemotherapy in second-line therapy. However, neoadjuvant PD-1 inhibitor combined with chemotherapy has not been tested in locally advanced ESCC. We conducted this study to evaluate the efficacy and safety of pd-1 inhibitor in neoadjuvant chemotherapy. Methods In this study, we administered 28 adults with untreated, surgically resectable locally advanced ESCC. PD-1 inhibitor with chemotherapy [albumin paclitaxel 100 mg/m2 on days 1 and 8 + carboplatin with an area under the curve (AUC) of 5 on day 1] were administered every 3 weeks intravenously, and surgery was performed approximately 3-5 weeks after the second dose. The primary purpose of the study was to evaluate the feasibility and safety of this regimen. Results In all, 28 locally advanced ESCC patients were enrolled, 27 patients received surgery, 9 (33.3%) patients' postoperative pathological specimens suggested pCR, and 11 (40.7%) patients' primary tumor suggested complete response. Neoadjuvant PD-1 inhibitor with chemotherapy had an acceptable side-effect profile, 26 patients' tumors were completely resected (96.3% were R0). According to the RESIST v.1.1, the response in all 27 patients was evaluated by a computed tomography (CT) scan before surgery, showing 12 patients with complete response (CR), 12 with partial response (PR), and 3 with stable disease (SD). For surgical procedures, 15 (55.6%) patients underwent minimal invasive surgery, 4 (14.8%) underwent right transthoracic open esophagectomy, and 8 (29.6%) underwent hybrid approaches. Conclusions The novel treatment of PD-1 inhibitor with chemotherapy in the neoadjuvant setting for locally advanced ESCC produced satisfactory outcomes: an unprecedentedly high pCR rate for neoadjuvant chemotherapy, a high R0 resection rate, and a low-toxicity profile were achieved. The long-term efficiency of this novel treatment and the validity of the present findings should be confirmed with longer follow-up and prospective comparative trials.

Circular RNA (circRNA) is an important factor for regulating the progression of many cardiovascular diseases, including acute myocardial infarction (AMI). However, the role of circ_0124644 in AMI progression remains unclear. Hypoxia was used to induce cardiomyocytes injury. The expression of circ_0124644, microRNA (miR)-590-3p, and SRY-box transcription factor 4 (SOX4) mRNA was measured by qRT-PCR. Cell counting kit 8 (CCK8) assay and flow cytometry were utilized to detect cell viability, cell cycle progression, and apoptosis. The protein levels of apoptosis markers and SOX4 were determined by western blot (WB) analysis, and the levels of oxidative stress markers were assessed using commercial Assay Kits. Dual-luciferase reporter assay, RIP assay, and RNA pull-down assay were employed to confirm the interaction between miR-590-3p and circ_0124644 or SOX4. Circ_0124644 was upregulated in AMI patients and hypoxia-induced cardiomyocytes. Hypoxia could inhibit cardiomyocytes viability, cell cycle process, and promote apoptosis and oxidative stress, while silencing circ_0124644 could alleviate hypoxia-induced cardiomyocytes injury. In terms of mechanism, circ_0124644 could target miR-590-3p. MiR-590-3p overexpression could relieve hypoxia-induced cardiomyocytes injury. Also, the suppressive effect of circ_0124644 knockdown on hypoxia-induced cardiomyocytes injury could be reversed by miR-590-3p inhibitor. Moreover, SOX4 was found to be a target of miR-590-3p, and its overexpression also could reverse the regulation of miR-590-3p on hypoxia-induced cardiomyocytes injury. Circ_0124644 silencing could alleviate hypoxia-induced cardiomyocytes injury by regulating the miR-590-3p/SOX4 axis, suggesting that it might be a target for alleviating AMI.

Thyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052-3.393IU/ml, 1.01-1.54ng/dl, and 2.51-3.66pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

BACKGROUND:Researches on programmed cell death (PD-1) as neoadjuvant immunotherapy for resectable non-small cell lung cancer is underway, which brings hope for individuals with the disease. However, a study dedicated to lung squamous cell carcinoma (LUSC) specifically has yet to be conducted. Now, data from our pilot prospective research neoadjuvant study provide new insights in the field of neoadjuvant regimen for LUSC. METHODS:Between June 2019 and July 2020, 37 adults with untreated, surgically resectable stage IIB-IIIB LUSC were enrolled into this prospective study. Patients received 2 cycles of pembrolizumab (2 mg/kg) with chemotherapy (albumin-bound paclitaxel 100 mg/m2 on days 1 and 8 + carboplatin AUC 5) via intravenous administration every 3 weeks, and underwent surgical treatment 3-4 weeks after the second cycle. The primary endpoint of the study was the tumor pathologic complete response (pCR) rate. The toxicity profile, tumor major pathological remission, complete resection rate, response rate, and operative and postoperative complications were also evaluated. RESULTS:The postoperative pathological specimens of 17 (45.9%) patients suggested pCR. Neoadjuvant pembrolizumab with chemotherapy had an acceptable side-effect profile, and no patients withdrew from the study preoperatively due to disease progression or toxicity. A major pathological response occurred in 24 (64.9%) resected tumors. All tumors were completely resected (R0, 100%). According to the Response Evaluation Criteria in Solid Tumors (RESIST), a response was evaluated before surgery in 32 (86.5%) patients by computed tomography. Twenty-five (67.6%) patients underwent thoracoscopic surgery. No deaths or postoperative major complications requiring reoperation occurred. Recurrence or metastasis was found in 2 patients during follow-up of 2-14 months. CONCLUSIONS:The early outcomes of pembrolizumab with chemotherapy in the neoadjuvant setting as a novel treatment for resectable stage IIB-IIIB LUSC showed a high pCR rate that has not been seen previously, as well as a high R0 resection rate and a low toxicity profile. The long-term efficacy of this novel treatment and the validity of the present findings should be confirmed with longer follow-up and prospective comparative trials.

With the recent developments in information technology, real world big data studies (RWBDSs) have attracted increasing attention in the field of medicine. In RWBDSs, clinical laboratory data is an important part of the wider scope of real-world medical data, and its standardized use is critical for the generation of high-quality real world evidence. To improve the core functioning and competitiveness of clinical laboratories as well as provide high-quality medical services for patients, it is important to construct an information analysis model and perform RWBDSs.However, among the majority of developing countries, as well as in some developed countries, due to the poorly developed neglect of data formatting standards information construction and the lack of consideration for, and experience with, the ideas and methods of RWBDSs, many clinical laboratories are unable to make use of the vast amount of data stored in their systems. Additionally, in the literature, there remain many areas that require improvements, such as the correct misuse of research methods, appropriate unreasonable data presentation methods, and optimal opaque methods for data cleaning, storage, and mining.In this review, we describe both the advantages and disadvantages of RWBDSs in laboratory medicine. In addition, we summarize the current application and methods of RWBDS in laboratory medicine from seven different perspectives: the establishment of a reference interval, patient data-based real time quality control, diagnostic or prognostic modeling, epidemiological investigation, laboratory management, analysis of sources of variations for analytes, and external quality assessment. Finally, we discuss the future prospects of this research. This review can provide the basis for clinical laboratories to carry out real world research; additionally, it promotes and standardizes RWBDS in laboratory medicine.

BACKGROUND:While many studies have established reference intervals (RIs) for thyroid hormones using patient data, this approach has not been validated. Therefore, in this study, we aimed to validate an approach for establishing RIs for thyroid hormones only using patient data from clinical laboratories.METHODS:We established two derived databases: derived database* and derived database#. Reference individuals in derived database* were selected using strict exclusion criteria, and the RIs established by the database were considered standard RIs (RIs*). Individuals in derived database# were the physical examination population, whose information was downloaded directly from the Laboratory Information System, and RIs established from this database were evaluated (RIs#). The comparative confidence interval (CI) method and consistency of the decision results based on external databases were used to compare RIs* and RIs#.RESULTS:RIs# and RIs* for the thyroid hormones tested were similar. The 90% CIs of the upper and lower limits of RIs for most thyroid hormones overlapped between RIs# and RIs*, and the limit of RIs# was within the 90% CI of RIs*. The consistency rates for the results of the RIs* and RIs# in the external database were greater than 98% for all thyroid hormones tested.CONCLUSION:It was possible to establish RIs for thyroid hormones using only patient data from clinical laboratories after adopting appropriate statistical methods.

Breast cancer (BC) is the most common cancer in women and the second leading cause of their cancer death. Establishing an accurate BC prognosis is very difficult because of its heterogeneity. Elevated TFF1 levels in serum were associated with development of BC, TFF1 expression was upregulated in BC compared to the healthy breast tissue. The aim of this study was to investigate the function of TFF1 in BCs, and to assess whether serum TFF1 could be used in formulating a prognosis for BC patients. In silico analyses were carried out to determine the expression of TFF1 mRNA in different types of BC and the association between TFF1 expression and survival of BC patients. Expression of TFF1 protein was checked in 52 paraffin-embedded tissues of BCs by immunochemistry, and serum concentration of TFF1 in 70 BC patients and 32 healthy controls was measured by ELISA. Functional activities of TFF1 in BC cells were determined by CCK-8 assay, colony formation, BrdU-DNA synthesis, and assays for migration and invasion. Results showed that expression of TFF1 mRNA was correlated with expression of biomarkers of luminal cancers including ESR1, GATA3, FOXA1, MYB and XBP1. In addition, patients with ER+BC had higher expression of TFF1 than those with ER- (p < 0.05). There was also lower expression of TFF1 in triple-negative breast cancer (TNBC) than in non-TNBC (p < 0.05), which corresponds with the level of serum TFF1 in TNBC patients, compared with non-TNBC patients (p < 0.001). Furthermore, expression of TFF1 was associated with tumor size (p = 0.002), nodal status (p < 0.001), histological grade (p < 0.001), ER status (p = 0.012), PR status (p < 0.001) and HER2 (p < 0.001), while serum TFF1 was only statistically different among BC with ER+, PR + and HER2+ (p = 0.04139, 0.0018, 0.0004). Elevated TFF1 expression correlated with increased overall survival of BC patients (p = 0.00068). Finally, TFF1 was found to inhibit the cell growth, colony formation, migration and invasion of BC cells in vitro. All these results suggest that expression of TFF1 was related to ER status of BC and that expression of TFF1 was lower in TNBC than in non-TNBC. TFF1 was found to inhibit proliferation, migration and invasion of BC cells in vitro. Expression of TFF1 was associated with clinical characters of patients with BC. Serum TFF1 could be used to predict prognosis of patients with BC, especially non-TNBC.

With the recent developments in information technology, real world big data studies (RWBDSs) have attracted increasing attention in the field of medicine. In RWBDSs, clinical laboratory data is an important part of the wider scope of real-world medical data, and its standardized use is critical for the generation of high-quality real-world evidence. To improve the core functioning and competitiveness of clinical laboratories as well as provide high-quality medical services for patients, it is important to construct an information analysis model and perform RWBDSs. However, among the majority of developing countries, as well as in some developed countries, due to the poorly developed neglect of data formatting standards information construction and the lack of consideration for, and experience with, the ideas and methods of RWBDSs, many clinical laboratories are unable to make use of the vast amount of data stored in their systems. Additionally, in the literature, there remain many areas that require improvements, such as the correct misuse of research methods, appropriate unreasonable data presentation methods, and optimal opaque methods for data cleaning, storage, and mining. In this review, we describe both the advantages and disadvantages of RWBDSs in laboratory medicine. In addition, we summarize the current application and methods of RWBDS in laboratory medicine from seven different perspectives: the establishment of a reference interval, patient data-based real time quality control, diagnostic or prognostic modeling, epidemiological investigation, laboratory management, analysis of sources of variations for analytes, and external quality assessment. Finally, we discuss the future prospects of this research. This review can provide the basis for clinical laboratories to carry out real world research; additionally, it promotes and standardizes RWBDS in laboratory medicine.

Little is known about fine particulate matter (PM2.5) exposure among pregnant women in rural China. This study aims to characterize exposure to PM2.5 among pregnant women in rural China, and investigate potential risk factors of personal exposure to PM2.5. The data were obtained from a birth cohort study that enrolled 606 pregnant women in Xuanwei, a county known for its high rates of lung cancer. The personal exposure to PM2.5 was measured using small portable particulate monitors during each trimester of pregnancy. Participants were interviewed using structured questionnaires that sought information on risk factors of PM2.5 exposure. The daily exposure to PM2.5 among the pregnant women ranged from 19.68 to 97.08 μg/m3 (median = 26.08). Exposure to PM2.5 was higher in winter and autumn than other seasons (p < 0.05); higher during the day than during the night (p < 0.001); and greater during cooking hours than during the rest of the day (p < 0.001). Using a mixed effects model, domestic solid fuel for cooking (β = 1.75, p < 0.001), winter and autumn (β = 2.96, p < 0.001), cooking ≥ once per day (β = 1.58, p < 0.05), heating with coal (β = 1.69, p < 0.001), secondhand smoke exposure (β = 1.59, p < 0.001) and township 1(β = 2.39, p < 0.001) were identified as risk factors for personal exposure to PM2.5 of pregnant women throughout pregnancy. Indirect effects of season and township factors on personal PM2.5 exposure were mediated by heating, cooking and domestic fuel using. In conclusion, PM2.5 levels in Xuanwei exceeded WHO guidelines. Seasonal and township factors and individual behaviors like domestic solid fuel using for cooking, heating with coal and secondhand smoke exposure are associated with higher personal PM2.5 exposure among pregnant women in rural China.

BACKGROUND:Cardiac troponin is the cornerstone biomarker for the diagnosis of acute myocardial infarction. The aims of this study were to evaluate the association of biological and temporal factors with plasma cardiac troponin I (cTnI) concentration in a large group of Chinese outpatients and to explore which factor (sex, age, time of blood sampling, and season of the year) had the largest influence on plasma cTnI levels. METHODS:Analytical data with outpatient cTnI results were downloaded from the laboratory information system from January 1, 2012 to September 20, 2018. All cTnI measurements were performed with a Siemens Dimension EXL automatic chemiluminescence immunoassay analyzer. A statistical method was used to strictly exclude outliers. A total of 86,381 outpatients were enrolled in the study. RESULTS:In individuals over 60 years old, cTnI levels gradually increased with age in both males and females. cTnI reached its highest levels in individuals over 80 years old (0.030 μg/L in males and 0.027 μg/L in females). In individuals over 70 years old, cTnI levels were significantly higher in males than in females (P < .05). cTnI concentration varied between individuals with different times of blood sampling. In both men and women, cTnI concentrations reached a maximum at 05:00 (0.030 μg/L and 0.026 μg/L, respectively) and peaked again at 20:00 (0.029 μg/L and 0.023 μg/L, respectively). Additionally, there were significant differences in cTnI levels between the four seasons of the year (P < .05). In winter, cTnI levels were usually higher than in spring. Linear regression analysis showed that the factor "age ≥ 80" had the greatest impact on cTnI levels. CONCLUSION:Plasma cTnI levels were significantly influenced by sex, age, time of blood sampling, and season of the year. Thus, in order to avoid incorrect identification of cTnI values as abnormal, a cTnI reference interval should be established, taking into consideration the sex and age of the individual, the time of day of blood sampling, and the season of the year.