Multi-organ proteomic landscape of COVID-19 autopsies.

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.

Proteomics-Derived Biomarker Panel Facilitates Distinguishing Primary Lung Adenocarcinomas With Intestinal or Mucinous Differentiation From Lung Metastatic Colorectal Cancer.

The diagnosis of primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) remains challenging due to the overlapping histomorphological, immunohistochemical (IHC), and genetic characteristics with lung metastatic colorectal cancer (lmCRC). This study aimed to explore the protein biomarkers that could distinguish between PAIM and lmCRC. To uncover differences between the two diseases, we used tandem mass tagging-based shotgun proteomics to characterize proteomes of formalin-fixed, paraffin-embedded tumor samples of PAIM (n = 22) and lmCRC (n = 17).Then three machine learning algorithms, namely support vector machine (SVM), random forest, and the Least Absolute Shrinkage and Selection Operator, were utilized to select protein features with diagnostic significance. These candidate proteins were further validated in an independent cohort (PAIM, n = 11; lmCRC, n = 19) by IHC to confirm their diagnostic performance. In total, 105 proteins out of 7871 proteins were significantly dysregulated between PAIM and lmCRC samples and well-separated two groups by Uniform Manifold Approximation and Projection. The upregulated proteins in PAIM were involved in actin cytoskeleton organization, platelet degranulation, and regulation of leukocyte chemotaxis, while downregulated ones were involved in mitochondrial transmembrane transport, vasculature development, and stem cell proliferation. A set of ten candidate proteins (high-level expression in lmCRC: CDH17, ATP1B3, GLB1, OXNAD1, LYST, FABP1; high-level expression in PAIM: CK7 (an established marker), NARR, MLPH, S100A14) was ultimately selected to distinguish PAIM from lmCRC by machine learning algorithms. We further confirmed using IHC that the five protein biomarkers including CDH17, CK7, MLPH, FABP1 and NARR were effective biomarkers for distinguishing PAIM from lmCRC. Our study depicts PAIM-specific proteomic characteristics and demonstrates the potential utility of new protein biomarkers for the differential diagnosis of PAIM and lmCRC. These findings may contribute to improving the diagnostic accuracy and guide appropriate treatments for these patients.

Transformation to diffuse large B-cell lymphoma and its impact on survival in patients with marginal zone lymphoma: A population-based study.

Some patients with marginal zone lymphoma (MZL) experience histological transformation to diffuse large B-cell lymphoma (DLBCL). Because of the paucity of long-term data on transformation, we conducted a population-based study to estimate the risk of transformation and its impact on survival in MZL. Using the Surveillance, Epidemiology and End Results database, we identified 23 221 patients with histology-proven MZL between 2000 and 2018. Competing risk method, Kaplan-Meier and Cox proportional hazards regression were performed to analyze time-to-event outcomes. Based on 420 events of transformation, the 10-year cumulative incidence rate of transformation is 2.23% (95% CI: 2.00%-2.46%) in MZL, 1.5% (95% CI: 1.3%-1.8%), 2.7% (95% CI: 2.3%-3.2%) and 5.8% (95% CI: 4.6%-7.1%) in extranodal, nodal and splenic MZL (EMZL, NMZL and SMZL), respectively. Patients with SMZL (subdistribution hazard ratio [SHR], 2.96; 95% CI: 2.21-3.96) or NMZL (SHR, 1.49; 95% CI: 1.17-1.90) have a higher risk of transformation than those with EMZL. For each MZL subtype, patients with transformation had a significantly shorter overall survival. Patients with transformation >18 months since MZL diagnosis had longer OS than those who presented within 18 months (5-year rate, 87.4% [95% CI: 83.7%-91.2%] vs 47.9% [95% CI: 38.8%-59.0%]; P < .001). Compared to patients with matched de novo DLBCL, those whose DLBCL was transformed from MZL had a shorter OS (5-year rate, 56.6% [95% CI: 51.9%-61.8%] vs 46.1% [95% CI: 40.9%-51.9%]; P < .001). We concluded that patients with SMZL had the highest risk of transformation. Regardless of MZL subtype, transformation resulted in significantly increased mortality.

Accurate interpretation of p53 immunohistochemical patterns is a surrogate biomarker for TP53 alterations in large B-cell lymphoma.

BACKGROUND: To clarify the relationship between p53 immunohistochemistry (IHC) staining and TP53 alterations (including mutations and deletions) in large B-cell lymphomas (LBCLs) and to explore the possibility of p53 IHC expression patterns as surrogate markers for TP53 alterations. METHODS: A total of 95 patients diagnosed with LBCLs were selected, and paraffin samples were taken for TP53 gene sequencing, fluorescence in situ hybridization and p53 IHC staining. The results were interpreted by experienced pathologists and molecular pathologists. RESULTS: Forty-three nonsynonymous TP53 mutations and p53 deletions were detected in 40 cases, whereas the remaining 55 cases had wild-type TP53 genes. The majority of TP53 mutations (34/43, 79.1%) occurred in exons 4-8, and R248Q was the most common mutation codon (4/43, 9.3%). The highest frequency single nucleotide variant was C > T (43.6%). p53 expression was interpreted as follows: Pattern A: p53 staining was positive in 0%-3% of tumor cells, Pattern B: p53 staining was positive in 4-65% of tumor cells, Pattern C: more than 65% of tumor cells were stained positive for p53. The p53 IHC expression patterns were associated with TP53 alterations. Gain of function variants and wild-type TP53 tended to exhibit type C and B p53 expression patterns, but loss of function variants were exclusively seen in type A cases. Additionally, interpretation of the staining by various observers produced significant reproducibility. CONCLUSIONS: The p53 IHC expression patterns can be used to predict TP53 alterations and are reliable for diverse alteration types, making them possible surrogate biomarkers for TP53 alterations in LBCLs.

Incidence and survival of patients with primary gastrointestinal melanoma: a population-based study.

BACKGROUND: Primary gastrointestinal melanoma (PGIM) has received more attention because of its inferior prognosis. Less is known about the incidence and survival rate of PGIM. METHODS: PGIM data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence was estimated by age, sex, race, and primary site. Trends in incidence were described as annual percent change (APC). Cancer-specific survival (CSS) and overall survival (OS) rates were estimated and compared using log-rank tests. Cox regression analyses were performed to identify independent prognostic factors. RESULTS: The overall incidence of PGIM was 0.360/1,000,000 with a significant upward trend (APC = 1.77%; 95% CI 0.89%-2.67%, p < 0.001) from 1975 to 2016. Most PGIM occurred in the large intestine (0.127/1,000,000) and anorectum (0.182/1,000,000), and both incidences were almost 10 times higher than those of other sites, including the esophagus, stomach, and small intestine. The median survival time was 16 months (IQR, 7-47 months) for CSS and 15 months (IQR, 6-37 months) for OS, and the 3-year CSS and OS rates were 29.5% and 25.4%, respectively. Older age, advanced stage, absence of surgery, and melanoma in the stomach were the independent risk indicators of survival and associated with worse CSS and OS. CONCLUSION: The incidence of PGIM has been increasing over the past decades and the prognosis is poor. Thus, further studies are warranted to improve the survival, and more attention should be paid to the patients that are elderly, patients with advanced stage, and patients with melanoma in the stomach.

Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis.

BACKGROUND: Anaplastic lymphoma kinase (ALK) overexpression and gene alterations have been detected in several mesenchymal tumors, with significant implications for diagnosis, therapy and prognosis. However, few studies have investigated the correlation between ALK expression status and clinicopathological characteristics in patients with gastrointestinal stromal tumors (GISTs). METHODS: A total of 506 GIST patients were enrolled. Sanger sequencing was employed to detect c-KIT and PDGFRA gene mutations. The tissue microarray (TMA) technique and immunohistochemistry were employed to identify the ALK (clone: 1A4 and D5F3) expression status in the tumor tissues. The ALK gene variants of IHC-positive cases were analyzed by fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). The clinicopathological data were analyzed using SPSS Statistics 26.0. RESULTS: Among the 506 GIST patients, the c-KIT mutation accounted for 84.2% (426/506), followed by PDGFRA mutation (10.3%, 52/506), while the wild-type accounted for the least (5.5%, 28/506). ALK-positive expression was detected in PDGFRA-mutant GISTs (7.7%, 4/52) but negative for c-KIT-mutant or wild-type GISTs by IHC. Four ALK IHC-positive patients were all male. The tumors all occurred outside the stomach. The predominant patterns of growth were epithelioid (2/4), spindle (1/4), and mixed type (1/4). They were all identified as high-risk classification according to the National Institutes of Health (NIH) classification. Aberrant ALK mutations were not identified by DNA-based NGS except in one of the 4 cases with amplification by FISH. CONCLUSION: Our study revealed 7.7% (4/52) of ALK expression in PDGFRA-mutant GISTs, indicating that molecular tests were required to rule out the possibility of PDGFRA-mutant GISTs when encountering ALK-positive mesenchymal tumors with CD117-negative or weakly positive in immunohistochemical staining.

Study on the relationship between hormone and Lp(a) in Chinese overweight/obese patients.

BACKGROUND: Obesity is a risk factor for metabolic diseases and often influences hormone change. Lipoprotein (a) (Lp(a)) is associated with various metabolic diseases, but there are few studies on the relationship between Lp(a) and hormones in obese patients. This study investigated the the relationship between Lp(a) and hormones in Chinese overweight/obese people. METHODS: A total of 410 overweight/obese patients (Body mass index (BMI) ≥ 25 kg/m2) were included and underwent sociodemographic data investigations and relevant clinical examinations. Lp(a) was analyzed by colorimetric enzymatic assays and hormone was measured with chemiluminescence immunoassay method. According to Lp(a) levels, they were categorized into 3 groups: the lower Lp(a) group (Lp(a) levels < 30 mg/dl), the moderate Lp(a) group (Lp(a) levels between 30 mg/dl and 120 mg/dl) and the higher Lp(a) group (Lp(a) levels > 120 mg/dl). The differences of hormone levels among the three groups were compared and the relationship between Lp(a) and hormones was analyzed by Spearman's rank correlation. RESULTS: The higher Lp(a) group had significantly lower testosterone (TES) levels compared with the lower and moderate Lp(a) groups in the case of gender, age and BMI matching. Lp(a) concentration was negatively correlated with TES levels in all participants and the negative association between Lp(a) and TES levels was also observed when the analysis was stratified by gender. Additionally, the TES was statistically related with Lp(a) levels in the multiple linear regression model (95% confidence interval: - 0.451 to - 0.079). CONCLUSIONS: TES levels was negatively associated with Lp(a) levels in Chinese overweight/obese patients.

Elevated serum Meteorin-like levels in patients with hyperthyroidism.

BACKGROUND: Meteorin-like (Metrnl) is a newly discovered adipomyokine that regulates systemic energy homeostasis. Both thyroid hormones and Metrnl increase energy expenditure and induce browning of adipose tissue. Thus, the aim of this study was to investigate serum Metrnl levels in hyperthyroid patients and the association of serum Metrnl levels with hyperthyroidism. METHODS: The study included 88 patients with newly diagnosed untreated overt hyperthyroidism and 100 age- and sex- matched healthy controls. Serum Metrnl levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Serum Metrnl levels were significantly elevated in patients with hyperthyroidism compared with controls. Linear regression analyses indicated that serum Metrnl levels were independently associated with FT3 (ß = 0.324, P = 0.001), FT4 (ß = 0.293, P = 0.001), and TSH (ß = -0.234, P = 0.006) after full adjustment. Additionally, further logistic regression analyses revealed that the highest Metrnl tertile was significantly associated with hyperthyroidism compared with the lowest tertile (P for trend < 0.001). The relationship remained significant even after adjusting for potential confounders. Meanwhile, each one-unit increase in circulating Metrnl was independently associated with hyperthyroidism (OR 1.021, 95%CI 1.007-1.036, P < 0.01). CONCLUSION: Serum Metrnl levels were elevated in patients with hyperthyroidism and were independently associated with hyperthyroidism.

Association of hyperuricemia with apolipoprotein AI and atherogenic index of plasma in healthy Chinese people: a cross-sectional study.

BACKGROUND: The atherogenic index of plasma (AIP) is a predictor for cardiovascular diseases (CVD), while hyperuricemia is an independent risk factor for a variety of CVD. Apolipoprotein AI has been found to be a protective factor for CVD. However, the role of APO AI in the association between plasma uric acid and AIP among healthy Chinese people needs to be further explored. AIMS: To evaluate the relationship between blood uric acid and AIP level in healthy Chinese people. To evaluate the relationship between blood uric acid and Apolipoprotein AI in healthy Chinese people. METHOD: A total of 3501 normal and healthy subjects who had physical examinations were divided into the hyperuricemia (HUA) group and the normouricemia (NUA) group. RESULT: The AIP of HUA group was significantly higher than that of NUA group [0.17±0.30 vs. -0.08±0.29]. Apo AI (1.33 ± 0.21 vs. 1.47 ± 0.26 g/l) and HDL-c (1.12 ± 0.27 vs. 1.36 ± 0.33 mmol/l) were significantly lower in the HUA group than in the NUA group. LDL-C (2.81 ± 0.77 vs. 2.69 ± 0.73 mmol/l), Apo B (0.96 ± 0.20 vs. 0.89 ± 0.20 g/l), FBG (5.48 ± 0.48 vs. 5.36 ± 0.48 mmol/l) and HOMA-IR [2.75 (1.92-3.91) vs. 2.18 (1.50-3.12)] was significantly higher in HAU group than the NUA group. Increases in plasma UA were associated with increases in AIP (ß = 0.307, p < 0.01) and decreases in Apo AI (ß = - 0.236, p < 0.01). CONCLUSION: Hyperuricemia is an independent risk factor for high AIP level. Inhibition of Apolipoprotein AI may be one of the mechanisms of UA which is involved in the progression of cardiovascular disease.

Partial response to pralsetinib in an advanced pulmonary sarcomatoid carcinoma patient harboring a KIF5B-RET rearrangement: a case report.

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare and unconventional non-small-cell lung cancer (NSCLC) that appears to be aggressive, with a poor prognosis and response to conventional treatment. Approximately 30% of PSCs have potentially targetable genomic alterations, but few studies have involved RET gene fusions, and corresponding targeted therapies are lacking. CASE PRESENTATION: In this report, we describe a patient with PSC harboring a KIF5B-RET gene fusion who was initially diagnosed with stage IVb lung cancer. Due to the poor performance status, the patient was unable to tolerate any radiotherapy or chemotherapy. Based on the next-generation sequencing (NGS) result of RET gene fusion, the patient was treated with pralsetinib. Two months after the treatment, the patient achieved a partial response. CONCLUSIONS: Our case indicates that RET is one of the main driver oncogenes of PSC and provides useful information for precise RET inhibitor administration in the future. Thus, the use of comprehensive genomic profiling may provide important treatment options for PSC.

Pseudognaphalium affine Extract Alleviates COPD by Inhibiting the Inflammatory Response via Downregulation of NF-κB.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with limited therapeutic options. Pseudognaphalium affine (D. Don) Anderb. is a medicinal and edible plant used to treat cough, asthma, and COPD for a long time in folk medicine. The objective of this study is to evaluate the effect of Pseudognaphalium affine (D. Don) Anderb. extract (GAE) and investigate the possible underlying mechanism in vivo and in vitro. In vivo, the administration of GAE in a rat COPD model could significantly ameliorate lung damage and pulmonary function by inhibiting the production of pro-inflammatory cytokines. Western blot and real-time PCR results showed that GAE could suppress nuclear translocation of nuclear factor-kappa B (NF-κB), which indicated that GAE down-regulated the NF-κB pathway. Moreover, GAE protected against tumor necrosis factor (TNF)-α induced inflammatory response in BEAS-2B and inhibited the NF-κB pathway. All data suggested that GAE exhibited its anti-COPD effect by inhibiting pro-inflammatory cytokines, which may be associated with the inhibition of the NF-κB pathway.

High quality in vitro expansion of human endothelial progenitor cells of human umbilical vein origin.

The limited availability of qualified endothelial progenitor cells (EPCs) is a major challenge for regenerative medicine. In the present study, we isolated human EPCs from human umbilical vein endothelial cells (HUVECs) by using magnetic micro-beads coated with an antibody against human CD34. Flow cytometric assay showed that majority of these cells expressed VEGFR2 (KDR), CD34 and CD133, three molecular markers for early EPCs. It was also found that a bioreactor micro-carrier cell culture system (bio-MCCS) was superior to dish culture for in vitro expansion of EPCs. It expanded more EPCs which were in the early stage, as shown by the expression of characteristic molecular markers and had better angiogenic potential, as shown by matrix-gel based in vitro angiogenesis assay. These results suggest that HUVECs might be a novel promising resource of EPCs for regenerative medicine and that a bio-MCCS cell culture system might be broadly used for in vitro expansion of EPCs.

Increased Thyroid DPP4 Expression Is Associated With Inflammatory Process in Patients With Hashimoto Thyroiditis.

CONTEXT: Dipeptidyl peptidase-4 (DPP4) is originally described as a surface protein in lymphocytes. Lymphocyte infiltration and subsequent destruction of thyroid tissue have been considered as the central pathological mechanism in Hashimoto thyroiditis (HT). OBJECTIVE: The present study aimed to investigate DPP4 expression in peripheral blood and thyroid tissue in HT patients, and explore the role of DPP4 in the pathophysiological process of HT. METHODS: This case-control study recruited 40 drug-naive HT patients and 81 control individuals. Peripheral blood and thyroid specimens were collected for assessing the expression and activity of DPP4. Moreover, single-cell RNA sequencing (scRNA-seq) analysis of 6 "para-tumor tissues" samples from scRNA-seq data set GSE184362 and in vitro cell experiments were also conducted. RESULTS: The HT patients had similar DPP4 serum concentration and activity as the controls. However, the expression and activity of DPP4 was significantly increased in the thyroid of the HT group than in the control group. The scRNA-seq analysis showed that DPP4 expression was significantly increased in the HT group, and mainly expressed in T cells. Further in vitro studies showed that inhibition of lymphocyte DPP4 activity with sitagliptin downregulated the production of inflammatory factors in co-cultured thyroid cells. CONCLUSION: DPP4 expression was significantly increased in the thyroid of the HT group compared with the control group, and was mainly localized in the lymphocytes. Inhibition of lymphocyte DPP4 activity reduced the production of inflammatory factors in co-cultured thyroid cells. Therefore, inhibition of DPP4 may have a beneficial effect by alleviating inflammatory reactions in HT patients.

Identification of EGFR R776H germline mutations in a patient with multifocal lung adenocarcinoma: A case report and literature review.

The advancement of molecular pathology techniques has led to the discovery of rare EGFR mutations for targeted therapy in lung cancer. Additionally, a substantial body of evidence indicates a connection between the development of lung cancer and genetic variations in the EGFR gene. Here, we present a case report of a patient with multifocal lung adenocarcinoma who possessed a rare germline mutation, EGFR R776H. An investigation into the family history of the patient exposed the notable incidence of lung adenocarcinoma, indicating a plausible genetic vulnerability to the ailment. To be specific, the patient's older brother and sister both suffered from lung cancer, which underlines the hereditary predisposition. Furthermore, it should be noted that the patient's daughter has inherited the germline mutation and also presented with multiple lung ground-glass nodules, emphasizing the clinical importance of this genetic variation. Following the lobectomy, the patient received treatment with almonertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), and at the latest follow-up, the patient has achieved partial remission. This case highlights the significance of taking into account germline possibilities when multiple lesions carry the same mutation. It stresses the importance of acquiring a comprehensive family history and performing genetic testing on leukocytes. Moreover, for the infrequent EGFR R776H mutation, third generation EGFR-TKIs may be a viable option.

Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer.

BACKGROUND: Tumor budding (TB) has emerged as a promising independent prognostic biomarker in colorectal cancer (CRC). The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC. However, existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies. Consequently, this study investigated the correlation among TB categories, clinicopathological features, and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification. AIM: To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC. METHODS: The clinical data of 547 CRC patients were collected for this retrospective study. Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines. RESULTS: Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy (P = 0.004), clinical stage IV (P < 0.001), ≥ 4 regional lymph node metastases (P = 0.004), left-sided colonic cancer (P = 0.040), and Bd 2-3 (P = 0.002) were independent prognostic factors in patients with stage III-IV CRC. Moreover, the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3, both in the tumor stroma and its invasive margin. CONCLUSION: TB has an independent predictive prognostic value in patients with stage III-IV CRC. It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

The impact of urban green space on the health of middle-aged and older adults.

Introduction: Urban green space is one of the most closely related ecosystem services to residents' lives, and it can be regarded as a preventive public health measure. Residents living in parks and other green environments can help improve their physical and mental health, reduce stress and even prevent crime and violence. Therefore, based on the actual situation in China, this paper analyzes the relationship between urban green space and the health of middle-aged and older adults and its mechanisms. Methods: This study used multiple linear regression, based the data from the China Health and Retirement Longitudinal Study (CHARLS) in 2013, 2015, and 2018, to explore the relationship between urban green space and the health of middle-aged and older adults. At the same time, group regression was conducted to identify the heterogeneity of health effects of urban green space. Results: The research shows that the increase of urban green space areas can significantly improve the health status of middle-aged and older adults. After a series of robustness tests, the results are still valid. In addition, the health effects of urban green space are different because of gender, age, education level, marital status residence, geographical location of the respondents and park quantity distribution. Further research found that reducing hot weather and optimizing air quality are the potential mechanisms of urban green space affecting the health of middle-aged and older adults, providing new evidence for the causal mechanism between urban green space and the health of middle-aged and older adults. Discussion: This study expanded the research scope of the impact of urban green space on the health of middle-aged and older adults, covering a representative sample in China. The results show that urban green space has an important impact on the health of middle-aged and older adults. Policy suggestions are made to help cities optimize the landscape and residents to enjoy ecology.

Effect of dapagliflozin on proteomics and metabolomics of serum from patients with type 2 diabetes.

BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduced the risk of cardiovascular and renal outcomes in patients with type 2 diabetes (T2D), but the underlying mechanism has not been well elucidated. The circulating levels of proteins and metabolites reflect the overall state of the human body. This study aimed to evaluate the effect of dapagliflozin on the proteome and metabolome in patients with newly diagnosed T2D. METHODS: A total of 57 newly diagnosed T2D patients were enrolled, and received 12 weeks of dapagliflozin treatment (10 mg/d, AstraZeneca). Serum proteome and metabolome were investigated at the baseline and after dapagliflozin treatment. RESULTS: Dapagliflozin significantly decreased HbA1c, BMI, and HOMA-IR in T2D patients (all p < 0.01). Multivariate models indicated clear separations of proteomics and metabolomics data between the baseline and after dapagliflozin treatment. A total of 38 differentially abundant proteins including 23 increased and 15 decreased proteins, and 35 differentially abundant metabolites including 17 increased and 18 decreased metabolites, were identified. In addition to influencing glucose metabolism (glycolysis/gluconeogenesis and pentose phosphate pathway), dapagliflozin significantly increased sex hormone-binding globulin, transferrin receptor protein 1, disintegrin, and metalloprotease-like decysin-1 and apolipoprotein A-IV levels, and decreased complement C3, fibronectin, afamin, attractin, xanthine, and uric acid levels. CONCLUSIONS: The circulating proteome and metabolome in newly diagnosed T2D patients were significantly changed after dapagliflozin treatment. These changes in proteins and metabolites might be associated with the beneficial effect of dapagliflozin on cardiovascular and renal outcomes.

Pylorus-preserving versus Pylorus-resecting: Impact on dynamic changes of nutrition and body composition in pancreatic cancer patients before and after pancreatoduodenectomy.

OBJECTIVES: To investigate if different methods of pancreatoduodenectomy (with or without pyloric preservation) would have different impacts on postoperative nutrition and body composition changes among pancreatic cancer patients. METHODS: Demographic and clinicopathological data, perioperative data were collected, body composition (e.g. skeletal muscle cross-sectional area [CSA], visceral fat area [VFA]) were evaluated with abdominal CT before and after surgery. Sarcopenia patients' proportion changes were also recorded. RESULTS: The hospital stay in the PRPD group was significantly less than that in the PPPD group (p < 0.05). A significant difference was found in CSA, skeletal muscle index (SMI), VFA, VFA/CSA and albumin (ALB) in both groups between preoperative, 3, and 12 months after surgery. The loss of visceral fat in the PRPD group was more prominent than that in the PPPD group at 3 months and 12 months after surgery (p < 0.05). VFA/CSA was higher in the PPPD group than in the PRPD group (3 months: p < 0.05, 12 months: p < 0.001). The proportion of sarcopenic patients increased significantly over time in the PPPD and PRPD groups (p < 0.001). CONCLUSIONS: Postoperative CSA and VFA continued to significantly decrease in both PPPD and PRPD groups, while the incidence of sarcopenia continued to increase. Compared with PRPD, PPPD has a protective effect on visceral fat. PPPD may contribute to better maintaining visceral fat mass and blood ALB levels. CT quantification can be an objective and effective method to evaluate the nutritional status of pancreatic cancer patients during the pre- and postoperative period and can provide a useful objective basis for guiding clinical treatment.

The serum concentration and activity of DPP4 is positively related with the severity of hyperthyroidism in patients with Graves' disease.

OBJECTIVE: Graves' disease (GD) is an organ-specific autoimmune disease. The production of anti-thyrotropin receptor antibodies (TRAb) is associated with a loss of immune tolerance. Dipeptidyl peptidase-4 (DPP-4) is expressed on multiple immune cells. This study aimed to investigate the relationship between serum concentration/activity of DPP4 and the severity of hyperthyroidism in GD patients. METHODS: A total of 82 newly diagnosed drug-naive patients with GD hyperthyroidism, 20 patients with non-autoimmune thyrotoxicosis and 122 age- and sex- matched healthy controls were enrolled. The clinical parameters and serum concentration and activity of DPP4 were measured. RESULTS: The GD group had increased serum concentration and activity of DPP4 than the healthy controls and patients with non-autoimmune thyrotoxicosis, while no significant difference was observed in the latter two groups. Multivariate linear regression indicated that the serum concentration/activity of DPP4 were positively associated with FT3, FT4 and TRAb levels in the GD patients. And the positive association between serum concentration/activity of DPP4 and TRAb was remained even after adjustment for confounding factors (all p < 0.05). CONCLUSIONS: The GD patients had significantly increased serum concentration/activity of DPP4. And the serum concentration/activity of DPP4 was positively associated with the severity of hyperthyroidism in GD patients.Key messagesThe activity and concentration of DPP4 in patients with Graves' disease were higher than those in healthy controls.There was a significant positive correlation between serum DPP4 concentration and TRAb levels in patients with Graves' disease.In patients with Graves 'disease, serum DPP4 activity was positively correlated with TRAb levels.

T Lymphoblastic Lymphoma Hiding in Mature Plasmacytoid Dendritic Cell Proliferation: A Case Report and Literature Review.

To the best of the author's knowledge, studies of mature plasmacytoid dendritic cell proliferation associated with T lymphoblastic lymphoma were extremely rare in the literature. Here, we report a patient who underwent both mature plasmacytoid dendritic cell proliferation and T lymphoblastic lymphoma. With the findings of lymph node biopsy taken from the right cervical and inguinal regions, we identified eye-catching mature plasmacytoid dendritic cells that were considered to be responsible for this lesion at the beginning, until the immunostaining of Ki67 and TDT showed a small group of positive cells hiding in these plasmacytoid dendritic cells. A bone marrow biopsy was also performed on this patient. Microscopically, the hematopoietic tissue was almost completely replaced by lymphoblastoid cells with condensed chromatin, inconspicuous nucleoli and scanty cytoplasm, which were basically the same as those seen in the lymph nodes in morphology. However, there was no sign of plasmacytoid dendritic cells or Langerhans cells in the bone marrow biopsy. With the help of bone marrow biopsy, our final diagnosis of the lymph node was T lymphoblastic lymphoma coexisting with mature plasmacytoid dendritic cell proliferation. Although accumulations of plasmacytoid dendritic cells may occur in some infections or reactive lymphadenopathy, the presence of extensive nodules or infiltration of plasmacytoid dendritic cells strongly reminds the pathologist to carefully evaluate the bone marrow or peripheral blood status of the patient to exclude a hidden myeloid or other neoplasm.