Risk Factors for Systemic Inflammatory Response Syndrome After Percutaneous Transhepatic Cholangioscopic Lithotripsy.

Background: There is a lack of validated predictive models for the occurrence of systemic inflammatory response syndrome (SIRS) after percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) for the treatment of hepatolithiasis. This is the first study to estimate the incidence of SIRS after PTCSL. Methods: A retrospective analysis of 284 PTCSL sessions for the treatment of hepatolithiasis at our institution between January 2019 and January 2023 was performed. The development of SIRS after PTCSL was the primary study endpoint. Independent risk factors for SIRS after PTCSL were identified using univariate and multivariate logistic regression analyses. A nomogram prediction model was constructed using these independent risk factors, and the predictive value was assessed using receiver operating characteristic (ROC) curves. Results: The incidence of SIRS after PTCSL was 20.77%. According to multivariate analysis, the number of PTCSL sessions (odds ratio [OR]=0.399, 95% confidence interval [CI]=0.202-0.786, p=0.008), stone location (OR=2.194, 95% CI=1.107-4.347, p=0.024), intraoperative use of norepinephrine (OR=0.301, 95% CI=0.131-0.689, p=0.004), intraoperative puncture (OR=3.476, 95% CI=1.749-6.906, P<0.001), preoperative gamma-glutamyltransferase (OR=1.002, 95% CI=1.001-1.004, p=0.009), and preoperative total lymphocyte count (OR=1.820, 95% CI=1.110-2.985, p=0.018) were found to be independent risk factors for the development of SIRS after PTCSL. These six independent risk factors were used to construct a nomogram prediction model, which showed satisfactory accuracy with an area under the ROC curve of 0.776 (95% CI: 0.702-0.850). Conclusion: The number of PTCSL sessions, stone location, intraoperative use of norepinephrine, intraoperative puncture, preoperative gamma-glutamyltransferase, and preoperative total lymphocyte count may predict the occurrence of SIRS after PTCSL. This prediction model may help clinicians identify high-risk patients in advance.

Tenascin-C as a potential biomarker and therapeutic target for esophageal squamous cell carcinoma.

PURPOSE: To establish a prognostic model of esophageal squamous cell carcinoma (ESCC) patients based on tenascin-C (TNC) expression level and clinicopathological characteristics, and to explore the therapeutic potential of TNC inhibition. METHODS: The expression of TNC was detected using immunohistochemistry (IHC) in 326 ESCC specimens and 50 normal esophageal tissues. Prognostic factors were determined by Cox regression analyses and were incorporated to establish the nomogram. The effects of TNC knockdown on ESCC cells were assessed in vitro and in vivo. Transcriptome sequencing (RNA-seq) and gene set enrichment analysis (GSEA) were performed to reveal signaling pathways regulated by TNC knockdown. The therapeutic significance of TNC knockdown combined with small-molecule inhibitors on cell proliferation was examined. RESULTS: TNC protein was highly expressed in 48.77 % of ESCC tissues compared to only 2 % in normal esophageal epithelia (p < 0.001). The established nomogram model, based on TNC expression, pT stage, and lymph node metastasis, showed good performance on prognosis evaluation. More importantly, the reduction of TNC expression inhibited tumor cell proliferation and xenograft growth, and mainly down-regulated signaling pathways involved in tumor growth, hypoxia signaling transduction, metabolism, infection, etc. Knockdown of TNC enhanced the inhibitory effect of inhibitors targeting ErbB, PI3K-Akt, Ras and MAPK signaling pathways. CONCLUSION: The established nomogram may be a promising model for survival prediction in ESCC. Reducing TNC expression enhanced the sensitivity of ESCC cells to inhibitors of Epidermal Growth Factor Receptor (EGFR) and downstream signaling pathways, providing a novel combination therapy strategy.

Early life exposure to Chinese famine and risk of digestive system cancer in midlife.

To investigate whether early-life exposure to the Great Famine of 1959-1961 in China was associated with the risk of digestive system cancer. The prospective cohort study involved 17 997 participants from the Kailuan Study (Tangshan, China) that began in 2006. All participants were divided into three groups based on their date of birth. The unexposed group (born from 1 October 1962 to 30 September 1964), fetal-exposed group (born from 1 October 1959 to 30 December 1961), and early-childhood-exposed group (born from 1 October 1956 to 30 December 1958). The Cox proportional hazards model was used to analyze the association between early famine exposure and digestive system cancer. During the mean follow-up period of (10.4 ± 2.2) years, a total of 223 digestive system cancer events occurred. Including 54 cases in the unexposed group (62.14/100 000 person-years), 57 cases in the fetal-exposed group (114.8/100 000 person-years), and 112 cases in the early-childhood-exposure group (122.2/100 000 person-years). After adjusting covariates, compared with the unexposed group, the HR and 95% CI were 1.85 (1.28, 2.69) for participants in the fetal-exposed group and 1.92 (1.38, 2.66) for participants in the early-childhood-exposed group. No interactions were observed in our study. After classifying digestive system cancers, the HR and 95% CI were 2.02 (1.03, 3.97) for colorectal cancer for participants in the fetal-exposed group and 2.55 (1.43, 4.55) for participants in the early-childhood-exposed group. The HR and 95% CI were (1.13, 3.83) of liver cancer for participants in the fetal-exposed group and 1.15 (0.63, 2.10) for participants in the early-childhood-exposed group. Early-life famine exposure was associated with a higher risk of digestive system cancer in adulthood. Fetal-exposed individuals might increase the risk of colorectal cancer and liver cancer, and early childhood-exposed might increase the risk of colorectal cancer.

The effect of cumulative lipid accumulation product and related long-term change on incident stroke: The Kailuan Study.

BACKGROUND AND AIMS: A single measurement lipid accumulation product (LAP) level has been shown to increase cardiovascular disease, but cumulative LAP on stroke effects is uncertain. METHODS AND RESULTS: This study included 43,089 participants, free of any cardiovascular diseases at baseline, from the Kailuan Study. The cumulative LAP was determined by multiplying the average LAP index and the time interval between two consecutive examinations, resulting in their categorization into four quartile groups. The higher LAP exposure was defined as participants with LAP values exceeding 90% of this population during each health survey. The association between cumulative LAP and stroke was assessed using multivariable Cox proportional hazard models. During a median follow-up period of 11.0 (10.6-11.3) years, 2461 participants developed stroke (of which 2220 were ischemic stroke, 320 were hemorrhagic stroke, and 79 were concurrent). After adjusting for potential confounders, the risk of stroke gradually increased in Groups Q2 to Q4 compared to Q1, with hazard ratios (HRs) ranging from 1.19 (95% CI: 1.05-1.36) to 1.50 (95% CI: 1.30-1.70). Specifically, the risk of ischemic stroke showed an increase from 1.21 (1.06-1.39) to 1.56 (1.36-1.79), while no statistically significant effect was observed for hemorrhagic stroke. The longer duration of higher LAP index exposure was also associated with increased stroke risk. Similar results were obtained in the stratification and sensitivity analyses. CONCLUSION: Cumulative LAP was positively and significantly associated with incident stroke, especially ischemic stroke, and a longer duration of exposure to higher LAP may increase the risk of stroke.

The association between sarcopenia and functional disability in older adults.

OBJECTIVES: Sarcopenia is associated with functional disability in older adults. However, no consistent conclusions have been reached considering the differences in the measurement and criteria of sarcopenia. We aimed to examine the association between sarcopenia status and functional disability based on China Health and Retirement Longitudinal Study (CHARLS). DESIGN: A nationally representative longitudinal study. SETTING AND PARTICIPANTS: Participants aged at least 60 years old from the CHARLS 2015y were included. MEASUREMENTS: Sarcopenia was assessed according to the Asian Working Group for Sarcopenia 2019 algorithm. The outcomes of this study were basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs). The logistic regression model was conducted to analyze the cross-sectional and longitudinal associations between sarcopenia status and ADLs and IADLs disability. RESULTS: In the cross-sectional study, 37.2% of the 6893 participants were defined as having sarcopenia. Any form of sarcopenia was associated with ADLs and IADLs disability. During three years of follow-up, 786 (16.5%) participants developed new-onset ADLs disability, and 980 (22.5%) participants developed new-onset IADLs disability. Compared with the no-sarcopenia, participants with possible sarcopenia (OR: 1.62, 95%CI: 1.34-1.95), sarcopenia (OR: 1.58, 95%CI: 1.18-2.11), or total sarcopenia (OR: 1.58, 95%CI: 1.34-1.88) had a higher risk of ADLs disability. While, the risk of IADLs disability for participants with possible sarcopenia (OR: 1.68, 95%CI: 1.41-2.00), sarcopenia (OR: 1.87, 95%CI: 1.40-2.51), or total sarcopenia (OR: 1.71, 95%CI: 1.45-2.00) was still significantly increased. With statistical interaction between sarcopenia status and residence or sex in ADLs and IADLs disability, older adults in urban, with ORs ranging from 2.14 to 2.44, were at a higher risk of functional disability than those in rural. Possible sarcopenia was associated with a much higher risk of ADLs disability (OR: 1.68, 95%CI: 1.26-2.25) in males and a higher risk of IADLs disability (OR: 1.98, 95%CI: 1.56-2.52) in females. CONCLUSIONS: Sarcopenia was associated with an increased risk of ADLs and IADLs disability among older Chinese adults. Even possible sarcopenia still significantly impacted ADLs and IADLs disability, and this association varied by sex and residence.

Measurement of cumulative high-sensitivity C-reactive protein and monocyte to high-density lipoprotein ratio in the risk prediction of type 2 diabetes: a prospective cohort study.

BACKGROUND: Converging data have suggested that monocytic inflammation and C-reactive protein (CRP) are biologically intertwined processes and are involved in diabetogenesis. This study aimed to investigate the association between systemic inflammation assessed by joint cumulative high-sensitivity C-reactive protein (CumCRP) and monocyte to high-density lipoprotein ratio (CumMHR) and incident type 2 diabetes (T2D) and their predictive value for T2D in a general population. METHODS: A total of 40,813 nondiabetic participants from a prospective real-life cohort (Kailuan Study, China) were followed biennially from 2010/2011 until December 31, 2020. Multivariable Cox regression analyses were conducted to evaluate the adjusted hazard ratios (aHRs) of incident diabetes. RESULTS: During a median follow-up of 7.98 (IQR: 5.74-8.87) years, 4848 T2D cases developed. CumMHR and CumCRP were alone or jointly associated with incident T2D after adjusting for potential confounders. Elevated CumMHR levels significantly increased the risk of incident diabetes in each CumCRP strata (P-interaction: 0.0278). Participants with concomitant elevations in CumMHR and CumCRP levels had the highest risk (aHR: 1.71, 95% CI 1.52-1.91) compared to both in the low strata. Notably, the coexposure-associated T2D risk was modified by age, sex, hypertension, dyslipidemia, and prediabetes status. C-statistics increased from 0.7377 to 0.7417 when CumMHR and CumCRP were added into the multivariable-adjusted model, with a net reclassification improvement (%) of 12.39 (9.39-15.37) (P < 0.0001). CONCLUSIONS: Cumulative hsCRP and MHR were both independently and jointly associated with an increased risk of T2D and their addition to established risk factors should improve risk prediction and reclassification of diabetes.

Multi-trajectories of triglyceride-glucose index and lifestyle with Cardiovascular Disease: a cohort study.

BACKGROUND: Previous studies using trajectory models focused on examining the longitudinal changes in triglyceride-glucose (TyG) levels and lifestyle scores separately, without exploring the joint evolution of these two factors. This study aimed to identify the multi-trajectories of TyG levels and lifestyle scores and assess their association with the risk of cardiovascular disease (CVD). METHODS: The study enrolled 47,384 participants from three health surveys of the Kailuan Study. The TyG index was computed as Ln [fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2], and the lifestyle scores were derived from five factors, including smoking, alcohol consumption, physical activity, sedentary behaviors, and salt intake. A group-based multi-trajectory model was adopted to identify multi-trajectories of TyG levels and lifestyle scores. The association of identified multi-trajectories with incident CVD was examined using Cox proportional hazard model. RESULTS: Five distinct multi-trajectories of TyG levels and lifestyle scores were identified. During a median follow-up period of 10.98 years, 3042 participants developed CVD events (2481 strokes, 616 myocardial infarctions, and 55 co-current stroke and myocardial infarctions). In comparison to group 3 with the lowest TyG levels and the best lifestyle scores, the highest CVD risk was observed in group 5 characterized by the highest TyG levels and moderate lifestyle scores (HR = 1.76, 95% CI: 1.50-2.05). Group 2 with higher TyG levels and the poorest lifestyle scores had a 1.45-fold (95% CI 1.26-1.66) risk of CVD, and group 1 with lower TyG levels and poorer lifestyle scores had a 1.33-fold (95% CI 1.17-1.50) risk of CVD. Group 4, with moderate TyG levels and better lifestyle scores, exhibited the lowest CVD risk (HR = 1.32, 95% CI: 1.18-1.47). CONCLUSIONS: Distinct multi-trajectories of TyG levels and lifestyle scores corresponded to differing CVD risks. The CVD risk caused by a high level TyG trajectory remained increased despite adopting healthier lifestyles. These findings underscored the significance of evaluating the combined TyG and lifestyle patterns longitudinally, and implementing early interventions to reduce CVD risk by lowering TyG levels.

Combined effect of adiposity and elevated inflammation on incident type 2 diabetes: a prospective cohort study.

BACKGROUND: Adiposity and elevated inflammation are two hallmarks of hyperglycemia. However, it is unknown whether clustering of elevated inflammation and adiposity interact act on diabetogenesis and lead to a greater risk for incident type 2 diabetes (T2D). METHODS: Adiposity was indicated by body mass index, waist circumference and ultrasonography-measured fatty liver degrees. Elevated inflammation was indicated as high-sensitivity C-reactive protein levels ≥ 2 mg/L. Time-to-event survival analyses were conducted to investigate the joint effect of adiposity and inflammation on incident T2D on both multiplicative and additive scales. RESULTS: Among 82,172 non-diabetic participants from a prospective cohort in China, 14,278 T2D occurred over a median follow-up of 11 years. In the multivariable-adjusted model, elevated inflammation [1.12 (1.08‒1.16)] and adiposity [1.76 (1.69‒1.83) for overweight/obesity, 1.49 (1.44‒1.55) for central obesity, and 2.02 (1.95‒2.09) for fatty liver] were significantly associated with incident diabetes. Higher adiposity-associated risks and incidence rates of diabetes were observed with elevated inflammation. When studying the joint effect, the adjusted HRs were 1.77 (1.69‒1.85) for overweight/obesity, 1.14 (1.06‒1.23) for elevated inflammation, and 2.08 (1.97‒2.19) for their joint effect, with a relative excess risk due to interaction of 0.17 (0.05‒0.28). The attributable proportions were 71.30% for overweight/obesity, 12.96% for elevated inflammation, and 15.74% for their interaction. Similar results were observed when adiposity was assessed as waist circumference or fatty liver. CONCLUSIONS: Adiposity and elevated inflammation synergically lead to greater risks of incident diabetes than addition of each individual exposure. Strategies simultaneously targeting both risks should produce more benefits for diabetes prevention than through initiatives directed at each separate risk.

Clinical characteristics of three distinct types of pancreatitis with overlapping etiologies: A ten-year retrospective cohort study.

BACKGROUND: Hypertriglyceridemia (HTG) is frequently observed in non-HTG-induced acute pancreatitis (AP), such as in the early stage of acute biliary pancreatitis (ABP). There is overlap in the etiologies of ABP, HTG-AP, and biliary-hypertriglyceridemia acute pancreatitis (BHAP), which may be perplexing for clinicians. METHODS: We retrospectively analyzed 394 AP patients. The patients were divided into three groups based on etiology. We analyzed the differences among the three groups of patients in terms of general information, laboratory parameters, and prognosis. RESULTS: The mean age of patients in the ABP group was significantly higher than that in the HTG-AP and BHAP groups (p < 0.001). Females made up a greater percentage of the ABP group, whereas males made up the majority in the HTG-AP and BHAP groups. The ABP group had the highest PCT, AMS, LPS, ALT, AST, GGT, TBIL, DBIL, APACHE II, and BISAP scores. TG and BMI were highest in the HTG-AP group. AST and GGT levels were substantially greater in BHAP patients than those in HTG-AP. The BHAP group had the greatest incidence of organ failure, systemic complications, and local complications. CONCLUSION: ABP usually develops in people aged 50-59 years. HTG-AP primarily affects people aged 30-39 years. However, the peak incidence age of BHAP falls between the two aforementioned age groups (40-49 years). We also found that patients with BHAP seem to be in an intermediate state in terms of some biochemical markers and demographic characteristics. Furthermore, BHAP may have the worst clinical outcomes compared with HTG-AP and ABP.

VEGF/Nrp1/HIF-1α promotes proliferation of hepatocellular carcinoma through a positive feedback loop.

To investigate the role of neuropilin1 (Nrp1) in glucose metabolism and proliferation of hepatocellular carcinoma (HCC) cells and to analyze its mechanism of action. The CRISPR gene knockout technique was used to knock out the Nrp1 gene in two HCC cell lines. The effect of Nrp1 on the proliferation of HCC cells was assessed in the CCK8 assay and plate cloning assay. The expression levels of glucose consumption, lactate production, and essential proteins of the glycolytic pathway were detected to explore the effect of Nrp1 on glucose metabolism in HCC cells. Using CoCl2 to revert the expression of hypoxia inducible factor-1α (HIF-1α), the role of HIF-1α in the pro-HCC cell metabolism of Nrp1 were demonstrated. The protein synthesis inhibitor CHX and proteasome inhibitor MG-132 was used to analyze the molecular mechanism of action of Nrp1 on HIF-1α. The Kaplan-Meier method was used to calculate survival rates and plot survival curves. Based on the CCK8 assay and plate cloning assay, we found that Nrp1 knockout significantly inhibited the proliferation of HCC cells. Nrp1 inhibitor suppressed lactate production and glucose consumption in HCC cells. Knockout of Nrp1 decreased the expression of glycolytic pathway-related proteins and HIF-1α protein. Furthermore, by joint use of CoCl2 and NRP1 knockout, we confirmed that reverting HIF-1α expression could reverse the effect of Nrp1 knockout on HCC cell metabolism in vitro. Mechanistically, Nrp1 showed a close correlation with the stability of HIF-1α protein in protein stability assay. Finally, we revealed that high expression of Nrp1 in HCC tissues was associated with poor overall survival and disease-free survival of the patients. Nrp1 accelerates glycolysis and promotes proliferation of HCC by regulating HIF-1α protein stability and through the VEGF/Nrp1/HIF-1α positive feedback loop.

Elevated expression of the RNA-binding protein IGF2BP1 enhances the mRNA stability of INHBA to promote the invasion and migration of esophageal squamous cancer cells.

BACKGROUND: The mechanisms underlying the occurrence and development of esophageal squamous cell carcinoma (ESCC) remains to be elucidated. The present study aims to investigate the roles and implications of IGF2BP1 overexpression in ESCC. METHODS: IGF2BP1 protein expression in ESCC samples was assessed by immunohistochemistry (IHC), and the mRNA abundance of IGF2BP1 and INHBA was analyzed with TCGA datasets and by RNA in situ hybridization (RISH). The methylation level of the IGF2BP1 promoter region was detected by methylation-specific PCR (MSP-PCR). Cell viability, migration, invasion and in vivo metastasis assays were performed to explore the roles of IGF2BP1 overexpression in ESCC. RNA immunoprecipitation sequencing (RIP-seq) and mass spectrometry were applied to identify the target RNAs and interacting proteins of IGF2BP1, respectively. RIP-PCR, RNA pulldown, immunofluorescence (IF), gene-specific m6A PCR and RNA stability assays were used to uncover the molecular mechanisms underlying the malignant phenotypes of ESCC cells caused by IGF2BP1 dysregulation. BTYNB, a small molecular inhibitor of IGF2BP1, was evaluated for its inhibitory effect on the malignant phenotypes of ESCC cells. RESULTS: IGF2BP1 overexpression was detected in ESCC tissues and associated with the depth of tumor invasion. In addition, IGF2BP1 mRNA expression in ESCC cells was negatively correlated with the level of its promoter methylation. Knockdown of IGF2BP1 inhibited ESCC cell invasion and migration as well as tumor metastasis. Mechanistically, we observed that IGF2BP1 bound and stabilized INHBA mRNA and then resulted in higher protein expression of INHBA, leading to the activation of Smad2/3 signaling, thus promoting malignant phenotypes. The mRNA level of INHBA was upregulated in ESCC tissues as well. Furthermore, IGF2BP1 interacted with G3BP stress granule assembly factor 1 (G3BP1). Knockdown of G3BP1 also down-regulated the INHBA-Smad2/3 signaling. BTYNB abolished this activated signaling and significantly attenuated the malignant phenotypes of ESCC cells. CONCLUSIONS: Elevated expression of IGF2BP1 is a frequent event in ESCC tissues and might be a candidate biomarker for the disease. IGF2BP1 overexpression promotes the invasion and migration of ESCC cells by activating the INHBA-Smad2/3 pathway, providing a potential therapeutic target for ESCC patients with high expression of IGF2BP1.

High-intensity focused ultrasound versus transarterial chemoembolization for hepatocellular carcinoma: a meta-analysis.

PURPOSE: The application of high-intensity focused ultrasound (HIFU) in hepatocellular carcinoma (HCC) was promising. However, whether the effect of HIFU is comparable with that of transarterial chemoembolization (TACE) has not been determined. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, WanFang Data, CqVip, CNKI, and CBM databases were searched for randomized controlled trials (RCTs), cohort studies, and case-control studies. The methodological quality of each study was evaluated. When there is no statistical heterogeneity, the fixed effect model would be used to merge data. Otherwise, the random effect model would be utilized. Sensitivity analyses were conducted by excluding one study each time. Subgroup analyses were conducted based on age, sex, tumor number, relative number of the patients with Child-Pugh C grade in each group, the percentage of patients with Child-Pugh C grade in the whole study, and tumor load. Publication bias was evaluated by Egger's test and Begg's test. RESULTS: Six cohort studies including 188 patients from HIFU group and 224 patients from TACE group were obtained for further analysis. The meta-analysis suggested HIFU and TACE showed no differences in postoperative 1-year overall survival (OS) rate, tumor response (including complete response, partial response, stable disease, and progressive disease), and postoperative complications. Moreover, compared with TACE, HIFU showed higher postoperative 6-month and 2-year OS rates. Subgroup analyses, meta regression analysis and sensitivity analyses indicated the findings above were reliable. Additionally, no potential publication bias was detected. CONCLUSION: For HCC, when compared with TACE, HIFU might show comparable safety but better effect. Considering the limitations of current studies, more well-designed studies are needed to validate our conclusion.

Supra-additive effect of chronic inflammation and atherogenic dyslipidemia on developing type 2 diabetes among young adults: a prospective cohort study.

BACKGROUND: Both elevated inflammation and atherogenic dyslipidemia are prominent in young-onset diabetes and are increasingly identified as biologically intertwined processes that contribute to diabetogenesis. We aimed to investigate the age-specific risks of type 2 diabetes (T2D) upon concomitant chronic inflammation and atherogenic dyslipidemia. METHODS: Age-stratified Cox regression analysis of the risk of incident diabetes upon co-exposure to time-averaged cumulative high-sensitivity C-reactive protein (CumCRP) and atherogenic index of plasma (CumAIP) among 42,925 nondiabetic participants from a real-world, prospective cohort (Kailuan Study). RESULTS: During a median 6.41 years of follow-up, 3987 T2D developed. Isolated CumAIP and CumCRP were significantly associated with incident T2D in the entire cohort and across all age subgroups. Both CumAIP and CumCRP were jointly associated with an increased risk of diabetes (P-interaction = 0.0126). Compared to CumAIP < -0.0699 and CumCRP < 1 mg/L, co-exposure to CumAIP ≥ - 0.0699 and CumCRP ≥ 3 mg/L had a significant hazard ratio (HR) [2.55 (2.23-2.92)] after adjusting for socio-demographic, life-style factors, family history of diabetes, blood pressure, renal function and medication use. The co-exposure-associated risks varied greatly by age distribution (P-interaction = 0.0193): < 40 years, 6.26 (3.47-11.28); 40-49 years, 2.26 (1.77-2.89); 50-59 years, 2.51 (2.00-3.16); 60-69 years, 2.48 (1.86-3.30); ≥ 70 years, 2.10 (1.29-3.40). In young adults (< 45 years), both exposures had a significant supra-additive effect on diabetogenesis (relative excess risk due to interaction: 0.80, 95% CI 0.10-1.50). CONCLUSIONS: These findings highlight the need for age-specific combined assessment and management of chronic inflammation and dyslipidemia in primary prevention against T2D, particularly for young adults. The clinical benefit derived from dual-target intervention against dyslipidemia and inflammation will exceed the sum of each part alone in young adults.

Association of cardiovascular health score trajectory and risk of subsequent cardiovascular disease in non-diabetic population: a cohort study.

BACKGROUND: Diabetes is an important risk factor for cardiovascular disease (CVD), but in the non-diabetic population, high glucose values within the normal range are also positively associated with CVD risk. There is a lack of concern for people without diabetes and evidence is lacking regarding the association between changes in cardiovascular health score (CVHS) and CVD risk in the non-diabetic population. METHODS: The current study included 37,970 non-diabetic participants free of CVD events in or before 2010 from the Kailuan Study and calculated CVHS according to the overall status of 7 cardiovascular health metrics between the 2006 and 2010 waves. Latent mixture models were used to explore the subgroups with different development trends included in the context of the Kailuan non-diabetic population and to identify the trajectory of each subgroup. The outcomes of the current study were CVD events, including myocardial infarction and stroke. CVHS trajectory was developed to predict subsequent CVD risk from 2010 to 2020. The Cox proportional hazard model was established to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of CVD across different trajectory patterns. RESULTS: Five distinct CVHS trajectory patterns were identified, including low-stable pattern (n = 2835), moderate-increasing pattern (n = 3492), moderate-decreasing pattern (n = 7526), high-stable I pattern (n = 17,135), and high-stable II pattern (n = 6982). Compared with the low-stable pattern, participants with the high-stable II pattern had a lower subsequent risk of CVD (HR = 0.22, 95%CI = 0.18-0.28); In stratification analysis, the lower risk for CVD was observed in females (HR = 0.10, 95%CI = 0.05-0.23, P for interaction < 0.05) and those aged < 60 years (HR = 0.16, 95%CI = 0.11 to 0.22, P for interaction < 0.05). CONCLUSIONS: CVHS trajectory patterns were associated with an altered CVD risk in the non-diabetic population. When stratified by age and sex, the association was stronger in young adults and females.

Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most frequent and potentially life-threatening complications following pancreatic surgery. Fibrin sealants have been used in some centres to reduce POPF rate. However, the use of fibrin sealant during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2020. OBJECTIVES: To evaluate the benefits and harms of fibrin sealant use for the prevention of POPF (grade B or C) in people undergoing pancreatic surgery compared to no fibrin sealant use. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 09 March 2023, together with reference checking, citation searching, and contacting study authors to identify additional studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 14 RCTs, randomising 1989 participants, comparing fibrin sealant use versus no fibrin sealant use for different locations: stump closure reinforcement (eight trials), pancreatic anastomosis reinforcement (five trials), or main pancreatic duct occlusion (two trials). Six RCTs were carried out in single centres; two in dual centres; and six in multiple centres. One RCT was conducted in Australia; one in Austria; two in France; three in Italy; one in Japan; two in the Netherlands; two in South Korea; and two in the USA. The mean age of the participants ranged from 50.0 years to 66.5 years. All RCTs were at high risk of bias. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included eight RCTs involving 1119 participants: 559 were randomised to the fibrin sealant group and 560 to the control group after distal pancreatectomy. Fibrin sealant use may result in little to no difference in the rate of POPF (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.73 to 1.21; 5 studies, 1002 participants; low-certainty evidence) and overall postoperative morbidity (RR 1.20, 95% CI 0.98 to 1.48; 4 studies, 893 participants; low-certainty evidence). After fibrin sealant use, approximately 199 people (155 to 256 people) out of 1000 developed POPF compared with 212 people out of 1000 when no fibrin sealant was used. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto odds ratio (OR) 0.39, 95% CI 0.12 to 1.29; 7 studies, 1051 participants; very low-certainty evidence) and total length of hospital stay (mean difference (MD) 0.99 days, 95% CI -1.83 to 3.82; 2 studies, 371 participants; very low-certainty evidence). Fibrin sealant use may reduce the reoperation rate slightly (RR 0.40, 95% CI 0.18 to 0.90; 3 studies, 623 participants; low-certainty evidence). Serious adverse events were reported in five studies (732 participants), and there were no serious adverse events related to fibrin sealant use (low-certainty evidence). The studies did not report quality of life or cost-effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included five RCTs involving 519 participants: 248 were randomised to the fibrin sealant group and 271 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF (RR 1.34, 95% CI 0.72 to 2.48; 3 studies, 323 participants; very low-certainty evidence), postoperative mortality (Peto OR 0.24, 95% CI 0.05 to 1.06; 5 studies, 517 participants; very low-certainty evidence), reoperation rate (RR 0.74, 95% CI 0.33 to 1.66; 3 studies, 323 participants; very low-certainty evidence), and total hospital cost (MD -1489.00 US dollars, 95% CI -3256.08 to 278.08; 1 study, 124 participants; very low-certainty evidence). After fibrin sealant use, approximately 130 people (70 to 240 people) out of 1000 developed POPF compared with 97 people out of 1000 when no fibrin sealant was used. Fibrin sealant use may result in little to no difference both in overall postoperative morbidity (RR 1.02, 95% CI 0.87 to 1.19; 4 studies, 447 participants; low-certainty evidence) and in total length of hospital stay (MD -0.33 days, 95% CI -2.30 to 1.63; 4 studies, 447 participants; low-certainty evidence). Serious adverse events were reported in two studies (194 participants), and there were no serious adverse events related to fibrin sealant use (very low-certainty evidence). The studies did not report quality of life. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two RCTs involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto OR 1.41, 95% CI 0.63 to 3.13; 2 studies, 351 participants; very low-certainty evidence), overall postoperative morbidity (RR 1.16, 95% CI 0.67 to 2.02; 2 studies, 351 participants; very low-certainty evidence), and reoperation rate (RR 0.85, 95% CI 0.52 to 1.41; 2 studies, 351 participants; very low-certainty evidence). Fibrin sealant use may result in little to no difference in the total length of hospital stay (median 16 to 17 days versus 17 days; 2 studies, 351 participants; low-certainty evidence). Serious adverse events were reported in one study (169 participants; low-certainty evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report POPF, quality of life, or cost-effectiveness. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealant use may result in little to no difference in the rate of POPF in people undergoing distal pancreatectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF in people undergoing pancreaticoduodenectomy. The effect of fibrin sealant use on postoperative mortality is uncertain in people undergoing either distal pancreatectomy or pancreaticoduodenectomy.

Association of trajectories of non-high-density lipoprotein cholesterol concentration with risk of cardiovascular disease: the Kailuan Study.

OBJECTIVES: This study aimed to assess the association between longitudinal change in non-high-density lipoprotein cholesterol (non-HDL-C) and subsequent cardiovascular disease (CVD) risk. DESIGN: A retrospective study. SETTING: Data were obtained from the Kailuan Study, a dynamic cohort study initiated in 2006 in Tangshan, China. PARTICIPANTS: The current study included 41 085 participants (mean age 53.9±11.6 years) free of CVD events in or before 2012. The non-HDL-C trajectory was developed according to the repeated measurement during 2006-2012 surveys to predict the CVD risk from 2012 to 2020. PRIMARY OUTCOME MEASURES: CVD events included myocardial infarction and stroke. RESULTS: 3 discrete non-HDL-C trajectories were identified: low-increasing (n=20 038), moderate-increasing (n=17 987) and high-increasing (n=3060). During 8 years of follow-up, 1797 CVD events were documented. Relative to the low-increasing pattern, adjusted HRs were 1.25 (95% CI: 1.13 to 1.38) for the moderate-increasing pattern and 1.46 (95% CI: 1.24 to 1.71) for the high-increasing pattern after adjustment for potential confounders such as age, sex, education background, smoking status, drinking status, physical activity, body mass index, low-density lipoprotein cholesterol, hypertension, diabetes and lipid-lowering medications. CONCLUSIONS: Changes in non-HDL-C were significantly associated with subsequent risk of CVD events, and participants with a high-increasing pattern had a higher CVD risk. Long-term monitoring of non-HDL-C could be useful to improve the prediction of CVD risk. TRIAL REGISTRATION NUMBER: ChiCTR-TNC-1100148.

Fractional flow reserve measured via left internal mammary artery after coronary artery bypass grafting: Two case reports.

BACKGROUND: The fractional flow reserve (FFR) has made the treatment of coronary heart disease more precise. However, there are few reports on the measurement of FFR via the left internal mammary artery (LIMA). Herein, we described the determination of further treatments by measuring FFR via the LIMA in 2 cases after coronary artery bypass grafting (CABG). CASE SUMMARY: Case 1 was a 66-year-old male who was admitted due to "chest tightness after CABG." The patient underwent CABG 7 years prior due to coronary heart disease. Coronary artery angiography showed complete occlusion of the left anterior descending artery (LAD), and subtotal occlusion of the third segment of the right coronary artery. On arterial angiography, there was 85% stenosis at the distal end of the anastomosis of the LIMA-LAD graft. FFR via LIMA was determined at 0.75. Thus, balloon dilation was performed in Case 1. FFR after balloon dilation was 0.94. Case 2 was a 60-year-old male who was admitted due to "chest tightness after CABG." The patient underwent CABG 6 years prior due to coronary heart disease. There was 60% segmental stenosis in the middle segment of LAD and 75% anastomotic stenosis. FFR measured via LIMA was 0.83 (negative); thus the intervention was not performed. Case 2 was given drug treatments. At the 3-mo follow-up, there was no recurrence of chest tightness or shortness of breath in both cases. They are currently under continual follow-up. CONCLUSION: We provided evidence that FFR measurement via grafted blood vessels, especially LIMA, after CABG is a good method to determine the intervention course.

Aptamer-based Upconversion Fluorescence Sensor for Doxorubicin Detection.

Doxorubicin is a common chemotherapeutic drug used to treat a variety of cancers. Monitoring the concentration of doxorubicin in human biological fluids is vital for treatment. In this work, we report an aptamer-functionalized, 808 nm-excited core-shell upconversion fluorescence sensor for specific detection of doxorubicin (DOX). Upconversion nanoparticles and DOX are used as energy donors and energy acceptors respectively. Aptamers immobilized on the surface of upconversion nanoparticles act as the molecular recognition element for DOX. The binding of DOX to the immobilized aptamers results in the fluorescence quenching of the upconversion nanoparticles via a fluorescence resonance energy transfer process. The relative fluorescence intensity exhibits a good linear response to DOX concentration in the range of 0.5 µM to 55 µM with a detection limit of 0.5 µM. The aptasensor displays high specificity and anti-interference against other antibiotics, common ions, and biomolecules owing to strong and specific interactions of aptamers towards DOX. The sensor is further applied for the detection of DOX in urine with spike recoveries of nearly 100%.

Nested Phosphorothioated Hybrid Primer-Mediated Isothermal Amplification for Specific and Dye-Based Subattomolar Nucleic Acid Detection at Low Temperatures.

Developing dye-based isothermal nucleic acid amplification (INAA) at low temperatures such as 37 °C remains a technical challenge. Here, we describe a nested phosphorothioated (PS) hybrid primer-mediated isothermal amplification (NPSA) assay which only utilizes EvaGreen (a DNA-binding dye) to achieve specific and dye-based subattomolar nucleic acid detection at 37 °C. The success of low-temperature NPSA essentially depends on employing Bacillus smithii DNA polymerase, a strand-displacing DNA polymerase with wide range of activation temperature. However, the NPSA's high efficiency entails nested PS-modified hybrid primers and the additives of urea and T4 Gene 32 Protein. To address the inhibition of urea on reverse transcription (RT), one-tube two-stage recombinase-aided RT-NPSA (rRT-NPSA) is established. By targeting human Kirsten rat sarcoma viral (KRAS) oncogene, NPSA (rRT-NPSA) stably detects 0.2 aM of KRAS gene (mRNA) within 90 (60) min. In addition, rRT-NPSA possesses subattomolar sensitivity to detect human ribosomal protein L13 mRNA. The NPSA/rRT-NPSA assays are also validated to obtain consistent results with PCR/RT-PCR methods on qualitatively detecting DNA/mRNA targets extracted from cultured cells and clinical samples. As a dye-based, low-temperature INAA method, NPSA inherently facilitates the development of miniaturized diagnostic biosensors.