Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

Value of Pretreatment Inflammation-nutrition Score to Predict Non-response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer.

Objective: To investigate the value of pretreatment inflammatory-nutritional biomarkers in predicting the pathological response of locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (nCT). Methods: This retrospective study included eligible participants who underwent nCT followed by radical surgery. Pretreatment inflammatory nutritional biomarkers were calculated within one week prior to nCT. Correlations between biomarkers and pathological responses were analyzed. The cut-off values of the pretreatment biomarkers for predicting non-response were determined using receiver operating characteristic (ROC) curve analysis. The inflammation-nutrition score was calculated using the lymphocyte level, neutrophil-to-lymphocyte ratio (NLR), and prognostic nutritional index (PNI). Results: A total of 235 patients were retrospectively recruited between January 2017 and September 2022. Lower lymphocyte levels, lymphocyte monocyte ratio (LMR), and PNI, and higher NLR and platelet-to-lymphocyte ratio (PLR) were observed in patients without response. Multivariate logistic regression analysis revealed that NLR could independently predict non-response to nCT in patients with LARC. The sensitivity and specificity of the inflammation-nutrition score for predicting nonresponse were 71.2% and 61.7%, respectively. Conclusion: The pretreatment inflammation-nutrition score is a practical parameter for predicting non-response to nCT in patients with LARC. Patients with high scores were more likely to respond poorly to nCT.

A novel nomogram for the preoperative prediction of sentinel lymph node metastasis in breast cancer.

BACKGROUND OR PURPOSE: A practical noninvasive method to identify sentinel lymph node (SLN) status in breast cancer patients, who had a suspicious axillary lymph node (ALN) at ultrasound (US), but a negative clinical physical examination is needed. To predict SLN metastasis using a nomogram based on US and biopsy-based pathological features, this retrospective study investigated associations between clinicopathological features and SLN status. METHODS: Patients treated with SLN dissection at four centers were apportioned to training, internal, or external validation sets (n = 472, 175, and 81). Lymph node ultrasound and pathological characteristics were compared using chi-squared and t-tests. A nomogram predicting SLN metastasis was constructed using multivariate logistic regression models. RESULTS: In the training set, statistically significant factors associated with SLN+ were as follows: histology type (p < 0.001); progesterone receptor (PR: p = 0.003); Her-2 status (p = 0.049); and ALN-US shape (p = 0.034), corticomedullary demarcation (CMD: p < 0.001), and blood flow (p = 0.001). With multivariate analysis, five independent variables (histological type, PR status, ALN-US shape, CMD, and blood flow) were integrated into the nomogram (C-statistic 0.714 [95% CI: 0.688-0.740]) and validated internally (0.816 [95% CI: 0.784-0.849]) and externally (0.942 [95% CI: 0.918-0.966]), with good predictive accuracy and clinical applicability. CONCLUSION: This nomogram could be a direct and reliable tool for individual preoperative evaluation of SLN status, and therefore aids decisions concerning ALN dissection and adjuvant treatment.

Role of Ultrasound Lung Comets in the Diagnosis of Acute Heart Failure in Emergency Department: A Systematic Review and Meta-analysis.

OBJECTIVE: A new technique of transthoracic lung ultrasonography (TLS) has emerged and demonstrated promising results in acute heart failure diagnosis at an early stage. However, the diagnostic value of ultrasound lung comets (ULCs) for acute heart failure (AHF) performed in busy emergency department (ED) is uncertain. The present meta-analysis aimed to assess the diagnostic efficiency of ULCs in AHF. METHODS: We conducted a search on online journal databases to collect the data on TLS performed for diagnosing AHF published up to the end of July 2017. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (SROC) curve were calculated. The post-test probability of AHF was calculated by using Bayes analysis. RESULTS: We enrolled a total of 15 studies involving 3,309 patients. The value of sensitivity, specificity, PLR, NLR, DOR, area under the SROC curve, and Q* index was 85%, 91%, 8.94, 0.14, 67.24, 0.9587, and 0.9026, respectively. We detected significant heterogeneity among included studies, and therefore, all these results were analyzed under the random-effect model. We also explored possible sources of heterogeneity among the studies by using meta-regression analysis. Results suggest that the time interval between patient's admission to bedside TLS examination was closely related to TLS accuracy. CONCLUSION: This meta-analysis demonstrated that detecting ULCs is a convenient bedside tool and has high accuracy for early AHF diagnosis in ED. TLS could be recommended to be applied for early diagnosis of AHF in ED.

Primary advanced esophago-gastric melanoma: A rare case.

Primary esophageal or gastric melanoma is a very rare disease with early metastasis. Due to its atypical symptom and less efficiency of chemotherapy and radiotherapy, the prognosis of esophageal or gastric melanoma is still very poor. Surgical resection remains the preferential treatment for esophageal or gastric melanoma. Here we present an extremely rare case of primary advanced esophago-gastric melanoma. Debulking surgery was performed without chemotherapy or radiotherapy. However, abdominal recurrence and hepatic metastases were found within one month by a postoperative follow-up computed tomography. Three and a half months after surgical resection, the patient died of extensive abdominal metastasis.

[Characteristics of real-life glucose profiles monitored by continuous glucose monitoring system in persons with normal glucose tolerance].

OBJECTIVE: To decipher the characteristics of real-life glucose profiles in normal glucose tolerance (NGT) persons by continuous glucose monitoring system (CGMS). METHODS: Forty NGT subjects confirmed by oral glucose tolerance test (OGTT) completed a 3-day period of glucose monitoring via CGMS. RESULTS: The values of 24 h mean blood glucose (MBG), standard deviation of MBG (SDBG), mean amplitude of glycemic excursions (MAGE), largest amplitude of glycemic excursions (LAGE) and means of daily differences (MODD) were 6.0 ± 0.7, 0.9 ± 0.1, 1.9 ± 0.8, 2.9 ± 1.4 and 1.1 ± 0.1 mmol/L respectively. Two of them experienced asymptomatic hypoglycemia defined as glucose concentration < 2.8 mmol/L. And 72.5% (29/40) subjects reached glucose concentrations > 7.8 mmol/L for 5.2 ± 4.6 hours. In addition to higher glucose concentration (FPG: 5.0 ± 0.4 vs 4.8 ± 0.3 mmol/L, MBG: 6.4 ± 0.7 vs 5.7 ± 0.5 mmol/L), the subjects with glucose concentrations > 7.8 mmol/L showed more dramatic glucose excursion represented by higher SDBG (1.1 ± 0.3 vs 0.6 ± 0.2 mmol/L), MAGE (2.3 ± 1.1 vs 1.1 ± 0.3 mmol/L), LAGE (3.3 ± 1.2 vs 2.0 ± 1.0 mmol/L) and MODD (1.2 ± 0.4 vs 0.9 ± 0.3 mmol/L) versus those with glucose concentrations within 7.8 mmol/L. CONCLUSION: CGMS provides more detailed information of real-life glucose profiles in NGT subjects. And 72.5% NGT subjects in the present study spent a considerable amount of time at pre-diabetic or even diabetic glucose levels characterized by more predominant glucose excursion.

Inhibition of PDGF, TGF-ß, and Abl signaling and reduction of liver fibrosis by the small molecule Bcr-Abl tyrosine kinase antagonist Nilotinib.

BACKGROUND & AIMS: Nilotinib is a novel tyrosine kinase inhibitor of Bcr-Abl and other kinases. In this study, we have examined its activity as an anti-fibrotic agent. METHODS: The in vitro effect of Nilotinib on rat and human HSCs was assessed using proliferation assays and Western blotting. The in vivo antifibrotic efficacy of Nilotinib was assessed in mice with liver fibrosis induced by CCl(4) and bile duct ligation (BDL). RESULTS: Nilotinib inhibited proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. Nilotinib induced apoptosis of HSCs, which was correlated with reduced bcl-2 expression, increased p53 expression, cleavage of PARP, as well as increased expression of PPARγ and TRAIL-R. Nilotinib also induced cell cycle arrest, accompanied by increased expression of p27 and downregulation of cyclin D1. Interestingly, Nilotinib not only inhibited activation of PDGFR, but also TGFRII through Src. Nilotinib significantly inhibited PDGF and TGFß-simulated phosphorylation of ERK and Akt. Furthermore, PDGF- and TGFß-activated phosphorylated form(s) of Abl in human HSCs were inhibited by Nilotinib. In vivo, Nilotinib reduced collagen deposition and α-SMA expression in CCl(4) and BDL-induced fibrosis. These beneficial effects were associated with suppressed expression of procollagen-(I), TIMP-1, CD31, CD34, VEGF, and VEGFR. Nilotinib could induce HSC undergoing apoptosis in vivo, which was correlated with downregulation of bcl-2. We also observed reduced expression of phosphorylated ERK, Akt, and Abl in the Nilotinib-treated CCl(4) and BDL livers. In addition to its antifibrotic activity, the drug was hepatoprotective and reduced the elevations of ALT and AST after CCl(4) and BDL. CONCLUSIONS: These studies uncover a novel role of Bcr-Abl activity in treatment of liver fibrosis through multiple mechanisms and indicate that Nilotinib represents a potentially effective antifibrotic agent.

[Cost-effectiveness analysis on continuous subcutaneous insulin infusion and multi-point daily insulin injections in the treatment program of type 2 diabetes].

OBJECTIVE: To observe the cost-effectiveness of using continuous subcutaneous insulin infusion (CS II) and multi-point daily insulin injections (MDI) in controlling blood sugar in the newly hospitalized type 2 diabetes patients. METHODS: Retrospective analysis on 86 cases taking CS II and 103 cases using MDI on a 'blood sugar control program' among the newly hospitalized patients with type 2 diabetes. The period for observation was 2 weeks, using cost-effectiveness analysis methods to evaluate the two treatment programs. RESULTS: After two weeks of treatment, the effectiveness in the control of blood sugar in CS II group was similar to the MDI group, with no significant difference (P<0.05) and the adverse reactions were similar. Costs in the CS II program (Yuan/person) was less than in the MDI program (1478.34 vs. 1620.46), with significant differences (P< 0.05). The cost-effectiveness ratios (C/E) were 15.07 in the CS II group, and 16.34 in the MDI group, with no significant difference (P>0.05). In order to further reduce the cost of CS II group as a reference, the incremental cost-effectiveness ratio (DeltaC/DeltaE) of the MDI group was 129.20. CONCLUSION: Costs-effective of the CS II program was better than the MDI one in treating the newly hospitalized patients with type 2 diabetes, suggesting that CS II program might be a better choice for hospitals to carry on an intensive insulin therapy program.

[Effects of leptin on RAAS and nitric oxide production in isolated rat glomeruli].

OBJECTIVE: To investigate the changes in angiotensinogen (AGT), angiotensin II type 1 receptor (AT(1)R), endothelial nitric oxide synthase (eNOS) mRNA and protein expressions and nitric oxide (NO) content in the rat glomeruli in response to leptin stimulation. METHODS: The glomeruli isolated from male SD rats were stimulated with 3 nmol/L leptin for 2 h. Real-time PCR and Western blotting were performed to analyze the mRNA and protein expressions of AGT, AT(1)R and eNOS in the glomeruli, and nitrite concentration in the glomeruli was measured by nitrate reductase assay. RESULTS: In comparison with the control group, exposure to leptin increased the mRNA levels of AGT, ATR(1) and eNOS in the isolated glomeruli by 2.69-/+0.17, 3.77-/+0.16 and 2.56-/+0.29 folds (P=0.024, 0.018 and 0.044), and their protein levels by 2.06-/+0.10, 2.67-/+0.08 and 1.61-/+0.13 folds (P=0.021, 0.015 and 0.032), respectively. The NO production in the glomeruli was also increased by 2.77-/+0.14 folds (P=0.000) following leptin exposure. CONCLUSION: Leptin exposure of isolated rat glomeruli directly causes activation of the internal renal renin-angiotensin system and enhanced NO production, suggesting that leptin plays a role in the pathogenesis of maladaptation in renal hemodynamics in obesity.

[Renal protective effects of sulodexide in diabetic rats and its anti-oxidative mechanism].

OBJECTIVE: To investigate the renal protective effects of sulodexide and its anti-oxidative stress mechanism in diabetic rats. METHOD: Thirty male SD rats were randomized into 3 equal groups, namely the control group, diabetic group, and sulodexide treatment group. Twelve weeks after establishment of rat diabetic models and administration of sulodexide, the rats were sacrificed for measurement of the urine volume, body mass, kidney mass/body weight ratio, plasma glucose, and glycosylated hemoglobin (HbA1c). Malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) activities in the renal tissue or serum were tested. Electron microscopy was performed to observe the pathological changes in the kidneys. RESULTS: The urine volume, renal mass/body mass ratio, serum glucose, HbA1C, and serum and renal MDA levels all significantly increased in the diabetic rats in comparison with the normal controls (P<0.05). But the body weight and activities of SOD, CAT, and GSH-PX in the renal tissue in the normal control group were significantly higher than those in the diabetic and sulodexide group. After 12 weeks of sulodexide treatment, SOD, CAT, and GSH-PX activities in the renal tissue of rats were significantly increased in comparison with those in the diabetic rats (P<0.05). Electron microscopy showed obvious irregular thickening of the glomerular capillary basement membrane in the diabetic group with vacuolization in the mitochondria in the epithelial cells, and such pathological changes were significantly alleviated in the sulodexide treatment group. CONCLUSIONS: Sulodexide can effectively lower the urinary albumin excretion rate, improve the ultrastructural renal pathologies and prevent glomerular basement membrane thickening in diabetic rats, probably in association with the reduction of the MDA levels and enhancement of SOD, CAT, and GSH-PX activities.