Predictive Value of Pretreatment Neutrophil to Albumin Ratio in Response to Neoadjuvant Chemotherapy of Breast Cancer.

Background: The immune system appears to play a crucial role in how breast cancer responds to chemotherapy. In this study, we investigated a peripheral marker of immune and inflammation named the neutrophil to albumin ratio (NAR) to explore its potential relationship with pathological complete response (pCR) in locally advanced breast cancer patients who underwent neoadjuvant chemotherapy (NAC). Methods: We conducted a retrospective analysis of 212 consecutive breast cancer patients who received NAC. The NAR was calculated by examining the complete blood cell count and albumin level in peripheral blood before starting NAC. Through ROC curve analysis, we determined the optimal cutoff value for NAR as 0.0877. We used Pearson's chi-square test or Fisher's exact test to evaluate the relationship between NAR and pCR, as well as other clinical and pathological characteristics. Logistic regression models were employed for univariate and multivariate analyses. Results: The results of both univariate and multivariate logistic regression analyses showed that NAR was associated with tumor pathological regression. The NAR high group had a higher pCR rate compared to the NAR low group (OR 3.127 [95% CI 1.545-6.328]; p = 0.002). Conclusion: According to this study, it was observed that patients with breast cancer who had high levels of NAR were more likely to achieve pCR when undergoing NAC.

KLF11 promotes the proliferation of breast cancer cells by inhibiting p53-MDM2 signaling.

Abnormal Krüppel-like factor 11 (KLF11) expression is frequently found in tumor tissues and is associated with cancer prognosis, but its biological functions and corresponding mechanisms remain elusive. Here, we demonstrated that KLF11 functions as an oncoprotein to promote tumor proliferation in breast cancer cells. Mechanistically, at the transcription level, KLF11 decreased TP53 mRNA expression. Notably, KLF11 also interacted with and stabilized MDM2 through inhibiting MDM2 ubiquitination and subsequent degradation. This increase in MDM2 in turn accelerated the ubiquitin-mediated proteolysis of p53, leading to the reduced expression of p53 and its target genes, including CDKN1A, BAX, and NOXA1. Accordingly, data from animals further confirmed that KLF11 significantly upregulated the growth of breast cancer cells and was inversely correlated with p53 expression. Taken together, our findings reveal a novel mechanism for breast cancer progression in which the function of the tumor suppressor p53 is dramatically weakened.

Analysis of risk factors for carotid intima-media thickness in patients with type 2 diabetes mellitus in Western China assessed by logistic regression combined with a decision tree model.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes (T2DM). Carotid intima-media thickness (CIMT) is considered a preclinical stage of atherosclerosis. Therefore, it is necessary to identify the related risk factors for CIMT to facilitate the early prevention of CVD. Previous studies have shown that visceral fat area (VFA) is a risk factor for T2DM and CVD. However, few studies have focused on the effects of VFA on CIMT associated with T2DM. Moreover, considering that the body fat distribution shows regional and racial heterogeneity, the purpose of this study was to investigate the predictive value of VFA and other risk factors for CIMT associated with T2DM in Western China. METHODS: In a cross-sectional study, a total of 1372 patients with T2DM were divided into the CIMT (-) group (n = 965) and the CIMT (+) group (n = 407) based on CIMT values. In addition to the univariate analyses, logistic regression analysis and a decision tree model were simultaneously performed to establish a correlation factor model for CIMT. RESULTS: Univariate analyses showed that sex, smoking status, age, heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), height, weight, body mass index (BMI), waist circumference, hip circumference, waist-hip ratio, VFA, subcutaneous fat area, and the levels of 2-h C-peptide, serum creatinine, urea nitrogen and uric acid were significantly different between the two groups (all p < 0.05). Smoking, increased VFA, female sex and increased BMI were risk factors in the logistic regression analyses (OR = 5.759, OR = 1.364, OR = 2.239, OR = 1.186, respectively). In the decision tree model, smoking was the root node, followed by sex, waist circumference, VFA and chronic kidney disease (CKD) in order of importance. CONCLUSIONS: In addition to smoking, sex and BMI, VFA has a significant effect on CIMT associated with T2DM in the Chinese Han population in Western China. In addition, the decision tree model could help clinicians make more effective decisions, with its simplicity and intuitiveness, making it worth promoting in future medical research.Trial registration ChiCTR, ChiCTR1900027739. Registered 24 November 2019-Retrospectively registered, http://www.chictr.org.cn/index.aspx.

Hypoparathyroidism with Fahr's syndrome: A case report and review of the literature.

BACKGROUND: Hypoparathyroidism with basal ganglia calcification is clinically rare. Here, we report a case of Fahr's syndrome due to hypoparathyroidism and review the literature in terms of etiology, clinical manifestation, diagnosis, and treatment. CASE SUMMARY: A 62-year-old man experienced repeated twitching of both hands in recent 10 years. On July 28, 2017, the patient was admitted to our hospital due to slow response and speech difficulties. On medical examinations, he had a positive Chvostek sign, while no Albright's hereditary osteodystrophy signs or history of neck surgery or radiation, and his family members had no similar medical history. Laboratory examinations revealed hypocalcemia, hyperphosphatemia, and low parathyroid hormone (PTH) levels. Computed tomography revealed basal ganglia calcification. Based on these investigations, a diagnosis of Fahr's syndrome due to hypoparathyroidism was suggested. After receiving intravenous calcium gluconate to relieve symptoms, the patient continued to take oral calcium carbonate and calcitriol for treatment. CONCLUSION: The possibility of hypoparathyroidism should be considered in patients with chronic hypocalcemia, recurrent tetany, and even neuropsychiatric symptoms. Hypoparathyroidism is a common cause of basal ganglia calcification. Therefore, it is recommended that blood calcium, phosphorus, and PTH levels should be measured in all individuals with basal ganglia calcification to exclude hypoparathyroidism.

Infliximab ameliorating depression-like behavior through inhibiting the activation of the IDO-HAAO pathway mediated by tumor necrosis factor-α in a rat model.

In recent years, some studies have suggested that the activation of inflammatory system plays a role in the occurrence of depression. Tumor necrosis factor-α (TNF-α), as one of the preinflammatory cytokines, has been reported to be involved in the occurrence of various diseases including depression. Infliximab, an antagonist of TNF-α, is usually used to treat some autoimmune diseases such as Crohn's disease and can perhaps be used to treat other diseases. In this study, the antidepressant effect and a possible mechanism of infliximab were investigated by studying the depression-like behavior and expression of TNF-α, indoleamine 2, 3-dioxygenase (IDO), and 3-hydroxyl amino acid oxygenase (HAAO) from the cortex and hippocampus in rat exposed to chronic unpredicted stress. Forty male Sprague-Dawley rats were divided into a control group (CG), an infliximab-treated control group, a model group (MG), and an infliximab-treated model group (IFXM). Infliximab (5 mg/kg once week) was administered to the infliximab-treated control group and IFXM rats by an intraperitoneal injection, whereas an equivalent volume of vehicle was administered to CG and MG rats. Rat behaviors and the expression of TNF-α, IDO, and HAAO in the cortex and hippocampus were determined. It was found that a significant relief in depression-like behaviors was observed with a downregulation of TNF-α, IDO, and HAAO expression in the IFXM rats compared with MG rats. The results show the antidepressant effect of infliximab and suggest that its mechanism is partly related to inhibition of IDO-HAAO pathway activation mediated by TNF-α in rat brain.

Characterization and resistance mechanisms of cisplatin-resistant human hepatocellular carcinoma cell line.

OBJECTIVE: To study the biological characteristics and resistant mechanisms of the cisplatin-resistant human hepatocellular carcinoma (HCC) cell line. METHODS: The study took place in the Department of Pharmacology, Chongqing Medical University, Chongqing, China, between April 2005 and November 2007. A resistant HCC cell line (QGY/CDDP) was established by stepwise increasing cisplatin (CDDP) concentration and intermittent administration. Drug-chemo sensitivity was detected by 3-4,5-dimethylthiazol-2yl-2,5- diphenyltetrazolium bromide (MTT) assay. Cell doubling time was determined by cell counting, and cell cycle analysis was performed by flow cytometric (FCM) assay. Intracellular platinum accumulation was detected by atomic absorption spectrometry and the expression of P-glycoprotein (P-gp) and glutathione S-transferase-pi (GST-pi) were analyzed by FCM assay. RESULTS: QGY/CDDP cell line was established after 3 months with stable resistance to CDDP and exhibited cross-resistance to many other chemotherapeutic agents. Compared with parental cell line, cell doubling time of QGY/CDDP prolonged; and the cell proportion decreased in S and G2/M-phase and increased in G0/G1-phase. In QGY/CDDP cells, intracellular platinum accumulation decreased and GST-pi expression increased, but P-gp expression kept stable. CONCLUSION: QGY/CDDP cell line shows the typical and stable resistant phenotype and characteristics of resistant cells. Its mechanisms of resistance to CDDP may be mediated by reduced accumulation of intracellular platinum and higher GST-pi expression, but it is not associated with P-gp expression.

[Morphological study of severe acute respiratory syndrome (SARS)].

OBJECTIVE: Seven cases of autopsy from SARS patients are studied to investigate the pathogenesis and the pathologic changes of the major organs. METHODS: Detailed gross and microscopic examination of the autopsy specimen is performed, including lung, heart, liver, kidney, spleen and lymph nodes. RESULTS: All of the lungs are markedly enlarged and consolidated. Microscopically, pulmonary edema is a prominent finding, especially at the early stage of the disease (5 days after the onset). The alveolar spaces are filled with fibrinous exudates and lined with hyaline membrane. In 5 cases that undergo over 3 weeks of the course, the main pattern is organization of intra-alveolar deposit, along with fibroblastic proliferation in the alveolar septa, which leads to obliteration of alveolar space and pulmonary fibrosis. All of the lungs show bronchopneumonia, scattered hemorrhage, and proliferation of alveolar epithelial cells with desquamation. Microthrombi are seen in 6 cases. Fungal infection is noted in 2 cases. One of them is disseminative, involving bilateral lungs, heart, and kidney; the other one is diagnosed in hilar lymph nodes. In immune system, hilar and abdominal lymph nodes are usually congested and hemorrhagic, with depletion of lymphocytes, and accompanied with subcapsular sinus histiocytosis. One of the cases shows enlargement of abdominal lymph nodes, which have reduced number of germinal centers. Spleen exhibits atrophy of white pulps, and even lost of white pulps in some areas. The red pulp is markedly congested and hemorrhagic. In 5 cases, cardiomegale is prominent. Thrombosis (2 cases), focal myocarditis (1 case), and fungal myocarditis (1 case) are observed. In addition, liver shows massive necrosis (1 case) and nodular cirrhosis (1 case). CONCLUSIONS: Lung is the major organ affected by SARS, demonstrated as diffuse alveolar damage. It is postulated that viral infection induces severe damage of alveolar epithelial and capillary endothelial cells, leads to pulmonary edema, intra-alveolar fibrin deposit, and hyaline membrane formation. Consequently, intra-alveolar organization and alveolar septal fibrosis causes loss of alveolar spaces, eventually, pulmonary fibrosis and atelectasis. The immune system is often affected, and presented as depletion of lymphoid tissue in lymph nodes and spleen. Secondary infection is a common complication, which should be paid close attention in the management of SARS patients.