A retrospective study: exploring preoperative hyponatremia in elderly patients with hip fractures.

BACKGROUND: This research aims to examine the frequency, age-related distribution, and intensity of preoperative hyponatremia among elderly individuals with hip fractures. This study aims to provide valuable insights into the diagnosis of preoperative hyponatremia in this patient population. METHODS: This research involved the analysis of clinical data obtained from 419 elderly individuals with hip fractures (referred to as the fracture group) and 166 elderly individuals undergoing routine health examinations (designated as the control group). A comprehensive comparison was conducted, examining baseline characteristics such as age, gender, and comorbidities between these two groups. We further investigated variations in the incidence rate of hyponatremia, age distribution, and the severity of hyponatremia. Additionally, a subgroup analysis compared patients with femoral neck fractures to those with intertrochanteric femur fractures, specifically examining the incidence rate and severity of hyponatremia in these distinct fracture types. RESULTS: The incidence of cerebrovascular disease was found to be higher in the fracture group as compared to the control group in our research. Nevertheless, no significant differences in general health and other comorbidities were observed between the two groups. Notably, the fracture group exhibited a greater preoperative prevalence of hyponatremia, with its severity increasing with age. Furthermore, among elderly patients with intertrochanteric femur fractures, the incidence of preoperative hyponatremia was not only higher but also more severe when compared to those with femoral neck fractures. CONCLUSION: Elderly individuals experiencing hip fractures exhibit a notable prevalence of preoperative hyponatremia, predominantly mild to moderate, with an escalating occurrence linked to advancing age. This phenomenon is especially conspicuous among patients with intertrochanteric fractures, warranting dedicated clinical scrutiny. The administration of sodium supplementation is advisable for the geriatric demographic as deemed necessary. Addressing hyponatremia becomes crucial, as it may play a role in the etiology of hip fractures in the elderly, and rectifying this electrolyte imbalance could potentially serve as a preventive measure against such fractures.

Primary sigmoid squamous cell carcinoma with liver metastasis: A case report.

BACKGROUND: The pathological type of simple squamous carcinoma in colorectal malignancies is rare. Simple squamous cell carcinoma of the colorectum occurs most frequently in the rectum. The clinicopathological features and biological behaviors of squamous colorectal carcinoma are unclear, and its prognosis may be worse than that of simple adenocarcinoma. Studies on squamous colorectal cancer are currently limited to case reports, and there is no standard treatment protocol. Therefore, more case reports are required to fully understand squamous colorectal cancer. CASE SUMMARY: We reported the case of a 56-year-old woman who complained of constipation for 2 years. Colonoscopy revealed a sigmoid colon tumor, and the pathological result of colonoscopy was squamous carcinoma. After completing the relevant assessment, the patient was clinically diagnosed with cT4aN0M0, stage IIB, and surgery was performed. Based on postoperative pathological results, the patient was diagnosed with pT4bN0M0, stage IIC. Six cycles of adjuvant chemotherapy were administered after surgery. Liver metastasis and abdominal wall mass were found more than 1 mo after the end of the last chemotherapy session. Targeted local treatment was not performed because the liver had multiple metastases, but I125 particle implantation of the abdominal wall mass was performed. Two cycles of first-line chemotherapy were administered after the surgery. The patient underwent 14 mo of treatment and eventually died from the tumor. CONCLUSION: Squamous carcinoma of sigmoid colon is a rare tumor with unclear pathogenesis. Its clinicopathological diagnosis should be paid close attention.

EGFR tyrosine kinase inhibitors alone or in combination with chemotherapy for non-small-cell lung cancer with EGFR mutations: A meta-analysis of randomized controlled trials.

OBJECTIVE: The objective of this study was to perform a meta-analysis comparing the efficiency of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with chemotherapy to EGFR TKI treatment alone in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Following keyword queries in databases and identification of randomized control trials for inclusion, hazard ratios (HRs), relative risks (RRs), and associated 95% confidence intervals (95% CIs) were determined. RESULTS: Ten randomized controlled trials involving 1354 participants with NSCLC were evaluated. We found that a combined approach of chemotherapy with EGFR TKIs significantly improved overall survival (OS) compared with EGFR TKI alone in our patient cohort (HR = 0.47, 95% CI = 0.31-0.72). In addition, a higher overall response rate (ORR) was found for patients who received combined treatment compared to chemotherapy alone (RR = 2.17, 95% CI = 1.51-3.12). Furthermore, concomitant use of chemotherapy with TKIs significantly improved the progression-free survival (PFS) when compared to the use of TKIs alone (HR = 0.68, 95% CI = 0.49-0.95). Moreover, there was a higher ORR among patients who received combined treatment as compared to those who were managed using TKIs only (RR=1.17, 95%CI=1.09-1.25). CONCLUSION: Our meta-analysis shows that EGFR TKIs with chemotherapy confer better OS and ORR compared to either treatment alone, similarly, the combined treatment showed better PFS and ORR profiles than the use of TKI alone.

Prognostic value of ribonucleotide reductase subunit M1 (RRM1) in non-small cell lung cancer: A meta-analysis.

BACKGROUND: Ribonucleotide reductase subunit 1 (RRM1) is a potential prognostic factor for non-small cell lung cancer (NSCLC). This study evaluates prognostic value of RRM1 in NSCLC patients by meta-analyzing outcomes reported in literature. METHOD: Data were acquired from research articles retrieved after literature search in online databases. Random effects meta-analyses were conducted by pooling hazard ratios (HR). Meta-analyses of standardized mean differences (SMD) were used to evaluate overall survival (OS) and progression-free survival (PFS) between low and high RRM1 expression groups. Metaregression analyses were conducted to evaluate the factors that could affect prognostic relationship of RRM1 with treatment and survival outcomes. RESULTS: 23 studies (3148 patients) were included. RRM1 expression was not meaningfully associated with prognosis of NSCLC even when the reference (HR = 1) was either low RRM1 expression (0.918 [95% CI 0.833, 1.003]) or high RRM1 expression (0.834 [0.625, 1.043]). OS was significantly longer in low RRM1 expression group compared to high RRM1 expression group (SMD 0.73 [0.36, 1.09]; P < 0.0001). PFS was not significantly different between low and high RRM1 expression groups (SMD 0.08 [-0.29, 0.45]; p = 0.68). Age was inversely associated with HR (p = 0.001) even when reference was low RRMI (p = 0.027) or high RRM1 (p = 0.006). Age was positively associated with OS in both low and high RRM1 groups. CONCLUSION: In meta-analysis of studies which used gemcitabine-based therapies, higher RRM1 expression is found to associated with shorter OS but not PFS. HR depicting relationship between RRM1 expression and OS/PFS/treatment response could not demonstrate a prognostic role of RRM1 in NSCLC patients.

Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi­1 leukemia cells.

Histone deacetylase (HDAC) inhibitors have been reported to inhibit tumor angiogenesis via the downregulation of angiogenic factors. Our previous in vitro studies demonstrated that valproic acid (VPA) exerted antitumor effects on Kasumi­1 cells, which are human acute myeloid leukemia cells with an 8;21 chromosome translocation. In the present study, the effects of VPA on tumor angiogenesis were investigated in mice transplanted with Kasumi­1 cells. Semi­quantitative reverse transcription­polymerase chain reaction, western blotting and immunohistochemistry were used to detect the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR2) and basic fibroblast growth factor (bFGF). The tumor microvessel density was measured following staining with an anti­CD34 antibody. Chromatin immunoprecipitation was used to study the effect of VPA­induced histone hyperacetylation on VEGF transcription. An intraperitoneal injection of VPA inhibited tumor growth and angiogenesis in mice transplanted with Kasumi­1 cells. The mRNA and protein expression of VEGF, VEGFR2 and bFGF were inhibited by VPA treatment. In addition, VPA downregulated HDAC, increased histone H3 acetylation and enhanced the accumulation of hyperacetylated histone H3 on the VEGF promoters. The findings of the present study indicate that VPA, an HDAC inhibitor, exerts an antileukemic effect through an anti­angiogenesis mechanism. In conclusion, the mechanism underlying VPA­induced anti­angiogenesis is associated with the suppression of angiogenic factors and their receptors. VPA may increase the accumulation of acetylated histones on the VEGF promoters, which possibly contributes to the regulation of angiogenic factors.

[Effect of valproic acid against angiogenesis of Kasumi-1 xenograft tumor in nude mice].

This study was aimed to investigate the effect of valproic acid (VPA), a histone deacetylase inhibitor, on angiogenesis of acute myeloid leukemia in vivo and vitro, and to explore its molecular mechanism. Human t (8;21) AML cell line Kasumi-1 cells were treated with VPA at different concentration for 3 d, the mRNA and protein expression levels of Ang1 and Ang2 were determined by semi-quantitative RT-PCR and Western blot respectively. Nude mice model with xenograft Kasumi-1 tumor was established by subcutaneous inoculation of Kasumi-1 cells. The CD34, Ang1 and Ang2 protein levels were analyzed by immunohistochemistry method. The mRNA and protein expression levels of Ang1, Ang2 and VEGF were determined by semi-quantitative RT-PCR and Western blot. The results showed that in vitro, VPA at 3 mmol/L downregulated the Ang mRNA relative expression level for Ang1 from 0.360 ± 0.116 to 0.040 ± 0.008, Ang2 from 0.540 ± 0.049 to 0.146 ± 0.038. The animal experiment further verified that VPA 500 mg/kg, ip, for 14 d, reduced the relative expression of Ang1, Ang2 and VEGF mRNA and proteins in Kasumi-1 tumor of nude mice, and reduced microvascular density in xenograft tumor of nude mice (8.470 ± 0.300 vs 2.600 ± 0.200). It is concluded that VPA significantly inhibits tumor angiogenesis through the regulation of angiopoietins, thereby inhibits the proliferation and metastasis of leukemia cells.

[Effects of histone deacetylase inhibitor on the expression of angiogenesis related factors in Kasumi-1 leukemic cell line].

OBJECTIVE: To investigate the effects of two histone deacetylase (HDAC) inhibitors, valproic acid (VPA) and TSA, on the expression of vascular endothelial growth factor (VEGF) and its receptor KDR of the leukemia cell line Kasumi-1 cells, and to explore their potential mechanism in leukemia angiogenesis. METHOD: Kasumi-1 cells were treated with VPA and TSA at different concentrations for 3 days. The mRNA and protein expression levels of VEGF and KDR were determined by semi-quantitative RT-PCR and Western blot, and the bFGF mRNA by semi-quantitative RT-PCR. RESULTS: As compared with that of control groups, VPA at 3 mmol/L downregulated the VEGF mRNA expression level for VEGF(121) from 0.632 ± 0.014 to 0.034 ± 0.004 and for VEGF(165) from 0.526 ± 0.021 to 0.015 ± 0.001, for KDR mRNA from 0.258 ± 0.034 to 0.038 ± 0.000, and for bFGF mRNA from 0.228 ± 0.017 to 0.086 ± 0.015. TSA downregulated the VEGF mRNA and KDR mRNA at concentration of 100 nmol/L, but its effect on bFGF mRNA only at higher concentration. CONCLUSION: HDAC inhibitors might inhibit the leukemia angiogenesis by regulating the expression of VEGF and its recptor.

[Reversed effect of valproic acid on transcription inhibition of AML1-ETO fusion protein of kasumi-1 leukemic cell line].

This study was aimed to investigate the mechanism of histone deacetylase (HDAC) inhibitor, valproic acid (VPA), reversing transcription inhibition of AML1-ETO fusion protein in Kasumi-1 cell line. The mRNA expressions of AML1-ETO, AML1 and cyclin D2 were detected by semi-quantitation RT-PCR after treating kasumi-1 cells with VPA at different doses/and different time points. The results indicated that the mRNA expression of AML1-ETO showed no obvious change, when kasumi-1 cells were treated with VPA. Compared with control group, the expression level of AML1 mRNA significantly increased in a dose-dependent manner. Compared with control group, the expression level of cyclin D2 mRNA significantly decreased when kasumi-1 cells had been treated with 3 mmol/L VPA as well as kasumi-1 cells were treated with different concentrations of VPA for 3 days. In conclusion, VPA could remove transcription inhibition of AML1-ETO fusion protein, increase transcription of AML1 and down-regulate mRNA expression of AML1 target gene cyclin D2 through HDAC inhibiting activity.

[Inhibitory effect of valproic acid on cell cycle of Kasumi-1 cell line and its mechanism].

OBJECTIVE: To investigate the influence of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on cell cycle of Kasumi-1 cells, and explore its molecular mechanism. METHODS: Kasumi-1 cells were treated with VPA at different concentration and different time cell cycle changes were analyzed by flow cytometry. Cyclin D1 and p21(WAF1/CIP) gene, a cyclin-dependent kinase inhibitor, were determined by semi-quantitative RT-PCR and Western blot. RESULTS: (1) VPA blocked the Kasumi-1 cells in G(0)/G(1) phase. (2) Compared with control group, 3 mmol/L VPA treated Kasumi-1 cells for different times caused their mRNA expression of cyclin D1 decreased. Treated with VPA at different concentration for 3 days, the mRNA expression decreased in a dose-dependent manner. (3) VPA induced p21(WAF1/CIP) mRNA expression increased in a time- and dose-dependent manner. The p21(WAF1/CIP) protein increased with increasing concentration of VPA at day 3. The p21(WAF1/CIP) protein significantly increased with 3 mmol/L VPA treatment for 2 d (2.498 +/- 0.240). CONCLUSION: VPA can arrest Kasumi-1 cell in G(0)/G(1) phase through the regulation of cyclin D1 and p21(WAF1/CIP).