Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

Fascia Iliaca Compartment Block for Perioperative Pain Management of Geriatric Patients with Hip Fractures: A Systematic Review of Randomized Controlled Trials.

Background: With continuous increase of the aging population, the number of geriatric patients with fragility hip fractures is rising sharply, and timely surgery remains the mainstay of treatment. However, adequate and effective pain control is the precondition of satisfactory efficacy. This systematic review aimed to summarize the use of fascia iliaca compartment block (FICB) as an analgesic strategy for perioperative pain management in geriatric patients with hip fractures. Methods: PubMed and Embase databases were searched for English published randomized controlled trials (RCTs) reporting application of FICB for pain control of the older adults with hip fractures between January 1st, 2000, and May 31st, 2020. The modified Jadad scale was used to evaluate quality of the RCTs included. Primary outcomes of the eligible RCTs were presented and discussed. Results: A total of 27 RCTs with 2478 cases were included finally. The present outcomes suggested, after admission or in the emergency department (ED), FICB can provide patients with equal or even better pain relief compared with the conventional analgesia methods, which can also reduce additional analgesic consumptions. While, before positioning for spinal anesthesia (SA), FICB is able to offer superior pain control, facilitating SA performance, after surgery FICB can effectively alleviate pain with decreased use of additional analgesics, promoting earlier mobilization and preventing complications. Conclusions: FICB is a safe, reliable, and easy-to-conduct technique, which is able to provide adequate pain relief during perioperative management of geriatric patients with hip fractures.

Clinical characteristics, treatment, and prognosis of squamous cell carcinoma arising from extremity chronic osteomyelitis: a synthesis analysis of one hundred and seventy six reported cases.

PURPOSE: Squamous cell carcinoma (SCC) arising from extremity chronic osteomyelitis (COM) has not been well-understood due to its low prevalence. This study aimed to synthesize the cases recently published to clarify their clinical characteristics, treatment, and prognosis. METHODS: PubMed, Embase, and Cochrane Library databases were searched for English literature reporting cases diagnosed of SCC originating from extremity COM between January 1, 1990, and September 30, 2019. The National Institutes of Health (NIH) assessment tool was used to evaluate the quality of reports included, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to summarize the quality of available evidence. The data synthesized for analysis were clinical features, treatment strategy, and incidences of local recurrence, metastasis, all-cause, and SCC-related deaths. In addition, potential factors that might have influenced treatment efficacy and prognosis of SCC were also investigated. RESULTS: Included for this analysis were 60 studies of 176 patients (a male-to-female ratio of 6.7). COM mostly occurred following trauma (73%), the tibia was the most frequent site (61%), and a sinus tract was the most common symptom (61%). The mean duration from COM to SCC was 27 years. Positive rate of pathogen culture was 90%, with 73% being polymicrobial. Limb amputation was performed in 80.5% of the patients. Incidences of local recurrence, metastasis after treatment, all-cause, and SCC-related mortalities were 16.7%, 12%, 31.1%, and 12.6%, respectively. Patients with local lymphadenopathy at diagnosis had significantly higher risks of local recurrence (P = 0.01), SCC-related (P = 0.02), and all-cause deaths (P = 0.01) than those without. Patients with moderately-to-poorly differentiated SCC types had significantly higher risks of local recurrence (P = 0.01) and all-cause death (P = 0.02) than those with a well-differentiated type. CONCLUSIONS: SCC arising from extremity COM favoured males and the tibia. Although limb amputation was the mainstay of treatment, the overall incidences of local recurrence, metastasis, and SCC-related death exceeded 10%. Patients with local lymphadenopathy at diagnosis of SCC and those with moderately-to-poorly differentiated SCC types should be followed up closely. TRIAL REGISTRATION: CRD42020154221.

Associations between Interleukin Gene Polymorphisms and Risks of Developing Extremity Posttraumatic Osteomyelitis in Chinese Han Population.

This case-control study aimed to investigate potential associations between interleukin (IL) gene polymorphisms and the risks of developing extremity posttraumatic osteomyelitis (PTOM) in Chinese Han population. Altogether, 189 PTOM patients and 200 healthy controls were genotyped of IL-1α (rs17561, rs1800587), IL-1ß (rs16944, rs1143627, rs1143634, rs2853550), IL-1RN (rs4251961, rs419598, rs315951), IL-4 (rs2243248, rs2243250), IL-6 (rs1800795, rs1800796, rs1800797), IL-8 (rs4073, rs2227306, rs2227307), IL-10 (rs3024491, rs3024496, rs1800871, rs1800872, rs1800896), IL-17A (rs2275913), and IL-17F (rs763780) using the SNaPshot genotyping method. Statistical differences were observed regarding the genotype distributions of rs16944 (P = 0.049) and rs4251961 (P = 0.007) between the patients and healthy controls. In addition, significant associations were found between rs16944 and the risk of PTOM development by dominant (OR = 1.854, P = 0.017), homozygous (OR = 1.831, P = 0.041), and heterozygous (OR = 1.869, P = 0.022) models, and of rs1143627 by dominant (OR = 1.735, P = 0.032) and homozygous (OR = 1.839, P = 0.040) models. Moreover, significant links were also identified between rs4251961 and the susceptibility to PTOM by dominant (OR = 0.446, P = 0.005) and heterozygous (OR = 0.409, P = 0.003) models, and of rs1800796 by dominant (OR = 4.184, P = 0.029), homozygous (OR = 4.378, P = 0.026), and heterozygous (OR = 3.834, P = 0.046) models. The present outcomes demonstrated that rs16944, rs1143627, and rs1800796 associate with increased risks, while rs4251961 links to a decreased risk of PTOM development in Chinese Han population.

Survey and analysis of the nutritional status in hospitalized patients with malignant gastric tumors and its influence on the quality of life.

BACKGROUND/OBJECTIVES: The assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients' quality of life (QOL). METHODS: We reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients. RESULTS: By using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p < 0.001), female (p = 0.007), residence in a village (p = 0.004), a lower level of education (p < 0.001), and self-paying (p < 0.001) were indicated as risk factors of patients with gastric cancer to be suffering from severe malnutrition. There was a negative correlation between PG-SGA and various nutritional parameters (p < 0.05). The quality of life was significantly different in gastric cancer patients with different nutritional status (p < 0.01). CONCLUSION: Malnutrition of hospitalized patients with gastric cancer in China is common and seriously affects the patients' quality of life. The nutritional status should be evaluated in a timely manner and reasonable nutritional intervention should be provided as soon as possible. The PG-SGA was fit for using as a clinical nutrition assessment method, being worthy of clinical application.

IL-11 activated by lnc-ATB promotes cell proliferation and invasion in esophageal squamous cell cancer.

IL-11 exerts important functions involved in tumorigenesis and cancer progression. However, the underlying functional role of IL-11 in esophageal squamous cell cancer (ESCC) is not well known. In this paper, we demonstrated that IL-11 expression was increased in esophageal cancer compared with normal tissues, whereas knockdown of IL-11 could inhibit the proliferation and invasion of Eca109 and KYSE410 ESCC cells. Besides, we found that the stability and expression of IL-11 was regulated by lnc-ATB in Eca109 and KYSE410 ESCC cells. More importantly, we found that knockdown of IL-11 partly abolished lnc-ATB-mediated the proliferation and invasion of Eca109 and KYSE410 ESCC cells. Collectively, these results indicated that IL-11 mediated by lnc-ATB increased the proliferation and invasion of ESCC cells, which may provide a promising therapeutic option for suppressing ESCC progression.

Determinants and nutritional assessment value of hand grip strength in patients hospitalized with cancer.

BACKGROUND AND OBJECTIVES: Hand grip strength (HGS) has emerged as a predictor of the nutritional status. However, many factors may modify the malnutrition-HGS association. This study explored the nutritional assessment value and determinants of HGS in patients hospitalized with cancer. METHODS AND STUDY DESIGN: In this multicenter, retrospective, observational study (11,314 patients), the Receiver operator characteristic curve was used to observe HGS and nutritional status sensitivity/specificity. Sex; age; height; weight; mid-upper arm circumference (MAMC); Patient-Generated Subjective Global Assessment (PG-SGA) score; Karnofsky score; physical function (PF) domain; cognitive function (CF) domain; global health and quality of life (QL) domain of EORTC QLQ-C30 (a quality of life instrument designed by the European Organization for Research and Treatment of Cancer); and albumin, prealbumin, and hemoglobin levels were included in a Stepwise analysis model to identify the factors influencing HGS. RESULTS: HGS showed a very low diagnostic value and accuracy for identifying severe malnourishment (area under the curve, 0.615-0.640; p<0.01). HGS positively correlated with sex; height; weight; MAMC; Karnofsky score; QL, PF, and CF domains; and hemoglobin and prealbumin levels (Beta= 0.02-0.42, p<=0.05), and negatively with age (Beta=-0.19, p<0.01). However, the PG-SGA score was excluded because of its very limited contribution to HGS variability. CONCLUSIONS: HGS is a mutifactorial index. The use of HGS cutoff values to identify malnutrition is markedly challenging. Thus, HGS may be of limited use as a predictor of nutritional status.

Repression of DOK7 mediated by DNMT3A promotes the proliferation and invasion of KYSE410 and TE-12 ESCC cells.

Increasing evidence shows that aberrant epigenetic regulation of tumor suppressor genes is a contributing factor to their altered expression in esophageal squamous cell carcinoma (ESCC). In the current study, we investigate the role of DOK7 in ESCC cells. We found that enforced expression of DOK7 inhibited the proliferation and invasion of ESCC cells. We also found that treatment of ESCC cells with the DNA methylation inhibitor, 5-aza-2-deoxycytidine (5-azadC), induced the demethylation of DOK7 in promoter and DOK7 expression. Moreover, silencing DNMT3A decreased methylation of DOK7 and increased DOK7 expression, followed by repressing the proliferation and invasion of ESCC cells. Collectively, our data indicated that silencing DNMT3A inhibits proliferation and invasion in ESCC cells by inducing demethylation of DOK7.

Clinical characteristics of acute lymphoblastic leukemia in male and female patients: A retrospective analysis of 705 patients.

The aim of the present study was to compare the clinical characteristics of acute lymphoblastic leukemia (ALL) that occurred in male and female patients at one institution in Southern China. The medical electronic records of Nanfang Hospital, affiliated to Southern Medical University, were searched for patients with a definite diagnosis of ALL that were diagnosed between January 1, 2001 and December 31, 2012. The clinical data of the patients were collected and analyzed. A total of 705 eligible patients were identified. The gender ratio of male to female patients was 1.84:1. The average ages at the time of diagnosis were 16.43 and 19.54 years for male and female patients, respectively (P=0.007). No significant differences were identified in the seasonal occurrence distribution, blood group distribution or ratio for the presence of the Ph chromosome between males and females. However, a higher incidence of T-cell type ALL was identified in males (P=0.023). The present study reveals that ALL demonstrates a male predominance, but similar clinical characteristics of ALL are present in males and females in Southern China.

Association between MTHFR C677T polymorphism and risk of acute lymphoblastic leukemia: a meta-analysis based on 51 case-control studies.

BACKGROUND: Studies and systematic reviews have reached inconsistent conclusions on the role of 5, 10-methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T in acute lymphoblastic leukemia (ALL) risk. MATERIAL AND METHODS: The present meta-analysis comprising of 51 case-control studies, including 7892 cases and 14 280 controls was performed to reevaluate the association between MTHFR C677T polymorphism and ALL risk. RESULTS: Statistical differences were found in the dominant model (TT+CT vs. CC, odd ratio (OR)=0.89, 95% CI, 0.79-1.00, P=0.04) and the CT vs. CC (OR=0.89, 95% CI, 0.80-1.00, P=0.05), but not in the allele contrast model (T vs. C, OR=0.92, 95% CI, 0.84-1.01, P=0.08), additive model (TT vs. CC, OR=0.87, 95% CI, 0.73-1.05, P=0.15), or recessive model (TT vs. CT+CC, OR=0.94, 95% CI, 0.81-1.10, P=0.44) in overall populations. In the subgroup analyses stratified by age (children and adults) and ethnicity (Asian and Caucasian), no significant associations between MTHFR C677T polymorphism and ALL risk were observed. CONCLUSIONS: The current study found no sufficient evidence of a protective role of MTHFR C677T polymorphism in ALL susceptibility.

Design, synthesis and evaluation of multifunctional salphen derivatives for the treatment of Alzheimer's disease.

A series of salphen derivatives (1-26) have been designed, synthesized, and evaluated as chemical reagents that target and modulate multiple facets of Alzheimer's disease. Most of the compounds exhibit a significant ability to inhibit self-induced and Cu(2+)-induced ß-amyloid (Aß1-42) aggregation, and to function as potential antioxidants and biometal chelators. In particular, the antioxidant activity of compound 2 is 2.6-fold of the trolox value by using the ABTS radical scavenging method, and it also shows a significant ability to inhibit self-induced and Cu(2+)-induced ß-amyloid (Aß1-42) aggregation (70.3%, 20 µM and 85.7%, 50 µM, respectively). Moreover, it is capable of decreasing reactive oxygen species (ROS) induced by Cu(2+)-Aß, shows a good neuroprotective effect in human SH-SY5Y neuroblastoma cells and can cross the blood-brain barrier. In addition, compound 2 retains the activities of antioxidant, anti Aß aggregation and neuroprotection after capturing the metal ions Cu(2+), Fe(3+) and Zn(2+) (its metal complexes 18, 22 and 23). Taken together, these results suggest that compound 2 might be a promising lead compound for AD treatment.

Design, synthesis and evaluation of novel tacrine-(ß-carboline) hybrids as multifunctional agents for the treatment of Alzheimer's disease.

A series of tacrine-(ß-carboline) hybrids (11a-q) were designed, synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (BuChE) and self-induced ß-amyloid (Aß) aggregation, Cu(2+)-induced Aß (1-42) aggregation, and to chelate metal ions. Especially, 11 l presented the greatest ability to inhibit cholinesterase (IC50, 21.6 nM for eeAChE, 63.2 nM for hAChE and 39.8 nM for BuChE), good inhibition of Aß aggregation (65.8% at 20 µM) and good antioxidant activity (1.57 trolox equivalents). Kinetic and molecular modeling studies indicated that 11 l was a mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 11 l could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). These results suggested that 11 l might be an excellent multifunctional agent for AD treatment.

Design, synthesis and biological evaluation of benzylisoquinoline derivatives as multifunctional agents against Alzheimer's disease.

A novel series of benzylisoquinoline derivatives were designed, synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). The screening results showed that most of the compounds significantly inhibited cholinesterases (ChEs), human cholinesterases (h-ChEs) and self-induced ß-amyloid (Aß) aggregation. In particular, compound 9k showed the strongest acetylcholinesterase (AChE) inhibitory activity, being 1000-fold and 3-fold more potent than its precursor benzylisoquinoline (10) and the positive control galanthamine, respectively. In addition, 9k was a moderately potent inhibitor for h-ChEs. Compared with precursor benzylisoquinoline (36.0% at 20µÐœ), 9k (78.4% at 20µÐœ) could further inhibit Aß aggregation. Moreover, 9k showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Therefore, compound 9k might be a promising lead compound for AD treatment.

Design, synthesis and biological evaluation of imine resveratrol derivatives as multi-targeted agents against Alzheimer's disease.

A series of imine resveratrol derivatives (1-20) have been designed, synthesized, and evaluated as multi-targeted compounds for the treatment of Alzheimer's disease (AD). In vitro studies show that most of the molecules exhibit a significant ability to inhibit self-induced and Cu(2+)-induced ß-amyloid (Aß1₋42) aggregation, and to function as potential antioxidants and biometal chelators. In particular, compound 9 is a potential lead compound for AD treatment (for compound 9, IC50 = 14.1 µM for the antioxidant activity using DPPH free radical method; 64.6% at 20 µM for self-induced Aß aggregation). Moreover, it is capable of decreasing reactive oxygen species (ROS) induced by Cu-Aß and shows good neuroprotective effects in human SH-SY5Y neuroblastoma cells. Taken together, these results suggest that 9 might be a promising lead compound for AD treatment.

Design, synthesis and evaluation of novel tacrine-rhein hybrids as multifunctional agents for the treatment of Alzheimer's disease.

A series of tacrine-rhein hybrid compounds have been designed and synthesized as novel multifunctional potent ChE inhibitors. Most of the compounds inhibited ChEs in the nanomolar range in vitro effectively. Compound 10b was one of the most potent inhibitors and was 5-fold more active than tacrine toward AChE, and it also showed a moderate BuChE inhibition with an IC50 value of 200 nM. Kinetic and molecular modeling studies of 10b also indicated that it was a mixed-type inhibitor binding simultaneously to the active and peripheral sites of AChE. In inhibition of the AChE-induced Aß aggregation assay, compound 10b (70.2% at 100 µM) showed the greatest inhibitory activity. In addition, 10b showed metal-chelating property and low hepatotoxicity. These results suggested that 10b might be an excellent multifunctional agent for AD treatment.

Multifunctional tacrine-flavonoid hybrids with cholinergic, ß-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease.

A new series of tacrine-flavonoid hybrids (13a-u) had been designed, synthesized, and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of the molecules exhibited a significant ability to inhibit ChE and self-induced amyloid-ß (Aß1₋42) aggregation. Kinetic and molecular modeling studies also indicated compounds were mixed-type inhibitors, binding simultaneously to active, peripheral and mid-gorge sites of AChE. Particularly, compound 13k was found to be highly potent and showed a balanced inhibitory profile against ChE and self-induced Aß1₋42 aggregation. Moreover, it also showed excellent metal chelating property and low cell toxicity. These results suggested that 13k might be an excellent multifunctional agent for AD treatment.

[Anti-apoptotic effect of Astragalus Polysaccharide on myeloid cells].

This study was aimed to assess the effect of Astragalus Polysaccharide (ASPS) on in-vitro hematopoiesis. CFU-GM assays were used to determine the effect of ASPS and thrombopoietin (TPO) on granulocytic-monocyte progenitor cells. The CFU assays were also used to investigate the effect of ASPS on the proliferation of HL-60 cells.HL-60 cells were cultured with serum-free RPMI 1640 medium and treated with or without of different concentrations of ASPS. After 72 h incubation, the number of cells were counted.In addition, the caspase-3 and JC-1 expression was determined by flow cytometry with Annexin V/PI double staining. The results showed that ASPS (100, 200 µg/ml) and TPO (100 ng/ml) significantly promoted CFU-GM formation in vitro. Various concentrations of ASPS and TPO also promoted the colony formation of HL-60 cells, the largest effect of ASPS was observed at a concentration of 100 µg/ml. There were no synergistic effects between TPO and ASPS on cellular proliferation. The results also showed that ASPS significantly protected HL-60 cells from apoptosis in condition of serum-free medium culture, suppressed caspase 3 activation, and reduced the cell apoptosis. It is concluded that ASPS can significantly promote the formation of bone marrow CFU-GM and the proliferation of HL-60 cells, the optimal concentration of ASPS is at 100 µg/ml. In the absence of serum inducing apoptosis, ASPS also significantly reduced the apoptosis of HL-60 cells via suppressing the activation of caspase-3.

[Application of wavelet transform and neural network in the near-infrared spectrum analysis of oil shale].

In the present study, an innovative method is proposed, employing both wavelet transform and neural network, to analyze the near-infrared spectrum data in oil shale survey. The method entails using db8 wavelet at 3 levels decomposition to process raw data, using the transformed data as the input matrix, and creating the model through neural network. To verify the validity of the method, this study analyzes 30 synthesized oil shale samples, in which 20 samples are randomly selected for network training, the other 10 for model prediction, and uses the full spectrum and the wavelet transformed spectrum to carry out 10 network models, respectively. Results show that the mean speed of the full spectrum neural network modeling is 570.33 seconds, and the predicted residual sum of squares (PRESS) and correlation coefficient of prediction are 0.006 012 and 0.843 75, respectively. In contrast, the mean speed of the wavelet network modeling method is 3.15 seconds, and the mean PRESS and correlation coefficient of prediction are 0.002 048 and 0.953 19, respectively. These results demonstrate that the wavelet neural network modeling method is significantly superior to the full spectrum neural network modeling method. This study not only provides a new method for more efficient and accurate detection of the oil content of oil shale, but also indicates the potential for applying wavelet transform and neutral network in broad near-infrared spectrum analysis.