Response of phytoplankton composition to environmental stressors under humidification in three alpine lakes on the Qinghai-Tibet Plateau, China.

Owning to their extreme environmental conditions, lakes on the Qinghai-Tibet Plateau have typically displayed a simplistic food web structure, rendering them more vulnerable to climate change compared to lakes in plains. Phytoplankton, undergoing a changing aquatic environment, play a crucial role in the material cycle and energy flow of the food chain, particularly important for the unique fish species of the Tibetan Plateau. To identify the changing environment indexes and determine the response of phytoplankton composition to the environment change in alpine lakes, three lakes-Lake Qinghai, Lake Keluke and Lake Tuosu-were selected as study areas. Seasonal sampling surveys were conducted in spring and summer annually from 2018 to 2020. Our findings revealed there were significant changes in physicochemical parameters and phytoplankton in the three lakes. Bacillariophyta was the predominant phytoplankton in Lake Qinghai from 2018 to 2020, with the genera Synedra sp., Navicula sp., Cymbella sp. and Achnanthidium sp. predominated alternately. Lake Keluke alternated between being dominated by Bacillariophyta and cyanobacteria during the same period. Dolichospermum sp., a cyanobacteria, was prevalent in the summer of 2018 and 2019 and in the spring of 2020. In Lake Tuosu, Bacillariophyta was the predominant phytoplankton from 2018 to 2020, except in the summer of 2019, which was dominated by cyanobacteria. Synedra sp., Oscillatoria sp., Pseudoanabaena sp., Chromulina sp. and Achnanthidium sp. appeared successively as the dominant genera. Analysis revealed that all three lakes exhibited higher phytoplankton abundance in 2018 that in 2019 and 2020. Concurrently, they experienced higher average temperatures in 2018 than in the subsequent years. The cyanobacteria, Bacillariophyta, Chlorophyta and overall phytoplankton increased with temperature and decreased with salinity and NH4-N. Besides, the ratios of cyanobacteria, and the ratios of Bacillariophyta accounted in total phytoplankton increased with temperature. These findings suggest that cyanobacteria and phytoplankton abundance, especially Bacillariophyta, may have an increase tendency in the three alpine lakes under warm and wet climate.

Association of lymphocyte subsets with the efficacy and prognosis of PD­1 inhibitor therapy in advanced gastric cancer: results from a monocentric retrospective study.

PURPOSE: This retrospective study aimed to investigate the changes in peripheral blood lymphocyte subsets before and after immunotherapy in patients with advanced gastric cancer and their relationship n with the therapeutic efficacy and clinical prognosis. METHODS: Peripheral blood lymphocyte subsets, including CD4 + T cells, CD8 + T cells, CD4+/CD8 + ratio, NK cells, Treg cells, and B cells, were collected from 195 patients with advanced gastric cancer who were admitted to the First Hospital of Shanxi Medical University with immunotherapy from January 2020 to October 2021, at the time of diagnosis of advanced gastric cancer, before immunotherapy and after 3 cycles of immunotherapy. T-tests were used to examine the factors influencing the patients' peripheral blood lymphocyte subsets and the changes after immunotherapy. To examine the relationship between lymphocyte subsets and treatment outcomes, ROC curves were plotted using a logistic regression. Kaplan-Meier curve was drawn, and the Log Rank test was carried out to compare the differences in PFS between the different groups. Cox proportional hazards regression model was used to analyze the factors affecting PFS after calibration of other variables. RESULTS: The proportion of peripheral blood lymphocyte subsets in patients with advanced gastric cancer was affected by age and PD-L1 level. Compared to the baseline, the treatment effective group had higher proportions of CD4 + T cells, a higher CD4+/CD8 + ratio, NK cells and Treg cells, and lower proportions of CD8 + T cells and B cells in the peripheral blood after three cycles of immunotherapy. In the treatment-naive group, there were no significant differences in the lymphocyte subsets. With cut-off values of 30.60% and 18.00%, baseline CD4 + T cell and NK cell ratios were independent predictors of immunotherapy efficacy and PFS. Treg cell ratio, gender, PD-L1 levels, and MMR status all predicted PFS independently. CONCLUSION: The proportion of peripheral blood lymphocyte subsets was modified in patients who responded to PD-1 inhibitors. Different lymphocyte subpopulation levels can be used as biomarkers to predict immunotherapy efficacy and clinical prognosis in patients with advanced gastric cancer.

Peripheral blood nutrient indices as biomarkers for anti­PD­1 therapy efficacy and prognosis in patients with advanced gastric cancer.

Immunotherapy offers survival benefits for patients with advanced gastric cancer, but not all populations can benefit from immunotherapy. Good nutritional status is fundamental to a patient's immune function and may have an impact on the efficacy of immunotherapy. The present study aimed to investigate changes in prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI) and albumin-globulin ratio (AGR) values before and after immunotherapy in patients with advanced gastric cancer. The study also aimed to determine the potential association of the aforementioned values with patient outcomes and prognosis. Body mass index (BMI), serum albumin, total protein, peripheral blood lymphocyte, neutrophil, carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9) and a-fetoprotein (AFP) data were collected from 195 patients with advanced gastric cancer who underwent immunotherapy from January 2020 to October 2021. In addition, PNI, ALI and AGR values were calculated based on variables in blood collected from the patients within 3 days prior to immunotherapy and 3 weeks after immunotherapy. The results demonstrated that low PNI was associated with elevated CEA levels. Moreover, low ALI levels were associated with reduced BMI levels, elevated AFP levels, PD-L1 negative and first-line treatment. Comparison of responding and non-responding groups revealed that patients who responded to immunotherapy had higher PNI and AGR values than patients who did not respond, both before and after treatment, but had lower CEA and CA19-9 levels after treatment. Furthermore, in the non-responding group, PNI and AGR values were decreased and CEA values were increased following treatment compared with those prior to treatment. The objective response and disease control rates were higher in the high PNI and AGR groups compared with the low PNI and AGR groups, respectively. Moreover, PNI and AGR were found to be independent predictors of the short-term efficacy of immunotherapy for advanced gastric cancer, with cut-off values of 47.18 and 1.29, respectively. Univariate analysis revealed that ALI was associated with the progression-free survival (PFS) of patients, while multivariate analysis demonstrated that baseline PNI and AGR were independent predictors of PFS. In conclusion, tumor progression leads to a decline in the nutritional level of patients, and the present study indicated that effective immunotherapy may alleviate this deterioration to a certain extent. Furthermore, PNI and AGR exhibit potential in predicting the efficacy of immunotherapy and the prognosis of patients with advanced gastric cancer, and may exhibit potential as biomarkers in clinical practice.

Hyperthermic intrathoracic/intraperitoneal chemotherapy versus conventional intrapleural/intraperitoneal chemotherapy for the malignant effusion: a multi-center randomized clinical trial.

OBJECTIVE: To compare the efficacy and safety of hyperthermic intrathoracic/intraperitoneal chemotherapy versus conventional intrapleural/intraperitoneal chemotherapy in the treatment of malignant pleural or peritoneal effusion. METHODS: A randomized clinical trial was carried out in 8 cancer centers across China. Patients with malignant pleural or peritoneal effusion were randomly assigned to the study group or control group. Patients in the study group were treated with cisplatin-based hyperthermic intrathoracic chemotherapy (HITHOC) or hyperthermic intraperitoneal chemotherapy (HIPEC), while the control group was treated with conventional intrapleural or intraperitoneal chemotherapy using same chemotherapeutic regime as the study group. The objective response rate (ORR) was analyzed as primary outcome. Quality-of-life (QOL) score was recorded as secondary outcome using the questionnaire 30 (QLQ-C30) of the European Organization for Research and Treatment of Cancer (EORTC). The efficacy and safety of the two treatments were compared. RESULTS: Total 135 patients were recruited and randomized in this study, with 67 patients in the study group and 68 patients in the control group. The ORR in the study group (80.70%) was significantly higher than that in the control group (31.03%, p < 0.001). However, neither changes of QOL scores, nor incidence rates of adverse events were significantly different between the two groups (p = 0.076 and 0.197, respectively). CONCLUSION: Efficacy of HITHOC or HIPEC is superior to that of conventional modality for the treatment of malignant effusion with comparable side effects.

Safety and effectiveness of apatinib in elderly patients with metastatic gastric cancer: a sub-analysis from the large-scale, prospective observational study of apatinib for gastric cancer treatment in a real-world clinical setting (AHEAD-G202).

Background: Apatinib was shown to improve the survival of Chinese patients with refractory metastatic gastric cancer (mGC). As an orally administered drug, it has been widely used in elderly patients because the dosing schedule can be adjusted flexibly. However, data on the efficacy and safety of apatinib in elderly patients is scarce. The aim of this study was to evaluate the toxicity and effectiveness of apatinib for elderly patients with mGC in a real-world setting. Methods: Data from the sub-population of patients who were ≥65 years enrolled in the AHEAD-G202 trial were analyzed. Patients with mGC were prospectively registered and initially received ≤850 mg oral apatinib daily combined or not combined with chemotherapy, at the investigator's discretion. The primary endpoint was safety. The secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 117 patients were included. There were 51 (43.59%) patients in the low-dose (250 mg) group, 60 (51.28%) patients in the mid-dose (425 to 500 mg) group, and 6 (5.13%) patients in the high-dose (850 mg) group according to the initial daily doses. Hypertension (6.84%) was the only grade 3-4 adverse event (AE) with a prevalence of more than 5% and across the low-dose (11.76%), mid-dose (3.33%) and high-dose group (0%). The median OS and PFS were 7.13 months (95% CI: 5.04 to 9.22 months) and 4.27 months (95% CI: 3.24 to 5.29 months), respectively. The OS and PFS were similar among the 65-74 and ≥75 years groups (χ2=1.406, P=0.306; χ2=0.378, P=0.066, respectively). The OS and PFS were also comparable among the 3 dose groups. Conclusions: Elderly patients with mGC can tolerate and benefit from apatinib therapy. A lower initial daily dosing strategy may be a suitable choice for elderly patients in clinical practice.

MicroRNA-548b inhibits proliferation and invasion of hepatocellular carcinoma cells by directly targeting specificity protein 1.

[This retracts the article DOI: 10.3892/etm.2019.7812.].

Multicomponent Stress-Strength Model Based on Generalized Progressive Hybrid Censoring Scheme: A Statistical Analysis.

The statistical inference of the reliability and parameters of the stress-strength model has received great attention in the field of reliability analysis. When following the generalized progressive hybrid censoring (GPHC) scheme, it is important to discuss the point estimate and interval estimate of the reliability of the multicomponent stress-strength (MSS) model, in which the stress and the strength variables are derived from different distributions by assuming that stress follows the Chen distribution and that strength follows the Gompertz distribution. In the present study, the Newton-Raphson method was adopted to derive the maximum likelihood estimation (MLE) of the model parameters, and the corresponding asymptotic distribution was adopted to construct the asymptotic confidence interval (ACI). Subsequently, the exact confidence interval (ECI) of the parameters was calculated. A hybrid Markov chain Monte Carlo (MCMC) method was adopted to determine the approximate Bayesian estimation (BE) of the unknown parameters and the high posterior density credible interval (HPDCI). A simulation study with the actual dataset was conducted for the BEs with squared error loss function (SELF) and the MLEs of the model parameters and reliability, comparing the bias and mean squares errors (MSE). In addition, the three interval estimates were compared in terms of the average interval length (AIL) and coverage probability (CP).

Exosomal MiR-423-3p inhibits macrophage M2 polarization to suppress the malignant progression of cervical cancer.

BACKGROUND: Cervical cancer (CC) is the leading cause of death among women-related cancers. MicroRNAs (miRNAs) exerting important impacts in the development of CC is widely recognized. MiR-423-3p was found to be with low expression in the plasma exosomes of patients with CC. Exo-miRNAs have been documented to be potential modulators of cancer progression, and exosomes have been reported to be associated with macrophage polarization. AIM: We aim to verify the potential function exosomal miR-423-3p may exert in CC cells as well as its underlying mechanism. METHODS: A co-culture model of exosomes and CC cells was established and the function of exosomal miR-423-3p was verified through Transwell, colony formation and other assays. A co-culture model of exosomes and macrophages, together with mechanism experiments in vitro and in vivo was taken to verify the molecular mechanism of exosomal miR-423-3p in CC. RESULTS: Exosomal miR-423-3p inhibited macrophage M2 polarization so as to suppress CC cell progression as well as tumor growth. MiR-423-3p regulated macrophage M2 polarization by targeting cyclin-dependent kinase 4 (CDK4) mRNA, and it inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) via CDK4 to silence Interleukin 6 (IL-6) expression. CONCLUSION: Exosomal miR-423-3p inhibited macrophage M2 polarization to suppress the progression of CC cells.

Distribution of microplastics in benthic sediments of Qinghai Lake on the Tibetan Plateau, China.

Although several studies of microplastics (MPs) with size <5 mm in lake sediments focused on lakeshore areas, there have been no studies of distributions of MPs from lakeshores to the center of a lake. To test our hypothesis that MPs decrease from lakeshore to the center, a study was conducted on the largest brackish lake on the remote and high-altitude Tibetan Plateau, China. Abundances and characteristics of MPs in 14 samples of surface sediment collected from a river bay, a lake bay, and a lake central area were investigated. Distributions were influenced by river inflow, tourism, and minimal activity of humans, respectively around Qinghai Lake. The mean abundance of MPs in sediments of Qinghai Lake was 393 ± 457 items/kg, dry mass (dm). Based on the range of MP abundances in surface sediments of lakes worldwide, Qinghai Lake was classified as being moderately polluted with MPs. The dominant color, shape, size, and polymer type of MPs in sediments were transparent, fiber, 0.05-1 mm, and polypropylene, respectively. The river bay had a mean abundance of MPs two-fold greater than either the bay or central area of the lake. This indicates that the river catchment caused more pollution with MPs, while the central area of the lake was not a sink for MPs. Spatial trends of MPs in sediments from the shore to the center of the lake differed among areas, and were significantly related to wind, lake current, sedimentation rate, water- and sediment-properties, water depth, and proximity to land sources of MPs.

Association of lymphocyte subsets with efficacy and prognosis of immune checkpoint inhibitor therapy in advanced non-small cell lung carcinoma: a retrospective study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have achieved promising effects in patients with non-small cell lung cancer (NSCLC). However, not all patients with NSCLC benefit from immunotherapy. There is an urgent need to explore biomarkers that could predict the survival outcomes and therapeutic efficacy in advanced NSCLC patients treated with immunotherapy. In this study, we aimed to assess the changes in peripheral blood lymphocyte subsets and their association with the therapeutic efficacy and clinical prognosis of advanced NSCLC patients treated with immunotherapy. METHODS: A total of 276 patients with advanced NSCLC were enrolled. Peripheral blood lymphocyte subsets including CD4+ T cells, CD8+ T cells, CD4+/CD8+ ratio, NK cells, Tregs and B cells were collected before any treatment, before immunotherapy or chemotherapy, and after 4 cycles of immunotherapy or chemotherapy. T-test was used to analyze the factors influencing lymphocyte subsets and their changes before and after therapy. Logistic regression was used to plot ROC curves and analyze the relationship between lymphocyte subsets and therapeutic efficacy. Log-rank test and Cox regression model were used to evaluate the relationship between lymphocyte subsets and progression-free survival (PFS). RESULTS: Gender, distant metastasis, and EGFR mutation status are known to affect the proportion of peripheral blood lymphocyte subsets in patients with advanced NSCLC. The proportions of CD4+ T cells, CD8+ T cells, Tregs and B cells were found to decrease after chemotherapy as compared to the baseline. The proportion of CD4+ T cells, CD8+ T cells, CD4+/CD8+ ratio, NK cells and Tregs were higher after immunotherapy than after chemotherapy. Compared to the baseline, the effective group showed significant increase in the proportions of CD4+ T cells, CD4+/CD8+ ratio, NK cells and Tregs, and the number of CD8+ T cells was significantly lower in the peripheral blood after 4 cycles of immunotherapy. On the contrary, the ineffective group did not show any significant differences in the above parameters. Baseline CD4+ T cells and NK cells were independent predictors of immunotherapy efficacy and PFS. Baseline Tregs were independent predictor of immunotherapy efficacy. CONCLUSION: Immune checkpoint inhibitors induced changes in the proportion of peripheral blood lymphocyte subsets in patients that responded well to immunotherapy. The levels of the different lymphocyte subsets could serve as valuable predictive biomarkers of efficacy and clinical prognosis for NSCLC patients treated with immunotherapy.

Phytoplankton Composition and Their Related Factors in Five Different Lakes in China: Implications for Lake Management.

In this paper, two trophic lakes: Lake Taihu and Lake Yanghe, and three alpine lakes: Lake Qinghai, Lake Keluke, and Lake Tuosu, were investigated to discover the connections between environmental factors and the phytoplankton community in lakes with differences in trophic levels and climatic conditions. Three seasonal data, including water quality and phytoplankton, were collected from the five lakes. The results demonstrated clear differences in water parameters and phytoplankton compositions in different lakes. The phytoplankton was dominated by Bacillariophyta, followed by Cyanobacteria and Chlorophyta in Lake Qinghai, Lake Keluke, and Lake Tuosu. It was dominated by Cyanobacteria (followed by Chlorophyta and Bacillariophyta in Lake Yanghe) and Cyanobacteria (followed by Chlorophyta and Cryptophyta in Lake Taihu). The temperature was an essential factor favoring the growth of Cyanobacteria, Chlorophyta, and Bacillariophyta, especially Cyanobacteria and Chlorophyta. The pH had significantly negative relationships with Cyanobacteria, Chlorophyta, and Bacillariophyta. Particularly, a high pH might be a strong and negative factor for phytoplankton growth in alpine lakes. A high salinity was also an adverse factor for phytoplankton. Those results could provide fundamental information about the phytoplankton community and their correlated factors in the alpine lakes of the Tibetan Plateau, contributing to the protection and management of alpine lakes.

TRIM21 improves apatinib treatment in gastric cancer through suppressing EZH1 stability.

Gastric cancer (GC) is a common tumor with high metastatic rate worldwide. Promoting chemosensitivity is effective for improving therapeutic outcome and survival rate for GC patients. Tripartite motif-containing 21 (TRIM21), a member of TRIM-containing proteins, plays crucial roles in regulating numerous cellular events involved in tumor progression. However, it's regulatory effects on GC growth and drug sensitivity are still unclear. In the present study, we identified that TRIM21 expression was remarkably decreased in human GC tissues compared with the adjacent normal ones, and its down-regulation was closely linked to higher recurrence and lower overall survival rate among GC patients. We then found that apatinib (APA)-reduced GC cell proliferation was significantly abolished by TRIM21 knockdown; however, promoting TRIM21 expression further improved the sensitivity of GC cells to APA treatment, as proved by the remarkably decreased cell viability and colony formation. Furthermore, TRIM21 over-expression dramatically enhanced apoptosis, while its knockdown markedly diminished apoptotic cell death in APA-incubated GC cells. Moreover, stem cell properties of GC cells were also restrained by TRIM21. Our in vivo experiments showed that APA-repressed tumor growth was considerably abolished by TRIM21 knockdown, whereas being further elevated by TRIM21 over-expression. In addition, we showed that TRIM21 markedly decreased enhancer of zeste homolog 1 (EZH1) protein expression levels in GC cells, and importantly, a direct interaction between TRIM21 and EZH1 was verified. Of note, our in vitro studies revealed that EZH1 over-expression remarkably abolished the function of TRIM21 to restrain cell viability and induce apoptosis in APA-incubated GC cells, indicating that EZH1 suppression was necessary for TRIM21 to inhibit GC progression. Together, our findings demonstrated that TRIM21 may be a novel therapeutic target for GC treatment through reducing EZH1 to improve chemosensitivity.

Diagnostic and prognostic nomograms for bone metastasis in small cell lung cancer.

OBJECTIVE: Patients with bone metastasis (BM) of small cell lung cancer (SCLC) have a poor prognosis. We aimed to identify predictors and prognostic factors in patients with BM of SCLC and construct nomograms to predict BM. METHODS: We retrospectively analyzed 18,187 cases from the Surveillance, Epidemiology, and End Results database reported between 2010 and 2016. Differences in overall survival (OS) and cancer-specific survival (CSS) were evaluated after propensity score matching. Independent predictors for BM and prognostic factors for patients with BM of SCLC were determined using univariate and multivariate regression analyses. Two nomograms were constructed and evaluated using C-statistics. RESULTS: BM was observed in 4014 (22.07%) patients. Kaplan-Meier survival analysis revealed significant differences between BM and non-BM groups. The median OS for patients with and without BM was 6 and 7 months, respectively. The median CSS for patients with and without BM was 9 and 13 months, respectively. Age, sex, tumor size, N stage, chemotherapy, surgery, radiotherapy, and liver/brain/lung metastases were related to BM and independent prognostic factors for OS and CSS. Diagnostic and prognostic nomograms were generated. CONCLUSION: Our nomograms predicted the incidence of BM and the 5-month survival rate of patients with SCLC and BM.

Pleckstrin 2 is a potential drug target for colorectal carcinoma with activation of APC/ß­catenin.

The tumor suppressor gene adenomatous polyposis coli (APC) is frequently inactivated or absent in colorectal carcinoma (CRC). Loss­of­function of APC promotes the expression of ß­catenin, which is critical for CRC development. Since ß­catenin acts as an important transcription factor, blockage of ß­catenin may have side effects, including impairment of tissue homeostasis and regeneration, thus limiting the application of ß­catenin inhibitors for the treatment of patients with CRC. Therefore, identifying a novel substrate of APC/ß­catenin may provide essential clues to develop effective drugs. Small interfering RNA technology and lentivirus­mediated overexpression were performed for knockdown and overexpression of pleckstrin 2 (PLEK2) in CRC cells. Cell Counting Kit­8 and colony formation assays, and cell cycle analysis and cell apoptosis detection were used to detect the capacity of cell proliferation, cell cycle distribution and apoptosis. The present study demonstrated that the APC/ß­catenin signaling cascade transcriptionally activated PLEK2 in CRC cells. PLEK2 expression was markedly increased in CRC tissues. There was an inverse correlation between APC and PLEK2 expression in patients with CRC. In vitro, overexpression of PLEK2 increased the proliferation of CRC cells. Opposite results were observed in the cells with knockdown of PLEK2. Furthermore, PLEK2 promoted cell cycle progression and suppressed apoptosis. In summary, upregulation of PLEK2 contributed to CRC proliferation and colony formation activated by the APC/ß­catenin signal pathway. Targeting PLEK2 may be important for the treatment of patients with CRC with activation of the APC/ß­catenin signaling pathway.

Exploring the malnutrition status and impact of total parenteral nutrition on the outcome of patients with advanced stage ovarian cancer.

BACKGROUND: Ovarian cancer is a common cancer type in women and is often associated with onset of malnutrition. Total parenteral nutrition (TPN) is a nutritional intervention method that has been reported to have controversial effect on cancer patients. In the present retrospective study, we sought to explore the prevalence of malnutrition assessed by the Nutritional Risk Index (NRI) and its association with survival in advanced stage ovarian cancer patients. We also compared the post-operative outcome of the malnourished patients treated with either TPN or conservative management. RESULTS: A total of 415 patients with advanced stage ovarian cancer were separated into 4 nutrition groups based on the NRI scores. We found that a number of factors were significantly different among the 4 nutrition groups, including age, serum albumin level, BMI and NRI; among which serum albumin level and NRI were identified to be independent predictors of progression-free and overall survival. In the moderately and severely malnourished patients, those who were treated with TPN had significantly shorter hospitalization period, lower serum albumin level and lower BMI after surgery. In addition, serum albumin level, use of TPN and number of patients with complications were closely related to the hospital stay duration. CONCLUSION: Malnutrition status is closely associated with survival of advanced stage ovarian cancer patients. These patients may benefit from TPN treatment for reduced hospitalization, especially with the onset of hypoalbuminemia.

HCP5 contributes to cisplatin resistance in gastric cancer through miR-128/HMGA2 axis.

The long non-coding RNA HLA complex P5 (HCP5) is extensively related to cancer chemoresistance, while its function in gastric cancer (GC) has not been well elucidated yet. Here, the role and mechanism of HCP5 in regulating the chemoresistance of GC to cisplatin (DDP) was investigated. Our results revealed that HCP5 was increased in GC patients and indicated a poor prognosis. HCP5 knockdown weakens DDP resistance and reduced apoptosis of GC cells. miR-128 was decreased in GC patients and sponged by HCP5. HMGA2 was targeted by miR-128 and was increased in GC patients. HCP5 aggravated the resistance of GC cells to DDP in vitro by elevating HMGA2 expression via sponging miR-128. HCP5 silencing inhibited GC cells growth, resistance to DDP, and Ki-67 expression in vivo. In summary, HCP5 contributed to DDP resistance in GC cells through miR-128/HMGA2 axis, providing a promising therapeutic target for GC chemoresistance.

KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated ß-catenin pathway.

OBJECTIVE: Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. METHODS: CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and ß-catenin. RESULTS: Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients' differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of ß-catenin signaling pathway, confirmed using ß-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-ß-catenin in human HCC patients. CONCLUSION: We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated ß-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

Advanced breast cancer with cachexia: A case report.

RATIONALE: Cachexia is a clinically relevant syndrome in cancer that is associated with reduced tolerance to anticancer therapy, reduced quality of life, and reduced survival rates. Cachexia is most prevalent in pancreatic, gastric, colorectal, lung, and head and neck cancers. It is rarely documented in breast cancer patients. PATIENT CONCERNS: In our case report of a breast cancer patient with bone metastasis who was monitored throughout the course of her treatment, we document the development of cachexia using image analyses in relation to her metastatic burden. In the 2-year period, from April 10, 2015, to February 09, 2017, she lost 16% of her baseline weight. During this time, she was repeatedly hospitalized for chest tightness, edema of both lower limbs, numbness and pain in the left lower extremity and backache. DIAGNOSES: Our patient was a 46-year-old premenopausal woman when she was firstly diagnosed. Several years after surgery for invasive ductal carcinoma of the left breast, she had multiple systemic bone metastases (the thoracic spine, the ribs, etc), lung metastasis, bilateral axillary lymph node metastasis, and metastasis of the right neck lymph node in IV area. INTERVENTIONS: The patient completed 6 cycles of postoperative adjuvant chemotherapy and long-term endocrine therapy after a radical mastectomy for breast cancer. During the fourth progression, 6 cycles of rescue chemotherapy were performed. Local lumbosacral radiotherapy, and lumbar surgery were carried out to relieve symptoms after several progressions. OUTCOMES: She became extremely thin, weighing only 50 kg at admission on July 23, 2018. This eventually led to multiple organ failure and death. LESSONS: We noted a strong negative correlation between the abdominal muscle area and the metastatic tumor area at the second lumbar vertebral (L2) level. The monitoring of abdominal muscle wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and the extent of metastatic disease. This is especially true with breast cancer, where metastasis to bone is frequent. Our data from a computational tomography radiological quantification, may provide clinicians with early indications of the extent of cachexia in metastatic breast cancer patients.

Total Parenteral Nutrition Treatment Improves the Nutrition Status of Gynecological Cancer Patients by Improving Serum Albumin Level.

BACKGROUND: Malnutrition is often observed in gynecological cancer patients, however its prevalence in these patients remains largely unexplored. Total parenteral nutrition (TPN) is a nutritional intervention method that has controversial treatment outcome on gynecological cancer patients. The present retrospective study is designed to evaluate the nutrition status and TPN treatment outcome on patients diagnosed with endometrial, cervical or ovarian malignant tumors. METHODS: Medical records of a total of 263 patients treated at the First Hospital of Shanxi Medical University, China were included. Nutrition status was assessed by patient-generated subjective global assessment (PG-SGA). Patients were grouped based on nutrition status, cancer type or treatment strategy for clinical characteristic comparison. Multivariable logistic regression analysis was used to identify predictors for malnutrition status and hospital stay duration. RESULTS: Presence of endometrial and cervical cancer, body weight before nutritional intervention and serum albumin level (P < 0.001 for all) were found to be significant predictors for malnutrition status in gynecological cancer patients. In the malnourished patients, those who were treated with TPN had significantly lower serum albumin levels before and after treatment (P < 0.001) and PG-SGA scores after treatment. Also, TPN treatment could significantly increase the serum albumin levels in these patients after 1 week. In addition, shorter hospitalization period was needed for TPN-treated endometrial (P = 0.019) and ovarian (P < 0.001) patients. Moreover, serum albumin levels (P < 0.001), use of TPN treatment (P = 0.025) and nutrition status (P = 0.010) were identified to be independent predictors for hospital stay duration. CONCLUSION: Our results suggest that malnutrition is a significant clinical manifestation in gynecological cancer patients who may benefit from TPN treatment for reduced hospitalization and improved serum albumin levels.