[Clinicopathological features of metastatic melanoma in effusion cytology of serosal cavity].

Objective: To investigate the clinical, cytomorphology, immunocytochemical and molecular features of metastatic melanoma in serosal cavity effusion. Methods: Cytological specimens of 14 patients with melanoma in the chest and abdomen were collected from 2017 to 2023, at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. SOX10, S-100 protein, PRAME, BRAF V600E, HMB45, and Melan A were detected by immunocytochemical methods. Fourteen cases were tested for routine antibody combinations, including Claudin4, HEG1, Calretinin, CD68, etc. Four of the patients had biopsy or surgical samples of metastatic solid lesions of primary sites, and further next-generation sequencing (NGS) or amplification refractory mutation system (ARMS)-PCR molecular test was performed. In addition, 30 cases of serosal effusion samples were collected as control groups (10 cases of benign mesothelial cell reactive hyperplasia, 10 cases of mesothelioma, and 10 cases of metastatic lung adenocarcinoma). Results: Among the 14 cases of melanoma, there were 7 males and 7 females, with ages ranging from 35 to 86 years, and an average age of 57 years, there 10 cases aged ≥50 years. The tumor cells in the serosal effusion varied in morphology and degree of atypia. SOX10 was positive in all 14 cases (14/14), S-100 protein was positive in 10 cases (10/14), PRAME was positive in 12 cases (12/14), BRAF V600E was positive in 10 cases (10/14), HMB45 was positive in 12 cases (12/14), and Melan A was positive in 13 cases (13/14). In 4 patients with histological correlation, the cytological and histological expression of SOX10, BRAF V600E, and PRAME was positive in all 4 cases (4/4); S-100 protein was positive in 2 cases (2/4); and HMB45 and Melan A were positive in 3 cases (3/4). Using NGS or ARMS-PCR, missense mutations of BRAF V600E were detected in all 4 patients; TERT promoter mutations was detected in 1 case; and CDKN2A terminating mutations and MSI1 deletion mutations were detected in the other case. SOX10, S-100, HMB45, Melan A, PRAME and BRAF V600E were all negative in 30 control samples of serosal cavity effusion. Conclusion: By observing the morphology of tumor cells, immunocytochemical test of several combination markers, especially the expression of SOX10, BRAF V600E and PRAME, can help to improve the positive diagnosis rate of melanoma in serous cavity effusion.

[Analysis of clinical and genetic characteristics of the severe liver disease phenotype in patients with hepatolenticular degeneration].

Objective: To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD). Methods: Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ(2) test according to different data. Results: Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations (n=65), patients with homozygous p.Arg778Leu mutations (n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time (P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group (P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids (ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion: Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.

How lignin biosynthesis responds to nitrogen in plants: a scoping review.

Nitrogen (N) plays a critical role in the functioning of key amino acids and synthetic enzymes responsible for the various stages of lignin biosynthesis. However, the precise mechanisms through which N influences lignin biosynthesis have not been fully elucidated. This scoping review explores how lignin biosynthesis responds to N in plants. A systematic search of the literature in several databases was conducted using relevant keywords. Only 44 of the 1842 selected studies contained a range of plant species, experimental conditions, and research approaches. Lignin content, structure, and biosynthetic pathways in response to N are discussed, and possible response mechanisms of lignin under low N are proposed. Among the selected studies, 64.52% of the studies reter to lignin content found a negative correlation between N availability and lignin content. Usually, high N decreases the lignin content, delays cell lignification, increases p-hydroxyphenyl propane (H) monomer content, and regulates lignin synthesis through the expression of key genes (PAL, 4CL, CCR, CAD, COMT, LAC, and POD) encoding miRNAs and transcription factors (e.g., MYB, bHLH). N deficiency enhances lignin synthesis through the accumulation of phenylpropanoids, phenolics, and soluble carbohydrates, and indirect changes in phytohormones, secondary metabolites, etc. This review provides new insights and important references for future studies on the regulation of lignin biosynthesis.

[Analysis of the effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture].

Objective: To examine the feasibility and clinical effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture. Methods: This is a retrospective case series study. From February 2021 to February 2023, the clinical data of 24 patients (30 feet) with Achilles tendon contracture treated with all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening were analyzed retrospectively. There were 10 males and 14 females, aged (32.8±16.1) years (range: 9 to 62 years). There were 8 cases of left side only, 10 cases of right side only and 6 cases of bilateral. There were 14 cases (16 feet) of foot varus, 4 cases (6 feet) of foot valgus, and 6 cases (8 feet) without deformity. All patients underwent all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening. The surgical effects were evaluated using the maximum dorsal extension angle of ankle joint in knee extension position, the visual analogue scale (VAS) of pain, the American Orthopedic Foot and Ankle Society ankle-hindfoot score(AOFAS-AH). Paired sample t test was used to compare the scores before and after operation. Results: All patients successfully completed the operation, and the operation time of Achilles tendon lengthening was (22.0±5.7)minutes (range: 15 to 35 minutes) and the intraoperative blood loss was (6.5±2.7)ml (range: 2 to 15 ml). All patients primarily healing without any complications such as sural nerve injury, Achilles tendon rupture, important blood vessel injury, and obvious decrease of lift heel strength of achilles tendon. All 24 patients were followed up for (17.2±4.5) months (range: 12 to 28 months). One patient suffered from lift heel's weakness in one foot after operation, and recovered after repeated lift heel functional exercises. The ankle dorsiflexion function of two patients with calf triceps spasm were not improved after operation, and it was obviously improved after botulinum toxin injection. At the last follow-up, the maximum dorsal extension angle of ankle joint in knee extension position increased from -9.2°±7.6°(range:-25° to 5°) preoperatively to 14.5°±7.0°(range:0° to 28°)(t=24.83, P<0.01); the VAS score was reduced from (4.5±1.7) points (range:1 to 8 points) preoperatively to (1.5±0.9) points (range:0 to 3 points) (t=9.53, P<0.01), the AOFAS-AH was increased from (60.5±11.4)points (range:38 to 85 points) to (90.8±5.4) points (range:80-100 points)(t=14.21, P<0.01). Conclusions: All-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture not only provides Achilles tendon lengthening, but also avoids complications such as Achilles tendon rupture and sural nerve injury. It is an effective method for the treatment of Achilles tendon contracture.

Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Development and validation of the Sinonasal Endoscopic Score (SiNES) for chronic rhinosinusitis.

BACKGROUND: Although there are several endoscopic grading systems for chronic rhinosinusitis (CRS), they are limited in their range and applicability. We developed a SiNonasal Endoscopic Score (SiNES) that builds upon the strengths of previous systems while addressing their limitations. METHODS: The SiNES system was developed by consensus after multiple rounds of guided discussions. Face, content, and convergent validity were investigated. It was validated using an independent sample of 79 CRS individuals from two referral centres from September 2021 to February 2022. Each patient underwent a sinonasal endoscopy and filled PROM questionnaires. Three independent rhinologists graded endoscopic videos using the SiNES and modified Lund-Kennedy (MLK) scores. Inter-rater and test-retest reliability were assessed via the intraclass correlation coefficient (ICC). SiNES and MLK scores were correlated with PROMs using a Spearman correlation and canonical correlation analysis (CCA). RESULTS: The SiNES system evaluates five anatomical spaces regarding edema, discharge, and scarring. Face, content, and convergent validity were deemed satisfactory by the study authors and an independent panel of Otolaryngologists. Inter-rater reliability was excellent for the SiNES and good for the MLK score. Test-retest reliability was excellent for both systems. Total SiNES was correlated with self-reported smell loss. CONCLUSIONS: The SiNES system is an accurate and reliable grading framework applicable to all CRS subtypes. It can be utilized in clinical and research settings and improves upon previously published systems.

[Analysis on occupational dust or harmful gas exposure and protection in people aged 40 and above in China, 2019-2020].

Objective: To understand the current status of occupational exposure to dust or harmful gases and occupational protection in people aged ≥40 years in China, and provide data support for the prevention and control of occupational dust or harmful gas exposure. Methods: The data were obtained from the surveillance for chronic obstructive pulmonary disease (COPD) in adults aged ≥40 years selected by multi-stage stratified cluster sampling from 125 surveillance points in 31 provinces (autonomous regions and municipalities) during 2014-2015 and 2019-2020, and relevant information about occupational dust or harmful gas exposure and protection measures were collected through face-to-face interviews. Occupational dust or harmful gas exposure rate and occupational protection rate were estimated by using weighting complex sampling methods, and then the results were compared. Results: From 2014 to 2015 and from 2019 to 2020, a total of 71 061 and 71 023 individuals aged ≥40 years were surveyed, respectively. The rate of occupational exposure to dust or hazardous gas was 33.8% (95%CI: 29.9%-37.7%) during 2019-2020. The occupational exposure rate was higher in men than in women and in rural residents than in urban residents. With the increase of education level, the rate of occupational exposure to dust or harmful gas showed a downward trend. The protection rate against occupational dust or hazardous gas exposure was 47.9% (95%CI: 43.2%-52.6%) during 2019-2020. Compared with 2014-2015, the rate of occupational exposure to dust or hazardous gas decreased by 10.7 percentage points in different gender, area and occupational groups and the occupational protection rate increased by 21.9 percentage points during 2019-2020. The decrease in occupational exposure rate was higher in western China than in eastern and central China, and the increase in occupational protection rate was higher in western China than in eastern and central China. Conclusions: The rate of occupational exposure to dust or harmful gas decreased and the rate of occupational protection against dust or harmful gas exposure increased in China during 2019-2020. However, about one-third of the population still suffer from the occupational exposure, and less than half of them take protection measures. It is necessary to pay more attention to the key populations, such as workers with lower cultural level and rural migrant workers, in occupational health practice.

[Analysis on passive smoking exposure in adults aged 40 years and above in China, 2019-2020].

Objective: To understand the passive smoking exposure status in adults aged ≥40 years in China. Methods: Local residents aged ≥40 years were enrolled as study subjects from 125 areas of chronic obstructive pulmonary disease (COPD) surveillance during 2014-2015 and 2019-2020 in 31 provinces of China. A total of 74 559 adults aged ≥40 years were selected through multi-stage stratified cluster sampling for a face to face questionnaire survey and the data from 64 142 study subjects were used for the analysis. The passive smoking exposure rate, the proportions of the adults reporting passive smoking exposure at four types of places and the proportion of the adults living with daily smokers were described by using complicated sampling weighting method, the related factors were analyzed and the results were compared with the data of COPD surveillance during 2014-2015. Results: The passive smoking exposure rate in the adults aged ≥40 years was 46.4% (95%CI: 44.1%-48.8%) in China during 2019-2020, and the rate was higher in women (47.2%, 95%CI:44.8%-49.7%) than in men (44.8%, 95%CI:42.0%-47.6%) and lower in the older people. The office workers had the highest passive smoking exposure rate. The proportions of those reporting passive smoking exposure at homes, workplaces, restaurants, and public transports were 24.3% (95%CI:22.2%-26.4%)、23.3% (95%CI:21.1%-25.5%)、6.6% (95%CI:5.3%-7.9%) and 2.2% (95%CI:1.6%-2.7%). The higher education level the adults had, the less passive smoking exposure at home they reported. The proportions of those living with daily smokers before 14 years old and since 14 years old were 56.4% and 59.2%. Compared with the data during 2014-2015, the overall passive smoking exposure rate in the adults aged ≥40 years during 2019-2020 showed an increase, and the difference was not significant (P=0.356); The passive smoking exposure rate at homes declined, but the exposure rate at workplaces increased, with the biggest increase found in those being engaged in farming, forestry, husbandry, fishery and water conservancy. Multivariate analysis indicated that the factors influencing the passive smoking exposure and the exposure proportions at different places included gender, age, occupation, and education level. Conclusions: The passive smoking exposure rate in China is still high, especially in those being engaged in farming, forestry, husbandry, fishery and water conservancy. It is necessary to strengthen supervision of the enforcement of current smoking bans in public places and promote the legislation of ban smoking in public places. More attention should be paid to smoking ban and protection against passive smoking exposure in women, people with lower education level and people being engaged in in farming, forestry, husbandry, fishery and water conservancy.

[Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia].

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

[Prevalence of exposure to household cooking oil fumes in women aged 40 years and older in China, 2019].

Objective: To understand the prevalence of exposure to household cooking oil fumes in women ≥40 years old. Methods: The data were from Chronic Obstructive Pulmonary Disease (COPD) Surveillance in China during 2019-2020, which selected permanent residents ≥40 years old from 125 counties (districts) in 31 provinces (autonomous regions and municipalities) across the country by multi-stage stratified cluster random sampling method. The relevant demographic information and cooking oil fumes were collected by face-to-face interview. Our study served 37 164 women with complete cooking practice information as the subject. After complex sample weighting, we analyzed the prevalence of cooking oil fumes exposure in women from cooking time, kitchen characteristics, and Self-reported cooking oil fumes exposure. Results: In 2019, 83.9% (95%CI: 82.1%-85.7%) and 4.5% (95%CI: 3.8%-5.2%) of Chinese women ≥40 years old cooked daily and often, respectively. The average daily cooking duration is 1.8 hours/day, 31.1% of women who cooked daily more than 2.0 hours, and the average cumulative cooking years of cooking women were 32.8 years. 79.3% of cooking women used ventilation devices, and 3.2% cooked in the living room. 8.9% and 7.2% of cooking women in south China and northwest China cooked in the living room, significantly higher than in other regions (P=0.036). The self-reported exposure rate to cooking oil fumes was 81.0% (95%CI: 79.3%-82.7%). Rural, older, lower education level and women engaged in agriculture had a higher proportion of cooking daily, average daily cooking duration, cumulative cooking years, the proportion of cooking in the living room, and rate of self-reported cooking oil fumes exposure, but a lower proportion of using ventilation devices during cooking (P<0.001). Conclusions: The exposure to household cooking oil fumes was serious in Chinese women, and some women still did not take any ventilation measures when cooking. More attention should be paid to the exposure to home cooking oil fumes and its health hazards in women, especially those with lower socioeconomic status.

[Seroprevalence of the specific antibody against Toxoplasma gondii among patients with hematological diseases].

OBJECTIVE: To investigate the seroprevalence of Toxoplasma gondii infections among patients with hematological diseases, so as to provide insights into improving the prognosis and quality of life among patients with hematological diseases. METHODS: A total of 240 patients with hematological diseases (including 170 patients with hematological tumors and 70 patients with non-tumor hematological diseases) admitted to The Affiliated Hospital of Putian University during the period from January 1, 2021 through October 10, 2023 and 500 healthy volunteers in the hospital during the same period were enrolled. Subjects' demographics and serum samples were collected, and serum specific IgG and IgM antibodies against T. gondii were detected using the chemiluminescence assay, with any of a positive IgG or IgM antibody defined as a positive T. gondii infection. The seroprevalence of specific IgG and IgM antibodies against T. gondii was compared between patients with hematological diseases and healthy volunteers. RESULTS: The mean age (F = 2.034, P > 0.05) and gender distribution (χ2 = 0.462, P > 0.05) were comparable among patients with hematological tumors, patients with non-tumor hematological diseases and healthy volunteers, and there was no significant difference in the proportion of history of cat or dog contacts between patients with hematological diseases and healthy volunteers (χ2 = 0, P > 0.05). The seroprevalence of anti-T. gondii antibody was significantly higher among patients with hematological diseases than among healthy volunteers (15.8% vs. 0.6%; χ2 = 71.902, P < 0.01), and there was a significant difference in the seroprevalence of anti-T. gondii antibody among patients with hematological tumors (18.2%), patients with non-tumor hematological diseases (10.0%) and healthy volunteers (χ2 = 78.327, P < 0.01). The seroprevalence of anti-T. gondii antibody was significantly higher among patients with hematological tumors and non-tumor hematological diseases than among healthy volunteers (both P values < 0.05), while no significant difference was seen in the seroprevalence of anti-T. gondii antibody between patients with hematological tumors and non-tumor hematological diseases (P > 0.05). In addition, the proportion of history of cat or dog contacts was significantly higher among patients with hematological diseases that were positive for serum anti-T. gondii anti-body than among those negative for serum anti-T. gondii antibody (21.1% vs. 5.4%; χ2 = 8.653, P < 0.05). CONCLUSIONS: There is a high seroprevalene rate of T. gondii infections among hematological diseases, which is significantly greater than that among healthy volunteers.

[Associations of circulating leptin levels with colorectal adenoma and colorectal cancer: a case-control and Mendelian randomization study].

OBJECTIVE: To explore the causal association between circulating leptin levels and the risk of colorectal adenoma and colorectal cancer. METHODS: We collected demographic and clinical data and serum samples from 497 patients with colorectal adenoma, 955 patients with colorectal cancer, and 911 healthy individuals from the First Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang Cancer Hospital, Zhuji People's Hospital, and Lin'an District First People's Hospital. Instrumental variables of leptin were selected and genotyping tests were performed. A logistic regression model and stratified analysis were used to evaluate the association of serum leptin levels with colorectal adenoma, colorectal cancer, and the progression of colorectal adenoma to colorectal cancer. Genetic risk score (GRS) and single nucleotide polymorphisms (SNPs) were further used as instrumental variables in one-sample and two-sample Mendelian randomization analyses leveraging two-stage least squares and inverse-variance weighted methods to estimate the causal association of leptin levels with the risk of colorectal adenoma, colorectal cancer, and progression of colorectal adenoma to colorectal cancer. RESULTS: High levels of leptin, compared with its lowest quartile, were positively correlated with colorectal adenoma (P=0.005) and negatively with colorectal cancer (P < 0.001) and the risk of progression of colorectal adenoma to colorectal cancer (P < 0.001). Mendelian randomization analysis showed that GRS of leptin, either weighted or not, was not significantly correlated with the risk of colorectal adenoma, colorectal cancer, or the progression of colorectal adenoma to colorectal cancer, nor did the two-sample Mendelian randomization study support an association between leptin and the risk of colorectal cancer (P>0.05). CONCLUSION: Although the case-control study suggests probable correlations of leptin with the risk of colorectal adenoma, colorectal cancer, and colorectal adenoma progression to colorectal cancer, Mendelian randomization studies did not support a causal association of leptin with the risks of colorectal adenoma, colorectal cancer, or colorectal adenoma progression to colorectal cancer.

The effects of 6-gingerol on proliferation, differentiation, and maturation of osteoblast-like MG-63 cells

We investigated whether 6-gingerol affects the maturation and proliferation of osteoblast-like MG63 cells in vitro. Osteoblast-like MG63 cells were treated with 6-gingerol under control conditions, and experimental inflammation was induced by tumor necrosis factor-α (TNF-α). Expression of different osteogenic markers and cytokines was analyzed by real-time PCR, Western blotting, and enzyme-linked immunosorbent assay. In addition, alkaline phosphatase (ALP) enzyme activity and biomineralization as markers for differentiation were measured. Treatment with 6-gingerol resulted in insignificant effects on the proliferation rate. 6-Gingerol induced the differentiation of osteoblast-like cells with increased transcription levels of osteogenic markers, upregulated ALP enzyme activity, and enhanced mineralized nodule formation. Stimulation with TNF-α led to enhanced interleukin-6 and nuclear factor-κB expression and downregulated markers of osteoblastic differentiation. 6-Gingerol reduced the degree of inflammation in TNF-α-treated MG-63 cells. In conclusion, 6-gingerol stimulated osteoblast differentiation in normal physiological and inflammatory settings, and therefore, 6-gingerol represents a promising agent for treating osteoporosis or bone inflammation.

Overexpression of ribonuclease inhibitor defines good prognosis and suppresses proliferation and metastasis in human colorectal cancer cells via PI3K/AKT pathway

Purpose: We aim to evaluate the diagnostic value of ribonuclease inhibitor (RI) in colorectal cancer (CRC) and investigate the important role of RI in cell growth and metastasis of CRC. Methods/patients: In this study, the expression of RI was evaluated in human CRC samples with different histological grade and the association between RI expression and clinicopathological parameters was investigated. Furthermore, the exogenous RI gene was introduced into human HT29 CRC cells and the effects of RI on cell proliferation and metastasis were determined in vitro. The PI3K/Akt signaling pathway and some related protein molecules were detected. Results: RI is downregulated in CRC tissues compared to adjacent normal tissues and its expression is inversely associated with histological grade, pathological stage, and venous invasion, respectively. Multivariate analysis showed that RI expression was an independent prognostic factor for overall survival. In addition, the exogenous overexpression of RI reduced the proliferation and migration of HT29 CRC cell line in vitro by inhibiting the PI3K/Akt signaling pathway and suppressing the expression of vascular endothelial growth factor (VEGF) and upregulating phosphatase and tensin homolog (PTEN). Conclusions: RI represents an important predictor of progression in patients with CRC and suppresses proliferation and metastasis in CRC cells through inhibiting PI3K/AkT pathway (AU)

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Therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia using Fe2O3 nanoparticles

This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe2O3 nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe2O3 nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe2O3 MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe2O3 MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe2O3 nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (<24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe2O3 MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe2O3 MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells.

High interstitial fluid pressure promotes tumor progression through inducing lymphatic metastasis-related protein expressions in oral squamous cell carcinoma

OBJECTIVE: The present study was carried out to analyze the interstitial fluid pressure (IFP) values in patients with oral squamous cell carcinoma and identify the relationship between the IFP and tumor prognosis. METHODS: We investigated tumor lymphatic metastasis-related protein (VEGFC, VEGFD and VEGFR3) expressions change on SCC-4 and SCC-9 cells subjected to increased extracellular pressure in vitro and analyzed the relationship between these proteins and IFP, and prognosis of patients with oral squamous cell carcinoma. RESULTS: The results showed that the elevated extracellular pressure significantly resulted in a dramatic increase of VEGFC, VEGFD and VEGFR3 protein expressions in OSCC. More important, the activation of VEGFC, VEGFD and VEGFR3 proteins through IFP elevation contributed to poor prognosis for patients with OSCC. CONCLUSIONS: These results suggest an important potential clinical application of measuring IFP, which can be used as a generic marker of prognosis evaluation and response to therapy. Furthermore, VEGFC, VEGFD and VEGFR3 may be useful targets in developing novel and specific therapeutic tool for OSCC patients with high IFP (AU)

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Defining prognostic factors of survival after wxternal beam radiotherapy treatment of hepatocellular carcinoma with lymph node metastases

PURPOSE: To identify independent predictors of survival in patients with lymph node (LN) metastases from hepatocellular carcinoma (HCC) after external beam radiotherapy (EBRT). METHODS: There were 191 patients with LN metastases from HCC received EBRT enrolled in the study cohort. EBRT was designed to focus on the LNs and a median dose of 50 Gy (range 40-60 Gy) was delivered. Treatment response was assessed by the WHO response criteria. Factors such as demographic data, tumor characteristics, and treatment modalities were determined before EBRT. Predictors of survival were identified by univariate and multivariate analysis. RESULTS: The median survival was 8.0 months for all patients. Factors including Child-Pugh status (p = 0.009), intrahepatic tumor control (p = 0.015), LN location (p = 0.015), and response to EBRT (p < 0.001) were significant prognostic factors predicting for survival by multivariate analysis. The objective regression rate (ORR), which is the sum of complete and partial response rates, was as high as 79.1 %. As determined by multivariate analysis, the factors of LN location near liver (p = 0.002), smaller LN size (p = 0.021), and higher EBRT dose (p < 0.001) were associated with higher ORR values. CONCLUSION: This study provides detailed information about survival outcomes and prognostic factors. Child-Pugh B value, uncontrolled intrahepatic tumor, LN location far from liver, and no response to EBRT are the unfavorable independent predictors (AU)