Objective To investigate whether cisplatin induces tumor necrosis factor-α(TNF-α)secretion in human head and neck squamous cell carcinoma(HNSCC)cells to trigger RIP1/RIP3/MLKL-dependent necroptosis of the cells.Methods HNSCC cell lines HN4 and SCC4 treated with cisplatin(CDDP)or the combined treatment with CDDP and z-VAD-fmk(a caspase inhibitor)or Nec-1(a necroptosis inhibitor)for 24 h were examined for changes in cell viability using CCK8 assay and expressions of caspase-8 and necroptosis pathway proteins(RIP1/RIP3/MLKL)using Western blotting.The changes in migration of the cells were assessed with cell scratch assay,and the expressions of epithelial-mesenchymal transition(EMT)marker proteins N-cadherin,vimentin,and E-cadherin as well as the expressions of NF-κB(p65)and TNF-α were detected with Western blotting.Results The IC50 of cisplatin was 10 μg/mL in HN4 cells and 15 μg/mL in SCC4 cells.Cisplatin treatment significantly decreased the expressions of caspase-8,N-cadherin and vimentin and increased the expressions of E-cadherin,the necroptosis pathway proteins(RIP1/RIP3/MLKL),TNF-α,and NF-κB(p65),and these changes were obviously inhibited by treatment with Nec-1.Cisplatin stimulation also significantly lowered migration of the cells,and this inhibitory effect was strongly attenuated by Nec-1 treatment.Conclusion Cisplatin activates nuclear factor-κB signaling in HNSCCs to promote TNF-α autocrine and induce RIP1/RIP3/MLKL-dependent necroptosis,thus leading to inhibition of cell proliferation.

Objective To investigate whether cisplatin induces tumor necrosis factor-α(TNF-α)secretion in human head and neck squamous cell carcinoma(HNSCC)cells to trigger RIP1/RIP3/MLKL-dependent necroptosis of the cells.Methods HNSCC cell lines HN4 and SCC4 treated with cisplatin(CDDP)or the combined treatment with CDDP and z-VAD-fmk(a caspase inhibitor)or Nec-1(a necroptosis inhibitor)for 24 h were examined for changes in cell viability using CCK8 assay and expressions of caspase-8 and necroptosis pathway proteins(RIP1/RIP3/MLKL)using Western blotting.The changes in migration of the cells were assessed with cell scratch assay,and the expressions of epithelial-mesenchymal transition(EMT)marker proteins N-cadherin,vimentin,and E-cadherin as well as the expressions of NF-κB(p65)and TNF-α were detected with Western blotting.Results The IC50 of cisplatin was 10 μg/mL in HN4 cells and 15 μg/mL in SCC4 cells.Cisplatin treatment significantly decreased the expressions of caspase-8,N-cadherin and vimentin and increased the expressions of E-cadherin,the necroptosis pathway proteins(RIP1/RIP3/MLKL),TNF-α,and NF-κB(p65),and these changes were obviously inhibited by treatment with Nec-1.Cisplatin stimulation also significantly lowered migration of the cells,and this inhibitory effect was strongly attenuated by Nec-1 treatment.Conclusion Cisplatin activates nuclear factor-κB signaling in HNSCCs to promote TNF-α autocrine and induce RIP1/RIP3/MLKL-dependent necroptosis,thus leading to inhibition of cell proliferation.

Objective:To investigate the association between body mass index (BMI) and the risk of chronic obstructive pulmonary disease (COPD).Methods:This study employed a single-center, cross-sectional design combined with online Mendelian randomization (MR) analysis. A total of 16 187 pieces of lung function data for COPD screening from the “Happy Breathing” project in the Jingzhou area between September 2021 and October 2023 were initially collected. Cases with missing questionnaire information, failed quality control, or isolated restrictive or small airway dysfunction were excluded, resulting in a final dataset of 3 999 cases, comprising 2 330 non-COPD and 1 669 COPD cases. Binary COPD status was set as the outcome variable, with BMI as the exposure variable. A smooth curve plot was used to depict the relationship between BMI and COPD prevalence; if non-linearity was observed, a two-piece linear regression model was employed to calculate threshold effects, adjusting for potential confounders such as age, sex, smoking history, biomass fuel exposure, and COPD awareness. Subsequently, online genome-wide association study (GWAS) data were utilized for MR analysis to explore any potential causal link between high BMI and COPD development.Results:Analysis of the “Happy Breathing” COPD screening data from the Jingzhou area revealed a nonlinear relationship between BMI and COPD risk. For BMI values <23.7 kg/m2, each 1 kg/m2 increase in BMI was associated with an 18% decrease in COPD risk ( OR=0.82, 95% CI: 0.79-0.85). However, for BMI >23.7 kg/m2, no significant association was found between increasing BMI and COPD risk ( OR=1.00, 95% CI: 0.96-1.05). MR analysis using online GWAS data suggested no potential causal relationship between high BMI and COPD occurrence, with both heterogeneity and pleiotropy tests yielding P>0.05. Conclusion:There may be a nonlinear relationship between BMI and the risk of COPD, with no apparent association between BMI and COPD risk for values above 23.7 kg/m2.

Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.

Objective To investigate the changes of brain function and cognitive function in patients with acute cerebellar stroke using amplitude of low-frequency fluctuation (ALFF) and functional connection (FC).Methods The cognitive function assessment and resting state functional magnetic resonance (rs-fMRI) scan were performed on patients with acute cerebellar stroke hospitalized in Taizhou People's Hospital or Nanjing Brain Hospital from May 2017 to June 2018.The differences of ALFF and FC values were compared.Pearson correlation analysis was used to understand the correlation between FC values and cognitive function scores.A total of 32 patients with acute cerebellar stroke and 34 healthy controls were included.Results Compared with the healthy controls,the scores of Montreal Cognitive Assessment (23.97 ± 6.04 vs 26.56 ± 2.93,t=-2.237,P=0.029),the Rey Auditory Verbal Learning Test (RAVLT;3(2) vs 6(2),Z=-4.136,P=0.000) were significantly lower,and the time consuming of Trail Making Test(TMT)-B ((251.56 ± 112.62) s vs (164.76± 52.37) s) was significantly higher (t=4.054,P=0.000) in the patients with acute cerebellar stroke.The rs-fMRI results showed significant group differences in ALFF values at the four brain regions,including the right frontal lobe,left hippocampus,right cingulate gyrus and cerebellum posterior lobe.The regions that showed significant group differences were set as regions of interest (ROIs),and then the functional connectivity between ROIs and the whole brain were analyzed.The results showed significant positive correlation between the RAVLT scores and the FC values from the left hippocampus to the left frontal lobe (r=0.272,P=0.031).The FC values from the right cingulate gyrus to right inferior parietal lobule were found to be correlated positively with the scores on the TMT-B (r=0.410,P=0.023).Conclusions The patients with cerebellar stroke had cognitive impairment,mainly in memory and executive function.The changes of ALFF and FC values in related brain area from cerebellar stroke enrich our understanding of cerebellar involvement in cognitive performance.

Objective To study the characteristics of colorectal cancer patients in Yunnan Tumor Hospital, and to provide the basis for the prevention and treatment of colorectal cancer. Methods Retrospective analysis was used to review colorectal cancer patients who were diagnosed first and received the main treatment in Yunnan Cancer Hospital from March 2005 to December 2014.According to the sampling principle ,there were 100 cases each year , with a total of 1000 cases. The clinical and pathological data were analyzed, including age, gender, pathogenesis, pathological type, and TNM stage. Results The average age of the 1000 patients enrolled in the survey was (63.4±12.8) years old, the male and female age group (60-69) accounted for the highest proportion.both men and women aged between 60 and 69 had a high occurance rate, and male patients were more than the female with a fraction of 1.42:1. Rectum is the most common primary site, accounting for 57%, followed by ascending colon, sigmoid colon, straight B junction, transverse colon, descending colon, and cecum. Adenocarcinoma was the main pathological type, accounting for 89.4%.Stage Ⅲ was the most common in TNM staging, accounting for 35.9%, followed by stage Ⅱ, Ⅰ, and stage Ⅳ. Most rectal cancers were found at stage Ⅲ, and colon cancer at stage Ⅱ . Conclusion The proportion of colorectal cancer in the age group (60-69 years) was the highest; the proportion of middle-aged and male was significant.The high incidence of colorectal cancer was 60～69 years old, especially males.The main part of colorectal cancer was located in the rectum.Adenocarcinoma was the most common pathological type. Most patients were later stage when diagnosed.

Objective To investigate the relationships between expressions of HPV and EBV in larynge-al carcinoma. Methods DNA flow-through hybridization and gene chip genotyping technology(HybriMax)and real-time quantitative PCR were used for 37 subtypes of HPV detection and quantitative detection of EBV in 101 cases of laryngeal cancer paraffin embedded tissue specimens. 43 cases of vocal cord polyp of paraffin embedded tissue specimens were used as the controls. Results The positive rate of laryngeal carcinoma was 13.86% in group HPV and 9.3% in the control group ,with no statistically significant difference between the positive expres-sions of HPV in the laryngeal carcinoma group and control group(P>0.05). The positive rate of laryngeal carci-noma was 63.37% and 13.95%,respectively ,in group EBV ,and the control group ,with significant difference between them(P < 0.05). In respect of the positive rate by comparing differently differentiated EBV in laryngeal carcinoma ,there was no significant difference in the positive expression of EBV in well differentiated and differen-tiated laryngeal carcinoma(P>0.05),but the difference was statistically significant in highly differentiated EBV as compared with those with low differentiation type,medium differentiation and poor differentiation(P < 0.05). There was no significant difference between the groups in view of sex ,age and course of disease in the patients (P > 0.05). Conclusions The incidence of laryngeal carcinoma is closely related with EBV infection ,possibly relationed with HPV and high-risk subtypes of HPV have a certain role in the process of induced laryngeal carcino-ma. The gender ,age and duration of disease have no significant correlation with EBV infection. This study will provide a basis for further invesgitation of pathogenesis of laryngeal cancer and prevention and treatment of larynge-al cancer.

Objective To explore the relationship between accessory renal artery(ARA)and essential hypertension,and the possible mechanism using CT angiography(CTA).Methods The patients who underwent CTA examination on renal artery were reviewed retrospectively in our hospital.A variety of CTA reconstruction techniques were used to observe the type and number of ARA,as well as the diameter of ARA and the main renal artery.Results A total of 126 ARA(66 left ARA and 60 right ARA)were found in 253 patients. 10% of the patients had more than two ARAs.In 164 patients with essential hypertension,ARA detection rate was 40.2%(66/164).In the non-hypertension patients,the proportion of ARA was 31.5%(28/89).There was higher proportion of young(P=0.002)and male (P=0.022)patients in ARA hypertension group compared with ARA non-hypertension group.There were no significant differences on the prevalence of type(P=0.826)and number of ARA(P=0.501)between these two groups.In all of the patients with single ARA,no significant differences were detected on the ratios of diameter of ARA and main renal artery between the two groups(P=0.32). However,in ARA hypertension group,the diameter of main renal artery on the ARA side was significantly smaller than that on the opposite side(P=0.01).In non-hypertension ARA group,no statistical difference was found between the diameter of bilateral main renal arteries(P=0.06).Conclusion ARA is more prevalent in essential hypertensive patients,especially in young male.The decrease of the diameter of main renal artery in the ARA side may be a possible mechanism for essential hypertension.

Amyloidosis ; Cardiomyopathy, Hypertrophic ; Humans