N-Acetylcysteine-Derived Carbon Dots for Free Radical Scavenging in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is associated with oxidative stress induced reactive oxygen species (ROS) dynamic equilibrium disturbance. Nanozymes, as nanomaterials with enzyme-like activity, can regulate intro-cellular ROS levels. In this study, a new carbon dots nanozyme, N-acetylcysteine-derived carbon dots (NAC-CDs), is developed and proved to be an ideal antioxidant and anti-senescent agent in IVDD management. The results confirmed the NAC-CDs have satisfactory biocompatibility and strong superoxide dismutase (250 U mg-1 ), catalase, glutathioneperoxidase-like activity, and total antioxidant capacity. Then, the powerful free radical scavenging and antioxidant ability of NAC-CDs are demonstrated in vitro as observing the reduced ROS in H2 O2 induced senescent nucleus pulposus cells (NPCs), in which the elimination efficiency of toxic ROS is more than 90%. NAC-CDs also maintained mitochondrial homeostasis and suppressed cellular senescence, subsequently inhibited the expression of inflammatory factors in NPCs. In vivo, evaluations of imaging and tissue morphology assessments suggested that disc height index, magnetic resonance imaging grade and histological score are significantly improved from the degenerative models when NAC-CDs is applied. In conclusion, the study developed a novel carbon dots nanozyme, which efficiently rescues IVDD from ROS induced NPCs senescence and provides a potential strategy in management of IVDD in clinic.

Controlled-release of apatinib for targeted inhibition of osteosarcoma by supramolecular nanovalve-modified mesoporous silica.

Targeted delivery of antitumor drugs has been recognized as a promising therapeutic modality to improve treatment efficacy, reduce the toxic side effects and inhibit tumor recurrence. In this study, based on the high biocompatibility, large specific surface area, and easy surface modification of small-sized hollow mesoporous silica nanoparticles ß-cyclodextrin (ß-CD)-benzimidazole (BM) supramolecular nanovalve, together with bone-targeted alendronate sodium (ALN) were constructed on the surface of small-sized HMSNs. The drug loading capacity and efficiency of apatinib (Apa) in HMSNs/BM-Apa-CD-PEG-ALN (HACA) were 65% and 25%, respectively. More importantly, HACA nanoparticles can release the antitumor drug Apa efficiently compared with non-targeted HMSNs nanoparticles in the acidic microenvironment of the tumor. In vitro studies showed that HACA nanoparticles exhibited the most potent cytotoxicity in osteosarcoma cells (143B cells) and significantly reduced cell proliferation, migration and invasion. Therefore, the drug-efficient release of antitumor effect of HACA nanoparticles is a promising way to treat osteosarcoma.

The association between muscle-to-fat ratio and cardiometabolic risks: The China National Health Survey.

BACKGROUND: The relationship between muscle mass and fat mass might be an indicator to assess the cardiometabolic risk independently from overweight/obesity, but evidence from a representative general Chinese population is lacking. OBJECTIVE: To understand the age- and sex-specific associations between muscle-to-fat ratio (MFR) and cardiometabolic risks in Chinese population. METHODS: 31,178 (12,526 men and 18,652 women) subjects from the China National Health Survey were included. Muscle mass and fat mass were assessed by a bioelectrical impedance device. MFR was calculated as muscle mass divided by fat mass. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), serum lipids, fasting plasma glucose and serum uric acid were measured. General linear regressions, quantile regressions and restricted cubic-spline (RCS) regressions were applied to assess the effect of MFR on cardiometabolic profiles. RESULTS: Per unit increase of MFR was associated with a 0.631 (0.759-0.502) mmHg SBP decrease in men, 2.648 (3.073-2.223) in women; 0.480 (0.568-0.392) mmHg DBP decrease in men, 2.049 (2.325-1.774) in women; a 0.054 (0.062-0.046) mmol/L total cholesterol decrease in men, 0.147 (0.172-0.122) in women; 0.084 (0.098-0.070) mmol/L triglycerides decrease in men, 0.225 (0.256-0.194) in women; a 0.045 (0.054-0.037) mmol/L low-density lipoprotein decrease in men, 0.183 (0.209-0.157) in women; a 2.870 (2.235-3.506) µmol/L serum uric acid decrease in men, 13.352 (14.967-11.737) in women; and a 0.027 (0.020-0.033) mmol/L high-density lipoprotein increase in men, 0.112 (0.098-0.126) mmol/L in women. The effect in overweight/obese people was much significant than in under/normal weight counterparts. The RCS curves revealed both linear and non-linear relationships between increased MFR and lower cardiometabolic risk. CONCLUSIONS: Muscle-to-fat ratio is independently associated with multiple cardiometabolic parameters among Chinese adults. Higher MFR is related with better cardiometabolic health, and the effect is much significant in overweight/obese people and women.

Normative values of hand grip strength in a large unselected Chinese population: Evidence from the China National Health Survey.

BACKGROUND: Hand grip strength (HGS) is a powerful indicator of sarcopenia and other adverse health outcomes. Normative values for HGS for general Chinese people with a broad age spectrum are lacking. This study aims to establish normative values of HGS and explore the correlations between HGS and body composition among unselected people aged 8-80 in China. METHODS: From 2012 to 2017, 39 655 participants aged 8-80 years in the China National Health Survey were included. Absolute HGS was measured using a Jamar dynamometer. The relative HGS was normalized by body mass index. Body composition indexes included body mass index, body fat percentage, muscle mass, fat mass index (FMI) and muscle mass index (MMI). Sex-specific smoothed centile tables for the P1 , P5 , P25 , P50 , P75 , P95 and P99 centiles of HGS and body composition were generated using lambda-mu-sigma method. The correlations between muscle strength and body composition were estimated by partial Spearman correlation analysis. RESULTS: The median values (25th and 75th percentile) of HGS in boys and girls (8-19 years old) were 22 (14, 34) kg and 18 (12, 22) kg, respectively; in men and women aged 20-80 were 39 (33, 44) kg and 24 (20, 27) kg, respectively. Values of upper and lower HGS across ages had three periods: an increase to a peak in the 20 s in men (with the 5th and 95th values of 30 and 55 kg, respectively) and 30 s in women (with the 5th and 95th values of 18 and 34 kg, respectively), preservation through midlife (20s-40 s), and then a decline after their 50 s. The lowest HGS values in both sexes were in the 70- to 80-year-old group, with the 5th and 95th percentile values of 16 and 40 kg in men, and 10 and 25 kg in women. There were substantial sex differences in body composition in the life course (all P values <0.001). In ageing, the decrease of muscle strength was faster than that of muscle mass in both sexes. The correlations between muscle mass and HGS were most robust than other correlations, especially in women (0.68 vs. 0.50), children and adolescents. CONCLUSIONS: Our study established the age- and sex-specific percentile reference values for hand grip strength in an unselected Chinese population across a broad age-spectrum. The rich data can facilitate the practical appraisal of muscle strength and promote early prediction of sarcopenia and other impairments associated with neuromuscular disorders.

Fat-to-Muscle Ratio Is Independently Associated with Hyperuricemia and a Reduced Estimated Glomerular Filtration Rate in Chinese Adults: The China National Health Survey.

BACKGROUND: The effects of the fat-to-muscle ratio (FMR) on hyperuricemia and a reduction in the estimated glomerular filtration rate (eGFR) are still unclear. METHODS: Data from the China National Health Survey were used to explore the associations of the FMR with hyperuricemia and reduced eGFR. The fat mass and muscle mass were measured through bioelectrical impedance analysis. Mediation analysis was used to estimate the mediated effect of hyperuricemia on the association between the FMR and reduced eGFR. RESULTS: A total of 31171 participants were included. For hyperuricemia, compared with the Q1 of the FMR, the ORs (95% CI) of Q2, Q3 and Q4 were 1.60 (1.32-1.95), 2.31 (1.91-2.80) and 2.71 (2.15-3.43) in men and 1.91 (1.56-2.34), 2.67 (2.12-3.36) and 4.47 (3.40-5.89) in women. For the reduced eGFR, the ORs (95% CI) of Q2, Q3 and Q4 of the FMR were 1.48 (1.18-1.87), 1.38 (1.05-1.82) and 1.45 (1.04-2.04) in men aged 40-59, but no positive association was found in younger men or in women. Hyperuricemia mediated the association between the FMR and reduced eGFR in men. The OR (95% CI) of the indirect effect was 1.08 (1.05-1.10), accounting for 35.11% of the total effect. CONCLUSIONS: The FMR was associated with hyperuricemia and reduced eGFR, and the associations varied based on sex and age. The effect of the FMR on the reduced eGFR was significantly mediated by hyperuricemia in men.

RIPK3 modulates sarcoma through immune checkpoint HAVCR2.

Sarcomas is a complex group of malignant diseasse with undetermined molecular mechanisms. Receptor interacting serine/threonine kinase 3 (RIPK3) is a necroptosis- and apoptosis-related marker that has been implicated in several immune-associated diseases and aggressive malignant tumours. In the present study, publicly available transcriptome sequencing data were collected from The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research To Generate Effective Treatments (TARGET) databases and extensive data mining was performed, focusing on RIPK3 and its potential function in the modulation of gene expression and signaling pathways, immune checkpoints and cell infiltration. Analysis of TCGA and TARGET data revealed 603 up- and 260 downregulated genes in the higher RIPK3 expression group compared with the lower RIPK3 expression groups, with transmembrane channel like 8 and transmembrane protein 97 as the top up- and downregulated genes, respectively. Further pathway analysis revealed that the overexpressed genes were enriched in 'cytokine-cytokine receptor interaction'. Higher RIPK3 was found to be associated with improved survival, the immune checkpoint gene hepatitis A virus cellular receptor 2 (HAVCR2) and an improved response to immune blockade therapy. The potential modulation of HAVCR2 expression by RIPK3 was confirmed by reverse transcription-quantiative PCR in KHOS and 143B human osteosarcoma cell lines. Immune cell infiltration analysis revealed that RIPK3 was positively associated with macrophage and monocyte infiltration, suggesting that RIPK3 executes its function through these immune cells. These findings led to the hypothesis that increased RIPK3 expression may result in improved survival, possibly by regulating the immune checkpoint HAVCR2. In conclusion, the present study comprehensively elucidated the RIPK3 profile with regard to sarcoma survival, transcriptome expression, immune checkpoint therapy and immune cell infiltration. These findings suggest that RIPK3 is potentially a therapeutic target for sarcoma.

[Expression of TCF3 in Burkitt's Lymphoma and Its Proliferative Effect and Prognostic Significance].

OBJECTIVE: To observe the mutation and expression of TCF3 gene in Burkitt's lymphoma (BL), and explore its effect on the proliferation of BL cells and clinical efficacy and prognosis. METHODS: The mutation and expression of TCF3 in tumor tissues from BL patients were observed by the second-generation sequencing and real-time quantitative PCR. The proliferation and apoptosis of lymphoma cells after TCF3 knocked down were observed by siRNA interference technique and CCK-8 method. Survival analysis was used to observe the relationship between TCF3 mutation and the treatment efficacy and prognosis of BL patients. RESULTS: There were high frequency mutation rate (mutation rate was 23.7%) and high expression of TCF3 in BL patients. After TCF3 knocked down, cell proliferation was inhibited and apoptosis was promoted. In TCF3-siRNA group and control group, the cell proliferation rate at 48 h was (50.2±5.9)% and (96.6±11.4)%, and apoptosis rate was 30.1% and 1.5%, respectively, which showed significantly different between the two groups (P<0.001, P=0.005). The complete remission rate of patients with TCF3 mutation was low. The complete remission rate of mutant group and wild-type group was 44.4% and 82.8%, respectively (P=0.023). The 2-year progression-free survival rate and overall survival rate of the patients with TCF3 mutation was 55.6% and 61.0%, respectively, which was lower than 83.2% and 85.2% of the patients without mutation, but the differences were not statistically significant. CONCLUSION: There are mutation and abnormal expression of TCF3 in patients with BL. Patients with TCF3 mutations have low remission rate and poor prognosis.

Oxidation leaching of chromium from electroplating sludge: Ultrasonic enhancement and its mechanism.

The oxidation leaching of chromium from electroplating sludge was investigated, and ultrasonication was introduced for the enhancement of the leaching process. Two different types of Cr-bearing electroplating sludge were selected for the study, and the effects of the reagent dosage, temperature, and ultrasonic pulse ratio on the leaching efficiency were tested through oxidation leaching experiments. The experimental results show that hydrogen peroxide and sodium hypochlorite exhibit different leaching effects on different types of electroplating sludge. The control of reagent dosage is crucial for the oxidation leaching of Cr, while the effect of temperature turns out to be small. Hydrogen peroxide turns out to be a more effective oxidizer for chromium sludge, and the leaching efficiency of Cr could be promoted from 77.52% to 87.08% using ultrasonic enhancement under optimum conditions. Interestingly, sodium hypochlorite exhibited better leaching efficiency than hydrogen peroxide for the mixed sludge since the organic matter in the mixed sludge will lead to the rapid decomposition and consumption of hydrogen peroxide. The leaching efficiency of Cr from the mixed sludge could also be promoted from 56.82% to 67.10% using ultrasonic enhancement under optimum conditions. According to the scanning electron microscope imaging, ultrasonic enhancement can create voids and cracks on the surface of the sludge particles, hence promoting the contact between electroplating sludge and leaching agents, and promoting the oxidation leaching efficiency. In addition, ultrasound seems to be able to remove the coverings on the surface of the mixed sludge particles, which may facilitate the oxidation reaction.

The Mediation Effect of Body Composition on the Association Between Menopause and Hyperuricemia: Evidence From China National Health Survey.

Reproductive factors have been demonstrated to be associated with hyperuricemia. Body composition is an essential determinant influencing serum uric acid (SUA), but it is largely unknown whether increased SUA was influenced by changed body composition during the menopausal transition. As a secondary analysis of China National Health Survey from 2012-to 2017, this study included 18,997 women aged 20 to 80. Menarche age and menopause information were collected by questionnaire interview. Body mass index (BMI), body fat percentage (BFP), fat mass index (FMI), and fat-free mass index (FFMI) were used as body composition indexes. Hyperuricemia was defined as SUA higher than 360µmol/L (approximately 6 mg/dl). Mediation analysis was performed to explore the direct and indirect effects of menopause on hyperuricemia. A 1:2 age-matched case-control data set (n=6202) was designed to control age-related confounders and was used in multivariable analyses. After adjustment of covariates, postmenopausal women had 14.08 (10.89-17.27) µmol/L higher SUA than their premenopausal counterparts. Overweight/obesity and higher levels of BFP, FMI, and FFMI were all found to be positively associated with hyperuricemia. The mediation analysis showed that the total effect of menopause on hyperuricemia was positive, but was substantially mediated by body composition indexes. Forty-five percent of the total effect can be attributed to the indirect effect mediated by BMI (OR for the natural indirect effect (NIE): 1.09, 95%CI: 1.04-1.13), and over 80% mediated by BFP (OR for NIE: 1.23, 95%CI: 1.16-1.29). However, FFMI did not present the mediated role in the association (OR for NIE: 0.99, 95%CI: 0.96-1.02). The findings revealed that body composition, especially the fat mass indexes, significantly mediated the association between menopause and hyperuricemia. The role of body composition as mediator constitutes clinical and public health significance that should be recognized and considered in healthcare for women experiencing their menopause transition.

CircPCBP2 promotes the stemness and chemoresistance of DLBCL via targeting miR-33a/b to disinhibit PD-L1.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy with a high relapse rate of up to 40%. The prognosis of the disease needs improvement and requires a understanding of its molecular mechanism. We investigated the mechanisms of DLBCL development and its sensitivity to chemotherapy by focusing on circPCBP2/miR-33a/b/PD-L1 axis. Human DLBCL specimens and cultured cancer cell lines were used. Features of circPCBP2 were systematically characterized through Sanger sequencing, Actinomycin D, RNase R treatment, and FISH. The expression levels of circPCBP2, miR-33a/b, PD-L1, stemness-related markers, ERK/AKT and JAK2/STAT3 signaling were measured using qRT-PCR, western blotting, and immunohistochemistry. Stemness of DLBCL cells was assessed through spheroid formation assay and flow cytometry. Cell viability and apoptosis upon cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment were determined using MTT assay and flow cytometry, respectively. Interactions of circPCBP2-miR-33a/b and miR-33a/b-PD-L1 were validated using dual luciferase activity assay and RNA-RIP. Nude mouse xenograft model was used to assess the function of circPCBP2 in DLBCL growth in vivo. circPCBP2 was upregulated in human DLBCL specimens and cultured DLBCL cells while miR-33a/b was reduced. Knockdown of circPCBP2 or miR-33a/b overexpression inhibited the stemness of DLBCL cells and promoted cancer cell apoptosis upon CHOP treatment. circPCBP2 directly bound with miR-33a/b while miR-33a/b targeted PD-L1 3'-UTR. circPCBP2 disinhibited PD-L1 signaling via sponging miR-33a/b. miR-33a/b inhibitor and activating PD-L1 reversed the effects of circPCBP2 knockdown and miR-33a/b mimics, respectively. circPBCP2 knockdown restrained DLBCL growth in vivo and potentiated the anti-tumor effects of CHOP. In conclusion, circPCBP2 enhances DLBCL cell stemness but suppresses its sensitivity to CHOP via sponging miR-33a/b to disinhibit PD-L1 expression. circPCBP2/miR-33a/b/PD-L1 axis could serve as a diagnosis marker or therapeutic target for DLBCL.

Odorous gas emissions from sewage sludge composting windrows affected by the turning operation and associated health risks.

The treatment and disposal of sewage sludge (SL) has long been a challenging task in China. Open windrow composting, coupled with mechanical turning, is preferred in small cities and rural areas, due to low costs and ease of operation. However, the emission of odorous volatile organic compounds (VOCs) from open composting windrows, as well as related health risks, has aroused strong protests from surrounding populations. This study investigated VOC emissions (including hydrogen sulphide) from five open SL composting windrows at a single site, before, during and after turning operations, and across different seasons. As expected, the highest VOC concentration (6676 µg m-3) was measured while turning the windrows, whilst an additional emission peak was observed at all windrows at different times after turning, which was determined by the raw material mixing ratio (SL: woodchips), as well as ambient and windrow temperatures. In general, higher VOCs emissions and odour concentrations were measured in summer, and odour pollution was mainly caused by sulphur and oxygenated compounds, due to their high odour activity values (OAVs). Methyl mercaptan, dimethyl disulphide, dimethyl sulphide, diethyl sulphide, acetaldehyde and ethyl acetate were identified as the odour pollution indicators for the composting facility. The results from a health risk assessment showed that acetaldehyde was the most hazardous compound, with both non-carcinogenic and carcinogenic risks exceeding acceptable levels. The carcinogenic risks of benzene and naphthalene were also above acceptable levels; however, their risks were insignificant at the studied site due to the low concentrations.

Joint Effect of Beer, Spirits Intake, and Excess Adiposity on Hyperuricemia Among Chinese Male Adults: Evidence From the China National Health Survey.

Alcohol intake and excess adiposity are associated with serum uric acid (SUA), but their interaction effect on hyperuricemia (HUA) remains unclear. Using data from the China National Health Survey (CNHS) (2012-2017), we analyzed the additive interaction of beer, spirits intake, excess adiposity [measured by body mass index (BMI), body fat percentage (BFP), and visceral fat index (VFI)] with HUA among male participants aged 20-80 from mainland China. The relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (SI) were calculated to assess the interaction effect on the additive scale. Both RERI and AP larger than 0 and SI larger than 1 indicate a positive additive interaction. Among 12,592 male participants, the mean SUA level was 367.1 ± 85.5 µmol/L and 24.1% were HUA. Overweight/obese men who were presently drinking spirits had an odds ratio (OR) of 3.20 (95%CI: 2.71-3.79) than the never drink group, with RERI, AP, and SI of 0.45 (95%CI: 0.08-0.81), 0.14 (95%CI: 0.03-0.25), and 1.25 (95%CI: 1.02-1.54), respectively. However, although combined exposures on beer intake and excess adiposity had the highest OR compared with no beer intake and nonobese participants, there was no additive interaction, with RERI, AP, and SI in the overweight/obesity and the beer intake group of 0.58 (-0.41-1.57), 0.17 (-0.08-0.41), and 1.30 (0.85-1.97), respectively. Other excess adiposity indexes revealed similar estimates. Our findings suggested that the exposures of both excess adiposity and alcohol drink could result in an additive interaction effect on HUA: the combined risk of excess adiposity with spirits intake but not with beer was greater than the sum of the effects among Chinese male adults.

Body mass index was linked with multi-cardiometabolic abnormalities in Chinese children and adolescents: a community-based survey.

BACKGROUND: Evidence on how body mass index (BMI) influence cardiometabolic health remains sparse in Chinese children and adolescents, especially in south China. We aim to investigate the effect of overweight and/or obesity on high blood pressure (HBP), dyslipidemia, elevated serum uric acid (SUA) and their clustering among children and adolescents in an island in South China. METHODS: Using multi-stage cluster sampling method, 1577 children and adolescents aged 7-18 in Hainan province, south China, participated in the survey. The association between body mass index and cardiometabolic indexes were explored. Overweight and obesity were classified according to criteria of World Health Organization for children and adolescents aged 5 to 19. Restricted cubic spline models were used to examine the possible non-linear association between BMI and cardiometabolic profiles. Multivariable logistic regression models were fitted to examine the effect size of BMI on cardiometabolic disorders including HBP, elevated SUA and dyslipidemia. Comorbidity of at least two cardiometabolic abnormalities (HBP, dyslipidemia, elevated SUA) was defined as clustering of cardiometabolic risk factors. RESULTS: Comparing with normal weight and underweight subjects, overweight/obese youths had higher levels of BP, SUA, triglyceride, low-density lipoprotein but lower level of high-density lipoprotein. Overweight/obese youth had higher risk of dyslipidemia (OR:2.89, 95%CI: 1.65-5.06), HBP (OR:2.813, 95%CI: 1.20-6.59) and elevated SUA (OR: 2.493, 95%CI: 1.45-4.27), respectively, than their counterparts. The sex-, age-adjusted prevalence of abnormalities clustering was 32.61% (95% CI: 20.95% to 46.92%) in overweight/obesity group, much higher than in the under/normal weight group (8.85%, 95%CI: 7.44% to 10.48%). CONCLUSION: Excess adiposity increased the risk of elevated serum uric acid, serum lipids, blood pressure and their clustering among children and adolescents in south China.

The Effect of Body Weight and Alcohol Consumption on Hyperuricemia and Their Population Attributable Fractions: A National Health Survey in China.

INTRODUCTION: The prevalence of hyperuricemia (HUA) is increasing worldwide; understanding of population attributable fraction of modifiable risk factors (MRFs) is important for disease prevention. Given the sparse evidence on how MRFs influence HUA in mainland China, we aimed to explore the effect of excess body weight and alcohol consumption and their population attributable fractions of HUA based on a national survey in mainland China. METHODS: Using data from the China National Health Survey which included 31,746 Han Chinese of 20-80 years of age from 10 provinces, we estimated the prevalence and MRFs (overweight/obesity and alcohol consumption) of HUA. HUA was defined as serum uric acid >417 µmol/L in men and >340 µmol/L in women. Restricted cubic-spline models were used to demonstrate the linear and nonlinear associations between exposures and HUA. The adjusted population attributable risk (PAR) was calculated to understand the relative importance of each MRF. RESULTS: The prevalence of HUA was 25.1% in men and 15.9% in women. The population fraction of HUA cases that could be avoided by weight loss was 20.6% (19.3%-22.0%) in men and 18.1% (17.1%-19.0%) in women. The PAR of alcohol consumption was 12.8% (8.5%-17.1%) in men. Participants from Southwest China (Yunnan) had the highest HUA prevalence (47.9% in men and 29.9% in women) but with lower PAR of MRFs, especially in men (16.7%). Subjects in North China had lower HUA prevalence but higher PAR of MRFs. Around 44.8% male HUA cases in Inner Mongolia (26.9% of HUA prevalence) and 37.7% cases in Heilongjiang (34.4% of HUA prevalence) were attributable to overweight/obesity and alcohol consumption. CONCLUSION: There are significant sex and geographic difference on PAR of HUA due to MRFs. More tailored prevention strategies are needed to prevent HUA through weight loss and reduction of alcohol consumption.

Case Report: Adult degenerative scoliosis in two patients treated with percutaneous spinal endoscopic-assisted lumbar interbody fusion and percutaneous pedicle screw fixation.

Adult degenerative scoliosis (ADS) is a serious disease that often affects middle-aged and elderly people. ADS does not only cause sagittal and coronal deformity of the lumbar spine but also causes severe back and leg pain secondary to the compression of the neural structures. Open surgery remains the main method for correcting the occurring deformity and decompression of the neural structures; however, its benefit is limited in cases of large trauma. Minimally invasive spinal (MIS) surgery is an alternative method that has recently witnessed rapid development. It has the advantage of providing rapid recovery with less trauma as compared to conventional open surgery. We report two cases of ADS treated with percutaneous spinal endoscopic-assisted lumbar interbody fusion (EALIF) and percutaneous pedicle screw fixation. Both cases had moderate deformities of the lumbar spine (load-sharing classification 4-7 points) with severe back and leg pain, and they underwent successful MIS surgery. At 6 months of follow-up, the visual analog scale and Oswestry disability index scores of both patients improved and the deformity was corrected. For moderate ADS, percutaneous spinal EALIF and percutaneous pedicle screw fixation may achieve an effective correction of the deformity with direct decompression of neural structures.

Transcription factor 3 (TCF3) combined with histone deacetylase 3 (HDAC3) down-regulates microRNA-101 to promote Burkitt lymphoma cell proliferation and inhibit apoptosis.

To explore the function of transcription factor 3 (TCF3) on the proliferation and apoptosis of Burkitt lymphoma cells and its mechanism. qRT-PCR was performed to determine the expression of TCF3, histone deacetylase 3 (HDAC3), and microRNA-101 (miR-101) in the Burkitt lymphoma (BL) tumor tissues and lymph node tissues with reactive lymph node hyperplasia (RLNH). We found that the expression of TCF3 and HDAC3 was up-regulated in BL tumor tissues and lymphoma cells, and the miR-101 expression was down-regulated. And TCF3 and HDAC3 were negatively correlated with the expression of miR-101, respectively. In addition, knockdown of TCF3 can inhibit BL cell proliferation, reduce cell viability and promote cell apoptosis, retain the cell cycle in the G0/G1 phase, and inhibit the expression of Akt/mTOR pathway-related proteins (p-Akt and p-mTOR). When miR-101 was overexpressed, the results were the same as when TCF3 was knocked down. Moreover, we used Co-immunoprecipitation (Co-IP) to detect the interaction between TCF3 and HDAC3, and performed the Chromatin immunoprecipitation (ChIP) experiment to detect the enrichment of TCF3 and HDAC3 in the promoter region of miR-101. We found that TCF3 can interact with HDAC3 and is enriched in the miR-101 promoter region. In conclusion, TCF3 combined with HDAC3 down-regulates the expression of miR-101, thereby promoting the proliferation of BL cells and inhibiting their apoptosis.

Effect of fat mass index, fat free mass index and body mass index on childhood blood pressure: a cross-sectional study in south China.

BACKGROUND: Evidence on how different body composition indexes, such as body mass index (BMI), fat mass index (FMI) and fat free mass index (FFMI), influence blood pressure (BP) in Chinese children and adolescents is sparse. The aim of this study is to assess the effect of different body composition on BP in participants aged 7-18 in south China. METHODS: A cross-sectional study was conducted in 2013. A total of 1,609 children and adolescents from urban and rural areas in Hainan Province, South China, were selected using multi-stage stratified cluster sampling method. Each participant underwent anthropometric and BP tests. BMI, FMI and FFMI were calculated and analyzed as body composition indexes. RESULTS: In the population level stratified by sex, FFMI had the highest r-value (Partial Spearman correlations) of correlation with systolic BP in boys (rs=0.305, P<0.001) and girls (rs=0.237, P<0.001). FMI was found to have the highest r-value of correlation with DBP in boys (rs=0.154, P<0.001). The quantile regression model indicated that, within each age group, all body composition indexes was positively associated with systolic BP, and FFMI has the greatest value of regression coefficient (4.38, 95% CI: 3.81-4.95). But for diastolic BP, positive associations with BMI, FMI and FFMI were only observed in the 11-12 years group. Restrict cubic spline models showed that there were both linear and non-linear relations between BMI, FMI and BP, but for FFMI, there was only linear association with BP. CONCLUSIONS: The relation between BP and FFMI was stronger than with BMI and FMI. Combined measurement of body composition should be considered to help health professionals interpret body mass data from children and adolescents with varied stature and age.

[PX-12 Promoting Apoptosis of Multiple Myeloma Cell Line H929 Induced by Bortezomib].

OBJECTIVE: To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib. METHODS: MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 µmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H2DCFDA probe labeling. RESULTS: MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G2/M phase was increased to 28% and 40%, respectively. The cells in bortezomib group also showed a similar distribution after being treated. After treated with PX-12 and bortezomib, the cells in G1 phase were decreased significantly to 19% and 12% in S phase, but increased significantly to 68% in G2/M phase, which was significantly different from PX-12 group and bortezomib group (P<0.01). After culture for 72 hours, the apoptosis rate was 71.3% in the combination group, which was significantly higher than that in PX-12 group, bortezomib group, and control group (20.6%, 33.3%, 10.6%)(P<0.01). After culture for 24 hours, the intracellular ROS level in the combination group was 12015±430.2, which was higher than that in the PX-12 group, bortezomib group, and control group (6729±352.8, 2651±228.3, 1098±164.6, respectively) (P<0.01). CONCLUSION: PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.

CircKDM4C upregulates P53 by sponging hsa-let-7b-5p to induce ferroptosis in acute myeloid leukemia.

To investigate the role of circKDM4C in acute myeloid leukemia (AML), the expression of circKDM4C, hsa-let-7b-5p, and P53 was measured by qRT-RCR. AML cell lines(K-562 and HL-60) were transfected correspondingly and investigated for cell proliferation, migration, and invasion abilities by CCK-8, colony formation, transwell, and wound healing assays, respectively. The levels of P53, ACSL4, PTGS2, GPX4, and FTH1 in the K-562, and HL-60 cells were measured by western blotting. Also, circKDM4C mediated regulation of ferroptosis was studied. The Phen Green SK probe and confocal laser scanning microscope were used to assess the cellular iron levels. The reactive oxygen species levels were analyzed by fluorescence-activated cell sorting using the C11-BODIPY probe. Bioinformatics analysis predicted the putative binding sites among circKDM4C, hsa-let-7b-5p, and P53. These were verified using the dual-luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation assays. Finally, in vitro findings were also verified in vivo using the nude mice. CircKDM4C was significantly down-regulated in AML patients. The overexpression of circKDM4C in AML cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. We found that circKDM4C acts as a sponge of hsa-let-7b-5p and thereby regulates p53 which is a target gene of hsa-let-7b-5p. Also, the expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to AML patients. Moreover, we found that circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53. This work emphasizes the role of circKDM4C in AML patients, which could be explored for the therapeutic role.