PABPN1 functions as a predictive biomarker in colorectal carcinoma.

PURPOSE: PABPN1 acts as a modulator of poly(A) tail length and alternative polyadenylation. This research was aimed to explore the role of PABPN1 in colorectal cancer (CRC). METHODS: Public databases were performed to analyze expression, location, roles of prognosis and tumor immunity and interaction with RNAs and proteins of PABPN1. To investigate PABPN1 expression in tissues, 78 CRC specimens were collected to conduct IHC, and 30 pairs of frozen CRC and corresponding adjacent normal tissues were used to conduct qRT-PCR and WB. In addition, in vitro experiments were then carried out to identify the role of PABPN1 in CRC. RESULTS: Compared with normal tissues, PABPN1 expression was significant higher in CRC. Its high level predicted poor outcome of CRC. Th1 and Treg had significant negative relationships not only with PABPN1 expression, but also with six molecules interacting with PABPN1, including IFT172, KIAA0895L, RECQL4, WDR6, PABPC1 and NCBP1. In addition, PABPN1 had negative relationships with quite a few immune markers, such as CSF1R, IL-10, CCL2 and so on. In cellular experiments, silencing PABPN1 inhibited proliferation and promoted apoptosis in HCT-116 CRC cells. CONCLUSION: In summary, PABPN1 might become a novel biomarker and correlate with tumor immunity in CRC.

Effects of an anterior ankle-foot orthosis on walking mobility in stroke patients: get up and go and stair walking.

OBJECTIVE: To examine the effects of an anterior ankle-foot orthosis (AAFO) on walking mobility in stroke patients. DESIGN: Cross-sectional and repeated-measures study design. SETTING: A university's neurologic rehabilitation department. PARTICIPANTS: Ambulant stroke patients (N=21). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Walking mobility was measured by the Timed Up and Go (TUG) test and the Timed Up and Down Stairs (TUDS) test. The paired t test was used to determine the difference between the mobility performances measured with and without the AAFO. RESULTS: There were significant differences between mobility performances with and without an AAFO in the TUG test (P=.038) and the TUDS test (P=.000). CONCLUSIONS: This study supports the effect of an AAFO on walking mobility in stroke patients. The findings demonstrate that stroke patients wearing an AAFO may ambulate with greater speed and safety on level surfaces and stairs.

Tacrolimus reversibly reduces insulin secretion, induces insulin resistance, and causes islet cell damage in rats.

OBJECTIVE: To investigate the diabetogenic effects of the immunosuppressive agent tacrolimus, the reversibility of these effects upon treatment discontinuation, and the underlying mechanisms in a rat model. MATERIALS AND METHODS: 60 healthy male rats were randomly divided into three groups for intragastric administration of tacrolimus either at 4 mg/kg/d or 2 mg/kg/d or an equal volume of normal saline (control). The treatment was administered for 5 months, followed by a 5-month period of no intervention. Fasting plasma glucose and insulin levels were used to calculate the homeostasis model assessment of ß-cell function (HOMA-ß) and insulin sensitivity index (ISI). RESULTS: Tacrolimus treatment significantly increased blood glucose concentrations (p < 0.05) and lowered HOMA-ß and ISI (p < 0.01) in a time- and dose-dependent manner. Five months after tacrolimus treatment, significant islet cell injury was observed. However, 5 months after tacrolimus discontinuation, blood glucose concentrations significantly declined, HOMA-β and ISI levels significantly increased, and islet cell morphology noticeably improved. CONCLUSIONS: In conclusion, tacrolimus treatment of healthy rats increased blood glucose concentrations in a time- and concentration-dependent manner. Development of tacrolimus-induced diabetes and reversibility after tacrolimus discontinuation may involve factors of and interactions between the insulin secretion pathway, local and/or systemic insulin resistance, and islet cell damage.

The Influence of Prenatal Breastfeeding Self-Efficacy on Breastfeeding Behavior of Taiwanese Pregnant Women.

BACKGROUND: The benefits of breastfeeding for mothers and infants are well known. However, in Taiwan, the average breastfeeding rate remains below the World Health Organization recommendations. Breastfeeding self-efficacy is a known predictor of breastfeeding. RESEARCH AIMS: To determine: (1) the relationship of sociodemographic factors to prenatal breastfeeding self-efficacy, and (2) the relationship of sociodemographic factors and prenatal breastfeeding self-efficacy to breastfeeding behavior at 8 weeks postpartum among women living in Taiwan. METHODS: This was a prospective cohort study of 206 pregnant women collected in an outpatient clinic located in Taiwan. The validated Chinese version of the Prenatal Breastfeeding Self-Efficacy Scale (PBSES) was used to measure self-efficacy for breastfeeding during pregnancy. At 8 weeks postpartum, participants were contacted by telephone to obtain information regarding infant feeding method and duration. RESULTS: The mean age of the pregnant women was 32 years, and the mean prenatal breastfeeding self-efficacy score was 78.6 (SD = 10.6). Scores differed across levels of maternal education, previous breastfeeding experience, and support systems. Prenatal breastfeeding self-efficacy scores were highest among participants reporting spouse support versus other types of support. Maternal age and prenatal breastfeeding self-efficacy were predictive of breastfeeding duration. A 1-year increase in maternal age was associated with a 6% lower likelihood of breastfeeding for at least 2 months postpartum, and a 1-point increase in the prenatal breastfeeding self-efficacy score was associated with a 14% increase in the likelihood of breastfeeding for at least 2 months postpartum. CONCLUSIONS: Prenatal breastfeeding self-efficacy may help predict breastfeeding continuation among Taiwanese women in the first 2 months postpartum.

Association between triglyceride-glucose index and colorectal polyps: A retrospective cross-sectional study.

BACKGROUND: Colorectal polyps (CPs) are frequently occurring abnormal growths in the colorectum, and are a primary precursor of colorectal cancer (CRC). The triglyceride-glucose (TyG) index is a novel marker that assesses metabolic health and insulin resistance, and has been linked to gastrointestinal cancers. AIM: To investigate the potential association between the TyG index and CPs, as the relation between them has not been documented. METHODS: A total of 2537 persons undergoing a routine health physical examination and colonoscopy at The First People's Hospital of Kunshan, Jiangsu Province, China, between January 2020 and December 2022 were included in this retrospective cross-sectional study. After excluding individuals who did not meet the eligibility criteria, descriptive statistics were used to compare characteristics between patients with and without CPs. Logistic regression analyses were conducted to determine the associations between the TyG index and the prevalence of CPs. The TyG index was calculated using the following formula: Ln [triglyceride (mg/dL) × glucose (mg/dL)/2]. The presence and types of CPs was determined based on data from colonoscopy reports and pathology reports. RESULTS: A nonlinear relation between the TyG index and the prevalence of CPs was identified, and exhibited a curvilinear pattern with a cut-off point of 2.31. A significant association was observed before the turning point, with an odds ratio (95% confidence interval) of 1.70 (1.40, 2.06), P < 0.0001. However, the association between the TyG index and CPs was not significant after the cut-off point, with an odds ratio (95% confidence interval) of 0.57 (0.27, 1.23), P = 0.1521. CONCLUSION: Our study revealed a curvilinear association between the TyG index and CPs in Chinese individuals, suggesting its potential utility in developing colonoscopy screening strategies for preventing CRC.

Retraction note to: Association between triglyceride-glucose index and colorectal polyps: A retrospective cross-sectional study.

[This retracts the article on p. 55 in vol. 16, PMID: 38464818.].

Anoikis-related signature identifies tumor microenvironment landscape and predicts prognosis and drug sensitivity in colorectal cancer.

Background: Anoikis, a mechanism of programmed apoptosis, plays an important role in growth and metastasis of tumors. However, there are still few available comprehensive reports on the impact of anoikis on colorectal cancer. Method: A clustering analysis was done on 133 anoikis-related genes in GSE39582, and we compared clinical features between clusters, the tumor microenvironment was analyzed with algorithms such as "Cibersort" and "ssGSEA". We investigated risk scores of clinical feature groups and anoikis-associated gene mutations after creating a predictive model. We incorporated clinical traits to build a nomogram. Additionally, the quantitative real-time PCR was employed to investigate the mRNA expression of selected anoikis-associated genes. Result: We identified two anoikis-related clusters with distinct prognoses, clinical characteristics, and biological functions. One of the clusters was associated with anoikis resistance, which activated multiple pathways encouraging tumor metastasis. In our prognostic model, oxaliplatin may be a sensitive drug for low-risk patients. The nomogram showed good ability to predict survival time. And SIRT3, PIK3CA, ITGA3, DAPK1, and CASP3 increased in CRC group through the PCR assay. Conclusion: Our study identified two distinct modes of anoikis in colorectal cancer, with active metastasis-promoting pathways inducing an anti-anoikis subtype, which has a stronger propensity for metastasis and a worse prognosis than an anoikis-activated subtype. Massive immune cell infiltration may be an indicator of anoikis resistance. Anoikis' role in the colorectal cancer remains to be investigated.

Mouse betaine-homocysteine S-methyltransferase deficiency reduces body fat via increasing energy expenditure and impairing lipid synthesis and enhancing glucose oxidation in white adipose tissue.

Betaine-homocysteine S-methyltransferase (BHMT) catalyzes the synthesis of methionine from homocysteine. In our initial report, we observed a reduced body weight in Bhmt(-/-) mice. We initiated this study to investigate the potential role of BHMT in energy metabolism. Compared with the controls (Bhmt(+/+)), Bhmt(-/-) mice had less fat mass, smaller adipocytes, and better glucose and insulin sensitivities. Compared with the controls, Bhmt(-/-) mice had increased energy expenditure, with no changes in food intake, fat uptake or absorption, or in locomotor activity. The reduced adiposity in Bhmt(-/-) mice was not due to hyperthermogenesis. Bhmt(-/-) mice failed to maintain a normal body temperature upon cold exposure because of limited fuel supplies. In vivo and ex vivo tests showed that Bhmt(-/-) mice had normal lipolytic function. The rate of (14)C-labeled fatty acid incorporated into [(14)C]triacylglycerol was the same in Bhmt(+/+) and Bhmt(-/-) gonadal fat depots (GWAT), but it was 62% lower in Bhmt(-/-) inguinal fat depots (IWAT) compared with that of Bhmt(+/+) mice. The rate of (14)C-labeled fatty acid oxidation was the same in both GWAT and IWAT from Bhmt(+/+) and Bhmt(-/-) mice. At basal level, Bhmt(-/-) GWAT had the same [(14)C]glucose oxidation as did the controls. When stimulated with insulin, Bhmt(-/-) GWAT oxidized 2.4-fold more glucose than did the controls. Compared with the controls, the rate of [(14)C]glucose oxidation was 2.4- and 1.8-fold higher, respectively, in Bhmt(-/-) IWAT without or with insulin stimulus. Our results show for the first time a role for BHMT in energy homeostasis.

Role of LncRNA MIR99AHG in breast cancer: Bioinformatic analysis and preliminary verification.

Objective: This research was aimed to preliminarily explore the clinical roles and potential molecular mechanisms of MIR99AHG and its significant transcripts in breast cancer (BRCA). Methods: Public databases were utilized to analyze the expression and prognostic roles of MIR99AHG and its transcripts. Relationships between MIR99AHG expression and immune cells infiltration were analyzed in Xiantao platform. In addition, co-expressed genes and interacting proteins of MIR99AHG were predicted. CancerSEA analyzed its relationship with functional states. Next, CNV status, DNA methylation, interacting transcription factors (TFs) and ceRNA network were analyzed to explore its possible mechanisms. Then, RNA ISH and FISH assays were used to detect its expression and location in BRCA tissues and cell lines, respectively. Finally, qRT-PCR was utilized to investigate MIR99AHG expression in cell lines. Results: Compared with the corresponding normal tissues, MIR99AHG expression levels were lower in all BRCA subtypes, and luminal B's was the lowest one. And MIR99AHG expression was negatively related to the tumor stage. In addition, 4 transcripts (ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5) of MIR99AHG showed significant differences in the expression. Databases also suggested that the high MIR99AHG expression levels indicated good prognosis, especially in patients without lymph node metastasis. Xiantao found that MIR99AHG was positively related to 17 immune cells and negatively linked with 2 immune cells. CancerSEA analysis showed no relationships between MIR99AHG and functional states. From GEPIA and BCIP databases, 19 co-expressed genes were highly related to these four significant transcripts of MIR99AHG. StarBase, RNAct and HDOCK showed that several tumor-associated proteins, including U2AF65, hnRNPC, AEBP2, CHIC1 and so on, might interact with MIR99AHG. Genetically, BRCA had a higher proportion of MIR99AHG CNV loss than CNV gain, and the high level of DNA methylation indicated a good prognosis. Furthermore, 19 TFs were predicted to combine with the promoter of MIR99AHG. Then, we screened out 10 miRNAs potentially interacting with the significant transcripts of MIR99AHG, and five were significantly increased in breast tumors compared to normal tissues, including miR-194-5p, miR-320 b and so on, which could combine 14 mRNAs. Through ISH and FISH assays, we verified that MIR99AHG was down-regulated in BRCA samples and cell lines in comparison to non-tumor tissues and mammary epithelial cell line (MCF10A), and MIR99AHG was located both in cytoplasm and nucleus. qRT-PCR assay also showed the lower expression of MIR99AHG in breast cancer cells than that in MCF10A. Conclusion: These results indicate that MIR99AHG can be a favorable prognostic indicator for BRCA. ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5 are significant transcripts and their down-regulation may play crucial roles in the progression of BRCA.

Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas.

Betaine-homocysteine S-methyltransferase (BHMT) uses betaine to catalyze the conversion of homocysteine (Hcy) to methionine. There are common genetic polymorphisms in the BHMT gene in humans that can alter its enzymatic activity. We generated the first Bhmt(-/-) mouse to model the functional effects of mutations that result in reduced BHMT activity. Deletion of Bhmt resulted in a 6-fold increase (p < 0.01) in hepatic and an 8-fold increase (p < 0.01) in plasma total Hcy concentrations. Deletion of Bhmt resulted in a 43% reduction in hepatic S-adenosylmethionine (AdoMet) (p < 0.01) and a 3-fold increase in hepatic S-adenosylhomocysteine (AdoHcy) (p < 0.01) concentrations, resulting in a 75% reduction in methylation potential (AdoMet:AdoHcy) (p < 0.01). Bhmt(-/-) mice accumulated betaine in most tissues, including a 21-fold increase in the liver concentration compared with wild type (WT) (p < 0.01). These mice had lower concentrations of choline, phosphocholine, glycerophosphocholine, phosphatidylcholine, and sphingomyelin in several tissues. At 5 weeks of age, Bhmt(-/-) mice had 36% lower total hepatic phospholipid concentrations and a 6-fold increase in hepatic triacyglycerol concentrations compared with WT (p < 0.01), which was due to a decrease in the secretion of very low density lipoproteins. At 1 year of age, 64% of Bhmt(-/-) mice had visible hepatic tumors. Histopathological analysis revealed that Bhmt(-/-) mice developed hepatocellular carcinoma or carcinoma precursors. These results indicate that BHMT has an important role in Hcy, choline, and one-carbon homeostasis. A lack of Bhmt also affects susceptibility to fatty liver and hepatocellular carcinoma. We suggest that functional polymorphisms in BHMT that significantly reduce activity may have similar effects in humans.

Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake.

Elevated homocysteine (Hcy) concentrations are associated with increased risk of several chronic diseases. Hcy can be removed by methylating it to form methionine via either the betaine homocysteine S-methyltransferase (BHMT) or the methionine synthase (MS) pathway. BHMT uses betaine as the methyl donor, whereas MS uses 5-methyltetrahydrofolate. We previously found that mice with the gene encoding Bhmt deleted (Bhmt(-/-)) had altered Hcy metabolites in tissues. This study aimed to determine whether folate supplementation of Bhmt(-/-) mice reverses, and folate deficiency exacerbates, these metabolic changes. Bhmt(-/-) mice and their littermates (Bhmt(+/+) mice) were fed a folate-deficient (FD; 0 mg/kg diet), a folate control (FC; 2 mg/kg diet), or a folate-supplemented (FS; 20 mg/kg diet) diet for 4 wk. Bhmt(-/-) mice had higher plasma Hcy and hepatic S-adenosylhomocysteine (AdoHcy) concentrations and had lower hepatic S-adenosylmethionine (AdoMet) concentrations compared with Bhmt(+/+) mice for all diets. Although the FD diet increased plasma Hcy (P < 0.05) and hepatic AdoHcy (P < 0.001) concentrations in Bhmt(+/+) mice compared with FC and FS mice, the FD diet had no effect on the metabolites measured in Bhmt(-/-) mice. The FS diet did not ameliorate elevated plasma Hcy and elevated hepatic AdoHcy concentrations but did increase hepatic AdoMet concentrations in Bhmt(-/-) mice (P < 0.001) compared with FD and FC mice. We conclude that the BHMT pathway is a major route for the elimination of Hcy in mice and that the MS pathway has little excess capacity to methylate the Hcy that accumulates when the BHMT pathway is blocked.

Nanotechnology in Kidney and Islet Transplantation: An Ongoing, Promising Field.

Organ transplantation has evolved rapidly in recent years as a reliable option for patients with end-stage organ failure. However, organ shortage, surgical risks, acute and chronic rejection reactions and long-term immunosuppressive drug applications and their inevitable side effects remain extremely challenging problems. The application of nanotechnology in medicine has proven highly successful and has unique advantages for diagnosing and treating diseases compared to conventional methods. The combination of nanotechnology and transplantation brings a new direction of thinking to transplantation medicine. In this article, we provide an overview of the application and progress of nanotechnology in kidney and islet transplantation, including nanotechnology for renal pre-transplantation preservation, artificial biological islets, organ imaging and drug delivery.

Integrative analysis of a necroptosis-related gene signature of clinical value and heterogeneity in diffuse large B cell lymphoma.

Background: Diffuse large B-cell lymphoma (DLBCL), which is considered to be the most common subtype of lymphoma, is an aggressive tumor. Necroptosis, a novel type of programmed cell death, plays a bidirectional role in tumors and participates in the tumor microenvironment to influence tumor development. Targeting necroptosis is an intriguing direction, whereas its role in DLBCL needs to be further discussed. Methods: We obtained 17 DLBCL-associated necroptosis-related genes by univariate cox regression screening. We clustered in GSE31312 depending on their expressions of these 17 genes and analyzed the differences in clinical characteristics between different clusters. To investigate the differences in prognosis across distinct clusters, the Kaplan-Meier method was utilized. The variations in the tumor immune microenvironment (TME) between distinct necroptosis-related clusters were investigated via "ESTIMATE", "Cibersort" and single-sample geneset enrichment analysis (ssGSEA). Finally, we constructed a 6-gene prognostic model by lasso-cox regression and subsequently integrated clinical features to construct a prognostic nomogram. Results: Our analysis indicated stable but distinct mechanism of action of necroptosis in DLBCL. Based on necroptosis-related genes and cluster-associated genes, we identified three groups of patients with significant differences in prognosis, TME, and chemotherapy drug sensitivity. Analysis of immune infiltration in the TME showed that cluster 1, which displayed the best prognosis, was significantly infiltrated by natural killer T cells, dendritic cells, CD8+ T cells, and M1 macrophages. Cluster 3 presented M2 macrophage infiltration and the worst prognosis. Importantly, the prognostic model successfully differentiated high-risk from low-risk patients, and could forecast the survival of DLBCL patients. And the constructed nomogram demonstrated a remarkable capacity to forecast the survival time of DLBCL patients after incorporating predictive clinical characteristics. Conclusion: The different patterns of necroptosis explain its role in regulating the immune microenvironment of DLBCL and the response to R-CHOP treatment. Systematic assessment of necroptosis patterns in patients with DLBCL will help us understand the characteristics of tumor microenvironment cell infiltration and aid in the development of tailored therapy regimens.

Effects of Hinged versus Floor-Reaction Ankle-Foot Orthoses on Standing Stability and Sit-to-Stand Performance in Children with Spastic Diplegic Cerebral Palsy.

Hinged ankle-foot orthoses (HAFOs) and floor reaction ankle-foot orthoses (FRAFOs) are frequently prescribed to improve gait performance in children with spastic diplegic cerebral palsy (CP). No study has investigated the effects of FRAFO on sit-to-stand (STS) performance nor scrutinized differences between the application of HAFOs and FRAFOs on postural control. This study compared the effects of HAFOs and FRAFOs on standing stability and STS performance in children with spastic diplegic CP. Nine children with spastic diplegic CP participated in this crossover repeated-measures design research. Kinematic and kinetic data were collected during static standing and STS performance using 3-D motion analysis and force plates. Wilcoxon signed ranks test was used to compare the differences in standing stability and STS performance between wearing HAFOs and FRAFOs. The results showed that during static standing, all center of pressure (COP) parameters (maximal anteroposterior/mediolateral displacement, maximal velocity, and sway area) were not significantly different between FRAFOs and HAFOs. During STS, the floor reaction force in the vertical direction was significantly higher with FRAFOs than with HAFOs (p = 0.018). There were no significant differences in the range of motion in the trunk, knee, and ankle, the maximal velocity of COP forward displacement, completion time, and the force of hip, knee, and ankle joints between the two orthoses. The results suggest both FRAFOs and HAFOs have a similar effect on standing stability, while FRAFOs may benefit STS performance more compared to HAFOs.

Deletion of murine choline dehydrogenase results in diminished sperm motility.

Choline dehydrogenase (CHDH) catalyzes the conversion of choline to betaine, an important methyl donor and organic osmolyte. We have previously identified single nucleotide polymorphisms (SNPs) in the human CHDH gene that, when present, seem to alter the activity of the CHDH enzyme. These SNPs occur frequently in humans. We created a Chdh(-/-) mouse to determine the functional effects of mutations that result in decreased CHDH activity. Chdh deletion did not affect fetal viability or alter growth or survival of these mice. Only one of eleven Chdh(-/-) males was able to reproduce. Loss of CHDH activity resulted in decreased testicular betaine and increased choline and PCho concentrations. Chdh(+/+) and Chdh(-/-) mice produced comparable amounts of sperm; the impaired fertility was due to diminished sperm motility in the Chdh(-/-) males. Transmission electron microscopy revealed abnormal mitochondrial morphology in Chdh(-/-) sperm. ATP content, total mitochondrial dehydrogenase activity and inner mitochondrial membrane polarization were all significantly reduced in sperm from Chdh(-/-) animals. Mitochondrial changes were also detected in liver, kidney, heart, and testis tissues. We suggest that men who have SNPs in CHDH that decrease the activity of the CHDH enzyme could have decreased sperm motility and fertility.

Postsurgical Stability of Temporomandibular Joint of Skeletal Class III Patients Treated with 2-Jaw Orthognathic Surgery via Computer-Aided Three-Dimensional Simulation and Navigation in Orthognathic Surgery (CASNOS).

OBJECTIVE: The aim of this study is to clarify the postsurgical stability of temporomandibular joints in skeletal class III patients treated with 2-jaw orthognathic surgery which was performed utilizing computer-aided three-dimensional simulation and navigation in orthognathic surgery (CASNOS) protocol. MATERIALS AND METHODS: 23 consecutive nongrowing skeletal class III patients with mandibular prognathism associated with maxillary retrognathism treated with 2-jaw orthognathic surgery between 2018 and 2019 were enrolled in this study. The surgery was planned according to the standardized protocol of CASNOS (computer-aided three-dimensional simulation and navigation in orthognathic surgery). Computed tomography (CT) scans were performed in all patients 3 weeks presurgically and 6 months postsurgically. ITKSNAP and 3D Slicer software were used to reconstruct three-dimensional facial skeletal images, to carry out image segmentation, and to superimpose and quantify the TMJ position changes before and after surgery. Amount of displacement of the most medial and lateral points of the condyles and the change of intercondylar angles were measured to evaluate the postsurgical stability of TMJ. RESULTS: A total amount of 23 skeletal class III patients (female : male = 12 : 11) with age ranged from 20.3 to 33.5 years (mean: 24.39 ± 4.8 years old) underwent Le Fort I maxillary advancement and BSSO setback of the mandible. The surgical outcome revealed the satisfactory correction of their skeletal deformities. The mean displacement of the right most lateral condylar point (RL-RL') was 1.04 ± 0.42 mm and the mean displacement of the left most lateral condylar point (LL-LL') was 1.19 ± 0.41 mm. The mean displacement of the right most medial condylar point (RM-RM') was 1.03 ± 0.39 mm and the left most medial condylar point (LM-LM') was 0.96 ± 0.39 mm. The mean intercondylar angle was 161.61 ± 5.08° presurgically and 159.28 ± 4.92° postsurgically. CONCLUSION: The postsurgical position of TM joint condyles in our study only presented a mild change with all the landmark displacement within a range of 1.2 mm. This indicates the bimaxillary orthognathic surgery via 3D CASNOS protocol can achieve a desired and stable result of TMJ position in treating skeletal class III adult patients with retrognathic maxilla and prognathic mandible.

Impact of rhizosphere microorganisms on arsenic (As) transformation and accumulation in a traditional Chinese medical plant.

Panax notoginseng is an important traditional medicinal plant, but the commercial value is threatened by root-rot disease caused by rhizosphere microbes and a potential health risk caused by plant arsenic (As) accumulation. Whether rhizospheric microbes isolated from P. notoginseng rhizosphere soil could impact As uptake and transport into P. notoginseng is not yet known. Among the three root-rot disease-causing pathogens Fusarium flocciferum (PG 1), Fusarium oxysporum (PG 2), and Fusarium solani (PG 3) and one root-rot disease biocontrol fungus Trichoderma koningiopsis (FC 1) and five biocontrol-exerting bacterial species Bacillus siamensis (BC 1), Delftia acidovorans (BC 2), Brevibacillus formosus (BC 3), Mortierella alpine (BC 4), and Bacillus subtilis (BC 5), one As-resistant pathogen and four biocontrol microorganisms with As-resistant ability were identified. The As-transforming ability of the identified fungi and bacteria was ranked in the order of FC 1 > PG 1 and BC 2 > BC 3 > BC 1, respectively. Then, the As-resistant biocontrol and pathogenic microbes were initiated to colonize the rhizosphere of 1-year-old P. notoginseng seedlings growing in artificially As(V)-contaminated soil to evaluate the impact of microbe inoculation on P. notoginseng As uptake and transport capacity. Concentration of As in P. notoginseng tissues decreased in the order of the sequence stem > root > leaf. Compared to treatment without colonization by microorganism, inoculation with microorganisms increased As root uptake efficiency and root As concentration, especially under treatment of inoculation by BC 2 and PG 1 + BC 2. As transport efficiency from root to stem decreased by inoculation with microorganism, especially under treatment with inoculation of BC 2 and PG 1 + BC 2. However, the impact of microorganism colonization on As stem to leaf transport efficiency was not obvious. In summary, inoculation with rhizosphere microbes may increase As accumulation in P. notoginseng root, especially when using bacteria with high As transformation ability. Therefore, it is necessary to evaluate the As transformation capacity before applying biological control microorganism to the rhizosphere of P. notoginseng.

The Dark Side of Pyroptosis of Diffuse Large B-Cell Lymphoma in B-Cell Non-Hodgkin Lymphoma: Mediating the Specific Inflammatory Microenvironment.

Background: Diffuse large B-cell lymphoma (DLBCL) is a common aggressive B-cell non-Hodgkin lymphoma (B-NHL). While combined chemotherapy has improved the outcomes of DLBCL, it remains a highly detrimental disease. Pyroptosis, an inflammatory programmed cell death, is considered to have both tumor-promoting and tumor-suppressing effects. The role of pyroptosis in DLBCL has been gradually appreciated, but its value needs further investigation. Methods: We analyzed mutations and copy number variation (CNV) alterations of pyroptosis-related genes (PRGs) from The Cancer Genome Atlas (TCGA) cohort and evaluated the differences in expression in normal B cells and DLBCL patients in two Gene Expression Omnibus (GEO) datasets (GSE12195 and GSE56315). Based on the expression of 52 PRGs, we divided 421 DLBCL patients from the GSE31312 dataset into distinct clusters using consensus clustering. The Kaplan-Meier method was used to prognosis among the three clusters, and GSVA was used to explore differences in the biological functions. ESTIMATE and single-sample gene-set enrichment analysis (ssGSEA) were used to analyze the tumor immune microenvironment (TME) in different clusters. A risk score signature was developed using a univariate survival analysis and multivariate regression analysis, and the reliability and validity of the signature were verified. By combining the signature with clinical factors, a nomogram was established to predict the prognosis of DLBCL patients. The alluvial diagram and correlation matrix were used to explore the relationship between pyroptosis risk score, clinical features and TME. Results: A large proportion of PRGs are dysregulated in DLBCL and associated with the prognosis. We found three distinct pyroptosis-related clusters (cluster A, B, and C) that differed significantly with regard to the prognosis, biological process, clinical characteristics, chemotherapeutic drug sensitivity, and TME. Furthermore, we developed a risk score signature that effectively differentiates high and low-risk patients. The nomogram combining this signature with several clinical indicators showed an excellent ability to predict the prognosis of DCBCL patients. Conclusions: This work demonstrates that pyroptosis plays an important role in the diversity and complexity of the TME in DLBCL. The risk signature of pyroptosis is a promising predictive tool. A correct and comprehensive assessment of the mode of action of pyroptosis in individuals will help guide more effective treatment.

Inhibitory effect of microRNA-608 on lung cancer cell proliferation, migration, and invasion by targeting BRD4 through the JAK2/STAT3 pathway.

Lung cancer is the leading cause of cancer-related mortality around the world. This malignancy has a 5-year survival rate of 21%, because most of the patients are diagnosed in the middle or late stage of the disease when local metastasis and tumor invasion have already progressed. Therefore, the investigation of the pathogenesis of lung cancer is an issue of crucial importance. MicroRNAs (miRNAs) seem to be involved in the evolution and development of lung cancer. MicroRNA-608 is likely to be downregulated in lung cancer tissues. Regarding this, the current study involved the determination of the fundamental mechanism of microRNA-608 in the development of lung cancer. Based on the results of quantitative reverse transcription polymerase chain reaction (RT-qPCR), the expression level of microRNA-608 was downregulated in 40 lung cancer tissues, compared to that in the adjacent normal tissues. The results of dual-luciferase reporter assay revealed that bromodomain-containing protein 4 (BRD4) was the direct target of microRNA-608. Accordingly, the lung cancer tissues had an elevated expression level of BRD4, in contrast to the adjacent normal tissues. The results of Cell Counting Kit 8 assay demonstrated that the high expression of microRNA-608 notably restrained lung cancer cell proliferation. The scratch wound and transwell assays showed that the upregulation of microRNA-608 suppressed the migration and invasion of lung cancer cells. Finally, the western blot assay showed that in the microRNA-608 mimics group, the expression levels of BRD4, p-JAK2, p-STATA3, CD44, and MMP9 were significantly decreased, compared with those in the negative control miRNA mimics group. Our results indicate that high expression of microRNA-608 inhibits the proliferation, migration, and invasion of lung cancer cells by targeting BRD4 via the JAK2/STAT3 pathway.

Do physical disabilities affect self-perceived quality of life in adolescents?

PURPOSE: We examined to what extent physical disabilities (PD) affect self-perceived quality of life (QOL) among adolescents. METHOD: A survey was conducted on 157 adolescents (aged 15.6 +/- 1.6 years) with PD, who were attending high schools in Taiwan; 855 students (15.3 +/- 1.6 years) from the same geographic regions and without a disability were recruited as controls. The Student Version of the Comprehensive Quality of Life Scale (COMQOL-S) was used to assess their subjective and objective well-being. RESULTS: No significant differences in overall objective QOL score were found between the two groups but the PD group was poorer in health and material well-being. Adolescents with PD scored significantly higher in overall subjective QOL and all the seven domains examined. Stratified analysis showed that older students and female students with PD had lower life satisfaction in some domains. There were no significant differences in overall objective (62.1 +/- 8.3 vs. 60.9 +/- 6.4; p = 0.55) or subjective (72.3 +/- 12.6 vs. 74.4 +/- 13.6; p = 0.15) QOL between students in mainstream and special schools. CONCLUSIONS: With national health care and educational coverage, the QOL of adolescents with PD in Taiwan do not seem to be affected by the disabilities, regardless of whether they are in mainstream or special schools. However, the negative effect of PD on QOL becomes a concern with increasing age; females with PD also appear to have a lower subjective QOL in health and emotion.