Head and neck squamous cell carcinoma-specific prognostic signature and drug sensitive subtypes based on programmed cell death-related genes.

Background: As a complex group of malignancies, head and neck squamous cell carcinoma (HNSC) is one of the leading causes of cancer mortality. This study aims to establish a reliable clinical classification and gene signature for HNSC prognostic prediction and precision treatments. Methods: A consensus clustering analysis was performed to group HNSC patients in The Cancer Genome Atlas (TCGA) database based on genes linked to programmed cell death (PCD). Differentially expressed genes (DEGs) between subtypes were identified using the "limma" R package. The TCGA prognostic signature and PCD-related prognostic genes were found using a least absolute shrinkage and selection operator (LASSO) regression analysis and univariate Cox regression analysis. The robustness of the LASSO analysis was validated using datasets GSE65858 and GSE41613. A cell counting kit-8 (CCK-8) test, Western blot, and real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) were used to evaluate the expression and viability of prognostic genes. Results: Four molecular subtypes were identified in PCD-related genes. Subtype C4 had the best prognosis and the highest immune score, while subtype C1 exhibited the most unfavorable outcomes. Three hundred shared DEGs were identified among the four subtypes, and four prognostic genes (CTLA4, CAMK2N1, PLAU and CALML5) were used to construct a TCGA-HNSC prognostic model. High-risk patients manifested poorer prognosis, more inflammatory pathway enrichment, and lower immune cell infiltration. High-risk patients were more prone to immune escape and were more likely to be resistant to Cisplatin and 5-Fluorouracil. Prognosis prediction was validated in external datasets. The expression of CTLA4, CAMK2N1, PLAU and CALML5 was enhanced in CAL-27 and SCC-25 cell lines, and CALML5 inhibited CAL-27 and SCC-25 cell viability. Conclusion: This study shares novel insights into HNSC classification and provides a reliable PCD-related prognostic signature for prognosis prediction and treatment for patients with HNSC.

Anatomical and Interpositional Bursa Preservation Showed Similar Improved Tendon to Bone Healing Compared With the Bursa Removal in a Rat Rotator Cuff Tear Model.

PURPOSE: To compare the effects of anatomical preservation (AP) and interpositional preservation (IP) of subacromial bursa tissue on tendon-to-bone healing in a rat model of rotator cuff tear. METHODS: In this study, 48 male Sprague-Dawley rats (average weight 283 g) underwent bilateral supraspinatus tendons severed by sharp incision and repaired immediately. The subacromial bursa tissues were completely removed in 16 rats, who served as the control (CON) group. The other 32 rats were randomly divided into 2 groups AP and IP between tendon and bone. Eight rats of each group were sacrificed for bilateral shoulders at 3 and 9 weeks after the operation, including 5 rats for biomechanical tests and 3 for histologic analysis. RESULTS: No significant differences in terms of biomechanical properties were observed among the groups 3 weeks after surgery. At 9 weeks, the maximum load and stiffness of the AP (32.95 ± 6.33 N, P = .029; 12.49 ± 3.17 N/mm, P < .001; respectively) and IP (33.58 ± 8.47 N, P = .015; 11.63 ± 2.84 N/mm, P = .010, respectively) groups were significantly superior to that of the CON group (26.59 ± 4.47 N; 8.42 ± 2.33 N/mm, respectively). More organized collagen and more mature tendon insertion were observed in AP and IP groups at the interface at 9 weeks, which means better tendon-to-bone healing compared with the CON group. CONCLUSIONS: The subacromial bursa plays a positive role in tendon-bone healing. Either anatomical preservation or interpositional preservation between tendon and bone can similarly facilitate the process of healing. CLINICAL RELEVANCE: Considering the additional surgical time and surgical manipulation, preserving the subacromial bursa at the anatomical position seems to be a better way to promote rotator cuff healing.

MicroRNA-206 relieves irradiation-induced neuroinflammation by regulating connexin 43.

Radiation therapy has been widely used for the treatment of various types of cancer; however, it may cause neuroinflammation during the pathological process of the disease. Astrocytes, the most abundant cell type in the central nervous system, have been confirmed to play vital roles in various diseases. Connexin (Cx)43, the main Cx type in astrocytes, which has been identified as a direct target gene of microRNA (miR)-206, was found to be involved in diseases pathologies in regions with astrocytes. The aim of the present study was to investigate the mechanism through which γ-radiation may cause astrocyte neuroinflammation and determine the specific mechanism underlying the effects of miR-206 in irradiation-induced HA-1800 cells. A dual-luciferase reporter system was used to predict and verify the target binding site between Cx43 and miR-206. HA-1800 cell viability and apoptosis were determined using a MTT assay and flow cytometry, respectively. In addition, the HA-1800 cells were induced by γ-radiation, then the protein and mRNA expression levels of Cx43, miR-206 and cleaved-caspase-3 were determined using western blot and reverse transcription-quantitative PCR analyses, respectively. ELISA was also performed to evaluate the concentrations of different inflammatory cytokines (TNF-α, IL-ß, IL-6 and IFN-γ). The dual-luciferase reporter system indicated that Cx43 was a direct target of miR-206. miR-206 mimics increased the expression level of miR-206 in the astrocytes. Irradiation suppressed cell proliferation, increased apoptotic cells and enhanced cleaved-caspase-3 expression and inflammatory cytokines secretion in astrocytes. Furthermore, miR-206 was found to be downregulated and its expression was inversely associated with that of Cx43 in γ-radiation-induced astrocytes. Overexpression of miR-206 enhanced miR-206 and suppressed Cx43 expression, while Cx43 was upregulated in HA-1800 cells transfected with miR-206 mimic + Cx43-plasmid. However, the expression level of miR-206 was not significantly different in the Cx43-plasmid transfected group. In addition, it was found that miR-206 mimics relieved irradiation-induced neuroinflammation, which was confirmed by increased cell viability, and reduced cell apoptosis and cleaved caspase-3 protein expression, as well as decreased inflammatory cytokine secretion. Furthermore, all the effects of miR-206 mimics on γ-radiation-induced astrocytes were reversed by Cx43-plasmid. In summary, the results of the present study indicated that miR-206 may relieve irradiation-induced neural damage by regulating Cx43, which may provide a novel research direction and a potential therapeutic target for the clinical treatment of inflammation-associated neuronal injury following irradiation.

Persistent Helicobacter pylori infection for more than 3 years leads to elevated serum homocysteine concentration: A retrospective cohort study based on a healthy Chinese population.

BACKGROUND AND AIM: The relationship between the Helicobacter pylori (H. pylori) infection and homocysteine is unclear. We evaluated the effect of H. pylori on serum homocysteine in a healthy Chinese population. METHODS: A total of 21 184 individuals aged over 18 years underwent 13 C/14 C urease breath test (13 C/14 C-UBT) and blood tests and 5042 individuals with follow-up intervals greater than 6 months. Homocysteine levels are classified according to the Chinese expert consensus. RESULTS: The rates of H. pylori infection of normal level, mild level, moderate level, and severe level were 40.9%, 43.8%, 45.8%, and 46.6%, respectively (P = 0.000). H. pylori infection increased the risk of higher homocysteine concentration (OR = 1.406, P = 0.000). In the case-control study, the rates of persistent negative, new infection, persistent infection, and eradication infection were 43.6%, 11.2%, 22.9%, and 22.3%, respectively. The percentage of changes in serum homocysteine levels varied significantly among the different H. pylori infection statuses only in mild level (P = 0.024). Mean changed homocysteine values were higher in the subgroup of persistent infection than in the persistent negative subgroup (P = 0.004) and the eradication infection subgroup (P = 0.034). Serum homocysteine values were elevated only in the subgroup with over 3 years interval time and persistent infection (n = 107, mean paired differences = 1.1 ± 4.6 µmol/L, P = 0.014). CONCLUSIONS: There is a relationship between H. pylori and serum homocysteine, and persistent infection leads to elevation of the latter.

Helicobacter pylori is not a contributing factor in gallbladder polyps or gallstones: a case-control matching study of Chinese individuals.

OBJECTIVE: To investigate the relationship between Helicobacter pylori (H. pylori) infection and gallstones or gallbladder polyps. METHODS: This retrospective analysis included 27,881 individuals who underwent health examinations that included a H. pylori test and an abdominal ultrasound scan. Patients were divided into four groups: gallbladder polyp (P group), gallstone (S group), gallstone and gallbladder polyp (SP group), and no gallbladder disease (N group). Case-control matching was used to select the participants in the control group. RESULTS: The mean ages of participants in the P, S, and SP groups were all significantly higher than the mean age of participants in the N group. The proportions of participants with each type of body mass index significantly differed between the N and P groups, and between the N and S groups. In total 45.7% of participants exhibited H. pylori infection. After case-control matching, the proportion of participants with H. pylori infection did not significantly differ according to the presence or absence of gallbladder polyps. Similar results were observed regarding gallstones, as well as gallstones and gallbladder polyps. CONCLUSION: H. pylori infection might not be related to gallbladder polyps or gallstones.

Persistent infection of Helicobacter pylori affects weight loss in obese population compared with persistent negative: A case-control study based on healthy Chinese.

BACKGROUND: The relationship between Helicobacter pylori (H pylori) and body mass index (BMI) is still inconclusive. Not only the high rate of H pylori infection but also the increasing higher BMI levels are endangering Chinese today. METHODS: The aim of this research was to evaluate the association between different situations of H pylori infection and BMI values or levels in Chinese healthy population. A total of 39 091 individuals aged from 18 years to 80 years, performed healthy examination including a 13 C/14 C urease breath test (13 C/14 C-UBT), were included. Among them, 30 224 individuals only had one time of health examination, and 8867 had two or more times. A case-cohort data of 8752 with an interval time more than 6 months, collected by the first and the last time, were established from the latter. BMI groups are classified according to the China recommendation: low weight (<18.5 kg/m2 ), normal weight (18.5 ~ 23.9 kg/m2 ), overweight (24.0 ~ 27.9 kg/m2 ), and obesity (≥28.0 kg/m2 ). RESULTS: The rate of H pylori infection among low weight, normal weight, overweight, and obesity was 43.2%, 44.7%, 46.4%, and 48.0%, respectively (P = .000). H pylori infection increased the risk of higher level of BMI (OR = 1.077, 95% confidence interval = 1.036-1.119, χ2  = 14.048, P = .000) with adjustments for sex and age. In the case-control study, the rate of persistent negative, persistent infection, new infection, and eradicated infection was 39.5%, 25.8%, 15.8%, and 18.9%, respectively, with a median interval time of 13 months. The mean obesity BMI descend values in the persistent negative subgroup were lower than those in the persistent infection subgroup (-0.21 ± 1.19 kg/m2 vs -0.003 ± 1.01 kg/m2 , P = .021). But the change of BMI classifications had no difference between the subgroups of H pylori infection in different BMI levels. CONCLUSIONS: H pylori infection was positively correlated with higher BMI levels. And H pylori persistent infection had a negative effect on the fall of BMI values in Chinese obese population.

Microvesicles containing miR-34a induce apoptosis of proximal tubular epithelial cells and participate in renal interstitial fibrosis.

Function and potential mechanism of microvesicles (MVs) containing microRNA34a in renal interstitial fibrosis were investigated. A rat model of renal interstitial fibrosis was established by unilateral ureteral ligation (UUO). Rat proximal tubular epithelial cell line (NRK-52E) was used to explore the effect of MVs containing microRNA-34a on tubular epithelial cells during fibrosis, which were secreted by tubulointerstitial fibroblasts. Regardless of the UUO renal interstitial fibrosis model, or the TGF-ß1-treated renal tubular epithelial cells, microRNA-34a was increased in the MVs secreted by tubulointerstitial fibroblasts. miR-34a could be transmitted through the damaged tubule basement membrane to proximal tubular epithelial cells, where it induced apoptosis of renal tubular epithelial cells by inhibiting the expression of Bcl-2, further aggravating renal interstitial fibrosis. MicroRNA-34a secreted by damaged renal interstitial fibroblasts can promote renal tubular epithelial cell apoptosis and participate in renal interstitial fibrosis by inhibiting Bcl-2.

The impact of early enteral nutrition on pediatric patients undergoing gastrointestinal anastomosis a propensity score matching analysis.

This study was conducted to assess the clinical advantages of early enteral nutrition (EEN) in pediatric patients who underwent surgery with gastrointestinal (GI) anastomosis.EEN has been associated with clinical benefits in various aspect of surgical intervention, including GI function recovery and postoperative complications reduction. Evaluable data documenting clinical advantages with EEN for pediatric patients after surgery with GI anastomosis are limited.We retrospectively reviewed the medical records of 575 pediatric patients undergoing surgical intervention with GI anastomosis. Among them, 278 cases were managed with EEN and the remaining cases were set as late enteral nutrition (LEN) group. Propensity score (PS) matching was conducted to adjust biases in patient selection. Enteral feeding related complications were evaluated with symptoms, including serum electrolyte abnormalities, abdominal distention, abdominal cramps, and diarrhea. Clinical outcomes, including GI function recovery, postoperative complications, length of hospital stay, and postoperative follow-up, were assessed according to EEN or LEN.Following PS matching, the baseline variables of the 2 groups were more comparable. There were no differences in the incidence of enteral feeding-related complications. EEN was associated with postoperative GI function recovery, including time to first defecation (3.1 ±â€Š1.4 days for EEN vs 3.8 ±â€Š1.0 days for LEN, risk ratio [RR], 0.62; 95% confidence interval [CI] 0.43-1.08, P = .042). A lower total episodes of complication, including infectious complications and major complications were noted in patients with EEN than in patients with LEN (117 [45.9%] vs 137 [53.7%]; OR, 0.73, 95% CI 0.52-1.03, P = .046). Mean postoperative length of stay in the EEN group was 7.4 ±â€Š1.8 days versus 9.2 ±â€Š1.4 days in the LEN group (P = .007). Furthermore, the incidence of adhesive small bowel obstruction was lower for patients with laxative administration compared with control, but no significant difference was attained (P = .092)EEN was safe and associated with clinical benefits, including shorten hospital stay, and reduced overall postoperative complications on pediatric patients undergoing GI anastomosis.