m6Am Methyltransferase PCIF1 Regulates Periodontal Inflammation.

N6,2'-O-dimethyladenosine (m6Am), a common mRNA modification in eukaryotic capped mRNAs, plays a pivotal role in cellular functions and disease progression. However, its involvement in host inflammation remains elusive. Here, we demonstrate that loss of m6Am methyltransferase phosphorylated CTD interacting factor 1 (PCIF1) attenuates periodontal inflammation in whole-body and myeloid lineage-specific knockout mouse models. Pcif1 deletion inhibits macrophage phagocytosis and migration through m6Am-Csf1r signaling. In addition, colony-stimulating factor-1 receptor (CSF1R) is identified as a potential target for the treatment of periodontitis. We thus reveal a previously unrecognized role for PCIF1-mediated m6Am modification in governing macrophage responses and periodontal inflammation.

Exploring emotional well-being, spiritual, religious and personal beliefs and telomere length in chronic pain patients-A pilot study with cross-sectional design.

Living with chronic pain is associated with substantial suffering and high societal costs. Patient reported outcomes (PROM's) and cellular ageing should be considered in pain management. The aim of this study was to explore correlations of PROM's and cellular ageing (telomere length [TL] and telomerase activity [TA]) amongst patients with chronic non-malignant pain. This was an explorative pilot study with cross-sectional design and recruitment was done at two pain rehabilitation facilities in Sweden, with inpatient setting/integrative care and outpatient setting/multimodal care, respectively. Eighty-four patients were enrolled by referral to pain rehabilitation in Sweden. The main outcome measures collected after admission in addition to TL and TA were the following PROMs: Numerical Rating Scale (NRS), Chronic Pain Acceptance Questionnaire (CPAQ), Hospital Anxiety and Depression Scale (HADS), Five Facets Mindfulness Questionnaire (FFMQ), WHO Quality of Life-Spiritual, Religious and Personal Beliefs (WHOQoL-SRPB) and EuroQol 5 Dimensions (EQ-5D). All the PROM's showed evidence of poor overall health status among the participants. TL correlated negatively with HADS score (r = -.219, p = .047) and positively with WHOQoL-SRPB (r = .224, p = .052). TL did not correlate with any of the pain measures. TA correlated positively with pain spread (r = .222, p = .049). A mediation of the direct effect of spiritual well-being on TL by anxiety and depression could be shown (b = 0.008; p = .045). The correlations between TL and SRPB and anxiety and depression suggest some importance of emotional and SRPB dimensions in pain management, with implications for cellular aging, which may warrant further study. Trial registration: ClinicalTrials.gov Identifier: NCT02459639.

[Goods syndrome in chronic active SARS-CoV-2 infection: a case report].

A 54-year-old female patient presented with recurrent cough and sputum production over the past year and was hospitalized several times. CT examination revealed exudative lesions in both lungs, which were partially absorbed after treatment. However, they recurred shortly after discharge, and the patient had to be readmitted. In the past year, the patient had been hospitalized six times, and her throat swabs were positive for SARS-CoV-2 at four different points in time. After receiving anti-infective and antiviral treatment in other hospitals, the above symptoms were relieved. The patient tested negative for SARS-CoV-2, but symptoms recurred soon after. Eventually, the diagnosis of Goods syndrome was made based on the presence of B-cell loss, decreased immunoglobulin levels, an inverted CD4+/CD8+ ratio on admission, and a previous history of thymoma.

Early-age heat exposure improved growth performance and heat tolerance in broilers.

A total of 440 one-day-old healthy male Arbor Acres broilers were equally assigned to a control group (CTL) and an early-age high-temperature exposure (EHT) group (4 replicates per group, 55 chickens per replicate). At d 3, the broilers in CTL group were reared in the normal temperature 33 ± 1°C, while the broilers in EHT group were exposed to 36 ± 1°C for 24 h. At d 43, all broilers were treated with an acute high temperature 35 ± 1°C for 5 h. The results showed that average daily gain in EHT group was decreased at d 3, but average daily gain in EHT group was increased at d 36 to 42 (P < 0.05). Plasma GLU level in EHT group was lower in broilers at d 7 or facing subsequently high temperature for 5 h (P < 0.05). The relative expression of myogenic differentiation (MyoD) gene in pectoralis major and myogenic factor 5 (Myf5) gene in biceps femoris were significantly improved at d 42 after early-age heat exposure (P < 0.05). Broilers in EHT group have a higher temperature tolerance with a lower mortality than control broilers (P < 0.05). Broilers in EHT group have a lower rectal temperature and a higher comb and ear temperature when facing subsequently acute high temperature than control broilers (P < 0.05). In addition, our study demonstrated that early-age heat exposure significantly decreased the mortality and increased the heat tolerance of broilers when facing an acute short-term heat exposures. Early-age heat exposure increased the process of myogenesis via up-regulating the MyoD and Myf5 gene expression in skeletal muscle, which accelerated average daily gain.

Determining the optimal timing of adjuvant chemotherapy initiation after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: Studies on several malignancies have suggested that the time to commencement of adjuvant chemotherapy (AC) is associated with survival outcomes. There have, however, been no relevant reports of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: This clinical study examined newly diagnosed patients between April 2017 and December 2020. The primary endpoint was progression-free survival (PFS). Inverse probability of treatment weighting was used to control for confounding factors. Cox models with restricted cubic splines, Kaplan-Meier method and log-rank tests were used to evaluate the relationship between AC timing and survival. RESULTS: A total of 551 patients were identified [median age, 45 years (interquartile range 36-52 years); 383 (69.5%) male]. Restricted cubic splines demonstrated that the timing of AC initiation had a U-shaped association with PFS. The risk of disease progression decreased within 37 days and subsequently increased. From 37 to 90 days, each additional 7-day delay conferred worse PFS of 1.32 months {hazard ratio (HR): 1.14 [95% confidence interval (CI) 1.01-1.28], P = 0.04}. The cut-off value of the receiver operating characteristic curve for initiation was 69.5 days. At a median follow-up of 48 months, the PFS was significantly better in patients initiated within 69.5 days [HR: 2.18 (95% CI 1.17-4.06), log-rank P = 0.009], with a higher 3-year rate [78.8% (95% CI 75.1% to 82.7%) versus 59.0% (95% CI 42.2% to 82.5%)] than beyond 69.5 days. Positive results were also observed in secondary endpoints. The initiation group was an independent prognostic factor [HR: 2.28 (95% CI 1.42-3.66), P < 0.001]. CONCLUSIONS: The optimal timing of AC initiation is ∼37 days after concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. A delay beyond 69.5 days is associated with compromised survival. Efforts should be made to address the reasons for delays and ensure the timely initiation of AC.

[Application of cell blocks to assist in precise cytological diagnosis of serous effusion].

Objective: To investigate the importance of cell block and immunohistochemistry in the accurate diagnosis of serous effusion. Methods: A retrospective study was conducted on 3 124 cases of serous effusion from the Department of Pathology, Beijing Hospital from 2018 to 2022, include 2 213 cases of pleural effusion, 768 cases of peritoneal effusion, 143 cases of pericardial effusion. There were 1 699 males (54.4%) and 1 425 females (45.6%), average age 69 years old. Of which 1 292 cases were prepared with cell blocks and examined with immunohistochemical stain. Results: The percentage of malignant diagnosis increased from 64.9% (839/1 292) to 84.0% (1 086/1 292) after cell block preparation, and 1 086 cases were accurately diagnosed with histological type and/or origin of primary tumor. The undetermined diagnosis of suspected malignancy decreased from 13.3% (172/1 292) to 0.1% (1/1 292) and that of atypical hyperplasia from 18.8% (243/1 292) to 0.4% (5/1 292). The negative result for malignancy rate increased from 3.0% (38/1 292) to 15.5% (200/1 292). The differences highlighted above were statistically significant (Pearson's chi-squared test=12.739, P<0.01). Conclusion: Application of immunohistochemistry based on cell block can significantly improve malignant diagnosis in serous effusion, identify tumor origin and histological type as well as decrease the uncertain diagnosis.

PF-06952229, a selective TGF-ß-R1 inhibitor: preclinical development and a first-in-human, phase I, dose-escalation study in advanced solid tumors.

BACKGROUND: PF-06952229 is a selective small-molecule inhibitor of transforming growth factor-ß (TGF-ß) receptor 1. We evaluated its antitumor activity in preclinical studies and its safety, tolerability, pharmacokinetics, and pharmacodynamics in a phase I study (NCT03685591). PATIENTS AND METHODS: In vitro and in vivo preclinical studies were conducted. Patients (aged ≥18 years) received PF-06952229 monotherapy [20-500 mg, oral b.i.d., 7 days on/7 days off, 28-day cycles, Part 1A (P1A)] for advanced/metastatic solid tumors and combination therapy [250/375 mg with enzalutamide, Part 1B (P1B)] for metastatic castration-resistant prostate cancer (mCRPC). Primary endpoints were dose-limiting toxicity (DLT), adverse events (AEs), and laboratory abnormalities. Efficacy, pharmacokinetic parameters, and biomarker modulation were assessed. RESULTS: PF-06952229 showed activity in preclinical murine tumor models including pSMAD2 modulation in tumors. The study (NCT03685591) enrolled 49 patients (P1A, n = 42; P1B, n = 7). DLTs were reported in 3/35 (8.6%) P1A patients receiving PF-06952229 375 mg (anemia, intracranial tumor hemorrhage, and anemia and hypertension, all grade 3, n = 1 each). The most frequent grade 3 treatment-related AEs (TRAEs) were alanine aminotransferase increased and anemia (9.5% each). There were no grade 4-5 TRAEs. Plasma PF-06952229 exposures were dose proportional between 80 and 375 mg. Pharmacodynamic studies confirmed target modulation of pSMAD2/3 (peripheral monocytes). One P1A patient with prostate cancer receiving PF-06952229 375 mg monotherapy achieved confirmed partial response (31-month duration of response). A total of 8 patients (P1A, n = 6; P1B, n = 2) achieved stable disease. CONCLUSIONS: Antitumor activity of PF-06952229 was observed in preclinical studies. PF-06952229 was generally well tolerated with manageable toxicity; a small group of patients achieved durable responses and/or disease stabilization.

Short-term effects of air pollutants and meteorological factors on outpatients with allergic airway disease in Ningbo, China, 2015-2021.

OBJECTIVES: The allergic airway disease, such as allergic rhinitis, chronic rhinosinusitis, asthma, is a general term of a range of inflammatory disorders affecting the upper and lower airways and lung parenchyma. This study aimed to investigate the short-term effects of air pollutants and meteorological factors on AAD-related daily outpatient visits. STUDY DESIGN: An ecological study. METHODS: Data on outpatient visits due to AAD (n = 4,554,404) were collected from the platform of the Ningbo Health Information from January 1, 2015 to December 31, 2021. A Quasi-Poisson generalized additive regression model was established to analyze the lag effects of air pollution on daily outpatient visits for AAD. Restricted cubic spline functions were used to explore the potential non-linear relationships between air pollutants and meteorological and daily outpatient visits for AAD. RESULTS: PM2.5, PM10, SO2, NO2, or CO were associated with daily outpatient visits for AAD, and there was a significant increasing trend in the cumulative lag effects. SO2 had the largest effect at Lag07, with a 25.3% (95% CI: 21.6%-29.0%) increase in AAD for every 10 µg/m3 increase in exposure concentration. Subgroup analysis showed that the 0-18 years old age group had the strongest effects, especially for AR, and all effects were stronger in the cold season. CONCLUSIONS: Given that patients aged 0-18 are more susceptible to environmental changes, protective measures specifically for children should be taken during dry and cold weather conditions with poor air quality.

[Epidemiological characteristics of human respiratory syncytial virus in Hubei Province from 2016 to 2023].

Objective: To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with acute respiratory infection (ARIs) in sentinel hospitals of the Hubei influenza surveillance network from 2016 to 2023. Methods: ARIs samples [including influenza-like cases (ILI) and severe acute respiratory infection (SARI)] were collected from influenza surveillance sentinel hospitals in Hubei Province from 2016 to 2023, and case information was collected. HRSV virus nucleic acid typing was performed by fluorescence quantitative PCR method, and the data were collated, plotted and analyzed. Results: From 2016 to 2023, 12 779 cases of ILI and 9 166 cases of SARI were collected. The positive rate of HRSV was the highest in<5 years of age group [15.77% (168/1 065)], among which the positive rate was the highest in 2 to 5 years of age group of ILI cases [13.60% (31/228)], and the positive rate was the highest in 0 to 2 years of age group of SARI cases [25.97% (60/231)] (all P values<0.001). The positive rate of HRSV in SARI cases was 2.31%-25.97%, higher than that in ILI cases (0-13.60%) (P=0.016). HRSV was prevalent in autumn and winter from 2016 to 2020 and in spring in 2023. Alternating epidemics of HRSV virus type A and B in Hubei Province from 2016 to 2023 (dominant epidemics of type B in 2016 and 2020; dominant epidemics of type A in 2017-2019 and 2023). Conclusion: SARI and ILI patients under five years old are the main infection groups of HRSV. The seasonal prevalence characteristics of HRSV in Hubei Province from 2016 to 2023 shift from autumn and winter to spring.

Association of gut microbiota with acute kidney injury: a two-sample Mendelian randomisation and case-control study.

Epidemiologic studies have implicated the gut microbiota in acute kidney injury (AKI), but the causal relationship is unclear. Using Mendelian randomisation, we explored the causal role of gut microbiota in the development of acute kidney injury after excluding confounding and reverse causality. Mendel randomised (MR) study was conducted using data from intestinal microbiota and genome-wide association studies (GWAS) disease of acute kidney injury and the sequencing data of case-control study confirmed this finding. The summary statistics of intestinal microbiota (n = 13,266) conducted by MiBioGen Alliance was taken as the exposure, while the statistics of acute kidney injury obtained from FinnGen Alliance data (2,383 cases and 212,841 controls) were taken as the results. A total of 42 patients were included in this case-control study. Evidence for the protective causal associations of the genus Flavonifractor id.2059 with AKI was found in inverse variance weighting (odds ratio = 0.48 [95% confidence interval, 0.32-0.72]; P = 0.0003). Additionally, a case-control study showed that the relative abundance of the genus Flavonifractor id.2059 ( P = 0.0169) in septic non-AKI patients was higher than that in septic AKI patients. Compared with S-AKI patients who died within 28 days, the relative abundance of the genus Flavonifractor id.2059 in surviving patients was higher ( P = 0.0281). Phylogenetic analysis showed that OTU68 and HQ455040.1334-739 (genus Flavonifractor, Genetic similarity: 100%), as well as OTU2271 and LT598575.1365-770 (genus Pseudoflavonifractor, Genetic similarity: 100%), have closest genetic ties. Correlation analysis showed that the genus Flavonifractor id.2059 was related to the creatinine value (Spearman correlation: -0.379, P = 0.013). The present study demonstrates that the genus Flavonifractor id.2059 is associated with a reduced risk of AKI, revealing potential implications for the prevention and treatment of acute kidney injury.

[Establishing reference ranges of serum vitamin K in healthy children].

Objective: To establish and validate reference intervals of serum vitamin K for healthy children in China. Methods: A cross-sectional study was conducted from January 2020 to May 2023, involving 807 healthy children aged 0 to 14 years, selected by stratified random sampling based on the population distribution of children in eastern, central, western, and northeastern China. Sample collection was carried out in 16 hospitals across 12 provinces, autonomous regions, and municipalities. Basic information of the children was collected using a standardized self-design questionnaire. Serum levels of vitamin K1 and vitamin K2 (menaquinone-4 (MK-4), menaquinone-7 (MK-7)) were measured using liquid chromatography-tandem mass spectrometry. The reference intervals was established by direct approach. The children were divided into different groups by age. Inter-group comparisons were conducted using the Kruskal-Wallis non-parametric test, and the reference intervals (P2.5-P97.5) were determined using non-parametric methods. Screening 40 healthy children for small sample validation based on age groups within the reference range(25 from eastern, 10 from central, and 5 from western regions). Results: The age of the 807 children was 5.00 (2.00, 9.81) years, and 495 (61.3%) were males and 312 (38.7%) females. Reference intervals were established for 795 children, of whom 303 children were aged 1 month to 3 years and 492 were aged 4 to 14 years. The reference intervals for serum vitamin K1 were 0.09-4.54 µg/L for children aged 1 month to 3 years, and 0.10-1.73 µg/L for 4-14 years. For MK-7, the intervals were 0.07-1.42 µg/L for 1 month to 3 years and 0.19-2.03 µg/L for 4-14 years. The reference intervals for MK-4 in children aged 1 month to 14 years were 0-0.42 µg/L. The measured values of serum vitamin K1, MK-4, and MK-7 in the validation samples did not exceed the reference limit in more than 2 samples. Conclusion: Reference intervals for vitamin K1, MK-4, and MK-7 in healthy children aged 1 month to 14 years have been established and validated, and can be used to assess vitamin K nutritional status in children.

Low serum adiponectin levels are associated with an increased risk of diabetes in obese dogs.

OBJECTIVES: Adiponectin plays an important role in carbohydrate and lipid metabolism. However, the evidence regarding the association between adiponectin and diabetes mellitus in obese dogs is sparse. The aim of this study is to investigate the associations of adiponectin with the risk of diabetes mellitus in obese dogs on the basis of a prospective cohort study. MATERIALS AND METHODS: Serum adiponectin levels in obese dogs recruited from three small animal hospitals between 2015 and 2018 were measured by ELISA. Electronic health records were used to record the incidence of diabetes mellitus during follow-up for 3 years. RESULTS: A total of 862 dogs were included. Amongst the 862 dogs, 51 developed diabetes. Adiponectin levels were associated with diabetes mellitus after adjusting for sex, age, breed, exercise, body condition score, fasting plasma glucose, serum triglyceride and total cholesterol. When adjusting for sex, age, breed, exercise, body condition score, fasting plasma glucose, serum triglyceride and total cholesterol, the adjusted hazard ratios were 7.83 (95% confidence interval: 2.67 to 30.13) in the lowest adiponectin group and 1.96 (95% CI: 1.10 to 8.55) in the medium adiponectin group relative to that in the highest adiponectin group. The area under a curve of adiponectin's Receiver operating characteristic curve was 0.81 (95% CI: 0.76 to 0.86). CLINICAL SIGNIFICANCE: Low adiponectin is associated with diabetes mellitus and has a high risk of incident diabetes mellitus, implying the potential of adiponectin as a predictive biomarker of diabetes mellitus in obese dogs.

[Hinokiol regulates the cell cycle and apoptosis of nasopharyngeal carcinoma CNE1 cells via Hippo-YAP signaling pathway].

Objective: To explore the effects of hinokiol on the cell cyle and apoptosis of CNE1 nasopharyngeal carcinoma cells and the relevant molecular mechanism. Methods: The CNE1 cells were cultured in vitro and incubated with different concentrations of honokiol, and the cells were divided into blank control group, 10 µmol/L, 20 µmol/L and 40 µmol/L hinokiol treatment groups, and 10 µg/ml cisplatin group. Cell viability was determined by methylthiazolyldiphenyl- tetrazolium bromide (MTT) method, the cell cycle distribution was detected by flow cytometry, mitochondrial membrane potential was detected by mitochondrial membrane potential test kit, apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and the proteins expression of proliferating cell nuclear antigen (PCNA) and G1/S specific cyclin D1 (cyclin D1) were detected by immunoblotting. RNA-Seq was conducted in the hinokiol-treated cells. The mRNA expression of yes-associated protein delta (YAP) was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The proteins expression of phosphor-YAP (p-YAP) and nuclear YAP were detected by immunoblotting, the nuclear distribution of YAP protein was detected by immunofluorescence in the cells with or without treated with the mammalian STE20-like kinase 1/2 (MST1/2) inhibitor (XMU-MP-1), hinokiol, and XMU-MP-1+hinokiol. Statistical analysis of the data was conducted using GraphPad Prism 8.0 software. Resluts Compared with the control group, the cell viablity of CNE1 cells, the levels of mitochondrial membrane potential, the proteins expression of PCNA and cyclin D1 in hinokiol treatment groups were markedly decreased (all P values<0.05), while the proportion of G0/G1 phase cells and the ratio of TUNEL-positive cells were significantly increased (both P values<0.05). Transcriptome analysis showed that differential genes were mainly enriched in Wnt signaling pathway, tumor necrosis factor pathway, and Hippo signaling pathway. The mRNA level of YAP and the protein expression of YAP in the nucleus were decreased and the level of p-YAP protein was increased in cells treated with hinokiol, which were significantly different from control group (all P values<0.05). Compared with the hinokiol group, XMU-MP-1+hinokiol groups showed the decrease of p-YAP protein expression (1.157±0.076 vs 0.479±0.038, t=37.120, P<0.05), the increase of YAP protein expression in the nucleus (0.143±0.012 vs 0.425±0.031, t=29.181, P<0.05), the reduced proportion of cells in G0/G1 phase [(72.494±3.309)% vs (58.747±2.865)%, t=17.265, P<0.05], and the decrease of apoptosis ratio [(53.158±3.376)% vs (29.621±2.713)%, t=28.584, P<0.05]. Conclusion: Hinokiol can arrest the cell cycle and induce the cell apoptosis of CNE1 cells via Hippo/YAP signaling pathway.

[Ultrasonic convex array probe applied to increase success rate of external cephalic version without anesthesia].

Objective: To explore the feasibility of using ultrasonic convex array probe compressing abdominal wall to increase success rate of external cephalic version (ECV) without anesthesia in full-term and near-term pregnancy. Methods: Totally 190 singleton and non-cephalic presentation pregnant women in 36-39+4 weeks of gestation performed ECV from April 2019 to August 2023 in the First Affiliated Hospital of Nanjing Medical University were analyzed. According to whether use the ultrasound probe compressing fetal breech or not, the pregnant women were divided into two groups: 81 cases in the probe-compressing group (including primipara 61 cases and multipara 20 cases) and 109 cases in the non-probe-compressing group(including primipara 72 cases and multipara 37 cases). Clinical data, ECV related factors and complications were analyzed and compared between the two groups. Results: (1) The overall success rate of ECV was 64.2% (122/190). There was no significant difference in the success rate of ECV between probe-compressing group and non-probe-compressing group [69.1% (56/81) vs 60.6% (66/109), χ2=1.490, P=0.222]. The total vaginal delivery rate after successful ECV was 81.1% (99/122), while 71.1% (54/76) in primipara and 97.8% (45/46) in multipara, respectively. (2) Compare to the non-probe-compressing group, the success rate of ECV in primipara was significantly higher in the probe-compressing group [45.8% (33/72) vs 70.5% (43/61)], but the gestational age was shorter and the height was higher in the probe-compressing group (all P<0.05). The success rate of ECV of multipara in the probe-compressing group (65.0%, 13/20) was lower than that in the non-probe-compressing group (89.2%, 33/37), but there was no significant difference between the two groups (P>0.05). (3) Multivariate logistic regression analysis showed that abdominal wall compressed by ultrasound probe (OR=2.601, 95%CI: 1.113-6.075; P=0.027) and amniotic fluid index (AFI; OR=1.010, 95%CI: 1.001-1.020; P=0.028) were positive factors for the successful rate of ECV in primipara pregnant women. (4) The main complication of ECV was transient fetal heart rate reduction (8.9%,17/190), the incidence in the probe-compressing group was significantly higher than that in the non-probe-compressing group [14.8% (12/81) vs 4.6% (5/109); χ2=5.967, P=0.015]. No statistical differences were found in rates of complications between the ECV successful and unsuccessful pregnant women, and between probe-compressing and non-probe-compressing groups (all P>0.05). No adverse maternal and neonatal outcomes related to ECV were observed. Conclusions: The ultrasonic convex array probe compressing could significantly improve the success rate of ECV in primipara without increasing the incidence of adverse maternal and fetal outcomes. The success rate of ECV in primipara is influenced by AFI and operation mode.

Retraction Note: Valsartan reduces AT1-AA-induced apoptosis through suppression oxidative stress mediated ER stress in endothelial progenitor cells.

The article "Valsartan reduces AT1-AA-induced apoptosis through suppression oxidative stress mediated ER stress in endothelial progenitor cells" by Z.-C. Wang, J. Qi, L.-M. Liu, J. Li, H.-Y. Xu, B. Liang, B. Li, published in Eur Rev Med Pharmacol Sci 2017; 21 (5): 1159-1168 - PMID: 28338173 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer (link: https://pubpeer.com/publications/8FA8D4C63DE61DDB6C89537AD04B24), the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The authors have been informed about the journal's investigation but remained unresponsive and have not provided the study's raw data. The journal's investigation revealed a Figure duplication in Figure 2C between panels AT1-AA (2.5 µM), AT1-AA (5 µM), AT1-AA (10 µM), and AT1-AA+Valsartan. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/12342.

[Overexpression of CDHR2 inhibits proliferation of breast cancer cells by inhibiting the PI3K/Akt pathway].

OBJECTIVE: To investigate the mechanism by which CDHR2 overexpression inhibits breast cancer cell growth and cell cycle pragression via the PI3K/Akt signaling pathway. METHODS: Bioinformatic analysis was performed to investigate CDHR2 expression in breast cancer and its correlation with survival outcomes of the patients. Immunohistochemistry was used to examine CDHR2 expressions in surgical specimens of tumor and adjacent tissues from 10 patients with breast cancer. CDHR2 expression levels were also detected in 5 breast cancer cell lines and a normal human mammary epithelial cell line using qRT-PCR and Western blotting. Breast cancer cell lines MDA-MB-231 and MCF7 with low CDHR2 expression were transfected with a CDHR2-overexpressing plasmid, and the changes in cell proliferation and cell cycle were evaluated using CCK-8 assay, EdU assay, and cell cycle assay; the changes in expressions of PI3K/Akt signaling pathway and cell cycle pathway proteins were detected with Western blotting. RESULTS: Bioinformatic analysis showed low CDHR2 expression level in both breast cancer and adjacent tissues without significant difference between them (P > 0.05), but breast cancer patients with a high expression of CDHR2 had a more favorable prognosis. Immunohistochemistry, qRT-PCR and Western blotting showed that the expression of CDHR2 was significantly down-regulated in breast cancer tissues and breast cancer cells (P < 0.01), and its overexpression strongly inhibited cell proliferation, caused cell cycle arrest, and significantly inhibited PI3K and Akt phosphorylation and the expression of cyclin D1. CONCLUSION: Overexpression of CDHR2 inhibits proliferation and causes cell cycle arrest in breast cancer cells possibly by inhibiting the PI3K/Akt signaling pathway.

[Sodium butyrate and sorafenib synergistically inhibit hepatocellular carcinoma cells possibly by inducing ferroptosis through inhibiting YAP].

OBJECTIVE: To investigate whether sodium butyrate (NaB) and sorafenib synergistically induces ferroptosis to suppress proliferation of hepatocellular carcinoma cells and the possible underlying mechanisms. METHODS: CCK8 assay and colony formation assay were used to assess the effects of NaB and sorafenib, alone or in combination, on proliferation of HepG2 cells, and ferroptosis of the treated cells was detected with GSH assay and C11-BODIPY 581/591 fluorescent probe. TCGA database was used to analyze differential YAP gene expression between liver cancer and normal tissues. The effects of NaB and sorafenib on YAP and p-YAP expressions in HepG2 cells were invesitigated using Western blotting. RESULTS: NaB (2 mmol/L) significantly reduced the IC50 of sorafenib in HepG2 cells, and combination index analysis confirmed the synergy between sorafenib and NaB. The ferroptosis inhibitor Fer-1 and the YAP activator (XMU) obviously reversed the growthinhibitory effects of the combined treatment with NaB and sorafenib in HepG2 cells. The combined treatment with NaB and sorafenib, as compared with the two agents used alone, significantly inhibited colony formation of HepG2 cells, further enhanced cellular shrinkage and dispersion, and decreased intracellular GSH and lipid ROS levels, and these effects were reversed by Fer-1 and XMU. TCGA analysis revealed a higher YAP mRNA expression in liver cancer tissues than in normal liver tissues. NaB combined with sorafenib produced significantly stronger effects than the individual agents for downregulating YAP protein expression and upregulating YAP phosphorylation level in HepG2 cells. CONCLUSION: NaB combined with sorafenib synergistically inhibit hepatocellular carcinoma cell proliferation possibly by inducing ferroptosis via inhibiting YAP expression.

[A multicenter prospective clinical trial on the effect of domestic bone level implants on single tooth implantation and restoration].

Objective: To evaluate the clinical application effects of a domestic bone-level implant system for restoring single tooth loss, and provide clinical evidence for the promotion and application of domestic implants. Methods: A prospective, multicenter clinical trial was conducted from April 2018 to January 2020 in three institutions: Department of Oral Implantology, School & Hospital of Stomatology, Wuhan University, Department of Stomatology, The First Affiliated Hospital of Zhejiang University School of Medicine, and Department of Stomatology, The Third Hospital of Hebei Medical University. The trial planned to include 100 patients for single tooth implantation and restoration, followed up for 1 year, to evaluate the implantation success rate and other related outcomes. Results: This study screened a total of 142 patients and ultimately included 100, comprising 43 males and 57 females with age of (47.0±12.2) years. Ninety-eight out of 100 patients completed a one-year follow-up (98.0%), while 2 patients terminated the trial early due to implant loosening (2.0%). After a one-year follow-up, the implants of the 98 patients were all functioning successfully, with a success rate of 98.0% (98/100). The patients were satisfied with the overall restoration effect. Conclusions: This study indicates that the domestic bone-level implant system has achieved favorable short-term clinical outcomes for single-tooth implantation and restoration.