Females have lower salivary flow than males, before and after radiation therapy for head/neck cancer.

OBJECTIVE: To compare salivary flow rates between females and males, before and after radiation therapy (RT) for head and neck cancer (HNC). METHODS: Prospective observational multicenter cohort study (OraRad). Stimulated whole salivary flow was measured before RT and at 6 and 18 months after RT. RESULTS: Mean (95% confidence interval) salivary flow in g/min before RT was 0.81 (0.71, 0.90) in females (n = 107) and 1.20 (1.15, 1.25) in males (n = 391) (p < 0.001); at 6 months was 0.34 (0.24, 0.44) in females and 0.50 (0.44, 0.55) in males (p = 0.01); at 18 months was 0.49 (0.38, 0.59) in females and 0.70 (0.64, 0.75) in males (p < 0.001). Median nadir salivary flow after RT was 0.22 in females and 0.35 in males (p < 0.001). A lower nadir salivary flow in females, but not males, was associated with an increased risk for tooth failure (p = 0.02). CONCLUSIONS: Females with HNC have lower stimulated whole salivary flow than males, before and after RT. Low salivary flow after RT may be a risk factor for tooth failure among females. The lower pre-RT salivary flow rates in females, combined with prior literature in other populations, indicates that, in general, females have lower stimulated salivary flow than males.

Bone morphogenetic protein receptor 1α promotes osteolytic lesion of oral squamous cell carcinoma by SHH-dependent osteoclastogenesis.

Oral squamous cell carcinoma (OSCC) is an aggressive tumor that usually invades the maxilla or mandible. The extent and pattern of mandibular bone invasion caused by OSCC are the most important factors determining the treatment plan and patients' prognosis. Yet, the process of mandibular invasion is not fully understood. The following study explores the molecular mechanism that regulates the mandibular invasion of OSCC by focusing on bone morphogenetic protein receptor 1α (BMPR1α) and Sonic hedgehog (SHH) signals. We found that BMPR1α was positively correlated to bone defect of OSCC patients. Mechanistically, BMPR1α signaling regulated the differentiation and resorption activity of osteoclasts through the interaction of OSCC cells and osteoclast progenitors, and this process was mediated by SHH secreted by tumor cells. The inhibition of SHH protected bone from tumor-induced osteolytic activity. These results provide a potential new treatment strategy for controlling OSCC from invading the jawbones.

Development and validation of nomogram for prediction of malignant transformation in oral leukoplakia: A large-scale cohort study.

PURPOSE: Oral leukoplakia (OL) is the well-known disorder of oral mucosa, which has potential to be malignant and can lead to squamous cell carcinoma (OSCC). In the following study, we developed a comprehensive nomogram for predicting the malignant progression of OL, based on analysis of clinicopathological variables. METHODS: A retrospective analysis of patients diagnosed with OL was performed between 1998 and 2017 at the Peking University School and Hospital of Stomatology. OL was confirmed by pre-treatment biopsy. The candidate risk factors for OL malignant transformation were screened from clinicopathological variables using the Cox proportional hazard regression analysis. The nomogram model was generated based on the COX regression results and was validated through Harrell concordance index (c-index) and calibration plots RESULTS: The incidence of OL malignant transformation (MT) was 12.2% (107/875), and the mean follow-up time was 4.5 years. The risk factors (age, histologic grade, site of lesion and smoking habit) derived from Cox proportional hazard regression analysis were incorporated in a novel nomogram model for prediction of MT severity. The c-index value of the nomogram model was 0.752, which confirmed the prediction ability; and was further confirmed by calibration plots results. CONCLUSION: Our data suggest that patients with OL who are over 50 years old, non-smokers with dysplasia, and OL lesions involving the lip, the floor of mouth, and tongue have an enhanced risk of MT. The established nomogram model has the predictive value of malignant progression, which is conductive to screen high-risk patients and guide treatment strategy.

Spatio-temporal analysis and risk modeling of foot-and-mouth disease outbreaks in China.

FMD is an acute contagious disease that poses a significant threat to the health and safety of cloven-hoofed animals in Asia, Europe, and Africa. The impact of FMD exhibits geographical disparities within different regions of China. The present investigation undertook an exhaustive analysis of documented occurrences of bovine FMD in China, spanning the temporal range from 2011 to 2020. The overarching objective was to elucidate the temporal and spatial dynamics underpinning these outbreaks. Acknowledging the pivotal role of global factors in FMD outbreaks, advanced machine learning techniques were harnessed to formulate an optimal prediction model by integrating comprehensive meteorological data pertinent to global FMD. Random Forest algorithm was employed with top three contributing factors including Isothermality(bio3), Annual average temperature(bio1) and Minimum temperature in the coldest month(bio6), all relevant to temperature. By encompassing both local and global factors, our study provides a comprehensive framework for understanding and predicting FMD outbreaks. Furthermore, we conducted a phylogenetic analysis to trace the origin of Foot-and-mouth disease virus (FMDV), pinpointing India as the country posing the greatest potential hazard by leveraging the spatio-temporal attributes of the collected data. Based on this finding, a quantitative risk model was developed for the legal importation of live cattle from India to China. The model estimated an average probability of 0.002254% for FMDV-infected cattle imported from India to China. TA sensitivity analysis identified two critical nodes within the model: he possibility of false negative clinical examination in infected cattle at destination (P5) and he possibility of false negative clinical examination in infected cattle at source(P3). This comprehensive approach offers a thorough evaluation of FMD landscape within China, considering both domestic and global perspectives, thereby augmenting the efficacy of early warning mechanisms.

Laser-induced breakdown spectroscopy-guided synergistic phototherapy: A theranostic platform mediated by a single laser wavelength.

Currently, cancer theranostic studies have only focused on integrating existing medical imaging techniques with therapeutic modalities. Obviously, this strategy is not a real theranostic method, as diagnosis and therapy are based on different principles and require independent operation. Here, a cancer theranostic method was established by laser-induced breakdown spectroscopy (LIBS)-mediated synergistic photothermal/photodynamic therapy, which was activated by a single 1064-nm light for simultaneous tumor localization and treatment. PEGylated cobalt phosphate (CoP@PEG) nanoparticles (NPs) with strong near-infrared (NIR)-II absorbance, high photothermal conversion efficiency and a reactive oxygen species generation effect were fabricated, and they produced excellent antitumor outcomes under 1064-nm excitation, as evidenced by the substantial increase in HepG2 cell death in vitro and complete tumor elimination in vivo. Meanwhile, the diagnostic method of the LIBS imaging system used in the present study also uses 1064-nm light. The LIBS imaging system can provide fast, real-time analysis and imaging of elements and facilitate the localization of the tumor site by monitoring the distribution of CoP@PEG NPs for precise tumor treatment. We postulate that this theranostic platform will promote the development of further theranostic research.

Porphyromonas, Treponema, and Mogibacterium promote IL8/IFNγ/TNFα-based pro-inflammation in patients with medication-related osteonecrosis of the jaw.

Objective: Refractory infection is an important factor affecting the progression of medication-related osteonecrosis of the jaw (MRONJ) from clinical stage I to stage II/III. The aim of this study was to explore the distribution of bacteria and their association with the inflammatory pathway of stage II/III MRONJ. Materials and Methods: Nine specimens of fresh inflammation tissue, located next to the necrotic bone or sequestrum, were collected from MRONJ patients. Nine specimens from normal oral mucosa were collected from healthy patients. The 16S rRNA gene sequencing method was used to determine the distribution characteristics of the bacterial colony. The protein microarray analysis was used to detect the expression of inflammatory cytokines. Results: The average relative abundance of Bacteroidetes, Spirochaetes, Synergistetes, and Tenericutes was higher, while Proteobacteria and Actinobacteria were lower in the MRONJ group. Most pro-inflammatory cytokines were up-regulated in the MRONJ group; yet, only IFNγ, TNFα, and IL8 showed statistical differences (P < 0.05). Porphyromonas and Treponema were positively correlated with IL8, and Mogibacterium was positively correlated with IFNγ and TNFα. Conclusions: IL8/IFNγ/TNFα pro-inflammatory effect caused by Porphyromonas, Treponema, and Mogibacterium may be the leading cause of advancing MRONJ and thus may be used as a new target for infection control.

Three-dimensional culture of dental pulp pluripotent-like stem cells (DPPSCs) enhances Nanog expression and provides a serum-free condition for exosome isolation.

Stem cell-derived exosomes have been identified as novel cell-free therapeutics for regenerative medicine. Three-dimensional (3D) culture of stem cells were reported to improve their "stemness" and therapeutic efficacy. This work focused on establishing serum-free 3D culture of dental pulp pluripotent-like stem cells (DPPSCs)-a newly characterized pluripotent-like stem cell for exosome production. DPPSCs were expanded in regular 2D culture in human serum-supplemented (HS)-medium and transferred to a micropatterned culture plate for 3D culture in HS-medium (default) and medium supplemented with KnockOut™ serum replacement (KO-medium). Bright-field microscopy observation throughout the culture period (24 days) revealed that DPPSCs in KO-medium formed spheroids of similar morphology and size to that in HS-medium. qRT-PCR analysis showed similar Oct4A gene expression in DPPSC spheroids in both HS-medium and KO-medium, but Nanog expression significantly increased in the latter. Vesicles isolated from DPPSC spheroids in KO-medium in the first 12 days of culture showed sizes that fall within the exosomal size range by nanoparticle tracking analysis (NTA) and express the canonical exosomal markers. It is concluded that 3D culture of DPPSCs in KO-medium provided an optimal serum-free condition for successful isolation of DPPSC-derived exosomes for subsequent applications in regenerative medicine.

[Analysis of hidden blood loss and its risk factors in the treatment of osteoporotic vertebral compression fractures with PVP].

OBJECTIVE: To investigate the influencing factors of hidden blood loss (HBL) during the treatment of percutaneous vertebroplasty (PVP). METHODS: The clinical data of 125 patients with osteoporotic vertebral compression fractures (OVCFs) treated with percutaneous vertebroplasty from March 2016 to December 2017 were retrospectively analyzed. All patients underwent X rays of the AP and lateral lumbar spine, double oblique, and dynamic positions. Lumbar spine CT, MRI, and dual energy X ray bone densitometer (DXA) were used to confirm the diagnosis. There were 55 males and 70 females, 10 cases of thoracic vertebrae, 89 cases of thoracolumbar vertebrae, 26 cases of lumbar vertebrae, 87 cases with single segment, 29 cases with double segment,and 9 cases with 3 segments. The vertebral compression height ratios of 67 patients were less than 1 / 3, and the ratios for 41 patients were from 1 / 3 to 2 / 3,for 17 patients were more than 2 / 3. Blood routine examination were performed before and 3 days after surgery to analyze hidden blood loss and to explore its risk factors. RESULTS: The average hidden blood loss was (317±156) ml in 125 patients. Multiple linear regression analysis revealed a history of diabetes(P=0.011),surgical segments(P=0.036),number of segments (P<0.001),vertebral height loss rate (P=0.002),vertebral height recovery rate (P<0.001) and bone cement leakage rate (P=0.003) were positively correlated with hidden blood loss. Moreover,it was found that the blood loss was higher in those with higher vertebral height loss rate than in those with lower vertebral height loss rate, and the blood loss was higher in those with good vertebral height recovery than those with poor vertebral height recovery. Additionally,the cement leakage was also an important factor in increasing hidden blood loss. However,there was no significant correlation between bone mineral density(P=0.814) or history of hypertension(P=0.055) and hidden blood loss. CONCLUSION: Patients with OVCFs have a large amount of hidden blood loss after PVP treatment, which needs attention. At the same time, the history of diabetes, surgical segments, number of segments, bone cement leakage rate, vertebral height loss rate and vertebral height recovery rate are the risk factors for hidden blood loss.

A Comparative Study on the Health Status and Behavioral Lifestyle of Centenarians and Non-centenarians in Zhejiang Province, China-A Cross-Sectional Study.

Background: The growth rate of centenarians was unusually rapid in recent decades, ushering in an era of longevity. This study aims to explore the difference between centenarians and non-centenarians using quantitative research, and to scientifically guide residents to develop the correct lifestyle and health care ways. Methods: From October 2013 to August 2017. A cross-sectional survey was conducted on 271 centenarians and 570 non-centenarians by using a questionnaire to assess longevity and health issues which was developed for the needs of the study, who came from 29 counties and districts in 11 cities of Zhejiang province, China. Two hundred and fifty-five valid questionnaires were returned, with an effective response rate of 94.1%. Meanwhile, data of 526 non-centenarians from Zhejiang province was collected as a control group, with an effective response rate of 92.3%. Results: The prevalence rates of tumor, stomach and duodenal ulcer, diabetes, bronchial asthma, and chronic obstructive pulmonary disease, tuberculosis among centenarians were all lower than those among non-centenarians. The oral health of centenarians is better than that of non-centenarians. The consumption of coarse cereals, pasta, other staple foods and fruits among centenarians was higher than that of non-centenarians. The percentage of centenarians who smoke or engage in recreational activities every day was lower than that of non-centenarians. Conclusions: We should give full play to the role of preventive medicine and health management to safeguard the health of residents. Pay attention to oral health, and develop the good habit of loving teeth. The diet should be rich and varied, and increase the intake of grains and fruits. Give up smoking, limit alcohol, spirit-preserving with calming, follow the law of scientific regimen.

Post-irradiation myokymia and neuromyotonia in unilateral tongue and mentalis muscles: report of a case.

We report a 52-year-old man with slowly progressive dysarthria and dysphagia for about 11 years after radiation therapy of nasopharyngeal carcinoma. Neurological examination revealed atrophy and myokymia on the left side of the tongue and in the left mentalis muscles. Electrical discharges of myokymia and neuromyotonia were also observed in the aforementioned muscles, suggesting increased motor axonal membrane excitability involving the left hypoglossal nerve and the marginal mendibular branch of the left facial nerve. Magnetic resonance imaging of the brain did not show any evidence of tumor recurrence, indicating that irradiation probably plays an important role in pathogenesis. Focal myokymia with concomitant neuromyotonia in unilateral tongue and mentalis muscles could be an unusual delayed manifestation after radiation therapy.