Effect of a Thermosensitive Hydroxybutyl Chitosan Hydrogel on Postoperative Sequalae and Quality of Life After Impacted Mandibular Third Molar Extraction.

BACKGROUND: Third molar (M3) extraction is a common surgery in oral and maxillofacial surgery, and composite wound dressings such as hydroxybutyl chitosan (HBC) may improve postoperative sequala following M3 removal. PURPOSE: The study purpose was to measure and compare differences in pain, swelling, trismus, wound healing, and quality of life (QOL) between the HBC and the control sides in patients undergoing M3 removal. STUDY DESIGN, SETTING, SAMPLE: This study is a double-blind, split-mouth, randomized clinical trial. Patients who required M3 removal between June 2022 and May 2023 were included. Exclusion criteria included seafood allergies, smoking, poor oral hygiene, and systemic diseases. PREDICTOR VARIABLE: The predictor variable was the socket treatment technique. Subjects were randomly assigned to the HBC or control (physiological saline) side. MAIN OUTCOME VARIABLE: The primary outcome variables, including pain assessed by visual analog scale, swelling, and maximal incisional opening, were measured on the first, third, and seventh postoperative days. The secondary outcome variables included QOL and wound healing score measured on the third and seventh days after surgery. COVARIATES: The covariates included age, sex, and operation time. ANALYSES: The Shapiro‒Wilk test was used to evaluate the normality of the data distribution. The paired t test or Wilcoxon signed-rank test was adopted. Statistical significance was set at P < .05. RESULTS: The study included 60 patients (mean age: 25.81 ± 4.91; 23 (38%) males, 37 (62%) females). A statistically significant difference in the level of pain (HBC: 37.58 ± 4.39 mm, control: 47.00 ± 4.33 mm, day 1, P < .001; 21.88 ± 3.25 mm, 35.95 ± 1.57 mm, day 3, P < .001), maximal incisional opening (23.92 ± 1.38 mm, 18.22 ± 1.82 mm, day 1, P < .001; 30.00 ± 1.61 mm, 23.78 ± 1.70 mm, day 3, P < .001), and swelling (6.86 ± 0.70 mm, 7.15 ± 0.80 mm, day 3, P = .006) was detected after surgery. A statistically significant difference in QOL was detected (HBC: 13.70 ± 1.65, control: 18.60 ± 2.14, day 3, P < .001). CONCLUSION AND RELEVANCE: The application of HBC hydrogels to wounds after impacted mandibular M3 extraction reduces postoperative sequalae, promotes wound healing and improves postoperative QOL.

Preoperative Contrast-Enhanced CT-Based Deep Learning Radiomics Model for Distinguishing Retroperitoneal Lipomas and Well­Differentiated Liposarcomas.

RATIONALE AND OBJECTIVES: To assess the efficacy of a preoperative contrast-enhanced CT (CECT)-based deep learning radiomics nomogram (DLRN) for predicting murine double minute 2 (MDM2) gene amplification as a means of distinguishing between retroperitoneal well-differentiated liposarcomas (WDLPS) and lipomas. METHODS: This retrospective multi-center study included 167 patients (training/external test cohort, 104/63) with MDM2-positive WDLPS or MDM2-negative lipomas. Clinical data and CECT features were independently measured and analyzed by two radiologists. A clinico-radiological model, radiomics signature (RS), deep learning and radiomics signature (DLRS), and a DLRN incorporating radiomics and deep learning features were developed to differentiate between WDLPS and lipoma. The model utility was evaluated based on the area under the receiver operating characteristic curve (AUC), accuracy, calibration curve, and decision curve analysis (DCA). RESULTS: The DLRN showed good performance for distinguishing retroperitoneal lipomas and WDLPS in the training (AUC, 0.981; accuracy, 0.933) and external validation group (AUC, 0.861; accuracy, 0.810). The DeLong test revealed the DLRN was noticeably better than clinico-radiological and RS models (training: 0.981 vs. 0.890 vs. 0.751; validation: 0.861 vs. 0.724 vs. 0.700; both P < 0.05); however, no discernible difference in performance was seen between the DLRN and DLRS (training: 0.981 vs. 0.969; validation: 0.861 vs. 0.837; both P > 0.05). The calibration curve analysis and DCA demonstrated that the nomogram exhibited good calibration and offered substantial clinical advantages. CONCLUSION: The DLRN exhibited strong predictive capability in predicting WDLPS and retroperitoneal lipomas preoperatively, making it a promising imaging biomarker that can facilitate personalized management and precision medicine.

Near-infrared fluorescence imaging technology guided margin design in oral squamous cell carcinoma: a single-centre retrospective study.

Objective: The margin status of oral squamous cell carcinoma patients is considered to be predictive of recurrence and long-term survival. Therefore, precise intraoperative margin assessment is crucial. This study investigated the feasibility of using near-infrared fluorescence imaging technology to guide margin design in oral squamous cell carcinoma patients. Methods: In this retrospective study, indocyanine green solution was intravenously injected preoperatively into patients. Intraoperatively, the surgical area was illuminated using a near-infrared fluorescence imaging system, which caused the lesion to fluoresce in the surgical area. Surgery was performed with the assistance of fluorescence imaging. The fluorescence intensity of the lesion area and surrounding normal tissue was recorded during surgery. Intraoperative margins were sent for rapid pathology, and postoperative margin pathology results were documented. Results: Sixteen patients were included in this study (7 males, 9 females), with an average age of 65.65 ± 12.37 years. Preoperative biopsy and postoperative pathology confirmed oral squamous cell carcinoma in all patients. No cancer cells were found in the margin pathology results. The average fluorescence intensity of the lesion area was 214 ± 4.70, and that of the surrounding normal tissue was 104.63 ± 3.14. There was no significant difference in the fluorescence intensity values of the lesion areas among all patients (F=0.38, P>0.05). There was a significant difference in fluorescence intensity between the lesion area and surrounding normal tissue (t=33.76, P<0.05). Conclusion: Near-infrared fluorescence imaging technology can aid in real-time imaging differentiation of lesion areas based on differences in fluorescence intensity during surgery. The use of this technology can assist surgeons in assessing the safety margin and reliably guide surgery.

Exploring the neuroprotective role of artesunate in mouse models of anti-NMDAR encephalitis: insights from molecular mechanisms and transmission electron microscopy.

BACKGROUND: The pathway involving PTEN-induced putative kinase 1 (PINK1) and PARKIN plays a crucial role in mitophagy, a process activated by artesunate (ART). We propose that patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis exhibit insufficient mitophagy, and ART enhances mitophagy via the PINK1/PARKIN pathway, thereby providing neuroprotection. METHODS: Adult female mice aged 8-10 weeks were selected to create a passive transfer model of anti-NMDAR encephalitis. We conducted behavioral tests on these mice within a set timeframe. Techniques such as immunohistochemistry, immunofluorescence, and western blotting were employed to assess markers including PINK1, PARKIN, LC3B, p62, caspase3, and cleaved caspase3. The TUNEL assay was utilized to detect neuronal apoptosis, while transmission electron microscopy (TEM) was used to examine mitochondrial autophagosomes. Primary hippocampal neurons were cultured, treated, and then analyzed through immunofluorescence for mtDNA, mtROS, TMRM. RESULTS: In comparison to the control group, mitophagy levels in the experimental group were not significantly altered, yet there was a notable increase in apoptotic neurons. Furthermore, markers indicative of mitochondrial leakage and damage were found to be elevated in the experimental group compared to the control group, but these markers showed improvement following ART treatment. ART was effective in activating the PINK1/PARKIN pathway, enhancing mitophagy, and diminishing neuronal apoptosis. Behavioral assessments revealed that ART ameliorated symptoms in mice with anti-NMDAR encephalitis in the passive transfer model (PTM). The knockdown of PINK1 led to a reduction in mitophagy levels, and subsequent ART intervention did not alleviate symptoms in the anti-NMDAR encephalitis PTM mice, indicating that ART's therapeutic efficacy is mediated through the activation of the PINK1/PARKIN pathway. CONCLUSIONS: At the onset of anti-NMDAR encephalitis, mitochondrial damage is observed; however, this damage is mitigated by the activation of mitophagy via the PINK1/PARKIN pathway. This regulatory feedback mechanism facilitates the removal of damaged mitochondria, prevents neuronal apoptosis, and consequently safeguards neural tissue. ART activates the PINK1/PARKIN pathway to enhance mitophagy, thereby exerting neuroprotective effects and may achieve therapeutic goals in treating anti-NMDAR encephalitis.

Chemical Mineralization of AMD into Schwertmannite Fixing Iron and Sulfate Ions by Structure and Adsorption: Paving the Way for Enhanced Mineralization Capacity.

Abundant iron and sulfate resources are present in acid mine drainage. The synthesis of schwertmannite from AMD rich in iron and sulfate could achieve the dual objectives of resource recovery and wastewater purification. However, schwertmannite cannot emerge spontaneously due to the Gibbs free energy greater than 0. This results in the iron and sulfate in AMD only being able to use the energy generated by oxidation in the coupling reaction to promote the formation of minerals, but this only achieved partial mineralization, which limited the remediation of AMD through mineralization. In order to clarify the mechanism of iron and sulfate removal by the formation of schwertmannite in AMD, kinetic and thermodynamic parameters were crucial. This work used H2O2 oxidation of Fe2+ as a coupling reaction to promote the formation of schwertmannite from 64.4% of iron and 15.7% of sulfate in AMD, and determined that 99.7% of the iron and 89.9% of sulfate were immobilized in the schwertmannite structural, and only a small fraction was immobilized by the adsorption of schwertmannite, both of which were consistent with second-order kinetics models. The thermodynamic data suggested that reducing the concentration of excess sulfate ions or increasing the energy of the system may allow more iron and sulfate to be immobilized by forming schwertmannite. Experimental verification using the reaction of potassium bicarbonate with the acidity in solution to increase the energy in the system showed that the addition of potassium bicarbonate effectively promoted the formation of schwertmannite from Fe3+ and SO42-. It provided a theoretical and research basis for the direct synthesis of schwertmannite from Fe3+ and SO42- rich AMD for the removal of contaminants from water and the recovery of valuable resources.

Tackling barriers to scale up human papillomavirus vaccination in China: progress and the way forward.

The human papillomavirus (HPV) vaccine is the first vaccine developed specifically targeting the prevention of cervical cancer. For more than 15 years, China has expedited a series of efforts on research and development of the domestically manufactured HPV vaccines, producing local population-based evidence, promoting free HPV vaccination from pilots, and launching action plans to tackle barriers in the scale-up of HPV vaccination. To further roll out the HPV vaccination program in China, several challenges should be addressed to support the steps forward. The availability of more locally manufactured HPV vaccines, pricing negotiation and local evidence supporting the efficacy of one-dose schedule would greatly alleviate the continued supply and financial constraints in China. Meanwhile, more attention should be paid to girls living in low-resource areas and males to ensure equal access to the HPV vaccination. Furthermore, linkage to secondary prevention and further real-world monitoring and evaluation are warranted to inform effective cervical cancer prevention strategies in the post-vaccine era.

Racial disparities in conditional survival of patients with bladder cancer: a population-based study.

BACKGROUND: Traditional estimates can only provide static predictions of cancer outcomes and cannot assess the evolving effect of race on patient survival. This study aims to reveal the dynamic survival of patients with bladder cancer and to explore the evolving effect of race on patient prognosis. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) registry, 99,590 white, 6,036 African American, and 4,685 Asian/Pacific Islander (API) patients with bladder cancer were identified. Conditional cancer-specific survival (CSS) rates, which could reflect the dynamic survival prediction of cancer patients, represented the primary outcomes, and were estimated by the Kaplan-Meier algorithm. The evolving effect of race on patient survival was evaluated by multivariable Cox regression in combination with conditional survival (CS) estimates. RESULTS: The 5-year CSS for African American patients who had survived 1, 2, 3, 4, or 5 years after definitive therapy improved from the baseline calculation by + 5.8 (84.4%), + 9.5 (87.4%), + 12.8 (90.0%), + 14.4 (91.3%), and + 14.7% (91.5%), respectively. The increasing trend also held for overall white and API patients, and for all patient subsets when CS was calculated according to different levels of sex, age, and disease stage. African Americans, despite having the worst survival at baseline, could have CSS comparable to their white and API counterparts after 4 years of survivorship. In addition, the risk of death for African Americans tended to decrease with increasing survival, and the risk was no longer significantly different from that of whites after 4 years of survival. CONCLUSIONS: While having the worst initial predicted outcomes, African Americans may eventually achieve comparable survival to white and API patients given several years of survivorship. As patient survival increases, African American race may lose its role as an indicator of poorer prognosis.

Stochastic Propagation of Fatigue Cracks in Welded Joints of Steel Bridge Decks under Simulated Traffic Loading.

The fatigue cracking of orthotropic steel bridge decks (OSDs) is a difficult problem that hinders the development of steel structures. The most important reasons for the occurrence of fatigue cracking are steadily growing traffic loads and unavoidable truck overloading. Stochastic traffic loading leads to the random propagation behavior of fatigue cracks, which increases the difficulty of the fatigue life evaluations of OSDs. This study developed a computational framework for the fatigue crack propagation of OSDs under stochastic traffic loads based on traffic data and finite element methods. Stochastic traffic load models were established based on site-specific, weigh-in-motion measurements to simulate fatigue stress spectra of welded joints. The influence of the transverse loading positions of the wheel tracks on the stress intensity factor of the crack tip was investigated. The random propagation paths of the crack under stochastic traffic loads were evaluated. Both ascending and descending load spectra were considered in the traffic loading pattern. The numerical results indicated that the maximum value of KI was 568.18 (MPa·mm1/2) under the most critical transversal condition of the wheel load. However, the maximum value decreased by 66.4% under the condition of transversal moving by 450 mm. In addition, the propagation angle of the crack tip increased from 0.24° to 0.34°-an increase ratio of 42%. Under the three stochastic load spectra and the simulated wheel loading distributions, the crack propagation range was almost limited to within 10 mm. The migration effect was the most obvious under the descending load spectrum. The research results of this study can provide theoretical and technical support for the fatigue and fatigue reliability evaluation of existing steel bridge decks.

Trend in Cervical Cancer Incidence and Mortality Rates in China, 2006-2030: A Bayesian Age-Period-Cohort Modeling Study.

BACKGROUND: There are no studies extrapolating the incidence and mortality of cervical cancer in China by comparing incidence and deaths pattern between geographic and age groups. METHODS: We applied age-period-cohort models to assess region-level trends in incidence and mortality from 2006 to 2016, with piecewise linear regression in a Bayesian framework to predict these trends to 2030. RESULTS: Between 2006 and 2016, age-standardized incidence rates (ASIR) for females aged 15 to 84 years increased by 3.7% (95% confidence interval, 3.1%-4.3%) annually from 11.01 to 16.41 per 100,000 females in China. In the 25 to 39 age groups, the incidence rates decreased in urban regions and inversely increased in rural regions. The age-standardized mortality rates (ASMR) increased from 3.18 to 4.83, with annual increases of about 3.6% (1.5%-5.8%). From 2017 to 2030, the ASIR is expected to increase from 17.13 (15.91-18.46) to 23.22 (20.02-27.01) by 2.5% per year (P < 0.05). Meanwhile, the average age at diagnosis is predicted to grow from 53.1 to 60.5 years. In the 15 to 54 age groups, the incidence rates decreased in urban regions but increased in rural regions. The ASMR is expected to increase consistently from 4.82 (4.38-5.31) to 9.13 (7.35-11.39) by 5.0% per year (P < 0.05). CONCLUSIONS: Cervical cancer incidence and mortality rates are projected to increase in China. In addition, the urban-rural incidence gap is estimated to widen further among young women. IMPACT: Cervical cancer prevention should consider the trend and diversity in incidence patterns between urban and rural regions.

Single-nucleus RNA sequencing unveils critical regulators in various hippocampal neurons for anti-N-methyl-D-aspartate receptor encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neuropsychiatric disease with variable clinical manifestations caused by NMDAR autoantibody. The underlying molecular underpinnings of this disease are rarely characterized on a genomic scale. Anti-NMDAR encephalitis mainly affects the hippocampus, however, its effect on gene expression in hippocampal neurons is unclear at present. Here, we construct the active and passive immunization mouse models of anti-NMDAR encephalitis, and use single-nucleus RNA sequencing to investigate the diverse expression profile of neuronal populations isolated from different hippocampal regions. Dramatic changes in cell proportions and differentially expressed genes were observed in excitatory neurons of the dentate gyrus (DG) subregion. In addition, we found that ATP metabolism and biosynthetic regulators related genes in excitatory neurons of DG subregion were significantly affected. Kcnq1ot1 in inhibitory neurons and Meg3 in interneurons also changed. Notably, the latter two molecules exhibited opposite changes in different models. Therefore, the above genes were used as potential targets for further research on the pathological process of anti-NMDAR encephalitis. These data involve various hippocampal neurons, which delineate a framework for understanding the hippocampal neuronal circuit and the potential molecular mechanisms of anti-NMDAR encephalitis.

Combined use of 3D printing and computer-assisted navigation in the clinical treatment of multiple maxillofacial fractures.

OBJECTIVES: In the field of computer-assisted surgery, 3D printing technology and computer-aided navigation (CAN) technology have led to advances in craniofacial surgery. However, the application of these two techniques in maxillofacial fractures is mostly limited to unilateral zygomatic bone and zygomatic arch fractures, and few studies have investigated their use for multiple maxillofacial fractures. This study summarizes the combined application of 3D printing technology and CAN for complex maxillofacial fractures to guide clinical practice. MATERIALS AND METHODS: Twenty-six patients with multiple maxillofacial fractures from 09/2017 to 03/2021 were retrospectively studied and divided according to surgical method into an experimental group (navigation-aided surgery combined with a 3D-printed guide) and a control group (navigation-aided surgery only). The surgical time was compared between the groups, and posttreatment computed tomography and follow-up visits were conducted at 1 week and 3 months, respectively, to compare the quality of treatment in terms of infection, occlusal disorder, restricted mouth opening, midline displacement, and bilateral asymmetry. RESULTS: According to our results, the combined use of CAN and 3D printing significantly improved the treatment results of double-sided maxillofacial fractures (rs = 0.448, P < 0.05). The surgical time of the experimental group was significantly shorter than that of the control group (Z = -2.083, P < 0.05). CONCLUSIONS: This study broadens our understanding of the treatment of multiple maxillofacial fractures. The combined use of 3D printing technology and CAN effectively shortened the operation time and achieved a better therapeutic effect.

Prognostic Role of Preoperative Onodera's Prognostic Nutritional Index (OPNI) in Gastrointestinal Stromal Tumors: a Systematic Review and Meta-analysis.

PURPOSE: The inflammatory parameters of peripheral blood are related to the prognosis of various cancers. The aim of this meta-analysis is to explore the prognostic value of preoperative OPNI in gastrointestinal stromal tumors (GIST). METHODS: The following search strategies were used to locate all literature published up to May 1, 2022: PubMed, Web of Science, CBM, EMBASE, and Cochrane, using the keywords "Prognosis," "survival," "Nutritional Assessment," "Nutrition Index," and "PNI," "OPNI," "Gastrointestinal stromal tumor," and "GIST." Studies that did not report an associated cumulative hazard ratio (HR) of recurrence-free survival (RFS) were excluded. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (CI) were calculated by a fixed-effects model. Subgroups were analyzed for heterogeneity of studies, and Egger's test was applied to assess the risk of publication bias. RESULTS: Through the inclusion and exclusion criteria, 8 articles with a total of 2462 patients with gastrointestinal stromal tumors were selected for analysis. The HR summary of univariate analysis of RFS was 2.73 (95% CI: 2.17-3.43, P < 0.0001), and there was no heterogeneity, which indicated that the prognosis of gastrointestinal stromal tumors with low OPNI before operation was poor. Except for one article that did not give the HR of RFS under the condition of multi-factor analysis, the other 7 articles gave the HR of RFS and summarized it to 1.81 (95% CI: 1.40-3.83, P < 0.0001). Although there was slight heterogeneity in the multifactorial analysis, the publication bias risk and sensitivity assessment showed that the results were still reliable (p > 0.05). CONCLUSION: The results of this systematic review and meta-analysis show that decreased preoperative OPNI is closely associated with poor long-term survival (RFS) in GIST patients. Monitoring OPNI in GIST patients may help with risk stratification and individualized treatment.

Analysis of the disease constituent ratio and prognosis of patients undergoing ambulatory surgery in oral and maxillofacial medicine: A monocentric retrospective analysis of 427 patients.

BACKGROUND: Ambulatory surgery and single-visit surgery are becoming increasingly accepted and practiced. MATERIALS AND METHODS: The clinical data of patients undergoing ambulatory surgery were collected, and information on their chief complaint and basic information was specifically included. Follow-up phone calls were conducted 1 and 3 days, 1 and 2 weeks, and 1 month after treatment. Information on their recovery and well-being was collected. RESULTS: A total of 427 patients (males: 224, females: 203, average age: 23.07±11 years) were recruited for this study. A total of 43.55% of the patients chose ambulatory surgery. A total of 62.9% of them selected it for convenience, while 43.55% selected it for pain reduction. The top three diseases treated by ambulatory surgery were impacted teeth (56.7%), jaw cyst (14.75%) and supernumerary teeth (10.07%). Postoperative complications occurred in 248 of the 427 patients, with an incidence rate of 58.08%. The complication that occurred most frequently was postoperative pain (56.44%). Complications frequently occurred on Day 3 after the operation and resolved after 2 weeks. CONCLUSION: After being diagnosed, ambulatory surgery is an effective mode of treatment for oral and maxillofacial diseases. Oral hygiene, professional postoperative follow-up visits and rigorous anesthesia evaluation are very important for ambulatory surgery for oral and maxillofacial diseases.

CXCL7 aggravates the pathological manifestations of neuromyelitis optica spectrum disorder by enhancing the inflammatory infiltration of neutrophils, macrophages and microglia.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS). Our previous study indicated that neutrophil-related chemokine CXCL7 is elevated in the cerebrospinal fluid (CSF) of NMOSD patients. To study the potential function of CXCL7 during NMOSD, we measured the chemokines level in CSF of follow-up patients, and established three NMOSD mouse models by injecting aquaporin4 (AQP4)-IgG. Astrocytes loss, inflammatory infiltration, and myelin sheath damage were detected by western blot or immunofluorescence analysis. We found CXCL7 was significantly increased in the serum and CSF of model mice, and exogenous CXCL7 caused serious astrocyte injury, obvious microglia activation, and increased infiltration of neutrophils and macrophages, resulting in secondary demyelination. Consistently, knocking down the CXCL7 reversed the loss of AQP4, and attenuated the inflammatory response. Collectively, our data indicates that CXCL7 aggravates NMOSD-like pathological damage to astrocytes and myelin sheath mainly via promoting neuroinflammatory response.

Mitofusin 2 confers the suppression of microglial activation by cannabidiol: Insights from in vitro and in vivo models.

Currently, there is increasing attention on the regulatory effects of cannabidiol (CBD) on the inflammatory response and the immune system. However, the mechanisms have not yet been completely revealed. Mitofusin 2 (Mfn2) is a mitochondrial fusion protein involved in the inflammatory response. Here, we investigated whether Mfn2 confers the anti-inflammatory effects of CBD. We found that treatment with CBD decreased the levels of tumor necrosis factor α, interleukin 6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and ionized calcium-binding adaptor molecule-1 (Iba1) in lipopolysaccharide (LPS)-challenged microglia. CBD also significantly suppressed the increase in reactive oxygen species (ROS) and the decline of mitochondrial membrane potential in BV-2 cells subjected to LPS. Interestingly, CBD treatment increased the expression of Mfn2, while knockdown of Mfn2 blocked the effect of CBD. By contrast, overexpression of Mfn2 reversed the increase in the levels of iNOS, COX-2, and Iba1 induced by Mfn2 small interfering RNA. In mice challenged with LPS, we found that CBD ameliorated the anxiety responses and cognitive deficits, increased the level of Mfn2, and decreased the expression of Iba1. Since neuro-inflammation and microglial activation are the common events that are observed in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, we treated EAE mice with CBD. Mice that received CBD showed amelioration of clinical signs, reduced inflammatory response, and increased myelin basic protein level. Most importantly, the adeno-associated virus delivery of short hairpin RNA against Mfn2 reversed the protective effects of CBD. Altogether, these results indicate that Mfn2 is an essential immunomodulator conferring the anti-inflammatory effects of CBD. Our results also shed new light on the mechanisms underlying the protective effects of CBD against inflammatory diseases including multiple sclerosis.

Temporal Trends and Projection of Cancer Attributable to Human Papillomavirus Infection in China, 2007-2030.

BACKGROUND: Information on temporal trends of cancer attributable to human papillomavirus (HPV) in China is limited. METHODS: Cancer incidence and mortality during 2007 to 2015 were extracted from the Chinese Cancer Registry Annual Report and the national population from the National Bureau of Statistics. HPV-attributable cancer burden and the average annual percentage change during 2007 to 2015 were estimated and cancer burden during 2016 to 2030 was projected. RESULTS: HPV-attributable cancer cases have increased by 3.8% [95% confidence interval (CI), 2.9%-4.8%] annually from 85,125 to 113,558 and age-standardized incidence rate (ASIR) rose by 3.0% (95% CI, 2.5%-3.5%) from 4.67 to 5.83 per 100,000 persons during 2007 to 2015. Cervical, female anal, and vulva cancer cases have increased by 3.8% (95% CI, 2.8%-4.7%), 6.5% (95% CI, 1.2%-12.2%), and 3.7% (95% CI, 1.6%-5.8%) per year. Male anal and oropharyngeal cancer cases have elevated by 7.5% (95% CI, 2.8%-12.5%) and 4.4% (95% CI, 2.4%-6.3%) annually. The increases of cervical and anal cancer were most rapid among those aged 50 and older. HPV-attributable cancer deaths and mortality rate have risen by 4.7% (95% CI, 2.9%-6.7%) and 3.3% (95% CI, 0.9%-5.8%) respectively. HPV-attributable cancer cases and ASIR are projected to reach 214,077 and 9.35 of 100,000 persons by 2030 respectively, with 87.7% being cervical cancer, and anal cancer cases are expected to triple. CONCLUSIONS: HPV-attributable cancer burden has largely increased in the past and will keep rising for the next decade. Cervical cancer control should be the priority and anal cancer prevention should be addressed. IMPACT: This study supplies fundamental evidence for policy-making on HPV-attributable cancer control.

lncRNA H19 Promotes Ox-LDL-Induced Dysfunction of Human Aortic Endothelial Cells through the miR-152/VEGFA Axis.

Objective: lncRNA H19 (H19) elevation is related to the risk of coronary artery disease. DIANA-lncBase database analysis suggested that microRNA-152 (miR-152) and H19 have binding sites. Here, the effect and mechanism of H19 and miR-152 in the oxidized low-density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs) were explored. Methods: The expression of H19, miR-152, and vascular endothelial growth factor (VEGF)-A in the HAECs treated with 5 µg/mL ox-LDL was detected by qRT-PCR. MTT, wound-healing assay, and tube formation assay were analyzed to evaluate the angiogenic activity of H19 and miR-152 in the HAECs cells knocked down H19. Dual-luciferase assay was performed to verify the targeting relationship of miR-152 to either H19 or VEGFA, respectively. Western blot was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and vimentin) and VEGFA protein in the cells. Results: After ox-LDL treatment, the expression of H19 and VEGFA was significantly increased, miR-152 expression was remarkably decreased. H19 was mainly expressed in the cytoplasm of HAECs. Knocking down H19 or overexpression of miR-152 significantly inhibited the cellular proliferation, migration, tube formation, and EMT trend of the HAECs. On the contrary, miR-152 interference reversed H19 silencing-mediated effects in the ox-LDL-induced HAECs. The dual-luciferase assay showed that miR-152 had a targeting relationship with H19 and VEGFA. MiR-152 was negatively corrected with the VEGFA expression. Conclusion: Ox-LDL negatively regulates miR-152 via H19, promotes the expression of VEGFA, and induces the dysfunction of HAECs.

High Level of Soluble CD146 In Cerebrospinal Fluid Might be a Biomarker of Severity of Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Background: Disruption of the blood-brain barrier (BBB) is an important pathophysiological process of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. A recent multi-center study showed that soluble (s) CD146 is a potential biomarker for monitoring early BBB damage and central nervous system inflammation, but little is known about sCD146 in anti-NMDAR encephalitis. Method: Twenty-three anti-NMDAR encephalitis patients and seventeen controls with non-inflammatory neurological diseases were recruited. sCD146 and inflammatory cytokines in cerebrospinal fluid (CSF) and serum were detected by ELISA. Modified Rankin scale (mRS) scores were used to assess the neurological status of each patient. A follow-up review was completed three months after discharge. Results: sCD146 levels in the CSF of patients with the acute stage anti-NMDAR encephalitis were significantly increased compared with controls and accompanied by increases in TNF-α, IL-6 and IL-10. CSF sCD146 was positively correlated with neuroinflammatory factors in the CSF and with mRS score. Three months after effective treatment, CSF sCD146 in patients was significantly decreased but remained significantly different compared with the controls. Conclusion: Our data suggested that higher expression of CSF sCD146 correlated with more serious neurological damage. Therefore, levels of CSF sCD146 may represent a promising indicator for monitoring disease and optimizing clinical treatment decisions in the early stages of anti-NMDAR encephalitis.

The novel ZEB1-upregulated protein PRTG induced by Helicobacter pylori infection promotes gastric carcinogenesis through the cGMP/PKG signaling pathway.

Helicobacter pylori (H. pylori) is listed as a class I carcinogen in human gastric cancer; however, the underlying mechanisms are poorly understood. In this study, we identified Protogenin (PRTG) was upregulated in both gastric cancer tissues and H. pylori-infected tissues by analyzing dysregulated genes in TCGA and GEO databases. Importantly, upregulated PRTG predicted poor prognosis of gastric cancer patients and integrative analysis revealed that PRTG served as an oncogenic protein in gastric cancer and was required for H. pylori-mediated tumorigenic activities in in vitro cellular and in vivo tumor-bearing mouse models. Mechanistically, H. pylori infection enhanced PRTG expression by promoting transcriptional factor ZEB1 stabilization and recruitment to the PRTG promoter, and which then activated the sub-following cGMP/PKG signaling pathway in bioinformatic and cellular studies. Cellular studies further confirmed that PRTG depended on activating cGMP/PKG axis to promote proliferation, metastasis, and chemoresistance of gastric cancer cells. The PKG inhibitor KT5823 played synergistic anti-tumor effects with cisplatin and paclitaxel to gastric cancer cells in in vitro cellular and in vivo tumor-bearing mouse models. Taken together, our findings suggested that H. pylori infection depends on ZEB1 to induce PRTG upregulation, and which leading to the development and progression of gastric cancer through activating cGMP/PKG signaling pathway. Blocking PRTG/cGMP/PKG axis, therefore, presents a promising novel therapeutic strategy for gastric cancer.

Anti-NMDAR encephalitis induced in mice by active immunization with a peptide from the amino-terminal domain of the GluN1 subunit.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesia, and seizures. However, the underlying mechanisms of this disease remain unclear, in part because of a lack of suitable animal models. METHODS: This study describes a novel female C57BL/6 mouse model of anti-NMDAR encephalitis that was induced by active immunization against NMDARs using an amino terminal domain (ATD) peptide from the GluN1 subunit (GluN1356-385). RESULTS: Twelve weeks after immunization, the immunized mice showed significant memory loss. Furthermore, antibodies from the cerebrospinal fluid of immunized mice decreased the surface NMDAR cluster density in hippocampal neurons which was similar to the effect induced by the anti-NMDAR encephalitis patients' antibodies. Immunization also impaired long-term potentiation at Schaffer collateral-CA1 synapses and reduced NMDAR-induced calcium influx. CONCLUSION: We established a novel anti-NMDAR encephalitis model using active immunization with peptide GluN1356-385 targeting the ATD of GluN1. This novel model may allow further research into the pathogenesis of anti-NMDAR encephalitis and aid in the development of new therapies for this disease.