Cross-cultural adaptation and psychometric properties of the Mainland Chinese version of the manchester orofacial pain disability scale (MOPDS) among college students.

BACKGROUND: Orofacial pain (OFP) is a highly prevalent disorder in mainland China that predisposes to an associated physical and psychological disability. There is lack of a good properties mainland Chinese version of instrument to examine OFP. This study aims to cross-cultural adaptation and evaluate psychometrics properties of the Manchester Orofacial Pain Disability Scale (MOPDS) in mainland Chinese Mandarin context. METHODS: Translation and cross-cultural adaption of the mainland Chinese version MOPDS were conducted following accepted guidelines of self-report measures. Chinese college students (N = 1039) completed the mainland Chinese version of the MOPDS for item analysis, reliability and validity tests, and measurement invariance analysis, and after a one-month interval, around 10% of the sample (n = 110) were invited to retest. To conduct the CFA and measurement invariance analysis, Mplus 8.4 was used. IBM SPSS Statistics 26 software were used for all additional studies. RESULTS: We found that the mainland Chinese version of MOPDS contains 25 items, divided into two categories: physical disability and psychological disability. The scale demonstrated excellent internal reliability, test-retest reliability, and validity. The measurement invariance results proved that the scale could be applied to people of different gender, age, and health consultation status. CONCLUSIONS: The results demonstrated the mainland Chinese version of MOPDS has good psychometric properties and can be used to measure the level of physical and psychological disability of Chinese OFP peoples.

Tooth ultrastructure changes induced by a nonsense mutation in the FAM83H gene: insights into the diversity of amelogenesis imperfecta.

OBJECTIVES: The current research on single-nucleotide polymorphism (SNP) mutation sites at different positions of the FAM83H gene and their phenotypic changes leading to amelogenesis imperfecta (AI) is inconsistent. We identified a previously reported heterozygous nonsense mutation c.1192C>T (p.Q398*) in the FAM83H gene and conducted a comprehensive analysis of the dental ultrastructure and chemical composition changes induced by this mutation. Additionally, we predicted the protein feature affected by this mutation site. The aim was to further deepen our understanding of the diversity of AI caused by different mutation sites in the FAM83H gene. METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to confirm the mutation sites. Physical features of the patient's teeth were investigated using various methods including cone beam computer tomography (CBCT), scanning electron microscopy (SEM), contact profilometry (roughness measurement), and a nanomechanical tester (nanoindentation measurement). The protein features of wild-type and mutant FAM83H were predicted using bioinformatics methods. RESULTS: One previously discovered FAM83H heterozygous nonsense mutation c.1192C>T (p.Q398*) was detected in the patient. SEM revealed inconsistent dentinal tubules, and EDS showed that calcium and phosphorus were lower in the patient's dentin but higher in the enamel compared to the control tooth. Roughness measurements showed that AI patients' teeth had rougher occlusal surfaces than those of the control tooth. Nanoindentation measurements showed that the enamel and dentin hardness values of the AI patients' teeth were both significantly reduced compared to those of the control tooth. Compared to the wild-type FAM83H protein, the mutant FAM83H protein shows alterations in stability, hydrophobicity, secondary structure, and tertiary structure. These changes could underlie functional differences and AI phenotype variations caused by this mutation site. CONCLUSIONS: This study expands the understanding of the effects of FAM83H mutations on tooth structure. CLINICAL RELEVANCE: Our study enhances our understanding of the genetic basis of AI and may contribute to improved diagnostics and personalized treatment strategies for patients with FAM83H-related AI.

Factorial structure and measurement invariance of the Chinese version of the Oral Health Impact Profile-14 among clinical populations and non-clinical populations: an evidence for public oral investigations.

OBJECTIVE: Oral health-related quality of life (OHRQoL) is a multidimensional concept that is commonly used to examine the impact of oral health status on quality of life. The purpose of this study was to examine the optimal factor model of the Chinese version of the Oral Health Impact Profile (OHIP-14) questionnaire in clinical populations, measurement invariance across clinical status and gender cohorts. This would ensure equal validity of the Chinese version of OHIP-14 in different populations and further support public oral investigations. METHODS: The Chinese version of OHIP-14 was used to investigate 490 dental patients and 919 college students. Confirmatory factor analysis (CFA), item analysis and reliability, measurement invariance, and the t-test were used for data analyses. RESULTS: We found that the 7-factor structure had the best-fit index in the sample (CFI = 0.970, TLI = 0.952; SRMR = 0.029, RMSEA = 0.052(0.040,0.063)). The reliability of the scales was satisfactory (Cronbach's α = 0.942). The error variance invariance fitted the data adequately in measurement invariance, indicating that measurement invariance is acceptable both across the clinical and non-clinical populations (∆CFI=-0.017, ∆RMSEA = 0.010) and across genders in the clinical population (∆CFI = 0.000, ∆RMSEA=-0.003). T-test for scores showed that the clinical populations scored significantly higher than the non-clinical populations, as did the overall score (t = 7.046, p < 0.001, d = 0.396), in terms of functional limitation (t = 2.178, p = 0.030, d = 0.125), physical pain (t = 7.880, p < 0.001,d = 0.436), psychological discomfort (t = 8.993, p < 0.001, d = 0.514), physical disability (t = 6.343, p < 0.001, d = 0.358), psychological disability (t = 5.592, p < 0.001, d = 0.315), social disability (t = 5.301, p < 0.001,d = 0.304), social handicap (t = 4.452, p < 0.001, d = 0.253), and that in the non-clinical populations, females scored significantly higher than males, as did in terms of physical pain (t = 3.055, p = 0.002, d = 0.280), psychological discomfort (t = 2.478, p = 0.014, d = 0.222), and psychological disability (t = 2.067, p = 0.039, d = 0.188). CONCLUSION: This study found that the Chinese version of OHIP-14 has measurement invariance between the clinical and non-clinical populations and across genders in the clinical populations, and can be widely used in OHRQoL assessment for public oral investigations.

[Study on lignans from Xanthii Fructus].

This project is to investigate lignans from the dried fruits of Xanthium sibiricum (Xanthii Fructus). The chemical constituents were extract by 70% ethanol and isolated by silica gel, ODS, Sephadex LH-20, MCI column chromatography. Based on comparison of their spectral data with those reported in literature, they were elucidated as (-)-pinoresinol (1), balanophonin A (2), diospyrosin (3), dehydrodiconiferyl alcohol (4), 2-(4-hydroxy-3-methoxyphenyl)-3-(2-hydroxy-5-methoxyphenyl)-3-oxo-1-propanol (5), (-)-simulanol (6), (-)-7R,8S-dehydrodiconiferyl alcohol (7), chushizisin E (8), dihydrodehydrodiconiferyl alcohol (9), 7R,8S-dihydrodehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside (10), erythro-1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (11), leptolepisol D (12), 8-O-4' neolignan 4-O-ß-glucopyranoside (13), (-)-1-O-ß-D-glucopyranosyl-2-{2-methoxy-4-[1-(E)-propen-3-ol]phenoxyl}-propane-3-ol(14), 1-(4-hydroxy-3-methoxy)-phenyl-2-[4-(1,2,3-trihydroxypropyl)-2-methoxy]-phenoxy-1,3-propandiol (15), threo-dihydroxy dehydrodiconiferyl alcohol (16), (-)-(2R)-1-O-ß-D-glucopyranosyl-2-{2-methoxy-4-[(E)-formylviny1]phenoxyl} propane-3-ol (17). Compound 2-17 were isolated from the genus Xanthium for the first time. Compound 1 were isolated form Xanthii Fructus for the first time.

Activation of Cdk5/p25 and tau phosphorylation following chronic brain hypoperfusion in rats involves microRNA-195 down-regulation.

Chronic brain hypoperfusion (CBH) is a common clinical feature of Alzheimer's disease and vascular dementia, but the underlying molecular mechanism is unclear. Our previous study reported that the down-regulation of microRNA-195 (miR-195) promotes amyloidogenesis via regulation of amyloid precursor protein and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) expression at the post-transcriptional level in CBH rats with bilateral common carotid artery occlusion (2VO). CBH owing to unilateral common carotid artery occlusion (UCCAO) increases tau phosphorylation levels at multiple phosphorylation sites in the brain, but the molecular mechanism is poorly understood. The purpose of this study was to investigate whether miR-195 could both deregulate amyloid metabolism and indirectly deregulate tau phosphorylation in CBH. We observed that 2VO leads to tau hyperphosphorylation at Ser202/Thr205, Ser262, Thr231, and Ser422 and to the conversion from cyclin-dependent kinase 5 (Cdk5)/p35 to Cdk5/p25 in rat hippocampi. Endogenous miR-195 was knocked down using over-expression of its antisense molecule (pre-AMO-miR-195) via a lentivirus (lenti-pre-AMO-miR-195); this knockdown increased the tau phosphorylation at Ser202/Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over-expression of miR-195 using lenti-pre-miR-195 decreased the tau phosphorylation and Cdk5/p25 activation. Further in vitro studies demonstrated that miR-195 over-expression prevented tau hyperphosphorylation and Cdk5/p35 activity, which were increased by miR-195 inhibition. A dual luciferase reporter assay showed that miR-195 bound to the Cdk5r1 gene, which encodes p35 protein, in the 3'UTR and inhibited p35 expression. We concluded that tau hyperphosphorylation involves the down-regulation of miR-195, which is mediated by Cdk5/p25 activation in 2VO rats. Our findings demonstrated that down-regulation of miR-195 led to increased vulnerability via the regulation of multiple targets. Schematic diagram of miR-195 mediated Aß aggregation and tau hyperphosphorylation in chronic brain hypoperfusion (CBH). First, CBH results in the elevation of nuclear factor-κB (NF-κB), which binds with the promoter sequences of miR-195 and negatively regulates the expression of miR-195. Second, down-regulated miR-195 induces up-regulation of APP and BACE1 and leads to an increase in Aß levels. Third, some of the elevated Aß then enter the intracellular space and activate calpain, which promotes the conversion of Cdk5/p35 to Cdk5/p25 and catalyzes the degradation of IκB; IκB is an inhibitor of NF-κB, which activates NF-κB. Cdk5/p25 directly phosphorylates Tau. Fourth, down-regulated miR-195 induces an up-regulation of p35, which provides the active substrates of p25. Our findings demonstrated that the down-regulation of miR-195 plays a key role in the increased vulnerability to dementia via the regulation of multiple targets following CBH.

[Therapeutic Material Basis of Chemical Subdivisions of Anemarrhenae Rhizoma on Anti-inflammatory and Immunomudulatory Effects].

OBJECTIVE: To study the relationship between chemical subdivision and immune suppressive activity in order to find out the anti-inflammatory and immunomudulatory pharmacological activity material basic of Anemarrhenae Rhizoma. METHOD: C57 mice was induced by 2,4-Dinitrofluorobenzene to build immune inflammation which was also called contact allergic dermatitis. The influence of Anemarrhenae Rhizoma decoction and chemical subdivisions on immune organ, ear edema and the Th1/Th2 immune balance was measured by analytical balance and Elisa method. The inflammatory factor TNF-α and NO level excreted by macrophage RAW264. 7 induced by LPS were also investigated. RESULT: AA decoction, timosaponin and polysaccharides significantly reduced the immune organ index and ear edema degree (P < 0.05), protein expression of IFN-γ was inhibited by AA timosaponin fraction and polysaccharides fraction. In vitro experiments showed that the proliferation of spleen cells was inhibited by timosaponin and polysaccharides after induced by ConA (P < 0.05). The release of NO and TNF-α induced by LPS significantly decreased by Anemarrhenae Rhizoma decoction and timosaponin (P < 0.05). CONCLUSION: The significant anti-inflammatory and immunomudu latory effects of AA are related to timosaponin and polysaccharides.

[Exploring effective components of laxative effect of Anemarrhenae Rhizoma based on Chinese herbal processing theory].

Anemarrhena asphodeloides processed by salt and raw product was compared including both chemical composition and laxative function in order to find the possible active substance to cure constipation. Processed and raw Anemarrhenae laxative effect on experimental constipation models was observed as well as chemical composition using UPLC-MS technology and the total sugar content was determined by phenol sulfuric acid method. Processed Anemarrhenae water extract improved excrement more than raw which has significant difference compared with the blank group (P < 0.05). On the other hand, the total ion flow spectrum showed no significant difference in most substance, but the total sugar content was significantly higher than raw product. Anemarrhenae ancient be recognized benefitting for draining body water in traditional Chinese medicine which has been lost in modern books because it is manifested as excellent laxative effect not diuretic effect. Saccharides carbohydrate may have closely relationship with this magically effect.

MicroRNA-195 protects against dementia induced by chronic brain hypoperfusion via its anti-amyloidogenic effect in rats.

Previous studies have demonstrated that chronic brain hypoperfusion (CBH) causes Aß aggregation by upregulating expression of amyloid precursor protein (APP) and ß-site APP cleaving enzyme 1 (BACE1) protein, which is accompanied by cognitive impairment, but the mechanisms are not fully understood. In this study, we evaluated the effect of microRNA on memory impairment in rats induced by CBH. We show here that CBH generated by bilateral common carotid artery occlusion (2VO) significantly decreased the learning and memory ability in rats, as assessed by Morris water maze, and upregulated expression of APP and BACE1 proteins in the hippocampus and cortex of rats, as evaluated by Western blot and immunofluorescence. In reciprocal, qRT-PCR analysis showed that microRNA-195 (miR-195) was downregulated in both the hippocampus and cortex of rats following CBH, and in the plasma of dementia patients. APP and BACE1 proteins were downregulated by miR-195 overexpression, upregulated by miR-195 inhibition, and unchanged by binding-site mutation or miR-masks, indicating that APP and BACE1 are two potential targets for miR-195. Knockdown of endogenous miR-195 by lentiviral vector-mediated overexpression of its antisense molecule (lenti-pre-AMO-miR-195) elicited dementia in rats, whereas overexpression of miR-195 using lenti-pre-miR-195 reduced dementia vulnerability triggered by 2VO. Additionally, chromatin immunoprecipitation analysis showed that NFκB was bound to the promoter region of miR-195 and inhibited its expression. We conclude that miR-195 may play a key role in determining dementia susceptibility in 2VO rats by regulating APP and BACE1 expression at the post-transcriptional level, and exogenous complement of miR-195 may be a potentially valuable anti-dementia approach.

Expression of amyloid-associated miRNAs in both the forebrain cortex and hippocampus of middle-aged rat.

BACKGROUND: Aging is associated with the gradual cognitive decline and shows the typical senile plaque formation in the brain, which results from the aggregation of beta amyloid (Aß) peptide following the abnormal proteolytic processing of amyloid precursor protein (APP) by ß-secretase (BACE1) and γ-secretase. Accumulating evidence indicates that several microRNAs (miRNAs) are involved in the Alzheimer's disease (AD) by regulating the expression of APP and BACE1 proteins. However, the cognitive ability and the expression profile of the APP- and BACE1-associated miRNAs in the middle-aged population are largely unknown. METHODS: The learning and memory ability in rats were determined by Morris Water Maze test. The protein levels of APP and BACE1 were detected by western blotting. The quantitative polymerase chain reaction was used to identify the miRNAs levels in forebrain cortex and the hippocampus. RESULTS: Middle-aged rats have declined learning ability without changes in the memory ability, and increased APP and BACE1 protein expression in the forebrain cortex. Computational analysis using Targetscan and Pictar databases reveals that totally 4 predicted miRNAs have conserved binding site with APP, namely miR-106b, -17-5p, -153, -101. All of them showed decreased expression in both the forebrain cortex and hippocampus. Among the 10 predicted miRNAs targeting BACE1, different expression profiles were identified in the forebrain cortex (decreased: miR-9, -19a, -135a, -15b, -16, -195, -29c, -214; increased: miR-124; no change: miR-141) and the hippocampus (decreased: miR-9, -15b, -16, -195, -29c, -124; increased: miR-19a, -135a, -214, -141) in the middle-aged rats compared with the young rats. CONCLUSION: Our results provided the first evidence that middle-aged rats have begun displaying cognitive disability with abnormal expression of APP- and BACE1-related miRNAs in the hippocampus and forebrain cortex.

NOD2 contributes to Parvimonas micra-induced bone resorption in diabetic rats with experimental periodontitis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide-binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2. METHODS: We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high-throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro-computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24 h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin-12 (IL-6) were detected by western blot. RESULTS: The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL-6. CONCLUSIONS: The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas.

Evaluation of the Efficacy of Stem Cells Therapy in the Periodontal Regeneration: A Meta-Analysis and Mendelian Randomization Study.

Stem cell therapy for periodontal defects has shown good promise in preclinical studies. The purpose of this study was to evaluate the impact of stem cell support on the regeneration of both soft and hard tissues in periodontal treatment. PubMed, Cochrane Library, Embase, and Web of Science were searched and patients with periodontal defects who received stem cell therapy were included in this study. The quality of the included articles was assessed using Cochrane's tool for evaluating bias, and heterogeneity was analyzed using the I2 method. An Mendelian randomization investigation was conducted using abstract data from the IEU public databases obtained through GWAS. Nine articles were included for the meta-analysis. Stem cell therapy effectively rebuilds periodontal tissues in patients with periodontal defects, as evidenced by a reduction in probing depth, clinical attachment level  and bone defect depth . And delta-like homolog 1 is a protective factor against periodontal defects alternative indicator of tooth loosening. The findings of this research endorse the utilization of stem cell treatment for repairing periodontal defects in individuals suffering from periodontitis. It is recommended that additional extensive clinical investigations be carried out to validate the efficacy of stem cell therapy and encourage its widespread adoption.

Development, validation and psychometric evaluation of the Chinese version of the biopsychosocial impact scale in orofacial pain patients.

Background: The objective of this study was to develop the Chinese version of the biopsychosocial impact scale (BPIm-S) to assess functional limitation and psychosocial distress in orofacial pain (OFP) patients in mainland China, and investigate the factor structure, reliability and validity, measurement invariance, as well as scores differences across genders, age and educational status among OFP patients. Methods: The BPIm-S was developed and evaluated in four stages: (1) concept selection and item generation; (2) a pilot study assessing face and content validity; (3) the factors structure, reliability, convergent validity, and measurement invariance; and (4) concurrent validity and clinical responsiveness. Exploratory (EFA) and confirmatory factor analyses (CFA) were performed on data gathered from 406 OFP patients to assess construct validity. Composite Reliability (CR) and the Average Variance Extracted (AVE) were used to assess internal convergent validity. CR, internal consistency, and split-half reliability were also performed to determine the reliability. Multigroup CFA (MGCFA) was used to assess measurement invariance across genders, age and educational status. Mann-Whitney test compared scores across different genders, age and educational status. Participants completed the BPIm-S, visual analog scale (VAS), brief pain inventory facial (BPI-F), General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9), and spearman's correlation coefficient was used to evaluate the concurrent validity and item-total correlations. A total of 12 patients with OFP completed the BPIm-S twice to test clinical responsiveness. To conduct the CFA and measurement invariance analysis, Mplus 8.4 was used. IBM SPSS Statistics 21 software and SPSSAU, a web-based data science algorithm platform tool, were used for all additional studies. Results: For the preliminary version, 17 items were chosen. A total of four items were removed following the pilot research. The remaining 13 items of the BPIm-S comprised an overall summary scale. Excellent reliability (Item-to-total correlations ranged from 0.763 to 0.912) and strong internal consistency (Cronbach's α = 0.970, functional limitation, 0.962, and psychosocial distress, 0.977) were discovered. CFA also validated the structural validity of the 13-item scale. EFA was performed and a two-factor structure was investigated. In addition, MGCFA corroborated the measurement invariance of the BPIm-S across gender, age, and educational status. Patients over the age of 30, those with a medium level of education, and those with a low level of education showed substantially greater levels of functional limitation and psychological distress (Wilcoxon test, p < 0.001). Both concurrent validity and clinical responsiveness were assessed to be of good quality. Conclusion: The BPIm-S demonstrated good psychometric qualities and is a reliable tool that can now be used by clinicians to evaluate functional limitation and psychosocial distress among OFP patient.

Causal effects of the gut microbiome on COVID-19 susceptibility and severity: a two-sample Mendelian randomization study.

Background: The coronavirus disease 2019 (COVID-19) caused a global pandemic, with potential severity. We aimed to investigate whether genetically predicted gut microbiome is associated with susceptibility and severity of COVID-19 risk. Methods: Mendelian randomization (MR) analysis of two sets with different significance thresholds was carried out to infer the causal relationship between the gut microbiome and COVID-19. SNPs associated with the composition of the gut microbiome (n = 5,717,754) and with COVID-19 susceptibility (n = 14,328,058), COVID-19 severity (n = 11,707,239), and COVID-19 hospitalization (n = 12,018,444) from publicly available genome-wide association studies (GWAS). The random-effect inverse variance weighted (IVW) method was used to determine causality. Three more MR techniques-MR Egger, weighted median, and weighted mode-and a thorough sensitivity analysis were also used to confirm the findings. Results: IVW showed that 18 known microbial taxa were causally associated with COVID-19. Among them, six microbial taxa were causally associated with COVID-19 susceptibility; seven microbial taxa were causally associated with COVID-19 severity ; five microbial taxa were causally associated with COVID-19 hospitalization. Sensitivity analyses showed no evidence of pleiotropy or heterogeneity. Then, the predicted 37 species of the gut microbiome deserve further study. Conclusion: This study found that some microbial taxa were protective factors or risky factors for COVID-19, which may provide helpful biomarkers for asymptomatic diagnosis and potential therapeutic targets for COVID-19.

Oral Health-Related Quality of Life among Chinese Chronic Orofacial Pain Patients with Psychological Health Problems: A Moderated Mediation Model.

Psychological therapies are important for comprehensive chronic orofacial pain (COFP) treatment. This study is to validate the effects of psychological factors on oral health-related quality of life (OHRQoL) among COFP patients in China. Pain catastrophizing, which is a subjective cognitive emotion used to manage the psychological aspects of pain among COFP patients, was examined in relation to COFP severity and OHRQoL. All 479 participants were recruited in Changsha, Hunan Province, China. Cronbach's alpha coefficients (0.868-0.960), composite reliability scores (0.924-0.969), and average variance extracted from each construct (0.555-0.753) all indicated a good model fit. Pearson's correlation analysis showed that age and education status have a positive correlation with COFP severity, pain catastrophizing, and anxiety. COFP severity was related to anxiety, depression, and COFP-OHRQoL. Pain catastrophizing was related to employment status. Anxiety and depression symptoms indirectly mediated the correlation between COFP severity and COFP-OHRQoL. As a second-stage moderator, pain catastrophizing moderated the mediating effects of anxiety symptoms and depression symptoms. Our findings suggest that anxiety, depression, and pain catastrophizing should be evaluated jointly to improve COFP-OHRQoL among COFP patients. This evidence will help therapists to comprehensively treat patients for the best treatment effect.

Chitosan nanoparticles for sustained release of metformin and its derived synthetic biopolymer for bone regeneration.

Background: There are considerable socioeconomic costs associated with bone defects, making regenerative medicine an increasingly attractive option for treating them. Chitosan is a natural biopolymer; it is used in approaches for sustained slow release and osteogenesis, and metformin has osteoinductivity. Our study aimed to synthesize chitosan and human serum albumin (HSA) with a metformin nanoformulation to evaluate the therapeutic effects of this nanoformulation on bone defects in vitro. Methods: A pluripotent differentiation assay was performed in vitro on mouse bone marrow mesenchymal stem cells (BMSCs). Cell Counting Kit-8 was used to detect whether metformin was toxic to BMSCs. The osteogenesis-related gene expression of osteocalcin (OCN) and osteoprotegerin (OPG) from BMSCs was tested by real-time polymerase chain reaction (PCR). HSA, metformin hydrochloride, and chitosan mixtures were magnetically stirred to finish the assembly of metformin/HSA/chitosan nanoparticles (MHC NPs). The MHC NPs were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FT-IR). To test the expression of OCN and OPG, western blot were used. MHC NPs were evaluated in vitro for their osteoinductivity using alkaline phosphatase (ALP). Results: BMSCs successfully differentiated into osteogenic and adipogenic lineages in vitro. According to real-time PCR, a 50 µM concentration of metformin promoted osteogenesis in BMSCs most effectively by upregulating the osteogenic markers OCN and OPG. The microstructure of MHC NPs was spherical with an average nanosize of 20 ± 4.7 nm and zeta potential of -8.3 mV. A blueshift and redshift were observed in MHC NPs following exposure to wavelengths of 1,600-1,900 and 2,000-3,700 nm, respectively. The encapsulation (%) of metformin was more than 90%. The simulation study showed that MHC NPs have good stability and it could release metformin slowly in vitro at room temperature. Upon treatment with the studied MHC NPs for 3 days, ALP was significantly elevated in BMSCs. In addition, the MHC NPs-treated BMSCs upregulated the expression of OPG and OCN, as shown by real-time PCR and western blot. Conclusion: MHC NPs have a stable metformin release effect and osteogenic ability. Therefore, as a derived synthetic biopolymer, it is expected to play a role in bone tissue regeneration.

Type 1 diabetes, glycemic traits, and risk of dental caries: a Mendelian randomization study.

Background: Regarding past epidemiological studies, there has been disagreement over whether type 1 diabetes (T1DM) is one of the risk factors for dental caries. The purpose of this study was to determine the causative links between genetic susceptibility to T1DM, glycemic traits, and the risk of dental caries using Mendelian randomization (MR) approaches. Methods: Summary-level data were collected on genome-wide association studies (GWAS) of T1DM, fasting glucose (FG), glycated hemoglobin (HbA1c), fasting insulin (FI), and dental caries. MR was performed using the inverse-variance weighting (IVW) method, and sensitivity analyses were conducted using the MR-Egger method, weighted median, weighted mode, replication cohort, and multivariable MR conditioning on potential mediators. Results: The risk of dental caries increased as a result of genetic susceptibility to T1DM [odds ratio (OR) = 1.044; 95% confidence interval (CI) = 1.015-1.074; p = 0.003], with consistent findings in the replication cohort. The relationship between T1DM and dental caries was stable when adjusted for BMI, smoking, alcohol intake, and type 2 diabetes (T2DM) in multivariable MR. However, no significant correlations between the risk of dental caries and FG, HbA1c, or FI were found. Conclusion: These results indicate that T1DM has causal involvement in the genesis of dental caries. Therefore, periodic reinforcement of oral hygiene instructions must be added to the management and early multidisciplinary intervention of T1DM patients, especially among adolescents and teenagers, who are more susceptible to T1DM.

Prognostic biomarker GSTK1 in head and neck squamous cell carcinoma and its correlation with immune infiltration and DNA methylation.

Background: Glutathione S-transferase kappa 1 (GSTK1) is critical in sarcoma and breast cancer (BRCA) development. However, the clinical significance of GSTK1 in head and neck squamous cell carcinoma (HNSC) remains unclear. This study is the first investigation into the role of GSTK1 in HNSC. Methods: All original data were downloaded from the Cancer Genome Atlas (TCGA) dataset and verified by R Base Package 4.2.0. The expression of GSTK1 in various cancers was explored with TIMER and TCGA databases. Prognostic value of GSTK1 was analyzed via survival module of Kaplan-Meier plotter and Human Protein Atlas database and Cox regression analysis. The association between GSTK1 and clinical features was evaluated by Wilcoxon signed-rank test and logistic regression analysis. The relationship between GSTK1 and immune infiltration and methylation level was further explored. The expression of GSTK1 and its correlation with immune cell infiltration was verified by Immunohistochemical staining (IHC). Results: GSTK1 was lower in HNSC, BRCA, Lung squamous cell carcinoma, and Thyroid carcinoma than in para-carcinoma. Low GSTK1 expression was associated with worse overall survival in Bladder urothelial carcinoma, Kidney renal papillary cell carcinoma, BRCA, and HNSC. However, only in BRCA and HNSC, GSTK1 expression in tumors was lower than that in normal tissues. Cox regression analyses confirmed that GSKT1 was an independent prognostic factor of overall survival in HNSC patients. The decrease in GSTK1 expression in HNSC was significantly correlated with high T stage and smoker history. IHC showed that the expression level of GSTK1 in HNSC was lower than that in para-carcinoma. In addition, GSEA showed that three pathways related to immune infiltration were positively correlated, while two pathways related to DNA methylation were negatively correlated with expression of GSTK1. Further analysis showed that GSTK1 was moderately positively correlated with the infiltration level of T cells and Cytotoxic cells, which was further confirmed by IHC. The methylation level of GSTK1 was associated with prognosis in patients with HNSC. Conclusion: Low GSTK1 expression may be a potential molecular marker for poor prognosis in HNSC and provide new insight for the development of diagnostic marker or therapeutic target.

Clinical application and mechanism of traditional Chinese medicine in treatment of lung cancer.

ABSTRACT: Lung cancer is a malignant tumor characterized by a rapid proliferation rate, less survivability, high mortality, and metastatic potential. This review focuses on updated research about the clinical application of traditional Chinese medicine (TCM) as an adjuvant therapy to lung cancer treatment and the mechanisms of TCM effect on lung cancer in vitro and in vivo. We summarized the recent 5 years of different research progress on clinical applications and antitumor mechanisms of TCM in the treatment of lung cancer. As a potent adjuvant therapy, TCM could enhance conventional treatments (chemotherapy, radiation therapy, and epidermal growth factor receptors [EGFRs] tyrosine kinase inhibitors [TKIs]) effects as well as provide synergistic effects, enhance chemotherapy drugs chemosensitivity, reverse drug resistance, reduce adverse reactions and toxicity, relieve patients' pain and improve quality of life (QOL). After treating with TCM, lung cancer cells will induce apoptosis and/or autophagy, suppress metastasis, impact immune reaction, and therapeutic effect of EGFR-TKIs. Therefore, TCM is a promisingly potent adjuvant therapy in the treatment of lung cancer and its multiple mechanisms are worthy of an in-depth study.

[Structure and ecological functions of soil micro-food web.] / 土壤微食物网结构与生态功能.

Soil micro-food web, as a part of the detritus food webs, directly or indirectly participates in nutrient cycling by feeding on substrate and microorganisms and consequently influences the functions of terrestrial ecosystems. Here, we reviewed the research progress of soil micro-food web in recent years by focusing on its composition, structure and ecological function in soil ecosystem. The important roles of soil micro-food web in driving carbon (C) and nitrogen (N) transformation, organic matter decomposition and plant growth were reviewed through the description of energy channel and trophic cascade effects of soil micro-food web. At last, the research perspectives were put forward. Future researches should be combined with high-throughput sequencing and stable isotope techniques for better understanding the belowground ecological process and their feedback mechanisms to plant growth through modeling analysis.

[Treatment of acute respiratory distress syndrome using pressure and volume controlled ventilation with lung protective strategy].

OBJECTIVE: To investigate the significance and effect of pressure controlled ventilation (PCV) as well as volume controlled ventilation (VCV) by lung protective strategy on respiratory mechanics, blood gas analysis and hemodynamics in patients with acute respiratory distress syndrome (ARDS). METHODS: Fifty patients with ARDS were randomly divided into PCV and VCV groups with permissive hypercapnia and open lung strategy. Changes in respiratory mechanics, blood gas analysis and hemodynamics were compared between two groups. RESULTS: Peak inspiration pressure (PIP) in PCV group was significantly lower than that in VCV group, while mean pressure of airway (MPaw) was significantly higher than that in VCV after 24 hours mechanical ventilation. After 24 hours mechanical ventilation, there were higher central venous pressure (CVP) and slower heart rate (HR) in two groups, CVP was significantly higher in VCV compared with PCV, and PCV group had slower HR than VCV group, the two groups had no differences in mean blood pressure (MBP) at various intervals. All patients showed no ventilator-induced lung injury. Arterial blood oxygenations were obviously improved in two groups after 24 hours mechanical ventilation, PCV group had better partial pressure of oxygen in artery (PaO2) than VCV group. CONCLUSION: Both PCV and VCV can improve arterial blood oxygenations, prevent ventilator-induced lung injury, and have less disturbance in hemodynamic parameters. PCV with lung protective ventilatory strategy should be early use for patients with ARDS.