Metabolic profiling of peri-implant crevicular fluid in peri-implantitis.

OBJECTS: This study aims to explore the etiology of peri-implantitis by comparing the metabolic profiles in peri-implant crevicular fluid (PICF) from patients with healthy implants (PH) and those with peri-implantitis (PI). MATERIALS AND METHODS: Fifty-six patients were enrolled in this cross-sectional study. PICF samples were collected and analyzed using both non-targeted and targeted metabolomics approaches. The relationship between metabolites and clinical indices including probing depth (PD), bleeding on probing (BOP), and marginal bone loss (MBL) was examined. Additionally, submucosal microbiota was collected and analyzed using 16S rRNA gene sequencing to elucidate the association between the metabolites and microbial communities. RESULTS: Significant differences in metabolic profiles were observed between the PH and PI groups, with 179 distinct metabolites identified. In the PI group, specific amino acids and fatty acids were significantly elevated compared to the PH group. Organic acids including succinic acid, fructose-6-phosphate, and glucose-6-phosphate were markedly higher in the PI group, showing positive correlations with mean PD, BOP, and MBL. Metabolites that increased in the PI group positively correlated with the presence of Porphyromonas and Treponema and negatively with Streptococcus and Haemophilus. CONCLUSIONS: This study establishes a clear association between metabolic compositions and peri-implant condition, highlighting enhanced metabolite activity in peri-implantitis. These findings open avenues for further research into metabolic mechanisms of peri-implantitis and their potential therapeutic implications.

Small extracellular vesicles derived from lipopolysaccharide-preconditioned dental follicle cells inhibit cell apoptosis and alveolar bone loss in periodontitis.

OBJECTIVE: This study aimed to explore the effects of small extracellular vesicles derived from lipopolysaccharide-preconditioned dental follicle cells (L-D-sEV) on periodontal ligament cells from periodontitis affected teeth (p-PDLCs) in vitro and experimental periodontitis in mice. DESIGN: In vitro, the biological function of p-PDLCs and the underlying molecular mechanism were investigated by flow cytometry, Western blot, and quantitative real-time PCR (qRT-PCR) analysis. Eighteen-eight-week-old male C57BL/6 mice were randomly divided into three groups: control (Con), periodontitis (Peri), and L-D-sEV groups. Mice periodontitis model was induced by placing the 5-0 silk thread (around the maxillary second molar) and P.gingivalis (1 ×107 CFUs per mouse). In vivo, the alveolar bone loss, osteoclast activity, and macrophage polarization were measured by micro-computed tomography and histological analysis. RESULTS: In vitro, the RANKL/OPG ratio and phosphorylation of JNK and P38 protein levels of p-PDLCs were significantly decreased after L-D-sEV administration. Besides, flow cytometry and qRT-PCR analysis showed that L-D-sEV reduced apoptosis of p-PDLCs, down-regulated apoptosis-related genes Caspase-3 and BCL-2-Associated X expression, and up-regulated B-cell lymphoma-2 gene levels. In vivo, L-D-sEV administration significantly reduced alveolar bone loss, inhibited osteoclast activity, and induced M2 polarization. The histological analysis showed that iNOS/CD206, RANKL/OPG, p-JNK/JNK, and p-P38/P38 ratios were significantly lower in the L-D-sEV group than in the Peri group. CONCLUSIONS: L-D-sEV administration alleviated alveolar bone loss by mediating RANKL/OPG-related osteoclast activity and M2 macrophage polarization, alleviating p-PDLCs apoptosis and proliferation via the JNK and P38 pathways.

Research on long-term migration behaviors of heavy metals after close-distance coal seam backfill mining.

The backfill mining of coal-based solid waste in goaf poses a potential risk of heavy metal pollution to the groundwater environment, and the migration behavior of heavy metals differs significantly under the disturbance of backfill mining in close-distance multi-layer coal seams and single-layer coal seams. In this study, a migration model of heavy metals after solid backfilling in the goaf of shallow-buried close-distance thick coal seams was established, and the impact of the overburden damage and the layered distribution of the filling body on the long-term migration behavior of heavy metals were analyzed. The results show that the migration of heavy metals after close-distance coal seam backfill mining exhibits a higher risk of heavy metal pollution. The peak permeability of overburden after close-distance coal seam backfill mining is about 600 × 10-19 m2 higher than that after single-layer coal seam backfill mining. The migration distance of heavy metals in the floor after backfill mining of close-distance coal seams is 7.41 m farther than that of single-layer coal seam backfill mining, and its migration time of heavy metals to the surface is 27 a earlier than that of single-layer coal seam. This research provides theoretical and empirical support for the ecological risk assessment and heavy metal pollution control in close-distance coal seam backfill mining. ENVIRONMENTAL IMPLICATION: The main filling material of close-distance coal seams backfill mining is coal gangue. Heavy metal elements such as Mn and Cr will be released in the underground environment for a long time, and the migration behavior of heavy metal elements will have an impact on the groundwater environment for more than 1000 years. This research provides theoretical and empirical support for the ecological risk assessment of close-distance coal seam backfill mining and the mitigation of heavy metal pollution.

Ultrasound-activated piezo-hot carriers trigger tandem catalysis coordinating cuproptosis-like bacterial death against implant infections.

Implant-associated infections due to the formation of bacterial biofilms pose a serious threat in medical healthcare, which needs effective therapeutic methods. Here, we propose a multifunctional nanoreactor by spatiotemporal ultrasound-driven tandem catalysis to amplify the efficacy of sonodynamic and chemodynamic therapy. By combining piezoelectric barium titanate with polydopamine and copper, the ultrasound-activated piezo-hot carriers transfer easily to copper by polydopamine. It boosts reactive oxygen species production by piezoelectrics, and facilitates the interconversion between Cu2+ and Cu+ to promote hydroxyl radical generation via Cu+ -catalyzed chemodynamic reactions. Finally, the elevated reactive oxygen species cause bacterial membrane structure loosening and DNA damage. Transcriptomics and metabolomics analysis reveal that intracellular copper overload restricts the tricarboxylic acid cycle, promoting bacterial cuproptosis-like death. Therefore, the polyetherketoneketone scaffold engineered with the designed nanoreactor shows excellent antibacterial performance with ultrasound stimulation and promotes angiogenesis and osteogenesis on-demand in vivo.

Research on coal mining intensity based on the DPSIR-SPA model.

High-intensity mining has become a major trend in future coal mining. However, it will unavoidably worsen the harm done to the natural environment of mining sites by coal mining, which is already prone to doing so. So, how may coal mining intensity (CMI) be decreased? Minimize the harm that coal mining causes to the environment and offer a theoretical basis for protecting the environment in mining sites. In order to achieve this, based on the existing literature on CMI, we first redefine the concept of CMI, analyze its influencing factors, propose an evaluation index system, and introduce the theory of set pair analysis (SPA) to build a quantitative evaluation model of CMI. We then propose an adjustment strategy for the CMI and conduct a verification analysis using the Halagou Coal Mine and Caojiatan Coal Mine as an example. The results show that the Halagou and Caojiatan Coal Mine belong to the higher-intensity mining stage. It is consistent with existing research. Moreover, the development trend of CMI in the Halagou Coal Mine is analyzed in conjunction with the set pair potential theory, and specific measures to reduce CMI are given, from the perspective of coal mining. It provides the basis for the source protection of the ecological environment in the mining area. Theoretically, this study can help both the quantitative assessment of mining intensity and the source protection of the mining ecological environment. Besides, it offers specific guidelines for building environmentally friendly mines.

Prusogliptin (DBPR108) monotherapy in treatment-naïve patients with type 2 diabetes: A randomized, double-blind, active and placebo-controlled, phase 3 study.

AIM: This study aimed to assess the efficacy and safety of prusogliptin (DBPR108), a novel and highly selective dipeptidyl peptidase-4 inhibitor, in individuals with type 2 diabetes who had not been using glucose-lowering agents regularly for the 8 weeks before the screening period. MATERIALS AND METHODS: In this multicentre, randomized, double-blind, phase 3 study, adult patients with type 2 diabetes were randomly assigned to receive either DBPR108 100 mg, sitagliptin 100 mg, or placebo once daily during the initial 24-week double-blind treatment period, followed by a 28-week open-label extension period during which all patients received DBPR108 100 mg once daily. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) levels from baseline to week 24. RESULTS: In total, 766 patients were enrolled and received DBPR108 100 mg (n = 462), sitagliptin 100 mg (n = 152), or placebo (n = 152). The mean age of all patients was 54.3 ± 10.5 years, with 58% being men. The median duration of type 2 diabetes was 0.38 (0.02, 2.65) years, and the mean HbA1c (SD) at baseline was 7.94% (0.62), 7.88% (0.61) and 7.83% (0.59) for DBPR108, sitagliptin and placebo groups, respectively. At week 24, the least square mean (SE) changes from baseline in HbA1c were -0.63% (0.04%) for DBPR108, -0.60% (0.07%) for sitagliptin and -0.02% (0.07%) for placebo. The mean treatment difference between DBPR108 and placebo was -0.61% (95% CI -0.77% to -0.44%), and between DBPR108 and sitagliptin was -0.03% (95% CI -0.19% to 0.13%). These results indicate that DBPR108 was superior to placebo and non-inferior to sitagliptin. DBPR108 also significantly reduced fasting and postprandial plasma glucose levels and had little effect on body weight. The mean (SD) changes in HbA1c from baseline to week 52 were -0.50% (0.97%) for the DBPR108 group, -0.46% (0.96%) for the sitagliptin group and -0.41% (0.95%) for the placebo group. The incidence of adverse events was comparable across all three groups. CONCLUSIONS: DBPR108 showed superiority to placebo and non-inferiority to sitagliptin in terms of glycaemic control over the initial 24 weeks in treatment-naïve patients with type 2 diabetes. Furthermore, its efficacy was sustained for up to 52 weeks.

Assessment of aortic and peripheral arterial stiffness in patients with knee osteoarthritis by ultrasound Doppler derived pulse wave velocity.

Information regarding regional arterial stiffness assessment in osteoarthritis (OA) was scarce and sometimes contradictory. We aimed to investigate the aortic, lower limb peripheral arterial stiffness and their associations with knee OA. Patients with primary knee OA and matched non-OA controls were prospectively enrolled from two medical centers in China. The carotid-femoral pulse wave velocity (cfPWV) and femoral-ankle pulse wave velocity (faPWV) were measured using a novel ultrasound technique. A total of 238 participants (including 128 patients with knee OA and 110 controls) were included. In OA patients, cfPWV was significantly higher than that of non-OA controls (9.40 ± 1.92 vs 8.25 ± 1.26 m/s, P < 0.0001). However, faPWV measurements in OA patients (12.10 ± 2.09 m/s) showed no significant difference compared with that of the controls (11.67 ± 2.52 m/s, P = 0.130). Multiple regression analysis revealed that cfPWV was independently associated with knee OA (P < 0.0001) after adjusting for the confounding factors including age, gender, smoking, mean blood pressure, body mass index, heart rate, high-sensitivity C-reactive protein and lipids profiles. In contrast, faPWV did not show independent association with knee OA (P = 0.372) when after adjusting for confounding factors. In addition, Spearman's correlation analysis showed cfPWV had a significant correlation with Kellgren-Lawrence score (rs = 0.2333, P = 0.008), but no correlation was founded between faPWV with Kellgren-Lawrence score (rs = 0.1624, P = 0.067) in OA patients. This study demonstrated that stiffening of aorta, but not lower limb arteries, was independently associated with knee OA. Our findings may call for further implementation of routine aortic stiffness assessments so as to evaluate cardiovascular risk in patients with OA.

Ultrathin Layered Structure and Oxygen Vacancies Mediated Efficient Charge Separation toward High Photocatalytic Activity in BiOIO3 Nanosheets.

Previous bismuth-based photocatalysts usually employ a strong acid solution (e.g., HNO3 solution) to obtain an ultrathin structure toward high photocatalytic activity. In this work, the ultrathin layered BiOIO3 nanosheets are successfully synthesized using just the glucose hydrothermal solution. The high-concentration glucose solution shows the obvious acidity after the hydrothermal process, which leads to the quick decrease in thickness of BiOIO3 nanosheets from ∼45.58 to ∼5.74 nm. The ultrathin structure can greatly improve charge carriers' separation and transfer efficiency. The generation of reductive iodide ions brings about oxygen vacancies in the ultrathin nanosheets, then the defect energy level is formed, causing the decreased band gap and improving the visible light absorption. Compared to thick BiOIO3 nanosheet with little oxygen vacancies, much higher carrier separation efficiency and visible light absorption are achieved in the ultrathin nanosheets with oxygen vacancies, resulting in an excellent photocatalytic performance (0.1980 min-1 for RhB degradation), which is much higher than most other bismuth-based photocatalysts. The superoxide radicals (•O2-) and holes (h+) are the major active species responsible for high photocatalytic activity. This work affords an environmentally friendly strategy to synthesize ultrathin photocatalysts with superior photocatalytic properties.

Treatment of gastric paralysis after gastric schwannoma by electroacupuncture: A case report and literature review.

OBJECTIVE: We identified the potential role of electroacupuncture (EA) as an alternative therapy to traditional Chinese medicine (TCM) in a rare case of postoperative gastroparesis after gastric schwannoma (GS). CLINICAL PRESENTATION: A 31-year-old woman presented with impaired gastric emptying after gastrectomy for GS and was diagnosed with postoperative gastroparesis syndrome (PGS). The symptoms were slightly relieved after routine placement of the jejunal tube; however, symptoms such as dietary intolerance and impaired gastric emptying persisted. After the consultation, the patient agreed to undergo EA therapy. INTERVENTION AND RESULTS: The patient was able to tolerate oral intake after seven days of EA treatment, and the frequency and amount of food intake increased. The jejunal tube was removed at the outpatient follow-up two weeks after discharge, and the patient resumed a semi-liquid diet and was able to eat small amounts of rice. Reexamination of the upper digestive tract angiography showed that part of the contrast agent passed through the pyloric sinus, which showed improvement. CONCLUSION: EA stimulation increased tolerance to transoral feeding in patients with postoperative gastroparesis and facilitated the passage of contrast agents through the pyloric sinus. No adverse effects were observed during treatment, and the treatment was well accepted and tolerated by patients. A review article noted the benefits of acupuncture for gastrointestinal disorders but lacked high-quality evidence to support this.1 Therefore, the therapeutic role of EA needs to be further elucidated to provide high-quality evidence-based medical evidence for its clinical use.

Toward Type I/II ROS Generation Photoimmunotherapy by Molecular Engineering of Semiconducting Perylene Diimide.

As prospective phototheranostic agents for cancer imaging and therapy, semiconducting organic molecule-based nanomedicines are developed. However, near-infrared (NIR) emission, and tunable type I (O2 • - ) and type II (1 O2 ) photoinduced reactive oxygen species (ROS) generation to boost cancer photoimmunotherapy remains a big challenge. Herein, a series of D-π-A structures, NIR absorbing perylene diimides (PDIs) with heavy atom bromide modification at the bay position of PDIs are prepared for investigating the optimal photoinduced type I/II ROS generation. The heavy atom effect has demonstrated a reduction of molecular ∆EST and promotion of the intersystem crossing processes of PDIs, enhancing the photodynamic therapy (PDT) efficacy. The modification of three bromides and one pyrrolidine at the bay position of PDI (TBDT) has demonstrated the best type I/II PDT performance by batch experiments and theoretical calculations. TBDT based nanoplatforms (TBDT NPs) enable type I/II PDT in the hypoxic tumor microenvironment as a strong immunogenic cell death (ICD) inducer. Moreover, TBDT NPs showing NIR emission allow in vivo bioimaging guided phototherapy of tumor. This work uses novel PDIs with adjustable type I/II ROS production to promote antitumor immune response and accomplish effective tumor eradication, consequently offering molecular guidelines for building high-efficiency ICD inducers.

Comparison of Diagnostic Values of ACR TI-RADS versus C-TIRADS Scoring and Classification Systems for the Elderly Thyroid Cancers.

Purpose: To compare the diagnostic value of the Thyroid Imaging Reporting and Data System (TI-RADS) of the American College of Radiology (ACR) versus the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) scoring and classification system for elderly thyroid cancers. Patients and Methods: A total of 512 nodules from 465 patients aged ≥60 with surgical pathology-proven thyroid nodules were enrolled in our study. The ultrasound features of thyroid nodules were independently evaluated by the ACR TI-RADS and C-TIRADS classification systems, and the receiver operating characteristic curve (ROC) was plotted. The optimal cut-off values of the ACR TI-RADS and C-TIRADS scoring and classification systems for diagnosing elderly thyroid nodules were estimated, and the diagnostic efficacy was analyzed. Results: The ACR TI-RADS and C-TIRADS scores and classifications of thyroid cancers were both higher than benign nodules (both P < 0.05). The area under the curve (AUC) of ACR TI-RADS and C-TIRADS scoring and classification systems were 0.861, 0.897, 0.879, and 0.900, respectively, and the AUC of the scoring system was greater than the classification system for both criteria. When the Youden index was the highest, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the ACR TI-RADS scoring and classification systems were consistent, ie, they were 89.66%, 41.70%, 89.93%, and 59.00%, respectively; the sensitivity, specificity, PPV, and NPV of the C-TIRADS scoring and classification systems were also consistent, ie, they were 88.71%, 44.26%, 90.23%, 59.69%, respectively. The diagnostic efficacy between the two systems was not statistically significant. Conclusion: ACR TI-RADS and C-TIRADS systems had relatively high diagnostic efficacy for elderly thyroid cancer. The diagnostic efficiency of the scoring systems of ACR TI-RADS and C-TIRADS were higher than the classification systems. In addition, the two systems had high clinical practical values, while there is still a significant risk of missed diagnosis.

Comparing Diagnostic Efficacy of C-TIRADS Positive Features on Different Sizes of Thyroid Nodules.

Purpose: To explore the diagnostic value of positive features in the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for thyroid nodules of different sizes. Patients and Methods: A total of 1864 patients with 2347 thyroid nodules were selected from January 2021 to December 2022 and assessed according to C-TIRADS. According to the maximum diameter, nodules were divided into the A1 group (≤10 mm), A2 group (>10 mm,<20 mm), and A3 group (≥20 mm). With surgical pathology as the golden standard, the receiver operating characteristic curves (ROC) were constructed, and each group's area under the curve (AUC) was calculated. The diagnostic value of positive features in C-TIRADS for different sizes of thyroid nodules was analyzed. Results: In all groups, malignant thyroid nodules had a higher incidence of positive features than benign nodules (P < 0.05). In A1 group, the diagnostic efficiency of C-TIRADS positive features for thyroid nodules was vertical orientation> ill-defined/irregular margin or extrathyroidal extension> solid composition> markedly hypoechoic> microcalcifications. The AUCs were 0.718, 0.675, 0.609, 0.558, and 0.581, respectively. In A2 group, the diagnostic efficacy of each positive features for thyroid nodules was ill-defined/irregular margins or extra-thyroid invasion> solid composition> microcalcifications> markedly hypoechoic> vertical orientation. The AUCs were 0.854, 0.730, 0.719, 0.670, and 0.609, respectively. In A3 group, the diagnostic efficacy of each positive features for thyroid nodules was ill-defined/irregular margin or extrathyroidal extension> microcalcifications> solid composition> vertical orientation> markedly hypoechoic. The AUCs were 0.847, 0.778, 0.767, 0.584, and 0.560, respectively. Conclusion: C-TIRADS positive features exhibited different diagnostic efficacy for thyroid nodules of various sizes, especially for thyroid nodules ≤10 mm, for which all positive features had low diagnostic efficacy.

Interpersonal matching of autistic trait levels in typically developed individuals is associated with spontaneous gaze following and initiation during face-to-face social interaction.

OBJECTIVES: People with autism spectrum disorders (ASD) usually exhibit typical behaviours and thoughts that are called autistic traits. Autistic traits are widely and continuously distributed among typically developed (TD) and ASD populations. Previous studies have found that people with ASD have difficulty in following the eye gaze of social peers. However, it remains unknown whether TD adults with high or low autistic traits also differ in spontaneous gaze following and initiation in face-to-face social interactions. To fill this gap, this study used a novel and naturalistic gaze-cueing paradigm to examine this research question. DESIGN: A 4 (group: high-high, high-low, low-high or low-low autistic traits) × 3 (congruency: congruent, neutral, or incongruent) mixed-measures design was used. METHODS: Typically developed adults who were high or low in autistic traits completed a visual search task while a confederate who was high or low in autistic traits sat facing them. Critically, the match of autistic traits within a participant-confederate pair was manipulated. The confederate gazed at (congruent) or away from (incongruent) the location of the target prior to the appearance of the target. Participants were not explicitly instructed to follow the confederate's gaze. RESULTS: Autistic traits were associated with spontaneous gaze following and initiation in face-to-face social interactions. Specifically, only when both the participant and confederate were low in autistic traits did the incongruent gaze cues of confederates interfere with the participants' responses. CONCLUSIONS: Autistic traits impeded gaze following and initiation by TD adults. This study has theoretical and practical implications regarding autistic trait-induced social deficits and indicates a new approach for social skill interventions.

Research on coal mine safety management based on digital twin.

Coal mine safety management is the foundation and decisive factor of coal mining. The manual detection model is the main way for traditional coal mine safety management, which has problems such as inefficient identification of safety risks in coal mines, poor control accuracy and slow response measures and so on. Therefore, to make up for the shortcomings in the traditional coal mine safety management model, this paper introduces digital twin technology into coal mine safety management to achieve intelligent and efficient management of coal mine safety accidents. Firstly, we introduce the digital twin technology, select the five-dimensional model as the modeling basis, based on the existing twin model architecture, analyze the types of coal mine accidents and disasters, select the most destructive gas accidents as the research object, construct a twin safety management model for coal mine gas accidents using the digital twin five-dimensional model. Secondly, analyses of the actual operation mechanism of the digital twin model, and the advantages of the twin model in achieving prior prevention, rapid response and accurate control of gas incidents are pointed out. Finally, the house of quality of the gas accident digital twin model is established through the quality functional deployment tool, and key technical requirements for the construction of the twin model are given to accelerate the application of the gas accident twin model in the field. This study innovatively introduces digital twin technology into the field of coal mine safety management, proposes the application scenarios of emerging technologies such as digital twins in the coal mine field, and provides the possibility of multi-scene application of smart mine construction and technologies such as digital twins.

How urban versus rural residency relates to COVID-19 vaccine hesitancy: A large-scale national Chinese study.

RATIONALE: Although urban-rural residency has been shown to influence individual COVID-19 vaccine hesitancy, the differences between urban and rural China have yet to be uncovered. OBJECTIVE: This study aims to assess the current prevalence and factors associated with COVID-19 vaccine hesitancy in urban and rural areas and explore whether the rural versus urban residency is associated with COVID-19 vaccine hesitancy. METHODS: A national, cross-sectional, online survey among Chinese urban and rural adults (≥18 years old) was conducted from 6th to August 9, 2021. A questionnaire was used to collect data on sociodemographic factors, perceptions of the COVID-19 pandemic and vaccination status. A multivariable logistic regression model was used to identify the factors that influence COVID-19 vaccine hesitancy. Propensity score matching (PSM) analysis was performed to explore the association between urban versus rural residency and COVID-19 vaccine hesitancy. RESULTS: In total, 29,925 participants (80.56% urban participants) were recruited. Urban participants had a higher COVID-19 vaccine hesitancy than their rural counterparts (9.39% vs. 4.26%). After adjusting for potential confounders, we found that COVID-19 vaccine hesitancy among females was lower than that in males in both urban (aOR = 0.78, 95% CI [0.69-0.88]) and rural areas (aOR = 0.54, 95% CI [0.39-0.75]). The lack of trust towards vaccine producers was found to be associated with vaccine hesitancy among the urban participants (aOR = 2.76, 95% CI [2.22-3.43]). The rural floating population had a lower COVID-19 vaccine hesitancy than the rural permanent residents (aOR = 0.58, 95% CI [0.42-0.80]). PSM analysis revealed a 2.38% difference in COVID-19 vaccine hesitancy between urban and rural participants. CONCLUSIONS: Urban participants were more hesitant to receive the COVID-19 vaccine than rural participants. Priority should be placed on boosting confidence in the healthcare system to reduce COVID-19 vaccine hesitancy among urban residents. Furthermore, we advocate for extra incentives and vaccination education for rural permanent residents.

Dental follicle cells-derived small extracellular vesicles inhibit pathogenicity of Porphyromonas gingivalis.

OBJECTIVE: It aims to explore the effect of dental follicle cells-derived small extracellular vesicles (D-sEVs) with or without lipopolysaccharides (LPS) pretreating on the pathogenicity of Porphyromonas gingivalis (P. gingivalis). METHODS: The antibacterial effects of D-sEV were evaluated by measuring the growth, biofilm formation, gingipains, and type IX secretion system (T9SS) expression of P. gingivalis. And the influence of D-sEV on P. gingivalis adhesion, invasion, cytotoxicity, and host immune response was examined in gingival epithelial cells (GECs). Then P. gingivalis treated with D-sEV was applied to investigate the pathogenicity in experimental periodontitis of mice. RESULTS: It showed that both D-sEV and P. gingivalis LPS-pretreated D-sEV (L-D-sEV) could target P. gingivalis, inhibit their growth and biofilm formation, and hinder the attachment and invasion in GECs, therefore remarkably decreasing P. gingivalis cytotoxicity and the expression of IL-1ß and IL-6 in GECs. In addition, they significantly reduced the expression of P. gingivalis virulence factors (gingipains and T9SS). In vivo, it showed that the bacteria in the gingiva were significantly decreased after sEV treatment. Meanwhile, less bone loss and fewer inflammatory cells infiltration and osteoclast formation in D-sEV and L-D-sEV groups. CONCLUSION: Both D-sEV and L-D-sEV were proven to inhibit the pathogenicity of P. gingivalis and thus prevented the development of periodontitis.

The landscape of T and B lymphocytes interaction and synergistic effects of Th1 and Th2 type response in the involved tissue of IgG4-RD revealed by single cell transcriptome analysis.

OBJECTIVES: To investigate the landscape of T-B cell interaction, immune receptor profiles and effects of different types of immune responses in the involved tissues of IgG4-RD. METHODS: Single cell RNA sequencing, bulk sample RNA sequencing, immune receptor repertoire analysis (both BCR and TCR), multi-color flow cytometry, and in-vitro assays with model cells (e.g. EBV-immortalized B cells from IgG4-RD patient) and histologic methods were applied to investigate the immunopathological features of IgG4-RD from multiple aspects. RESULTS: Ectopic germinal center formation was observed in IgG4-RD patients at advanced disease stage, and a large part of B cells in involved tissue were germinal center B cell-like. Germinal center reaction in IgG4-RD led to the irregularities of both TCR and BCR clones in the involved tissues, and limited clonal overlaps among different samples. Enhanced Th1- and Th2-type responses were observed in involved tissues of IgG4-RD and patients with both increased Th1- and Th2-type response related cell subsets possessed more severe inflammatory indices. Analyses to the origin of IGHG4 transcripts in IgG4-RD indicated that IgG4 could be switched from IgM directly, or from other IgG subclasses. In vitro assays with EBV-immortalized B cells, fibroblasts and epithelial cells revealed the effects of Th1-type and Th2-type responses on germinal center reaction, ectopic expression of MHC-II molecules, and formation of tertiary lymphoid structures. CONCLUSIONS: Synergistic effects of Th1- and Th2-type responses were involved in the pathogenesis of IgG4-RD via their influences on both acute inflammatory processes and the chronicity and complexity of IgG4-RD.

Kanglaite (Coix Seed Extract) as Adjunctive Therapy in Cancer: Evidence Mapping Overview Based on Systematic Reviews With Meta-Analyses.

Background: Several quantitative systematic reviews of Kanglaite (KLT), an herb preparation used to treat cancer and malignant pleural effusion, have been published in recent years. However, the clinical evidence reported in these studies has not been pursued further and the methodological quality of these meta-analyses remains unknown. Therefore, an overview was designed to map the evidence landscape based on the published meta-analyses on KLT in cancer treatment. Methods: Two bibliographic databases (PubMed and Embase) were searched from inception to 25 November 2021. Two independent reviewers were involved in study selection, data abstraction, and methodological quality assessment using AMSTAR 2. The principal features of publications and the clinical outcomes of efficacy and safety were synthesized narratively, and results of methodological quality were reported as frequencies and percentages with the corresponding 95% confidence intervals. The evidence map was used to visualize the overall quality. Excel 2016 and Stata 17/SE were used for data analysis. Results: Thirteen meta-analyses published in English were included for in-depth analysis. Among them, the year of publication ranged from 2008 to 2021, and the number of included patients ranged from 488 to 2,964. Regarding the cancer type, seven articles focused on non-small cell lung cancer, two on malignant pleural effusion, and four reviews on digestive system malignancies, such as hepatocellular carcinoma and pancreatic cancer. Almost all included meta-analyses reported that KLT as adjunctive therapy could improve various efficacy outcomes (such as disease response rates, quality of life, immune indicators) and reduce the rate of occurrence of adverse reactions, such as nausea and vomiting, leukopenia, and anemia. In terms of their methodological quality, three meta-analyses were of low quality, whereas 10 studies were critically low in quality. The methodological flaws main involved items 2 ("predesigned protocol and registration informatio''), 3 ("rationale of study design for inclusion"), 4 ("comprehensive search strategy''), 5 ("literature selection in duplicate''), 7 ("list of excluded studies with reasons''), 8 ("adequate information on included studies''), 10 ("funding support for included primary studies''), and 12 ("evaluation of the potential impact of risk of bias'') based on the AMSTAR 2 tool. Conclusion: Current evidence reveals that KLT is effective and safe as an adjunctive treatment for non-small cell lung cancer, malignant pleural effusion, and digestive system malignancies (such as hepatocellular carcinoma). However, the results assessed in this overview should be further verified using well-designed and clearly reported clinical trials and meta-analyses of KLT.

Efficacy and safety of DBPR108 (prusogliptin) as an add-on to metformin therapy in patients with type 2 diabetes: A 24-week, multi-centre, randomized, double-blind, placebo-controlled, superiority, phase III clinical trial.

AIM: To evaluate the efficacy and safety of DBPR108 (prusogliptin), a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, as an add-on therapy in patients with type 2 diabetes (T2D) that is inadequately controlled with metformin. MATERIALS AND METHODS: In this 24-week, multi-centre, randomized, double-blind, placebo-controlled, superiority, phase III study, adult T2D patients with HbA1c levels ranging from 7.0% to 9.5% on stable metformin were enrolled and randomized (2:1) into the DBPR108 + metformin and placebo + metformin groups. The primary endpoint was the change from baseline in HbA1c at week 24 of DBPR108 versus placebo as an add-on therapy to metformin. RESULTS: At week 24, the least-square mean (standard error) change from baseline in HbA1c was significantly greater in the DBPR108 group (-0.70% [0.09%]) than in the placebo group (-0.07% [0.11%]) (P < .001), with a treatment difference of -0.63% (95% confidence interval: -0.87%, -0.39%) on the full analysis set. A higher proportion of patients achieved an HbA1c of 6.5% or less (19.7% vs. 8.5%) and an HbA1c of 7.0% or less (50.0% vs. 21.1%) at week 24 in the DBPR108 + metformin group. Furthermore, add-on DBPR108 produced greater reductions from baseline in fasting plasma glucose and 2-hour postprandial plasma glucose without causing weight gain. The overall frequency of adverse events was similar between the two groups. CONCLUSIONS: DBPR108 as add-on therapy to metformin offered a significant improvement in glycaemic control, was superior to metformin monotherapy (placebo) and was safe and well-tolerated in patients with T2D that is inadequately controlled with metformin.