Clinical efficacy of a new type of Sports Rehabilitation Therapy Bed.

Objective: To prove that the "sports rehabilitation bed" is a device aimed at improving the precision of stretching, which can help to reduce the difficulty of rehabilitation therapy, cut down the manpower input of rehabilitation therapy, and shorten the therapy duration as well. Methods: This was a clinical comparative study. Twenty patients who underwent stretching therapy in Sichuan Province Orthopedic Hospital from June 2020 to August 2020 were randomly selected to carry out a control study on both lower extremities. The experimental group was given sports rehabilitation bed to assist rehabilitation therapy, while the control group was given conventional bare-handed stretching rehabilitation therapy. The stretching angle, stretching value, and the effective rate of stretching therapy between the two groups to analyze the clinical value of the new sports rehabilitation therapy bed. Results: The stretching angle in the experimental group when using the sports rehabilitation therapy bed for stretching was lower than the conventional bare-handed stretching in the control group (T<0, P=0.05), with a statistically significant difference; the stretching values of the experimental group were lower than those of the control group(P<0.01), with a statistically significant difference. Moreover, the response rate of stretching therapy in the experimental group was lower than that in the control group(P<0.05), with a statistically significant difference. Conclusion: Sports rehabilitation therapy beds can results in the advantages of effectively preventing iatrogenic injury in the process of stretching, and providing a more accurate and convenient stretching therapy method than the current commonly used bare-handed stretching for sports rehabilitation and intervention.

Revolutionary Point-of-Care Wearable Diagnostics for Early Disease Detection and Biomarker Discovery through Intelligent Technologies.

Early-stage disease detection, particularly in Point-Of-Care (POC) wearable formats, assumes pivotal role in advancing healthcare services and precision-medicine. Public benefits of early detection extend beyond cost-effectively promoting healthcare outcomes, to also include reducing the risk of comorbid diseases. Technological advancements enabling POC biomarker recognition empower discovery of new markers for various health conditions. Integration of POC wearables for biomarker detection with intelligent frameworks represents ground-breaking innovations enabling automation of operations, conducting advanced large-scale data analysis, generating predictive models, and facilitating remote and guided clinical decision-making. These advancements substantially alleviate socioeconomic burdens, creating a paradigm shift in diagnostics, and revolutionizing medical assessments and technology development. This review explores critical topics and recent progress in development of 1) POC systems and wearable solutions for early disease detection and physiological monitoring, as well as 2) discussing current trends in adoption of smart technologies within clinical settings and in developing biological assays, and ultimately 3) exploring utilities of POC systems and smart platforms for biomarker discovery. Additionally, the review explores technology translation from research labs to broader applications. It also addresses associated risks, biases, and challenges of widespread Artificial Intelligence (AI) integration in diagnostics systems, while systematically outlining potential prospects, current challenges, and opportunities.

Revisions to the requirement of the Japanese clinical study data for biosimilar developments in Japan.

BACKGROUND: The 'Questions and Answers (Q&A)' document regarding Japanese biosimilar guideline elucidated that Japanese participant enrollment in at least one comparative clinical study was required for the marketing authorization application (MAA) of biosimilars in Japan. RESEARCH DESIGN AND METHODS: To discuss the requirement of Japanese clinical study data for biosimilar development, the trend in comparative clinical studies conducted for approved biosimilars of monoclonal antibodies and fusion proteins was analyzed, and the consistency of the results between the overall population and the Japanese population according to the publicly available information was reviewed. RESULTS: The number of comparative clinical studies enrolling Japanese participants was 25 cases, and the type and percentage were 13 (52%) and 12 (48%) cases of comparative pharmacokinetic study and comparative efficacy study, respectively. In all comparative clinical studies, consistent results between the overall population and the Japanese population were shown. CONCLUSIONS: Our study indicated that Japanese participant enrollment in comparative clinical studies may not always be necessary for biosimilar development when certain conditions are satisfied. This has been described in the revised Q&A document published by the Ministry of Health, Labour and Welfare in January 2024.

Clinical validation of the novel fluorescent glomerular filtration rate tracer agent relmapirazin (MB-102).

The fluorescent compound relmapirazin has been rationally designed for use in point-of-care measurement of glomerular filtration rate (GFR), with attributes including negligible protein binding, negligible metabolites in vivo, negligible tubular secretion, and excellent chemical and photo stability. Twenty-four nonclinical assays were performed in accordance with FDA requirements yielding negligible toxicology concerns. Here, a clinical study was performed to validate relmapirazin as a GFR tracer in patients by comparison to iohexol. This was evaluated in 120 adults at three clinical sites with eGFR values ranging from normal to Stage 4 chronic kidney disease. Relmapirazin and iohexol were administered intravenously in consecutive boluses to each subject and serial blood samples obtained over the subsequent 12 hours. Plasma concentrations were measured and the corresponding plasma GFR for each agent was determined using a standard two-compartment pharmacokinetic assessment. Urine from each subject was collected for the entire 12-hour study period to measure the amount of administered dose appearing in the urine. A near perfect linear regression correlation was observed between the GFRs measured by these two tracers (r2=0.99). Bland-Altman analysis confirmed agreement between these two measures of GFR (limits of agreement -7.0 to +5.6 mL/min; mean of -0.7 mL/min). The GFR determined by relmapirazin was independent of GFR stratification by chronic kidney disease stage, and importantly by race. The percent of the administered relmapirazin dose recovered in the urine was greater than or equal to that of iohexol with no reported severe adverse events. Thus, relmapirazin may be used as a GFR tracer agent in humans.

INTERACT: a randomized phase 2 study of the DAAO inhibitor luvadaxistat in adults with schizophrenia.

Deficits in N-methyl-d-aspartate receptor (NMDAR) signaling are implicated in the pathogenesis of schizophrenia. Luvadaxistat (TAK-831/NBI-1065844) is an investigational d-amino acid oxidase (DAAO) inhibitor that increases d-serine levels at NMDAR coagonist sites. INTERACT is a phase 2 randomized, placebo-controlled study that evaluated the efficacy and safety of three doses of luvadaxistat, covering a range of DAAO occupancy and d-serine levels, in patients with schizophrenia with persistent negative symptoms. The study included a 14-day, single-blinded placebo run-in period and a 12-week, double-blinded treatment period. The primary efficacy endpoint was the 12-week change from baseline in Positive and Negative Syndrome Scale-Negative Symptom Factor Score (PANSS NSFS). Secondary efficacy endpoints included the 12-week changes from baseline in Brief Assessment of Cognition in Schizophrenia (BACS) score and Schizophrenia Cognition Rating Scale (SCoRS) score. Safety endpoints included adverse event assessments. The full analysis set included all randomized patients (N = 256 [placebo, n = 87; luvadaxistat 50 mg, n = 58; 125 mg, n = 56; 500 mg, n = 55]); 228 patients completed the study. No significant improvements in PANSS NSFS were observed at any dose versus placebo at week 12. Improvements were observed with luvadaxistat 50 mg versus placebo in cognitive endpoints: BACS composite score (nominal one-sided p = 0.031) and SCoRS interviewer total score (nominal one-sided p = 0.011). Luvadaxistat did not significantly improve negative symptoms of schizophrenia. However, luvadaxistat 50 mg met the prespecified secondary endpoints for cognitive performance (BACS) and function (SCoRS), warranting further investigation in patients with cognitive impairment associated with schizophrenia. Luvadaxistat was well-tolerated in INTERACT, with no new safety signals observed. ClinicalTrials.gov: NCT03382639.

Therapeutic potential of limonene-based syringic acid nanoemulsion: Enhanced ex-vivo cutaneous deposition and clinical anti-psoriatic efficacy.

Nanoemulsions have carved their position in topical delivery owing to their peculiar features of forming a uniform film on the skin and conquering stratum corneum barrier and hence fostering dermal penetration and retention. The present work developed syringic acid nanoemulsion (SA-NE) by spontaneous emulsification as an anti-psoriatic remedy via the dermal route. SA-NE were prepared with either lauroglycol90, limonene or their combination (oil phase) and tween80 (surfactant) with variable concentrations. The physicochemical characteristics of SA-NE were assessed together with Ex-vivo skin deposition and dermal toxicity. The effectiveness of optimal formula in psoriatic animal model and psoriatic patients was investigated using PASI scoring and dermoscope examination. Results showed that, SA-NE containing mixture of lauroglycol 90, limonene and 10 % tween80 (F5), was selected as the optimal formula presenting stable nanoemulsion for 2-month period, showing droplet size of 177.6 ± 13.23 nm, polydispersity index of 0.16 ± 0.06, zeta potential of -21.23 ± 0.41 mV. High SA% in different skin strata and no dermal irritation was noticed with limonene-based SA-NE also it showed high in-vitro anti- inflammatory potential compared to the blank and control formulations. A preclinical study demonstrated that limonene-based SA-NE is effective in alleviating psoriasis-like skin lesions against imiquimod-induced psoriasis in rats. Clinically, promising anti-psoriatic potential was asserted as all patients receiving F5 experienced better clinical improvement and response to therapy, achieving ≥ 50 % reduction in PASI scores versus only 35 % responders in the Dermovate® cream group. Collectively, the practical feasibility of limonene-based SA-NE topical delivery can boost curative functionality in the treatment of psoriatic lesions.

Radiographic outcomes of lateral sinus floor elevation at sites without perforations and sites with perforations managed with a resorbable membrane: A retrospective study.

AIM: To evaluate the radiographic outcomes of lateral sinus floor elevation with simultaneous implant placement at sites without sinus membrane perforation (SMP) and sites with SMP managed with a resorbable membrane. MATERIALS AND METHODS: One hundred and thirty-nine patients and 170 implants (56 perforation, 114 non-perforation) were included. Cone-beam computed tomography (CBCT) images were taken before surgery (T0), immediately after surgery (T1) and 6 months after surgery (T2). Post-operative augmentation parameters, including endo-sinus bone gain (ESBG) along the implant axis, mean new bone height (NBH) surrounding the implant and augmentation volume (AV), were measured at T1 and T2. RESULTS: At T1, there were no significant differences in ESBG, NBH and AV between the two groups. At T2, although ESBG did not significantly differ between the two groups, NBH (8.50 ± 1.99 mm vs. 9.99 ± 2.52 mm, p = .039) and AV (519.37 ± 258.38 mm3 vs. 700.99 ± 346.53 mm3, p < .001) were significantly lower in the perforation group. The shrinkage of graft material from T1 to T2, including ΔESBG (p = .002), ΔNBH (p < .001) and ΔAV (p < .001), was higher in the perforation group. CONCLUSIONS: SMP during LSFE with simultaneous implant placement is associated with greater resorption of the grafted area at a 6-month follow-up.

Comprehensive insights into areca nut: active components and omics technologies for bioactivity evaluation and quality control.

Areca nut (AN), the fruit or seed of Areca catechu Linn, has many uses, including chewing and medicinal purposes. It has sparked worries about health due to the presence of alkaloids. Chewing AN may have a variety of negative consequences; however, the medicinal use of AN has no notable adverse effects. To completely understand and effectively use AN, researchers have investigated its chemical makeup or biological activity, analyzed the variations between different AN species and different periods, and improved extraction and processing procedures. Today, an increasing number of researchers are exploring the underlying reasons for AN variations, as well as the molecular mechanisms of biosynthesis of chemical components, to comprehend and change AN at the genetic level. This review presents an overview of the clinical study, pharmacology, and detection of the main bioactive components in AN, and the main factors influencing their content, delving into the omics applications in AN research. On the basis of the discussions and summaries, this review identifies current research gaps and proposes future directions for investigation.

Bifidobacterium adolescentis SBT2786 Improves Sleep Quality in Japanese Adults with Relatively High Levels of Stress: A Randomized, Double-Blind, Placebo-Controlled Study.

Sleep disorders associated with lifestyle changes and unhealthy habits are major public health concerns. Our previous study showed that Bifidobacterium adolescentis SBT2786 has a potent sleep-promoting effect on fruit flies. Fruit flies share many similarities with mammals, making them suitable model organisms for studying sleep. Thus, in the present study, we conducted a randomized, double-blind, placebo-controlled clinical trial to test whether SBT2786 has sleep-enhancing effects in humans. In this study, 61 participants in the SBT2786 group and 65 participants in the placebo group were analyzed. The results showed that SBT2786 increased sleep time; however, it predominantly increased light sleep and did not improve subjective sleep quality. Interestingly, mood improvement was observed. A subgroup analysis was conducted on participants with high stress levels, and results showed that these participants experienced an increase in sleep duration and an improvement in sleepiness upon waking up and reported feeling well-rested during the day. We concluded that SBT2786 may improve sleep quality, particularly in individuals experiencing high levels of stress, and that SBT2786 can be used as a dietary supplement to improve sleep and mood.

Clinical comprehensive treatment protocol for managing diabetic foot ulcers: A retrospective cohort study.

BACKGROUND: Diabetic foot ulcers (DFUs) are a common complication of diabetes, often leading to severe infections, amputations, and reduced quality of life. The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications. A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs. The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing, reduced amputation rates, and improved overall patient outcomes compared to standard treatment protocols. AIM: To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol. METHODS: This retrospective study included 62 patients with DFUs, enrolled between January 2022 and January 2024, randomly assigned to the experimental (n = 32) or control (n = 30) group. The experimental group received a comprehensive treatment comprising blood circulation improvement, debridement, vacuum sealing drainage, recombinant human epidermal growth factor and anti-inflammatory dressing, and skin grafting. The control group received standard treatment, which included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. Time taken to reduce the white blood cell count, number of dressing changes, wound healing rate and time, and amputation rate were assessed. RESULTS: The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate, wound healing time, and amputation rate. Additionally, the comprehensive treatment protocol was safe and well tolerated by the patients. CONCLUSION: Comprehensive treatment for DFUs is more effective than standard treatment, promoting granulation tissue growth, shortening hospitalization time, reducing pain and amputation rate, improving wound healing, and enhancing quality of life.

Clinical research self-efficacy in academic veterinary clinicians in the United States.

OBJECTIVE: Clinical research is a growing part of the academic clinician's job, and documenting areas of low self-efficacy can inform training initiatives. SAMPLE: 182 US academic veterinary clinicians. METHODS: A survey of academic veterinary clinicians was distributed to 31 US institutions. Self-efficacy was assessed with a modified Clinical Research Appraisal Instrument-12. The relationship between research self-efficacy and completion of formal research training and years of experience was evaluated. RESULTS: Respondents were predominantly junior to midcareer faculty. The lowest reported confidence was in performing advanced statistical analyses (3; 0 to 10). Other low-confidence tasks included designing a qualitative methods study (4; 0 to 10), terminating a collaboration that isn't working (5; 0 to 10), describing a funding agency's review/award process (5; 0 to 10), establishing a timeline for a grant application (5; 0 to 10), establishing collaborator and consultant agreements (5; 0 to 10), and asking staff to leave the project team (5; 0 to 10). Completion of a formal research training program was significantly associated with improved self-efficacy in many tasks. Years of experience was also associated, especially in project management and interpersonal interactions. CLINICAL RELEVANCE: These results highlight the need for targeted training opportunities for academic veterinary clinicians in biostatistical support, qualitative study design methods, and aspects of communication and interpersonal skills that are important for developing and leading effective research teams. Range of confidence suggests that development opportunities in all domains will improve self-efficacy for some clinicians. Future studies should focus on the impact of formal training sessions on various domains of self-efficacy and on targeted mentoring in supporting confidence in more experiential learning domains.

Quantitative summary on the human pharmacokinetic properties of cannabidiol to accelerate scientific clinical application of cannabis.

Cannabidiol (CBD) is a non-psychoactive substance that exerts numerous pharmacological benefits, including anti-inflammatory and antioxidant properties. It has received attention as a useful substance for the treatment of intractable pain, seizures, and anxiety, and related clinical trials have continued. However, the CBD pharmacokinetic results between reports are highly variable, making it difficult to clearly identify the pharmacokinetic properties of CBD. The main purpose of this study was to identify CBD clinical pharmacokinetic properties through meta-analysis. In particular, we sought to derive valid, interpretable independent variables and interpret their pharmacokinetic parameter correlations in relation to the large inter-individual and inter-study variability in CBD pharmacokinetics. For this study, CBD-related clinical trial reports were extensively screened and intercomparisons were performed between internal data sets through systematic classification and extraction of pharmacokinetic parameter values. The candidate independent variables associated with interpretation of CBD pharmacokinetic diversity established and explored in this study were as follows: diet, tetrahydrocannabinol (THC) combination, sample matrix type, liver and renal function, exposure route, dosage form, CBD exposure dose, cannabis smoking frequency, multiple exposure. The results of this study showed that CBD pharmacokinetics were influenced (increased plasma exposure by approximately 2-5 times) by diet immediately before or during CBD exposure, and that THC was not expected to have an antagonistic effect on the CBD absorption. The influence of changes in liver function would be significant in CBD pharmacokinetic diversity. Due to decreased liver function, the plasma exposure of CBD increased 2.57-5.15 times compared to healthy adults, and the half-life and clearance showed a 2.58-fold increase and a 5.15-fold decrease, respectively. CBD can be rapidly absorbed into the body (time to reach maximum concentration within 3.18 h) by oral, transdermal, and inhalation exposures, and lipid emulsification and nanoformulation of CBD will greatly improve CBD bioavailability (up to approximately 2 times). The pharmacokinetics of CBD generally follow linear kinetic characteristics. The importance of this study is that it suggests key factors that should be considered in terms of pharmacokinetics in further clinical trials and formulations of CBD in the future.

Characterization of luminal contents from the fasted human proximal colon.

To treat colonic diseases more effectively, improved therapies are urgently needed. In this respect, delivering drugs locally to the colon is a key strategy to achieve higher local drug concentrations while minimizing systemic side effects. Understanding the luminal environment is crucial to efficiently develop such targeted therapies and to predict drug disposition in the colon. In this clinical study, we collected colonic contents from an undisturbed fasted proximal colon via colonoscopy and characterized their composition with regard to drug disposition. Colonic pH, osmolality, protein content, bile salts, lipids, phospholipids and short-chain fatty acids were investigated in 10 healthy volunteers (8 male and 2 female, age 19-25). The unique environment of the proximal colon was reflected in the composition of the sampled luminal fluids and the effect of the microbiota could be observed on the pH (median 6.55), the composition of bile salts (majority deconjugated and secondary), and the abundance of short-chain fatty acids. At the same time, an increase in phospholipid concentration, osmolality and total protein content compared to reported ileal values was seen, likely resulting from desiccation. Lipids could only be found in low quantities and mainly in the form of cholesterol and free fatty acids, showing almost complete digestion and absorption by the time luminal contents reach the colon. All characteristics also displayed the considerable intersubject variability found in different regions of the gastrointestinal tract. This study contributes to an improved understanding of the luminal conditions in the proximal colon and facilitates the development of new predictive tools to study colonic drug absorption.

Hand, foot, and mouth disease: could EPs® 7630 be a treatment option? A prospective randomized open-label multicenter clinical study.

Purpose: Hand, foot and mouth disease (HFMD) is a viral contagious disease of children caused by human enteroviruses (EVs) and coxsackieviruses (CVs). There is no specific treatment option for HFMD. EPs® 7630's anti-infective and immunomodulatory properties have previously been demonstrated in several in vitro and in vivo studies; however, the use of this herbal medicine in children with HFMD has not previously been investigated. Methods: This prospective randomized multicenter clinical study included 208 children with HFMD. The diagnosis was made by pediatricians. The patients who were within the first 48 h of symptom onset (according to the first onset of fever and skin findings) were enrolled. The study participants were assigned into 2 groups as EPs® 7630 and control groups. All patients were followed up twice more, 48 h after the first admission and on the 5th-7th day. Another phone evaluation was conducted for those with continued complaints from the previous visit. Results: The median age was 27 (12-112) months. The male-female ratio was 0.98. One hundred thirty one (63%) of 190 patients had no history of household contact. EPs® 7630 group included 94 and control group included 96 patients. A significant difference was found between the groups in terms of complaint scores at the visits made at the 48th h of the treatment and on days 5-7 (p < 0.001). The mean ± SD disease duration of EPs® 7630 users was significantly shorter 6.07 ± 0.70 days (95% CI: 5.92-6.21)] than the control group [8.58 ± 0.94 days (95% CI: 8.39-8.77)] (p < 0.001). Besides, the hospitalization rate among the EPs® 7630 users were significantly lower (p = 0.019). No side effects were observed, except for unpleasant taste, which was reported in 5 patients (EPs® 7630 group). Conclusion: Considering its efficacy and safety profile EPs® 7630 may represent a feasible herbal-based treatment option for children with HFMD. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT06353477).

A randomized, placebo-controlled study of chitosan gel for the treatment of chronic diabetic foot ulcers (the CHITOWOUND study).

INTRODUCTION: To assess the efficacy of a chitosan-based gel (ChitoCare) for the treatment of non-healing diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS: Forty-two patients with chronic DFUs were randomized to the ChitoCare or placebo gel for a 10-week treatment period and 4-week follow-up. The primary study end point was the rate of complete wound closure at week 10, presented as relative rate. RESULTS: Thirty patients completed the 10-week treatment and 28 completed the 4-week follow-up. The ChitoCare arm achieved 16.7% complete wound closure at week 10 vs 4.2% in the placebo arm (p=0.297), 92.0% vs 37.0% median relative reduction in wound surface area from baseline at week 10 (p=0.008), and 4.62-fold higher likelihood of achieving 75% wound closure at week 10 (p=0.012). Based on the results of the Bates-Jensen Wound Assessment Tool, the wound state at week 10 and the relative improvement from the baseline were significantly better (median 20 vs 24 points, p=0.018, and median 29.8% vs 3.6%, p=0.010, respectively). CONCLUSIONS: ChitoCare gel increased the rate of the DFU healing process. Several secondary end points significantly favored ChitoCare gel. TRIAL REGISTRATION NUMBER: NCT04178525.

Profibrogenic role of IL-15 through IL-15 receptor alpha-mediated trans-presentation in the carbon tetrachloride-induced liver fibrosis model.

Background: Inflammatory cytokines play key pathogenic roles in liver fibrosis. IL-15 is a proinflammatory cytokine produced by myeloid cells. IL-15 promotes pathogenesis of several chronic inflammatory diseases. However, increased liver fibrosis has been reported in mice lacking IL-15 receptor alpha chain (IL-15Rα), suggesting an anti-fibrogenic role for IL-15. As myeloid cells are key players in liver fibrosis and IL-15 signaling can occur independently of IL-15Rα, we investigated the requirement of IL-15 and IL-15Rα in liver fibrosis. Methods: We induced liver fibrosis in Il15-/- , Il15ra-/- and wildtype C57BL/6 mice by the administration of carbon tetrachloride (CCl4). Liver fibrosis was evaluated by Sirius red and Mason's trichrome staining and α-smooth muscle acting immunostaining of myofibroblasts. Gene expression of collagens, matrix modifying enzymes, cytokines and chemokines was quantified by RT-qPCR. The phenotype and the numbers of intrahepatic lymphoid and myeloid cell subsets were evaluated by flow cytometry. Results: Both Il15-/- and Il15ra-/- mice developed markedly reduced liver fibrosis compared to wildtype control mice, as revealed by reduced collagen deposition and myofibroblast content. Il15ra-/- mice showed further reduction in collagen deposition compared to Il15-/- mice. However, Col1a1 and Col1a3 genes were similarly induced in the fibrotic livers of wildtype, Il15-/- and Il15ra-/- mice, although notable variations were observed in the expression of matrix remodeling enzymes and chemokines. As expected, Il15-/- and Il15ra-/- mice showed markedly reduced numbers of NK cells compared to wildtype mice. They also showed markedly less staining of CD45+ immune cells and CD68+ macrophages, and significantly reduced inflammatory cell infiltration into the liver, with fewer pro-inflammatory and anti-inflammatory monocyte subsets compared to wildtype mice. Conclusion: Our findings indicate that IL-15 exerts its profibrogenic role in the liver by promoting macrophage activation and that this requires trans-presentation of IL-15 by IL-15Rα.

Desensitizing efficacy of a universal dentin adhesive containing mesoporous bioactive glass on dentin hypersensitivity: a randomized clinical trial with a split-mouth model.

This split-mouth blinded randomized controlled study compared the efficacy of a desensitizing agent with oxalate/resin polymer and a universal adhesive containing mesoporous bioactive glass (MBG) for dentin hypersensitivity (DH) relief, using Schiff sensitivity score (SSS) and visual analog scale (VAS). Split quadrants containing teeth with DH were treated with either MS Coat ONE or Hi-Bond Universal with MBG as the functional additive. Assessments at baseline, immediately post-application, and at 1- and 2-week follow-ups used standardized stimulus protocols (air, cold, and acid). The SSS difference was the primary outcome, while the VAS difference was the secondary outcome. A mixed linear effect model performed statistical analysis. Immediate DH reduction occurred in response to air stimuli, with a significant decrease in Group HB than in Group MS (p = 0.0178). Cold stimulus reduction exhibited a gradual cumulative effect, with consistently greater reductions in Group HB than in Group MS (p ≤ 0.0377). Both groups effectively managed acidic stimuli, with no significant differences (p > 0.05). The VAS scores decreased gradually over the follow-up period (p < 0.0001). This study highlights the differential efficacy of treatments for various DH triggers and recommends specific approaches based on different stimulus types. The universal adhesive containing MBG demonstrated DH relief potential, promising efficacy identical to or superior to that of a dedicated desensitizing agent. Further research exploring the long-term efficacy and underlying mechanisms is warranted. The universal adhesive containing MBG can be adopted as an in-office desensitizing agent for DH relief. The desensitizing efficacy of universal adhesive matches or surpasses dedicated agents for air and cold stimuli.

Application of emerging technologies in ischemic stroke: from clinical study to basic research.

Stroke is a primary cause of noncommunicable disease-related death and disability worldwide. The most common form, ischemic stroke, is increasing in incidence resulting in a significant burden on patients and society. Urgent action is thus needed to address preventable risk factors and improve treatment methods. This review examines emerging technologies used in the management of ischemic stroke, including neuroimaging, regenerative medicine, biology, and nanomedicine, highlighting their benefits, clinical applications, and limitations. Additionally, we suggest strategies for technological development for the prevention, diagnosis, and treatment of ischemic stroke.

Antitumor activity and safety of the PD-1 inhibitor retifanlimab in patients with recurrent microsatellite instability-high or deficient mismatch repair endometrial cancer: Final safety and efficacy results from cohort H of the POD1UM-101 phase I study.

OBJECTIVE: Retifanlimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1 being investigated in several solid tumor types. We report final results from patients with recurrent microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) endometrial cancer treated with retifanlimab in a POD1UM-101 expansion cohort. METHODS: Eligible patients (≥18 years; histologically proven/unresectable/recurrent, MSI-H/dMMR endometrial cancer; checkpoint inhibitor naive) received retifanlimab 500 mg intravenously every 4 weeks for ≤2 years. Primary endpoint was safety/tolerability. RESULTS: At data cutoff (May 17, 2023), 76 patients had received at least one retifanlimab dose. Median (range) age was 67 (49-88) years; 88.2% of patients had recurrent metastatic disease and 80.3% had visceral metastases. Seventy-five patients (98.7%) had received at least one prior systemic therapy. Median retifanlimab exposure was 10.0 (0.03-25.9) months; 23 patients completed treatment. 38 patients (50.0%) had grade ≥3 treatment-emergent adverse events (TEAEs), most commonly anemia (n = 10 [13.2%]). 63 patients (82.9%) had treatment-related AEs (TRAEs; grade ≥3, n = 14 [18.4%]); most common was fatigue (n = 14 [18.4%]). Two patients had TEAEs that led to death; no TRAEs were fatal. 39 patients had objective responses (51.3%; 95% CI, 39.6-63.0%); 19 patients (25.0%) had complete response and 20 (26.3%) had partial response. Median progression-free survival was 12.2 months; 30 patients (76.9%) had duration of response (DOR) ≥12 months. Median DOR was not reached after median follow-up time of 26.0 months. CONCLUSIONS: Retifanlimab was generally well tolerated and demonstrated encouraging anti-tumor activity in patients with pre-treated recurrent MSI-H/dMMR endometrial cancer.

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia: A Prospective, Randomized, Open, Parallel Controlled and Multicenter Clinical Study.

OBJECTIVE: This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia. METHODS: A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups. RESULTS: After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01). CONCLUSION: The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.