Effects of exosomes derived from platelet-rich plasma on osteogenic differentiation of dental pulp stem cells.

Platelet-rich plasma (PRP) can cause osteogenic differentiation of dental pulp stem cells (DPSCs). However, the effect of exosomes derived from PRP (PRP-Exos) on osteogenic differentiation of DPSCs remains unclear. Herein, we evaluated the impact of PRP-Exos on osteogenic differentiation of DPSCs. PRP-Exos were isolated and identified by transmission electron microscopy (TEM) and western blotting (WB). Immunofluorescence staining was performed to evaluate endocytosis of PRP-Exos by DPSCs. Alkaline phosphatase staining, alizarin red staining, western blot and qRT-PCR were carried out to evaluate the DPSCs osteogenic differentiation. The sequencing microRNA (miRNA) was conducted to determine the microRNA profile of PRP-Exos treated and untreated DPSCs. The results showed that endocytosis of PRP-Exos stimulated DPSCs odontogenic differentiation by elevated expression of ALP, DMP-1, OCN, and RUNX2. ALP activity and calcified nodules formation of PRP-Exos treated DPSCs were considerably elevated relative to that of the control group. MicroRNA sequencing revealed that 112 microRNAs considerably varied in PRP-Exos treated DPSCs, of which 84 were elevated and 28 were reduced. Pathway analysis suggested that genes targeted by differentially expressed (DE) miRNAs were contributed to many signaling cascades, such as the Wnt cascade. 65 genes targeted by 30 DE miRNA were contributed to Wnt signaling. Thus, it can be infered that PRP-Exos could enhance osteogenic differentiation and alter the miRNA expression profile of DPSCs.

Chronic nonspecific cheilitis associated with tislelizumab treatment in a patient with a history of tongue squamous cell carcinoma: a case report.

BACKGROUND: Chronic nonspecific cheilitis is a complex condition characterized by persistent lip peeling and discomfort. This case report explores the clinical progression of a patient with history of tongue squamous cell carcinoma and subsequent Tislelizumab treatment, presenting with persistent lip peeling. CASE PRESENTATION: A patient with a history of tongue squamous cell carcinoma (T2N0M0), treated with chemotherapy, surgery, and Tislelizumab, presented with six months of persistent lip peeling. Clinical examination revealed distinct features of chronic nonspecific cheilitis with infectious angular cheilitis (Oral Candidiasis). A tailored treatment plan, emphasizing oral hygiene practices and local treatments with Sodium Bicarbonate, Tacrolimus ointment, and Chlortetracycline ointment. Follow-up visits demonstrated sustained improvement, highlighting the significance of individualized approaches. CONCLUSIONS: This case underscores the importance of recognizing and managing oral manifestations in patients with a history of cancer and immunotherapy. The patient's response to treatment suggests that a multifaceted approach, combining local therapy with lifestyle modifications, can be effective in managing chronic nonspecific cheilitis associated with immunotherapy. Routine follow-up appointments, guided by personalized medicine principles, contribute to sustained patient well-being.

Fatal hemorrhagic varicella in a patient with abdominal pain: a case report.

BACKGROUND: Varicella is normally a self-limited childhood disease caused by varicella-zoster virus infection. However, it sometimes causes severe diseases, especially in immunocompromised individuals. We report a case of severe varicella in a young woman. CASE PRESENTATION: A 19-year-old woman presented to the emergency department with abdominal pain and a rash after taking methylprednisolone for 2 weeks for systemic lupus erythematosis. The laboratory data showed leukocytosis, thrombocytopenia, an elevated level of the liver transaminases and disseminated intravascular coagulation. Computed tomography of the abdomen revealed multiple air-fluid levels in the intestines. Hemorrhagic varicella was considered and antiviral therapy as well as immunoglobin were applied. Her condition deteriorated and she eventually died due to multi-organ failure and refractory shock. Next-generation sequencing performed on fluid from an unroofed vesicle confirmed the diagnosis of varicella. CONCLUSION: In its severe form, VZV infection can be fatal, especially in immunocompromised patients. Hemorrhagic varicella can be misdiagnosed by clinicians because of unfamiliar with the disease, although it is associated with a high mortality rate. In patients with suspected hemorrhagic varicella infection, antiviral therapies along with supportive treatment need to be initiated as soon as possible in order to minimize the case fatality rate.

A class of promising acaricidal tetrahydroisoquinoline derivatives: synthesis, biological evaluation and structure-activity relationships.

As part of our continuing research on isoquinoline acaricidal drugs, this paper reports the preparation of a series of the 2-aryl-1-cyano-1,2,3,4-tetrahydroisoquinolines with various substituents on the N-phenyl ring, their in vitro acaricidal activities against Psoroptes cuniculi, a mange mite, and discusses their SAR as well. The structures of all compounds, including 12 new ones, were elucidated by analysis of UV, IR, NMR, ESI-MS, HR-MS spectra and X-ray diffraction experiments. All target compounds showed varying degrees of activity at 0.4 mg/mL. Compound 1 showed the strongest activity, with a 50% lethal concentration value (LC50) of 0.2421 µg/mL and 50% lethal time value (LT50) of 7.79 h, comparable to the standard drug ivermectin (LC50 = 0.2474 µg/mL; LT50 = 20.9 h). The SAR showed that the substitution pattern on the N-aromatic ring exerted a significant effect on the activity. The substituents 2'-F, 3'-F, 2'-Cl, 2'-Br and 2'-CF3 remarkably enhanced the activity. Generally, for the isomers with the same substituents at different positions, the order of the activity was ortho > meta > para. It was concluded that the target compounds represent a class of novel promising candidates or lead compounds for the development of new tetrahydroisoquinoline acaricidal agents.

Dissociative photoionization of glycerol and its dimer occurs predominantly via a ternary hydrogen-bridged ion-molecule complex.

The photoionization and dissociative photoionization of glycerol are studied experimentally and theoretically. Time-of-flight mass spectrometry combined with vacuum ultraviolet synchrotron radiation ranging from 8 to 15 eV is used to investigate the nature of the major fragments and their corresponding appearance energies. Deuterium (1,1,2,3,3-D5) and (13)C (2-(13)C) labeling is employed to narrow down the possible dissociation mechanisms leading to the major fragment ions (C3H(x)O2(+), C2H(x)O2(+), C2H(x)O(+), CH(x)O(+)). We find that the primary fragmentation of the glycerol radical cation (m/z 92) occurs only via two routes. The first channel proceeds via a six-membered hydrogen-transfer transition state, leading to a common stable ternary intermediate, comprised of neutral water, neutral formaldehyde, and a vinyl alcohol radical cation, which exhibits a binding energy of ≈42 kcal/mol and a very short (1.4 Å) hydrogen bond. Fragmentation of this intermediate gives rise to experimentally observed m/z 74, 62, 44, and 45. Fragments m/z 74 and 62 both consist of hydrogen-bridged ion-molecule complexes with binding energy >25 kcal/mol, whereas the m/z 44 species lacks such stabilization. This explains why water- or formaldehyde-loss products are observed first. The second primary fragmentation route arises from cleaving the elongated C-C bond. Also for this channel, intermediates comprised of hydrogen-bridged ion-molecule complexes exhibiting binding energies >24 kcal/mol are observed. Energy decomposition analysis reveals that electrostatic and charge-transfer interactions are equally important in hydrogen-bridged ion-molecule complexes. Furthermore, the dissociative photoionization of the glycerol dimer is investigated and compared to the main pathways for the monomeric species. To a first approximation, the glycerol dimer radical cation can be described as a monomeric glycerol radical cation in the presence of a spectator glycerol, thus giving rise to a dissociation pattern similar to that of the monomer.

Prevascularization techniques for dental pulp regeneration: potential cell sources, intercellular communication and construction strategies.

One of the difficulties of pulp regeneration is the rapid vascularization of transplanted engineered tissue, which is crucial for the initial survival of the graft and subsequent pulp regeneration. At present, prevascularization techniques, as emerging techniques in the field of pulp regeneration, has been proposed to solve this challenge and have broad application prospects. In these techniques, endothelial cells and pericytes are cocultured to induce intercellular communication, and the cell coculture is then introduced into the customized artificial vascular bed or induced to self-assembly to simulate the interaction between cells and extracellular matrix, which would result in construction of a prevascularization system, preformation of a functional capillary network, and rapid reconstruction of a sufficient blood supply in engineered tissue after transplantation. However, prevascularization techniques for pulp regeneration remain in their infancy, and there remain unresolved problems regarding cell sources, intercellular communication and the construction of prevascularization systems. This review focuses on the recent advances in the application of prevascularization techniques for pulp regeneration, considers dental stem cells as a potential cell source of endothelial cells and pericytes, discusses strategies for their directional differentiation, sketches the mechanism of intercellular communication and the potential application of communication mediators, and summarizes construction strategies for prevascularized systems. We also provide novel ideas for the extensive application and follow-up development of prevascularization techniques for dental pulp regeneration.

Recurrent pulmonary tuberculosis after treatment success: a population-based retrospective study in China.

OBJECTIVES: Post-treatment recurrence remains a challenge for the global control of tuberculosis (TB). This study investigated longitudinal data on pulmonary TB recurrence rates and risk factors for recurrence among successfully treated smear-positive tuberculosis cases in China. METHODS: Between 1st January 2009 and 31st December 2016 we evaluated 33 441 treatment-naïve patients diagnosed with sputum-smear-positive, non-multidrug-resistant TB in Hangzhou, China. We included the data of 9828 patients with TB who were treated successfully. RESULTS: A total of 4.9% of the cases were recurrent (479/9828), identified within a median observation period lasting 1565 days. Altogether, 51.1% (245/479) of the recurrences occurred within 1 year. The cumulative 2- and 5-year recurrence rates were 3.90% (95% confidence interval (CI) 3.3-4.5%) and 5.4% (95%CI 4.8-6.0%), respectively. Prolonged treatment (over 7 months) occurred in 64.7% (6363/9828), with a median treatment duration of 242 days (interquartile range 195-348 days). Male sex (adjusted hazard ratio (aHR) (95%CI) 1.61 (1.30-2.00), p < 0.001), age 60 years old or older (aHR (95%CI) 2.03 (1.70-2.44), p < 0.001), pulmonary cavity (aHR (95%CI) 1.51 (1.25-1.82), p < 0.001) and sputum positivity at 2 months (aHR (95%CI) 1.39 (1.05-1.81), p 0.02) all increased the risk of TB recurrence. Prolonged treatment was associated with reduced TB recurrence (aHR (95%CI) 0.73 (0.61-0.88), p 0.001). CONCLUSIONS: Recurrence remains a problem for successfully treated patients with sputum-smear-positive pulmonary TB, especially those with independent risk factors. Further analysis of prolonged treatment is required.

Evaluation of the risk of fracture in type 2 diabetes mellitus patients with incretins: an updated meta-analysis.

INTRODUCTION: The effect of incretins including dipeptidyl peptidase 4 inhibitors (DPP4-Is) and glucagon-like peptide1 receptor agonists (GLP1-ras) in the treatment of type 2 diabetes increasing the risk of fracture remains controversial. No meta-analysis has been written to discuss this from the prospective interventional studies. The objective was to evaluate the association between the use of incretins and fracture risk. MATERIAL AND METHODS: Multiple databases were searched for original articles that investigated the relationship between the use of incretin agents and fracture risk, up to December 2019. Trials using the Mantel-Haenszel method to calculate OR and 95% CI were pooled. The multiple sensitivity, heterogeneity, publication bias, and quality were analysed among the studies to evaluate the robustness of results. RESULTS: The fixed-effects model was used on account of the I² test for heterogeneity (I² = 0.0%). Incretins were not associated with fracture risk [0.97 (95% CI: 0.88-1.08)]. But in the subgroup analysis, when sitagliptin 100 mg per day (OR 0.495, 95% CI: 0.304-0.806) or liraglutide 1.8 mg per day was administered (OR 0.621, 95% CI: 0.413-0.933), it reduced fracture risk. The sensitivity analysis and publication bias prompted the robustness of results. CONCLUSIONS: This meta-analysis suggested that the current use of incretins not only is safe for fracture in type 2 diabetes patients from RCT studies, but also, when sitagliptin 100 mg or liraglutide 1.8 mg per day was administered, it may exhibit protective effects on bone metabolism.

Degeneration in the Zygapophysial Joint of the Fifth Lumbar Vertebra: The V-Shaped Sign Revealed by Bone Scintigraphy.

OBJECTIVE: The aim of the study was to explore the nature of a V-shaped sign in the backbone of the fifth lumbar vertebra revealed by whole-body bone scintigraphy (WBBS). METHODS: A local single-photon emission computed tomography (SPECT) scan plus a computed tomography (CT) scan were performed on 41 patients in our department who had a V-shaped sign in the backbone of the fifth lumbar vertebra detected by WBBS. Image fusion was conducted to understand the manifestations of the changes in the V-shaped sign in the CT images in WBBS and to determine the nature of the lesion. RESULTS: All 41 patients presented with degenerative changes observed in the bilateral posterior zygapophysial joint of the fifth lumbar vertebra in the CT imaging bone window, bone hyperplasia of the articular process, joint surface hardening, and a joint gap. The vacuum sign could also be seen in some of these patients. CONCLUSION: The typical V-shaped sign in the posterior zygapophysial joint of the fifth lumbar vertebra revealed by WBBS suggests degenerative changes in the zygapophysial joint of the fifth lumbar vertebra.

Integrative Nutritional Counseling Combining Chinese Medicine and Biomedicine for Chinese Americans with Type 2 Diabetes: A Mixed-Methods Feasibility Study.

Objectives: This study describes the development and feasibility of Integrative Nutritional Counseling (INC), a Chinese medicine (CM)+biomedicine-based nutrition curriculum for Chinese Americans with type 2 diabetes. Although Chinese Americans often incorporate CM principles into their diet, scant research has explored how to integrate CM with biomedical nutrition standards in a culturally appropriate manner or if such a program could improve diabetes self-management. Design: This is a 1-month pre-post study design including three points of contact: baseline, in-person class, and 1-month follow-up. Subjects: Participants (n = 15) were Cantonese-speaking/reading Chinese Americans diagnosed with type 2 diabetes who had used some form of CM/medicinal foods in the last 12 months. Interventions and Outcome Measures: The INC program included baseline surveys and a CM intake interview conducted by a licensed acupuncturist. The acupuncturist generated a CM diagnosis, which was shared with the participant, and used this diagnosis to tailor brief nutrition education. To bolster this brief education, a bilingual registered dietitian provided a 2-h group education class in Cantonese to all participants, during which time participants also received a Chinese/English INC booklet. Participants completed surveys immediately after the class and at 1-month follow-up, with qualitative exit interviews. Results: Participants reported improved attitudes and dietary habits aligning directly with INC, and improvement in biomedically valued measures of type 2 diabetes, such as weight loss, and CM-valued measures of digestion/elimination and hot/cold feeling. Satisfaction with INC was high, but challenges included confusion with some INC information, structural barriers, and comorbidities. Conclusions: Chinese Americans with type 2 diabetes and interventionists found integrative nutrition approaches acceptable and feasible. Future research should examine INC with a larger population and explore optimal delivery of INC given reported challenges.

Transcriptional signatures of human peripheral blood mononuclear cells can identify the risk of tuberculosis progression from latent infection among individuals with silicosis.

CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02430259).

Perioperative and Long-Term Outcomes of Robot-Assisted Partial Nephrectomy: A Systematic Review.

BACKGROUND: Adoption of the robotic surgical platform for small renal cancers has rapidly expanded, but its utility compared to other approaches has not been established. The objective of this review is to assess perioperative and long-term oncologic and functional outcomes of robot-assisted partial nephrectomy (RAPN) compared to laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN). METHODS: A search in PubMed, Embase, and Cochrane (2010-2019) was conducted. Of 3877 articles screened, 7 observational studies were included. RESULTS: RAPN was associated with 24-50 mL less intraoperative blood loss compared to LPN and 39-84 mL less than OPN. RAPN also demonstrated trends of other postoperative benefits, such as shorter length of stay and fewer major complications. Several studies reported better long-term functional kidney outcomes, but these findings were inconsistent. Recurrence and cancer-specific survival (CSS) were similar across groups. While RAPN had a 5-year CSS of 90.1%-97.9%, LPN and OPN had survival rates of 85.9%-86.9% and 88.5-96.3% respectively. CONCLUSIONS: RAPN may be associated with a lower estimated blood loss and comparable long-term outcomes when compared to other surgical approaches. However, additional randomized or propensity matched studies are warranted to fully assess long-term functional kidney and oncologic outcomes.

Efficacy and safety of weekly rifapentine and isoniazid for tuberculosis prevention in Chinese silicosis patients: a randomized controlled trial.

OBJECTIVE: The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. METHODS: Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. RESULTS: A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. DISCUSSION: Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02430259.

Updates on the risk factors for latent tuberculosis reactivation and their managements.

The preventive treatment of latent tuberculosis infection (LTBI) is of great importance for the elimination and control of tuberculosis (TB) worldwide, but existing screening methods for LTBI are still limited in predicting the onset of TB. Previous studies have found that some high-risk factors (including human immunodeficiency virus (HIV), organ transplantation, silicosis, tumor necrosis factor-alpha blockers, close contacts and kidney dialysis) contribute to a significantly increased TB reactivation rate. This article reviews each risk factor's association with TB and approaches to address those factors. Five regimens are currently recommended by the World Health Organization, and no regimen has shown superiority over others. In recent years, studies have gradually narrowed down to the preventive treatment of LTBI for high-risk target groups, such as silicosis patients, organ-transplantation recipients and HIV-infected patients. This review discusses regimens for each target group and compares the efficacy of different regimens. For HIV patients and transplant recipients, isoniazid monotherapy is effective in treating LTBI, but for others, little evidence is available at present.

The Risk of Tuberculosis in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor-α Antagonist: A Metaanalysis of Both Randomized Controlled Trials and Registry/Cohort Studies.

OBJECTIVE: Tumor necrosis factor-α (TNF-α) antagonists have significantly improved treatment results in rheumatoid arthritis (RA), but have also increased the risk of tuberculosis (TB). Etanercept (ETN), adalimumab (ADA), infliximab (IFX), golimumab, and certolizumab pegol are the 5 drugs currently available on the market. This article aimed to evaluate the risk of TB infection from these 5 drugs for patients with RA. METHODS: We searched PubMed, EMBASE, COCHRANE library, OVID, and EBSCO for randomized controlled trials (RCT) of TNF-α antagonist versus control and registry/longitudinal cohort studies of 1 TNF-α antagonist versus another. The Mantel-Haenszel test was adopted to analyze risk ratio (RR) in this metaanalysis. RESULTS: Fifty RCT and 13 non-RCT were included in this study. No significant difference in TB risk was found in the RCT because of the short observational periods. In the non-RCT, TNF-α antagonist was associated with a higher TB risk in patients with RA (RR 4.03, 95% CI 2.36-6.88), and the TB incidence rates of IFX and ADA were 2.78 and 3.88 times, respectively, higher than that of ETN. Further, preventive treatment for latent TB infection (LTBI) was shown to reduce the TB risk by 65% (RR 0.35, 95% CI 0.15-0.82). CONCLUSION: This study demonstrated a significant increase in TB risk in patients with RA treated with TNF-α antagonists; among them, ETN is least likely to cause active TB. The study also proposes the necessity of LTBI prophylaxis in patients with RA.

Isolation and Characterization of a Neurotrophic Factor-like Substance from Venom of Agkistrodon acutus.

A neurotrophic factor-like substance from Agkistrodon acutus was isolated by ion exchange and gel filtration chromatography and was found to be homogenous by electrophoresis. Itsmolecular weight was estimated to be approximately 26 kD by gel filtration. A characteristic of the substance was that the protein consisted of two subunits which were bound one to another noncovalently. The analytical isoelectric focusing revealed its isoelectric point of 7.8. The biological activity of the substance was comparable to that of mouse 2.5 S NGF. It rescued PC12 cells from apoptosis at the concentration interval of 1 100 &mgr;g/L and could induce PC12 cells differentiate to sympathetic-like neurons.