Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

Background: Patients who report to be difficult to anesthetize for dental procedures are commonly encountered.Determining their frequency and shared characteristics could improve understanding of pain management failures. Methods: Categorical and continuous variables of 24 demographic, medical history, and dental history variables were compared in a deidentified cross-sectional study using electronic health records (EHR) of patients at the University of Iowa College of Dentistry. Individuals who self-reported to be difficult to anesthetize in their dental health history form were compared to those who reported no complications with local anesthesia. Descriptive, univariate regression, and multivariable regression statistical analyses were completed on the demographic, medical history, and dental history EHR variables. Results: A total of 12,400 deidentified patient records met the inclusion criteria with a 11.4% (n = 1,411) prevalence of difficult to anesthetize self-reports. Eight categorical variables were found to have statistically significant (95% confidence interval [CI]) adjusted odds ratios (AOR) in the multivariable regression of difficult to anesthetize reporting patients: female gender (AOR = 1.61, 95% CI: 1.32-1.96, P < 0.001), dental fear (AOR = 3.60, 95% CI: 3.01-4.31, P < 0.001), mental health disorders (AOR = 1.21, 95% CI: 1.00-1.46, P < 0.045), problems with general anesthesia (AOR = 1.46, 95% CI: 1.11-1.89, P = 0.005), neurologicalerve disorders (AOR = 1.30, 95% CI: 1.05-1.60, P = 0.015), temporomandibular joint clicking/popping (AOR = 1.31, 95% CI: 1.08-1.60, P = 0.006), needle anxiety (AOR = 29.03, 95% CI: 23.80-35.52, P < 0.001), and history of root canal treatment (AOR 0.82, 95% CI: 0.68-0.99, P = 0.035). Conclusion A clinically relevant percentage of patients self-reported being difficult to anesthetize for dental procedures. The relationship between local anesthesia inadequacies and variables such as female gender, dental fear, mental health, and neurological disorders requires further investigation. The use of evidence-based local anesthesia approaches and communication practices is suggested to minimize pain experienced and subsequent fear of dental care.

Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

Background: Patients who report to be difficult to anesthetize for dental procedures are commonly encountered.Determining their frequency and shared characteristics could improve understanding of pain management failures. Methods: Categorical and continuous variables of 24 demographic, medical history, and dental history variables were compared in a deidentified cross-sectional study using electronic health records (EHR) of patients at the University of Iowa College of Dentistry. Individuals who self-reported to be difficult to anesthetize in their dental health history form were compared to those who reported no complications with local anesthesia. Descriptive, univariate regression, and multivariable regression statistical analyses were completed on the demographic, medical history, and dental history EHR variables. Results: A total of 12,400 deidentified patient records met the inclusion criteria with a 11.4% (n = 1,411) prevalence of difficult to anesthetize self-reports. Eight categorical variables were found to have statistically significant (95% confidence interval [CI]) adjusted odds ratios (AOR) in the multivariable regression of difficult to anesthetize reporting patients: female gender (AOR = 1.61, 95% CI: 1.32-1.96, P < 0.001), dental fear (AOR = 3.60, 95% CI: 3.01-4.31, P < 0.001), mental health disorders (AOR = 1.21, 95% CI: 1.00-1.46, P < 0.045), problems with general anesthesia (AOR = 1.46, 95% CI: 1.11-1.89, P = 0.005), neurologicalerve disorders (AOR = 1.30, 95% CI: 1.05-1.60, P = 0.015), temporomandibular joint clicking/popping (AOR = 1.31, 95% CI: 1.08-1.60, P = 0.006), needle anxiety (AOR = 29.03, 95% CI: 23.80-35.52, P < 0.001), and history of root canal treatment (AOR 0.82, 95% CI: 0.68-0.99, P = 0.035). Conclusion A clinically relevant percentage of patients self-reported being difficult to anesthetize for dental procedures. The relationship between local anesthesia inadequacies and variables such as female gender, dental fear, mental health, and neurological disorders requires further investigation. The use of evidence-based local anesthesia approaches and communication practices is suggested to minimize pain experienced and subsequent fear of dental care.

Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

Background: Patients who report to be difficult to anesthetize for dental procedures are commonly encountered.Determining their frequency and shared characteristics could improve understanding of pain management failures. Methods: Categorical and continuous variables of 24 demographic, medical history, and dental history variables were compared in a deidentified cross-sectional study using electronic health records (EHR) of patients at the University of Iowa College of Dentistry. Individuals who self-reported to be difficult to anesthetize in their dental health history form were compared to those who reported no complications with local anesthesia. Descriptive, univariate regression, and multivariable regression statistical analyses were completed on the demographic, medical history, and dental history EHR variables. Results: A total of 12,400 deidentified patient records met the inclusion criteria with a 11.4% (n = 1,411) prevalence of difficult to anesthetize self-reports. Eight categorical variables were found to have statistically significant (95% confidence interval [CI]) adjusted odds ratios (AOR) in the multivariable regression of difficult to anesthetize reporting patients: female gender (AOR = 1.61, 95% CI: 1.32-1.96, P < 0.001), dental fear (AOR = 3.60, 95% CI: 3.01-4.31, P < 0.001), mental health disorders (AOR = 1.21, 95% CI: 1.00-1.46, P < 0.045), problems with general anesthesia (AOR = 1.46, 95% CI: 1.11-1.89, P = 0.005), neurologicalerve disorders (AOR = 1.30, 95% CI: 1.05-1.60, P = 0.015), temporomandibular joint clicking/popping (AOR = 1.31, 95% CI: 1.08-1.60, P = 0.006), needle anxiety (AOR = 29.03, 95% CI: 23.80-35.52, P < 0.001), and history of root canal treatment (AOR 0.82, 95% CI: 0.68-0.99, P = 0.035). Conclusion A clinically relevant percentage of patients self-reported being difficult to anesthetize for dental procedures. The relationship between local anesthesia inadequacies and variables such as female gender, dental fear, mental health, and neurological disorders requires further investigation. The use of evidence-based local anesthesia approaches and communication practices is suggested to minimize pain experienced and subsequent fear of dental care.

γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
Humans ; Receptors, Antigen, T-Cell, gamma-delta ; Immunotherapy, Adoptive ; T-Lymphocytes ; Immunotherapy ; Neoplasms/therapy*

Objective To construct chimeric antigen receptors modified γδT cells targeting at BCMA(BCMA CAR-γδT)and to evaluate its efficacy of anti-multiple myeloma in vitro.Methods Lentiviral vectors containing BCMA single-chain variable fragment were constructed and transiently transfected into 293T cells.The expression of foreign genes was verified by fluorescence microscopy and Western blot;the lentivirus was packaged and the virus titer was determined by flow cytometry.Human peripheral blood αβT cells were infected and γδT cells were examined for its infection efficiency;LDH release method was used to detect the cytotoxic activity of BCMA CAR-γδT cells against human multiple myeloma cell lines in vitro,and the difference of cytotoxic activity between CAR-γδT cells and CAR-αβT cells was compared by Incucyte S3 Live-Cell Analysis Instrument.Results Twenty-four hours after BCMA-CAR lentiviral vector was transferred into 293T cells,the expression of exogenous ZsGreen was microscopied by fluorescence microscope;CD3ζ was detected by Western blot,which showed that BCMA-CAR could be success-fully expressed.The lentivirus was packaged,collected and concentrated(virus titer of 2.23×108 Tu/mL).Infected αβT cells and γδT cells from human peripheral blood in MOI=5,and the results of flow cytometry showed that infection efficiency of αβT cells was 59.18%±2.56%,γδT cells was 48.15±9.86%.The cytotoxic activity of CAR-γδT cells against human myeloma cell lines MM1.S,H929 with high expression of BCMA and K562 cells with over-expression of BCMA was higher than that of empty vector control γδ T cells,which were signifi-cantly enhanced(P＜0.001),but there was no difference in cell lines negative for BCMA expression;Live-Cell Analysis Instrument results showed that the cytotoxic activity of BCMA CAR-γδT cells and BCMA CAR-αβT cells against H929 in vitro was significantly better than their vector control cells.There was no difference in the cytotoxic activities of BCMA CAR-γδT cells as compared with against BCMA negative cell lines,and so do BCMA CAR-T cells.Conclusions Cytotoxic activity of BCMA CAR-γδT targeting at BCMA in vitro was significantly enhanced,which is expected to serve as a novel allogeneic γδT cell product for cell a-doptive immunotherapy of multiple myeloma.

Objective To verify the function of exosomes from 293T cells over-expressing membrane-localized IL-3 in vitro,so as to lay a foundation for in vivo function verification in animal models of Alzheimer's disease.Methods Using the patented structure of the group,a recombinant IL-3 lentiviral vector was constructed and virus-infected 293T cells were packaged.Stable cell strain over-expressing IL-3 was screened.The membrane localization of IL-3 was verified by flow cytometry and immuno-fluorescence.Il-3-exosomes were purified by ultra filtration centrifugation,the exosmic morphology was observed by transmission electron microscope,the size distribution and concentration of exosomes were detected by nano-flow analysis,and the expression of IL-3 and exosome related marker proteins were detected by Western blot.The effect of BV-2 on the phagocytosis of Aβ amyloid was detected by immuno-fluores-cence.Results Through vector construction,virus infection,screening and verification of puromycin,293T cell strain with stable over-expression membrane-anchored IL-3 was obtained.The purified exosomes were collected and the structures of double-layer membrane vesicles with a diameter of 50-100 nm were observed under transmission electron microscope.Western blot results proved the presence of CD63,ALIX,TSG101 and other exosome marker proteins and these molecules were rich in IL-3 as compared with the control,that suggested the successful purifica-tion of IL-3-exosomes.The results of immuno-fluorescence assay showed that IL-3-exosomes promoted the phagocy-tosis of Aβ amyloid by BV-2 cells in vitro.Conclusions The gene modified 293T cell exosomes membrane-anchored expression of IL-3 can play a role of both IL-3 and exosomes in vitro,which promote the phagocytosis of microglia,there for provides a new idea for the clinical treatment of Alzheimer's disease.

γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.