Toll-like receptor(TLR)7 and 8 are members of the TLRs family,mainly involved in the recognition of single stranded RNA,activating the host's immune response.TLR7/8 regulators are related to the treatment of various diseases such as antiviral,anti-tumor,and autoimmune dis-eases.The development and application of TLR7/8 ligands still receive widespread attention.Up to now,the reported parent nucleus structures of TLR7/8 ligands include purine,pyrimidine,pterine,imidazoloquinoline,thiazoloquinoline,and quinazoline.This article mainly focuses on the structure-activity relationship of several ligands,such as imidazolo[4,5-c]quinoline,8-oxoadenosine,pyridino[2,3-c]pyrimidine,and indole,in order to provide information for the screening,design,or struc-tural modification of TLR7/8 agonists or inhibitors in the future,and to provide new strategies for the prevention or treatment of animal immunosuppressive diseases.

BACKGROUND:With the continuous development of medical technology,the treatment of distal radius fractures is facing the need for more precise and personalized treatment.The traditional splint fixation method has some limitations in clinical application,which often has defects such as unstable fixation and easy to occur pressure sores.The validation of the improved 3D printed splint with rapid grid-free simulation is expected to lead to more accurate and effective treatment options for distal radius fractures.OBJECTIVE:To explore the design method of 3D printed splint for distal radius fracture based on clinical defect improvement and verify its clinical efficacy by rapid grid-free analysis.METHODS:Clinical defects of splint fixation of extended distal radius fracture were retrospectively analyzed,and 3D printed small splint was designed with specific improvement.The digital models of traditional splint and improved new 3D printed splint were made by Computer Aided Design drawing.Total,bone,soft tissue,and splint displacement and stress distribution were calculated through simulation analysis using rapid grid-free analysis tools.RESULTS AND CONCLUSION:(1)Compared with the traditional splint,the improved new 3D printing splint exerteded more balanced pressure on the skin without obvious stress concentration,and had better body surface adhesion.The displacement was smaller and the movement range was more reasonable.(2)An 3D printed splint based on clinical defect improvement can be designed.Rapid grid-free analysis verifies the advantages of the improved 3D splint,providing a basis for clinical application.

BACKGROUND:With the continuous development of medical technology,the treatment of distal radius fractures is facing the need for more precise and personalized treatment.The traditional splint fixation method has some limitations in clinical application,which often has defects such as unstable fixation and easy to occur pressure sores.The validation of the improved 3D printed splint with rapid grid-free simulation is expected to lead to more accurate and effective treatment options for distal radius fractures.OBJECTIVE:To explore the design method of 3D printed splint for distal radius fracture based on clinical defect improvement and verify its clinical efficacy by rapid grid-free analysis.METHODS:Clinical defects of splint fixation of extended distal radius fracture were retrospectively analyzed,and 3D printed small splint was designed with specific improvement.The digital models of traditional splint and improved new 3D printed splint were made by Computer Aided Design drawing.Total,bone,soft tissue,and splint displacement and stress distribution were calculated through simulation analysis using rapid grid-free analysis tools.RESULTS AND CONCLUSION:(1)Compared with the traditional splint,the improved new 3D printing splint exerteded more balanced pressure on the skin without obvious stress concentration,and had better body surface adhesion.The displacement was smaller and the movement range was more reasonable.(2)An 3D printed splint based on clinical defect improvement can be designed.Rapid grid-free analysis verifies the advantages of the improved 3D splint,providing a basis for clinical application.

Objective: To investigate the epidemiological characteristics of epidemic encephalitis B in Huzhou City, Zhejiang Province from 2007 to 2023, so as to provide the evidence for formulating prevention and control measures for epidemic encephalitis B. Methods: Epidemic encephalitis B case data in Huzhou City from 2007 to 2023 were collected through the National Notifiable Disease Reporting System of the Chinese Disease Prevention and Control Information System. The temporal, regional and population distribution characteristics of laboratory-confirmed epidemic encephalitis B cases were analyzed using the descriptively epidemiological method. Results: A total of 49 laboratory-confirmed epidemic encephalitis B cases were reported in Huzhou City from 2007 to 2023, and the average annual incidence was 0.10/105, showing a significant downward trend (P<0.05). The epidemic encephalitis B cases were concentrated from July to August, and July was the peak month, with 40 cases accounting for 81.63%. There was a statistically significant difference in the average annual incidences of epidemic encephalitis B among counties (districts) (P<0.05). Nanxun District had the highest reported incidence, with an average annual incidence of 0.23/105. There were 30 male cases and 19 female cases, with a male-to-female ratio of 1.58∶1. The youngest case was 5 months old, and the oldest was 49 years old. The children under 15 years were in the majority, with 42 cases accounting for 85.71%. Most of the cases were scattered children, with 25 cases accounting for 51.02%. There were 22 cases with no vaccination history and 21 cases with an unknown vaccination history, accounting for 44.90% and 42.86% respectively. All cases presented with fever. Other main clinical symptoms included listlessness, drowsiness, vomiting and headache, with 47, 40, 33 and 29 cases respectively, accounting for 95.92%, 81.63%, 67.35% and 59.18%, respectively. Conclusions The incidence of epidemic encephalitis B in Huzhou City remained at a relatively low level from 2007 to 2023, with Nanxun District being the high-risk area and July being the peak month for disease incidence. Fever and listlessness were the predominant clinical manifestations. Strengthening vaccination for children under 15 years should be prioritized.

Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .

ObjectiveTo investigate the seroprevalence of Japanese encephalitis virus (JEV) IgG antibodies among the healthy individuals in Huzhou City, Zhejiang Province, so as to provide a scientific basis for the development of prevention and control strategies for Japanese B encephalitis (JE). MethodsA cross-sectional study was conducted from 2023 to 2024. Serum samples were collected from healthy individuals across 12 age groups (<8 months, 8 months‒<2 years, 2‒<4 years, 4‒<6 years, 6‒<8 years, 8‒<10 years, 10‒<15 years, 15‒<20 years, 20‒<30 years, 30‒<40 years, 40‒<50 years, 50‒ years) and tested for JEV IgG antibody to determine positivity rates. ResultsThe overall JEV IgG antibody seroprevalence rate was 57.75 % among the healthy individuals in Huzhou City. The positivity rates for the age groups of <8 months, 8 months‒<2 years, 2‒<4 years, 4‒<6 years, 6‒<8 years, 8‒<10 years, 10‒<15 years, 15‒<20 years, 20‒<30 years, 30‒<40 years, 40‒<50 years, and 50‒ years were 10.14%, 23.76%, 77.31%, 66.88%, 73.87%, 58.33%, 41.67%, 55.06%, 47.00%, 61.00%, 62.00%, and 92.00%, respectively, with a statistically significant difference observed in different age groups (χ²=243.996, P<0.001). Seroprevalence rates also differed significantly between males and females (χ²=9.999, P=0.002). Among subjects vaccinated with 0,1 or 2 doses of live attenuated Japanese encephalitis virus vaccine (JEV-L), the IgG antibody seroprevalence rate was 4.76%, 27.27% and 72.33%, respectively (χ²=108.568, P<0.001). Within the 2 doses group, the IgG antibody seroprevalence rate at <1 year, 1 year, 2 years and 3‒5 years after immunization were 80.85%, 77.36%, 66.67% and 65.45%, respectively, indicating a declining trend with time increased since vaccination (Z=-2.024, P=0.043). ConclusionAdults aged 50‒ years maintain high antibody levels, whereas levels are lower among the age groups of <2 years and 8‒<30 years and wane with time since vaccination in Huzhou City. It is recommended to maintain the routine JE vaccination schedule while exploring booster vaccination strategies for the age groups of 8‒<30 years, in order to enhance population immunity against JEV.

Objective To explore the application value of preoperative nebulized inhalation of esket-amine in pediatric snoring surgery under general anesthesia.Methods A total of 145 children who were sched-uled to undergo elective pediatric snoring surgery in this hospital from January to December 2023 were select-ed and divided into the control group,the NC group and the ES group by random number table method,with 48,49,48 cases in each group,respectively.The control group was given routine preoperative preparations,the NC group was nebulized and inhaled normal saline before the operation,and the ES group was nebulized and inhaled esketamine solution before the operation.The awakening time,extubation time,post-anesthesia care u-nit(PACU)stay time,direct care time,choking cough score after awakening,visual analogue scale(VAS)for pain,restlessness score,incidence of restlessness and occurrence of adverse reactions were compared among the three groups of children.Results Compared with the control group and the NC group,the recovery time,ex-tubation time,PACU stay time,direct care time,choking cough score after awaking,VAS,restlessness score and the incidence of restlessness in the ES group were significantly decreased(P＜0.05).There was no statis-tically significant difference in the above indicators between the NC group and the control group(P＞0.05).No adverse reactions occurred in any of the three groups of children during the recovery period from general anesthesia.Conclusion Preoperative nebulized inhalation of esketamine can effectively accelerate the recovery and extubation time of children undergoing general anesthesia for snoring surgery,alleviate choking,pain and restlessness reactions,and reduce direct care time.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.