Objective: To investigate the effect of neurite outgrowth inhibitor extracellular peptide residues 1-40 (NEP1-40) combined with poly (lactic-co-glycolic acid) (PLGA) and gelatin electrospun fiber membrane on facial nerve repair in rats. Methods: According to the principle of random grouping, 108 male SD rats were divided into four groups (n = 27 in each group, approved by the ethics committee), namely, the sham group, control group, PLGA group, and NEP1-40 + PLGA group. A facial nerve fracture model was established for all of the groups except for the sham group. The control group received no further treatment, the PLGA group and the NEP1-40+PLGA group were supported by PLGA membrane, and the NEP1-40+PLGA group received one immediate local injection of NEP1-40 (5 μg/μL) at a dose of 10 μL. Facial nerve function analysis, electrophysiological examination, transmission electron microscope observation, HE staining, and immunohistochemical staining of myelin marker S100β and axonal marker β3-tubulin were used to evaluate the recovery of injured facial nerves of rats at 2, 4 and 8 weeks. Results : At 8 weeks, the facial nerve function score of the NEP1-40+PLGA group was better than that of the control group and PLGA group (P < 0.001), and facial nerve function was significantly restored. Electrophysiological examination of nerve action potentials at the injured facial nerve showed that the amplitude in the NEP1-40+PLGA group was higher than that of the control group and PLGA group (P < 0.001), but there was no significant difference in latency and conduction velocity results between the groups (P > 0.05). At 2, 4, and 8 weeks, transmission electron microscopy showed that the number of myelinated nerve fibers and myelin sheath thickness in the cross-section of the injured facial nerve in the NEP1-40+PLGA group were greater than those in the other groups (P < 0.05). At 8 weeks, HE staining showed that the facial nerves in the control group had partially recovered, but the overall cell distribution was uneven and the boundary with surrounding tissues was slightly blurred. In contrast, the NEP1-40+PLGA group had a relatively uniform cell distribution and a clearer boundary with surrounding tissues. At 2, 4, and 8 weeks, the immunohistochemical results showed that in the cross-section of the injuried facial nerve, NEP1-40 increased the expression of neural markers S100 β and β3-tubulin, especially β3-tubulin, which was close to normal levels (P > 0.05) Conclusion NEP1-40 is beneficial for the generation of new myelin sheaths and axons at the site of injury, and it can promote the repair and regeneration of injured facial nerves to a certain extent, thus accelerating the recovery of injured nerve function.

Objective To investigate the clinical characteristics and influencing factors of thyroid function abnormality (TFA) in patients with malignant tumors receiving programmed death-1 (PD-1) inhibitor therapy, and its correlation with PD-1 inhibitors. Methods A retrospective analysis was conducted on the clinical data and biochemical indicators of 669 patients with malignant tumors who received PD-1 inhibitor therapy. Of these, 561 patients maintained normal thyroid function (normal group), while 108 developed TFA (TFA group). Baseline characteristics, PD-1 inhibitor type, tumor type, and other indice were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to identify related factors for TFA development. Additionally, the relationship between PD-1 inhibitors and TFA types was further analyzed within the TFA group. Results The rates of patients treated with pembrolizumab and with respiratory tumors were significantly higher in TFA group than those in the normal group (P＜0.01). Multivariate logistic regression analysis revealed that treatment with pembrolizumab and with respiratory tumor increased 5.350 and 1.514 times than tislelizumab and digestive tumor for risk of TFA development, respectively (P＜0.01). Within the TFA group, hypothyroidism was the predominant type (75, 69.4%); treatment with pembrolizumab increased 2.999 times than tislelizumab for development risk of hyperthyroidism (P＝0.042). Conclusions Among patients with malignant tumors treated with PD-1 inhibitors, pembrolizumab is more frequently associated with TFA, and patients with respiratory tumors were at a higher risk of developing TFA. Clinicians should closely monitor thyroid function in patients with respiratory tumors treated with pembrolizumab.

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

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Establishing a comprehensive mechanism for the initiation and review of investigator-initiated trial(IIT) plays an important role in ensuring the scientific validity of clinical research and improving research quality.Since 2021, Zhongshan Hospital affiliated to Fudan University had actively explored improvements in the project management of IIT. The hospital had established a standardized grading review management process, developed an integrated clinical research management system, established a three-level clinical research training system, built a methodological support platform, and formulated research plan templates, gradually formed a standardized grading project approval review management mode. As of February 2024, the hospital had completed 400 quick reviews and more than 400 expert letter reviews based on the integrated clinical research management system. The efficiency and quality of IIT project approval had been improved. At the same time, over 40 academic salons and forums had been held, cultivating a group of young clinical research talents, providing data management training for more than 30 clinical departments, and promoting the improvement of the quality of research protocol. In the future, hospitals should further optimize their information systems, expand the influence of their training systems, enhance the capabilities of their methodological support platforms, and improve the efficiency of the application of clinical research protocol templates, so as to escort the establishment and implementation of high-quality clinical research projects and provide references for other hospitals′ IIT project management.

Objective:To explore whether transjugular intrahepatic portosystemic shunt (TIPS) can improve the prognosis of esophagogastric variceal bleeding (EGVB) combined with sarcopenia in cirrhotic patients.Methods:A retrospective cohort study was performed. A total of 464 cases with cirrhotic EGVB who received standard or TIPS treatment between January 2017 and December 2019 were selected. Regular follow-up was performed for the long-term after treatment. The primary outcome was transplantation-free survival. The secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). The obtained data were statistically analyzed. The t-test and Wilcoxon rank-sum test were used to compare continuous variables between groups. The χ2 test, or Fisher's exact probability test, was used to compare categorical variables between groups. Results:The age of the included patients was 55.27±13.86 years, and 286 cases were male. There were 203 cases of combined sarcopenia and 261 cases of non-combined sarcopenia. The median follow-up period was 43 months. The two groups had no statistically significant difference in follow-up time. There was no statistically significant difference in transplant-free survival between the TIPS group and the standard treatment group in the overall cohort ( HR=1.31, 95% CI: 0.97-1.78, P=0.08). The TIPS patient group with cirrhosis combined with sarcopenia had longer transplant-free survival (median survival: 47.76 vs. 52.45, χ2=4.09; HR=1.55, 95 CI: 1.01~2.38, P=0.04). There was no statistically significant difference in transplant-free survival between the two kinds of treatments for patients without sarcopenia ( HR=1.22, 95% CI: 0.78~1.88, P=0.39). Rebleeding time was prolonged in TIPS patients with or without sarcopenia combination (patients without combined sarcopenia: median rebleeding time: 39.48 vs. 53.61, χ2=18.68; R=2.47, 95 CI: 1.67~3.65, P<0.01; patients with sarcopenia: median rebleeding time: 39.91 vs. 50.68, χ2=12.36; HR=2.20, 95 CI: 1.42~3.40, P<0.01). TIPS patients had an increased 1-year OHE incidence rate compared to the standard treatment group (sarcopenia patients: 6.93% vs. 16.67%, χ2=3.87, P=0.049; patients without sarcopenia combination: 2.19% vs. 9.68%, χ2=8.85, P=0.01). There was no statistically significant difference in the long-term OHE incidence rate between the two kinds of treatment groups ( P>0.05). Conclusion:TIPS can significantly prolong transplant-free survival compared to standard treatment as a secondary prevention of EGVB concomitant with sarcopenia in patients with cirrhosis. However, its advantage is not prominent for patients with cirrhosis in EGVB without sarcopenia.

Objective:To investigate the impact of early removal of nasogastric tubes on functional recovery after total gastrectomy for gastric cancer patients, to provide scientific evidence for enhanced recovery after surgery strategies in gastric cancer.Methods:A retrospective cohort study was conducted on 102 gastric cancer patients who underwent total gastrectomy at Beijing Friendship Hospital affiliated with the Capital Medical University from March 2018 to July 2022. Patients were divided into two groups based on whether the gastric tube was removed within 24 hours post-operation: the early removal group (within 24 hours, 55 patients) and the non-early removal group (beyond 24 hours, 47 patients). The recovery outcomes, including time to first flatus, time to fluid intake, length of hospital stay, and the incidence of postoperative complications, were compared between the two groups. Non-normally distributed data were expressed as M( Q1, Q3) and compared using the Wilcoxon rank-sum test. Categorical data were expressed as frequencies or percentages and compared using the chi-square test or Fisher′s exact test. To minimize the impact of potential confounders, multivariable linear regression and logistic regression analyses adjusted for propensity scores were further employed to compare quantitative and qualitative data between the groups. Statistical analyses were performed using R software. Results:The exhaust time, water intake time, and hospital stay in the early removal group were 3.0(2.0, 3.5) days, 4.0(3.0, 5.0) days, and 7.0(7.0, 8.0) days, respectively, while those in the non-early removal group were 4.0(3.0, 5.0) days, 6.0(5.0, 7.0) days, and 8.0(7.5, 11.0) days, respectively. Statistically significant differences were observed between the two groups ( P<0.05). However, there was no significant difference in the incidence of postoperative complications between the two groups (5.45% vs 17.02%, P=0.060). Propensity score-adjusted regression analysis suggested that early tube removal might reduce the risk of postoperative complications ( P=0.042). Conclusion:Early removal of nasogastric tubes can significantly accelerate functional recovery after total gastrectomy for gastric cancer patients and may reduce the risk of postoperative complications, providing important clinical guidance for enhanced recovery after surgery management in gastric cancer.

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.
Child ; Child, Preschool ; Consensus ; Dental Caries/prevention & control* ; Dental Caries Susceptibility ; Humans ; Oral Health