Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

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*

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective To develop a diagnostic model combining the CT angiography(CCTA)-derived myocardial radiomics signatures with the CT-derived fractional flow reserve(CT-FFR)based on coronary CCTA and investigate the diagnostic accuracy of the hybrid model for hemodynamically significant coronary artery disease(CAD).Methods The patients presenting stable angina pectoris,diagnosed with CAD,and clinically referred for CCTA examination and invasive coronary angiography were prospectively recruited.Radiomics features of the left ventricular myocardium were extracted from the three main perfusion territories demarcated according to the coronary blood supply.The extracted features were first selected by the minimum redundancy maximum relevance feature ranking method.A least absolute shrinkage and selection operator Logistic regression algorithm with leave-one-out cross-validation was then employed to construct a radiomics model.The CT-FFR value was generated for each blood vessel.The area under the receiver operating characteristics curve(AUC_ROC),sensitivity,and specificity were adopted to evaluate the performance of each model against the reference standard invasive coronary angiography/FFR.Results A total of 70 patients[42 men and 28 women;(61±10) years old] were included in this study and complemented CCTA examination,with 175 vessels and the corresponding myocardial territories undergoing invasive coronary angiography/FFR.A total of 1 656 specific radiomics parameters were extracted,from which 14 features were selected to establish the radiomics model.The AUC_ROC,sensitivity,and specificity were 0.797(95%CI=0.732-0.861),77.1%,and 73.7%for the radiomics model,0.892(95%CI=0.841-0.943),81.4%,and 88.8%for the CT-FFR model,and 0.928(95%CI=0.890-0.965),83.3%,and 88.4%for the hybrid model,respectively.The hybrid model outperformed the radiomics model and CT-FFR alone(P=0.040).Conclusions The radiomics signatures of the vessel-related myocardium from CCTA could provide incremental value to the diagnostic performance of CT-FFR and improve vessel-specific ischemia detection.The hybrid model combining CT-FFR with radiomics signatures is potentially feasible for improving the diagnostic accuracy for hemodynamically significant CAD.
Coronary Angiography/methods* ; Tomography, X-Ray Computed ; Humans ; Hemodynamics ; Coronary Artery Disease/diagnostic imaging* ; Male ; Female ; Middle Aged ; Aged ; Radiomics ; Angina Pectoris/diagnostic imaging* ; China ; Image Processing, Computer-Assisted ; Coronary Vessels/diagnostic imaging*

Objective:In this retrospective study, the accuracy and outcomes of segmental Le Fort I surgery with the aid of 3D-printed surgical templates and occlusal splints and dental model surgery were evaluated.Methods:Clinical data of patients receiving segmental Le Fort I surgery in the Department of Orthognathic and Temporo-Mandibular Joint Surgery of West China Stomatological Hospital of Sichuan University from January 2014 to June 2019 were retrospectively analyzed. The accuracy of virtual surgical planning(VSP) and the difference between VSP and dental model surgery were evaluated by postoperative complications, color distance maps, and quantitative accuracy analysis.The amount of surgical displacement of the maxilla in the three-dimensional direction before and after surgery, the occurrence of postoperative complications and the patients'satisfaction survey were analyzed in both groups. Paired t-tests were used for the linear distance and angle between the preoperative design model and the final virtual surgery model in the digital surgery group. Independent samples t-test was used for each marker point’s preoperative and postoperative displacements in the three-dimensional direction between the digital surgery group and the dental model group. The proportion of postoperative complications in the 2 groups was tested using the Pearson chi-square test, and the difference was considered statistically significant at P<0.05. Results:There were 129 patients in the digital surgery group, 35 males and 94 females, aged (24.5±6.5) years, and 92 patients in the dental model surgery group, 28 males and 64 females, aged (27.7±5.4) years.The overall mean linear difference was 1.23±0.35 mm, and the overall mean angular difference was 2.48°±0.31°. The vertical displacement of U3R, U6L in the digital surgery group was (6.72±1.57)mm and (4.73±2.07)mm. The vertical displacement of U3R, U6L in the group of dental model surgery was (4.07±2.14)mm and (1.62±1.82)mm.The significant deviation difference in U3R-Y and U6L-Y between two groups could be detected. The complications in two groups showed a significant difference. Except for one case of root injury, there was no serious complication recorded in the digital surgery group. However, there were three cases of palatal fistulas, four cases of root injury and two cases of bone dehiscence in the dental model group. 94.5% of patients in the digital surgery group are satisfied with the surgical results, while 89.1% in the dental model group.Conclusion:Compared with dental model surgery, segmental Le Fort I surgery is highly accurate under the guidance of surgical templates and occlusal splint which has better postoperative results and effectively reduces the occurrence of surgical complications.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Objective:In this retrospective study, the accuracy and outcomes of segmental Le Fort I surgery with the aid of 3D-printed surgical templates and occlusal splints and dental model surgery were evaluated.Methods:Clinical data of patients receiving segmental Le Fort I surgery in the Department of Orthognathic and Temporo-Mandibular Joint Surgery of West China Stomatological Hospital of Sichuan University from January 2014 to June 2019 were retrospectively analyzed. The accuracy of virtual surgical planning(VSP) and the difference between VSP and dental model surgery were evaluated by postoperative complications, color distance maps, and quantitative accuracy analysis.The amount of surgical displacement of the maxilla in the three-dimensional direction before and after surgery, the occurrence of postoperative complications and the patients'satisfaction survey were analyzed in both groups. Paired t-tests were used for the linear distance and angle between the preoperative design model and the final virtual surgery model in the digital surgery group. Independent samples t-test was used for each marker point’s preoperative and postoperative displacements in the three-dimensional direction between the digital surgery group and the dental model group. The proportion of postoperative complications in the 2 groups was tested using the Pearson chi-square test, and the difference was considered statistically significant at P<0.05. Results:There were 129 patients in the digital surgery group, 35 males and 94 females, aged (24.5±6.5) years, and 92 patients in the dental model surgery group, 28 males and 64 females, aged (27.7±5.4) years.The overall mean linear difference was 1.23±0.35 mm, and the overall mean angular difference was 2.48°±0.31°. The vertical displacement of U3R, U6L in the digital surgery group was (6.72±1.57)mm and (4.73±2.07)mm. The vertical displacement of U3R, U6L in the group of dental model surgery was (4.07±2.14)mm and (1.62±1.82)mm.The significant deviation difference in U3R-Y and U6L-Y between two groups could be detected. The complications in two groups showed a significant difference. Except for one case of root injury, there was no serious complication recorded in the digital surgery group. However, there were three cases of palatal fistulas, four cases of root injury and two cases of bone dehiscence in the dental model group. 94.5% of patients in the digital surgery group are satisfied with the surgical results, while 89.1% in the dental model group.Conclusion:Compared with dental model surgery, segmental Le Fort I surgery is highly accurate under the guidance of surgical templates and occlusal splint which has better postoperative results and effectively reduces the occurrence of surgical complications.

Objective:To explore the feasibility of constructing automatic intensity-modulated radiotherapy (IMRT) plans for cervical cancer based on Pinnacle scripts and to assess the advantages of this method in designing treatment plans for cervical cancer.Methods:A retrospective analysis was conducted for 40 cases of cervical cancer treated with IMRT in the department of radiation oncology of the First Affiliated Hospital of Bengbu Medical University. Among them, the data of 25 cases were employed as a reference for the initialization of objective functions. The scripts for automatic plans were designed in the Pinnacle planning system. For the remaining 15 cases, automatic and manual IMRT plans were designed (also referred to as the automatic planning group and the manual planning group, respectively). The design times of both groups were compared. Furthermore, both the dosimetric parameters of target volumes and the irradiation doses to organs at risk (OARs) were also compared between the two groups using dose-volume histograms.Results:Compared to the manual planning group, the automatic planning group exhibited a statistically significant decrease in the average design time of 32.81 min ( t = -12.91, P < 0.05), a statistically significant increase in the conformity index of the target areas of 0.01 ( t = -0.08, P < 0.05), and a decrease in the uniformity index of the target areas of 0.02. Compared to those of the manual planning group, the bladder′s V40 and V45 and the rectum′s V40 and V45 of the automatic planning group decreased by 6.88%, 4.12%, 9.93%, and 12% on average, respectively ( t = -4.49, -4.46, -3.62, -5.80, P < 0.05). Minimal differences were observed in the V30, V50, and Dmax of the small intestine between both groups, without statistically significant differences in V30 and Dmax ( P > 0.05). Compared to the manual planning group, the automatic planning group displayed decreases in the V45 and Dmeanof the bilateral femoral head of 7.9% and 106.83 cGy, respectively and a decrease in the spinal Dmax of 100.14 cGy, with statistically significant differences ( t = -6.00, -2.52, -2.55, P < 0.05). Conclusions:Automatic IMRT plans for cervical cancer, constructed based on Pinnacle scripts, can significantly reduce irradiation doses to OARs and enhance the efficiency of the plan design while ensuring dose uniformity and conformality of target areas.