Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

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

Humans ; China/epidemiology* ; SARS-CoV-2 ; COVID-19

Objective:This study aimed to compare the detection efficacy of transrectal ultrasound-guided transrectal cognitive fusion targeted+ systematic prostate biopsy and transperineal cognitive fusion targeted + systematic biopsy in patients with suspected prostate cancer (PCa). In addition, the relative clinical characteristics of PCa were evaluated.Methods:A total of 385 patients with suspected prostate cancer in the affiliated hospital of Qingdao University from May 2019 to November 2019 were retrospectively analyzed. All patients met the prostate biopsy criterion, who underwent transrectal(n=275)and transperineal(n=110)prostate biopsy respectively. There were no significant differences of mean age [(70.7±7.3)years vs.(69.2±8.4) years], PSA [(55.12±116.96)ng/ml vs. (63.41±315.34)ng/ml], prostate volume [(55.96±35.26)ml vs. (64.35±55.99)ml] between two groups. According to preoperative prostate magnetic resonance imaging combined with intraoperative ultrasound, 2-4 needles targeted puncture of suspected lesion were performed, followed by 12 needle systematic prostate biopsy. The detection rate of prostate cancer between two biopsy ways were compared. The related factors of PCa including age, prostate volume and PSA level were collected for univariable and multivariable logistic analysis. The cancer detection rate was compared and logistic regression was used to assess the impact of patient characteristics on PCa detection.Results:For all patients, the detection rate with cancer between transrectal group and transperineal group were 121/275(40.0%) and 67/110(60.9%), respectively. The transperineal group detected a higher rate of PCa ( P=0.003)and more clinically significant prostate cancers (csPCa) (54.6% vs.36.7%, P=0.001) than that of the transrectal group, there were significant differences between two groups ( P<0.05). Univariate and multivariate logistic regression analysis revealed that PSA( OR=1.025, P=0.001) and prostate volume( OR=0.984, P=0.001)were two independent factors for the detection rate of prostate cancer between two biopsy ways( P<0.05). The effect of age on the detection rate of PCa in the transperieal group was significantly lower than that of the transrectal group( OR=0.037, P=0.238 vs. OR=0.053, P=0.002). Conclusion:The transperieal biopsy could find more PCa than the transrectal biopsy. PSA level and prostate volume could affect the detection rate of cancer between two prostate biopsy ways.

Objective    To evaluate the data of preoperative aortic root CT angiography (CTA), compare it with two-dimensional transthoracic echocardiography and investigate the correlation of the two measurements with the actual intraoperative measurement data. Methods    Clinical data of 53 patients with aortic valve diseases who underwent aortic valve repair in our hospital from January 2018 to August 2020 were retrospectively analyzed, including 38 males and 15 females with an average age of 42.9±18.3 years ranging from 10 to 77 years. Preoperative two-dimensional transthoracic echocardiography (TTE) and aortic root CTA measurements were collected, including aortic valve annulus (AVA), aortic sinus (Sinus) and sino-tubular junction (STJ). In comparison with the intraoperative measurements during the aortic valve repair surgery, the consistency analysis was performed. Results    Both the preoperative echocardiography AVA measurements and the CT AVA measurements were positively correlated with the intraoperative AVA measurements (P<0.001). Compared with the echocardiography AVA data [correlation coefficient (ρ)=0.74, mean squared error (MSE)=12.78], the CT AVA data were more accurate and consistent with the intraoperative AVA measurements (ρ=0.95, MSE=2.72). CT AVA data had a higher correlation coefficient with the intraoperative measurements, compared to that of  the echocardiography AVA data (P<0.001). Conclusion    In comparison with two-dimensional transthoracic echocardiography, preoperative morphological evaluation of aortic root CTA is more consistent with the actual intraoperative measurements during aortic valve repair surgery.

【Objective】 To optimize the existing spin-EB method and promote human induced pluripotent stem cells (hiPSCs) differentiate into megakaryocytes (MKs). 【Methods】 In this study, the initial inoculation amount of hiPSCs was increased from 3 500 cells/well to 8 000 cells/well, and the size of EB was increased. By observing the generation time of EB- hematopoietic cells during differentiation, and detecting the proliferation of CD34⁺ hematopoietic progenitor cells and CD41⁺ MKs in different stages, it was studied whether the optimized scheme could promote the differentiation of hiPSCs into hematopoietic progenitor cells(HPCs) and MKs. 【Results】 By increasing the initial inoculation amount of hiPSCs and the size of EB, the differentiation of hiPSCs into HPCs and MKs and the cell production efficiency can be promoted. 【Conclusion】 Our research describes an optimized and repeatable differentiation method, which can produce hematopoietic progenitor cells and mature MKs from hiPSCs in a relatively short time with higher yield. It is of great clinical significance and broad scientific research prospect to continuously optimize the culture scheme of hiPSCs differentiation to produce MKs and platelets in vitro, and to promote large-scale platelet generation in vitro in transfusion medicine.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

Objective To investigate the translation and rotation of healthy elbow joints during active flexion and extension, so as to provide references for the treatment of elbow instability and injuries. Methods Ten healthy subjects with no history of upper extremity trauma were recruited. Dual fluoroscopic imaging system (DFIS) was applied to quantify six-degree-of-freedom (6-DOF) kinematics of humeroulnar and humeroradial joint from full extension to maximum flexion in supination position. Correlation analysis was used to evaluate the relationship between the 6-DOF kinematics of the elbow joint. Results Valgus angle of humeroulnar joint gradually decreased from 15.2°±3.1° to 5.3°±2.3° with the flexion increasing. Valgus angle of humeroradical joint gradually decreased from 19.7°±4.2° to 8.2°±2.4° from full extension to maximum flexion. The valgus angle of humeroulnar and humeroradial joint was linearly related to the flexion angle during flexion and extension. The internal rotation of humeroulnar joint was quadratic nonlinearly related to the flexion angle during motion. The maximum internal rotation of the ulnar was 4.0°±4.9° at 110° flexion, and the maximum external rotation was 5.1°±4.2°. The internal rotation of humeroulnar joint gradually increased from 3.2°±16.0° to 27.2°±18.0°. Conclusions During normal flexion and extension of the elbow, the valgus angle of humeroulnar joint decreased linearly, while the internal and external rotation angle showed a nonlinear change, which first rotated internally and then rotated externally. The valgus angle of humeroradial joint decreased linearly and the internal rotation angle increased linearly. Therefore, humeroulnar joint is not a hinge joint during elbow flexion and extension. There is a kinematic difference between humeroulnar joint and humeroracial joint. For clinical treatment of complex elbow injuries, elbow instability and elbow replacement, different motion characteristics in joints should be considered to improve the outcome after surgery.

Objective To explore the management of spontaneous intraspinal hematoma.Methods From January 2011 to July 2018,29 cases with spontaneous intraspinal hematoma were admitted to our department.Date on etiology,clinical presentation,radiological features,treatment strategy and prognosis were analyzed retrospectively.The prognosis was assessed by American Spinal Injury Association impairment scale (ASIA) before and after the treatment.Results Total of 29 cases,only 10 cases (34.5％) revealed specific etiology,including 7 cases of spinal vascular malformation,2 of tumor apoplexy,1 of cavernous hemangioma.After 2 weeks of conservative treatment,3 patients with grade D and 3 patients with grade E were assessed for spinal function.The average interval from onset to surgery was(9.4±7.5) days,the ASIA after two weeks of the operation was as follows:5 patients were assessed at grade A,5 patients at grade C,8 patients at grade D and 4 patients at grade E.28 patients were followed up for (48.7±23.1) months on average,6 patients without surgery were E,22 cases with surgery were as follows:4 cases A,18 cases D/E.Conclusions The etiology of spontaneous intraspinal hematoma is hard to define even after complete preoperative examination and exploratory operation.The preoperative neurologic functions are important predicting factors for the prognosis of spontaneous intraspinal hematoma.For patients who had neurologic function deficit,surgical treatment should be performed urgently to remove the hematoma and release the decompression of spinal cord.The majority of these patients can achieve a positive prognosis after surgery.