Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

TRIM32(tripartite motif protein 32,TRIM32)plays an important role in cell differentiation and proliferation and is involved in a variety of biological processes,including signal transduction,apop-tosis,and gene expression regulation.In the previous study,our group found that TRIM32 knockout mice are less susceptible to methamphetamine(MA)addiction.The aim of this study was to investigate the effect of silencing TRIM32 by siRNA(small interfering RNA)transfection on the apoptosis of neuronal cells caused by MA addiction and its mechanism.In this paper,the expression of TRIM32 was silenced by siRNA in PC 12 cells,and subgroups were established:the normal control group,MA-treated group,TRIM32-silencing group,and TRIM32-silenceing+MA-treated group.The apoptosis of cells in each group was detected using in situ terminal deoxynucleotyl transferase-mediated dUTP-biotin nick end labe-ling assay(TUNEL staining),and the results showed that the percentage of cells in the TRIM32-silence-ing+MA-treated group was lower than the MA-treated group(P＜0.01),indicating that TRIM32 silen-cing could inhibit MA-induced apoptosis.We also detected the changes of mitochondrial membrane po-tential in each group,which was increased in the TRIM32-silenceing+MA-treated group compared with the MA treatment group(P＜0.05),indicating that TRIM32 silencing could regulate the MA-induced de-crease in mitochondrial membrane potential.The results of cellular immunofluorescence and Western blotting showed that the protein levels of cystatinase-3(caspase-3),cleaved-caspase-3(cleaved-caspase-3),and cytochrome c(Cyt-C)were significantly down-regulated in the TRIM32-silencing+MA-treated group compared with the MA-treated group(P＜0.01)and phosphatidylinositol 3-kinase(PI3K)and phospho-protein kinase B(p-AKT)were significantly up-regulated(P＜0.01),suggesting that silencing of TRIM32 to inhibit apoptosis may be achieved by modulating the PI3K/AKT signaling pathway.On the basis of this in-depth study,the PI3K/AKT inhibitor LY294002 was added to the experiment,and the results confirmed that LY294002 could partially block apoptosis by silencing TRIM32(P＜0.05),which further confirmed that TRIM32 silencing inhibited MA through activation of the PI3K/AKT signaling.In conclusion,silencing TRIM32 could inhibit the mitochondrial apoptotic pathway triggered by MA addic-tion,thus exerting a neuroprotective effect,and the mechanism may be related to the PI3K/AKT signa-ling pathway.

Objective:To investigate the clinical characteristics and prognosis of single center adult chronic myeloid leukemia in chronic phase(CML-CP).Methods:Clinical data of 41 adult CML-CP patients in Department of Hematology,Shanghai Fengxian District Central Hospital from January 2015 to May 2021 were retrospectively analyzed.The clinical characteristics and prognosis of patients between＜60 years group and ≥ 60 years group were compared.Results:The 41 patients included 27(65.9％)males and 14(34.1％)females.The median age of the patients was 56(19-84)years,with 22 cases(53.7％)＜60 years and 19 cases(46.3％)≥60 years.Univariate analysis indicated that the proportions of patients with comorbidities,intermediate/high-risk Sokal score,myelofibrosis,and lactate dehydrogenase ≥1 000 U/L were significantly increased in ≥60 years group compared with＜60 years group at initial diagnosis(all P＜0.05).There were no statistical differences in the distribution of sex,ELST score,white blood cell count,platelet count,peripheral blood basophil percentage,peripheral blood eosinophil percentage and bone marrow primitive cell percentage between the two groups(P＞0.05).The proportion of patients taking reduced-dose imatinib in≥60 years group significantly increased(P＜0.001).Patients＜60 years had a higher proportion of molecular biological remission after treatment of tyrosine kinase inhibitors(TKIs)than patients ≥ 60 years(P＜0.001).The incidence of non-hematologic adverse reactions to TKI therapy significantly increased in patients ≥ 60 years(P＜0.001).Multivariate analysis showed that no adverse factors affecting the efficacy and prognosis of TKI.Conclusion:Compared with adult CML-CP patients＜60 years,patients ≥ 60 years gain fewer benefits from TKI treatment and increased adverse reactions.

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12β-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.
Humans ; Female ; Marsdenia ; Molecular Docking Simulation ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Ovarian Neoplasms/genetics* ; Databases, Genetic ; Plant Extracts ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVES: To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN. METHODS: The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups. RESULTS: A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05). CONCLUSIONS There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.
Child ; Humans ; Antineoplastic Agents, Phytogenic/adverse effects* ; Cohort Studies ; Peripheral Nervous System Diseases/diagnosis* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Vincristine/adverse effects* ; Infant ; Child, Preschool ; Adolescent

Cancer is a major public health problem worldwide, causing an more serious burden of disease. Inflammation is considered a predisposing factor for cancer with close relationship with its incidence. In recent years, the public and epidemiologists has paid more attention to the association between nutrition and cancer and other chronic diseases in the perspective of inflammation. This paper summarizes the development and application of the diet-related inflammatory index in cancer epidemiological studies based on the literature retrieval of common diet-related inflammatory index. Firstly, we highlight the common diet-related inflammatory indices and their construction methods, such as the Dietary Inflammatory Index, a literature-derived diet-related inflammatory index, and the Empirical Dietary Inflammatory Index, an empirically derived diet-related inflammatory index, and so on. Secondly, the epidemiological research progress on the commonly used diet-related inflammatory indices is briefly introduced. Finally, the advantages and disadvantages of the two types of this inflammatory indices are also briefly described for the purpose of providing reference for nutrition epidemiological studies of cancer and other chronic diseases in China.
Humans ; Diet ; Inflammation ; Neoplasms/epidemiology* ; Epidemiologic Studies ; Chronic Disease

Objective: To evaluate the efficacy and prognosis of orthopedic surgical resection surgery in patients with newly diagnosed multiple myeloma (NDMM). Methods: This retrospective cohort study collected clinical data of patients with NDMM who underwent surgery due to spinal cord compression or pathological long-bone fractures at the Peking Union Medical College Hospital from 1 January 2003 to 31 December 2021. Patients who received biopsy or vertebroplasty/kyphoplasty were excluded and patients with the same degree of bone disease and who did not undergo any surgical intervention were selected as controls. Visual analogue scale (VAS) and physical status (ECOG) scores, progression-free survival (PFS), and overall survival (OS) were compared. Statistical analysis included the χ²-test, t-test, and Kaplan-Meier methods. Results: Baseline data were compared between the surgical group (n=40 with 43 interventions) and the non-surgical group (n=80), and included sex, age, paraprotein type, International Staging System (ISS), number of lytic lesions, cytogenetic abnormalities, first-line treatment, and the proportion of patients receiving autologous stem cell transplantation (ASCT) (all P>0.05). Serum M protein levels in the surgical group were significantly lower than those of the non-surgical group [(21.95±16.44) g/L vs. (36.18±20.85) g/L, P=0.005]. The surgical lesions involved the axial skeleton (79.1%, 34/43) or the extremities (20.9%, 9/43). VAS and ECOG scores improved significantly after surgery (VAS: 2.30±0.80 vs. 6.60±1.50, P<0.001; ECOG: 2.09±0.59 vs. 3.09±0.73, P<0.001). The median follow-up time was 51 months. Kaplan-Meier survival analysis suggested that the median PFS (25 vs. 29 months) and OS (46 vs. 60 months) were comparable between the surgical and non-surgical intervention groups (both P>0.05). Subgroup analysis showed that among patients with ISS Ⅰ or those who had received ASCT, PFS in the surgical group was similar to that of the non-surgical intervention group (both P>0.05), while OS was worse (P=0.005, 0.017). Patients with ISS Ⅱ/Ⅲ scores or without ASCT had similar PFS and OS between the surgical and non-surgical intervention groups (all P>0.05). Cox multivariate analysis suggested that ISS and ASCT were independent prognostic factors for OS (ISS: HR=0.42, 95%CI 0.19-0.93, P=0.031; ASCT: HR=0.41, 95%CI 0.18-0.97, P=0.041), while orthopedic surgery did not influence survival (P=0.233). Conclusion: For patients with NDMM, orthopedic surgical resection decreased bone-related complications and improved quality of life, but did not affect survival.
Humans ; Prognosis ; Multiple Myeloma/diagnosis* ; Hematopoietic Stem Cell Transplantation/methods* ; Retrospective Studies ; Quality of Life ; Transplantation, Autologous ; Orthopedic Procedures ; Treatment Outcome

Objective: To explore an automatic landmarking method for anatomical landmarks in the three-dimensional (3D) data of the maxillary complex and preliminarily evaluate its reproducibility and accuracy. Methods: From June 2021 to December 2022, spiral CT data of 31 patients with relatively normal craniofacial morphology were selected from those who visited the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The sample included 15 males and 16 females, with the age of (33.3±8.3) years. The maxillary complex was reconstructed in 3D using Mimics software, and the resulting 3D data of the maxillary complex was mesh-refined using Geomagic software. Two attending physicians and one associate chief physician manually landmarked the 31 maxillary complex datasets, determining 24 anatomical landmarks. The average values of the three expert landmarking results were used as the expert-defined landmarks. One case that conformed to the average 3D morphological characteristics of healthy individuals' craniofacial bones was selected as the template data, while the remaining 30 cases were used as target data. The open-source MeshMonk program (a non-rigid registration algorithm) was used to perform an initial alignment of the template and target data based on 4 landmarks (nasion, left and right zygomatic arch prominence, and anterior nasal spine). The template data was then deformed to the shape of the target data using a non-rigid registration algorithm, resulting in the deformed template data. Based on the unchanged index property of homonymous landmarks before and after deformation of the template data, the coordinates of each landmark in the deformed template data were automatically retrieved as the automatic landmarking coordinates of the homonymous landmarks in the target data, thus completing the automatic landmarking process. The automatic landmarking process for the 30 target data was repeated three times. The root-mean-square distance (RMSD) of the dense corresponding point pairs (approximately 25 000 pairs) between the deformed template data and the target data was calculated as the deformation error of the non-rigid registration algorithm, and the intra-class correlation coefficient (ICC) of the deformation error in the three repetitions was analyzed. The linear distances between the automatic landmarking results and the expert-defined landmarks for the 24 anatomical landmarks were calculated as the automatic landmarking errors, and the ICC values of the 3D coordinates in the three automatic landmarking repetitions were analyzed. Results: The average three-dimensional deviation (RMSD) between the deformed template data and the corresponding target data for the 30 cases was (0.70±0.09) mm, with an ICC value of 1.00 for the deformation error in the three repetitions of the non-rigid registration algorithm. The average automatic landmarking error for the 24 anatomical landmarks was (1.86±0.30) mm, with the smallest error at the anterior nasal spine (0.65±0.24) mm and the largest error at the left oribital (3.27±2.28) mm. The ICC values for the 3D coordinates in the three automatic landmarking repetitions were all 1.00. Conclusions: This study established an automatic landmarking method for three-dimensional data of the maxillary complex based on a non-rigid registration algorithm. The accuracy and repeatability of this method for landmarking normal maxillary complex 3D data were relatively good.
Male ; Female ; Humans ; Adult ; Imaging, Three-Dimensional/methods* ; Reproducibility of Results ; Algorithms ; Software ; Tomography, Spiral Computed ; Anatomic Landmarks/anatomy & histology*

OBJECTIVE: To explore an efficient and automatic method for determining the anatomical landmarks of three-dimensional(3D) mandibular data, and to preliminarily evaluate the performance of the method. METHODS: The CT data of 40 patients with normal craniofacial morphology were collected (among them, 30 cases were used to establish the 3D mandibular average model, and 10 cases were used as test datasets to validate the performance of this method in determining the mandibular landmarks), and the 3D mandibular data were reconstructed in Mimics software. Among the 40 cases of mandibular data after the 3D reconstruction, 30 cases that were more similar to the mean value of Chinese mandibular features were selected, and the size of the mandibular data of 30 cases was normalized based on the Procrustes analysis algorithm in MATLAB software. Then, in the Geomagic Wrap software, the 3D mandibular average shape model of the above 30 mandibular data was constructed. Through symmetry processing, curvature sampling, index marking and other processing procedures, a 3D mandible structured template with 18 996 semi-landmarks and 19 indexed mandibular anatomical landmarks were constructed. The open source non-rigid registration algorithm program Meshmonk was used to match the 3D mandible template constructed above with the tested patient's 3D mandible data through non-rigid deformation, and 19 anatomical landmark positions of the patient's 3D mandible data were obtained. The accuracy of the research method was evaluated by comparing the distance error of the landmarks manually marked by stomatological experts with the landmarks marked by the method of this research. RESULTS: The method of this study was applied to the data of 10 patients with normal mandibular morphology. The average distance error of 19 landmarks was 1.42 mm, of which the minimum errors were the apex of the coracoid process [right: (1.01±0.44) mm; left: (0.56±0.14) mm] and maximum errors were the anterior edge of the lowest point of anterior ramus [right: (2.52±0.95) mm; left: (2.57±1.10) mm], the average distance error of the midline landmarks was (1.15±0.60) mm, and the average distance error of the bilateral landmarks was (1.51±0.67) mm. CONCLUSION The automatic determination method of 3D mandibular anatomical landmarks based on 3D mandibular average shape model and non-rigid registration algorithm established in this study can effectively improve the efficiency of automatic labeling of 3D mandibular data features. The automatic determination of anatomical landmarks can basically meet the needs of oral clinical applications, and the labeling effect of deformed mandible data needs to be further tested.
Humans ; Imaging, Three-Dimensional/methods* ; Mandible/diagnostic imaging* ; Software ; Algorithms ; Anatomic Landmarks/anatomy & histology*