Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Objective:To understand the current status and existing issues of intellectual property ownership arrangements in international cooperation agreements concerning human genetic resources, and to explore suggestions for medical institutions to strengthen the management of Sino-foreign cooperation agreements, in order to safeguard the rights of medical institutions to benefit-sharing and promote the sustainable development of international cooperation involving human genetic resources.Methods:This study reviewed the international cooperative scientific research projects approved or completed for filing by Peking University Cancer Hospital on the National Health Commission′s Government Service Platform from July 2019 to December 2024. This study analyzed the nature of the research and the provisions regarding patent rights and intellectual property rights of other scientific and technological achievements in the hospital′s international cooperation agreements with sponsors. Existing issues in intellectual property ownership arrangements was summarized, and corresponding recommendations were proposed.Results:A total of 390 international cooperation projects on human genetic resources were analyzed. Among them, there were 66 exploratory research projects, 138 marketing research projects, and 186 projects included both exploratory research and marketing research. Among the cooperation agreements containing exploratory research, 78.6% did not specify the specific connotation of exploratory research. All agreements stipulated that the hospital alone or jointly held the patent rights for the achievements generated from exploratory research. 15.1% of the agreements restricted the geographical scope of the patent rights, 13.1% restricted the hospital′s implementation of the patent rights, 8.7% unilaterally restricted the hospital's external licensing and transfer of the patent rights, and 43.7% did not stipulate the ownership of other scientific and technological achievements other than the patent rights.Conclusions:There is a lack of clear and standardized regulations regarding the scope of exploratory research. The intellectual property arrangements in the agreements show an interest-oriented tendency. The sponsors restrict the implementation, transfer, and licensing of shared patent rights by medical institutions through agreements. For other scientific and technological achievements derived from the cooperation, apart from patent rights, medical institutions have not fully exercised the rights stipulated by law. It is recommended that medical institutions clearly specify the scope of application of exploratory research. They should pay attention to the stipulations of specific rights such as the right to enforce, transfer, and license patents. They should also make full use of the enabling provisions of the law, clearly define in the agreement the ownership of other scientific and technological achievements and the distribution of rights and interests, so as to achieve a balance of interests with their partners.

Objective To investigate the ameliorative effect of deferoxamine(DFO)on cognitive impairment in a rat model of type 1 diabetes mellitus(T1DM)and to elucidate the molecular mechanisms underlying cerebral iron overload in T1DM rats.Methods Thirty-six healthy male SD rats(weighing 180～250 g)were randomly assigned into a blank control group(Ctrl),a T1DM model group and a DFO group,with 12 rats in each group.A single dose of 65 mg/kg streptozotocin(STZ)was intraperitoneally injected to the rats to establish a T1DM model,and those with fasting blood glucose≥16.7 mmol/L at 3 d later were designated as the T1DM group.Intracerebroventricular administration of DFO(5 μg/kg·d)was given to the DFO group for 28 consecutive days since 21 d after STZ injection.Morris water maze test was carried out to assess the spatial learning and memory abilities.Nissl staining and immunofluorescence assay were applied to observe neuronal morphology and number in the hippocampus and cortex.The iron content in the hippocampus was measured with inductively coupled plasma mass spectrometry(ICP-MS).The expression levels of iron metabolism related proteins were detected with Western blotting.Results In the T1DM group,significant declines in learning and memory abilities(P<0.01)and impaired neuronal morphology and reduced neuronal counts in the hippocampal CA1 region(P<0.01),CA3 region(P<0.01),and cortex(P<0.05)were observed when compared with those in the Ctrl group.ICP-MS analysis showed a marked increase in the hippocampal iron content in the T1DM group(P<0.01).Western blot results demonstrated that T1DM rats exhibited obviously up-regulated expression of iron storage proteins FTH and FTL in both the hippocampus(P<0.01,P<0.05)and the cortex(P<0.05,P<0.01),enhanced expression of iron import protein DMT1 in both the hippocampus and the cortex(P<0.05),while decreased expression of iron export protein FPN1 in the hippocampus(P<0.01)and the cortex(P<0.05).DFO treatment significantly ameliorated all above abnormalities.Conclusion The declines in learning and memory in T1DM rats are closely associated with neuronal damage induced by cerebral iron overload.Iron import protein DMT1 and export protein FPN1 jointly regulate cerebral iron content in T1DM rats.DFO reduces brain iron levels and mitigates iron overload-mediated neuronal injury by modulating the expression of DMT1 and FPN1.

Objective:To understand the current status and existing issues of intellectual property ownership arrangements in international cooperation agreements concerning human genetic resources, and to explore suggestions for medical institutions to strengthen the management of Sino-foreign cooperation agreements, in order to safeguard the rights of medical institutions to benefit-sharing and promote the sustainable development of international cooperation involving human genetic resources.Methods:This study reviewed the international cooperative scientific research projects approved or completed for filing by Peking University Cancer Hospital on the National Health Commission′s Government Service Platform from July 2019 to December 2024. This study analyzed the nature of the research and the provisions regarding patent rights and intellectual property rights of other scientific and technological achievements in the hospital′s international cooperation agreements with sponsors. Existing issues in intellectual property ownership arrangements was summarized, and corresponding recommendations were proposed.Results:A total of 390 international cooperation projects on human genetic resources were analyzed. Among them, there were 66 exploratory research projects, 138 marketing research projects, and 186 projects included both exploratory research and marketing research. Among the cooperation agreements containing exploratory research, 78.6% did not specify the specific connotation of exploratory research. All agreements stipulated that the hospital alone or jointly held the patent rights for the achievements generated from exploratory research. 15.1% of the agreements restricted the geographical scope of the patent rights, 13.1% restricted the hospital′s implementation of the patent rights, 8.7% unilaterally restricted the hospital's external licensing and transfer of the patent rights, and 43.7% did not stipulate the ownership of other scientific and technological achievements other than the patent rights.Conclusions:There is a lack of clear and standardized regulations regarding the scope of exploratory research. The intellectual property arrangements in the agreements show an interest-oriented tendency. The sponsors restrict the implementation, transfer, and licensing of shared patent rights by medical institutions through agreements. For other scientific and technological achievements derived from the cooperation, apart from patent rights, medical institutions have not fully exercised the rights stipulated by law. It is recommended that medical institutions clearly specify the scope of application of exploratory research. They should pay attention to the stipulations of specific rights such as the right to enforce, transfer, and license patents. They should also make full use of the enabling provisions of the law, clearly define in the agreement the ownership of other scientific and technological achievements and the distribution of rights and interests, so as to achieve a balance of interests with their partners.

Objective To investigate the effect of fibroblast growth factor receptor 3(FGFR3)on articular cartilage superficial zone cells(SPZCs).Methods C57 mice were randomly divided into two groups:a sham operated group(sham group)and a group of surgically induced unstable medial meniscus model group(DMM group).The histological morphology of articular cartilage was microscopied by Safranin O/Fast Green-stained in 4 weeks and 8 weeks after surgery.Apoptosis and FGFR3 protein expression were detected by immunohistochemical staining mi-croscopy.Primary SPZCs were separated and randomly divided into control group and Fgfr3 knockdown treatment group.The genes and protein expression related to chondrocyte extra cellular matrix synthesis,degradation and chondrocytehypertrophy were detected by RT-qPCR and Western blot.Results Compared with the sham group,the keen cartilage of mice in DMM group showed a pioneer damage of SPZCs after surgery;Immunohistochemistry results showed an increase in chondrocyte apoptosis and a decrease in expression of MMP-13 and FGFR3(P＜0.05).Primary SPZCs were transfected with small interfering RNA(siRNA)to knockdown Fgfr3;RT-qPCR results showed that the mRNA expression of genes related to the synthesis of cartilage extracellular matrix aggrecan and Col2 was reduced;And the mRNA expression of extracellular matrix degradation-related genes Mmp13 and Adamts5 was increased.The mRNA expression of chondrocyte hypertrophy-related genes Col10 and Mmp13 was increased.Western blot and RT-qPCR results were consistent and the expression l of MMP13 protein was significantly increased,while the expression of collagenⅡand aggrecan protein was significantly decreased(P＜0.05).Conclusions Knockdown of Fgfr3 induces damage to primary SPZCs in mice resulting in early osteoarthritis(OA)development.

Objective By using high-resolution magnetic resonance angiography to display the vascular wall imaging so as to evaluate the relationship between plaque characteristics and postoperative in-stent restenosis(ISR)in patients with middle cerebral artery stenosis.Methods A total of 66 patients with symptomatic atherosclerotic middle cerebral artery stenosis,who were admitted to the Affiliated Hospital of Chengde Medical College of China from January 2019 to March 2023,were enrolled in this study.Before stent implantation,all the 66 patients completed high-resolution magnetic resonance angiography.According to the postoperative imaging follow-up results,the patients were divided into ISR group and non-ISR group.The preoperative plaque characteristics,which were assessed by high-resolution magnetic resonance imaging,were compared between the two groups.Results ISR group had 14 patients and non-ISR group had 52 patients.Most of the plaques were located in the inferior lateral wall(37.8％)and the ventral lateral wall(28.7％),in which no statistically significant difference existed between the two groups(P＞0.05).Compared with non-ISR group,in ISR group the negative remodeling degree was obviously higher and the difference between the two groups was statistically significant(x2=6.026,P=0.049).The plaque load in ISR group and non-ISR group was 79.09±8.82 and 69.46±10.49 respectively,and the difference between the two groups was statistically significant(t=3.143,P=0.003).The homocysteine level in ISR group and non-ISR group was(16.02±4.24)mol/L and(12.05±3.34)mol/L respectively,and the difference between the two groups was statistically significant(t=3.717,P＜0.001).In ISR group,there were more significantly contrast-enhanced plaques(78.5％vs.42.3％),with statistically significant difference(x2=6.311,P=0.043).Multivariate logistic regression analysis showed that plaque load(OR=1.225,95％CI:1.040-1.443,P=0.015)and homocysteine level(OR=1.676,95％CI:1.150-2.442,P=0.007)were the independent risk factors for ISR.ROC curve analysis showed that in predicting ISR,the AUC,specificity and sensitivity of the plaque load were 0.765(95％CI:0.622-0.908,P=0.002),0.731 and 0.714 respectively,which of the homocysteine level were 0.767(95％CI:0.623-0.911,P=0.002),0.942 and 0.500 respectively.The combination use of plaque load and homocysteine level could achieve the best predictive effect,its AUC,specificity and sensitivity were 0.887(95％CI:0.794-0.981,P＜0.001),0.904 and 0.714 respectively.Conclusion The plaque load assessed by high-resolution magnetic resonance imaging and the homocysteine level have higher specificity and sensitivity in predicting ISR in patients with middle cerebral artery stenosis.

Objective:To investigate the effect of methylene blue (MB) on motor dysfunction and its mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse models.Methods:Forty healthy male C57BL/6 mice were randomly divided into 4 groups: control group, model group, low-dose treatment group and medium-dose treatment group ( n=10); PD mouse models were established by intraperitoneal injection of 25 mg/kg/d MPTP for a consecutive 7 d; low-dose treatment group and medium-dose treatment group were pretreated intraperitoneally with MB 2 mg/kg/d or MB 10 mg/kg/d for a consecutive 3 d, respectively; and then, MPTP 25 mg/kg/d+MB 2 mg/kg/d or MPTP 25 mg/kg/d+MB 10 mg/kg/d were injected intraperitoneally into the low-dose treatment group or medium-dose treatment group for a consecutive 7 d (MPTP and MB were given at 12 h of interval). Eight d after modeling, open field experiment, pole climbing experiment and rod rotating experiment were carried out to evaluate the spontaneous movement, coordination, endurance and motor ability. And then, the mice were sacrificed; immunofluorescent staining was used to observe tyrosine hydroxylase (TH) expression in the substantia nigra; Western blotting was used to detect the expressions of TH, α-synuclein, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-Caspase-1 and Gasdermin D (GSDMD) in the striatum and substantia nigra of mice. Contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-18 in the substantia nigra and striatum of mice were detected by ELISA. Results:Compared with the control group, the model group had shortened residence time in rod rotating, prolonged descent time in rod climbing, reduced total movement distance in open field, decreased number of TH-positive cells in the substania nigra, decreased TH protein levels in the substania nigra and striatum, and increased NLRP3, ASC, cleaved-Caspase-1, GSDMD and GSDMD-N protein levels in the substania nigra and striatum, and increased TNF-α, IL-1β and IL-18 contents in the substania nigra and striatum, with significant differences ( P<0.05). Compared with the model group, low-dose treatment group and medium-dose treatment group had prolonged residence time in rod rotating, shortened descent time in rod climbing, increased total movement distance in open field, increased number of TH-positive cells in the substania nigra, and increased TH protein levels in the substania nigra and striatum, decreased NLRP3, ASC, and cleaved-Caspase-1 levels in the substania nigra and striatum, and decreased TNF-α, IL-1β and IL-18 contents in the substania nigra and striatum, with significant differences ( P<0.05). No statistical differences in the above indexes were noted between the low-dose treatment group and medium-dose treatment group ( P>0.05). Conclusion:Low-/medium-dose MB can ameliorate motor dysfunction in PD mouse models, whose mechanism may be related to downregulate NLRP3 inflammasome and inhibit neuroinflammatory response to reduce dopaminergic neuron pyroptosis.

Objective:To investigate the effects of endocrine drugs on tumor markers and endometrium after breast cancer surgery.Methods:Eighty-eight patients with endocrine therapy for breast cancer admitted to the Heping Hospital Affiliated to Changzhi Medical College from November 2018 to March 2022 were selected, 44 patients taken orally tamoxifen citrate tablets were enrolled in the study group, 44 patients taken orally anastrozole tablets were enrolled in the control group, the patients in the two groups were treated for 12 months. The tumor markers, endometrial thickness were compared between the two groups before treatment and 12 months after treatment. The drug safety was compared too.Results:After treatment, the serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and glycochain antigen 15-3 (CA15-3) in both groups were decreased, and the level of tumor markers in the study group were lower than those in the control group: (3.01 ± 0.23) μg/L vs.(3.89 ± 1.15) μg/L, (4.22 ± 1.21) kU/L vs. (7.38 ± 2.19) kU/L, (16.76 ± 2.19) kU/L vs. (19.87 ± 2.21) kU/L, there were statistical differences ( P<0.05). The endometrial thickness in the study group at 6 months and 12 months after treatment were higher than those in the control group: (7.23 ± 0.22) mm vs. (6.21 ± 0.19)mm, (7.98 ± 0.24) mm vs. (6.47 ± 0.22) mm, there were statistical differences ( P<0.05). At 12 months after treatment, the scores of functional dimension, emotional dimension, social/family dimension and physical dimension in functional assessment of cancer therapy (FACT-G) scale in the study group were significantly higher than those in the control group ( P<0.05). There was no statistically significant difference in adverse reactions between the two groups ( P>0.05). Conclusions:Tamoxifen citrate tablets can effectively inhibit the levels of serum tumor markers and improve the quality of life of patients, and anastrozole tablets can significantly reduce the endometrial thickness of breast cancer patients.

Saliva testing is a vital method for clinical applications, for its noninvasive features, richness in substances, and the huge amount. Due to its direct anatomical connection with oral, digestive, and endocrine systems, clinical usage of saliva testing for these diseases is promising. Furthermore, for other diseases that seeming to have no correlations with saliva, such as neurodegenerative diseases and psychological diseases, researchers also reckon saliva informative. Tremendous papers are being produced in this field. Updated summaries of recent literature give newcomers a shortcut to have a grasp of this topic. Here, we focused on recent research about saliva biomarkers that are derived from humans, not from other organisms. The review mostly addresses the proceedings from 2016 to 2022, to shed light on the promising usage of saliva testing in clinical diagnostics. We recap the recent advances following the category of different types of biomarkers, such as intracellular DNA, RNA, proteins and intercellular exosomes, cell-free DNA, to give a comprehensive impression of saliva biomarker testing.
Humans ; Saliva/metabolism* ; Biomarkers/metabolism* ; RNA ; Exosomes/metabolism*

Objective:To study the expression of Proline rich protein11 (PRR11) in breast cancer and its relationship with clinical biological behavior, prognosis and survival.Methods:A prospective analysis method was used to select 80 patients with breast cancer from Jan. 2018 to Jan. 2019. Immunohistochemical S-P method was used to detect the expression of PRR11 in cancer tissues. Patients with positive expression of PRR11 were set as the study group ( n=47) and the patients with negative expression of PRR11 were set as the control group ( n=33) . All patients were followed up for 3 years to analyze and compare the survival rates of patients with positive and negative expression of PRR11. The relationship between PRR11 expression and clinical biological behavior, prognosis and survival was analyzed by Cox risk ratio review model. Results:80 patients were followed up for 3 years. It was found that the prognosis of patients with negative PRR11 expression was significantly better than that of patients with positive PRR11 expression ( χ2=5.75, P<0.001) . Chi square test was used to analyze the correlation between the expression of PRR11 and tumor size, TNM stage, lymph node metastasis, distant metastasis, histological grade, Ki67 expression and hormone receptor status ( P<0.05) . The expression of PRR11 in breast cancer tissues with larger tumors, distant metastasis and later staging was relatively high ( P<0.05) . Univariate Cox regression analysis showed that histological grade, TNM stage and PRR11 were independent risk factors affecting the prognosis of breast cancer patients ( P<0.001) . The AUC of prognosis prediction in patients with breast cancer was 0.812, and the 95% CI was 0.635-0.796. When PRR11 expression was positive, the sensitivity was 81.47%, and the specificity was 85.57%. Conclusions:The expression of PRR11 is relatively high in the late stage breast cancer tissue. The expression of PRR11 is closely related to the clinical biological behavior of breast cancer size, TNM stage and lymph node metastasis. The survival rate of patients with high PRR11 expression is low, and the positive expression of PRR11 is an independent risk factor affecting the prognosis of breast cancer patients. PRR11 detection has preferable clinical application value in predicting the prognosis of breast cancer.