Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

[摘 要] 目的：探讨贝母素乙对结肠癌HCT116细胞增殖的抑制作用及其分子机制。方法：利用不同浓度的贝母素乙处理人结肠癌细胞HCT116和正常结肠上皮细胞CCD841 CON，通过CCK-8法和结晶紫染色法检测贝母素乙对HCT116和CCD841 CON细胞增殖活力的影响，流式细胞术和WB法检测贝母素乙对HCT116细胞周期及其细胞周期相关蛋白表达的影响。构建HCT116移植瘤裸鼠模型和AOM/DSS结肠癌小鼠模型，观察贝母素乙对小鼠模型肿瘤生长和OS的影响，免疫组化法和WB法检测对移植瘤或肿瘤组织中细胞周期相关蛋白CDK4、CDK6和cyclin D1表达的影响。结果：贝母素乙可显著抑制结肠癌HCT116细胞的增殖能力（P<0.01），诱导HCT116细胞周期G0/G1期阻滞（P<0.01），降低CDK4、CDK6和cyclin D1的蛋白表达水平（均P<0.01）。荷瘤小鼠实验结果显示，贝母素乙（0.75 mg/kg）显著抑制HCT116细胞移植瘤的生长并延长荷瘤裸鼠的OS（P<0.05或P<0.01），降低AOM/DSS模型小鼠的体质量、延长OS、减少癌变肠组织的肿瘤个数和肿瘤体积，下调肿瘤组织中CDK4、CDK6和cyclin D1的蛋白表达（P<0.01或P<0.05）。结论：贝母素乙通过下调CDK4、CDK6和cyclin D1的表达水平，引起细胞周期G0/G1期阻滞，从而抑制结肠癌HCT116细胞的增殖。

Objective:To analyze the safety and therapeutic efficacy of laparoscopic pancreaticoduodenectomy (LPD) and laparoscopic total pancreatectomy (LTP) in the treatment of pancreatic cancer.Methods:Clinical data of 87 patients with pancreatic head and neck cancer who underwent LPD or LTP in the Department of General Surgery at Peking Union Medical College Hospital from December 2018 to August 2023 were retrospectively analyzed. The surgical approach, operative time, intraoperative blood loss volume, conversion rate to open surgery, perioperative mortality, re-operative rate, rate of major postoperative complications, postoperative hospital stay, number of lymph nodes harvested, tumor pathological stage, R 0 resection rate, initiation of postoperative chemotherapy and survival outcomes were recorded. The follow-up period extended until September 2023. Results:Among the 87 patients, 78(89.7%) underwent LPD and 9(10.3%) underwent LTP. PV-SMV vascular resection and reconstruction was performed in 16 cases (18.4%), and 11 cases totally underwent laparoscopy. Five cases (5.7%) required conversion to open surgery. The mean operative time was 279.8±74.0 minutes, and the mean intraoperative blood loss volume was 520.1±743.2 ml. The overall length of hospital stay was 15.9±6.3 days, with a mean postoperative hospital stay of 11.5±6.0 days. The rate of major postoperative complications was 19.5%, including 4 cases (4.6%) of postoperative bile leakage, 6 cases (6.9%) of postoperative gastric emptying disorders, and 3 cases (3.4%) of postoperative bleeding. There was one case (1.1%) with secondary surgery and one case (1.1%) with perioperative death. Among LPD patients, 5 cases (6.4%) had postoperative grade B or higher pancreatic fistula. Advanced age (≥70 years) did not increase the incidence of perioperative complications. All patients achieved R 0 resection. The mean number of lymph nodes harvested was 25.9±11.4. The median time to initiation of postoperative chemotherapy was 2.13±1.43 months. The median overall survival was 16 months. Conclusions:In a high-volume center for pancreatic diseases, LPD and LTP are safe and feasible for the treatment of pancreatic cancer, which could achieve satisfactory anti-tumor efficacy and improve patients' prognosis.

Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.

Purpose To investigate the difference of cerebral blood flow between sleep deprivation and rest wakefulness.Materials and Methods Fifty subjects were recruited from universities in Xi'an from October 2020 to December 2021.The psychomotor vigilance test(PVT)task was used to measure sustained attention.Arterial spin labeling technique was used to analyze and compare the relative cerebral blood flow(rCBF)between sleep deprivation and rest wakefulness.The correlation between altered rCBF of specific brain regions and PVT task performance after sleep deprivation was analyzed.Results Compared with rest wakefulness,rCBF in bilateral dorsolateral prefrontal lobe,bilateral parietal lobule,left orbital middle frontal gyrus,bilateral middle temporal gyrus,right posterior central gyrus,and bilateral angular gyrus was significantly decreased after sleep deprivation.The rCBF of bilateral thalamus,left precuneus,right medial prefrontal lobe,left posterior cingulate gyrus,and left inferior temporal gyrus was significantly increased(FDR corrected,P<0.05,cluster size≥20 voxels).The changes of rCBF in left dorsolateral prefrontal lobe and right parietal lobule were significantly negatively correlated with the PVT task performance(r=-0.56,P<0.001;r=-0.64,P<0.001),and the change of rCBF of left precuneus was significantly positively correlated with the PVT task performance(r=0.72,P<0.001).Conclusion The abnormal changes of CBF in default mode network,frontoparietal network-related brain regions and thalamic may be the important neural mechanism of sustained attentional decline after sleep deprivation.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To explore the relationship between the levels of serum complement C3 and C4 and the degree of renal pathological injury in patients with IgA nephropathy (IgAN).Methods:It was a retrospective study. The clinical and pathological data of patients with primary IgAN diagnosed by renal biopsy in the Department of Nephrology of the Second People's Hospital of Qujing City, Yunnan Province from December 1, 2019 to December 31, 2022 were collected. According to the IgAN Oxford classification criteria, the patients were divided into mild renal pathological injury group (mild group, <3 pathologic types) and severe renal pathological injury group (severe group, ≥3 pathological types). The levels of serum C3 and C4 and other clinical data were compared between the two groups. Spearman correlation method was used to analyze the correlation between serum C3, C4 levels and estimated glomerular filtration rate (eGFR) during renal biopsy.Multivariate logistic regression model was used to analyze the influencing factors of the pathological injury degree in IgAN patients and the forest map depicted the effect of risk factors.Results:A total of 164 IgAN patients were included in the study, including 77 males (47.0%), aged (35.5±12.9) years old. There were 60 patients in the mild group and 104 patients in the severe group. Compared with the mild group, the patients in the severe group were older, had higher levels of serum C4, serum uric acid, low density lipoprotein cholesterol and 24 h urinary protein, higher proportions of hypertension, glucocorticoids/immunosuppressant therapy, C3 deposition in renal tissues and microscopic hematuria, and had lower hemoglobin and serum C3 level (all P<0.05). The results of Spearman correlation analysis showed that the level of serum C3 was positively correlated with eGFR ( r=0.303, P<0.001), and the level of serum C4 was negatively correlated with eGFR ( r=-0.238, P=0.002). Multivariate logistic regression analysis results showed that serum C3 (every 0.01 g/L increase, OR=0.976, 95% CI 0.957-0.996, P=0.018), serum C4 (every 0.01 g/L increase, OR=1.091, 95% CI 1.020-1.166, P=0.011), hemoglobin ( OR=0.969, 95% CI 0.950-0.988, P=0.002), and serum uric acid ( OR=1.005, 95% CI 1.001-1.009, P=0.012) were independent related factors of renal pathological damage (severe injury /mild injury) in IgAN patients. Conclusions:Serum C3 and C4 are independent related factors of the severity of renal pathological injury in IgAN patients.

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ²=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ²=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.
Humans ; Cytomegalovirus ; Retrospective Studies ; Cohort Studies ; Prospective Studies ; Cytomegalovirus Infections/prevention & control* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Graft vs Host Disease/prevention & control* ; Recurrence ; Antiviral Agents/therapeutic use*