Objective In response to the clinical needs for personalized wrist orthoses,a topological optimization design method was proposed to achieve an integrated macro-and micro-structural optimization of a personalized,lightweight,and comfortable wrist orthosis.Methods A composite biomechanical finite element model of the wrist orthosis and upper limb was established to quantify the effects of the orthosis geometry on its fixation performance and comfort.A multi-condition topological optimization and microstructure design approach was employed to optimize the non-load-bearing areas of the orthosis.The orthosis was manufactured using three-dimensional(3D)-printed polyether ether ketone(PEEK),and the feasibility of the design was validated.Results While maintaining mechanical strength,the weight of the 3D-printed PEEK orthosis was reduced by 28％compared to the traditional orthoses.Both the pressure at the skin contact interface and the results of a subjective questionnaire indicated that test subjects experienced a high level of comfort wearing the orthosis.Conclusions The orthosis design achieved personalization,lightweight structure,and high comfort while ensuring mechanical strength and fixation performance.

Objective In response to the clinical needs for personalized wrist orthoses,a topological optimization design method was proposed to achieve an integrated macro-and micro-structural optimization of a personalized,lightweight,and comfortable wrist orthosis.Methods A composite biomechanical finite element model of the wrist orthosis and upper limb was established to quantify the effects of the orthosis geometry on its fixation performance and comfort.A multi-condition topological optimization and microstructure design approach was employed to optimize the non-load-bearing areas of the orthosis.The orthosis was manufactured using three-dimensional(3D)-printed polyether ether ketone(PEEK),and the feasibility of the design was validated.Results While maintaining mechanical strength,the weight of the 3D-printed PEEK orthosis was reduced by 28％compared to the traditional orthoses.Both the pressure at the skin contact interface and the results of a subjective questionnaire indicated that test subjects experienced a high level of comfort wearing the orthosis.Conclusions The orthosis design achieved personalization,lightweight structure,and high comfort while ensuring mechanical strength and fixation performance.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies

BACKGROUND: Malignant pleural effusion is one of the common clinical manifestations of patients with lung adenocarcinoma. Patients with pleural effusion at the initial diagnosis of lung adenocarcinoma usually indicate poor prognosis. Epidermal growth factor receptor (EGFR) mutations mainly occur in patients with lung adenocarcinoma. Patients with different mutant subtypes have different prognosis. The clinical characteristics and prognostic factors of patients with EGFR mutated lung adenocarcinoma of different molecular subtypes combined with pleural effusion at initial diagnosis are still unclear. This study was designed to explore the clinical characteristics and prognostic factors of these patients in order to provide management recommendations for them. METHODS: A retrospective analysis of the clinical characteristics, treatment, outcomes and progression-free survival (PFS) of first-line treatment in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis admitted to Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital from January 2012 to June 2021 was performed. Pearson's chi-square test or Fisher's exact test were performed for comparison between groups. Kaplan-Meier method was performed for survival analysis and Cox proportional risk regression model was performed for multivariate analysis. RESULTS: 76 patients met the inclusion criteria in this study. The incidences of EGFR classical mutations 19del, 21L858R and non-classical mutations were 46.0%, 38.2% and 15.8%, respectively among these patients. There was no significant difference between the three mutations in terms of gender, age, presence of dyspnea at presentation, whether other distant metastases were combined, site of pleural effusion, volume of pleural effusion, presence of other combined effusions, tumor-node-metastasis (TNM) stage, presence of other gene mutations, and treatment of pleural effusion (P>0.05). In patients with EGFR classical mutations 19del or 21L858R or non-classical mutations subtype, the proportion of chemotherapy in first-line regimens were 17.1%, 20.7% and 58.3%, respectively (P=0.001); and first-line disease control rates were 94.3%, 75.9% and 50%, respectively (P=0.003); pleural effusion control rates were 94.3%, 79.3% and 66.7%, respectively (P=0.04); PFS were 287 d, 327 d and 55 d, respectively (P=0.001). Univariate analysis showed that EGFR mutation subtype, control of pleural effusion, first-line treatment agents, and first-line treatment efficacy were significantly associated with PFS (P<0.05). Cox multifactorial analysis showed that only EGFR mutation subtype and first-line treatment efficacy were independent prognostic factors for PFS (P<0.05). CONCLUSIONS PFS was significantly better for classical mutations than for non-classical mutations in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis. Improving the efficacy of first-line therapy is the key to improve the prognosis of these patients.
Adenocarcinoma of Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Pleural Effusion/complications* ; Prognosis ; Retrospective Studies

Objective:To investigate the application value of totally laparoscopic trans-abdominal-hiatal approach in the radical resection of Siewert type Ⅱ adenocarcinoma of esophago-gastric junction (AEG).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 45 patients with Siewert type Ⅱ AEG who were admitted to the Affiliated Hangzhou First People′s Hospital, Zhejiang University School of Medicine from May 2017 to December 2020 were collected. There were 28 males and 17 females, aged from 35 to 85 years, with a median age of 64 years. All patients underwent radical resection of AEG by totally laparoscopic trans-abdominal-hiatal approach with gastrointestinal anastomosis using proximal gastrectomy with double-tract anastomosis or total gastrectomy with esophagojejunointestinal anastomosis and digestive reconstruction using transdiaphragmatic-hiatal superior overlap esophagojejunostomy. Observation indicators: (1) surgical and postoperative situations; (2) postoperative histopathological examination; (3) follow-up and survival situations. Follow-up using outpatient examination and telephone interview was performed to detect survival of patients and tumor recurrence and metastasis up to March 2021. Measurement data with normal distribution were presented as Mean± SD and measure-ment data with skewed distribution were presented as M(range). Results:(1) Surgical and post-operative situations: all 45 patients underwent radical resection of AEG by totally laparoscopic transabdominal-hiatal approach successfully, including 35 cases undergoing total gastrectomy with esophagojejunointestinal anastomosis and 10 cases undergoing proximal gastrectomy with double-tract anastomosis. The total operation time, time of lower mediastinal lymph node dissection, time of superior overlap esophagojejunostomy, volume of intraoperative blood loss, time for initial out-of-bed activities, time to first flatus, time to initial liquid diet intake, time to drainage tube removal of the 45 patients were (235±32)minutes, (25±8)minutes, (45±10)minutes, (70±13)mL, (20±8)hours, (2.3±0.2)days, (2.6±0.8)days and (6.2±1.1)days, respectively. Eleven of 45 patients under-went postoperative complications and none of patient died during perioperative period. The post-operative duration of hospital stay of 45 patients was (10±3)days. (2) Postoperative histopatho-logical examination: all 45 patients had negative upper surgical margin. The length of proximal margin, tumor diameter, total number of lymph lodes harvested and number of lower mediastinal lymph nodes harvested were (2.5±0.5)cm, (2.9±0.8)cm, 35.0±4.0 and 2.4±0.8, respectively. Patholo-gical examination showed adenocarcinoma in all 45 patients with pTNM staging as 5 cases of stage ⅠB, 8 cases of stage ⅡA, 21 cases of stage ⅡB and 11 cases of stage ⅢA. (3) Follow-up and survival situations: 45 patients were followed up for 3 to 46 months, with a median follow-up time of 26 months. During follow-up, 8 of 45 patients died. Of the 37 patients survived, 3 cases underwent liver metastasis and 3 cases underwent bone metastasis, lung metastasis or peritoneal metastasis respec-tively.Conclusion:Total laparoscopic transabdominal-hiatal approach is safe and feasible in the treatment of Siewert type II AEG with a satisfactory clinical efficacy.

Objective To investigate the safety and feasibility of totally laparoscopic transabdominalhiatal approach in the treatment of Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods The retrospective and descriptive study was conducted.The clinicopathological data of 11 patients with Siewert type Ⅱ AEG who were admitted to Affiliated Hangzhou First People's Hospital of Zhejiang University School of Medicine from May 2017 to July 2018 were collected.There were 8 males and 3 females,aged 56-72 years,with an average age of 63 years.Patients underwent radical resection of AEG by totally laparoscopic transabdominalhiatal approach.Observation indicators:(1) surgical situations and postoperative recovery;(2) postoperative pathological examination;(3) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative adjuvant chemotherapy,complications,food intake,anastomosis patency,tumor recurrence and metastasis,and survival up to December 2018.Measurement data with normal distribution were presented as Mean±SD,measurement data with skewed distribution were presented as M (range),and count data were represented as absolute number or percentage.Results (1) Surgical situations and postoperative recovery:all the patients underwent totally laparoscopic radical resection of Siewert type Ⅱ AEG by transabdominal-hiatal approach,without conversion to open surgery or perioperative death.Of the 11 patients,8 underwent total gastrectony including 3 combined with splenic hilar lymph node dissection and 3 underwent proximal gastrectomy with double-tract reconstruction.Operation time,time of superior overlap esophagojejunostomy,volume of intraoperative blood loss,time for initial out-of-bed activities,time to first flatus,time to initial liquid diet intake,time of drainage tube removal were respectively (245± 39)minutes,(60± 12) minutes,(75±23) mL,(24± 8) hours,(2.4± 0.5) days,(3.5 ± 0.8) days,(8.2 ± 1.3) days respectively.There was no serious complication including postoperative hemorrhage,anatomotic fistula or death.Three patients had left pleural effusion,and were cured after thoracic drainage.The duration of postoperative hospital stay was (11.0±3.0) days.(2) Postoperative pathological examination:all the 11 patients had negative upper surgical margin.The length of proximal margin,tumor diameter,total number of lymph lodes harvested,and number of lower mediastinal lymph lodes harvested were (2.1 ±0.2) cm,(2.6±0.9) cm,(36.0±4.0)/case and (2.3± 0.8)/case.Pathological examination showed adenocarcinoma in all the 11 patients.pTNM staging:2 cases were in stage Ⅰ B,4 cases in stage Ⅱ A,3 cases in stage Ⅱ B and 2 cases in stage Ⅲ A.(3) Follow-up and survival situations:11 patients were follow-up for 6-19 months,with a median time of 9 months.Chemotherapy regimeus were formulated according to the pathological examination.Nine patients received postoperative adjuvant chemotherapy,and 2 in stage Ⅱ B received no postoperative adjuvant chemotherapy.During the follow-up,11 patients had no obvious reflux symptom or choking feeling,and the anastomosis was patent as evaluated by oral contrast agent and gastroscopy.There was no tumor recurrence and metastasis or death in the 11 patients.Conclusion Totally laparoscopic transabdominal-hiatal approach applied in the radical resection is safe and feasible for the treatment of Siewert type Ⅱ AEG,with good short-term outcomes.

Objective: To evaluate modified overlap esophagojejunostomy in digestive tract reconstruction of totally laparoscopie total gastrectomy(TLTG)in patients of gastric carcinoma. Methods: The clinicalpathological data of 68 patients admitted to Hangzhou First People′s Hospital from Jun 2015 to Aug 2018 Undergoing totally laparoscopie total gastrectomy and modified overlap esophagojejunostomy were analyzed retrospectively. Results: Procedures were successful in all 68 patients without conversion to open surgery and no perioperative death.The operation time, esophagojejunostomy time, volume of intraoperative blood loss and incision length were respectively (210±30)min, (25±12)min, (50±20)ml and(3.5±1.1)cm. Time for initial out of bed activity, time of initial anal exsufflation, time for postoperative fluid diet intake and duration of postoperative hospital stay were (24±8)h, (2.4±0.5)d, (3.1±0.8)d, and (8±3.6)d. There was anastomotic fistula in one and recovered by conservative treatment, total number of harvested LNs in 68 patients were (38.9±2.3). By pTNM staging: 6 cases in stage ⅠB, 10 cases in stage ⅡA, 20 cases in stage ⅡB , 15 cases in stage ⅢA, 12 cases in stage ⅢB, 5 cases in stage ⅢC. 59 patients were followed up from 3 to 42 months. One with liver metastasis after 22 months, others were all tumor-free. Conclusion The modified overlap esophagojejunostomy method is safe and feasible in digestive tract reconstruction of totally laparoscopie total gastrectomy for gastric carcinoma.

BACKGROUND: Peritoneal carcinomatosis is a rare clinical event in lung cancer and the prognosis is very poor. There are limited data on what factors predict peritoneal progression and affect the outcome. The aim of this study is to investigate investigate the factors associated with peritoneal carcinomatosis. METHODS: The patients with non-small cell lung cancer (NSCLC) from the Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital were eligible for retrospective analysis between August 2010 and August 2018. Clinical factors such as age, gender, histology, pleural effusion and gene mutations with epidermal growth factor receptor/anaplastic lymphoma kinase/ROS proto-oncogene 1 receptor tyrosine kinase (EGFR/ALK/ROS1) were analyzed. Overall survival (OS) was calculated by the Kaplan-Meier method. RESULTS: 1.44% (12/836) patients in this study developed peritoneal carcinomatosis and 12 patients with adenocarcinoma had metachronous NSCLC diagnosis and PC. Malignant pleural effusion rates at baseline and at PC diagnosis were separately 50% (6/12) and 100.0% (12/12). Among the 12 patients, 9 patients harbored EGFR/ALK/ROS1 mutation. The outcome of patients with EGFR/ALK/ROS1 mutation was significantly better than that of patients without EGFR/ALK/ROS1 mutation, the mOS1 and mOS2 were separately 26.0 months and 6.0 months versus 10.0 months and 1.5 months (P<0.05). The mOS2 of patients with aggressive treatment after PC diagnosis was 6.0 months, significantly better than 1.0 month of patients with best supportive care (P<0.05). The mOS2 of the patients with angiogenesis inhibitors based-treatment after PC diagnosis was 8.5 months, significantly longer than that of patients with other treatments (P<0.05). CONCLUSIONS Adenocarcinoma and malignant pleural effusion are highly associated with peritoneal carcinomatosis in patients with advanced NSCLC. Aggressive treatment for lung cancer with PC is encouraged when possible. More patients with PC may benefit from the treatment strategies with angiogenesis inhibitors. Further prospective trials are urgently needed.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; pathology ; therapy ; Female ; Humans ; Lung Neoplasms ; diagnosis ; pathology ; therapy ; Male ; Middle Aged ; Peritoneal Neoplasms ; secondary ; Prognosis ; Retrospective Studies

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), indexes of systemic inflammation, have been associated with worse survival for many types of cancer. The aim of this study is to investigate the impact of NLR and PLR on overall survival (OS) and to explore the value of changes in the NLR and PLR with treatment as a response indicator in non-small cell lung cancer (NSCLC). METHODS: A total of 68 NSCLC patients in Peking University Third Hospital were eligible for retrospective analysis between April 2008 and April 2015. The pretreatment and posttreatment NLR and PLR in all patients were calculated based on complete blood counts. Potential prognostic factors such as age, gender, performance status, histology, stage, response to chemotherapy, NLR and PLR were analyzed. NLR and PLR were assessed at baseline and during chemotherapy treatment. OS was calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the associations of the PLR, NLR and clinical features with OS. RESULTS: Among the 68 cases, the values of the posttreatment NLR after two cycles of chemotherapy (NLR2) and the pretreatment NLR (NLR0) were (2.69±2.06) and (3.94±2.12), respectively. NLR2 was significantly lower than NLR0 (P=0.000). There was no difference between the pretreatment PLR (PLR0) and the posttreatment PLR after two cycles of chemotherapy (PLR2) (P<0.05). NLR2 significantly correlated with the response of first line treatment with two or four cycles of chemotherapy. The proportion of high NLR2 in the patients with progression disease was 100.0%, significantly higher than the proportion of high NLR2 in the patients with partial response or stable disease. NLR0, PLR0 and NLR2 were significantly correlated with the OS (P<0.05), but not with age, performance status, histology, stage, status and regimens of treatment (P>0.05). According to univariate analysis, the OS was significantly associated with NLR0, PLR0, NLR2, the response of 2 and 4 cycles of first line chemotherapy, status and regimens of second line treatment (P<0.05), but not with stage, status of third line or beyond treatment and radiotherapy (P>0.05). The multivariate analysis showed that NLR0 (P=0.004), the response with 4 cycles of first line chemotherapy (P=0.022) and status of second line treatment (P=0.007) were independent prognostic indicators in the 68 patients. CONCLUSIONS The study showed that NLR0 was well connected with outcomes and NLR2 was well connected with the response to first line chemotherapy in patients with advanced non-small cell lung cancer. Therefore, NLR may be a biomarker for predicting the outcomes and response of first line chemotherapy and a potential target for management of non-small cell lung cancer.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; pathology ; radiotherapy ; Disease-Free Survival ; Female ; Humans ; Leukocyte Count ; Lung Neoplasms ; blood ; drug therapy ; pathology ; radiotherapy ; Lymphocytes ; cytology ; drug effects ; Male ; Middle Aged ; Neutrophils ; cytology ; drug effects ; Retrospective Studies ; Treatment Outcome