Objective:To explore the effects of computer-navigated surgery and traditional surgery on the functional and oncological outcomes of pelvic chondrosarcoma.Methods:Retrospective analysis of 136 cases of pelvic chondrosarcoma surgically treated at Beijing Jishuitan Hospital from January 2000 to December 2017. There were 65 males and 71 females with an average age of 46.07±13.37 years (range 13-73 years). There were 120 primary cases and 16 secondary cases, of which 109 cases were ordinary chondrosarcoma (7 cases with pathological differentiation grade I, 83 cases with grade II. There were 109 cases of common type chondrosarcoma (7 cases of pathological differentiation grade I, 83 cases of grade II, 19 cases of grade III), 21 cases of dedifferentiated chondrosarcoma, 3 cases of mesenchymal type, 2 cases of clear cell type, 1 case of mucinous type; 12 cases of malignant degeneration of multilocular chondrosarcoma of bone; 104 cases of Enneking staging stage IB, 32 cases of stage IIB. According to the pelvis zone classification, there were 14 cases of pelvic zone I, 1 case of zone II, 13 cases of zone III, 16 cases of zone I+II, 16 cases of zone I+IV, 47 cases of zone II+III, 25 cases of zone I+II+III, 25 cases of zone I+II+III, 4 cases of zone I + II + III + IV. All cases were classified as intracapsular, marginal, or wide resection according to the resection boundary classification. There were 45 cases in computer-navigated surgery (navigated group) and 91 cases in non-navigated surgery group. The demographic data, preoperative tumor staging, surgical characteristics, surgical boundary classification, oncological indexes, reconstruction methods, postoperative complications, and bone and soft tissue tumor function score (Musculoskeletal Tumor Society score, MSTS) were compared between the two groups.Results:No surgical complications related to the computerized navigation system occurred in the navigation group. The postoperative follow-up time was 68.56±37.82 months (range 6-197 months) and 76.85±52.60 months (range 5-225 months) for the navigation and non-navigation groups, respectively. The MSTS was 25.43±2.85 and 24.56±4.19 points in the navigation and non-navigation groups, respectively, with no significant difference ( t=1.191, P=0.237). There were 10 cases of marginal resection and 35 cases of wide resection in the navigation group, and 12 cases of intracapsular resection, 32 cases of marginal resection and 47 cases of wide resection in the non-navigation group with significant difference (χ 2=10.977, P=0.004). There were 4 cases (8.9%, 4/45) of local recurrence after surgery in the navigation group and 20 cases (21.9%, 20/91) in the non-navigation group, with significant difference (χ 2=4.040, P=0.046). There were 2 cases of final amputation and 2 cases of re-excision with recurrence in the navigation group and 6 cases of final amputation and 14 cases of re-excision in the non-navigation group. Distant metastases occurred in 3 cases (7%, 3/45) in the navigation group and 18 cases (20%, 18/91) in the non-navigation group wtih significant difference (χ 2=4.478, P=0.034). The five-year postoperative survival rates of the navigation and non-navigation groups were 93.3% and 72.6%, and the three- and five-year progression-free survival rates were 91.1% and 84.4% and 74.8% and 62.7%, respectively, with significant differences (χ 2=5.081, P=0.024; χ 2=6.800, P=0.009). The five-year survival rate of stage IB tumors was 96.7% in the navigation group and 84.5% in the non-navigation group with significant difference (χ 2=3.897, P=0.048); the five-year survival rate of stage IIB tumors was 75.0% in the navigation group and 35.0% in the non-navigation group with no significant difference ( P>0.05). Postoperative complications included 15 cases of postoperative infection, 16 cases of deep vein thrombosis, 14 cases of double lower limb inequality, 2 cases of prosthesis dislocation, 2 cases of lymphedema, 1 case of hernia and 1 case of allograft bone resorption. There was no significant difference of complication rates between the two groups ( P>0.05). Conclusion:Computer navigation-assisted resection of pelvic chondrosarcoma was better in obtaining a safe surgical border of the tumor compared with traditional surgery, reducing the rate of local recurrence of the tumor and thus effectively improved the survival and prognosis of patients.

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.
Humans ; Male ; Animals ; Mice ; Semen/metabolism* ; Dyneins/metabolism* ; Cilia/metabolism* ; Mutation ; Ciliary Motility Disorders/genetics*

OBJECTIVE: To investigate short-term effectiveness and clinical application advantages of orthopedic robot-assisted resection for osteoid osteoma compared with traditional open surgery. METHODS: A retrospective analysis was conducted on clinical data of 48 osteoid osteoma patients who met the selection criteria between July 2022 and April 2023. Among them, 23 patients underwent orthopedic robot-assisted resection (robot-assisted surgery group), and 25 patients received traditional open surgery (traditional surgery group). There was no significant difference ( P>0.05) in gender, age, disease duration, lesion location and size, and preoperative visual analogue scale (VAS) score, and musculoskeletal tumor society (MSTS) score between the two groups. The surgical time, intraoperative blood loss, intraoperative lesion localization time, initial localization success rate, infection, and recurrence were recorded and compared. VAS scores before surgery and at 24 hours, 1, 3, 6, and 9 months after surgery and MSTS score before surgery and at 3 months after surgery were assessed. RESULTS: All patients completed the surgery successfully, with no significant difference in surgical time between the two groups ( P>0.05). Compared to the traditional surgery group, the robot-assisted surgery group had less intraoperative blood loss, shorter lesion localization time, and shorter hospitalization time, with significant differences ( P<0.05). The initial localization success rate was higher in the robot-assisted surgery group than in the traditional surgery group, but the difference between the two groups was not significant ( P>0.05). All patients in both groups were followed up, with the follow-up time of 3-12 months in the robot-assisted surgery group (median, 6 months) and 3-14 months in the traditional surgery group (median, 6 months). The postoperative MSTS scores of both groups improved significantly when compared to those before surgery ( P<0.05), but there was no significant difference in the changes in MSTS scores between the two groups ( P>0.05). The postoperative VAS scores of both groups showed a gradually decreasing trend over time ( P<0.05), but there was no significant difference between the two groups after surgery ( P>0.05). During follow-up, except for 1 case of postoperative infection in the traditional surgery group, there was no infections or recurrences in other cases. There was no significant difference in the incidence of postoperative infection between the two groups ( P>0.05). CONCLUSION Orthopedic robot-assisted osteoid osteoma resection achieves similar short-term effectiveness when compared to traditional open surgery, with shorter lesion localization time.
Humans ; Robotics ; Blood Loss, Surgical ; Osteoma, Osteoid/surgery* ; Retrospective Studies ; Treatment Outcome ; Postoperative Complications ; Bone Neoplasms/surgery*

Pseudomonas aeruginosa is a common pathogen of respiratory infections. The conventional diagnostic methods for Pseudomonas aeruginosa have certain weakness, for example, sputum culture is time-consuming and of low sensitivity; and polymerase chain reaction cannot be popularized clinically due to its high cost. Meanwhile, detection of volatile organic compounds is a sensitive, rapid, portable and inexpensive diagnostic method. This review focuses on the detection of volatile organic compounds in the diagnosis of Pseudomonas aeruginosa respiratory infection, discusses the existing problems, and puts forward relevant suggestions to provide reference for clinical application and future researches.

Objective:To observe the clinical characteristics and guideline compliance of chronic obstructive pulmonary disease (COPD) patients with initial triple therapy in real-life world.Methods:This study is a cross-sectional study. The subjects of the study were COPD patients admitted to 13 hospitals in Hunan Province and Guangxi Zhuang Autonomous Region from December 2016 to December 2021. The initial treatment was triple inhaled drugs. The data collected included gender, age, diagnosis, body mass index (BMI), history of acute exacerbation (AE) in the past year, pulmonary function, COPD Assessment Test (CAT) score, modified British Medical Research Council Dyspnea Questionnaire (mMRC), inhaled drugs and other indicators. The characteristics and differences of COPD patients before and after 2020 were analyzed.Results:7 184 patients with COPD were enrolled in this study, including 2 409 COPD patients treated with initial triple therapy, accounting for 33.5%(2 409/7 184). Taking January 1st, 2020 as the cut-off point, 1 825 COPD patients (75.8%) received initial treatment with triple inhaled drugs before 2020 and 584 patients (24.2%) after 2020 were included in this study. Compared with COPD patients before 2020, the COPD patients after 2020 had higher FEV 1% [(40.9±15.5 )% vs (39.3±15.5)%, P=0.040], lower CAT [(15.8±6.5)point vs (17.5±6.2)point, P<0.001], less AE in the past year [1(0, 2)times vs 1(0, 2)times, P=0.001] and higher rate of non-AE [255(43.7%) vs 581(37.1%), P=0.006]. In addition, before 2020, patients with COPD were mainly treated with open triple drugs (1 825/1 825, 100%); after 2020, 306 patients (52.4%) received open triple inhaled drugs, and 278 patients (47.6%) received closed triple inhaled drugs. Conclusions:In real-life world, most of patients with COPD treated with triple therapy have severe lung function, obvious symptoms and high risk of acute exacerbation. The real-world prescribing of triple therapy in patients with COPD does not always reflect recommendations in guidelines and strategies, and overtreatment is common. After 2020, prescribing triple therapy for COPD patients is more positive and worse consistency with guideline.

Objective:To investigate the efficacy and safety of albumin-bound paclitaxel combined with epirubicin and cyclophosphamide in neoadjuvant chemotherapy for breast cancer.Methods:Clinicopathological data of 48 breast cancer patients who received neoadjuvant chemotherapy and surgery from August 2018 to November 2019 in Shaanxi Provincial Cancer Hospital were retrospectively analyzed. The primary endpoints were pathological complete remission (pCR) rate, objective response rate (ORR) and clinical benefit rate (CBR). The secondary endpoint was the adverse reactions of chemotherapy.Results:The incompletion rate of the protocol-specified courses in all patients was 10.4% (5/48). The pCR rate was 31.2% (15/48), the ORR was 87.5% (42/48), and the CBR was 95.8% (46/48). No statistic difference of pCR rate was obtained in subgroups of patients' age, clinical stage, histological grade, cN stage, and human epidermal growth factor receptor 2 (HER2) status (all P > 0.05), but it was higher in the Ki-67 high-expression group (Ki-67 positive index ≥30%) [46.7% (14/30) vs. 16.7% (3/18), χ2 = 4.427, P = 0.035]. Common adverse reactions which almost were grade 1-2 included leucopenia (93.8%, 45/48), neutropenia (93.8%, 45/48), arthralgia (27.1%, 13/48), fatigue (22.9%, 11/48), peripheral neuropathy (18.8%, 9/48), and nausea and vomiting (18.8%, 9/48). The overall incidence rate of grade 3-4 adverse reactions was 18.8% (9/48). Conclusion:The albumin-bound paclitaxel combined with epirubicin and cyclophosphamide can achieve high pCR rate in neoadjuvant chemotherapy for breast cancer, and the regimen is well tolerated.

Objective:To explore the influence of bromodomain-containing protein 4 (BRD4) inhibitor on wild-type Kras differentiated thyroid carcinoma (DTC) and its mechanism.Methods:The DTC cell line Kras WT TPC-1 was selected and the mutant Kras G12D TPC-1 cells were constructed. CCK-8 assay was used to detect the effect of BRD4 inhibitor JQ-1 on the proliferation activity of Kras WT TPC-1 cells. Kras WT TPC-1 cells were treated with 0.2 μmol/L JQ-1 (JQ-1 group), and a negative control group (NC group) was set. Transwell invasion assay and flow cytometry were used to detect the effect of JQ-1 on the invasion and apoptosis of Kras WT TPC-1 cells. The effect of JQ-1 on the expressions of BRD4, miR-106b-5p and P21, and the effect of P21 inhibitor UC2288 on the expressions of P21 and BRD4 were detected. Kras WT TPC-1 cells were divided into JQ-1+ NC-OE group, JQ-1+ p21-OE group (overexpression of p21) and JQ-1+ p21-OE+ miR-106b-5p mimic group (overexpression of p21 and miR-106b-5 at the same time), and the proliferation, invasion and apoptosis of cells in each group were detected. TPC-1 cells were divided into Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, and the cell proliferation, invasion and apoptosis of each group were detected. Results:JQ-1 inhibited the proliferation activity of Kras WT TPC-1 cells in a dose-dependent and time-dependent manner. In the NC group and JQ-1 group, the numbers of cell invasion were 124.67±9.61 and 82.67±8.02, and the apoptosis rates were (5.91±0.34)% and (10.33±1.10)%, respectively, with statistically significant differences ( t=5.812, P=0.004; t=6.653, P=0.003). JQ-1 significantly inhibited the expressions of BRD4 and miR-106b-5p, and promoted the expression of P21 in Kras WT TPC-1 cells. UC2288 significantly inhibited P21 expression, but had no significant effect on BRD4 expression. In the JQ-1+ NC-OE group, JQ-1+ p21-OE group and JQ-1+ p21-OE+ miR-106b-5p mimic group, the proliferation activities at 24 h of Kras WT TPC-1 cells was 0.46±0.03, 0.35±0.04 and 0.44±0.03 ( F=8.720, P=0.017), and the proliferation activity of JQ-1+ p21-OE group was significantly lower than that of the JQ-1+ NC-OE group ( P<0.05). The numbers of cell invasion in the three groups were 83.00±9.17, 56.67±6.03 and 79.67±10.07 ( F=8.347, P=0.018), and the number of cell invasion in the JQ-1+ p21-OE group was significantly lower than that in the JQ-1+ NC-OE group ( P=0.009). The apoptosis rates of the three groups were (10.00±0.49)%, (15.39±1.14)% and (10.32±0.80)% ( F=37.764, P<0.001), and the apoptosis rate of the JQ-1+ p21-OE group was significantly higher than that in the JQ-1+ NC-OE group ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between JQ-1+ p21-OE+ miR-106b-5p mimic group and JQ-1+ NC-OE group (all P>0.05). In Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, the cell proliferation activities at 24 h were 0.50±0.05, 0.39±0.04, 0.68±0.08 and 0.64±0.05 ( F=17.776, P<0.001). Compared with the Kras WT group, cell proliferation activity in the Kras WT+ JQ-1 group was significantly decreased, while that in the Kras G12D group was significantly increased (both P<0.05). The numbers of cell invasion in the four groups were 129.33±11.50, 86.00±9.54, 161.67±13.01 and 146.33±13.20 ( F=22.598, P<0.001). Compared with the Kras WT group, the number of cell invasion in the Kras WT+ JQ-1 group was significantly decreased ( P=0.002), and that in the Kras G12D group was significantly increased ( P=0.010). The apoptosis rates in the four groups were (6.17±0.50)%, (10.42±0.73)%, (3.43±0.47)% and (3.41±0.32)% ( F=119.170, P<0.001). Compared with the Kras WT group, the apoptosis rate in the Kras WT+ JQ-1 group was significantly increased ( P<0.001), and that in the Kras G12D group was significantly decreased ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between Kras G12D+ JQ-1 group and Kras G12D group (all P>0.05). Conclusion:BRD4 inhibitor can specifically inhibit the development of wild-type Kras DTC via regulating the molecular axis of BRD4/miR-106b-5p/P21, but has no significant effect on the proliferation, invasion and apoptosis of mutant Kras DTC tumor cells.

Objective:To investigate the oncological efficacy and functional evaluation of total elbow arthroplasty (TEA) for the reconstruction of tumor around elbow joint.Methods:A retrospective case series study was made on the clinical data of 26 patients who underwent total elbow joint replacement after tumor resection in Beijing Jishuitan Hospital from June 1988 to June 2019. According to the inclusion and exclusion criteria, 23 patients were enrolled in the final study, there were 14 males and 9 females, the mean and median age was 37.6±19.9 and 35.0 years respectively. 23 patients included 3 cases of giant cell tumor, 4 cases of metastatic cancer, 4 cases of Ewing's sarcoma, 2 cases of osteosarcoma, 2 cases of aneurysmal bone cyst, 1 angiosarcoma, 1 primary malignacy in giant cell tumor, 1 low-grade central osteosarcoma, 1 parosteosarcoma, 1 synovial sarcoma, 1 plasma cell myeloma, 1 tendon sheath giant cell tumor and 1 case of mixed tumor. There were 6 cases of benign tumor, 4 cases of low grade sarcoma and 13 cases of high grade malignancy. With 19 cases of distal humerus, 3 cases of proximal ulna and 1 case of elbow. Each patient underwent tumor resection followed by restrictive tumor prosthesis and semi-restrictive of coonrad-morrey prosthesis were used for reconstruction.The duration of the operation, the amount of blood loss, epidemiological data, reconstruction length, oncology parameter, complications and functional evaluation were enrolled and statistical analyzed.Results:The mean length of the osteotomy followed by reconstruction was 12.5±3.9 cm, the mean operative time was 154.1±50.1 minutes, and the mean bleeding was 262.2±100.9 ml. Thirteen patients were treated with customized tumor limited prosthesis while 10 patients with Coonrad-Morrey semi-limited prosthesis. The 5-year survival rates of 23 patients was 64.3%, benign tumors, low-grade and high-grade malignancies were 100%, 100% and 39.7%, respectively. Three cases of lung cancer and three cases of Ewing's sarcoma died during the follow-up period (6/23, 26.1%), one case of giant cell tumor and one case of synovial sarcoma developed local recurrence (2/23, 8.7%). The median range of motion for the elbow increased from 35 to 85 degrees ( t=-13.787, P<0.05), the median NRS score decreased from 5.0 to 0.5 ( t=14.391, P<0.05). Postoperative complications occurred in 9 cases (9/23, 39.1%), the recent complications were nerve injury in 4 cases and infection in 1 case, late complications were prosthesis loosening and failure in 4 cases, the 5 year survival rate of prosthesis was 82.0%. The mean and median MSTS 93 score was 84.5%±11.0% and 88.3% respectively. Conclusion:The local control around the elbow is satisfactory after tumor resection. Total elbow arthroplasty can relieve pain and significantly improve function.

Alanine Transaminase ; Amikacin ; Anti-Bacterial Agents ; Aztreonam ; Bilirubin ; Carbapenems ; Ceftazidime ; China ; Creatinine ; Cross Infection ; Escherichia coli ; Fibrosis ; Fungi ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Hemorrhage ; Hospitals, Teaching ; Humans ; International Normalized Ratio ; Klebsiella pneumoniae ; Length of Stay ; Leukocyte Count ; Linezolid ; Methicillin-Resistant Staphylococcus aureus ; Mortality ; Multivariate Analysis ; Prevalence ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Vancomycin

Blocking the programmed death-ligand 1 (PD-L1) on tumor cells with monoclonal antibody therapy has emerged as powerful weapon in cancer immunotherapy. However, only a minority of patients presented immune responses in clinical trials. To develop an alternative treatment method based on immune checkpoint blockade, we designed a novel and efficient CRISPR-Cas9 genome editing system delivered by cationic copolymer aPBAE to downregulate PD-L1 expression on tumor cells specifically knocking out Cyclin-dependent kinase 5 () gene . The expression of PD-L1 on tumor cells was significantly attenuated by knocking out , leading to effective tumor growth inhibition in murine melanoma and lung metastasis suppression in triple-negative breast cancer. Importantly, we demonstrated that aPBAE/Cas9-Cdk5 treatment elicited strong T cell-mediated immune responses in tumor microenvironment that the population of CD8 T cells was significantly increased while regulatory T cells (Tregs) was decreased. It may be the first case to exhibit direct PD-L1 downregulation CRISPR-Cas9 genome editing technology for cancer therapy. It will provide promising strategy for preclinical antitumor treatment through the combination of nanotechnology and genome engineering.