Objective:To investigate the feasibility of surface-guided hypo-fractionated radiotherapy for intracranial metastasis with open face mask immobilization.Methods:Nineteen patients treated with hypo- fractionated radiotherapy for intracranial metastasis in our hospital were included. Before the start of treatment, each patient underwent simulation with open face mask immobilization. During the treatment, cone-beam CT(CBCT)images were collected for verification each time. Laser-guided positioning was used for the first time in the treatment, and surface images were captured after six-dimensional position correction as the reference images for subsequent treatment. Subsequent treatment was randomly divided into laser-guided positioning group(LG, 85/F)and optical surface-guided positioning group(SG, 101/F). The six-dimensional error data of patients with two positioning methods were compared and expressed as mean ± standard deviation. Meanwhile, the correlation and consistency between the optical surface error data and the gold standard CBCT error data were compared in the laser-guided fraction. GraphPad Prism 6.0 software was used for data processing and mapping, and SPSS 21.software was used for mean analysis and normality test. Pearson correlation analysis was used to analyze the correlation, and Bland-Altman plot analysis was used to test the coincidence between two methods.Results:Compared with the laser-guided positioning, the 3D error of optical surface-guided positioning was reduced from(0.35±0.16)cm to(0.14±0.07)cm. The Pearson coefficient of correlation along all three directions was less than 0.01,R 2 was 0.91,0.70 and 0.78 on Lat, Lng and Vrt, and R 2 was 0.75,0.85 and 0.77 on Pitch, Roll and Rtn(all P<0.01), respectively. The measurement results of two methods were positively correlated. The Bland-Altman plot analysis showed that the 95% limits of agreement were within preset 3 mm tolerance([-0.29 cm, 0.19 cm], [-0.25 cm, 0.25 cm], [-0.27 cm, 0.19 cm]), and the 95% limits of agreement were within preset 3° tolerance(Pitch[-1.76°,1.76°], Roll[-1.54°,1.60°], ROT[-2.18°,1.69°]), indicating agreement between two methods. Conclusions:The optical surface-guided positioning can reduce the setup errors in the hypo-fractionated radiotherapy for intracranial metastasis with open face mask immobilization. The optical surface error and CBCT error have good correlation and agreement.

Objective:Based on the current medical environment, to learn about cognition status of doctor-patient relationship among medical students and analyze causes of the tension between doctors and patients.Methods:Using the self-designed questionnaire "Clinical Medical Students' Cognition Survey on Occupational Status and Doctor-Patient Relationship", a cross-sectional survey was conducted on 527 medical students from 5-year and 7-year clinical program in Batch 2014 in a medical university in Heilongjiang Province. The survey mainly analyzed the causes of the tension between doctors and patients from the level of medical staff, patients and their families, hospitals and society. SPSS 22.0 was used for descriptive statistics and chi-square test.Results:The results showed that 93.7% of the medical students believed that the current doctor-patient relationship was not harmonious. There were cognitive differences among medical students in different gender ( P=0.029), first contact clinical grade ( P=0.003) and professional identity ( P<0.001). Conclusion:Medical students have a poor evaluation towards the current doctor-patient relationship. In order to construct harmonious doctor-patient relationship in the future, we can try to take measures such as carrying out relevant courses of doctor-patient communication, improving the medical students' communication skills and enhancing their professional identity.

Objective:To investigate the effect of indocyanine green angiography (ICGA) in the design of pre-expanded perforator flaps in the reconstruction of large defects.Methods:From October 2018 to October 2019, there were 22 patients undergoing facial and cervical reconstructive surgeries based on pre-expanded perforator flaps in the back region in Shanghai Ninth Peoples′ Hospital. 12 male and 10 female patients, ranging from 4 to 26 years old with an average age of 19, were all suffered from inferior facial and cervical defects after burns. Single-pedicled or multi-pedicled perforator flaps from back region were designed for treatment. ICGA was conducted after flap dissection intra-operatively to evaluate perfusion areas of perforators, which helped surgeons to determine whether supercharging should be conducted. After flap transplantation, ICGA was conducted again to evaluate the blood supply. Statistics of post-operative complications such as flap necrosis were collected.Results:the average flap size was 27 cm ×17 cm. With the guidance of ICGA, 15 cases remained the design of single pedicle including 5 superficial cervical artery (SCA) flaps and 10 free circumflex scapular artery (CSA) perforator flaps. Supercharging was performed in 7 cases: including 2 SCA flaps supercharged with CSA perforator and 5 free CSA perforator flaps supercharged with thoracodorsal artery (TDA) perforator. Venous thrombus occurred in 1 case but recovered after re-anastomosis of vessels. Except for 2 tip necroses, 20 flaps survived completely one week postoperatively. 2 tip necroses were recovered after dressing changes. All the patients were followed up for 5 to 16 months, with good flap color and texture, and improved function of head and neck.Conclusions:ICGA can be used as a safe and effective intraoperative detection method to guide the selection of appropriate perforators and the decisions on whether to conduct supercharging, which optimizes flap design and improves the success of surgery.

Objective:To investigate the effect of indocyanine green angiography (ICGA) in the design of pre-expanded perforator flaps in the reconstruction of large defects.Methods:From October 2018 to October 2019, there were 22 patients undergoing facial and cervical reconstructive surgeries based on pre-expanded perforator flaps in the back region in Shanghai Ninth Peoples′ Hospital. 12 male and 10 female patients, ranging from 4 to 26 years old with an average age of 19, were all suffered from inferior facial and cervical defects after burns. Single-pedicled or multi-pedicled perforator flaps from back region were designed for treatment. ICGA was conducted after flap dissection intra-operatively to evaluate perfusion areas of perforators, which helped surgeons to determine whether supercharging should be conducted. After flap transplantation, ICGA was conducted again to evaluate the blood supply. Statistics of post-operative complications such as flap necrosis were collected.Results:the average flap size was 27 cm ×17 cm. With the guidance of ICGA, 15 cases remained the design of single pedicle including 5 superficial cervical artery (SCA) flaps and 10 free circumflex scapular artery (CSA) perforator flaps. Supercharging was performed in 7 cases: including 2 SCA flaps supercharged with CSA perforator and 5 free CSA perforator flaps supercharged with thoracodorsal artery (TDA) perforator. Venous thrombus occurred in 1 case but recovered after re-anastomosis of vessels. Except for 2 tip necroses, 20 flaps survived completely one week postoperatively. 2 tip necroses were recovered after dressing changes. All the patients were followed up for 5 to 16 months, with good flap color and texture, and improved function of head and neck.Conclusions:ICGA can be used as a safe and effective intraoperative detection method to guide the selection of appropriate perforators and the decisions on whether to conduct supercharging, which optimizes flap design and improves the success of surgery.

Objective:To analyze the surgical method and clinical effect of modified anterolateral approach in the treatment of posterolateral tibial plateau fractures.Methods:From January 2014 to December 2017, 21 patients with posterolateral tibial plateau fractures were treated by the modified anterolateral approach in the second people's Hospital of Tangshan, Hebei Province were retrospectively analyzed.The outpatient department conducted regular reexaminations 1, 3, 6 and 12 months after the operation.Rasmussen radiology score, hospital for special surgery (HSS) score of knee function and Lysholm score were used to evaluate the postoperative knee function, and the score results were statistically analyzed.Results:The Rasmussen radiological score of 21 patients immediately after surgerywas (16.96±1.67), ranging from 15.00 to 18.00, with excellent in 15 cases, good in 6 cases, and the excellent and good rate was 100%.Rasmussen radiology score (16.57±1.51) in the last follow-up, ranging from 15.00 to 18.00, showed no significant difference between the last follow-up and the immediate postoperative ( t=0.935, P>0.05). At the last follow-up, the HSS score of knee joint function was (88.55±7.25), ranging from 80.00 to 9.00.At the last follow-up, Lysholm score (86.64±4.34), ranging from 82.00 to 90.00, was excellent in 15 cases, good in 6 cases, and excellent in 100%. Conclusion:The modified anterolateral approach for the treatment of posterolateral tibial plateau fractures is effective and simple, and can achieve good clinical results.

Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.
Animals ; Antibodies, Bispecific ; immunology ; Antibodies, Monoclonal ; immunology ; pharmacokinetics ; CD3 Complex ; metabolism ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; ErbB Receptors ; metabolism ; Female ; Humans ; Lymphocyte Activation ; immunology ; Mice, SCID ; Neoplasms ; immunology ; pathology ; Rats, Sprague-Dawley ; T-Lymphocytes, Cytotoxic ; immunology

Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.
Animals ; DNA, Mitochondrial ; genetics ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; MELAS Syndrome ; genetics ; Male ; Mice ; Microsatellite Repeats ; genetics ; Mitochondria ; genetics ; metabolism ; Mutation ; genetics

Objective To analysis the change of hip joint in healthy infants by ultrasound,and establish the normal reference value of the developmental dysplasia of the hip(DDH). Methods A total of 8 000 healthy infants from 0 to 24 weeks were collected from the Multi-center study of 10 children′s medical centers. Among them,3 855 infants(2 065 females and 1 790 males) with complete data and follow-up were included in this study. All subjects were divided into 6 groups ( ＜4,4～7,8～11,12～15,16～19 and≥20 weeks group). α angle,femoral head length and width,femoral head coverage ratio by acetabulum ( FHC) were measured in the coronal view on the neutral position;distance from pubis to femoral head ( P-H) and distance from ischium to femoral head ( I-H ) were measured in the transverse view on neutral position;distance from femoral head topubis ( H-P) was measured in the posterolateraltransverse view on the flexion position. The results of each group changes with age were analysised. Results ① The α angle of healthy infants from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05),but there was no significant difference between 16～19 and ≥20 weeks group( P ＞0.05). ②The femoral head length and width of all age groups were increased with age,the difference among all the groups was statistically significant( all P ＜0.05). ③ FHC from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05) except between 16～19 and ≥20 weeks group( P ＞0.05). ④ The P-H and I-H in all age groups showed no statistically significant ( all P＞0.05). ⑤The H-P of all age groups were increased with age,the difference between the groups were statistically significant(all P ＜0.05).Conclusions The development of hip joints have the certain regular developmental pattern in healthy infants less than 5 months of birth and are relatively constant after birth more than 5 months. The ultrasound normal reference value of the hip joints can be used for the early diagnosis of the DDH.

Objectives To investigate whether the presence of metabolic syndrome (MS) modifies overall survival and cardiovascular (CV) outcomes among patients undergoing long-term peritoneal dialysis (PD) and to explore suitable diagnostic criterion for PD patients.Methods A total of 258 patients on PD in Peking University Third Hospital between October 2008 and March 2009 were enrolled and followed until June 2017.According to the diagnostic criteria of WHO,IDF and ATP Ⅲ,the patients were divided into MS group and non-MS group.The median following time was 51.9 (26.8,97.9) months.Overall survival and cardiovascular death were analyzed by the Kaplan-Meier method.The analyses were also done among non-diabetic PD patients.The influence of MS and its components on outcomes was analyzed by Cox regression models.Results Among 258 PD patients,106(41.1％) fulfilled the WHO criteria,121(46.9％) the IDF criteria,and 167(64.7％) the ATP criteria.139 cases were dead,among which 50(36.0％) cases were caused by CV diseases.The patients with MS had worse outcomes than those without MS by WHO and IDF criteria (cumulative survival rates of WHO criteria:21.3％ vs 44.8％,P ＜ 0.01;cumulative surviva rats of IDF criteria:23.3％ vs 45.7％,P ＜ 0.01).It was the same even in non-diabetic PD patients.The patients with MS had more CV death than those without MS by WHO and IDF criteria (both P ＜ 0.05).Among non-diabetic PD patients,the results remained the same only by IDF criteria (P ＜ 0.05).By ATP criteria,above analyses showed no difference.By multivariate Cox regression analysis,MS and serum albumin (all P ＜ 0.01) were independently associated with increased risk for overall and cardiovascular survival.Among MS components,waist girth,low-density lipoprotein cholesterol (LDL-C) levels and blood sugar (all P ＜ 0.01) were significant risk factors for adverse survival outcomes.Conclusions In patients undergoing PD,both overall survival and cardiovascular survival were worse in patients with MS than those without MS.Waist girth,blood sugar and serum LDL-C were the main risk factors.For PD patients the IDF criterion for MS was recommended.

Objective To observe the clinical efficacy of percutaneous nephrolithotomy ( PCNL ) with Holmium laser and no help of irrigating pump in the treatment of renal calculi in 127 cases.Methods From January 2012 to November 2017 ,a total of 127 patients with renal calculi have suffered mini -PCNL with Holmium laser and no help of irrigating pump by using 16F or 18F Urovision percutaneous nephrostomy kit in Peking University Shougang Hospital ,the Hospital of Mentougou District and the Traditional Chinese Medicine Hospital of Mentougou District were collected.The operation time, intraoperative blood loss, hospitalization stay, lithotripsy rate, stone clearance and principal complications of operation were analyzed statistically .Results The first phase success rate of percutaneous nephrostomy was 100％, lithotripsy rate was 24.4％, stone clearance rate was 24.4％.The operation time was (36.1 ±15.6)min.The intraoperative blood loss was (45.4 ±31.7)mL.But postoperative abdominal X-ray showed that 96 patients with residual calculi ≥ 4mm needed to receive the second look PCNL .These 96 patients reached 100.0％ of lithotripsy rate and 100.0％ of stone clearance postoperatively .The operation time was ( 64.5 ± 31.1)min.The intraoperative blood loss was (23.1 ±21.9)mL.No severe complications such as massive hemorrhage occurred.The hospitalization stay was (12 ±5 ) d.Conclusion Larger renal calculus except complete staghorn calculus,and upper ureteral calculus are the indications for PCNL with Holmium laser and no help of irrigating pump . It is safe and feasible to perform PCNL with Holmium laser and no help of irrigating pump .