Objective To study the effects of intramedullary pressure on the fluid flow behavior in bones.Methods Multi-scale models of macro bone tissue and macro-meso osteon groups were established using the COMSOL Multiphysics software.Considering the interrelationship of different pore scales,such as the bone marrow cavity,Haversia canal,and bone lacunar-canaliculus,the pore pressure and flow rate of hollow bone tissues and bone tissues with intramedullary pressure were compared,and the effects of the amplitude and frequency of intramedullary pressure on the pressure and flow velocity of the liquid in the bone were analyzed.Results When intramedullary pressure was considered,the pore pressure in bone tissues with intramedullary pressure was 6.4 kPa higher than that in hollow bone tissues.The flow pressure increased significantly with an increase in the intramedullary pressure amplitude,but the flow velocity remained unchanged.The frequency of intramedullary pressure had little effect on pore pressure and flow velocity.Conclusions The multi-scale pore model established in this study can accurately analyze bone fluid flow behavior.These results are of great significance for an in-depth understanding of force conduction in the bone.

Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

Objective To analyze the effect of Xiaozhi Decoction in the treatment of hyperlipidemiain different classification of physical constitution in TCM.Methods We screened 206 patients with Hyperlipidemia in our hospital and had been treated with drugs during May 2020 to March 2023.Totally 103 patients in the TCM group were treated with Xiaozhi Decoction,103 patients in the western medicine group were treated with atorvastatin.Selected total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and liver transaminase before and after a period of treatment.The non-high-density lipoprotein cholesterol(non-HDL-C)will be calculated,too.Results In the Phlegm-Dampness constitution,TC,TG,LDL-C and non-HDL-C decreased significantly all in the TCM group(P<0.05);TC,TG and non-HDL-C decreased significantly all in the western medicine group(P<0.05).The TCM group is superior to the western medicine group in TC,LDL-C,non-HDL-C(P<0.05).In the Qi-Deficiency constitution,TC,TG,LDL-C and non-HDL-C decreased significantly all in the TCM group(P<0.05);TC,LDL-C and non-HDL-C decreased significantly all in the western medicine group(P<0.05).The TCM group is superior to the western medicine group in non-HDL-C(P<0.05).In the Blood-Stasis constitution,TC,TG,LDL-C and non-HDL-C decreased significantly all in the western medicine group only(P<0.05).The western medicine group is superior to the TCM group in TC,LDL-C,non-HDL-C(P<0.05).In the Yin-Yang Harmony constitution,TC and non-HDL-C decreased significantly both in the TCM group(P<0.05).TC,LDL-C and non-HDL-C decreased significantly all in the western medicine group(P<0.05).The western medicine group is superior to the TCM group in TC,LDL-C,non-HDL-C(P<0.05).Conclusion Xiaozhi Decoction is superior to the the atorvastatin in the treatment of hyperlipidemia for the Phlegm-Dampness constitution and Qi-deficiency constitution groups.But it is not superior to the atorvastatin in the treatment of hyperlipidemia for the Blood-Stasis constitution and Yin-Yang Harmony constitution groups.

OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.

Objective:To evaluate the efficacy and safety of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost in the treatment of brain metastases of lung cancer.Methods:Forty lung cancer patients with brain metastases who received whole-brain radiotherapy with simultaneous integrated boost and hippocampal avoidance in Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2020 were enrolled in this study. Brain MRI, survival follow-up and evaluation of side effects were performed before radiotherapy and at 1, 3, 6 and 12 months after radiotherapy, respectively. Overall survival (OS), progression-free survival (PFS) and changes in cognitive function were analyzed. Continuous data were described as Mean ± SD. Categorical data were described by frequency and composition ratio or percentage. Survival analysis was conducted by Kaplan-Meier method. Influencing factors of survival were identified by univariate and multivariate Cox's regression analyses.Results:A total of 40 patients were enrolled in the study. The median follow-up time was 14.2 months and the median OS, PFS and intracranial PFS of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis showed that male gender and newly diagnosed stage Ⅳ disease were associated with worse OS and PFS, respectively. The Hopkins verbal learning test-revised (HVLT-R) scores at baseline and 1, 3 and 6 months after radiotherapy were 21.94±2.99, 20.88±3.12, 20.03±3.14, and 19.78±2.98, respectively. The HVLT-R score at 6 months after radiotherapy was decreased by approximately 9.8% compared with the baseline. No grade 3 or above toxic and side effect occurred in the entire cohort.Conclusion:Hippocampal avoidance whole-brain irradiation with simultaneous integrated boost is a safe and effective treatment for brain metastases of lung cancer, which is expected to reduce the impact of radiotherapy on cognitive function.

Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.

Objective:To evaluate the safety and tolerance of sequential thoracic radiotherapy combined with PD-1/PD-L1 inhibitors in patients with extensive-stage small cell lung cancer (ES-SCLC) after induction systemic therapy.Methods:ES-SCLC patients from a phase I trial and a real-world study were enrolled for those who received thoracic radiotherapy after induction systemic treatment (chemotherapy/chemotherapy combined with PD-1/PD-L1 inhibitors) and consolidated with PD-1/PD-L1 inhibitors. These two studies were both approved by the Ethics Committee of Chinese Academy of Medical Sciences Cancer Hospital (Clinical Trials.gov number, NCT03971214, NCT04947774).Results:Between January 2019 and March 2021, a total of 11 patients with ES-SCLC were analyzed, aged 52-73 years, with a median age of 62 years. Among them, five patients (45.5%) received induction chemotherapy and six patients (54.5%) received chemotherapy combined with PD-1/PD-L1 inhibitor, and then all received intensity-modulated thoracic radiotherapy after evaluation of systemic treatment efficacy. Two patients developed treatment-related grade G3-5 toxicity (18.2%, 1 treatment-related pneumonitis and 1 radiation esophagitis). G 1-G 2 hematologic toxicity, pneumonia, and anorexia were common mild toxicities. Only one patient (9.1%) terminated immunotherapy due to immune-related pneumonitis. During a median follow-up time of 12.5 months (range: 3.5-16.4 months), the median disease progression-free survival and overall survival was 7.4 months (95% CI: 6.9-8.0 months) and 14.6 months (95% CI: 9.0-20.2 months), respectively. Conclusions:Sequential thoracic radiotherapy followed by PD-1/PD-L1 inhibitor is safe and feasible in patients with ES-SCLC after induction therapy. Given that both thoracic radiotherapy and immunotherapy benefits the ES-SCLC in survival, this comprehensive treatment modality warrants further investigation.

Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.

Objective:To evaluate the efficacy and safety of total aortic arch replacement in elderly patients with Stanford type A aortic dissection(TAAD).Methods:In this retrospective study, a total of 481 TAAD patients treated with total arch replacement in our hospital from January 2016 to January 2020 were divided into three groups: aged≤59 years, 60-69 years and ≥70 years.The differences between three groups in surgical method, extracorporeal circulation time, blocking time, circulatory time, stopping time, surgical time, ventilator use time, ICU time, hospitalization time, treatment rate of continued renal replacement, fatality rate, and cause of death were statistically analyzed and compared.Results:There were statistically significant differences in the stopping time between any two groups of the three groups(all P<0.05). The older the age, the shorter the circulatory arrest time.The difference of ventilator time and ICU time between ≤59 and 60-69 years was statistically significant( P<0.01). Patients with continuous renal replacement(CRRT)were 19.0%(71/373)in ≤59 years, 23.1%(18/78)in 60~69 years, and 26.7%(8/30)over 70 years.In-hospital mortality was 35/373(9.4%)in the group of ≤59 years old, 11/78(14.1%)in the group of 60~69 years old, and 5/30(16.7%)in the group of ≥70 years old.There was no death in patients undergoing type Ⅱ hybrid surgery. Conclusions:Age is one of the important death factors after total aortic arch replacement in TAAD patients.Total aortic arch replacement is an acceptable surgical method for elderly patients with TAAD.Hybridization may reduce hospitalization death in elderly patients.

Objective:To establish a double antibody sandwich ELISA for detecting the specific antigen of Seoul virus (SEOV) L99 strain and to provide a means for antigen detection in the development, production and verification of vaccine against hemorrhagic fever with renal syndrome (HFRS).Methods:Monoclonal antibodies (McAbs) aganist L99 virus were induced in mice using four hybridoma cell lines and purified by Protein-A affinity chromatography. The purity, titer and specificity of McAbs were determined by SDS-PAGE, indirect ELISA and Western blot, respectively. Four McAbs were paired with each other and the additivity indices of paired McAbs were analyzed. After labeling McAbs with horseradish peroxidase (HRP), the concentrations of the coated and labeled antibodies were optimized by orthogonal test, and then a double antibody sandwich ELISA for virus antigen detection was established. Type Ⅱ HFRS inactivated vaccine standard was used as a quantitative standard to verify the sensitivity, linearity, specificity, accuracy and precision of the developed method. The applicability of the method was verified by testing three batches of vaccine stock solutions.Results:Four McAbs were at titers of greater than 1∶10 6 and their purity was all greater than 98%. The McAbs secreted by 1D5, 3A4 and 5B7 cells could specifically recognize the nucleocapsid protein of SEOV L99. There was cross-reaction between McAb secreted by 1D5 cells and Hantaan virus PS-6. The McAbs secreted by 3A4 and 1D5 were used as coating and labeling antibodies based on the results of antibody pairs. The working concentrations of the coating antibody and the horseradish peroxidase (HRP)-labeled antibody were 20 μg/ml and 1∶4 000, respectively. The minimum detection limit of the established method for the detection of SEOV L99 antigen was 0.078 1 μg/ml, and the linear range was 0.078 1-2.500 0 μg/ml with a R2 value of more than 0.99. There was no cross reaction with other HFRS vaccine. The virus antigen recovery rate was between 95.8% and 108.7%, and the coefficients of variation of precision was less than 10%. Three batches of Type II HFRS inactivated vaccine stocks were detected by this method and the results was dose-dependent. Conclusions:This study successfully established a double antibody sandwich ELISA method for specific detection of SEOV L99 strain antigen in the production of bivalent HFRS vaccines produced from hamster kidney cells.