Objective To investigate the lonely behavior characteristics and related factors of chronic obstruetive pulmonary disease(COPD)patients.Methods 99 eases with stable patients with COPD and 90 healthy subjects were surveyed by SDS,ESLI.Relevant factors were analyzed.Results Patients with COPD showed difierent degrees of emotional isolation[(9.90±3.97),(6.15±5.22),F=82.539,P＜0.01)]and social intercourse isolation[(8.00±3.53),(4.31±2.46),F=73.540,P＜0.01)].Emotional isolation was mainly.Moderate emotional isolation and general social intercourse isolation were predominant,and emotional(r=0.399,t=3.476,P＜0.01)and social intercourse isolation(r=0.372,t=3.154,P＜0.01)were related to depression.Conclusion Patients with COPD presented obvious emotion and social intercourse isolation behavior.

Objective To study the functional connectivity (FC) pattern of thalamus in patients with Alzheimer' s disease (AD).Methods In the present study,resting state functional magnetic resonance imaging (MRI) data were obtained from 30 patients with AD and 26 subjects with normal cognition (NC).The altered functional connectivity pattern in AD was evaluated by comparing to NC.Then a correlation analysis was performed between the strength of FC of the identified regions and various clinical variables for evaluating the relationships between the strength of FC and the cognitive abilities (MMSE,immediate recall and delayed recall of Auditory Verbal Learning Test) of the AD patients.Results The MMSE(19.7 ± 4.1),immediate recall (2.8 ± 1.7) and delayed recall (0.7 ± 1.3) of Auditory Verbal Learning Test in AD patients were lower than NC group (28.8 ± 1.0,5.9 ± 1.2,5.7 ± 2.2 ; t =11.09,8.09,10.51,all P ＜0.05).Compared to NC,AD patients showed decreased FC between the left thalamus and several regions of brain including right posterior/middle cingulate cortex (PCC/MCC.R),left medial prefrontal cortex (MPFC.L) and right superior frontal gyms/medial prefrontal cortex (SFG/MPFC.R).For the right thalamus,decreased FC was found in SFG/MPFC.R,PCC/MCC.R and right hippocampus.We also found increased FC between the bilateral thalamus and many regions of brain including inferior temporal gyrus,medial temporal gyrus,SFG,postcentral gyrus,paracentral lobule,inferior frontal gyms and insula.Significant correlations between the fitted FC strength and clinical variables were also detected.Conclusions FC pattern of thalamus in AD group is impaired.Increased FC in AD may indicate the presence of a compensatory mechanism.The alteration is related with cognitive function in AD.

Objective: To identify Tongren Wujibaifeng Pills and Xiaoshuanzaizao Pills respectively by analysis of IR fingerprint. Methods: Both drugs were extracted with hexane, ether and butanone and then the extracts obtained were measured with FT IR spectrometer. Results: By analizing IR fingerprint of 25 batches Tongren Wujibaifeng Pills and 31 batches Xiaoshuanzaizao Pills, we found that different batches of the same drug have stable and repeatable fingerprint. Conclusion: By using IR fingerprint, either Tongren Wujibaifeng Pills and Xiaoshuanzaizao Pills can be identified. It provides a rapid method for drug identification and quality control.

AIM: To identify the Chinese medicinal granule by measuring IR fingerprints. METHODS: 13 kinds of granules were extracted with butanone respectively and then the obtained extracts were measured with the FT IR spectrometer. RESULTS: By IR fingerprint of 13 kinds of granules drugs, different batches of the same crude drug had a stable and repeatable fingerprint. CONCLUSION: By using IR fingerprint, Chinese medicinal granule can be identified and provides a rapid method for drug identification and quality control.

Objective To evaluate the technique and outcome of arthroscopic reconstruction of posterior cruciate ligament(PCL)with preservation of the remnants.Methods From January 2006 to January 2009.16 knees in 16 patients with PCL tear were verified with arthroscopy.All the damaged PCL were reconstructed with single bundle of autogenous quadrupled hamstring tendons under arthroscopy without remove of the remnants of PCL.Endo-button and Bio-absorbabh interference screw were used for direct anatomic fixation of the reconstructed ligament.Results No severe complication occurred in early stage after operation in the 16 patients.All of them were followed up from 4 to 14 months with an average of (7.4±2.1)months.Lysholm score was remarkable improved from mean(61.3±8.7)preoperative scores to mean(91.7±6.3)scores at the latest follow up(P＜0.05).Furthermore,there was a significant improvement in IKDC scofe from abnormal (grade C)in 9 knees and severely abnormal (grade D)in 7 knees preoperatively to normal(grade A)in 11 knees,nearly normal(grade B)in 5 knees at the follow up.All of the 16 patients returned to the same sports level before injury.Conclusion Arthroscopic reconstruction of PCL with preservadon of the remnants has advantages of minimal inmmrticular interference,and potential facility to revagculization and reinnervation of the reconstlucted ligament.

Objective To analyze the clinical efficacy of gamma-ray fractionated stereotactic radiotherapy (FSRT) in the treatment of intracranial metastatic polycystic tumors.Methods Forty cases with 61 metastatic polycystic tumors were selected from 189 patients with 373 intracranial metastatic tumors admitted to our hospital from 2013 to 2015.All cases received gamma-ray FSRT.The isodose line at 50％ was defined as the prescription dose.The prescription dose was ranged from 40 to 48 Gy/10-12f.The survival rate was calculated by Kaplan-Meier method.The single factor analysis was performed by Log-rank method.Results The median follow-up time was 21months (range:6-39 months).The median survival time was 15.3 months.The 6-month,1-and 2-year local control rate was 93％,82％ and 79％,respectively.The 1-and 2-year survival rate was 63％ and 30％.Single factor analysis demonstrated that the volume of cysts and the volume of lesions were not significantly correlated with local control rate (P=0.17 and 0.48).Conclusion Gamma-ray FSRT can be adopted to treat intracranial metastatic polycystic tumors,which yields similar clinical efficacy to metastatic solid tumors.It deserves wide application in clinical practice due to high local control rate and safety.

OBJECTIVE: The purpose of this study was to prospectively investigate the value of the myocardial extracellular volume fraction (ECV) in predicting myocardial functional outcome after revascularization of coronary chronic total occlusion (CTO). MATERIALS AND METHODS: Thirty patients with CTO underwent cardiovascular magnetic resonance (CMR) before and 6 months after revascularization. Three baseline markers of functional outcome were evaluated in the dysfunctional segments assigned to the CTO vessels: ECV, transmural extent of infarction (TEI), and unenhanced rim thickness (RIM). At the global level, the ECV values of the whole myocardium with and without a hyperenhanced region (global and remote ECV) were respectively measured. RESULTS: In per-segment analysis, ECV was superior to TEI and RIM in predicting functional recovery (area under receiver operating characteristic curve [AUC]: 0.86 vs. 0.75 and 0.73, all p values < 0.010), and it emerged as the only independent predictor of regional functional outcome (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.77–0.89; p < 0.001) independent of collateral circulation. In per-patient analysis, global baseline ECV was indicative of ejection fraction (EF) at the follow-up examination (β = −0.61, p < 0.001) and changes in EF (β = −0.57, p = 0.001) in multivariate regression analysis. A patient with global baseline ECV less than 30.0% (AUC, 0.93; sensitivity 94%, specificity 80%) was more likely to demonstrate significant EF improvement (OR: 0.38; 95% CI: 0.17–0.85; p = 0.019). CONCLUSION: Extracellular volume fraction obtained by CMR may provide incremental value for the prediction of functional recovery both at the segmental and global levels in CTO patients, and may facilitate the identification of patients who can benefit from revascularization.
Collateral Circulation ; Coronary Vessels* ; Follow-Up Studies ; Humans ; Infarction ; Magnetic Resonance Imaging* ; Myocardial Infarction ; Myocardial Ischemia ; Myocardium ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity

Ninety percent of clinical drug development fails despite implementation of many successful strategies, which raised the question whether certain aspects in target validation and drug optimization are overlooked? Current drug optimization overly emphasizes potency/specificity using structure‒activity-relationship (SAR) but overlooks tissue exposure/selectivity in disease/normal tissues using structure‒tissue exposure/selectivity-relationship (STR), which may mislead the drug candidate selection and impact the balance of clinical dose/efficacy/toxicity. We propose structure‒tissue exposure/selectivity-activity relationship (STAR) to improve drug optimization, which classifies drug candidates based on drug's potency/selectivity, tissue exposure/selectivity, and required dose for balancing clinical efficacy/toxicity. Class I drugs have high specificity/potency and high tissue exposure/selectivity, which needs low dose to achieve superior clinical efficacy/safety with high success rate. Class II drugs have high specificity/potency and low tissue exposure/selectivity, which requires high dose to achieve clinical efficacy with high toxicity and needs to be cautiously evaluated. Class III drugs have relatively low (adequate) specificity/potency but high tissue exposure/selectivity, which requires low dose to achieve clinical efficacy with manageable toxicity but are often overlooked. Class IV drugs have low specificity/potency and low tissue exposure/selectivity, which achieves inadequate efficacy/safety, and should be terminated early. STAR may improve drug optimization and clinical studies for the success of clinical drug development.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.