AMIGO2 attenuates innate cisplatin sensitivity by suppression of GSDME-conferred pyroptosis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer. Cisplatin is commonly used in the treatment of many malignant tumours including NSCLC. The innate drug sensitivity greatly affects the clinical efficacy of cisplatin-based chemotherapy. As a plasma membrane adhesion molecule, amphoterin-induced gene and ORF-2 (AMIGO2) initially identified as a neurite outgrowth factor has been recently found to play a crucial role in cancer occurrence and progression. However, it is still unclear whether AMIGO2 is involved in innate cisplatin sensitivity. In the present study, we provided the in vitro and in vivo evidences indicating that the alteration of AMIGO2 expression triggered changes of innate cisplatin sensitivity as well as cisplatin-induced pyroptosis in NSCLC. Further results revealed that AMIGO2 might inhibit cisplatin-induced activation of (caspase-8 and caspase-9)/caspase-3 via stimulating PDK1/Akt (T308) signalling axis, resulting in suppression of GSDME cleavage and the subsequent cell pyroptosis, thereby decreasing the sensitivity of NSCLC cells to cisplatin treatment. The results provided a new insight that AMIGO2 regulated the innate cisplatin sensitivity of NSCLC through GSDME-mediated pyroptosis.

Association between post-stroke smoking and stroke recurrence in first-ever ischemic stroke survivors: based on a 10-year prospective cohort.

BACKGROUND: Whether smoking is a risk factor for ischemic stroke (IS) recurrence in IS survivors is still uncovered, and evidences are sparse. Meanwhile, an add-on effect of clopidogrel was observed in myocardial infarction patients who smoked, but whether the paradox exists in IS patients is still unsolved. The objectives of this study are to explore the association between smoking behavior after index stroke and IS recurrence and to explore whether the paradox exists. METHODS: A prospective cohort of first-ever IS patients was conducted between 2010 and 2019. The prognosis and smoking features of enrolled patients were obtained via telephone follow-up every 3 months. Fine-gray model with interaction terms was applied to measure the relationships between stroke recurrence and smoking behaviors after index stroke and to explore the add-on effect of clopidogrel in smoking patients. RESULTS: There were 171 (24.26%) recurrences and 129 (18.30%) deaths during follow-up in 705 enrolled IS patients. One hundred forty-six (20.71%) patients smoked after index stroke. The hazard ratios (HRs) and 95% confidence intervals (CIs) of interaction terms between antiplatelet drug and follow-up smoking (smoking status and daily smoking amount) were 1.092 (95% CI: 0.524, 2.276) and 0.985 (95% CI: 0.941, 1.031), respectively. A significantly higher risk of recurrence was observed in patients with a higher daily smoking amount during follow-up (per cigarette), with HR being 1.027 (95% CI: 1.003, 1.052). CONCLUSIONS: Smoking could elevate the risk of IS recurrence, and IS survivor should be advised to quit or smoke less. Add-on effect of clopidogrel may not exist in smoking strokers taking clopidogrel.

Specific changes and clinical significance of plasma D-dimer during pregnancy and puerperium: a prospective study.

BACKGROUND: Pregnant and puerperal women are high-risk populations for developing venous thromboembolism (VTE). Plasma D-dimer (D-D) is of good value in the diagnosis of exclusion of VTE in the nonpregnant population. Since there is no consensus reference range of plasma D-D applicable to pregnant and puerperal women, the application of plasma D-D is limited. To investigate the change characteristics and the reference range of plasma D-D levels during pregnancy and puerperium and to explore the pregnancy- and childbirth-related factors affecting plasma D-D levels and the diagnostic efficacy of plasma D-D for excluding VTE during early puerperium after caesarean section. METHODS: A prospective cohort study was conducted with 514 pregnant and puerperal women (cohort 1), and 29 puerperal women developed VTE 24-48 h after caesarean section (cohort 2). In cohort 1, the effects of the pregnancy- and childbirth-related factors on the plasma D-D levels were analyzed by comparing the differences in plasma D-D levels between different groups and between different subgroups. The 95th percentiles were calculated to establish the unilateral upper limits of the plasma D-D levels. The plasma D-D levels at 24-48 h postpartum were compared between normal singleton pregnant and puerperal women in cohort 2 and women from the cesarean section subgroup in cohort 1, binary logistic analysis was used to analyze the relevance between plasma D-D level and the risk of VTE developing 24-48 h after caesarean section, and a receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of plasma D-D for excluding VTE during early puerperium after caesarean section. RESULTS: The 95% reference ranges of plasma D-D levels in the normal singleton pregnancy group were ≤ 1.01 mg/L in the first trimester, ≤ 3.17 mg/L in the second trimester, ≤ 5.35 mg/L in the third trimester, ≤ 5.47 mg/L at 24-48 h postpartum, and ≤ 0.66 mg/L at 42 days postpartum. The plasma D-D levels of the normal twin pregnancy group were significantly higher than those of the normal singleton pregnancy group during pregnancy (P < 0.05), the plasma D-D levels of the GDM group in the third trimester were significantly higher than those of the normal singleton pregnancy group (P < 0.05). The plasma D-D levels of the advanced age subgroup at 24-48 h postpartum were significantly higher than those of the nonadvanced age subgroup (P < 0.05), and the plasma D-D levels of the caesarean section subgroup at 24-48 h postpartum were significantly higher than those of the vaginal delivery subgroup (P < 0.05). The plasma D-D level was significantly correlated with the risk of VTE developing at 24-48 h after caesarean section (OR = 2.252, 95% CI: 1.611-3.149). The optimal cut-off value of plasma D-D for the diagnosis of exclusion of VTE during early puerperium after caesarean section was 3.24 mg/L. The negative predictive value for the diagnosis of exclusion of VTE was 96.1%, and the area under the curve (AUC) was 0.816, P < 0.001. CONCLUSIONS: The thresholds of plasma D-D levels in normal singleton pregnancy and parturient women were higher than those of nonpregnant women. Plasma D-D had good value in the diagnosis of exclusion of VTE occurring during early puerperium after caesarean section. Further studies are needed to validate these reference ranges and assess the effects of pregnancy- and childbirth-related factors on plasma D-D levels and the diagnostic efficacy of plasma D-D for excluding VTE during pregnancy and puerperium.

[Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Predicting Preeclampsia During Pregnancy].

Objective: To investigate the changes of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in women with normal pregnancy women and pregnant women with preeclampsia (PE) and the value of using NLR and PLR in the first trimester to predict PE. Methods: We retrospectively collected the clinical data of 485 pregnant women (97 had PE and 388 were of normal pregnancy) who were admitted to West China Second University Hospital and had their babies delivered there between January 1 and December 31, 2016 and 30 healthy women who were not pregnant and who had physical examination at the hospital over the same period. The subjects' NLR and PLR were calculated and compared. Logistic regression analysis was done to study the risk factors of PE, and the receiver operating characteristic curves were used to assess the value of using NLR and PLR in the first trimester to predict PE. Results: There was no significant difference in NLR or PLR between the PE group and the normal pregnancy group in the first, second and third trimesters. Compared with that of the normal non-pregnant group, the NLR of the PE group and the normal pregnancy group started to rise in the first trimester, reached the maximum in the second trimester, and decreased in the third trimester; PLR started to decrease in the second trimester and reached the lowest level in the third trimester, exhibiting significant differences ( P<0.05). In the three trimesters, NLR and PLR were not associated with the severity of PE, maternal age, or pre-pregnancy BMI. The predictive model combining factors including pre-pregnancy obesity, advanced maternal age, and nulliparity showed an area under the curve ( AUC) of 0.84 for predicting PE. When NLR in the first trimester or PLR in the first trimester were added to the combined model of pre-pregnancy obesity, advanced maternal age, and nulliparity, the AUC subsequently derived were both 0.85. Conclusion: NLR and PLR are not independent influencing factors of PE and cannot improve the predictive value for PE.

Immune-Related Pneumonitis Was Decreased by Addition of Chemotherapy with PD-1/L1 Inhibitors: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials (RCTs).

PURPOSE: Immune-related pneumonitis (IRP) has attracted extensive attention, owing to its increased mortality rate. Conventional chemotherapy (C) has been considered as an immunosuppressive agent and may thus reduce IRP's risk when used in combination with PD-1/L1 inhibitors. This study aimed to assess the risk of IRP with PD-1/L1 inhibitors plus chemotherapy (I+C) versus PD-1/L1 inhibitors alone (I) in solid cancer treatment. METHOD: Multiple databases were searched for RCTs before January 2021. This NMA was performed among I+C, I, and C to investigate IRP's risk. Subgroup analysis was carried out on the basis of different PD-1/L1 inhibitors and cancer types. RESULTS: Thirty-one RCTs (19,624 patients) were included. The I+C group exhibited a lower risk of IRP in any grade (RR, 0.60; 95% CI, 0.38-0.95) and in grade 3-5 (RR, 0.44; 95% CI, 0.21-0.92) as opposed to the I group. The risk of any grade IRP with PD-1 plus chemotherapy was lower than that with PD-1 monotherapy (RR, 0.50; 95% CI, 0.28-0.89), although grade 3-5 IRP was similar. There was no statistically meaningful difference in the risk of any grade IRP between PD-L1 plus chemotherapy and PD-L1 inhibitors monotherapy (RR, 0.95; 95% CI, 0.43-2.09) or grade 3-5 IRP (RR, 0.71;95% CI, 0.24-2.07). In addition, compared with the I group, the I+C group was correlated with a decreased risk in IRP regardless of cancer type, while a substantial difference was only observed in NSCLC patients for grade 3-5 IRP (RR, 0.39; 95% CI, 0.15-0.98). CONCLUSION: In comparison to PD-1/L1 inhibitor treatment alone, combining chemotherapy with PD-1/L1 inhibitors might reduce the risk of IRP in the general population. Furthermore, PD-1 inhibitors in combination with chemotherapy were correlated with a decreased risk of IRP compared to PD-1 inhibitor treatment alone. In contrast to the I group, the I+C group exhibited a lower risk of IRP, especially for NSCLC patients.

Feasibility of utilizing ultra-low-dose contrast medium for pancreatic artery depiction using the combination of advanced virtual monoenergetic imaging and high-concentration contrast medium: an intra-patient study.

OBJECTIVES: The least amount of contrast medium (CM) should be used under the premise of adequate diagnosis. The purpose of this study is to evaluate the feasibility of utilizing ultra-low-dose (224 mgI/kg) CM for pancreatic artery depiction using the combination of advanced virtual monoenergetic imaging (VMI+) and high-concentration (400 mgI/mL) CM. MATERIALS AND METHODS: 41 patients who underwent both normal dose CM (ND-CM, 320 mgI/kg) and low dose CM (LD-CM, 224 mgI/kg) thoracoabdominal enhanced CT for tumor follow-up were prospectively included. The VMI+ at the energy level of 40-kev for LD-CM images was reconstructed. CT attenuation, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of the abdominal artery, celiac artery, and superior mesenteric artery (SMA) and qualitative scores of pancreatic arteries depiction were recorded and compared among the three groups (ND-CM, LD-CM, and VMI+ LD-CM images). ANOVA and Friedman tests were used for statistical analysis. RESULTS: All quantitative and qualitative parameters on LD-CM images were lower than that on ND-CM images (all p < 0.01). There were no significant differences of all arteries' qualitative scores between ND-CM and VMI+ LD-CM images (all p > 0.05). VMI+ LD-CM images had the highest mean CT and CNR values of all arteries (all p < 0.0001). The CM volume was 52.6 ± 9.4 mL for the ND-CM group and 37.0 ± 6.7 mL for the LD-CM group. CONCLUSION: Ultra-low-dose CM (224 mgI/kg) was feasible for depicting pancreatic arteries. Inferior angiographic image quality could be successfully compensated by VMI+ and high-concentration CM.

Associations between Lesion Locations and Stroke Recurrence in Survivors of First-ever Ischemic Stroke: A Prospective Cohort Study.

Several studies have indicated that stroke survivors with multiple lesions or with larger lesion volumes have a higher risk of stroke recurrence. However, the relationship between lesion locations and stroke recurrence is unclear. We conducted a prospective cohort study of first-ever ischemic stroke survivors who were consecutively enrolled from January 2010 to December 2015. Stroke recurrence was assessed every 3 months after post-discharge via telephone interviews by trained interviewers. Lesion locations were obtained from hospital-based MRI or CT scans and classified using two classification systems that were based on cerebral hemisphere or vascular territory and brain anatomical structures. Flexible parametric survival models using the proportional hazards scale (PH model) were used to analyze the time-to-event data. Among 633 survivors, 63.51% (n=402) had anterior circulation ischemia (ACI), and more than half of all ACIs occurred in the subcortex. After a median follow-up of 2.5 years, 117 (18.48%) survivors developed a recurrent stroke. The results of the multivariate PH model showed that survivors with non-brain lesions were at higher risk of recurrence than those with right-side lesions (HR, 2.79; 95%CI, 1.53, 5.08; P=0.001). There was no increase in risk among survivors with left-side lesions (HR, 0.97; 95%CI, 0.53, 1.75; P=0.914) or both-side lesions (HR, 1.24; 95%CI, 0.75, 2.07; P=0.401) compared to those with right-side lesions. Additionally, there were no associations between stroke recurrence and lesion locations that were classified based on vascular territory and brain anatomical structures. It was concluded that first-ever ischemic stroke survivors with non-brain lesion had higher recurrence risk than those with right-side lesion, although no significant associations were found when the lesion locations were classified by vascular territory and brain anatomical structures.

Risk factors and pregnancy outcomes associated with retinopathy in patients presenting with severe preeclampsia: A retrospective cohort study.

The visual system was reported to be affected in over half of patients with preeclampsia (PE), though fundus examination was performed only among patients complaining of visual symptoms. Delayed diagnosis and treatment of PE-related retinopathy may lead to permanent visual impairment. Therefore, we hypothesize that some clinical or laboratory parameters could predict severity of retinal damage.The aim of the study was to explore the risk factors for retinopathy in severe preeclampsia (sPE) and investigate pregnancy outcomes with different degrees of retinopathy.This retrospective cohort study included women with sPE who underwent ophthalmoscopy and delivered after admission to West China Second University Hospital, between June 2013 and December 2016. Clinical and laboratory characteristics were retrieved from medical records. Patients confirmed with retinopathy were followed up with telephones. Multiple logistic regression analysis was performed to identify risk factors of PE-related retinopathy.Five hundred thirty-four patients were included, of which 17.6% having stage-1/2 retinopathy, 14.6% having stage-3/4 retinopathy, and 67.8% having normal retina. Compared with patients without retinopathy, patients with stage 3/4 retinopathy were more likely to have preterm-birth and low-birth-weight babies. Significant risk factors for stage 3/4 retinopathy in sPE included severe hypertension (odds ratio [OR] 2.24, 95% confidence interval [CI]: 1.10-4.56), elevated white blood cell (WBC) counts (OR 1.88, 95% CI: 1.05-3.35), decreased platelet counts (OR 2.12, 95% CI: 1.07-4.48), lactate dehydrogenase (LDH) concentration of >800 IU/L (OR 2.31, 95% CI: 1.05-5.06), low hemoglobin (HGB) concentrations of <110 g/L (OR 3.73, 95% CI: 1.21-11.47), 24-hour proteinuria of 2 to 5 g (OR 6.39, 95% CI: 2.84-14.39), and >5 g (OR 8.66, 95% CI: 3.67-20.44).This study confirms the association between retinopathy and preterm-birth and low-birth weight in sPE. The risk factors for severe PE-related retinopathy, including severe hypertension, platelet and WBC count, HGB and LDH concentration, and proteinuria, are associated with the development of retinopathy. Routine and repeated fundus examination is recommended for maternal monitoring in sPE.

Comparative Efficacy and Safety of Antipsychotic Drugs for Tic Disorders: A Systematic Review and Bayesian Network Meta-Analysis.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of antipsychotic drugs for tic disorders (TDs) in a network meta-analysis. METHODS: PubMed, Embase, Cochrane Library, and 4 Chinese databases were searched. Randomized controlled trials (RCTs) evaluating the efficacy of antipsychotic drugs for TDs were included. RESULTS: Sixty RCTs were included. In terms of tic symptom score, compared with placebo, haloperidol, risperidone, aripiprazole, quetiapine, olanzapine, and ziprasidone can significantly improve tic symptom score (standardized mean differences [SMD] ranged from -12.32 to -3.20). Quetiapine was superior to haloperidol, pimozide, risperidone, tiapride, aripiprazole, and penfluridol for improving tic symptom score (SMD ranged from -28.24 to -7.59). Compared with tiapride, aripiprazole could significantly improve tic symptom score (SMD=-4.27). Compared with all other drugs, penfluridol was not effective. Atypical antipsychotics were generally well tolerated. CONCLUSIONS: Atypical antipsychotics (risperidone and aripiprazole) appear to be the most robust evidence-based options for the treatment of TDs. Quetiapine may be a promising therapy. Ziprasidone and olanzapine are also effective, but the evidence is lacking. Further high-quality directly comparing different pharmacological treatment studies are justified.

Identification of a crucial amino acid responsible for the loss of specifying FGFR1-KLB affinity of the iodinated FGF21.

Previous studies suggest that specific binding to the complex consisting of fibroblast growth factor receptor-1 (FGFR1) and the coreceptor beta-Klotho (KLB) is the premise for human FGF19 and FGF21 activating the downstream signaling cascades, and regulating the metabolic homeostasis. However, it was found that human FGF21 loses its ability to bind to FGFR1-KLB after iodination with Na125 I and chloramine T, whereas human FGF19 retained its affinity for FGFR1-KLB even after iodination. The molecular mechanisms underlying these differences remained elusive. In this study, we first demonstrated that an intramolecular disulfide bond was formed between cysteine-102 and cysteine-121 in FGF21, implying that the oxidation of the cysteine to cysteic acid, which may interfere with the active conformation of FGF21, did not occur during the iodination procedures, and thus ruled out the possibility of the two conserved cysteine residues mediating the loss of FGF21 binding affinity to FGFR1-KLB upon iodination. Site-directed mutagenesis and molecular modeling were further applied to determine the residue(s) responsible for the loss of FGFR1-KLB affinity. The results showed that mutation of a single tyrosine-207, but not the other five tyrosine residues in FGF21, to a phenylalanine retained the FGFR1-KLB affinity of FGF21 even after iodination, whereas replacing the corresponding phenylalanine residue with tyrosine in FGF19 did not alter its binding affinity to FGFR1-KLB, but decreased the receptor binding ability of the iodinated protein, suggesting that tyrosine-207 is the crucial amino acid responsible for the loss of specifying FGFR1-KLB affinity of the iodinated FGF21.

[Relative Survival of Patients with Ischemic Stroke].

OBJECTIVE: To estimate the relative survival ratio of patients with ischemic stroke and its risk factors. METHODS: Lifetable and Ederer Ⅱ methods were used to estimate the relative survival ratio of patients with ischemic stroke. The Poission error structure model was adopted to determine the risk factors associated with survival. RESULTS: The patients had 99%, 98%, 98% and 99% relative survival ratio 1 year, 3 years, 5 years and 7 years after stroke, respectively. The relative excess risk of death increased with age [53-62 yr. vs. <53 yr., relative excess risk (RER=26.975, 95%CI: 1.668-410.90, P=0.020 1], higher mRS scores (≥3 vs. <3 points, RER=14.700, 95%CI: 1.05-206.45, P=0.047 3), and under body mass (vs. normal body mass, RER=10.082, 95%CI: 2.076-48.958, P=0.004 2). CONCLUSION: Ischemic stroke patients have a good prognosis, with slightly lower survival rates than the matched general populations. Those who are older, under body mass, and have a higher mRS score have lower survival rates.

[Health Utility of Patients with Stroke Measured by EQ-5D and SF-6D].

OBJECTIVE: To compare EQ-5D and SF-6D for measuring health utility of stroke patients in health economic evaluation studies. METHODS: A prospective cohort study was conducted on 596 stroke patients in the West China Hospital of Sichuan University from 2010 to 2016. Data were collected at baseline through face to face interviews and at the follow-up stages through telephone interviews with a three-month interval. EQ-5D and SF-6D were used for measuring health utility scores of the participants. The consistency of the two instruments was assessed using Bland-Altman plot and Intraclass correlation coefficient (ICC) . Logistic regression models were established to identify predictors of health utility. RESULTS: The participants had a mean utility score of 0.78 (95% confidence interval:0.76, 0.80) in EQ-5D,compared with 0.74 (95% confidence interval: 0.73, 0.76) in SF-6D,and a median (interquartile range) of 0.86 (0.68, 1.00) in EQ-5D and 0.73 (0.62, 0.86) in SF-6D. The 95% limits of agreement between the two instruments ranged from -0.28 to 0.35,with an ICC of 0.67 (95% confidence interval: 0.62,0.71). EQ-5D had a higher ceiling effect. The health utility score of stroke patients changed there rapidly in acute phase (less than 3 months) but barely changed there after.Severity of stroke was a major predictor of health utility scores. CONCLUSION: The two instruments generate inconsistent results in health utility. SF-6D is better for measuring health utility in patients with stroke in China.

[Application of Competing Risks Model in Predicting Smoking Relapse Following Ischemic Stroke].

OBJECTIVE: To determine factors associated with smoking relapse in men who survived from their first stroke. METHODS: Data were collected through face to face interviews with stroke patients in the hospital, and then repeated every three months via telephone over the period from 2010 to 2014. Kaplan-Meier method and competing risk model were adopted to estimate and predict smoking relapse rates. RESULTS: The Kaplan-Meier method estimated a higher relapse rate than the competing risk model. The four-year relapse rate was 43.1% after adjustment of competing risk. Exposure to environmental tobacco smoking outside of home and workplace (such as bars and restaurants) (P=0.01), single (P<0.01), and prior history of smoking at least 20 cigarettes per day (P=0.02) were significant predictors of smoking relapse. CONCLUSION: When competing risks exist, competing risks model should be used in data analyses. Smoking interventions should give priorities to those without a spouse and those with a heavy smoking history. Smoking ban in public settings can reduce smoking relapse in stroke patients.

[Sample Size Calculation using SAS for Phaseâ ¡in Two-stage Clinical Trials of Anti-tumor Drugs].

OBJECTIVE: To compare Gehan two-stage design and Simon two-stage design in sample size calculations for phase Ⅱ clinical trials of anti-tumor drugs. METHODS: We explained the sample size calculation methods with a single-stage design, Gehan two-stage design, and Simon optimal two-stage and minimax two-stage designs in line with the principle of exact binomial probability. By setting up different parameters in SAS macro program, the advantages and disadvantages of these designs were compared. RESULTS: The minimax two-stage design does not increase the maximum sample size compared with the single-stage design. Compared with the Gehan two-stage design, the Simon two-stage design has the advantage of being able to determine an early termination of trials when no or low anti-tumor activities are evident. CONCLUSION: Simon two-stage design is better than single-stage design and Gehan two-stage design. The minimax design is more popular than the optimal design.

Long-term trends and predictors of smoking behaviors among men following first-ever ischemic stroke.

Continued smoking following stroke is associated with adverse outcomes including increased risk of mortality and secondary stroke. The aim of this study was to examine the long-term trends in smoking behaviors and factors associated with smoking relapse among men who survived their first-ever stroke. Data collection for this longitudinal study was conducted at baseline through face-to-face interviews and follow-up was completed every 3 months via telephone, beginning in 2010 and continuing through 2014. Cox proportional hazard regression models were used to identify predictors of smoking relapse behavior. At baseline, 372 male patients were recruited into the study. Totally, 155 (41.7%) of these patients stopped smoking for stroke, and 61 (39.3%) began smoking again within 57 months after discharge with an increasing trend in the number of cigarettes smoked per day. Exposure to environmental tobacco smoke at places outside of home and work (such as bars, restaurants) (HR, 2.34; 95% CI, 1.04-5.29, P=0.04), not having a spouse (HR, 0.12; 95% CI, 0.04-0.36; P=0.0002) and smoking at least 20 cigarettes per day before stroke (HR, 2.42; 95% CI, 1.14-5.14, P=0.02) were predictors of smoking relapse. It was concluded that environmental tobacco smoke is an important determinant of smoking relapse among men who survive their first stroke. Environmental tobacco smoke should be addressed by smoke-free policies in public places.

[Clinical Trial of Intraoperative Tissue Identification for Breast-Conserving Surgery Using Bio-impedance Spectroscopy].

OBJECTIVE: To evaluate the effectiveness of bio-impedance spectroscopy (BIS) analysis for marginal tissue malignancy/benignancy identification during Breast-Conserving Surgery (BCS). METHODS: A multicenter parallel-group clinical trial was conducted with the patients who received breast conserving surgery in 2 hospitals. One hundred and fifty breast tissue specimens were collected and analyzed by BIS, frozen section biopsy and paraffin section biopsy respectively. Results were compared and statistical analysis was implemented. RESULTS: For BIS technique to identify malignant/benign marginal tissues, the sensitivity was 92.98%, and the specificity was 94.62%. The coherence of BIS results and frozen section biopsy results was significant, and the Kappa value was higher than 0.75. The mean measuring time of BIS was 2.63 min, which was shorter than frozen section biopsy (18.97 min) and paraffin section biospy (1.12 d). CONCLUSION: BIS technique likely has high accuracy in tissue identification so has potential to be adopted as a real-time indicator for marginal tissue malignancy/benignancy identification during breast-conserving surgery.

Assessment of Utilization and Cost-Effectiveness of Telemedicine Program in Western Regions of China: A 12-Year Study of 249 Hospitals Across 112 Cities.

BACKGROUND: The imbalance in healthcare between urban and rural areas is still a problem in China. In recent decades, China has aimed to develop telemedicine. We assessed the implementation, utilization, and cost-effectiveness of a large telemedicine program across western China. MATERIALS AND METHODS: In 2002-2013, a government-sponsored major telemedicine program was established by West China Hospital of Sichuan University (hub), covering 249 spoke hospitals in 112 cities throughout western China and in 40 medical expertise areas. We analyzed the cross-sectional data from 11,987 consultations conducted at West China Hospital using the telemedicine network over a 12-year period. The types of diseases as well as the diagnosis and treatment changes were assessed. We also performed a cost-savings analysis and a one-way sensitivity analysis. RESULTS: Of the 11,987 teleconsultations, we noted that neoplasms (19.4%), injuries (13.9%), and circulatory diseases (10.3%) were the three most common diagnoses. Teleconsultations resulted in a change of diagnosis in 4,772 (39.8%) patients, and 3,707 (77.7%) of them underwent major diagnosis changes. Moreover, it led to a change of treatment in 6,591 (55.0%) patients, including 3,677 (55.8%) changes not linked to diagnosis changes. The telemedicine network resulted in an estimated net saving of $2,364,525 (if the patients traveled to the hub) or $3,759,014 (if the specialists traveled to the spoke hospitals). CONCLUSIONS: The introduction of telemedicine in China, linking highly specialized major hospitals (hub) with hundreds of small rural hospitals (spoke), can greatly improve the quality, efficiency, and cost-effectiveness of healthcare delivery and utilization. This new Internet-based healthcare model should be utilized more widely in developing countries.

Identification of galectin-1 as a novel mediator for chemoresistance in chronic myeloid leukemia cells.

Multidrug resistance protein-1 (MDR1) has been proven to be associated with the development of chemoresistance to imatinib (Glivec, STI571) which displays high efficacy in treatment of BCR-ABL-positive chronic myelogenous leukemia (CML). However, the possible mechanisms of MDR1 modulation in the process of the resistance development remain to be defined. Herein, galectin-1 was identified as a candidate modulator of MDR1 by proteomic analysis of a model system of leukemia cell lines with a gradual increase of MDR1 expression and drug resistance. Coincidently, alteration of galectin-1 expression triggers the change of MDR1 expression as well as the resistance to the cytotoxic drugs, suggesting that augment of MDR1 expression engages in galectin-1-mediated chemoresistance. Moreover, we provided the first data showing that NF-κB translocation induced by P38 MAPK activation was responsible for the modulation effect of galectin-1 on MDR1 in the chronic myelogenous leukemia cells. Galectin-1 might be considered as a novel target for combined modality therapy for enhancing the efficacy of CML treatment with imatinib.

[Determination of the Association Between Smoking and Recurrence of Ischemic Stroke using a Competing Risks Model].

OBJECTIVE: To determine the association between smoking and ischemic stroke recurrence. METHODS: We conducted a prospective follow-up study of patients with first incidence of stroke. A competing risks model was used to establish the association between smoking and stroke recurrence. RESULTS: A total of 594 stroke patients were recruited. Among the 361 male patients, 59 recurrent events and 13 competing events occurred. Among the 233 female patients (all were non-smokers), 49 recurrent events and 11 competing events occurred. Adjusted for confounding factors, male nonsmokers exposed to passive smoking had a SHR of 3. 040 in comparison with those without exposure to smoking and the P value was borderline significant. Those who smoked 100-200 cigarettes a year had a SHR of 0. 947. The other groups with exposure to smoking had a greater than 1 SHR, but without statistical significance. Moreover, no significant associations between recurrence of ischemic stroke and smoking index/cumulative smoking were found. The female nonsmokers who had exposure to passive smoking only at follow-ups had a SHR of 1. 4 (and all other groups had less than 1 SHR). But no statistical significances were found in the comparisons. CONCLUSION: Further research with a larger sample size is needed to establish the association between smoking and recurrence of ischemic stroke.

Aripiprazole for the treatment of tic disorders in children: a systematic review and meta-analysis.

BACKGROUND: Tic disorders (TDs) are common neuropsychiatric disorders in children. Typical antipsychotics, such as haloperidol and pimozide have been prescribed to control tic symptoms as first-line agents. However, adverse effects have led to the use of newer atypical antipsychotics. Aripiprazole is one of alternatives. The aim of this study was to evaluate the efficacy and safety of aripiprazole for children with TDs. METHODS: Randomized controlled trials (RCTs), quasi-RCTs and control studies evaluating aripiprazole for children with tic disorders were identified from PubMed, Embase, Cochrane library, Cochrane Central, four Chinese database and relevant reference lists. Quality assessment referred to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Twelve studies involving 935 participants were included. The general quality of included studies was poor. Only one study used placebo as a control and others used positive drug controls. Participants were aged between 4 and 18 years. The period of treatment ranged from 8 to 12 weeks. Seven studies (N = 600 patients) used the YGTSS scale as the outcome measurement, and there was no significant difference in reduction of the total YGTSS score between the aripiprazole and positive control groups (MD = -0.48, 95 % CI [-6.22, 5.26], P = 0.87, I(2) = 87 %). Meta-analysis of four of the studies (N = 285 patients) that compared aripiprazole with haloperidol showed that there was no significant difference in reduction of the total YGTSS score (MD = 2.50, 95 % CI [-6.93, 11.92], P = 0.60, I(2) = 88 %). Meta-analysis of two studies (N = 255 patients) that compared aripiprazole with tiapride showed that there was no significant difference in reduction of the total YGTSS score (MD = -3.15, 95 % CI [-11.38, 5.09], P = 0.45, I(2) = 86 %). Adverse events (AEs) were reported in 11 studies. Drowsiness (5.1 %-58.1 %), increased appetite (3.2 %-25.8 %), nausea (2 %-18.8 %) and headache (2 %-16.1 %) were common AEs. CONCLUSION: In conclusion, aripiprazole appears to be a promising therapy for children with TDs. Further well-conducted RCTs are required to confirm this issue.