Volume 129 · Issue 24 · 2016

The medium-to-long-term use of antimuscarinics alone or in combination with an α-blocker in men with an enlarged prostate is still controversial. This double-blind, placebo-controlled, randomized clinical trial aimed to investigate the efficacy and safety of medium-to-long-term use of tolterodine extended release (ER) with or without tamsulosin in patients with benign prostate hyperplasia (BPH) and larger prostate size.

Totally, 152 patients (age ≥50 years) with BPH, International Prostate Symptom Score (IPSS) ≥12, quality-of-life (QoL) score ≥3, and total prostate volume ≥25 ml were enrolled in this study. The patients were randomized into four groups (n = 38 in each) to receive tolterodine ER placebo plus tamsulosin placebo, 0.2 mg tamsulosin plus tolterodine ER placebo, 4 mg tolterodine ER plus tamsulosin placebo, or tolterodine ER plus tamsulosin once daily for 24 weeks. IPSS (total, storage, and voiding subscales), QoL, maximum urinary flow rate (Q_max), and postvoid residual volume (PVR) were collected at baseline, and at weeks 4, 12, and 24.

Compared with placebo, tolterodine ER plus tamsulosin significantly improved total IPSS (-7.15, -12.20, and -14.66 vs. -3.51, -5.78, and -7.23), storage IPSS (-3.56, -5.63, and -6.66 vs. -1.52, -1.21, and -2.43), voiding IPSS (-2.88, -5.10, and -6.48 vs. -1.52, -3.03, and -2.97), QoL (-1.21, -2.40, and -3.21 vs. -0.39, -1.41, and -1.60), Q_max (2.21, 7.97, and 9.72 ml/s vs. 2.15, 2.44, and 2.73 ml/s), and PVR (-17.88, -26.97, and -27.89 ml vs. -12.03, -11.16, and -16.73 ml) at weeks 4, 12, and 24, respectively; the differences were all statistically significant (P < 0.05). Adverse events (AEs) were not increased with treatment progression. Tolterodine ER alone did not improve total IPSS (-4.61, -6.79, and -5.70), voiding IPSS (-0.64, -1.83, and -1.45), QoL (-0.69, -1.21, and -1.41), or Q_max (-0.79, 2.83, and 1.11 ml/s), compared with placebo (all P > 0.05). However, a gradual increase in PVR (10.03, 10.41, and 12.89 ml) and more urinary AEs suggestive of urinary retention (11/38 vs. 4/38) were observed.

Medium-to-long-term use of tolterodine ER plus tamsulosin should be recommended in patients with BPH and an enlarged prostate volume.

www.chictr.org.cn, ChiCTR-TRC-09000596; http://www.chictr.org.cn/showproj.aspx?proj=8939.

Antihypertensive drugs have been linked to new-onset osteoporotic fracture (NOF), and different classes of antihypertensive drugs may alter the risk for the development of NOF; however, the classic effect of different antihypertensive drugs on the development of NOF in the elderly has not been well studied during long-term follow-up.

In this study, we investigated the association between different classic antihypertensives and the development of NOF in the elderly. This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance in Central Taiwan, China including case patients with NOF aged 65–80 years from January 2002 to December 2012 and non- NOF controls. Prescriptions for antihypertensives before the index date were retrieved from a prescription database. We estimated the hazard ratios (HRs) of NOF associated with antihypertensive use. Non-NOF controls served as the reference group.

A total of 128 patients with NOF were identified from among 1144 patients with hypertension during the study period. The risk of NOF after adjusting age, sex, comorbidities, and concurrent medications was higher among the users of angiotensin-converting enzyme (ACE) inhibitors (HR, 1.64; 95% confidence interval [CI], 1.01–2.66) than among nonusers. Patients who took calcium channel blockers (CCBs) (HR, 0.70; 95% CI, 0.49–0.99) were at a lower risk of developing NOF than nonusers. Loop diuretics, thiazide diuretics, angiotensin receptor blocker, beta-blocker, and alpha-blocker were not associated with the risk of NOF.

Elderly with hypertension who take CCBs are at a lower risk of NOF and that the use of ACE inhibitors was associated with a significantly increased risk of developing NOF during the 11-year follow-up.

Our previous studies have demonstrated that the levels of 5-hydroxytryptamine (5-HT) and 5-HT 2A receptor (5-HT_2AR) in serum and platelet were associated with depression and myocardial infarction (MI), and pretreatment with ginseng fruit saponins (GFS) before MI and depression had an effect on the 5-HT system. In this study, the effects of GFS on the 5-HT system in the Sprague-Dawley (SD) rats with MI, depression, and MI + depression were evaluated.

A total of eighty SD rats were allocated to four groups: MI, depression, MI + depression, and control groups (n = 20 in each group). Each group included two subgroups (n = 10 in each subgroup): Saline treatment subgroup and GFS treatment subgroup. The levels of 5-HT, 5-HT_2AR, and serotonin transporter (SERT) were quantified in serum, platelet lysate, and brain tissue through the enzyme-linked immunosorbent assay method, respectively.

Compared with those in the saline treatment subgroups, the levels of 5-HT in serum and platelet lysate statistically significantly increased in the GFS treatment subgroups of MI, depression, and MI + depression groups (serum: all P = 0.000; platelet lysate: P = 0.002, 0.000, 0.000, respectively). However, the 5-HT levels in brain homogenate significantly decreased in the GFS treatment subgroups compared with those in the saline treatment subgroups in MI and depression groups (P = 0.025 and 0.044 respectively), and no significant difference was observed between saline and GFS treatment subgroups in MI + depression group (P = 0.663). Compared with that in GFS treatment subgroup of control group, the 5-HT_2AR levels in the platelet lysate significantly decreased in GFS treatment subgroups of MI, depression, and MI + depression groups (all P = 0.000). Compared to those in the saline treatment subgroups, the serum SERT levels significantly decreased in the GFS treatment subgroups in MI, depression, and MI + depression groups (P = 0.009, 0.038, and P = 0.001, respectively), while the SERT levels of platelet lysate significantly decreased in GFS treatment subgroup of MI group (P = 0.000), significantly increased in GFS treatment subgroup of depression group (P = 0.019), and slightly changed in GFS treatment subgroup of MI + depression group (P = 0.219). No significant changes for SERT levels in brain homogenate could be found between the saline and GFS treatment subgroups in MI, depression, and MI + depression groups (P = 0.421, 0.076 and P = 0.642). Conclusions: This study indicated that GFS might inhibit the reuptake of 5-HT from serum to platelet according to decreased 5-HT_2AR in platelet and SERT in serum and platelet. The change of 5-HT in serum after GFS treatment was inconsistent with that in the brain. It seemed that GFS could not pass through the blood-brain barrier to affect the central serotonergic system.

Locally advanced pancreatic carcinoma (LAPC) is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation (IRE) has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC.

Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE.

All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed (16%): two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge.

IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy.

The detection of solitary pulmonary nodules (SPNs) that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography (CT) imaging results remains a significant challenge. The 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) positron emission tomography (PET)/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared ¹⁸F-FDG and 3-deoxy-3-[¹⁸F]-fluorothymidine (¹⁸F-FLT) in lung cancer PET/CT imaging.

The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established (n= 12), and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values (SUVs), and Ki-67 proliferation marker expression were investigated.

The cell-tracer binding ratio for the A549 cells using the ¹⁸F-FDG was greater than the ratio using ¹⁸F-FLT (P < 0.05). The Ki-67 expression showed a significant positive correlation with the ¹⁸F-FLT binding ratio (r = 0.824, P < 0.01). The tumor-to-nontumor uptake ratio of ¹⁸F-FDG imaging in xenografts was higher than that of ¹⁸F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of ¹⁸F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of ¹⁸F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of ¹⁸F-FDG and ¹⁸F-FLT (r = 0.658, P < 0.05 and r = 0.724, P < 0.01, respectively).

The ¹⁸F-FDG uptake ratio is higher than that of ¹⁸F-FLT in A549 cells at the cellular level. ¹⁸F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs.

Pediatric infectious endophthalmitis is a serious sight-threatening disease for children. The purpose of this study was to investigate the etiology, microbiological spectrum, and visual outcomes of infectious endophthalmitis in children at a single institution in China.

It is a retrospective study of the medical records of all patients under 14 years of age with histories of infectious endophthalmitis, treated at a single institution from January 1, 2009 to January 1, 2015. The clinical characteristics, etiology, microbiological spectrum, and management, as well as the visual outcomes, were analyzed. The Kappa test and Chi-square test were used in the statistical evaluation.

A total of 271 children were identified, with a mean age of 5.61 ± 2.93 years (range 5 months to 14 years). Ocular trauma (94.8%) and previous ocular surgery (3.0%) were the most common etiologies. Overall, 147 (54.2%) cases had positive cultures, and 176 organisms were isolated from these patients. A single species was isolated in 120 (81.6%) cases, with multiple organisms in 27 (18.4%) cases, and the most commonly identified organisms were coagulase-negative Staphylococcus and Streptococcus species, comprising 29.5% and 26.8% of the isolates, respectively. Moreover, of 176 isolates, 142 (80.8%) were Gram-positive organisms, 23 (13.0%) were Gram-negative organisms, and 11 (6.2%) were fungi. The final visual outcomes were 20/200 or better in 66 (24.4%) eyes, counting fingers to 20/200 in 34 (12.5%), hand motions in 30 (11.1%), light perception in 33 (12.2%), no light perception in 32 (11.8%), and 9 (3.3%) eyes were enucleated or eviscerated. The visual outcomes were not available in 67 (24.7%) patients.

Penetrating ocular trauma is the most frequent cause of pediatric endophthalmitis in China. Streptococcus and Staphylococcus species are the most commonly identified organisms in exogenous pediatric endophthalmitis whereas Fusarium species are commonly seen in endogenous endophthalmitis. In this research, in spite of aggressive management with antibiotics and vitrectomy, the visual prognosis was found to be generally poor.

Retinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema model and explore the related VEGF expression and observe the responses to anti-VEGF drugs in this model.

A rat retinal edema model was established by inducing photochemical reaction using a 532 nm laser after the intravenous injection of Erythrosin B. Immediately after the laser treatment, models were given intravitreal injections of Ranibizumab or Conbercept to inhibit VEGF expression, and the changes of retinal thickness were measured. Retinal edema was observed using fundus photography (FP), optical coherence tomography (OCT), and fluoresce in fundus angiography (FFA) at 0, 1, 2, 4, 7 and 14 days after intervention. The retinal VEGF expression was measured using enzyme-linked immunosorbent assay (ELISA) and western blotting at each time point. The rat retinal edema model was also used to verify the function of anti-VEGF polypeptide ZY1.

Both retinal edema and vascular leakage were clearly observed at 1, 2 and 4 days after photochemical induction and the retinal thickness increased notably over the same period. The retinal VEGF expression peaked at day 1 and retina became thickening simultaneously. After the interventions, the VEGF expression of the Ranibizumab and Conbercept groups decreased at each time point compared to the edema group (26.90 ± 3.57 vs. 40.29 ± 6.68, F= 31.269 on day 1 and 22.36 ± 1.12 vs. 29.92 ± 0.93 F = 163.789 on day 2, both P < 0.01); the mean RT (278 ± 4 vs. 288 ± 3, F = 134.190 on day 1 and 274 ± 7 vs. 284 ± 6, F = 64.367 on day 2, both P < 0.05) and vascular leakage in these groups also decreased. The same results were observed in the ZY1 group, particularly at day 2 (P < 0.05).

This retinal edema model induced by a photochemical reaction is reliable and repeatable. Induced edema increases expression of VEGF. This model can be used to test new drugs.

Coronary microembolization (CME) has been frequently seen in acute coronary syndromes and percutaneous coronary intervention. Small animal models are required for further studies of CME related to severe prognosis. This study aimed to explore a new mouse model of CME.

The mouse model of CME was established by injecting polystyrene microspheres into the left ventricular chamber during 15-s occlusion of the ascending aorta. Based on the average diameter and dosage used, 30 C57BL/6 male mice were randomly divided into five groups (n = 6 in each): 9 μm/500,000, 9 μm/800,000, 17 μm/200,000, 17 μm/500,000, and sham groups. The postoperative survival and performance of the mice were recorded. The mice were sacrificed 3 or 10 days after the surgery. The heart tissues were harvested for hematoxylin and eosin staining and Masson trichrome staining to compare the extent of inflammatory cellular infiltration and fibrin deposition among groups and for scanning transmission electron microscopic examinations to see the ultrastructural changes after CME.

Survival analysis demonstrated that the cumulative survival rate of the 17 μm/500,000 group was significantly lower than that of the sham group (0/6 vs. 6/6, P = 0.001). The cumulative survival rate of the 17 μm/200,000 group was lower than those of the sham and 9 μm groups with no statistical difference (cumulative survival rate of the 17 μm/200,000, 9 μm/800,000, 9 μm/500,000, and sham groups was 4/6, 5/6, 6/6, and 6/6, respectively). The pathological alterations were similar between the 9 μm/500,000 and 9 μm/800,000 groups. The extent of inflammatory cellular infiltration and fibrin deposition was more severe in the 17 μm/200,000 group than in the 9 μm/500,000 and 9 μm/800,000 groups 3 and 10 days after the surgery. Scanning transmission electron microscopic examinations revealed platelet aggregation and adhesion, microthrombi formation, and changes in cardiomyocytes.

The injection of 500,000 polystyrene microspheres at an average diameter of 9 μm is proved to be appropriate for the mouse model of CME based on the general conditions, postoperative survival rates, and pathological changes.

Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles (MNPs) to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. Drugs coated with MNPs are becoming a promising way for better leukemia treatment. This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe₃O₄ (Wog-MNPs-Fe₃O₄) as an antileukemia agent.

After incubated for 48 h, the antiproliferative effects of MNPs, wogonin, or Wog-MNPs-Fe₃O₄ on K562/A02 cells were determined by methyl thiazolyl tetrazolium (MTT) assay. The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe₃O₄ were determined by flow cytometer (FCM) assay. The cell cycle arrest in K562/A02 cells was determined by FCM assay. The elementary molecular mechanisms of these phenomena were explored by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR).

With cell viabilities ranging from 98.76% to 101.43%, MNP-Fe₃O₄ was nontoxic to the cell line. Meanwhile, the wogonin and Wog-MNPs-Fe₃O₄ had little effects on normal human embryonic lung fibroblast cells. The cell viabilities of the Wog-MNPs-Fe₃O₄ group (28.64–68.36%) were significantly lower than those of the wogonin group (35.53–97.28%) in a dose-dependent manner in 48 h (P < 0.001). The apoptotic rate of K562/A02 cells was significantly improved in 50 µmol/L Wog-MNPs-Fe₃O₄ group (34.28%) compared with that in 50 µmol/L wogonin group (23.46%; P < 0.001). Compared with those of the 25 and 50 µmol/L wogonin groups, the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 µmol/L Wog-MNPs-Fe₃O₄ groups (all P < 0.001). The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe₃O₄ group compared with those of the wogonin group (all P < 0.001).

This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells. Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells, MNPs could enhance the therapeutic effects of wogonin on leukemia cells. These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.

Sepsis is the leading cause of death among critically ill patients. Herein, we conducted a national survey to provide data on epidemiology and treatment of sepsis in the clinical practice in China, which has no detailed epidemiological data available on sepsis.

This was a prospective cross-sectional survey from December 1, 2015 to January 31, 2016 in all provinces/municipalities of the mainland of China. The primary outcome of this study was the incidence of sepsis, and the secondary outcome was its etiology in China. Patients with sepsis admitted to the Intensive Care Units were included in this study. The demographic, physiological, bacteriological, and therapeutic data of these patients were recorded. The incidence of sepsis was estimated using the data from the sixth census in China, reported by the Chinese National Health and Family Planning Commission and the National Bureau of Statistics as the standard population. The independent risk factors for increased mortality from sepsis were calculated.

This study indicated the incidence and outcome of sepsis in China. It also showed the most common etiology of different sites and types of infection, which could guide empiric antibiotic therapy. Moreover, it provided information on the independent risk factors for increased mortality due to sepsis. The findings provide evidence to guide clinical management and may help improve the outcome in septic patients.

ClinicalTrials.gov, NCT02448472; https://clinicaltrials.gov/show/NCT02448472.

The effectiveness of neoadjuvant chemoradiotherapy (NCRT) treatment for patients with esophageal carcinoma (EC) remains controversial. The aim of this study was to compare the effect of NCRT followed by surgery (NCRTS) with surgery alone (SA) for EC.

The PubMed, EMBASE, and the Cochrane Library databases were electronically searched up to August 2015 for all the published studies that investigated EC patients receiving either NCRTS or SA, and the reference lists were also manually examined for the eligible studies. The risk ratio (RR) with 95% confidence intervals (CIs) as effective size was determined to assess the 1-, 3-, 5-year survival rates (SRs), postoperative morbidity, and postoperative mortality. Heterogeneity was determined using the Q-test. The Begg’s test and Egger’s test were used for assessing any potential publication bias.

Of 1120 identified studies, 16 eligible studies were included in this analysis (involving 2549 patients). Overall, the pooled results suggested that NCRTS was associated with significantly improved 1-year (RR: 1.07, 95% CI: 1.02–1.13), 3-year (RR: 1.26, 95% CI: 1.14–1.39), and 5-year (RR: 1.36, 95% CI: 1.18–1.56) SRs. However, the results also indicated that NCRTS had no or little effect on postoperative morbidity (RR: 0.93, 95% CI: 0.82–1.05) and postoperative mortality (RR: 1.17, 95% CI: 0.56–2.44).

Compared with SA, NCRTS can increase 1-, 3-, and 5-year SRs in patients with EC.

Controversial results about the therapeutic value of radiofrequency ablation (RFA) and liver resection (LR) in the treatment of colorectal cancer liver metastasis (CRCLM) have been reported. Thus, we performed the present meta-analysis to summarize the related clinical evidences.

A systematic literature search was conducted using PubMed (Medline), EMBASE, Cochrane Library, and Web of Science, for all years up to April 2016. Pooled analyses of the overall survival (OS), progression-free survival (PFS), and morbidity rates were performed.

A total of 14 studies were finally enrolled in the meta-analysis. Patients treated by LR gained a longer OS and PFS than those of patients treated by RFA. Patients in the RFA group had lower morbidity rates than those of patients in the LR group. Publication bias analysis revealed that there was no significant publication bias in the meta-analysis.

Patients with CRCLM gained much more survival benefits from LR than that from RFA. RFA rendered lower rates of morbidities. More well-designed randomized controlled trails comparing the therapeutic value of LR and RFA are warranted.

The arrival of precision medicine plan brings new opportunities and challenges for patients undergoing precision diagnosis and treatment of malignant tumors. With the development of medical imaging, information on different modality imaging can be integrated and comprehensively analyzed by imaging fusion system. This review aimed to update the application of multimodality imaging fusion technology in the precise diagnosis and treatment of malignant tumors under the precision medicine plan. We introduced several multimodality imaging fusion technologies and their application to the diagnosis and treatment of malignant tumors in clinical practice.

The data cited in this review were obtained mainly from the PubMed database from 1996 to 2016, using the keywords of "precision medicine", "fusion imaging", "multimodality", and "tumor diagnosis and treatment".

Original articles, clinical practice, reviews, and other relevant literatures published in English were reviewed. Papers focusing on precision medicine, fusion imaging, multimodality, and tumor diagnosis and treatment were selected. Duplicated papers were excluded.

Multimodality imaging fusion technology plays an important role in tumor diagnosis and treatment under the precision medicine plan, such as accurate location, qualitative diagnosis, tumor staging, treatment plan design, and real-time intraoperative monitoring. Multimodality imaging fusion systems could provide more imaging information of tumors from different dimensions and angles, thereby offing strong technical support for the implementation of precision oncology.

Under the precision medicine plan, personalized treatment of tumors is a distinct possibility. We believe that multimodality imaging fusion technology will find an increasingly wide application in clinical practice.

在过去的几十年里，循证医学的引入促使了临床实践的范式转变。一项重要进展是让卫生保健专业人员根据国家和国际当局（如国家卫生和护理卓越研究所[NICE]；世界卫生组织[世卫组织]）以及专业机构发布的循证实践指南或其他指导文件（如专家共识声明）的建议做出明智的决定。

近几十年来，中国糖尿病（DM）的患病率显著上升。最近，据报道，在中国成年人的代表性样本中，DM的估计患病率为11.6%，糖尿病前期的患病率为50.1%。^[1]此外，中国普通人群对糖尿病的知晓率、治疗率和控制率不成比例地低，引发了对未来糖尿病相关发病率和死亡率高的担忧。

在全膝关节置换术（TKA）中恢复外翻膝关节的机械排列和软组织平衡取决于畸形的起源和软组织状态。^[1,2,3]

致编辑：超重和肥胖青少年的发病率逐年上升，主要原因是不健康的饮食和缺乏体育锻炼。^[1]的确，体重指数上升趋势的改变已经引起了全世界的关注和批评。^[2]

致编者：男，38岁，因短暂性失语，右侧四肢无力入院。作为一名习惯性吸烟者，他在3年前和10年前分别被诊断患有高血压和高脂血症。关于家族史，他说他的父亲患有脑梗塞。