Urinary stone analysis on 12,846 patients: a report from a single center in China

We reported a retrospective review of the urinary stone compositions in 12,846 patients. Data on urinary stone compositions analyzed between January 2003 and December 2012 in our center were collected. Infrared spectroscopy was used for stone analysis. Predominant stone component was recorded. Patients were divided into four age groups: 0–18, 19–40, 41–60, and 61–92, and five categories by components. In order to determine the change of stone characteristics with respect to time, data were also divided into two periods, 2003–2007 and 2008–2012. A total of 12,846 stones were included in this study. The age of the patients ranged from 1 to 92 years with 7,736 males and 5,110 females. Stone made of single component was rare, 2.61 %. Calcium oxalate stone was the most common component at 82.56 %. Calcium oxalate and uric acid stones were more common in male than in female. The incidence of calcium phosphate stones and uric acid stones had increased during the past 5 years, while calcium oxalate stones decreased. We found the highest incidence of stone disease in the 41–60 years old group and the lowest in the 1–18 years old for both genders. Calcium oxalate was the dominant component in every group but was more prevalent in 19–40 years group. The percentage of magnesium ammonium phosphate stone and uric acid stone increased with age.     

Cavernous Angiomas of the Cauda Equina: Clinical Characteristics and Surgical Outcomes

Cavernous angioma (CA) is a rare hamartomatous vascular lesion, consisting of abnormal, dilated, and packed sinusoidal vascular channels without interposed nervous tissue. CAs of the cauda equina are exceedingly rare and have been previously reported in the literature as case reports. The aim of this study was to discuss the clinical presentation and the outcomes of microsurgery for these rare lesions. We retrospectively reviewed the records of 10 patients who underwent microsurgery for CAs of the cauda equina. All patients had performed pre- and postoperative magnetic resonance imaging (MRI). CAs of the cauda equina generally exhibited mixed intensity on T₁- and T₂-weighted images. Contrast-enhanced T₁-weighted images showed heterogeneous enhancement. The hemosiderin ring which surrounded the cauda equina CA was rare. Gross total resection was achieved in all cases. All patients were followed up, with a mean duration of 41.1 months. Long-term neurological function was improved in nine patients and remained stable in one patient. No recurrence was observed on MRI. CAs should be considered in the differential diagnosis of cauda equina tumors. Because of the excessive vascularity of CAs, en bloc resection is recommended. For symptomatic patients, early surgery should be performed before neurological deficits deteriorate.     

纳米树脂美学修复前牙缺损牙的临床观察

将80名患者的96颗不同程度龋损或者有缺损的牙齿,随机分2组：实验组48颗（40例患者）采用纳米树脂充填,对照组48颗（40例患者）采用瓷冠类修复,观察0．5～1年,发现实验组和对照组的患者满意率及修复后并发症控制成功率无明显差异。使用纳米树脂可以使患者就诊次数少、牙体损伤小、术后并发症少,费用低。     

关于血细胞计数仪白细胞分类的评价

美国Coulter 有集团公司生产的JT3型血球计数仪能计数全血细胞同时也能得出白细胞分类的结果.我们用此仪器测试258份门诊病人静脉血标本,同人工显微镜检查结果进行了比较.证明此仪器淋巴细胞和粒细胞的分析结果准确可靠,相关系数分别为0.951和0.930,单核细胞相关系数为0.468.对于嗜酸和嗜碱细胞增高,此仪器可作出定性提示,准确性较高.可疑有异常细胞的标本,此仪器能在报告上示出报警信号,阳性率为22%,其中真阳性占32%.假阴性结果占阴性标本的0.5%.JT3计数仪操作简便,分析标本速度快,白细胞分类结果可以作为常规血液检查的筛选手段.     

iCIK过继性细胞治疗口腔鳞状细胞癌的回顾性研究

目的研究改良的细胞因子诱导杀伤细胞（iCIK）过继性治疗口腔鳞状细胞癌（OSCC）的疗效。方法回顾2008年7月至2013年4月60例OSCC患者,根据治疗方式分为iCIK组（手术治疗＋iCIK治疗）及对照组（手术治疗）,不良预后者术后行放疗或放化疗。统计两组的复发转移率、生存率、无病生存期及总生存期。分析iCIK组培养前后外周血单个核细胞（PBMC）及iCIK细胞的T细胞亚群比例及Th1细胞因子分泌水平。结果 iCIK组复发转移率低于对照组（16.67％vs 40.00％,χ2＝4.022, P＝0.045）,且无病生存期高于对照组（50.96±3.69 vs 38.15±4.90,χ2＝4.163,P＝0.041）。但两组的死亡率及总体生存期差异无统计学意义。 iCIK培养后T细胞及CTL细胞比例、IL-2及IFN-γ水平显著增高。不良反应发生率为1.17％,无严重不良反应。结论 iCIK辅助治疗可延长OSCC患者无病生存期,减少复发或转移的发生,但未改变最终的预后,长期疗效有待进一步观察。 iCIK高表达CD3＋CD8＋,分泌高浓度的Th1细胞因子,具有较强的细胞免疫及抗肿瘤能力,且治疗安全性良好。     

From the Cover: Molecular determinants of Hv1 proton channel inhibition by guanidine derivatives

The voltage-gated proton channel Hv1 plays important roles in proton extrusion, pH homeostasis, and production of reactive oxygen species in a variety of cell types. Excessive Hv1 activity increases proliferation and invasiveness in cancer cells and worsens brain damage in ischemic stroke. The channel is composed of two subunits, each containing a proton-permeable voltage-sensing domain (VSD) and lacking the pore domain typical of other voltage-gated ion channels. We have previously shown that the compound 2-guanidinobenzimidazole (2GBI) inhibits Hv1 proton conduction by binding to the VSD from its intracellular side. Here, we examine the binding affinities of a series of 2GBI derivatives on human Hv1 channels mutated at positions located in the core of the VSD and apply mutant cycle analysis to determine how the inhibitor interacts with the channel. We identify four Hv1 residues involved in the binding: aspartate 112, phenylalanine 150, serine 181, and arginine 211. 2GBI appears to be oriented in the binding site with its benzo ring pointing to F150, its imidazole ring inserted between residue D112 and residues S181 and R211, and the guanidine group positioned in the proximity of R211. We also identify a modified version of 2GBI that is able to reach the binding site on Hv1 from the extracellular side of the membrane. Understanding how compounds like 2GBI interact with the Hv1 channel is an important step to the development of pharmacological treatments for diseases caused by Hv1 hyperactivity.The Hv1 voltage-gated proton channel (also known as HVCN1 or voltage-sensor–only protein) regulates the production of superoxide and other reactive oxygen species by NADPH oxidase (NOX) enzymes in a variety of cell types, including microglial cells (1) and leukocytes (2). NOX activity causes membrane depolarization and intracellular accumulation of protons. Hv1 allows sustained NOX activity by repolarizing the membrane and extruding excess protons from the cell (3–5).Hv1 has been shown to enhance brain damage in a mouse model of ischemic stroke through its NOX-modulating activity (1). The channel was also found overexpressed in many B-cell malignancies (6) and breast and colorectal cancer tissues (7, 8). High Hv1 activity was shown to increase invasiveness of breast cancer cells and be associated with shorter overall and recurrence-free survival in breast cancer patients (7). These findings highlight that excessive activity of the Hv1 channel can have serious pathological consequences in ischemic stroke and cancer and that small-molecule inhibitors targeting Hv1 could lead to the development of new neuroprotective or anticancer drugs.The Hv1 protein is made of four membrane-spanning segments (S1–S4) (9, 10), and it is related to the voltage-sensing domains (VSDs) of other voltage-gated ion channels (11) and voltage-sensitive phosphatases (VSPs) (12). The inner end of the S4 segment is connected to a coiled-coil domain responsible for protein dimerization (13, 14). As a result, the channel is made of two VSD subunits, each containing a gated proton pore (15–17).The block of voltage-gated sodium, potassium, and calcium channels by small molecules has been studied for decades. Its mechanism has been elucidated for many drugs, and in the majority of cases, the inhibitors were found to bind to different regions of the pore domain (18, 19). With the exception of peptide toxins (20, 21), not much is known about compounds interacting with VSDs (22), and only recently have there been successful attempts to produce small-molecule drugs that specifically target these domains in voltage-gated ion channels (23, 24).We have recently shown that some guanidine derivatives have the ability to inhibit Hv1 activity and that one of these compounds, 2-guanidinobenzimidazole (2GBI), binds the channel''s VSD only in the open conformation (25). We have also found that the binding site is within the proton permeation pathway and faces the cytoplasm.Here, we explore the chemical space available to guanidine derivatives for Hv1 binding. We then use a mutation cycle analysis approach to identify the residues in the channel that contribute to the binding environment of 2GBI and establish the overall orientation of the blocker within the VSD in the open conformation. Our results suggest that residues D112, F150, S181, and R211 are located close to each other deep within the membrane and in the proximity of the intracellular vestibule of the VSD, where they can interact with the blocker. We discuss our binding model in the context of a recent crystal structure of the channel (26).     

Ultrasound-guided double-tract percutaneous cholecystostomy combined with a choledochoscope for performing cholecystolithotomies in high-risk surgical patients

Background

Cholecystolithiasis is the most common disease treated by general surgery, with an incidence of about 0.15–0.22 %. The most common therapies are open cholecystectomy (OC) or laparoscopic cholecystectomy (LC). However, with a greater understanding of the function of the cholecyst, more and more patients and surgeons are aware that preserving the functional cholecyst is important for young patients, as well as patients who would not tolerate anesthesia associated with either OC or LC. Based on these considerations, we have introduced a notable, minimally invasive treatment for cholecystolithotomy.

Methods

We performed a retrospective review of patients with cholecystolithiasis who were unable to tolerate surgery or who insisted on preserving the functional cholecyst. Our particular approach can be simply described as ultrasound-guided percutaneous cholecystostomy combined with a choledochoscope for performing a cholecystolithotomy under local anesthesia.

Results

Ten patients with cholecystolithiasis were treated via this approach. All except one patient had their gallbladder stones totally removed under local anesthesia, without the aggressive procedures associated with OC or LC. The maximum number of gallbladder stones removed was 16, and the maximum diameter was 13 mm without lithotripsy. After the minimally invasive surgery, the cholecyst contractile functions of all patients were normal, confirmed via ultrasound after a high-fat diet. Complications such as bile duct injury, biliary fistula, and bleeding occurred significantly less often than with OC and LC. The recurrence rates for each of 2 post-operative years were about 11.11 % (1/9, excluding a failure case) with uncertainty surrounding recurrence or residue, and 22.22 % (2/9, including one non-recurrence patient with follow-up time of 22 months), respectively.

Conclusions

Ultrasound-guided percutaneous cholecystostomy combined with choledochoscope is a safe, efficient, and minimally invasive cholecystolithotomy method. We recommend this technique for the management of small stones (less than 15 mm) in high-risk surgical patients.