Prostate Cancer, Castration-Resistant Prostate Cancer (CRPC), Radium-223 Dichloride Injection for Bone Metastasized Prostate Cancer

Purpose: The purpose of this paper is to discuss the most important facts about prostate cancer, its treatments and efficacy, the type of prostate cancer that does not improve with hormonal therapy (Castration-Resistant Prostate Cancer-CRPC), and the recently approved Radium-223 dichloride targeted therapy for CRPC that has metastasized to bones. Prostate cancer is the third most common malignancy diagnosed worldwide and the most common malignant disease in men. Also, the incidence of prostate cancer varies between regions. So it’s important to have a proper understanding of all above points to prevent the further development and spread of cancer and improve the cure rate. Design: The paper begins by discussing what prostate cancer is, the risk factors, clinical manifestations, and the treatments for prostate cancer. It covers the clinical manifestations, pathology, screening (cancer biomarker Prostate Specific Antigen, Digital Rectal Examination—DRE, prostate biopsy, and imaging) and treatments for prostate cancer. The paper then delves into the main treatment methods for prostate cancer, including how Castration-Resistant Prostate Cancer (CRPC) differs from normal prostate cancer after hormone suppression therapy. Additionally, it discusses the effectiveness of the recently introduced Radium-223 dichloride injection as a radiation-targeted therapy for treating CRPC that has metastasized to bones. This section covers the properties of radium-223 dichloride injection, its pharmacokinetics, pharmacodynamics, absorption and volume of distribution, half-life, metabolism, route of elimination, clearance, toxicity, adverse effects, and mechanism of action at the tumor site. It also discusses preclinical studies related to radium-223 dichloride injection and its effectiveness in treating CRPC patients with bone metastasis. Conclusion: Prostate cancer is a common cancer that can be treated with surgery or hormonal therapy. However, if the cancer progresses despite hormonal therapy, Radium-223 dichloride injection can be used as a radiation target therapy to treat patients with CRPC and symptomatic bone metastases. This treatment kills tumor cells in bones and reduces associated pain with minimal damage to surrounding normal tissue. However, the metastatic disease cannot be cured and can only offer palliation for the patient. Suggestions: Based on the facts, Radium-223 target therapy is effective in treating and providing palliation for cancers. It is suggested to further develop the usage of radiation target therapy and to test the safety and efficacy of more than 6 injections of Radium-223 dichloride and its combination with currently used chemotherapy drugs for bone metastasized CRPC. This paper aims to contribute to future research designs related to cancer therapies using radiation and to design new studies and practical implementations, especially regarding the usage of radium-223 dichloride.

Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice

AIM: To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis.METHODS: The mice were randomly divided into 2 groups(n = 50), control group and model group. The mice in model group were given ethanol(10%) in drinking water after injection of dibutyltin dichloride(DBTC)(8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein( 60 % ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin(FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen typeⅠ(COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinases-1(TIMP-1) m RNA in the pancreas was assessed by real time PCR.RESULTS: DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group(P < 0.05). The level of COL1A1 and FN in pancreas increased. The expression of MMP-1 m RNA in pancreas decreased, but TIMP-1 m RNA increased at model group.CONCLUSION: DBTC joint Ethanol drinking can induce chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and handy experimental method. The model is suitable to study the mechanism of pancreatic fibrosis in chronic pancreatitis.

Study on the Physical and Dissociation Properties of Disulfur Dichloride under Electric Fields

Disulfur dichloride is a hazardous substance, which is irritating to the eyes. It is significant to study the physical and dissociation properties under external electric fields. The bond length, energy, dipole moment, orbital energy level distribution, infrared spectra and dissociation properties of disulfur dichloride molecule under different external fields are obtained by using the density functional theory at the B3LYP/6-311++G(d, p) basis set level. In addition, ultraviolet-visible absorption spectra of the molecule in different electric fields are studied with configuration interaction-single excitation(CIS)/6-311++G(d, p) method. According to the results, it has been found that as the electric field exerted along the positive direction of the z-axis increases, the two sulfur-chlorine(S-Cl) bond lengths become longer and tend to break, while the sulfur-sulfur(S-S) bond length becomes shorter and the energy gap decreases. The infrared spectrum and ultraviolet-visible absorption spectra both exhibit red shift under electric field. Moreover, by scanning the potential energy surface of disulfur dichloride about S-Cl bond, the dissociation barrier decreases with the increase of positive electric field. When the external electric field arrives at 0.040 atomic units, the barrier disappears, meaning the dissociation of disulfur dichloride. The present results offer an important reference to further study of disulfur dichloride.

Ab initio Study of Anharmonic Force Field and Spectroscopic Constants for Germanium Dichloride

平衡结构，光谱学常数，和为金者二氯化物的几 isotopomers 的非谐的力量地的 Ab initio 学习(70 GeCl 2,72 GeCl 2, 和 76 GeCl 2) 在理论使用的 MP2 和 CCSD (T) 层次被执行了 cc-pVTZ 基础集合。计算几何学，旋转常数，颤动旋转相互作用常数，泛音频率，非谐的常数，四次并且 sextic 离心的失真常数，立方、四次的力量常数与试验性的数据相比。为 Ge 同位素的小集体差别，为金者二氯化物的同位素的效果弱得多。协议为这二个方法是令人满意的，但是 CCSD (T) 结果的偏差比 MP2 的稍微大，因为 CCSD (T) s 在 hypervalent Cl 的电子关联的不适当的处理原子。

SYNTHESIS OF ORGANOGERMANE OLIGOMERS VIA LIGAND SUBSTITUTION POLYMERIZATION FROM 1, 4-DIOXANE COMPLEX OF GERMANIUM DICHLORIDE

Some organogermanium oligomers with different side groups were synthesized via ligand substitution polymerization from I, l-dioxane complex of germanium dichloride with different organolithium compounds. The oligomers were isolated through either precipitation from methanol or extraction using toluene with a yield of no less than 50%. The weight average molecular weight (M-w) of the oligomers is ranging from 1.4 x 10(3) to 5.9 x 10(3) depending on the type and alkyl length of the organolithium compounds used.

Synthesis,Crystal Structure and Quantum Chemistry of a Hydration Dibenzyltin Dichloride

A novel organotin hydration dibenzyltin dichloride has been synthesized and its crystal structure was determined by X-ray diffraction. The crystal belongs to monoclinic, space group Pc with a = 1.1918（5）, b = 0.6199（2）, c = 1.1074（5）nm, β = 106.899（7）°, V= 0.7828（8）nm3, Z = 2, Dc = 1.654 g/cm3,μ（MoKa） = 19.59 cm^-1, F（000） = 384, R = 0.0564 and RwR = 0.1427. The Sn-C bonds are 0.2140（9） and 0.2152（5） nm, Sn-Cl are 0.2385（4） and 0.2497（3） nm, and Sn-O is 0.2388（7） nm. The tin atom is five-coordinated in a distorted trigonal bipyramidal configuration. The study on the title complex has been performed with quantum chemistry calculation by means of G98W package on the Lanl2dz basis set. The stability of the complex as well as the orbital energies and composition characteristics of some frontier molecular orbitals has been investigated.

Syntheses and Structures of Sil abridged Hafnocene Dichlorides

The present paper covers three silabridged hafnocene dichlorides(1, 2 and 3) prepared by sequential reactions of α, ω-dichloropermethyl polysilane with cyclopentadienyl sodium, n-butyl lithium and hafnium tetrachloride. Their structures were characterized by elemental analyses, UV, 1H(13C) NMR and MS. Furthermore the crystal and molecular structures of 1 and 2 were determined by X-ray diffraction method. The crystal of 1 is monoclinic, space group C2/c with a=1. 3401(4), b=0. 9977(3), c = 1. 0922(4) nm; β=94. 07(1)° V=3. 6342 nm3, Z = 2, Dc = 2.155 g·cm-3. The final deviation factor R = 0. 064. The crystal of 2 is monoclinic, space group P21/c with a=0.0847(1), b=1.5181(1), c=2.9824(2) nm; β= 94. 07(1)°? V=3.634 nm3; Dc= l. 805 g·cm-3. The final deviation factor R = 0. 033. The relationship between the silabridged structure and spectral properties is also discussed.

Process for the Preparation of Chromones, Isoflavones and Homoisoflavones Using Vilsmeier Reagent Generated from Phthaloyl Dichloride and DMF

Vilsmeier reagent formed from phthaloyl dichloride and DMF was found to be very effective for converting 2-hydroxyacetophenones, deoxybenzoins and dihydrochalcones into corresponding chromones, isoflavones and homoisoflavones with excellent yield. This method offers significant advantages such as efficiency and mild reaction conditions with shorter reaction time.

Photocatalytic Degradation of Ethylene Dichloride in Water Using Nano TiO₂Supported on Clinoptilolite as a Photocatalyst

In this article one of the advanced oxidation processes (AOP) combined methods, photocatalyst /H2O2, is utilized in order to study photodegradation of ethylene dichloride (EDC) in water. Nano Titanium (IV) Oxide, supported on Clinoptilolite (CP) (Iranian natural zeolite) using solid-state dispersion (SSD) method for improvement of its photocatalytic properties. The results show that the TiO2/Clinoptilolite (SSD) is an active photocatalyst. The effects of five important photocatalytic reaction parameters including the initial concentration of ethylene dichloride, the ratio of TiO2/Clinoptilolite, the catalyst concentration, H2O2 concentration and pH in photodegradation of ethylene dichloride were examined. In this experiments, the design and also the optimum parameters were obtained by Taguchi Method, using Design Expert8&reg;software. Taguchi's L27 (5^3) orthogonal array design was employed for the experimental plan. Four parameters were found to be significant whereas, pH was found to be an insignificant parameter after conducting experiments. A first order reaction with K = 0.007 min-1 was observed for the photocatalytic degradation reaction.

Studies on Chiral Thiophosphoric Acids and Their Derivatives 15.The Asymmetric Cyclizations of L-prolinol with (Thio)phosphoro(-no)dichlorides

The cyclizations of L-(+)-prolinol 1 derived from L-proline with (thio)phosphoro(-no)dichlorides 2 give 1,2,3-azaphosphaoxabicyclo[3.3.0] 3 consisting of unequal amounts of diastereoisomers, eight pairs of which have been successfully separated by silica gel column chromatography or recrystallization.

Dimethyltin Dichloride-Dibenzyl Sulfoxide,a Compound Crystallizing with Seven Molecules in the Asymmetric Unit

Dimethyltin dichloride-dibenzyl sulfoxide,（（CH3）2SnCl2·O=S（CH2C6H5）2）,crystallizes in the orthorhombic space group P212121 with a superstructure of dimensions a = 11.9290（1）,b = 19.50490（1）,c = 55.7390（6） ; Z = 28. The geometry of the five-coordinated tin atom in each of the seven independent adduct molecules is a square pyramid that is displaced towards a cis-trigonal bipyramid; the extent of displacement along the Berry pseudorotation pathway ranges from 20 to 45%.

SYNTHESIS OF 1H，1＇H BIS（BENZ－△~4－IMIDAZOLINE）2，2＇－SPIRO－TITANIUM DICHLORIDE

New model compound 1H,1′H-Bis（benz-Δ^4-imidazoline)2,2′-spiro-titanium dichloride was prepared and the structure of the compound was determined by 1R,MS and elementary analysis.

Highly sensitive ratiometric fluorescent fiber matrices for oxygen sensing with micrometer spatial resolution

Oxygen(O_(2))-sensing matrices are promising tools for the live monitoring of extracellular O_(2) consumption levels in long-term cell cultures.In this study,ratiometric O_(2)-sensing membranes were prepared by electrospinning,an easy,low-cost,scalable,and robust method for fabricating nanofibers.Poly(ε-caprolactone)and poly(dimethyl)siloxane polymers were blended with tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)dichloride,which was used as the O_(2)-sensing probe,and rhodamine B isothiocyanate,which was used as the reference dye.The functionalized scaffolds were morphologically characterized by scanning electron microscopy,and their physicochemical profiles were obtained by Fourier transform infrared spectroscopy,thermogravimetric analysis,and water contact angle measurement.The sensing capabilities were investigated by confocal laser scanning microscopy,performing photobleaching,reversibility,and calibration curve studies toward different dissolved O_(2)(DO)concentrations.Electrospun sensing nanofibers showed a high response to changes in DO concentrations in the physiological-pathological range from 0.5%to 20%and good stability under ratiometric imaging.In addition,the sensing systems were highly biocompatible for cell growth promoting adhesiveness and growth of three cancer cell lines,namely metastatic melanoma cell line SK-MEL2,breast cancer cell line MCF-7,and pancreatic ductal adenocarcinoma cell line Panc-1,thus recreating a suitable biological environment in vitro.These O_(2)-sensing biomaterials can potentially measure alterations in cell metabolism caused by changes in ambient O_(2)content during drug testing/validation and tissue regeneration processes.

配体调控Cp_(2)TiCl_(2)催化合成单、双取代苯并咪唑衍生物的研究

以邻苯二胺和芳香醛为反应起始物,在50℃,乙醇为溶剂,0.02 mmol L-苯丙氨酸为催化剂条件下,催化合成产物为单取代苯并咪唑类化合物,产率可达到70%;而在50℃,以乙醇为溶剂,0.04 mmol L-苯丙氨酸为Brønsted acid配体,0.02 mmol Cp_(2)TiCl_(2)为Lewis acid的条件下,则催化生成1,2-二取代苯并咪唑类化合物,产率可达到97%.底物普适性较好,且后处理简单.同时利用NMR分析对机理进行了初步的研究.

二氯化二硫为原料合成硫双威绿色工艺研究

以灭多威、S_(2)Cl_(2)为原料合成硫双威,采用吡啶兼作碱化剂和溶剂,灭多威溶解在吡啶中,反应在液相体系中进行,利于传质、传热并提高反应效果。利用正交实验得到最佳工艺条件为:反应温度30℃,时间6 h,原料灭多威、S_(2)Cl_(2)和吡啶的摩尔比为1:0.7:6.5,醇洗剂用量为500 g甲醇/mol灭多威。灭多威的转化率达92.5%,硫双威收率达89.6%,产品为白色粉末状、颜色一致、粒度分布均匀,含量大于97.8%,热分解率低于2.4%。硫双威合成过程无废水产生,吡啶及副产物吡啶盐酸盐采用碱化处理、共沸蒸馏回收,甲醇采用精馏回收。该工艺路线绿色、环保,可推广到工业生产中。

O,O-二烷基硫代磷酰氯制备过程中一氯化硫处理进展

O,O-二烷基硫代磷酰氯是一种重要的农药中间体,可用于制备多种有机磷类杀虫剂。基于五硫化二磷合成O,O-二烷基硫代磷酰氯是目前研究热点,综述了以五硫化二磷为原料合成O,O-二烷基硫代磷酰氯过程中一氯化硫的处理方法,并分析了各种方法的优缺点。

双子季铵盐缓蚀剂的合成及缓蚀性能研究

以特定胺和环氧氯丙烷反应,形成了二氯取代物,再通过与油酸二乙烯三胺咪唑啉发生反应,形成双季铵盐缓蚀剂。采用红外光谱扫描,通过特征峰的分析,验证合成产物确为目标产物;通过挂片失重实验,测试双子季铵盐缓蚀剂的缓蚀性能;通过SEM进行腐蚀挂片表面形貌观察;经过现场LPR测试,腐蚀速率低于在用药剂。结果表明:双子季铵盐缓蚀具有优秀的缓蚀性能;该双子季铵盐缓蚀剂与硫脲、巯基乙醇等具有增效作用。

低缠结超高相对分子质量聚乙烯的制备及表征

为解决传统Ziegler-Natta催化剂(简称Z-N催化剂)制备的超高相对分子质量聚乙烯(UHMWPE)缠结程度较高、加工困难等问题,以MgCl_(2)、TiCl_(4)、异辛醇、正硅酸四乙酯(或邻苯二甲酸二己酯)为主要原料,采用化学反应法制备了氯化镁负载型Z-N催化剂cat1(或cat2)。分别以cat1、cat2为主催化剂、三乙基铝为助催化剂,采用淤浆聚合工艺制备了低缠结UHMWPE,测定了cat1、cat2的粒径分布和金属元素质量分数,考察了聚合温度、时间对催化剂催化活性和UHMWPE的黏均相对分子质量(M_(v))的影响,并使用流变分析法和DSC热力学退火法对UHMWPE的缠结程度进行了表征。结果表明,制备的cat1、cat2与设计相符,在聚合反应温度分别为65和70℃、反应5 h时,cat1、cat2催化活性分别达到27700、37700 g PE/g cat,制备的UHMWPE的Mv分别为6.01×10^(6)、5.03×10^(6),起始储能模量分别为0.21、0.13 MPa,缠结程度低于商品化UHMWPE。

新型有机磷-氮协同阻燃剂的合成与应用

以三聚氰胺钠盐和苯基磷酰二氯为原料,合成了新型有机磷-氮阻燃剂苯基磷酰二三聚氰胺(PPBM)。最佳合成工艺为:氮气保护下,三聚氰胺钠盐和苯基磷酰二氯的物质的量比为2.1∶1,三聚氰胺钠盐溶解于四氯化碳后,苯基磷酰二氯缓慢滴入,75℃下反应6 h后加蒸馏水反应1 h,抽滤,蒸馏水洗涤,干燥,收率为92.4%。傅里叶变换红外光谱、核磁共振氢谱的表征结果显示合成产物与目标化合物PPBM结构一致,热重-差热分析结果表明,PPBM具有良好的热稳定性和较高的残炭率。将PPBM应用于886A不饱和聚酯树脂中,垂直燃烧测试、极限氧指数测定的结果表明,PPBM具有较好的膨胀成炭性和优良的阻燃效果。通过燃烧后残炭的扫描电子显微镜表征分析了PPBM的阻燃机理,同时也进一步证明了PPBM具有良好的磷-氮协同增效阻燃性能。

PSMA/^(18)F-FDG PET显像在前列腺癌骨转移^(223)Ra治疗中的应用体会

目的分享前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)和/或^(18)F-氟代脱氧葡萄糖(^(18)F-fluoroodexyglucose,^(18)F-FDG)正电子发射断层显像(positron emission tomography,PET)在前列腺癌(prostate cancer,PCa)骨转移患者氯化镭-^(223)(radium-^(223) dichloride,^(223)Ra)治疗中的应用心得,以期为国内开展^(223)Ra治疗提供借鉴。方法本研究为描述性分析。研究对象为2021年9月—2023年1月北京协和医院因骨转移行^(223)Ra治疗的PCa患者。记录^(223)Ra治疗效果及患者生存状态,并对治疗前后骨扫描及PET显像特征(包括PSMA PET和/或^(18)F-FDG PET)进行总结。结果共入选9例接受不同针次^(223)Ra治疗的PCa患者(另外2例拟行^(223)Ra,因基线PET显像检出存在内脏转移而排除),包括8例转移性去势抵抗性前列腺癌患者,1例转移性激素敏感性前列腺癌患者。9例患者共接受36针^(223)Ra治疗,其中6针、5针、4针、2针、1针治疗者分别为3例、1例、2例、2例、1例;治疗中期或治疗结束时,部分缓解1例,病情稳定1例,疾病进展6例,余1例于1针^(223)Ra治疗后转为内分泌治疗,未进行疗效评估。截至末次随访时(2023年3月15日),9例患者中,死亡4例(1例死因为心力衰竭,3例为疾病进展),存活5例。死亡或疾病进展患者的基线PET显像所示的转移灶与骨扫描图像存在不一致性,前者可发现更多的骨转移灶;在治疗过程中PET显像可更精准地进行病情评估,尤其PSMA PET显像可避免因骨闪烁现象导致治疗效果评价不准确的现象。结论PSMA PET和/或^(18)F-FDG PET显像可检出内脏转移灶,辅助临床进行^(223)Ra治疗病例筛选,且基线PSMA PET和/或^(18)F-FDG PET显像特征与骨扫描结果存在不一致时,提示^(223)Ra治疗效果可能较差;在治疗过程中,相较于骨扫描,PSMA PET和/或^(18)F-FDG PET显像(尤其PSMA PET)对疗效的评价更为准确。