Usefulness of Newly Devised Clomiphene Citrate Administration Method Compared with the Conventional Method in Ovulation and Pregnancy

Objective: Since not all women wish to conceive a child through aggressive treatment, we investigated the usefulness of modified repeated intracyclic clomiphene citrate (CC) therapy (repeated CC therapy) as a newly devised administration method. Methods: We evaluated the effects of CC administration on menstrual cycle length and retrospectively compared ovulation and pregnancy in 220 women who received CC at our hospital. Patients in the conventional method group received 50 mg per day for five days, starting on the fifth day of menstruation (withdrawal bleeding). Groups with and without menstrual cycle shortening after conventional CC administration were compared. The repeated CC therapy group was also compared with the non-shortened group. Repeated CC therapy was administered for the first five days as in the conventional method, and a second five-day repeat treatment was administered after an interval of five to seven days. Pregnancy rates, including indirect pregnancies, were evaluated by three different methods. Results: Ovulation and pregnancy rates were significantly better in the shortened group than in the non-shortened group (P < 0.001 and P = 0.010, respectively). Even in the non-shortened group, ovulation and pregnancy rates including indirect pregnancies were significantly improved when ovulation was observed with repeated CC therapy (P < 0.001 and P = 0.022, respectively). Conclusions: For patients whose menstrual cycle was not improved or shortened, repeated CC therapy as the newly devised CC administration method is useful as the next step after the conventional CC administration method.

Analysis of the Effect of High-Dose Segmental Citrate Anticoagulation in High Flux Hemodialysis

Objective:To analyze the clinical effect of high-dose citrate in segmental extracorporeal anticoagulation for high-throughput hemodialysis.Methods:The subjects included in this study were admitted to the hospital for maintenance hemodialysis treatment from January 2021 to January 2023.All patients had a high risk of bleeding and received 4%trisodium citrate anticoagulant treatment,administered at a rate of 200 mL/h before and after the dialyzer.The anticoagulant effects achieved by the patients were observed and analyzed.Results:The total number of patients who received high-dose segmented citrate extracorporeal anticoagulation dialysis treatment was 50,with each patient undergoing 100 treatments.During the treatment,2 patients had to end the treatment early due to transmembrane pressure exceeding 30 mmHg and an increase in venous pressure exceeding 250 mmHg;the treatment times for these patients were 20 minutes and 200 minutes,respectively.The remaining patients successfully completed the 4-hour treatment.Blood pH and calcium ion concentration in the venous pot were monitored.It was observed that before dialysis,after 2 hours of dialysis,and at the end of dialysis,the blood pH of the patients remained within a relatively normal range.Although some patient levels changed after dialysis,they remained within the normal range.No adverse reactions(such as numbness of the limbs or convulsions)were observed during the anticoagulant treatment.Conclusion:Administering 4%trisodium citrate at a rate of 200 mL/h before and after the dialyzer achieves a good anticoagulant effect,maintains the patient’s blood gas levels within the normal range at the end of dialysis,and causes no adverse reactions.

Management of regional citrate anticoagulation for continuous renal replacement therapy:guideline recommendations from Chinese emergency medical doctor consensus

Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.

几种常用的核染色标记物pH 6.0 Citrate和pH 9.0 Tris/EDTA修复液的比较

目的探讨pH 6.0 Citrate和pH 9.0 Tris/EDTA两种修复液在常用的免疫组化核染色标记物中的染色效果。方法选取本科室常用的3种核/浆标记抗体以及22种核标记抗体分别采用pH 6.0 Citrate和pH 9.0 Tris/EDTA微波热修复进行比较。结果在25种抗体中,其中有11种分别用pH 6.0 Citrate和pH 9.0 Tris/EDTA微波修复染色效果基本一致,在其余14种抗体中,有11种用pH 9.0 Tris/EDTA微波热修复方法进行修复时,阳性信号明显增强;而有3种抗体用pH 6.0 Citrate微波热修复方法进行修复时,阳性信号稍增强。结论对于这25种抗体来说,如果用微波加热的方法进行抗原修复,那么pH 9.0 Tris/EDTA优于PH 6.0 Citrate。

治疗伴有中至严重血小板减少的骨髓纤维化新药——枸橼酸帕西替尼(pacritinib citrate)

骨髓纤维化是一种罕见的骨髓进行性恶性肿瘤,破坏健康血细胞的正常产生,导致骨髓衰竭和严重贫血。帕西替尼(pacritinib)的激酶谱显示其对急性髓系白血病、骨髓增生异常综合征、慢性单核粒细胞白血病和慢性淋巴细胞白血病具有潜在的治疗作用。枸橼酸帕西替尼最初由美国细胞疗法公司开发,2009年1月与美国S*BIO和Onyx制药公司签订开发和商业化协议,成立美国CTI生物制药公司,重点开发枸橼酸帕西替尼,用于治疗骨髓增生和移植物抗宿主病等疾病。2012年4月,成立CTI生物制药公司,与美国S*BIO和Onyx制药公司重新签订协议,CTI将收回帕西替尼全球开发权利。2020年10月13日CTI生物制药公司向美国食品药品管理局(FDA)提交滚动新药申请,寻求批准枸橼酸帕西替尼用于治疗严重血小板减少症(血小板计数<50×10^(9)·L^(-1))的骨髓纤维化。2022年2月28日,美国FDA批准枸橼酸帕西替尼胶囊上市,商品名Vonjo®,用于治疗成人血小板计数<50×10^(9)·L^(-1)的中高危原发性或继发性(真性红细胞增多症后或原发性血小板增多症)的骨髓纤维化。该文对枸橼酸帕西替尼胶囊的非临床和临床药理毒理学、临床研究、不良反应、适应证、剂量与用法、用药注意事项及知识产权状态和国内外研究进展等进行介绍。

Removal of citrate and hypophosphite binary components using Fenton,photo-Fenton and electro-Fenton processes

Both citrate and hypophosphite in aqueous solution were degraded by advanced oxidation processes （Fe^2＋/H2O2, UV/Fe^2＋/H2O2, and electrolysis/Fe^2＋/H2O2） in this study. Comparison of these techniques in oxidation efficiency was undertaken. It was found that Fenton process could not completely degrade citrate in the presence of hypophosphite since it caused a series inhibition. Therefore, UV light （photo-Fenton） or electron current （electro-Fenton） was applied to improve the degradation efficiency of the Fenton process. Results showed that both photo-Fenton and electro-Fenton processes could overcome the inhibition of hypophosphite, especially the electro-Fenton.

Can mosapride citrate reduce the volume of lavage solution for colonoscopy preparation?

AIM:To evaluate the possibility of reducing the volume of polyethylene glycol(PEG)-electrolyte solution using adjunctive mosapride citrate for colonoscopy preparation. METHODS:This was a single-center,prospective, randomized,investigator-blinded,non-inferiority study involving 252 patients of both sexes,aged from 20 to 80 years,scheduled for screening or diagnostic colonoscopy in our department.A total of 126 patients was randomized to receive 1.5 L PEG-electrolyte solution plus 15 mg of mosapride(1.5 L group),and 126 received 2 L PEG-electrolyte solution plus 15 mg of mosapride(2 L group).Patients completed a questionnaire on the acceptability and tolerability of the bowel preparation process.The efficacy of bowel preparation was assessed using a 5-point scale based on the Aronchick scale.The primary end point was adequate bowel preparation rates(score of excellent/good/fair) vs(poor/inadequate).Acceptability and tolerability,as well as disease detection,were secondary end points. RESULTS:A total of 244 patients was included in the analysis.There were no significant differences between the 2 L and 1.5 L groups in age,sex,body mass index, number of previous colonoscopies,and the preparation method used previously.The adequate bowel preparation rates were 88.5%in the 2 L group and 82.8%in the 1.5 L group[95%lower confidence limit(LCL)for the difference=-14.5%,non-inferiority P=0.019]in the right colon.In the left colon,the adequate bowel preparation rates were 89.3%in the 2 L group and 81.1%in the 1.5 L group(95%LCL=-17.0%,non-inferiority P=0.066).Compliance,defined as complete (100%)intake of the PEG solution,was significantly higher in the 1.5 L group than in the 2 L group(96.8% vs 85.7%,P=0.002).The proportion of abdominal distension(none/mild/moderate/severe)was significantly lower in the 1.5 L group than in the 2 L group (36/65/22/3 vs 58/48/18/2,P=0.040).Within the subgroup who had undergone colonoscopy previously, a significantly higher number of patients in the 1.5 L group than in the 2 L group felt that the current preparation was easier than the previous one(54.1%vs 28.0%,P=0.001).The disease detection rate was not significantly different between the two groups. CONCLUSION:Although the 1.5 L group had better acceptability and tolerability,15 mg of mosapride may be insufficient to compensate for a 0.5-L reduction of PEG solution.

Competitive and cooperative adsorption of arsenate and citrate on goethite

The fate of arsenic in natural environments is influenced by adsorption onto metal （hydr）oxides. The extent of arsenic adsorption is strongly affected by coexisting dissolved natural organic acids. Recently, some studies reported that there existed competitive adsorption between arsenate and citrate on goethite. Humic acid is known to interact strongly with arsenate by forming complexes in aqueous solution, hence it is necessary to undertake a comprehensive study of the adsorption of arsenate/citrate onto goethite in the presence of one another. The results showed that at the arsenate concentrations used in this study （0.006-0.27 mmol/L）, citrate decreased arsenate adsorption at acidic pH but no effect was observed at alkaline pH. In comparison, citrate adsorption was inhibited at acidic pH, but enhanced at alkaline pH by arsenate. This was probably due to the formation of complex between arsenate and citrate like the case of arsenate with humic acid. These results implied that the mechanism of the adsorption of arsenate and citrate onto goethite in the presence of one another involved not only competition for binding sites, but the cooperation between the two species at the watergoethite interface as well.

Assessment of heme oxygenase-1 （HO-1） activity in the cavernous tissues of sildenafil citrate-treated rats

Aim： To assess heine oxygenase-1 （HO-1） activity in the cavemous tissue of sildenafil citrate-treated rats. Methods： One hundred and ninety-two Sprague-Dawley male rats, divided into four equal groups, were investigated. Group 1, the control group, received regular animal chow; group 2 received sildenafil citrate by intragastric tube; group 3 received sildenafil and HO inhibitor （zinc protoporphyrin, ZnPP）; and group 4 received sildenafil and nitric oxide synthase （NOS） inhibitor L-nitroarginine methyl ester （L-NAME）. Twelve rats from each group were killed after 0.5 h, 1 h, 2 h and 3 h of drug administration. Then HO-1 activity, cGMP levels and NOS enzymatic activity in the cavernous tissues were estimated. Results： In cavemous tissue, HO-1 activity, NOS enzymatic activity and cGMP concentration increased significantly in sildenafil-treated rats compared to other groups throughout the experiment. Rats receiving either HO or NOS inhibitors showed a significant decrease in these parameters. HO- 1 cavemous tissue activity and NOS enzymatic activity demonstrated a positive significant correlation with cGMP levels （r = 0.646, r = 0.612 respectively; P 〈 0.001）. Conclusion： The actions of PDE5 inhibitor sildenafil citrate in the cavernous tissue are partly mediated through the interdependent relationship between both HO-1 and NOS activities.

Effect of calcium citrate on bone integration in a rabbit femur defect model

Objective:To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Methods:Twenty-four male Japanese white rabbits were randomly divided into three groups (Group A.B.C)in this study.Under anesthesia,defects of four sizes(1.2,1.5,2.0 and 2.5 mm) were created in each of the rabbits.Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur(Experimental),while in the contralateral femur(Control) nothing was implanted.The defects were analyzed using radiography and histological analysis by using Imagepro-Plus 6.0 software after animal was sacrificed at 4th(Group A),6th(Group B) and 8th(Group C) weeks postoperatively.Four samples were analyzed for each size of defect and each healing period.Results:The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative 4th and 6th weeks,It showed significant difference between the experimental group and the control group when these defects were less than or equal to 2.0 mm.No statistical difference was observed when these defects were larger than 2.0 mm at all healing periods except at the 4th week.Conclusions:Calcium citrate affects the early periods of hone defects healing mechanism in Japanese white rabbits positively,especially when the defect is not too large,We suggest further studies on calcium citrate to determine the effects of various dosages,administration ways and the experimental time on the bone defects.

Treatment preferences in men with erectile dysfunction： an open label study in Korean men switching from sildenafil citrate to tadalafil

To evaluate patient preferences for sildenafil citrate or tadalafil （PDE-5 inhibitors available for the treatment of erectile dysfunction [ED]） and assess potential reasons for these preferences. Methods： This open-label study was conducted on Korean men taking sildenafil, at least 6 weeks prior to study entry, for ED. Following screening, patients continued sildenafil treatment for 4 weeks, then after a 1-week washout period, switched to tadalafil for 8 weeks. Patients then continued with their treatment of choice during an extension phase. Psychosocial factors （time concern, spontaneity, sexual self-confidence） were evaluated using Psychological and Interpersonal Relation- ship Scales （PAIRS）, while timing of dose to sexual attempt patterns were assessed from patient diaries. Results： The present study enrolled 160 Korean men （mean age 55 years） with prior median sildenafil use of 585 days. During the extension phase, 73.7% of patients elected to take tadalafil, whereas 26.3% chose sildenafil （P 〈 0.001）. After switching from sildenafil to tadalafil, mean PAIRS time concern scores decreased from 2.54 to 2.42 （P = 0.002）, with no statistically significant differences observed between the sildenafil and tadalafil assessment phases in sexual spontaneity and self-confidence scores. Sexual attempts made 〉 4 h to 〈 36 h post-dose occurred in 4.5% of patients during the sildenafil assessment phase compared with 17.5% during the tadalafil assessment phase. Conclusion： After experiencing both sildenafil and tadalafil, the majority of patients exhibited a preference for tadalafil. This preference might be influenced by psychosocial factors, such as decreased time concerns, and a broader window of opportunity available for sexual activity.

Clomiphene Citrate Induces ROS-Mediated Apoptosis in Mammalian Oocytes

The clomiphene citrate (CC), a nonsteroidal triphenylethylene compound, is a first line of medicine used for the induction of ovulation in anovulatory women worldwide. In spite of high ovulation induction with the use of CC, the pregnancy rate is much lower. Such a discrepancy could be due to the peripheral anti-estrogenic effect of CC, particularly at the level of ovary, endometrium and cervical mucus. CC induces ovulation by binding to the estrogen receptors and generates hypoestrogrnic state in hypothalamus leading to release of pituitary gonadotropins. CC may have a direct effect at the level of ovary but the molecular mechanism remains unclear. Animal studies suggest that the CC induces apoptosis in granulosa cells and results hypoestrogenic state in the ovary. Reduced estradiol 17β level in the ovary affects development and maturation of oocyte leading to oocyte apoptosis. Further, CC increases hydrogen peroxide (H2O2) level and thereby bax protein expression and DNA fragmentation in cumulus-granulosa cells as well as in oocytes. The exogenous supplementation of either estradiol 17β or melatonin reduces H2O2 level in ovary, delays meiotic cell cycle progression in oocyte and protects oocyte apoptosis. Hence, supplementation of estradiol 17β or melatonin along with CC could be beneficial to protect granulosa cell as well as oocyte apoptosis and inhibit deterioration of oocyte quality. Thus, maintenance of oocyte quality may overcome the adverse effect caused due to CC treatment during infertility management.

Synthesis, Crystal Structure and Characterization of a New Zinc Citrate Complex

A new Zn-citrate coordination complex {K[Zn（C6H5O7）（H2O）]}n（1） was synthesi- zed via hydrothermal reaction. In the crystal structure of complex 1, each citrate serves as thequadricdentate ligand coordinating to three Zn（II） ions, forming a zigzag chain, and such chains are further connected into a 3D network by the K＋ linkers. Crystal data for complex 1： triclinic, space group Pī, α = 7.3487（9）, b = 7.5397（6）, c = 9.6772（8） A, α = 76.894（8）, β = 68.260（10）, γ = 65.155（10）°, V = 450.34（7） ？3 and Z = 2. Other characterizations by elemental analysis, IR, TG and fluorescence were also described.

Study of <i>in Vitro</i>Interaction of Sildenafil Citrate with Bovine Serum Albumin by Fluorescence Spectroscopy

In vitro interaction of sildenafil citrate (SC) with bovine serum albumin (BSA) was investigated at two excitation wavelengths of BSA (280 nm and 293 nm) at two different temperatures (298 K and 308 K) by fluorescence emission spectroscopy. The study showed that quenching of BSA fluores-cence by sildenafil citrate was the result of formation BSA-SC complex with probable involvement of both tryptophan and tyrosine residues of BSA. Fluorescence quenching constant was determined from Stern-Volmer equation, and both static quenching and dynamic quenching were showed for BSA by SC at the conditions. Van’t Hoff equation was used to measure the thermodynamic parameters ΔG, ΔH, and ΔS at the temperatures which indicated that the hydrogen bond and the hydrophobic forces played major roles for BSA-SC complexation. The binding number (n) was found to be ≈1 indicating that one mole BSA bound with one mole SC. The binding affinity of SC to BSA was calculated at different temperatures. The binding constant was decreased with increasing temperatures indicating that stability of BSA-SC complex decreased with increasing temperatures.

Stability-indicating HPLC-DAD methods for determination of two binary mixtures:Rabeprazole sodium-mosapride citrate and rabeprazole sodium-itopride hydrochloride

Two selective stability-indicating HPLC methods are described for determination of rabeprazole sodium （RZ）-mosapride citrate （MR） and RZ-itopride hydrochloride （IO） mixturcs in the presence of their ICH-stress formed degradation products. Separations were achieved on X-Bridge CI 8 column using two mobile phases： the first for RZ-MR mixture consisted of acetonitrile： 0.（125 M KH,PO4 solution： TEA （30：69：1 v/v; pH 7.0）; the second for RZ-IO mixture was at ratio of 25：74：1 Iv/v： pH 9.25J. The detection wavelength was 283 nm. The two methods were validated and wdidation acceptance criteria were met in all cases. Peak purity testing using contrast angle theory, relative absorbance and log A versus the wavelengths plots were presented. The % recoveries of the intact drugs were between 99.1% and 102.2% with RSD% values less than 1.6%. Application of the proposed HPLC methods indicated that the methods could be adopted to follow the stability of their formulations.

Citrate-based biomaterial design and their applications

1.Introduction Biodegradable polymeric biomaterials have been fabricated into various biomedical implants such as drug delivery nanoparticles,tissue engineering scaffolds and orthopedic devices.Using biodegradable polymers as implant materials is beneficial as the implants are degraded and cleared by the body once their missions are complete,leaving no foreign materials in the body.Driven by the versatile needs in biomedical engineering,searching for ideal functional biodegradable polymers has been an endless effort in the past decades.Among biodegradable polymers,citrate-based biodegradable elastomeric(CABE)polymers have recently received increasing attention because their compliance under force can closely resemble the elastic

Randomized controlled trial of Letrozole versus Clomiphene citrate for induction of ovulation in polycystic ovarian syndrome (PCOS): A Malaysian experience

Background: The purpose of this study was to compare the effectiveness of Letrozole versus Clomiphene citrate for ovulation induction in polycystic ovarian syndrome (PCOS) with infertility. Methods: This was a prospective randomized trial involving 150 women with PCOS attending the Infertility Clinic at three hospitals in Malaysia. During the initial visit, anthropometric measurements and baseline investigations were performed. Patients were randomized to 5.0 mg Letrozole daily (75 patients) or 100 mg Clomiphene citrate daily (75 patients) from the fifth until the ninth day of menstruation. Serial transvaginal scans were performed to see the dominant follicles, endometrial thickness and number of follicles. Transvaginal scans were performed serially to look for evidence of ovulation. Results: The subjects were homogenously distributed. The difference between Letrozole and Clomiphene citrate for ovulation rate was 59 (78.7%) versus 40 (53.3%). Patients taking Letrozole exhibited a mean endometrial thickness (ET) at mid cycle of menses (Day 11-D14) of9.2 mm(SD ± 2.3) versus8.4 mm(SD ± 2.2) for patients taking Clomiphene citrate, and these differences were statistically significant

Cleansing efficacy and safety of bowel preparation protocol using sodium picosulfate/magnesium citrate considering subjective experiences:An observational study

BACKGROUND Research data from patient reports indicate that the least bearable part of colonoscopy is the administration of laxatives for bowel preparation.AIM To observe the intestinal cleansing efficacy and safety of sodium picosulfate/magnesium citrate and to discuss the patients’experiences due to the procedure.METHODS Subjects hospitalized in the International Medical Center Ward of Peking University International Hospital,Beijing,China,from April 29 to October 29,2020,for whom the colonoscopy was planned,were enrolled.Bowel preparation was performed using sodium picosulfate/magnesium citrate.The effect of bowel cleansing was evaluated according to the Ottawa Bowel Preparation Scale,defecation conditions and adverse reactions were recorded,and the comfort level and subjective satisfaction concerning medication were evaluated by the visual analogue scale/score(VAS).RESULTS The bowel preparation procedure was planned for all patients enrolled,which included 42 males and 22 females.The results showed an average liquid rehydration volume of 3000 mL,an average onset of action for the first dose at 89.04 min,an average number of bowel movements of 4.3 following the first dose,an average onset of action for the second dose at 38.90 min and an average number of bowel movements of 5.0 after the second dose.The total average Ottawa Bowel Preparation Scale score was 3.6,with 93.55%of bowel preparations in the“qualified”and 67.74%in the“excellent”grade.The average VAS score of effect on sleep was 0,and the average VAS score of perianal pain was also 0.The average VAS score for ease of taking and taste perception of the bowel cleanser was 10.Side effects included mild to moderate nausea(15.63%),mild vomiting(4.69%),mild to moderate abdominal pain(7.81%),mild to moderate abdominal distension(20.31%),mild palpitation(7.81%)and mild dizziness(4.69%).CONCLUSION Sodium picosulfate/magnesium citrate is effective and safe for bowel preparation before colonoscopy with high subjective patient acceptance,thus improving overall patient compliance.

Synthesis,Crystal Structure and Luminescent Property of a One-dimensional Europium Citrate Complex

A new compound, [Eu（Hcit）（H2O）2]·H2O]n （1, Hcit^3-= C（OH）（COO-）（CH2COO-）2）, has been synthesized under hydrothermal reactions of europium oxide, MnCl2·4H2O and citric acid at 120 ℃ for three days. The compound was characterized by single-crystal X-ray diffraction analyses, IR and TGA. Complex 1 crystallizes in monoclinic, space group P21/n with a = 6.179（1）, b = 9.688（2）, c = 16.990（3） A, β = 91.98（3）°, Z = 4, V = 1016.4（3） A^3, C6H11EuO10, Mr = 395.11, Dc = 2.582 g/cm3, μ = 6.218 mm-1, F（000） = 760, R = 0.0183 and wR = 0.0411. Single-crystal X-ray analysis reveals that complex 1 displays 1D ladder chains along the a axis, with dinuclear Eu2O2 units serving as ＂steps＂ and carboxylate groups as ＂uprights＂, which are connected by hydrogen bonds. The solid-state luminescent property of complex 1 was investigated at room temperature. Upon excitation at 394 nm, compound 1 exhibits interesting luminescent properties with several intense bands in the visible region and the most intense and sharp emission being in the red region at 615 nm. The TGA and XRD results prove that complex 1 undergoes facile thermal decomposition to form Eu2O3 at about 870 ℃.