三氧化二砷联合化疗治疗难治复发多发性骨髓瘤的临床疗效分析

目的：分析三氧化二砷联合化疗治疗复发难治性多发性骨髓瘤(MM)的临床疗效。方法：收集复发难治性MM21例，分为原发难治性和复发难治性MM2组，应用三氧化二砷联合化疗，观察其总体和各组的有效率及副作用的发生情况。结果：治疗后，总有效率达90.5％，原发难治组及复发难治组的有效率分别为88．8％和91．7％。长期随访治疗7例，均保持持续缓解状态。未发现严重毒副作用。结论：三氧化二砷联合化疗治疗难治复发MM具有良好的疗效。     

地西他滨联合硼替佐米和地塞米松治疗复发或难治性多发性骨髓瘤的疗效分析

目的 观察地西他滨联合硼替佐米和地塞米松（VD）化疗方案在复发或难治性多发性骨髓瘤患者中的疗效和不良反应。方法 回顾性分析2017年1月至2019年12月于河南省肿瘤医院血液科收治的28例应用地西他滨联合VD方案治疗的复发或难治性多发性骨髓瘤患者的安全性、缓解率以及无进展生存期（PFS）。结果 中位随访时间为8.22(2.00～32.90)个月。总体缓解率为21.43%,其中4例（14.29%）获得完全缓解,2例（7.14%）获得非常好的部分缓解。最常见的不良反应是血小板降低（85.71%）、贫血（78.57%）、中性粒细胞减少（64.29%）和恶心（64.29%）。经过积极的治疗后,大部分不良反应可得到有效的控制和恢复。结论 对于多次复发的多发性骨髓瘤患者,地西他滨联合VD方案尚不能作为一种有效的治疗手段。     

去甲氧柔红霉素联合治疗老年性急性非淋巴细胞白血病初治患者的远期疗效

目的:评价去甲氧柔红霉素(IDA)在老年性急性非淋巴细胞白血病初治患者治疗中的远期疗效。方法:应用IDA加阿糖胞苷(Arac)治疗老年急性非淋巴细胞白血病初治患者27例(治疗组),并与柔红霉素加Arac治疗方案(对照组)对比分析。结果:治疗组与对照组完全缓解(CR)率分别为66.7%和52.1%,部分缓解(PR)率分别为14.8%和16.7%,差异无统计学意义(P>0.05);但治疗组获得CR后维持CR时间为(46.44±31.54)个月,较对照组(22.40±14.95)个月明显延长(P<0.01),所有CR患者中治疗组与对照组3年无病存活率分别为61.1%和20%,差异有统计学意义(P<0.05),5年无病存活率分别为33.3%和8%,差异无统计学意义(P>0.05)。结论:IDA加Arac作为老年性急性非淋巴细胞白血病初治患者的诱导缓解方案能明显延长患者的CR期,有较好的远期疗效。     

硼替佐米治疗难治/复发性多发性骨髓瘤的疗效观察

目的:了解硼替佐米对难治/复发性多发性骨髓瘤的疗效及不良反应。方法:采用VATD方案(硼替佐米1.3mg/m2,d1,4,8,11;表阿霉素10mg/d,d1~4;甲泼尼龙240~500mg/d,d1~4,8~11;沙立度胺100~200mg/d,d1~11;或VD方案(硼替佐米1.3mg/m2,d1,4,8,11;甲泼尼龙240~500mg/d,d1~4,8~11)治疗11例难治/复发性多发性骨髓瘤。结果:11例患者中,完全/接近完全缓解(CR)率:9.1%(1/11),部分缓解(PR)率:36.4%(4/11);总有效率(CR加PR)为45.5%(5/11)。不良反应主要有末梢神经炎,胃肠道反应,血小板减少等,均可耐受。结论:硼替佐米对部分已对化疗耐药的难治/复发性多发性骨髓瘤仍然有效,并且效果显著;与化疗无交叉耐药,并能延长患者生存期;为多发性骨髓瘤的治疗提供了一种全新的方法。虽然有一些不良反应但都可耐受。     

苯达莫司汀联合化疗治疗复发难治性多发性骨髓瘤的疗效观察

目的 观察苯达莫司汀联合化疗在复发难治性多发性骨髓瘤患者中的疗效及安全性。方法 回顾性分析2020年5月至2021年1月在河南省肿瘤医院血液科收治的32例应用苯达莫司汀联合化疗的复发难治性多发性骨髓瘤（MM）患者的临床资料。结果 32例复发难治性MM患者中31例可进行疗效评估,总体缓解率（ORR）为51.6%,其中完全缓解（CR）4例（12.9%）,非常好的部分缓解（VGPR）3例（9.7%）,部分缓解（PR）9例（29.0%）。前期接受三线及以上治疗的患者ORR明显低于接受一、二线治疗的。最常见的血液学和非血液学不良反应分别是是血小板降低（62.5%）和恶心、呕吐（56.3%）,但给予对症治疗后,症状缓解,均未影响正常治疗进程。结论 对于复发难治性多发性骨髓瘤患者,苯达莫司汀联合化疗可以作为一种安全可行的治疗方案。     

改良的以硼替佐米为基础的化疗方案治疗老年复发/难治性多发性骨髓瘤的疗效

目的探讨改良的以硼替佐米为基础的化疗方案(P-CTD方案)对老年复发/难治性多发性骨髓瘤的治疗效果。方法选择44例老年复发/难治性多发性骨髓瘤患者,21例患者接受CTD方案治疗(环磷酰胺、沙利度胺、地塞米松),23例患者接受P-CTD方案(硼替佐米、环磷酰胺、沙利度胺、地塞米松)进行治疗。上述患者共接受4个疗程的治疗,治疗结束后参照国际骨髓瘤工作组(IMWG)制定的多发性骨髓瘤疗效判定标准评估疗效,WHO标准判断不良反应。结果 CTD组患者接受治疗后,完全缓解(CR)和很好的部分缓解(VGPR)3例(14.3%),部分缓解(PR)8例(38.1%),病情稳定(SD)4例(19%),病情进展(PD)6例(28.6%),总有效(CR+VGPR+PR)11例(52.4%)。P-CTD组患者治疗后CR和VGPR 8例(34.8%),PR 11例(47.8%),SD 1例(4.3%),PD 3例(13%),总有效19例(82.6%),P-CTD组缓解率优于CTD组(P<0.05)。两组患者各种不良反应相似(P>0.05)。结论 CTD方案和P-CTD方案均具有良好的安全性,P-CTD方案的缓解率优于CTD方案。     

多发性骨髓瘤92例临床分析

目的　对多发性骨髓瘤(MM)的临床特点进行总结,为诊断和治疗提供参考。方法　对92例MM患者的临床资料进行回顾分析。结果　(1)初始化疗采用M2、VAD或MP方案有效率无显著性差异。(2)初始VAD方案化疗是否有效与患者预后相关。初治有效组和无效组中位生存期分别为43. 1个月与4. 0个月(P<0. 05)。(3)骨膦可防治骨骼进一步的破坏,但骨X线片未显示明显的骨质再钙化。化疗中加用骨膦治疗可延长患者的生存期(P<0. 05)。结论　初始VAD方案化疗有效者预后较好,中位生存期可达43. 1个月,加用骨膦治疗可延长生存期。在细胞遗传学和基因表达谱基础上行个体化治疗可能会提高疗效。     

羟基脲加干扰素治疗原发性血小板增多症的临床疗效研究

目的 :观察羟基脲加干扰素治疗原发性血小板增多症 (PT)的临床疗效。方法 :根据有无临床症状 ,将 38例PT患者分为有临床症状组及无临床症状组 ,根据用药情况再将 38例PT患者分为单用化疗组 (羟基脲0 .5 qd～0 .5tid ,加高三尖杉 )、α干扰素组 (上述化疗加α干扰素 3× 10 6IU qod～biw)和γ干扰素组 (上述化疗加γ干扰素 (1～ 3)× 10 6IUqd～qod)。 结果 :有临床症状组的患者发病时外周血血小板计数明显高于无临床症状组 (P <0 .0 1)。单用化疗组、α干扰素组与γ干扰素组疗效相似 ,总有效率分别为 91.7%、80 .0 %和 10 0 % (P >0 .0 5 )。三组治疗前后血小板计数分别为 (1137.0 0± 5 5 6 .5 0 )vs(74 4 .5 0± 4 84 .4 3)× 10 9/L、(114 6 .0 0± 32 5 .5 0 )vs(44 3.81± 2 13.0 2 )× 10 9/L和 (10 6 9.0 0± 2 4 3.70 )vs(44 0 .6 4± 14 1.72 )× 10 9/L。本研究中给予α干扰素无效的 2例患者改用γ干扰素 ,结果 1例取得缓解 ,1例进步。结论 :对于高危患者 ,若经济条件有限 ,可给予羟基脲、高三尖杉并抗栓胶囊等治疗 ,该治疗方法疗效明确 ,费用较低 ,副作用较少。对于α干扰素疗效欠佳的患者 ,可以考虑改用γ干扰素     

急性B淋巴细胞白血病患者检测微小残留病的临床意义

采用多参数流式细胞仪对50例成人B淋巴细胞白血病(B-ALL)患者缓解后的微小残留病(M RD)进行检测,结果显示,B-ALL完全缓解组和正常对照组骨髓M RD分别为(5.9462±4.8964)%和(0.5845±0.2014)%,二者比较有显著性差异(P<0.01);B-ALL持续缓解与复发者的骨髓M RD分别为(4.1436±1.6125)%和(42.3514±20.6451)%,二者比较有显著性差异(P<0.01)。诱导缓解至治疗3个月时M RD阳性患者复发率高,预后不良。提示对B-ALL患者用流式细胞术进行缓解后M RD检测,有利于其复发预测及早期个体化治疗选择。     

伊沙佐米治疗难治复发多发性骨髓瘤临床疗效及相关毒副反应研究

目的:探讨伊沙佐米治疗难治复发多发性骨髓瘤的临床疗效及相关毒副反应。方法:2018-08-2019-08我院对15例难治复发多发性骨髓瘤患者行以伊沙佐米为基础化疗,随访分析治疗后反应率及相关毒副反应,并对相关临床指标进行分析。结果:经以伊沙佐米为基础诱导化疗诱导治疗后2例(13.3%)患者达到完全缓解,3例(20.0%)达到部分缓解,总有效率为33.3%。在治疗前,治疗无效组的血肌酐及β2微球蛋白浓度明显高于治疗有效组(均P0.05)。伊沙佐米为基础诱导化疗常见的毒副反应包括中细粒细胞减少5例,血小板减少3例,血红蛋白下降3例,皮疹2例,肺部感染3例,肝功能异常1例,恶心5例,乏力6例。结论:伊沙佐米对部分难治复发多发性骨髓瘤安全有效,是难治复发多发性骨髓瘤的治疗新选择。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.