Insights into oxazaphosphorine resistance and possible approaches to its circumvention.

The oxazaphosphorines cyclophosphamide, ifosfamide and trofosfamide remain a clinically useful class of anticancer drugs with substantial antitumour activity against a variety of solid tumors and hematological malignancies. A major limitation to their use is tumour resistance, which is due to multiple mechanisms that include increased DNA repair, increased cellular thiol levels, glutathione S-transferase and aldehyde dehydrogenase activities, and altered cell-death response to DNA damage. These mechanisms have been recently re-examined with the aid of sensitive analytical techniques, high-throughput proteomic and genomic approaches, and powerful pharmacogenetic tools. Oxazaphosphorine resistance, together with dose-limiting toxicity (mainly neutropenia and neurotoxicity), significantly hinders chemotherapy in patients, and hence, there is compelling need to find ways to overcome it. Four major approaches are currently being explored in preclinical models, some also in patients: combination with agents that modulate cellular response and disposition of oxazaphosphorines; antisense oligonucleotides directed against specific target genes; introduction of an activating gene (CYP3A4) into tumor tissue; and modification of dosing regimens. Of these approaches, antisense oligonucleotides and gene therapy are perhaps more speculative, requiring detailed safety and efficacy studies in preclinical models and in patients. A fifth approach is the design of novel oxazaphosphorines that have favourable pharmacokinetic and pharmacodynamic properties and are less vulnerable to resistance. Oxazaphosphorines not requiring hepatic CYP-mediated activation (for example, NSC 613060 and mafosfamide) or having additional targets (for example, glufosfamide that also targets glucose transport) have been synthesized and are being evaluated for safety and efficacy. Characterization of the molecular targets associated with oxazaphosphorine resistance may lead to a deeper understanding of the factors critical to the optimal use of these agents in chemotherapy and may allow the development of strategies to overcome resistance.     

Pharmacokinetics of tacrolimus and mycophenolic acid are altered, but recover at different times during hepatic regeneration in rats.

Hepatic regeneration is very critical to the success of living donor liver transplantation, which allows a reduced size liver to grow in size to accommodate the requirements of both the donor and the recipient. The objectives of this study were to evaluate 1) the hepatic metabolism of the two immunosuppressive drugs, tacrolimus and mycophenolic acid (MPA), and 2) the pharmacokinetics of tacrolimus and mycophenolic acid at various time points after initiation of hepatic regeneration by partial hepatectomy in rats. The hepatic intrinsic clearance of tacrolimus was decreased to 70% and 51% of the control level at the 24th h and the 6th day, respectively, but returned to normal level by day 14. The total body clearance of tacrolimus was reduced transiently but recovered completely by day 18. The hepatic intrinsic clearance of MPA was decreased to 52% and 51% of that in control rats at the 24th h and the 6th day, respectively, but recovered to normal level by day 14. The total body clearance of MPA was reduced at the 24th h but recovered by day 6. The magnitude of reduction in the clearance of tacrolimus and MPA was much smaller than what was predicted from in vitro data. The elimination clearance of MPA glucuronide was also impaired during hepatic regeneration but recovered to normal level with time. In conclusion, the pharmacokinetics of tacrolimus and mycophenolic acid were altered during hepatic regeneration but recovered completely at different rates over time. Caution must be exercised in extrapolating in vitro data to in vivo conditions during hepatic regeneration.     

芪丹颗粒剂治疗肺间质纤维化105例临床研究

目的:观察芪丹颗粒剂对肺间质纤维化患者的临床疗效.方法:选择105例肺间质纤维化患者作为治疗组,给予芪丹颗粒剂,对照组60例,给予强的松0.5mg/kg,两组疗程均为3～6个月,每1～3个月随诊1次.观察两组患者治疗后的症状、体征、肺部高分辨率CT(HRCT)及肺功能变化.结果:治疗6个月后,治疗组症状、体征改善率优于对照组(P＜0.05或P＜0.01);治疗组治疗3个月和6个月后,肺HRCT和肺功能改善率优于对照组(P＜0.05或P＜0.01).结论:芪丹颗粒剂可以不同程度地改善肺间质纤维化患者症状和体征,使患者肺功能停止恶化,且用药期间未见任何副作用,耐受性良好.     

米非司酮致子宫内膜简单型增生二例临床分析

近年来，随着米非司酮应用的日趋广泛，其并发症亦不断增加，尤其是一些少见的以及一些始料未及的并发症，更应引起注意。我院2004年门诊诊治的二例病例，1例为子宫肌瘤剜除术后，1例为子宫腺肌症，在连续口服米非司酮4～6个月后，出现不规则的阴道多量流血，后经诊断性刮宫，二例病理检查均提示为子宫内膜简单型增生。现报道如下：     

三叉神经痛的辨证施治略述

三叉神经痛是指三叉神经分布范围内反复出现的阵发性短暂剧烈疼痛。罹患此病，轻者影响正常生活，重者痛不欲生。患者自觉痛如刀割、锥刺、火灼、电击、常伴有同侧面部肌肉抽搐，一般无感觉缺失等神经传导功能障碍。并常见到有激发点（扳机点）的存在，即如在刷牙、洗脸、进食、言语等动作时，接触三叉神经分布区某一部皮肤或粘膜等，均可激发疼痛发作。     

Prediction of Hidden Blood Loss During Posterior Spinal Surgery

Objective Identification of the risk factors for extraordinary hidden blood loss (HBL) could clarify the underlying causes and provide more appropriate management. This study aims to identify the predictors of HBL in spinal surgery.     

保罗青光眼植入物治疗青光眼的初步观察

目的：初步评估保罗青光眼植入物在青光眼治疗中的有效性和安全性。

方法：回顾性分析2022-03/2023-01接受保罗青光眼植入物治疗的青光眼患者10例10眼的临床资料。至少随访12 mo,观察手术前后视力、眼压和抗青光眼用药数量等指标的变化。

结果：纳入患者末次随访时视力较术前无明显变化; 术前眼压19-60(中位数28)mmHg,末次随访时眼压为10-18(中位数14)mmHg。术前所有患者均需使用2-4种抗青光眼药物,末次随访时仅1例患者需使用。4例患者末次随访时角膜内皮细胞密度较术前明显下降,未发生角膜相关并发症。截至末次随访,10例患者均获得手术成功。

结论：保罗青光眼植入物具有显著的降眼压疗效,角膜内皮细胞损害可能是其存在的隐患。     

特发性视神经炎患者视盘及黄斑区血流密度的定量研究

目的：评估特发性视神经炎(ON)患者的患眼和未受累对侧眼的视盘及黄斑的血流密度改变情况,为特发性ON的治疗和随访提供一定的临床指导。

方法：横断面研究。收集2019-12/2021-12于扬州大学附属苏北人民医院眼科确诊的初次发病且病程≤3 mo的单眼特发性ON患者16例,分为患眼组16眼与未受累对侧眼组16眼,另收集性别、年龄相匹配的健康者20例20眼作为对照组。所有眼均行视盘区4.5 mm×4.5 mm及黄斑区6 mm×6 mm光相干断层扫描血管成像(OCTA)检查,收集视盘区及黄斑区各血流指标,并对三组间各指标进行对比及分析。

结果：与对照组及未受累对侧眼组相比,ON患眼组视盘全区域及视盘周围各分区毛细血管、全部血管血流密度均降低(P<0.05)。与未受累对侧眼组相比,ON患眼黄斑区整体及中心凹周围全部分区SCP血流密度均显著降低(P<0.05),旁中心凹SCP血流密度仅在上半侧及上侧分区显著降低(P<0.05)。与对照组相比,ON患眼组黄斑中心凹周围下半侧、鼻侧、下侧SCP密度降低(均P<0.05)。与对照组相比,未受累对侧眼组黄斑区整体及各分区SCP血流密度均增加(P<0.05),旁中心凹SCP血流密度增加(P<0.05),但下半侧、鼻侧分区改变无统计学差异(P>0.05),中心凹周围SCP血流密度增加仅在上半侧及上侧分区有统计学意义(P<0.05)。

结论：病程3 mo以内的ON患者会出现视盘周围各分区血管密度的降低和黄斑中心凹周围部分分区SCP血流密度的降低,同时伴随着对侧眼黄斑区部分分区的SCP血流密度的增加。     

Ocular surface in patients with different degrees of myopia

AIM: To investigate the clinical features of the ocular surface in patients with different degrees of myopia. METHODS: A cross-sectional study was conducted involving 122 participants with myopia in Beijing Tongren Hospital from February to June, 2023. After completing the Ocular Surface Disease Index (OSDI) score scale, measurements were taken for refraction, biometric parameters and ocular surface parameters. The prevalence, severity and related parameters of the dry eye among different groups based on axial length (AL) were compared. Correlation analysis was performed between ocular surface parameters and refraction/biometric measurement parameters. RESULTS: Statistically significant differences were observed in refractive error, corneal thickness, anterior chamber depth, and subfoveal choroidal thickness among the groups (all P<0.05). With the increase in AL, the incidence and severity of dry eye increased significantly (P<0.05). Moreover, the tear film break-up time (BUT) shortened (P<0.05), and the corneal fluorescein staining (CFS) points increased significantly (P<0.05). OSDI scores were positively correlated with AL and spherical equivalent (SE; both P<0.05); BUT was negatively correlated with AL, SE, and corneal astigmatism (AST; all P<0.05); Schirmer I test (SIT) results were negatively correlated with AL and SE (both P<0.05). CONCLUSION: AL elongation is a risk factor for dry eye onset in myopic participants. The longer the AL, the more severe the dry eye is, with the increased CFS spots and tear film instability. Additionally, SE and AST exhibit negative correlations with dry eye symptom scores and ocular surface parameters.     

军事训练伤致腕部尺骨撞击综合征的非手术治疗

目的探讨军事训练伤致尺骨撞击综合征的非手术治疗方法及效果。方法2001年12月—2005年12月,对因训练伤后确诊为腕部尺骨撞击综合征的43例患者给予腕部外固定、关节内注射、局部理疗及口服非甾体类抗炎药物治疗。结果非手术治疗后,19例(44.2%)患者腕部、手部症状出现显著改善,患者恢复伤前工作及训练;13例(30.2%)症状改善,但不能恢复原有工作及训练,仍有11例(25.6%)腕部症状无改善,总有效率为74.4%。结论对训练伤导致尺骨撞击综合征非手术治疗有效,早期诊断、早期治疗是保证疗效的关键。