Opinion paper: Stimulation of complement amplification or activation of the alternative pathway of complement?

In this opinion paper, we suggest that the scheme of the complement system should be redrawn in order to better illustrate its potencies. This can be achieved by putting the amplification loop of the alternative complement pathway at the center of the complement system. This arrangement emphasizes that C3b molecules, generated by any pathway, can stimulate complement amplification. Furthermore, it allows one to differentiate between this type of stimulation of amplification and that driven by those immune complexes that capture dimeric C3b molecules, which are more potent C3 convertase precursors than C3b. Schemes similar to the one drawn may help to better illustrate the interplay of the pathways and convey a clearer comprehension of the mechanics of the complement system.     

依托六级电子病历建设医院高警示药品闭环管理

目的：依托六级电子病历建设,提升我院高警示药品管理水平。方法：依据电子病历要求,将涉及高警示药品的每个重要医疗活动节点进行链式记录,纳入闭环管理。结果：通过医院六级电子病历信息化改造,将高警示药品纳入闭环管理,提高了医院对病人完整医疗信息的获取和处理能力,大大减少了用药差错,将高警示药品潜在的、可能导致严重后果的用药差错消灭在萌芽状态;缩短了各流程的时间,使病人及时、准确、安全用药;促进药师参与临床,提升临床药学服务水平。结论：我院高警示药品管理工作由原来的经验管理向科学管理发展,即从传统的末端、事后管理转向过程管理,最终实现从粗放式管理转向精细化管理,真正做到医疗质量的事前管理和实时监控,有效地规范了医护人员的行为,有利于提高医疗效率、保障医疗安全。     

Evaluation of use of essential fatty acids in topical ophthalmic preparations for dry eye

PurposeEssential fatty acids (EFAs) as dietary supplements are used in treating dry-eye for reducing inflammation at the ocular surface. Their topical application in eye drops to deliver fatty acid (FA) directly to the ocular surface requires thorough investigation. Being lipids in nature EFAs can interact with tear lipids and affect tear stability. This study aimed at investigating the biophysical interactions of EFAs with Meibomian lipids.MethodsRheology of mixtures of Human Meibomian lipids with EFAs (LA-linoleic acid, ALA-alpha-linolenic acid), OA (oleic acid), and GLA (gamma-linolenic acid) was studied using Langmuir trough technology on an artificial tear solution at the ocular surface temperature. Pressure-area profiles were used to determine compressibility and elasticity of the mixed films.ResultsLA enhanced spreading of Meibomian lipids and increased their compressibility and elasticity which can be beneficial for tear stability. ALA condensed Meibomian lipids film with less elasticity deemed unfavourable for tear stability. OA expanded Meibomian lipids but decreased elasticity at high compressions making films less stable. GLA had little or no favourable effect on tear stability. Higher concentrations of FAs made films less stable.ConclusionsEFAs or OA in topical ophthalmic preparations can affect spread and stability of the tear film lipid layer. Rheology of mixed films should be tested using Langmuir trough technology to determine suitable type and amount of a lipid additive for therapeutic eye drops. In topical applications, the omega-6 LA (not omega-3 FA) at low concentrations (20 mol%) can be beneficial for enhancing tear stability in dry eye patients.     

Loop diuretics are open-channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics

BACKGROUND AND PURPOSE

Loop diuretics are widely used to inhibit the Na⁺, K⁺, 2Cl⁻ co-transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel. Here, we investigated the mechanism of CFTR inhibition by loop diuretics and explored the effects of chemical structure on channel blockade.

EXPERIMENTAL APPROACH

Using the patch-clamp technique, we tested the effects of bumetanide, furosemide, piretanide and xipamide on recombinant wild-type human CFTR.

KEY RESULTS

When added to the intracellular solution, loop diuretics inhibited CFTR Cl⁻ currents with potency approaching that of glibenclamide, a widely used CFTR blocker with some structural similarity to loop diuretics. To begin to study the kinetics of channel blockade, we examined the time dependence of macroscopic current inhibition following a hyperpolarizing voltage step. Like glibenclamide, piretanide blockade of CFTR was time and voltage dependent. By contrast, furosemide blockade was voltage dependent, but time independent. Consistent with these data, furosemide blocked individual CFTR Cl⁻ channels with ‘very fast’ speed and drug-induced blocking events overlapped brief channel closures, whereas piretanide inhibited individual channels with ‘intermediate’ speed and drug-induced blocking events were distinct from channel closures.

CONCLUSIONS AND IMPLICATIONS

Structure–activity analysis of the loop diuretics suggests that the phenoxy group present in bumetanide and piretanide, but absent in furosemide and xipamide, might account for the different kinetics of channel block by locking loop diuretics within the intracellular vestibule of the CFTR pore. We conclude that loop diuretics are open-channel blockers of CFTR with distinct kinetics, affected by molecular dimensions and lipophilicity.     

围术期整体护理在宫颈上皮内瘤样病变行高频电波刀环切术后的应用效果

目的：探讨宫颈上皮内瘤样病变高频电波刀环形电切术治疗的围术期护理效果。方法选取2011年6月～2013年6月需于本院进行高频电波刀环形电切术治疗的宫颈上皮内瘤样病变患者110例,按数字随机法将患者分为观察组和对照组,每组55例。患者均进行常规高频电波刀环形电切术治疗。对照组采取常规护理,观察组采取围术期整体护理。比较两组的治疗效果、平均住院时间、并发症发生情况以及患者满意度。结果观察组治愈率为96.36%,高于对照组的83.64%,差异有统计学意义（P〈0.05）。与对照组比较,观察组平均住院时间缩短,总并发症发生率降低,患者满意度提高,差异有统计学意义（P〈0.05）。结论围术期整体护理有利于患者的治疗,可缩短患者的住院时间,减少各类并发症的发生并提高患者的满意度,值得临床推广应用。     

Assessment of bronchial obstruction and its reversibility by shape indexes of the flow‐volume loop in asthmatic children

Asthma assessment by spirometry is challenging in children as forced expiratory volume in 1 s (FEV1) is frequently normal at baseline. Bronchodilator (BD) reversibility testing may reinforce asthma diagnosis but FEV1 sensitivity in children is controversial. Ventilation inhomogeneity, an early sign of airway obstruction, is described by the upward concavity of the descending limb of the forced expiratory flow‐volume loop (FVL), not detected by FEV1. The aim was to test the sensitivity and specificity of FVL shape indexes as β‐angle and forced expiratory flow at 50% of the forced vital capacity (FEF50)/peak expiratory flow (PEF) ratio, to identify asthmatics from healthy children in comparison to “usual” spirometric parameters. Seventy‐two school‐aged asthmatic children and 29 controls were prospectively included. Children performed forced spirometry at baseline and after BD inhalation. Parameters were expressed at baseline as z‐scores and BD reversibility as percentage of change reported to baseline value (Δ%). Receiver operating characteristic curves were generated and sensitivity and specificity at respective thresholds reported. Asthmatics presented significantly smaller zβ‐angle, zFEF50/PEF and zFEV1 (p ≤ .04) and higher BD reversibility, significant for Δ%FEF50/PEF (p = .02) with no difference for Δ%FEV1. zβ‐angle and zFEF50/PEF exhibited better sensitivity (0.58, respectively 0.60) than zFEV1 (0.50), and similar specificity (0.72). Δ%β‐angle showed higher sensitivity compared to Δ%FEV1 (0.72 vs. 0.42), but low specificity (0.52 vs. 0.86). Quantitative and qualitative assessment of FVL by adding shape indexes to spirometry interpretation may improve the ability to detect an airway obstruction, FEV1 reflecting more proximal while shape indexes peripheral bronchial obstruction.     

宫颈环形电圈切除术治疗宫颈上皮内瘤变的临床效果观察

目的：探讨宫颈环形电圈切除术（LEEP术）治疗宫颈上皮内瘤变（CIN）的临床效果。方法选取2009年6月~2014年6月本院收治的CINⅡ、Ⅲ期患者100例,其中,44例行子宫颈冷刀锥切术（CKC组）,56例行宫颈LEEP术（LEEP组）,观察两组的手术、术后恢复情况,术后并发症、病变复发情况。结果两组患者均顺利完成手术,术中切割宫颈组织时患者有下腹胀痛和阴道局部发热感,患者多可耐受;LEEP组的术中出血量明显少于CKC组（P<0.05）、阴道排液时间与宫颈创面修复时间较CKC组明显缩短（P<0.05）。两组的手术时间、住院时间比较,差异无统计学意义（P>0.05）;LEEP组的脱痂期出血及感染发生率明显低于CKC组（P<0.05）,两组的子宫颈狭窄发生率、复发率比较,差异无统计学意义（P>0.05）;观察组的术后并发症发生率低于CKC组（P<0.05）。结论 LEEP术治疗CIN能够缩短手术时间,减少术中出血量,降低术中缝合止血率,并发症少,受术者易于接受。     

胆肠Roux-en-Y吻合术联合留置皮下空肠盲袢取石治疗肝内胆管结石患者疗效研究*

目的 探讨采用胆肠Roux-en-Y吻合术联合留置皮下空肠盲袢治疗肝内胆管结石(IHS)患者的临床疗效。方法 2018年9月～2021年6月我院诊治的71例IHS患者,其中33例(对照组)接受常规胆肠Roux-en-Y吻合术,另38例(观察组)接受胆肠Roux-en-Y吻合术联合留置皮下空肠盲袢取石治疗。采用ELISA法检测血清C反应蛋白(CRP)和白细胞介素-6(IL-6),使用全自动荧光免疫定量分析仪检测血清降钙素原(PCT)。结果 在术后1个月,观察组临床有效率为94.7%,显著高于对照组的75.8%(P<0.05);观察组血清GGT和ALT水平分别为(71.9±6.2)U/L和(38.7±5.9)U/L,显著低于对照组【分别为(95.8±6.9)U/L和(62.6±6.8)U/L,P<0.05】;观察组血清CRP和IL-6水平分别为(60.8±8.1)mg/L和(89.8±20.1)pg/mL,显著高于对照组【分别为(38.3±9.2)mg/L和(65.7±23.5)pg/mL,P<0.05】;观察组结石残留发生率为7.9%,显著低于对照组的21.2%(P<0.05)。结论 采用胆肠Roux-en-Y吻合术联合留置皮下空肠盲袢取石治疗HIS患者临床疗效较好,可提高结石清除率,防止术后返流性感染,同时也为复发结石、胆管狭窄或梗阻等提供了一条方便的进入肝内胆管的永久性胆道通路,是较为实用的治疗IHS的手术方法。     

Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis

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