基于“同病异治”原则治疗类风湿性关节炎中药的研究进展

类风湿性关节炎是一种常见的慢性自身免疫性复杂疾病, 病因尚不明确, 治疗困难, 国内常以传统中医药手段将其辨证分型, 遵循“同病异治”的原则对其进行治疗。中医药辨证治疗类风湿性关节炎历史悠久, 效果显著, 同时中药方剂多靶点、多成分的特点使其更有效的缓解各自适应证患者的炎症症状。近年来传统中医药与西医的关联日渐加深, 西医技术与手段在中药治疗 RA 上的广泛应用, 不仅使 RA 不同证型的差异更加清晰, 中医辨病更加准确, 更在针对类风湿性关节炎适应证的中药方剂在临床、药效、生物学与治疗机制方面的研究取得了较大进展。文章基于中医“同病异治” “辨证分型”的原则, 对治疗类风湿性关节炎代表方剂与其研究进展进行综述。     

基于数据挖掘的中医药治疗小儿湿疹组方用药规律研究

目的：通过应用中医传承辅助平台（V 2.5）挖掘中医药治疗小儿湿疹的组方用药规律,并对高频药物、用药模式及治疗思路进行探讨。方法：搜集国家知识基础设施数据库（CNKI）、中国学术期刊数据库（CSPD）及中文科技期刊数据库（CCD）中2000—2021年应用中医药治疗小儿湿疹的相关文献,经过筛选后建立方药数据库,运用中医传承辅助平台（V 2.5）集成的改进互信息法、关联规则Apriori算法、复杂系统熵聚类与无监督熵聚类等算法对药物频次、性味归经、用药模式、规则分析及新处方等结果进行输出,并进行网络可视化展示。结果：纳入处方200首,共涉及206味中药,高频药物包括甘草、白鲜皮、薏苡仁、茯苓、生地黄、金银花、蝉蜕、地肤子、防风、牡丹皮等,药性以寒性（52.76%）居多,药味以甘（38.89%）、苦（33.37%）、辛（21.96%）味为主,归经以胃经（1 138次）、脾经（1 088次）、肝经（1 061次）居多,并且得到药物之间的关联规则,以及新处方6个。结论：小儿湿疹用药以补虚药、利水渗湿药、清热药、清热解毒药、解表药为主,治疗以疏风清热,燥湿健脾,养血活血为主要大法,分析结果与本病诊疗指南较为吻合,可为小儿湿疹的临床治疗及新药开发提供参考。     

健脾祛湿方对脾虚湿盛型高脂血症大鼠血脂、胃肠功能、水液代谢的影响及作用机制

目的：观察健脾祛湿方对脾虚湿盛型高脂血症大鼠血脂、胃肠功能、水液代谢的影响及作用机制。方法：将56只SD大鼠随机分为空白组（n=8）和造模组（n=48）,采用“劳倦过度+饮食不节+高脂饲料喂养”复制脾虚湿盛型高脂血症大鼠模型。造模4周后,根据总胆固醇（TC）水平将造模组随机分成6组：即模型组,血脂康组,参苓白术颗粒组,健脾祛湿方低、中、高剂量组,每组8只。分组后开始给药,灌胃剂量为1 mL/100 g,空白组、模型组给予生理盐水,其余组给予相应的受试物,连续给药6周。测定血脂四项TC、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-Ch）和高密度脂蛋白胆固醇（HDL-Ch）,胃肠激素,即胃动素（MTL）、促胃液素（GAS）和血管活性肠肽（VIP）,水液调节激素醛固酮（ALD）、抗利尿激素（ADH）和心房利尿钠肽（ANP）,以及白蛋白（ALB）和总蛋白（TP）,采用苏木精-伊红（HE）染色法观察胃、结肠组织形态,免疫荧光法检测结肠水孔蛋白(AQP)3、胃AQP4的表达位置及水平,采用蛋白质印迹法（Western Blotting）检测结肠、胃组织中闭合蛋白（Occludin）的表达量。结果：与正常组比较,模型组大鼠血清TC、TG、LDL-Ch水平升高（P<0.001）,HDL-Ch水平降低（P<0.05）,血清MTL、GAS水平降低（P<0.001,P<0.01）,VIP升高（P<0.001）,ALD、ADH升高（P<0.05,P<0.001）,ANP水平显著降低（P<0.001）,TP、ALB水平降低（P<0.001,P<0.05）。结肠绒毛、胃黏膜出现大量脱落情况,结肠AQP3荧光强度降低,胃AQP4荧光表达增强,结肠、胃组织Occludin表达水平降低。与模型组比较,血脂康组、参苓白术颗粒组、健脾祛湿方低、中、高剂量组大鼠血清TC、TG、LDL-Ch水平呈下降趋势,HDL-C水平升高,MTL、GAS显著升高,VIP水平显著降低,ALD、ADH水平降低,ANP显著升高,结肠、胃组织形态结构有所改善。结肠AQP3荧光表达增强,胃AQP4荧光强度减弱,结肠、胃组织Occludin表达水平增强。结论：健脾祛湿方可降低脾虚湿盛型高脂血症大鼠血脂,有健脾祛湿之功,其作用机制可能是通过调节Occludin、AQP3、AQP4的表达,保护紧密连接结构的完整性达到促进胃肠消化吸收功能,改善水液代谢障碍的作用。     

Patient Satisfaction with AbobotulinumtoxinA for Aesthetic Use in the Upper Face: A Systematic Literature Review and Post-hoc Analysis of the APPEAL Study

BACKGROUND: AbobotulinumtoxinA (AboBoNT-A; Dysport^®; Ipsen, Boulogne-Billancourt, France/Azzalure^®; Galderma, Lausanne, Switzerland) is a botulinum neurotoxin type A approved for aesthetic use in the treatment of glabellar lines in adult patients under 65 years in Europe, the United States, and other countries. OBJECTIVE: We sought to analyze current literature on patient satisfaction with aboBoNT-A for upper facial aesthetic indications. METHODS: A systematic review of literature databases (PubMed/MEDLINE, Embase, the Cochrane Library, and Google Scholar) was performed to identify English-language publications reporting on patients with aesthetic indications (including glabellar lines and wrinkles) receiving aboBoNT-A, that assessed patient and/or physician satisfaction with treatment, with no restrictions on comparator studies. Structured data extraction was used to enable inter-study analysis. A post-hoc analysis was also performed to assess patient satisfaction by sex and age, using results from the noninterventional APPEAL study of patients’ satisfaction with aboBoNT-A for treating glabellar lines. RESULTS: Overall, 22 original research papers were identified. Patient satisfaction rates for aboBoNT-A treatment were significantly higher versus placebo from two weeks to between three and five months postinjection. At two to three weeks postinjection, patient satisfaction rates were 52% and 99% across studies. In studies with later time points, patient satisfaction rates were 85 to 87 percent at 5 months and between 25 and 100 percent at 6 months post-injection. Physician satisfaction was also high (97%–100%, across three treatments). No notable differences in patient satisfaction by sex or age were observed in the APPEAL study. CONCLUSION: High rates of patient satisfaction have been achieved with aboBoNT-A treatment for upper facial aesthetic indications. Despite the current recommended interval of ≥12 weeks, satisfaction with the aesthetic results of aboBoNT-A therapy is still evident up to 6 months post-injection in some patients.     

Factors affecting antibody responses to immunizations in infants born to women immunized against pertussis in pregnancy and unimmunized women: Individual-Participant Data Meta-analysis

BackgroundExploring factors that affect immune responses to immunizations in infants born to women immunized with tetanus-diphtheria-acellular-pertussis (Tdap) in pregnancy compared with unimmunized women is important in designing immunization programs.MethodsIndividual-participant data meta-analysis of 8 studies reporting post-immunization immunoglobulin G (IgG) levels to vaccine antigens in infants born to either women immunized with Tdap in pregnancy or unimmunized women, using mixed-effects models.ResultsIn infants of Tdap-immunized women, two-fold higher levels of anti-pertussis toxin (PT) and anti-diphtheria-toxoid (DT) IgG pre-primary immunization were associated with 9% and 10% lower post-primary immunization levels, (geometric mean ratio [GMR], PT: 0.91; 95% CI, 0.88–0.95,n = 494, DT: 0.9; 0.87–0.93,n = 519). Timing of immunization in pregnancy did not affect post-primary immunization anti-Bordetella pertussis, anti-tetanus-toxoid (TT) and anti-DT IgG levels. Spacing of infant immunization did not affect post-primary immunization anti-B. pertussis and anti-DT levels. In infants of Tdap-immunized women, two-fold higher levels of anti-PT and anti-filamentous haemagglutinin (FHA) IgG pre-primary immunization were associated with lower post-booster immunization levels, (GMR, PT: 0.91; 0.85–0.97,n = 224, FHA: 0.92; 0.85–0.99,n = 232). Timing of immunization in pregnancy did not affect post-booster immunization anti-Bordetella pertussis, anti-tetanus-toxoid (TT) and anti-DT IgG levels. Spacing of infant immunization did not affect post-booster immunization anti-PT, anti-pertactin (PRN), anti-TT and anti-DT IgG levels.In infants of unimmunized women, two-fold higher IgG levels of some vaccine antigens pre-primary immunization were associated with 8–17% lower post-primary immunization levels (GMR, PT 0.92, 95% CI:0.88–0.97, n = 373; FHA:0.88, 95% CI:0.85–0.92,n = 378; PRN:0.84, 95% CI:0.81–0.88, n = 367; TT:0.88, 95% CI:0.83–0.93, n = 241; DT: 0.83, 95% CI:0.79–0.87,n = 278). Two-fold higher levels of anti-FHA IgG pre-primary immunization were associated with 8% lower post-booster immunization levels (GMR, 0.92; 95% CI: 0.86–0.99,n = 138).DiscussionIncreased IgG levels pre-primary immunization is associated with reduced post-primary and post-booster immunization levels for some antigens in infants of women immunized or unimmunized in pregnancy, but their clinical significance is uncertain.     

揿针穴位埋针对社区H型高血压 痰湿壅盛证的临床疗效研究

摘 要：目的： 探讨揿针穴位埋针对社区 H型高血压痰湿壅盛证的临床疗效,为 H型高血压的治疗提供参考。方法： 将 80例H型高血压痰湿壅盛证患者按照随机单盲法分为对照组（n=40）和治疗组（n=40）。对照组给予含马来酸依那普利叶 酸片（依叶片）的降压方案进行治疗。治疗组在对照组基础上给予揿针穴位埋针法进行治疗,连续治疗 28天后进行临床疗 效比较。结果： 治疗后,治疗组患者Hcy水平、中医证候积分较对照组显著降低;且治疗组证候积分比对照组显著减少;治 疗组患者血脂水平较对照组显著改善。结论： 在依叶片降压方案治疗的基础上,给予揿针穴位埋针可显著改善 H型高血压 痰湿壅盛证患者的血压、Hcy和血脂水平,且安全性较高,对肝肾功能无影响。     

Functional coupling between heterologously expressed dopamine D(2) receptors and KCNQ channels

Activation of KCNQ potassium channels by stimulation of co-expressed dopamine D₂ receptors was studied electrophysiologically in Xenopus laevis oocytes and in mammalian cells. To address the specificity of the interaction between D₂-like receptors and KCNQ channels, combinations of KCNQ1–5 channels and D₂-like receptors (D_2L, D₃, and D₄) were investigated in Xenopus oocytes. Activation of either receptor with the selective D₂-like receptor agonist quinpirole (100 nM) stimulated all the KCNQ currents, independently of the subunit combination, indicating a common pathway of receptor-channel interaction. The KCNQ4 current was investigated in further detail and was increased by 19.9±1.6% (n=20) by D_2L receptor stimulation. The effect could be mimicked by injection of GTPS and prevented by injection of Bordetella pertussis toxin, indicating that channel stimulation was mediated via a G protein of the G_i/o subtype. Cells of the human neuroblastoma line SH-SY5Y were co-transfected transiently with KCNQ4 and D_2L receptors. Stimulation of D_2L receptors increased the KCNQ4 current (n=6) as determined in whole-cell patch-clamp recordings. The specificity of the dopaminergic activation of the KCNQ channels was confirmed by co-expression of other neuronal K⁺ channels (BK, K_V1.1, and K_V4.3) with the D_2L receptor in Xenopus oocytes. None of these K⁺ channels responded to stimulation of the D_2L receptor. In the mammalian brain, dopamine D₂ receptors and KCNQ channels co-localise postsynaptically in several brain regions, so modulation of neuronal excitability by dopamine release could in part be mediated via an effect on KCNQ channels.     

Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum

The organization of the thalamic projections to the ventral striatum in the rat was studied by placing injections of the retrograde tracer cholera toxin subunit B in the ventral striatum and small deposits of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in individual midline and intralaminar thalamic nuclei. In order to provide a complete map of the midline and intralaminar thalamostriatal projections, PHA-L injections were also made in those parts of the intralaminar nuclei that project to the dorsal striatum. The relationship of thalamic afferent fibres with the compartmental organization of the ventral striatum was assessed by combining PHA-L tracing and enkephalin immunohistochemistry. The various midline and intralaminar thalamic nuclei project to longitudinally oriented striatal sectors. The paraventricular thalamic nucleus sends most of its fibres to medial parts of the nucleus accumbens and the olfactory tubercle, whereas smaller contingents of fibres terminate in the lateral part of the nucleus accumbens and the most ventral, medial, and caudal parts of the caudate-putamen complex. The projections of the parataenial nucleus are directed towards central and ventral parts of the nucleus accumbens and intermediate mediolateral parts of the olfactory tubercle. The intermediodorsal nucleus projects to lateral parts of the nucleus accumbens and the olfactory tubercle and to ventral parts of the caudate-putamen. The projection of the rhomboid nucleus is restricted to the rostrolateral extreme of the striatum. A diffuse projection to the ventral striatum arises from neurons ventral and caudal to the nucleus reuniens rather than from cells inside the nucleus. Fibres from the central medial nucleus terminate centrally and dorsolaterally in the rostral part of the nucleus accumbens and medially in the caudate-putamen. Successively more lateral positions in the caudate-putamen are occupied by fibres from the paracentral and central lateral nuclei, respectively. The lateral part of the parafascicular nucleus projects to the most lateral part of the caudate-putamen, whereas projections from the medial part of this nucleus terminate in the medial part of the caudate-putamen and in the dorsolateral part of the nucleus accumbens. Furthermore, a rostral to caudal gradient in a midline or intralaminar nucleus corresponds to a dorsal to ventral and rostral to caudal gradient in the striatum. In the ventral striatum, thalamic afferent fibres in the "shell" region of the nucleus accumbens avoid areas of high cell density and weak enkephalin immunoreactivity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Killer toxin production in Pichia acaciae is associated with linear DNA plasmids

Summary We have identified a strain of the yeast Pichia acaciae which produces a killer toxin active against the yeast Debaryomyces tamarii. The killer phenotype was associated with the presence of two DNA plasmids, pPacl-1 (13.6 kilobase pairs) and pPacl-2 (7.3 kilobase pairs). P. acaciae strains, cured of these plasmids by irradiation with ultraviolet light, lacked killer activity and were sensitive to toxin produced by the parental strain. A partially cured strain, GS-1215, missing only the smaller plasmid, pPacl-2, also exhibited loss of both toxin activity and immunity. Exonuclease studies revealed that both plasmids were linear double-stranded DNA molecules with 5 protected ends. The P. acaciae system differs from that of the well-studied Kluyveromyces lactis killer system both in the range of susceptible strains and in the sizes of the plasmids involved. Our studies contradict previous reports that Pichia killer systems are invariably chromosomal.     

Recent advances in understanding the pathogenesis of the hemolytic uremic syndromes

One of the requirements for an agent to cause hemolytic uremic syndrome (HUS) is its ability to injure endothelial cells. Shiga-like toxin (SLT) can do this. SLT is produced byEscherichia coli andShigella dysenteriae serotype 1; both have been implicated as causes of typical HUS. Endothelial cells have receptors (GB₃) for SLT and the toxin can inhibit eukaryotic protein synthesis, thereby causing cell death. Glomerular endothelial cell injury or death results in a decreased glomerular filtration rate and many of the perturbations seen in HUS. It is no longer certain that hemolysis is the result of a microangiopathy. Cell injury results in release of von Willebrand multimers; if these are ultra-large, thrombosis may ensue. There is also increasing evidence that neutrophils have a role in the pathogenesis of typical HUS.Streptococcus pneumoniae can also cause HUS and care must be taken to avoid giving plasma to patients withS. pneumoniae-associated HUS. There is compelling evidence that types of HUS are inherited by autosomal recessive and autosomal dominant modes. Patients with autosomal recessive HUS may have recurrent episodes. Mortality and morbidity rates are high for the inherited forms.