四妙清瘟败毒饮治疗儿童热毒炽盛型传染性单核细胞增多症临床研究

目的:观察四妙清瘟败毒饮治疗儿童热毒炽盛型传染性单核细胞增多症的临床疗效。方法:选取热毒炽盛型传染性单核细胞增多症儿童患者116例,随机分为治疗组和对照组,每组58例。治疗组患者给予四妙清瘟败毒饮联合更昔洛韦进行治疗,对照组患者给予更昔洛韦进行治疗,治疗期间每天观察患儿体温、咽部症状、肝脾及淋巴结情况;每3 d复查1次血常规(含白细胞计数、异常淋巴细胞比率);每5 d复查1次肝功能、肝脾彩色超声及CD_4~+、CD_8~+、CD_4~+/CD_8~+T细胞亚群。结果:1治疗后治疗组患儿的白细胞计数、异型淋巴细胞比率、肝功能中谷丙转氨酶、外周血CD_4~+、CD_8~+、CD_4~+/CD_8~+T细胞亚群及平均住院时间均较对照组明显缩短时间,差异有统计学意义(P0.05或P0.01);2治疗组患儿体温恢复正常时间、咽峡炎痊愈时间、淋巴结缩小时间、肝脾回缩至正常时间及症状和体征总积分均较对照组患儿恢复时间短,且症状和总积分较治疗前明显下降,差异有统计学意义(P0.05或P0.01);3经治疗组患儿整体有效率明显高于对照组,差异有统计学意义(P0.01)。结论:四妙清瘟败毒饮联合更昔洛韦治疗儿童热毒炽盛型传染性单核细胞增多症能够明显改善患儿的临床症状和体征,缩短白细胞、异常淋巴细胞比率、肝脾肿大、CD_4~+、CD_8~+、CD_4~+/CD_8~+T细胞亚群等实验室异常指标的恢复时间,缩短患儿住院时间,减轻患儿及家庭的负担。     

基于“祛邪为第一要义”从清热化湿论治新型冠状病毒肺炎

结合验案分析,基于"祛邪为第一要义"探讨新型冠状病毒肺炎从清热化湿论治的思路与方法。认为新型冠状病毒肺炎主要是属于"湿热"性质的疫病,治疗应强调清热化湿,以"祛邪为第一要义",辅以扶正。在中医祛邪与扶正理论指导下,通过宣肺平喘、通腑泻热、芳香化湿等治法,祛邪为主,肺肠合治,可以使发热减轻或消退,使大便通畅,从而截断病情进展,避免或减少危重症的发生及死亡的风险;通过清热化湿、疏肝健脾、凉血化瘀等治法,祛邪兼以扶正,肺与肝、脾合调,可以改善肝功能损伤,减少病情加重的风险;通过补气健脾等扶正治法,可以改善患者的精神和体力,促使病毒更快转阴,缩短病程,促进患者早日康复。     

Synergism through combination of chemotherapy and oxidative stress-induced autophagy in A549 lung cancer cells using redox-responsive nanohybrids: A new strategy for cancer therapy

A combination of various therapeutic approaches has emerged as a promising strategy for cancer treatment. A safe and competent nano-delivery system is thus in urgent demand to facilitate the simultaneous transport of various therapeutic agents to cancer cells and a tumor region to achieve synergistic effect. Gold nanoparticles (GNPs) and mesoporous silica nanoparticle (MSNs) were fabricated herein as potential candidates for drug delivery. Serving as gatekeepers, GNPs (5 nm in diameter) were attached onto the amino-functionalized MSNs (denoted as NMSNs) via a relatively weak gold–nitrogen bonding. The resulting nanohybrids (denoted as GCMSNs) were uptaken by cells, and the detachment of GNPs and subsequent intracellular drug release from NMSNs were achieved by competitive binding of intracellular glutathione to GNPs. In addition to the function of gatekeeping, GNPs also play another role as the oxidative stress elicitor. Our in vitro studies revealed that GCMSNs induced higher oxidative stress in lung cancer cells (A549) than in normal cells (3T3-L1). This growth inhibitory effect found in the cancer cells was likely induced by mitochondria dysfunction originated from the GCMSN-induced, oxidative stress-triggered mitochondria-mediated autophagy. The redox-responsive nanohybrids were further loaded with camptothecin and the intensified synergistic therapeutic effects were observed associated with combined chemotherapy and oxidative stress strategy. The results clearly demonstrate that such unique nanohybrids hold great promise for selective and effective cancer treatments.     

Preparation and identification of multifunctional mesoporous silica nanoparticles for in vitro and in vivo dual-mode imaging,theranostics, and targeted tracking

Mesoporous silica nanoparticles (MSNs) can provide a structural foundation for a new generation of nanocarriers with a broad range of functionalities. Multifunctional MSNs can serve as all-in-one diagnostic and therapeutic tools that can be used to simultaneously visualize and treat various diseases, such as cancer. This research study is the first time that two lanthanide-based imaging systems have been combined to incorporate controlled drug release and targeted tracing into a single MSN-based nano-platform for a novel theranostic drug delivery system. Doping lanthanide ions, i.e., europium (Eu) and gadolinium (Gd) ions, into an MSN structure (EuGd-MSNs) imparts fluorescence and magnetism to the nanostructure that can be used to develop magnetic resonance imaging (MRI) and biological fluorescence tools. Current cancer research has revealed that most human cancer cells express a large number of folate receptors on their surface. Grafting folic acid (FA) onto the EuGd-MSN surface (EuGd-FA-MSNs) imparts a targeting function to the MSN because of the specificity of the binding of FA to cell surface receptors. Furthermore, grafting anticancer drugs, such as camptothecin (CPT), onto the surface of these MSNs by forming disulfide bonds (EuGd-SS-CPT-FA-MSNs) enables intracellular controlled drug release. A high concentration of intracellular glutathione cleaves the disulfide bond to release the drug and treat the disease. The results of in vitro and in vivo studies show that the functionalized MSNs can be successfully used as a platform to integrate dual-imaging, targeting, and therapeutic treatment in multifunctional diagnosis drug delivery systems.     

Distribution of temperature changes and neurovascular coupling in rat brain following 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) exposure

(+/?)3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) is an abused psychostimulant that produces strong monoaminergic stimulation and whole‐body hyperthermia. MDMA‐induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP‐3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA‐induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature‐sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethyl‐1,4,7,10‐tetraacetate (DOTMA^4?)). The MDMA‐induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA‐induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA‐induced warming across brain regions. MDMA‐induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as potential heat generation) may vary regionally, neuroprotection may require different cooling strategies. Copyright © 2015 John Wiley & Sons, Ltd.     

Systematic in vitro and in vivo study on porous silicon to improve the oral bioavailability of celecoxib

Mesoporous materials are promising candidates for improving dissolution rate of poorly water-soluble drugs in vitro and their bioavailability in vivo. In the present study, sixteen batches of celecoxib-loaded PSi particles with pore sizes ranging from 17 to 58 nm and celecoxib content from 5 to 36 w-% were prepared and a detailed physicochemical characterization of the drug was performed by several methods. Interaction between co-culture of Caco-2/HT29-MTX cells and unloaded PSi particles was tested in toxicity assays, and increased toxicity for particles with large pore size was observed. Dissolution rate of celecoxib was improved in vitro by lowering the drug loading degree which hindered the recrystallization of celecoxib on the external surface of the particles. The fastest permeation of loaded celecoxib through the co-culture monolayer as well as the highest bioavailability in rats was observed with the particles with small pore size and low loading degree. New insights were obtained on how various parameters of the mesoporous delivery system affect the state of the drug inside the pores and its release in vitro and in vivo.     

Development and validation of a quantitative competitive ELISA for potency testing of equine anti rabies sera with other potential use

In case of a bite by a rabies infected animal, the World Health Organisation recommends a prophylactic treatment including the administration of Human Rabies Immunoglobulins (HRIGs) or highly purified F(ab′)₂ fragments produced from Equine Rabies Immunoglobulin (F(ab′)₂ – ERIGs). According to international regulation, quality control of F(ab′)₂ – ERIGs lots requires potency testing by the in vivo Mouse Neutralisation Test (MNT) prior marketing. However, the strategy of the 3Rs (Reduce, Refine, Replace) for animal testing required by the European Directive encourages the replacement of the in vivo potency test by an in vitro assay. In this context, a competitive ELISA method (c-ELISA) has been developed by the Agence Nationale de Sécurité du Médicament et des Produits de Santé where F(ab′)₂ – ERIGs are in competition with a monoclonal antibody recognizing the trimeric native form of the rabies glycoprotein. After a full validation study, the c-ELISA has been applied to commercial batches of F(ab′)₂ – ERIGs. A correlation study with the MNT demonstrated a similarity between the two methods (r = 0.751). Moreover, the c-ELISA method which does not need any species specific reagent has been applied to HRIGs potency testing as an alternative method to Rapid Fluorescent Focus Inhibition Test (RFFIT), thus avoiding the handling of live rabies virus in BSL3 containment. In conclusion, the c-ELISA has shown its potential to replace MNT and possibly RFFIT for the quantification of rabies immunoglobulin. After optimisation it may be used for the quantification of rabies immunoglobulin in any animal species, notably for rabies immunogenicity assay in mice.     

Symptoms During or Shortly After Isolated Carpal Tunnel Release and Problems Within 24?hours After Surgery

This study used the National Survey of Ambulatory Surgery (NSAS) database to measure the incidence of and risk factors for symptoms in the ambulatory surgery center and problems within 24 h after isolated carpal tunnel release (CTR). The NSAS contained records on 400,000 adult patients with carpal tunnel syndrome who were treated with CTR in 2006, based on ICD-9 codes. The type of anesthesia used and factors associated with symptoms and problems were sought in bivariate and multivariable statistical analyses. The mean duration of the procedure was 16 ± 8.8 min. Only 5 % were performed under local anesthesia without sedation, 45 % with IV sedation, 28 % regional anesthesia, and 19 % general anesthesia. Symptoms in the ambulatory surgery center or a problem within 24 h after discharge were recorded in 10 % of patients, all of them minor and transient, including difficulties with pain and its treatment. The strongest risk factors were male sex, age of 45 years and older, and participation of an anesthesiologist. Local anesthesia and regional anesthesia were associated with more perioperative symptoms and postoperative problems. Most CTR are performed with some sedation in the United States. CTR is a safe procedure: one in 10 patients will experience a minor issue in the perioperative or immediate postoperative period.     

Risk factors for complications of open trigger finger release

BackgroundOpen trigger finger release is generally considered a simple low-risk procedure. Reported complication rates vary widely from 1 to 43 %, mostly based on small studies. Our goal was to determine the incidence of complications in a large consecutive series, while also identifying potential risk factors.MethodsAll open trigger finger releases performed from 2006 to 2009 by four fellowship-trained hand surgeons at a single institution were retrospectively reviewed. There were 795 digits released in 543 patients. Complications were defined as signs or symptoms requiring further treatment and/or considered unresolved by 1 month postoperatively. Complications requiring operative intervention were regarded as major. Multivariable analysis was performed to determine possible risk factors for complications.ResultsThere were 95 documented complications among 795 digits (12 %). The most common complications involved persistent pain, stiffness, or swelling, persistent or recurrent triggering, or superficial infection. Most were treated nonoperatively with observation, therapy, steroid injection, or oral antibiotics. There were 19 reoperations (2.4 %), mostly including revision release, tenosynovectomy, and irrigation and debridement. Male gender, sedation, and general anesthesia were independently associated with complications, while age, diabetes, hypothyroidism, recent injection, and concurrent procedures were not associated.ConclusionsOpen trigger finger release is generally a low-risk procedure, although there is potential for complications, some requiring reoperation. Male gender, sedation, and general anesthesia may be associated with greater risk. Surgeons should be careful to thoroughly discuss the risk of both major and minor complications when counseling patients.     

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.