中药配方颗粒临床应用国际专家共识

中药配方颗粒以中医药理论为指导,结合现代制剂新技术,选定最佳工艺,经现代化的制药技术提取、浓缩、干燥、制粒,精制而成。中药配方颗粒稳定、安全、便捷、有效。中药配方颗粒产业链相较于中药饮片可以实现从田间到车间的全程化、过程化控制,在药材来源、饮片炮制、加工工艺、质量检测、产品的销售流通等环节实现标准化管理。中药配方颗粒可部分替代中成药。目前中药配方颗粒仅涵盖常用的800余种中药,因此对许多临床并不常用的中药品种,中药配方颗粒并不能取代饮片。临床研究与动物实验中大量使用配方颗粒,从而使得科研人员不再对中药饮片进行提取与质量控制。应尽快从提高生产工艺、建立质量标准、完善监管制度、拓展临床应用等方面解决困扰配方颗粒发展所面临的问题。

Intermittent tri-weekly docetaxel plus bicalutamide in patients with castration-resistant prostate cancer： a single-arm prospective study using a historical control for comparison

Whether continuous docetaxel （DTX） chemotherapy offers an advantage over intermittent therapy for castration-resistant prostate cancer （CRPC） is unknown. In this study, we evaluated the efficacy, toxicity and quality of life （QoL） of intermittent tri-weekly DTX with bicalutamide in CRPC. Forty-two patients （group A） with CRPC were enrolled. The patients received intravenous DTX （75 mg m^-2） once tri-weekly with oral bicalutamide （50 mg） once daily. Patients had a DTX holiday when the prostate-specific antigen （PSA） level declined ≥ 50%. DTX was restarted in patients with a PSA increase ≥ 25%. Sixty patients （group B） who had matching characteristics and had continuously received DTX without bicalutamide for 10-12 cycles were also enrolled. There were no statistically significant differences in progression-free survival （8 months vs. 9 months, P=0.866） or overall survival （19 months vs. 21 months, P=0.753） between groups A and B; however, the proportions of patients in group A with all grades of neutropenia （33% vs. 58%, P=0.013） and nausea/vomiting （11% vs. 29%, P=0.024） were significantly less compared to group B. A significant improvement in the global health and fatigue scores was recorded for group A post-chemotherapy compared to pre-chemotherapy （P〈0.05）. The fatigue, nausea/ vomiting and appetite loss scores in group B were increased post-chemotherapy compared to pre-chemotherapy （P〈0.05）. In conclusion, intermittent tri-weekly DTX plus bicalutamide is well tolerated and has the potential to achieve comparable disease control with an improvement in QoL for oatients with CRPC.

Multi-energy synergistic optimization in steelmaking process based on energy hub concept

The production process of iron and steel is accompanied by a large amount of energy production and consumption. Optimal scheduling and utilization of these energies within energy systems are crucial to realize a reduction in the cost, energy use, and CO_2 emissions.However, it is difficult to model and schedule energy usage within steel works because different types of energy and devices are involved. The energy hub(EH), as a universal modeling frame, is widely used in multi-energy systems to improve its efficiency, flexibility, and reliability.This paper proposed an efficient multi-layer model based on the EH concept, which is designed to systematically model the energy system and schedule energy within steelworks to meet the energy demand. Besides, to simulate the actual working conditions of the energy devices, the method of fitting the curve is used to describe the efficiency of the energy devices. Moreover, to evaluate the applicability of the proposed model, a case study is conducted to minimize both the economic operation cost and CO_2 emissions. The optimal results demonstrated that the model is suitable for energy systems within steel works. Further, the economic operation cost decreased by 3.41%, and CO_2 emissions decreased by approximately 3.67%.

International expert consensus on clinical application of traditional Chinese medicine formula granules

Guided by the theory of traditional Chinese medicine(TCM),TCM formula granules are made through the optimal process of extraction,concentration,drying,and granulation by combining modern new preparation technologies and pharmaceutical technologies.TCM formula granules are stable,safe,convenient,and effective.Compared with TCM decoction pieces,TCM formula granules can achieve the full process control of its industry chain from field to workshop and standardize the management of the origin of medicinal materials,processing of decoction pieces,processing technology,quality inspection,sales,and products distribution.TCM formula granules can partially replace Chinese patent medicines.Only available for around 800 common varieties of TCM,TCM formula granules cannot replace decoction pieces for many types which are not commonly used in clinical practice.A large number of formula granules are used in clinical and animal studies so that investigators no longer need to extract and control the quality of TCM decoction pieces.How to improve the production process,establish the quality standard,perfect the regulatory system,and expand the clinical application are the problems we need to solve as soon as possible for the better development of formula granules.

Design, Fabrication, and Modeling of CMOS-Compatible Double Photodiode

A double photodiode (PD) constructed by p+/N-well junction and N-well/p-sub junction was designed and fabricated in a UMC 0.18-μm CMOS process. Based on the device structure and mechanism of double PD, a novel small-signal equivalent circuit model considering the carrier transit effect and the parasitic RC time constant was presented. By this model with complete electronic components, the double PD can be incorporated in a commercial circuit simulator. The component values were extracted by fitting the measured S-parameters using simulated annealing algorithm, and a good agreement between the measurement and the simulation results was achieved. © 2017, Tianjin University and Springer-Verlag Berlin Heidelberg.

Analysis of feasibility of application of Beishu point acupressure therapy in treating gastroesophageal reflux disease via AMPK / ULK1 mediated autophagy pathway based on "adjusting central axis via pivot" theory

Gastroesophageal reflux disease(GERD)is a digestive system disease characterized by uncomfortable symptoms caused by reflux of gastric contents.It has increased sharply with the development of my country’s society and economy.If there is no reasonable and effective Prevention and treatment measures will inevitably increase the financial burden of patients,and also pose a major threat to the quality of life and health of patients.Cell signal transduction mediated by various receptors participates in the regulation mechanism of the body's various levels of biological functions.By inhibiting or activating its functions,the purpose of curing diseases can be achieved,and cell signal transduction has been used in traditional Chinese medicine.Studying.The theory of"adjusting the central axis"was explored by Professor Xie Sheng through decades of clinical experience.It has been proven in practice to treat GERD.It starts from the model of TCM viscera and expounds that the pathogenesis of GERD involves multiple viscera.Multi-system and multi-factor,explain the correlation of the disease with a variety of zang-fu syndromes,and use this as a basis to guide the clinical use of hidden prescriptions.The back-shu pointer therapy can prevent GERD by correcting the unbalanced state of the viscera and qi machine,and promoting the junction of the two channels of Ren and Du.Based on the theory of"adjusting the hub by the pivot",this article expounds the pathogenesis of GERD from the perspective of traditional Chinese medicine.By consulting the literature and combining with the previous research,it proposes to analyze the methods and methods of Backshu pointer therapy to prevent and treat GERD from the AMPK/ULK1 mediated autophagy pathway.

Effects of Qishi Shengjiang Guiyuan Granules on Inflammatory Response and T Lymphocyte Subsets in Peripheral Blood of Rats with GERD-Associated Idiopathic Pulmonary Fibrosis

[Objectives] To explore the effects of Qishi Shengjiang Guiyuan Granules on inflammatory response and T lymphocyte subsets in peripheral blood of rats with idiopathic pulmonary fibrosis (IFP) associated with gastroesophageal reflux disease (GERD).[Methods] Twenty-four SPF SD rats were randomly divided into control group, model group, Chinese medicine group and western medicine group, with 6 rats in each group. Except the control group, the other three groups were used to establish the rat model of GERD combined with IPF by injecting hydrochloric acid into the lower end of esophagus and inhaling diluted bleomycin (5 mg/kg). Rats in the Chinese medicine group (14 g/kg), rats in the western medicine group (4.17 g/kg), rats in the control group and the model group were given the same volume of saline by gavage for 14 d. Morphological and pathological changes of esophageal and lung tissues were observed under light microscope, and T lymphocyte subsets (CD + 3, CD + 4, CD + 8) and the ratio of CD + 4/CD + 8 in peripheral blood were detected by flow cytometry.[Results] Compared with the control group, the pulmonary tissue of the model group showed that the pulmonary interstitium was obviously thickened, the alveoli were mutually fused, the structure was obviously destroyed, the original alveolar structure was disappeared, the inflammatory cell infiltration was around the pulmonary capillaries and the alveolar space, and the basal cell hyperplasia and inflammatory cell infiltration were at the lower end of the esophagus. Compared with the model group, the degree of inflammatory cell infiltration and lung tissue damage in the Chinese medicine group and the western medicine group was significantly reduced, the inflammatory infiltration in the lower esophagus was significantly reduced, and the cell proliferation was reduced. Compared with the control group, the CD + 3, CD + 4, CD + 8, CD + 4/CD + 8 in the peripheral blood of the rats in the model group, the Chinese medicine group and the western medicine group decreased ( P <0.01). Compared with the model group, CD + 3, CD + 4, and CD + 4/CD + 8 increased ( P >0.05, P >0.05, P <0.01), CD + 8 decreased ( P >0.05). Compared with the Chinese medicine group, CD + 3, CD + 4, and CD + 4/CD + 8 increased ( P >0.05, P >0.05, P <0.01) and CD + 8 decreased ( P >0.05) in the western medicine group.[Conclusions] Qishi Shengjiang Guiyuan Granules can effectively improve the inflammation of the lower esophagus and lung tissues of the pulmonary fibrosis rats with GERD and IFP, and regulate the number of T lymphocyte subsets CD + 3, CD + 4, CD + 8 cells and CD + 4/CD + 8 ratio in peripheral blood.

Asymmetry in circulation system and cardiovascular diseases

Asymmetries in the human vascular system and cardiovascular disease are widespread.Vascular physiological asymmetry can manifest in the morphological structure and blood flow state,whereas pathological asymmetry can reflect differences in the occurrence and cure of bilateral vascular diseases.The causes associated with these asymmetrical differences may be demand-driven or due to vascular grading or asymmetries in other physiological systems.This article aims to review the asymmetry of several typical arteries,including cerebral,cervical,and limb arteries,and lists possible causes to emphasize the necessity of considering asymmetric factors in the prevention,treatment,and rehabilitation of vascular diseases.Future research on asymmetries in the vascular system may improve the risk assessment and personalized treatment of vascular diseases.

Altered Wnt Signaling Pathway in Cognitive Impairment Caused by Chronic Intermittent Hypoxia： Focus on Glycogen Synthase Kinase-3β and β-catenin

Background： Cognitive impairment is a severe complication caused by obstructive sleep apnea （OSA）. The mechanisms of causation are still unclear. The Wntβ-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wntβ-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia （CIH）, the most characteristic pathophysiological component of OSA. Methods： We divided 32 4-week-old male C57/BL mice into four groups of eight each： a CIH ＋ normal saline （NS） group, CIH ＋ LiCI group, sham CIH ＋ NS group, and a sham CIH ＋ LiCI group. The spatial learning performance of each group was assessed by using the Morris water maze （MWM）. Protein expressions of glycogen synthase kinase-β （GSK-β） and β-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region. Results： Mice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-313 activity increased, and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCI decreased the activity of GSK-β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH. Conclusions： Wntβ-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCI might attenuate CIH-induced cognitive impairment via Wntβ-catenin signaling pathway.

Spiro-conjugated indenodiarylethenes: enabling steric-induced electronic tuning of photochromic and photoluminescent properties by spiro-conjugation

Light-operated excited-state photochemical reactions and the resulting photochromic materials have gained significant attention for their promising technological applications in molecular electronic and photonic devices.To obtain photochromic materials(e.g.,diarylethenes)with desired properties,the way to tune energy processes of the excited state is essentially important,from both fundamental and practical viewpoints.The modified diarylethenes mostly focused on structural improvements to achieve efficient photochromism.We report here two new spiro-conjugated indenodiarylethenes(named,SFI-Th and SFI-Sul)with an orthogonally arranged spiroπ-scaffold.The spiro fluorene sterically constrains the free volume of photoactive side aromatic rings,while the spiro-conjugation points toward modulation of the decaying channels of excited-state energy,thus allowing for tuning photochromic performances.These spirodiarylethenes SFI-Th and SFI-Sul are readily accessible with low cost and show distinct photochromic and photoluminescent properties.On one hand,the SFI-Th bearing bisthienyl side rings,is an excellent photochromic switch showing high thermal stability and high fatigue resistance in both solution and amorphous state,likely benefited from steric-induced excited-state energy transfer into reversible photochemical reactions,owing to higherπ-orbital spiro-conjugation between the two molecular halves.On the other hand,the SFI-Sul with bissulfonyl side rings,most notably,displays quantitative photocyclization to yield SFI-Sulc upon excitation.However,the ring-closed SFI-Sulc has an extremely slow photocycloreversion,and meanwhile immediately switches on emissive state with a strong fluorescence(Φf=0.57 in amorphous powder state).We study the modulated roles of spiroπ-scaffold in both cases computationally and experimentally,and attribute the facilitated photochemical reaction to the positively electronic effects of spiro-conjugation,and the photo-responsive radiative transition to the negatively electronic effects of spiro-conjugation,respectively.In all,this work demonstrates that the spiro-conjugation is a new and efficient strategy to deliver excitation energy transfer(EET)for featured photochromic properties,due to its advantage in steric-induced electronic modulation.

Spiro-fused bicyclo[3,2,2]octatriene-cored triptycene:synthesis,molecular packing,and functional aggregates

Aggregate science has led to the existence of functional properties at the aggregate level that significantly differs from those of corresponding single-molecule species,leading to a number of novel conceptual materials with state-dependent functionality.For developing such materials,new molecular scaffolds that allow modulating the structural and functional properties of aggregates in a controlled manner could be extremely helpful.In this study,we report a class of spiro-fused bicyclo[3,2,2]octatriene triptycene derivatives with a unique 3 D molecular scaffolding structure that displays aggregation-induced emission(AIE)activity with bright solid-state blue luminescence.The core scaffold features a Y-shaped bicyclo[3,2,2]octatriene backbone and a vertical crossover arrangement of adjacent spiro-conjugated rings.Unlike classic bicyclo[2,2,2]octatrienes with high rigidity,this stereoscopic bicyclo[3,2,2]octatriene containing a seven-membered ring allows retaining certain flexibility in the molecular scaffold,which results in a weak fluorescence in dilute solutions(Φ_(F)<10%).However,the corresponding molecular aggregates emit intense fluorescence(Φ_(F)=50%-75%)and show prominent AIE activity because of the restriction of intramolecular scaffold motions.Moreover,in principle,these stereoscopic scaffold constructions with partially restricted flexibility facilitate the assembly of multiple different crystalline packing structures in both porous and nonporous forms depending on the growth conditions of crystalline aggregates.The obtained crystals with regular voids(12.85×6.89Aeach)show reversible luminescence in response to the adsorption/desorption of iodine vapor.These materials based on an unusual 3 D scaffold exhibit a high degree of structural modulation at the aggregate level and demonstrate potential applications in chemical sensing and flexible optoelectronics,which may open up the exploration of highly stereoscopic molecular building blocks for developing functional aggregates.

Bipolar phototransistor in a vertical Au/graphene/MoS2 van der Waals heterojunction with photocurrent enhancement

Bipolar phototransistors have higher optical responsivity than photodiodes and play an important role in the field of photoelectric conversion.Two-dimensional materials offer a good optical responsivity and have the potential advantages of heterogeneous integration,but mass-production is difficult.In this study,a bipolar phototransistor is presented based on a vertical Au/graphene/MoS2 van der Waals heterojunction that can be mass-produced with a silicon semiconductor process using a simple photolithography process.Au is used as the emitter,which is a functional material used not just for the electrodes,MoS2 is used for the collector,and graphene in used for the base of the bipolar phototransistor.In the bipolar phototransistor,the electric field of the dipole formed by the Au and graphene contact is in the same direction as the external electric field and thus enhances the photocurrent,and a maximum photocurrent gain of 18 is demonstrated.A mechanism for enhancing the photocurrent of the graphene/MoS2 photodiode by contacting Au with graphene is also described.Additionally,the maximum responsivity is calculated to be 16,458 A/W,and the generation speed of the photocurrent is 1.48×10^-4A/s.

Comparative study on hemodynamic environments around patient-specific carotid atherosclerotic plaques with different symmetrical features

Atherosclerotic plaque near the carotid sinus is a key risk factor for ischemic stroke.Although disturbed hemodynamic environments around atherosclerotic plaque had been investigated in many studies,the effect of their symmetrical features,especially longitudinal asymmetrical characteristics,had not been comparatively studied.In this study,three-dimensional carotid bifurcation models were established based on CT images of three patients with 50%stenosis and with different symmetrical features of carotid atherosclerotic plaques including concentric plaque,eccentric plaque,or eccentric longitudinal asymmetrical plaque.A healthy subject was chosen as the control.Wall shear stress(WSS)and oscillating shear index in the regions of upstream,downstream,downstream shoulders and regions around the point of maximum stenosis were analyzed.The results indicated that the maximum WSS around the eccentric longitudinal asymmetrical plaque were 8.6 times larger than that of the eccentric plaque and 1.9 times larger than that of the concentric plaque.And the distributions of WSS and OSI around the eccentric longitudinal asymmetric plaque were more disordered than those of the others.Our results highlighted the risk of the eccentric longitudinal asymmetrical plaque on plaque development and rupture and might provide a new index for evaluating the development of atherosclerosis.

Fluorogenic detection of mercury ion in aqueous environment using hydrogel-based AIE sensing films

A“turn-on”fluorescent sensing strategy was developed for ultrasensitive detection of heavy metal mercury ion(Hg2+)directly in water.It utilized an aqueous soluble aggregation-induced emission(AIE)-active probe,named 1,1,2,2-tetrakis(4-(1Htetrazol-5-yl)phenyl)ethene(TPE-4TA),composing of a luminescent tetraphenylene core and multiple anionic tetrazolate spawns.The probe retained dark when molecularly dissolved in water.However,mercury ions can ligate with multiple tetrazolate groups to form infinite coordination polymer particles spontaneously,thus inducing a fluorogenic AIE response for in situ analysis.Moreover,by embedding this AIE sensing molecules in a hydrophilic polyvinyl alcohol substrate,the resulting hydrogel film allowed in situ detection of Hg^(2+)on a laser-induced fluorescence analysis setup in aqueous environment.This strategy worked effectively in common aqueous environments with pH from 4 to 7.5 and showed high sensitivity(limit of detection down to 0.38 ppb/1.9 nM),good selectivity and a wide linearity range for quantification.This work may lead to a reliable and promising platform for on-site environmental water analysis.

A novel lambda negative-resistance transistor in the 0.5 μm standard CMOS process

A novel negative-resistance transistor (NRT) with a Lambda shaped I-V characteristic is demonstrated in the 0.5 μm standard CMOS process. To save on the number of component devices, this device does not use standard device models provided by CMOS processes, but changes a MOSFET and a BJT into a single device by fabricating them in the same n-well, with a p-type base layer as the MOSFET's substrate. The NRT has a low valley current of -6.82 nA and a very high peak-to-valley current ratio of 3591. The peak current of the device is -24.49 μA which is low enough to reduce the power consumption of the deivce, and the average value of its negative resistance is about 32 kΩ. Unlike most negative-resistance devices which have been fabricated on compound semiconductor substrates in recent years, this novel NRT is based on a silicon substrate, compatible with mainstream CMOS technology. Our NRT dramatically reduces the number of devices, minimizing the area of the chip, has a low power consumption and thus a further reduction in cost.

Clinical characteristics of hypersensitivity pneumonitis:non-fibrotic and fibrotic subtypes

Background:The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis(HP)guidelines.The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis(NFHP)and fibrotic hypersensitivity pneumonitis(FHP)and explore factors associated with the presence of fibrosis.Methods:In this prospective cohort study,patients diagnosed with HP through a multidisciplinary discussion were enrolled.Collected data included demographic and clinical characteristics,laboratory findings,and radiologic and histopathological features.Logistic regression analyses were performed to explore factors related to the presence of fibrosis.Results:A total of 202 patients with HP were enrolled,including 87(43.1%)NFHP patients and 115(56.9%)FHP patients.Patients with FHP were older and more frequently presented with dyspnea,crackles,and digital clubbing than patients with NFHP.Serum levels of carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 153,gastrin-releasing peptide precursor,squamous cell carcinoma antigen,and antigen cytokeratin 21-1,and count of bronchoalveolar lavage(BAL)eosinophils were higher in the FHP group than in the NFHP group.BAL lymphocytosis was present in both groups,but less pronounced in the FHP group.Multivariable regression analyses revealed that older age,<20%of lymphocyte in BAL,and≥1.75%of eosinophil in BAL were risk factors for the development of FHP.Twelve patients developed adverse outcomes,with a median survival time of 12.5 months,all of whom had FHP.Conclusions:Older age,<20%of lymphocyte in BAL,and≥1.75%of eosinophil in BAL were risk factors associated with the development of FHP.Prognosis of patients with NFHP was better than that of patients with FHP.These results may provide insights into the mechanisms of fibrosis in HP.

Stable Quadruple Helical Tetraradicaloid with Thermally Induced Intramolecular Magnetic Switching

We report an air-stable tetraradicaloid based on a rarely explored perylenequinonoid(PQ)core,namely,tetrabenzo-annulated tetracyclopenta[b,e,k,n]perylene(TBCP),which has a quadruple helical structure.As validated by X-ray crystallographic analysis and theoretical calculations,the nonplanar TBCP possesses unique hybrid resonance structures of two open-shell singlet diradicaloids.Remarkably,magnetic measurements reveal that TBCP in powder form shows unusual magnetic hysteresis upon heating followed by cooling,corresponding to interconversion of structure isomers with different magnetic properties.Such electronic properties can be rationalized as the response of structural changes to external thermal stimuli,accompanied by a subtle balance of two types of intramolecular magnetic interactions between four-site spin centers.The results provide a novel organic polyradicaloid as an unprecedented example of a functional material with the potential for intramolecular magnetic switching.