[Expert consensus on Tongsaimai Tablets/Capsules in treatment of peripheral vascular diseases in clinical practice].

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.

Multidisciplinary approach to scheduling surgery for diabetic foot: a case report.

BACKGROUND: The treatment of diabetic foot ulcers in this case is complex and multidisciplinary, and an interdisciplinary team is extremely beneficial. CASE PRESENTATION: We performed the intervention on an old type 2 diabetes patient with poor health, whose left toes were severely necrotic. Surgery, including debridement and patella truncation, had positive effects on lower extremity circulation, infection control, cavity treatment, bone destruction, surgical debridement, recovery of foot function, and nursing. After 5 months, the patient's foot ulcer had healed, and walking function was preserved. CONCLUSIONS: Scheduling interventional surgery and debridement are the key point in a complicated diabetic foot ulcers case, and multidisciplinary collaboration in treatment of diabetic foot is significantly important.

Synchronous transitions of up and down states in a network model based on stimulations.

The phenomenon of spontaneous periodic up and down transitions is considered to be a significant characteristic of slow oscillations. Our previous theoretical studies have shown that the single neuron and network model can both exhibit spontaneous up and down transitions. Another characteristic of up and down dynamics is the synchronicity. So in this paper, we focused on the synchronized characteristic of up and down transitions in the network based on stimulations. Spontaneous activities showed no synchronous transitions between neurons. However, the external stimulation, mainly the stimulation frequency and the number of neurons stimulated on were related to the synchronous transitions of up and down states. The simulation results suggested that simultaneous high frequency excitation or firing of neurons in the network was responsible for the generation of synchronous transitions of up and down states. Through the observation and analysis of the findings, we have tried to explain the reason for synchronous up and down transitions and to lay the foundation for further work on the role of these synchronized transitions in cortex activity.

Neural Energy Supply-Consumption Properties Based on Hodgkin-Huxley Model.

Electrical activity is the foundation of the neural system. Coding theories that describe neural electrical activity by the roles of action potential timing or frequency have been thoroughly studied. However, an alternative method to study coding questions is the energy method, which is more global and economical. In this study, we clearly defined and calculated neural energy supply and consumption based on the Hodgkin-Huxley model, during firing action potentials and subthreshold activities using ion-counting and power-integral model. Furthermore, we analyzed energy properties of each ion channel and found that, under the two circumstances, power synchronization of ion channels and energy utilization ratio have significant differences. This is particularly true of the energy utilization ratio, which can rise to above 100% during subthreshold activity, revealing an overdraft property of energy use. These findings demonstrate the distinct status of the energy properties during neuronal firings and subthreshold activities. Meanwhile, after introducing a synapse energy model, this research can be generalized to energy calculation of a neural network. This is potentially important for understanding the relationship between dynamical network activities and cognitive behaviors.

The Haoqin-Huaban formula alleviates UVB-induced skin damage through HOXA11-AS-mediated stabilization of EZH2.

Exposure of skin to ultraviolet B (UVB) irradiation induces oxidative damage, immune suppression, inflammation, and skin cancer. Recently, an increase in the use of traditional Chinese medicine decoction with antioxidant properties has emerged as protection for skin tissues against UVB-induced damage. The aim of this study was to investigate mechanisms of the protective effect of the Haoqin-Huaban formula (HQHB) on UVB-induced skin damage. First, cell survival, apoptosis, and oxidative stress were evaluated upon UVB irradiation in the presence of HQHB using HaCaT cells and mice as model systems. Subsequently, bioinformatic analyses, RNA pulldown assays, RNA immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation were conducted to verify the regulation among HQHB, hypoxia-inducible factor 1α (HIF-1α), HOXA11-AS and enhancer of zeste homolog 2 (EZH2) in HaCaT cells. In this study, we found that administration of HQHB inhibited, in a dose-dependent manner, UVB-induced skin damage by eliminating oxidative stress. HQHB was found to upregulate HOXA11-AS expression by activating HIF-1α. Furthermore, HOXA11-AS stabilized the EZH2 protein by inhibiting its ubiquitination and proteasomal degradation. Consequently, rescue assays demonstrated that HOXA11-AS promoted proliferation and inhibited apoptosis in HaCaT cells by reducing oxidative stress. Taken together, our results help to elucidate the function and regulatory mechanism of HQHB in reducing UVB-induced skin damage.

Serum Intestinal Metabolites are Raised in Patients with Psoriasis and Metabolic Syndrome.

Purpose: Psoriasis is an immune-mediated chronic inflammatory disease. Metabolic syndrome (MetS) is characterized by central obesity, hypertension, dyslipidemia, diabetes and insulin resistance (IR). Increasing evidence indicates that psoriasis is associated with MetS. This study aimed to explore some metabolite indexes which could evaluate the severity or predict the risk of psoriasis patients associated with MetS. Patients and methods: It was a case-control study conducted in Beijing Hospital of Traditional Chinese Medicine. Sixty healthy volunteers (HC), 100 patients with psoriasis (Ps), 100 patients with MetS (MetS) and 80 patients with both psoriasis and MetS (Ps+MetS) were entered between January 2016 and December 2018. Blood samples were taken after at least 12 hours fasting and the contents of trimethylamine N-oxide (TMAO), carnitine, choline and betaine in serum were measured by Liquid Chromatography Mass Spectrometry (LC-MS/MS). Besides, the serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol (CHO), triglyceride (TG), blood glucose (BG), creatinine (Cr), urea nitrogen (BUN), uric acid (UA) were determined. Results: The non-healthy groups had different degrees of dyslipidemia, Ps-MetS> Ps >MetS. Compared with HC, the Ps had a higher level of TG; The MetS had the lowest level of HDL; The Ps+Mets had the highest level of TG and CHO. The Ps and Ps+MetS both had high level of UA, but there was no difference between the two groups. As for intestinal metabolites, the Ps had significant differences in TMAO, carnitine, and betaine in comparison with HC. The MetS had the highest level of TMAO. There was positive correlation between PASI and TMAO and betaine. Conclusions: TMAO and betaine could serve as indexes reflecting the severity of psoriasis. TG, CHO, LDL and UA could serve as risk factors of MetS in psoriatic patients.

Dopamine-Mediated Major Depressive Disorder in the Neural Circuit of Ventral Tegmental Area-Nucleus Accumbens-Medial Prefrontal Cortex: From Biological Evidence to Computational Models.

Major depressive disorder (MDD) is a serious psychiatric disorder, with an increasing incidence in recent years. The abnormal dopaminergic pathways of the midbrain cortical and limbic system are the key pathological regions of MDD, particularly the ventral tegmental area- nucleus accumbens- medial prefrontal cortex (VTA-NAc-mPFC) neural circuit. MDD usually occurs with the dysfunction of dopaminergic neurons in VTA, which decreases the dopamine concentration and metabolic rate in NAc/mPFC brain regions. However, it has not been fully explained how abnormal dopamine concentration levels affect this neural circuit dynamically through the modulations of ion channels and synaptic activities. We used Hodgkin-Huxley and dynamical receptor binding model to establish this network, which can quantitatively explain neural activity patterns observed in MDD with different dopamine concentrations by changing the kinetics of some ion channels. The simulation replicated some important pathological patterns of MDD at the level of neurons and circuits with low dopamine concentration, such as the decreased action potential frequency in pyramidal neurons of mPFC with significantly reduced burst firing frequency. The calculation results also revealed that NaP and KS channels of mPFC pyramidal neurons played key roles in the functional regulation of this neural circuit. In addition, we analyzed the synaptic currents and local field potentials to explain the mechanism of MDD from the perspective of dysfunction of excitation-inhibition balance, especially the disinhibition effect in the network. The significance of this article is that we built the first computational model to illuminate the effect of dopamine concentrations for the NAc-mPFC-VTA circuit between MDD and normal groups, which can be used to quantitatively explain the results of existing physiological experiments, predict the results for unperformed experiments and screen possible drug targets.

Modeling the grid cell activity on non-horizontal surfaces based on oscillatory interference modulated by gravity.

Internal representation of the space is a fundamental and crucial function of the animal's brain. Grid cells in the medial entorhinal cortex are thought to provide an environment-invariant metric system for the navigation of the animal. Most experimental and theoretical studies have focused on the horizontal planar codes of grid cell, while how this metric coordinate system is configured in the actual three-dimensional space remains unclear. Evidence has implied the spatial cognition may not be fully volumetric. We proposed an oscillatory interference model with a novel gravity and body plane modulation to simulate grid cell activity in complex space for rodents. The animal can perceive the rotation of its body plane along the local surface by sensing the gravity, causing the modulation to the dendritic oscillations. The results not only reproduce the firing patterns of the grid cell recorded from known experiments, but also predict the grid codes in novel environments. It further demonstrates that the gravity signal is indispensable for the animal's navigation, and supports the hypothesis that the periodic firing of the grid cell is intrinsically not a volumetric code in three-dimensional space. This will provide new insights to understand the spatial representation of the actual world in the brain.

Energy features in spontaneous up and down oscillations.

Spontaneous brain activities consume most of the brain's energy. So if we want to understand how the brain operates, we must take into account these spontaneous activities. Up and down transitions of membrane potentials are considered to be one of significant spontaneous activities. This kind of oscillation always shows bistable and bimodal distribution of membrane potentials. Our previous theoretical studies on up and down oscillations mainly looked at the ion channel dynamics. In this paper, we focus on energy feature of spontaneous up and down transitions based on a network model and its simulation. The simulated results indicate that the energy is a robust index and distinguishable of excitatory and inhibitory neurons. Meanwhile, one the whole, energy consumption of neurons shows bistable feature and bimodal distribution as well as the membrane potential, which turns out that the indicator of energy consumption encodes up and down states in this spontaneous activity. In detail, energy consumption mainly occurs during up states temporally, and mostly concentrates inside neurons rather than synapses spatially. The stimulation related energy is small, indicating that energy consumption is not driven by external stimulus, but internal spontaneous activity. This point of view is also consistent with brain imaging results. Through the observation and analysis of the findings, we prove the validity of the model again, and we can further explore the energy mechanism of more spontaneous activities.

"Efficacy and safety of Liangxue Jiedu decoction for the treatment of progressive psoriasis vulgaris: a multicenter, randomized, controlled study".

OBJECTIVE: To determine the clinical efficacy and safety of Liangxue Jiedu decoction (LJD) for the treatment of progressive psoriasis vulgaris and to provide the basis for the development of a standardized treatment protocol for psoriasis vulgaris. METHODS: In this multicenter, randomized, controlled study, patients with blood-heat type psoriasis were randomly assigned to receive either Chinese herbal medicine (LJD; treatment group) or Western Medicine (cetirizine hydrochloride, vitamin C, and vitamin B complex; control group). Psoriasis Area and Severity Index (PASI) scores were calculated in addition to the number of patients who achieved ≥ 50% or ≥ 75% improvement in PASI score from baseline. The change in symptoms of Chinese medicine (color of rash, burning sensation, itchiness, severity of irritation, and anger) was evaluated and safety was assessed as adverse events and laboratory analysis. t test, independent sample non-parametric test and χ2 test were used to analyze the results. RESULTS: A total of 238 participants were included in the study [treatment group, n = 122 (PP analysis 117); control group, n = 116 (PP analysis 104)]. LJD treatment was associated with a significant improvement in skin lesions and symptoms compared with Western Medicine treatment. At the end of the 8-week treatment period, 23.77% (PP analysis 24.79%) of patients in the treatment group had achieved PASI75 and 57.38% (PP analysis 58.97%) had achieved PASI50; the corresponding figures in the control group were 9.48% (9.62%) and 25.00% (25.00%), respectively. The between-group differences were statistically significant (P < 0.05). CONCLUSION: Treatment of psoriasis vulgaris of the blood-heat type using LJD was associated with significantly better outcomes compared with those achieved using standard Western Medicine.

The place cell activity is information-efficient constrained by energy.

Spatial representation is a crucial function of animal's brain. However, there is still no uniform explanation of how the spatial code is formed in different dimensional spaces to date. The main reason why place cell exhibits unique activity pattern is that the animal needs to retrieve and process spatial information. In this paper, we constructed a constrained optimization model based on information theory to explain the place field formation across species in different dimensional spaces. We proposed the following question that, using only limited amount of neural energy, how to organize the spiking locations (place field) in the available environment to obtain the most efficient spatial information representation? We solved this conditional functional extremum problem by variational techniques. The results showed that on the condition of limited neural energy, the place field will comply with a Gaussian-form distribution automatically to convey the largest amount information per spike. We also found that the animal's natural habitat property and locomotion experience statistics affected the symmetry of spatial representation in different dimensions. These findings not only reconcile the argument of whether the spatial codes of place cell are isotropic, but also provide an explanation of place field formation by an information-theoretic approach. Furtherly, this research revealed the energy economical and information efficient properties underlie the spatial representation system of the brain.

A cortical model with multi-layers to study visual attentional modulation of neurons at the synaptic level.

Visual attention is a selective process of visual information and improves perceptual performance by modulating activities of neurons in the visual system. It has been reported that attention increased firing rates of neurons, reduced their response variability and improved reliability of coding relevant stimuli. Recent neurophysiological studies demonstrated that attention also enhanced the synaptic efficacy between neurons mediated through NMDA and AMPA receptors. Majority of computational models of attention usually are based on firing rates, which cannot explain attentional modulations observed at the synaptic level. To understand mechanisms of attentional modulations at the synaptic level, we proposed a neural network consisting of three layers, corresponding to three different brain regions. Each layer has excitatory and inhibitory neurons. Each neuron was modeled by the Hodgkin-Huxley model. The connections between neurons were through excitatory AMPA and NMDA receptors, as well as inhibitory GABAA receptors. Since the binding process of neurotransmitters with receptors is stochastic in the synapse, it is hypothesized that attention could reduce the variation of the stochastic binding process and increase the fraction of bound receptors in the model. We investigated how attention modulated neurons' responses at the synaptic level on the basis of this hypothesis. Simulated results demonstrated that attention increased firing rates of neurons and reduced their response variability. The attention-induced effects were stronger in higher regions compared to those in lower regions, and stronger for inhibitory neurons than for excitatory neurons. In addition, AMPA receptor antagonist (CNQX) impaired attention-induced modulations on neurons' responses, while NMDA receptor antagonist (APV) did not. These results suggest that attention may modulate neuronal activity at the synaptic level.

Lower Limb Nonhealing Ulcers Associated With Chronic Diabetes: A Case Series.

INTRODUCTION: Chronic, nonhealing skin ulcers of the lower limbs associated with diabetes pose a clinical challenge as their treatment requires more sophisticated and delicate approaches than in patients without diabetes. OBJECTIVE: Herein, the authors demonstrate and discuss the implementation of their use of topical traditional Chinese medicines in several sample cases of lower limb nonhealing ulcers in patients with diabetes. MATERIALS AND METHODS: A series of diabetic ulcer cases were treated with various approaches. First, the approach employed with each patient was determined based on ulcer location, depth, inflammatory extent, and local circulation. Next, an exploratory incision was performed to evaluate eschar condition. Finally, the therapy applied was modified depending on specific case characteristics. RESULTS: The primary therapeutic approaches employed were: (1) selective partial ablation, including fenestration and encroachment; (2) debridement, which avoids secondary injury when local circulation is good; and (3) the turning-over method, in which necrotic tissue is cleaned down to the basal layer via application of a topical Chinese medicine that reduces inflammation and promotes chronic ulcer healing. CONCLUSIONS: These therapeutic approaches alleviated local inflammatory damage and adverse systemic reactions, which is an important basis for further treatment (eg, anti-infection treatment, blood glucose reduction, blood pressure control, organ function improvement, circulation promotion, and nutritional support).

Effect of Traditional Chinese Medicine plus narrow-band medium-wave ultraviolet B radiation on moderate-to-severe psoriasis vulgaris in a case series.

OBJECTIVE: To investigate the efficacy and safety of Traditional Chinese Medicine (TCM) therapy combined with ultraviolet B light therapy in the treatment of moderate-to-severe psoriasis. METHODS: Patients with moderate-to-severe psoriasis (skin lesion area > 10% of the body surface area) for 2 consecutive years were treated with TCM (oral and external use of herbal medicines, acupuncture, and herbal bathing) and narrow-band medium-wave ultraviolet B light treatment for 12 weeks. The treatment effect was evaluated based on the Psoriasis Area Severity Index (PASI), the achievement of a 50% reduction in the PASI (PASI50), the achievement of a 75% reduction in the PASI (PASI75), pruritus score, Dermatology Life Quality Index, and safety. RESULTS: A total of 95 outpatients were enrolled, and 92 subjects (96.8%) completed the 12-week treatment course. At baseline, the average proportion of the body surface area covered by skin lesions was 12.4%, and the average PASI was 17.7. All patients had previously been treated with conventional medicine (89.1% of patients received ultraviolet light treatment, 50.0% received glucocorticoids, and 21.7% received acitretin). After the 12-week treatment course, 22 patients (23.9%) achieved PASI75, and 43 (46.7%) achieved PASI50. The post-treatment pruritus score and Dermatology Life Quality Index of all treated patients were significantly lower than the respective baseline values (P < 0.0001). No adverse effects were detected by the monitoring of blood, urine, stools, liver and kidney function, and echocardiography. CONCLUSION: Comprehensive therapy comprising TCM therapy combined with ultraviolet B light therapy achieved good outcomes for patients with moderate-to-severe psoriasis.

Intrinsic sodium currents and excitatory synaptic transmission influence spontaneous firing in up and down activities.

Periodic up and down transitions of membrane potentials are considered to be a significant spontaneous activity. These kinds of oscillations always accompany with some spontaneous firing in up state. Our previous theoretical studies mainly looked at the subthreshold up and down transitions and characteristics of up and down dynamics. In this paper, we focus on suprathreshold spontaneous firing of up and down transitions based on improved network model and its stimulations. The simulated results indicate that fast sodium current is critical to the generation of spontaneous neural firing. While persistent sodium current plays a part in spontaneous fluctuation. Both intrinsic fast and persistent sodium dynamics influence spontaneous firing rate and synchronous activity in up and down behavior. Meanwhile, blocking excitatory synaptic transmission decreases neural firing and reveals spontaneous firing. These simulated results are basically in accordance with experimental results. Through the observation and analysis of the findings, we prove the validity of the model so we can further adopt this model to study other properties and characteristics of the network, laying the foundation for further work on cortex activity.

An Energy Model of Place Cell Network in Three Dimensional Space.

Place cells are important elements in the spatial representation system of the brain. A considerable amount of experimental data and classical models are achieved in this area. However, an important question has not been addressed, which is how the three dimensional space is represented by the place cells. This question is preliminarily surveyed by energy coding method in this research. Energy coding method argues that neural information can be expressed by neural energy and it is convenient to model and compute for neural systems due to the global and linearly addable properties of neural energy. Nevertheless, the models of functional neural networks based on energy coding method have not been established. In this work, we construct a place cell network model to represent three dimensional space on an energy level. Then we define the place field and place field center and test the locating performance in three dimensional space. The results imply that the model successfully simulates the basic properties of place cells. The individual place cell obtains unique spatial selectivity. The place fields in three dimensional space vary in size and energy consumption. Furthermore, the locating error is limited to a certain level and the simulated place field agrees to the experimental results. In conclusion, this is an effective model to represent three dimensional space by energy method. The research verifies the energy efficiency principle of the brain during the neural coding for three dimensional spatial information. It is the first step to complete the three dimensional spatial representing system of the brain, and helps us further understand how the energy efficiency principle directs the locating, navigating, and path planning function of the brain.

Changes in Bacterial Profiles and Antibiotic Sensitivity Before and After Wound Bed Preparation for Diabetic Foot Ulcers.

We aimed to investigate the characteristics of bacterial profiles and antibiotic sensitivity in diabetic foot ulcers before and after wound bed preparation. This study involved 423 diabetic patients with Wagner grades 1 to 4 foot ulcers. Secretion culture was performed before wound bed preparation. The observation endpoint was when the wound showed a tendency toward healing and a specialist determined that stopping antibiotic treatment would not affect wound healing. A second secretion culture was performed after the observation endpoint. We obtained results from both secretion cultures from 411 patients. The proportion of multi-drug-resistant (MDR) gram-positive bacteria was 22.0% and 47.8% before and after treatment, respectively; that for gram-negative bacteria was 3.5% and 19.2%, respectively (P < .05). Pretreatment antibiotic sensitivity of staphylococci and other gram-positive bacteria was 48.7% and 44.8%, respectively; the rates decreased significantly after treatment to 36.8% (P = .031) and 34.8% (P = .027), respectively. Pretreatment antibiotic sensitivity of common and nonfermenting rare gram-negative bacteria was 55.4% and 54.6%, respectively, which decreased substantially after treatment to 33.2% (P = .002) and 32.9% (P = .003), respectively. Wound healing was achieved in 92.7% of patients. Pretreatment and posttreatment C-reactive protein levels were 124.759 ± 71.58 mg/dL and 82.8 ± 53.61 mg/dL, respectively (P < .05). In conclusion, following wound bed preparation for diabetic foot ulcers, MDR bacteria numbers were increased and antibiotic sensitivity was decreased; inflammation was decreased. These findings warrant future studies for confirmation.

Neurodynamics of up and down transitions in a single neuron.

Recent experimental studies have revealed that up and down transitions exist in membrane potential of neurons. This paper focuses on the neurodynamical research of these transitions in a single neuron since it is the basic to study the transitions in the neural network for further work. The results show there exists two stable levels in the neuron called up and down states. And transitions between these two states are bidirectional or unidirectional with the values of parameters changing. We also study the periodic spontaneous activity of the transitions between up and down states without any inputting stimulus which coheres with the experimental results.

Roles of the co-culture of human umbilical cord Wharton's jelly-derived mesenchymal stem cells with rat pancreatic cells in the treatment of rats with diabetes mellitus.

The aim of the present study was to investigate the roles of the co-culture of human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hUC-MSCs) with rat pancreatic cells in the treatment of rats with diabetes mellitus. hUC-MSCs were isolated and passaged, followed by Transwell co-culture with rat pancreatic cells. The induced islet-like cell clusters were transplanted into the renal capsule in rats with streptozotocin (STZ)-induced diabetes mellitus. The effects of co-culture on blood glucose levels in rats were observed. The isolated hUC-MSCs expressed the specific surface markers, including cluster of differentiation 44 (CD44) (91.4%), CD29 (91.3%) and CD105 (99.2%). Following co-culture with hUC-MSCs for 7 and 10 days, the rat pancreatic cells were strongly stained by pancreatic and duodenal homeobox-1 and human insulin. The insulin and C-peptide concentrations were increased significantly compared to the pure culture group. One week following the transplantation of induced islet-like cells into the renal capsule, the blood glucose level of rats in the STZ experimental group was significantly lower than that of the STZ control group. There were notable 5-bromo-2'-deoxyuridine-positive nuclei and insulin-positive cytoplasm in the renal capsule following cell transplantation. Therefore, co-culture of hUC-MSCs with rat pancreatic cells can lower the blood glucose levels in rats with diabetes mellitus.