Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

[Temperature-Dependent Photoluminescence Property Studies of SiN(x) Films with nc-Si].

Silicon nitride (SiN(x)) films containing nanocrystalline silicon (nc-Si) were deposited on crystalline silicon substrate by facing-target sputtering technique. Thermal annealing process was performed at 450 degrees C for 50 min in a conventional furnace under FG(10% H2, 90% N2) ambient. The photoluminescece (PL) properties of the SiN(x) films with nc-Si were investigated by steady/transient PL spectra measurements by Fluorescence spectrometer with different temperatures. The PL processes could be attributed to the quantum confinement effect of nc-Si and the defects in the film. The PL peak position exhibits a small blue shift with the increasing of the excitation energy, which indicates that the PL portion of the nc-Si increased with smaller size. In addition, the PL lifetime increases and the PL intensity exhibits exponential increase as a result of the decreased temperature which supressed the nonradiative recombination process and then improved the radiative recombination. The PL lifetime of the film significantly reduces with the decreasing of the detection wavelength, which indicates that the PL process related to the the quantum confinement effect strongly depends on temperature.

Sinomenine ameliorates fibroblast-like synoviocytes dysfunction by promoting phosphorylation and nuclear translocation of CRMP2.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and arthritic pain. Sinomenine (SIN), derived from the rhizome of Chinese medical herb Qing Teng (scientific name: Sinomenium acutum (Thunb.) Rehd. Et Wils), has a longstanding use in Chinese traditional medicine for treating rheumatoid arthritis. It has been shown to possess anti-inflammatory, analgesic, and immunosuppressive effects with minimal side-effects clinically. However, the mechanisms governing its effects in treatment of joint pathology, especially on fibroblast-like synoviocytes (FLSs) dysfunction, and arthritic pain remains unclear. AIM: This study aimed to investigate the effect and underlying mechanism of SIN on arthritic joint inflammation and joint FLSs dysfunctions. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) was induced in rats and the therapeutic effects of SIN on joint pathology were evaluated histopathologically. Next, we conducted a series of experiments using LPS-induced FLSs, which were divided into five groups (Naïve, LPS, SIN 10, 20, 50 µg/ml). The expression of inflammatory factors was measured by qPCR and ELISA. The invasive ability of cells was detected by modified Transwell assay and qPCR. Transwell migration and cell scratch assays were used to assess the migration ability of cells. The distribution and content of relevant proteins were observed by immunofluorescence and laser confocal microscopy, as well as Western Blot and qPCR. FLSs were transfected with plasmids (CRMP2 T514A/D) to directly modulate the post-translational modification of CRMP2 protein and downstream effects on FLSs function was monitored. RESULTS: SIN alleviated joint inflammation in rats with CIA, as evidenced by improvement of synovial hyperplasia, inflammatory cell infiltration and cartilage damage, as well as inhibition of pro-inflammatory cytokines release from FLSs induced by LPS. In vitro studies revealed a concentration-dependent suppression of SIN on the invasion and migration of FLSs induced by LPS. In addition, SIN downregulated the expression of cellular CRMP2 that was induced by LPS in FLSs, but increased its phosphorylation at residue T514. Moreover, regulation of pCRMP2 T514 by plasmids transfection (CRMP2 T514A/D) significantly influenced the migration and invasion of FLSs. Finally, SIN promoted nuclear translocation of pCRMP2 T514 in FLSs. CONCLUSIONS: SIN may exert its anti-inflammatory and analgesic effects by modulating CRMP2 T514 phosphorylation and its nuclear translocation of FLSs, inhibiting pro-inflammatory cytokine release, and suppressing abnormal invasion and migration. Phosphorylation of CRMP2 at the T514 site in FLSs may present a new therapeutic target for treating inflammatory joint's destruction and arthritic pain in RA.

Sinomenine regulates immune cell subsets: Potential neuro-immune intervene for precise treatment of chronic pain.

Chronic pain is a disease of long-lasting pain with unpleasant feelings mediated by central and (or) peripheral sensitization, its duration usually lasts more than 3 months or longer than the expected recovery time. The patients with chronic pain are manifested with enhanced sensitivity to noxious and non-noxious stimuli. Due to an incomplete understanding of the mechanisms, patients are commonly insensitive to the treatment of first line analgesic medicine in clinic. Thus, the exploration of non-opioid-dependent analgesia are needed. Recent studies have shown that "sinomenine," the main active ingredient in the natural plant "sinomenium acutum (Thunb.) Rehd. Et Wils," has a powerful inhibitory effect on chronic pain, but its underlying mechanism still needs to be further elucidated. A growing number of studies have shown that various immune cells such as T cells, B cells, macrophages, astrocytes and microglia, accompanied with the relative inflammatory factors and neuropeptides, are involved in the pathogenesis of chronic pain. Notably, the interaction of the immune system and sensory neurons is essential for the development of central and (or) peripheral sensitization, as well as the progression and maintenance of chronic pain. Based on the effects of sinomenine on immune cells and their subsets, this review mainly focused on describing the potential analgesic effects of sinomenine, with rationality of regulating the neuroimmune interaction.

An Apriori Algorithm-Based Association Analysis of Analgesic Drugs in Chinese Medicine Prescriptions Recorded From Patients With Rheumatoid Arthritis Pain.

Chronic pain, a common symptom of people with rheumatoid arthritis, usually behaves as persistent polyarthralgia pain and causes serious damage to patients' physical and mental health. Opioid analgesics can lead to a series of side effects like drug tolerance and addiction. Thus, seeking an alternative therapy and screening out the corresponding analgesic drugs is the key to solving the current dilemma. Traditional Chinese Medicine (TCM) therapy has been recognized internationally for its unique guiding theory and definite curative effect. In this study, we used the Apriori Algorithm to screen out potential analgesics from 311 cases that were treated with compounded medication prescription and collected from "Second Affiliated Hospital of Zhejiang Chinese Medical University" in Hangzhou, China. Data on 18 kinds of clinical symptoms and 16 kinds of Chinese herbs were extracted based on this data mining. We also found 17 association rules and screened out four potential analgesic drugs-"Jinyinhua," "Wugong," "Yiyiren," and "Qingfengteng," which were promised to help in the clinical treatment. Besides, combined with System Cluster Analysis, we provided several different herbal combinations for clinical references.

Potential Neuroimmune Interaction in Chronic Pain: A Review on Immune Cells in Peripheral and Central Sensitization.

Chronic pain is a long-standing unpleasant sensory and emotional feeling that has a tremendous impact on the physiological functions of the body, manifesting itself as a dysfunction of the nervous system, which can occur with peripheral and central sensitization. Many recent studies have shown that a variety of common immune cells in the immune system are involved in chronic pain by acting on the peripheral or central nervous system, especially in the autoimmune diseases. This article reviews the mechanisms of regulation of the sensory nervous system by neutrophils, macrophages, mast cells, B cells, T cells, and central glial cells. In addition, we discuss in more detail the influence of each immune cell on the initiation, maintenance, and resolution of chronic pain. Neutrophils, macrophages, and mast cells as intrinsic immune cells can induce the transition from acute to chronic pain and its maintenance; B cells and T cells as adaptive immune cells are mainly involved in the initiation of chronic pain, and T cells also contribute to the resolution of it; the role of glial cells in the nervous system can be extended to the beginning and end of chronic pain. This article aims to promote the understanding of the neuroimmune mechanisms of chronic pain, and to provide new therapeutic ideas and strategies for the control of chronic pain at the immune cellular level.

Neuronal CRMP2 phosphorylation inhibition by the flavonoid, naringenin, contributes to the reversal of spinal sensitization and arthritic pain improvement.

BACKGROUND: Rheumatoid arthritis patients usually suffer from arthritic chronic pain. However, due to an incomplete understanding of the mechanisms underlying autoimmune disorders, the management of arthritic pain is unsatisfactory. Here, we investigated the analgesic effect and underlying mechanism of the natural flavonoid naringenin (NAR) in collagen-induced arthritis (CIA) pain. METHODS: NAR was injected (i.p.) once per day for 42 days after initial immunization, and rats were sacrificed on the 28th (the 21st day after final immunization, PID 21) and 42nd days (PID 35). The inflammatory factors, central sensitization indicators, and CRMP2 phosphorylation, as well as the anti-rheumatoid activity and analgesic effect of NAR, were further investigated. RESULTS: We found that NAR decreased the arthritis score and paw swelling, as well as the mechanical and thermal pain. The immunofluorescence results also showed a dose dependent effect of NAR on reducing the expressions of spinal cFos, IBA-1, and GFAP on the 28th (PID 21) and 42nd day (PID 35). NAR decreased the phosphorylation of CRMP2 S522 and the expression of the kinase CDK5 in the spinal dorsal horn, but pCRMP2 Y479 was unchanged. In addition, CRMP2 was co-localized with NEUN, but not IBA-1 or GFAP, indicating the involvement of neural CRMP2 phosphorylation in CIA-related pain. Finally, CRMP2 S522 phosphorylation selective inhibitor (S)-lacosamide also alleviated arthritic pain. CONCLUSIONS: Taken together, our results demonstrate that NAR alleviates inflammation and chronic pain in CIA model, which might be related to its inhibition of neuronal CRMP2 S522 phosphorylation, potentially mitigating the central sensitization. Our study provide evidence for the potential use of NAR as non-opioid-dependent analgesia in arthritic pain.

[Study on the transient and steady state property of fluorescence of free radical photoinitiator].

The fluorescence characteristic of various free radical photoinitiators was investigated by fluorescence spectroscopy. The influence of conjugated structure on fluorescence spectrum was analyzed from the molecular structure. The results show that: the wave length of fluorescence excitation spectrum gradually augments with the conjugative effect enhancement, and so does the peak of fluorescence emission spectrum. The transient fluorescence spectrum of photoinitiator is affected by electron groups and the fluorescence decay of photoinitiators with electron-withdrawing groups is faster than that of photoinitiators with electron-donating groups. The excitation peak of photoinitiator has evident red shift with the polarity of solvent increasing, which shows that transition type is pi-pi* transition, and the fluorescence decay is postponed with the solvent glutinosity changing. When the photoinitiator density is at 10(-2) mol x L(-1), the fluorescence decay is evidently fast because of quenching effect caused by self-absorption and collisions between particles.

Aberrant methylation of UBE2Q1 promoter is associated with poor prognosis of acute-on-chronic hepatitis B pre-liver failure.

ABSTRACT: Acute-on-chronic hepatitis B liver failure (ACHBLF) is one severe liver disease with rapid progression and high mortality. Identification of specific markers for the prediction of ACHBLF has important clinical significance. We explored the feasibility of UBE2Q1 gene promoter methylation as an early prediction and prognosis biomarker of ACHBLF.UBE2Q1 promoter methylation frequency was detected in 60 patients with acute-on-chronic hepatitis B pre-liver failure (Pre-ACHBLF), 40 patients with chronic hepatitis B and 20 cases of healthy control (HC). The UBE2Q1 mRNA was detected by quantitative real-time polymerase chain reaction.The methylation frequency of the UBE2Q1 promoter in pre-ACHBLF patients was 38.33%, which was significantly lower than that in chronic hepatitis B patients (60.00%) and HCs (65.00%). The UBE2Q1 mRNA expression in pre-ACHBLF patients with UBE1Q1 non-methylation was significantly higher than that in patients with UBE1Q1 promoter methylation. Further analysis showed that hypomethylation of the UBE2Q1 promoter was positively correlated with total bilirubin and international normalized ratio levels in patients with pre-ACHBLF, but negatively correlated with PTA level. COX multivariate analysis showed that the model for end-stage liver disease score and UBE2Q1 promoter hypomethylation status were potential early warning factors that can predict the progression of pre-ACHBLF to ACHBLF. The sensitivity and specificity of UBE2Q1 promoter methylation status combined with the model for end-stage liver disease score for early diagnosis of ACHBLF were 92.9% and 75.0%, respectively. The area under the receiver-operating characteristic curve was 0.895.The hypomethylation of UBE2Q1 promoter is associated with severity of Pre-ACHBLF, which could serve as a potential prognostic biomarker for pre-ACHBLF.

Inconsistent Time-Dependent Effects of Tetramethylpyrazine on Primary Neurological Disorders and Psychiatric Comorbidities.

The aim of this study was to investigate the time dependent effects of tetramethylpyrazine (TMP, main activity compound of Ligusticum chuanxiong Hort) on two neurological disorders and their neuropsychiatric comorbidities. 6 Hz corneal rapid kindling was used to induce epileptogenesis and the inflammatory pain was induced by intra-articular Complete Freund's adjuvant (CFA) injection. The mechanical pain thresholds were measured using von Frey hair (D4, D11, D18, D25 after CFA first injection), and the vertical rearings of the mice was observed. To test the neuropsychiatric comorbidities, anxiety-like behaviors of mice were examined by open field and elevated plus maze tests. Two behavioral despair models, tail suspension test and forced swimming test were also used to evaluate the depressive like behaviors. The results showed that TMP administered from the initial day (D1-D35 in kindling model, D0-D14 and D0-D28 in CFA model) of modeling retarded both the developments of 6 Hz corneal rapid kindling epileptogenesis and the CFA induced inflammatory pain. In comparison, late periods administration of TMP (D21-D35 in kindling and D14-D28 in CFA model) showed no effect on the epileptogenesis and the generalized seizures (GS) of kindling, but alleviated maintenance of CFA induced inflammatory pain. Furthermore, we also found all TMP treatments from the initial day of modeling alleviated the co-morbid depressive and anxiety-like behaviors in both models; however, late periods treatments did not, either in kindling or the CFA induced inflammatory pain. BDNF/ERK signaling impairment was also tested by western blot, and the results showed that TMP administered from the initial day of modeling increased the hippocampal BDNF/ERK expression, whereas late period administration showed no effects. Overall, our findings reveal the inconsistent time dependent effects of Tetramethylpyrazine on neurological disorders and their relative neuropsychiatric comorbidities, and provide novel insight into the early application of TMP that might enhance hippocampal BDNF/ERK signaling to alleviate neuropsychiatric comorbidities in neurological diseases.

[Effect of different sensitization on the photoelectron time action in AgCl emulsion].

The temporal behaviors of free photoelectrons and shallow-trapped electrons were measured in the cubic AgCl emulsion with the microwave absorption and dielectric spectrum detection technique. The results indicate that the chemical sensitization makes the photoelectron decay slower than that of the unsensitized AgCl emulsion, and the decay time is prolonged in the sulfur-plus-gold sensitized emulsion, because the shallow electron trap effect of sulfur-plus-gold sensitization center restrains the recombination of photoelectron and hole. The photoelectron decay is pricked up and the decay time is shorter in sensitized emulsion than that in the unsensitized AgCl emulsion, because the J-aggregates increase the interstice silver ion density in the AgCl microcrystal and accelerate the recombination of interstice silver ions and electrons. The decay time of photoelectron in chemistry-and-spectra sensitized emulsion is also prolonged, and the shallow electron trap effect of chemical sensitization center is more distinct under the condition of spectra sensitization.

[The absorption spectrum of green-sensitive cyanine dyes J-aggregate adsorbed on silver chloride microcrystals].

The silver chloride microcrystals emulsion which are sensitized by the adsorbed green-sensitive cyanine dye of different concentration, was studied by using the absorption spectrum. The experiments show that when the sensitizing concentration is less than 0.02 mL (5.0 mg x mL(-1))/40 g emulsion, the dye J-aggregate is not formed on the surface of silver chloride microcrystals; when the dye concentration is more than 0.2 mL (5.0 mg x mL(-1)/40 g emulsion, the dye J-aggregate is formed on the surface of silver chloride microcrystals; compare to the M-state of dye, the maximal absorption peak of J-aggregate shifted to a longer wavelength by about 50 nm. It was found, when the J-aggregate is formed, the absorption in the wavelength range of more than 450 nm is increased.

[Effects of chemical sensitization on photoelectron time-resolved spectrum].

The time-resolved spectra of free photoelectrons and shallow-trapped electrons in the T-grains AgBrI emulsion were simultaneously detected with microwave absorption and dielectric spectrum detection technique. The results indicate that the electron trap effects of sulfur sensitization centers and sulfur-plus-gold sensitization centers are different with equal quantities of Na2S2O3 added. The sulfur sensitization centers acted as a deep electron trap to pick up the electronic decay because of increasing the number of deep trapped electrons, while the sulfur-plus-gold sensitization centers as a shallow electron trap decrease the electronic decay through effectively controlling the recombination between the electrons and the holes. The depth of sulfur-plus-gold sensitization center is shallower than that of sulfur sensitization center after the KAuCl4 is added. The effects of sulfur sensitization center and sulfur-plus-gold sensitization center on the photoelectron decay are different in different sections of decay curves through the change in electron time-resolved spectra.

[Automated ribotyping of Salmonella and Staphylococcus aureus in food poisoning of Guangdong province].

OBJECTIVE: To understand the genetic polymorphism of Salmonella and Staphylococcus aureus in Guangdong province, as well as to explore methods for identifying and tracing the source of these two foodborne pathogens. METHODS: Using the automated ribotyping system, two foodborne pathogens were tested with either EcoR I or Pvu II restriction enzymes. BioNumerics software was then applied for image analysis, database establishment and other corresponding analysis. RESULTS: Digestion of 32 Salmonella isolates with Pvu II yielded 19 different ribotypes, and digestion of 14 Salmonella isolates with EcoR I yielded 2 different ribotypes. Staphylococcus aureus isolates showed greater genetic diversity, whereas EcoR I digestion of 49 different isolates yielded 31 different ribotypes. CONCLUSION: Unique Salmonella and Staphylococcus aureus isolates could be identified through ribotyping. Although Salmonella serotyping and ribotyping were not strongly correlated, the combination of both restriction enzymes could be used to more effectively identify the genetic relationship among different strains as well as the source of food poisoning. Thus, not only could the genetic relationships amongst the different strains be inferred through ribotyping skills, the source of food poisoning and mode of transmission could also be determined under the use of this method.

[Molecular typing of Listeria monocytogenes isolated from foodstuff in Guangdong province by pulsed-field gel electrophoresis].

OBJECTIVE: To establish molecular typing of Listeria monocytogenes isolates by pulsed-field gel electrophoresis (PFGE) for studying the epidemiologic characteristics of Listeria monocytogenes isolated from foodstuff in Guangdong province and to build up PFGE typing database of Listeria monocytogenes isolates for identifying the infectious resource of the outbreaks and other epidemiologic investigation. METHODS: "Standardized Protocol for Molecular Subtyping of Listeria monocytogenes by PFGE" was followed. BioNumerics software was applied on image analysis, database establishment, comparative and corresponding analysis. RESULTS: 107 Listeria monocytogenes isolates were typed by PFGE, 41 PFGE types were observed among the isolates. The PFGE types were dispersive among these isolates. Listeria monocytogenes isolates were most frequently isolated in raw chicken while the most PFGE types were found in this type of food. The positive rate was relatively high in cold and iced foods. Only 1-2 DNA fragment difference occurred in 26 Listeria monocytogenes isolates by PFGE, so high degree of relatedness remained among these isolates. There were unique PFGE patterns in the regions of Shaoguan and Huizhou. From time to time, a number of isolates remained close relationship. CONCLUSION: PFGE typing of the 107 Guangdong Listeria monocytogenes isolates demonstrated relative genetic diversity but a number of the isolates showed close relatedness.