Flexible and printable integrated biosensors for monitoring sweat and skin condition.

Wearable and flexible sensors are playing increasing roles in health monitoring (like physiological electrical signals and components of biofluids). Therein, sweat as a carrier of informative biomarkers would attract great attention for health status identification. However, most wearable biosensors have a short lifetime with complex fabrication processes and expensive costs, which would largely limit the application scene to some extent. Here, we developed a state-of-the-art flexible and integrated sensor patch with screen-printing technology for in-situ and real-time monitoring of electrolyte balance and skin state. The screen-printed sensor patch was easily fabricated, highly reproducible, disposable and relatively stable, which was extremely for sweat sensors with low cost. The state of art sensors on the patch of Na+, pH, skin impedance and temperature all showed excellent performance with high linearity (coefficient of determinations (R2) are 0.998, 0.994, 0.998 and 0.997, respectively). Besides, the detection ranges of Na+ and pH sensors are wide enough for sweat analysis of 10-100 mM and 2-8, respectively. The proposed device provides a new strategy for real-time sweat analysis, preventing dehydration and skin state monitoring during exercise.

High-Throughput Aptamer Microarrays for Fluorescent Detection of Multiple Organophosphorus Pesticides in Food.

A novel high-throughput aptamer microarray fluorescent method based on thioflavin T (ThT) was established for the sensitive detection of phoxim, parathion, fensulfothion, and isocarbophos. In this work, the aptamers in binding buffer tended to have the antiparallel G-quadruplex structure, which can bind ThT and release its potential fluorescence signal. However, when the organophosphorus pesticides (OPs) were present, partial aptamers preferred to bind them, forcing the displacement of ThT from the G-quadruplex and resulting in the significant decrease in fluorescence signal. Under optimal experimental conditions (12T spacer, 300 nM aptamer, and 80 µM ThT), the OP aptamer microarray has low limits of detection of 25.4 ng/mL for phoxim, 12.0 ng/mL for parathion, 7.7 ng/mL for fensulfothion, and 9.9 ng/mL for isocarbophos. The accuracy and reliability of the method is further verified by testing the recovery rate of OPs spiked in two different complicated sample matrices (pears and radishes). It is worth mentioning that not only the developed aptamer microarray technology has low sensitivity and a broad spectrum, but it also allows for high-throughput and rapid analysis of a variety OPs, which overcomes some of the shortcomings of other OP detection methods.

Group 2 innate lymphoid cells suppress the pathology of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a severe central nervous system (CNS) autoimmune disease that primarily damages the optic nerves and spinal cord. Group 2 innate lymphoid cells (ILC2) are potent producers of type 2 cytokines that orchestrate immune and inflammatory responses. However, the role of ILC2 in CNS autoimmune diseases remains unknown. In patients with NMOSD, we identified a significant reduction of ILC2 in peripheral blood, which was correlated with disease severity. Using a mouse model of NMOSD induced by intracerebral injection of NMOSD-IgG with complement, we found CNS infiltration of ILC2 mainly expressing interleukin (IL)-5 and IL-13. The depletion of ILC2 led to increased CNS lesion volume, reduced CNS glucose metabolism, and augmented astrocyte injury and demyelination. The exacerbated NMOSD pathology was accompanied by increased accumulation of Iba1+ cells and complement activity in CNS lesions. In addition, the expansion of ILC2 using IL-33 attenuated NMO pathology. Collectively, these findings suggest a beneficial role of ILC2 in NMOSD, which deserves further investigation for future design of immune therapies to treat patients with NMOSD.

Expression of TRAF6 in peripheral blood B cells of patients with myasthenia gravis.

BACKGROUND: Tumor necrosis factor receptor-associated factor 6 (TRAF6) can regulate the activation of inflammatory signaling pathways by acting as an E3 ubiquitin ligase, which enhances B cell activation. This study aimed to evaluate the expression of TRAF6 in the peripheral blood B cells of myasthenia gravis (MG) patients and analyze the relationships between TRAF6 expression and clinical characteristics. METHOD: In our study, the expression level of TRAF6 in peripheral blood B cells of 89 patients was measured by flow cytometry compared with that of healthy subjects. The effects of disease severity, MG classification and immunotherapy on TRAF6 expression level were also analyzed. RESULTS: In our study, TRAF6 expression was elevated in CD19+ B cells and CD19+CD27+ memory B cells in generalized MG (GMG) patients compared with ocular MG (OMG) patients (p = 0.03 and p = 0.03, respectively). There was a significant positive correlation between the TRAF6 expression level and disease severity in both OMG patients and GMG patients (CD19+ B cells: OMG: p < 0.001, r = 0.89; GMG: p = 0.001, r = 0.59; CD29+CD27+ B cells: OMG: p = 0.001, r = 0.80; GMG: p = 0.048, r = 0.38). TRAF6 expression was significantly elevated in CD19+ B cells and CD19+CD27+ memory B cells in GMG with acute aggravation compared with GMG in MMS (p = 0.009 and p = 0.028, respectively). In the eleven MG patients who were followed, TRAF6 expression in B cells and memory B cells was significantly decreased after treatment (p = 0.03 and p < 0.01, respectively). CONCLUSION: TRAF6 is potentially a useful biomarker of inflammation in patients with MG, and might be used to evaluate the effectiveness of treatment.

The incidence and prevalence, diagnosis, and treatment of multiple sclerosis in China: a narrative review.

In 2018, the first list of rare diseases was published by the National Health Council of China, and multiple sclerosis (MS) was included in this list. Since then, the Chinese government and neurologists have made efforts to improve the clinical outcomes of patients with MS. During last few years, the incidence of MS in China was also investigated. The early and accurate diagnosis of MS was improved due to the application and promotion of magnetic resonance imaging and new diagnosis criteria. The market for and medical insurance access to disease-modifying therapies (DMTs) has been greatly accelerated, which has provided more treatment options and improved clinical outcomes for patients with MS, as well as reduced treatment cost. The pattern of MS in China is gradually changing, from delayed to early diagnosis, and from no treatment to treatment with DMTs during remission. This narrative review aimed to summarize an update to the status of MS in China, including incidence and prevalence, diagnosis, and available treatments. This would help to better understand the diagnosis and treatment gap between mainland China and other Asian regions, demonstrating the necessity of accurate diagnosis and optimized treatment of MS in China.

Nuclear factor-kappa B and effector molecules in photoaging.

Nuclear factor-kappa B (NF-κB) has important but complex functions in the photoaging of the human skin. This protein complex is activated upon UV irradiation and plays a key role in the signalling pathway of the inflammatory cascade. NF-κB induces the expression of various proinflammatory cytokines, such as tumour necrosis factor (TNF) and interleukin-1 (IL-1). These proinflammatory cytokines can in turn stimulate the activation of NF-κB, forming a vicious cycle. These processes cause chronic inflammation and contribute to skin ageing. In addition, the activation of NF-κB upregulates the expression of matrix metalloproteinases (MMPs) and leads to the degradation of structural proteins in the dermis. NF-κB disrupts the barrier function of the skin under prolonged and repeated UV stimulations in these ways. Such activity causes chronic skin damage, followed by the formation of wrinkles, dryness, roughness, laxity, and other photoaging manifestations. This study on the NF-κB signalling pathway and effector molecules provides a new perspective to understand and prevent photoaging.

Relative Entropy of Distance Distribution Based Similarity Measure of Nodes in Weighted Graph Data.

Many similarity measure algorithms of nodes in weighted graph data have been proposed by employing the degree of nodes in recent years. Despite these algorithms obtaining great results, there may be still some limitations. For instance, the strength of nodes is ignored. Aiming at this issue, the relative entropy of the distance distribution based similarity measure of nodes is proposed in this paper. At first, the structural weights of nodes are given by integrating their degree and strength. Next, the distance between any two nodes is calculated with the help of their structural weights and the Euclidean distance formula to further obtain the distance distribution of each node. After that, the probability distribution of nodes is constructed by normalizing their distance distributions. Thus, the relative entropy can be applied to measure the difference between the probability distributions of the top d important nodes and all nodes in graph data. Finally, the similarity of two nodes can be measured in terms of this above-mentioned difference calculated by relative entropy. Experimental results demonstrate that the algorithm proposed by considering the strength of node in the relative entropy has great advantages in the most similar node mining and link prediction.

The prevalence of anti-neurofascin-155 antibodies in patients with neuromyelitis optica spectrum disorders.

Anti-neurofascin-155 (NF155) antibodies have been observed in two cases with neuromyelitis optica spectrum disorders (NMOSD). This study investigated the prevalence of anti-NF155 antibodies in patients with NMOSD and the clinical features of anti-NF155 antibody-positive patients. Sera from 129 patients with NMOSD were screened with anti-NF155 antibodies by cell-based assay (CBA) and re-examined using immunostaining of teased mouse sciatic nerve fibres. Fifty-six patients with multiple sclerosis (MS) and 50 healthy controls (HC) were also enrolled for detecting anti-NF155 antibodies. A total of 12.40% (16 of 129) of patients with NMOSD were positive for anti-NF155 antibodies confirmed by both CBA and immunostaining. Immunoglobulin (Ig) G1 was the predominant subclass. However, none of 56 MS patients or 50 HC were positive for anti-NF155 antibodies. Anti-NF155 antibody-positive NMOSD patients had a higher proportion of co-existing with autoimmune diseases (p < 0.001) and higher positive rates of serum non-organ-specific autoantibodies, including anti-SSA antibodies (p < 0.001), anti-SSB antibodies (p = 0.008), anti-Ro-52 antibodies (p < 0.001) and rheumatoid factor (p < 0.001). Five anti-NF155 antibody-positive NMOSD patients who took part in the nerve conduction study showed mildly abnormal results. Differences in some nerve conduction study parameters were observed between anti-NF155 antibody-positive and negative patients. Anti-NF155 antibodies occurred in a small proportion of NMOSD patients. Anti-NF155 antibody-positive NMOSD patients tended to co-exist with autoimmune diseases.

Trends in Workplace Violence Involving Health Care Professionals in China from 2000 to 2020: A Review.

The safety of health care workers in China has received an increasing amount of attention owing to numerous incidents of hospital-based violence against medical professionals. When pictures and videos of violent injuries are posted on the internet with real-time data, such as gender or location, researchers can access the information to learn about the incident, its causes, and/or threats to survival. We examined the causes and risk factors for workplace violence by analyzing relevant data retrieved from reports by Chinese internet media for all incidents from 2000 to 2020. We present frequency data on hospital-based violence against medical professionals. A total of 345 incidents occurred in health care settings. The person who committed the violent act was a patient or sick person in the workplace or a co-worker in 95.4% of the incidents; 54 of the incidents resulted in the victim's murder. We provide the characteristics and risk factors of violent criminals. We describe China's past and current clinical practices and health care policies, and we discuss the challenges faced by medical professionals who are victims of hospital-based violence from the perspectives of patients, physicians, hospital leaders, and the government. We conclude by making recommendations for preventing violence in hospital settings. It is urgent for the public to understand that the occupational safety of health care workers must be protected, and treatment should be provided to patients in a harmonious and safe environment. This review aims to describe the trends in workplace violence involving health care professionals in China from 2000 to 2020 and to discuss possible strategies for improving working conditions in hospitals and other health care settings.

Research progress on skin photoaging and oxidative stress.

Skin photoaging, which is a kind of exogenous aging, refers to skin elasticity degradation, skin roughening, and wrinkle formation processes because of cascading reactions of a series of kinases after growth factor receptors and cytokine receptors are activated on a cell surface under the UV effect. An extensively recognized skin photoaging mechanism is free radical-oxidative stress concept, proposed by Sohal who represents the authority of the US aging studies. Over the past decade, many new developments in the oxidative stress mechanism have been achieved in terms of the occurrence, development, prevention, and treatment of photodamage.

Increased serum IL-36γ levels are associated with disease severity in myasthenia gravis patients.

BACKGROUND: Interleukin 36 (IL-36), as a gradually recognized cytokine, is involved in the occurrence and evolution of autoimmune diseases. Nevertheless, the relationship between myasthenia gravis (MG) and IL-36 is rarely reported. METHODS: We evaluated the serum levels of IL-36 (IL-36α, IL-36ß and IL-36γ) by enzyme-linked immunosorbent assay (ELISA). Further, clinical parameters in 97 MG patients and 49 healthy controls (HCs) were carefully measured. RESULTS: Serum IL-36γ levels were significantly elevated in the MG patients compared with the HCs (p < 0.0001). Compared to those in remission, patients in the acute phase exhibited higher levels of IL-36α and IL-36γ (p = 0.038 and p = 0.011, respectively). Furthermore, patients with generalized MG (GMG) exhibited markedly higher serum IL-36γ levels than those with ocular MG (OMG) (p = 0.003). CONCLUSIONS: The serum levels of IL-36γ in patients with MG were increased and positively correlated with disease severity and may thus have potential as a serological MG marker.

Behavioural thermoregulation by the endangered crocodile lizard (Shinisaurus crocodilurus) in captivity.

Understanding the factors that may affect behavioural thermoregulation of endangered reptiles is important for their conservation because thermoregulation determines body temperatures and in turn physiological functions of these ectotherms. Here we measured seasonal variation in operative environmental temperature (Te), body temperature (Tb), and microhabitat use of endangered crocodile lizards (Shinisaurus crocodilurus) from a captive population, within open and shaded enclosures, to understand how they respond to thermally challenging environments. Te was higher in open enclosures than in shaded enclosures. The Tb of lizards differed between the open and shaded enclosures in summer and autumn, but not in spring. In summer, crocodile lizards stayed in the water to avoid overheating, whereas in autumn, crocodile lizards perched on branches seeking optimal thermal environments. Crocodile lizards showed higher thermoregulatory effectiveness in open enclosures (with low thermal quality) than in shaded enclosures. Our study suggests that the crocodile lizard is capable of behavioural thermoregulation via microhabitat selection, although overall, it is not an effective thermoregulator. Therefore, maintaining diverse thermal environments in natural habitats for behavioural thermoregulation is an essential measure to conserve this endangered species both in the field and captivity.

Increased serum IL-36ß and IL-36γ levels in patients with neuromyelitis optica spectrum disorders: association with disease activity.

BACKGROUND: Interleukin 36 (IL-36) cytokines belong to the IL-1 family and play an important role in some autoimmune diseases. However, the relationship between IL-36 and neuromyelitis optica spectrum disorders (NMOSD) remains unclear. METHODS: We determined serum IL-36α, IL-36ß and IL-36γ levels and assessed correlations with clinical characteristics in 50 NMOSD patients and 30 healthy controls (HC). RESULTS: The concentrations of serum IL-36ß and IL-36γ were significantly higher in patients with NMOSD than in HCs and decreased during remission. Serum IL-36ß levels were positively correlated with the annual relapse rate (ARR), spinal cord lesion length and Expanded Disability Status Scale (EDSS) scores. CONCLUSIONS: Serum IL-36ß and IL-36γ levels were related to disease activity in NMOSD patients and may be important biomarkers of NMOSD.

Confocal laser scanning microscopy, a diagnostic alternative for five pigmented lesions on the face: An observational study.

OBJECTIVE: To describe the confocal laser scanning microscopy (CLSM) features of five different facial hyperpigmentation diseases and to highlight the features that can be used to differentiate between the diseases. MATERIALS AND METHODS: Confocal laser scanning microscopy features of skin lesions of 406 patients with different facial hyperpigmentation diseases (chloasma, naevus fusco-caeruleus zygomaticus, naevus of Ota, freckles and Riehl melanosis) were retrospectively analysed. All patients were diagnosed clinically. The features of each layer of the skin in the involved regions and at the junction of the lesion with normal skin were studied, and the characteristic features of each disease were identified. The CLSM probe was applied perpendicular to the skin surface. Scanning was performed with medical ultrasonic coupling agent applied between the adhesive window and skin and between the lens and adhesive window. The skin was scanned layer by layer, and the best cross-sectional images were stored in the computer for analysis. RESULTS: Chloasma lesions showed significantly increased pigment content in the epidermal basal layer and, in some cases, varying degrees of pigment particle deposition in the upper dermis. Naevus fusco-caeruleus zygomaticus and naevus of Ota lesions showed normal epidermal pigment content, with cord-like high-refractive pigment masses scattered in the dermis; cord-like or dendritic melanocytes were seen between collagen fibre bundles in the upper and middle dermis, but no inflammatory cell infiltration was seen. Freckles lesions showed increased numbers of pigment particles in the basal layer, but no abnormal changes in the dermis. Riehl melanosis was characterised by liquefaction degeneration of the basal cells, accompanied by considerable monocyte and melanophage infiltration in the dermal papilla. CONCLUSIONS: Used in combination with clinical manifestations, CLSM can be a useful auxiliary method for diagnosis of naevus fusco-caeruleus zygomaticus, naevus of Ota, chloasma, freckles and Riehl melanosis.

Impacts of maternal characteristics and temperature on juvenile survival in the crocodile lizard: Implications for conservation.

Captive breeding is an important conservation measure that may restore and enhance wild populations of rare and endangered species. Multiple anthropogenic hazards have brought the crocodile lizard, Shinisaurus crocodilurus, to the brink of extinction. We initiated a captive breeding program and quantified female reproductive traits, including reproductive timing, litter size, litter mass, and neonate size. To identify the internal and external factors affecting female reproductive function, we then analyzed how maternal age is related to body size, temperature, and female reproductive traits. We found that larger female crocodile lizards produced more offspring than smaller ones, as both litter size and litter mass were positively related to maternal body size. In contrast, neonate size was independent of maternal body size. Maternal reproductive output varied among different age groups. Young and old females had significantly smaller living litter size and mass than middle-aged females. Among captive females, one-third exhibited early parturition in autumn and winter instead of the following spring, a pattern probably associated with higher ambient temperatures in captivity. Although female reproductive output and neonatal body size did not differ between early- and normal-parturition females, offspring from the former group died earlier than those from the latter. Our study highlights the danger of climate change in hastening parturition, a phenomenon that could significantly hamper neonate survival and impede population recruitment.

Advances on chimeric antigen receptor-modified T-cell therapy for oncotherapy.

Tumor treatment is still complicated in the field of medicine. Tumor immunotherapy has been the most interesting research field in cancer therapy. Application of chimeric antigen receptor T (CAR-T) cell therapy has recently achieved excellent clinical outcome in patients, especially those with CD19-positive hematologic malignancies. This phenomenon has induced intense interest to develop CAR-T cell therapy for cancer, especially for solid tumors. However, the performance of CAR-T cell treatment in solid tumor is not as satisfactory as that in hematologic disease. Clinical studies on some neoplasms, such as glioblastoma, ovarian cancer, and cholangiocarcinoma, have achieved desirable outcome. This review describes the history and evolution of CAR-T, generalizes the structure and preparation of CAR-T, and summarizes the latest advances on CAR-T cell therapy in different tumor types. The last section presents the current challenges and prospects of CAR-T application to provide guidance for subsequent research.

Neuromyelitis optica spectrum disorders with and without connective tissue disorders.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) often coexist with connective tissue disorders (CTD). The aim of this study was to investigate and compare the features of NMOSD with and without CTD. METHODS: NMOSD patients with (n = 18) and without CTD (n = 39) were enrolled, and the clinical, laboratory, and magnetic resonance imaging (MRI) features of the two groups were assessed. RESULTS: Most of the demographic and clinical features examined were similar between NMOSD patients with and without CTD. Serum immunoglobulin G (IgG), percentage of γ-globulin and seropositivity for several other autoantibodies were significantly elevated in NMOSD patients with CTD (P < 0.05). NMOSD with CTD was marked by longer spinal cord lesions and a lower frequency of short transverse myelitis (TM) than NMOSD without CTD (P < 0.05). NMOSD with CTD also featured more T1 hypointensity and T2 bright spotty lesions (BSLs) on MRI than NMOSD without CTD (P = 0.001 and 0.011, respectively). There were no other differences in laboratory, MRI and clinical characteristics between different NMOSD subtypes. CONCLUSIONS: A few characteristics differed between NMOSD with and without CTD. NMOSD patients with CTD had higher serum IgG, longer spinal cord lesions, a lower frequency of short TM and more T1 hypointensity and T2 BSLs on spinal MRI than NMOSD patients without CTD.

Augmentation of Circulating Follicular Helper T Cells and Their Impact on Autoreactive B Cells in Myasthenia Gravis.

Myasthenia gravis (MG) is a chronic humoral immunity-mediated autoimmune disorder of the neuromuscular junction characterized by muscle weakness. Follicular helper T (Tfh) cells may be the key Th cell subset that promotes MG development, as their major function is helping B cell activation and Ab production. Aberrance of thymus-derived Tfh cells might be implicated in autoimmune diseases including MG; just how circulating Tfh cells, especially those from patients with a normal thymus, contribute to MG pathogenesis remains to be uncovered. In this article, we characterize a population of circulating CD4(+)CXCR5(+)PD-1(+) Tfh cells in ocular and generalized MG patients without thymic abnormalities and demonstrate that the circulating Tfh cells are significantly enriched in generalized MG patients but not in ocular MG patients compared with healthy subjects, whereas a proportion of follicular regulatory T cells decreased in MG patients. In addition, the frequency of plasma cells and B cells was higher and the serum levels of IL-6/IL-21 were also elevated in these MG patients. The activated Tfh1 and Tfh17 in Tfh cells are the major source for IL-21 production in MG patients. A strong correlation between Tfh cells and the plasma cell frequency and anti-acetylcholine receptor Ab titers was evident in generalized MG patients. In particular, we found that Tfh cells derived from MG patients promoted B cells to produce Abs in an IL-21 signaling-dependent manner. Collectively, our results suggest that circulating Tfh cells may act on autoreactive B cells and thus contribute to the development of MG in patients without thymic abnormalities.

Machine Learning-Based Sensor Data Modeling Methods for Power Transformer PHM.

An emerging prognostic and health management (PHM) technology has recently attracted a great deal of attention from academies, industries, and governments. The need for higher equipment availability and lower maintenance cost is driving the development and integration of prognostic and health management systems. PHM models depend on the smart sensors and data generated from sensors. This paper proposed a machine learning-based methods for developing PHM models from sensor data to perform fault diagnostic for transformer systems in a smart grid. In particular, we apply the Cuckoo Search (CS) algorithm to optimize the Back-propagation (BP) neural network in order to build high performance fault diagnostics models. The models were developed using sensor data called dissolved gas data in oil of the power transformer. We validated the models using real sensor data collected from power transformers in China. The results demonstrate that the developed meta heuristic algorithm for optimizing the parameters of the neural network is effective and useful; and machine learning-based models significantly improved the performance and accuracy of fault diagnosis/detection for power transformer PHM.

Correlations of cancer pain degree with levels of ß-EP, CGRP and PGE2 and the effects of oxycontin on them.

PURPOSE: To analyze the effects of Oxycontin on ß-endorphin (ß-EP), calcitonin gene-related peptide (CGRP) and prostaglandin E2 (PGE2) in treating patients with cancer pain, and to investigate and discuss the role and value of Oxycontin in treating cancer pain. METHODS: A total of 95 patients (60 male and 35 female) were enrolled in the study, who were diagnosed in our hospital with malignant tumors complicated with pain from May 2016 to July 2017. All received Oxycontin for pain relief in addition to conventional treatment. The role of Oxycontin was analyzed by collecting the patients' general information, age, gender, Karnofsky performance status (KPS) score, site of pain and degree of pain, and by detecting the remission rates of clinical symptoms, average analgesic time, number of pain outbreak per day, levels of ß-EP, CGRP and PGE2, as well as changes of KPS score, Zubrod performance status (ZPS) score and quality of life (QoL) score of the enrolled patients before treatment and at 1 week afer treatment. RESULTS: (1) Afer treatment with Oxycontin, the remission rate of clinical symptoms was signifcantly increased, the average analgesic time was extended remarkably and the number of pain outbreaks per day was decreased notably. All the differences were statistically signifcant (p<0.05). (2) For patients with cancer pain receiving Oxycontin, the main adverse reactions were nausea and vomiting (15.37%), followed by constipation, abdominal distension and anorexia. (3) At 1 week afer Oxycontin therapy, the KPS score and QoL score of the enrolled patients were increased, while the ZPS score was decreased, and the differences were statistically signifcant (p<0.05). (4) At 1 week afer treatment with Oxycontin, the levels of ß-EP, CGRP and PGE2 of the enrolled patients were signifcantly lowered (p<0.05). (5) The levels of ß-EP, CGRP and PGE2 with regard to the average analgesic time were negatively correlated with ß-EP (r=-0.765, p<0.01), CGRP (r=-0.673, p<0.01) and PGE2 (r=-0.801, p<0.01). CONCLUSIONS: On treating patients with cancer pain, Oxycontin can signifcantly decrease the ß-EP, CGRP and PGE2 levels, ameliorate the clinical symptoms, effectively relieve the pain and improve the QoL to some extent.