Supplementation of hyaluronic acid injections with vitamin D improve knee function by attenuating synovial fluid oxidative stress in osteoarthritis patients with vitamin D insufficiency.

Objectives: There is still controversy about the effect of vitamin D supplementation on osteoarthritis (OA). The purpose of this study was to investigate the effects of vitamin D supplementation with Hyaluronic acid (HA) injection on OA. Methods: We investigated serum vitamin D levels and oxidative stress (OS) in synovial fluid from patients with OA who underwent total knee arthroplasty (grade IV, n = 24) and HA injection (grade II and III, n = 40). The effects of HA injection with or without oral vitamin D supplementation on synovial fluid OS and knee pain and function were then further investigated. Finally, patients underwent HA injection were divided into two groups according to vitamin D levels (vitamin D < or > 30 ng/ml), and the efficacy of the two groups were compared. Results: The results showed that the levels of glutathione peroxidase (GSH-PX) (P < 0.05) in the synovial fluid were lower in patients with stage IV OA than that in patients with stage II-III OA, while the levels of malondialdehyde (MDA) (P < 0.05) and lactate dehydrogenase (LDH) (P < 0.01) were significantly higher. Moreover, we found that age, BMI and vitamin D levels were significantly associated with the levels of oxidants and/or antioxidants in synovial fluid, and that vitamin D was significantly negatively correlated with BMI (R = -0.3527, p = 0.0043). Supplementation of HA injections with vitamin D significantly reduced the OS status in synovial fluid, attenuated knee pain and improved knee function in OA patients with vitamin D insufficiency. Conclusion: We conclude that maintenance of vitamin D sufficiency may be beneficial for the treatment of OA by improving OS in synovial fluid.

Research on safety early warning of uranium tailings dam based on abnormal radioactive indexes of water leachate.

The radioactive index value of the leachate of the uranium tailings dam is affected by the internal damage of the dam. Therefore, a way of using the deviation of the radioactive index concentration in the leachate to warn the instability of the dam is innovatively proposed in this paper. Firstly, the SSA-BP algorithm is used to predict and analyze the five groups of parameters U, Ra, ∑ α, ∑ ß and Rn. Then, the deviation between the actual value and the predicted value is computed. Finally, an early warning is given based on the entropy weight extension decision-making model. The model is verified by the leachate environment monitoring data of a uranium tailings dam in southern China from 2016 to 2020, which shows that the model can effectively caution of the instability of the uranium tailings dam and provides a reference for the subsequent decommissioning management.

Elucidation of the underlying mechanism of Hua-ban decoction in alleviating acute lung injury by an integrative approach of network pharmacology and experimental verification.

The pathogenic hyper-inflammatory response has been regarded as the major cause of the severity and death related to acute lung injury (ALI). Hua-ban decoction (HBD) is a classical prescription in traditional Chinese medicine (TCM). It has been extensively used to treat inflammatory diseases; however, its bioactive components and therapeutic mechanisms remain unclear. Here, we established a lipopolysaccharide (LPS)-induced ALI model that presents a hyperinflammatory process to explore the pharmaco-dynamic effect and underlying molecular mechanism of HBD on ALI. In vivo, we confirmed that in LPS-induced ALI mice, HBD improved pulmonary injury by via down-regulating the expression of proinflammatory cytokines, including IL-6, TNF-α, and macrophage infiltration, as well as macrophage M1 polarization. Moreover, in vitro experiments in LPS-stimulated macrophages demonstrated that the potential bioactive compounds of HBD inhibited the secretion of IL-6 and TNF-α. Mechanically, the data revealed that HBD treatment of LPS-induced ALI acted via NF-κB pathway, which regulated macrophage M1 polarization. Additionally, two major HBD compounds, i.e., quercetin and kaempferol, showed a high binding affinity with p65 and IkBα. In conclusion, the data obtained in this study demonstrated the therapeutic effects of HBD, which indicates the possibility for the development of HBD as a potential treatment for ALI.

Yanghe Decoction Effectively Alleviates Lung Injury and Immune Disorder in Asthmatic Mice Induced by Ovalbumin.

Objective: To probe into the ameliorative effect of Yanghe Decoction on pulmonary injury and immunologic derangement in asthmatic mice. Methods: C57BL/6 mice were randomized into control (Con), Model, and Yanghe Decoction (YHF) groups, with 12 in each. The asthma model of adult female mice was induced by ovalbumin in the Model group, and the YHF group was treated by Yanghe Decoction on the basis of asthma modeling. The Con group received the same amount of normal saline. Inspiratory resistance (Ri), expiratory resistance (Re), lung compliance (CL), and maximal voluntary ventilation (MVV) were measured after modeling. Lung tissue was collected for the measurement of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, and tumor necrosis factor-α (TNF-α) by ELISA kits. Combined with HE staining and PAS staining, the pathological alterations of the lung in each group were observed, and CD4+, Th2, and Th1 contents were determined by flow cytometry (FCM). Results: The pulmonary function (PF) test revealed notably reduced Ri and Re as well as enhanced CL and MVV in asthmatic mice after the application of Yanghe Decoction. Yanghe Decoction dramatically ameliorated the pathological changes of lung tissue in asthmatic mice, as demonstrated by the staining results. ELISA results showed that Yanghe Decoction validly reduces lung tissue IL-4, IL-5, IL-6, IL-13, TNF-α and upregulates IL-10 in asthmatic mice. FCM indicated that Yanghe Decoction obviously reduced the number of Th1 and Th2 cells in asthmatic mice, although it caused the decrease of CD4+ cells, but the difference was not statistically significant. Conclusions: Yanghe Decoction can effectively ameliorate the inflammatory reaction, immune cell disorder, and PF injury in ovalbumin-induced asthmatic mice.

Evaluation of efficacy and safety of Qiangzhu-qinggan formula as an adjunctive therapy in adult patients with severe influenza: study protocol for a randomized parallel placebo-controlled double-blind multicenter trial.

BACKGROUND: Influenza can fall into three categories according to severity: mild influenza, severe influenza, and critical influenza. Severe influenza can result in critical illness and sometimes death particularly in patients with comorbidities, advanced age, or pregnancy. Neuraminidase inhibitors (NAIs) are the only antiviral drugs in widespread use for influenza. However, the effectiveness of NAIs against severe influenza is uncertain. New effective drugs or regimens are therefore urgently needed. Qiangzhu-qinggan (QZQG) formula has been found to be effective against influenza virus infection during long-term application in China, which lacks support of evidence-based clinical trial till now. This study is designed to assess the efficacy and safety of QZQG formula as an adjuvant therapy in adult patients with severe influenza. METHODS: This protocol is drawn up in accordance with the SPIRIT guidelines and CONSORT Extension for Chinese herbal medicine formulas. This is a randomized, placebo-controlled, double-blind, multicenter trial. Two hundred twenty-eight adults with severe influenza are randomly assigned in a 1:1 ratio to QZQG or placebo for 7 days. All participants need to receive 1 day of screening before randomization, 7 days of intervention, and 21 days of observation after randomization. The primary outcome is the proportion of clinical improvement, defined as the proportion of patients who met the criteria of 3 points or less in the seven-category ordinal scale or 2 points or less in National Early Warning Score 2 within 7 days after randomization. DISCUSSION: This is the first randomized, controlled, parallel, double-blind clinical trial to evaluate the efficacy and safety of traditional Chinese herbal formula granules as an adjuvant therapy in adult patients with severe influenza. This study aims to redefine the value of traditional Chinese herbal medicines in the treatment of virus-related respiratory infectious diseases and serves as an example of evidence-based clinical trials of other Chinese herbal medicines.

Efficacy of integrating short-course chemotherapy with Chinese herbs to treat multi-drug resistant pulmonary tuberculosis in China: a study protocol.

BACKGROUND: Tuberculosis (TB) caused Mycobacterium tuberculosis (M.tb) is one of infectious disease that lead a large number of morbidity and mortality all over the world. Although no reliable evidence has been found, it is considered that combining chemotherapeutic drugs with Chinese herbs can significantly improves the cure rate and the clinical therapeutic effect. METHODS: Multi-drug resistant pulmonary tuberculosis (MDR-PTB, n = 258) patients with Qi-yin deficiency syndrome will be randomly assigned into a treatment group (n = 172) or control/placebo group (n = 86). The treatment group will receive the chemotherapeutic drugs combined with Chinese herbs granules (1 + 3 granules), while the control group will receive the chemotherapeutic drugs combined with Chinese herbs placebo (1 + 3 placebo granules). In addition, MDR-PTB (n = 312) patients with Yin deficiency lung heat syndrome will be randomly assigned to a treatment (n = 208) or control/placebo (n = 104) group. The treatment group will receive the chemotherapeutic regimen combined with Chinese herbs granules (2 + 4 granules), while the control group will receive the chemotherapeutic drugs and Chinese herbs placebo (2 + 4 placebo granules). The primary outcome is cure rate, the secondary outcomes included time to sputum culture conversion, lesion absorption rate and cavity closure rate. BACTEC™ MGIT™ automated mycobacterial detection system will be used to evaluate the M.tb infection and drug resistance. Chi-square test and Cox regression will be conducted with SAS 9.4 Statistical software to analyze the data. DISCUSSION: The treatment cycle for MDR-PTB using standardized modern medicine could cause lengthy substantial side effects. Chinese herbs have been used for many years to treat MDR-PTB, but are without high-quality evidence. Hence, it is unknown whether Chinese herbs enhances the clinical therapeutic effect of synthetic drugs for treating MDR-PTB. Therefore, this study will be conducted to evaluate the clinical therapeutic effect of combining Chinese herbs and chemotherapeutic drugs to treat MDR-PTB cases. It will assist in screening new therapeutic drugs and establishing treatment plan that aims to improve the clinical therapeutic effect for MDR-PTB patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (ChiCTR1900027720) on 24 November 2019 (prospective registered).

Baicalin Inhibits Cell Proliferation and Inflammatory Cytokines Induced by Tumor Necrosis Factor α (TNF-α) in Human Immortalized Keratinocytes (HaCaT) Human Keratinocytes by Inhibiting the STAT3/Nuclear Factor kappa B (NF-κB) Signaling Pathway.

BACKGROUND Baicalin is a flavone isolated from the root of Scutellaria baicalensis and is used in traditional Chinese medicine. Psoriasis is a persistent and recurrent chronic inflammatory skin disease that is characterized by inflammation and increased proliferation of keratinocytes. This study aimed to investigate the effects of baicalin on HaCaT immortalized human keratinocytes in vitro and the molecular mechanisms involved. MATERIAL AND METHODS HaCaT keratinocytes were cultured in increasing concentrations of baicalin at 6.25 µM, 12.5 µM, and 25 µM. The in vitro model of psoriasis was established using HaCaT cells treated with tumor necrosis factor-alpha (TNF-alpha). The MTT assay was used to asses cell viability and apoptosis. Western blot was used to measure the expression of Bcl-2, Bax, pro-caspase-3, and cleaved caspase-3, and enzyme-linked immunosorbent assay (ELISA) was performed to detect inflammatory cytokines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the levels of STAT3 and p65 mRNA. RESULTS Baicalin reduced cell viability and induced apoptosis of HaCaT human keratinocytes in a dose-dependent manner. Increased cell viability and the expression of inflammatory cytokines by HaCaT cells induced by TNF-alpha were significantly inhibited by baicalin. Baicalin significantly inhibited the activation of the STAT3/NF-kappaB pathway in HaCaT cells stimulated by TNF-alpha. CONCLUSIONS Baicalin inhibited the proliferation and expression of inflammatory cytokines in HaCaT immortalized human keratinocytes in vitro through the inhibition of the STAT3/NF-kappaB signaling pathway.

Antinociceptive and anti-inflammatory effect of Naringenin in different nociceptive and inflammatory mice models.

Inflammation is the vital defensive response triggered by our immune system against an infection or deleterious stimuli. This response in due course affects its own biological system leading to serious diseases like arteriosclerosis, osteoporosis, pancreatitis, cancer etc. Currently, researchers focused on utilizing phytochemicals as anti-inflammatory drugs since the drugs presently available in the market causes serious side effects and are less potent. Flavonoids are polyphenols which imparts colours to the plants and fruits. These flavonoids serve as phytonutrients to plants and they also possess antioxidant, anti-inflammatory and anti-cancer properties. Naringenin is one such flavonoid classified under flavones groups present in citrus fruits and vegetables. The present study is aimed to identify and confirm the antinociceptive and anti-inflammatory efficacy of Naringenin in different mice models. The antinociceptive effect of Naringenin was analyzed by both thermal induced and chemical induced nociceptive mice models. Carrageenan-induced paw edema test was performed to detect the anti-inflammatory effect of Naringenin and it is confirmed by analyzing the leukocyte infiltration in peritoneal cavity. Air pouch model test is performed to estimate the inhibitory property of Naringenin against proinflammatory cytokines. The potency of drug Naringenin was confirmed by treating along with opioid inhibitors naloxone and the results compared with standard drugs. To assess the muscle relaxant property of Naringenin open field test was performed. The overall results of Naringenin in different nociceptive and inflammatory mice models suggest that, Naringenin is a potent anti-inflammatory drug which relieves pain effectively and can be used in pain management therapy.