Clinical significance of long non-coding RNA NORAD in rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. Methods Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. Results NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. Conclusions There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.

Research progress on invasive cervical resorption / 口腔疾病防治

@#Tooth absorption can be divided into physiological absorption and pathological absorption. Root absorption of mature deciduous teeth is physiological absorption. Pathological absorption includes internal absorption and external absorption. Internal absorption, also known as intramedullary absorption, includes inflammatory absorption and alternative absorption. External tooth absorption originates from the outer surface of the root or the neck of the tooth and can be divided into inflammatory absorption, alternative absorption, pressure resorption and invasive cervical resorption. Invasive cervical resorption (ICR) is pathological damage caused by many factors, which usually begins in the cemento-enamel junction and extends peripherally or horizontally in the dentin. It hardly invades the pulp. Orthodontic devices, trauma, bleaching, systemic diseases, and the use of certain medications can all lead to invasive cervical resorption. The clinical manifestations of ICR are usually asymptomatic or not obvious, and most of which are found in imaging examinations. Because caries and internal absorption are often misdiagnosed through plain apical radiography, cone beam computed tomography (CBCT) can help to better understand the situation of invasive cervical resorption. Because the pathogenesis and etiology of invasive cervical resorption are not fully understood, clinical negligence and inadequate treatment of invasive cervical resorption can even cause unnecessary tooth loss. This article reviews the latest research progress on the histopathologic features, pathogenic mechanism, susceptibility factors, diagnosis and treatment of ICR, with special emphasis on susceptibility factors and their mechanisms.

Dimethyl fumarate inhibits NLRP3/AIM2 inflammasomes to prevent spleen radiation injury ZHANG / 中国药理学通报

Aim To investigate the protective effect of dimethyl fumarate on spleen injury induced by gamma radiation in mice and the related mechanism. Methods C57BL/6 mice were randomly divided into the blank control group, radiation model group and DMF administration group, which were administered once at 12 h before irradiation and once at 0. 5 h, 12 h, 24 h and 48 h after irradiation. The 30-day survival rate, body weight and pathological injury of spleen were measured after a one-time total body irradiation of Co 7 rays (8 Gy). TUNEL staining was used to detect apoptosis of spleen cells. Enzyme-linked immunoassay ( ELISA) was applied to detect the contents of TNF-a, IL-1 p, IL-6, IL-18, NLRP3 and AIM2 in spleen. Western blot test and immunofluorescence staining test was employed to verify the changes of NLRP3 and AIM2 contents in spleen tissue after irradiation. Results DMF could obviously improve the survival rate of irradiated mice, improve the weight loss of irradiated mice, re-duce the pathological injury of spleen, and inhibit the apoptosis of spleen cells after irradiation. ELISA results showed that DMF could significantly inhibit the increase of spleen inflammatory cytokines TNF-a, IL-lp, IL-6, IL-18 and inflammasome components NL-RP3 and AIM2 induced by irradiation. Western blot and tissue immunofluorescence staining also confirmed that DMF could inhibit the increase of NLRP3 and AIM2 inflammasome protein levels caused by irradiation. Meanwhile, NLRP3 agonist and AIM2 agonist could antagonize the radiation protection effect of DMF on spleen cells. Conclusion DMF can ameliorate spleen injury of Co 7-ray injured mice, and its mechanism is closely related to NLRP3/AIM2 inflamma-somes, which can be used as a potential protective drug for radiation injury.

Effect of safflower yellow on learning and memory ability of APP/PS1 at different months based on TLR4/NF-KB signaling pathway / 中国药理学通报

Aim To investigate the effect of safflower yellow (SY) on learning and memory ability of APP/ PS1 mice at different disease stages, and to explore the mechanism of SY anti- Alzheimer's disease by using 3-,6- and 9-month-old APP/PS 1 transgenic mice as experimental animal models. Methods Behavioral experiments were conducted to observe the effects of SY on learning and memory of APP/PS1 mice of different months. ELISA was used to detect the effect of SY on the expression of inflammatory factors in cortex of mice of different months. Western blot was used to detect the microglia activation marker protein, and its mechanism of action was further analyzed. Results SY could enhance the learning and memory ability of mice aged 3, 6 and 9 months, reduce the content of IL-6 and increase the content of TGF-β1 in brain tissue, up-regulate the expression levels of arginase-1 (arg-1) and triggering receptor expressed on myeloid cells 2 (tREM2) in brain tissue of mice of different months, and down-regulate the expression levels of inducible nitric oxide synthase (iNOS), Toll-like receptors 4 (tlr4) and nuclear factor-kappa B (nf-KB). Conclusions Compared with 3- and 9-month-old mice, SY is the most effective in improving learning memory in 6-month-old APP/PS1 mice. SY inhibits TLR4/NF-KB pathway activation by inducing TREM2 expression in brain tissue of APP/PS 1 transgenic mice, promotes microglia phenotype shift to anti-inflammatory phenotype, reduces chronic neuroinflammatory response, and improves learning memory in APP/PS1 mice at all months of age.

Protective effect and mechanism of Longshengzhi capsules on cerebral ischemia-reperfusion injury in rats / 中国药房

OBJECTIVE To explore the protective effect and mechanism of Longshengzhi capsules on cerebral ischemia- reperfusion injury in rats. METHODS The model of middle cerebral artery occlusion （MCAO） was established by using the improved thread occlusion method. The experiment was divided into six groups： sham surgery group （only separating blood vessels without inserting thread plugs， given the same volume of normal saline）， model group （modeling， given the same volume of normal saline）， nimodipine group （positive control， modeling， dose of 20 mg/kg）， and low-dose， medium-dose， and high-dose groups of Longshengzhi capsules （modeling， doses of 0.72， 1.44 and 2.88 g/kg， respectively）， with 10 mice in each group. Each group was given corresponding medication solution/normal saline by gavage， once a day， for 7 consecutive days. One hour after the last administration， the Zea Longa scoring method was used to score the neurological deficits in each group of rats， and the ABC enzyme-linked immunosorbent assay was used to detect the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rats； TTC staining was used to observe the volume of cerebral infarction in rats and calculate the cerebral infarction volume ratio. Hematoxylin eosin staining was used to observe the pathological changes in the brain tissue of rats. Immunohistochemical staining was used to detect the positive expression of NLRP3 protein in the brain tissue of rats. Real-time fluorescence quantitative PCR was used to detect mRNA relative expressions of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the brain tissue of rats. Western blot assay was adopted to detect the relative expressions of TLR4， NLRP3 and phosphorylated NF-κB （p-NF-κB） protein in the brain tissue of rats and its intracellular NF-κB protein. RESULTS Compared with the sham surgery group， the neural dysfunction score， serum levels of TNF-α and IL-6， cerebral infarction volume ratio， relative expression levels of NF-κB and TLR4 mRNA， as well as protein relative expressions of TLR4， NLRP3 and p-NF-κB in the brain tissue， and relative protein expression of intracellular NF-κB were increased significantly in the model group （P＜0.01）； the enlarged gap and significant edema were observed in cortical nerve cells of brain tissue in rats， with a large amount of inflammatory cell infiltration； the positive expression of NLRP3 protein in brain tissue of rats obviously increased. Compared with the model group， the levels of the above indicators in the medium-dose and high-dose groups of Longshengzhi capsules， as well as the Nimodipine group， were reversed to varying degrees， and most differences were statistically significant （P＜0.05 or P＜0.01）； the pathological morphology observation showed a significant improvement， and the positive expression of NLRP3 protein in the brain tissue of rats was obviously reduced. CONCLUSIONS Longshengzhi capsules may inhibit TLR4/NF-κB/NLRP3 signaling pathway and neuroinflammatory response， thereby achieving a protective effect against cerebral ischemia-reperfusion injury in rats.

Improvement of Skin Barrier and Anti-inflammatory Mechanism of Huangliansan on Atopic Dermatitis in Mice / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect of Huangliansan on atopic dermatitis （AD） model mice induced by 2， 4-dinitrochlorobenzene （DNCB）. MethodA total of 42 male BALB/c mice were randomly divided into normal group， model group， hydrocortisone group， low， medium， and high-dose groups （0.3， 0.6， 1.2 g·kg-1） of Huangliansan oil， and water extract group （0.6 g·kg-1） of Huangliansan. In addition to the normal group， DNCB was applied on the back of mice in other groups to establish the AD model. On the 15th day after DNCB stimulation， each group was given the corresponding drug or solvent， and the changes in skin lesions， dermatitis score， and frequency of scratching were observed and recorded. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the skin and spleen. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA levels of filaggrin （FLG）， lorophane （LOR）， and involucrin （IVL） in skin， as well as immunoglobulin E （lgE）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interferon-γ （IFN-γ） in spleen. ResultCompared with the normal group， the model group showed symptoms of skin swelling and scab， and the score of dermatitis， the frequency of scratching， and the spleen index were increased （P<0.05）. The expression levels of FLG， LOR， and IVL in skin tissue were significantly decreased （P<0.01）， and the mRNA expressions of IgE， IL-4， IL-6， IL-1β， and TNF-α in the spleen were significantly increased， while the expression level of IFN-γ was significantly decreased （P<0.01）. Compared with the model group， the symptoms of skin erythema， scaly， and scab of mice in each drug group were alleviated to varying degrees， and the score of dermatitis， the frequency of scratching， and the spleen index were decreased （P<0.05， P<0.01）. In addition， the expression levels of FLG， LOR， and IVL in the skin of mice in the drug group were increased （P<0.05， P<0.01）， and the mRNA expression of IgE， IL-4， IL-6， IL-1β， and TNF-α in spleen were decreased. IFN-γ was increased （P<0.05， P<0.01）， and the lesions of the skin and spleen were improved to varying degrees. The medium-dose group of Huangliansan oil and hydrocortisone group had the most obvious manifestations （P<0.05， P<0.01）. The indexes in the medium-dose group of Huangliansan oil were better than those in the water extract group of Huangliansan. ConclusionHuangliansan may improve the expression level of skin barrier protein， inhibit the expression of helper T cell 2 （Th2）-related inflammatory factors， increase the expression of helper T cell 1 （Th1） inflammatory factors， restore the skin barrier function and Th1/Th2 balance in the spleen， regulate the inflammatory response in the spleen of AD mice， and thus relieve AD. Huangliansan oil is more effective than water extract.

Effects of oxycodone hydrochloride and dezocine on hemodynamics and levels of inflammatory factors in patients receiving gynecological laparoscopic surgery under general anesthesia

Abstract We aimed to compare the effects of oxycodone hydrochloride and dezocine on hemodynamics and inflammatory factors in patients receiving gynecological laparoscopic surgery under general anesthesia. A total of 246 patients were divided into group A and B (n=123). Hemorheology indices were recorded 5 min after anesthesia (T0), 1 min after pneumoperitoneum (T1), when position was changed 5 min after pneumoperitoneum (T2), 15 min after pneumoperitoneum (T3), 1 min (T4) and 5 min (T5) after position was restored. Visual analogue scale scores 1, 2, 6, 12, 24 and 48 h after operation were recorded. Postoperative adverse reactions and visceral pain were observed. The expression levels of inflammatory factors were detected by enzyme-linked immunosorbent assay 12 h after operation. Compared with group A, group B had higher heart rate and mean arterial pressure at T2, lower central venous pressure and cardiac output at T1-T3, and higher systemic vascular resistance at T1-T5 (P<0.05). The incidence rate of pain syndrome in group A was lower (P<0.05). Group A had lower tumor necrosis factor-alpha and interleukin-6 expression levels and higher interleukin-10 level than those of group B (P<0.05). For gynecological laparoscopic surgery, oxycodone preemptive analgesia has superior outcomes to those of dezocine

Functional study of Zinc in regulating M1 polarization of tumor associated macrophages during radical resection of lung cancer / 中华胸心血管外科杂志

Objective:To explore the molecular mechanism of zinc donor regulating macrophage polarization, and to explore the correlation between serum zinc content and the clinical index during radical resection of lung cancer.Methods:One hundred and thirty-two patients who undergoing radical resection of lung cancer were enrolled in this study. The serum zinc content was detected by atomic absorption spectrophotometry before operation. The patients were allocated into high-Zn group and low-Zn group. The blood samples of the included subjects were collected before operation (before), immediately after operation (POP1) and 6 hours after operation (POP2), and the plasma high-sensitivity C-reactive protein (hs-CRP) and catalase were detected. The correlation between serum zinc content and clinical features were analyzed. Metrological statistics was performed by using t test or Mann- Whitney test, and counting statistics was performed by χ2 test. Results:The POP1-hs-CRP[(1.69±0.66)mg/L vs. (1.99±0.43)mg/L, POP2-hs-CRP[(3.51±1.01)mg/L vs. (4.59±0.78)mg/L] and other indicators of high-Zn group were significantly lower than those of low-Zn group.Conclusion:There is a negative correlation between serum zinc content and the inflammation during radical resection of lung cancer, suggesting that appropriate zinc supplementation has a protective effect on radical resection of lung cancer patients.

Construction and evaluation of a prognostic model for severe acute pancreatitis based on CT scores and inflammatory factors / 中华危重病急救医学

Objective:To construct a prognostic model for severe acute pancreatitis (SAP) based on CT scores and inflammatory factors, and to evaluate its efficacy.Methods:128 patients with SAP diagnosed admitted to the First Hospital Affiliated to Hebei North College from March 2019 to December 2021 were enrolled and given Ulinastatin combined with continuous blood purification therapy. The levels of C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-8), tumor necrosis factor-α (TNF-α), and D-dimer were measured before and on the third day of treatment. An abdominal CT was performed on the third day of treatment to assess the modified CT severity index (MCTSI) and extra-pancreatic inflammatory CT score (EPIC). Patients were divided into the survival group ( n = 94) and the death group ( n = 34) according to the 28-day survival prognosis after admission. The risk factors for the SAP prognosis were analyzed using Logistic regression, which was then used to build nomogram regression models. The value of the model was evaluated using the concordance index (C-index), calibration curves and decision curve analysis (DCA). Results:Before treatment, the levels of CRP, PCT, IL-6, IL-8 and D-dimer in the death group were higher than those in the survival group. After treatment, the levels of IL-6, IL-8 and TNF-α in the death group were higher than those in the survival group. MCTSI and EPIC scores in the survival group were lower than those in the death group. Logistic regression analysis shows that, pre-treatment CRP > 140.70 mg/L, D-dimer > 2.00 mg/L, and post-treatment IL-6 > 31.28 ng/L, IL-8 > 31.04 ng/L, TNF-α > 31.04 ng/L, and MCTSI > 8 points were all independent risk factors for SAP prognosis [odds ratios ( OR) and 95% confidence intervals (95% CI) were 8.939 (1.792-44.575), 6.369 (1.368-29.640), 8.546 (1.664-43.896), 5.239 (1.108-24.769), 4.808 (1.126-20.525), 18.569 (3.931-87.725), all P < 0.05]. Model 1 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α) had a lower C-index than that model 2 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI; 0.988 vs. 0.995). The mean absolute error (MAE) and mean square error (MSE) of model 1 (0.034, 0.003) were higher than those of model 2 (0.017, 0.001). When the threshold probability was in the range of 0-0.66 or 0.72-1.00, the net benefit of model 1 was lower than that of model 2. When the threshold probability was in the range of 0.66-0.72, the net benefit of model 1 was higher than that of model 2. In addition, model 2 had a higher C-index than acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) and bedside index of acute pancreatitis severity (BISAP, 0.995 vs. 0.833, 0.751). Model 2 had a lower MAE (0.017) and MSE (0.001) than APACHEⅡ (0.041, 0.002). Model 2 had a lower MAE than BISAP (0.025). Model 2 had a higher net benefit than both APACHEⅡ and BISAP. Conclusion:The prognostic assessment model of SAP consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI has high discrimination, precision and clinical application value, and is superior to APACHEⅡ and BISAP.

Effect of Compound Duzhong Jiangu Granules on joint function, quality of life and inflammatory factors in patients with Kashin-Beck disease / 中华地方病学杂志

Objective:To study the effect of Compound Duzhong Jiangu Granules on joint function, quality of life and inflammatory factors in patients with Kashin-Beck disease.Methods:By group design, 135 patients with Kashin-Beck disease in Chongxin County, Pingliang City, Gansu Province, were selected and divided into intervention group (100 cases treated with Compound Duzhong Jiangu Granules, 12 g/bag, 1 bag/time, 3 times/day, treatment for 1 month) and control group (35 cases treated with ibuprofen, 0.3 g/capsule, 1 capsule/time, 2 times/day, treatment for 2 weeks) according to the randomized, single-blind principle. The changes of joint dysfunction index score, joint function improvement rate, total scores of Kashin-Beck disease quality of life (KBDQOL) and scores of each dimension were analyzed before treatment, 1 month and 3 months after treatment. The serum levels of interleukin-6 (IL-6), nuclear factor κB (NFκB)-p65, inducible nitric oxide synthase (NOS2), nitric oxide (NO), and prostaglandin E2 (PGE2) were detected by enzyme-linked immunosorbent assay before treatment and 1 month after treatment.Results:The total scores of joint dysfunction index of the intervention group and the control group 1 month after treatment and 3 months after treatment were lower than those before treatment, but 3 months after treatment was higher than 1 month after treatment ( P < 0.001). One month after treatment, the total effective rates of joint function improvement in the intervention group and the control group were 68.00% (68/100) and 54.55% (18/33), respectively; 3 months after treatment, the total effective rates of the intervention group and the control group were 36.00% (36/100) and 39.39%(13/33), respectively. The total scores and scores of each dimension of KBDQOL were not significant for the main effect of the group ( P > 0.05), but significant for the main effect at the time point ( P < 0.05), and there was no interactive effect ( P > 0.05). There were significant differences in the scores of social support and mental status dimensions in the intervention group at different time points ( P < 0.001). And in the intervention group, the total score, the scores of physical function, activity limitation, economy and overall health dimensions were statistically significant between before treatment and 1 month after treatment, 1 month after treatment and 3 months after treatment( P < 0.05); however, there was no significant difference between before treatment and 3 months after treatment ( P > 0.05). One month after treatment, the serum PGE2 levels of both groups were decreased ( P < 0.05), and there was no difference in other inflammatory factors at different groups and time points ( P > 0.05). Conclusion:Compound Duzhong Jiangu Granules can effectively inhibit the inflammatory reaction of patients with Kashin-Beck disease, promote the improvement of joint function and improve the quality of life in various aspects.

Preliminary study on the mechanism of dexmedetomidine regulating lncRNA HOTAIR to improve lung injury in septic mice / 中华急诊医学杂志

Objective:To investigate the mechanism of dexmetomidine (DEX) in improving lung injury in septic mice.Methods:Male C57BL/6 mice were randomly assigned to the blank group (NC), sham operation group (sham), cecal ligation and puncture group (CLP), and Dex treatment group (CLP+DEX), 36 mice per group. Mice in the CLP group were intraperitoneally injected with 1 mL sterile saline 15 min before CLP, and mice in the CLP + DEX group were intraperitoneally injected with 50 μg/kg DEX 15 min before CLP. The survival rate was recorded within 24 h after CLP. The mice were sacrificed at 0, 3, 6, 12, and 24 h after CLP, and lung tissues were collected. The expression levels of cytokines (IL-6, IL-1β, TNF-α) and lncRNA-HOTAIR in the lung of mice were detected by qPCR. RAW264.7 cell were cultured in vitro, LPS (100 ng/mL) and DEX (1 μ mol/L) were used to establish a cell model for studying the mechanism of Dex, and the expression of cytokines (IL-6, IL-1β, TNF-α) and lncRNA-HOTAIR in RAW264.7 cell model were detected by qPCR. In addition, the effect of lncRNA-HOTAIR on sepsis was explored in vivo and in vitro by knockdown or overexpression of HOTAIR.Results:The survival rate of the CLP+DEX group was higher than that of the CLP group within 24 h after surgery, and the levels of IL-6, IL-1β, and TNF-α in the lungs were significantly lower than those in the CLP group at 6, 12, and 24 h after surgery ( P<0.05). In addition, the level of lncRNA HOTAIR showed that the expression level of lncRNA HOTAIR in the lungs of mice were decreased after Dex treatment, and were decreased 1.1 times ( P<0.05), 4.0 times ( P<0.01) and 3.8 times ( P<0.01) at 6, 12, and 24 h, respectively. Compared with the NC group, knockdown of HOTAIR significantly decreased the levels of IL-1β, IL-6, and TNF-α in septic mice ( P<0.05), and overexpression of HOTAIR significantly increased the levels of IL-1β, IL-6, and TNF-α in septic mice ( P<0.01). Conclusions:DEX can reduce the production of inflammatory factors in the lungs of septic mice and improve the survival rate of septic mice. The mechanism may be related to the inhibition of HOTAIR expression.

Induced pluripotent stem cell-derived exosome attenuates the inflammatory response in microglia / 中华急诊医学杂志

Objective:To investigate the effects of induced pluripotent stem cell-derived exosome (iPSC-Exo) on releasing inflammatory factors from microglia induced by lipopolysaccharide (LPS).Methods:iPSC derived from the tubular epithelial cells of sepsis encephalopathy patients were resuscitated and cultured. The iPSC-Exo was isolated by low-temperature ultracentrifugation and analyzed by transmission electron microscopy, Western blot and high sensitivity flow cytometry (HSFCM). Based on the concentration of iPSC-Exo, human microglia line HMO6 cells activated by LPS (100 ng/mL) were divided into four groups randomly: LPS+ phosphate buffer solution (PBS) group, LPS+iPSC-Exo 10 5 group, LPS+iPSC-Exo 10 6 group and LPS+iPSC-Exo 10 7 group. The control group was added equal PBS but not LPS. After culture for 24 h, the concentrations of malondialdehyde in cells were detected. Quantitative RT-PCR was used to measure the mRNA expression levels of macrophage inflammatory protein 2 (MIP2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in the cells and enzyme-linked immunosorbent assay (ELISA) was used to assess the concentration of these cytokines in the supernatant. Under the same concentration of iPSC-Exo, one-way ANOVA and SNK- q test were used for comparison between groups. Results:The extracts showed spherical membrane structure by transmission electron microscopy. HSFCM showed the mean diameter of the extracts was (74.66±15.60) nm and the concentration around 2.98×10 10/mL. Western blot analysis showed high expression of exosome markers CD63, Alix and TSG101, but not GM130. Intracellular MDA concentration and mRNA expression levels and protein concentration of MIP2, TNF-α, IL-1β and IL-6 in the LPS+PBS group were significantly higher than those in the control group (all P<0.01). With the increase of iPSC-Exo concentration, the intracellular MDA concentration decreased gradually ( P<0.01), the mRNA expression levels of inflammatory factors showed a gradual downward trend (all P<0.05). Each inflammatory cytokine in the supernatant declined in a manner that was almost consistent with mRNA. Concentrations of MDA remained constant in the control group. Conclusions:iPSC-Exo derived from the tubular epithelial cells of sepsis encephalopathy patients alleviate oxidative stress and inflammation effect of microglia induced by LPS, and the modulatory effect is dose-dependent.

Clinical study of self-made Xingqi Jiedu Decoction combined with goserelin in the treatment of endometriosis / 国际中医中药杂志

Objective:To evaluate the curative effect of self-made Xingqi Jiedu Decoction combined with goserelin for endometriosis (EMT).Methods:Randomized controlled trial. A total of 84 patients with EMT in the hospital were enrolled as observation objects between July 2019 and July 2021. According to random number table method, they were divided into the control group (subcutaneous injection of goserelin) and the observation group (self-made Xingqi Jiedu Decoction on basis of control group), 42 in each group. All were treated for 6 months. TCM syndromes were scored before and after treatment. The severity of pelvic pain was evaluated by VAS. The levels of FSH, LH and estradiol (E 2) were detected by full-automatic chemiluminescence immunoassay and corresponding reagents, and levels of serum IL-1β, IL-8 and TNF-α were detected by ELISA. The adverse events were recorded, and clinical curative effect was evaluated. Results:The differences in total response rate between observation group and control group was statistically significant [95.24% (40/42) vs. 80.95% (34/42); χ2=4.09, P=0.043]. After treatment, scores of TCM syndromes and VAS in observation group were significantly lower than those in the control group ( t=14.30, 7.32, P<0.01). After treatment, FSH [(5.36±1.03) U/L vs. (6.20±1.35) U/L, t=3.21], E 2[(230.57±36.84) pmol/L vs. (265.28±37.53) pmol/L, t=4.28] and LH [(8.15±1.18) U/L vs. (9.24±2.01) U/L, t=3.03] in the observation group were significantly lower than those in the control group ( P<0.01). The levels of IL-1β, IL-8 and TNF-α in the observation group were significantly lower than those in the control group ( t=5.05, 5.07, 3.82, P<0.01). During treatment, differences in incidence of adverse reactions between observation group and control group was statistically significant [19.05% (8/42) vs. 4.76% (2/42); χ2=4.09, P=0.043]. Conclusion:The self-made Xingqi Jiedu Decoction combined with goserelin can improve hormone level, inhibit inflammatory response and improve clinical curative effect in EMT patients.

Research progress on mechanism of epithelial mesenchymal transition induced by chrysotile exposure / 环境与职业医学

As a mineral material widely used in life, chrysotile is a public health concern for its fibrogenicity and carcinogenicity. Currently, more than 50 countries have completely banned the import and use of chrysotile, but China is still the world's largest consumer and second largest producer of chrysotile, with a large occupationally exposed population. Investigations have shown that chrysotile miners are significantly more likely to develop pulmonary fibrosis, lung cancer, and mesothelioma than workers in other occupations. Chrysotile-induced cancers generally have a decades-long latency period and are difficult to diagnose and treat in a timely manner. Therefore, the cancer fatality due to chrysotile exposure is significant and is a leading contributor to occupational cancer death. Epithelial mesenchymal transition is a key step in the biological processes of chronic inflammation, fibrosis, carcinogenesis, and cancer metastasis in tissues and organs, also plays an important role in pulmonary fibrosis, lung cancer, and other diseases due to chrysotile exposure. This paper summarized the mechanisms of chrysotile inducing epithelial interstitial transition from dynamics of inflammatory factors, mitogen-activated protein kinase pathways, oxidative stress, and other biological pathways, and proposed possible research directions for further study on chrysotile-induced epithelial mesenchymal transition, aiming to provide a reliable basis and reference for in-depth research on pulmonary fibrosis, lung cancer, and other diseases due to chrysotile exposure.

Protective effects and mechanism of Dachengqi decoction on intestinal septic mice / 中国药房

OBJECTIVE To study the protective effects of Dachengqi decoction （DCQD） on intestinal septic mice， and to explore the possible mechanisms from the Toll-like receptor 4（TLR4）/myeloid differentiation factor 88（MyD88） signaling pathway. METHODS The SPF male C57BL/6J mice were randomly divided into Sham group， Sham+DCQD-H group， model （CLP） group， DCQD-L group， DCQD-H group and Positive group. The model of intestinal sepsis was established by cecal ligation and puncture in CLP group， DCQD-L group， DCQD-H group and Positive group. Three days before the operation and seven days after the operation， DCQD-L group and DCQD-H group were given DCQD intragastrically at 4， 8 g/kg （calculated by crude drug）， respectively. Positive group was given ulinastatin intraperitoneally 2 h before operation and 7 d after the operation （at 50 000 U/kg）. In Sham group and Sham+DCQD-H group， only cecum of mice was exposed without ligation and puncture. Sham+DCQD- H group was given DCQD intragastrically （8 g/kg，calculated by crude drug） 3 days before the operation and 7 days after the operation. Both the Sham group and CLP group were given normal saline 0.2 mL intragstrically and intraperitoneally each day， for 10 consecutive days. After the operation， the severity of sepsis was assessed， and the 7 d survival rate of mice was assessed. One hour after the last medication， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum and ileum of mice were determined； the pathological and morphological changes of mice’s liver， lung， kidney and ileum were observed； mRNA expressions of the TLR4 and MyD88 in ileum were tested. RESULTS Compared with CLP group， sepsis score， the levels of TNF-α and IL-6 in serum and ileum （except for IL-6 in ileum of DCQD-L group）， damage score of the liver， lung， kidney and ileum， mRNA expressions of TLR4 and MyD88 in ileum were all decreased significantly in DCQD-L group and DCQD-H group （P＜0.05 or P＜0.01）， while 7 d survival rate （except for DCQD-L group） was increased significantly （P＜0.05）. The damage to liver tissue in mice was significantly improved， and inflammation infiltration and apoptosis were reduced； lung tissue damage had been alleviated， with varying degrees of improvement in alveolar atrophy， bleeding and edema； the renal tissue damage was improved and weakened dilation of renal tubular lumen was weakened； the damage and edema of ileal tissue were significantly improved. CONCLUSIONS DCQD may exert a protective role on intestinal septic model mice. The mechanism may be related to the inhibition of systemic inflammation， the reduction of multiple organ damage， and down-regulation of TLR4/MyD88 signaling pathway.

Protective Effects of Zhi Ciweipi Water Extracts on Dextran Sulfate Sodium Salt⁃Induced Ulcerative Colitis in Mice / 中国生物化学与分子生物学报

Ulcerative colitis (UC) is a disease characterized by chronic inflammation of the intestinal mucosa. However, its exact pathogenesis is not fully understood. Zhi Ciweipi (ZCWP), as a traditional Chinese medicine (TCM), has demonstrated suitable anti-inflammatory effects in the treatment of patients with bloody stool and hemorrhoids. However, its therapeutic effects on ulcerative colitis have yet to be investigated in depth. The aim of this study was to investigate the protective effect of the aqueous extract of ZCWP against dextran sulfate sodium salt (DSS)-induced ulcerative colitis in mice and its possible mechanism of action. Successful simulation of ulcerative colitis was achieved by providing mice with drinking water containing 3% DSS. The HE staining results revealed that the aqueous extract of ZCWP could significantly reduce DSS-induced colonic injuries. Transcriptome sequencing analysis identified 10 key inflammation-related genes (IL⁃6, IL⁃1β, CSF2, TNF, IL10, IFN⁃γ, CXCL1, CXCL2, CXCL9, CXCL10), all of which were significantly downregulated (P<0. 05) in response to treatment with the aqueous extract of ZCWP according to qRT-PCR and Western blotting analyses. The immunofluorescence results further indicated that the aqueous extract of ZCWP was able to reduce the DSS-induced increase in the proportion of M1-type macrophages in the colon. Using single-cell sequencing, we thoroughly investigated the signaling relationships between different cell types, which revealed particularly strong communication between M1-type macrophages and fibroblasts. Subsequent qRT-PCR and Western blot analyses verified that the aqueous extract of ZCWP significantly downregulated the expression of DSS-induced fibrosis-related genes in colonic tissues (P<0. 05). In conclusion, the results of this study suggest that the aqueous extract of prepared ZCWP exerts a protective effect against DSS-induced ulcerative colitis by inhibiting M1-type macrophage polarization, downregulating the expression of inflammatory factors, and preventing strong communication between M1-type macrophages and fibroblasts. These findings not only reveal the therapeutic mechanism by which ZCWP aqueous extract treats colitis, but also provide a new theoretical basis for its application in clinical practice.

Effects of estradiol on depressive-like behavior of ovariectomized rats and its possible mechanism / 解剖学报

Objective To examine the effect of estradiol (E2) treatment on ovariectomy (OVX) induced depressive-like behavior and possible mechanism by measuring inflammatory biomarkers levels oi interleukin-6 (IL-6) and tumor necrosis tactor-(x (TNF-ot) and brain-derived neurotrophic factor (BDNF) expression in amygdaia nucleus. Methods Thirty nine healthy aduit 缶male SD rats were randomly divided into three groups : sham operation group (SO), ovariectomized group (OVX) and ovariectomized estradiol treatment group (OVX + E2). After 6 weeks of E2 treatment, depressive like behavior was evaluated by opening field test (OFT) and sugar water preference test (SPT). The levels of inflammatory factors IL-6 and TNF-a in amygdala were measured by ELESA, and the expression of BDNF in rat amygdala was detected by immunohistochemical staining. Results The result of the SPT showed that OVX significantly decreased the sugar intake and sugar preference rate of rats, and E2 treatment significantly increased sugar water intake and sugar water preference rate of rats. The result of the OFT showed that OVX significantly decreased the numbers of crossing and rearing of rats, and reduced the time spent in the centre ; E2 treatment significantly increased the numbers of crossing and rearing of rats, and prolonged the time spent in the centre. ELESA and immunohistochemical analysis found the levels of IL-6 and TNF-a in amygdala increased significantly, while the average absorbance (AA) of BDNF in the amygdala reduced significantly (P<0.01 respectively) of rats in OVX group when compared with the SO group. And the levels of IL-6 and TNF-a in amygdala decreased significantly (P<0.01 respectively), while the A4 of BDNF increased significantly (P< 0.05) in the amygdala of rats in the OVX+EX group when compared with the OVX group. The difference was statistically significant. Conclusion E2 treatment improved depression-like behavior of OVX rats is partly due to increased antiinflammatory and activated the BDNF expression in amygdaloid nucleus, thus enhancing the neuroprotective effect of OVX rats.

Study on the improvement of Qingdaipowder Gel for external use on mice with specific dermatitis / 中国临床药理学与治疗学

AIM: To study the effect of Qingdaipowder Gel (QDPG) on mice specific dermatitis (AD) model and the antibacterial effect of the ethanol extract of Qingdaipowder. METHODS: AD model of mice was established by repeated skin induction with 2,4-dinitrochlorobenzene (DNCB). Fifty-six mice were randomly divided into blank group, model group, Hydrocortisone Butyrate Cream group (Hyd, 1.5 mg/cm

Effect of gingival stem cells-derived exosomes on interlukin (IL)-6 and tumor necrosis factor (TNF)-α expression in rats with periodontitis / 预防医学

Objective @#To evaluate the effect of gingival stem cells-derived exosomes (GMSC-Exos) treatment on the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in rats with periodontitis, so as to provide the evidence for periodontitis treatment.@*Methods@#Forty specific pathogen-free (SPF) rats at ages of 8 weeks were randomly divided into 4 groups, including the blank group, periodontitis group, GMSC-Exos group and PBS group. Rats in the periodontitis group, GMSC-Exos group and PBS group were modeled for periodontitis using the ligature method. Rats in the blank group and periodontitis group were given no treatment, while rats in the GMSC-Exos group and PBS group were given 20 μL GMSC-Exos and PBS by injection, respectively. The periodontal index was measured in all rats 4 weeks post-treatment, and the TNF-α and IL-6 levels were measured in rat serum samples using enzyme-linked immunosorbent assay (ELISA). The TNF-α and IL-6 gene expression was quantified using the polymerase chain reaction (PCR) assay in the gingival tissues of the rat left upper maxillary area, and the periodontal tissues in the left upper maxillary areas were sampled for pathological examinations. Periodontal clinical indexes, IL-6 and TNF-α levels were compared in each group.@*Results@#The gingival sulcus bleeding index, gingival index, probing depth, and plaque index in the GMSC-Exos group (1.87±0.41, 1.03±0.19, 1.91±0.09 and 1.11±0.17) were higher than those in the blank group (0.96±0.31, 0.83±0.31, 1.09±0.05 and 1.01±0.38), but lower than those in the periodontitis group (2.65±0.50, 1.36±0.22, 2.61±0.07 and 1.51±0.26) and PBS group (2.44±0.50, 1.23±0.20, 2.49±0.10 and 1.39±0.28) (all P<0.05). The serum IL-6 and TNF-α levels in the GMSC-Exos group [(205.97±11.47) and (90.11±8.57) pg/mL] were higher than those in the blank group [(143.10±4.87) and (80.07±5.13) pg/mL], but lower than those in the periodontitis group [(367.33±13.89) and (158.29±13.10) pg/mL] and PBS group [(364.23±13.62) and (140.60±11.73) pg/mL] (all P<0.05). The IL-6 and TNF-α mRNA expression in the rat gingival tissues in the GMSC-Exos group (1.09±0.14 and 1.61±0.29) was higher than that in the blank group (0.99±0.10 and 1.06±0.14), but lower than that in the periodontitis group (1.63±0.09 and 3.63±0.26) and PBS group (1.58±0.11 and 3.79±0.32) (all P<0.05). Pathological examinations showed alleviation of periodontal tissue destruction, inflammatory cell infiltration and alveolar bone resorption, and no obvious root dental root regeneration in the junctional combined epithelium in the GMSC-Exos group relative to the periodontitis group and the PBS group. @*Conclusion@#Administration of GMSC-Exos may reduce periodontal inflammation and alveolar bone resorption by inhibiting IL-6 and TNF-α expression in rats with periodontitis.

Effects of acupuncture on neurologic function and serum inflammatory factors after thrombolysis in acute ischemic stroke / 中国针灸

OBJECTIVE@#To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS).@*METHODS@#A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups.@*RESULTS@#After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05).@*CONCLUSION@#Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.