BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

Neural oscillatory changes play a critical role in pain and analgesia research. Previous studies on pain-related neural oscillations have primarily utilized electroencephalogram (EEG) power spectral analysis, revealing a strong correlation between alpha ( α) power and subjective pain perception. However, alpha power may be influenced by the baseline of the power spectrum, making it difficult to accurately capture the true changes in alpha oscillations. This study employed power spectral analysis and further applied a power spectral parameterization method, which decomposed the power spectrum into periodic and aperiodic components, to compare EEG α power in 50 primiparous women who underwent severe pain during the first stage of labor before and after epidural analgesia. The results indicated no significant differences in α power between pre- and post-analgesia conditions. However, following power spectral parameterization, the aperiodic component of the EEG significantly decreased after analgesia, whereas the periodic component of α power showed a significant increase. This study not only validates the effectiveness and validity of the power spectral parameterization method in analgesia research but also uncovers the differential regulatory mechanism by which analgesia modulates the periodic and aperiodic components of α oscillations.
Humans ; Electroencephalography/methods* ; Female ; Adult ; Alpha Rhythm ; Pregnancy ; Young Adult ; Analgesia, Epidural

Objective:To investigate the risk factors of the occurrence of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis and the effect of proton pump inhibitor (PPI) on OHE.Methods:This study was led by the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) and Shanghai East Hospital of Tongji University School of Medicine, and a total of 13 hospitals participated. From July 31, 2020 to December 10, 2021, a total of 184 liver cirrhosis patients without prior OHE and with ≥2-year follow-up from the above 2 leading hospitals, and other hospitals such as Guangzhou Eighth People′s Hospital of Guangzhou Medical University and Affiliated Hospital of Zunyi Medical University were enrolled. According to whether OHE occurred during the 2-year follow-up period, the 184 patients were divided into OHE group (22 cases) and non-OHE group (162 cases). The clinical data of all the patients were collected, including the laboratory parameters such as international normalized ratio (INR), the usage of PPI, the occurrence of gastrointestinal bleeding, infection, liver cancer and other complications, and survival status. Multivariate logistic regression model was used to analyze the independent risk factors for OHE in patients with liver cirrhosis. Kaplan-Meier survival curve was performed to analyze the effect of PPI on the survival rate of patients with liver cirrhosis. Chi-square test and Cochran-Mantel-Haenszel test were used for statistical analysis.Results:The result of multivariate logistic regression analysis showed that INR ( OR=11.331, 95% confidence interval (95% CI) 2.415 to 53.156, P =0.002) and PPI ( OR=6.794, 95% CI 2.359 to 19.567, P<0.001) were independent risk factors for OHE in patients with liver cirrhosis. The rate of PPI usage of the OHE group was higher than that of the non-OHE group (72.7%, 16/22 vs. 30.9%, 50/162), and the difference was statistically significant ( χ2=14.76, P<0.001). After the patients with gastrointestinal bleeding, infection and liver diseases-related deaths were excluded respectively, the rates of PPI usage of the OHE group were still higher than that of the non-OHE group (8/12 vs. 21.3%, 27/127; 11/16 vs. 25.0%, 35/140; 12/15 vs. 29.0%, 45/155), and the differences were all statistically significant ( χ2=9.71, 11.20 and 15.94; all P<0.01). Kaplan-Meier survival curve analysis showed that the 2-year cumulative survival rate of liver cirrhosis patients with PPI usage was lower than that of the patients without PPI usage (86.4%, 57/66 vs. 95.8%, 113/118), and the difference was statistically significant ( χ2=5.37, P =0.020). Conclusion:PPI is an independent risk factor for OHE in patients with liver cirrhosis, and may increase the risk of liver disease-related death.

Objective:To investigate the risk factors of the occurrence of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis and the effect of proton pump inhibitor (PPI) on OHE.Methods:This study was led by the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) and Shanghai East Hospital of Tongji University School of Medicine, and a total of 13 hospitals participated. From July 31, 2020 to December 10, 2021, a total of 184 liver cirrhosis patients without prior OHE and with ≥2-year follow-up from the above 2 leading hospitals, and other hospitals such as Guangzhou Eighth People′s Hospital of Guangzhou Medical University and Affiliated Hospital of Zunyi Medical University were enrolled. According to whether OHE occurred during the 2-year follow-up period, the 184 patients were divided into OHE group (22 cases) and non-OHE group (162 cases). The clinical data of all the patients were collected, including the laboratory parameters such as international normalized ratio (INR), the usage of PPI, the occurrence of gastrointestinal bleeding, infection, liver cancer and other complications, and survival status. Multivariate logistic regression model was used to analyze the independent risk factors for OHE in patients with liver cirrhosis. Kaplan-Meier survival curve was performed to analyze the effect of PPI on the survival rate of patients with liver cirrhosis. Chi-square test and Cochran-Mantel-Haenszel test were used for statistical analysis.Results:The result of multivariate logistic regression analysis showed that INR ( OR=11.331, 95% confidence interval (95% CI) 2.415 to 53.156, P =0.002) and PPI ( OR=6.794, 95% CI 2.359 to 19.567, P<0.001) were independent risk factors for OHE in patients with liver cirrhosis. The rate of PPI usage of the OHE group was higher than that of the non-OHE group (72.7%, 16/22 vs. 30.9%, 50/162), and the difference was statistically significant ( χ2=14.76, P<0.001). After the patients with gastrointestinal bleeding, infection and liver diseases-related deaths were excluded respectively, the rates of PPI usage of the OHE group were still higher than that of the non-OHE group (8/12 vs. 21.3%, 27/127; 11/16 vs. 25.0%, 35/140; 12/15 vs. 29.0%, 45/155), and the differences were all statistically significant ( χ2=9.71, 11.20 and 15.94; all P<0.01). Kaplan-Meier survival curve analysis showed that the 2-year cumulative survival rate of liver cirrhosis patients with PPI usage was lower than that of the patients without PPI usage (86.4%, 57/66 vs. 95.8%, 113/118), and the difference was statistically significant ( χ2=5.37, P =0.020). Conclusion:PPI is an independent risk factor for OHE in patients with liver cirrhosis, and may increase the risk of liver disease-related death.

Objective: To explore the possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus 2019-nCov pneumonia by systematically review earlier coronavirus studies. Methods: Systematically retrieve relevant clinical studies from Chinese and English databases such as CNKI,VIP, Wangfang Data,CBM,PubMed, Web of Science,EMBASE. In addition, information from Chinese bio-medical journals, WHO, US CDC, Chinese CDC websites and the references from published relevant articles were retrieved. The inclusion period is from January 2003 to January 24, 2020. The criteria for inclusion are: (1) studies that aim to compare LPV/r and placebo/standard for SARS, MERS; (2) studies that include at least one clinical outcome; (3) studies with diagnosis criteria meeting WHO requirement on SARS or MERS; (4) data from multiple reports but originated from one study, where we extract information from all reports; (5) guidelines, includes: national or academic guidelines/experts 'consensus. The exclude criteria are: 1) only have abstracts but no full information; 2) in vitro studies. Two reviewers independently review articles and extract data on study design, patients, diagnosis criteria, regimen, and clinical outcomes (mortality, morbidity, quality of life, steroids dosage, chest image and adverse responses). Results: Two hundred and thirty potential article were found by screening, and narrow down to forty-four articles for evaluation and finally four studies were included. The results of included studies indicate the early use of LPV/r regimen can reduce the mortality of SARS and MERS, and reduce steroids dosing. Conclusions ILPV/r can be used as a component of experimental regimen for treat 2019-nCoV pneumonia. It strongly suggests that initiating real world studies to explore the true clinical effects of LPV/r on 2019-nCoV patients.

Objective:To explore the possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus 2019-nCov pneumonia by systematically review earlier coronavirus studies.Methods:Systematically retrieve relevant clinical studies from Chinese and English databases such as CNKI,VIP, Wangfang Data,CBM,PubMed, Web of Science,EMBASE. In addition, information from Chinese biomedical journals, WHO, US CDC, Chinese CDC websites and the references from published relevant articles were retrieved. The inclusion period is from January 2003 to January 24, 2020. The criteria for inclusion are: (1) studies that aim to compare LPV/r and placebo/standard for SARS, MERS; (2) studies that include at least one clinical outcome; (3) studies with diagnosis criteria meeting WHO requirement on SARS or MERS; (4) data from multiple reports but originated from one study, where we extract information from all reports; (5) guidelines, includes: national or academic guidelines/experts 'consensus. The exclude criteria are: 1) only have abstracts but no full information; 2) in vitro studies. Two reviewers independently review articles and extract data on study design, patients, diagnosis criteria, regimen, and clinical outcomes (mortality, morbidity, quality of life, steroids dosage, chest image and adverse responses).Results:Two hundred and thirty potential article were found by screening, and narrow down to forty-four articles for evaluation and finally four studies were included. The results of included studies indicate the early use of LPV/r regimen can reduce the mortality of SARS and MERS, and reduce steroids dosing.Conclusions:ILPV/r can be used as a component of experimental regimen for treat 2019-nCoV pneumonia. It strongly suggests that initiating real world studies to explore the true clinical effects of LPV/r on 2019-nCoV patients.

Objective To observe the solo-allied expression of Survivin, Smad4/dpc4 and APC gene, and study the relationship between the three genes and biological behavior of colorectal cancer. Methods The expressions of Survivin, Smad4/dpc4 and APC gene were detected by SP immunohistochem-istry among the cases from 40 eu-intestine ,80 large intestinal adenoma and 80 CRC. Results The positive rate of survivin protein in the eu-intestine, the large intestinal adenoma and CRC was 0,35.0% ,75.0% , respectively. The positive rate of Smad4/dpc4 protein was 100% , 95. 0% , 78. 8% , and the positive rate of APC protein was 100% ,80.0% ,45.0% , respectively. In the eu-intestine, APC + Smad4/dpc4 Z- expressed in 40 cases, with the incidence of 100%. In the large intestinal adenoma, APC + Smad4 expressed in 38 patients, with the incidence of 47. 5% , and the three genes expressed in 29 patients with the incidence of 23. 8%. In the CRC, two genes expressed in 57 patients, with the incidence of 71. 3% , and three genes expressed in 28 patients, with the incidence of 35.0%. Conclusion The detection of survivin was a new indicator in early diagnosis of CRC. It was significant in the diagnosis of CRC that energetic search for the positive rate level realm of survivin. The catastrophe or absence of Smad4/dpc4 gene not only induced the genesis of CRC but also encouraged its growth. Smad4/dpc4 was ant- carcinomatous gene intimately correlated to the CRC. Detection of APC gene had very important significance, it could be helpful to conduct the research of tumorous aetiology, nosogenesis and early diagnosis. The allied detection of Survivin, Smad4/dpc4, APC gene played a very important role in early diagnosing and healing the CRC.

ObjectiveTo study the effect and mechanisms of nourishing Piyin Remedy (nPR) and bovine brain extract (bBE) on experimental spinal cord injury (SCI) of rat.Methods80 healthy SD rats were divided into 5 equal groups randomly: bBE group supplied through subarachnoid cavity, normal saline (NS) group supplied through subarachnoid cavity, nPR group, NS orally taken group, combined group. Animal models were made by Allen's equipment on T8～T9 segment. The spinal nerve function, somatosensory evoked potentials (SEP), retrograde and label technique of horseradish peroxidase, gross observation, histological and morphometric analysis were taken as the observed indices.ResultsThe values of observed indices of bBE group and nPR group improved evidently compared with their own control groups; that of combined group was prior to sole administration.ConclusionnPR can hold back the secondary SCI and accelerate the recovery of spinal nerve function; bBE can stimulate the improvement of injuried nerve fibers; the joint of nPR and bBE can make a synergic effect.