BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.

BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.

BACKGROUND:Acute liver injury can result from a variety of causes,and if not treated in time,it will develop into acute liver failure and seriously affect the life safety of patients.As the liver is the largest immune organ and metabolic organ,there is no optimal treatment for acute liver injury.The adipose tissue-derived mesenchymal stem cell has multi-differentiation potential and immunomodulatory activity,so it has been gradually becoming an effective tool for the treatment of acute liver injury.OBJECTIVE:To review the progress and molecular mechanism of adipose tissue-derived mesenchymal stem cell and its modification in different ways in the treatment of acute liver injury.METHODS:Relevant articles published from 2000 to 2023 were retrieved from PubMed,Web of Science,and CNKI databases.English search terms were"acute liver injury,liver injury,adipose tissue-derived mesenchymal stem cell,liver injury repair,stem cell transplantation,stem cell repair,cell surface engineering,stem cell modification."Chinese search terms were"acute liver injury,liver injury,adipose tissue-derived mesenchymal stem cell,liver injury repair,stem cell transplantation,stem cell repair,stem cell modification."Totally 62 articles of the latest research progress in this field were summarized and analyzed.RESULTS AND CONCLUSION:(1)Adipose tissue-derived mesenchymal stem cell as a potential stem cell with multi-directional differentiation has biological advantages in the treatment of acute liver injury.Compared with the other two major types of mesenchymal stem cell that is bone marrow mesenchymal stem cell and umbilical cord mesenchymal stem cell,they are more widely sourced,easily accessible and have fewer ethical issues,and more self-renewal than bone marrow mesenchymal stem cell.(2)Adipose tissue-derived mesenchymal stem cell may play a therapeutic role in acute liver injury by regulating immune responses,differentiating into hepatocytes,and secreting growth factors and exosomes.It can reduce the expression of inflammatory factors in serum and the infiltration of inflammatory cells in liver tissue,also can inhibit the pyroptosis and autophagy levels to promote regeneration of sinusoidal endothelial cells and hepatocyte,and ultimately improve liver damage.At present,no studies have shown which mechanism is the best mechanism for adipose tissue-derived mesenchymal stem cells to treat acute liver injury,and most opinions believe that these molecular mechanisms interact with each other to play a synergistic role in treatment.(3)Biomaterials modification and drug pretreatment can improve the efficacy of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury.On the one hand,biomaterials and drug modifications can enhance the functions of adipose tissue-derived mesenchymal stem cell,such as enhancing the ability of proliferation and migration,increasing the level of growth factors secreted,and enhancing the anti-inflammatory ability and promoting the survival of adipose mesenchymal stem cells at the injury site.On the other hand,biomaterials and drug modifications can inhibit the activation of inflammatory cells at the injured site and promote the growth of blood to improve the success rate of transplantation.(4)In summary,adipose tissue-derived mesenchymal stem cell plays an important role in the treatment of acute liver injury by secreting growth factors and exosomes,regulating the immune response,and promoting liver regeneration.With the development of science and technology,biomaterials and drug modification can enhance the self-renewal ability of adipose tissue-derived mesenchymal stem cell and improve the local microenvironment of acute liver injury.It provides a new way to promote the clinical application of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury.

Endoplasmic reticulum stress(ERS)plays a crucial role in cellular self-protection.In response to environmental changes,cells activate the unfolded protein response(UPR)and endoplasmic reticulum-associated protein degradation pathways to restore homeostasis.Increasing experimental evidence indicates that hypoxia and inflammation negatively impact synoviocytes in rheumatoid arthritis(RA),leading to the activation of three key endoplasmic reticulum transmembrane proteins:inositol-requiring enzyme 1,protein kinase R-like endoplasmic reticulum kinase,and activating transcription factor 6.These proteins mediate UPR pathways that are implicated in the pathological progression of RA.Targeting ERS-related molecules has emerged as a promising therapeutic strategy for RA.This article reviews the impact of ERS on the pathogenesis of RA and discusses drugs that modulate ERS as potential treatments for the disease.

BACKGROUND:Acute liver injury can result from a variety of causes,and if not treated in time,it will develop into acute liver failure and seriously affect the life safety of patients.As the liver is the largest immune organ and metabolic organ,there is no optimal treatment for acute liver injury.The adipose tissue-derived mesenchymal stem cell has multi-differentiation potential and immunomodulatory activity,so it has been gradually becoming an effective tool for the treatment of acute liver injury.OBJECTIVE:To review the progress and molecular mechanism of adipose tissue-derived mesenchymal stem cell and its modification in different ways in the treatment of acute liver injury.METHODS:Relevant articles published from 2000 to 2023 were retrieved from PubMed,Web of Science,and CNKI databases.English search terms were"acute liver injury,liver injury,adipose tissue-derived mesenchymal stem cell,liver injury repair,stem cell transplantation,stem cell repair,cell surface engineering,stem cell modification."Chinese search terms were"acute liver injury,liver injury,adipose tissue-derived mesenchymal stem cell,liver injury repair,stem cell transplantation,stem cell repair,stem cell modification."Totally 62 articles of the latest research progress in this field were summarized and analyzed.RESULTS AND CONCLUSION:(1)Adipose tissue-derived mesenchymal stem cell as a potential stem cell with multi-directional differentiation has biological advantages in the treatment of acute liver injury.Compared with the other two major types of mesenchymal stem cell that is bone marrow mesenchymal stem cell and umbilical cord mesenchymal stem cell,they are more widely sourced,easily accessible and have fewer ethical issues,and more self-renewal than bone marrow mesenchymal stem cell.(2)Adipose tissue-derived mesenchymal stem cell may play a therapeutic role in acute liver injury by regulating immune responses,differentiating into hepatocytes,and secreting growth factors and exosomes.It can reduce the expression of inflammatory factors in serum and the infiltration of inflammatory cells in liver tissue,also can inhibit the pyroptosis and autophagy levels to promote regeneration of sinusoidal endothelial cells and hepatocyte,and ultimately improve liver damage.At present,no studies have shown which mechanism is the best mechanism for adipose tissue-derived mesenchymal stem cells to treat acute liver injury,and most opinions believe that these molecular mechanisms interact with each other to play a synergistic role in treatment.(3)Biomaterials modification and drug pretreatment can improve the efficacy of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury.On the one hand,biomaterials and drug modifications can enhance the functions of adipose tissue-derived mesenchymal stem cell,such as enhancing the ability of proliferation and migration,increasing the level of growth factors secreted,and enhancing the anti-inflammatory ability and promoting the survival of adipose mesenchymal stem cells at the injury site.On the other hand,biomaterials and drug modifications can inhibit the activation of inflammatory cells at the injured site and promote the growth of blood to improve the success rate of transplantation.(4)In summary,adipose tissue-derived mesenchymal stem cell plays an important role in the treatment of acute liver injury by secreting growth factors and exosomes,regulating the immune response,and promoting liver regeneration.With the development of science and technology,biomaterials and drug modification can enhance the self-renewal ability of adipose tissue-derived mesenchymal stem cell and improve the local microenvironment of acute liver injury.It provides a new way to promote the clinical application of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury.

Endoplasmic reticulum stress(ERS)plays a crucial role in cellular self-protection.In response to environmental changes,cells activate the unfolded protein response(UPR)and endoplasmic reticulum-associated protein degradation pathways to restore homeostasis.Increasing experimental evidence indicates that hypoxia and inflammation negatively impact synoviocytes in rheumatoid arthritis(RA),leading to the activation of three key endoplasmic reticulum transmembrane proteins:inositol-requiring enzyme 1,protein kinase R-like endoplasmic reticulum kinase,and activating transcription factor 6.These proteins mediate UPR pathways that are implicated in the pathological progression of RA.Targeting ERS-related molecules has emerged as a promising therapeutic strategy for RA.This article reviews the impact of ERS on the pathogenesis of RA and discusses drugs that modulate ERS as potential treatments for the disease.

ObjectiveTo analyze the epidemic characteristics of measles and rubella in Pudong New Area of Shanghai from 2013 to 2022， and to provide data support for the elimination of measles and rubella. MethodsEnzyme linked immunosorbent assay was used to detect IgM antibodies in serum samples. The sequence of 630 nucleotides at the C-terminal of N gene of measles virus was amplified by reverse transcription-polymerase chain reaction and the phylogenic tree was constructed. ResultsA total of 1 529 suspected cases of measles were detected from 2013 to 2022， among which the positive rate of measles IgM antibody was 33.55% （513/1 529）. The highest positive rate （20.73%） was from March to May ， and the positive rate of rubella IgM antibody was 6.80% （104/1 529）. The positive rate of both IgM was higher in males than that in females （P<0.05）. The IgM against measles was mainly detected in 0‒ years old （63.16%， 96/152） and 20‒ years old （45.61%， 161/353）. The IgM against rubella was mainly detected in 10‒20 years old （27.27%， 18/66）. The IgM antibody could be detected more easily from 4 to 28 days after eruption， and the IgM antibody positive rate of measles/rubella from 2020 to 2022 was significantly lower than previous years （2013‒2019）. There were 2 D8 genotype strains， and the rest were H1a gene subtypes. ConclusionThe positive rate of IgM antibodies against measles/rubella in Pudong New Area of Shanghai decreased significantly. People aged 0‒ years and 20‒ years old are more susceptible to measles， and rubella is concentrated in 10‒ years old. It is necessary to strengthen the vaccination of school-age children， in order to achieve the goal of eliminating measles. The age group with high risk of exposure should be checked for vaccination status to ensure the enhanced immunization， and the surveillance of imported measles cases should be strengthened.

Objective:To explore the effect of different concentrations of Chinese herbal formula,Er-miao-san(EMS)immune regulatory gene on Gnαq expression in rats with collagen-induced arthritis(CIA).Methods:In the study,we established a CIA model,and randomly divided into model groups,EMS group with 1.5,3.0 and 4.5 g/kg(L-EMS,M-EMS,H-EMS)were adminis-tered to CIA rats by gavage,methotrexate was used as a positive control group(MTX).The rats in each group were given correspond-ing drugs for treatment,and the normal control group and model group were given the same amount of normal saline gavage.ELISA detects the expression of IL-1β,IL-6 and TNF-α in rats'serum.The mRNA and protein expression of Gnαq were analyzed using qRT-PCR and Western blot.The localization of Gnαq was performed by IHC.Results:The joint of rats in CIA group showed obvious damage,tissue hyperplasia and inflammatory infiltration;the joint tissue destruction and proliferation of MTX and EMS groups were reduced;the expressions of IL-1β,IL-6 and TNF-α in CIA group were extremely increased(P<0.01).The expressions of IL-1β(except H-EMS group),IL-6 and TNF-α in MTX and EMS groups were significantly lower than those in CIA group(P<0.05).The expressions of IL-1β,IL-6 and TNF-α in L-EMS group were lower than those in the M-EMS and H-EMS groups(P<0.05,P<0.01).The expression of Gnαq mRNA and protein in spleen and joints of CIA group were higher than those of Control group(P<0.01).The expression of Gnαq mRNA and protein in spleen and joints of EMS and MTX groups were lower than those of CIA group(P<0.05).The expression of Gnαq mRNA and protein in the dose of 1.5 g/kg of EMS group was lower than those of the other groups(P<0.01,P<0.05).Different degree of posi-tive signal was detected in spleen and joints in different groups.Conclusion:Gnαq is expressed in spleen and joints of CIA rats,may participate in the formation of inflammatory response in CIA rats,and then mediate the formation and development of RA by down-reg-ulating the expression of Gnαq.

Objective:To explore the effects of the toolkit program for managing symptom clusters of adverse reactions to chemotherapy for ovarian cancer based on the comprehensive symptom management model on the symptom status, self-care ability and quality of life of ovarian cancer patients, and to provide guidance for clinical guidance on symptom management of adverse reactions to chemotherapy for ovarian cancer patients.Methods:A non-simultaneous before-and-after control was used to facilitate the selection of 45 ovarian cancer chemotherapy patients from the Department of Gynecology, Fenyang Hospital, Shanxi Province, from August 2022 to January 2023 as the control group, and 45 ovarian cancer chemotherapy patients from February to July 2023 as the experimeatal group. Routine care was used in the control group, and the experimental group used the Symptom Cluster Management Toolkit program based on the control group. Before intervention and after the end of the first, second, and third chemotherapy cycles, two groups of patients were evaluated using the Functional Assessment of Cancer Therapy-Generic scale and Exercise of Self-Care Agency Scale; after the end of the first, second, and third chemotherapy cycles, Adverse Reaction Events Evaluation Criteria 5.0 was used to evaluate the two groups. The symptom status, self-care ability, and quality of life between two groups of patients were compared.Results:Finally 43 cases in control group and 41 cases in experimental group were included, age of control group was (59.37 ± 8.61) years old and experimental group was (57.10 ± 9.97) years old. After intervention, at the end of the first, second, and third chemotherapy cycles were assessed for side effects, respectively: the nausea rating of the experimental group were 1 (1, 2), 1(1, 2), 2(1, 2), and the control group were 2 (1, 2), 2(1, 2), 2(1, 2); the vomiting rating of the experimental group were 1 (1, 2), 1(1, 2), 1(1, 2), and the control group were 2 (1, 2), 2(1, 2), 2(1, 2); peripheral sensory nerve disorder rating of the experimental group were 1 (1, 1), 1(1, 1), 1(1, 2), and the control group were 1 (1, 1), 1(1, 2), 2(1, 2); peripheral motor nerve disorder rating of the experimental group were 1 (1, 1), 1(1, 1), 1(1, 1), and the control group had a 1 (1, 1), 1(1, 2), 2(1, 2); the cognitive impairment rating of the experimental group were 1 (1, 1), 1(1, 1), 1(1, 1), and the control group were 1 (1, 1), 1(1, 2), 1(1, 2). All the differences were all statistically significant (Wald χ2 were from 4.41 to 6.54, all P<0.05); the control group′s self-care competence scores at the end of the first, second, and third cycles of chemotherapy for patients with ovarian cancer were (106.30 ± 13.03), (109.53 ± 13.85) and (111.95 ± 13.49) points, and (113.68 ± 11.33), (118.95 ± 11.39) and (123.66 ± 11.67) points in the experimental group, and the level of self-care ability of the experimental group was higher than that of the control group when comparing the two groups ( F = 8.61, P<0.05); and the level of quality of life at the end of the first, second, three chemotherapy cycles were (65.35 ± 7.58), (68.58 ± 7.61) and (70.95 ± 7.56) points in the control group, and (70.51 ± 5.89), (74.10 ± 5.70) and (77.00 ± 5.55) points in the experimental group, and the level of quality of life in the experimental group was higher than that of the control group in the comparison between groups ( F = 10.16, P<0.05). Conclusions:The application of the toolkit intervention program for the management of symptom clusters of adverse reactions to chemotherapy in patients with ovarian cancer can reduce the symptom load of patients, improve self-care ability, and improve the quality of life.

Objective:To explore the effects of the toolkit program for managing symptom clusters of adverse reactions to chemotherapy for ovarian cancer based on the comprehensive symptom management model on the symptom status, self-care ability and quality of life of ovarian cancer patients, and to provide guidance for clinical guidance on symptom management of adverse reactions to chemotherapy for ovarian cancer patients.Methods:A non-simultaneous before-and-after control was used to facilitate the selection of 45 ovarian cancer chemotherapy patients from the Department of Gynecology, Fenyang Hospital, Shanxi Province, from August 2022 to January 2023 as the control group, and 45 ovarian cancer chemotherapy patients from February to July 2023 as the experimeatal group. Routine care was used in the control group, and the experimental group used the Symptom Cluster Management Toolkit program based on the control group. Before intervention and after the end of the first, second, and third chemotherapy cycles, two groups of patients were evaluated using the Functional Assessment of Cancer Therapy-Generic scale and Exercise of Self-Care Agency Scale; after the end of the first, second, and third chemotherapy cycles, Adverse Reaction Events Evaluation Criteria 5.0 was used to evaluate the two groups. The symptom status, self-care ability, and quality of life between two groups of patients were compared.Results:Finally 43 cases in control group and 41 cases in experimental group were included, age of control group was (59.37 ± 8.61) years old and experimental group was (57.10 ± 9.97) years old. After intervention, at the end of the first, second, and third chemotherapy cycles were assessed for side effects, respectively: the nausea rating of the experimental group were 1 (1, 2), 1(1, 2), 2(1, 2), and the control group were 2 (1, 2), 2(1, 2), 2(1, 2); the vomiting rating of the experimental group were 1 (1, 2), 1(1, 2), 1(1, 2), and the control group were 2 (1, 2), 2(1, 2), 2(1, 2); peripheral sensory nerve disorder rating of the experimental group were 1 (1, 1), 1(1, 1), 1(1, 2), and the control group were 1 (1, 1), 1(1, 2), 2(1, 2); peripheral motor nerve disorder rating of the experimental group were 1 (1, 1), 1(1, 1), 1(1, 1), and the control group had a 1 (1, 1), 1(1, 2), 2(1, 2); the cognitive impairment rating of the experimental group were 1 (1, 1), 1(1, 1), 1(1, 1), and the control group were 1 (1, 1), 1(1, 2), 1(1, 2). All the differences were all statistically significant (Wald χ2 were from 4.41 to 6.54, all P<0.05); the control group′s self-care competence scores at the end of the first, second, and third cycles of chemotherapy for patients with ovarian cancer were (106.30 ± 13.03), (109.53 ± 13.85) and (111.95 ± 13.49) points, and (113.68 ± 11.33), (118.95 ± 11.39) and (123.66 ± 11.67) points in the experimental group, and the level of self-care ability of the experimental group was higher than that of the control group when comparing the two groups ( F = 8.61, P<0.05); and the level of quality of life at the end of the first, second, three chemotherapy cycles were (65.35 ± 7.58), (68.58 ± 7.61) and (70.95 ± 7.56) points in the control group, and (70.51 ± 5.89), (74.10 ± 5.70) and (77.00 ± 5.55) points in the experimental group, and the level of quality of life in the experimental group was higher than that of the control group in the comparison between groups ( F = 10.16, P<0.05). Conclusions:The application of the toolkit intervention program for the management of symptom clusters of adverse reactions to chemotherapy in patients with ovarian cancer can reduce the symptom load of patients, improve self-care ability, and improve the quality of life.