Hyaluronic acid (HA) possesses excellent biocompatibility, biodegradability, and non-immunogenicity, and exhibits active targeting capability to receptors such as cluster of differentiation 44 (CD44). Therefore, HA has become an important material for the design and preparation of drug delivery carriers in recent years. HA is rich in functional groups that can be chemically modified, but different modification methods and sites can affect its biological properties. This paper summarizes and discusses the effects of chemical modification on the biological properties of HA based on the formation mechanisms of such properties, as well as the derivatization and characterization methods of HA, so as to provide some reference for rational research on chemical modification of HA.

To investigate the effect of Xuebijing injection (XBJ) on cGAS/STING pathway in alleviating sepsis-induced acute lung injury (ALI), the mouse sepsis-induced ALI model was established by cecal ligation and puncture (CLP), and the cell inflammation model was constructed by LPS stimulating RAW264.7 cells. The effects of XBJ on lung tissue injury and cGAS/STING pathway-related protein expression in septic mice were investigated by HE staining, ELISA, and Western blot. The results showed that XBJ intervention could alleviate lung tissue injury, reduce serum IL-6, TNF-α, IFN-β, IL-1-β levels, and the expression of cGAS, STING, p-TBK1, and p-IRF3 proteins in lung tissue in vivo, and reduce the mRNA level of related inflammatory factors in RAW264.7 cells and the expression of cGAS/STING pathway proteins in vitro. The results showed that XBJ could play a role in the prevention and treatment of sepsis-induced ALI by inhibiting the inflammatory response via inhibition of the activation of cGAS/STING pathway. This study provides a new molecular mechanism for the clinical prevention and treatment of sepsis-induced acute lung injury with XBJ.

Objective:To explore the effect of 8-week treadmill exercise on myocardial fibrosis in mice with T2DM and its molecular mechanism. Method:Eight m/m mice were used as the control group,and 32 db/db mice were randomly divided into control group,model group,exercise intervention group,inhibitor alone group and exercise combined with in-hibitor intervention group.Fasting blood glucose was monitored weekly.After 8 weeks,triglycerides(TG)and total cholesterol(TC)were measured.Masson staining was used to observe the degree of myocardial fibrosis,and immunofluorescence staining was used to observe the expression of Collagen Ⅰ and α-SMA.Westem Blot was used to detect the expression levels of fibrosis,inflammation,pyroptosis and p38MAPK related proteins. Result:The model group showed a significant increase in fasting blood glucose,TG and TC(P＜0.0001),Col-lagen Ⅲ(P＜0.05)and TGF-β1(P＜0.01)expression compared with control group.Compared to the model group,Masson staining in the other groups showed a significant improvement in disordered myocardial cell ar-rangement and a decrease in blue collagen fibers between the interstitial tissue and perivascular tissue;immuno-fluorescence staining also showed that the expression levels of Collagen Ⅰ and α-SMA and the expression lev-els of fibrosis-related proteins were significantly decreased in these groups.The expression levels of inflamma-tion and pyroptosis related proteins in the exercise intervention group were significantly lower than those in the model group.Compared to the model group,the phosphorylation level of p38MAPK in the exercise inter-vention group and the simple inhibitor group was significantly decreased(P＜0.05,P＜0.01),but the phosphory-lation level was not further decreased after the combined intervention.Compared to the model group,the ex-pression levels of NLRP3 and GSDMD-N in the single inhibitor group were significantly decreased(P＜0.05),and the combined intervention further inhibited the expression of Caspase-1(P＜0.05),Cleaved-Caspase-1(P＜0.05),and GSDMD-N(P＜0.001). Conclusion:Eight-week treadmill exercise can significantly improve myocardial fibrosis in db/db mice.The mechanism may reduce the phosphorylation of p38MAPK and pyroptosis of cardiomyocytes,thus improving myocardial fibrosis in db/db mice.The combination of treadmill exercise and SB203580 can further reduce py-roptosis.

Objective:To evaluate the efficacy and safety of omalizumab in the treatment of chronic urticaria in children.Methods:A retrospective study was conducted. Patients with chronic urticaria were collected from the Department of Dermatology, Hunan Children′s Hospital from January to December 2021, and divided into a control group and a combination group according to different medication regimens. The patients in the combination group received subcutaneous injections of omalizumab (150 mg, once every 4 weeks) combined with conventional-dosage antihistamines, while the patients in the control group were only treated with double-dosage or multiple types of antihistamines. The course of treatment was 3 to 6 months. The clinical efficacy and adverse reactions were evaluated at 3, 6, and 12 months after the start of treatment, and the recurrence was evaluated at 3 and 6 months after the end of treatment.Results:A total of 46 children with chronic urticaria were collected. There were 23 children (13 males and 10 females) in the combination group, aged from 6 to 17 years and including 16 aged from 6 to 12 years and 7 aged from 13 to 17 years; according to the total serum IgE levels before treatment, the patients in the combination group were divided into an increased IgE subgroup (11 cases) and a normal IgE subgroup (12 cases). In the control group, there were 13 males and 10 females, aged from 6.33 to 16 years and including 15 aged from 6 to 12 years and 8 aged from 13 to 17 years. At 3, 6, and 12 months after the start of treatment, the response rates in the combination group were all 86.96% (20/23), which were all significantly higher than those in the control group (52.17% [12/23], 56.52% [13/23], 56.52% [13/23], P = 0.010, 0.022, 0.022, respectively). In the combination group, the response rates at 3, 6, and 12 months after the start of treatment were all 14/16 in the children aged 6 to 12 years and 6/7 in those aged 13 to 17 years, and there were no significant differences between the two age groups (all χ2 = 0.01, P = 0.907) ; in the control group, the response rates were 5/15, 6/15 and 5/15 respectively in the children aged 6 to 12 years, which were all significantly lower than those in the combination group ( P = 0.002, 0.006, 0.006, respectively). In the combination group, the response rates at 3, 6, and 12 months after the start of treatment were all 9/11 in the increased IgE subgroup and 11/12 in the normal IgE subgroup, and there were no significant differences between the two subgroups (all P = 0.484). During the treatment, no serious adverse reactions were observed in the combination group or control group, and mild somnolence only occurred in 2 children in the control group. At 3 months after the end of treatment, no recurrence was observed in 16 patients in the combination group, 2 out of 6 patients experienced recurrence in the control group, and the recurrence rate was lower in the combination group than in the control group ( P = 0.030) ; at 6 months after the end of treatment, no recurrence was observed in 16 patients in the combination group, 3 out of 6 patients experienced recurrence in the control group, and the recurrence rate was lower in the combination group than in the control group ( P = 0.022) . Conclusion:Omalizumab combined with conventional-dosage antihistamines could improve the clinical efficacy and reduce the recurrence rate in the treatment of chronic urticaria in children, with few adverse reactions.

Objective:By reviewing and analyzing the construction practice of the National Clinical Research Center for Obstetrics and Gynecology and the relevant experience of enhancing its technological influence, this study aimed to provide effective suggestions for its subsequent high-quality development.Methods:We analyzed and summarized the core strategies and achievements of the construction of the National Clinical Research Center for Obstetrics and Gynecology.Results:Over the past decade, the National Clinical Research Center for Obstetrics and Gynecology has continuously planned research directions, conducted high-level clinical research, built a national collaborative research network, strengthened management and research platform linkage construction, and made positive contributions to leading the development of China's obstetrics and gynecology and reproductive fields.Conclusions:The sustainable development of the National Center for Clinical Research on Diseases in the future needs to balance the characteristics of overall planning, cutting-edge leadership, and flexible switching, as well as highlight the main responsibility of serving clinical technology innovation, explore interdisciplinary domestic and international exchanges and cooperation, build a high-quality talent team for clinical medical research, and coordinate with the overall layout of clinical medicine in China to ensure people′s lives and health.

Objective To examine the pattern of changes in 12 cytokines(IFN-α,IFN-γ,TNF-α,IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,and IL-17)in the cerebrospinal fluid(CSF)of patients with central nervous system(CNS)infections and their clinical significance.Methods Fifty-two patients clinically diagnosed with CNS infec-tions at our hospital were enrolled in the study.CSF was collected for CSF analysis,biochemical analysis,and cytology.Changes in the CSF levels of 12 cytokines were measured by flow cytometry.Results Only IL-5,IL-6,and IL-8 were sig-nificantly increased in the CSF,and the corresponding positive rates were 23.08%,42.31%,and 96.15%,respectively.High levels of IL-5,IL-6,and IL-8 were positively correlated with white blood cell(WBC)count and neutrophil percent-age but negatively correlated with lymphocyte percentage in the CSF.Consistent with the WBC count,IL-5,IL-6,and IL-8 levels in the CSF were significantly decreased after effective treatment.Conclusion The levels of IL-5,IL-6,and IL-8 in CSF can be used as potential markers for the diagnosis,treatment,and severity assessment of CNS infections.

Objective This study was to develop a HPLC-MS/MS method for determination of etomidate and etomidate acid in blood samples.Methods The blood samples were deproteinized with acetonitrile and supernatant was achieved by shake,sonication,centrifuge and filtration using 0.22 μm membrane.Then,supernatant was performed on an analytical column Poroshell 120 EC-C18(150 mm×3.0 mm,2.7 μm)and flowed with 0.1%formic acid(mobile phase A)and acetonitrile(mobile phase B).The gradient elution at a flow rate of 0.8 mL/min was determined using an electrospray ionization source in positive ion mode and multiple reaction monitoring mode.Results The linearities of etomidate and etomidate acid in blood samples were good within the corresponding range and the correlation coefficients(r)were over 0.9988.The limit of detection(LOD)of etomidate and etomidate acid were 19.94 and 40.25 ng/mL,and the limit of quantitation(LOQ)of them were 50 and 100 ng/mL,respectively.Moreover,matrix effects were ranged from 1.47%to 10.34%and recoveries ranged from 82.81%to 90.07%.The detection of a positive case using our method was successfully determined to be 1 138.89 and 3 126.41 ng/mL for the contents of etomidate and etomidate acid,respectively.Conclusion Our study has further confirmed that this method with simple pretreatment,little sample usage and wide linear range,can be successfully applied to the detection of forensic sciences on etomidate and etomidate acid.

Objective To analyze the domestic antibody drug safety and risk research status,the latest research hotspots and frontiers in the current ten years.Methods CiteSpace 6.2.R2 software was used to analyze all literature related to the safety and risk of antibody drugs in CNKI,WanFang data and Vip database from 2012 to 2022.Results A total of 2 773 pieces of literature were obtained from the three databases,which were imported into CiteSpace after deduplication,and finally,1 870 pieces were included in the analysis.In the past decade,the number of articles published in the field of antibody drugs safety and risk research has remained at about 100 articles per year from 2012 to 2019,since 2020,the number of articles published has started to increase,and the annual number of articles published has increased to around 300 articles from 2021 to 2022.The network graph of domestic institutional cooperation showed that there was a lack of cooperation among the research institutions of antibody drug safety and risk research,mainly due to the fact that hospitals were conducting research in this field,and the types of research subjects were relatively single.The author collaboration network graph showed that the core teams in this research field,such as Li Bo,Yang Yanwei,and Lin Zhi,had the closest collaboration,while there was less collaboration among high-yield authors,additionally,some experts and scholars conducted research on their own as individuals or small groups,the research focused on adverse reactions,safety,bevacizumab,Rituximab,Meta-analysis,etc.Conclusion In the past decade,domestic research has mainly focused on the clinical efficacy and safety of antibody drugs,with few scholars exploring the risk of antibody drugs,therefore,in the future,it is necessary to pay attention to the research on the risks of antibody drugs.

OBJECTIVE To explore the protective mechanism of amifostine on acute radiation injury mice. METHODS Thirty C57BL/6J mice were randomly divided into normal control group， model group and amifostine group （150 mg/kg）， with 10 mice in each group. Thirty minutes before irradiation， the mice in the amifostine group were intraperitoneally injected with amifostine； normal control group and model group were given constant volume of normal saline intraperitoneally； then acute radiation injury was induced by 4 Gy X-ray radiation in both model group and amifostine group. The white blood cell count （WBC）， platelet count and red blood cell （RBC） count in mice were detected 2 hours before irradiation and on days 1， 4， 7， 10 and 14 after irradiation； the changes in the proportion of WBC （neutrophils， lymphocytes and monocytes） on the 7th day after irradiation were analyzed. The 16S rRNA high-throughput sequencing was used to analyze the structure of gut microbiota in mice feces on the 7th day after irradiation， then its correlation with WBC was analyzed. RESULTS The counts of WBC on the 1st， 4th， 7th and 10th day after irradiation， platelet count on the 10th day after irradiation and RBC count on the 1st day after irradiation in the amifostine group were significantly higher than those in model group （P＜0.05）. Compared with normal control group，β diversity of gut microbiome showed significant change， relative abundance of Firmicutes increased and that of Bacteroidetes decreased in model group. Amifostine could reverse the change in β diversity of gut microbiome， and the relative abundance of Bacteroidetes and Firmicutes. The model group consisted of four distinct species， namely Allobaculum， Erysipelotrichia， Erysipelotrichales and Erysipelotrichaceae， which were significantly negatively correlated with the proportion of peripheral blood lymphocytes （P＜0.01）； amifostine group consisted of two distinct species， namely Lactobacillus murinus and L. crispatus， which were significantly negatively correlated with the proportion of neutrophils （P＜0.05）. CONCLUSIONS Amifostine significantly improves irradiation-induced injury by regulating dysbiosis of LY201816） gut microbiota.

ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules （SSNX） in alleviating myocardial ischemia-reperfusion injury （MIRI） in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley （SD） rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group， model group， SSNX group （90 mg·kg^-1） and trimetazidine group （5.4 mg·kg^-1）. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were detected by micro method. Changes in mitochondrial membrane potential （△Ψm） and the degree of mitochondrial permeability transition pore （mPTP） opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate （ATP） level was detected by the luciferase assay. The messenger ribonucleic acid （mRNA） and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 （DRP1）， mitochondrial fission 1 protein （FIS1）， optic atrophy protein 1 （OPA1）， mitochondrial outer membrane fusion protein 1 （MFN1）， and MFN2 were detected by real-time polymerase chain reaction （real-time PCR） and Western blot. ResultCompared with the sham operation group， the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP， the level of △Ψm and ATP content decreased， the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased， and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group，SSNX significantly increased serum SOD activity， reduced MDA content， increased intracellular ATP level and △Ψm， reduced the opening level of mPTP， downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1， and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1， and increases the expressions of fusion related factors OPA1 and MFN1， inhibiting mitochondrial fission and increasing mitochondrial fusion， thereby alleviating MIRI.