OBJECTIVE To investigate the improvement effect and mechanism of desloratadine citrate disodium in mice with hypersensitivity pneumonitis （HP）. METHODS Sixty mice were randomly divided into blank control group （normal saline）， model group （normal saline）， prednisone group （positive control， 20 mg/kg） and desloratadine citrate disodium low-， medium- and high-dose groups （0.5， 1， 2 mg/kg）， with 10 mice in each group. Except for the blank control group， mice in other groups were intraperitoneally injected with ovalbumin （OVA） and exposed to OVA inhalation to establish the HP model. On day 22 post- modeling， mice in each group were administered the corresponding drugs or normal saline， once a day， for 11 consecutive days. After the last administration， lung function and airway hyperreactivity were assessed. The levels of interleukin-1β （IL-1β）， IL-4 and IL-6 in serum as well as the levels of IL-8， IL-13 and IL-17A in bronchoalveolar lavage fluid were determined. Pathological changes in lung tissue of mice were evaluated using Masson staining. Furthermore， the expressions of fibrosis-related proteins， including transforming growth factor β1 （TGF-β1）， type Ⅲ collagen （Col-Ⅲ） and fibronectin （FN） were determined in lung tissues. RESULTS Compared with the blank control group， the model group showed significant deterioration in lung function （P＜ 0.01）， while airway resistance and serum levels of IL-1β， IL-4， IL-6 and the levels of IL-8， IL-13 and IL-17A in the bronchoalveolar lavage fluid were increased significantly （P＜0.01）. The lung tissues exhibited alveolar collapse， atrophy， and structural disarray， along with the formation of extensive deposits of blue collagen fibers， the percentage of positive staining increased significantly （P＜0.01）. Additionally， the expression levels of TGF-β1， Col-Ⅲ， and FN proteins in the lung tissues were also increased significantly （P＜0.01）. After intervention with desloratadine citrate disodium， the pathological changes in the lung tissues of mice in each dosage group of desloratadine citrate disodium showed varying degrees of improvement， and most of the aforementioned indicator levels were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Desloratadine citrate disodium can improve the lung function and airway hyperreactivity of HP mice， inhibit the release of inflammatory factors in serum and bronchoalveolar lavage fluid， and reduce the deposition of collagen fibers. Its mechanism of action may be related to anti-inflammatory， immunomodulatory， and antifibrotic effects.

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective To explore the application of Plan-Do-Check-Act(PDCA)cycle management to continuously im-prove the service quality of outpatient pharmacy and enhance patient satisfaction.Methods To address the problem of long wait-ing time for patients in outpatient pharmacy,we applied PDCA cycle to investigate the factors affecting patients'waiting time in the process of medicine collection,analyze the current situation,determine the expected goals,formulate the service quality im-provement plan of outpatient pharmacy,implement the improvement plan,follow up and supervise,and summarize and analyse the problems regularly until it was solved.Results After implementing the PDCA cycle in the management,the service quality of outpatient pharmacy was improved,the waiting time was significantly shortened and the satisfaction of medical treatment was in-creased.Conclusion The application of PDCA cycle method is effective in improving the service quality of outpatient pharmacy.Therefore,it is recommended for broader implementation.

Objective To explore the functional improvement effect of acupuncture and moxibustion therapy of traditional Chinese medicine(mainly acupuncture on the three yang meridians of the hand,moxibustion on the governor vessel,and moxibustion through drugs)on cervical spondylosis of wind cold blocking collateral type.Methods 120 patients with wind cold obstruction type cervical spondylosis admitted to our hospital from July 2021 to July 2023 were randomly divided into two groups,with 60 cases in each group,using a random number table method.The control group was treated with conventional cervical traction,while the observation group was treated with traditional Chinese medicine acupuncture and moxibustion on the basis of the control group(mainly acupuncture at the hand Sanyang meridian+moxibustion at the governor's meridian+moxibustion through drugs).Compare the TCM syndrome scores,NDI,HO-1,LpPLA2,clinical efficacy,adverse reactions,hospitalization costs,and duration between two groups.Results After 4 weeks of treatment,the effective rate of disease in the observation group with wind cold obstructing cervical spondylosis(96.67%)was higher than that in the control group(83.33%),while the traditional Chinese medicine syndrome score,NDI score,HO-1,LpPLA2 in the observation group were lower than those in the control group(P<0.05).No adverse reactions were observed in both groups.Conclusion Traditional Chinese medicine acupuncture and moxibustion therapy(mainly acupuncture of the three yang meridians of the hand,governor vessel moxibustion,and herbal penetration moxibustion)has significant clinical effect in the application of cervical spondylosis of wind cold blocking collateral type,which can effectively improve clinical symptoms and biochemical indicators,promote the rehabilitation of cervical function,and has high safety.

Antimicrobial resistance has emerged as a critical global public health concern since the 21 st century. On May 27, 2023, the 76th World Health Assembly endorsed the first global infection prevention and control strategy, proposing the direction of the Global Action Plan for Antimicrobial Resistance (AMR). This article provides an overview of the current global landscape of microbial resistance and the key research topics outlined by WHO in the fight against antimicrobial resistance. Combining with the current trends of bacterial resistance in China and the challenges of drug resistance prevention and control, this paper explores the response measures of medical institutions in clinical and laboratory settings, and advocates for interdisciplinary collaboration to promote the rational application of antimicrobial drugs as the most effective way to combat drug resistance.

Objective:To establish an epidemiological cut-off value (ECV) for antifungal drugs against Cryptococcus neoformans in East China through a multicenter in vitro drug susceptibility test. Methods:A retrospective collection of 479 clinical isolates of Cryptococcus neoformans was conducted by the East China Invasive Fungal Infection Group (ECIFIG) from January 1, 2017 to December 31, 2022. Mass spectrometry and gene sequencing were used for identification. A unified drug susceptibility testing system was established in the fungal laboratories across three sub centers in Shanghai, Jiangxi, and Jiangsu provinces. Drug susceptibility testings of Cryptococcus neoformans were independently completed in each center after passing consistency evaluation. Epidemiological breakpoints were established against fluconazole, voriconazole, amphotericin B, 5-fluorocytosine, isaconazole, posaconazole and itraconazole following the principles and procedures of the Clinical and Laboratory Standards Institute (CLSI) M57. Results:External consistency evaluation revealed that the minimum inhibitory concentration values ??for all drugs in each center did not differ by more than one dilution gradient. A new ECV type of Cryptococcus neoformans in East China was established, including fluconazole 16 mg/L, voriconazole 0.12 mg/L, amphotericin B 1 mg/L, 5-fluorocytosine 8 mg/L, isavuconazole 0.12 mg/L, posaconazole 0.5 mg/L, and itraconazole 0.5 mg/L. Conclusion:This study preliminarily revealed the drug susceptibility characteristics of clinical Cryptococcus neoformans in East China and established the ECVs for antifungal drugs against Cryptococcus neoformans in the region.

Objective:To clarify whether CLDN5 is involved in the pathogenesis of sensitive skin (SS) through inflammation.Methods:From January 2018 to March 2020, in the Dermatology Laboratory of the First Affiliated Hospital of Kunming Medical University, facial tissues were collected from 5 patients diagnosed with sensitive skin and 5 cases of normal facial skin. The organizational experiment was divided into two groups: SS group and normal skin (NS) group. The cell experiment was divided into two groups: sh-CLDN5 group in which CLDN5 was knocked down and sh-NC group with normal expression of CLDN5. After paraffin embedding and sectioning, immunohistochemical staining was performed to determine the expression of claudin-5 in sensitive skin and normal skin. In cell experiments, lentivirus shRNA was transfected into HaCaT cells. Three cases in sh-CLDN5 group and three cases in sh-NC group were collected for transcriptome sequencing, and differentially expressed pro-inflammatory factor mRNA was screened from the sequencing results. Western blot or ELISA was used to verify the protein level expression of differentially expressed pro-inflammatory cytokines mRNA in HaCaT cells, and Western blot was used to detect the expression of key proteins in MAPK pathway and NF-κB in the sh-CLDN5 group and sh-NC group.Results:Immunohistochemical staining showed that claudin-5 was localized in the interstitial cells of the normal skin granular layer. Patients with sensitive skin had thinner epidermis than normal skin and significantly reduced claudin-5 expression. In HaCaT cells, the expression of pro-inflammatory cytokine IL-23A was increased, and IL-8 was elevated in the sh-CLDN5 group [(272.91±30.25) pg/ml, n=3] compared with sh-NC group [(55.58±7.07) pg/ml, n=3] ( P<0.01). There was no statistically significant difference in secretion volume between sh-NC group [(8.04±1.34) pg/ml, n=3] and sh-CLDN5 group [(12.15±3.07) pg/ml, n=3]. The expression of P-JNK, p-ERK, and P-p38 in the MAPK pathway was significantly increased ( P<0.01). Conclusions:CLDN5 is an important gene involved in the pathogenesis of SS. CLDN5 upregulates IL-23A and IL-8 in HaCaT and activates the MAPK pathway, which is involved in the process of early SS inflammation.

To investigate the correlation of polymorphisms at the rs1837253 and rs3806933 loci of the thymic stromal lymphopoietin(TSLP)gene with asthma susceptibility and Eos,IgE,and FeNO levels in children.A total of 143 asthmatic children were selected as the study group,and 112 healthy children undergoing routine health examinations at the same hospital were chosen as the control group.The MassARRAY SNP genotyping technology was used to detect the genotypes at two loci,while serum IgE levels were determined by using the turbidimetric scattering method.The distribution differences in genotype and allele frequencies between the two groups were analyzed,along with the effects of different genotypes on Eos,IgE,and FeNO levels.There was no statistically significant difference in the distribution of rs1837253 allele and genotype frequencies as well as rs3806933 allele frequencies between the two groups(P＞0.05).However,asthma group rs3806933 CT genotype frequency was higher than the control group,and CC genotype frequency was lower than the control group(P＜0.05).Compared with the wild-type genotypes,children who carried rs1837253 CT+CC and rs3806933 CT,CT+TT genotypes had an increased risk of asthma(CT+CC vs TT:OR=2.737,95%CI:1.514-4.945;CT vs CC:OR=2.058,95%CI:1.194-3.543;CT+TT vs CC:OR=1.843,95%CI:1.109-3.062).There was an overall statistical difference in Eos counts among the three genotypes at the rs1837253 locus in the asthma group(P＜0.05,correction for multiple comparisons P＞0.05),but not in the control group(P＞0.05).There were no statistically significant differences in Eos%,IgE,and FeNO levels among the genotypes at the two loci and no significant difference in Eos counts among genotypes at the rs3806933 loci(P＞0.05).Taken together,polymorphisms at rs1837253 and rs3806933 loci in the promoter region of the TSLP gene are associated with asthma susceptibility in children.rs3806933 CT genotype may serve as a potential genetic marker for asthma,and rs1837253 CT+CC and rs3806933 CT+TT genotypes are risk factors for asthma in children;the rs1837253 locus polymorphism tended to affect blood Eos counts,while the two SNPs were not associated with Eos%,serum IgE,and FeNO levels.