BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

Portal vein thrombosis(PVT)is a common and severe complication in patients with liver cirrhosis,and alterations in portal hemodynamics are closely associated with the development of PVT.The presence of large spontaneous splenorenal shunt(SSRS)may lead to reductions in portal vein perfusion and blood flow velocity,which may compromise the anticoagulant effect on PVT.This article reports the treatment strategies of SSRS embolization combined with anticoagulant therapy that help to achieve complete recanalization of the portal vein;however,high-quality clinical studies are still needed to further validate and support the effectiveness of this strategy.

Aim To evaluate the in vitro anti-chronic obstructive pulmonary disease(COPD)effects of six batches of Rhizoma Pinelliae(RP)ethanol extracts by the technique for order preference by similarity to an i-deal solution(TOPSIS),so as to establish a new method for comprehensive quality evaluation of RP.Methods Cigarette smoke extract(CSE)and lipopo-lysaccharide(LPS)were utilized to establish an airway inflammation model of Beas-2b human normal lung cells.MTT assay was employed to determine the toxici-ty and pharmacological concentrations of Pinellia Ter-nata(PT)and six different batches RP of their ethanol extracts.EC50 and IC50 values were calculated accord-ingly.Additionally,relevant markers were assessed u-sing qRT-PCR and the superoxide dismutase(SOD)assay kit.Finally,a comprehensive evaluation invol-ving multiple indices was performed using the TOPSIS method for both PT and the six batches of RP extracts.Results According to the IC50 values of seven differ-ent Pinellia ternata,the toxicity ranking was as fol-lows:PT＞RP④＞RP①＞RP⑤＞RP③＞RP⑥＞RP ②.On the other hand,the expressions of TNF-α,IL-6 and IL-8 were down-regulated in the treatment group compared with those of the model group by qRT-PCR.In addition,the levels of SOD de-creased in all groups after treatment.All the data were normalized and the comprehensive ranking results were obtained through TOPSIS analysis as follows:RP⑥＞RP⑤＞RP②＞RP①＞RP③＞RP④＞PT.Con-clusions The ethanol extracts of different Rhizoma Pinelliae varieties all demonstrate the capacity to sup-press inflammation and oxidative stress induced by LPS and CSE.The comprehensive evaluation indicates that the quality of the ⑥ batch of RP shows the highest quality.Moreover,the TOPSIS method can serve as an assessment approach for medicinal materials,offering a pathway for controling the varying quality of herbal ma-terials available in the market.

Portal vein thrombosis(PVT)is a common and severe complication in patients with liver cirrhosis,and alterations in portal hemodynamics are closely associated with the development of PVT.The presence of large spontaneous splenorenal shunt(SSRS)may lead to reductions in portal vein perfusion and blood flow velocity,which may compromise the anticoagulant effect on PVT.This article reports the treatment strategies of SSRS embolization combined with anticoagulant therapy that help to achieve complete recanalization of the portal vein;however,high-quality clinical studies are still needed to further validate and support the effectiveness of this strategy.

Objective::To compare the analgesic effects of ibuprofen administered orally via two modes combined with a conventional, patient-controlled intravenous analgesia pump on maternal pain after cesarean section (CS).Methods::This prospective, randomized, controlled study enrolled females who underwent CS from August 2022 to August 2023 at Peking University First Hospital, Beijing, China. Participants were randomly assigned to either an as-needed ibuprofen group (300 mg orally upon request) or a scheduled ibuprofen group (300 mg every 12 hours for 48 hours). The primary outcomes assessed were postoperative pain levels using the Wong-Baker Faces Pain Scale-Revised and cumulative oxycodone consumption at multiple time points up to 48 hours post-delivery. Secondary outcomes included recovery parameters (time to first flatus, ambulation, and lactation initiation), patient satisfaction with pain control, and postpartum depression scores evaluated by the Edinburgh Postnatal Depression Scale on postoperative day 3. Normally distributed data analyzed with t-tests; non-normal data with Mann-Whitney U tests; categorical variables with chi-square or Fisher’s exact tests (SPSS 26.0, P < 0.05). Results::After excluding 61 non-eligible cases, 339 patients were included (171 as-needed vs. 168 scheduled). The scheduled group showed significantly better pain control at 12 hours (4.00 (2.00-5.50) vs. 4.00 (4.00-6.00), P < 0.001), 24 hours (4.00 (2.00-4.00) vs. 4.00 (2.00-6.00), P < 0.001), and 36 hours (2.00 (2.00-4.00) vs. 4.00 (2.00-4.00), P < 0.001), and 48 hours (2.00 (2.00-4.00) vs. 2.00 (2.00-4.00), P = 0.004) post-delivery and lower levels of oxycodone consumption at 36 hours (10.20 (8.20-13.35) vs. 11.00 (8.80-14.40), P = 0.042) and 48 hours (12.40 (10.40-15.95) vs. 13.80 (11.00-16.00), P = 0.020) postpartum compared with those in the as-needed group. Additionally, the time to the return of bowel movements was shorter in the scheduled group than in the as-needed group (23.50 (16.94, 31.47) vs. 27.00 (19.88, 35.97), P = 0.004). Differences in post-delivery ambulation, lactation initiation, satisfaction levels, and depression scores were not significantly different between the two groups. Conclusion::The results of this study promote the use of ibuprofen (scheduled oral administration) combined with a conventional, patient-controlled intravenous analgesia pump for achieving better post-CS pain control than an as-needed dosage regimen.Registration::Chinese Clinical Trial Registry, ChiCTR2400082474.

Objective To construct a cloud-based platform for healthcare-associated infection(HAI)management based on multi-source data fusion and data visualization,and evaluate its application effectiveness.Methods A ter-tiary first-class cancer hospital was selected as the research object.Aligned with graded hospital accreditation stan-dards and based on grid-based management and responsibility zone mode,a platform was constructed in 2023 with low-code technology,multi-source data fusion,and visualization function.The self-comparison method was adopted to compare occurrence of HAI before and after the operation of the platform.A questionnaire survey was adopted to assess the experience and workload reduction feelings of full-time and part-time infection surveillance and control profe-ssionals using the platform.Results 81.56％of the surveyed respondents believed that the platform could re-duce the workload of infection surveillance and control.Compared with before the trial operation,the hospital achieved an annual reduction of 11 200 yuan in paper costs,with associated labor savings of approximately 4 482.5 hours.The incidence of HAI cases in the whole hospital decreased from 0.67％to 0.45％.The pathogen detection rate before therapeutic use of antimicrobial agents increased from 51.26％to 71.54％.Differences were both statis-tically significant(both P＜0.05).The detection number and proportion of carbapenem-resistant Pseudomonas aeruginosa(CRPA)and extended-spectrum β-lactamase-producing Klebsiella pneumoniae(ESBL-KP)in HAI cases decreased(54.55％vs 36.47％and 51.14％vs 32.50％,respectively,both P＜0.05).Conclusion The construc-tion and application of smart HAI management cloud-based platform can reduce cost,improve management quality,and provide a theoretical basis and technical paradigm for the construction of smart HAI management system.

Objective::To compare the analgesic effects of ibuprofen administered orally via two modes combined with a conventional, patient-controlled intravenous analgesia pump on maternal pain after cesarean section (CS).Methods::This prospective, randomized, controlled study enrolled females who underwent CS from August 2022 to August 2023 at Peking University First Hospital, Beijing, China. Participants were randomly assigned to either an as-needed ibuprofen group (300 mg orally upon request) or a scheduled ibuprofen group (300 mg every 12 hours for 48 hours). The primary outcomes assessed were postoperative pain levels using the Wong-Baker Faces Pain Scale-Revised and cumulative oxycodone consumption at multiple time points up to 48 hours post-delivery. Secondary outcomes included recovery parameters (time to first flatus, ambulation, and lactation initiation), patient satisfaction with pain control, and postpartum depression scores evaluated by the Edinburgh Postnatal Depression Scale on postoperative day 3. Normally distributed data analyzed with t-tests; non-normal data with Mann-Whitney U tests; categorical variables with chi-square or Fisher’s exact tests (SPSS 26.0, P < 0.05). Results::After excluding 61 non-eligible cases, 339 patients were included (171 as-needed vs. 168 scheduled). The scheduled group showed significantly better pain control at 12 hours (4.00 (2.00-5.50) vs. 4.00 (4.00-6.00), P < 0.001), 24 hours (4.00 (2.00-4.00) vs. 4.00 (2.00-6.00), P < 0.001), and 36 hours (2.00 (2.00-4.00) vs. 4.00 (2.00-4.00), P < 0.001), and 48 hours (2.00 (2.00-4.00) vs. 2.00 (2.00-4.00), P = 0.004) post-delivery and lower levels of oxycodone consumption at 36 hours (10.20 (8.20-13.35) vs. 11.00 (8.80-14.40), P = 0.042) and 48 hours (12.40 (10.40-15.95) vs. 13.80 (11.00-16.00), P = 0.020) postpartum compared with those in the as-needed group. Additionally, the time to the return of bowel movements was shorter in the scheduled group than in the as-needed group (23.50 (16.94, 31.47) vs. 27.00 (19.88, 35.97), P = 0.004). Differences in post-delivery ambulation, lactation initiation, satisfaction levels, and depression scores were not significantly different between the two groups. Conclusion::The results of this study promote the use of ibuprofen (scheduled oral administration) combined with a conventional, patient-controlled intravenous analgesia pump for achieving better post-CS pain control than an as-needed dosage regimen.Registration::Chinese Clinical Trial Registry, ChiCTR2400082474.