ObjectiveTo investigate the effects of Yishen Juanbi pills （YSJB）-containing bone marrow fluid on the migration and differentiation phenotypes of CD4⁺T lymphocytes based on the stromal cell-derived factor-1/chemokine receptor 4 （SDF-1/CXCR4） signaling pathway. MethodsPrimary CD4⁺T lymphocytes were isolated from mice using magnetic bead separation and identified for purity by flow cytometry. A CD4⁺T lymphocyte culture system was then established to observe the effects of SDF-1 on CD4⁺T-cell migration and differentiation. On this basis， the experimental groups included the Sham group， the ovariectomy （OVX） group， the Sham+collagen-induced arthritis （CIA） group， the OVX+CIA group， the Sham+CIA+YSJB group （2.16 g·kg^-1）， the OVX+CIA+YSJB group （2.16 g·kg^-1）， and the OVX+CIA+methotrexate （MTX） group （1.5 mg·kg^-1）. Bone marrow fluid from each group was prepared according to previous methods and added to the CD4⁺ T-cell culture system at 5% （v/v）. Transwell assays were used to examine CD4⁺T-cell migration in each group. Real-time PCR was used to measure the mRNA expression levels of interleukin （IL）-17， tumor necrosis factor-α （TNF-α）， retinoic-acid-related orphan receptor γt （RORγt）， IL-10， transforming growth factor-β （TGF-β）， forkhead box P3 （FoxP3）， CXCR4， phosphoinositide 3-kinase （PI3K）， and protein kinase B （Akt）. Western blot was used to detect the expression of helper T （Th）17/regulatory T （Treg） cell signature factors （RORγt， FoxP3）， CXCR4， PI3K， phosphorylated （p）-PI3K， Akt， and p-Akt. In a separate set of experiments， cells were divided into the Sham group， OVX+CIA group， OVX+CIA+CXCR4 antagonist AMD3100 group， and OVX+CIA+YSJB+AMD3100 group to observe changes in the above indicators following AMD3100 intervention. ResultsCompared with the Sham group， the number of migrated cells in the lower chamber was significantly increased in the Sham+CIA and OVX+CIA groups （P<0.05， P<0.01）. The mRNA expression of RORγt， IL-17， TNF-α， CXCR4， PI3K， and Akt was significantly upregulated， whereas FoxP3， IL-10， and TGF-β mRNA expression was significantly decreased （P<0.05， P<0.01）. Protein expression of RORγt， CXCR4， p-PI3K/PI3K， and p-Akt/Akt was significantly increased， while FoxP3 protein expression was markedly decreased （P<0.05， P<0.01）. Compared with the OVX+CIA group， the OVX+CIA+YSJB group and OVX+CIA+MTX group showed significantly reduced migration （P<0.05）， mRNA expression of RORγt， IL-17， TNF-α， CXCR4， PI3K， and Akt was also significantly decreased， while FoxP3， IL-10， and TGF-β mRNA expression was significantly increased （P<0.05， P<0.01）. RORγt protein expression was significantly downregulated， and FoxP3 protein expression markedly upregulated （P<0.05）. In the OVX+CIA+YSJB group， CXCR4， p-PI3K/PI3K， and p-Akt/Akt protein expression was significantly decreased （P<0.05）. Compared with the OVX+CIA group， RORγt， CXCR4， PI3K， and Akt mRNA expression in CD4⁺T cells was significantly decreased in the OVX+CIA+AMD3100 group and the OVX+CIA+YSJB+AMD3100 group， while FoxP3 mRNA and protein expression was significantly upregulated （P<0.05， P<0.01）. RORγt， CXCR4， p-PI3K/PI3K， and p-Akt/Akt protein expression was also markedly decreased （P<0.05， P<0.01）. Compared with the OVX+CIA+AMD3100 group， the OVX+CIA+YSJB+AMD3100 group showed significantly decreased RORγt and Akt mRNA expression （P<0.05） and significantly lower p-Akt/Akt protein expression （P<0.05）. ConclusionYSJB-containing bone marrow fluid suppresses CD4⁺T-cell migration and regulates Th17/Treg balance by downregulating Th17-associated signature factors and upregulating Treg-associated signature factors through inhibition of the SDF-1/CXCR4 signaling pathway and PI3K/Akt signaling pathway. The SDF-1/CXCR4 signaling pathway is one of the targets through which YSJB inhibits CD4⁺T-cell differentiation.

ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE₁), and the margin of exposure for carcinogenic toxicity (MOE₂). An MOE₁ greater than 200 and an MOE₂ greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP₅₀ values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)^-1, respectively. For pregnant women in Shanghai in 2023, the P₅₀ values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)^-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)^-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.

ObjectiveTo analyze the current status of per⁃ and polyfluoroalkyl substances (PFASs) contamination in animal⁃derived foods in Shanghai and to assess the risk of dietary exposure among local residents, thereby providing a scientific basis for future dietary safety and risk management. MethodsA total of 300 commonly consumed animal⁃derived food samples were collected in Shanghai in 2023 and tested for 17 types of PFASs. Based on local dietary consumption data, the weekly exposure intake (EWI) of four representative PFASs was calculated using the exposure assessment model recommended by Food and Agriculture Organization (FAO) and the World Health Organization (WHO). The calculated EWI was compared with the tolerable weekly intake (TWI) set by the European Food Safety Authority (EFSA) to assess the health risks associated with dietary intake of PFASs. ResultsThe predominant PFASs detected in aquatic products were PFUnDA (98.67%), PFTrDA (98.00%), and PFOS (95.33%), with PFUnDA having the highest median mass fraction (0.378 ng·g^-1). In meat samples, PFBA (54.17%), PFOA (20.83%), and PFOS (18.33%) were mainly detected, with PFBA showing the highest median mass fraction (0.027 ng·g^-1). In egg samples, the most frequently detected compounds were PFBA (90.00%), PFOA (63.33%), PFOS (50.00%), PFDA (50.00%), PFNA (50.00%), and PFHxDA (50.00%), with PFBA again having the highest median mass fraction (0.068 ng·g^-1). The median mass fractions of the four key PFASs (PFOA, PFOS, PFNA, and PFHxS) in aquatic products were significantly higher than those in meat products and eggs (all P<0.001), and there were statistically significant differences in the median mass fractions of the four PFASs among different types of aquatic products (all P<0.05). The EWI of the four PFASs was 2.970 ng·kg^-1 for the mean consumption group and 6.676 ng·kg^-1 for the high consumption group (P₉₅), with females having higher EWI values than males. ConclusionPFOS, PFOA, and PFBA are the major PFAS contaminants in animal⁃derived foods consumed by Shanghai residents, with aquatic products having the highest levels of contamination. The EWIs of four PFASs among Shanghai residents did not exceed EFSA’s recommended TWI at average consumption levels. However, the EWIs for high⁃consumption populations exceeded the EFSA⁃recommended TWI, posing potential health risks to these populations. Aquatic products contribute the most to dietary PFAS exposure. It is necessary to strengthen PFAS monitoring in aquatic products and conduct targeted risk assessments for high⁃consumption groups.

Background Deoxynivalenol (DON), a priority contaminant for food safety risk monitoring, is produced by Fusarium spp. infesting crops, and its common derivatives are 3-acetyl-DON (3A-DON) and 15-acetyl-DON (15A-DON), which have been shown to possess gastrointestinal toxicity, immunotoxicity, reproductive toxicity, and cytotoxicity. Due to the stable physicochemical properties of the DON family of toxins (DONs), they cannot be effectively removed during food processing, thus following the food chain, entering the human body, and posing health risks. Objective To understand the contamination status of DONs in commercial foods (cereals and bakery products) in Shanghai in 2022–2023, and to assess the exposure risk of DONs in pregnant women by combining their dietary consumption data. Methods Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to determine the contamination level of DONs in 1 100 food samples (cereals and baked goods) collected in 2022 and 944 samples collected in 2023 from Shanghai. The dietary monitoring data of pregnant women in Shanghai from 2016 to 2017 were adopted. The monitoring employed the food frequency questionnaire distributed among pregnant women through a combination of online telephone enquiry and offline on-site face-to-face survey to estimate their food consumption levels. An exposure assessment model was established to calculate the exposure level to DONs, and the probability distribution of the DONs exposure level in the pregnant women group in Shanghai was obtained by applying @Risk 7.5 software and simulating the calculation according to the Monte Carlo principle. With reference to the tolerable daily intake (TDI) of DONs [1.00 µg·(kg·d)⁻¹] proposed by the Joint FAO/WHO Expert Committee on Food Additives, the risk of exposure to DONs from commercial cereals and bakery products in pregnant women in Shanghai was assessed. Results DONs were detected in cereal and bakery samples collected in 2022 and 2023 with different levels of contamination. The level of DONs in cereal foods in 2023 (mean: 36.33 µg·kg⁻¹) decreased compared to 2022 (mean: 23.64 µg·kg⁻¹). However, the positive rate (71.67%) and level (mean: 51.22 µg·kg⁻¹) of DONs in bakery products increased significantly compared with 2022 (positive rate: 10.00%, mean: 24.39 µg·kg⁻¹). The mean consumption of cereals in 783 pregnant women was 222.48 g·d⁻¹ and the mean consumption of bakery products was 36.07 g·d⁻¹, and there was no statistically significant difference in the intake of all types of cereals and bakery products across the early, middle, and late stages of pregnancy. The modelled intakes of DONs via commercial cereals and bakery products for pregnant women in Shanghai were calculated to be 0.20 and 0.57 µg·(kg·d)⁻¹ in 2022 for the mean level and the 95th percentile level, respectively, and 0.16 µg·(kg·d)⁻¹ and 0.35 µg·(kg·d)⁻¹ in 2023, respectively. The results of the health risk assessment showed that pregnant women in Shanghai had 2.6% and 1.4% probability of exposure to DONs from cereal consumption in 2022 and 2023, respectively. Conclusion The risk of exposure of pregnant women in Shanghai to DONs via commercial cereals and bakery products is relatively low (1.4%-2.6%). However, considering the physical sensitivity of pregnant women, they should avoid consuming moldy grains and appropriately reduce intake of bakery products.

ObjectiveTo construct a comprehensive evaluation indicator system for clinical practice guidelines of traditional Chinese medicine （TCM） that is scientific， systematic， and reflects the characteristics of TCM. MethodsA systematic search was conducted in Chinese and English databases， including CNKI， Wanfang， VIP， SinoMed， PubMed， Embase， and Cochrane Library， to include literature on domestic and international guideline evaluation tools and TCM-related research. Document analysis and CiteSpace were utilized for keyword co-occurrence and clustering analysis. ResultsA total of 65 relevant studies were included， from which seven core thematic domains were identified. Based on the research objectives， a two-step construction strategy was adopted： first， an external evaluation framework was established by referencing international tools to cover methodological rigor and procedural standardization； second， an internal evaluation framework was developed to reflect the distinctive features of TCM clinical practice， including syndrome differentiation and efficacy feedback. Through expert consensus， the indicator system was refined， resulting in a dual-layered structure comprising 8 primary indicators， 22 secondary indicators， and 62 evaluation criteria. ConclusionThe comprehensive evaluation system for TCM clinical practice guidelines， based on bibliometric analysis and core element extraction， integrates both theoretical integrity and practical applicability. This study provides a preliminary research foundation for further optimization， validation， and development of a refined comprehensive evaluation system.

Rheumatic diseases,as a complex class of chronic immune-mediated disorders,involve interplay among genetics,environment,and immunity in their pathogenesis,which remains incompletely elucidated to date.In recent years,with the advancement of epigenetic research,particularly in the field of RNA modifications,the role of m6 A methylation in rheumatic diseases has increasingly garnered attention.Traditional Chinese medicine(TCM),as the indigenous medical system of China,has accumulated extensive experience in the treatment of rheumatic diseases.This article systematically reviewed the research progress of TCM in treating rheumatic diseases such as rheumatoid arthritis,systemic lupus erythematosus,Sj?gren's syndrome,ankylosing spondylitis,and osteoarthritis,as well as improving bone metabolism abnormalities closely related to rheumatic diseases,through regulating m6 A methylation.The aim is to provide novel insights into the treatment of rheumatic diseases with TCM and to offer theoretical support for the development of related functional drugs.

Objective:To investigate the predictive value of systemic immune inflammation index for the efficacyof neoadjuvant chemotherapy in triple negative breast cancer patients, and analyzed the relationship between pathological complete response (pCR) and prognosis.Methods:The clinical data of 146 patients with triple-negative breast cancer admitted to the 926th Hospital of the Joint Service Support Force of the PLA from January 2018 to December 2020 were retrospectively collected. All patients received neoadjuvant chemotherapy. After chemotherapy, the patients were divided into pCR group (62 cases) and non-pCR group (84 cases) according to whether the patients achieved pCR. Pathological characteristics and systemic immunoinflammatory index levels of the two groups were compared. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of systemic immunoinflammatory index for pCR after neoadjuvant chemotherapy in patients with triple-negative breast cancer, and survival curves were drawn to compare the disease-free survival of the two groups.Results:The rate of axillary lymph node metastasis in pCR group was lower than that in non-pCR group: 37.10% (23/62) vs. 64.29% (54/84), there was statistical difference ( χ2 = 10.58, P<0.01). There were no significant differences in TNM stage, Ki-67 level and histological grade between the two groups ( P>0.05). Compared with the non -pCR group, the systemic immune inflammation index in the pCR group was significantly reduced: 617.42 ± 166.40 vs. 853.67 ± 202.41, P<0.01. Systemic immune inflammation index was valuable in predicting non-pCR of triple negative breast cancer patients after neoadjuvant chemotherapy, and the area under the curve was 0.807 (95% CI: 0.738 - 0.875, P<0.01). Compared with the non-pCR group, the disease-free survival of patients in the pCR group was significantly prolonged ( P = 0.033). Conclusions:Systemic immune inflammation index was related to the efficacy of neoadjuvant chemotherapy in triple negative breast cancer patients, and can be used as a biological indicator to predict the efficacy of neoadjuvant chemotherapy in triple negative breast cancer.

This article outlines the current situation and characteristics of hospital-associated infections in elderly patients so as to reveal multiple influencing factors for the high prevalence of hospital-associated infection among the elderly patients,analyze the potential outcomes induced by the infections and observe the influence on progno-sis.The risk assessment tools were explored and stressed on their core status in monitoring of infections,risk management and quality control.The individualized prevention and control programs targeting at the elderly patients with hospital-associated infections were proposed,including precise management of antibiotics,immune regulation and multidisciplinary collaboration,which stress on the kye value of health care workers in carrying out the evidence-based prevention and control measures and evaluate the interventional effectiveness through process-outcome dual indexes so as to provide systematic solutions for reducing the risk of hospital-associated infection in the elderly patients.

BACKGROUND:Osteoarthritis is a progressive joint condition identified by ongoing deterioration of the cartilage matrix,and there is currently no effective drug treatment plan.Metformin-modified exosomes isolated from bone marrow-derived mesenchymal stem cells can become a new method for treating osteoarthritis due to their avoidance of oral drug adverse reactions and immunogenicity.OBJECTIVE:To study the controlling impact of exosomes from metformin-altered bone marrow-derived mesenchymal stem cells on chondrocytes.METHODS:Rabbit bone marrow-derived mesenchymal stem cells and chondrocytes were cultured in vitro.Bone marrow-derived mesenchymal stem cells derived exosomes and metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes were collected using a high-speed centrifuge.Chondrocytes were cultured with exosome-containing culture medium for 24 hours and then treated with 100 μmol/L H2O2 for 24 hours.The capability changes of two extracellular vesicles on chondrocyte proliferation and migration were detected using CCK8 assay and scratch healing experiment,respectively.Western blot analysis and RT-qPCR were employed to examine the alterations in the expression of type Ⅱ collagen,P16 protein,and their mRNA in chondrocytes.Western blot analysis was utilized to assess the changes in the expression of MKK7/JNK pathway proteins.ELISA kits were utilized to measure the activity of cell superoxide dismutase and the levels of malondialdehyde in chondrocytes.RESULTS AND CONCLUSION:(1)In an oxidative stress environment,the proliferation and migration abilities of chondrocytes were weakened.The two types of exosomes could restore the proliferation and migration abilities of chondrocytes to a certain extent.Metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes had a significantly better improvement effect(P＜0.05).(2)Compared with normal bone marrow mesenchymal stem cell-derived exosomes,metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes could more effectively increase type Ⅱ collagen expression and superoxide dismutase activity(P＜0.05),and were also more effective in reducing P16 expression and malondialdehyde levels(P＜0.05).(3)The two types of exosomes could inhibit the expression of MKK7 and p-JNK proteins to a certain extent,and the inhibitory effect of metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes was more significant(P＜0.05).The results show that in an oxidative stress environment,metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes resist chondrocyte aging and promote chondrocyte proliferation by inhibiting the MKK7/JNK pathway.

Rheumatic diseases,as a complex class of chronic immune-mediated disorders,involve interplay among genetics,environment,and immunity in their pathogenesis,which remains incompletely elucidated to date.In recent years,with the advancement of epigenetic research,particularly in the field of RNA modifications,the role of m6 A methylation in rheumatic diseases has increasingly garnered attention.Traditional Chinese medicine(TCM),as the indigenous medical system of China,has accumulated extensive experience in the treatment of rheumatic diseases.This article systematically reviewed the research progress of TCM in treating rheumatic diseases such as rheumatoid arthritis,systemic lupus erythematosus,Sj?gren's syndrome,ankylosing spondylitis,and osteoarthritis,as well as improving bone metabolism abnormalities closely related to rheumatic diseases,through regulating m6 A methylation.The aim is to provide novel insights into the treatment of rheumatic diseases with TCM and to offer theoretical support for the development of related functional drugs.