Objective To investigate the application value of bedside ultrasound monitoring of quadriceps muscle changes in mechanically ventilated children in the early treatment of ICU-acquired muscle weakness (ICU-AW). Methods Eighty-two pediatric ICU patients with mechanical ventilation for>48 hours were selected. On the day of admission (D₀) and on day 7 (D₇), bedside ultrasound was performed to measure the thickness and cross-sectional area of the rectus femoris and vastus intermedius muscles. Patients were classified using Medical Research Council scores into control group (n = 63) and muscle weakness group (n = 19). Muscle parameters and atrophy rates were compared between groups. Diagnostic performance was assessed using receiver operating characteristic curves. Results The incidence of ICU-AW was 23.17%. At both D₀ and D₇, the average thickness of the rectus femoris, the average thickness of the vastus intermedius, the average area of the rectus femoris, and the average area of the vastus intermedius were significantly different between the two groups (P<0.05). The atrophy rates of the thickness of the rectus femoris and the area of the vastus intermedius were lower in the control group than in the muscle weakness group at both D₀ and D₇ (P<0.05). The area under the receiver operating characteristic curve for quadriceps parameters in diagnosing ICU-AW was 0.871, with a sensitivity of 89.47% and a specificity of 79.37%. Conclusion Bedside ultrasound dynamic monitoring of quadriceps changes enables early identification of ICU-AW and provides a basis for clinical intervention.

Objective: To evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.

Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.

ObjectiveTo investigate the mechanism by which Shaoyaotang regulates the miRNA-155-mediated suppressor of cytokine signaling 1 （SOCS1）/Janus kinase 1 （JAK1）/signal transducer and activator of transcription 1 （STAT1） signaling pathway and thereby affects macrophage polarization. MethodsThe cell-counting kit-8 （CCK-8） assay was used to detect the effect of drug-containing serum of Shaoyaotang at different concentrations on the viability of RAW 264.7 cells. A cell model of inflammation was established by stimulating RAW264.7 cells with lipopolysaccharide （LPS） at a concentration of 10 mg·L^-1 The modeled cells were assigned by the random number table method into seven groups： LPS-induced M1 polarization （model）， M1+miRNA-155 mimics， M1+miRNA-155 inhibitor， M1+Shaoyaotang-containing serum， M1+miRNA-155 mimics+Shaoyaotang-containing serum， M1+miRNA-155 inhibitor+Shaoyaotang-containing serum， and M1+blank serum. Enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］. Immunofluorescence assay was used to detect the expression of macrophage polarization markers ［inducible nitric oxide synthase （iNOS） and macrophage mannose receptor 1 （CD206）］. Real-time PCR was employed to measure the expression of miRNA-155 in cells. Western blot was performed to determine the protein levels of SOCS1， STAT1， and JAK1. ResultsCompared with the LPS-induced M1 polarization （model） group， the M1+miRNA-155 mimics group showed up-regulated expression of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS （P<0.05） and down-regulated expression of CD206 （P<0.05）. In both the M1+miRNA-155 inhibitor group and the M1+Shaoyaotang-containing serum group， the expression levels of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS were down-regulated （P<0.05）， while those of SOCS1 and CD206 were up-regulated （P<0.05）. Compared with the M1+miRNA-155 mimics group， the M1+miRNA-155 mimics+Shaoyaotang-containing serum group showed down-regulated expression of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS （P<0.05） and up-regulated expression of SOCS1 and CD206 （P<0.05）. Compared with the M1+miRNA-155 inhibitor group， the M1+miRNA-155 inhibitor+Shaoyaotang-containing serum group showed down-regulated expression of miRNA-155， JAK1， STAT1， TNF-α， IL-6， IL-1β， and iNOS （P<0.05） and up-regulated expression of SOCS1 and CD206 （P<0.05）. ConclusionShaoyaotang regulates macrophage polarization by modulating miRNA-155 expression and interfering with the SOCS1/JAK1/STAT1 signaling pathway. The findings provide new experimental evidence for the treatment of ulcerative colitis with Shaoyaotang.

The application of immunosuppressants has significantly reduced the incidence rate of rejection reaction after liver transplantation， but the clinical efficacy of immunosuppressants is greatly affected by individual differences between patients. This article systematically reviews the recent research advances in the interaction between immunosuppressants and gut microbiota， with a focus on the regulatory role and mechanism of intestinal microflora communities on the efficacy of immunosuppressants. Studies have shown that intestinal microbiome is one of the key factors influencing the efficacy of immunosuppressive therapy after liver transplantation. This review aims to provide a theoretical basis for in-depth research in this field and provide new insights for developing individualized immunosuppressive treatment regimens based on the regulation of intestinal microflora.

OBJECTIVE To evaluate the cost-utility of iguratimod combined with methotrexate in the treatment of patients with active rheumatoid arthritis （RA） who failed monotherapy with conventional synthetic disease-modifying antirheumatic drugs （csDMARDs）.METHODS A cost-utility analysis was performed. A Markov model was constructed from the perspective of China’s healthcare system with a cycle length of 6 months to simulate the costs and health outcomes [quality-adjusted life years （QALYs）] of iguratimod combined with methotrexate versus different combined csDMARDs regimens over a 30-year time horizon. Efficacy and safety data were synthesized from randomized controlled trials via network meta-analysis. Cost parameters were derived from the Menet Database， published literature and other sources. The discount rate was set at 4.5%， and the willingness-to-pay （WTP） threshold was twice China’s per capita gross domestic product in 2025 （199 330.00 yuan/QALY）. One-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to verify the robustness of the results.RESULTS Compared with methotrexate+sulfasalazine and sulfasalazine+leflunomide， iguratimod+methotrexate was a dominant regimen. Compared with methotrexate+leflunomide， the incremental cost-effectiveness ratio of iguratimod+methotrexate was 60 577.10 yuan/QALY， which was lower than the WTP threshold. Sensitivity analyses and scenario analysis confirmed favorable robustness of the above findings.CONCLUSIONS From the perspective of China’s healthcare system， iguratimod+methotrexate is cost-effective for active RA patients failing csDMARD monotherapy， in comparison with methotrexate+leflunomide， methotrexate+sulfasalazine and sulfasalazine+leflunomide regimens.

Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

Objective In this study, the resistance of Blattella germanica to D-cyphenothrin in Guangdong Province was analyzed. Further, the contact activity of eight types of plant essential oils against B. germanica and their synergistic effects with D-cyphenothrin were tested and screened, providing a basis for slowing down insecticide resistance in pests and developing plant synergists. Methods The drip test method was used to measure the resistance levels of B. germanica to D-cyphenothrin in four cities of Guangdong Province:Zhongshan City, Foshan City, Zhuhai City, and Jiangmen City. In addition, the contact killing activities of eight types of plant essential oils against B. germanica, namely, garlic, cinnamon, clove, camphor, eucalyptus leaves, tea tree, Angelica dahurica and peppermint, and their synergistic activities with D-cyphenothrin were evaluated. Results Except for B. germanica in the Xiaolan area of Zhongshan, which was moderately resistant, B. germanica in the other four towns in Guangdong were all highly resistant. Among the eight essential oils tested, garlic essential oil had the strongest toxic activity against B. germanica, with LD50 values of 45.01 μg/individual. A concentration of 2% essential oil plus D-cyphenothrin (LD20)was used to screen for synergistic activity. After 24 h of treatment, Angelica dahurica, garlic, peppermint, camphor, and tea tree essential oils showed synergistic activity. Of these, A. dahurica essential oil had the strongest synergistic activity, with a synergistic coefficient of 125%. Conclusions The essential oil of garlic had the strongest toxic activity against B. germanica, and the essential oils of A. dahurica and garlic together had the strongest synergistic activity with D-cyphenothrin, thereby providing a reference for developing natural plant synergists.

ObjectiveTo observe the dynamic changes in heparin-binding protein (HBP), coagulation function indicators, and vascular endothelial injury markers in SD rats with sepsis, analyze the associations among these indicators, and elucidate the regulatory role of HBP in sepsis-associated coagulation disorders. MethodsEighteen specific pathogen-free (SPF) male SD rats aged 8–12 weeks were selected to establish a sepsis model using cecal ligation and puncture (CLP). Blood samples were collected from the heart at 0 hours before modeling and at 3, 6, and 9 hours post-modeling. Thromboelastography (TEG) with standard and heparinase cups was used to determine the difference in reaction time (R value) between the two cups (ΔR), thereby evaluating coagulation function and the endogenous heparin effect. Plasma levels of HBP, heparan sulfate (HS), syndecan-1 (SDC-1), and thrombomodulin (TM) were measured by enzyme-linked immunosorbent assay (ELISA). Samples with ΔR≥2 min were grouped as the ΔR≥2 min group, while those with ΔR<2 min were grouped as the ΔR<2 min group. Correlation and receiver operating characteristic (ROC) curve analyses were performed to evaluate the relationship between HBP and various indicators, as well as its predictive efficacy for ΔR values. ResultsΔR, HS, SDC-1 and HBP significantly increased after modeling compared with 0 hours (P<0.01). The HS, SDC-1, and HBP levels in the ΔR≥2 min group were significantly higher than those in the ΔR<2 min group (P<0.05 or P<0.01). HBP showed a significant positive correlation with ΔR and HS (P<0.05), while ΔR was significantly positively correlated with HS (r=0.799, P<0.01) and weakly positively correlated with SDC-1 (r=0.289, P<0.05). HS, HBP, and SDC-1 demonstrated significant predictive value for ΔR≥2 min (P<0.01). ConclusionIn the early stages of sepsis, the release of HS-like anticoagulant substances from the glycocalyx following its degradation can lead to coagulation disorders, while HBP can reflect the pathological process and play an important regulatory role in the occurrence and development of sepsis-related coagulation disorders.