Objective: To investigate the mechanism by which serum amyloid P component (SAP) alleviates periodontitis in mice, providing an experimental basis to establish SAP as a novel therapeutic agent for periodontitis. Methods: Ethical approval was obtained from the Institutional Animal Ethics Committee. Periodontitis models were established in wild-type (WT) mice and SAP-transgenic (SAP-Tg) mice, divided into four groups: WT control (WT group), WT periodontitis (WT+P group), SAP-Tg control (Tg group), and SAP-Tg periodontitis (Tg+P group). On day 7, the mice were euthanized, and periodontal tissues, teeth, and alveolar bone were collected. SAP protein expression was detected by enzyme-linked immunosorbent assay (ELISA). Micro-CT and HE staining were used to measure alveolar bone resorption (distance from the cementoenamel junction to the alveolar bone crest). Tartrate-resistant acid phosphatase (TRAP) staining was performed to assess osteoclast number, and immunohistochemistry (IHC) was employed to evaluate macrophage infiltration. The expression levels of inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by qRT-PCR. Oral microorganism composition was analyzed using 16S ribosomal RNA (16S rRNA) gene sequencing. Additionally, macrophages from WT and SAP-Tg mice were isolated to establish an in vitro inflammation model, divided into WT+LPS and Tg+LPS groups. The expression of macrophage polarization-related genes including inducible nitric oxide synthase (iNOS), CD86, CD163, and CD206) were assessed by qRT-PCR. After the induction of osteoclast differentiation, TRAP staining was performed. Results: ELISA results demonstrated that periodontal tissues from Tg+P group mice exhibited higher levels of SAP expression compared to the WT+P group. Micro-CT and HE staining analyses revealed that the Tg+P group showed reduced alveolar bone resorption, indicated by a shorter distance between the cementoenamel junction and alveolar bone crest, compared to the WT+P group. Furthermore, TRAP staining results indicated a decrease in osteoclast numbers in the Tg+P group compared to the WT+P group. IHC and qRT-PCR results indicated reduced macrophage infiltration and decreased expression of IL-1β, IL-6, and TNF-α in the Tg+P group. Oral microorganism sequencing showed no significant difference in periodontitis-associated pathogenic bacteria between WT+P and Tg+P groups. In vitro experiments demonstrated that compared to the WT+LPS group, the Tg+LPS group exhibited downregulated M1 macrophage markers (iNOS and CD86) and upregulated M2 macrophage markers (CD163 and CD206). TRAP staining confirmed fewer osteoclasts in the Tg+LPS group. Conclusion SAP overexpression effectively alleviates periodontitis severity in mice by inhibiting M1 macrophage polarization, reducing pro-inflammatory cytokine expression, and suppressing osteoclast differentiation, thereby attenuating alveolar bone resorption.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

AIM To investigate the clinical effects of Feining Paidu Decoction combined with conventional treatment on patients with Mycoplasma pneumoniae lobar pneumonia.METHODS Ninety patients were randomly assigned into control group(45 cases)for 2-week intervention of conventional treatment,and observation group(45 cases)for 2-week intervention of both Feining Paidu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,inflammatory indices(WBC,N,CRP,ESR,PCT),inflammatory cytokines(TNF-α,IL-6,IL-8),coagulation indices(PLT,TT,PT,APTT,Fib,D-D),pulmonary imaging intergal and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,inflammatory indices,inflammatory cytokines,PLT,pulmonary imaging intergal(P<0.05),especially for the observation group(P<0.05);the observation group exhibited prolonged TT,PT,APTT(P<0.05),and decreased Fib,D-D(P<0.05),which were more obvious than those in the control group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with Mycoplasma pneumoniae lobar pneumonia,Feining Paidu Decoction combined with conventional treatment can safely and effectively alleviate clinical symptoms,and improve inflammatory responses,coagulation functions.

Objective:To analyze and summarize the efficacy and safety of thalidomide in the treatment of refractory systemic juvenile idiopathic arthritis（sJIA）.Methods:The clinical data of ten patients with refractory sJIA admitted to Department of Nephrology and Immunology in Children's Hospital of Hebei Province from January 2015 to March 2022 were collected，and the clinical manifestations，efficacy and safety of thalidomide in the treatment of refractory sJIA were analyzed retrospectively. Systemic juvenile arthritis disease activity score（sJADAS）was used to evaluate the efficacy of the treatment. Statistical analysis was performed by repeated measurements using general linear models.Results:Among the 10 children（4 males and 6 females）with refractory sJIA，the average age of onset was（7.5±3.3）years. Seven patients were complicated with macrophage activation syndrome at an early stage of disease.The average course of disease was（4.4±1.7）years，and the longest course of disease was 8.3 years. Before the application of thalidomide，all the 10 children experienced relapses（ranging from 2 to 10 times）. The indices of 10 children treated with thalidomide at 6 months and 12 months were compared with those before treatment. Peripheral blood leukocytes［（10.19±3.67）×10 9/L，（8.53±2.83）×10 9/L vs.（16.11±7.81）×10 9/L， F=7.918，11.084， P=0.020，0.009］，C-reactive protein［19.13（0.38，35.21）mg/L，8.05（0.10，18.00）mg/L vs. 59.34（24.20，131.90）mg/L， F=7.030，12.731， P=0.026，0.006］，sJADAS scores［6.00（1.50，12.50）scores，3.00（0，12.50）scores vs. 20.00（11.50，28.00）scores， F=14.710，17.870， P=0.004，0.002］were decreased significantly. The doses of prednisone［0.13（0，0.45）mg/（kg·d），0.02（0，0.06）mg/（kg·d）vs. 0.42（0.16，1.47）mg/（kg·d）， F=5.890，7.623， P=0.041，0.022］were significantly decreased.All the differences were statistically significant. Prednisone was successfully discontinued in 7 cases. Tocilizumab was gradually withdrawn in 3 cases，and tocilizumab administration interval was prolonged in 1 case. None of the 10 children had serious adverse reactions. Conclusion:Thalidomide is clinically effective in the treatment of sJIA，and can reduce the required dose of prednisone and prolong the tocilizumab free remission.

Objective:To compare the similarities and differences of macrophage activation syndrome（MAS）combined with systemic juvenile idiopathic arthritis（sJIA）versus with juvenile onset systemic lupus erythematosus（JSLE）.Methods:The clinical data of 48 children with MAS admitted to the Department of Nephrology and Immunology in Children's Hospital of Hebei Province from May 2015 to January 2023 were retrospectively analyzed. The patients were divided into sJIA-MAS and JSLE-MAS group，and the clinical manifestations，laboratory indicators and treatment of the two groups were compared.Results:Among the 48 children（14 males and 34 females）with MAS，the average age of onset was 9.5（3.0，11.8）years. There were 28 cases（11males and 17 females）of sJIA-MAS and 20 cases（3 males and 17 females）of JSLE- MAS. All the 48 children with MAS had fever and hyperferinemia，and the fever with sJIA-MAS was mostly continued fever or remittent fever. Respiratory tract infection was the most common trigger in sJIA-MAS［15 cases（53.6%）］，and disease activity was the most common trigger in JSLE-MAS［13 cases（65.0%）］.Additionally，viral infections（EB virus and cytomegalovirus）were also one of the triggers in MAS［sJIA：7 cases（25%），JSLE：4 cases（20%）］.Compared with JSLE-MAS，the number of days with fever［15.0（12.0，21.0）days vs. 6.0（4.0，9.5）days， Z=-3.812， P=0.001］and the length of hospital stay［29.0（26.3，39.8）days vs.26.0（19.3，30.8）days， Z=-1.958， P=0.049］were longer in sJIA. Compared with JSLE-MAS，ALT［（685.32±561.67）U/L vs.（139.61±124.44）U/L， t=4.973， P=0.001］，AST［784.00（235.25，1 251.25）U/L vs.189.50（53.25，374.08）U/L， Z=-3.283， P=0.001］，CRP［11.48（3.56，28.89）mg/L vs.1.91（0.53，8.98）mg/L， Z=-3.200， P=0.001］，ferritin［32 167.0（12 384.8，65 963.8）μg/L vs.2 003.5（922.5，11 430.0）μg/L， Z=-4.130， P=0.001］，ferritin max/ESR min［1 353.35（355.75，4 342.53）vs.91.92（34.94，291.53）， Z=-4.120， P=0.001］were higher in sJIA.The decrease of CRP was greater in sJIA［80.04（45.64，143.71）mg/L vs.10.20（6.27，25.64）mg/L， Z=-4.433， P=0.001］.Compared with sJIA-MAS，peripheral white blood cell counting［4.05（2.90，7.73）×10 9/L vs.1.56（1.15，3.47）×10 9/L， Z=-3.577， P=0.001］and platelet counting［（162.68±92.19）×10 9/L vs.（110.10±72.99）×10 9/L， t=2.118， P=0.040］were lower in JSLE-MAS. Kidney involvement was more common in JSLE-MAS［10 cases（50%）vs.0 cases（0%）， χ 2=17.684， P=0.001］.There was no significant difference in the incidence of sJIA-MAS and JSLE-MAS meeting the criteria of hemophagocytic lymphohistiocytosis［6 cases（21.4%）vs.5 cases（25.0%）， χ 2=0.084， P=0.772］. Conclusion:Compared with JSLE-MAS，sJIA-MAS is more dangerous and difficult to control，while JSLE-MAS involves more organs，among which the blood system and kidney are more common.

Aim To investigate the regulatory and an-ti-tumour effects of baicalein on mouse hepatocellular carcinoma cells and mouse macrophage co-cultures.Methods In vitro experiments,mouse hepatocellular carcinoma cell H22 and mouse macrophage RAW264.7 were randomly divided into a blank group and different concentrations of gradient administration group(5,10,20,40,80 mg·L-1),and the cell activity was detec-ted by CCK-8 assay;the two kinds of cells were co-cultured in Transwell chambers of 6-well plates for 48 h,and were randomly divided into the blank,model,and low,medium,and high baicalin groups(10,20,40 mg·L-1).Cell scratch and invasion assays,ELISA kits were used to detect TNF-α and IL-10 factor levels,and Western blot was used to determine the lev-els of CCNA2 and related proteins.The levels of TNF-α and IL-10 were detected by ELISA kits,and the ex-pression levels of CCNA2 and related proteins were de-tected by Western blot.In vivo experiments,H22 sub-cutaneous tumour model was established and randomly divided into the blank,positive,model and drug-ad-ministered groups.Mouse spleen,thymus and tumour indices were counted,and immunohistochemistry and Western blot were employed to detect the expression levels of CCNA2 and macrophage-related indexes in tumour tissues.Results Different doses of baicalein had a significant inhibitory effect on H22 and no signif-icant cytotoxicity on M0-type RAW264.7;the mor-phology of M0-type RAW264.7 cells was changed after co-culture,TNF-α was elevated and IL-10 was re-duced in the baicalein group;the results of the cell scratch assay and invasion assay found that baicalein inhibited M2-type macrophage invasion and metastasis;Arg1,p-p38/p38,p-stat3/stat3,N-cadherin,CCNA2 decreased significantly and Inos and E-cadherin in-creased significantly in the baicalein group;CCNA2,CD206 expression decreased significantly and CD86 expression increased significantly in the administered group.Conclusions Baicalein reverses M2-type mac-rophage polarisation and pro-carcinogenic functions and inhibits M2-type macrophage migration and invasion by modulating M2-type macrophage-related signalling pathways.

Objective To analyze the expression levels of the three different subtypes of peroxisome proliferator-activated receptors(PPARs),including PPAR-α,PPAR-β and PPAR-γ,in the ectopic lesion tis-sues of the patients with endometriosis(EMs)in order to provide new methods for this disease diagnosis.Methods The ectopic endometrial tissue samples from 30 patients with EMs treated by laparoscopic surgery in this hospital from April to December 2021 were selected as the experimental group,and the ovarian lesion tissue samples from 30 patients with mature cystic teratoma of the ovary(MCTO)during the same period treated by laparoscopic surgery were selected as the control group.The expression levels of PPAR-α,PPAR-βand PPAR-γ in lesion tissues were detected by using immunohistochemistry,and their expression differences between the experimental group and control group were analyzed.The receiver operating characteristic(ROC)curve was utilized to evaluate the diagnostic value of the ratios of PPAR-α/PPAR-β,PPAR-α/PPAR-γ,and PPAR-β/PPAR-γ for EMs.Results The expression levels of PPAR-α,PPAR-β and PPAR-γ in the lesion tis-sues of the experimental group were significantly higher than those of the control group(P＜0.05).In the pa-tients with EMs,PPAR-α was predominantly expressed(P＜0.05),whereas in the patients with MCTO,PPAR-γ was predominantly expressed(P＜0.05).In the ROC curve of PPAR-α/PPAR-β ratio for diagnosing EMs,when the cutoff value was 1.251,the area under the curve(AUC)was 0.65(95％CI:0.51-0.80),the sensitivity was 90.00％,and the specificity was 50.00％.In the ROC curve of PPAR-α/PPAR-γ ratio for diag-nosing EMs,when the cutoff value was 0.817,AUC was 0.88(95％CI:0.78-0.99),the sensitivity was 96.67％and the specificity was 80.00％.In the curve of the PPAR-β/PPAR-γ ratio for diagnosing EMs,when the cutoff value was 0.755,AUC was 0.91(95％CI:0.82-1.00),the sensitivity was 100.00％,and the speci-ficity was 86.67％.Conclusion The expression of PPAR-α in the ectopic lesion tissues of the patients with EMs is significantly higher than that of PPAR-β and PPAR-γ,while in lesion tissues of the patients with MC-TO,the PPAR-γ expression is predominant.The PPAR-β/PPAR-γ ratio may become a potential biomarker for diagnosing EMs.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Dioscoreae Rhizoma formula granules are made from decoction pieces by decocting， extracting， separating， concentrating， drying and granulating， which have the advantages of simple dispensing， convenient use and easy to take without decoction. However， because Dioscoreae Rhizoma is rich in starch and mucus components， its extract powder and formula granules are poorly soluble and difficult to dissolve or disperse completely within 5 min， and the insoluble material is difficult to dissolve completely even after 24 h in water， which affects the quality evaluation of the formula granules and medication psychology of patients. Therefore， by studying the dissolution process and mechanism of Dioscoreae Rhizoma extract and its formula granules， it was found that the special chemical composition of Dioscoreae Rhizoma， the denaturation of starch and its compounding with protein and other substances during the high temperature extraction process， and the contraction of coating membrane during the spray drying process were combined to form the special microstructure of coating membrane covering starch granules， and it is the root cause of poor solubility of Dioscoreae Rhizoma formula granules. Based on the research on the structure， property and function of the powder， this paper proposed a technical strategy to improve the solubility of Dioscoreae Rhizoma formula granules by powder modification process， and experimentally demonstrated that the modified Dioscoreae Rhizoma formula granules could completely dissolve within 2 min， which solved the technical problem and could provide reference for the improvement of solubility of other similar varieties， and promote the high-quality development of traditional Chinese medicine formula granule industry.