Objective:To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM).Methods:A retrospective cohort study design was performed . Eight-nine Children diagnosed as TBM during January 1 st 2016 and December 31 st 2023 in Department of Infectious Disease, Children′s Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results:The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions:The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.

Objective To observe the distribution of atypical memory B cells in peripheral blood of children with frequently relapsing nephrotic syndrome(FRNS).Methods A total of 60 children with primary ne-phrotic syndrome(PNS)admitted to the hospital from October 2020 to March 2023 were selected as the re-search objects.According to the response to glucocorticoid(GC),they were divided into non-frequently relap-sing nephrotic syndrome(NFRNS)group(25 cases)and FRNS group(35 cases).A total of 20 age-and gen-der-matched healthy children were enrolled as the control group.The changes of atypical memory B cells in each group before and after GC treatment were compared,and the correlation between the changes and clinical data was analyzed.Results Before GC treatment,The percentages of total B cells(CD19+CD20+),total memory B cells(CD19+CD20+CD27+),resting memory B cells(CD19+CD20+CD21+CD27+)and atypical memory B cells(CD19+CD20+CD21-CD27-)in FRNS group and NFRNS group were significantly higher than those in control group.And the FRNS group was significantly higher than the NFRNS group(P＜0.05).After GC treatment,the percentages of total B cells,total memory B cells,resting memory B cells,acti-vated memory B cells(CD19+CD20+CD21-CD27+)and atypical memory B cells in FRNS group and NFRNS group were lower than those before GC treatment(P＜0.05).The FRNS group had a significantly higher pro-portion of atypical memory B cells than the NFRNS group and the control group(P＜0.05).Before GC treat-ment,the 24 h urinary protein in FRNS group and NFRNS group were higher than those in control group,and the levels of immunoglobulin G and albumin were lower than those in control group.The 24 h urinary protein in FRNS group was significantly higher than that in NFRNS group(P＜0.05).Before GC treatment,there was a positive correlation between 24 h urinary protein and the proportion of atypical memory B cells in FRNS group(P＜0.05).Conclusion There is abnormal distribution of atypical memory B cells in peripheral blood of FRNS children.The increase of atypical memory B cells can be used as a marker of recurrence of FRNS af-ter GC treatment.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective:To investigate the effects of reduced nicotinamide adenine dinucleotide phosphooxidase 4 (NOX4) inhibitors GKT137831 and M2-type macrophages on oxidative stress markers NOX4, nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the rat hepatic stellate cell line (HSC-T6).Methods:Rat bone marrow macrophages were extracted and induced using interleukin (IL)-4 to differentiate them into M2 phenotype macrophages. HSC-T6 activation was performed with 5 μg/L transforming growth factor β1 (TGF-β1). The proliferation condition of HSC-T6 cells stimulated by the NOX4 inhibitor GKT137831 at a concentration gradient of 5 to 80 μmol/L after 48 hours was detected using the Cell Counting Kit-8 (CCK-8) assay. The optimal drug concentration was chosen and divided into an HSC co-culture group (the control group) and five experimental groups: the TGF-β1 stimulation group, the TGF-β1 +GKT137831 stimulation group, the M2-type macrophage + HSC co-culture group, the M2-type macrophage +TGF-β1 stimulation group, and the M2-type + TGF-β1 + GKT137831 stimulation group. Reactive oxygen species (ROS) production level was detected in each cell using the DCFH-DA probe method. NOX4, α-smooth muscle actin (α-SMA), Nrf2, and HO-1 levels in each group of HSC cells were detected using the qRT-PCR method and the Western blot method. The t-test was used to compare the two groups. The one-way ANOVA method was used to compare multiple groups. Results:Intracellular ROS increased significantly following TGF-β1 stimulation. ROS relative levels in each cell group were 1.03±0.11, 3.88±0.07, 2.90±0.08, 0.99±0.06, 3.30±0.05, 2.21±0.11, F ?=?686.1, P ?=?0.001, respectively. The mRNA and protein expressions of NOX4, α-SMA, Nrf2, and HO-1 were significantly increased ( P ?

OBJECTIVE：To investigate the consistency and difference of f luorescence immunochromatographic and liquid chromatography-tandem mass spectrometry （LC-MS/MS）and enzyme multiplied immunoassay technique （EMIT）in the blood concentration monitoring of mycophenolic acid. METHODS ：Fluorescence immunochromatography ，LC-MS/MS and EMIT were used to detect the blood concentration of mycophenolic acid in 61 blood samples of children treated with mycophenolate mofetil ester orally at different time points. Kolmogorov-Smirnov method ，Wilcoxon pairing test ，Passing-Bablok regression ，Cusum method，Spearman correlation analysis ，Bland-Altman scatter diagram were adopted for statistical analysis. RESULTS ：Blood concentrations of mycophenolic acid ，which were determined by fluorescence immunochromatography ，LC-MS/MS and EMIT ， showed non-normal distribution. Passing-Bablok regression analysis showed that regression equation of fluorescence immunochromatography and LC-MS/MS ，fluorescence immunochromatographic method and EMIT were CFI=0.928 3CLC-MS/MS+0.961 7 and CFI＝0.880 7CEMIT－0.488 2（FI means fluorescence immunochromatographic ）. Spearman correlation analysis showed that the correlation coefficients between fluorescence immunochromatography and LC-MS/MS ，fluorescence immunochromatography and EMIT were 0.968 and 0.929， respectively （P＜0.000 1）. Bland Altman scatter plot analysis showed that 3.28％ of the 358341451@qq.com difference between fluorescence immunochromatography and LC-MS/MS was outside the consistency limit （±1.96SD）， and 1.64％ of the difference between fluorescence immuno- chromatography and EMIT was outside the consistency limit （± 1.96SD）. Wilcoxon pairing test showed that the results of fluorescence immunochromatography were higher than those of LC-MS/MS （Z＝3.76，P＝0.000 2）and lower than those of EMIT （Z＝－5.96，P＜0.000 1）. CONCLUSIONS ：Fluorescence immunochromatography shows good consistency and correlation with LC-MS/MS and EMIT ；the blood concentrations of mycophenolic acid detected by fluorescence immunochromatography were higher than those by LC-MS/MS and lower than those by EMIT . It can be used for bedside rapid detection. When using the test results of different methods for clinical medication ，the differences of test methods need to be considered.

Objective: To explore the clinical effects of perforator flaps in the reconstruction of hypertrophic scar contracture deformities in the large joints of extremities after severe burns. Methods: From January 2008 to January 2018, 72 patients (53 males and 19 females, aged 5 to 63 years) with hypertrophic scar contracture deformities and functional disorder in the large joints of extremities after severe burns were admitted to the Department of Burns of Beijing Jishuitan Hospital. Scar hyperplasia and contracture deformity were located at shoulder joints of 28 patients, elbow joints of 15 patients, hip joints of 7 patients, knee joints of 17 patients, and ankle joints of 5 patients. The wound area of patients after the scars were excised and released ranged from 7 cm×6 cm to 34 cm×12 cm. The wounds were repaired with corresponding unexpanded perforator flaps or expanded perforator flaps according to the joint location and existing soft tissue conditions. The size of flaps ranged from 7 cm×6 cm to 35 cm×14 cm. The donor sites of 51 patients were sutured directly; the donor sites of 21 patients were repaired by segmented grafts or mesh grafts. The adopted surgeries, the survival of flaps after surgery, and the functional recovery of the joints during follow-up were recorded. Results: Among the 72 patients, 53 patients had perforator flap repairing surgery only; 19 patients had perforator flap repairing surgery and skin grafting. Among them, 12 patients had expanded perforator flaps, 60 patients had unexpanded perforator flaps. The perforator flaps were performed free transplantation in 9 patients, pedicled transplantation in 61 patients, and groin transplantation in 2 patients. At last, 67 flaps survived completely, while 5 flaps had distal-end necrosis which were healed after dressing change or skin grafting after debridement. During follow-up of 6 months to 3 years, the joint function of all the patients was obviously improved. The abduction angles of shoulder joints were over 110°; the hip, knee, and elbow joints could reach the straight position, and the flexion was normal; the foot drop deformity was corrected, and the appearance of flaps was good with obvious extension compared with the original state. Conclusions Perforator flaps are suitable for reconstruction of hypertrophic scar contracture deformities in the large joints of extremities of patients after severe burns. They can restore the joint function to the greatest extent as well as repair the wounds.

Since the first edition of Tw-DRGs was developed in Taiwan in 2002, the system introduction of the hospital management level has been successfully completed. This paper detailed the organizational structure of DRGs case management in local hospitals ( DRGs promotion group, front-end medical care, ICD end, and the medical expenses reporting). It also introduced the operation process of identifying, locking and adjusting process of the pre-hospital, in-hospital and post-hospital aspects of inpatients, and provides in the end useful experiences for the promotion of DRGs case management in China′s mainland hospitals.

Objective: To explore the experience of transportation of mass severe burn patients for long distance by air ambulance with fixed wing. Methods: The organization and implementation process of transportation of 5 patients in the devastating forest fire of Greater Khingan on 2nd, May 2017, for long distance by air ambulance with fixed wing were reviewed and analyzed. All the patients were severely burned and complicated with inhalation injury. Four hours after accident, the relevant authority dispatched national medical team with 2 specialists of burn, 1 specialist of intensive care medicine, 1 head nurse of burn intensive care unit (ICU) to treat and cure the patients before transportation. Three patients had tracheotomy and four patients had escharotomy. Patients and their relatives, expert group of transportation, and aircrew members were arranged according to the scheme before transportation. Patients were monitored and treated with the equipments of air ambulance during the transportation. Patients were transferred to the burn ICU in our hospital from the airport through the green channel. Results: All the five patients were transported to the destination safely for long distance of 1 700 kilometres and air flight 3.5 hours one way by air ambulance with fixed wing in 4 batches at 26 to 44 hours post burn, and transported from tarmac to burn ICU of our hospital. All the patients were in stable condition during the transportation and had successful subsequent rescue. All the patients were discharged in three months. Conclusions It is feasible to transfer mass severe burn patients for long distance by air ambulance with fixed wing, and it is safer and more effective to transfer according to the standardization process, and the opportunity of transportation of severe burn patients can be moved up to shock stage.

Objective To investigate the effect of microRNA-134-5p (miR-134-5p) targeting epidermal growth factor receptor (EGFR) on the growth of ovarian cancer cells.Methods The ovarian cancer cell lines SKOV3 and A2780 served as the study objects and were divided into the control group (transfecting miR-NC) and experimental group (transfecting miR-134-5p) according to the treatment method.The expression levels of EGFR gene and downstream target protein were detected by qRT-PCR and western blot.The cell cycle distribution and apoptosis were detected by flow cytometry.The proliferation ability of ovarian cancer cells was detected by MTT assay and colony forming assay.Results The expressions of EGFR and downstream target protein in the experimental group were significantly down-regulated.EGFR mRNA in SKOV3 cells was downregulated to 48％ (P＜0.05),and EGFR mRNA in A2780 cells was down-regulated to 47％ (P＜0.05).The cell cycle of cells in the experimental group was significantly inhibited (P＜0.05),and miR-134-5p induced apoptosis through the EGFR target protein (P＜0.05).The proliferation activity and colony forming ability of the experimental group were significantly inhibited (P＜0.05).Conclusion miR-134-5p could promote the cellular cycle arrest and apoptosis,and reduces the proliferation ability of ovarian cancer cells by targetedly inhibiting the EGFR gene.

Objective To investigate the roles of SENP1 in regulation of biological characteristics of NK cells.Methods Lentivirus-mediated-Senp1-small-hairpinRNA (shRNA) transduction was applied to NK92 cells.The expression of SENP1 in NK92 cells was determined by real-time PCR and Western blot.The proliferation of NK92 cells was detected by CCK-8 assay.The apoptosis of NK92 cells was determined by Annexin Ⅴ and PI labeling.The cytotoxicity of NK92 cells against K562 cells was evaluated by luciferase reporter assay.Results Treatment of NK92 cells with IL-21 resulted in SENP1 upregulation.Lentivirus mediated SENP1 knockdown reduced proliferation and increased apoptosis in NK-92 cells,but SENP1 inhibition had slight impact on the cytotoxic ability of NK92 cells to kill K562 cells.Conclusion SENP1 mediates the regulatory effect of IL-21 on the proliferation and survival of NK92 cells.