Objective:To investigate the safety of tocilizumab (TCZ) in the treatment of children with systemic juvenile idiopathic arthritis (sJIA).Methods:Data of children aged 2 to 18 years with the diagnosis of sJIA and treated with TCZ from June 1, 2017 to June 30, 2022 at our hospital were retrospectively collected. The clinical medication characteristics, incidence, severity and outcome of adverse drug reactions (ADR) were statistically analyzed. Univariate and multivariate analysis were used to analyze the risk factors of TCZ-induced ADR. Univariate comparison between groups were compared to the measured data followed by t test for normal distribution, and the counting data were paired with Chi-square test. Binary logistic regression analysis was used for multivariate analysis. Results:A total of 83 eligible children were enrolled. The age at TCZ initiation was (8.5±3.7) years old. Most of the children received oral glucocorticoid (86.8%) and/or methotrexate (72.3%) prior to TCZ treatment. The mean time of TCZ duration was (1.2±0.9) years, the total TCZ exposure was 92.70 patient years. Fifty-five (66.3%) children reported 123 ADR, with a rate of 132.69/100 patient years. Forty-two (50.6%) children reported 103 general ADR, with a rate of 111.11/100 patient years. Eighteen (21.7%) children reported 20 serious ADR, with a rate of 21.57/100 patient years. The results of univariate analysis showed that the dosage of glucocorticoid in ADR group was higher than that in non-ADR group [(0.76±0.50) mg·kg -1·d -1vs. (0.52±0.41) mg·kg -1·d -1, t=2.27, P=0.026], and the difference was statistically significant. However, there were no significant differences in gender [(male 23, female 32) cases vs. (male 9, female 19) cases, χ2=0.73, P=0.392], age at TCZ initiation [(8.5±3.8) years old vs. (9.0±3.1) years old, t=-0.65, P=0.516], duration of TCZ treatment [(1.24±1.00) years vs. (1.05±0.90) years, t=0.87, P=0.385], methotrexate doses weekly [(8.0±5.2) mg/m 2vs. (7.6±5.1) mg/m 2, t=0.39, P=0.696], and history of drug or food allergy (11 cases vs. 5 cases, χ2=0.06, P=0.815) between the two groups. The results of binary logistic regression analysis showed that the combined use of oral glucocorticoids was an independent risk factor for TCZ-induced ADR [ OR (95% CI) =3.05 (1.11, 8.36), P=0.030]. The risk of ADR was 3.05 times higher in the combined daily dose of glucocorticoids ≥0.76 mg/kg prednisone equivalent than that of < 0.76 mg/kg. Common general ADR to TCZ include infections (38.83/100 patient years) and abnormalities in laboratory parameters (37.76/100 patient years) such as elevated glutamic-pyrupiane transaminase (18.34/100 patient years), dyslipidemia (12.94/100 patient years), and hemocytopenia (5.39/100 patient years). The serious ADR included serious infection (9.71/100 patient years) and serious infusion reaction(7.55/100 patient years). All ADR were improved after drug withdrawal or symptomatic treatment, and no deaths occurred. Conclusion:TCZ has a good safety profile in the treatment of sJIA. Serious infections and severe infusion reactions often lead to discontinuation of the drug. The combination of glucocorticoids≥0.76 mg/kg prednisone equivalent is an independent risk factor for TCZ-induced ADR. Monitoring should be strengthened during the application of TCZ, and ADR should be detected and treated as early as possible to reduce the risk of medication related adverse reactions.

【Objective】 To investigate the value of three hemolysis tests and carboxyhemoglobin (COHb) level in the diagnosis of hemolytic disease of the fetus and newborn (HDFN). 【Methods】 From January 1, 2019 to December 31, 2022, the neonates hospitalized in the Department of Neonatology of Hebei Provincial Children's Hospital with suspected hemolytic disease who had serological testing were retrospectively enrolled in the study. They were distributed into HDFN group and non-HDFN group according to the final diagnosis. Their clinical and laboratory data were collected and analyzed, and the COHb level was detected by blood gas analyzer. 【Results】 A total of 378 neonates with HDFN and 217 neonates without HDFN were included in the study. Most of the neonates in HDFN group were full-term infants (348/378, 92.1%), with median gestational age of 39.1 (38.3, 40.0) weeks. Three hundred and fifty-four cases (354/378, 93.7%) were ABO-HDFN and the rest were Rh HDFN. There were significant differences in the level of serum total bilirubin, hemoglobin, COHb and reticulocyte percentage at admission between the two groups(P<0.05). The positive rate of three hemolysis tests in HDFN group decreased with the increase of the days after birth. The highest positive rate (more than 80%) was observed within 2 days after birth. Correlation analysis showed a negative relationship between the COHb level and the age (rs = -0.434, P<0.001) . Among the three hemolysis tests in HDFN group, the positive rate of antibody release test was the highest (69.0%), followed by the free antibody test (55.6%) and the direct antiglobulin test (DAT) (36.0%). Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off value of COHb was 1.15%.The sensitivity of COHb ≥ 1.15% was 51.8%, higher than single DAT (36.0%) . The diagnosis effectiveness of three hemolysis tests couldn't be improved when combined with COHb detection(Z = -0.727, P>0.05) . 【Conclusion】 The three hemolysis tests are important in the diagnosis of HDFN, among which the antibody release test has the highest sensitivity. COHb has certain value for the diagnosis of HDFN, but joint testing cannot improve the diagnosis effectiveness of three hemolysis tests. Hemolysis tests and/or COHb detection should be conducted for neonates at risk of hemolysis as early as possible after birth.

The Master of Public Health (MPH) is one of the internationally recognized ways of training professionals in the medical and health field. With the outbreak of COVID-19 pandemic, the need for talents who can serve the national public health emergency management system has accelerated. This article makes the comparison of public health education in China and the UK, starting from the reasons and advantages of medical education in two countries, selecting several universities with high rankings in public health in China and the UK as the research objects, collecting and summarizing their programme descriptions, from the enrollment mode, training objectives, cultivation mode and degree types, curriculum settings, etc., in the MPH programme descriptions in order to find the advantages of MPH education in the UK, which can be used for reference in the education and training of public health talents in China, and is of great significance for the improvement and optimization of MPH education in China.

Objective To investigate the efficacy and safety of fluzopril in the treatment of platinum-sensitive recurrent epithelial ovarian cancer.Methods A total of 107 patients with platinum-sensitive recurrent epithelial ovarian cancer admitted to the First Affiliated Hospital of Henan University of Science and Technology from January 2019 to December 2020 were selected as the subjects.According to treatment methods,the patients were divided into control group(n=50)and observation group(n=57).The patients in the control group received a first-line chemotherapy regimen of paclitaxel combined with platinum:on the first day,intravenous infusion with paclitaxel injection 135 mg·m-2 was administered;on day 1-3,intravenous drip with cisplatin 50-60 mg·m-2 was administered;21 days was one chemotherapy cycle.On the basis of the treatment in the control group,the patients in the observation group were given fluzoparide capsules orally,150 mg each time,twice a day,and the treatment continued until disease progression or unacceptable toxic reactions occurred;21 days was one chemotherapy cycle.The patients in both groups received three consecutive chemotherapy cycles.The clinical efficacy,prognosis within 2 years after chemotherapy,Karnofsky Performance Status(KPS)score before and after chemotherapy,and incidence of adverse reactions during chemotherapy of patients between the two groups were compared.Results After 3 cycles of chemo-therapy,the disease control rate and objective remission rate of patients in the observation group were significantly higher than those in the control group(x2=5.420,4.220;P＜0.05).Following up to 24 months,the progression free survival of patients in the observation group was significantly longer than that in the control group(t=6.702,P＜0.05);there was no statistically significant difference in 1-year survival rate of patients between the two groups(x2=0.415,P＞0.05);the 2-year survival rate of patients in the observation group was significantly higher than that in the control group(x2=5.420,P＜0.05).Before chemotherapy,there was no statistically significant difference in KPS scores of patients between the two groups(t=0.537,P＞0.05);the KPS scores of patients in the two groups after three cycles of chemotherapy were significantly higher than those before chemotherapy(t=5.604,9.378;P＜0.05);after three cycles of chemotherapy,the KPS score of patients in the observation group was significantly higher than that in the control group(t=2.608,P＜0.05).The patients in both groups experienced hematological and non-hematological adverse reactions during chemotherapy;the main hematological adverse reactions was bone marrow suppression,most of which were Ⅲ ° and Ⅳ ° adverse reactions;the non-hematological adverse reactions included alo-pecia,gastrointestinal reactions,and liver and kidney dysfunction,most of which were Ⅰ°and Ⅱ°adverse reactions.There were no chemotherapy related deaths of patients in both groups.The incidence rates of anemia,thrombocytopenia,neutropenia,leuko-penia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated alanine amino-transferase(ALT)of patients during chemotherapy in the control group were 68.00％(34/50),72.00％(36/50),58.00％(29/50),68.00％(34/50),22.00％(11/50),26.00％(13/50),24.00％(12/50),46.00％(23/50),30.00％(15/50),50.00％(25/50),20.00％(10/50),10.00％(5/50),respectively;the incidence rates of anemia,thrombocytopenia,neutropenia,leukopenia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated ALT of patients during chemotherapy in the observation group were 61.40％(35/57),63.16％(36/57),49.12％(28/57),52.63％(30/57),21.05％(12/57),22.81％(13/57),24.56％(14/57),42.11％(24/57),29.82％(17/57),47.37％(27/57),21.05％(12/57),10.53％(6/57),respectively.There was no statistically significant difference in the incidences of anemia,thrombocytopenia,neutropenia,leukopenia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated ALT of patients during chemotherapy between the control group and the observation group(x2=0.047,0.000,0.041,0.694,0.056,0.000,0.208,0.041,0.184,0.160,0.233,0.102;P＞0.05).Conclusion For patients with platinum-sensitive recurrent ovarian cancer,the combination of paclitaxel and platinum chemo-therapy combined with fluzopril can effectively improve the anti-tumor effect,prolong the progression-free survival,improve survival rate and quality of life,and the adverse reactions are controllable.

Lung transplantation is the only effective treatment of most end-stage lung diseases. Airway anastomotic complications are the main obstacles affecting the postoperative survival and quality of life of lung transplant recipients. Airway anastomotic stenosis is the most common airway anastomotic complication after lung transplantation. In recent years, improvements in the recipient selection, organ preservation, surgical techniques, postoperative intensive care management, immunosuppression, antifungal and endoscopic treatment have decreased the incidence of airway anastomotic stenosis and improved the surgical efficacy of lung transplantation and the survival of the recipients. In this article, the pathogenesis, risk factors, diagnosis and treatment of airway anastomotic stenosis after lung transplantation were reviewed, aiming to provide novel ideas for clinical research, diagnosis and treatment of airway anastomotic stenosis following lung transplantation.

Objective:To investigate the clinicpathological characteristics of post-transplant lymphoproliferative disorders (PTLD) in transplanted lung, and to improve its diagnosis and treatment.Methods:The clinicopathological characteristics of PTLD in three transplanted lungs were evaluated at Wuxi People′s Hospital Affiliated to Nanjing Medical University from 2014 to 2019. HE, immunohistochemical staining and in situ hybridization were performed. The relevant literature of PTLD was reviewed.Results:All three patients had chronic obstructive pulmonary disease (COPD) before lung transplantation. After receiving both lung transplants, they were all treated with anti-rejection drugs tacrolimus or mycophenolate mofetil, and combined with antiviral and/or rituximab. The time from transplantation to diagnosis of PTLD was four years, seven months, and five months, respectively. Two patients died one month and five months after initial diagnosis, and one patient was alive with no disease after one year. Histologically, all cases were monomorphic B-cell PTLD (diffuse large B-cell lymphoma, unspecified), and the tumor cells were positive for Epstein-Barr virus by in situ hybridization; one of the late-onset patients had herpes simplex virus infection.Conclusions:PTLD in the post-transplant lung tissue shows unique morphology and clinical characteristics, and is closely related to Epstein-Barr virus infection. Patients who receive lung transplantation due to COPD are more susceptible to develop PTLD, while late-onset ones occur more commonly in the hilum of lungs, and the prognosis is relatively poor.

Objective To study the action of kaempferol (KAE) against Candida albicans biofilms and explore the potential mechanisms. Methods Biofilm metabolic activity assay was used to investigate the action of KAE against C. albicans biofilm formation as well as mature biofilm. The inhibition of KAE in hyphal formation was examined by microscope. The water-hydrocarbon two-phase separation assay was used to test the effect of KAE on the cell surface hydrophobicity of C. albicans. The mRNA expression of the genes involved in biofilm formation was determined by real time RT-PCR. Results KAE showed inhibition effect on C. albicans biofilm formation in a dose-dependent manner. Moreover, KAE inhibited mature biofilm. The biomass of biofilm was reduced upon KAE treatment. KAE inhibited hyphal formation and reduced the cell surface hydrophobicity of C. albicans. In the presence of KAE, the mRNA expression of the genes involved in biofilm formation was changed, with the up-regulation of BCR1,NRG1,TUP1 and down-regulation of HWP1,EFG1,CPH1,ALS1,ALS3 and CSH1. Conclusion KAE showed antifungal activity against C. albicans biofilm. The mechanisms may relate to the inhibition of hyphal formation and reduction of cell surface hydrophobicity.

Objective To evaluate the clinical efficacy ofZi Wu Liu Zhu Na Jia needling (acupuncture based on midnight-noon ebb-flow theory) in treating spastic hemiplegia after cerebral stroke by using surface electromyography (sEMG).Method Fifty-two patients with spastic hemiplegia due to cerebral stroke were randomized into a treatment group and a control group, 26 cases each. The two groups were both intervened by conventional rehabilitation training. In addition, the treatment group was givenZi Wu Liu Zhu Na Jia needling and the control group was given ordinary acupuncture. The two groups were treated once a day, 15 sessions as a course. The ambulation ability, muscle tension, neurological deficit score (NDS), Fugl-Meyer Assessment Scale (FMA), and Berg Balance Scale (BBS) were evaluated before the intervention and after 2 treatment courses, and the sEMG signals were also collected and analyzed.Result The Holden's Functional Ambulation Classification (FAC) and Modified Ashworth Scale scores were significantly changed in the two groups after the intervention (P<0.01). After the intervention, the FAC and MAS scores in the treatment group were significantly different from those in the control group (P<0.05). The NDS, FMA and BBS scores were significantly changed in the two groups after the treatment (P<0.05). The NDS, FMA and BBS scores in the treatment group were significantly different from those in the control group after the treatment (P<0.05). Of the sEMG signals, H/M max in the treatment group was significantly different from that in the control group after the intervention (P<0.01).Zi Wu Liu Zhu Na Jia needling with rehabilitation training can significantly mitigate the muscle tension and promote the activities of daily living in patients with spastic hemiplegia after cerebral stroke.

Objective To investigate the indirect decompression effect of oblique lateral interbody fusion (OLIF) in the treatment of mild to moderate degenerative lumbar stenosis.Methods From October 2014 to November 2016,23 patients with mild to moderate lumbar spinal stenosis underwent OLIF combined with or without posterior pedicle screw fixation;9 males and 14 females with average age of 59.2±11.6 years old;8 cases at L3,4 segment and 15 cases at L4,5 segment.All cases were followed up for more than 6 months.Thin layer scanning of CT and two-dimensional reconstruction images were used to measure the vertical diameter and area of intervertebral foramen.Intervertebral disc height and spinal canal anteroposterior diameter were measured on median sagittal MRI sequence,and the anteroposterior diameter and the cross-sectional area of the spinal canal were measured on cross-sectional MRI sequence.The clinical effects were assessed by the visual analogue score (VAS) and the Oswestry disability index (ODI) for low back pain,lower limb pain and lower limb numbness.Results Compared with those measurements pre-operatively,the post-operative intervertebral disc height increased by 78.6％±13.4％.The post-operative left vertical diameter of intervertebral foramen increased by 36.7％±7.8％,and the post-operative left area of intervertebral foramen increased by 36.6％± 8.7％,and the post-operative right vertical diameter of intervertebral foramen increased by 40.7％±9.6％,and the post-operative right area of intervertebral foramen increased by 40.0％±8.9％.The post-operative anteroposterior diameter of sagittal spinal canal were increased 32.6％ ± 5.9％,and the post-operative anteroposterior diameter of cross-sectional spinal canal were increased 34.4％±6.8％,and the post-operative cross-sectional area of the spinal canal were increased 47.5％±7.2％.All of the differences were statistically significant between pre-operative and post-operative measurements.The VAS score for low back pain was 6.2± 1.7 pre-operatively,and 1.1±0.5 post-operatively.The ODI for low back pain was 81.2％± 18.2％ pre-operatively,and 6.1％±2.0％ post-operatively.The VAS score for lower limb pain was 5.6±1.4 pre-operatively,and 0.8±0.3 post-operatively.And the VAS score for lower limb numbness was 6.6±2.0 pre-operatively,and 3.4± 1.2 post-operatively.All of the differences were statistically significant between pre-operative and post-operative evaluations.Conclusion There were obvious radiological evidences and remarkable clinical effect of indirect decompression using OLIF technique in treatment of mild to moderate lumbar spinal stenosis at early post-operative stage.However further long-term follow-up studies with multicenter large sample were still needed.

Objective To explore the variation in the gene mutation patterns and risk factors of HBV polymerase region (P) in chronic viral hepatitis (CHB) patients with nucleoside analogues therapy.Methods A total of 108 chronic hepatitis B patients with viral breakthrough after the treatment of nucleoside analogues were selected as the study subjects.The PCR product direct sequencing method was used to analyze the genetic variation of HBV P region.Results Among 108 cases,69 cases were detected by gene drug resistance,and the mutation type amount to 12,among which rtM204I was the most common (30.4％),and the second was rtL180M/rtM204I combined mutation (13％).The proportion of the major nucleoside analogues resistance highest proportion of lamivudine was 62.3％,followed by adefovir dipivoxil (21.7％) and telbivudine (15.9％).There were 33 cases with a single site mutation,29 cases with two sites mutation and 7 cases with three and above sites mutation.In the 7 cases,1 case was treated with lamivudine,1 case with entecavir,and the remaining 5 cases with irregular combined or sequential use of lamivudine,adefovir dipivoxil and entecavir.Conclusion The amino acid of HBV P gene resistant mutation is complex and varied,and rtM204V/I mutation is the most common type.Three and above sites mutation is associated with irregular combined or sequential use of lamivudine,adefovir dipivoxil and entecavir.