Objective:To analyze the clinical, genetic mutation characteristics, and treatment prognosis of type 2A hereditary hemochromatosis (HH) in China.Methods:Peripheral blood samples and clinical data of patients with primary iron overload were collected through the China Registry of Genetic/Metabolic Liver Disease from June 2015 to November 2023. HH-related genes were detected by Sanger sequencing. Clinical characteristics and gene mutation characteristics of HH patients carrying HJV gene mutations were analyzed.Results:Among the 37 cases with primary iron overload, ten cases (27.0%, 10/37) had detectable HJV gene mutations, which included four homozygous mutations, five compound heterozygous mutations, and one monoheterozygous mutation. p.Q6H and p.C321X (80.0%, 8/10) were the most common mutated sites. The average age of onset was 30.7±14.7 years. The age of diagnosis was 35.7±16.2 years, with male-to-female ratio of 7:3. Ferritin and transferrin saturation were (5 267±905) ng/ml, and 94.3%±1.2%, respectively. Magnetic resonance imaging showed iron overload in the liver, pancreas, and myocardium. Liver biopsy showed diffuse iron deposition within hepatocytes. All ten cases had elevated transaminases; one case (1/10, 10.0%) had liver cirrhosis; four cases (4/10, 40.0%) had heart failure and arrhythmia; five cases (5/10, 50.0%) had diabetes; six cases (6/10, 60.0%) had hypogonadism; six cases (6/10, 60.0%) had skin pigmentation; and six cases (6/10, 60.0%) had fatigue symptoms. All six cases underwent bloodletting therapy, and ferritin levels dropped to about 100 ng/ml. Two cases of oral administration of the iron chelator deferasirox did not meet the ferritin level standard, and one case died from acute heart failure following a confirmed diagnosis during hospitalization.Conclusion:The HJV gene may be one of the main pathogenic genes of HH in China. The p.Q6H and p.C321X mutations were one of the hotspot mutations. The onset age of HJV gene-related HH was between 20 and 30 years old, and their condition was severe. Therefore, early bloodletting treatment can have a favorable outcome.

Objective:To investigate the clinical application value of qualitative and quantitative analysis of Sonazoid contrast-enhanced ultrasound(CEUS)in the 4 category of breast lesions of the Breast Imaging Reporting and Data System(BI-RADS)of diagnosis.Methods:A total of 53 patients with breast lesions(All 53 lesions were BI-RADS 4 category)who underwent biopsy or surgery in Chengdu First People's Hospital from April 2022 to April 2023 were selected.According to the pathological results of breast nodules,they were respectively divided into benign and malignant groups.All patients had underwent Sonazoid CEUS before biopsy or surgery.The differences of the qualitative and quantitative indexes of the breast nodules CEUS between benign and malignant groups were compared.The indexes with statistical significances were fitted into regression equation.And then,the receiver operating characteristic(ROC)curves were drawn for obtaining area under curve(AUC).The differences of enhanced strengths of breast nodules and surrounding normal tissues in CEUS were coded to intuitive color images,and generated dynamic vascular model(DVP)parameter picture by using Sonoliver software.The differences of image colors between benign and malignant breast nodules were analyzed.Results:According to the results of biopsy or surgical pathology,the 53 breast nodules were respectively divided into benign group(34 cases)and malignant group(19 cases).In qualitative indexes of Sonazoid-CEUS for breast nodules,the most appearance of the malignant nodules showed 13 cases were the enlargement of enhancement range(68.4%),and 14 cases were uneven enhancement(73.7%)and 12 cases were peripheral perforating blood flow(63.2%),and the differences of them between benign and malignant group were statistically significant(x2=10.268,9.642,5.717,P＜0.05),respectively.In the quantitative index of Sonazoid-CEUS for breast nodules,the rise time(RT)and mean transition time(mTT)of breast nodules of malignant group were significantly shorter than those of benign group,and the differences were statistically significant(Z=-1.985,-2.272,P＜0.05).After the above indexes were fitted into multiple factors analysis,the regression equations of predicting malignant nodules by using qualitative and quantitative indexes were respectively established.The AUC values of ROC curves of qualitative and quantitative analyses were respectively 0.723 and 0.902.The result of qualitative analysis was significantly better than that of quantitative analysis(Z=-1.965,P＜0.05).In DVP parametric images,the nodules of 23 cases(67.6%)of 32 nodules of benign group appeared lesions,and the most in region of interesting(ROI)appeared monotonous red/yellow filling,and 15 cases(78.9%)of 19 cases of malignant group appeared lesions,and the ROI inside appeared patchy red/yellow filling of disordered,irregular,scattered or clumpy shape.Conclusion:Sonazoid CEUS can discriminate benign and malignant nodules of breast BI-RADS 4 category,and the diagnostic efficacy of qualitative indexes is better than that of quantitative indexes..

Objective: To analyze the impact of persistent obesity on their lung function, so as to offer insights for implementing intervention measures to increase lung function in obese school age children. Methods: A total of 335 children from the Sheyang Mini Birth Cohort established in 2009 in Yancheng City, Jiangsu Province, who participated in the follow up at the ages of 7 years (2016) and 10 years (2019), were selected as the study participants. Physical measurements including height, weight, and lung function were recorded. According to the World Health Organization standard, that is, gender and age specific to correct the body mass index to calculate the body mass index Z score, was used to evaluate the obesity status of children at the age of 7 and 10. Children were divided into four groups, including sustained non obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Meanwhile, the lung function prediction equations recommended by the Global Lung Function Initiative were used to standardize the lung function indexes of children. Pulmonary function differences among these groups were examined, and the relationship between childhood obesity and pulmonary function was longitudinally analyzed using generalized estimating equations. Results: The prevalence of obesity were 9.0% and 16.1% at the age of 7 and 10 years, respectively. The proportion of both newly classified and persistent obesity group were 8.1%, respectively. The forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were (1 269.90±202.70) and (1 415.70±230.00) mL, respectively, at the age of 7 years. FEV 1 and FVC at the age of 10 years were (1 440.80±403.20) and (1 555.60±517.60) mL, respectively. Cross sectional analysis at age 7 showed that forced expiratory flow at 75% vital capacity (FEF 75 ) ( β=-0.52, 95%CI =-0.96--0.07) and maximal mid expiratary flow (MMEF) ( β=-0.45, 95%CI =-0.89--0.00) were significantly lower in obese children compared to their non obese peers ( P < 0.05). Longitudinal analysis indicated that obese children had lower levels of lung pulmonary function, with a statistically significant difference in FEV 1 ( β=-0.44, 95%CI=-0.85--0.02, P <0.05). There was no significant difference among the various obesity groups ( P >0.05), while gender stratified results revealed significant reductions in FEV 1/FVC in newly classified obese girls at age 10 years ( β=-1.76, 95%CI =-3.13--0.38) and in MMEF in persistently obese girls at age 10 years ( β=-1.44, 95%CI = -2.79- -0.09) ( P <0.05). Conclusion Obesity may contribute to reduced lung function levels in school aged children, with newly classified and persistent obesity having more pronounced effects on lung function in girls.

Objective:To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS).Methods:A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children′s Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results:There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ2=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ2=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence ( OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis ( OR=11.64 (1.27-106.72), P=0.030). Conclusions:OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.

ObjectiveTo investigate the mechanism of Lycium barbarum polysaccharides （LBP） in promoting the activation of RAW264.7 macrophages. MethodRAW264.7 macrophages were stimulated with LBP at different concentrations （50， 100， 200 mg·L^-1）， and those stimulated with lipopolysaccharide （LPS） at 100 μg·L^-1 and galactose （Gal） at 100 mg·L^-1 as positive controls. After 24 h of LBP stimulation， the cell counting kit-8 （CCK-8） was used to detect the survival rate of RAW264.7 macrophages treated with LBP （0， 50， 100， 200， 400， 800 mg·L^-1）. The levels of interleukin-6 （IL-6） and interleukin-12 （IL-12） in cell culture supernatant were detected by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression of p38 mitogen-activated protein kinase （MAPK）， extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， and nuclear factor κB （NF-κB） in Toll-like receptor 4 （TLR4）/Toll-like receptor 2 （TLR2）/macrophage galactose-type lectin （MGL） pathway of RAW264.7 macrophages was detected by Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCCK-8 results showed that compared with the results in the blank group， the survival rate of RAW264.7 macrophages decreased in the 400， 800 mg·L^-1 LBP groups （P<0.05）. ELISA results showed that compared with the blank group， 50 mg·L^-1 LBP could promote the secretion of IL-12 in RAW264.7 macrophages （P<0.01）. Compared with the blank group， 100 mg·L^-1 LBP and 200 mg·L^-1 LBP could promote the secretion of IL-6 in RAW264.7 macrophages （P<0.05， P<0.01）. Western blot results showed that compared with the blank group， the LBP groups （50， 100， 200 mg·L^-1） enhanced protein expression levels of MAPK key molecules （p-p38 MAPK， p-ERK， p-NF-κB， and p-JNK） in TLR4， TLR2， and MGL pathways （P<0.05， P<0.01）. Compared with the model group， the 200 mg·L^-1 LBP group could promote the expression level of p-NF-κB protein in RAW264.7 macrophages （P<0.01）. Real-time PCR results showed that compared with the blank group， the LBP groups （50， 100， and 200 mg·L^-1） enhanced the mRNA expression levels of MAPK key molecules （p38 MAPK， ERK， NF-κB， and JNK） in TLR4 and TLR2 pathways （P<0.05， P<0.01）. Compared with the model group， the 50 and 200 mg·L^-1 LBP groups could promote the mRNA expression levels of JNK and ERK2 in RAW264.7 macrophages （P<0.05， P<0.01）. ConclusionLBP can regulate the activation of RAW264.7 macrophages and participate in the immune response through the TLR2/TLR4/MGL pathway.

Objective:To understand the current situation of professional identity and burnout among nurses in health management department in Henan province, and analyze their correlation.Methods:This is a cross-sectional study. A general data questionnaire, the Nurse Professional Identity Scale and Nursing Burnout Scale were used to conduct an online questionnaire survey on 204 nurses from the health management departments of 6 tertiary A hospitals in Henan Province (Henan Provincial People′s Hospital, the First Affiliated Hospital of Henan University of Chinese Medicine, Henan Hospital of Traditional Chinese Medicine, Fuwai Central China Cardiovascular Hospital, Henan Chest Hospital and Zhengzhou branch of Henan Orthopedic Hospital) from March 1, 2023 to May 1, 2023. A total of 204 questionnaires were issued and 204 were recovered, with an effective rate of 100%. The correlation between professional identity and burnout was analyzed, and the general data was included into the regression equation as the control variables and the multiple linear regression analysis was carried out.Results:Among the 204 nurses in the health management department, 114 (55.9%) had a medium level and 25 (12.3%) had a low level of professional identity, 137 (67.1%) had job burnout. There was a significant negative correlation between professional identity and burnout ( r=-0.244, P<0.01). The results of multiple step-up regression showed that cognitive evaluation, frustration coping, social support, marital status, age and position were the main influencing factors of job burnout (all P<0.05). Conclusions:The professional identity and burnout of nurses in health management department are at a medium level. The higher the level of professional identity identity, the lower the burnout, and marriage, age and position were related to job burnout.

Objective:Investigate the prognostic value of high density lipoprotein (HDL) level in patients with streptococcal bloodstream infection.Methods:A total of 698 patients with streptococcal bloodstream infection admitted to the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019 were enrolled. Serum lipid and other clinical data of patients with positive blood culture within 48 h were recorded. The patients were followed up by telephone from January to March in 2020, and the end-point events were recorded, which were all-cause death 60 days after the diagnosis of streptococcal bloodstream infection. The patients were divided into two groups according to the levels of HDL: low HDL group (HDL ≤0.84 mmol/L) and high HDL group (HDL > 0.84 mmol/L). Univariate and multivariate Cox regression analysis were used to analyze the 60-day prognostic factors of patients with streptococcus bloodstream infection. The receiver operating characteristic (ROC) curve was used to explore predictive value of HDL level for 60-day prognosis of patients. Kaplan-Meier survival curve was used to compare the cumulative survival of patients with different HDL levels.Results:(1) A total of 491 patients were enrolled according to the inclusion criteria, and 461 patients were followed up successfully, with a follow-up rate of 93.89%. There were 373 survival patients and 88 death patients at 60 days, with a 60-day mortality rate of 19.09% (88/461). (2) There were significant differences in age, total cholesterol (TC), HDL, low density lipoprotein (LDL), platelets, albumin, fibrinogen, triglyceride (TG), creatinine, alanine aminotransferase, aspartate aminotransferase, white blood cell, PCT, total bilirubin, direct bilirubin, and respiratory failure and shock between the survival group and death group. (3) Multivariate Cox regression analysis showed that HDL ( RR=1.922, 95% CI: 1.186-3.117, P=0.008), aspartate aminotransferase ( RR=1.953, 95% CI: 1.233-3.094, P=0.004), shock ( RR=15.196, 95% CI: 6.953-33.211, P< 0.001), and respiratory failure ( RR=9.509, 95% CI: 4.232-21.367, P < 0.001) were independent risk factors for 60-day mortality of patients with streptococcal bloodstream infection. (4) The ROC curve analysis showed that HDL alone had a certain value in predicting the 60-day prognosis of patients with streptococcal bloodstream infection. The area under ROC curve (AUC) was 0.602, and the AUC of the combined predictive value of HDL, aspartate aminotransferase, shock and respiratory failure was 0.960, with a sensitivity of 92% and a specificity of 92%. (5) Kaplan-Meier survival curve analysis showed that the cumulative survival rate of patients without endpoint event in the HDL > 0.84 mmol/L group was higher than that in the HDL ≤ 0.84 mmol/L group, but without statistically significant difference (Log-Rank test: χ20.843, P<0.358). Conclusions:Patients with low HDL level of streptococcal bloodstream infection have an increased risk of 60-day death. HDL is an independent risk factor for 60-day death in patients with streptococcal bloodstream infection, and can be used as an indicator to evaluate the prognosis of patients with streptococcal bloodstream infection.

Background::Sepsis is a serious disease caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis.Methods::We conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit (ICU) admission in two sites. All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days.Results::From September 27, 2018 to February 12, 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group ( P = 0.032). Cox regression showed that the aminophylline group had a lower hazard of death (hazard ratio = 0.312, 95% confidence interval: 0.129-0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time ( P = 0.039 by the log-rank test). The effects of aminophylline on vasopressor dose, oxygenation index, and sequential organ failure assessment score were time-dependent with treatment. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial. Conclusions::Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis.Trial registration::ChiCTR.org.cn, ChiCTR1800019173.

Objective:To identify gene variants and investigate clinical features of nonmuscle myosin heavy chain 9-related disease (MYH9-RD).Methods:In this retrospective study, the data of patients with MYH9-RD admitted to Shenzhen Children′s Hospital from July 2017 to September 2020 were extracted. The gene variants, clinical features and laboratory tests results were summarized.Results:Among the 6 children, 4 were males and 2 were females, aged 4.0 (0.5-7.6) years. Main clinical manifestations included thrombocytopenia (6 cases), epistaxis (3 cases), petechias (2 cases), traumatic hematoma (1 case), and abnormal liver enzymes (1 case). One patient had no family history, and the other 5 cases were pedigrees. Two pedigrees (2 cases) had long-term microscopic hematuria, one pedigree (2 cases) had history of early cataract, and three pedigrees (5 cases) had chronic mild elevation of liver enzymes. Four MYH9 gene variants were found in 12 patients, including c.2104C>T(p.R702C) in exon 17, c.4270G>A(p.D1424N) in exon 31, c.5521G>A (p.E1841K) in exon 39, and c.5797C>T (p.R1933X) in exon 41. According to the family pedigrees analysis, except for the case of variant in exon 17 which was spontaneous mutation with no family history, the other variants were from their father or mother. The complete blood count results showed a decreased platelet number in these patients, and the counting results of the automated hematology analyzer were significantly lower than that of manual counting method ((33.4±17.2) × 10? vs. (60.4±21.0) × 10 9/L, t=-5.83, P<0.05). The examination of the peripheral blood smear revealed the presence of thrombocytopenia with giant platelets and granulocyte inclusion bodies. The MYH9 gene variant (R702C) located at the N-terminus head domain of non-muscle myosin heavy chain ⅡA (NMMHC-ⅡA), which has ATPase activity, led to severe reduction of platelet number (<20×10 9/L) and obscure granulocyte inclusion bodies. However, higher platelet numbers (40×10 9-80×10 9/L) and obvious granulocyte inclusion bodies were observed in patients with tail-position mutations at C-terminus. Conclusions:The clinical phenotypes of MYH9-RD were variable. The mutations in certain regions of MYH9 gene were related to platelet count and granulocyte inclusion bodies. MYH9-RD should be considered in individuals with unknown etiology and persistent thrombocytopenia which is non-responsive to conventional treatment, regardless of family history. Complete blood count and blood smear morphology examinations are the first steps to screen and diagnose the disease. The laboratory should pay attention to the morphological review rules and standardized reports.

OBJECTIVE：To investigate the r ole of clinical pharmacists on the therapy for human herpesvirus 7（HHV-7） infection in central nervous system. METHODS ：The clinical pharmacists participated in the treatment process of the hospitalized patient who was a 15-year-old patient with central nervous system infection. The doctor initially gave Levetiracetam tablets （500 mg，bid，po）to control epilepsy symptoms ，and Acyclovir for injection （500 mg，q8 h，ivgtt）for antiviral treatment. According to the large red wheal scattered rubella on the limbs and back of the patient ，clinical pharmacists recommended to give Dexamethasone sodium phosphate injection （10 mg，qd，iv）and Loratadine tablets （10 mg，qd，po）for anti-allergy treatment ；in view of involuntary shaking of limbs in the patient ，clinical pharmacists recommended to continue to give Dexamethasone sodium phosphate injection intravenously to control inflammation and Xingnaojing injection （20 mL，qd，ivgtt） to improve the convulsion. For HHV- 7 infection，based on consulting the relevant guidelines and existing treatment experience ，the clinical pharmacists recommended discontinuation of acyclovir ， dexamethasone combined with Human immunoglobulin （pH 0278）（17.5 g，qd，ivgtt）for impact therapy should be used and adverse drug reactions and therapeutic effects should be monitored at the same time. RESULTS ： The physiciansaccepted the suggestions of clinical pharmacists. The patient was improved and discharged from the hospital after 18 days of treatment. CONCLUSIONS ： During the treatment of ineffective case of clinic rare central nervous system infectious diseases with routine a ntiviral drugs ，clinical pharmacists assisted physicians to improve their treatment plan and ensure the effectiveness and safety of patient ’s medication.