Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective To investigate the need for and utilization of health services among six Zhiguo ethnic minority groups in Yunnan Province,aiming to provide further evidence for the improvement of healthcare.Methods Using stratified random sampling,1921 individuals from six Zhiguo ethnic minority groups,aged 15 and above,were investigated with a structured questionnaire between August and December 2022.A structured questionnaire was used to collect participants'information on health service needs and utilization.Results Am-ong the surveyed participants,the two-week prevalence rate was found to be 22.54%,while the prevalence rate of chronic diseases was 38.52%.Among the residents,the risk of two-week prevalence was higher for females(OR=1.564),individuals aged≥60 years(OR=1.727),and those who reported poorer health utility value(OR=5.277),while it was lower for residents of Keno(OR=0.470)and Lahu(OR=0.659)ethnicity,as well as those who reported higher EQ-VAS scores(OR=0.446/0.174).Meanwhile,residents aged≥45 years(OR=3.392/7.072)were at higher risk for chronic disease prevalence,while it was lower for Keno ethnicity(OR=0.409),unmarried individuals(OR=0.479),and those with higher education levels(OR=0.629/0.603),higher EQ-VAS scores(OR=0.208)P<0.05.Additionally,among the participants,the treat-ment rate for two-week illness was 14.32%,while the non-treatment rate stood at 36.49%.Furthermore,the one-year hospitalization rate was reported as 19.89%,with a corresponding rate of individuals who needed hospitalization but did not receive it being recorded at 15.86%.Among the residents,the likelihood of treatment for two-week illness was higher for females(OR=1.461)and residents aged≥45 years(OR=1.510/1.560),whereas it was lower for individuals with higher EQ-VAS scores(OR=0.445).The likelihood of hospitalization within one year was also higher for residents aged≥60 years(OR=2.029)and individuals of Nu(OR=1.599),Lisu(OR=1.688),and Keno(OR=1.968)ethnicity,whereas those with high EQ-VAS scores(OR=0.325)had a lower risk(P<0.05).Conclusion In Yunnan Province,the need for healthcare services among six Zhiguo ethnic minority groups in this study is relatively low;however,the high prevalence of chronic diseases raises concerns.The utilization of healthcare services appears to be relatively sufficient,but the utilization of outpatient services still needs to be improved.

OBJECTIVE: To identify pathogenic variants in two patients with suspected for Mowat-Wilson syndrome (MWS). METHODS: Genomic DNA was extracted from peripheral blood samples of the patients and his family members, and gene variants were analysis by Trio-whole exome sequences and copy number variation sequencing. RESULTS: Patient 1 was found to carried a de novo heterozygous c.2769C>A (p.Y923*) nonsense variant of ZEB2 gene. The variant was not found in his healthy parents and sister. Patient 2 carried a de novo heterozygous frameshift variant of the ZEB2 gene, namely c.315delC (p.A105Afs*3), which has not been previously reported. Both variants were predicted to be pathogenic and can lead to premature occurrence of stop codons. CONCLUSION The heterozygous c.2769C>A (p.Y923*) and c.315delC (p.A105Afs*3) variants of the ZEB2 gene probably underlay the pathogenesis in the two patients. Gene testing has facilitated confirmation of the diagnosis and genetic counselling.
DNA Copy Number Variations ; Facies ; Hirschsprung Disease ; Humans ; Intellectual Disability/genetics* ; Microcephaly/genetics* ; Zinc Finger E-box Binding Homeobox 2/genetics*

Objective To evaluate the condition of oxidative stress and immunosuppression in early stage of severe sepsis,and investigate the correlation between them. Methods A prospective random control study in-cluded patients group(n=51)and control group(n=31). The concentration of serum superoxide dismutase was measured by enzyme linked immunosorbent assay(ELISA),CD4+CD25+Treg% was measured by flow cytometry , respectively. The difference between two groups was compared and the correlation between parameters in patients group was evaluated. Results The concentration of serum SOD was lower than control group (P < 0.01). CD4+CD25+Treg% significantly high,compared to the control group(P < 0.01). There was no strong correlation be-tween parameters in patients group. Conclusion Oxidative stress and immunosuppression are exist in the early stage of severe sepsis.

Objective To investigate the role of NF-κB/survivin signal pathway in the intima hyperplasia of rat carotid balloon injury restenosis model.Methods NF-κB siRNA lentivirus vector(titer was 1 × 108 TU/ml)was established.Carotid balloon injury restenosis model was made in 33 SD rats.The rats were divided into 4 groups according to different processing methods,including negative control (NC) group (n =11),NF-κB siRNA group(n =11),NF-κB siRNA + YM155 (survivin inhibitor) (n =11),the uninjured carotid artery served as the normal control group(n =1 1).After 7 days,the carotid sample(n =5 each group)were harvested to detect the NF-κB and survivin mRNA expression by RT-PCR.The carotid sample were harvested on 28 days (n =6 each group) for HE staining and measuring intima hyperplasia.Immunohistochemical method was also used to detect the expression of intima proliferation cell nuclear antigen (PCNA) and media α-SM-actin.Results (1) After 7 days,NF-κB and survivin mRNA expression was significant higher in NC group than in normal control group (P ＜ 0.05),the NF-κB mRNA expression was significantly lower in NF-κB siRNA group than in NC group (P ＜ 0.05) and similar between NF-κB siRNA group and NF-κB siRNA + YM155 group.The survivin mRNA expression was significantly lower in NF-κB siRNA group compared to NC group (P ＜ 0.05) and significantly higher in NF-κB siRNA group than in NF-κB siRNA + YM155 group (P ＜0.05).(2) After 28 days,intima hyperplasia was observed in NC (0.13 ±0.01),NF-κB siRNA (0.11 ±0.01) and NF-κB siRNA +YM155 group(0.09 ±0.01)mm2(P ＜ 0.05).Media area was similar among NC group,NF-κB siRNA group and NF-κB siRNA + YM155 group (P ＞ 0.05).L/M ratio was gradually reduced among NC group(1.55 ± 0.07),NF-κB siRNA group(0.92 ± 0.08),NF-κB siRNA + YM155 group(0.76 ±0.06,all P ＜0.05).Similar results were found in the residual restenosis rate:NC group (58.71 ± 0.02) ％,NF-κB siRNA group (32.13 ± 0.05) ％,NF-κB siRNA + YM155 group (26.42 ± 0.03) ％ (all P ＜ 0.05) and expression of vascular smooth muscle cell PCNA:NC group(45.32 ± 7.21) ％,NF-κB siRNA group(36.54 ± 6.42) ％,NF-κB siRNA + YM155 group(28.57 ± 6.31)％ (all P ＜ 0.05).On the contrary,the IOD of α-SM-actin in media increased gradually:NC group (0.055 ± 0.006),NF-κB siRNA group (0.072 ± 0.011),NF-κB siRNA + YM155 group(0.084 ±0.008,all P ＜ 0.05).Conclusion Inhibiting NF-κB expression can significant decrease intima hyperplasia in this model,and this effect may be mediated by inhibiting survivin and reducing the proliferation of vascular smooth muscle cells.

Objective To discuss the etiology,clinical features and treatments of patients with pituitary adenomas having onset symptom of hyponatremia.Methods Retrospective analysis was performed on etiology,clinical features and treatment methods of 28 patients with pituitary adenomas having onset symptom ofhyponetramia,admitted to our hospital from Jantary 2003 to December 2012.Results Among 28 patients,27 had non-functional pituitary adenomas and one prolactinoma; 23 had pituitary macroadenomas and 5 giant adenomas; 22 achieved total tumor resection through transsphenoidal approach,2 subtotal removal and 4 received conservative therapy.In total,13 were combined with hypocortisolism,8 with hypothyroidism,5 with both hypocortisolism and hypothyroidism,and 2 with hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone in preoperative evaluation.Hyponatremia was corrected by hormone replacement therapy and water limitation during perioperative and postoperative period.Conclusions Pituitary adenomas with onset symptom of hyponatremia are mostly non-functional pituitary macroadenomas.Pituitary adenoma resection is the first-line treatment; hyponatremia and anterior pituitary hypofunction should be corrected in perioperative period,and close postoperative follow-up is necessary.

Objective To investigate the effects of the genetic polymorphisms in osteoporosis-related genes and the gene-gene interaction on bone mineral density (BMD) and osteoporotic fractures.Methods Thirty-nine single nucleotide polymorphism (SNP) sites in 23 genes that related to bone mineral density ( BMD ) and osteoporotic fractures were scanned in 683 Shanghai Han postmenopausal women.TaqMan SNP Genotyping Assay or Sequenom Mass ARRAY System were applied for genotyping analysis.The relation of these SNP sites with BMD and osteoporotic fractures were analyzed.Results Altogether,12 SNPs in 9 candidate genes ( rs7524102 and rs6696981 in ZBTB40 gene,rs9479055 in ESR1 gene,rs6993813,rs6469804,and rs11995824 in OPG gene,rs3736228 in LRP5 gene,rs1107748 in SOST gene,rs87938 in CTNNB1 gene,rs1366594 in MEF2C gene,rs7117858 in SOX6 gene,and rs10048146 in FOXL1 gene) were associated with BMD at lumbar spine(L1-L4) or total hip.In addition,rs11898505 in SPTBN1 gene was related to osteoporotic fractures ( OR 0.522,95％ CI 0.326-0.838,P =0.007 ).Gene-gene interaction involving rs1038304 in ESR1 gene,rs1366594 in MEF2C gene,and rs10048146 in FOXL1 gene was associated with osteoporotic fractures ( P =0.010 7 ).Conclusions ( 1 ) SNPs in gene ZBTB40,ESR1,OPG,LRP5,SOST,CTNNB1,MEF2C,SOX6,FOXL1,and SPTBN1 are associated with BMD of lumbar spine or total hip,as well as osteoporotic fractures.(2) Gene-gene interaction involving rs1038304,rs1366594,and rs10048146may contribute to the risk of osteoporotic fractures.

OBJECTIVETo describe the impact of the global economic crisis on the nutritional status of children in China during and after the crisis.

METHODSData from 1990 to 2010 were sourced from the National Food and Nutrition Surveillance System. Approximately 16 000 children under 5 years old were selected using a stratified random cluster method from 40 surveillance sites. Anthropometric and hemoglobin measurements for children under 5 were conducted. Nutritional status was determined according to WHO child growth standards.

RESULTSPrevalence of underweight and stunting in children under 5 had a downward trend. Underweight prevalence was close to normal (less than 5%), with prevalence of stunting 12.6% in 2009 and 12.1% in 2010 in rural areas. Prevalence of stunting in infants under 6 months and 6-12 months old in poorer rural areas increased from 5.7%-9.1% and 6.7%-12.5%, respectively, in 2008-2009. This trend also continued post-crisis in 2010. Prevalence of stunting in children left behind by mothers was 20%-30% higher than in children the same age in general and poorer rural areas. Prevalence of anemia in children did not change in rural areas, but prevalence of anemia in all age groups increased in poorer rural areas, especially in children under 24 months old. Level reached 30%-40% in 2009, and fluctuated in 2010.

CONCLUSIONThe nutritional status of children under 5 was comparatively stable during and after the global economic crisis, attributable to the Chinese government's policy response. The nutritional status in poorer rural areas fluctuated in response to the economic crisis and, thus, relevant action and intervention must be taken immediately to help the most vulnerable population in poorer rural areas. A proper national nutritional strategy for children under 2 years old, including nutrition supplementation for pregnant women and in-home fortification for complementary feeding, should be initiated.

Aging ; Anemia ; economics ; epidemiology ; Child Development ; physiology ; Child Nutrition Disorders ; economics ; epidemiology ; Child, Preschool ; China ; epidemiology ; Economic Recession ; Female ; Humans ; Infant ; Infant Nutrition Disorders ; economics ; epidemiology ; Male ; Nutritional Status ; physiology ; Population Surveillance ; Poverty ; Pregnancy ; Prevalence ; Rural Population ; Thinness ; Time Factors

Objective To investigate the inhibitory effect of downregulation of hepatitis B virus (HBV) core gene (HBcAg) expression by RNA interference and magnetic nanoparticles on both HBV DNA replication and expression in vitro. Methods HepG2 2.2.15 cells were transfected with U6 promoter plasmids coding for small interfering RNA (siRNA) targeting HBV core gene using magnetic nanoparticles. RT-PCR and Western blot were used to assess the mRNA and protein expression HBV core antigen. Real-time PCR was used to evaluate the suppression efficiency of HBV-DNA replication and expression; and radioimmunoassay was used for HBV surface antigen (HBsAg), core antigen (HBcAg), and e antigen (HBeAg) detection. Results We successfully constructed nanoparticles with siRNA plasmid targeting HBV core antigen; HBcAg mRNA and HBV core antigen protein levels were significantly reduced in the transfected cells. HBV-DNA downregulation was estimated at 4-5 logs and the HBsAg and HBeAg levels were also reduced compared with the controls. Conclusion Downregulation of HBV core gene using RNAi technology and magnetic nanoparticles can potentially be used as a therapeutic strategy for Hepatitis B.