Patients infected with human immunodeficiency virus （HIV） are susceptible to various opportunistic infections and tumors.These diseases often have complex clinical and pathological manifestations， poor prognosis and are difficult to manage.Thalidomide and its derivatives have a wide range of pharmacological effects including antiinflammatory， immunomodulatory and anti-tumor activities.In recent years， thalidomide and its derivatives have been increasingly used in HIV infection-related diseases， mainly including mucosal ulcer， prurigo nodosa， opportunistic infection， immune reconstruction inflammatory syndrome， Kaposi sarcoma， non-Hodgkin lymphoma and Castleman disease.This paper mainly reviews the application of thalidomide and its derivatives in the above diseases.
To investigate the diagnostic value of nasal eosinophil cationic protein （ECP）and myeloperoxidase （MPO） positive rate detection for viral respiratory infection in children with allergic rhinitis （AR）， and to evaluate the efficacy of nasal spray hormone combined with interferon.
Methods
Nasal lavage fluid was collected from enrolled children in Kunming Children's Hospital from April 2022 to April 2023， and 6 common respiratory viruses were detected through reverse transcription PCR （RT-PCR）.The severity grade of symptoms in those patients were assessed by Visual analogue scale （VAS） and the positive rate of ECP-MPO in the samples were detected by colloidal gold test paper.Nasal sprays of mometasone furoate combined with interferon were used to treat respiratory virus positive children with AR， and the degree of symptom improvement among children were analyzed.The count data were analyzed using Chisquare test， while the quantitative data （VAS score） were compared between groups using non-paired t-test or Mann Whitney U test based on whether distributed normally.
Results
The total detection rate of respiratory viruses among 362 enrolled children was 48% （174/362）， with the main virus detected being rhinovirus（40%， 145/362）.VAS scores of respiratory virus positive children who did not receive allergen specific immunotherapy （AIT） were significantly higher than those of virus negative children （4.776 ± 1.229 vs.4.193 ±1.392）， with significant difference （t = 2.776， P = 0.006）.Among the children with AR who did not receive AIT treatment and positive detection for respiratory viruses， those who received mometasone furoate combined with interferon alpha 2b and received nasal spray treatment for 7 days had significantly lower VAS scores than those who received mometasone furoate alone （3.380 ± 0.801 vs.2.705 ± 0.696）， with significant difference （t = 2.414，P = 0.015）.The double positive rate of ECP-MPO among children who received AIT （38%） was significantly lower than that of children who did not receive AIT （69%）， with significant difference （χ2 = 20.473， P ＜ 0.001）.The MPO positive rate of virus positive children （84%） was significantly higher than that of virus negative children （61%）（χ2 = 15.08， P ＜ 0.001） and the MPO positive rate of virus positive children who did not receive AIT was 99% （66/67），significantly higher than those children without infection （67%， 41/61） （χ2 = 22.80， P ＜ 0.001）.
Conclusions
The positive rate of respiratory virus among children with allergic rhinitis was close to 50%， mainly nasal virus.Children with combined respiratory viral infection had more severe allergic symptoms， and the combination of mometasone furoate and interferon treatment can significantly alleviate AR symptoms.ECP-MPO detection has certain diagnostic value for AR children with combined respiratory viral infection.
To analyze the risk factors of multidrug-resistant bacterial （MDRO） infection in neonatal intensive care unit （NICU） and the diagnostic value of hypersensitive C-reactive protein to albumin ratio （hs-CRP/ALB）.
Methods
Total of 105 neonates with MDRO infection in NICU of The Maternity and Child Care Hospital of Kunshan from October 2020 to October 2023 were collected as MDRO group， 150 neonates without MDRO infection as non-MDRO group， and 150 healthy newborns as healthy group during the same period.The risk factors for MDRO infection were analyzed by Logistic regression analysis.The diagnostic value of hs-CRP/ALB for neonatal MDRO infection were evaluated by receiver operating curve （ROC） analysis.
Results
Birth weight （OR = 2.065， 95%CI： 1.184-3.600， P = 0.011）， Apgar score （OR = 2.470， 95%CI： 1.294-4.717， P = 0.006）， duration of antibiotic use （OR = 2.576， 95%CI： 1.287-5.155， P = 0.008）， and deep venous catheterization （OR = 2.751， 95%CI： 1.268-5.971， P = 0.010） were all independent risk factors for neonatal MDRO.Compared with the healthy group， hs-CRP， ALB， white blood cell （WBC） count， neutrophil-to-lymphocyte ratio （NLR）， absolute neutrophil count （NEUT#） and hs-CRP/ALB in the MDRO group were significantly higher on the first and the third day after admission （all P ＜ 0.05）.Compared with non-MDRO group， there was no significant difference for hs-CRP， ALB， WBC， NLR， NEUT#and hs-CRP/ALB on the first day after admission in MDRO group （all P ＞ 0.05）， but on the third day after admission， hs-CRP， ALB， NLR and hs-CRP/ALB were statistically significant （all P ＜ 0.05）.On the third day，the sensitivity and specificity of hs-CRP/ALB for the diagnosis of neonates in MDRO group and non-MDRO group were 63.09% and 86.67%， respectively.Compared with the survival group， the death group showed significant differences in hs-CRP， ALB and hs-CRP/ALB on the third and the fifth day after admission （all P ＜ 0.05）， NLR was significantly different on the fifth day after admission （Z = 3.878， P ＜ 0.001）； NEUT#was significantly different on the third day after admission （Z = 2.533， P = 0.013）； However， there was no significant difference of WBC on the third and the fifth day after admission （all P ＞ 0.05）.Hs-CRP/ALB of all neonates infected with methicillin-resistant Staphylococcus aureus （MRSA）， vancomycin-resistat Enterococcus（VRE） and multidrug/pan-drug-resistant Pseudomonas aeruginosa （MDR/PDR-PA） were all higher than 0.36.Among the Methicillin-resistant coagulase-negative Staphylococci （MRCNS）， extended-spectrum β-lactamase（ESBLs）-producing Enterobacteriaceae， carbapenem-resistant Enterobacteriaceae （CRE） and carbapenemresistant Acinetobacter baumannii （CR-AB） infection-resistant neonates， hs-CRP/ALB ＞ 0.36 accounted for 83.33%， 86.67%， 80.00% and 80.00%， respectively.
Conclusions
The detection of hs-CRP/ALB ratio can be used to preliminarily determine the severity of neonatal infection and corresponding preventive measures should be taken for the risk factors of neonatal MDRO infection.
To explore the influencing factors and distribution characteristics of detectable serum hepatitis B virus （HBV） ribonucleic acid （RNA） of patients with chronic hepatitis B （CHB） and hepatitis B related cirrhosis who were treated with nucleos（t）ide analogues （NAs） after achieving complete virological response.
Method
This cross-sectional study involved the consecutive enrollment of 360 patients with CHB and 149 patients with hepatitis B related cirrhosis who attended outpatients of the Department of Hepatology， the Second Hospital of Shandong University from March 2020 and April 2024， all patients received NAs treatment and achieved complete virological response； HBV RNA was detected by real-time thermostatic amplification and detection technology （SAT）.Patients were divided into two groups based on whether HBV RNA was below the detection limit： HBV RNA detectable group （335 cases） and HBV RNA undetectable group （174 cases）.The influencing factors with detectable serum HBV RNA were analyzed by Multivariate Logistic regression analysis.The quantitative differences of HBV RNA among cases with different diagnoses， HBV e antigen （HBeAg） status and HBV surface antigen （HBsAg） levels were compared in the patients of HBV RNA detectable group.
Result
The positive rate of serum HBV RNA of 166 patients with HBeAg positive was 94.6% （157/166）， which was significantly higher than that of HBeAg negative patients ［51.9% （178/343）］ （χ2 = 90.582， P ＜ 0.001）； compared with HBV RNA undetectable group， patients in HBV RNA detectable group were with higher HBsAg level ［3.1 （2.6， 3.6） log10IU/ml］， with significant difference（Z =-6.239， P ＜ 0.001）.Multivariate Logistic regression analysis showed that hepatitis B related cirrhosis （OR = 2.305，95%CI： 1.419-3.742， P = 0.001）， HBeAg positivity （OR = 14.852， 95%CI： 7.212-30.586， P ＜ 0.001） and serum HBsAg ＞ 2.56 log10IU/ml （OR = 2.645， 95%CI： 1.654-4.232， P ＜ 0.001） were all risk factors for serum HBV RNA detectable.
Conclusions
Among patients who achieve complete virological response after NAs treatment， hepatitis B related cirrhosis， HBeAg positivity and high levels of HBsAg are all risk factors for serum HBV RNA detectable.HBV RNA detection can help evaluate viral transcription and replication status more comprehensively.
To explore the clinical characteristics of premature infants with eosinophilia （EOS）increase at different gestational ages， the influencing factors of infectious diseases and the correlation between incidences of different infectious diseases and the degree of EOS increase.
Methods
Total of 232 cases of EOSincreased preterm infants admitted to Leshan Maternal and Child Health Hospital from May 2020 to June 2022 were collected， retrospectively.According to the gestational age， the preterm infants were divided into the very preterm group （27 weeks ≤ gestational age ＜ 32 weeks）， the middle preterm group （32 weeks ≤ gestational age ＜ 34 weeks） and the late preterm group （34 weeks ≤ gestational age ＜ 37 weeks）， which were 50， 58 and 124 cases， respectively.After matching according to 1∶1∶1 tendency， there were 48 cases in every group.Gender， perinatal high maternal factors， pulmonary hemorrhage， cesarean section， antibiotic use， mechanical ventilation， blood transfusion， leukocyte increase， gastrointestinal abnormalities， intrauterine asphyxia，maternal conditions， infectious diseases， multiple fetuses， premature rupture of membranes， gestational diabetes mellitus， gestational hypertension， amniotic fluid contamination， placenta previa， intrauterine infection， feeding intolerance and birth gestational age， birth weight， birth head circumference， birth length，maternal age， gestational age， birth weight， birth head circumference， birth length， procalcitonin （PCT），interleukin-6 （IL-6） and tumor necrosis factor α （TNF-α） of the three groups were compared， respectively.According to whether complicated with infectious diseases， 144 matched children were divided into infectious disease group （41 cases） and non-infectious disease group （103 cases）.Birth weight， birth head circumference， birth length， cesarean section， multiple births， intrauterine asphyxia， premature rupture of membranes， gestational diabetes mellitus， gestational hypertension， amniotic fluid contamination， placenta previa， intrauterine infection， PCT， IL-6， TNF-α， gestational age and EOS count were compared between the two groups.The influencing factors of infectious diseases in children with increased EOS was analyzed by Logistic regression analysis.The correlation between the increase degree of EOS in preterm infants and incidences of common infectious diseases were analyzed by smooth curve fitting， while the threshold effect were analyzed.
Results
After matched， gestational age （F = 18.633， P ＜ 0.001）， birth weight （F = 5.387， P ＜ 0.001），head circumference at birth （F = 4.330， P ＜ 0.001）， length at birth （F = 4.708， P ＜ 0.001）， cesarean section（χ2 = 8.792， P = 0.012）， antibiotic use （χ2 = 13.580， P = 0.001）， infectious diseases ［necrotizing enterocolitis（χ2 = 6.257， P = 0.043）， septicemia （χ2 = 7.412， P = 0.024）， meningitis （χ2 = 7.304， P = 0.026）， pneumonia（χ2 = 7.304， P = 0.026）， urinary system infection （χ2 = 7.412， P = 0.024）］， laboratory indicators ［PCT （F =13.236， P ＜ 0.001）， IL-6 （F = 25.017， P ＜ 0.001）， TNF-α （F = 7.948， P = 0.001）］ in the very preterm， middle preterm and late preterm groups were significantly different.In infectious disease group， the proportion of cases with PCT ≥ 0.44 μg/L （χ2 = 31.109， P ＜ 0.001）， IL-6 ≥ 0.44 ng/L （χ2 = 20.990， P ＜ 0.001）， TNF-α ≥ 14.59 ng/L（χ2 = 9.536， P = 0.002）， gestational age （27 weeks ≤ 32 weeks） （χ2 = 6.206， P = 0.045）， EOS count ≥ 1.5 × 109/L （χ2 = 8.585，P = 0.003） and feeding intolerance （χ2 = 14.107， P ＜ 0.001） were significantly higher than those of noninfectious disease group， with significant differences.Logistic regression analysis showed that PCT ≥ 0.44 μg/L（OR = 2.284， 95%CI： 1.023-5.354， P = 0.021）， IL-6 ≥ 0.44 ng/L （OR = 6.216， 95%CI： 1.312-11.624， P =0.015）， TNF-α ≥ 14.59 ng/L （OR = 6.892， 95%CI： 1.245-9.654， P = 0.001）， gestational age （27 weeks ≤gestational age ＜ 32 weeks） （OR = 7.004， 95%CI： 3.654-16.324， P = 0.014）， EOS count ≥ 1.5 × 109/L （OR =5.610， 95%CI： 1.268～9.021， P = 0.004）， feeding intolerance （OR = 7.840， 95%CI： 2.364-11.654， P = 0.002）were all influencing factors of infectious diseases in children with increased EOS （all P ＜ 0.05）.Generalized addition model and curve fitting showed that the incidence rates of necrotizing enterocolitis， septicemia， meningitis，pneumonia and urinary system infection were non-linear positively related with EOS count of preterm infants；With the increase of EOS count， the incidences of infectious diseases of preterm infants increased， with significant differences （all P ＜ 0.05）.
Conclusions
PCT， IL-6， TNF-α， gestational age， EOS moderate to severe increase and feeding intolerance were all influencing factors of incidences of infectious diseases in children with EOS increase.Necrotizing enterocolitis， sepsis， meningitis， pneumonia and urinary system infection are all non-linearly positively correlated with EOS count in premature infants.
To investigate the metagenomics of gut microbiota in patients with severe pneumonia （SP） and the predictive value for the efficacy of antimicrobial agents.
Methods
Total of 126 patients with SP treated in Shijiazhuang People's Hospital from March 2022 to March 2024 were selected as the research objects， retrospectively.According to the efficacy of antibiotics， 126 cases were divided into effective group （84 cases） and ineffective group （42 cases）.Stool samples were collected from both groups for DNA extraction， followed by sequencing analysis of the V4 region of the 16S rRNA gene.The results of sequencing analysis were included in the metagenomics study.The abundance， microbial network and gene function of the patients were analyzed by independent sample t test， principal coordinate analysis（PCoA）， non-parametric analysis of covariance （PERMANOVA） and analysis of similarity （ANOSIM）.
Results
There were no significant differences in age， gender， BMI， drinking history， smoking history，complications， comorbidities and medication for underlying diseases between the two groups （all P ＞ 0.05）.The dilution curve and species accumulation curve showed that the sequencing amount of this system was sufficient and the sequencing depth was reasonable.The results of α diversity analysis showed that there were significant differences in Shannon index and Simpson index between the two groups （t = 3.958， P = 0.025；t = 6.583， P ＜ 0.001）.β diversity analysis showed that the two groups of samples were significantly separated（F = 6.665， P ＜ 0.001）.Total of 18 phyla were detected in the two groups of samples， mainly including Firmicutes， Proteobacteria， Bacteroidetes， Actinobacteria and Tenericutes.At the genus level， a total of 952 bacterial genera were detected， of which 8 genera had a relative abundance above 3%.The dominant species of the two groups were not consistent.The abundance comparison showed that： at the phylum level，the relative abundance of Firmicutes and Proteobacteria in the effective group was lower than that of the ineffective group （t = 14.889， P ＜ 0.001； t = 2.508， P = 0.013）， and the relative abundance of Bacteroidetes，Actinobacteria and Tenericutes in the effective group was higher than that in the ineffective group （t =17.776， P ＜ 0.001； t = 16.802， P ＜ 0.001； t = 1.997， P = 0.048）.At the genus level， the relative abundance of Enterococcus， Streptococcus， Klebsiella and Ruminococcus in the effective group was higher than that of the ineffective group （t = 16.663， P ＜ 0.001； t = 6.313， P ＜ 0.001； t = 9.826， P ＜ 0.001； t = 13.158， P ＜ 0.001）.The relative abundance of Bifidobacterium， Escherichia coli and Clostridium in effective group was lower than that of the ineffective group （t = 16.642， P ＜ 0.001； t = 18.814， P ＜ 0.001； t = 12.762， P ＜ 0.001）.Network analysis showed that the number of nodes and edges of the effective group was significantly higher than that of the ineffective group， and the structure of the microbial network was more complex than that of the ineffective group.Gene function enrichment analysis showed that the gene functions with higher relative abundance in the effective group were ATP binding， IMP biosynthesis process and chlorate biosynthesis process.The functions of genes with higher relative abundance in the ineffective group were cytoplasm and structural components of ribosomes.Pathway enrichment analysis showed that the signaling pathways with high relative abundance in the effective group were starch degradation， sucrose degradation and isoleucine biosynthesis.The signaling pathways with high relative abundance in the ineffective group were isoprene biosynthesis and methylerythritol phosphate pathway.
Conclusions
Enterococcus， Streptococcus and Klebsiella were the most abundant bacteria in samples of patients with SP effectively treated with antibiotics.Enterococcus， Escherichia coli and Bifidobacterium were the most abundant bacteria in samples of patients with SP ineffectively treated with antibiotics， and the metagenomics of intestinal microbial community has a certain predictive value for the efficacy of antibiotics.
To explore the clinical characteristics of severe Streptococcus agalactiae infection in small infants.
Methods
Clinical data of hospitalized infants with Streptococcus agalactiae positive in blood culture or cerebrospinal fluid bacterial culture from January 1st， 2016 to December 31st，2023 in the Pediatric Intensive Care Unit， Children's Hospital Affiliated to Capital Institute of Pediatrics was analyzed， retrospectively.
Results
Total of 23 infants were included， the ratio of male to female was 14∶9；the diagnostic age was 5-101 days， the infants under 3 months accounted for 95.7% （22 cases）.There were 13 cases （56.5%） diagnosed as septicemia and complicated with purulent meningitis， while 4 cases （17.4%）only with septicemia and 6 cases （26.1%） only with purulent meningitis.There were 12 cases （52.2%） of septic shock and 12 cases （52.2%） of multiple organ failure.Total of 8 cases （34.8%） were complicated with subdural effusion， 4 cases （17.4%） complicated with ventricular meningitis and 7 cases （30.4%） complicated with hydrocephalus.The hospitalization duration was 28 hours to 74 days.Total of 12 cases were cured，3 cases died and 8 cases were left with neurological sequelae.Compared with the cured group， the poor prognosis group had lower white blood cell count ［1.9 （1.1， 6.6） × 109/L vs.11.3 （3.6， 16.1） × 109/L： Z =-2.585， P = 0.010］ and lower platelet count ［152 （78， 233） × 109/L vs.301 （212， 412） × 109/L： Z =-2.523，P = 0.012］， higher white blood cell count in cerebrospinal fluid ［1 425 （290， 3 500） × 106/L vs. 153 （5， 1 495） ×106/L： Z =-2.093， P = 0.036］ at the beginning of illness； and had lower cerebrospinal fluid glucose ［0.2 （0.1，0.3） mmol/L vs.2.6 （0.7， 4.1） mmol/L： Z =-3.171， P = 0.002］， higher cerebrospinal fluid protein ［5 226 （2 935， 6 892） mg/L vs.937 （558， 2 997） mg/L： Z =-3.077， P = 0.002］， longer prothrombin time ［17.8 （14.5， 19.4） s vs.12.9 （11.9，15.0） s： Z =-3.016， P = 0.003］， longer activated partial thromboplastin time ［53.6 （44.2， 102.3） s vs.40.6（37.2， 47.8） s， Z =-2.893， P = 0.004］， lower pH ［7.3 （7.2， 7.4） vs.7.4 （7.3， 7.4）］： Z =-2.585， P = 0.010］，higher proportion of three or more antibiotics application （81.8% vs.33.3%： χ2 = 5.490， P = 0.019）， higher proportion of component blood transfusion （81.8% vs. 41.7%： χ2 = 3.884， P = 0.049） and shorter 28 day-non-ICU hospitalization duration ［0 （0， 1.0） d vs. 8.5 （0.3， 12.5） d： Z =-2.250， P = 0.024］.
Conclusions
The clinical manifestations of infection in small infants caused by Streptococcus agalactiae are severe， and they are sensitive to commonly used penicillin and cephalosporins.However， central nervous system involvement can easily lead to serious complications and residual neurological sequelae.
To investigate the clinical characteristics and treatment of a pediatric necrotizing pneumonia （NP） case with coinfection of Streptococcus pneumoniae and Epstein-Barr virus（EBV）.
Methods
A retrospective analysis was conducted on the medical records of a child with NP admitted to The Affiliated Qingyuan Hospital （Qingyuan People's Hospital）， Guangzhou Medical University in April 15th， 2024， and relevant literatures were reviewed by searching Wanfang data， China National Knowledge Infrastructure （CNKI） and PubMed.
Results
The patient was a 2-year-old female， who was admitted to our hospital due to coughing for longer than 10 days， recurrent fever for 6 days and dyspnea for 3 days.The chest CT showed consolidation and multiple cavity formation in the middle lobe of the right lung， accompanied by pleural effusion on the right side.Microbiological analysis was performed on the bronchoalveolar lavage fluid （BALF） sample.Traditional pathogen detection methods detected no pathogenic microorganisms；however， targeted next generation sequencing （tNGS） revealed Streptococcus pneumoniae and human gammaherpesvirus 4 （Epstein-Barr virus， EBV） with high read counts， as well as Haemophilusinfluenzae and Human mastadenovirus C with low read counts.The treatment measures included the use of antibiotics，expectorants， anticoagulants， glucocorticoids， intravenous immunoglobulin and other drugs， as well as bilevel positive airway pressure therapy （BiPAP）， flexible bronchoscopy intervention therapy， etc.After 21 days of treatment， the patient recovered clinically and discharged.During the follow-up of over 3 months，the child remained in good condition.Literatures showed that common pathogens causing NP in children in China include Mycoplasma pneumoniae， Streptococcus pneumoniae， Staphylococcus aureus， Pseudomonas aeruginosa， Haemophilus influenzae， adenovirus and influenza virus， etc.Currently， one adult case of EBVassociated NP has been documented in medical literature， whereas no pediatric case have been reported in either domestic or international studies.
Conclusions
EBV may be involved in the pathogenesis of NP in children， but the evidence is not yet sufficient.The tNGS based on pathogenic microorganisms can help the etiological diagnosis of NP in children and improve the precision of antimicrobial therapy， but need to be carefully interpreted in clinical practice.
