A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.

Objective To construct and apply a management plan for microaspiration of oropharyngeal secretions in ICU intubated patients.Methods Based on evidence summaries and expert consultation,a management plan for microaspiration of oropharyngeal secretions in ICU intubated patients was constructed,consisting of 19 items covering 7 aspects including identification of risk factors,position management,tube and cuff selection,cuff management,mechanical ventilation management,pain and sedation management,removal of oropharyngeal and subglottic secretions,and oral care.Convenience sampling was used to select 141 ICU intubated patients from a tertiary A comprehensive hospital in Suzhou from June,2022 to September,2023.Patients were divided into an experimental group(n=72)and a control group(n=69)according to the wards.The experimental group received the management plan for microaspiration of oropharyngeal secretions in ICU intubated patients.The control group received the nursing bundle for ventilator associated pneumonia(VAP).The incidence and time from intubation to microaspiration and VAP,duration of mechanical ventilation,ICU length of stay,and disease outcome were compared between the 2 groups.Results The incidence of microaspiration of oropharyngeal secretions,the duration of mechanical ventilation,time from intubation to microaspiration showed significant differences between the 2 groups(P<0.05).There were no significant differences in the incidence of ventilator associated pneumonia,ICU length of stay,and disease outcome between the 2 groups(P>0.05).The time from intubation to VAP in the experimental group was 7.5 days,and that in the control group was 3.8 days.Conclusion The application of the management plan for microaspiration of orophaiyngeal secretions in ICU intubated patients is beneficial for reducing the incidence of microaspiration,delaying the time from intubation to microaspiration and VAP,and shortening the duration of mechanical ventilation.

Objective     To explore the role of versican (VCAN) in ESCC prognosis based on bioinformatics data. Methods    First, three RNA microarray datasets of ESCC were downloaded from GEO database, which were then integrated and used to explore differentially expressed genes (DEGs). The subsequent analysis was conducted based on the results of these DEGs: (1) The STRING database was used to construct a protein-protein interaction (PPI) network;(2) molecular complex detection software was used to analyze the modules of the PPI network, of which the most significant modules were chosen, and hub genes were the genes included in the chosen modules; (3) high-throughput RNA sequencing data from TCGA and GTEx databases were used to verify the expression of these hub genes to confirm whether they were differentially expressed; (4) the survival curve analysis of confirmed DEGs was conducted to select genes that had significant influence on the survival of ESCC; (5) TIMER database was used to analyze the relationship between the gene expression of VCAN and the abundance of tumor-infiltrating immune cells (TIICs) and gene markers in these cells; (6) Targetscan and miRDB software were used to predict the miRNAs that could regulate VCAN, and Cytoscape software was used to construct the regulatory network. Results    A total of 630 DEGs and 32 hub genes were found, of which VCAN was an up-regulated DEG, and high expression of VCAN was significantly associated with poor prognosis of ESCC. Moreover, VCAN could also play a role in the immune microenvironment of ESCC, which was mainly manifested by a significant positive correlation between the abundance of VCAN and the abundance of M2 macrophages gene markers, some of which had been reported to be associated with poor prognosis of ESCC. Finally, we also found that VCAN could be regulated by 15 miRNAs in ESCC, some of which had been reported to be associated with ESCC prognosis. Conclusion    This study provides direct and indirect comprehensive evidence for the role of VCAN in ESCC prognosis. The direct evidence is that the survival curve shows that highly expressed VCAN is significantly associated with the poor prognosis of ESCC, and the indirect evidence is that VCAN is positively related to some markers which indicate poor prognosis in the ESCC immune microenvironment, and VCAN can be regulated by some prognostic miRNAs in ESCC.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

Objective:To evaluate the effect of propofol on dopaminergic neurons of mice with Parkinson′s disease (PD).Methods:Forty-eight pathogen-free healthy male C57BL/6 mice, aged 8-12 weeks, weighing 22-32 g, were divided into 3 groups ( n=16 each) using a random number table method: control group (group C), group PD and propofol group (group Pro). The neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropypridine (MPTP) was intraperitoneally injected for 7 consecutive days in PD and Pro groups, while the equal volume of normal saline was given for 7 consecutive days in group C. At 30 min after intraperitoneal injection of MPTP, propofol 25 mg/kg was intraperitoneally injected in group Pro, while the equal volume of normal saline was given daily in group C and group PD.At day 8 after the end of establishment of the model, gait analysis system experiment and rotarod test were used to record the step distance and retention time.The animals were sacrificed after the behavioral tests, and the brain tissues were removed for the dopamine neuron count in substantia nigra (by immunohistochemistry) and for determination of the expression of alpha-Synuclein (α-Syn) and Tyrosine hydroxylase (TH) in the substantia nigra (by Western blot). Results:Compared with group C, the step distance was significantly decreased, retention time were shortened, the dopamine neuron count in substantia nigra was decreased, the expression of TH was down-regulated, and expression of α-Syn in substantia nigra was up-regulated in group PD ( P<0.05), and no significant change was found in the parameters mentioned above in group Pro ( P>0.05). Compared with group PD, the step distance was significantly increased, retention time were prolonged, the dopamine neuron count in substantia nigra was increased, the expression of TH was up-regulated, and expression of α-Syn in substantia nigra was down-regulated in group Pro ( P<0.05). Conclusion:Propofol has protective effect on dopaminergic neurons of PD mice, and the mechanism may be related to the down-regulation of α-Syn expression in substantia nigra.

Objective:To investigate the changes of mean venous sinus pressure (MVP) and trans-stenosis pressure gradient in patients with idiopathic intracranial hypertension (IIH) under awake setting and general anesthesia.Methods:Thirty-eight patients with IIH accepted venous sinus stent implantation in our hospital from January 2010 to January 2020 were chosen in our study; their clinical data were analyzed retrospectively. The manometry results of these 38 patients were recorded under awake setting and general anesthesia before stenting; MVP and trans-stenosis pressure gradient were obtained and compared.Results:MVP in the superior sagittal sinus, torcular, transverse sinus and sigmoid sinus showed no significant difference between patients under awake setting and general anesthesia ( P>0.05). Mean trans-stenosis pressure gradient in patients under awake setting ([22.784±7.606] mmHg) was significantly higher as compared with that in patients under general anesthesia ([18.388±8.992] mmHg, P<0.05). Conclusion:Mean trans-stenosis pressure gradient in patients under awake setting is higher as compared with that in patients under general anesthesia, and selection for venous sinus stent implantation should be decided by trans-stenosis pressure gradient in patients under awake setting.

Chemerin is a cytokine that attracts much attention in the reproductive process. This study aimed to explore the effects of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) on the maintenance of early pregnancy. The expression levels of chemerin and CMKLR1 in the decidua tissues of 20 early normal pregnant women and 20 early spontaneous abortion women were examined by Western blot and real-time polymerase chain reaction analyses. CMKLR1 receptor antagonist (α-NETA) was then intrauterinely injected into normal pregnant mice model to assess its effect on the outcome of pregnancy and the phosphorylation rate of ERK1/2 in decidua tissues.We found that the expression level of chemerin in women who had experienced early spontaneous abortion was lower than in those who had experienced normal early pregnancy (P < 0.01); conversely, CMKLR1 expression was higher in the former than in the latter (P < 0.01). In a pregnant-mouse model, the embryo resorption rate of α-NETA group was higher than that in the negative control group (61.5% vs. 10.8%) (P < 0.001). Compared with the control group, ERK1/2 phosphorylation in decidua tissues decreased in the α-NETA-treated group (P < 0.01). These results suggested that the inhibition of the chemerin/CMKLR1 signaling pathway can lead to the abortion of mouse embryos, and that chemerin/CMKLR1 may play an important role in the maintenance of early pregnancy possibly by regulating ERK1/2 phosphorylation.
Adult ; Animals ; Chemokines ; analysis ; metabolism ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; metabolism ; Mice ; Pregnancy ; metabolism ; Pregnancy Rate ; Pregnancy, Animal ; Receptors, Chemokine ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Signal Transduction ; Young Adult

Objective To explore the effect of apolipoprotein E deficiency on astrocyte destruction in the ex vivo spinal cord slice model. Methods Vibratome-cut transverse spinal cord slices from C57BL/6 postnatal day 7 ApoE -/-mice and wild-type mice were cultured on transwell porous supports. After 7 days in the culture , spinal cord slices were exposed to LPS for 5 days. The expression of AQP4, GFAP and Iba1 was detected by immunofluorescence. The concentration of TNF-α and NO were detected by ELISA and method of nitrate reductase, respectively. Results Marked loss of AQP4 and GFAP staining were shown in LPS-affected groups, not in the control group, and the lesion score was higher in ApoE-/-group than WT-group (P<0.05). In addition, the expression of Iba1 and concentration of TNF-α, NO in the LPS-affected groups were more than that of the control group (P < 0.05), and they were higher in the ApoE-/-LPS group than the WT-LPS group (P < 0.05). Conclusions ApoE deficiency exacerbates astrocyte injury, likely through promoting the release of pro-inflammatory mediators from microglia.

Objective To investigate the clinical efficacy and prognosis of transcatheter arterial chemoembo-lization(TACE)combined with radiofrequency ablation(RFA)in treatment of liver cancer.Methods 64 patients of liver cancer were selected as the research subjects,and they were divided into two groups by randomized single blind method.32 cases in the control group adopted the TACE treatment,while 32 cases in the observation group were given TACE combined with RFA.The tumor shrinkage,complete necrosis rate,local recurrence rate,AFP levels and adverse reactions of the two groups were compared.The patients were followed up for 3 years to record survival.Results After treatment,the tumor shrinkage rate and complete necrosis rate of the observation group were 90.63% and 75.00%, which were significantly higher than 68.75% and 50.00% of the control group,the differences were statistically significant (χ2 =8.453,8.203,all P <0.05).The local recurrence rate of the observation group was 21.88%,which was significantly lower than 43.75% of the control group,the difference was statistically significant(χ2 =7.887,P <0.05).After treatment,the AFP level of the observation group was (70.11 ±6.45 )ng/L,which was significantly lower than (157.76 ±10.42)ng/L in the control group,the difference was statistically significant (t =7.433,P <0.05).The survival rates of 1 year,2 years and 3 years in the observation group were 84.38%,71.88%,56.25%, which were significantly higher than 65.63%,53.13%,31.25% in the control group (χ2 =8.677,8.203,8.985,all P <0.05).The incidence rate of postoperative adverse reaction had no significant difference between the two groups (χ2 =1.337,P >0.05 ).Conclusion TACE combined with RFA in treatment of liver cancer can significantly improve the effect of tumor necrosis rate,reduce the local recurrence rate and prolong the survival time of the patients, and it had less adverse reaction,higher safety,and which should be applied in clinical.

Objective To develop a scoring system to determine peptic ulcer risks and to evaluate its screening efficiency.Methods A total of 862 people who underwent gastroscopy for the first time ranging from 18 to 45 years old were enrolled in this study.They were divided into two cohorts with the method of simple random sampling,514 in the original cohort and 348 in the validation cohort.Information such as demographic characteristics,dietary intake,lifestyle,symptoms relating to peptic ulcer was obtained.A multivariable logistic regression method was used to determine independent predictors of peptic ulcer.Based on the logistic regression model,a scoring system was developed with a regression coefficient-based scoring method.Then the scoring system was internally and externally validated.Each value of calibration,discrimination and accuracy were computed and then compared with those of original cohort to assess its screening efficiency.Results Three variables (gender,smoking and melena) composed the scoring system with scores ranging from 0 to 4 points.It had good calibration (P =0.956) and discrimination (area under the ROC =0.70,95％CI:0.65-0.76).With 2.5 points as the screening cutoff value,the sensitivity,specificity,accuracy rate,positive predictive value,negative predictive value,positive likelihood ratio and negative likelihood ratio were 49.5％,82.2％,75.5％,41.6％,86.4％,2.78 and 0.61,respectively.In the validation cohort,the sensitivity,specificity,accuracy rate,positive predictive value,negative predictive value,positive likelihood ratio and negative likelihood ratio were 27.2％,92.7％,71.3％,64.6％,72.3％,3.89 and 0.79.The results above indicated that the screening efficiency of the scoring system in the original cohort was similar to that in the validation cohort.Conclusion The scoring system to determine peptic ulcer risks,containing gender,smoking and melena,has good screening efficiency and can be applied to predict the risks of peptic ulcer.