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 study the differences in toxicity between intravenous(iv)administration and aqueous solution exposure of Dichroa alkali salt(DAS)in zebrafish.METHODS ① Well-devel-oped zebrafish larvae of 2 d post fertilization(2 dpf)were randomly divided into the normal control(no treatment),solvent control(saline,iv),and DAS groups(0.125,0.25,0.50,1.00 and 2.00 mg·kg-1,iv)before being observed for 3 consecutive days after administration.A heart rate of 0 was determined as death of zebrafish,and the mortality rate,maximum non-lethal dose(MNLD),and 10 percent lethal dose(LD10)were calculated.The incidence of venous sinus congestion,pericardial edema,slowing heart rate and blood flow of zebrafish in the 0.50 and 2.00 mg·kg-1 groups were observed and calculated by somatoscopic microscopy at 4 h after drug administration.Zebrafish larvae were iv given DAS at doses of 0.041,0.136,0.412,and 0.452 mg·kg-1 while the malformation phenotypes of zebrafish larvae development were observed under a stereomicroscope for 3 consecutive days,including pericardial edema,abnormal heart rate,slow blood flow,loss of circulation,eye abnormalities,brain malforma-tions,jaw abnormalities,loss/degeneration of the liver,delayed yolk sac absorption,intestinal abnormal-ities,abnormal body coloration,body edema,curvature of the trunk/tail/nodal cord and muscle degener-ation before the incidence was calculated.②Zebrafish larvae were randomly divided into a normal control group and DAS aqueous solution exposure groups at concentrations of 2.5,5.0,10.0,25.0,50.0,75.0,and 100.0 mg·L-1,observed for 3 d until the mortality rate,LD10,and MNLD were calculated.Zebrafish were exposed to DAS aqueous solutions at concentrations of 0.32,1.06,3.20,and 11.00 mg·L-1,and the malformation phenotypes of zebrafish larvae development were observed under a stereomicro-scope for 3 consecutive days to calculate the incidence.RESULTS ① The MNLD and LD10 of DAS iv administered to zebrafish larvae were 0.412 and 0.452 mg·kg-1,respectively.Compared with the solvent control group,4 h after DAS iv administration,the incidence of sinus congestion,slow heart rate and pericardial edema in the 0.50 and 2.00 mg·kg-1 groups significantly increased(P<0.05,P<0.01),so was the incidence of slow blood flow in the 2.00 mg·kg-1 group(P<0.01).The rate of delayed yolk sac absorption was significantly increased in the 0.041,0.136,0.412,and 0.452 mg·kg-1 groups(P<0.05,P<0.01),so was the mortality rate in the 0.452 mg·kg-1 group(P<0.05),with pericardial edema observed in the dead zebrafish.② The MNLD and LD10 of DAS aqueous solution exposure for zebrafish larvae were 3.20 and 11.00 mg·L-1,respectively.Compared with the normal control group,the incidence of decreased heart rate and slow blood flow was significantly increased in the 3.20 and 11.00 mg·L-1 groups(P<0.01),so was the incidence of significantly darkened intestines in the 1.06,3.20,and 11.00 mg·L-1 groups(P<0.01).The incidence of delayed yolk sac absorption was significantly increased in the 0.32,1.06,3.20,and 11.00 mg·L-1 groups(P<0.05,P<0.01),so was the incidence of trunk curvature and lower jaw malformation in the 11.00 mg·L-1 group(P<0.01).CONCLUSION The toxic phenotypes of DAS are different between iv administration and aqueous solution exposure in zebrafish larvae.DAS aqueous solution exposure can not only lead to slow heart rate,slow blood rheology,delayed yolk sac absorption and intestinal blackening,but also induce neurodevelopmental toxicity.However,iv adminis-tration can effectively ward off significant gastrointestinal damage and neurodevelopmental toxicity.

Objective To retrieve,evaluate and summarize the best pertinent evidence on the placement and management of peripheral arterial catheters in critically ill children at home and abroad for clinical references.Methods A systematic search was conducted in related databases on the evidence of the placement and management of peripheral arterial catheters in critically ill children.The spectrum of eligible documents included clinical decisions,guidelines,evidence summaries,systematic reviews,expert consensuses,and norms.The search period was from the establishment of the databases to April 30,2023.The included literature was limited to English and Chinese languages.The quality of the literature was independently evaluated by evidence-based trained investigators and combined with professional judgment to extract information from the literature that met the quality standards.Results A total of 18 articles were included,including 3 guidelines,3 clinical decisions,8 evidence summaries,3 systematic reviews and 1 expert consensus.The best evidence included a total of 27 pieces of evidence in 4 areas,namely the assessment of indwelling peripheral arterial catheters,placement of peripheral arterial catheters,maintenance during the duration of indwelling peripheral arterial catheters,and removal.Conclusion This study summarized the most robust evidence pertaining to the management of peripheral arterial catheters in critically ill children,and provided an evidence-based basis for the standardized placement and management of peripheral arterial catheters in critically ill children.Nursing staff should carefully select and apply evidence according to the actual clinical situation,the wishes of children and parents.

Objective:To explore the consistency between modified 12+ X prostate biopsy under transrectal interventional ultrasound and postoperative Gleason score in prostate cancer patients.Methods:A retrospective study was conducted on 312 patients diagnosed with prostate cancer and underwent radical resection at Zhongshan People′s Hospital from January 2020 to December 2022. All patients underwent modified 12+ X prostate biopsy and prostate system biopsy under transrectal interventional ultrasound before surgery. Using the Gleason score of postoperative pathological specimens as the " gold standard", the detection rates of prostate cancer and clinically significant prostate cancer using modified 12+ X prostate biopsy and prostate system biopsy under transrectal interventional ultrasound were compared, and the consistency between the two methods alone or in combination and postoperative Gleason score was compared.Results:Among 312 patients, the positive detection rate of the improved 12+ X puncture biopsy combined with the system puncture biopsy was significantly higher than that of the individual detection (95.51% vs 80.77% vs 76.92%), with a statistically significant difference ( P<0.05). The improved 12+ X puncture biopsy combined with system puncture biopsy showed a clinically significant higher detection rate of prostate cancer in positive patients compared to the two tests alone (94.63% vs 77.78% vs 80.00%), with a statistically significant difference ( P<0.05). There was no statistically significant difference in the detection rate of clinically significant prostate cancer among patients who missed diagnosis, either alone or in combination with biopsy ( P>0.05). The upgrade rate of Gleason score after prostate improvement 12+ X puncture biopsy (25.00%) was significantly lower than that of prostate system puncture (44.17%), which was significantly higher than combined puncture biopsy (11.74%), with a statistically significant difference ( P<0.05). After 312 patients received combined puncture biopsy, urinary retention was found in 14 cases (4.49%), hematuria in 30 cases (9.62%), fever in 28 cases (8.97%), and blood in stool in 18 cases (5.77%). After symptomatic treatment, they basically improved within 3 days after puncture. Conclusions:The combination of modified 12+ X prostate biopsy with systematic biopsy under transrectal interventional ultrasound can improve the detection rate of prostate cancer, and has good consistency with the postoperative Gleason score of prostate cancer patients, which has good clinical application value.

  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 effects of propofol on inflammatory responses in substantia nigra in mice with Parkinson′s disease (PD) and its relationship with α-synuclein (α-syn) expression.Methods:Thirty-three SPF healthy male C57BL/6 mice, aged 12 weeks, weighing 24-26 g, were divided into 3 groups ( n=11 each) using a random number table method: control group (group Con), group PD and propofol group (group Pro). In PD and Pro groups, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) 30 mg/kg was intraperitoneally injected once a day for 5 consecutive days to induce PD.Propofol 50 mg/kg was intraperitoneally injected at 2 h after the last injection of MPTP in group Pro, while the equal volume of normal saline was given instead in Con and PD groups.The rotarod test was performed at 24 h after administration.The animals were then sacrificed and substantia nigra was removed for determination of contents of interleukin-1β (IL-1β) and tumor necrosis factor (TNF)-α (by enzyme-linked immunosorbent assay), the expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and p-caspase-1 (by Western blot) and the expression of α-syn (by immunofluorescence staining). Results:Compared with Con group, the first fall-off time was significantly shortened, the number of falling off was increased, the contents of IL-1β and TNF-α were increased, and the expression NLRP3, p-caspase-1and α-syn was up-regulated in substantia nigra in group PD ( P<0.05). Compared with PD group, the first fall-off time was significantly prolonged, the number of falling off was decreased, the contents of IL-1β and TNF-α were decreased, and the expression NLRP3, p-caspase-1and α-syn was down-regulated in substantia nigra in group Pro ( P<0.05). Conclusion:Propofol can improve behaviors of the mice through inhibiting inflammatory responses in substantia nigra, and the mechanism is related to down-regulating the expression of α-syn.

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 accuracy of 3.0 T MR in the diagnosis of full thickness tear and partial thickness tear of the supraspinatus-infraspinatus tendon, and to analyze the causes of missed diagnosis and misdiagnosis of the supraspinatus-infraspinatus tendon tear.Methods:The MRI diagnosis report and arthroscopic surgery records of 210 patients with shoulder joint injuries in Peking University Third Hospital were analyzed retrospectively. Taking the results of arthroscopic surgery as the gold standard, the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive values of 3.0 T MR for full thickness tear and partial thickness tear of the supraspinatus-infraspinatus tendon were calculated, and the reasons of missed diagnosis and misdiagnosis were analyzed.Results:In 210 patients with rotator cuff injury, the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of MRI for full thickness tear of the supraspinatus-infraspinatus tendon were 81.4% (171/210), 83.1% (98/118), 79.3% (73/92), 83.7% (98/117) and 78.4% (73/93) respectively. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of MRI for partial tears of the supraspinatus-infraspinatus tendons were 77.6% (163/210), 65.7% (44/67), 83.2% (119/143), 64.7% (44/68) and 83.8% (119/142) respectively. Among the 44 cases of missed diagnosis and misdiagnosis of the supraspinatus-infraspinatus tendon tear, 21 cases (47.7%) occurred in the junction supraspinatus and infraspinatus tendon-osseous (stop). Among the 7 cases of intra-tendon tear of supraspinatus and infraspinatus muscle, 6 cases were misdiagnosed cases, which was the most easily missed diagnosed type of partial tear. The reason for missed diagnosis was that the signal of partial tear was not high (no fluid signal was shown on T 2WI). Complex laceration was also a type of missed diagnosis in partial tears. Among the 4 cases of superior and inferior surface tendons combined with intra-tendon lacerations, 3 cases were missed diagnosed. Conclusion:3.0 T MR has higher accuracy for the diagnosis of full thickness tear and partial thickness tear of supraspinatus-infraspinatus tendon, but there is still a certain rate of misdiagnosis and missed diagnosis. A full understanding of the causes of misdiagnosis and missed diagnosis of MR in the diagnosis of rotator cuff tears of supraspinatus and infraspinatus tendons is helpful to further improve the accuracy of MR in the diagnosis of supraspinatus and infraspinatus tendon injuries of shoulder joint.

Animals ; Cdc20 Proteins/metabolism* ; Cell Line ; Embryo, Mammalian/embryology* ; Embryonic Development ; Female ; Infertility, Female/metabolism* ; Mice ; Mutation ; Oocytes/metabolism*

Objective To investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with CT-guided thermal ablation (radiofrequency ablation or microwave ablation) in treating intrahepatic cholangiocarcinoma.Methods The clinical data of 14 patients with pathologicallyproved intrahepatic cholangiocarcinoma,who were admitted to authors' hospital during the period from September 2009 to July 2013 to receive TACE with subsequent radiofrequency ablation (RFA) or microwave ablation (MWA),were retrospectively analyzed.A total of 18 lesions were detected in the 14 patients.The maximal diameter of the lesion (or the sum of maximal diameters if there were multiple lesions) ranged from 2.2 cm to 7.2 cm (mean 4.2±1.4 cm).After TACE,the lesion's complete ablation rate,surgical complications,tumor-free survival time and overall survival time were evaluated.Results Complete ablation was obtained in 15 lesions (83.3％,15/18).The incidence of moderate complications was 6.2％,and no severe complications or death occurred.After the treatment,the patients were followed up for 6-14 months,with a mean of (16.0±10.3) months.At the end of follow-up,6 patients (42.9％,6/14) died.The median tumor-free survival time in patients whose lesions obtained complete ablation was 17 months.The median survival time of all patients was 20 months.The 1-,2-and 3-year overall survival rates were 82.5％,41.3％ and 20.6％ respectively.Conclusion TACE combined with thermal ablation can be regarded as one of the treatment options for intrahepatic cholangiocarcinoma.