Japanese spotted fever(JSF)is an infectious disease caused by Rickettsia japonica,with nonspecific clinical symptoms and a high risk of misdiagnosis.We reported a case of JSF,in which Rickettsia japonica was detected in blood cells by metagenomic next-generation sequencing.The patient recovered after treatment with doxycycline.This report provides a reference for the clinical diagnosis and treatment of JSF.
Humans ; High-Throughput Nucleotide Sequencing ; Metagenomics ; Rickettsia/isolation & purification* ; Spotted Fever Group Rickettsiosis/microbiology*

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Objective: To investigate death and attrition in HIV-infected children under initial antiretroviral therapy (ART) and associated factors in Guangxi Zhuang autonomous region. Methods: This retrospective cohort study was conducted in HIV-infected children under initial ART in Guangxi from 2004 to 2019, data from ART information system of National comprehensive AIDS prevention and treatment information system. Cox proportional hazards models were used to assess factors associated with the death and attrition. Results: In 943 HIV-infected children, the overall mortality and attrition rates were 1.00/100 person-years and 0.77/100 person-years, respectively. The mortality and attrition rates within the first year of ART were 3.90/100 person-years and 1.67/100 person-years, respectively. The cumulative survival rate during the first, second, fifth and tenth year after ART was 96.14%, 95.80%, 93.68% and 91.54%, respectively. Multivariate Cox proportional hazards models results showed that being female (aHR=2.00, 95%CI: 1.17-3.40), CD4⁺T lymphocytes (CD4) counts before ART <200 cells/μl (aHR=2.79, 95%CI: 1.54-5.06), weight-for-age Z score before ART <-2 (aHR=2.38, 95%CI: 1.32-4.26), hemoglobin before ART <80 g/L (aHR=2.47, 95%CI: 1.24-4.92), initial ART with LPV/r (aHR=5.05, 95%CI: 1.15-22.12) were significantly associated with death; being female (aHR=2.23, 95%CI: 1.22-4.07) and initial ART with LPV/r (aHR=2.02, 95%CI: 1.07-3.79) were significantly associated with attrition. Conclusions: The effect of ART in HIV-infected children in Guangxi was better, but the mortality and attrition rates were high within the first year of treatment. It is necessary to strengthen the training in medical staff and health education in HIV-infected children and their parents in order to improve the treatment effect.
Anti-HIV Agents/therapeutic use* ; Child ; China/epidemiology* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Proportional Hazards Models ; Retrospective Studies

Objective: To investigate the impact of pretreatment drug resistance (PDR) on virological effect among HIV-infected patients having received antiretroviral therapy (ART) after three years. Methods: The baseline survey of PDR among HIV-infected patients was conducted in 2018, with a three-year follow up study. The clinic data and virological laboratory test variables were statistically analyzed. Results: Of the 2 433 participants, 41.6% (1 012/2 433) were aged between 18 and 34, 82.8% (2 015/2 433) were males, 46.9% (1 142/2 433) had education of high school or above, 22.4% (544/2 433) were farmers, 33.8% (823/2 433) were unmarried, 48.1% (1 169/2 433) were infected heterosexually and 41.3% (1 004/2 433) were with CRF07_BC. The prevalence of PDR was 4.5% (109/2 433). The prevalence of virological suppression failure (viral load ≥50 copies/ml) and drug resistance at three years follow up after ART was 8.1%(196/2 433) and 2.5%(60/2 433) respectively. The prevalence of virological suppression failure and drug resistance at three years follow up after ART were 18.3% (20/109) and 7.6% (176/2 324), and 4.6% (5/109) and 2.4% (55/2 324) among participants with PDR and non-PDR, respectively. The results of multivariate logistic regression model showed that illiteracy (aOR=3.26, 95%CI: 1.82-5.86), primary and junior high school education (aOR=1.54, 95%CI: 1.09-2.18), CD4⁺T lymphocyte count <200/μl (aOR=2.77, 95%CI: 1.75-4.37) and CD4⁺T lymphocyte count 200-499/μl (aOR=1.55, 95%CI: 1.10-2.18) at a three year follow up visit after ART, missed drugs in the past month (aOR=4.24, 95%CI: 2.92-6.17), and PDR (aOR=2.84, 95%CI: 1.67-4.85) were statistically significant with virological suppression failure on treatment. Conclusions: The prevalence of PDR in China at a low level currently, and the virological suppression failure rate is low after three years of ART. It is necessary to strengthen drug resistance monitoring of HIV-infected patients and pay attention to the influence of PDR on treatment effect.
Male ; Humans ; Adolescent ; Female ; Follow-Up Studies ; Viral Load ; Treatment Failure ; Drug Resistance ; HIV Infections/drug therapy*

OBJECTIVES: To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. METHODS: A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. RESULTS: After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). CONCLUSIONS Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.
Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; Angiogenesis Inhibitors/therapeutic use* ; Endothelial Growth Factors/therapeutic use* ; Hemorrhage ; Hypertension, Pregnancy-Induced ; Oxygen/therapeutic use* ; Retinopathy of Prematurity/drug therapy* ; Retrospective Studies ; Risk Factors ; Vascular Endothelial Growth Factor A

Objective: To screen and analyze the mutations of MITF gene in two children of type Ⅱ Waardenburg syndrome (WS2) from different families in Yunnan,China,and to explore the possible molecular pathogenesis. Methods: With informed consent, medical history collection, physical examinations, audiological evaluation, and high resolution computer tomography (HRCT) scan of temporal bone were performed on the two WS2 probands and their family members. Genomic DNA was extracted from peripheral blood of all individuals. The coding regions including all exons, part of introns and promoters of MITF, PAX3, SOX10, SNAI2, END3, ENDRB, and KITLG genes were sequenced by high-throughput sequencing. According to the results of high-throughput sequencing, pathogenic mutations detected in the probands and their parents were verified by Sanger sequencing. Results: The proband 1 carried c.641_643delGAA mutation in the 7th exon of MITF gene, which was a frame-shift mutation resulting in an amino acid change of p.214delR. It was a de novo mutation as the parents of proband 1 showed no variation on this site. The proband 2 carried heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene, which defected the function of MITF protein. Conclusion: Genetic examinations provide important evidence for diagnosis of Waardenburg syndrome. Heterozygous mutation c.641_643delGAA and heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene might be the molecular pathogenesis of the two WS2 probands in this study.
Asians/genetics* ; Child ; China ; Humans ; Mutation ; Pedigree ; SOXE Transcription Factors/genetics* ; Waardenburg Syndrome/genetics*

Child ; Correlation of Data ; Flow Cytometry ; Humans ; Immunophenotyping ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis

Objective: To investigate effect of curdione on the migration and invasion of human breast cancer HCC1937 cells and its mechanism.Method: HCC1937 cells were cultured in vitro and treated with curdione at various doses (0, 12.5, 25, 50, 100, 200, 400 μmol·L^-1) for 24, 48 h, the cell viability was detected by cell counting kit-8 method. curdione groups (12.5, 25, 50 μmol·L^-1) and blank group were established. The effect of curdione on the adhesion of HCC1937 cells was detected by the cell adhesion assay. The effect of curdione on migration of HCC1937 cells was detected by wound healing assay. The effect of curdione on the migration and invasion of HCC1937 cells were detected by transwell chamber assay. The effect of curdione on regulation of mitogen-activated protein kinase(MAPK)and protein kinase B(Akt)signaling pathways and the protein expressions of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) of HCC1937 cells were detected by the Western blot analysis. Effect of curdione on mRNA expressions of MMP-2 and MMP-9 of HCC1937 cells were detected by Real-time PCR.Result: Compared with the blank group, curdione (12.5, 25, 50 μmol·L^-1) groups had no significant effect on cell viability, but a remarkable effect on cell viability HCC1937 cells, and cell viability was gradually decreased with the increase of the concentration of curdione (P<0.05, P<0.01) in a time and dose-dependent manner. Compared with blank group, curdione groups (12.5, 25, 50 μmol·L^-1) had a significant effect on cell adhesion rate, migration rate and invasion rate of HCC1937 cells (P<0.05, P<0.01). Compared with the blank group, curdione groups (12.5, 25, 50 μmol·L^-1) could down-regulate phosphorylation levels of key proteins extracellular regulated protein kinases(ERK), c-Jun N-terminal kinase(JNK), Akt on MAPK and Akt signaling pathways (P<0.01), as well as the protein and mRNA expressions of MMP-2 and MMP-9 of HCC1937 cells.Conclusion: curdione can inhibit the migration and invasion of human breast cancer HCC1937 cells, and the mechanism may be related to down-regulation of phosphorylation levels of key proteins ERK, JNK, Akt on MAPK and Akt signaling pathways, so as to reduce the expressions of MMP2 and MMP-9.

Objective To explore the efficiency and safety of micafungin in preventing fungal infection in neutropenic stage in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The clinical data of 116 patients with allo-HSCT were collected, among whom 23 patients had a history of pulmonary fungal infection before transplantation. All patients were treated with micafungin for 50 mg daily from the beginning of pretreatment to recovery of neutropenia.Results Six patients were clinically diagnosed as pulmonary fungal infections. No serious adverse reactions were observed during the clinical observation, and concentration of cyclosporin A was not adjusted. By the end of follow-up, 83 patients survived. Conclusion Micafungin is safe and effective in preventing fungal infection in neutropenic stage after allo-HSCT without affecting the concentration of cyclosporine A in blood.

Objective To explore the efficiency and safety of micafungin in preventing fungal infection in neutropenic stage in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The clinical data of 116 patients with allo-HSCT were collected, among whom 23 patients had a history of pulmonary fungal infection before transplantation. All patients were treated with micafungin for 50 mg daily from the beginning of pretreatment to recovery of neutropenia.Results Six patients were clinically diagnosed as pulmonary fungal infections. No serious adverse reactions were observed during the clinical observation, and concentration of cyclosporin A was not adjusted. By the end of follow-up, 83 patients survived. Conclusion Micafungin is safe and effective in preventing fungal infection in neutropenic stage after allo-HSCT without affecting the concentration of cyclosporine A in blood.