OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

Objective:To explore the characteristics of SLCO1B1/ SLCO1B3 gene variants among children with Rotor syndrome (RS). Methods:Four children who were admitted to the Department of Hepatology of Hunan Children′s Hospital between January 2019 and January 2022 were selected as the study subjects. Trio-whole exome sequencing was carried out for the four families, and gel electrophoresis was used to verify an insertional variant of long-interspersed element-1 (LINE-1).Results:Genetic testing has identified three variants of the SLCO1B1 gene, including c. 1738C>T (p.R580*), c. 757C>T (p.R253*) and c. 1622A>C (p.Q541P), and two variants of the SLCO1B3 gene, including c. 481+ 22insLINE-1 and c. 1747+ 1G>A among the children. Three of them were found to harbor homozygous variants of the SLCO1B1/ SLCO1B3 genes, and one has harbored compound heterozygous variants. Sanger sequencing confirmed the existence of all variants, and gel electrophoresis has confirmed the existence of the LINE-1 insertional variant of about 6 kb within intron 6 of the SLCO1B3 gene in all children. Conclusion:The pathogenesis of the RS among the four children may be attributed to the variants of the SLCO1B1/ SLCO1B3 genes. The LINE-1 insertion variant of the SLCO1B3 gene may be common among Chinese RS patients.

ObjectiveTo analyze relevant literature on Lianhua Qingwen preparations and clarify the research advances and hot spots in this field， so as to provide references for clinical rational application and further research. MethodLiterature related to Lianhua Qingwen preparations in the recent 10 years was retrieved from six databases， including China National Knowledge Infrastructure（CNKI）， VIP， Wanfang Data， PubMed， and Web of Science， followed by management and analysis by NoteExpress and CiteSpace. ResultFinally， 344 and 76 Chinese and English research articles were included， and the number of publications increased in recent years. The research articles were published in 162 Chinese and 48 English journals. Shijiazhuang Yiling Pharmaceutical Co.， Ltd. and Guangzhou Medical University were institutions with the largest number of Chinese and English publications， respectively. LIU Minyan was the author who had published the most articles. Keywords with high frequency included clinical efficacy， Lianhua Qingwen， inflammatory factors， traditional Chinese medicine， and coronavirus disease-2019（COVID-19）. Nineteen clusters， including clinical efficacy， Chinese medicine， Lianhua Qingwen， COVID-19， and influenza A virus， and 47 emergent keywords， including herpes zoster， pneumonia， inflammatory factors， influenza， and gut microbiota， were generated. ConclusionCooperation and exchanges in this field are insufficient. Research focuses on the clinical efficacy of Lianhua Qingwen in the treatment of COVID-19 and other diseases， pharmacological action and mechanism of antiviral drugs， and micro-mechanism research focuses on related pathways and target proteins， as well as the combination of Chinese and western medicines.

OBJECTIVE: Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN. METHODS: Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4^-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN. RESULTS: The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4^-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure. CONCLUSION TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.
Animals ; Mice ; TRPV Cation Channels/metabolism* ; Intermediate Filaments/metabolism* ; Hippocampus/metabolism* ; Neurons/metabolism* ; Memory Disorders/metabolism*

OBJECTIVES: To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI. METHODS: In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups. RESULTS: Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05). CONCLUSIONS There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.
Infant ; Child ; Infant, Newborn ; Humans ; Child, Preschool ; Infant, Premature ; Prospective Studies ; Gastrointestinal Microbiome ; China ; Infant, Premature, Diseases ; Gestational Age

Objective:To explore the clinical and pathological characteristics and prognostic factors of gastric neuroendocrine carcinoma(G-NEC)and gastric mixed adenoendocrine carcinoma(G-MANEC).Methods:Retrospective analysis was conducted on the clinical data of 67 patients with G-NEC and G-MANEC who underwent surgical treatment at Heping Hospital Affiliated to Changzhi Medical College from May 2015 to May 2023.The study included an analysis of the pathological characteristics distinguishing G-NEC from G-MANEC.Results:Com-pared to gastric adenocarcinoma,patients with G-NEC and G-MANEC in the stomach showed a higher incidence of gastric cancer in the male gastric cardia and were diagnosed at a later age.Tumors with larger diameters increase susceptibility to anemia,low albumin levels,and in-vasion of nerves and vasculature.Deeper tumor infiltration is associated with increased local lymph node metastases,later TNM staging,and a higher likelihood of distant metastasis post-surgery.The prognosis of G-NEC and G-MANEC is worse than that of gastric adenocarcinoma(P=0.001).However,there is no statistically significant difference in the pathological characteristics(P>0.05)and prognosis analysis(P=0.212)between G-NEC and G-MANEC.Univariate survival analysis identified age,preoperative albumin,preoperative CEA,number of lymph node metastases,TNM staging,and postoperative distant metastasis as risk factors affecting patient's overall survival(OS).In the multivariate ana-lysis,age,preoperative albumin,TNM staging,and postoperative distant metastasiswere identified as independent risk factors for OS.Con-clusions:There is a significant difference in clinical characteristics between G-NEC,G-MANEC,and gastric adenocarcinoma,often diagnosed at an advanced stage,which is prone to distant metastasis post-surgery.Poor prognosis is observed in patients aged over 60 years,with pre-operative albumin<40g/L,TNM stage Ⅱ/Ⅲ,and postoperative distant metastasis.

OBJECTIVE: To investigate the effects of mTOR inhibitors everolimus (EVE) and gemcitabine (GEM) on the proliferation, apoptosis and cell cycle of diffuse large B-cell lymphoma (DLBCL) cell line U2932, and further explore the molecular mechanisms, so as to provide new ideas and experimental basis for the clinical treatment of DLBCL. METHODS: The effect of EVE and GEM on the proliferation of U2932 cells was detected by CCK-8 assay, the IC₅₀ of the two drugs was calculated, and the combination index (CI=) of the two drugs was calculated by CompuSyn software. The effect of EVE and GEM on apoptosis of U2932 cells was detected by flow cytometry with AnnexinV-FITC/PI staining. Flow cytometry with propidium iodide (PI) staining was used to detect the effect of EVE and GEM on the cell cycle of U2932 cells. Western blot assay was used to detect the effects of EVE and GEM on the channel proteins p-mTOR and p-4EBP1, the anti-apoptotic proteins MCL-1 and Survivin, and the cell cycle protein Cyclin D1. RESULTS: Both EVE and GEM could significantly inhitbit the proliferation of U2932 cells in a time- and dose-dependent manner (r=0.465, 0.848; 0.555, 0.796). According to the calculation of CompuSyn software, EVE combined with GEM inhibited the proliferation of U2932 cells at 24, 48 and 72 h with CI=<1, which had a synergistic effect. After treated U2932 cells with 10 nmol/L EVE, 250 nmol/L GEM alone and in combination for 48 h, both EVE and GEM induced apoptosis, and the difference was statistically significant compared with the control group (P<0.05). The apoptosis rate was significantly enhanced after EVE in combination with GEM compared with single-agent (P<0.05). Both EVE and GEM alone and in combination significantly increased the proportion of cells in G₁ phase compared with the control group (P<0.05). The proportion of cells in G₁ phase was significantly increased when the two drugs were combined (P<0.05). The expression of p-mTOR and effector protein p-4EBP1 was significantly downregulated in the EVE combined with GEM group, the expression of anti-apoptotic proteins MCL-1, Survivin and cell cycle protein cyclin D1 was downregulated too (P<0.05). CONCLUSION EVE combined with GEM can synergistically inhibit the proliferation of U2932 cells, and the mechanism may be that they can synergistically induce apoptosis by downregulating the expression of MCL-1 and Survivin proteins and block the cell cycle progression by downregulating the expression of Cyclin D1.
Humans ; Gemcitabine ; Everolimus/pharmacology* ; Survivin/pharmacology* ; Cyclin D1/pharmacology* ; Myeloid Cell Leukemia Sequence 1 Protein ; Cell Line, Tumor ; Cell Proliferation ; TOR Serine-Threonine Kinases ; Apoptosis ; Apoptosis Regulatory Proteins ; Cell Cycle Proteins ; Lymphoma, Large B-Cell, Diffuse

OBJECTIVE: To explore the genetic basis for a child with infantile liver failure syndrome type 2 (ILFS type 2). METHODS: Clinical features of the child were analyzed. Next generation sequencing was also carried out for him. RESULTS: The child was found to harbor compound heterozygous variants of the NBAS gene, which included a novel nonsense c.2746A>T (p.R916X, 1456) variant in exon 24 and a missense c.3596G>A (p.C1199Y) mutation in exon 31, which has been associated with ILFS type 2. The two variants were respectively inherited from his father and mother. CONCLUSION The compound heterozygous variants of c.3596G>A and c.2746A>T of the NBAS gene probably underlay the ILFS type 2 in this child.
Child ; Exons/genetics* ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Liver Failure ; Male ; Mutation

Objective:To explore the effect of family integrated care (FIC) combined with intelligent health education platform in health education for elderly patients with stroke.Methods:Eighty patients with stroke were included from the Department of Neurology of the Second Affiliated Hospital of Chongqing Medical University from June 2019 to May 2020. They were divided into the experimental group and the control group ( n=40, respectively) by the random number table method. Patients in the control group received routine FIC in the Department of Neurology. Additional intelligent health education platform was provided for the experimental group to carry out intensive education. The modified Barthel index scale, self-care compliance scale and hospital anxiety and depression scale (HADS) were used before and after the intervention to evaluate patient′s self-care ability, self-care compliance and the degree of anxiety and depression. Results:Finally, 39 patients in the experimental group (1 case lost to followed-up) and 37 patients in the control group (3 cases lost to followed-up) completed the study. After the intervention, the scores of the modified Barthel index and self-care compliance scale of the experimental group were significantly higher than those of the control group [(65.9±12.6) vs (60.1±11.9) points, (78.2±13.6) vs (71.4±14.6) points], the HADS score was significantly lower than the control group [(15.18±2.46) vs (19.46±2.40) points] (all P<0.05). The scores of the modified Barthel index scale and self-care compliance scale of the experimental group after the intervention were significantly higher than those before the intervention [(65.9±12.6) vs (40.8±12.5) points, (78.2±13.6) vs (54.6±15.9) points] (all P<0.05), the HADS score was significantly lower than before the intervention [(15.18±2.46) vs (21.74±3.52) points] (all P<0.05). Similarly,the scores of the modified Barthel index and self-care compliance scale of the control group after the intervention were significantly higher than before the intervention [(60.1±11.9) vs (41.6±9.72) points, (71.4±14.6) vs (54.3±14.8) points], the HADS score was significantly lower than before the intervention [(19.46±2.40) vs (21.38±3.09) points] (all P<0.05). Conclusion:FIC combined with intelligent health education platform can significantly improve the self-care ability and self-nursing compliance of elderly stroke patients, and markedly improve the degree of depression and anxiety.