Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective:To explore the optimal storage condition and time of umbilical cord blood from collection to preparation.Methods:Collect cord blood samples from 30 healthy newborns,with each new born's umbilical cord blood was divided into two parts on average.One part was stored in cold storage(4 ℃)and the other was stored at room temperature(20-24 ℃).Samples were taken at 24,36,48,60 and 72 h,respectively,total nucleated cells(TNC)count and TNC viability was analyzed.Flow cytometry was used to detect the ratio of viable CD34+cells to viable CD45+cells and viability of CD34+cells,and colony-forming unit-granulocyte-macrophage(CFU-GM)count was performed by hematopoietic progenitor cell colony culture.The change trend of each index over time was observed,and the differences in each index was compared between cold storage and room temperature storage under the same storage time.Results:The TNC count(r4℃=-0.9588,r20-24℃=-0.9790),TNC viability(r4℃=-0.9941,r20 24 ℃=-0.9970),CD34+cells viability(r4℃=-0.9932,r20-24℃=-0.9828)of cord blood stored in cold storage(4 ℃)and room temperature storage(20-24 ℃)showed a consistent downward trend with the prolongation of storage time.The percentage of viable CD34+cells(r4℃=0.9169,r20-24 ℃=0.7470)and CFU-GM count(r4℃=-0.2537,r20-24℃=-0.8098)did not show consistent trends.When the storage time was the same,the TNC count,TNC viability,CD34+cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature.Under the same storage time(24,36,48,60 or 72 h),TNC viability in room temperature storage was significantly lower than that in cold storage(P＜0.001),but TNC count,percentage of viable CD34+cells and CFU-GM count were not significantly different between room temperature storage and cold storage.When stored at room temperature for 24 h and 36 h,the viability of CD34+cells was significantly lower than that in cold storage(P＜0.001,P＜0.01),when the storage time for 48,60 and 72 h,there was no significant difference in the CD34+cells viability between room temperature storage and cold storage.Conclusion:It is recommended that cord blood be stored in cold storage(4 ℃)from collection to preparation,and processed as soon as possible.

Abstract: Objective　To investigate the clinical characteristics and diagnosis key points of brain abscess caused by Nocardia asiatica, and provide a clinical basis for diagnosing and treating intracranial infection caused by Nocardia. Methods　A case of pulmonary Nocardia asiatica complicated with brain abscess diagnosed at the Second Affiliated Hospital of Hainan Medical University was selected to analyze the clinical manifestations, cerebrospinal fluid characteristics, pulmonary and cranial imaging features, and treatment plan, and to summarize the diagnosis and treatment experience. Results　The patient was an elderly woman with a history of diabetes, dry cough was the first symptom without fever or headache. At the beginning of the course, it was diagnosed as pulmonary infection and tuberculosis in the local hospital, and received conventional antimicrobial and anti-tuberculosis therapies, but showed no improvement. The patient developed progressive limb weakness, followed by consciousness disorders, and coma. Cerebrospinal fluid (CSF) adenosine deaminase and lactate dehydrogenase were not abnormal, CSF pressure, protein and white blood cells were high, mainly with multiple nuclear cells. CSF glucose and chloride were normal in the early stage of the disease, but decreased significantly in the later stage. Metagenomic analysis of cerebrospinal fluid indicated Nocardia asiatica with a specific sequence number of 537. Lung CT showed exudation, abscess, and cavity in the right lung. Skull MRI scan + enhancement suggested multiple scattered abscesses in both cerebral hemispheres. The abscesses were of different sizes and showed ring enhancement, with extensive surrounding edema, and ventricular compression. After treatment with meropenem, linezolid, and compound sulfamethoxazole tablets, the cerebrospinal fluid recovered, and the lesions in the lungs and intracranial structures improved. Conclusions　Brain abscess caused by Nocardia asiatica is similar to the tuberculous brain in clinical symptoms, cerebrospinal fluid examination, craniocerebral imaging, so we should be alert to the possibility of Nocardia infection in patients with diabetes. At the same time, metagenomic testing of the cerebrospinal fluid can help confirm the diagnosis. The mortality and disability rates of brain abscess caused by Nocardia are high. Early diagnosis and treatment can improve the prognosis.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Sporadic Creutzfeldt-Jakob disease(sCJD)is a prion-caused degenerative disease of the central nervous system,with the typical clinical manifestation of rapidly progressive dementia.The course of disease is less than 1 year in most patients and more than 2 years in only 2% to 3% patients.We reported a case of sCJD with expressive language disorder and slow progression in this paper.By summarizing the clinical manifestations and the electroencephalograhpy,MRI,and pathological features,we aimed to enrich the knowledge about the sCJD with slow progression.
Humans ; Creutzfeldt-Jakob Syndrome/pathology* ; Brain/pathology* ; Magnetic Resonance Imaging ; Central Nervous System/pathology*

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

OBJECTIVE: To explore the effect and possible mechanism of dimethyl fumarate (DMF) on T-cell acute lymphoblastic leukemia (T-ALL), and provide experimental and theoretical basis for the clinical treatment of T-ALL. METHODS: Jurkat cells were treated with different concentrations of DMF for 24 hours, and then the proportion and absolute count of Ki67-positive Jurkat cells were analyzed by flow cytometry. Meanwhile, the protein levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and E3 ubiquitin ligase HACE1 in Jurkat cells treated with DMF for 24 hours were evaluated by Western blot. Nrf2 proteins were co-immunoprecipitated in Jurkat cells, and then HACE1 protein was assessed by Western blot. Plasmids of Flag-Nrf2 and different gradients of Flag-HACE1 were transfected into HEK293T cells, and the levels of Flag-Nrf2 were detected by Western blot after 48 hours. RESULTS: DMF could significantly inhibit the proportion and absolute count of Ki67-positive Jurkat cells, and DMF inhibited the proliferation of Jurkat cells in a dose-dependent manner (r=0.9595, r=0.9054). DMF could significantly up-regulate the protein levels of Nrf2 and E3 ubiquitin ligase HACE1 in Jurkat cells (P<0.01, P<0.01). HACE1 physically interacted with Nrf2 in Jurkat cells. Overexpression of Flag-HACE1 significantly increased the protein level of Flag-Nrf2 in a dose-dependent manner (r=0.9771). CONCLUSION DMF inhibits the proliferation of T-cell acute lymphoblastic leukemia cell. The mechanism may be that, DMF significantly up-regulates the protein levels of Nrf2 and E3 ubiquitin ligase HACE1, and HACE1 interacts with Nrf2 and positively regulates Nrf2 protein level.
Dimethyl Fumarate/pharmacology* ; HEK293 Cells ; Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; T-Lymphocytes ; Ubiquitin-Protein Ligases

ObjectiveTo investigate the preventive effects of Astragaloside IV （ASIV） on the formation of colonic adenomatous polyps （CAP） in high-fat-fed （HF） mice with adenomatous polyposis mutation （Apc ^Min/+） and its regulation mechanism on serum metabolite disorders. MethodsA total of 24 mice were evenly assigned to Apc ^Min/+ mice group （Con， n=8）， high-fat diet-fed Apc ^Min/+ mice group （HF， n=8）， and ASIV treatment group （HF-ASIV， n=8）. Apc ^Min/+ mice in HF group and HF-ASIV group were given high-fat diet for 8 consecutive weeks to construct CAP mouse model. Meanwhile， Apc ^Min/+ mice in HF-ASIV group were given 50 mg/kg ASIV every other day for 8 weeks. Daily amount of water intake， food intake and body weight of mice in each group were recorded. At the end of the 8th week， mice were sacrificed for serum and the distal and proximal colon. The number of colonic polyps in each group was recorded. Hematoxylin-eosin （H&E） staining was used to observe the morphological changes of the proximal colon. Immunohistochemistry （IHC） was applied to analyze the amount of COX2 positive cells in the proximal colon. The expression levels of IL-1 β and TNFα in intestinal wall were detected by QRT PCR. Non-targeted metabolic profiling of mouse gut by liquid-phase mass spectrometry was used to screen for differential metabolites and perform functional enrichment. ResultsNo mice died in each group during experiment.ASIV effectively reduced the size and the number of the CAPs that accompanied with the downregulation of inflammatory signaling molecules （COX-2， IL-1 β and TNFα）. Alcian blue and lysozyme staining showed ASIV improved the gut epithelium by promoting goblet and Paneth cells population. Significant differences in metabolite OPLS-DA scores between groups were noted （P < 0.001； P = 0.02）. Compared with HF group， 13 differential metabolites in the serum of HF-ASIV group were significantly recalled， and the levels of the metabolites functionally enriched to N-acetyl-α-D-glucosaminyl-diphosphate were significantly increased in the positive and negative ion modes （P < 0.05） ， which was negatively correlated with the number of medium-sized adenomas （P < 0.01）. ConclusionASIV reduced the number of colonic adenomatous polyps in high-fat-fed Apc ^Min/+ mice and was closely associated with reduced intestinal wall inflammation and regulation of serum metabolite N-acetyl-α-D-glucosamine-diphosphate levels.

Purpose: This study aimed to investigate the prevalence, risk factors, and effects of primary nocturnal enuresis (PNE) on physical and mental health in young adults in mainland China. Methods: An anonymous questionnaire was used to collect information including the sociodemographic characteristics, history of PNE, family history, daytime voiding symptoms, Pittsburgh Sleep Quality Index (PSQI) scores, Self-Esteem Scale (SES), and Self-Rating Depression Scale (SDS). A total of 22,500 university students from 23 provinces and 368 cities in mainland China were included. Results: In total, 21,082 questionnaires were collected, and 20,345 of them qualified for statistical analysis. The PNE prevalence was 1.17%, and the distribution of monosymptomatic nocturnal enuresis (MNE) and nonmonosymptomatic nocturnal enuresis (NMNE) was 66.1% and 33.9%, respectively. In total, 28% of respondents with PNE reported bedwetting daily, 31.6% between 1 and 7 times weekly, and 40.4% between 1 and 4 times monthly; 80% of PNE cases had no history of treatment. The prevalence of PNE in patients with a family history, frequency, urgency, urinary incontinence, and recurrent urinary tract infections was significantly higher than in those without these conditions (P<0.001). PNE was significantly correlated with the PSQI total score (sleep quality) (P=0.011). The SES score was lower and the SDS was higher (P<0.001) in the PNE group than in those without PNE. Conclusions In mainland China, the PNE prevalence among young adults was found to be high, and PNE had significant effects on physical and mental health. Risk factors included a family history, daytime voiding symptoms, and lack of treatment.

Objective: To observe the effects of acupuncture plus spinal manipulations on the physical functioning and levels of alkaline phosphatase (ALP), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and osteoprotegerin (OPG) in patients with ankylosing spondylitis (AS). Methods: A total of 128 AS cases were allocated into a control group and an observation group using random number table method, with 64 cases in each group. Patients in both groups took sulfasalazine and meloxicam. Patients in the observation group received additional acupuncture plus spinal manipulations. The efficacy, Bath AS functional index (BASFI), Bath AS disease activity index (BASDAI), and the levels of ALP, ESR, CRP and OPG were compared between the two groups after eight weeks of treatment. Results: After treatment, the symptom scores of traditional Chinese medicine in both groups were decreased (all P<0.05), and these scores in the observation group were significantly lower than in the control group (all P<0.05); the VAS, BASFI and BASDAI scores in both groups were decreased (all P<0.05), and these scores in the observation group were significantly lower than in the control group (all P<0.05); and the ALP, ESR, CRP and OPG levels in both groups were decreased (all P<0.05), and these levels in the observation group were significantly lower than in the control group (all P<0.05). The total efficacy rate was 92.2％ in the observation group, versus 78.1％ in the control group, presenting a statistical significance (P<0.05). Conclusion: Conventional medication combined with acupuncture and spinal manipulations can improve clinical symptoms, accelerate the recovery of physical functioning, and reduce the ALP, ESR, CRP and OPG levels.