OBJECTIVES: To explore the risk factors for hemorrhagic cystitis (HC) in children with β-thalassemia major (TM) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A retrospective analysis was conducted on clinical data of 247 children with TM who underwent allo-HSCT at Shenzhen Children's Hospital from January 2021 to November 2022. The children were divided into an HC group (91 cases) and a non-HC group (156 cases) based on whether HC occurred after operation. Multivariable logistic regression analysis was used to explore the risk factors for HC, and the receiver operating characteristic curve was used to analyze the predictive efficacy of related factors for HC. RESULTS: Among the 247 TM patients who underwent allo-HSCT, the incidence of HC was 36.8% (91/247). Univariate analysis showed age, incompatible blood types between donors and recipients, occurrence of acute graft-versus-host disease (aGVHD), positive urine BK virus deoxyribonucleic acid (BKV-DNA), and ≥2 viral infections were associated with the development of HC after allo-HSCT (P<0.05). Multivariable analysis revealed that incompatible blood types between donors and recipients (OR=3.171, 95%CI: 1.538-6.539), occurrence of aGVHD (OR=2.581, 95%CI: 1.125-5.918), and positive urine BKV-DNA (OR=21.878, 95%CI: 9.633-49.687) were independent risk factors for HC in children with TM who underwent allo-HSCT. The receiver operating characteristic curve analysis showed that positive urine BKV-DNA alone or in combination with two other risk factors (occurrence of aGVHD, incompatible blood types between donors and recipients) had a certain accuracy in predicting the development of HC after allo-HSCT (area under the curve >0.8, P<0.05). CONCLUSIONS Incompatible blood types between donors and recipients, occurrence of aGVHD, and positive urine BKV-DNA are risk factors for HC after allo-HSCT in children with TM. Regular monitoring of urine BKV-DNA has a positive significance for early diagnosis and treatment of HC.
Humans ; Child ; Retrospective Studies ; beta-Thalassemia/therapy* ; Cystitis/epidemiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Risk Factors ; Hemorrhage/etiology* ; Graft vs Host Disease/complications* ; DNA ; Polyomavirus Infections/epidemiology*

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofission-associated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of pan-inhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

Objective To investigate the pathogen distribution,imaging characteristics,and risk factors of pulmonary infection with multi-drug resistant organism (MDRO) in patients with severe craniocerebral injury,and establish and verify the risk prediction model. Methods A total of 230 patients with severe craniocerebral injury complicated with pulmonary infection were collected retrospectively.According to the 7∶3 ratio,they were randomly assigned into a modeling group (161 patients) and a validation group (69 patients).The risk factors of MDRO pulmonary infection were predicted with the data of the modeling group for the establishment of the risk prediction model.The data of the validation group was used to validate the performance of the model. Results Among the 230 patients,68 patients developed MDRO pulmonary infection.The isolated drug-resistant bacteria mainly included multi-drug resistant Acinetobacter baumannii,multi-drug resistant Klebsiella pneumoniae,multi-drug resistant Pseudomonas aeruginosa,and methicillin-resistant Staphylococcus aureus,which accounted for 45.21%,23.29%,16.44%,and 15.07%,respectively.The imaging characteristics included pleural effusion,lung consolidation,and ground-glass shadow,which accounted for 72.06%,63.24%,and 45.59%,respectively.Multivariate Logistic regression analysis showed that the independent risk factors for MDRO pulmonary infection included age ≥60 years (P=0.003),history of diabetes (P=0.021),history of chronic obstructive pulmonary disease (P=0.038),mechanical ventilation ≥7 d (P=0.001),transfer from other hospitals (P=0.008),and coma (P=0.002).A risk scoring model was established with the β value (rounded to the nearest integer) corresponding to each index in the regression equation.Specifically,the β values of age ≥60 years,history of diabetes,history of chronic obstructive pulmonary disease,mechanical ventilation ≥7 d,transfer from other hospitals,and coma were 1,1,1,2,2,and 1,respectively (value ≥4 indicated a high-risk population).The areas under the receiver operating characteristic curve of the modeling group and validation group were 0.845 and 0.809,respectively. Conclusions Multi-drug resistant Acinetobacter baumannii is the most common pathogen of MDRO pulmonary infection in patients with severe craniocerebral injury.Pleural effusion,lung consolidation,and ground-glass shadow were the most common imaging characteristics.The established risk model has high discriminant validity in both the modeling group and the validation group.
Coma ; Craniocerebral Trauma ; Drug Resistance, Multiple, Bacterial ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Middle Aged ; Pleural Effusion ; Pneumonia ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies

ObjectiveTo explore the effect of Qishengwan on ileal flora during its treatment of Alzheimer's disease （AD） under the guidance of the theory of "interior-exterior relationship between heart and small intestine". MethodThe AD model was established by bilateral intraventricular injection of β-amyloid 1-42 （Aβ_1-42）. The rats were then randomly divided into the blank group， sham-operated group， model group， low-， medium-， and high-dose （5.6， 11.2，22.4 g·kg^-1·d^-1） Qishengwan groups， and donepezil （0.46 mg·kg^-1·d^-1） group. After medication for 28 successive days， the spatial memory ability of rats was observed in water maze test， and the levels of Aβ_1-42， nuclear transcription factor-κB （NF-κB）， tumor necrosis factor-α （TNF-α）， and interleukin-6 （IL-6） in the hippocampus were analyzed by enzyme-linked immunosorbent assay （ELISA）. Additionally， the contents of the ileum were collected and subjected to 16SrRNA-sequencing analysis for figuring out the changes in ileal flora. ResultCompared with the blank group and sham-operated group， the model group exhibited significantly reduced stay time in the target quadrant and number of target quadrant and platform crossings （P<0.05， P<0.01） and elevated Aβ_1-42 content in the hippocampus （P<0.01） and central inflammatory factors NF-κB， TNF-α， and IL-6 （P<0.05， P<0.01）. Compared with the model group， Qishengwan at each dose significantly alleviated the impaired spatial memory function （P<0.05， P<0.01）， improved the deposition of Aβ_1-42 in the hippocampus of rats （P<0.05， P<0.01）， and reduced the expression of central nervous system inflammatory factors （P<0.05， P<0.01）， thus exerting a good therapeutic effect on AD rats. The 16SrRNA-sequencing analysis results showed that the structure of the ileal flora in the model group was significantly separated from those in the blank group and sham-operated group. The abundance of Lachnospiraceae NK4A136 group was significantly increased （P<0.01）， while that of Escherichia-Shigella was reduced （P<0.05， P<0.01）. Qishengwan at each dose significantly changed the ileal flora structure and regulated the relative abundance of Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Ruminococcaceae. ConclusionQishengwan has a positive therapeutic effect on AD. It can significantly enhance the memory and cognitive abilities in AD rats， which may be related to its regulation of the structure of rat ileal flora and the relative abundance of Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Ruminococcaceae， the attenuation of the central neuroinflammatory response， and the reduction of central Aβ_1-42 deposition.

AIM: To investigate the correlation between postoperative lens decentration and tilt and visual quality in eyes implanted with aspherical intraocular lens(IOL)by using a new anterior segment swept-source optical coherence tomography(OCT)CASIA2.METHODS: An observational study. A total of 90 eyes of 62 participants who underwent age-related cataract surgery at 1mo were included. Using CASIA2 by an experienced examiner, IOL tilt and decentration were obtained three consecutive times after mydriasis and the vector mean values were calculated. Double-pass optical quality analysis system(OQAS)and wavefront aberration instrument KR-1W were used for the visual quality measurements, including the total high-order aberration(tHOA), spherical aberration(SA), Coma, objective scatter index(OSI), modulation transfer function cut off frequency(MTF cut off)and Strehl ratio(SR)at 4 and 6mm pupil diameter.RESULTS: IOL decentration was positively correlated with SA(r=0.347, P=0.001)and OSI(r=0.343, P=0.002)at 4mm pupil diameter, and it was negatively correlated with MTF cut off(r=-0.244, P=0.032). There was no significant correlation between IOL decentration and tHOA, Coma and SR. IOL tilt was negatively correlated with MTF cut off(r=0.-345, P=0.002)and SR(r=-0.256, P=0.023)at 4mm pupil diameter, but it was not correlated with tHOA, SA, Coma and OSI. There were no significant correlations between the IOL decentration and tilt and tHOA, SA, Coma, MTF cut off and SR at 6mm pupil diameter.CONCLUSION: After aspherical IOL implantation in age-related cataract patients, IOL decentration was weakly correlated with SA at 4mm pupil diameter, while decentration and tilt were not significantly correlated with other higher-order aberrations. The decentration and tilt were weakly correlated with OSI value and MTF cut off value of the visual quality parameters. The results suggest that clinicians should pay more attention to higher-order aberrations and visual quality during precise cataract surgery.

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

Objective: Objective to investigate the health changes of patients with severe trimethyltin chloride (TMT) poisoning in four years. Methods: Six patients with severe TMT poisoning treated in the First Affiliated Hospital of Gannan Medical College in August 2016 were numbered 1, 2, 3, 4, 5 and 6 respectively. The patients were followed up 0.5, 2 and 4 years after poisoning and compared and analyzed. The follow-up contents include: symptom degree, score of simple mental intelligence examination scale (MMSE) and modified Rankin Scale (MRS) , cranial magnetic resonance imaging (MRI) , EEG, etc. Results: The symptoms of dizziness, headache, chest tightness, palpitation, nausea and vomiting decreased gradually in 6 patients. The symptoms of speech disorder and memory decline in No.1, 2 and 3 patients gradually increased, and the scores of MMSE and Mrs gradually decreased; Patients No.4, 5 and 6 had improved speech disorder, but their memory decreased, MMSE and Mrs scores were still flat, and mild cognitive impairment. The brain atrophy of No.1, 2 and 3 patients was aggravated, which showed obvious atrophy of hippocampus, temporal lobe, insular lobe and cerebellum and enlargement of ventricle; There was no significant change in brain atrophy in No.4, 5 and 6 patients. Conclusion: The neurotoxic symptoms in the later stage of severe TMT poisoning are still serious, and the neurotoxic time is long.
Atrophy ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Trimethyltin Compounds

Objective:To study the distribution characteristics of mineral elements in Gastrodia elata samples with different grades and specifications （variants） from diverse producing areas and their classification and identification evidences. Method:Fourteen mineral elements in 31 batches of Gastrodia elata samples of different grades and specifications （variants） from diverse producing areas were determined by atomic absorption spectrophotometry， Mo-Sb colorimetry， and curcumin colorimetry， and then subjected to correlation analysis （CA）， discriminant analysis （DA）， and principal component analysis （PCA）. Result:The content of K， N， and P in G. elata was the highest， enabling them to serve as the nutritional limiting factors affecting its growth. The G. elata samples could be identified by the variation trend of elements （K>N>P>Mg>Ca>Fe>B>Zn>Mn>Cu>Ni>Cr>Pb>Cd）. The comparison of G. elata samples from multiple producing areas showed that G. elata from Zhaotong has the highest P， Fe， and Cd content， that from Lijiang the highest K content， that form Luotian the highest Zn and Cr content， and that from Jinzhai the highest Cu and Pb content. The content of Mg， B， Pb， and Cr in G. elata f. elata was higher than that in G. elata f. glauca. It was found that the content of P， Cu， and Cd in commercially available G. elata products gradually increased with the decrease in the commercial grade， while that of Mg， Fe， B， and Ni mostly decreased. As revealed by CA， Fe was positively correlated with Mg， Cr， and B. The producing areas of G. elata samples could be effectively identified by DA with Cd， Pb， Cr， Cu， B， and Ni as the main variables， and the accuracy reached up to 85.71%. According to the PCA of mineral elements in G. elata f. glauca from Zhaotong， Yunnan Province， Fe， Cr， Mg， Cd， P， Mn， B， Pb， and Cu exerted a greater influence on G. elata. Conclusion:The determination of mineral elements in G. elata samples contributes to identifying their authenticity and origin due to the easy operation， accurate results， and good stability.

Objective: To evaluate the efficacy and safety of fibrinolysis strategy in patients with acute ST-segment elevation myocardial infarction (STEMI) during the COVID-19 epidemic, and to provide reference value for optimization of fibrinolytic process on the premise of prevention and control of COVID-19 transmission, including self-protection of medical staff. Methods: The efficacy and safety of fibrinolysis were retrospectively analyzed in 7 patients with acute STEM, who hospitalized from February 29, 2020 to April 3, 2020 in the Department of Cardiology, Wuhan Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. To optimize the fibrinolytic process on the premise of prevention and control of COVID-19 transmission, including self-protection of medical staff, a full-time medical team in charge of fibrinolysis under third-grade protection was established. The acute STEMI patients were treated immediately in a fixed and isolated area in emergency department before receiving green channel fibrinolysis. Blood samples for complete blood count, COVID-19 antibody test and nasopharyngeal swab samples for COVID-19 nucleic acid test were made before fibrinolysis, while the chest CT examination was accomplished after fibrinolysis. By comparing differences of time from the first electrocardiogram (ECG) to fibrinolysis before and after the improvement of fibrinolytic process, the effect of optimization of the fibrinolytic process was evaluated. Results: In the present study, seven patients with acute STEMI received fibrinolysis therapy, 6 of them achieved reperfusion and no bleeding was observed in all of the patients. Five out of the 7 patients were hospitalized after fibrinolysis, and the hospitalization days were 19.6 days on average. By following up to April 14, 2020, none of the 7 patients died. The first 2 patients were treated according to the routine medical procedure and the time from the first ECG to fibrinolysis were 201 and 106 minutes, respectively. After the optimization of the fibrinolytic process, the time from the first ECG to fibrinolysis of the last 5 patients were 42, 46, 51, 43 and 54 minutes, respectively，which was significantly shorter than that before optimization. Conclusions: During the COVID-19 epidemic, fibrinolysis in patients with acute STEMI is safe, effective and easy to implement. Therefore, it is recommended as the top priority for the patients with acute STEMI with indications for fibrinolysis. On the premise of prevention and control of COVID-19 transmission, including self-protection of medical staff, the duration of myocardial ischemia can be shortened by optimization of the fibrinolytic process.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/epidemiology* ; Epidemics ; Fibrinolytic Agents/therapeutic use* ; Humans ; Pandemics ; Pneumonia, Viral/epidemiology* ; Retrospective Studies ; SARS-CoV-2 ; ST Elevation Myocardial Infarction/drug therapy* ; Thrombolytic Therapy ; Time Factors ; Treatment Outcome

Objective: To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC). Methods: DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 Results: We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders. Conclusion In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.
Adult ; Aged ; Cancer Vaccines/therapeutic use* ; China ; Dendritic Cells/immunology* ; Female ; Humans ; Immunotherapy/methods* ; Injections, Intradermal ; Male ; Middle Aged ; Nasopharyngeal Carcinoma/therapy* ; Nasopharyngeal Neoplasms/therapy* ; T-Lymphocytes, Cytotoxic/immunology* ; Viral Matrix Proteins/therapeutic use* ; Young Adult