1.Clinical features and risk factors for invasive fungal sinusitis after allogeneic hematopoietic stem cell transplantation
Haixia FU ; Jiajia LI ; Yuanyuan ZHANG ; Yuqian SUN ; Xiaodong MO ; Tingting HAN ; Jun KONG ; Meng LYU ; Wei HAN ; Huan CHEN ; Yuhong CHEN ; Fengrong WANG ; Chenhua YAN ; Yao CHEN ; Jingzhi WANG ; Yu WANG ; Lanping XU ; Xiaojun HUANG ; Xiaohui ZHANG
Chinese Journal of Hematology 2024;45(1):22-27
Objective:To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT.Methods:Nineteen patients with IFR after allo-HSCT at Peking University People’s Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) .Results:Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10–59) years. The median IFR onset time was 68 (9–880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P=0.021) , hemorrhagic cystitis after transplantation ( P=0.012) , delayed platelet engraftment ( P=0.008) , and lower transplant mononuclear cell count ( P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P<0.01) . Conclusion:Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.
2.Clinical characteristics and risk factors for death of respiratory syncytial virus infection in adult patients after hematopoietic stem cell transplantation
Yao LI ; Feng ZHANG ; Chang LIU ; Xiaosu ZHAO ; Xiaodong MO ; Fengrong WANG ; Chenhua YAN ; Zhidong WANG ; Jun KONG ; Yuanyuan ZHANG ; Fengmei ZHENG ; Yang LIU ; Leqing CAO ; Daoxing DENG ; Xiaojun HUANG ; Xiaohui ZHANG
Chinese Journal of Hematology 2024;45(10):916-922
Objective:To summarize the clinical features associated with respiratory syncytial virus (RSV) infection in patients following the hematopoietic stem cell transplant (HSCT) and exploring the risk factors for death.Methods:Patients who had RSV infection after undergoing HSCT from October 2023 to January 2024 in the hematology department of Peking University People’s Hospital were enrolled in the study. The clinical characteristics of the participating patients were summarized. The clinical characteristics of the surviving and the dying patients were compared, and the risk factors of death were analyzed by binary logistic regression.Results:Among the 43 RSV-positive HSCT patients, 20 (46.5%) were hypoxemic, six (14.0%) were admitted to the ICU for further treatment, four (9.3%) required tracheal intubation assisted ventilation, and seven patients (16.3%) died. A comparison of the clinical features of the surviving patients and the deceased patients demonstrated that the deceased patients had a lower PLT when infected with RSV [74.5 (8.0-348.0) ×10 9/L vs 15.0 (10.0-62.0) ×10 9/L, P=0.003], a higher incidence of simultaneous bacterial infections (85.7% vs 41.7%, P=0.046), and a higher rate of hematological recurrence (71.4% vs 13.9%, P=0.004). Hematological recurrence ( OR=15.500, 95% CI 2.336-102.848, P=0.005), influenza A viral infection ( OR=14.000, 95% CI 1.064-184.182, P=0.045), and low PLT at the time of RSV infection ( OR=0.945, 95% CI 0.894-0.999, P=0.048) were the factors associated with death following HSCT. Conclusion:Patients infected with RSV after undergoing HSCT have a poor prognosis, and active prevention and treatment of RSV in the autumn and winter requires urgent attention.
3.Dosimetric comparison of anal sphincter and its substructures with different radiotherapy techniques for rectal cancer
Geng LI ; Fei DENG ; Yong-Jun LI ; Da-Li FENG ; Xin LI ; Zhuo KONG ; Ji-Ping WANG ; Min ZOU
Chinese Medical Equipment Journal 2024;45(8):63-67
Objective To compare the dosimetric effects of volume modulated arc therapy(VMAT)and intensity modulated radiation therapy(I M RT)on the anal sphincter(AS)and its sub-structures in neoadjuvant radiotherapy for rectal cancer to facilitate the selection of radiotherapy techniques.Methods Fifty rectal cancer patients receiving neoadjuvant radiotherapy were selected,and 2 types of radiotherapy plans,including coplanar double full-arc VMAT and coplanar seven-field homo-geneous IMRT,were designed based on the CT images of the patients,respectively.Under the premise of ensuring that the irradiated doses to the target area and the major organs at risk reached the standard and met the clinical requirements,AS and its substructures were added as the organs at risk for dosimetric evaluation.The absolute dose parameters and relative dose parameters of AS and its substructures were counted by dose-volume histograms.Statistical analysis was performed using IBM SPSS 22.0 software.Results The VMAT plan had the relative dose parameters V20,V30,and V40 of AS and its substructures lower those of the IMRT plan,the differences were statistically significant(P<0.05),while the differences in V5 and V 10 were not statistically significant(P>0.05).The VMAT plan had the absolute dose parameterDmeanlower while the D2%slightly higher than those of the IMRT plan,the differences were statistically significant(P<0.05).The difference in D98%between the two plans was not statistically significant(P>0.05).Conclusion During rectal cancer radiotherapy VMAT generally behaves better than IMRT in protecting AS and its sub-structures and decreasing injuries of AS and its sub-structures dosimetrically.[Chinese Medical Equipment Journal,2024,45(8):63-67]
4.Effects of paeoniflorin on TLR4/MyD88 pathway in liver of rats with metabolic dysfunction-associated fatty liver disease
Ting ZHANG ; Lingya KONG ; Jun DAI ; Longyi LI ; Zhihong MA
Chinese Journal of Pathophysiology 2024;40(11):2099-2105
AIM:To investigate the effect of paeoniflorin(PF)on TLR4/MyD88 signaling pathway in liver of rats with metabolic dysfunction-associated fatty liver disease.METHODS:SPF grade male SD rats were randomly divid-ed into four groups:normal control(NC)group,model control(MC)group,low-dose paeoniflorin(PL)group,and high-dose paeoniflorin(PH)group.The normal group was given standard diet,and the other three groups were given high-fat diet for 8 weeks.From the fifth week,rats in paeoniflorin groups were given low dose(25 mg·kg-1·d-1)or high dose(50 mg·kg-1·d-1)paeoniflorin for 4 weeks.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC)and triglyceride(TG)were measured by biochemical method.The levels of tumor necrosis factor(TNF)-α was detected by ELISA.Pathological change of the liver was detected with hematoxylin-eosin(HE)staining and oil red O staining,and evaluated semi-quantitatively with the nonalcoholic fatty liver disease activity score(NAS).The expres-sion levels of TLR4,MyD88 and phosphorylated nuclear factor(p-NF)-κB p65 in liver tissues were detected by immuno-histochemistry and Western blot.RESULTS:Compared with the NC group,rats in the MC group showed increased TC,TG,ALT,AST and TNF-α in serum(P<0.05),and more lipid droplets in hepatocytes and inflammatory cell infiltration in the portal area,with higher NAS,TLR4,MyD88 and p-NF-κB p65 proteins in liver tissue(P<0.05).However,pae-oniflorin could reduce TC,TG,ALT,AST and TNF-α in serum(P<0.05),improve histopathological changes of liver,decrease the NAS scoring(P<0.05),and inhibit hepatic TLR4/MyD88/p-NF-κB p65 expressions(P<0.05).CONCLU-SION:Paeoniflorin could improve the lipid metabolism disorder and reduce liver inflammation during MAFLD,and the latter effect might be in part related to the inhibition of TLR4/MyD88 signaling pathway.
5.Extraction and differentiation of mature and immature dendritic cells from Lewis rat bone marrow
Liqiang LI ; Minghao LI ; Liang LI ; Wenbo LI ; Jun ZHANG ; Lingmei KONG
Chinese Journal of Tissue Engineering Research 2024;28(25):4013-4017
BACKGROUND:Dendritic cells exhibit extremely strong antigen phagocytic function in the immature stage,and they can demonstrate great advantages in immune tolerance,cancer immunotherapy,and other aspects.However,due to the extremely low content of immature dendritic cells in living organisms,its clinical and scientific applications are severely limited. OBJECTIVE:To study the extraction and identification of mature and immature dendritic cells from Lewis rat bone marrow. METHODS:Bone marrow precursor cells were isolated from the bone marrow of Lewis rats,and immature dendritic cells were induced by 20 ng/mL of granulocyte colony-stimulating factor and 10 ng/mL of interleukin-4 for 7 days,and then mature dendritic cells were induced by adding 1 μg/mL of lipopolysaccharide to immature dendritic cells for 2 days.The morphology of dendritic cells was observed using inverted fluorescence microscopy.The surface-specific molecules of mature and immature dendritic cells were identified by flow cytometry,and the secretion levels of supernatant interleukin-10,interleukin-12,and interleukin-17A in mature and immature dendritic cells were detected by ELISA.The response of mature and immature dendritic cells to T lymphocyte stimulation was measured by mixed lymphocyte reaction. RESULTS AND CONCLUSION:(1)The dendritic cells showed an obvious protrusion structure under an ordinary inverted fluorescence microscope.(2)Flow cytometry showed low expression of CD40,CD86,and other co-stimulatory molecules in immature dendritic cells.On the contrary,mature dendritic cells highly expressed the above co-stimulatory molecules.(3)The secretion of interleukin-10 and interleukin-17A in immature dendritic cells was much higher than that in mature dendritic cells(P<0.01).Interleukin-12 secretion in immature dendritic cells was much lower than that in mature dendritic cells(P<0.05).(4)Mature dendritic cells stimulated T cells significantly better than immature dendritic cells,and the stimulation ability was stronger when the ratio of mature dendritic cells to T lymphocytes reached 1:10.(5)The results indicate that Lewis rat bone marrow precursor cells can differentiate into dendritic cells and distinguish between mature and immature dendritic cells by flow cytometry identification,related factor detection,and mixed lymphocyte reaction.
6.PDHA1 promotes proliferation,invasion and metastasis of triple-nega-tive breast cancer cells
Jiaqi LI ; Yong SUN ; Le LI ; Yuan LI ; Jun FAN ; Zhihua KONG ; Xiaoyun MAO ; Yong DAI
Chinese Journal of Pathophysiology 2024;40(2):244-254
AIM:One of the important characteristics of the occurrence and development of triple-negative breast cancer(TNBC)is dysregulated cell metabolism.The aim of this study is to investigate the mechanism of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),a key enzyme component in aerobic glycolysis,affecting the proliferation,metastasis and invasion of TNBC.METHODS:(1)The expression levels of PDHA1 in breast cancer tissues and adja-cent tissues were analyzed by UALCAN database,KM-plotter database,Gene MANIA database and TCGA database.The expression of PDHA1 was compared according to tumor pathological stage,subtype classification and breast cancer bio-markers.The function of PDHA1 in TNBC was explored by gene enrichment analysis.(2)Immunohistochemistry assays were used to detect the expression of PDHA1 in human TNBC tissue and adjacent tissue samples.(3)Stable PDHA1 knockout and PDHA1 rescue TNBC MDA-MB-231 cells were constructed.The proliferation of MDA-MB-231 cells was de-tected by colony formation assay and cell counting assay.The regulatory effect of PDHA1 on the invasion and migration of MDA-MB-231 cells was detected by in vitro scratch assay and Transwell migration assay.RESULTS:Database analysis showed that the group with high PDHA1 expression in breast cancer had shorter survival and worse prognosis.In clinical specimens,the expression of PDHA1 in cancer tissues was higher than that in adjacent normal tissues.Knockout of PDHA1 inhibited the proliferation,metastasis,invasion and epithelial-mesenchymal transition of MDA-MB-231 cells.CONCLUSION:PDHA1 is overexpressed in TNBC,and it promotes cell proliferation and facilitates TNBC metastasis through the epithelial-mesenchymal transition pathway.
7.Clinical trial of aripiprazole and risperidone in patients with schizophrenia and metabolic syndrome
Hai-Feng CHEN ; Ling-Jun KONG ; Bo CAO ; Duo-Cong LI
The Chinese Journal of Clinical Pharmacology 2024;40(8):1126-1130
Objective To compare the clinical effect of aripiprazole and risperidone in patients with schizophrenia and metabolic syndrome.Methods A retrospective analysis was performed on the case data of schizophrenia and metabolic syndrome.According to different treatment methods,they were divided into risperidone group(oral risperidone,2 mg once,twice a day)and aripiprazole group(oral aripiprazole,5 mg once,once a day).All were treated for 24 weeks and given lifestyle intervention.The clinical effect,scores of positive and negative symptom scale(PANSS),metabolic syndrome-related indexes[systolic blood pressure(SBP),diastolic blood pressure(DBP),body mass index(BMI),fasting blood glucose(FPG),triglyceride(TG)],cognitive function[MATRICS consensus cognitive battery(MCCB)],levels of serum brain-derived neurotrophic factor(BDNF),tyrosine kinase receptor B(TrkB)and glial cell line-derived neurotrophic factor(GDNF)were compared between the two groups.The adverse drug reactions were statistically analyzed in two groups.Results There were 60 cases in risperidone group and 60 cases in aripiprazole group.The total response rates of aripiprazole group and risperidone group were 91.67%and 76.67%,with significant difference(P<0.05).After treatment,scores of positive symptoms in PANSS in aripiprazole group and risperidone group were(10.04±1.55)and(11.52±1.62)points;negative symptom scores were(12.74±2.38)and(14.38±2.25)points;general psychopathology scores were(16.53±4.39)and(19.76±4.10)points;total scores of PANSS were(39.31±6.25)and(45.66±6.71)points;total scores of MCCB were(43.61±8.50)and(40.55±8.16)points;BMI were(24.05±2.52)and(25.73±2.86)kg·m-2;SBP were(123.61±7.64)and(128.75±8.59)mmHg;FPG were(5.69±0.60)and(6.38±0.62)mmol·L-1;TG levels were(1.76±0.20)and(2.01±0.22)mmol·L-1;levels of serum BDNF were(32.41±5.81)and(28.65±4.87)pg·mL-1;TrkB levels were(43.88±5.92)and(41.73±5.63)ng·mL-1;GDNF levels were(587.47±36.12)and(468.23±35.68)pg·mL-1,the differences between the two groups were all statistically significant(all P<0.05).There was no significant difference in the incidence of adverse drug reactions between aripiprazole group and risperidone group(15.00%vs.6.67%,P>0.05).Conclusion Compared with risperidone,clinical effect of aripiprazole is better in patients with schizophrenia and metabolic syndrome,which has fewer effects on body weight,blood pressure and glycolipid metabolism,and it may improve cognitive function by increasing levels of serum BDNF,TrkB and GDNF.
8.The Implementation, Clinical Progress and Technical Challenges of Implantable Brain-Computer Interface Systems
Wen-Can QIU ; Liang MA ; Hao-Yue GUO ; Jun-Jie YANG ; Xiao-Jian LI
Progress in Biochemistry and Biophysics 2024;51(10):2478-2497
The breakthrough progress of implantable brain-computer interfaces (iBCIs) technology in the field of clinical trials has attracted widespread attention from both academia and industry. The development and advancement of this technology have provided new solutions for the rehabilitation of patients with movement disorders. However, challenges from many aspects make it difficult for iBCIs to further implement and transform technologies. This paper illustrates the key challenges restricting the large-scale development of iBCIs from the perspective of system implementation, then discusses the latest clinical application progress in depth, aiming to provide new ideas for researchers. For the system implementation part, we have elaborated the front-end signal collector, signal processing and decoder, then the effector. The most important part of the front-end module is the neural electrode, which can be divided into two types: piercing and attached. These two types of electrodes are newly classified and described. In the signal processing and decoder section, we have discussed the experimental paradigm together with signal processing and decoder for the first time and believed that the experimental paradigm acts as a learning benchmark for decoders that play a pivotal role in iBCIs systems. In addition, the characteristics and roles of the effectors commonly used in iBCIs systems, including cursors and robotic arms, are analyzed in detail. In the clinical progress section, we have divided the latest clinical progress into two categories: functional rehabilitation and functional replacement from the perspective of the application scenarios of iBCIs. Functional rehabilitation and functional replacement are two different types of application, though the boundary between the two is not absolute. To this end, we have first introduced the corresponding clinical trial progress from the three levels: application field, research team, and clinical timeline, and then conducted an in-depth discussion and analysis of their functional boundaries, in order to provide guidance for future research. Finally, this paper mentions that the key technical challenges in the development of iBCIs technology come from multiple aspects. First of all, from the signal acquisition level, high-throughput and highly bio-compatible neural interface designing is essential to ensure long-term stable signal acquisition. The electrode surface modification method and electrode packaging were discussed. Secondly, in terms of decoding performance, real-time, accurate, and robust algorithms have a decisive impact on improving the reliability of iBCIs systems. The third key technology is from the perspective of practicality, we believe that the signal transmission mode of wireless communication is the trend of the future, but it still needs to overcome challenges such as data transmission rate and battery life. Finally, we believe that issues such as ethics, privacy, and security need to be addressed through legal, policy, and technological innovation. In summary, the development of iBCIs technology requires not only the unremitting efforts of scientific researchers, but also the participation and support of policymakers, medical professionals, technology developers, and all sectors of society. Through interdisciplinary collaboration and innovation, iBCIs technology will achieve wider clinical applications in the future and make important contributions to improving the quality of life of patients.
9.Full-field Anterior Chamber Angle Measurement Based on Optical Reflection Tomography
Bi-Wang LIU ; Jun-Ping ZHONG ; Hai-Na LIN ; Ya-Guang ZENG ; You-Ping YU ; Hong-Yi LI ; Ding-An HAN ; Jin-Ying CHEN
Progress in Biochemistry and Biophysics 2024;51(9):2240-2248
ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error
10.Two new isocoumarins from cave-derived Metarhizium anisopliae NHC-M3-2
Rong-xiang WU ; Jie-lan GUO ; Hua HUANG ; Jing-jing LIAO ; Yi HAO ; Fan-dong KONG ; Li-man ZHOU ; Chao-jun ZHANG
Acta Pharmaceutica Sinica 2024;59(9):2588-2593
Extracting extracts of secondary metabolites from the karst cave fungus

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