1.Survival time and influencing factors analysis of clinically diagnosed sporadic Creutzfeldt-Jakob disease patients in China from 2020 to 2022
Weiwei ZHANG ; Donglin LIANG ; Donghua ZHOU ; Yuan WANG ; Kang XIAO ; Wei ZHOU ; Xiaoping DONG ; Qi SHI
Acta Universitatis Medicinalis Anhui 2024;59(10):1842-1848
Objective To investigate the survival time of patients diagnosed with sporadic Creutzfeldt-Jakob disease in China between 2020 and 2022 and explore the associated factors influencing survival.Methods A retrospective analysis was conducted on clinically diagnosed cases with complete information on sporadic Creutzfeldt-Jakob dis-ease diagnosed by the China Creutzfeldt-Jakob disease surveillance network from 2020 to 2022,baseline information of patients was obtained from the case files,telephone follow-up was used to obtain the treatment and survival status of the patients after the diagnosis,life-table method was used for estimating the survival rate,Kaplan-Meier method was used for calculating the median survival time and the 95%CI,Cox regression model was used for univariate and multivariate analyses were used to screen for factors influencing survival time.Results The median survival time of the 300 patients was 5 months(95%CI:4.165-5.835).Univariate analysis revealed that factors such as age at onset,regional distribution,presence of corticobasal or extrapyramidal symptoms as initial manifestations,number of initial symptoms,presence of corticobasal or extrapyramidal functional abnormalities,number of major clinical manifestations,presence of typical electroencephalogram findings,and use of nasal feeding during the course of the disease were potential factors influencing survival time(P<0.1).Multivariate analysis showed that the risk of death in patients with onset age>65 years was 1.350 times higher than in patients with onset age ≤65 years(P=0.021,95.0%CI:1.046-1.742).Patients without pyramidal or extrapyramidal dysfunction had a 0.674-fold lower risk of death compared to those with these symptoms(P=0.020,95.0%CI:0.483-0.939).Patients who did not receive nasal feeding had a 1.817-fold higher risk of death compared to those who did(P<0.001,95.0%CI:1.406-2.349).Conclusion Age at onset,the presence of pyramidal or extrapyramidal functional abnormalities,and the use of nasal feeding during the disease course are factors influencing the survival time of pa-tients clinically diagnosed with sCJD.
2.Effect of differences in health care situations on the survival of patients with sporadic Creutzfeldt-Jakob disease
Weiwei ZHANG ; Donghua ZHOU ; Yuan WANG ; Kang XIAO ; Donglin LIANG ; Wei ZHOU ; Xiaoping DONG ; Qi SHI
Chinese Journal of Experimental and Clinical Virology 2024;38(1):37-42
Objective:To understand the medical care of patients with sporadic Creutzfeldt-Jakob disease in China and its relationship with survival time.Methods:A retrospective analysis was performed on data of 150 patients with sporadic Creutzfeldt-Jakob disease diagnosed by China′s Creutzfeldt-Jakob Disease Surveillance Network during the period of January 1, 2021 to December 31, 2022 in this study, and telephone follow-up with family members was used to obtain information of the patients′ care, treatment, and survival after diagnosis. Survival was estimated by life table method, median survival time and 95% confidence interval ( CI) were calculated by Kaplan-Meier method, log-rank method was used to compare the difference in survival time between different groups, and multifactorial analysis was performed by COX proportional risk regression model regarding the influencing factors on patients′ survival time. Results:The median survival time of 150 patients with sporadic Creutzfeldt-Jakob disease was 6 months, and the cumulative lifetime survival rates at 2, 6, 12, and 18 months were 62%, 39%, 22%, and 9%, respectively. The result of univariate analysis showed that the differences in survival time between groups with the presence or absence of cortical blindness in the first symptom, the presence or absence of respiratory support (oxygen therapy), the presence or absence of adjunctive medication, and the presence or absence of tube feeding (nasogastric) were meaningful ( P<0.1). Multifactorial COX regression analysis showed that the risk of death in patients without adjuvant medication was 1.429 times higher than that in patients with adjuvant medication (95.0% CI: 1.014-2.014), and the risk of death in patients without tube feeding (nasal feeding) was 1.479 times higher than that in patients with tube feeding (nasal feeding) (95% CI: 1.052-2.081). Conclusions:Whether or not adjuvant medication is administered and whether or not tube feeding (nasogastric) is used are factors that affect survival time in patients with sporadic Creutzfeldt-Jakob disease, and the administration of appropriate adjuvant medication and tube feeding (nasogastric) may contribute to prolonging survival time in patients with sporadic Creutzfeldt-Jakob disease.
3.Preliminary investigation of microarray-based analysis of DDX5 affecting head and neck squamous cell car-cinoma
Guoqi LIU ; Chunxia LIU ; Jingjing WANG ; Jinhua ZUO ; Fang WANG ; Jiaojiao SONG ; Donglin YU ; Xian-Grui MA ; Wenlong WANG
Journal of Practical Stomatology 2024;40(6):810-816
Objective:To investigate the expression and role of DEAD-box RNA helicases 5(DDX5 helicases)in head and neck squamous carcinoma(HNSCC).Methods:Tissue microarray microarray was used to assess relevant mRNA expression profile data,and R software was used to screen differential mRNAs(DEGs).The expression level of DDX5 was predicted using GEPIA 2,TCGA databases,and detected by immunohistochemistry,western blot and RT-qPCR in the HNSCC tissue and cell lines.Based on high-throughput sequencing data of DECs,differentially expressed miRNAs(DEMIs)relevant DDX5 competitive endogenous RNA network(ceRNA)was constructed.The software cytoscape was used to visualize the ceRNA network map and further screen the regulatory ax-is.Results:The results of microarray screening revealed that DDX5 expression in HNSCC was upregulated.Immunohistochemistry ver-ified that DDX5 was stronger expressed in the nuclei of squamous carcinoma cells.qPCR results suggested that significant expression of DDX5 mRNA at the tissue and cellular levels(P<0.05).Western blot results showed high expression of DDX5 protein in the tissues.The ceRNA network was constructed,from which the relevant HNSCC axis circRNA-039626-miR-222-5p-DDX5 was identified.Con-clusion:DDX5 is highly expressed in HNSCC,and the circRNA-039626-miR-222-5p-DDX5 axis may be a potential regulatory axis for the development of HNSCC.
4.Effect of TACE with drug-loaded microspheres versus with iodinated oil emulsion on liver fibrosis
Daqian HAN ; Hao LI ; Manzhou WANG ; Chao LIANG ; Jiacheng WANG ; Wenze XU ; Yangyang NIU ; Donglin KUANG ; Jianzhuang REN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2024;30(10):738-743
Objective:To compare the effects of drug-loaded microsphere TACE (D-TACE) and iodinated oil emulsion TACE (cTACE) on liver fibrosis in the treatment of advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 113 patients with HCC treated with D-TACE or cTACE at the First Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were retrospectively analyzed, including 96 males and 17 females, aged (56.8±9.8) years old. According to treatment protocol, patients were divided into two groups: the D-TACE group ( n=57) and the cTACE group ( n=56). Liver fibrosis panel, fibrosis index (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared between the groups at four timepoints: pre-treatment, one month after the first TACE, one month after the second TACE, and 12 months after the first TACE. Follow-ups were conducted through outpatient visits or telephone reviews to assess patient survivals. Data including the progression-free survival (PFS) and number of TACE sessions were compared between the two groups. Results:The D-TACE group received 2.84±1.12 sessions of treatment during the observation period, compared to 4.05±1.44 sessions of cTACE group ( t=4.94, P<0.001). The median PFS in D-TACE and cTACE groups were 10.0 and 5.0 months, respectively ( P<0.001). At one month after the second TACE and at 12 months after the first TACE, patients in cTACE group had a higher serum levels of fibrosis markers including hyaluronic acid, type IV collagen, type III procollagen N peptide and laminin than those in D-TACE group (all P<0.05). At the same timepoints, patients in cTACE group also had higher APRI, FIB-4 and LSM than those in D-TACE group (all P<0.05). Conclusion:Compared to cTACE, patients in D-TACE group received fewer sessions of treatment during the first year after initial TACE, and the degree of liver fibrosis was also lower in D-TACE group.
5.Effects of Unicompartmental and Total Knee Arthroplasty on the Biomechanical Characteristics of Patients with Knee Osteoarthritis During Stair Ascent and Descent
Chuanbao CAO ; Donglin SHI ; Guangwei CHAI ; Xin WANG ; Yanhong ZHANG ; Gang MA ; Shifang YAN
Journal of Medical Biomechanics 2024;39(4):670-676
Objective To explore the clinical efficacy of single unicompartmental knee arthroplasty(UKA)and total knee arthroplasty(TKA)for the treatment of knee osteoarthritis.Methods A total of 21 patients who underwent TKA and 15 who underwent UKA were randomly recruited.Biomechanical tests were performed before surgery and at 6th and 12th month after surgery.A Vicon infrared motion capture system and Kistler three-dimensional force plate were used to simultaneously acquire the kinematic and kinetic data of the patients during stair walking.Results During stair ascent,the peak knee flexion moment in the TKA group was significantly lower than that in the UKA group;the time to peak knee flexion/adduction moment,knee flexion moment impulse,and load rate of the peak knee adduction moment in the UKA group were significantly lower than those in the UKA group.During stair descent,the peak knee extension power in the UKA group was significantly lower before surgery and at 6th month after surgery;the load rate of the peak vertical ground reaction force was significantly higher before surgery and the peak knee extension moment was significantly greater at 6th month after surgery;at 12th month after surgery,there was no significant difference in the biomechanical characteristics during stair ascent and descent.Conclusions The TKA and UKA groups showed similar knee joint function after surgery;however,compared with the UKA group,the TKA group may adopt a different lower extremity biomechanical pattern.The UKA group showed better quadriceps control after surgery and improved postural control during stair descent,whereas the TKA group adopted a conservative stair gait strategy to reduce the knee load.Compared with the peak moment,the time to peak moment and load rate of the peak moment were more sensitive indicators for determining the difference in the knee load.
6.Cisplatin promotes TNF-α autocrine to trigger RIP1/RIP3/MLKL-dependent necroptosis of human head and neck squamous cell carcinoma cells
Hongxiao WANG ; Detao TAO ; Junjie MA ; Donglin ZHANG ; Zuoyuan SHEN ; Chao DENG ; Jingping ZHOU
Journal of Southern Medical University 2024;44(10):1947-1954
Objective To investigate whether cisplatin induces tumor necrosis factor-α(TNF-α)secretion in human head and neck squamous cell carcinoma(HNSCC)cells to trigger RIP1/RIP3/MLKL-dependent necroptosis of the cells.Methods HNSCC cell lines HN4 and SCC4 treated with cisplatin(CDDP)or the combined treatment with CDDP and z-VAD-fmk(a caspase inhibitor)or Nec-1(a necroptosis inhibitor)for 24 h were examined for changes in cell viability using CCK8 assay and expressions of caspase-8 and necroptosis pathway proteins(RIP1/RIP3/MLKL)using Western blotting.The changes in migration of the cells were assessed with cell scratch assay,and the expressions of epithelial-mesenchymal transition(EMT)marker proteins N-cadherin,vimentin,and E-cadherin as well as the expressions of NF-κB(p65)and TNF-α were detected with Western blotting.Results The IC50 of cisplatin was 10 μg/mL in HN4 cells and 15 μg/mL in SCC4 cells.Cisplatin treatment significantly decreased the expressions of caspase-8,N-cadherin and vimentin and increased the expressions of E-cadherin,the necroptosis pathway proteins(RIP1/RIP3/MLKL),TNF-α,and NF-κB(p65),and these changes were obviously inhibited by treatment with Nec-1.Cisplatin stimulation also significantly lowered migration of the cells,and this inhibitory effect was strongly attenuated by Nec-1 treatment.Conclusion Cisplatin activates nuclear factor-κB signaling in HNSCCs to promote TNF-α autocrine and induce RIP1/RIP3/MLKL-dependent necroptosis,thus leading to inhibition of cell proliferation.
7.Cisplatin promotes TNF-α autocrine to trigger RIP1/RIP3/MLKL-dependent necroptosis of human head and neck squamous cell carcinoma cells
Hongxiao WANG ; Detao TAO ; Junjie MA ; Donglin ZHANG ; Zuoyuan SHEN ; Chao DENG ; Jingping ZHOU
Journal of Southern Medical University 2024;44(10):1947-1954
Objective To investigate whether cisplatin induces tumor necrosis factor-α(TNF-α)secretion in human head and neck squamous cell carcinoma(HNSCC)cells to trigger RIP1/RIP3/MLKL-dependent necroptosis of the cells.Methods HNSCC cell lines HN4 and SCC4 treated with cisplatin(CDDP)or the combined treatment with CDDP and z-VAD-fmk(a caspase inhibitor)or Nec-1(a necroptosis inhibitor)for 24 h were examined for changes in cell viability using CCK8 assay and expressions of caspase-8 and necroptosis pathway proteins(RIP1/RIP3/MLKL)using Western blotting.The changes in migration of the cells were assessed with cell scratch assay,and the expressions of epithelial-mesenchymal transition(EMT)marker proteins N-cadherin,vimentin,and E-cadherin as well as the expressions of NF-κB(p65)and TNF-α were detected with Western blotting.Results The IC50 of cisplatin was 10 μg/mL in HN4 cells and 15 μg/mL in SCC4 cells.Cisplatin treatment significantly decreased the expressions of caspase-8,N-cadherin and vimentin and increased the expressions of E-cadherin,the necroptosis pathway proteins(RIP1/RIP3/MLKL),TNF-α,and NF-κB(p65),and these changes were obviously inhibited by treatment with Nec-1.Cisplatin stimulation also significantly lowered migration of the cells,and this inhibitory effect was strongly attenuated by Nec-1 treatment.Conclusion Cisplatin activates nuclear factor-κB signaling in HNSCCs to promote TNF-α autocrine and induce RIP1/RIP3/MLKL-dependent necroptosis,thus leading to inhibition of cell proliferation.
8.Clinical analysis of 14 patients aged ≤ 50 years with high-risk multiple myeloma treated with allogeneic hematopoietic stem cell transplantation
Pan PAN ; Jiali WANG ; Weihua ZHAI ; Qiaoling MA ; Donglin YANG ; Sizhou FENG ; Mingzhe HAN ; Aiming PANG ; Erlie JIANG
Chinese Journal of Hematology 2024;45(1):28-34
Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in young patients with high-risk multiple myeloma (HRMM) and analyzed the factors affecting patient prognosis.Methods:In this retrospective study, we analyzed the clinical data of 14 patients with HRMM with cytogenetic abnormalities or high-risk biological factors who underwent allo-HSCT at the Hematopoietic Stem Cell Transplantation Center of the Institute of Hematology & Blood Diseases Hospital between November 2016 and November 2022.Results:There were seven males and seven females included in the study, with a median age of 39.5 (31-50) years at the time of allo-HSCT. The median number of treatment lines before transplantation was 2 (1-6) . Before allo-HSCT, 42.9% (6/14) of the patients did not achieve complete remission, while 35.7% (5/14) of the patients achieved measurable residual disease positivity. After transplantation, all patients were evaluated for their treatment response, and the overall response rate was 100% (14/14) . All 14 patients successfully underwent allo-HSCT, with median engraftment times for neutrophils and platelets of 11 (10-14) days and 13 (9-103) days, respectively. Acute grade Ⅱ-Ⅳ graft-versus-host disease (GVHD) occurred in five patients (35.7%) , and two patients (14.3%) developed moderate-to-severe chronic GVHD. The median follow-up time after allo-HSCT was 18.93 (4.10-72.53) months, with an expected 2-year transplant-related mortality rate of 7.1% (95% CI 0%-21.1%) and an expected 2-year overall survival rate of 92.9% (95% CI 80.3%–100.0%) . Moreover, the expected 1-year and 2-year progression-free survival rates were 92.9% (95% CI 80.3%-100.0%) and 66.0% (95% CI 39.4%-100.0%) , respectively, and the 2-year cumulative incidence of relapse was 28.9% (95% CI 0%-56.7%) . Upfront allo-HSCT following complete remission after induced therapy and the presence of chronic GVHD might be favorable prognostic factors. Conclusion:allo-HSCT is an effective treatment for improving the prognosis of young patients with HRMM.
9.Analysis of the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome with blastomycosis and survival comparison of different subtypes after the WHO 2022 reclassification
Hui WANG ; Runzhi MA ; Aiming PANG ; Donglin YANG ; Xin CHEN ; Rongli ZHANG ; Jialin WEI ; Qiaoling MA ; Weihua ZHAI ; Yi HE ; Erlie JIANG ; Mingzhe HAN ; Sizhou FENG
Chinese Journal of Hematology 2024;45(5):445-452
Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022.Methods:A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed.Results:① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype ( P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points ( P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ ( P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% –80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively ( P=0.690) . Conclusion:Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient’s OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.
10.Sleep disorders and cerebellar regulation
Tong WANG ; Donglin ZHU ; Jingping SHI
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(10):943-948
As cerebellum is involved in sleep regulation, cerebellar dysfunction can lead to sleep disorders, and changes in cerebellar structure and function have also been observed in some patients with sleep disorders. However, the exact mechanism of cerebellum regulation of sleep is still unified. This review summarized the anatomical basis of cerebellar neuronal activity changes with sleep-wake cycle, the changes of cerebellar and brain connection circuits during sleep-wake cycle, the abnormal behaviors caused by cerebellar function/structure disorders, and the abnormal changes of cerebellar structure in patients with different sleep disorders. It is proposed that cerebellar is involved in regulating sleep, and there are different forms of sleep disorders in patients with cerebellar dysfunction. The structural and functional integrity of cerebellum are also affected by sleep, suggesting that there may be a causal relationship between cerebellar structural and functional abnormalities and sleep disorders. Based on the high plasticity of cerebellar neurons, the electrophysiological mechanisms of cerebellar involvement in sleep may be further explored by regulating the electrical activity of cerebellar neurons in the future, so as to verify the possibility of improving sleep disorders through cerebellar regulation.


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