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1.
Int J Gen Med ; 17: 2151-2161, 2024.
Article in English | MEDLINE | ID: mdl-38766597

ABSTRACT

Background: Previous studies have confirmed that high apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio was associated with increased mortality from heart failure (HF). Furthermore, the association of plasma apoB/apoA1 ratio with clinical characteristics and adverse cardiac remodeling is still limited in chronic HF with mildly reduced ejection fraction (HFmrEF) elderly patients. Therefore, this study investigated the association of apoB/apoA1 ratio with clinical characteristics and adverse cardiac remodeling in chronic HFmrEF elderly patients. Methods: A total of 587 Chinese elderly (≥65 years) with coronary heart disease (CHD), HFmrEF (EF 40-50%) and related blood biochemical data were collected retrospectively. The cross-sectional data of echocardiographic and blood parameters were compared between binary apoB/apoA1 groups. Results: In the elderly CHD patients with chronic HFmrEF, the univariate correlation analysis showed that apoB/apoA1 was correlated with younger age, increased prevalence of type 2 diabetes, erythrocytes, platelet/lymphocyte ratio (PLR), D-dimer, fibrinogen, high sensitivity C-reactive protein and uric acid, and adverse cardiac remodeling (All P < 0.05). However, multivariate logistic binary regression analysis found that high apoB/apoA1 ratio (≥0.62) was independently correlated with younger age, increased erythrocytes, PLR, D-dimer and uric acid, and adverse cardiac remodeling (All P < 0.05). Conclusion: In this retrospective study, the high apoB/apoA1 ratio is found to be associated with younger age, increased erythrocytes, PLR, D-dimer and uric acid, and adverse cardiac remodeling in Chinese CHD elderly with chronic HFmrEF.

2.
Target Oncol ; 19(3): 383-400, 2024 May.
Article in English | MEDLINE | ID: mdl-38643457

ABSTRACT

BACKGROUND: The clinical and genetic characteristics, as well as treatment outcomes, of diffuse large B-cell lymphoma (DLBCL) patients with different MYD88 and CD79B mutation status merit further investigation. OBJECTIVE: This study aims to investigate the distinctions in clinical manifestations, genetic characteristics, and treatment outcomes among MYD88-CD79Bco-mut, MYD88/CD79Bsingle-mut, and MYD88-CD79Bco-wt DLBCL patients. PATIENTS AND METHODS: Clinical and genetic characteristics, along with treatment outcomes among 2696 DLBCL patients bearing MYD88-CD79Bco-mut, MYD88/CD79Bsingle-mut, and MYD88-CD79Bco-wt treated with R-CHOP/R-CHOP-like regimens from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and six external cohorts were analyzed. Potential molecular mechanisms were investigated through Gene Set Enrichment Analysis and xCell methodology. RESULTS: In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable progression-free survival (PFS) and overall survival (OS) compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt. However, in the non-MCD subtype, patients with MYD88-CD79Bco-mut exhibited significantly inferior OS than MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while there was no significant OS difference between MYD88/CD79Bsingle-mut and MYD88-CD79Bco-wt (median OS: 68.8 [95% CI 22-NA] vs NA [95% CI 112-NA] vs 177.7 [95% CI 159-NA] months; MYD88-CD79Bco-mut vs MYD88/CD79Bsingle-mut: p = 0.02; MYD88-CD79Bco-mut vs MYD88-CD79Bco-wt: p = 0.03; MYD88/CD79Bsingle-mut vs MYD88-CD79Bco-wt: p = 0.33). Regarding patients with MYD88-CD79Bco-mut, there was no significant difference in PFS and OS between the MCD and non-MCD subtypes. Within the MYD88-CD79Bco-mut group, patients with PIM1mut had better PFS than PIM1wt (median PFS: 8.34 [95% CI 5.56-NA] vs 43.8 [95% CI 26.4-NA] months; p = 0.02). Possible mechanisms contributing to the superior PFS of PIM1mut patients may include activated lymphocyte-mediated immunity and interferon response, a higher proportion of natural killer T cells and plasmacytoid dendritic cells, as well as suppressed angiogenesis and epithelial-mesenchymal transition, along with lower fibroblast and stromal score. CONCLUSIONS: In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable PFS and OS compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while in the non-MCD subtype, they exhibited significantly inferior OS. There was no significant disparity in PFS and OS of MYD88-CD79Bco-mut between the MCD and non-MCD subtypes. The presence of PIM1mut within the MYD88-CD79Bco-mut group correlated with better PFS, which may result from an intricate interplay of immune processes and tumor microenvironment alterations.


Subject(s)
CD79 Antigens , Lymphoma, Large B-Cell, Diffuse , Mutation , Myeloid Differentiation Factor 88 , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Myeloid Differentiation Factor 88/genetics , CD79 Antigens/genetics , Prognosis , Male , Female , Treatment Outcome , Middle Aged , Aged , Adult
3.
J Org Chem ; 89(6): 3907-3911, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38427963

ABSTRACT

A catalytic enantioselective synthesis of bicalutamide derivatives with promising potentials in prostate cancer treatment has been disclosed. The key intermediates, α-hydroxy-ß-keto esters, were efficiently constructed through cinchoninium-mediated asymmetric oxohydroxylation of easily accessible alkenes with potassium permanganate. Good yields and high levels of asymmetric induction are achieved. This method provides a new synthetic route to bicalutamide analogues with high structural diversity, which will beneficially support subsequent structure-activity relationship studies and boost prostate cancer drug development.


Subject(s)
Anilides , Nitriles , Prostatic Neoplasms , Tosyl Compounds , Male , Humans , Molecular Structure , Stereoisomerism , Structure-Activity Relationship
4.
BMC Med Educ ; 24(1): 314, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38509547

ABSTRACT

BACKGROUND: Colleges and universities face an increased risk of public health emergencies. Among them, medical colleges and universities deserve more attention as they serve as the play a fundamental role in providing public health emergency services and in cultivating medical professionals. Effectively managing infectious disease prevention and control, as well as responding to public health emergencies in medical colleges and universities, is of great importance for enhancing the capacity of social emergency governance and improving the completeness of the public health system. This study aims to understand the management of public health emergencies in medical colleges in a city in southwest China, explore the factors associated with medical college students' evaluations, and provide recommendations for emergency management mechanisms in colleges and universities. METHODS: In total, 781 medical college students were selected through stratified random sampling and surveyed using a questionnaire. The main factors affecting students' evaluation of emergency management were analyzed using multiple linear regression and structural equation modeling. RESULTS: The overall emergency management situation in medical colleges was relatively complete, with satisfactory results. Medical college students' satisfaction with the timeliness of prevention measures was the highest, while the publicity and education were the lowest. Multiple linear regression analysis showed that grades, emergency education, -simulation training, -information reporting, and dynamic adjustment measures were associated with the evaluation of emergency management by medical students. CONCLUSIONS: Although the evaluation of emergency management in medical colleges was generally positive, certain limitations still existed. To improve the development of the public health system, colleges and universities should constantly reform and innovate emergency management mechanisms according to the important links in the prevention and control processes.


Subject(s)
Students, Medical , Humans , Public Health , Cross-Sectional Studies , Emergencies , Universities , China
5.
BMC Cancer ; 24(1): 204, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38350902

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is an aggressive tumor of the gastrointestinal tract, which is a major public health concern worldwide. Despite numerous studies, the precise mechanism of metastasis behind its progression remains elusive. As a member of the containing olfactomedin domains protein family, olfactomedin 2 (OLFM2) may play a role in tumor metastasis. It is highly expressed in colorectal cancer, and its role in the metastasis of CRC is still unclear. As such, this study seeks to explore the function of OLFM2 on CRC metastasis and its potential mechanisms. METHODS: Real-time fluorescence quantitative PCR and western blotting were used to study the expression of OLFM2 in human CRC and adjacent normal tissues. Knockdown and overexpression OLFM2 cell lines were constructed using siRNA and overexpression plasmids to explore the role of OLFM2 in the migration and invasion of CRC through transwell, and wound healing experiments. Finally, the expression of epithelial-mesenchymal transition (EMT) -related proteins and TGF-ß/Smad signaling pathway-related proteins was investigated using western blotting. RESULTS: In this study, we observed an elevation of OLFM2 expression levels in CRC tissues. To investigate the function of OLFM2, we overexpressed and knocked down OLFM2. We discovered that OLFM2 knockdown inhibited migration and invasion of colon cancer cells. Furthermore, E-cadherin expression increased while N-cadherin and Vimentin expression were opposite. It is no surprise that overexpressing OLFM2 had the opposite effects. We also identified that OLFM2 knockdown resulted in reduced TGF-ßR1 and downstream molecules p-Smad2 and p-Smad3, which are related to the TGF-ß / Smad pathway. In contrast, overexpressing OLFM2 significantly boosted their expression levels. CONCLUSION: The protein OLFM2 has been identified as a crucial determinant in the progression of CRC. Its mechanism of action involves the facilitation of EMT through the TGF-ß/Smad signaling pathway. Given its pivotal role in CRC, OLFM2 has emerged as a promising diagnostic and therapeutic target for the disease. These results indicate the potential of OLFM2 as a valuable biomarker for CRC diagnosis and treatment and highlight the need for further research exploring its clinical significance.


Subject(s)
Colorectal Neoplasms , Humans , Cell Line, Tumor , Cell Movement/genetics , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Signal Transduction , Smad Proteins/metabolism , Transforming Growth Factor beta/metabolism
6.
Medicine (Baltimore) ; 103(8): e37249, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38394530

ABSTRACT

BACKGROUND: Intestinal malrotation is an infrequent congenital anomaly primarily observed in neonates, and adult-onset cases are exceedingly rare. Studies on adult congenital intestinal malrotation are limited. METHODS: A case with congenital intestinal malrotation is reported in our study. The clinical data were collected and the treatment process and effect were evaluated. RESULTS: A 45-year-old female who had been experiencing vomiting for over 40 years was admitted to our hospital. According to the result of CT scan, intestinal volvulus accompanied by bowel obstruction was suspected. Then laparoscopic examination was applied to the patient and was ultimately diagnosed with adult congenital intestinal malrotation. We performed Ladd's procedure combined with gastrojejunostomy and Braun anastomosis. The patient recovered well and was successfully discharged from the hospital on the 13th day after surgery. After a 6-month follow-up, the symptom of vomiting was significantly alleviated and body weight was gained for 10 kg. She was very satisfied with the treatment. CONCLUSION: Adult congenital intestinal malrotation is a rare disease that is often misdiagnosed owing to nonspecific clinical manifestations. Therefore, awareness about this condition should be enhanced. Surgery remains the cornerstone of treatment for this disease. Combining gastrojejunostomy and Braun anastomosis with the traditional Ladd procedure can optimize surgical outcomes.


Subject(s)
Digestive System Abnormalities , Gastric Bypass , Intestinal Obstruction , Intestinal Volvulus , Infant, Newborn , Adult , Female , Humans , Middle Aged , Intestinal Volvulus/diagnosis , Intestinal Volvulus/surgery , Intestinal Volvulus/complications , Intestines/surgery , Intestinal Obstruction/surgery , Intestinal Obstruction/complications , Gastric Bypass/adverse effects , Vomiting/complications
7.
BMC Infect Dis ; 24(1): 76, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38212685

ABSTRACT

BACKGROUND: Brucellosis poses a significant public health concern. This study explores the spatial and temporal dynamic evolution of human brucellosis in China and analyses the spatial heterogeneity of the influencing factors related to the incidence of human brucellosis at the provincial level. METHODS: The Join-point model, centre of gravity migration model and spatial autocorrelation analysis were employed to evaluate potential changes in the spatial and temporal distribution of human brucellosis in mainland China from 2005 to 2021. Ordinary Least Squares (OLS), Geographically Weighted Regression (GWR), and Multi-scale Geographically Weighted Regression (MGWR) models were constructed to analyze the spatial and temporal correlation between the incidence rate of human brucellosis and meteorological and social factors. RESULTS: From 2005 to 2021, human brucellosis in China showed a consistent upward trend. The incidence rate rose more rapidly in South, Central, and Southwest China, leading to a shift in the center of gravity from the North to the Southwest, as illustrated in the migration trajectory diagram. Strong spatial aggregation was observed. The MGWR model outperformed others. Spatio-temporal plots indicated that lower mean annual temperatures and increased beef, mutton, and milk production significantly correlated with higher brucellosis incidence. Cities like Guangxi and Guangdong were more affected by low temperatures, while Xinjiang and Tibet were influenced more by beef and milk production. Inner Mongolia and Heilongjiang were more affected by mutton production. Importantly, an increase in regional GDP and health expenditure exerted a notable protective effect against human brucellosis incidence. CONCLUSIONS: Human brucellosis remains a pervasive challenge. Meteorological and social factors significantly influence its incidence in a spatiotemporally specific manner. Tailored prevention strategies should be region-specific, providing valuable insights for effective brucellosis control measures.


Subject(s)
Brucellosis , Animals , Cattle , Humans , China/epidemiology , Spatial Analysis , Brucellosis/epidemiology , Spatial Regression , Cities , Incidence , Spatio-Temporal Analysis
8.
PLoS Pathog ; 20(1): e1011967, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38271479

ABSTRACT

Given the serious neurological complications and deaths associated with enterovirus 71 (EV71) infection, there is an urgent need to develop effective antivirals against this viral infection. In this study, we demonstrated that two Cathelicidin-derived peptides, LL-18 and FF-18 were more potent against EV71 infection than the parent peptide LL-37, which is the mature and processed form of Cathelicidin. These peptides could directly bind to the EV71 virus particles, but not to coxsackievirus, indicative of their high specificity. The binding of peptides with the virus surface occupied the viral canyon region in a way that could block virus-receptor interactions and inhibit viral uncoating. In addition, these peptide analogues could also relieve the deleterious effect of EV71 infection in vivo. Therefore, Cathelicidin-derived peptides might be excellent candidates for further development of antivirals to treat EV71 infection.


Subject(s)
Enterovirus A, Human , Enterovirus Infections , Enterovirus , Humans , Cathelicidins/pharmacology , Virus Internalization , Antiviral Agents/metabolism
9.
AIDS Care ; 36(4): 561-568, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38088933

ABSTRACT

This study used a self-administered questionnaire to investigate the relationship between HIV/AIDS knowledge, social discrimination, HIV self-efficacy, sexual behavioral characteristics and HIV testing behavior among young students with a history of sexual activity in Chongqing. Propensity score matching was used to construct a control group with similar demographic characteristics to the HIV testing group, only without HIV testing behaviors. Structural equation modeling was used to conduct chain-mediated effect analysis. The HIV testing rate among young students with a history of sexual behavior was 17.16%. Young students with HIV testing behavior had higher levels of HIV/AIDS knowledge, lower social discrimination, better self-efficacy, and no difference in sexual behavior characteristic scores between the two groups (P = 0.062). The mediated effect values of social discrimination and self-efficacy were 0.022 and 0.063, respectively, while their chain mediated effect value was 0.007. There was no mediated effect of sexual behavior characteristics. The level of young students' HIV/AIDS knowledge does not directly influence their HIV testing behavior but plays a complete chain mediating effect on HIV testing behavior through social discrimination and self-efficacy. HIV testing behavior should be promoted through the perspectives of enhancing HIV/AIDS knowledge level, reducing social discrimination, and improving self-efficacy.


Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Humans , HIV Infections/diagnosis , Self Efficacy , Mediation Analysis , Health Knowledge, Attitudes, Practice , Sexual Behavior , Surveys and Questionnaires , Students , HIV Testing , Social Discrimination
10.
Photochem Photobiol ; 100(2): 380-392, 2024.
Article in English | MEDLINE | ID: mdl-38041414

ABSTRACT

We have employed the highly accurate multistate complete active space second-order perturbation theory (MS-CASPT2) method to investigate the photoinduced excited state relaxation properties of one unnatural base, namely Z. Upon excitation to the S2 state of Z, the internal conversion to the S1 state would be dominant. From the S1 state, two intersystem crossing paths leading to the T2 and T1 states and one internal conversion path to the S0 state are possible. However, considering the large barrier to access the S1 /S0 conical intersection and the strong spin-orbit coupling between S1 and T2 states (>40 cm-1 ), the intersystem crossing to the triplet manifolds is predicted to be more preferred. Arriving at the T2 state, the internal conversion to the T1 state and the intersystem crossing back to the S1 state are both possible considering the S1 /T2 /T1 three-state intersection near the T2 minimum. Upon arrival at the T1 state, the deactivation to S0 can be efficient after overcoming a small barrier to access T1 /S0 crossing point, where the spin-orbit coupling (SOC) is as large as 39.7 cm-1 . Our present work not only provides in-depth insights into the photoinduced process of unnatural base Z, but can also help the future design of novel unnatural bases with better photostability.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(6): 1852-1859, 2023 Dec.
Article in Chinese | MEDLINE | ID: mdl-38071072

ABSTRACT

OBJECTIVE: To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors. METHODS: Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed. RESULTS: The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34+ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34+ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024). CONCLUSION: Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/complications , Prognosis , Recurrence , Retrospective Studies
12.
Cereb Cortex ; 33(21): 10723-10735, 2023 10 14.
Article in English | MEDLINE | ID: mdl-37724433

ABSTRACT

Based on acoustoelectric effect, acoustoelectric brain imaging has been proposed, which is a high spatiotemporal resolution neural imaging method. At the focal spot, brain electrical activity is encoded by focused ultrasound, and corresponding high-frequency acoustoelectric signal is generated. Previous studies have revealed that acoustoelectric signal can also be detected in other non-focal brain regions. However, the processing mechanism of acoustoelectric signal between different brain regions remains sparse. Here, with acoustoelectric signal generated in the left primary visual cortex, we investigated the spatial distribution characteristics and temporal propagation characteristics of acoustoelectric signal in the transmission. We observed a strongest transmission strength within the frontal lobe, and the global temporal statistics indicated that the frontal lobe features in acoustoelectric signal transmission. Then, cross-frequency phase-amplitude coupling was used to investigate the coordinated activity in the AE signal band range between frontal and occipital lobes. The results showed that intra-structural cross-frequency coupling and cross-structural coupling co-occurred between these two lobes, and, accordingly, high-frequency brain activity in the frontal lobe was effectively coordinated by distant occipital lobe. This study revealed the frontooccipital long-range interaction mechanism of acoustoelectric signal, which is the foundation of improving the performance of acoustoelectric brain imaging.


Subject(s)
Brain , Frontal Lobe , Frontal Lobe/diagnostic imaging , Brain Mapping
13.
Entropy (Basel) ; 25(7)2023 Jul 04.
Article in English | MEDLINE | ID: mdl-37509966

ABSTRACT

This study aims to unravel the resource allocation problem (RAP) by using a consensus-based distributed optimization algorithm under dynamic event-triggered (DET) strategies. Firstly, based on the multi-agent consensus approach, a novel one-to-all DET strategy is presented to solve the RAP. Secondly, the proposed one-to-all DET strategy is extended to a one-to-one DET strategy, where each agent transmits its state asynchronously to its neighbors. Furthermore, it is proven that the proposed two types of DET strategies do not have Zeno behavior. Finally, numerical simulations are provided to validate and illustrate the effectiveness of the theoretical results.

14.
Eur J Haematol ; 111(3): 356-364, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37294015

ABSTRACT

BACKGROUND: Patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) have poor outcomes and few treatment options. We report the preliminary results of the efficacy and safety of PD-1 monoclonal antibody (mab) plus Rituximab for r/r DLBCL. METHODS: In this single-center, single-arm phase 2 and retrospective study, r/r DLBCL patients received PD-1 mab and Rituximab every 3 weeks. Immunohistochemistry, fluorescence in situ hybridization, and probe capture-based high-resolution sequencing were performed. Efficacy, safety and prognostic factors were analyzed. RESULTS: Between October 16th, 2018, and July 10th, 2022, 36 patients (10 patients in retrospective study and 26 patients in phase 2 study) were enrolled and received at least one dose of PD-1 mab combined with Rituximab. The objective response rate was 52.8%. The median progression free survival (PFS) and overall survival was 2.8 and 19.6 months, respectively. The median duration of response was 18.7 months. Rare grade 3 or 4 treatment related adverse events were observed. B2M mutations correlated with a significantly poor PFS (p = .013) and OS (p = .009) in DLBCL patients treated with this regimen. CONCLUSION: PD-1 mab combined with Rituximab could be a potential treatment option for r/r DLBCL with manageable safety profile.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Humans , Rituximab/adverse effects , Antibodies, Monoclonal/adverse effects , Programmed Cell Death 1 Receptor , Retrospective Studies , In Situ Hybridization, Fluorescence , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy
15.
Adv Mater ; 35(51): e2301063, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37285592

ABSTRACT

Neuromorphic computing has been attracting ever-increasing attention due to superior energy efficiency, with great promise to promote the next wave of artificial general intelligence in the post-Moore era. Current approaches are, however, broadly designed for stationary and unitary assignments, thus encountering reluctant interconnections, power consumption, and data-intensive computing in that domain. Reconfigurable neuromorphic computing, an on-demand paradigm inspired by the inherent programmability of brain, can maximally reallocate finite resources to perform the proliferation of reproducibly brain-inspired functions, highlighting a disruptive framework for bridging the gap between different primitives. Although relevant research has flourished in diverse materials and devices with novel mechanisms and architectures, a precise overview remains blank and urgently desirable. Herein, the recent strides along this pursuit are systematically reviewed from material, device, and integration perspectives. At the material and device level, one comprehensively conclude the dominant mechanisms for reconfigurability, categorized into ion migration, carrier migration, phase transition, spintronics, and photonics. Integration-level developments for reconfigurable neuromorphic computing are also exhibited. Finally, a perspective on the future challenges for reconfigurable neuromorphic computing is discussed, definitely expanding its horizon for scientific communities.

16.
J Cancer Res Clin Oncol ; 149(11): 8483-8494, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37093346

ABSTRACT

PURPOSE: This study aims to investigate the clinical and molecular differences between diffuse large B-cell lymphoma (DLBCL) patients with MYD88L265P and MYD88other. METHODS: DLBCL patients with MYD88 variations were collected from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS), and Suzhou Municipal Hospital from February 6th, 2007 to May 20th, 2022. Clinicopathological parameters and treatment outcomes between MYD88L265P and MYD88other were investigated. RESULTS: A total of 132 patients with MYD88 variations from a cohort of 475 DLBCL patients were included, among which, 78 were MYD88L265P, while 54 were MYD88other. MYD88L265P was more common in non-GCB subtype than MYD88other (83% vs. 60%, P = 0.004). Besides, MYD88L265P was significantly related to higher proportion of testicle/ central nervous system involvement (31% vs. 6%, P < 0.001), PIM1 mutation (71% vs. 39%, P < 0.001), and PIM1 hypermutation (28% vs. 11%, P = 0.018), compared with MYD88other. Compared with MYD88L265P, MYD88other were more likely to have higher percentage of advanced stage (60% vs. 42%, P = 0.044), extranodal site ≥ 2 (45% vs. 28%, P = 0.044), elevated LDH (55% vs. 35%, P = 0.033), positive CD10 expression (36% vs. 16%, P = 0.009), BCL-6 translocation (20% vs. 8%, P = 0.033), and NOTCH pathway gene alteration (24% vs. 13%, P = 0.040). In non-GCB DLBCL subtype, patients with MYD88other were significantly associated with worse progression free survival (PFS) than those with MYD88L265P when treated initially with R-CHOP/R-CHOP-like regimen (P = 0.010). CONCLUSION: The findings of this study indicate that DLBCL patients with MYD88L265P and MYD88other are likely to be two subgroups with different clinical and molecular characteristics. The survival of patients with MYD88other is not superior than those with MYD88L265P, even poorer when focusing on the non-GCB subtype.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Myeloid Differentiation Factor 88 , Humans , Prognosis , Myeloid Differentiation Factor 88/genetics , Mutation , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Treatment Outcome
17.
Article in English | MEDLINE | ID: mdl-36900871

ABSTRACT

Agricultural carbon emission is an significant cause of global climate change and many environmental and health problems. Achieving low-carbon and green development in agriculture is not only an inevitable choice for countries around the world to cope with climate change and the accompanying environmental and health problems, but also a necessary path for the sustainable development of global agriculture. The promotion of rural industrial integration is a practical way to realize sustainable agricultural growth and urban-rural integration development. The analysis framework of agriculture GTFP is creatively extended in this study to include the integration and growth of rural industries, rural human capital investment and rural land transfer. According to the sample data of 30 provinces in China from 2011 to 2020 and the systematic GMM estimation method, and through the combination of theoretical analysis and empirical testing, this paper discusses the influence mechanism of rural industrial integration development on agriculture GTFP growth, as well as the regulating role of rural human capital investment and rural land transfer. The results show that rural industrial integration has significantly promoted the growth of agriculture GTFP. Additionally, after decomposing agriculture GTFP into the agricultural green technology progress index and agricultural green technology efficiency index, it is found that rural industrial integration has a more obvious role in promoting agricultural green technology progress. Furthermore, quantile regression found that with the increase in agricultural GTFP, the promoting effect of rural industrial integration showed an "inverted U-shaped" feature. Through heterogeneity testing, it is found that the agriculture GTFP growth effect of rural industrial integration is more obvious in areas with high level of rural industrial integration. Additionally, as the nation places more and more focus on rural industrial integration, the promotion role of rural industrial integration has become more and more obvious. The moderating effect test showed that health, education and training, migration of rural human capital investment and rural land transfer all strengthened the promoting effect of rural industrial integration on agricultural GTFP growth to varying degrees. This study provides rich policy insights for China and other developing countries around the world to address global climate change and many related environmental and monitoring issues by developing rural industrial integration, strengthening rural human capital investment and promoting agricultural land transfer to achieve sustainable agricultural growth and reduce undesirable output outputs such as agricultural carbon emissions.


Subject(s)
Agriculture , Rural Population , Humans , China , Technology , Investments , Economic Development , Efficiency
18.
Transplant Cell Ther ; 29(6): 382.e1-382.e11, 2023 06.
Article in English | MEDLINE | ID: mdl-36944387

ABSTRACT

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is currently an effective treatment for malignant hematologic disease, but the immune deficiency and severe infection triggered by slow immune reconstitution are the main causes of high mortality and transplant failure. One of these outstanding problems is thymus damage, which is associated with graft-versus-host disease (GVHD), and preconditioning including irradiation and chemotherapy. Therefore, rapid repair of damaged thymus and rapid proliferation of thymus-derived donor T cells post-transplantation are key to solving the problem. This study was designed to accelerate the recovery of thymus-derived T cells post-transplantation. Wild-type mice with normal immunity were used as recipients in a haplo-HSCT mouse model to mimic clinical haplo-HSCT. A modified cell culture system using Notch ligand Delta4 and IL-7 was established that is capable of inducing and amplifying the differentiation and proliferation of hematopoietic stem cells into precursor T (preT) cells in vitro. The haplo-HSCT protocol included preT and G-CSF-mobilized donor splenic mononuclear cell (MNC) coinfusion in one group and MNC infusion alone in a second group. Thymic GVHD, thymic repair, and thymus-derived T cell development were compared in the 2 groups by polychromatic immunofluorescence tracking, flow cytometry, and detection of T cell receptor Vß. The thymus homing and T cell regeneration of allogenic preT cells were observed. The functions of preT cells in accelerating immune reconstitution, restoring thymic architecture, weakening graft-versus-host (GVH) effects, and enhancing immunotolerance post-transplantation were demonstrated. Further studies revealed that allogeneic preT cells induced by a culture system containing IL-7 and Delta4 highly express ccr9 and RANKL. Interestingly, RANK expression was promoted after preT cell thymus homing. These results suggest that the RANK/RANKL pathway may play an important role in thymus homing. Our results provide a potential therapeutic option to optimize haplo-HSCT, and also open up a new field of T cell therapy for artificial induction of allogeneic preT cells in vitro to repair the damaged thymus from irradiation and chemotherapy and to compensate for the recovery of immune function in patients with immune deficiency of various etiologies.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Animals , Mice , T-Lymphocytes , Interleukin-7/metabolism , Hematopoietic Stem Cell Transplantation/adverse effects , Thymus Gland/metabolism , Graft vs Host Disease/therapy
19.
Article in English | MEDLINE | ID: mdl-36834245

ABSTRACT

This paper attempts to explore the overall impact of its rural digitization process on agricultural carbon emissions and non-point source pollution in the context of China. By doing so, we analyze whether digitization has an impact on agricultural pollution reduction, analyze its conductive mechanism, and draw its policy implications. To this end, the paper innovatively incorporates new digital infrastructure and urbanization level into of the concept of agricultural eco-efficiency (AEE) and adopts the SBM-DEA model, entropy weighting method, and mixed regression to analyze, based on the sample data of the 30 provinces of China from 2011 to 2020. The results indicate that: (1) new digital infrastructure has a significant contribution to the improvement of AEE of China; (2) both information infrastructure and integration infrastructure have a significant positive effect on AEE, and the effect of information infrastructure is more effective, but there is an inverted "U"-shaped relationship between innovation infrastructure and AEE level; (3) the moderating effect mechanism suggests that the level of urbanization reinforces the contribution of new digital infrastructure to AEE; and (4) the heterogeneity test shows that the effect of new digital infrastructure on AEE is more significant in regions with well-developed traditional transportation facilities and in periods when the government pays more attention to agricultural ecological issues. The above results also provide rich insights for China and other similar developing countries on how to balance the agriculture digitization and AEE.


Subject(s)
Agriculture , Urbanization , China , Efficiency , Environmental Pollution , Economic Development
20.
J Neurosurg Spine ; 38(4): 503-511, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36640104

ABSTRACT

OBJECTIVE: The burden of spinal trauma in low- and middle-income countries (LMICs) is immense, and its management is made complex in such resource-restricted settings. Algorithmic evidence-based management is cost-prohibitive, especially with respect to spinal implants, while perioperative care is work-intensive, making overall care dependent on multiple constraints. The objective of this study was to identify determinants of decision-making for surgical intervention, improvement in function, and in-hospital mortality among patients experiencing acute spinal trauma in resource-constrained settings. METHODS: This study was a retrospective analysis of prospectively collected data in a cohort of patients with spinal trauma admitted to a tertiary referral hospital center in Dar es Salam, Tanzania. Data on demographic, clinical, and treatment characteristics were collected as part of a quality improvement neurotrauma registry. Outcome measures were surgical intervention, American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade improvement, and in-hospital mortality, based on existing treatment protocols. Univariate analyses of demographic and clinical characteristics were performed for each outcome of interest. Using the variables associated with each outcome, a machine learning algorithm-based regression nonparametric decision tree model utilizing a bootstrapping method was created and the accuracy of the three models was estimated. RESULTS: Two hundred eighty-four consecutively admitted patients with acute spinal trauma were included over a period of 33 months. The median age was 34 (IQR 26-43) years, 83.8% were male, and 50.7% had experienced injury in a motor vehicle accident. The median time to hospital admission after injury was 2 (IQR 1-6) days; surgery was performed after a further median delay of 22 (IQR 13-39) days. Cervical spine injury comprised 38.4% of the injuries. Admission AIS grades were A in 48.9%, B in 16.2%, C in 8.5%, D in 9.5%, and E in 16.6%. Nearly half (45.1%) of the patients underwent surgery, 12% had at least one functional improvement in AIS grade, and 11.6% died in the hospital. Determinants of surgical intervention were age ≤ 30 years, spinal injury level, admission AIS grade, delay in arrival to the referral hospital, undergoing MRI, and type of insurance; admission AIS grade, delay to arrival to the hospital, and injury level for functional improvement; and delay to arrival, injury level, delay to surgery, and admission AIS grade for in-hospital mortality. The best accuracies for the decision tree models were 0.62, 0.34, and 0.93 for surgery, AIS grade improvement, and in-hospital mortality, respectively. CONCLUSIONS: Operative intervention and functional improvement after acute spinal trauma in this tertiary referral hospital in an LMIC environment were low and inconsistent, which suggests that nonclinical factors exist within complex resource-driven decision-making frameworks. These nonclinical factors are highlighted by the authors' results showing clinical outcomes and in-hospital mortality were determined by natural history, as evidenced by the highest accuracy of the model predicting in-hospital mortality.


Subject(s)
Emergency Medical Services , Spinal Cord Injuries , Spinal Injuries , Humans , Adult , Spinal Cord Injuries/epidemiology , Spinal Cord Injuries/surgery , Retrospective Studies , Tanzania/epidemiology , Treatment Outcome , Spinal Injuries/epidemiology , Spinal Injuries/surgery , Decision Trees
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