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Abstract Background Atrial natriuretic peptide (ANP) has been associated with ischemic stroke (IS), but the underlying molecular mechanisms are not clear. The objective of this study was to examine whether DNA methylation and hydroxymethylation in the coding gene of ANP (NPPA) were associated with IS, as well as its functional outcome. Methods and results DNA methylation and hydroxymethylation in NPPA promoter region were quantified by targeted bisulfite sequencing and APOBEC-coupled epigenetic sequencing, respectively, in 615 IS patients and 610 age- and sex-matched healthy controls. True methylation was calculated as the quantified methylation level minus the quantified hydroxymethylation level. The functional outcome of IS was evaluated by the modified Rankin Scale (mRS) at a 3-month follow-up visit after onset. Multiple testing was controlled by the false discovery rate approach. Of the nine CpG sites assayed, hypomethylation at eight CpGs was not only associated with an increased risk of having IS but also predicted a higher mRS score after onset (all q

Background Erythropoietin (EPO) hypo-responsiveness is one of the main reasons for the low compliance rate of renal anemia in maintenance hemodialysis (MHD) patients, and it is also an independent risk factor for death in MHD patients. Early identification and early intervention is the key to improve prognosis. Blood inflammatory markers may be associated with EPO hypo-responsiveness in MHD patients. Objective To explore the correlation between systemic immune-inflammation index (SII) and EPO hypo-responsiveness in MHD patients. Methods A total of 180 patients who underwent regular MHD at the hemodialysis center of Henan Province Hospital of Traditional Chinese Medicine from June 2022 to June 2023 were selected as the study objects. EPO resistance index (ERI) was used to evaluate the EPO reactivity of the patients, and they were divided into EPO hypo-responsiveness group and non-EPO hypo-responsiveness group according to the ERI value. The general data and laboratory index data of the two groups were compared. Pearson correlation analysis and Spearman rank correlation analysis were used to assess the correlation of ERI with other various indicators. Multivariate Logistic regression analysis was used to explore the independent correlation factors of EPO hypo-responsiveness in MHD patients. The predictive value of SII for EPO hypo-responsiveness in MHD patients was analyzed using receiver operating characteristic (ROC) curves. Results A total of 180 patients with MHD were included, including 104 males (57.8%) and 76 females (42.2%), aged (56.1±8.6) years. There were 52 cases (28.9%) in EPO hypo-responsiveness group and 128 cases (71.1%) in non-EPO hypo-responsiveness group. There were significant differences in dialysis age, post-dialysis body weight, weekly rHuEPO dosage, white blood cells, neutrophils, lymphocytes, red blood cells, hemoglobin, platelets, albumin, parathyroid hormone, triglyceride, ERI, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and SII between EPO hypo-responsiveness group and non-EPO hypo-responsiveness group (P

Abstract The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456–2.785; P = 0.456, HR 0.685, 95%CI 0.256–1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188–11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163–1.117; P = 0.014, HR 0.317, 95%CI 0.113–0.887). By COX analysis, poor baseline performance status (ECOG-PS ≥ 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.

Abstract The intricate interplay between the host and its microbiota has garnered increasing attention in the past decade. Specifically, the emerging recognition of microorganisms within diverse cancer tissues, previously presumed sterile, has ignited a resurgence of enthusiasm and research endeavors. Four potential migratory routes have been identified as the sources of intratumoral microbial “dark matter,” including direct invasion of mucosal barriers, spreading from normal adjacent tissue, hematogenous spread, and lymphatic drainage, which contribute to the highly heterogeneous features of intratumor microbiota. Importantly, multitudes of studies delineated the roles of intratumor microbiota in cancer initiation and progression, elucidating underlying mechanisms such as genetic alterations, epigenetic modifications, immune dysfunctions, activating oncogenic pathways, and inducing metastasis. With the deepening understanding of intratumoral microbial composition, novel microbiota-based strategies for early cancer diagnosis and prognostic stratification continue to emerge. Furthermore, intratumor microbiota exerts significant influence on the efficacy of cancer therapeutics, particularly immunotherapy, making it an enticing target for intervention in cancer treatment. In this review, we present a comprehensive discussion of the current understanding pertaining to the developmental history, heterogeneous profiles, underlying originations, and carcinogenic mechanisms of intratumor microbiota, and uncover its potential predictive and intervention values, as well as several inevitable challenges as a target for personalized cancer management strategies.

Abstract Natural killer/T cell lymphoma (NKTCL) exhibits highly aggressive clinical behavior, and the outcomes for relapsed/refractory patients are still poor. Recently, the mechanism underlying the effect of Epstein-Barr virus (EBV) infection, which has not been fully defined in NKTCL, has attracted great attention. We explored how LMP1 promoted aerobic glycolysis via metabolic sequencing combined with mRNA sequencing and immunoprecipitation coupled to mass spectrometry. Experimental assays were used to determine the effects of LMP1 and its downstream pathway on the function and glucose metabolism of NKTCL cells. The correlations between LMP1 expression in patients and their clinical features, treatment response, and prognosis were analyzed. Results show that LMP1 enhances NKTCL cell proliferation in vitro and in vivo, inhibits apoptosis, and decreases gemcitabine sensitivity. In addition, LMP1 also enhances aerobic glycolysis in NKTCL cells, as indicated by increases in glucose uptake, lactate production, and extracellular acidification rate. Clinically, LMP1 expression is correlated with risk stratification, treatment response, and prognosis, and higher LMP1 expression indicates greater SUVmax for NKTCL patients. Mechanistically, LMP1 competitively binds to TRAF3 to promote cell proliferation and aerobic glycolysis by regulating the noncanonical NF-κB pathway. The application of an NF-κB pathway inhibitor or reactivation of the NF-κB pathway affects aerobic glycolysis and the biological function of NKTCL cells. In summary, this study is the first to describe and define in detail how LMP1 affects glucose metabolism in NKTCL and might provide a novel perspective for further treatment.

Eriocheir sinensis is an economically important aquatic animal. Its regulatory mechanisms underlying many biological processes are still vague due to the lack of systematic analysis tools. The protein–protein interaction network (PIN) is an important tool for the systematic analysis of regulatory mechanisms. In this work, a novel machine learning method, DGO-SVM, was applied to predict the protein–protein interaction (PPI) in E. sinensis, and its PIN was reconstructed. With the domain, biological process, molecular functions and subcellular locations of proteins as the features, DGO-SVM showed excellent performance in Bombyx mori, humans and five aquatic crustaceans, with 92–96% accuracy. With DGO-SVM, the PIN of E. sinensis was reconstructed, containing 14,703 proteins and 7,243,597 interactions, in which 35,604 interactions were associated with 566 novel proteins mainly involved in the response to exogenous stimuli, cellular macromolecular metabolism and regulation. The DGO-SVM demonstrated that the biological process, molecular functions and subcellular locations of proteins are significant factors for the precise prediction of PPIs. We reconstructed the largest PIN for E. sinensis, which provides a systematic tool for the regulatory mechanism analysis. Furthermore, the novel-protein-related PPIs in the PIN may provide important clues for the mechanism analysis of the underlying specific physiological processes in E. sinensis.

Background In patients with untreated CD20-positive diffuse large B-cell lymphoma (DLBCL), a phase 3 trial was carried out to evaluate the efficacy and safety of zuberitamab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; Hi-CHOP) versus rituximab plus CHOP (R-CHOP) treatment regimens.Methods In a 2:1 ratio, eligible patients were assigned randomly to receive treatment of six cycles of either 375 mg/m2 zuberitamab or rituximab together with conventional CHOP chemotherapy. The objective response rate (ORR) at C6D50 served as the primary endpoint, and a non-inferiority margin of 10% was established. The secondary endpoints included the complete response (CR) rate at C6D50, duration of response (DOR), progression-free survival (PFS) and event-free survival (EFS) judged by blinded-independent review committee (BIRC), overall survival (OS) and safety outcomes.Results Of the 487 randomized patients, 423 patients including 287 in the Hi-CHOP and 136 in the R-CHOP groups completed the C6D50 assessment. For the full analysis set (FAS) and per-protocol set (PPS), BIRC-assessed ORR at C6D50 for the Hi-CHOP and R-CHOP groups were 83.5% versus 81.4% and 95.3% versus 93.7%, respectively. The non-inferiority was confirmed as the lower limit of the two-sided 95% CI for the intergroup differences of −5.2% and −3.3%; both were >−10% in the FAS and PPS. The BIRC-assessed CR rate of Hi-CHOP was significantly higher in PPS (85.7% vs 77.3%, p=0.038), but comparable in FAS (75.2% vs 67.9%, p=0.092). After a median follow-up of 29.6 months, patients in the Hi-CHOP group had a slight advantage with regard to the DOR (HR 0.74, p=0.173), PFS (HR 0.67, p=0.057), EFS (HR 0.90, p=0.517) and OS (HR 0.60, p=0.059). Patients with the germinal-center B cell-like subtype who received Hi-CHOP exhibited statistically significant improvements in ORR (p=0.034) and CR rate (p=0.038) at C6D50, EFS (p=0.046) and OS (p=0.014). Treatment-emergent adverse event occurrence rates were comparable across groups (all p>0.05). Infusion-related responses occurred more often in the Hi-CHOP group (32.1% vs 19.9%, p=0.006), all of grade 1–3 severity.Conclusions Zuberitamab (375 mg/m2) plus CHOP was non-inferior to R-CHOP regarding ORR but exhibited a higher CR rate and was well tolerated in CD20-positive, previously untreated Chinese patients with DLBCL.Trial registration number Chinese Clinical Trial Registry, ChiCTR2000040602, retrospectively registered.

ObjectiveTo analyze the clinical prognostic factors and treatments for angioimmunoblastic T-cell lymphoma (AITL) and develop a novel prognostic model specifically for AITL.MethodWe retrospectively analyzed 231 patients with AITL from the First Affiliated Hospital of Zhengzhou University. Patients were enrolled between January 2014 and July 2023. The primary end points were overall survival (OS) and progression-free survival (PFS).ResultThe patients’ median age was 63 years, with 88.3% at an advanced stage (III/IV). The majority of patients (47.6%) received anthracycline-containing regimens, and there was no significant difference in survival compared with those treated with epigenetic-targeting and gemcitabine- containing regimens. The median PFS and OS were 6 and 17 months, respectively. In multivariate analysis, age >60 years, Eastern Cooperative Oncology Group performance status ≥2, elevated LDH, and splenomegaly were associated with inferior OS. Based on these four factors, a novel prognostic model (AITL model) was constructed that stratified patients into low‐, intermediate‐, and high‐risk groups, with 2-year OS estimates of 63.6%, 42.1%, and 18.6%, respectively.ConclusionCurrently, there is no consensus on the optimal initial therapy for AITL, and the efficacy of anthracycline-containing regimens remains suboptimal. The novel model developed herein demonstrates predictive significance for both OS and PFS, and exhibits better stratification and discrimination capabilities.

Lung cancer cells tend to develop resistance to cisplatin (DDP) during continuous chemotherapy, making it crucial to improve DDP sensitivity to enhance therapeutic outcomes. The levels of miR-149-3p in lung tissues and cells, as well as the biological behaviors of lung cancer cells, were analyzed. H446/DDP and A549/DDP cell lines were established to investigate how miR-149-3p affects lung cancer cells’ sensitivity to DDP. Bioinformatics analysis predicted transmembrane serine protease 4 (TMPRSS4) as a downstream target of miR-149-3p, which was subsequently confirmed. Western blot analysis was used to examine proteins related to migration, invasion, apoptosis, and TMPRSS4 expression. Additionally, a subcutaneous graft tumor model in nude mice was created to assess the impact of miR-149-3p on tumor growth. In lung cancer tissues and cells, miR-149-3p expression was reduced, while TMPRSS4 expression was elevated. Overexpression of miR-149-3p inhibited cancer progression, promoted apoptosis, and enhanced the chemosensitivity of lung cancer cells to DDP. Moreover, miR-149-3p negatively regulated TMPRSS4, reducing malignancy-associated characteristics of lung cancer cells and further improving their DDP sensitivity. In vivo, high miR-149-3p expression increased the chemosensitivity of cancer cells. In conclusion, miR-149-3p suppresses the aggressive progression of lung cancer by directly downregulating TMPRSS4 and enhances the responsiveness of lung cancer cells to DDP.

Objective: To assess the diagnostic ability of peripapillary vessel density (pVD) in primary open-angle glaucoma suspect (GS) patients. Methods: Sixteen primary open-angle GS patients (22 eyes) and 20 normal controls (22 eyes) were included. In the GS group, OCTA measurements of pVD (superior, inferior, nasal, temporal, and global), OCT measurements of retinal nerve fiber layer (RNFL) thickness, disc area, rim area and ganglion cell complex (GCC) thickness were examined. In the control group, pVD measurements were performed. The vessel density between the two groups was compared. The correlation between OCTA and OCT parameters was evaluated. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of OCTA measurements. Results: The global (P < 0.001), nasal (P = 0.003), and inferior (P = 0.002) quadrant pVD in GS group was considerably lower than the control group. The global pVD was positively correlated with the inferior RNFL thickness (r = 0.492, P = 0.023) and rim area (r = 0.483, P = 0.027). The inferior pVD was positively correlated with the inferior RNFL thickness (r = 0.648, P = 0.001), the nasal RNFL thickness (r = 0.441, P = 0.045), the rim area (r = 0.439, P = 0.046) and the GCC thickness (r = 0.472, P = 0.048). The global pVD had the best diagnostic value (AUC=0.825, sensitivity 86.36 %, specificity 72.73 %, cutoff value 45 %), followed by the inferior (AUC=0.749) and nasal (AUC=0.748) quadrant pVD. Conclusion: In primary open-angle GS patients, the global and inferior quadrant pVD was lower than that of normal people, and it was positively correlated with the inferior RNFL thickness and rim area. The diagnostic value of pVD for discriminating GS from normal people was excellent with high sensitivity and specificity.

On December 18, 2023, an Ms 6.2earthquake occurred in Jishishan County, Linxia Prefecture, Gansu Province, causing a large number of geological disasters and threatening people's lives and the safety of infrastructure. After the earthquake, Gansu and Qinghai provincial governments quickly deployed hundreds of geology professionals to carried out the investigation and verification geological disasters in the earthquake area. Based on the results of the earthquake geohazard investigation and verification, this paper analyses the characteristics, control factors and development trend of the earthquake-induced geohazards, and puts forward suggestions on disaster prevention and risk mitigation measures. Till December 23, a total of 2044 geohazards have been checked, including 78 new geohazards, 88 existing geohazards with intensified deformation due to earthquake, and 1 878 existing geohazards without obvious different from before. Most of new and intensified deforming geohazards are collapse, accounting for 67.5%, followed by landslide, accounting for 31.9%. Most of new and intensified deforming geohazards are small in scale, accounting for 84.9%, followed by medium, accounting for 10.8%. Disaster mode of new and intensified deforming geohazards are mostly small collapse threatening houses and roads. The co-seismic geohazards are densely distributed along the seismic fault, and the spatial density increases with the enhancement of earthquake intensity. Data from 206 groups of accelerate-meters within 50 km from the epicenter of the National Geological Safety Monitoring Network showed that the peak acceleration of the earthquake area was 30.4～1969.7 mg. and decayed logarithm with the increase of the distance from the epicenter. In addition, the surface deformation monitoring equipment also recorded the co-seismic displacement curve of a typical landslide. Analysis shows, earthquake put a deteriorate effect to rock and soil, which decreased their integration and strength. There is a magnificent geohazard after-effect of earthquake; collapse, landslide and debris flow will be much often than before. So the authors suggest: (1) update earthquake geohazard database as soon as possible, (2) work out targeted prevention and control measures for the geohazards with large potential danger, (3) conduct comprehensive remote sensing monitoring and research of earthquake-induced geohazard mechanism, (4) improve the meteorological early warning model and threshold. By all this efforts the risk of geohazards after earthquake will be reduced and controlled.

Abstract Molecular computing is an emerging paradigm that plays an essential role in data storage, bio-computation, and clinical diagnosis with the future trends of more efficient computing scheme, higher modularity with scaled-up circuity and stronger tolerance of corrupted inputs in a complex environment. Towards these goals, we construct a spatially localized, DNA integrated circuits-based classifier (DNA IC-CLA) that can perform neuromorphic architecture-based computation at a molecular level for medical diagnosis. The DNA-based classifier employs a two-dimensional DNA origami as the framework and localized processing modules as the in-frame computing core to execute arithmetic operations (e.g. multiplication, addition, subtraction) for efficient linear classification of complex patterns of miRNA inputs. We demonstrate that the DNA IC-CLA enables accurate cancer diagnosis in a faster (about 3 h) and more effective manner in synthetic and clinical samples compared to those of the traditional freely diffusible DNA circuits. We believe that this all-in-one DNA-based classifier can exhibit more applications in biocomputing in cells and medical diagnostics.

Precipitation strengthening plays a vital role in enhancing the mechanical properties of metallic materials, typically achieved through heat treatment. However, deformation-induced precipitation (DIP) in multicomponent alloys (MAs) without the assistance of annealing is rarely reported, owing to their inherent high entropy and sluggish diffusion effects. This work reveals the significant formation of nanoscale and microscale precipitates in the dual-phase Fe49.3Co23Ni23C0.85Mn1Si2.85 MA triggered by surface severe plastic deformation (SSPD) through industrial shot blasting. The SSPD process leads to the formation of ultrafine gradient structures comprising nanocrystalline and submicron-crystalline zones. Submicron SiO2 precipitates emerge at the interfaces of both these zones, while various Mn5Si3 and Si nanoparticles precipitate within the nanocrystalline zone. This phenomenon can be ascribed to the high density of generated substructures, the accelerated diffusion of atoms, and the reduction in solid solubility limits in the SPD-driven non-equilibrium state.

Artemia is a widely distributed small aquatic crustacean, renowned for its ability to enter a state of embryonic diapause. The embryonic diapause termination (EDT) is closely linked to environmental cues, but the precise underlying mechanisms remain elusive. In this study, ATAC-seq and RNA-seq sequencing techniques were employed to explore the gene expression profiles in Artemia cysts 30 min after EDT. These profiles were compared with those during diapause and 5 h after EDT. The regulatory mechanisms governing the EDT process were analyzed through Gene Ontology (GO) enrichment analysis of differentially expressed genes. Furthermore, the active G-protein-coupled receptors (GPCRs) were identified through structural analysis. The results unveiled that the signaling transduction during EDT primarily hinges on GPCRs and the cell surface receptor signaling pathway, but distinct genes are involved across different stages. Hormone-mediated signaling pathways and the tachykinin receptor signaling pathway exhibited heightened activity in the ‘0–30 min’ group, whereas the Wnt signaling pathway manifested its function solely in the ‘30 min–5 h’ group. These results imply a complete divergence in the mechanisms of signal regulation during these two stages. Moreover, through structural analysis, five GPCRs operating at different stages of EDT were identified. These findings provide valuable insights into the signal regulation mechanisms governing Artemia diapause.

Lymphoma is a highly heterogeneous lymphohematopoietic tumor. As our understanding of the biological and pathological characteristics of lymphoma improves, we are identifying an increasing number of lymphoma subtypes. Genotyping has enhanced our ability to diagnose, treat, and monitor the prognosis of lymphoma. Despite significant improvements in treatment effectiveness, traditional methods for assessing disease response and monitoring prognosis are imperfect, and there is no significant improvement in overall remission rates for lymphoma patients. Minimal Residual Disease (MRD) is often indicative of refractory disease or early relapse. For lymphoma patients, personalized MRD monitoring techniques offer an efficient means to estimate disease remission levels, predict early relapse risk, and assess the effectiveness of new drug regimens. In this review, we delve into the MRD procedures in lymphoma, including sample selection and requirements, detection methods and their limitations and advantages, result interpretation. Besides, we also introduce the clinical applications of MRD detection in lymphoma.

PurposeThis study aimed to evaluate the effectiveness of generative adversarial networks (GANs) in creating synthetic OCT images as an educational tool for teaching image diagnosis of macular diseases to medical students and ophthalmic residents.MethodsIn this randomized trial, 20 fifth-year medical students and 20 ophthalmic residents were enrolled and randomly assigned (1:1 allocation) into Group real OCT and Group GANs OCT. All participants had a pretest to assess their educational background, followed by a 30-min smartphone-based education program using GANs or real OCT images for macular disease recognition training. Two additional tests were scheduled: one 5 min after the training to assess short-term performance, and another 1 week later to assess long-term performance. Scores and time consumption were recorded and compared. After all the tests, participants completed an anonymous subjective questionnaire.ResultsGroup GANs OCT scores increased from 80.0 (46.0 to 85.5) to 92.0 (81.0 to 95.5) 5 min after training (p

Based on multiple measurements of ionization loss, the Time Projection Chamber (TPC) combines strong tracking ability with particle identification ability in a large momentum range, which is an important advantage of TPC detection technology over traditional ionization measurement technology. According to these two characteristics of TPC, applying it to the measurement of fission cross-section can greatly improve the measurement accuracy. During the measurement of the fission cross-section, the number of target nuclei is required to be accurately measured. So this paper introduces a method for measuring the number of 235U target nuclei using a fission TPC system. The measurement result agrees with the reference value, and relative error is around 1 %.

Abstract HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2–76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9–87.5%) and 75.4% (95% CI: 68.9–82.6%)( HR: 0.75, 95% CI 0.47–1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4–84.6%) and 73.0% (95% CI: 66.3–80.3%) (HR: 0.84, 95% CI 0.54–1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

BackgroundThe clinical value of preoperative immunochemotherapy and simple chemotherapy induction regimen in the conversion therapy of locally advanced unresectable esophageal squamous cell carcinoma (ESCC) is still unclear.MethodRetrospective analysis was conducted on patients with unresectable cT4b stage ESCC who underwent conversion surgery in our hospital from January 2020 to December 2022. According to the preoperative induction treatment plan, they were divided into induction immunochemotherapy group (iICT group) and induction chemotherapy group (iCT group). The conversion surgery rate, R0 resection rate, radiological and pathological tumor responses, safety, and short-term survival outcomes were analyzed.ResultsThe results showed that a total of 199 patients with cT4b locally advanced unresectable ESCC who underwent preoperative induction therapy were included in this study. Among them, there were 64 cases (32.2%) in the iICT group, 135 cases (67.8%) in the iCT group. There was a statistically significant difference in objective response rate (73.5% vs 48.9%) and conversion surgery rate (81.3% vs 66.7%), between the iICT and iCT groups (P=0.001 and P=0.019). Among the two groups of patients who underwent surgery, there were statistically significant differences in R0 resection rate (94.2% vs 82.2%) and pathological complete remission rate (23.1% vs 6.7%) between the iICT and iCT groups (P=0.043 and P=0.004). And there was no statistically significant difference in the incidence of grade 3 and above between two groups (P=0.928). The 2-year EFS of the iICT group and iCT group were 76.4% and 42.4%, respectively, with statistically significant differences (P=0.006).ConclusionsCompared with simple chemotherapy, the combination of PD-1 inhibitors and chemotherapy can achieve better conversion surgery rate, tumor response and event-free survival in the conversion therapy of locally advanced unresectable ESCC.

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological cancer. Due to its low incidence, researchers struggle to gather sufficient prospective data to inform clinical treatment. Objectives: We sought to summarize the clinical characteristics and current treatment methods of BPDCN and provide more specific guidance on treatment options. Design: A systematic literature review using data from 74 Chinese BPDCN patients. Date resources and methods: We retrospectively analyzed the clinical manifestations, treatment response, survival outcomes, and prognostic factors of six BPDCN patients treated at the First Affiliated Hospital of Zhengzhou University and 68 patients described in 28 articles published in the China Knowledge Network database since 2019. Results: In Chinese patients, the disease occurred with a male-to-female ratio of 2.52 and a median age of onset of 50 years in adults and 10 years in pediatric patients. Immunohistochemical analysis revealed distinctive immune phenotypes of BPDCN cells, characterized by high expression levels of CD4, CD56, CD123, and HLA-DR, while showing minimal to no expression of myeloperoxidase (MPO), CD20, and CD79a. There was no significant difference in the initial complete remission (CR) rate, relapse rate, and the overall survival (OS) time of patients receiving acute myeloid leukemia-like, acute lymphocytic leukemia-like, or non-Hodgkin’s lymphoma-like chemotherapy regimens. Univariate analysis identified CD3 expression, male gender, and central nervous system infiltration as hazardous factors. In multivariate analysis, age proved to be an independent prognostic indicator, indicating better prognosis and longer OS time in younger patients. Notably, hematopoietic stem cell transplantation (HSCT) emerged as a significant factor in improving the survival outcomes for individuals diagnosed with BPDCN. However, further investigation is needed to explore the role of HSCT and the best timing for its implementation in pediatric BPDCN patients. Conclusion: Administering HSCT during the initial CR state following inductive chemotherapy might extend the OS and improve the prognosis of patients with BPDCN.

Solid fuels are widely used in China and increase the concentrations of indoor air pollutants. Nevertheless, there is limited longitudinal evidence linking solid fuel use and Gastrointestinal (GI) and liver diseases. This study aimed to prospectively investigate the association between household solid fuel use and the risk of GI and liver diseases in middle aged and elderly adults. This work was based on the China Health and Retirement Longitudinal Study (CHARLS). Longitudinal data incorporate with cross-sectional data were analyzed. Compared with individuals using clean fuel for cooking, solid fuel users were observed to have higher risk of GI diseases (OR in 2011, 2013, 2015, 2018 wave separately: 1.37, 95 % CI: 1.24–1.50, P

Obtaining clean energy is of prime importance for planetary health and sustainable development. We aimed to assess the association between residential energy transition and the risk of chronic respiratory diseases. Using data from the Global Health Observatory and Global Burden of Diseases, Injuries, and Risk Factors Study, we delineated the spatial distribution and temporal trends of the population using clean fuels for cooking at a global scale. In the China Health and Retirement Longitudinal Study, we performed rigorous and well-structured multistage analyses incorporating both cross-sectional and prospective data analyses to examine the associations between solid fuel use, residential energy transition, duration of solid fuel use, and the risk of chronic respiratory diseases. Despite great progress, huge disparities in access to clean energy persist globally. Residential energy transition was associated with a lower risk of chronic respiratory diseases. In the period of 2011–2013, compared with persistent solid fuel users, both participants who switched from solid to clean fuels (adjusted risk ratio [RR] 0.78, 95% confidence interval [CI] 0.62–0.98) and persistent clean fuel users (adjusted RR 0.71, 95% CI 0.57–0.89) had significantly lower risk of chronic respiratory diseases (p

The conjunctiva of primary open angle glaucoma patients showed high level of oxidized low-density lipoprotein (ox-LDL), which is associated with the inflammatory response. Microglia and macrophages are the immune cells involved in retinal ganglion cell survival regulation; yet, their roles of the ox-LDL-induced inflammation in glaucoma remain elusive. Here we aimed to investigate the lipid uptake, inflammatory cytokine expression, and metabolomics profiles of human and murine-derived microglial and macrophage cell lines treated with ox-LDL. Under the same ox-LDL concentration, macrophages exhibited higher lipid uptake and expression of pro-inflammatory cytokines as compared to microglia. The ox-LDL increased the levels of fatty acid metabolites in macrophages and sphingomyelin metabolites in microglia. In summary, this study revealed the heterogeneity in the inflammatory capacity and metabolic profiles of macrophages and microglia under the stimulation of ox-LDL.

Abstract Background Brentuximab vedotin (BV) was approved as a therapy for patients with CD30‐positive lymphoma in China in 2020 based on the results of multiple clinical trails. Few Chinese real‐world data of its use are yet available. Herein, we present the application situation of BV in patients with lymphoma among different hospitals in Henan province in China under real‐world conditions. Methods This was a multicenter and retrospective study in 104 patients with lymphoma who received BV for the first time between August 2020 and September 2022 across eight centers in Henan province. Data on the clinical use, effectiveness and adverse events (AEs) of BV were extracted from patient medical records. Short‐term effectiveness was assessed based on objective response rate (ORR), complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Progression‐free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method. Safety was also evaluated in our study. Results 104 lymphoma patients were enrolled in our study, who had completed a median of two cycles (range,1–8) of BV‐based treatment. A total of 72.1% of patients were relapsed/refractory (R/R) lymphoma, and only 27.9% were previously untreated lymphoma who received BV in frontline treatment settings. Among them who received effectiveness evaluation, the ORR achieved 64.5% (CR 25.8%, PR 38.7%). After a median follow‐up of 11 months, the 6‐month PFS rate and OS rate achieved 77.2% and 90.1% respectively, and the 12‐month PFS rate and OS rate achieved 77.2% and 79.9% respectively. In general, BV‐based treatment was well‐tolerated, with 38.5% incidence of grade ≥3 AEs. The most commonly reported AEs were hematologic disorders, especially neutropenia, with the incidence reaching 50.0%. Conclusions BV‐based regimens could be a promising therapeutic option with remarkable effectiveness and moderate toxicity in treating Chinese lymphoma patients with CD30 expression.

Since 2019, the Ministry of Natural Resources has comprehensively promoted the research and development of universal equipment and the automatic monitoring and forewarning of geological hazard. As of June 2023, it has been applied to 55 000 potential points of geological hazard in 17 key geological hazard prevention provinces, and the national geological hazard monitoring and forewarning system has entered a rapid development stage. At present, the system receives more than 10 million monitoring data every day, and has made positive progress in massive data storage management, parallel processing of time series data, intelligent analysis of big data and multi-parameter risk early warning. However, there are many challenges in data security of the system, especially in data consistency, data tamper resistance and system reliability. On the basis of systematic research on the characteristics of the blockchain technology and its typical application in related fields, this paper proposes a “trusted data flow” technology based on distributed ledger and consensus mechanism, according to which the overall framework of “blockchain + NRWSL” is formed, and a prototype system is established. The test data show that the improved system can solve the problem of data inconsistency between provinces and Ministry of Natural Resources, identify and prevent illegal data tampering, ensure the stable operation of the system under multi-node failure conditions, and the overall performance loss of the system is less than 20%. The research results provide technical methods for the application of blockchain technology to geological hazard risk early warning systems at all levels in China, and also provide top-level design ideas for improving the security of geological hazard monitoring data and the early warning system.

Abstract Purpose Our study aims to discuss glaucoma patients’ needs and Internet habits using big data analysis and Natural Language Processing (NLP) based on deep learning (DL). Methods In this retrospective study, we used web crawler technology to crawl glaucoma-related topic posts from the glaucoma bar of Baidu Tieba, China. According to the contents of topic posts, we classified them into posts with seeking medical advice and without seeking medical advice (social support, expressing emotions, sharing knowledge, and others). Word Cloud and frequency statistics were used to analyze the contents and visualize the keywords of topic posts. Two DL models, Bidirectional Long Short-Term Memory (Bi-LSTM) and Bidirectional Encoder Representations from Transformers (BERT), were trained to identify the posts seeking medical advice. The evaluation matrices included: accuracy, F1 value, and the area under the ROC curve (AUC). Results A total of 10,892 topic posts were included, among them, most were seeking medical advice (N = 7071, 64.91%), and seeking advice regarding symptoms or examination (N = 4913, 45.11%) dominated the majority. The following were searching for social support (N = 2362, 21.69%), expressing emotions (N = 497, 4.56%), and sharing knowledge (N = 527, 4.84%) in sequence. The word cloud analysis results showed that ocular pressure, visual field, examination, and operation were the most frequent words. The accuracy, F1 score, and AUC were 0.891, 0.891, and 0.931 for the BERT model, 0.82, 0.821, and 0.890 for the Bi-LSTM model. Conclusion Social media can help enhance the patient-doctor relationship by providing patients’ concerns and cognition about glaucoma in China. NLP can be a powerful tool to reflect patients’ focus on diseases. DL models performed well in classifying Chinese medical-related texts, which could play an important role in public health monitoring.

Rainfall, especially local concentrated heavy rainfall, is one of the major factors triggering sudden geological hazards such as landslides and debris flow. According to historical disaster statistics in China, locally short-term concentrated heavy rainfall is the primary triggering factor for debris flows, accounting for approximately 70% of the total number of landslides. Recent alterations in seasonal rainfall patterns, with accelerated spring floods and plum rain in southern China, as well as delayed autumn rain in the northern regions, have led to an increase in geological disasters, expanded risk-prone areas, and prolonged risk management periods. Therefore, conducting rainfall monitoring is of great significance for landslides and debris flow early warning and prediction. To ensure precise early warnings and predictions, the accuracy, sensitivity, stability, and scientifically grounded installation of rainfall monitoring equipment are prerequisites. This study, comparing two types of rain gauges-- tipping bucket and piezoelectric—in terms of measurement principles, technical specifications, installation methods, and operational maintenance, conducted both indoor simulated rainfall experiments and field tests within complex scenes. The results reveal that the piezoelectric rain gauge maintains an error range within 4%. These findings highlight that in the context of complex geological hazard monitoring scenarios, the piezoelectric rain gauge proves more suitable than the tipping bucket rain gauge, regardless of measurement range, accuracy, installation, or post-installation maintenance considerations

Abstract Failure to recognize samples from the classes unseen during training is a major limitation of artificial intelligence in the real-world implementation for recognition and classification of retinal anomalies. We establish an uncertainty-inspired open set (UIOS) model, which is trained with fundus images of 9 retinal conditions. Besides assessing the probability of each category, UIOS also calculates an uncertainty score to express its confidence. Our UIOS model with thresholding strategy achieves an F1 score of 99.55%, 97.01% and 91.91% for the internal testing set, external target categories (TC)-JSIEC dataset and TC-unseen testing set, respectively, compared to the F1 score of 92.20%, 80.69% and 64.74% by the standard AI model. Furthermore, UIOS correctly predicts high uncertainty scores, which would prompt the need for a manual check in the datasets of non-target categories retinal diseases, low-quality fundus images, and non-fundus images. UIOS provides a robust method for real-world screening of retinal anomalies.

Abstract Fulminant myocarditis (FM) is a life-threatening inflammatory disease. However, the mechanisms underlying its acute onset are unknown. By dynamic cardiac function measurement, we discovered that the initiation of sudden hemodynamic collapse was on day 4 in the mouse model of FM. Single-cell RNA-sequencing study revealed that healthy cardiomyocytes (CMs) lost their contractile and metabolic function and differentiated into pro-angiogenic and pro-inflammatory CMs. Meanwhile, neutrophils, the most expanded immune cells, exhibited a unique developmental trajectory only after migrating to the heart, where they continuously attracted peripheral neutrophils via Cxcl2/Cxcl3, resulting in the acute accumulation of neutrophils in the heart. Well-differentiated cardiac-infiltrating neutrophils, rather than viruses, induced phenotypic changes in CMs. Moreover, neutrophils could amplify cytokine storm by recruiting and activating pro-inflammatory monocytes. Blockade of the self-recruiting loop of neutrophils by targeting the Cxcl2/Cxcl3-Cxcr2 axis substantially alleviated FM in mice. Collectively, we provide a comprehensive single-cell atlas of immune cells and CMs in FM, elucidate the disease pathogenesis, and suggest potential therapeutic strategies.

Purpose: Investigate the oxylipin profiles in the aqueous humor of primary open-angle glaucoma (POAG) patients. Methods: Aqueous humor samples were collected from 17 POAG patients and 15 cataract subjects and subjected to a liquid chromatography/mass spectrometry (LC-MS) analysis to detect the oxylipins. The prediction potential of the differential abundant oxylipins was assessed by the receiver operating characteristic (ROC) curves. Pathway and correlation analyses on the oxylipins and clinical and biochemical parameters were also conducted. Results: The LC-MS analysis detected a total of 76 oxylipins, of which 29 oxylipins reached the detection limit. The multivariate analysis identified five differential abundant oxylipins, 15-keto-prostaglandin F2 alpha (15-kPGF2α), Leukotriene B4 (LTB4), 12,13-Epoxyoctadecenoic acid (12,13-Epome), 15-Hydroxyeicosatetraenoic acid (15-HETE) and 11-Hydroxyeicosatetraenoic acid (11-HETE). The five oxylipins are enriched in the arachidonic acid metabolism and linoleic acid metabolism pathways. Pearson correlation analysis showed that 11-HETE was positively correlated with intraocular pressure and central corneal thickness and negatively with cup/disk area ratio in the POAG patients. In addition, 15-kPGF2α was moderately and positively correlated with the mean deviation (MD) of visual field defect, and LTB4 was moderately and negatively correlated with macular thickness. Conclusions: This study revealed the oxylipin profile in the aqueous humor of POAG patients. Oxylipins involved in the arachidonic acid metabolism pathway could play a role in POAG, and anti-inflammatory therapies could be potential treatment strategies for POAG.

The deteriorating thermal environment of tunnels and the increase in energy consumption of environmental control systems has become highlights in the subway field. In existing research related to analysis of subway tunnel thermal environments and thermal accumulation; there is no predictive law that accounts for thermal accumulation or the long-term change in subway tunnel thermal environments. In this study, a combination of simulations and experiments is used. First, the long-term evolution of tunnel thermal environments with and without thermal interference are predicted and analyzed. Then, the changes in the tunnel thermal environment after the use of capillary heat exchangers are explored. The research results indicate that the model of the system has high accuracy and reliability. When there is a capillary heat exchanger installed in the subway tunnel, the anti-seasonal heat storage characteristics of the system result in the tunnel temperature increasing significantly in summer and decreasing significantly in winter, with a small decrease in the average annual temperature. This study provides a theoretical reference for environment-based subway tunnel construction and the comprehensive utilization of tunnel waste heat.

Abstract Purpose The prognostic factors for diffuse large B‐cell lymphoma (DLBCL) have been fully explored, but prognostic information for bulky mass DLBCL patients is limited. This study aimed to analyze the prognostic value of MYC protein expression and other biological parameters in bulky mass DLBCL patients. Methods We defined a bulky mass as a maximum tumor diameter ≥7.5 cm and studied 227 patients with de novo bulky mass DLBCL. Results In all patients with bulky mass DLBCL, the 1‐year and 3‐year OS rates were 72.7% and 57.1%, respectively, and the 1‐year and 3‐year PFS rates were 52.0% and 42.5%, respectively. The MYC overexpression group (n = 140) showed significantly worse overall survival (OS; p = 0.019) and progression‐free survival (PFS; p = 0.001) than the non‐MYC overexpression group (n = 87). Subgroup analyses demonstrated that the MYC overexpression group was associated with inferior OS and PFS in the subgroups with the International Prognostic Index score of 3–5 (OS: p = 0.011; PFS: p

Abstract Background Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies. Methods In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry. Results The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model. Conclusions In summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL.

Abstract Background This study aimed to compare the efficacy and safety of high-dose methotrexate (HD-MTX) versus teniposide (TEN) in patients with newly diagnosed immunocompetent primary central nervous system lymphomas (PCNSLs). Methods The study included immunocompetent, adult patients with newly diagnosed PCNSL at 22 centers in China from 2007 to 2016. The patients received HD-MTX or TEN as first-line induction therapy. The objective response rate, progression-free survival, and overall survival were analyzed for each patient cohort. Results A total of 96 patients were eligible: 62 received HD-MTX, while 34 received teniposide. The overall response rate was 73.2% and 72.7% in the MTX and the TEN cohorts, respectively (P = 0.627). The median progression-free survival was 28.4 months [95% confidence interval (CI): 13.7–51.2] in the MTX cohort and 24.3 months (95% CI: 16.6–32.1) in the TEN cohort (P = 0.75). The median overall survival was 31 months (95% CI: 26.8–35.2) in the MTX cohort and 32 months (95% CI: 27.6–36.4) in the TEN cohort (P = 0.77). The incidence of any grade of coagulopathy/deep-vein thrombosis and gastrointestinal disorders was significantly higher in the MTX cohort than in the TEN cohort; no significant difference was found in the incidence of other adverse events between the two cohorts. Conclusions This was the first multicenter study using TEN as the main agent compared with HD-MTX in newly diagnosed primary CNS lymphoma. The TEN-based regimen was non-inferior to the HD-MTX-based regimen with similar overall responses. Classification of evidence This study provided Class III evidence that the teniposide-based regimen was non-inferior to high-dose methotrexate − based regimen with similar overall responses and long-time survival in immunocompetent patients with PCNSL.

Abstract Background National standardized training for resident doctors (STRD) in mainland China has been formally established since 2014 as a kind of postgraduate education. The purpose of this survey was to assess the satisfaction of the training residents in Guangdong Province on the ophthalmology STRD program after a duration of 5 years. Method A 48-item survey was sent to all postgraduate ophthalmology residents from bases in Guangdong Province to inquire about their attitude towards the program. The survey contained questions about demographic and work-related information, job satisfaction, psychological resilience, and job performance. All responses were verified, and invalid questionnaires were excluded. Statistical analyses were performed using SPSS software version 22.0 (SPSS, Inc., Chicago, IL). Multiple logistic regression analysis was used to evaluate the factors (demographic information, working environment, clinical exposure, supervision and hands-on training opportunities, and involvement in academic activities) impacting the overall satisfaction. P

Abstract Background PARP inhibitor (PARPi), as a kind of DNA damage repair inhibitor, has been shown to be effective in various solid tumors and hematologic malignancies. Natural killer/T cell lymphoma (NKTCL) is a highly aggressive malignancy, the treatment of which has long been a major challenge in the clinic. Here, we investigated the efficacy and mechanism of PARPi, and the therapeutic value of PARPi combined with cisplatin in NKTCL. Methods The cell proliferation, cell apoptosis, and cell cycle of NKTCL cells were detected respectively by CCK-8 and flow cytometry. The changes of mRNA expression and protein level were measured respectively by mRNA-sequencing, quantitative real-time PCR, western blotting, and immunofluorescence. LMO2 expression was detected by immunohistochemistry and western blotting. Targeted knockdown of LMO2 was conducted by short hairpin RNA. The tumor xenograft models were established to evaluate the efficacy of drugs in vivo. Results PARPi inhibited cell proliferation, promoted cell apoptosis, and induced S-phase cell cycle arrest in NKTCL cells. PARPi led to the accumulation of DNA damage by blocking DNA repair and DNA replication. Additionally, LMO2 deficiency reduced the sensitivity of NKTCL cells to PARPi. Finally, the combination of PARPi and cisplatin exhibited significant synergistic effects both in vitro and in vivo. Conclusions In summary, we found that PARPi exerted an anti-tumor effect via LMO2 and synergized with cisplatin in NKTCL, which provides the theoretical basis for the clinical application of PARPi.

BackgroundNodal T-follicular helper cell lymphomas (nTFHLs) represent a new family of peripheral T-cell lymphomas (PTCLs), and comparative studies of their constituents are rare.MethodsThis study retrospectively enrolled 10 patients with nTFHL-F and 30 patients with nTFHL-NOS diagnosed between December 2017 and October 2023 at six large comprehensive tertiary hospitals; 188 patients with nTFHL-AI were diagnosed during the same period at the First Affiliated Hospital of Zhengzhou University for comparison.ResultsCompared with nTFHL-AI, nTFHL-NOS patients exhibited better clinical manifestations, lower TFH expression levels, and a lower Ki-67 index. However, no differences in clinicopathological features were observed between nTFHL-F and nTFHL-AI patients as well as nTFHL-NOS patients. According to the survival analysis, the median OS for patients with nTFHL-NOS, nTFHL-AI, and nTFHL-F were 14.2 months, 10 months, and 5 months, respectively, whereas the median TTP were 14 months, 5 months, and 3 months, respectively. Statistical analysis revealed differences in TTP among the three subtypes(P=0.0173). Among the population of patients receiving CHOP-like induction therapy, there were significant differences in the OS and TTP among the nTFHL-NOS, nTFHL-AI, and nTFHL-F patients (P=0.0134, P=0.0205). Both the GDPT and C-PET regimens significantly improved the ORR, OS, and PFS in nTFHL patients.ConclusionThere are significant differences in the clinical manifestations, pathology, and survival outcomes among the three subtypes of nTFHLs. However, further research with a larger sample size, and involving clinical pathology and molecular genetics is needed to determine the distinctive biological characteristics of these tumors.

ABSTRACT: The thyroid gland is susceptible to chemical exposure such as organophosphate insecticides (OPIs). With the ubiquitous nature of these products, humans are simultaneously exposed to a multitude of chemicals. This study aimed to evaluate the association between an individual and a mixture of OPI metabolites and changes in serum thyroid hormone (TH) concentrations. The analyzed data were 1,434 participants from the United States National Health and Nutrition Examination Surveys (NHANES) cycle 2007‐2008. Generalized linear model (GLM) regression, weighted quantile sum (WQS), and adaptive least absolute shrinkage and selection operator (adaptive LASSO) regression were used to investigate the associations between urinary OPI metabolites and altered serum THs. In GLM, all of the five urinary OPI metabolites were inversely associated with free triiodothyronine (FT3) among the male subjects; meanwhile, higher thyroglobulin (Tg) was related to dimethylphosphate (DMP). Moreover, in WQS models, the metabolite mixture induced FT3 down-regulation (β = ‐0.209 (95% CI: ‐0.310, ‐0.114)), and caused an increased Tg concentration (β = 0.120 (95% CI: 0.024, 0.212)), however, any significant association was observed among female participants. Consistently, the weighted index and LASSO coefficient demonstrated dimethylthiophosphate (DMTP) as the strongest metabolite in the FT3 model (mean weight= 3.449e-01 and β =‐0.022, respectively), and dimethylphosphate (DMP) represented the highest association in the Tg model (mean weight= 9.873e-01 and β =‐0.020, respectively). Further research is required to confirm our results and investigate the clinical impacts of these disruptions.

ObjectiveTo analyze and compare the temporal trends in the incidence of anisometropia among Chinese school-aged children both before and during the COVID-19 pandemic, and to investigate the impact of the pandemic on the incidence of anisometropia.MethodsWe conducted a retrospective study comprising six distinct and independent longitudinal cohorts, each including children aged 6 to 13 years who visited the Joint Shantou International Eye Center between January 2010 and December 2021. Children were grouped into cohorts based on the year of their first eye clinic visit: 2010, 2012, 2014, 2016, 2018, or 2020. Only children without anisometropia at initial visits, followed for 18 ± 6 months, were included. The cumulative incidence and risk factors of anisometropia were analyzed using Kaplan–Meier estimation and Cox proportional hazards regression models. Subgroup analyses were performed based on sex, age groups, initial refractive error status, and initial interocular SE difference. Anisometropic children were further categorized into myopic and non-myopic, with subsequent subgroup analyses conducted.ResultsOf 11,235 children were recruited from six cohorts (2010: n = 1,366; 2012: n = 1,708; 2014: n = 1,896; 2016: n = 2,354; 2018: n = 2,514; 2020: n = 1,397), 869 children developed anisometropia during a mean follow-up of 17.5 ± 3.7 months. After adjustment of confounding factors, we found that the risk of anisometropia remained relatively stable before 2020 but significantly increased in the 2020 cohort (adjusted HR 2.93, 95% CI 2.23 to 3.86; p

Background. This study aims to investigate the agreement between the NK and KS formulas in predicting the vault after implantation of an EVO-implantable collamer lens (ICL). Methods. This retrospective study included 106 eyes of 57 patients who underwent ICL-V4c implantation. Preoperative vault prediction was conducted by utilizing the NK and KS formulas, with postoperative measurements by anterior segment optical coherence tomography (AS-OCT) at one month. The analysis focused on the consistency between predicted and achieved vaults, as well as the correlation between the achieved vault and various biometric parameters. Results. The mean achieved vault was 605.25 ± 212.72 µm, which was significantly smaller than the predicted vaults of 710.08 ± 195.08 and 673.80 ± 212.76 µm, using the NK and KS formulas, respectively (P

Abstract Background DNA methylation has previously been associated with ischemic stroke, but the specific genes and their functional roles in ischemic stroke remain to be determined. Here we aimed to identify differentially methylated genes that play a functional role in ischemic stroke in a Chinese population. Results Genome-wide DNA methylation assessed with the Illumina Methylation EPIC Array in a discovery sample including 80 Chinese adults (40 cases vs. 40 controls) found that patients with ischemic stroke were characterized by increased DNA methylation at six CpG loci (individually located at TRIM6, FLRT2, SOX1, SOX17, AGBL4, and FAM84A, respectively) and decreased DNA methylation at one additional locus (located at TLN2). Targeted bisulfite sequencing confirmed six of these differentially methylated probes in an independent Chinese population (853 cases vs. 918 controls), and one probe (located at TRIM6) was further verified in an external European cohort (207 cases vs. 83 controls). Experimental manipulation of DNA methylation in engineered human umbilical vein endothelial cells indicated that the identified differentially methylated probes located at TRIM6, TLN2, and FLRT2 genes may play a role in endothelial cell adhesion and atherosclerosis. Conclusions Altered DNA methylation of the TRIM6, TLN2, and FLRT2 genes may play a functional role in ischemic stroke in Chinese populations.

Abstract Background Multiple myeloma (MM) is an aggressive plasma cell malignancy, causing a number of deaths worldwide every year. Chimeric antigen receptor (CAR) transduced T‐cell therapy has been a promising immunotherapy against hematological malignancies. Methods In this study, we developed a second‐generation CAR construct and generated CAR‐T cells targeting CD38 molecule. Then effects of CAR‐T cells against MM cell lines were evaluated. Results CD38‐CAR‐T cells showed higher cytotoxicity to MM cell lines and primary MM cells than that of control T cells in vitro. Over 50% MM1.s and RPMI8226 cells were killed by CAR‐T cells even at effector to target ratio of 1:100. CAR‐T cells also showed an enhanced cytotoxicity against primary MM cells. CAR‐T cells could be activated and produced a variety of cytokines in a target‐dependent manner. In vivo test indicated that CAR‐T cells also showed significant antitumor effect on xenograft mice models. Conclusion These results indicated a promising therapeutic strategy of CD38‐CAR‐T cells against MM.

Abstract Background Recently the prevalence of precocious puberty development is increasing among Chinese children. Proper understanding of the risk factors for precocious puberty in children is pivotal as could help to improve children's health. This study aims to evaluate the effect of environmental factors on precocious puberty in children. Methods We matched the cases and controls by age at the ratio of 1:1 (201 cases and 201 controls) for girls and 1:4 (24 cases and 96 controls) for boys. We used conditional logistic regression to explore the effect of environmental factors on precocious puberty, and a random forest model to identify the most important risk factor. Results In the multivariate regression, cesarean section (OR = 1.99, 95% CI: 1.05, 3.76), child body mass index [BMI] (OR = 1.25, 95% CI: 1.10, 1.43), maternal BMI (OR = 1.13, 95%CI: 1.01, 1.26), and exposure to secondhand smoke several times a month but less than once a week (OR = 4.09, 95%CI: 1.79,9.35), and almost every day (OR = 6.48, 95% CI: 2.14, 19.56) were risk factors for precocious puberty in girls. While maternal height (OR = 0.82, 95% CI: 0.75, 0.88), paternal height (OR = 0.91, 95% CI: 0.85, 0.98), bedtime at night (OR = 0.30, 95% CI: 0.17, 0.51), and night sleep (OR = 0.43, 95% CI: 0.21, 0.86) were protective factors. In boys, only exposure to secondhand smoke several times a month but less than once a week (OR = 7.94, 95% CI: 1.25, 50.33) was a risk factor for precocious puberty. In the random forest model, Child BMI was the most important risk factor for precocious puberty in girls. Conclusions Our findings suggest that environmental factors were associated with precocious puberty in children, particularly in girls.

Abstract Background There is an urgent need for effective treatment of patients with relapsed/refractory diffuse large B‐cell lymphoma (R/R‐DLBCL). This trial investigated the efficacy of decitabine in combination with rituximab, cisplatin, cytarabine, dexamethasone (RDHAP) in R/R‐DLBCL. Methods 56 patients were divided into two groups (decitabine‐RDHAP group. n = 35; RDHAP group, n = 21). The primary endpoints were the overall response rate (ORR) and duration of remission (DOR). Secondary objectives were toxicity, progression‐free survival (PFS), and overall survival (OS). Results The ORR was 40% and 33% for decitabine‐RDHAP and RDHAP groups, respectively, with no difference between the groups. The DOR for the decitabine‐RDHAP regimen was higher than that for the RDHAP regimen (p = 0.044). After a median follow‐up of 12.0 months, the median PFS and OS were 7.0 and 17.0 months for in the decitabine‐RDHAP group and 5.0 and 9.0 months in the RDHAP group with no significant differences between the two groups (p = 0.47, 0.17). The incidence of adverse events was not significantly different between groups. Conclusion The decitabine‐RDHAP regimen is effective and well tolerated, and is a promising salvage regimen for R/R‐DLBCL.

Abstract The composition of the gut microbiome was previously found to be associated with clinical responses to dyslipidemia, but there is limited consensus on the dynamic change of the gut microbiota during pregnancy and the specific microbiome characteristics linked to dyslipidemia in pregnant women. We collected fecal samples from 513 pregnant women at multiple time points during pregnancy in a prospective cohort. Taxonomic composition and functional annotations were determined by 16S rRNA amplicon sequencing and shotgun metagenomic sequencing. The predictive potential of gut microbiota on the risk of dyslipidemia was determined. The gut microbiome underwent dynamic changes during pregnancy, with significantly lower alpha diversity observed in dyslipidemic patients compared to their healthy counterparts. Several genera, including Bacteroides, Paraprevotella, Alistipes, Christensenellaceae R7 group, Clostridia UCG-014, and UCG-002 were negatively associated with lipid profiles and dyslipidemia. Further metagenomic analysis recognized a common set of pathways involved in gastrointestinal inflammation, where disease-specific microbes played an important role. Machine learning analysis confirmed the link between the microbiome and its progression to dyslipidemia, with a micro-averaged AUC of 0.824 (95% CI: 0.782-0.855) combined with blood biochemical data. Overall, the human gut microbiome, including Alistipes and Bacteroides, was associated with the lipid profile and maternal dyslipidemia during pregnancy by perturbing inflammatory functional pathways. Gut microbiota combined with blood biochemical data at the mid-pregnancy stage could predict the risk of dyslipidemia in late pregnancy. Therefore, the gut microbiota may represent a potential noninvasive diagnostic and therapeutic strategy for preventing dyslipidemia in pregnancy.