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Abstract Background High levels of low-density lipoprotein cholesterol (LDL-C) can lead to the occurrence and development of atherosclerosis, which is one of the important risk factors for ischemic stroke (IS). However, details regarding the evolution of the IS burden attributable to high LDL-C in China has not been available. The objective of this study was to examine the changes over time, from 1990 to 2019, in the burden of IS attributed to high levels of LDL-C in China and to estimate the individual impacts of age, period, and cohort on the burden of IS associated with high LDL-C. Methods Detailed data on IS burden attributable to high LDL-C from 1990 to 2019 in China were extracted from the Global Burden of Disease (GBD) Study 2019. The numbers and age-standardized rates of IS-related mortality and disability-adjusted life years (DALYs) attributable to high LDL-C were assessed by age and sex. The annual percentage change (APC) and average annual percentage change (AAPC) in the burden of IS due to high LDL-C were analyzed using Joinpoint regression model. The age-period-cohort analysis was carried out to assess the individual impacts of age, period, and cohort on the trends over time of mortality and DALY rate. Results The number of IS-related deaths and DALYs due to high LDL-C in China were 182.7 thousand and 4.43 million in 2019, respectively, both more than double the corresponding numbers reported in 1990. However, despite these increased, the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) remained unchanged. In 2019, men under 84 years of age had higher death and under 79 years of age had higher DALYs than women. However, above these ages, the gender disparities were reversed. Furthermore, age-specific rates of death, as well as DALY of IS attributable to high LDL-C in 2019 increased with age for both women and men, except for death in adults over 95 years old; and were greater in men than in women. From 1990 to 2019, males consistently had a higher ASMR and ASDR than females in China. During 1990–2019, the ASMR in women slightly decreased before 1997, sharply increased from 1997 to 2004, and then continuously decreased from 2004 to 2019, with an overall AAPC value of -0.4% (95% CI -0.8%, -0.0%). However, for the ASMR of men in China, the overall trend is upward and the AAPC is 0.5%(95% CI 0.1%, 0.8%). The ASDR in women and men had the similar trend as the ASMR over the time, with an AAPC of -0.4% (95% CI -0.7%, -0.1%) and 0.3% (95% CI 0.1%, 0.5%), respectively. The age-period-cohort analysis indicated a rise in period effects and a decline in cohort effects on mortality and DALY rate associated with IS caused by high LDL-C in both genders. Age effect on mortality rates from IS due to high LDL-C showed an exponential increased with age in all women and men except for the 60–69 age group and over 95 age group. The age relative risk of IS DALY rate due to high LDL-C increased with age in both genders except for 65–74 age group and over 95 age group. Conclusions From 1990 to 2019, the burden of IS caused by high LDL-C in China significantly increased among both sexes combined and among men, while significantly decreased among women. Elderly have a substantial burden of IS attributable to high LDL-C. Therefore, effective and tailored strategies based on gender and age for IS primary prevention and management of IS and high LDL-C are urgently needed in China.

This study aims to propose a decision-making method based on artificial potential fields (APFs) and finite state machines (FSMs) in emergency conditions. This study presents a decision-making method based on APFs and FSMs for emergency conditions. By modeling the longitudinal and lateral potential energy fields of the vehicle, the driving state is identified, and the trigger conditions are provided for path planning during lane changing. In addition, this study also designed the state transition rules based on the longitudinal and lateral virtual forces. It established the vehicle decision-making model based on the finite state machine to ensure driving safety in emergency situations. To illustrate the performance of the decision-making model by considering APFs and finite state machines. The version of the model in the co-simulation platform of MATLAB and CarSim shows that the developed decision model in this study accurately generates driving behaviors of the vehicle at different time intervals. The contributions of this study are two-fold. A hierarchical vehicle state machine decision model is proposed to enhance driving safety in emergency scenarios. Mathematical models for determining the transition thresholds of lateral and longitudinal vehicle states are established based on the vehicle potential field model, leading to the formulation of transition rules between different states of autonomous vehicles (AVs).

From the connections between permutations and labeled simple graphs, we generalized the super-shuffle product and the cut-box coproduct on permutations to labeled simple graphs. We then proved that the vector space spanned by labeled simple graphs is a Hopf algebra with these two operations.

Background Studies have shown that in hypertensive patients, chronic kidney disease (CKD) is associated with a poor prognosis. Inflammation is a highly important factor in the progression of CKD. Detecting systemic inflammation and intervening promptly in patients with hypertension may help reduce the risk of CKD. The systemic inflammatory response index (SIRI) is a tool used to measure the systemic inflammatory response, but its relationship with CKD in patients with hypertension remains uncertain.Methods We utilized data from the National Health and Nutrition Examination Survey (NHANES), which was conducted between 1999 and 2018. The analysis included a total of 20,243 participants, categorized into three groups based on SIRI tertiles. Logistic regression analysis and restricted cubic spline analysis were used to examine the relationship between the SIRI and CKD.Results In patients with hypertension, there was a notable relationship between the SIRI and the odds of developing CKD. After full adjustment, there was a 31% greater likelihood of developing CKD associated with each incremental increase of 1 unit in the SIRI (OR: 1.31, 95% CI: 1.24–1.39, p

ABSTRACTObjective: An association exists between immune checkpoint inhibitors and hemophagocytic lymphohistiocytosis (HLH). Therefore, the main objective of this study was to collect data on this rare but potentially life-threatening immune-related adverse reaction to identify the medications that cause it, the clinical characteristics, and effective treatments.Methods: Literature in English and Chinese on immune checkpoint inhibitors causing HLH published from August 2014 to March 2024 was analyzed. Immune checkpoint inhibitors, immunotherapy, anti-PD-1, PD-L1 inhibitors, HLH, hemophagocytic lymphohistiocytosis, hemophagocytic syndrome keywords were used to find the literature on China Knowledge Network, Wanfang, PubMed and Emabase Databases.Results and discussion: Twenty-four studies were included, with a total of 27 patients (18 males and 9 females) with a mean age of 58 years (range 26–86). The mean time to the onset of symptoms was 10.3 weeks (7 days–14 months). The main clinical characteristics were fever, cytopenia, splenomegaly, methemoglobinemia, hypofibrinogenemia, and bone marrow biopsy showed phagocytosis. Twenty-two patients improved after the treatment with steroids, cytokine blocking therapy and symptomatic treatment, four patients died, and one patient was not described.Conclusion: HLH should be not underestimated as a potentially serious adverse effect of immune checkpoint inhibitors since appropriate treatments may save the life of patients.

Abstract Background The association between triglyceride–glucose (TyG) index and poor prognosis remains controversial. Whether renal function status affects the ability of the TyG index to predict poor prognosis has not yet been elucidated and merits further studies. Methods This retrospective cohort study included 22,031 participants from communities in the U.S. By juxtaposing the TyG categories with the estimated glomerular filtration rate (eGFR, either

IntroductionHelicobacter pylori (H.pylori, Hp) affects billions of people worldwide. However, the emerging resistance of Hp to antibiotics challenges the effectiveness of current treatments. Investigating the genotype-phenotype connection for Hp using next-generation sequencing could enhance our understanding of this resistance.MethodsIn this study, we analyzed 52 Hp strains collected from various hospitals. The susceptibility of these strains to five antibiotics was assessed using the agar dilution assay. Whole-genome sequencing was then performed to screen the antimicrobial resistance (AMR) genotypes of these Hp strains. To model the relationship between drug resistance and genotype, we employed univariate statistical tests, unsupervised machine learning, and supervised machine learning techniques, including the development of support vector machine models.ResultsOur models for predicting Amoxicillin resistance demonstrated 66% sensitivity and 100% specificity, while those for Clarithromycin resistance showed 100% sensitivity and 100% specificity. These results outperformed the known resistance sites for Amoxicillin (A1834G) and Clarithromycin (A2147), which had sensitivities of 22.2% and 87%, and specificities of 100% and 96%, respectively.DiscussionOur study demonstrates that predictive modeling using supervised learning algorithms with feature selection can yield diagnostic models with higher predictive power compared to models relying on single single-nucleotide polymorphism (SNP) sites. This approach significantly contributes to enhancing the precision and effectiveness of antibiotic treatment strategies for Hp infections. The application of whole-genome sequencing for Hp presents a promising pathway for advancing personalized medicine in this context.

Abstract Background HIV drug resistance increased with the widespread use of antiretroviral drugs, and posed great threat to antiretroviral therapy (ART). Pu’er Prefecture, lying in the southwest of Yunnan Province, China, borders Myanmar, Laos and Vietnam, is also the area where AIDS was discovered earlier, however, in which there has been no information on HIV drug resistance. Methods A cross-sectional survey of pretreatment drug resistance (PDR) was conducted in Pu’er Prefecture in 2021. Partial pol gene sequences were obtained to analyze drug resistance and construct genetic transmission network. HIV drug resistance was analyzed using the Stanford University HIVdb algorithm. Results A total of 295 sequences were obtained, among which 11 HIV-1 strain types were detected and CRF08_BC (62.0%, 183/295) was the predominant one. Drug resistance mutations (DRMs) were detected in 42.4% (125/295) of the sequences. The prevalence of PDR to any antiretroviral drugs, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 10.8% (32/295), 9.5% (28/295), 1.0% (3/295) and 0.3% (1/295), respectively. The risk of PDR occurrence was higher among individuals with CRF01_AE strain types. HIV-1 molecular network was constructed, in which 56.0% (42/75) of links were transregional, and 54.7% (41/75) of links were associated with Lancang County. Among the sequences in the network, 36.8% (35/95) harbored DRMs, and 9.5% (9/95) were drug resistance strains. Furthermore, 8 clusters had shared DRM. Conclusion The overall prevalence of PDR in this study was in a moderate level, but NNRTIs resistance was very approaching to the threshold of public response initiation. PDR was identified in the transmission network, and DRMs transmission was observed. These findings suggested that the consecutive PDR surveillance should be conducted in this region.

Abstract Background HIV/AIDS has transformed into a chronic controllable but not yet curable infectious disease as other chronic diseases to some extent. The additional of so called fourth 90% that included the improved health-related quality of life (HRQoL) for people living with HIV (PLWHIV) required solutions beyond antiretroviral therapy and viral load suppression. This study will explore the role of personality, social economic and prevention strategy effection on HRQoL among people living with HIV/AIDS. Methods A cross-sectional study was conducted among PLWHIV aged more than 16 years old in the 10 municipalities in Yunnan Province, China from October 2019 to May 2020, enrolling total 1997 participants. Individual-level HRQoL data were measured by 12-item Short Form Health Survey (SF-12) and EuroQol Five Dimensions Questionnaire (EQ-5D-5L). We assembled municipal-level data about social economic from Yunnan Statistical Yearbook in 2020 and strategy practice information from the self-evaluation system. We used the principal component analysis to build the social economic and strategy effect on each area respectively and one-way ANOVA was used to perform univariate analysis to identify the predictors with significant differences. Finally we used multi-level model (MLM) to explore the personality, social economic and strategy effects in health-related quality of life among PLWHIV. Results The global score for quality of life measured using EQ-5D-5L had an estimated mean score (standard deviation, SD) of 0.901 ± 0.146. The HRQoL score measured using PCS-12 had an estimated mean score (SD) of 46.62 ± 8.55. The mean MCS-12 score (SD) was estimated to be 47.80 ± 9.71. The area-level predictors explained a proportion of 13.6–17.2% for the between-area variation of the HRQoL scores, regardless of the total HRQoL, physical component and mental component. The impacts of stigma (P

Hopf algebras are important objects in algebraic combinatorics since they have strong stability. In particular, its dual space is an important tool to study the properties of the original Hopf algebra. Based on the classical shuffle Hopf algebra structure, we have proved that the shuffle product and deconcatenation coproduct on the standard factorizations of permutations define a graded shuffle Hopf algebra on permutations. In this paper, we figure out a new product and a new coproduct on permutations to get the duality of this graded shuffle Hopf algebra.

Background Effective means for early diagnosis are imperative to reduce death rate of non-small cell lung cancer (NSCLC) patients. We aimed to find out high-performance serologic markers to distinguish early-stage NSCLC patients from benign pulmonary nodule patients and healthy controls (HC). Cystatin-SN (CST1) is an active cysteine protease inhibitor of the CST superfamily, involving in the processes of inflammation and tumorigenesis. This is the first exploration of the diagnostic and prognostic values of serum CST1 in NSCLC. Methods We analyzed the transcriptome data from The Cancer Genome Atlas and the Gene Expression Omnibus database, screened biomarkers for NSCLC, and verified the candidate markers via the ONCOMINE database. Then, we performed ELISA, western blotting, and immunohistochemistry analysis to detect the expression levels of CST1 in NSCLC cell lines, tumor tissues, and serum samples of clinical cohorts. Results We identified 3 up-regulated secreted protein-encoding genes, validated the expression levels of CST1 in NSCLC tumor tissues and cell lines, and found that serum CST1 levels of NSCLC (4289 ± 2405 pg/mL) were significantly higher than those of PBN patients (1558 ± 441 pg/mL, P < .0001) and healthy controls (1529 ± 416 pg/mL, P < .0001). The AUC of the combination of CST1, Cytokeratin 19 fragment (Cyfra21-1), and Carcinoembryonic antigen (CEA) for distinguishing early-stage NSCLC from PBN/HC was as high as .914/0.925. Furthermore, our results suggested that the NSCLC patient with low serum CST1 level had a better survival rate. Conclusions Serum CST1 may serve as a novel diagnostic marker for differentiating early-stage NSCLC from PBN and HC, and could be used as a prognosis predictor in NSCLC patients.

Background: We evaluated the diagnostic value of plasma Macrophage inhibitory cytokine-1 (MIC-1) in distinguishing patients with nasopharyngeal carcinoma (NPC) and explored its complementary role with widely used Epstein-Barr virus (EBV) related markers, EBV capsid antigen-specific IgA (VCA-IgA) and EBV copy number. Methods: ELISA was used to analyze the plasma MIC-1 levels in 190 NPC patients, 72 VCA-IgA-positive healthy donors (VP), and 219 normal subjects with negative VCA-IgA (VN). 10 pairs of plasma samples before and after radiotherapy were also included. Results: The plasma MIC-1 levels were significantly higher in NPC patients (Median: 678.39 ng/mL) than those in VN and VP (310.29 and 294.59, p < 0.001). Receiver operating characteristic (ROC) curves of the MIC-1 concentrations revealed that the area under the ROC curve (AUC) was 0.790 (95% confidence interval [CI]: 0.748-0.832), with a sensitivity of 63.7%, and a specificity of 85.9% respectively, for distinguishing NPC patients from the healthy donors. Similarly, between NPC and VP, ROC was 0.796 (0.738-0.853) with sensitivity of 63.7%, and specificity of 88.9%. In addition, between NPC and VN, ROC was 0.788(0.744-0.832) with sensitivity of 63.7%, and specificity of 84.9%. Further, we found that MIC-1 could complement VCA-IgA and EBV DNA markers, with a negative rate of 88.9% in VCA-IgA-positive healthy controls, and a positive rate of 59.0% in EBV DNA negative NPC patients, respectively. Also, the MIC-1 plasma concentration dropped significantly after radiotherapy ( p = 0.027). Conclusions: MIC-1 can complement VCA-IgA titers and EBV DNA copy number tests in NPC detection, improve identification of EBV DNA-negative NPC patients, and distinguish NPC from VCA -IgA positive healthy controls.

The problem of computing products of Schubert classes in the cohomology ring can be formulated as theproblem of expanding skew Schur polynomial into the basis of ordinary Schur polynomials. We reformulate theproblem of computing the structure constants of the Grothendieck ring of a Grassmannian variety with respect to itsbasis of Schubert structure sheaves in a similar way; we address the problem of expanding the generating functions forskew reverse-plane partitions into the basis of polynomials which are Hall-dual to stable Grothendieck polynomials. From this point of view, we produce a chain of bijections leading to Buch’s K-theoretic Littlewood-Richardson rule.

In this paper, we first prove that any atom of a permutation obtained by the super-shuffle product of two permutations can only consist of some complete atoms of the original two permutations. Then, we prove that the super-shuffle product and the cut-box coproduct on permutations are compatible, which makes it a bialgebra. As this algebra is graded and connected, it is a Hopf algebra.

A series of ester and amide derivatives of triterpenoid saponin Pulsatilla saponin D (PSD) were designed, synthesized, and evaluated for their antiproliferative activity. Compounds 1 and 6 displayed 1.7–8.3 times more potent cytotoxicity (IC50 = 1.2–4.7 and 1.7–4.5 μM, respectively) against five human tumor cell lines (SMMC-7721, MCF-7, NCI-H460, A549, and HCT-116) in vitro and lower acute toxicity to mice in vivo than did PSD. Furthermore, compound 6 was observed to show potent tumor growth inhibition against mice H22 hepatocellular cells (49.8% at 20 mg/kg) and induce cell cycle at G1 phase and apoptosis in HCT-116 cells.

We introduce a new statistic, skip, on rational $(3,n)$-Dyck paths and define a marked rank word for each path when $n$ is not a multiple of 3. If a triple of valid statistics (area; skip; dinv) are given, we have an algorithm to construct the marked rank word corresponding to the triple. By considering all valid triples we give an explicit formula for the $(m,n)$-rational $q; t$-Catalan polynomials when $m=3$. Then there is a natural bijection on the triples of statistics (area; skip; dinv) which exchanges the statistics area and dinv while fixing the skip. Thus we prove the $q; t$-symmetry of $(m,n)$-rational $q; t$-Catalan polynomials for $m=3$..

We identify two seemingly disparate structures: supercharacters, a useful way of doing Fourier analysis on the group of unipotent uppertriangular matrices with coefficients in a finite field, and the ring of symmetric functions in noncommuting variables. Each is a Hopf algebra and the two are isomorphic as such. This allows developments in each to be transferred. The identification suggests a rich class of examples for the emerging field of combinatorial Hopf algebras.

Bergeron and Li have introduced a set of axioms which guarantee that the Grothendieck groups of a tower of algebras $\bigoplus_{n \geq 0}A_n$ can be endowed with the structure of graded dual Hopf algebras. Hivert and Nzeutzhap, and independently Lam and Shimozono constructed dual graded graphs from primitive elements in Hopf algebras. In this paper we apply the composition of these constructions to towers of algebras. We show that if a tower $\bigoplus_{n \geq 0}A_n$ gives rise to graded dual Hopf algebras then we must have $\dim (A_n)=r^nn!$ where $r = \dim (A_1)$.

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.

Abstract Though sterile diet, post‐transplantation surgery is a clinical strategy for patient care to prevent the infiltration of gut pathogens, less is known about its effects on the gut microbiome. Here, the gut microbiome dynamics of leukemia patients following a 120‐day “sterile‐normal” diet strategy posthematopoietic cell transplantation are examined. In contrast to the traditional idea, a sterile diet leads to the lowest gut microbiota diversity (p

Abstract Background Prospective observational studies have demonstrated that the machine learning (ML) -guided noninvasive chromosome screening (NICS) grading system, which we called the noninvasive chromosome screening-artificial intelligence (NICS-AI) grading system, can be used embryo selection. The current prospective interventional clinical study was conducted to investigate whether this NICS-AI grading system can be used as a powerful tool for embryo selection. Methods Patients who visited our centre between October 2018 and December 2021 were recruited. Grade A and B embryos with a high probability of euploidy were transferred in the NICS group. The patients in the control group selected the embryos according to the traditional morphological grading. Finally, 90 patients in the NICS group and 161 patients in the control group were compared statistically for their clinical outcomes. Results In the NICS group, the clinical pregnancy rate (70.0% vs. 54.0%, p