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The Chronic Care Model (CCM) is a framework that supports the proactive, planned, coordinated and patient-centered care of chronic diseases. The Patient Assessment of Chronic Illness Care (PACIC) scale is a valuable tool for evaluating patients’ perspectives on chronic care delivery based on the CCM. Few studies have examined its application in China. This study assesses hypertension care in Chinese patients and explores how PACIC scores relate to patient compliance. A cross-sectional study was conducted in Hangzhou, China, from June to August 2021, including 253 hypertensive patients from 5 county hospitals and 13 primary healthcare centers. The study used the PACIC scale to assess hypertension care delivery and the Compliance of Hypertensive Patients scale (CHPS) to measure patient compliance. Multiple linear regression analyses were used to explore the relationship between demographic characteristics and the total and domain scores of PACIC, as well as the association between CHPS and the domain scores of PACIC. The mean value of overall the PACIC score was 3.12 (out of 5). Problem solving/contextual domain had the highest average score for each item, while follow up/coordination domain had the lowest. Patient activation had negative effects on intention (β = −.18, P

Backgrounds Hemophagocytic lymphohistiocytosis (HLH) is an acute, rapidly progressive systemic inflammatory disorder that often occurs secondary to hematological malignancies among other conditions in adults. Although the annual incidence of HLH is increasing, detailed epidemiological knowledge of HLH is still limited, especially in patients with hematological malignancies.Objectives To analyze the impact of hematological malignancies on the epidemiology and outcomes of HLH.Study design Data from the National Readmission Database (NRD) from 2011 to 2020 were analyzed to explore the epidemiological trends and in-hospital outcomes of HLH patients, particularly those with hematological malignancies.Results Our analysis included 7579 HLH hospitalizations, with hematological malignancies implicated in 24.01% of cases. Our findings reveal a steady increase in HLH diagnoses from 145 cases in 2011 to 1848 in 2020, with the proportion linked to hematological malignancies remaining consistent. Patients with hematological malignancies-associated HLH exhibited higher rates of in-hospital mortality (31.6%) than those without (14.4%), and a higher 30-day readmission rate, underscoring a critical need for early detection and treatment revision.Conclusions Despite the increasing awareness and diagnosis of HLH, the prognosis of patients with HLH associated with hematological malignancies remains poor, highlighting the urgent need for improved management strategies and therapeutic interventions.

Background Evidence on maintenance therapy following frontline induction is sparse in primary light-chain amyloidosis (AL), especially for those who do not undergo autologous haematopoietic stem cell transplantation (ASCT).Methods We enrolled primary AL patients who achieved at least haematologic very good partial response (VGPR) by the 4th month at the frontline from December 2008 to June 2023 at Zhongshan Hospital, Fudan University. Those who followed maintenance therapy were identified as the maintenance group (n = 44), whereas those entering the observational phase were classified as the observational group (n = 24).Results After 7.2(interquartile range, 4.7–18.6) months of maintenance therapy, 9(20.5%), 14(31.8%) and 5 (11.4%) patients achieved improvement in haematologic, cardiac and renal response respectively. Five (11.4%) patients had minimal residual disease (MRD) response conversion from positive to negative based on maintenance therapy. In the observation group, none of the patients had haematologic response improvement, with 3(12.5%) and 1(4.2%) patient showing cardiac and renal response improvement during follow-up.Conclusion This study identified the clinical benefits of maintenance therapy in patients with AL who did not undergo ASCT in real-world practice.

Introduction Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab.Methods Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan–Meier method and Cox regression models.Results Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001–3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150–5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078–6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173–12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043).Conclusions Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6–VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

Capsaicinoids are produced uniquely in pepper fruits, and its level determines the commercial quality and health-promoting properties of pepper. So, it is particularly important to increase capsaicinoids content in pepper. Rhizosphere microbiota is critical to plant growth and performance, and affected by plant varieties. However, the impact of pepper varieties with different capsaicinoids yields on the rhizosphere microbiota is poorly understood. Using high-throughput sequencing of the 16S rRNA and internal transcribed spacer (ITS) region, we investigated the rhizosphere microbial community among five pepper varieties containing different capsaicinoids. Our results demonstrated that pepper variety significantly influenced the diversity and structure of rhizosphere microbial community. Bacterial diversity in varieties with high capsaicinoids content was significantly higher than in varieties with low capsaicinoids content, while fungal diversity was opposite to bacterial diversity. The correlation analysis revealed that 19 dominant bacterial genera (e.g., Chujaibacter, Rhodanobacter, and Gemmatimonas) were significantly correlated with capsaicinoids content, and nine of them were also significantly associated with soil nutrients, whereas only one fungal genus (Podospora) was significantly correlated with capsaicinoids content. Additionally, almost all genera which significantly correlated to capsaicinoids content were biomarkers of the five pepper varieties and the correlation was well corresponding to the capsaicinoids content. Overall, our results confirmed that the variety of pepper significantly affected the rhizosphere microbial community in the fields, and bacteria and fungi responded differently to capsaicinoids, which may affect the biosynthesis of capsaicinoids and contribute to further improvement of capsaicinoids production in pepper fruits.

IntroductionMicroorganisms exhibit intricate interconnections with tea plants; however, despite the well-established role of microorganisms in crop growth and development, research on microbes within the tea plant remains insufficient, particularly regarding endophytic microorganisms.MethodsIn this study, we collected samples of leaves and rhizosphere soils from ‘Zhuyeqi’, ‘Baojing Huangjincha#1’, ‘Baiye#1’, and ‘Jinxuan’ varieties planted.ResultsOur analyses revealed significant variations in tea polyphenol contents among tea varieties, particularly with the ‘Zhuyeqi’ variety exhibiting higher levels of tea polyphenols (>20% contents). Microbiome studies have revealed that endophytic microbial community in tea plants exhibited higher host specificity compared to rhizospheric microbial community. Analyses of across-ecological niches of the microbial community associated with tea plants revealed that soil bacteria serve as a significant reservoir for endophytic bacteria in tea plants, Bacillus may play a crucial role in shaping the bacterial community across-ecological niche within the tea plants with higher tea polyphenol levels. In the aforementioned analyses, the microbial community of ‘Zhuyeqi’ exhibited a higher degree of host specificity for leaf endophytic microorganisms, the topological structure of the co-occurrence network is also more intricate, harboring a greater number of potential core microorganisms within its nodes. A closer examination was conducted on the microbial community of ‘Zhuyeqi’, further analyses of its endophytic bacteria indicated that its endophytic microbial community harbored a greater abundance of biomarkers, particularly among bacteria, and the enriched Methylobacterium and Sphingomonas in ‘Zhuyeqi’ may play distinct roles in disease resistance and drought resilience in tea plants.ConclusionIn summary, this study has shed light on the intricate relationships of tea plant varieties with their associated microbial communities, unveiling the importance of microorganisms and tea varieties with higher tea polyphenols, and offering valuable insights to the study of microorganisms and tea plants.

Introduction: DNA ploidy (P), stroma fraction (S), and nucleotyping (N) collectively known as PSN, have proven prognostic accuracy in stage II colorectal cancer (CRC). However, few studies have reported on the prognostic value of the PSN panel in stage III colon cancer patients receiving capecitabine and oxaliplatin adjuvant chemotherapy. Objectives: This study aimed to validate PSN’s prognostic impact on stage III colon cancer, identifying candidates for optimized adjuvant chemotherapy duration. Design: A retrospective analysis was conducted on a cohort of stage III colon cancer patients from April 2008 to June 2020. Methods: Postoperative pathological samples from stage III colon cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy at Sun Yat-sen University Cancer Center were retrospectively collected. Automated digital imaging assessed PSN, categorizing risk groups. Kaplan–Meier, Cox regression, and time-dependent receiver operating characteristic analysis compared model validity. Results: Significant differences in 5-year disease-free survival (DFS) and overall survival (OS) were noted among PSN-based low-, moderate-, and high-risk groups (DFS: 92.10% versus 83.62% versus 79.80%, p = 0.029; OS: 96.69% versus 93.99% versus 90.12%, p = 0.016). PSN emerged as an independent prognostic factor for DFS [hazard ratio (HR) = 1.409, 95% confidence interval (CI): 1.002–1.981, p = 0.049] and OS (HR = 1.720, 95% CI: 1.127–2.624, p = 0.012). The PSN model, incorporating perineural invasion and tumor location, displayed superior area under the curve for 5-year (0.692 versus 0.553, p = 0.020) and 10-year (0.694 versus 0.532, p = 0.006) DFS than TNM stage. In the PSN high-risk group, completing eight cycles of adjuvant chemotherapy significantly improved 5-year DFS and OS compared to four to seven cycles (DFS: 89.43% versus 71.52%, p = 0.026; OS: 96.77% versus 85.46%, p = 0.007). Conclusion: The PSN panel effectively stratifies stage III colon cancer, aiding in optimized adjuvant chemotherapy duration determination.

Abstract Background For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. Methods Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (

Objectives The collapse of femoral head is a serious symptom of osteonecrosis of the femoral head (ONFH), resulting in hip pain and deformity. However, it is hardly possible to reestablish the femoral head nonoperatively once the collapse happens. Predicting femoral head collapse is of great value for the prognosis of ONFH. This study aimed to develop a new method to quantify the preserved thickness of femoral head and to assess its diagnostic contribution in predicting femoral head collapse on plain radiographs. Methods This was a single‐center retrospective study. A total of 101 hips (85 patients) with ARCO stage II from January 2008 to December 2016 were included in this study. The preserved thickness was measured on standard anteroposterior (AP) and frog‐leg (FL) radiographs. The anteroposterior view's preserved thickness ratio (APTR) and the frog‐leg view's preserved thickness ratio (FPTR) were calculated to show the preserved thickness ratio of the femoral head anteriorly and laterally. Univariate and multivariate logistic regression was performed to determine the risk factors for collapse. Sensitivity, specificity, and cut‐off values for APTR and FPTR were determined by the receiver operating characteristic (ROC) curve analysis. Kaplan–Meier (K‐M) analysis was applied to determine femoral head survival in ONFH patients. Results The mean age of the 27 females and 58 males was 38.93 years old. The mean follow‐up time was 74.62 (36–124) months in the non‐collapse group and 18.66 (3–82) months in the collapse group. Femoral head collapse was observed in 62 hips during the follow‐up period. Logistic regression analysis and ROC results showed that APTR

With the increasing development of logistics industry, an important question arises: which logistics format should an agricultural product seller select? Or when an agricultural product seller does select a certain logistics format? To answer this question, we explore three different green agricultural product supply chain models/scenarios: a self-managed logistics format(N); a third-party enterprise logistics format(S); and a platform logistics format(E). Using the game-theoretic model, we investigate the impact of the cost coefficient on the agricultural product seller's logistics preference under the three logistics scenarios. Our theoretical analyses show that when the cost coefficient is small, the agricultural product seller prefers to cooperate with the 3PL enterprise, but as the coefficient increases, the agricultural product seller prefers to choose her self-managed logistics. Therefore, to optimize the logistics strategy of the agricultural product seller under B2C mode, it is necessary to build a reasonable logistics management mechanism and a perfect logistics distribution system to reduce the logistics service cost coefficient.

Abstract Mutant KRAS (KRASMUT) is often exploited by cancers to shape tumor immunity, but the underlying mechanisms are not fully understood. Here we report that tumor-specific cytotoxic T lymphocytes (CTLs) from KRASMUT cancers are sensitive to activation-induced cell death (AICD). circATXN7, an NF-κB-interacting circular RNA, governs T cell sensitivity to AICD by inactivating NF-κB. Mechanistically, histone lactylation derived from KRASMUT tumor cell-produced lactic acid directly activates transcription of circATXN7, which binds to NF-κB p65 subunit and masks the p65 nuclear localization signal motif, thereby sequestering it in the cytoplasm. Clinically, circATXN7 upregulation in tumor-specific CTLs correlates with adverse clinical outcomes and immunotherapeutic resistance. Genetic ablation of circAtxn7 in CD8+ T cells leads to mutant-selective tumor inhibition, while also increases anti-PD1 efficacy in multiple tumor models in female mice. Furthermore, targeting circATXN7 in adoptively transferred tumor-reactive CTLs improves their antitumor activities. These findings provide insight into how lymphocyte-expressed circRNAs contribute to T-cell fate decisions and anticancer immunotherapies.

Abstract Objectives Intratumor heterogeneity (ITH) is an important factor for clinical outcomes in patients with multiple myeloma (MM). High ITH has been proven to be a key reason for tumor immune escape and treatment resistance. Neoantigens are thought to be associated with ITH, but the specific correlation and functional basis for this remains unclear. Methods We study this question through the whole‐exome sequencing (WES) data from 43 high ITH newly diagnosed MM patients in our center. Mutant allele tumor heterogeneity (MATH) was conducted to quantify ITH. The cutoff value for high intratumor heterogeneity was determined by comparing MATH of different kinds of tumors. NeoPredPipe was performed to predict neoantigens and binding affinity. Results Compared to other tumors, MM has a relatively low tumor mutation burden but a high ITH. Patients with high MATH had significantly shorter progression‐free survival times than those with low MATH (p = 0.001). In high ITH samples, there is a decrease in strong‐binding neoantigens (p = 0.019). The loss of strong‐binding neoantigens is a key factor for insensitivity to therapy (p = 0.015). Loss of heterozygosity in HLA was not observed. In addition, patients with fewer neoantigens loss had higher rates of disease remission (p = 0.047). CD8 + T cells (p = 0.012) and NK cells (p = 0.011) decreased significantly in patients with high neoantigens loss rate. A prediction model based on neoantigens was built to evaluate the strength of immune escape. Conclusion The loss of strong‐binding neoantigens explains why tumors with high ITH have a higher degree of immune escape and may be feasible for deciding the clinical treatment of MM.

Abstract Background Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown. Methods Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo. Results Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N6-methyladenosine (m6A) modification orchestrated efficient initiation of circ-YAP translation, requiring m6A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop. Conclusions Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis.

Abstract Stimuli-responsive elastic metamaterials augment unique subwavelength features and wave manipulation capabilities with a degree of tunability, which enables them to cut across different time scales and frequency regimes. Here, we present an experimental framework for robust local resonance bandgap control enabled by enhanced magneto-mechanical coupling properties of a magnetorheological elastomer, serving as the resonating stiffness of a metamaterial cell. During the curing process, ferromagnetic particles in the elastomeric matrix are aligned under the effect of an external magnetic field. As a result, particle chains with preferred orientation form along the field direction. The resulting anisotropic behavior significantly boosts the sensitivity of the metamaterial’s elastic modulus to the imposed field during operation, which is then exploited to control the dispersive dynamics and experimentally shift the location and width of the resonance-based bandgap along the frequency axis. Finally, numerical simulations are used to project the performance of the magnetically-tunable metamaterial at stronger magnetic fields and increased levels of material anisotropy, as a blueprint for broader implementations of in situ tunable active metamaterials.

Abstract Background For femoral neck fractures in young and middle-aged patients, both fibula allograft with cannulated screw fixation and ordinary cannulated screw fixation are clinically effective treatments. However, for unstable femoral neck fractures, ordinary cannulated screw fixation is characterized by a high risk of postoperative complications and a high rate of mechanical failure after internal fixation. For this study, we systematically compared the long-term efficacy and postoperative complications of these two procedures. Methods A total of 156 subjects diagnosed as femoral neck fractures participated in our study. Subjects in the combination group underwent fibula allograft with cannulated screw fixation (n = 76), and those in the control group were treated with ordinary cannulated screw fixation (n = 80). Baseline characteristics, perioperative outcomes, Harris hip score (HHS) and EuroQoL five-dimension questionnaire (EQ-5D); and the incidence of postoperative and bone healing complications in the two groups were recorded and compared. Results The average follow-up time was more than 10 years. Intra-operative blood loss significantly increased in the combination group compared with the control group (P

Artificial intelligence-powered recommendation systems have gained popularity as a tool to enhance user experience and boost sales. Platforms often need to make decisions about which seller to recommend and the strength of the recommendation when conducting recommendations. Therefore, it is necessary to explore the recommendation strategy of the platform in the case of duopoly competition. We develop a game model where two competing manufacturers sell products through an agency contract on a common platform, and they can decide whether or not to provide recommendations to the manufacturers. Our highlight lies in the endogenous recommendation strength of the platform. The findings suggest that it is optimal for the platform to offer recommendation services when the commission rate is high. The platform also prefers to only recommend one manufacturer in the market with low or high competition, but it prefers to recommend both manufacturers in moderately competitive markets. From the view of manufacturers, they can benefit from the recommendation service as long as the commission rate is not too low. Moreover, recommending only one manufacturer consistently yields stronger recommendations compared to recommending multiple manufacturers. However, the impact of recommendation on prices is influenced by the commission rate and product substitutability. These results have significant implications for platform decision making and provide valuable insights into the trade-offs involved in the development of recommendation systems.

BackgroundPicroside II (P-II) is the main bioactive constituent of Picrorhiza Kurroa, a traditional Chinese herb of interest for its proven anti-inflammatory properties. Its beneficial effects have been noted across several physiological systems, including the nervous, circulatory, and digestive, capable of treating a wide range of diseases. Nevertheless, the potential of Picroside II to treat osteoarthritis (OA) and the mechanisms behind its efficacy remain largely unexplored.AimThis study aims to evaluate the efficacy of Picroside II in the treatment of osteoarthritis and its potential molecular mechanisms.MethodsIn vitro, we induced cellular inflammation in chondrocytes with lipopolysaccharide (LPS) and subsequently treated with Picroside II to assess protective effect on chondrocyte. We employed the Cell Counting Kit-8 (CCK-8) assay to assess the impact of Picroside II on cell viability and select the optimal Picroside II concentration for subsequent experiments. We explored the effect of Picroside II on chondrocyte pyroptosis and its underlying molecular mechanisms by qRT-PCR, Western blot (WB) and immunofluorescence. In vivo, we established the destabilization of the medial meniscus surgery to create an OA mouse model. The therapeutic effects of Picroside II were then assessed through Micro-CT scanning, Hematoxylin-eosin (H&E) staining, Safranin O-Fast Green (S&F) staining, immunohistochemistry and immunofluorescence.ResultsIn in vitro studies, toluidine blue and CCK-8 results showed that a certain concentration of Picroside II had a restorative effect on the viability of chondrocytes inhibited by LPS. Picroside II notably suppressed the expression levels of caspase-1, IL-18, and IL-1β, which consequently led to the reduction of pyroptosis. Moreover, Picroside II was shown to decrease NLRP3 inflammasome activation, via the MAPK/NF-κB signaling pathway. In vivo studies have shown that Picroside II can effectively reduce subchondral bone destruction and osteophyte formation in the knee joint of mice after DMM surgery.ConclusionsOur research suggests that Picroside II can inhibit chondrocyte pyroptosis and ameliorate osteoarthritis progression by modulating the MAPK/NF-κB signaling pathway.

Colitis is a chronic bowel disease characterized by damage to the lining of the large intestine, with its precise underlying causes remaining incompletely understood. In this study, we provide evidence that circular RNA circNlgn plays a pivotal role in promoting the development of colitis. Colitis patients produce significant higher levels of circNlgn. Transgenic mice expressing circNlgn exhibit heightened susceptibility to colitis development and progression, primarily attributed to the presence of the protein isoform Nlgn173 encoded by circNlgn. Nlgn173 undergoes translocation into cell nuclei, where it interacts with actin, impeding the binding of actin-related protein 2 and 3 (Arp2/3) complex to actin molecules. Consequently, this leads to a reduction in actin polymerization. Mechanistically, Nlgn173 enhances tyrosine-53 phosphorylation of nuclear actin, diminishing its capacity to interact with the Arp2/3 complex and causing a decrease in filamentous actin levels. These alterations in actin dynamics result in inhibited cell cycle progression, increased apoptosis, and decreased proliferation of colonic epithelial cells, thereby exacerbating colitis development and progression. In contrast, the silencing of circNlgn or the targeted inhibition of Nlgn173 translation and nuclear translocation leads to the promotion of nuclear actin polymerization, enhanced cell survival, and reduced apoptosis and ultimately improves the outcome of colitis in vivo. Interestingly, nuclear actin polymerization is highly related with expression of PIAS3, which modulates signal transducer and activator of transcription 3 and NF-κB activity in colitis. Strategies such as circNlgn knockdown and targeting nuclear actin polymerization of the colonic epithelium may explore a novel avenue for acute ulcerative colitis clinical intervention.

Abstract Background To improve the early detection rate of multiple myeloma (MM), the M‐protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic‐based monoclonal immunoglobulin (M‐protein) screening integrated into the blood biochemistry panel. This study updated 7‐year follow‐up findings of MM patients diagnosed by screening‐driven and symptom‐driven approaches. Methods The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening‐driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma‐related end‐organ damage were categorized into the symptom‐driven group. Results There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening‐driven group, while 545 were to the symptom‐driven group. Compared to the symptom‐driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease‐related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression‐free survival (PFS) than the symptom‐driven group (62.2 vs. 24.9 months, p

ABSTRACTObjectives The clinical outcomes of multiple myeloma (MM) patients are highly variable in the real-world setting. Some MM patients may have clinical endings that do not abide by the book. We aim to describe features of MM patients with extreme survivals in real-world practice.Methods This retrospective study enrolled 941 patients consecutively visited a national medical center, China, between July 1995 and December 2021. Among patients, we identified two groups of MM patients with extreme survivals, 56 were in the long-term remission (LR) group with progression-free survival (PFS) ≥ 60 months, and 82 were in the rapid progression (RP) group with PFS ≤ 6 months.Results CRAB features, of which hypercalcemia, renal insufficiency, and anemia were more common in the RP group, except for bone disease, with a comparable incidence at diagnosis in both groups (88.8 vs 85.7%, P = 0.52). High-risk cytogenetics was detected in 45.7% of patients in the RP group. Of note, 14.3% of MM patients in the LR group harbored del (17p). According to the Revised International Staging System (R-ISS), 9% of patients belonged to stage I in the RP group, and 19% of patients in the LR group were found in stage III. There were 8 (15.7%) patients in the LR group only achieved partial response (PR) as the best response. Median time to best response (TBR) for LR and RP group patients was 4.6 and 1.4 months, respectively.Conclusions The disparities in the survivals of MM patients indicated that some unexpected factors have influenced the outcomes in the real-world setting.

Abstract Background Significant advances in multiple myeloma (MM) over the past 15 years led to exciting changes in the management of MM patients in China, which in turn brought about the early diagnoses, precise risk stratifications, and improved prognoses. Methods We summarized the dynamic changes in the management of newly diagnosed (ND) MM in a national medical center, crossing the old and novel drug era. Demographics, clinical characteristics, first‐line treatment, response rate, and survival were retrospectively collected among NDMMs diagnosed in Zhongshan Hospital Fudan University from January 2007 to October 2021. Results Of the 1256 individuals, median age was 64 (range 31–89) with 45.1% patients >65 years. About 63.5% were male, 43.1% were at ISS stage III and 9.9% had light‐chain amyloidosis. Patients with abnormal ratio of free light chain (80.4%), extramedullary disease (EMD, 22.0%), and high‐risk cytogenetic abnormalities (HRCA, 26.8%) were detected by novel detection techniques. The best confirmed ORR was 86.5%, including 39.4% with CR. Short‐ and long‐term PFS and OS rates persistently increased each year along with increasing novel drug applications. Median PFS and OS were 30.9 and 64.7 months. Advanced ISS stage, HRCA, light‐chain amyloidosis and EMD independently predicted an inferior PFS. First‐line ASCT indicated a superior PFS. Advanced ISS stage, elevated serum LDH, HRCA, light‐chain amyloidosis, and receiving PI/IMiD‐based regimen versus PI+IMiD‐based regimen independently indicated a poorer OS. Conclusions In brief, we illustrated a dynamic landscape of MM patients in a national medical center. Chinese MM patients evidently benefited from newly introduced techniques and drugs in this field.

Abstract Background Hypoxia is a hallmark of solid tumors and leads to the metabolic reprogramming of cancer cells. The role of epigenetic regulation between hypoxia and aberrant cholesterol metabolism in colorectal cancer (CRC) remains elusive. Methods Hypoxia-responsive circular RNAs (circRNAs) were identified by high throughput RNA sequencing between CRC cells cultured under normoxia or hypoxia. The protein-coding potential of circINSIG1 was identified by polysome profiling and LC–MS. The function of circINSIG1 was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. Results A novel hypoxia-responsive circRNA named circINSIG1 was identified, which was upregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Mechanistically, circINSIG1 encoded a 121 amino acid protein circINSIG1-121 to promote K48-linked ubiquitination of the critical cholesterol metabolism regulator INSIG1 at lysine 156 and 158 by recruiting CUL5-ASB6 complex, a ubiquitin E3 ligase complex, thereby inducing cholesterol biosynthesis to promote CRC proliferation and metastasis. The orthotopic xenograft tumor models and patient-derived xenograft models further identified the role of circINSIG1 in CRC progression and potential therapeutic target of CRC. Conclusions circINSIG1 presents an epigenetic mechanism which provides insights into the crosstalk between hypoxia and cholesterol metabolism, and provides a promising therapeutic target for the treatment of CRC.

Objectives: This study aimed to investigate the factors associated with maintenance of viral suppression after antiretroviral therapy (ART) discontinuation. Methods: Databases were searched for studies published between January 01, 2011, and July 01, 2022, that correlated the time of virus rebound with treatment interruption (TI). The corresponding data were extracted from these studies. A fixed-effects model was used to calculate pooled estimates. Results: Thirty-one studies were included in this analysis. Results showed that patients who started ART during acute or early infection had longer viral control than those who started ART during chronic infection. It has been reported that some broadly neutralizing HIV-1-specific antibodies can significantly prolong viral inhibition. The study also found that approximately 7.2% of patients achieved post-treatment control (PTC) approximately a year after TI. Conclusion: ART initiation in the acute or early phases can delay viral rebound after TI. Cell-associated HIV RNA and HIV DNA have been difficult to prove as able to predict viral rebound time. Many vaccines and antibodies have also been shown to be effective in prolonging viral control in people without PTC, and more research is needed to develop alternative ART therapies that can effectively inhibit or even eliminate HIV.

Evaluating and selecting appropriate contractors is critical to the success of specific construction projects in the building industry. Existing approaches for addressing this problem are unsatisfactory due to the ignorance of the multi-dimensional nature of the evaluation process and inappropriate consideration of existent risks. This study presents a DEA game cross-efficiency model with loss aversion for evaluating and selecting specific contractors. The competitiveness of the evaluation process is modeled using game theory with respect to the adoption of the cross-efficiency model. The attitude of the decision maker toward risks is tackled with the use of loss aversion, which is a phenomenon formalized in prospect theory. As a result, the proposed approach can adequately screen available contractors through prequalification and adequately consider the attitude of the decision maker toward risks, leading to effective decisions being made. An example is presented to demonstrate the applicability of the proposed model in evaluating and selecting appropriate contractors for specific construction projects. The results show that the proposed model is effective and efficient in producing a unique solution for contractor selection through appropriate modeling of the multi-dimensional contractor selection process and adequate consideration of the competition between the contractors and the attitude of the decision maker toward risks in practical situations.

Introduction: Alexithymia and perceived stress have been recognized as risk factors for suicide in patients with major depressive disorder (MDD). However, few studies have been conducted to examine the relationship between these factors. Methods: A cross-sectional study was conducted on 105 MDD patients. Alexithymia was assessed by the 20-Item Toronto Alexithymia Scale (TAS), perceived stress was assessed by the Perceived Stress Scale (PSS), severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD), and suicidal ideation was assessed by the self-report Beck Scale for Suicide Ideation (SSI). A sequential mediation model was established to test the mediating effects of perceived stress and severity of depression on the association between alexithymia and suicidal ideation. Results: 81 of the 105 participants (77.14 %) had suicidal ideation. Patients with suicidal ideation had greater difficulty in identifying feelings (DIF) (p = 0.046), higher severity of depression (p = 0.005) and perceived stress (p = 0.003). DIF subscale score of TAS was associated with perceived stress (r = 0.292, p = 0.003), severity of depression (r = 0.349, p

Abstract Oxaliplatin is a widely used chemotherapy drug for patients with advanced colorectal cancer (CRC); however, frequent drug resistance limits its therapeutic efficacy in patients. Here, this work identifies cyclin‐dependent kinase 1 (CDK1) as a critical contributor to oxaliplatin resistance via in vitro and in vivo CRISPR/Cas9 screening. CDK1 is highly expressed in oxaliplatin‐resistant cells and tissues due to the loss of N6‐methyladenosine modification. Genetic and pharmacological blockade of CDK1 restore the susceptibility of CRC cells to oxaliplatin in vitro and in cell/patient‐derived xenograft models. Mechanistically, CDK1 directly binds to and phosphorylates Acyl‐CoA synthetase long‐chain family 4 (ACSL4) at S447, followed by recruitment of E3 ubiquitin ligase UBR5 and polyubiquitination of ACSL4 at K388, K498, and K690, which leads to ACSL4 protein degradation. Reduced ACSL4 subsequently blocks the biosynthesis of polyunsaturated fatty acid containing lipids, thereby inhibiting lipid peroxidation and ferroptosis, a unique iron‐dependent form of oxidative cell death. Moreover, treatment with a ferroptosis inhibitor nullifies the enhancement of CRC cell sensitivity to oxaliplatin by CDK1 blockade in vitro and in vivo. Collectively, the findings indicate that CDK1 confers oxaliplatin resistance to cells by suppressing ferroptosis. Therefore, administration of a CDK1 inhibitor may be an attractive strategy to treat patients with oxaliplatin‐resistant CRC.

Relying on the rapid development of information and internet technologies, e-commerce has boomed over the past decade. As a link between manufacturers and consumers, the e-commerce platform has a crucial position in the online retailing market. The e-commerce platform not only provides an online marketplace through which the manufacturers directly sell products to consumers but also purchases and resells manufacturers’ products to consumers. Therefore, when the e-commerce platform provides services to manufacturers, it is faced with the selection of two sales methods: reselling or marketplace. Using a game theoretic model, we focus on the strategic interactions between an e-commerce platform and two brand manufacturers in four different business modes. The results show that the e-commerce platform profits more when both brand manufacturers directly sell products through the online marketplace. From the two brand manufacturers’ points of view, using the e-commerce platform as a reseller is always more profitable than directly selling, no matter which business mode they are in. The above findings have important implications for the selling decisions of the e-commerce platform and brand manufacturers. Furthermore, an interesting and counterintuitive result is that the new brand manufacturer benefits more than the existing brand manufacturer when consumers’ acceptance of the new brand products is becoming lower. When production costs are low, only the two brand manufacturers can achieve a mutually beneficial situation by selling products to the e-commerce platform. Moreover, the competition among brand manufacturers is beneficial to the e-commerce platform. Our research provides a theoretical basis for brand manufacturers and the e-commerce platform to make more rational decisions, and it updates the existing knowledge about brand competition and e-commerce platform’s business mode choices.

Abstract Background The diabetic heart exhibits a high sensitivity to ischaemia/reperfusion (I/R) injury. Diabetes mellitus (DM) can affect the efficacy of cardioprotective interventions and reduce the therapeutic potential of existing treatment options. This study aimed to investigate the feasibility of shifting from monotherapy to combination therapy in diabetic myocardial I/R injury. Methods 6–8 week rats were randomized into 10 groups: sham, I/R, ischaemia postconditioning (I-Post), nicorandil (Nic), combination therapy (I-Post + Nic), DM sham, DM I/R, DM I-Post, DM Nic and DM I-Post + Nic. The extent of myocardial injury was clarified by measuring CK-MB and NO levels in plasma, ROS content in myocardial tissues, and TTC/Evans Blue staining to assess the area of myocardial infarction. Pathological staining of cardiac tissue sections were performed to clarify the structural changes in myocardial histopathology. Finally, Western blotting was performed to detect the phosphorylation levels of some key proteins in the PI3K/Akt signalling pathway in myocardial tissues. Results We confirms that myocardial injury in diabetic I/R rats remained at a high level after treatment with I-Post or nicorandil alone. I-Post combined with nicorandil showed better therapeutic effects in diabetic I/R rats, and the combined treatment further reduced the area of myocardial injury in diabetic I/R rats compared with I-Post or nicorandil treatment alone (P

Inflammatory conditions often affect colorectal cancer patients, and their effect on their ongoing treatment is a pressing medical question. Here authors show that inflammation interferes with local anti-tumour immune response and inhibits response to immune checkpoint blockade therapy via immunosuppressive neutrophil leukocytes.

Ionic control of magnetism promises ultralow-field sensor, but current physical realizations of proton-based magneto-ionic sensor are limited due to the lack of effective solid-state sensing methods. Here, authors report magneto-ionics-based proton sensing under low working radiofrequency and magnetic fields.

Chemical energy ferroelectrics show limited control of the energy release rate. Here, the authors design spatially programmed energetic ferroelectrics with controlled energy release rates from machine learning-directed additive manufacturing and ice-templating assembly.

Objective Musculoskeletal pain is having growing impacts worldwide with clinical challenge in pain management. The purpose of the present study is to investigate the preferences of orthopedic surgeons of China for using medicine in musculoskeletal pain. Methods A questionnaire was developed, including the following domains, personal information, medication preference for pain treatment, and perceptions of topical medicine. Ten participants were selected to confirm the consistency of questionnaire. A cross‐sectional survey was conducted in orthopedic physicians with different specialties in different regions of China via the online survey platform. The participants' survey results were analyzed one‐way and multi‐way using chi‐square test and logistic regression. Results The pre‐survey analysis results of 10 randomly selected investigators were a mean weighted kappa coefficient of 0.76 (range 0.61–0.89), which indicated the substantial consistency of the present questionnaire. A total of 1099 orthopedic surgeons (mean age, 41.67 ± 8.31 years) responded to our survey, most of whom were male (90.72%), and most of whom worked in level III hospitals (63.24%) and trained in modern medicine (71.43%). Most surgeons who participated in the survey had used topical analgesics in their clinical work (95.81%), and most preferred to use topical analgesics (39.50%) or a combination of oral analgesics (28.87%). Primary reasons for preferring topical analgesics were as follows: less adverse reactions (68.01%); ease of use (60.90%); and not interfering with other oral medications (49.60%). The preference for prescribing topical analgesics increased with the education level of the respondent, where statistically significant differences were seen (P

Objective: Dragon’s Blood resin (DBR) is a traditional medicinal substance renowned for its diverse pharmacological effects, which consists of potent anti-inflammatory, antioxidant and angiogenic properties. This study aimed to elucidate its therapeutic mechanism in alleviating steroid-induced osteonecrosis of the femoral head (SIONFH).Methods: Techniques such as SPR and LC-MS were employed to identify and analyze the target proteins of DBR in bone marrow macrophages (BMMs). In vitro, BMMs were treated with RANKL and DBR, and TRAcP staining and actin belt staining were utilized to assess osteoclast activity. The inhibitory effects and underlying mechanisms of DBR on osteoclastogenesis and reactive oxygen species (ROS) generation were determined using real-time PCR, western blotting and immunofluorescence staining. An in vivo SIONFH rat model was set up to assess the curative impacts of DBR using micro-CT scanning and pathological staining.Results: Bioinformatic tools revealed a pivotal role of osteoclast differentiation in SIONFH. Proteomic analysis identified 164 proteins binding in BMMs. In vitro assessments demonstrated that DBR hindered osteoclastogenesis by modulating the expression of specific genes and proteins, along with antioxidant proteins including TRX1 and Glutathione Reductase. Notably, the resin effectively inhibited the expression of crucial proteins, such as the phosphorylation of JNK and the nuclear localization of p65 within the TRAF6/JNK and NFκB signaling pathways. In vivo experiments further confirmed that DBR mitigated the onset of SIONFH in rats by curbing osteoclast and ROS activities.Conclusion: These findings underscore the potential of Dragon’s Blood as an effective administration for early-stage SIONFH, shedding light on its therapeutic influence on ROS-mediated osteoclastic signaling pathways.

This study aimed to analyze in-hospital and early-to-interim outcomes of pure aortic regurgitation (AR) using transcatheter aortic valve replacement (TAVR) vs. surgical aortic valve replacement (SAVR). Background: Few studies have discussed and compared the safety and short-term prognosis of TAVR and SAVR in pure AR patients. As such, we looked to the National Readmissions Database (NRD) for records between 2016 and 2019 in order to identify patients diagnosed with pure AR who underwent SAVR or TAVR. We used the propensity score matching to minimize disparities between two groups. We included 23,276 pure AR patients: 1983 (8.5%) who underwent TAVR and 21,293 (91.5%) who underwent SAVR. We found 1820 matched pairs using propensity score matching. In the matching cohort, TAVR was associated with a low risk of in-hospital mortality. Although TAVR had lower incidences of 30-day all-cause readmission (hazard ratio (HR):0.73, 95% confidence interval (CI): 0.61–0.87; P

Over the course of millions of years, nature has evolved to ensure survival and presents us with a myriad of functional surfaces and structures that can boast high efficiency, multifunctionality, and sustainability. What makes these surfaces particularly practical and effective is the intricate micropatterning that enables selective interactions with microstructures. Most of these structures have been realized in the laboratory environment using numerous fabrication techniques by tailoring specific surface properties. Of the available manufacturing methods, additive manufacturing (AM) has created opportunities for fabricating these structures as the complex architectures of the naturally occurring microstructures far exceed the traditional ways. This paper presents a concise overview of the fundamentals of such patterned microstructured surfaces, their fabrication techniques, and diverse applications. A comprehensive evaluation of micro fabrication methods is conducted, delving into their respective strengths and limitations. Greater emphasis is placed on AM processes like inkjet printing and micro digital light projection printing due to the intrinsic advantages of these processes to additively fabricate high resolution structures with high fidelity and precision. The paper explores the various advancements in these processes in relation to their use in microfabrication and also presents the recent trends in applications like the fabrication of microlens arrays, microneedles, and tissue scaffolds.

Mask image projection-based vat photopolymerization (MIP-VPP) offers advantages like low cost, high resolution, and a wide material range, making it popular in industry and education. Recently, MIP-VPP employing liquid crystal displays (LCDs) has gained traction, increasingly replacing digital micromirror devices, particularly among hobbyists and in educational settings, and is now beginning to be used in industrial environments. However, LCD-based MIP-VPP suffers from pronounced pixelated aliasing arising from LCD’s discrete image pixels and its direct-contact configuration in MIP-VPP machines, leading to rough surfaces on the 3D-printed parts. Here, we propose a vibration-assisted MIP-VPP method that utilizes a microscale vibration to uniformize the light intensity distribution of the LCD-based mask image on VPP’s building platform. By maintaining the same fabrication speed, our technique generates a smoother, non-pixelated mask image, reducing the roughness on flat surfaces and boundary segments of 3D-printed parts. Through light intensity modeling and simulation, we derived an optimal vibration pattern for LCD mask images, subsequently validated by experiments. We assessed the surface texture, boundary integrity, and dimensional accuracy of components produced using the vibration-assisted approach. The notably smoother surfaces and improved boundary roughness enhance the printing quality of MIP-VPP, enabling its promising applications in sectors like the production of 3D-printed optical devices and others.

Abstract Excessive absorption of osteoclasts will break the balance between osteoclasts and osteoblasts, leading to bone loss, decreased bone density, and increased bone fragility. We have shown that Loureirin B (LrB) can inhibit osteoclasts. In this study, we demonstrated the targeting-inhibitory mechanism of LrB acting on osteoclast precursor. Using SPR, HPLC and MALDI-TOF-MS to capture and analyze the target protein of Loureirin B in bone marrow macrophages (BMMs), we used this method to detect all target proteins that LrB acts on BMMs, and analyzed the distribution and enrichment rate of the target protein by DAVID enrichment analysis. Ledock molecular docking was used to detect the binding of LrB. We used Western Blot for verification. The target proteins of LrB acting on BMMs were Serpine1, Atp6ap1, Dvl1, Rhd, Fzd2, MAPK1, MAP2K2, MAPK3 and so on. MAPK1, MAP2K2 and MAPK3 were the most relevant. LrB treatment attenuated the expression of phosphorylated JNK and p38 kinases of the MAPK signaling pathway. Our research further confirmed that LrB affects the MAPK signaling pathway in BMMs, thereby inhibiting the differentiation of BMMs into osteoclasts. This discovery can confirm the mechanism by which LrB acts on BMMs.

Nanoscale porous building blocks hold great promise for a range of thermal management technologies but often porous nanoparticle assemblies are intrinsically brittle. Here, the authors report 3D printing of porous silica voxels with polymeric additives to enable the coupling between additive manufacturing and hierarchical assembly for superior machinability and structural controllability.

Objective To report the medium‐term outcomes of surgical hip dislocation (SHD) combined with impacting bone grafts and implanting iliac bone flaps in the treatment of osteonecrosis of the femoral head (ONFH) and to define the indications for this treatment. Methods This was a single‐center retrospective study. In total, 64 patients (70 hips) with ONFH treated from January 2014 to December 2017 were included in this study. There were 51 males and 13 females aged 18–55 years with an average age of 32 years. All patients underwent surgery for SHD combined with impacting bone grafts and implanting iliac bone flaps. Preoperative and postoperative clinical outcomes were assessed. The clinical outcome was assessed using the Harris hip score (HHS) and the conversion rate of total hip arthroplasty (THA). Univariate and multivariate logistic regression analyses were performed to identify risk factors affecting the clinical outcome. Kaplan–Meier (K‐M) analysis was applied to calculate the survival rate of the femoral head. Results At the last follow‐up (60 ± 15.08 months), the HHS was excellent for 41 hips, good for 17 hips, fair for three hips, and poor for nine hips. All nine hips with poor HHS underwent THA, including five in the first 2 years following the index surgery and four between three and 5 years. The conversion rate of total hip arthroplasty was 12.86%. Univariate and multivariate logistic regression analyses showed that the duration of hip pain and JIC classification type were significantly associated with clinical outcomes. Elderly age and advanced ONFH stage tended to lead to worse surgical outcomes. The overall survival rate of JIC classification type C1 and duration of pain ≤6 months was 98.1% and 97.8% at 72 months, respectively, as estimated by the Kaplan–Meier method. Conclusion Surgical hip dislocation combined with impacting bone grafts and implanting iliac bone flaps in the treatment of ONFH had a good mid‐term clinical outcome, especially for patients with retention of the lateral column of the femoral head and hip pain less than 1 year.

Abstract Background Systemic lupus erythematosus (SLE) can cause placental dysfunctions, which may result in pregnancy complications. Long noncoding RNAs (lncRNAs) are actively involved in the regulation of immune responses during pregnancy. The present study aimed to determine the lncRNA expression profiles in placentas from women with SLE to gain new insights into the underlying molecular mechanisms in SLE pregnancies. Methods RNA sequencing (RNA-seq) analysis was performed to identify SLE-dysregulated lncRNAs and mRNAs in placentas from women with SLE and normal full-term (NT) pregnancies. Bioinformatics analysis was conducted to predict the biological functions of these SLE-dysregulated lncRNAs and mRNAs. Results RNA-seq analysis identified 52 dysregulated lncRNAs in SLE placentas, including 37 that were upregulated and 15 downregulated. Additional 130 SLE-dysregulated mRNAs were discovered, including 122 upregulated and 8 downregulated. Bioinformatics analysis revealed that SLE-dysregulated genes were associated with biological functions and gene networks, such as regulation of type I interferon-mediated signaling pathway, response to hypoxia, regulation of MAPK (mitogen-activated protein kinase) cascade, response to steroid hormone, complement and coagulation cascades, and Th1 and Th2 cell differentiation. Conclusions This is the first report of the lncRNA profiles in placentas from SLE pregnancies. These results suggest that the aberrant expression and the potential regulatory function of lncRNAs in placentas may play comprehensive roles in the pathogenesis of SLE pregnancies. SLE-dysregulated lncRNAs may potentially serve as biomarkers for SLE.

Myocarditis is challenging to diagnose because of its various clinical manifestations. Fulminant myocarditis (FM) is a severe type of myocarditis characterized by heart failure, malignant arrhythmia, cardiogenic shock, and cardiac arrest. Its early diagnosis and timely treatment are crucial for a positive long-term prognosis. Here we report a case of 42-year-old woman who presented with fever, chest pain, and cardiogenic shock. An initial examination showed increased myocardial enzyme levels and diffuse ST-segment elevation. Urgent coronary angiography excluded coronary artery stenosis. Echocardiography revealed decreased left ventricular systolic function. Cardiac magnetic resonance imaging revealed cardiomyocyte necrosis and interstitial inflammatory edema. The patient was diagnosed with FM and administered antiviral and anti-infective agents, glucocorticoid, immunoglobulin, and supported with temporary cardiac pacemaker and positive airway therapy, and treated with continuous renal replacement therapy. As her clinical condition deteriorated rapidly, we immediately started an intra-aortic balloon pump and veno-arterial extracorporeal membrane oxygenation. She was discharged on day 15 and recovered normally during follow-up. The early initiation of mechanical circulatory support and immunosuppression are life-saving tools for the treatment of FM.

Abstract Advanced materials, electrically conductive and oxidation resistant, are frontrunners for technological advancements in cutting‐edge high‐temperature electronics. Rational design and manufacturing of hierarchical material structures is indispensable to achieve such disparate functionalities. Here, high‐temperature copper–graphene conductors, through additive manufacturing, which prohibits oxygen adsorbates and serves as the barrier for oxygen migration to enable electric stability and reliability at high temperatures, are reported. The combination of graphene and alumina surface passivation enables the electric stability of copper–graphene under thermal impact above 1000 °C. The findings shown here, the synergistic combination of high conductivity and oxidation resistance, enunciate the passivation capabilities for additively manufactured flexible electronics operating under harsh conditions.

A 37-year-old woman presented with worsening intermittent chest pain and dyspnea in the previous year. Although the dyspnea was exertion-dependent, her chest pain was heavily dependent on her postural position, worsening in the supine position but alleviated by lying prone or by sitting up and leaning forward. She was cyanotic, and a diastolic murmur in the left third intercostal space was auscultated. An electrocardiogram recorded when she laid flat and had angina pectoris attacks showed ST-segment elevation in the aVR and depression in the II, III, aVF, and V3–V6 leads. However, when she sat up for a few minutes, her symptoms and ST-segment abnormalities disappeared. Echocardiography and cardiac computed tomography angiography revealed large unruptured aneurysms of the left and non-coronary sinuses, along with a dilated aortic root, severe aortic regurgitation, and right ventricular high pressure. Coronary angiography showed ∼90% pulsating stenosis of the left main coronary artery and ∼80% pulsating stenosis of the proximal left circumflex artery, presumably caused by pulsation of the dilated sinus of Valsalva aneurysm under blood pressure. Genetic testing revealed c.1781 C > G nonsense mutations in the FLNA gene. The patient underwent surgery, which confirmed dual unruptured left/non-coronary sinus of Valsalva aneurysms. Our case illustrates an unusual postural form of angina pectoris and false “pulmonary hypertension” caused by large dual unruptured left/non-coronary sinus of Valsalva aneurysms.

Sex differences have been noted in schizophrenia (SCZ) and diabetes mellitus (DM); however, the effect of sex on SCZ patients with DM remains unknown. We aimed to investigate sex differences in the prevalence, demographic and clinical correlates of DM in Chinese patients with chronic SCZ. A total of 988 Han Chinese SCZ patients (male/female: 638/350) were recruited from two psychiatric hospitals in China. We used the Positive and Negative Syndrome Scale (PANSS) to evaluate the psychopathological symptoms of the patients. In addition, serum glucose and lipid levels were assayed. The prevalence of DM in female patients (57/350, 16.29%) was higher than that in male patients (79/638, 12.38%). Binary logistic regression analyses confirmed that the prevalence of DM in female patients was higher than that in male patients (P

ObjectiveOsteonecrosis of the femoral head (ONFH) is a disabling and intractable orthopedic disease largely affecting young and middle-aged groups. Current standard of treatment relies on the collapse of femoral head as a predictor for prognosis. However, a wide range of variability in repair potentials is observed in patients with femoral head collapse. Therefore, the present study aimed to evaluate the accuracy of femoral head collapse as a predictor and to propose the necrotic lesion boundary as a novel yet reliable measure for ONFH prognosis.MethodsA retrospective cross-sectional study was conducted at the First Affiliated Hospital of Guangzhou University of Chinese Medicine, 203 hips with ONFH from 134 patients were included. The occurrences and progression of femoral head collapse were recorded. Necrosis lesion boundary was quantified and classified for each case based on anteroposterior view intact ratio (APIR) and the frog-leg view intact ratio (FLIR) as independent variables. Dependent variables were defined as progressive collapse or terminal collapse for Association Research Circulation Osseous (ARCO) stage II and III respectively. Logistic regression analysis, Receiver Operating Characteristic (ROC) curve and Kaplan-Meier (K-M) survival analysis was performed and results were interpreted.ResultsOut of the 106 hips in ARCO stage II, 31 hips collapsed with further progression, while 75 hips had no collapse or collapse with repair of the necrotic areas. Out of the 97 hips in ARCO stage IIIA, the collapse continued to progress in 58 hips while the necrotic areas were repaired in 39 hips. Logistic regression analysis demonstrated that both APIR and FLIR, were independent risk factors. Further ROC curve analysis indicated that the cutoff values of APIR and FLIR could be considered as indications for evaluating the prognosis of ONFH. Contrary to the traditional view of poor prognosis after femoral head collapse, K-M survival analysis demonstrated a high value of APIR and FLIR for ONFH prognosis.ConclusionThe present study found that the occurrence of collapse is an oversimplified predictor for ONFH prognosis. The collapse of the femoral head in ONFH does not predict a poor prognosis. The necrosis lesion boundary has a high value in predicting ONFH prognosis and informing clinical treatment strategies.

Abstract The roles of oncogenic KRAS in tumor immune evasion remain poorly understood. Here, mutant KRAS is identified as a key driver of tumor immune evasion in colorectal cancer (CRC). In human CRC specimens, a significant reduction in cytotoxic CD8+ T‐cell tumor infiltration is found in patients with mutant versus wild type KRAS. This phenomenon is confirmed by preclinical models of CRC, and further study showed KRAS mutant tumors exhibited poor response to anti‐PD‐1 and adoptive T‐cell therapies. Mechanistic analysis revealed lactic acid derived from mutant KRAS‐expressing tumor cells sensitized tumor‐specific cytotoxic CD8+ T‐cells to activation‐induced cell death via NF‐κB inactivation; this may underlie the inverse association between intratumoral cytotoxic CD8+ T‐cells and KRAS mutation. Importantly, KRAS mutated tumor resistance to immunotherapies can be overcome by inhibiting KRAS or blocking lactic acid production. Together, this work suggests the KRAS‐mediated immune program is an exploitable therapeutic approach for the treatment of patients with KRAS mutant CRC.

Objectives. To study trends of utilization, in-hospital outcomes, and short outcomes in patients undergoing transcatheter mitral valve repair (TMVR) vs. surgical mitral valve repair (SMVR) in atrial fibrillation (AF). Background. TMVR is a treatment option in inoperable or high-risk patients with mitral regurgitation (MR). AF is a common comorbidity of MR. Data comparing between TMVR and SMVR in MR patients with AF is lacking. Methods. The National Readmission Database from 2016 to 2019 was utilized to identify hospitalizations undergoing TMVR or SMVR with AF. Outcomes of interest included mortality, postoperative complications, length of stay, and 30-day readmission rate. Results. A total of 9,195 patients underwent TMVR and 16,972 patients underwent SMVR with AF; the number of AF undergoing TMVR was increasing from 1,342 in 2016 to 4,215 in 2019 and SMVR. The incidence of in-hospital mortality decreased from 2.6% in 2016 to 1.8% in 2019. We identified length of stay>5 days, dyslipidemia, cerebrovascular disease, heart failure with reduced ejection fraction, and urgent/emergent admissions as independent risk factors for in-hospital mortality. After matching, we included 4,680 patients in each group; the in-hospital death, transfusion, acute kidney injury, sepsis, stroke, and mechanical ventilation were lower in TMVR compared with SMVR. TMVR was associated with a similar rate of all-cause readmission at 30 days compared with SMVR. Conclusion. Patients with AF receiving TMVR have been increasing along with progressive improvement in in-hospital death and length of stay. Compared to SMVR, AF patients receiving TMVR had a lower rate of in-hospital death and postoperative complications.

IntroductionHypertension is a growing public health concern worldwide. It is a leading risk factor for all-cause mortality and may lead to complications such as cardiovascular disease, stroke, and kidney failure. Poor compliance of hypertensive patients is one of the major barriers to controlling high blood pressure. Compliance is not ideal among Chinese patients, and increasing patient self-care compliance with hypertension is necessary.MethodsThis article analyzes the status of self-care compliance, trust, and satisfaction among Chinese hypertensive patients using cross-sectional data from Zhejiang Province. We use a multi-group structural equation model (MGSEM) to compare the interrelationships across genders.ResultsThe study's findings show that the average trust, satisfaction, and compliance scores are 3.92 ± 0.55, 3.98 ± 0.61, and 3.33 ± 0.41, respectively. Female patients exhibit higher average total scores for trust and compliance than male patients. The SEM results indicate that trust has a direct positive association with compliance [β = 0.242, 95% CI: (0.068, 0.402)] and satisfaction [β = 0.260, 95% CI: (0.145, 0.367)], while their satisfaction is not directly associated with compliance. The results of MGSEM show that trust has an indirect effect on compliance in the male group through satisfaction [β = 0.051, P < 0.05, 95% CI: (0.012, 0.116)]. In the female group, trust has a direct effect on satisfaction [β = 0.235, P < 0.05, 95% CI: (0.041, 0.406)] and compliance [β = 0.319, P < 0.01, 95% CI: (0.086, 0.574)].DiscussionThis study reveals the mechanisms of self-care compliance, trust, and satisfaction among Chinese hypertensive patients. Its findings may serve as a reference for guiding primary healthcare providers to improve hypertension patients' compliance and implement gender-targeted health interventions.