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Abstract Background Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. Methods This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. Results Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). Conclusions Sirolimus’s long-term administration is not associated with adverse effects on children’s physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. Trial registration Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.

Abstract Background Addison’s disease and X-linked adrenoleukodystrophy (X-ALD) (Addison’s-only) are two diseases that need to be identified. Addison’s disease is easy to diagnose clinically when only skin and mucosal pigmentation symptoms are present. However, X-ALD (Addison’s-only) caused by ABCD1 gene variation is ignored, thus losing the opportunity for early treatment. This study described two patients with initial clinical diagnosis of Addison’s disease. However, they rapidly developed neurological symptoms triggered by infection. After further genetic testing, the two patients were diagnosed with X-ALD. Methods We retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics. Results Two patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison’s disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394–2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison’s-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum. Conclusions Patients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison’s disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison’s-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy.

By adjusting the inter-wire arc (IWA) posture, the skew-coupling arc (SCA) is proposed to address the polar effect in the cross arc, enabling decoupling control of heat, force, and mass transfer. Despite the advancement, the arc stabilization mechanism in the SCA remains poorly understood, hindering its application as a heat source in welding or additive manufacturing. To elucidate this mechanism, various influencing factors such as power supply characteristics, shielding gas composition, IWA posture, and plasma main arc (PMA) were analyzed. An electrical signal and high-speed camera synchronous acquisition system was utilized to analyze current-voltage waveforms and arc shapes. The results indicate that the arc stability of the SCA can be enhanced by ensuring specific external conditions. Constant voltage power supply enhances the self-regulating effect of the IWA, maintaining the IWA and the PMA in a hybrid state at all times. Introducing an oxidizing gas to the shielding gas can effectively suppress cathode spot climbing and stabilize the IWA. The vertical spacing between wires directly impacts the PMA deflection, while the wire horizontal angle has a lesser effect. The heat-regulating effect of the PMA column boosts the arc length regulation by the IWA. The current and the ion gas flow rate in the PMA minimally influence the SCA stability. These findings can provide a solid foundation for further applications of the SCA as heat source.

Abstract Objective This study aimed to examine prospective associations of different intensity levels and types of physical activity (PA) in early pregnancy with premature rupture of membranes (PROM) among Chinese pregnant women. Methods A total of 6284 pregnant women were included from the Tongji-Shuangliu Birth Cohort. Household/caregiving, occupational, sports/exercise and transportation activities during early pregnancy were investigated by the pregnancy physical activity questionnaire (PPAQ), and the diagnosis of PROM was ascertained during the whole pregnancy. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the associations between PA and PROM. Results Among the 6284 pregnant women, 1246 were identified to have PROM (19.8%). Women undertaking the highest level (3 third tertile) of PA during pregnancy appeared to have a lower risk of PROM [OR = 0.68, 95%CI 0.58–0.80) when compared to those at the lowest tertile of PA. Similarly, women with increased levels of light intensity activity, moderate-vigorous intensive, household/caregiving activity and meeting exercise guidelines during pregnancy were associated with reduced risks of PROM (OR = 0.69, 95% CI 0.59–0.81, OR = 0.70, 95% CI 0.60–0.82, OR = 0.62, 95% CI 0.53–0.73 and OR = 0.82, 95% CI 0.70–0.97, respectively). Conclusions High levels of PA of different intensities and PA of household/caregiving activities and meeting exercise guidelines during the first trimester were associated with a lower incidence of PROM. Trial registration The data of human participants in this study were conducted in accordance with the Helsinki Declaration. This study has been approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ([2017] No. S225). All participants provided written informed consent prior to enrollment. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations.

Abstract Background Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol. Methods The study uses a two by three factorial design. A total of 1200 young adults in Texas, age 18–26 years, who have not been previously fully vaccinated against HPV will be randomly assigned to one of six conditions to receive: (1) standard CDC information about HPV vaccination (control); (2) video narratives about HPV vaccination; (3) written narratives about HPV vaccination; or (4–6) enhanced access to HPV vaccine combined with (4) standard CDC information, (5) video narratives, or (6) written narratives. The two primary outcomes are the rate of HPV vaccination initiation by 3-month follow-up and rate of HPV vaccination completion by 9-month follow-ups. We will determine the impact of the individual level intervention (i.e., persuasive narratives through video or written format), the systemic level intervention (i.e., enhanced access to HPV vaccines), and the combination of both levels, on HPV vaccination initiation and completion. We will also use purposive sampling to select participants to take part in semi-structured interviews/focus groups to better understand the mechanisms of the intervention. Discussion Recruitment and data collection began in March 2022. We expect to complete data collection by March 2026. We expect that narratives, enhanced access, and the combination of both will improve HPV vaccination initiation and completion rates among young adults. If proven successful, these individual- and system-level interventions can be easily disseminated in regions with low HPV vaccination rates to improve HPV vaccination, and ultimately decrease HPV-related cancer burden. Trial Registration NCT05057312.

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease with an unknown etiology. RA cannot be fully cured and requires lengthy treatment, imposing a significant burden on both individuals and society. Due to the lack of specific drugs available for treating RA, exploring a key new therapeutic target for RA is currently an important task. Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the progression of RA, which release interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α resulting in abnormal inflammatory reaction in the synovium. A previous study has highlighted the correlation of m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) with inflammation-related diseases in human. However, the role of IGF2BP2 in the inflammatory reaction of FLSs during RA progression has not been assessed. In this study, IGF2BP2 expression was decreased in the synovial tissues of RA patients and collagen-induced arthritis (CIA) rats. Intra-articular injection of an adeno-associated virus (AAV) vector overexpressing IGF2BP2 relieved paw swelling, synovial hyperplasia and cartilage destruction in CIA rats. IGF2BP2 overexpression also inhibited lipopolysaccharide (LPS)-mediated RA fibroblast-like synoviocytes (RA-FLSs) migration and invasion accompanied by a decreased level of inflammatory factors in vitro. Conversely, IGF2BP2 suppression promoted RA-FLSs migration and invasion with an elevated level of inflammatory factors in vitro. The sequencing result showed that glutathione S-transferase Mu 5 (GSTM5), a key antioxidant gene, was the target mRNA of IGF2BP2. Further experiments demonstrated that IGF2BP2 strengthened the stability of GSTM5 mRNA, leading to weakened inflammatory reaction and reduced expression of matrix metalloproteinase 9 and 13 (MMP9, MMP13). Therefore, IGF2BP2-GSTM5 axis may represent a potential therapeutic target for RA treatment.

Abstract Objective The study aims to evaluate the accuracy of an MRI-based artificial intelligence (AI) segmentation cartilage model by comparing it to the natural tibial plateau cartilage. Methods This study included 33 patients (41 knees) with severe knee osteoarthritis scheduled to undergo total knee arthroplasty (TKA). All patients had a thin-section MRI before TKA. Our study is mainly divided into two parts: (i) In order to evaluate the MRI-based AI segmentation cartilage model’s 2D accuracy, the natural tibial plateau was used as gold standard. The MRI-based AI segmentation cartilage model and the natural tibial plateau were represented in binary visualization (black and white) simulated photographed images by the application of Simulation Photography Technology. Both simulated photographed images were compared to evaluate the 2D Dice similarity coefficients (DSC). (ii) In order to evaluate the MRI-based AI segmentation cartilage model’s 3D accuracy. Hand-crafted cartilage model based on knee CT was established. We used these hand-crafted CT-based knee cartilage model as gold standard to evaluate 2D and 3D consistency of between the MRI-based AI segmentation cartilage model and hand-crafted CT-based cartilage model. 3D registration technology was used for both models. Correlations between the MRI-based AI knee cartilage model and CT-based knee cartilage model were also assessed with the Pearson correlation coefficient. Results The AI segmentation cartilage model produced reasonably high two-dimensional DSC. The average 2D DSC between MRI-based AI cartilage model and the tibial plateau cartilage is 0.83. The average 2D DSC between the AI segmentation cartilage model and the CT-based cartilage model is 0.82. As for 3D consistency, the average 3D DSC between MRI-based AI cartilage model and CT-based cartilage model is 0.52. However, the quantification of cartilage segmentation with the AI and CT-based models showed excellent correlation (r = 0.725; P values

ObjectiveThe genomic characteristics， toxicity， drug resistance and genetic diversity of Listeria monocytogenes （Lm） isolated from food and patients based on whole genome sequencing （WGS） in Liaocheng City from 2019 to 2022 were investigated.MethodsThe Lm strains isolated from food and patients were detected by the drug sensitivity test and WGS. The whole genome sequencing data was spliced and assembled by MGAP to carry out gene prediction and functional annotation on the assembled genome， MLST， production of cg MLST minimum spanning tree. The genetic evolution of 18 domestic and foreign foodborne Lm isolated strains obtained from NCBI were analyzed by wg-SNP method.ResultsThe genome size of 33 Lm isolates was 2.89-3.41 Mb， and the CG content ranged from 37.81% to 37.97%. The strains could be divided into 6 ST types （ST9， ST121， ST8， ST87， ST155， ST101）， corresponding to 6 clonal complex groups （CC9， CC121， CC8， CC87， CC155， CC101）. The strains carried fosX and mprF resistance gene， 18 other virulence genes such as lplA1 and prsA2， with varying degrees of deletion of virulence genes. 2 strains were resistant to tetracycline and 1 strain was resistant to lincomycin. The stains carried virulence islands LIPI-1 and LIPI-2 without virulence islands LIPI-3 and LIPI-4. The genetic evolution analysis of wg-SNPs， cgMLST and phylogenetic tree based on single-copy core protein sequence showed that the molecular typing of 33 Lm strains was with high diversity in molecular typing. Patient derived strains were closely related to food isolates， and food isolates were closely related to foreign outbreak isolates in evolutionary relationships.ConclusionThe strains of Lm isolated from food and patients both carry virulence genes with certain potential pathogenic ability. The drug resistance of the isolated strains is not serious. Molecular types exhibit diversity. The close genetic relationship between strains from food sources and patient isolates suggests that the potential risks of foodborne infections in commercially available food.

BACKGROUND: An important issue for patients with cancer treated with novel therapeutics is how they weigh the effects of treatment on survival and quality of life (QOL). We compared QOL in patients enrolled to SWOG S1400I, a substudy of the LungMAP biomarker-driven master protocol. METHODS: SWOG S1400I was a randomized phase III trial comparing nivolumab plus ipilimumab vs nivolumab for treatment of immunotherapy-naïve disease in advanced squamous cell lung cancer. The primary endpoint was the MD Anderson Symptom Inventory-Lung Cancer severity score at week 7 and week 13 with a target difference of 1.0 points, assessed using multivariable linear regression. A composite risk model for progression-free and overall survival was derived using best-subset selection. RESULTS: Among 158 evaluable patients, median age was 67.6 years and most were male (66.5%). The adjusted MD Anderson Symptom Inventory-Lung Cancer severity score was 0.04 points (95% confidence interval [CI] = -0.44 to 0.51 points; P = .89) at week 7 and 0.12 points (95% CI = -0.41 to 0.65; P = .66) at week 13. A composite risk model showed that patients with high levels of appetite loss and shortness of breath had a threefold increased risk of progression or death (hazard ratio [HR] = 3.06, 95% CI = 1.88 to 4.98; P

To improve the prediction accuracy of chaotic time series and reconstruct a more reasonable phase space structure of the prediction network, we propose a convolutional neural network (CNN)-long short-term memory (LSTM) prediction model based on the incremental attention mechanism. Firstly, a traversal search is conducted through the traversal layer for finite parameters in the phase space. Then, an incremental attention layer is utilized for parameter judgment based on the dimension weight criteria (DWC). The phase space parameters that best meet DWC are selected and fed into the input layer. Finally, the constructed CNN-LSTM network extracts spatiotemporal features and provides the final prediction results. The model is verified using Logistic, Lorenz, and sunspot chaotic time series, and the performance is compared from the two dimensions of prediction accuracy and network phase space structure. Additionally, the CNN-LSTM network based on incremental attention is compared with LSTM, CNN, recurrent neural network (RNN), and support vector regression (SVR) for prediction accuracy. The experiment results indicate that the proposed composite network model possesses enhanced capability in extracting temporal features and achieves higher prediction accuracy. Also, the algorithm to estimate the phase space parameter is compared with the traditional CAO, false nearest neighbor, and C–C, three typical methods for determining the chaotic phase space parameters. The experiments reveal that the phase space parameter estimation algorithm based on the incremental attention mechanism is superior in prediction accuracy compared with the traditional phase space reconstruction method in five networks, including CNN-LSTM, LSTM, CNN, RNN, and SVR.

Abstract Background and aims Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) has an extremely poor prognosis. A previous study proved that low-dose radiotherapy (RT) could prolong the prognosis of HCC patients with PVTT. This study aims to explore the sensitivity of PVTT to RT treatment. Methods Patients were selected based on imaging diagnosis of HCC accompanied by PVTT and received combined treatment of radiotherapy, antiangiogenic drugs and immune checkpoint inhibitors, followed by hepatectomy or liver transplantation from January 2019 to August 2022. The efficacy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and pathological assessment. The sensitivity of tumor cells to the treatment was compared between the primary tumor (PT)and PVTT by analyzing their residual tumor and pathologic complete remission (PCR) incidence. Results Data from 14 patients were collected in the study. After combined treatment, the size of PVTT decreased more significantly than that of the primary tumor in the imaging study (p

Abstract In order to apply grouting material to the joints of fabricated buildings and make it meet the performance demands of low shrinkage, strong bond, and high toughness of joint materials for prefabricated buildings, the expansion agent (EA), neoprene latex (NL), and rubber particles (RP) were used to modify the grouting material, and the effects of different dosages of the three components on the working performance, mechanical properties, and expansion or shrinkage properties of the grouting material were investigated. The results show that the EA decreases the flexural strength-to-compressive strength ratio (FCR) of the grouting material and enhances the vertical expansion rate and bond strength. The dosage of EA and the curing conditions have a significant effect on the expansion rate of the hardened grouting material. The grouting material can still maintain its 0.0022% free expansion rate with a 7% EA dosage at 120 d. The NL significantly inhibits the vertical expansion of the fresh mortar but inhibits the drying shrinkage of the grouting material after hardening, improves the FCR and bond strength; the 7 d bond strength under a 5% NL dosage can reach 4.27 MPa. The RP inhibits the vertical expansion of the fresh mortar and the drying shrinkage after mortar hardening; with the increase of its dosage, the bond strength of the grouting material increases first and then decreases, the 28 d FCS of the grouting material peaked at 0.173 at 10% dosage.

Abstract Inherited retinal degenerations (IRDs) are a group of untreatable and commonly blinding diseases characterized by progressive photoreceptor loss. IRD pathology has been linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, a connection between excessive Ca2+ influx and photoreceptor loss has yet to be proven. Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes indicated links to several Ca2+-signalling related pathways. To explore these, rd1 and wt organotypic retinal explant cultures were treated with the intracellular Ca2+-chelator BAPTA-AM or inhibitors of different Ca2+-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca2+-release-activated channel (CRAC), and Na+/Ca2+ exchanger (NCX). Moreover, we employed the novel compound NA-184 to selectively inhibit the Ca2+-dependent protease calpain-2. Effects on the retinal activity of poly(ADP-ribose) polymerase (PARP), sirtuin-type histone-deacetylase, calpains, as well as on activation of calpain-1, and − 2 were monitored, cell death was assessed via the TUNEL assay. While rd1 photoreceptor cell death was reduced by BAPTA-AM, Ca2+-channel blockers had divergent effects: While inhibition of T-type VGCC and NCX promoted survival, blocking CNGCs and CRACs did not. The treatment-related activity patterns of calpains and PARPs corresponded to the extent of cell death. Remarkably, sirtuin activity and calpain-1 activation were linked to photoreceptor protection, while calpain-2 activity was related to degeneration. In support of this finding, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors. These results suggest that Ca2+ overload in rd1 photoreceptors may be triggered by T-type VGCCs and NCX. High Ca2+-levels likely suppress protective activity of calpain-1 and promote retinal degeneration via activation of calpain-2. Overall, our study details the complexity of Ca2+-signalling in photoreceptors and emphasizes the importance of targeting degenerative processes specifically to achieve a therapeutic benefit for IRDs. Video Abstract

Industrial water splitting has long been suppressed by the sluggish kinetics of the oxygen evolution reaction (OER), which requires a catalyst to be efficient. Herein, we propose a molecular-level proton acceptor strategy to produce an efficient OER catalyst that can boost industrial-scale water splitting. Molecular-level phosphate (-PO4) group is introduced to modify the surface of PrBa0.5Ca0.5Co2O5+δ (PBCC). The achieved catalyst (PO4-PBCC) exhibits significantly enhanced catalytic performance in alkaline media. Based on the X-ray absorption spectroscopy results and density functional theory (DFT) calculations, the PO4 on the surface, which is regarded as the Lewis base, is the key factor to overcome the kinetic limitation of the proton transfer process during the OER. The use of the catalyst in a membrane electrode assembly (MEA) is further evaluated for industrial-scale water splitting, and it only needs a low voltage of 1.66 V to achieve a large current density of 1 A cm−2. This work provides a new molecular-level strategy to develop highly efficient OER electrocatalysts for industrial applications.

Objective: To demonstrate the surgical techniques employed in the robotic single port (SP) transvaginal natural orifice transluminal endoscopic surgery (RSP-vNOTES) for hysterectomy utilizing a domestically developed robotic system in China. Methods: We performed two cases of RSP-vNOTES hysterectomy for patients presenting with persistent vaginal bleeding resulting in atypical endometrial hyperplasia per endometrial biopsy. Procedures were initiated with traditional TVH and seamlessly transitioned to the robotic platform when necessary to complete the entire process. The robotic docking process was executed smoothly. Two elbowed instruments, a bipolar grasper, a pair of monopolar scissors, and a facing-upward camera were used. The hysterectomies were carried out precisely, without complications. Bilateral salpingo-oophorectomy was performed in the first patient and bilateral salpingectomy in the second. The vaginal cuff was closed continuously through a transvaginal approach after undocking. Results: Both patients were discharged on the third postoperative day, with satisfactory surgical results and no complications. Conclusions: The domestically developed Chinese Robotic SP system demonstrates feasibility for RSP-vNOTES procedures of hysterectomy. This approach amalgamates the advantages of both vaginal and robotic surgeries, incorporating surgical triangulation with an elbowed function that simplifies surgical manipulation. However, further studies with larger sample sizes and potential comparative analyses are essential to validate the merits and safety of adopting this platform.

The occurrence of benign prostate hyperplasia (BPH) was related to disrupted sex steroid hormones, and metformin (Met) had a clinical response to sex steroid hormone-related gynaecological disease. However, whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear. Here, our clinical study showed that along with prostatic epithelial cell (PEC) proliferation, sex steroid hormones were dysregulated in the serum and prostate of BPH patients. As the major contributor to dysregulated sex steroid hormones, elevated dihydrotestosterone (DHT) had a significant positive relationship with the clinical characteristics of BPH patients. Activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor (AR)-mediated Yes-associated protein (YAP1)-TEA domain transcription factor (TEAD4) heterodimers. Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells. Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Objective To explore the correlation between the prolongating PR interval of electrocardiogram and the general information and biochemical indicators of diabetes patients with microvascular complications, and the predictive value of diabetes microvascular complications. Methods A total of 217 patients with diabetes who hospitalized in Department of Endocrinology, Xi'an Third Hospital from August 2020 to November 2022 were selected retrospectively. Among them, 149 patients only with diabetes were divided into control group, while 68 diabetes patients with microvascular complications were divided into observation group. The general data and biochemical indexes of all diabetes patients were collected, and the PR interval was measured by standard 12 lead synchronous electrocardiograph. The correlation between PR interval and general data and biochemical indicators in patients with microvascular complications of diabetes were analyzed. The predictive value of PR interval on microvascular complications in diabetes was analyzed by receiver operating characteristic (ROC) curve. Results Age, duration of diabetes, body mass index (BMI), hemoglobin A1c (HbA1c), PR interval in the observation group were higher than those in the control group (P＜0.01). PR interval of diabetes patients with microvascular complications was positively correlated with age, diabetes duration, BMI, HbA1c (P＜0.01). The AUC of PR interval for predicting microvascular complications in diabetes was 0.812 (95%CI:0.752-0.872), the sensitivity was 70.6%, the specificity was 78.5%, and the cut-off value was 212.61 ms. Prolonged PR interval was an independent risk factor for microvascular complications in diabetes (OR=2.475, 95%CI: 1.472-5.120, P＜0.01). Conclusion In patients with microvascular complications of diabetes, the PR interval in electrocardiogrom is significantly prolonged. Prolonged PR interval is an independent risk factor for microvascular complications in diabetes, which is helpful to predict the occurance of diatetic microvascular complications.

Background Community traditional Chinese medicine (TCM) service is an important step in promoting the construction of Healthy China. There are abundant academic research results in the field of community TCM service in China, but there is a lack of collation of these research results. Systematically sorting out the relevant literature in the field of community TCM service by using the method of bibliometrics can provide a macroscopic understanding of the research progress and hotspots in this field and reference for future research. Objective To sort out the hotspots and development trends of community TCM service research in China by using bibliometric methods. Methods On May 2 in 2022, CNKI, Wanfang Data Knowledge Service Platform and VIP were searched for relevant research literature on community TCM service research in China from January 2000 to April 2022. By using CiteSpace software, the visual analysis of the co-occurrence of authors included in the literature, keywords co-occurrence, clustering, timeline distribution, and burst terms were performed and the relevant graphs were plotted. Results A total of 1 440 papers were included, and the publication volume of community TCM services in China showed an overall increasing trend, with 75 papers (5.2%) published in 2000—2005, 382 papers (26.5%) in 2006—2011, and 983 papers (68.3%) in 2012—2022. The top three authors in the publication volume were Shi Yongxing (25 articles), Bao Yong (16 articles), and Liu Deng (14 articles). The top 5 high-frequency keywords in terms of centrality were "TCM" "Chinese medicine" "community" "general practitioner" and "general practice". The keyword clustering analysis formed 12 cluster labels, and the top three clusters by scale were "community" "TCM" and "general practitioner". The timeline distribution suggested that clusters such as "community" "TCM" "general practitioner" and "TCM nursing" were research hotspots in this field. From the perspective of burst terms, "family doctor" has the highest burst value (8.07), and "elderly people" "diabetes" "family doctor" "medical consortium" "general practice of TCM" and the "integrated medical care and elderly services" are future research directions. Conclusion The current status of community TCM service in China, development of TCM general practitioners and community TCM nurses, and the improvement of TCM service capabilities of community health care institutions are research hotspots. In the future, more attention will be paid to the digital compact TCM medical consortium based on the Internet platform and the contracted family doctor service model with the participation of TCM general practitioners, so as to better utilize the characteristics and advantages of community TCM services in integrated medical care and elderly services.

Summary: Purpose: Anxiety, depression, and poor quality of life (QOL) were considered important concerns that hindered the rehabilitation of breast cancer survivors. A number of studies have investigated the effects of physical activity, but they have not reached the same conclusions. This review aimed to identify the effects of physical activity on QOL, anxiety, and depression in breast cancer survivors. Methods: PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, SinoMed, CNKI, Vip, and WanFang databases were searched for the time period between January 1, 2012, and April 30, 2022. Studies were included if they were randomized controlled trials of the effects of physical activity on QOL, anxiety, or depression in breast cancer survivors. The tools of the Joanna Briggs Institute were used to assess the quality of the included studies. R software version 4.3.1 was used for meta-analysis. Results: A total of 26 studies, involving 2105 participants, were included in the systematic review. Among these, 20 studies involving 1228 participants were included in the meta-analysis. Compared with the control group, the results indicated that physical activity can significantly improve QOL(Hedges' g = 0.67; 95% CI 0.41–0.92) and reduce anxiety (Hedges' g = −0.28; 95% CI −0.46 to −0.10) in breast cancer survivors. However, the effect of physical activity on depression (Hedges' g = −0.46; 95% CI −0.99 to 0.06) was not statistically significant. Conclusions: Physical activity was an effective intervention to improve QOL and reduce anxiety in breast cancer survivors, as well as showed positive trends in depression, although without statistical significance. More well-designed studies are required to clarify the effects of different types of physical activities on the QOL, anxiety, and depression among breast cancer survivors. Registered number on PROSPERO: CRD42022363094.https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=363094.

Abstract Background Patients diagnosed with low-risk prostate cancer (PCa) are confronted with a difficult decision regarding whether to undergo definitive treatment or to pursue an active surveillance protocol. This is potentially further complicated by the possibility that patients and physicians may place different value on factors that influence this decision. We conducted a qualitative investigation to better understand patient and physician perceptions of factors influencing treatment decisions for low-risk PCa. Methods Semi-structured interviews were conducted among 43 racially and ethnically diverse patients diagnosed with low-risk PCa, who were identified through a population-based cancer registry, and 15 physicians who were selected to represent a variety of practice settings in the Greater San Francisco Bay Area. Results Patients and physicians both described several key individual (e.g., clinical) and interpersonal (e.g., healthcare communications) factors as important for treatment decision-making. Overall, physicians’ perceptions largely mirrored patients’ perceptions. First, we observed differences in treatment preferences by age and stage of life. At older ages, there was a preference for less invasive options. However, at younger ages, we found varying opinions among both patients and physicians. Second, patients and physicians both described concerns about side effects including physical functioning and non-physical considerations. Third, we observed differences in expectations and the level of difficulty for clinical conversations based on information needs and resources between patients and physicians. Finally, we discovered that patients and physicians perceived patients’ prior knowledge and the support of family/friends as facilitators of clinical conversations. Conclusions Our study suggests that the gap between patient and physician perceptions on the influence of clinical and communication factors on treatment decision-making is not large. The consensus we observed points to the importance of developing relevant clinical communication roadmaps as well as high quality and accessible patient education materials.

The interactions between corn amylose (CA) and Moringa oleifera seed salt-soluble protein (MOSP) were explored to improve the gel properties of MOSP. With increasing CA content, the MOSP-CA gel network structure was improved but the size of the gel porosity decreased firstly and then increased; the water holding retention (WHR) of MOSP-CA was decreased from approximately 94 % to 85.43 ± 2.54 %. The MOSP-CA-2.5 gel exhibited the best water holding stability (WHS), with a value of 37.1 ± 0.33 %. The MOSP-CA gel hardness increased with CA concentration, and MOSP-CA-2.5 showed relatively optimal cohesiveness, elasticity, adhesiveness, and chewiness. Meanwhile, MOSP-CA-2.5 exhibited gel strength. Incorporation of CA significantly increased the exposure of hydrophobic residues and the concentration-dependent increase in disulfide bonds in MOSP-CA gel. Thus, hydrophobic interactions, hydrogen bonds, and disulfide bonds collectively stabilized the structure of MOSP-CA gel. The findings would broaden the application of MOSP and improve the utilization value of MOSP in various industries.

BackgroundHepatic inflammatory myofibroblastic tumor (IMT) is an infrequent tumor with potential malignancy. However, it lacks specific clinical symptoms and usual imaging features.Case presentationA 34-year-old woman had a six-month history of fever and on-and-off pain in the upper right part of her abdomen that lasted for two weeks. Imaging tests revealed a liver mass initially thought to be liver malignancy, but subsequent histopathological examination after liver removal confirmed the diagnosis as hepatocellular inflammatory myofibroblastic tumor (HIMT).ConclusionHepatic inflammatory myofibroblastic tumor (IMT) is an uncommon growth with vague clinical symptoms and lab results. Surgical removal remains the primary treatment method, resulting in favorable prognostic outcomes.

BackgroundAsian Americans with metastatic cancer are an understudied population. The Describing Asian American Well-Being and Needs in Cancer (DAWN) Study was designed to understand the supportive care needs of Chinese-, Vietnamese-, and Korean-descent (CVK) patients with metastatic cancer. ObjectiveThis study aims to present the DAWN Study protocol involving a primarily qualitative, convergent, mixed methods study from multiple perspectives (patients or survivors, caregivers, and health care professionals). MethodsCVK Americans diagnosed with solid-tumor metastatic cancer and their caregivers were recruited nationwide through various means (registries, community outreach newsletters, newspapers, radio advertisements, etc). Potentially eligible individuals were screened and consented on the web or through a phone interview. The study survey and interview for patients or survivors and caregivers were provided in English, traditional/simplified Chinese and Cantonese/Mandarin, Vietnamese, and Korean, and examined factors related to facing metastatic cancer, including quality of life, cultural values, coping, and cancer-related symptoms. Community-based organizations assisted in recruiting participants, developing and translating study materials, and connecting the team to individuals for conducting interviews in Asian languages. Health care professionals who have experience working with CVK patients or survivors with metastatic solid cancer were recruited through referrals from the DAWN Study community advisory board and were interviewed to understand unmet supportive care needs. ResultsRecruitment began in November 2020; data collection was completed in October 2022. A total of 66 patients or survivors, 13 caregivers, and 15 health care professionals completed all portions of the study. We completed data management in December 2023 and will submit results for patients or survivors and caregivers to publication outlets in 2024. ConclusionsFuture findings related to this protocol will describe and understand the supportive care needs of CVK patients or survivors with metastatic cancer and will help develop culturally appropriate psychosocial interventions that target known predictors of unmet supportive care needs in Chinese, Vietnamese, and Korean Americans with metastatic cancer. International Registered Report Identifier (IRRID)DERR1-10.2196/50032

Valorization of food processing effluent (FPE) by microalgae cultivation for astaxanthin production is regarded as a potential strategy to solve the environmental pollution of food processing industry and promote the development of eco-friendly agriculture. In this review paper, microalgal species which have the potential to be employed for astaxanthin in FPE were identified. Additionally, in terms of CO2 emission, the performances of microalgae cultivation and traditional methods for FPE remediation were compared. Thirdly, an in-depth discussion of some innovative technologies, which may be employed to lower the total cost, improve the nutrient profile of FPE, and enhance the astaxanthin synthesis, was provided. Finally, specific effects of dietary supplementation of algal astaxanthin on the growth rate, immune response, and pigmentation of animals were discussed. Based on the discussion of this work, the cultivation of microalgae in FPE for astaxanthin production is a value-adding process which can bring environmental benefits and ecological benefits to the food processing industry and agriculture. Particularly, technological innovations in recent years are promoting the shift of this new idea from academic research to practical application. In the coming future, with the reduction of the total cost of algal astaxanthin, policy support from the governments, and further improvement of the innovative technologies, the concept of growing microalgae in FPE for astaxanthin will be more applicable in the industry.

The impact of apolipoprotein E ε4 (APOE4), the strongest genetic risk factor for Alzheimer's disease (AD), on human brain cellular function remains unclear. Here, we investigated the effects of APOE4 on brain cell types derived from population and isogenic human induced pluripotent stem cells, post-mortem brain, and APOE targeted replacement mice. Population and isogenic models demonstrate that APOE4 local haplotype, rather than a single risk allele, contributes to risk. Global transcriptomic analyses reveal human-specific, APOE4-driven lipid metabolic dysregulation in astrocytes and microglia. APOE4 enhances de novo cholesterol synthesis despite elevated intracellular cholesterol due to lysosomal cholesterol sequestration in astrocytes. Further, matrisome dysregulation is associated with upregulated chemotaxis, glial activation, and lipid biosynthesis in astrocytes co-cultured with neurons, which recapitulates altered astrocyte matrisome signaling in human brain. Thus, APOE4 initiates glia-specific cell and non-cell autonomous dysregulation that may contribute to increased AD risk.

Abstract Transition metal oxides are promising electrocatalysts for zinc-air batteries, yet surface reconstruction caused by the adsorbate evolution mechanism, which induces zinc-ion battery behavior in the oxygen evolution reaction, leads to poor cycling performance. In this study, we propose a lattice oxygen mechanism involving proton acceptors to overcome the poor performance of the battery in the OER process. We introduce a stable solid base, hydroxy BaCaSiO4, onto the surfaces of PrBa0.5Ca0.5Co2O5+δ perovskite nanofibers with a one-step exsolution strategy. The HO-Si sites on the hydroxy BaCaSiO4 significantly accelerate proton transfer from the OH* adsorbed on PrBa0.5Ca0.5Co2O5+δ during the OER process. As a proof of concept, a rechargeable zinc-air battery assembled with this composite electrocatalyst is stable in an alkaline environment for over 150 hours at 5 mA cm–2 during galvanostatic charge/discharge tests. Our findings open new avenues for designing efficient OER electrocatalysts for rechargeable zinc-air batteries.

Abstract Background The organ most commonly invaded in echinococcosis is the liver; the lungs, brain, kidneys, heart, and spleen are rarely invaded, and multi-organ involvement in echinococcosis is even rarer. No studies have reported renal invasion after liver transplantation for hepatic alveolar echinococcosis. Case presentation We report here a case of renal invasion 2 years after allogeneic liver transplantation in a 53-year-old female patient with hepatic alveolar echinococcosis combined with lung metastases. At the time of the first consultation, the lesion had been found to involve the second hepatic hilum combined with lung metastases, but the patient requested conservative treatment, and the lesion was not controlled by taking albendazole for 3 years. After discussion in the treatment group, it was decided to use allogeneic liver transplantation and lung segmental resection for surgical treatment, after which the patient was put on long-term oral immunosuppression. She was hospitalized 2 years later for low back pain and diagnosed with renal alveolar echinococcosis. Due to significant compression and left-sided renal insufficiency, the final option was to remove the diseased kidney. It is worth mentioning that signs of unexplained urinary tract infection were present throughout the course of treatment. Conclusion This study suggests that extra attention should be paid to the presence of cryptogenic lesions in patients with hepatic alveolar echinococcosis who already have definite metastatic lesions. Immunosuppressive drugs after liver transplantation in patients with hepatic echinococcosis may cause occult lesions to develop into active ones. In clinical practice, particular attention should be paid to patients with hepatic alveolar echinococcosis with long-term concomitant signs of unexplained urinary tract infections, which may be a precursor clinical feature of cryptogenic renal alveolar echinococcosis.

Abstract Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field. Graphical abstract

Abstract Background Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease’s development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM. Methods This systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes’ certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373. Results Four thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA1c) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA1c, with standard-treatment (STA-TRE) as reference (MD − 0.17, 95%CI − 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD − 11.72, 95%CI − 17.82 to − 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence. Conclusions The high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients.

Cowpea mild mottle virus (CPMMV) is a global plant virus that poses a threat to the production and quality of legume crops. Early and accurate diagnosis is essential for effective managing CPMMV outbreaks. With the advancement in isothermal recombinase polymerase amplification and lateral flow strips technologies, more rapid and sensitive methods have become available for detecting this pathogen. In this study, we have developed a reverse transcription recombinase polymerase amplification combined with lateral flow strips (RT-RPA-LFS) method for the detection of CPMMV, specifically targeting the CPMMV coat protein (CP) gene. The RT-RPA-LFS assay only requires 20 min at 40°C and demonstrates high specificity. Its detection limit was 10 copies/μl, which is approximately up to 100 times more sensitive than RT-PCR on agarose gel electrophoresis. The developed RT-RPA-LFS method offers a rapid, convenient, and sensitive approach for field detection of CPMMV, which contribute to controlling the spread of the virus.

Abstract Background As an emerging standard of care for portal vein cavernous transformation (PVCT), Meso-Rex bypass (MRB) has been complicated and variated. The study aim was to propose a new classification of PVCT to guide MRB operations. Methods Demographic data, the extent of extrahepatic PVCT, surgical methods for visceral side revascularization, intraoperative blood loss, operating time, changes in visceral venous pressure before and after MRB, postoperative complications and the condition of bypass vessels after MRB were extracted retrospectively from the medical records of 19 patients. Results The median age of the patients (13 males and 6 females) was 32.5 years, while two patients were underage. Causes of PVCT can be summarized as follows: thrombophilia such as dysfunction of antithrombin III or proteins C; secondary to abdominal surgeries; secondary to abdominal infection or traumatic intestinal obstruction, and unknown causes. Intraoperatively, the median operation time was 9.5 h (7–13 h), and the intraoperative blood loss was 300 mL (100-1,600 mL). Ten cases used autologous blood vessels while 10 used allogeneic blood vessels. The vascular anastomosis was divided into the following types according to the site and approach: Type (T) 1-PV pedicel type, T2-confluence type, T3-major visceral vascular type; and T4-collateral visceral vascular type. Furthermore, the visceral venous pressure before and after MRB dropped significantly from 36 cmH2O (28–44) to 24.5 cmH2O (15–31) (P

Abstract Background Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. Methods Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. Results Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. Conclusions The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.

This study aims to examine the internationalization of clusters, a driving force of the rising of multinational firms from emerging markets. We explored the question from the knowledge and relational dimension of clusters. We examine how the configuration of four factors, namely, component knowledge, architecture knowledge, horizontal competition, and vertical coordination, within a cluster jointly affect the degree of cluster internationalization by utilizing the Fuzzy Set Qualitative Comparative Analysis (fsQCA) method. Using Data of 34 township clusters in Suzhou City, China, we identified three models that lead to a high cluster internationalization level.

With remarkable advancements in the development of connected and autonomous vehicles (CAVs), the integration of teleoperation has become crucial for improving safety and operational efficiency. However, teleoperation faces substantial challenges, with network latency being a critical factor influencing its performance. This survey paper explores the impact of network latency along with state-of-the-art mitigation/compensation approaches. It examines cascading effects on teleoperation communication links (i.e., uplink and downlink) and how delays in data transmission affect the real-time perception and decision-making of operators. By elucidating the challenges and available mitigation strategies, the paper offers valuable insights for researchers, engineers, and practitioners working towards the seamless integration of teleoperation in the evolving landscape of CAVs.