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Background: Cotton is a major fiber and oil crop worldwide. Cotton production, however, is often threatened by abiotic environmental stresses. GRAS family proteins are among the most abundant transcription factors in plants and play important roles in regulating root and shoot development, which can improve plant resistance to abiotic stresses. However, few studies on the GRAS family have been conducted in cotton. Recently, the G. hirsutum genome sequences have been released, which provide us an opportunity to analyze the GRAS family in G. hirsutum. Results: In total, 150 GRAS proteins from G. hirsutum were identified. Phylogenetic analysis showed that these GRAS protins could be classified into 14 subfamilies including SCR, DLT, OS19, LAS, SCL4/7, OS4, OS43, DELLA, PAT1, SHR, HAM, SCL3, LISCL and G_GRAS. The gene structure and motif distribution analysis of the GRAS members in G. hirsutum revealed that many genes of the SHR subfamily have more than one intron, which maybe a kind of form in the evolution of plant by obtaining or losing introns. Chromosomal location and duplication analysis revealed that segment and tandem duplication maybe the reasons of the expension of the GRAS family in cotton. Gene expression analysis confirmed the expression level of GRAS members were up-regulated under different abiotic stresses, suggesting that their possible roles in response to stresses. What’s more, higher expression level in root, stem, leaf and pistil also indicated these genes may have effect on the development and breeding of cotton. Conclusions: This study firstly shows the comprehensive analysis of GRAS members in G. hirsutum. Our results provide important information about GRAS family and a framework for stress-resistant breeding in G. hirsutum. [ABSTRACT FROM AUTHOR]

Objectives: To explore the bone regeneration effect of different forms of concentrated growth factor (CGF) when combined with deproteinized bovine bone mineral (DBBM) for simultaneous implant-guided bone regeneration (GBR) and its impact on postoperative adverse reactions., Methods: Fifty-seven patients who underwent simultaneous implant GBR were selected for the study and divided into three groups. The study involved three groups: the gel phase concentrated growth factor (GPCGF) group, which used GPCGF-DBBM mixture; the liquid phase concentrated growth factor (LPCGF) group, which used LPCGF-DBBM mixture; and the control group, which used DBBM alone. The thickness of the buccal lateral bones was measured using cone beam computed tomography (CBCT), and patients were asked to complete questionnaires to assess primary adverse reactions during the first week after surgery. The data were analyzed using one-way ANOVA, Tukey test, and Kruskal-Wallis test., Results: The buccal lateral bone thickness in the GPCGF, LPCGF, and control groups decreased significantly at 6 months post-surgery compared to immediately after surgery. The change of bone thickness in the GPCGF group was lower than that in the control group (p < 0.01), and that in the LPCGF group did not differ from that in the control group (p > 0.05). During the postoperative week, statistically significant differences could be observed in bleeding, mouth opening, chewing, sleeping, speaking, daily routine, and pain (p < 0.05)., Conclusions: Compared to the DBBM applied alone, the GPCGF-DBBM mixture has more positive implications for reducing bone resorption, promoting bone reconstruction and relieving certain postoperative adverse effects in dental implants with simultaneous GBR. The GPCGF-DBBM mixture was superior to the LPCGF-DBBM mixture in alleviating adverse effects in terms of bleeding and speaking after GBR., Clinical Trials Registration Number: The Chinese Clinical Trial Registry, NO. ChiCTR2300070107 (03/04/2023)., Competing Interests: Declarations. Ethics approval and consent to participate: This randomized controlled clinical trial was approved by the ethically committee of Stomatological Hospital of Chongqing Medical University (No.2020-003). This randomized controlled clinical trial was performed in accordance with the guiding principles of the Declaration of Helsinki. All participants provided written informed consent to participate in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Severe hepatic steatosis can exacerbate Ischemia-reperfusion injury (IRI), potentially leading to early graft dysfunction and primary non-function. In this study, we investigated the heterogeneity of different subpopulations of Urine-derived stem cells (USCs) to explore the most suitable cell subtype for treating severe steatotic liver IRI., Methods: This study utilized scRNA-seq and Bulk RNA-seq to investigate the transcriptional heterogeneity between Spindle-shaped USCs (SS-USCs) and Rice-shaped USCs (RS-USCs). Additionally, rat fatty Liver transplantation (LT) model, mouse fatty liver IRI model, and Steatotic Hepatocyte Hypoxia-Reoxygenation (SHP-HR) model were constructed. Extracellular vesicles derived from SS-USCs and RS-USCs were isolated and subjected to mass spectrometry analysis. The therapeutic effects of Spindle-shaped USCs Exosomes (SS-USCs-Exo) and Rice-shaped USCs Exosomes (RS-USCs-Exo) were explored, elucidating their potential mechanisms in inhibiting ferroptosis and alleviating IRI., Results: Multiple omics analyses confirmed that SS-USCs possess strong tissue repair and antioxidant capabilities, while RS-USCs have the potential to differentiate towards specific directions such as the kidney, nervous system, and skeletal system, particularly showing great application potential in renal system reconstruction. Further experiments demonstrated in vivo and in vitro models confirming that SS-USCs and SS-USCs-Exo significantly inhibit ferroptosis and alleviate severe fatty liver IRI, whereas the effects of RS-USCs/RS-USCs-Exo are less pronounced. Analysis comparing the proteomic differences between SS-USCs-Exo and RS-USCs-Exo revealed that SS-USCs-Exo primarily inhibit ferroptosis and improve cellular viability by secreting exosomes containing Glutathione Peroxidase 4 (GPX4) protein. This highlights the most suitable cell subtype for treating severe fatty liver IRI., Conclusions: SS-USCs possess strong tissue repair and antioxidant capabilities, primarily alleviating ferroptosis in the donor liver of fatty liver through the presence of GPX4 protein in their exosomes. This highlights SS-USCs as the most appropriate cell subtype for treating severe fatty liver IRI., Competing Interests: Declarations. Ethics approval and consent to participate: All human urine samples were obtained with informed donor consent and under the approval of IRB of Affiliated Hospital of Qingdao University, Qingdao, China (Title of an ethical approved project, “Human Spindle-shaped Urine-derived Stem Cell Exosomes Alleviate Severe Fatty Liver Ischemia–Reperfusion Injury by Inhibiting Ferroptosis via GPX”, Approval number, KY2018-036-02 and date of approval, July 5, 2021). All experimental protocols were approved and carried out in accordance with the relevant guidelines and regulations of the Ethics Committee of Qingdao University, China (Title of an ethical approved project, “Exosomes Derived from Spindle-Shaped USCs Inhibit Fatty Liver Ischemia–Reperfusion Injury by Enhancing GPX4”, Approval number, 20210310C57BL4220211010061; 20210310SD4220211010062, and date of approval, March 1, 2021). All investigations were conducted according to the principles expressed in the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: The unique anatomy and biomechanics of the distal humerus make distal humeral shaft fractures a significant challenge in orthopedic surgery. Conventional posterior surgical approaches are associated with risks such as iatrogenic radial nerve injury and increased soft tissue trauma., Objective: This study aimed to assess the clinical efficacy of an inverted PHILOS plate using an anterior minimally invasive percutaneous approach for treating distal humeral shaft fractures., Methods: We enrolled 32 patients with distal humeral shaft fractures. The surgical technique involved an anterior minimally invasive percutaneous application of an inverted PHILOS plate. Outcome measures included operative time, intraoperative blood loss, incision length, fracture healing time, and functional scores (Constant-Murley and Mayo Elbow Performance Scores). Postoperative complications, including nerve injury and nonunion, were documented., Results: The mean operative time was 1.69 ± 0.66 h, with a median blood loss of 50 ml (IQR: 50-100 ml). The mean incision length was 10.9 ± 1.78 cm, and the mean time to fracture healing was 11.2 ± 3.68 weeks. Functional outcomes were satisfactory, with a mean Constant shoulder score of 92.69 ± 6.6 and a mean Mayo Elbow Performance Score of 91.4 ± 8.04. No instances of iatrogenic nerve injury or nonunion were observed., Conclusion: The anterior minimally invasive percutaneous approach using an inverted PHILOS plate is an effective method for treating distal humeral shaft fractures. This technique minimizes soft tissue damage, reduces the risk of iatrogenic radial nerve injury, and ensures reliable fracture stabilization, thus offering a promising alternative to conventional posterior approaches., Competing Interests: Declarations. Ethics approval and consent to participate: Institutional Review Board approval was received from the ethics committee of Fuzhou second hospital (2024308) and all consents were signed to participate and publish. Consent for publication: All presentations of case reports have consent for publication. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Pulmonary hypertension (PH) is a devastating disease marked by elevated pulmonary artery pressure, resulting in right ventricular (RV) failure and mortality. Despite the identification of several dysregulated genes in PH, the involvement of circular RNAs (circRNAs), a subset of long noncoding RNAs, remains largely unknown., Methods: In this study, high-throughput RNA sequencing was performed to analyze the genome-wide expression patterns of circRNAs in pulmonary arteries from three models of PH rats induced by hypoxia (Hyp), hypoxia/Sugen5416 (HySu), and monocrotaline (MCT). Differentially expressed circRNAs (DEcircRNAs) were identified, and a weighted gene coexpression network was constructed to explore circRNA networks associated with PH pathogenesis. A circRNA-miRNA-mRNA regulatory network was built, and the functional significance of targeted mRNAs was evaluated. Single-cell RNA sequencing provided insights into the distribution of cell type-specific circRNAs across PH progression., Results: Our analysis revealed 45 circRNAs exhibiting significant changes across all three PH rat models, with their host genes participating in the calcium signaling and muscle contraction. We identified 372 PH-related circRNA-miRNA-mRNA interactions, shedding light on the regulatory networks during PH development. Furthermore, we uncovered 186, 195 and 311 Hyp-, Hysu- and MCT-specific circRNAs, respectively. These circRNAs were enriched in distinct biological processes, emphasizing their unique regulatory roles. Single-cell spatial distribution analysis of these circRNAs in the pulmonary arteries of PH patients revealed that Hyp-specific circRNA predominantly appeared in the pulmonary vascular structural cells, while HySu- and MCT-specific circRNAs exhibited broader distribution, including significant enrichment in immune-related cells., Conclusion: Our study presents the first comprehensive view of circRNA regulatory networks in the pulmonary arteries of three PH rat models. We provide insights into PH-associated circRNAs, particularly their involvement in calcium signaling and muscle contraction., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments and related protocols were conducted in accordance with relevant guidelines and have been approved by the Animal Care and Use Committee of Shenzhen University (Ethical Approval Number: 2021003). All methods of animal experimentation in this study strictly adhered to the ARRIVE guidelines. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: This review explores recent advancements in anesthesia care, focusing on the integration of innovative practices to enhance patient outcomes across the perioperative period., Methods: Following the framework of Whitmore and Knafl, we systematically searched six databases (PubMed, Google Scholar, EMBASE, CINAHL, OVID, and Cochrane Library) for studies published from January 2020 to January 2024, relating to advancements in anesthesia care, best practice implementation, and patient outcomes. After independent screening and data extraction by two reviewers, the review focuses on innovations in anesthetic drugs, monitoring technologies, anesthesia techniques, and evidence-based practices in anesthesia and clinical guidelines., Results: Of the 25,984 studies retrieved, 26 met inclusion criteria. Recent developments in anesthetic drugs have improved safety and efficacy, reducing complications. Advanced monitoring devices, such as multiparameter and brain function monitors, have enhanced patient safety through real-time assessments. Innovations in regional anesthesia and ultrasound-guided nerve blocks have led to better pain management, reduced recovery time, and minimized morbidity. Additionally, evidence-based practices like comprehensive preoperative assessment, patient education, and multidisciplinary teamwork significantly improved patient outcomes., Conclusion: Integrating the latest innovations and best practices in anesthesia care is essential for optimizing patient outcomes. Ongoing research and adoption of advanced technologies are crucial to addressing current challenges and enhancing anesthesia quality. This review emphasizes the importance of a holistic approach from preoperative preparation to postoperative recovery to achieve optimal patient outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Few studies investigated the implications of post-PCI QFR and post-PCI ΔQFR (absolute increase of QFR) in de novo lesions of small coronary disease after drug-coated balloon (DCB)., Objectives: We sought to investigate the prognostic implications of post-PCI QFR and post-PCI ΔQFR in patients who received DCB only., Methods: Patients were divided according to the optimal cutoff value of the post-PCI QFR and the post-PCI ΔQFR. The primary outcome was major adverse cardiovascular events (MACE), including target vessel revascularization (TVR), cardiac death, and myocardial infarction (MI)., Results: The optimal cutoff values of QFR and ΔQFR for the MACE rate were 0.86 and 0.57, respectively. There were 175 patients (61.2%) with a high QFR (≥ 0.86) and 113 patients (39.5%) with a high ΔQFR (≥ 0.57) after PCI. The MACE rate was significantly higher in patients with a low QFR compared to a high QFR (5.7% vs. 27.0%, hazard ratio [HR]: 3.632, 95% confidence interval [CI]: 1.872 to 7.044, P < 0.001). The MACE rate was higher in patients with a low ΔQFR increase compared to those with high ΔQFR (4.4% vs. 20.2%, HR: 4.700, 95%CI: 2.430 to 9.089, P = 0.001). In multivariable model, a low post-PCI QFR and a low post-PCI ΔQFR was independent predictor of MACE (adjusted HR: 4.071, 95%CI: 2.037 to 8.135, P = 0.001)., Conclusions: After DCB in de novo lesions of small coronary disease, both post-PCI QFR and ΔQFR showed similar prognostic implications in MACE., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the ethical committee of Beijing Anzhen hospital and informed consent was provided by all of the patients according to hospital guidelines. All the experiment was conducted according to the Helsinki Declaration. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Immunotherapy utilizing dendritic cells (DCs) and cytokine-induced killer (CIK) cells is a promising treatment approach for solid tumors. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of DC-CIK immunotherapy by assessing overall survival, progression-free survival, overall response rate, disease control rate, and adverse events in relevant randomized controlled trials. The results of this analysis will contribute to optimizing treatment strategies and improving cancer immunotherapy outcomes., Method: This systematic review and meta-analysis adhered to PRISMA guidelines. A comprehensive search was conducted on multiple databases for RCTs studying the combination of DC-CIK immunotherapy for solid tumors. Inclusion criteria were RCTs comparing DC-CIK immunotherapy with control therapy and reporting OS, PFS, ORR, or DCR. Two authors independently performed study selection and data extraction, with disagreements resolved through consensus or consultation with a third reviewer. Extracted data included study characteristics, participant information, interventions, outcomes, and quality assessment. Statistical analysis was performed using Review Manager and Stata software. Heterogeneity was assessed using chi-square and I-squared statistics. Sensitivity analysis and assessment of publication bias were planned., Results: A total of 1013 records were initially retrieved, and after a thorough screening process, 13 randomized controlled trials (RCTs) were included in the meta-analysis. These studies involved a total of 1443 patients, with 730 receiving DC-CIK immunotherapy and 713 in the control groups. The included studies covered various cancer types, with the majority conducted in mainland China. The meta-analysis showed that DC-CIK immunotherapy was associated with improved overall survival (OS) and progression-free survival (PFS) compared to control therapy. Furthermore, DC-CIK immunotherapy demonstrated higher overall response rate (ORR) and disease control rate (DCR) compared to non-DC-CIK therapy. Adverse events were reported in both groups, with fever being more common in the DC-CIK immunotherapy group and bone marrow suppression and gastrointestinal reactions more common in the control group. Sensitivity analyses confirmed the stability of the results, while publication bias was observed for PFS and fever., Conclusions: DC-CIK immunotherapy shows promising efficacy and safety for solid tumors, improving survival rates and response rates. Further research is needed to optimize treatment regimens and identify predictive factors., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Purpose: The KRAS mutation is highly prevalent in NSCLC and is associated with poor efficacy of immunotherapy. Nevertheless, the impact of KRAS mutation, mutation subtypes, and co-mutations on the effectiveness of immunotherapy remains uncertain. This study aimed to assess the influence of the KRAS mutation on the effectiveness of immunotherapy in NSCLC, specifically examining different subtypes of KRAS mutations and co-mutations., Methods: We performed an extensive search of multiple databases, covering the period from January 1, 2000, to December 5, 2023. A total of 24 articles met our inclusion criteria and were included in this study. A comparative analysis assessed the influence of different subgroups, including KRAS mutation, KRAS wild-type, KRAS G12C mutation, KRAS G12D mutation, and KRAS with co-mutations in NSCLC with immunotherapy. The study outcomes include HR, with corresponding 95% CI and P-values for OS and PFS using Review Manager 5.4 software for the meta-analysis., Result: The KRAS mutation appears to have a more beneficial impact on OS (HR 0.54 [95% CI: 0.41-0.71]; P < 0.00001) and PFS (HR 0.63 [95% CI: 0.53-0.76]; P < 0.00001) in NSCLC patients receiving immunotherapy compared to those without immunotherapy. The presence of KRASG12C mutation has been found to have a positive impact on PFS (HR 0.39 [95% CI: 0.25-0.62]; P < 0.0001) in NSCLC patients who undergo immunotherapy, compared to those who did not receive immunotherapy. KRAS non-G12D mutation is considerably associated with longer OS (HR 1.52 [95% CI: 1.10-2.10]; P = 0.01). The clinical benefit in OS between patients without STK11 co-mutation and those who have KRAS mutation with STK11 is significant (HR 1.46 [95% CI: 1.10-1.93]; P = 0.008). Comparing the impact of OS patients without KEAP1/NFE2L2 mutation to those with KRAS and KEAP1/NFE2L2 co-mutations showed a significant impact (HR 1.89 [95% CI: 1.33-2.68]; P = 0.0004)., Conclusion: The KRAS mutation and KRAS G12C mutation confer benefits that impact OS and PFS in NSCLC patients treated with immunotherapy. However, the KRAS G12D mutation negatively impacts OS compared to the KRAS non-G12D mutation. Furthermore, KRAS co-mutations involving STK11 and KEAP1/NFE2L2 are associated with a negative impact on the efficacy of immunotherapy in NSCLC patients., (© 2024. The Author(s).)

Background: As the second most populous country in the world, China has a huge demand for health human resources. Over the past decade, the Chinese government has continuously increased investment in the health sector and implemented relevant policies and systems in an attempt to enhance the overall quantity and equity of health human resources. This study aims to analyze the equity and developmental trends in the allocation of health human resources in China from 2012 to 2021, providing reference and theoretical support for the government's further optimization of health human resources allocation., Methods: This study collected health human resources data from 31 provinces, municipalities, and autonomous regions in China from 2012 to 2021. The methods employed included Lorenz curves, Gini coefficients, and agglomeration degree analysis, which examined the developmental trends and equity of health human resources from the perspectives of population and geographical., Results: This study found that over the past decade, there has been a significant increase in the total quantity of health human resources in China, accompanied by an improvement in equity, although disparities still exist. There are notable variations in the distribution of health human resources based on geographical area, with disparities between different regions. Relative shortages of health human resources are observed in western regions, while some areas in the eastern and central regions exhibit an abundance or surplus of health human resources., Conclusion: Overall, health human resources in China have experienced stable development, with an incremental improvement in allocation equity, yet there remains considerable room for progress. It is imperative to continue strengthening policy guidance and regulation to facilitate the rational flow of health human resources, narrow regional disparities, and achieve the goal of universal health coverage., (© 2024. The Author(s).)

Objectives: Seeking a noninvasive predictor for BRAF V600E mutation status of pleomorphic xanthoastrocytomas (PXAs) is essential for their prognoses and therapeutic use of BRAF inhibitors. We aimed to noninvasively diagnose BRAF V600E-mutated PXAs using MRI morphologic, DWI and clinical parameters., Methods: The clinical findings, anatomical MRI characteristics, and diffusion parameters of 36 pathologically confirmed PXAs were retrospectively analyzed, and BRAF V600E-mutated (n = 16) and wild-type (n = 20) groups were compared. A binary logistic-regression analysis was performed, and a ROC curve was calculated to determine the independent predictors of BRAF V600E mutation status, diagnostic accuracy, and optimal cut-off value., Results: A comparison of findings between groups showed that BRAF V600E-mutated PXAs were more frequent in children and young adults (≤ 35 years; P = 0.042) who often had histories of seizures (P = 0.004). Furthermore, BRAF V600E-mutated PXAs generally presented as solitary masses (P = 0.024), superficial locations with meningeal attachment (P < 0.001), predominantly cystic with mural nodules (P = 0.005), and had greater minimal ADC ratio (ADC ratio ) values of the tumor and peritumoral edema (P < 0.001). Binary logistic regression showed that age ≤ 35 years, solitary mass, superficial locations with meningeal attachment, and a greater minimal ADC ratio of the tumor were independent predictors of BRAF V600E-mutated PXAs. The combination of all four independent predictors resulted in the highest sensitivity (100%) and specificity (90%), with AUC = 0.984., Conclusion: The BRAF V600E mutation status of PXAs could be noninvasively predicted using clinical and MRI characteristics., Critical Relevance Statement: The noninvasive diagnostic criteria for BRAF V600E-mutated PXAs could offer guidance for the administration of BRAF V600E mutation inhibitors in the future., (© 2024. The Author(s).)

Ovine contagious pustular dermatitis (ORF) is one of the main diseases of sheep and is a zoonotic disease caused by Ovine contagious pustular dermatitis virus (ORFV) infection, posing a significant constraint on sheep breeding industry and human health. The Tibetan medical formulation composed of Polygonum leucoides, Polygonum xanthoxylum and Acanthophora rotunda significantly regulated lymphocyte immune function following ORFV stimulation, although the mechanism remains unclear. In order to study the immunomodulatory effects and mechanism of three Tibetan medicinal extracts (Polygonum leucoides, Polygonum xanthoxylum, and Acanthophora rotunda) against ORFV in vitro, sheep peripheral blood lymphocytes were isolated in vitro and treated with different concentrations of Tibetan medicine compound extract solution after ORFV infection. The cytokine expression levels in lymphocytes were measured at 4 h, 8 h and 12 h. Additionally endogenous metabolites in lymphocytes at 0 h, 4 h, 8 h and 12 h were quantified by untargeted metabolomics method. The results showed that, the extracts could regulate the lymphocyte immune factors altered by ORFV, and regulate the lymphocyte immune function through cysteine and methionine metabolic pathways as well as the pyrimidine metabolic pathways, potentially alleviating the immune evasion induced by ORFV., (© 2024. The Author(s).)

Background: The emergence of the COVID-19 pandemic in December 2019 initiated a global transformation in healthcare practices, particularly with respect to hospital management. PCR testing mandates for medical treatment seekers were introduced to mitigate virus transmission., Aims: This study examines the impact of these changes on the management of patients with appendicitis., Methods: We conducted a retrospective analysis of medical records for 748 patients diagnosed with appendicitis who underwent surgery at a tertiary care hospital during two distinct periods, the pre-pandemic year 2019 and the post-pandemic year 2021. Patient demographics, clinical characteristics, laboratory data, surgical outcomes, and hospital stay duration were assessed., Results: While no significant differences were observed in the general characteristics of patients between the two groups, the time from hospital visit to operation increased significantly during the pandemic. Unexpectedly, delayed surgical intervention was associated with shorter hospital stays but did not directly impact complication rates. There was no discernible variation in the type of surgery or surgical timing based on symptom onset. The pandemic also prompted an increase in appendicitis cases, potentially related to coronavirus protein expression within the appendix., Conclusions: The COVID-19 pandemic has reshaped the landscape of appendicitis management. This study underscores the complex interplay of factors, including changes in hospital protocols, patient concerns, and surgical timing. Further research is needed to explore the potential link between COVID-19 and appendicitis. These insights are valuable for informing healthcare practices during and beyond the pandemic., (© 2024. The Author(s).)

Background: Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated., Methods: A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated., Results: The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS., Conclusion: Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly., (© 2024. The Author(s).)

Background: Lung adenocarcinoma (LUAD) has been a leading cause of cancer-related mortality worldwide. Early intervention can significantly improve prognosis. DNA methylation could occur in the early stage of tumor. Comprehensive understanding the epigenetic landscape of early-stage LUAD is crucial in understanding tumorigenesis., Methods: Enzymatic methyl sequencing (EM-seq) was performed on 23 tumors and paired normal tissue to reveal distinct epigenetic landscape, for compared with The Cancer Genome Atlas (TCGA) 450K methylation microarray data. Then, an integrative analysis was performed combined with TCGA LUAD RNA-seq data to identify significant differential methylated and expressed genes. Subsequently, the prognostic risk model was constructed and cellular composition was analyzed., Results: Methylome analysis of EM-seq comparing tumor and normal tissues identified 25 million cytosine-phosphate-guanine (CpG) sites and 30,187 differentially methylated regions (DMR) with a greater number of untraditional types. EM-seq identified a significantly higher number of CpG sites and DMRs compared to the 450K microarray. By integrating the differentially methylated genes (DMGs) with LUAD-related differentially expressed genes (DEGs) from the TCGA database, we constructed prognostic model based on six differentially methylated-expressed genes (MEGs) and verified our prognostic model in GSE13213 and GSE42127 dataset. Finally, cell deconvolution based on the in-house EM-seq methylation profile was used to estimate cellular composition of early-stage LUAD., Conclusions: This study firstly delves into novel pattern of epigenomic DNA methylation and provides a multidimensional analysis of the role of DNA methylation revealed by EM-seq in early-stage LUAD, providing distinctive insights into its potential epigenetic mechanisms., (© 2024. The Author(s).)

Background: Fractures of hands and feet are common in children, but relevant epidemiological studies are currently lacking. We aim to study the epidemiological characteristics of hand and foot fractures and growth plate injuries in children and provide a theoretical basis for their prevention, diagnosis, and treatment., Methods: We retrospectively analyzed the data of children with hand and foot fractures who were hospitalized at Shenzhen Children's Hospital between July 2015 and December 2020. Data on demographic characteristics, fracture site, treatment method, etiology of injury, and accompanying injuries were collected. The children were divided into four age groups: infants, preschool children, school children, and adolescents. The fracture sites were classified as first-level (the first-fifth finger/toe, metacarpal, metatarsal, carpal, and tarsal) and second-level (the first-fifth: proximal phalanx, middle phalanx, distal phalanx, metacarpal, and metatarsal) sites. The changing trends in fracture locations and injury causes among children in each age group were analyzed., Results: Overall, 1301 children (1561 fractures; 835 boys and 466 girls) were included. The largest number of fractures occurred in preschool children (n = 549, 42.20%), with the distal phalanx of the third finger being the most common site (n = 73, 15.57%). The number of fractures in adolescents was the lowest (n = 158, 12.14%), and the most common fracture site was the proximal phalanx of the fifth finger (n = 45, 29.61%). Of the 1561 fractures, 1143 occurred in the hands and 418 in the feet. The most and least common first-level fracture sites among hand fractures were the fifth (n = 300, 26.25%) and first (n = 138, 12.07%) fingers, respectively. The most and least common first-level foot fracture locations were the first (n = 83, 19.86%) and fourth (n = 26, 6.22%) toes, respectively. The most common first-level and second level etiologies were life related injuries (n = 1128, 86.70%) and clipping injuries (n = 428, 32.90%), respectively. The incidence of sports injuries gradually increased with age, accounting for the highest proportion in adolescents (26.58%). Hand and foot fractures had many accompanying injuries, with the top three being nail bed injuries (570 cases, 36.52%), growth plate injuries (296 cases, 18.96%), and distal severed fracture (167 cases, 10.70%). Among the 296 growth plate injuries, 246 occurred on the hands and 50 on the feet., Conclusions: In contrast to previous epidemiological studies on pediatric hand and foot fractures, we mapped the locations of these fractures, including proximal, shaft, distal, and epiphyseal plate injuries. We analyzed the changing trends in fracture sites and injury etiologies with age. Hand and foot fractures have many accompanying injuries that require attention during diagnosis and treatment. Doctors should formulate accident protection measures for children of different ages, strengthen safety education, and reduce the occurrence of accidental injuries., (© 2024. The Author(s).)

Polymeric micelle systems for drug delivery, monitor and chemotherapy have gained significant attention, and reductive polymeric micelle systems have become particularly attractive due to their controlled release behavior without additional assistance. However, there are challenges in accurately controlling drug and probe release from the nanoparticles and determining the loading content of drug and probe. To address these issues, we have developed a reduction-responsive Pt(IV) prodrug-based polymeric delivery system that can be dynamically monitored using aggregation-induced emission luminogens (AIE) based bioprobes. These polymeric micelle can self-assemble into nanoparticles and release both bio-active Pt(II) drug and bio-probe upon reduction activation. TPE molecules released in the inner endo/lysosomal microenvironment aggregate and fluoresce upon irradiation, thus allowing real-time tracking of drug biodistribution without additional contrast agents. Advantages of this system include position-specific chemical bond cleavage, control of platinum content, and monitoring of drug reduction and biodistribution., (© 2024. The Author(s).)

Background: The relationship between serum selenium (Se) and acute kidney injury after adult cardiac surgery (CSA-AKI) remains controversial. This study aimed to investigate the association of preoperative Se level with incident CSA-AKI., Method and Results: A retrospective cohort study was conducted on patients who underwent cardiac surgery. The primary outcome was incident CSA-AKI. Multivariable logistic regression models and natural cubic splines were used to estimate the association of Se levels and primary outcome. A total of 453 patient with a mean age of 62.97 years were included. Among all patients, 159 (35.1%) incident cases of CSA-AKI were identified. The level of preoperative Se concentration in patients with CSA-AKI was significant lower than that in patients without CSA-AKI. The higher preoperative Se level was significantly associated with decreased risk of CSA-AKI (adjusted OR 0.91, 95% CI: 0.87-0.99). Dose-response relationship curve revealed a nearly L-shape correlation between serum Se selenium levels and incident CSA-AKI., Conclusion: Our study suggested that a higher level of serum Se was significantly associated with lower risk of CSA-AKI. Further prospective studies are needed to clarify the causal relationship between serum Se level and incident CSA-AKI., (© 2024. The Author(s).)

Background: Lung adenocarcinoma (LUAD) has high morbidity and mortality. Despite substantial advances in treatment, the prognosis of patients with LUAD remains unfavorable. The ceRNA axis has been reported to play an important role in the pathogenesis of LUAD. In addition, cuproptosis is considered an important factor in tumorigenesis. The expression of CBX2 has been associated with the development of multiple tumors, including LUAD. However, the precise molecular mechanisms through which the cuproptosis-related ceRNA network regulates CBX2 remain unclear., Methods: The DEGs between tumor and normal samples of LUAD were identified in TCGA database. The "ConsensusClusterPlus" R package was used to perform consensus clustering based on the mRNA expression matrix and cuproptosis-related gene expression profile. Then, LASSO-COX regression analysis was performed to identify potential prognostic biomarkers associated with cuproptosis, and the ceRNA network was constructed. Finally, the mechanisms of ceRNA in LUAD was studied by cell experiments., Results: In this study, the AC144450.1/miR-424-5p axis was found to promote the progression of LUAD by acting on CBX2. The expression of AC144450.1 and miR-424-5p can be altered to regulate CBX2 and is correlated with cell proliferation and cell cycle of LUAD. Mechanistically, AC144450.1 affects the expression of CBX2 by acting as the ceRNA of miR-424-5p. In addition, a cuproptosis-related model were constructed in this study to predict the prognosis of LUAD., Conclusions: This study is the first to demonstrate that the AC144450.1/miR-424-5p/CBX2 axis is involved in LUAD progression and may serve as a novel target for its diagnosis and treatment., (© 2024. The Author(s).)

Background and Aims: We aimed to investigate the immune characteristics of intestinal CD8 + gamma delta T (CD8 + γδ T) cells in Crohn's disease (CD) and their correlation with disease activity., Methods: The study cohorts included 21 CD patients and 21 healthy individuals. CD8 + γδ T cells were isolated from human ileal mucosa for detection by flow cytometry. The activation or inhibition status of cells was detected by detecting the expression of activation marker HLA-DR and the immunosuppressive molecule PD-1 on cells. The cytotoxicity of cells was assessed by detecting the expression of cytotoxic molecules (Perforin, Granzyme B, and TRAIL) in cells. Ratios of investigated cells were calculated as prediction factors by receiver operating characteristic curve (ROC) analysis., Results: The study revealed a reduction in intestinal CD8 + γδT cells among active CD patients, with a more pronounced reduction observed in moderately active patients compared to mildly active patients. Moreover, active CD patients exhibited heightened activation levels in their intestinal CD8 + γδT cells, whereas the activation was comparatively weakened in moderately active patients compared with mildly active patients. Additionally, the cytotoxicity of intestinal CD8 + γδT cells was enhanced solely in mildly active patients, while it was impaired in moderately active patients compared with mildly active patients. Furthermore, HLA-DR + CD8 + γδT cell ratio, CD8 + γδT ratio, and CD8 + γδT count were identified as indicators in the diagnosis of active CD. Meanwhile, the ratios of Granzyme B + CD8 + γδT cell and Perforin + CD8 + γδT cell were identified as indicators that distinguish mildly moderately active CD cases., Conclusions: Intestinal CD8 + γδT was reduced in active CD patients, but their activation and cytotoxicity were enhanced. However, with increased disease activity, intestinal CD8 + γδ T cells became dysfunctional. CD-specific perturbations observed in various phenotypic markers in CD8 + γδ T cells can be used as indicators to assist in diagnosing CD patients., (© 2024. The Author(s).)

Background: There is a causal link between childhood socioeconomic status and health status in adulthood and beyond. It's vital to comprehend the relationship between childhood socioeconomic status and mental health among older Chinese individuals from the current generation who have undergone significant social changes in China. This understanding is critical to foster healthy demographic and social development in China., Methods: Using data from the 2020 China Family Panel Studies, we investigate the relationship between childhood socioeconomic status and depression in older adults. Additionally, we examine the mediating role of adult socioeconomic status and subjective well-being., Results: 1) Childhood socioeconomic status of Chinese older adults differences by region of residence, while depression levels differences by gender, region of residence, and marital status. 2) Adult socioeconomic status mediated the relationship between childhood socioeconomic status and depression in older adults. 3) Adult socioeconomic status and subjective well-being had a chain-mediated role in the relationship between childhood socioeconomic status and depression in older adults., Conclusions: In terms of childhood socioeconomic status, older adults in urban regions were significantly higher than those in rural regions. As for depression level, female older adults were more depressed than males; married older people have the lowest depression levels, while unmarried and widowed older people have higher depression levels; older adults in rural regions had higher depression levels than those in urban regions. Evidence from our study further suggests that childhood socioeconomic status can suppress the depression level in older adults through adult socioeconomic status; it can also further reduce the depression level in older adults through the chain mediation of adult economic status affecting subjective well-being. As depression is more prevalent among older individuals with a lower childhood socioeconomic status, it is vital to prioritize the extensive impact of childhood socioeconomic status as a distal factor and investigate "upstream" solutions to enhance childhood socioeconomic status and reduce the gap during the early years of life., (© 2024. The Author(s).)

HLX01 (HanliKang ® ) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL., (© 2024. The Author(s).)

Background: This work aimed to study natural humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: Chemiluminescent immunoassay (CLIA) was used to detect the neutralizing antibody (Nabs) and IgG., Results: Nabs peaked on days 57-96 after symptom onset and remained detected on days 97-132. The Nabs in the 32 patients who were dynamically monitored showed four changing patterns. The titers of Nabs and IgG were correlated, and three modes of relationship were found between them., Conclusions: Nabs showed a regular change in the course of coronavirus disease 2019 (COVID-19). The detection of Nabs is very important for monitoring the course of COVID-19 and predicting the strength of antibody protection., (© 2023. The Author(s).)

Background: Identifying individual characteristics based on trace evidence left at a crime scene is crucial in forensic identification. Microbial communities found in fecal traces have high individual specificity and could serve as potential markers for forensic characterization. Previous research has established that predicting body type based on the relative abundance of the gut microbiome is relatively accurate. However, the long-term stability and high individual specificity of the gut microbiome are closely linked to changes at the genome level of the microbiome. No studies have been conducted to deduce body shape from genetic traits. Therefore, in this study, the vital role of gut bacterial community characteristics and genetic traits in predicting body mass index (BMI) was investigated using gut metagenomic data from a healthy Chinese population., Results: Regarding the gut microbial community, the underweight group displayed increased α-diversity in comparison to the other BMI groups. There were significant differences in the relative abundances of 19 species among these three BMI groups. The BMI prediction model, based on the 31 most significant species, showed a goodness of fit (R 2 ) of 0.56 and a mean absolute error (MAE) of 2.09 kg/m 2 . The overweight group exhibited significantly higher α-diversity than the other BMI groups at the level of gut microbial genes. Furthermore, there were significant variations observed in the single-nucleotide polymorphism (SNP) density of 732 contigs between these three BMI groups. The BMI prediction model, reliant on the 62 most contributing contigs, exhibited a model R 2 of 0.72 and an MAE of 1.56 kg/m 2 . The model predicting body type from 44 contigs correctly identified the body type of 93.55% of the study participants., Conclusion: Based on metagenomic data from a healthy Chinese population, we demonstrated the potential of genetic traits of gut bacteria to predict an individual's BMI. The findings of this study suggest the effectiveness of a novel method for determining the body type of suspects in forensic applications using the genetic traits of the gut microbiome and holds great promise for forensic individual identification., (© 2023. The Author(s).)

Background: Congenital muscular torticollis (CMT) is a common musculoskeletal disease affecting infants and young children. If CMT is not treated correctly and timely, it can lead to limited head and neck movements, head and neck deviation, and abnormal posture. In order to improve patients' symptoms and alleviate the negative impact of the disease on their lives, we are committed to exploring the treatment of CMT., Methods: The general clinical and ultrasonographic data of 2599 children with CMT who received standardized treatment at Shenzhen Children's Hospital from 2004 to 2020 were retrospectively reviewed. According to given treatment, children with CMT were divided into the physiotherapy group, physiotherapy combined with glucocorticoid treatment group, and surgical treatment group. We divided children with CMT into local mass, uniform thickening, and atrophy according to ultrasound features. General clinical information, treatment, and ultrasound examination data in each group were compared. Additionally, electronic medical records of 2344 patients admitted due to CMT in 17 tertiary children's hospitals of China's Futang Research Center of Pediatric Development (FRCPD) from 2015 to 2019 were retrospectively analyzed. Data on sex, age, year of admission and discharge, and treatment costs during hospitalization were extracted from the first medical record pages according to the ICD codes. The data were assessed for normality using the Kolmogorov-Smirnov test. Depending on the data distribution, they were analyzed using parametric tests, such as the t-test, or non-parametric tests. Qualitative data are expressed as percentages (%) and analyzed using the chi-square or Fisher's exact probability test, with α = 0.05 as the test level. P < 0.05 was considered to be indicative of a statistically significant difference., Results: Three types of CMT were defined based on sternocleidomastoid muscle ultrasound examination characteristics: local mass, uniform thickening, and atrophy. Age at first diagnosis was 69.21 ± 108.41 days in local mass type group, 216.85 ± 324.09 days in uniform thickening group, and 417.88 ± 739.05 days in atrophy- type group; while age at first physiotherapy use was 94.06 ± 206.49 days, 255.00 ± 430.62 days, 540.92 ± 1059.29 respectively. The children included in local mass type group have shown a high success rate of conservative treatment, with a rate of 7.5% of children underwent surgery. Age at first diagnosis was 112.44 ± 224.12 days in the physiotherapy group, 115.87 ± 144.86 days in the physiotherapy combined with glucocorticoid treatment subgroup, whereas the age at first physiotherapy use was 137.38 ± 312.11 and 196.91 ± 344.26 days respectively. In the observation period (2015-2019) the mean age at surgery for CMT in 17 tertiary children's hospitals of the FRCPD was 50 months. Overall, 663 children with CMT were 1-2 years of age, accounting for the largest proportion (28.3%). Followed by 417 individuals (17.8%) were 7-14 years of age, indicating that there are still more children with CMT receiving surgical treatment later., Conclusions: Early diagnosis and treatment are essential to improve the conservative treatment success rate and achieve good prognosis in children with CMT. Our team's concept for treating CMT is as follows: after diagnosing the children, we will adopt the standardized protocol of treatment, with physiotherapy combined with the injection of glucocorticoid drugs and SCM release surgery, when needed. This program has a high conservative treatment success rate and may facilitate the achievement of better prognosis and reduced teratogenicity rate., (© 2023. The Author(s).)

Background: Distal radius fractures (DRF) account for one in five bony injuries in both primary and secondary trauma care. Enhanced recovery after surgery (ERAS) has been adopted successfully to improve clinical outcomes in multiple surgical disciplines; however, no study has investigated the effect of different degrees of compliance with ERAS protocol on short-term outcomes following distal radius surgery. We aimed to analyze whether different degrees of compliance with the ERAS pathway are associated with clinical improvement following surgery for DRF., Methods: We retrospectively analyzed all consecutive patients with ERAS who underwent surgery for DRF at our department between May 2019 and October 2022. Their pre-, peri-, and post-operative compliance with the 22 elements of the ERAS program were assessed. We compared parameters between low- (< 68.1%) and high-compliance (> 68.1%) groups, including patient complications, total length of hospitalization, discharge time after surgery, hospital costs, time taken to return to preinjury level performance level, number of visual analogue scale (VAS) pain scores > 3 points during hospitalization, disabilities of the arm, shoulder and hand (DASH) scores. We performed multiple linear regression analyses to assess the impact of ERAS compliance on the postoperative function level (DASH scores)., Results: No significant differences were detected between the high- and low-compliance groups with respect to demographics, including sex, age, body mass index (BMI), and comorbidities (P > 0.05). We observed significant differences between the high- and low-compliance groups in terms of the DASH score (32.25 ± 9.97 vs. 40.50 ± 15.65, p < 0.05) at 6 months postoperatively, the discharge time after surgery (2.45 ± 1.46 vs. 3.14 ± 1.50, p < 0.05), and number of times when the VAS pain score was > 3 points during hospitalization (0.88, [0.44, 1.31], p < 0.05). Our study demonstrated a significant negative association between ERAS compliance and the function level of patients postoperatively (DASH scores) when adjusted for age, comorbidity, sex, and BMI., Conclusions: This study provided a realistic evaluation and comparison of the ERAS protocol among patients with DRF and can guide clinical decision making. The ERAS protocol may improve outcomes after surgery, with high postoperative function levels and reduced pain and discharge time after surgery, without increased complication rates or hospital costs., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: UTX (encoded by KDM6A), a histone demethylase for H3K27me2/3, is frequently mutated in human cancers. However, its functional and regulatory mechanisms in colorectal cancer (CRC) remain unclear., Methods: Immunohistochemistry staining was used to investigate the clinical relevance of UTX in CRC. Additionally, we generated a spontaneous mouse CRC model with conditional Utx knockout to explore the role of UTX in the colorectal tumorigenesis. Post-translational regulation of UTX was determined by co-immunoprecipitation and immunoblot analyses., Results: Herein, we identify that downregulation of UTX, mediated by the Cullin 4B-DNA Damage Binding Protein-1-Constitutive Photomorphogenesis Protein 1 (CUL4B-DDB1-COP1) complex, promotes CRC progression. Utx deletion in intestinal epithelial cells enhanced the susceptibility to tumorigenesis in AOM/DSS-induced spontaneous mouse CRC model. However, this effect is primarily alleviated by GSK126, an inhibitor of histone methyltransferase EZH2. Mechanistically, EMP1 and AUTS2 are identified as putative UTX target genes mediating UTX functions in limiting intestinal tumorigenesis. Notably, the CUL4B-DDB1-COP1 complex is identified as the functional E3 ligase responsible for targeting UTX for degradation in CRC cells. Thus, Cop1 deficiency in mouse intestinal tissue results in UTX accumulation and restricts tumorigenesis. Furthermore, patient cohort analysis reveals that UTX expression is negatively correlated with clinical stage, favorable disease outcomes, and COP1 expression., Conclusions: In the current study, the tumor suppressor function and regulation of UTX in CRC provide a molecular basis and the rationale to target EZH2 in UTX-deficient CRC., (© 2023. YUMED Inc. and BioMed Central Ltd.)

Background: In 2003, China implemented free antiretroviral therapy (ART) for people living with HIV (PLHIV), establishing an eligibility threshold of CD4 < 200 cells/μl. Subsequently, the entry criteria were revised in 2012 (eligibility threshold: CD4 ≤ 350 cells/μl), 2014 (CD4 ≤ 500 cells/μl), and 2016 (treat-all). However, the impact of treat-all policy on HIV care and treatment indicators in China is unknown. We aimed to elucidate the immediate and long-term impact of the implementation of treat-all policy in China., Methods: Anonymized programmatic data on ART initiation and collection in PLHIV who newly started ART were retrieved between 1 January 2015 and 31 December 2019, from two provincial and municipal Centers for Disease Control and Prevention and ten major infectious disease hospitals specialized in HIV care in China. We used Poisson and quasi-Poisson segmented regression models to estimate the immediate and long-term impact of treat-all on three key indicators: monthly proportion of 30-day ART initiation, mean CD4 counts (cells/μl) at ART initiation, and mean estimated time from infection to diagnosis (year). We built separate models according to gender, age, route of transmission and region., Results: Monthly data on ART initiation and collection were available for 75,516 individuals [gender: 83.8% males; age: median 39 years, interquartile range (IQR): 28-53; region: 18.5% Northern China, 10.9% Northeastern China, 17.5% Southern China, 49.2% Southwestern China]. In the first month of treat-all, compared with the contemporaneous counterfactual, there was a significant increase in proportion of 30-day ART initiation [+ 12.6%, incidence rate ratio (IRR) = 1.126, 95% CI: 1.033-1.229; P = 0.007] and mean estimated time from infection to diagnosis (+ 7.0%, IRR = 1.070, 95% CI: 1.021-1.120; P = 0.004), while there was no significant change in mean CD4 at ART initiation (IRR = 0.990, 95% CI: 0.956-1.026; P = 0.585). By December 2019, the three outcomes were not significantly different from expected levels. In the stratified analysis, compared with the contemporaneous counterfactual, mean CD4 at ART initiation showed significant increases in Northern China (+ 3.3%, IRR = 1.033, 95% CI: 1.001-1.065; P = 0.041) and Northeastern China (+ 8.0%, IRR = 1.080, 95% CI: 1.003-1.164; P = 0.042) in the first month of treat-all; mean estimated time from infection to diagnosis showed significant increases in male (+ 5.6%, IRR = 1.056, 95% CI: 1.010-1.104; P = 0.016), female (+ 14.8%, IRR = 1.148, 95% CI: 1.062-1.240; P < 0.001), aged 26-35 (+ 5.3%, IRR = 1.053, 95% CI: 1.001-1.109; P = 0.048) and > 50 (+ 7.8%, IRR = 1.078, 95% CI: 1.000-1.161; P = 0.046), heterosexual transmission (+ 12.4%, IRR = 1.124, 95% CI: 1.042-1.213; P = 0.002) and Southwestern China (+ 12.9%, IRR = 1.129, 95% CI: 1.055-1.208; P < 0.001) in the first month of treat-all., Conclusions: The implementation of treat-all policy in China was associated with a positive effect on HIV care and treatment outcomes. To advance the work of rapid ART, efforts should be made to streamline the testing and ART initiation process, provide comprehensive support services, and address the issue of uneven distribution of medical resources., (© 2023. National Institute of Parasitic Diseases.)

Background: We created a clinical virtual reality application for vestibular rehabilitation. Our app targets contextual sensory integration (C.S.I.) where patients are immersed in safe, increasingly challenging environments while practicing various tasks (e.g., turning, walking). The purpose of this pilot study was to establish the feasibility of a randomized controlled trial comparing C.S.I. training to traditional vestibular rehabilitation., Methods: Thirty patients with vestibular dysfunction completed the Dizziness Handicap Inventory (DHI), Activities-Specific Balance Confidence Scale (ABC), Visual Vertigo Analog Scale (VVAS), Functional Gait Assessment (FGA), Timed-Up-and-Go (TUG), and Four-Square Step Test (FSST). Following initial assessment, the patients were randomized into 8 weeks (once per week in clinic + home exercise program) of traditional vestibular rehabilitation or C.S.I. training. Six patients had to stop participation due to the covid-19 pandemic, 6 dropped out for other reasons (3 from each group). Ten patients in the traditional group and 8 in the C.S.I group completed the study. We applied an intention to treat analysis., Results: Following intervention, we observed a significant main effect of time with no main effect of group or group by time interaction for the DHI (mean difference - 18.703, 95% CI [-28.235, -9.172], p = 0.0002), ABC (8.556, [0.938, 16.174], p = 0.028), VVAS, (-13.603, [-25.634, -1.573], p = 0.027) and the FGA (6.405, [4.474, 8.335], p < 0.0001). No changes were observed for TUG and FSST., Conclusion: Patients' symptoms and function improved following either vestibular rehabilitation method. C.S.I training appeared comparable but not superior to traditional rehabilitation., Trial Registration: This study (NCT04268745) was registered on clincaltrials.gov and can be found at https://clinicaltrials.gov/ct2/show/NCT04268745 ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: The present study aimed to investigate the preliminary safety and efficacy of rheolytic thrombectomy (RT) using an AngioJet Zelante DVT catheter or a Solent Omni catheter for acute proximal deep vein thrombosis (DVT)., Material and Methods: We conducted a retrospective review of 40 patients who were treated with an AngioJet RT between January 2019 and January 2021, and then the patients were divided into the ZelanteDVT group (n = 17) and the Solent group (n = 23). Data on demographics, clinical characteristics, technical success, clinical success, complications, and early follow-up were analysed., Results: No significant differences regarding demographics were detected (all p > .05). The technical success rates were both 100%. The ZelanteDVT group had a shorter duration of RT and a higher primary RT success than the Solent group (all p < .05), and the percentage of adjunctive catheter-directed thrombolysis (CDT) was 29.4% in the ZelanteDVT group, which was significantly lower than the 73.9% in the Solent group (p = .010). The clinical success rates for the ZelanteDVT group and Solent group were 100% (17/17) and 95.7% (22/23), respectively, and these values were high in the two groups (p > .05). Apart from transient macroscopic haemoglobinuria occurring in all the patients during the first 24 hours post-RT, none of the patients in either group suffered other procedure-related adverse events or major complications. Minor complications included bleeding events in 21.7% (5/23) of the patients in the Solent group and one (5.9%) patient in the ZelanteDVT group (p > .05). At 6 months, the frequency of PTS was 5.9% (1/17) in the ZelanteDVT group and 17.4% (4/23) in the Solent group (p > .05)., Conclusion: Both catheters are safe and effective in managing patients with proximal DVT, thus leading to improved clinical outcomes with few complications. The ZelanteDVT catheter was more effective than the Solent catheter in thrombectomy, thus allowing for faster extraction of the DVT with a shorter run time and lower proportions of patients with adjunctive CDT., (© 2023. The Author(s).)

Background: Stroke is the second leading cause of disease-related death and the third leading cause of disability worldwide. However, how to accurately warn of stroke onset remains extremely challenging. Recently, phenylacetyl glutamine (PAGln) has been implicated in the onset of stroke, but evidences from cohort studies of onset are lacking, especially in patients with first-onset or recurrent. It is necessary to deeply demonstrate the effectiveness of PAGln level on warning stroke onset., Methods: One hundred fifteen first onset stroke patients, 33 recurrent stroke patients, and 135 non-stroke controls were included in the analysis. Risk factors associated with stroke attacking were evaluated, and plasma PAGln levels were detected via HPLC-MS based method. LASSO regression, Pearson correlation analysis, and univariate analysis were carried out to demonstrate the associations between PAGln levels and risk factors of stroke. Random forest machine learning algorithm was used to build classification models to achieve the distinction of first-onset stroke patients, recurrent stroke patients, and non-stroke controls, and further demonstrate the contribution of PAGln levels in the distinction of stroke onset., Results: The median level of PAGln in the first-onset stroke group, recurrent stroke group, and non-stroke group was 933 ng/mL, 1014 ng/mL, and 556 ng/mL, respectively. No statistical correlation was found between PAGln level and subject's living habits, eating preferences, and concomitant diseases (hypertension, hyperlipidemia, and diabetes). Stroke severity indicators, mainly age and NIHSS score, were found associate with the PAGln levels. Machine learning classification models confirmed that PAGln levels, as the main contributing variable, could be used to distinguish recurrent stroke patients (but not first-onset stroke patients) from non-stroke controls., Conclusion: PAGln may be an effective indicator to monitor the recurrence in stroke patients., (© 2023. The Author(s).)

Background: Cancer patients with financial toxicity experience psychological distress and often miss medical appointments and quit treatments early, which could be a barrier to the effective management of oral chemotherapy drugs at home. This study explores whether financial toxicity predicts symptoms and unplanned healthcare utilization among cancer patients taking oral chemotherapy at home, which will contribute to the safe management of oral chemotherapy., Methods: Data in this study was from a prospective observational study, which was conducted between October 2018 and December 2019. 151 patients completed the Comprehensive Score for Financial Toxicity at discharge and completed the MD Anderson Symptom Inventory and unplanned healthcare utilization questionnaires after finishing one cycle of oral chemotherapy at home. Regression analyses were conducted to explore the associations of financial toxicity with symptoms and unplanned healthcare utilization., Results: Among 151participants, 88.08% reported severe or moderate financial toxicity, 43.05% reported symptom interference, and 31.79% reported unplanned healthcare utilization while taking oral chemotherapy at home. Patients between the age of 45-60y (p = 0.042) have higher financial toxicity, while those living in urban areas (p = 0.016) have lower financial toxicity. Patients with worse financial toxicity suffered increased symptoms of fatigue, emotional distress, disturbed sleep, and lack of appetite. Consequently, their mood and personal relation with other significant suffered. However, no statistical differences in unplanned healthcare utilization were found among patients with different levels of financial toxicity., Conclusion: Middle-aged adults and those living in suburban or rural areas experienced worse financial toxicity than other groups. Patients with worse financial toxicity experienced more severe psychological symptoms (e.g., fatigue, distress, disturbed sleep, and lack of appetite) and affective interference (e.g., mood and relations with others). Identifying at-risk patients is necessary to offer tailored support for psychological symptom management., (© 2023. The Author(s).)

Background: Shenling Baizhu Powder (SBP) is a traditional Chinese medicine (TCM) prescription, which has the good efficacy on gastrointestinal toxicity. In this study, we used gut microbiota analysis, metabonomics and network pharmacology to investigate the therapeutic effect of SBP on pyrotinib-induced diarrhea., Methods: 24 Rats were randomly divided into 4 groups: control group, SBP group (3.6 g/kg /bid SBP for 10 days), pyrotinib model group (80 mg/kg/qd pyrotinib) and pyrotinib + SBP treatment group. A 16S rRNA sequencing was used to detect the microbiome of rat fecal bowel. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 5.0. The antitumor effect of SBP on cells treated with pyrotinib was measured using a CCK-8 assay. Network pharmacology was used to predict the target and action pathway of SBP in treating pyrotinib-related diarrhea., Results: In vivo study indicated that SBP could significantly alleviate pyrotinib-induced diarrhea, reaching a therapeutic effect of 66.7%. SBP could regulate pyrotinib-induced microbiota disorder. LEfSe research revealed that the SBP could potentially decrease the relative abundance of Escherichia, Helicobacter and Enterobacteriaceae and increase the relative abundance of Lachnospiraceae, Bacilli, Lactobacillales etc. In addition, 25-Hydroxycholesterol, Guanidinosuccinic acid, 5-Hydroxyindolepyruvate and cAMP were selected as potential biomarkers of SBP for pyrotinib-induced diarrhea. Moreover, Spearman's analysis showed a correlation between gut microbiota and metabolite: the decreased 25-hydroxycholesterol in the pyrotinib + SBP treatment group was negatively correlated with Lachnospiraceae while positively correlated with Escherichia and Helicobacter. Meanwhile, SBP did not affect the inhibitory effect of pyrotinib on BT-474 cells and Calu-3 cells in vitro. Also, the network analysis further revealed that SBP treated pyrotinib-induced diarrhea through multiple pathways, including inflammatory bowel disease, IL-17 signaling pathway, pathogenic Escherichia coli infection and cAMP signaling pathway., Conclusions: SBP could effectively relieve pyrotinib-induced diarrhea, revealing that intestinal flora and its metabolites may be involved in this process., (© 2022. The Author(s).)

Background: Nutritional risk is prevalent in various diseases, but its association with contrast-induced acute kidney injury (CI-AKI) remains unclear. This study aimed to explore this association in patients undergoing coronary angiography (CAG)., Methods: In this retrospective cross-sectional study, 4386 patients undergoing CAG were enrolled. Nutritional risks were estimated by nutritional risk screening 2002 (NRS-2002), controlling nutritional status (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), respectively. CI-AKI was determined by the elevation of serum creatinine (Scr). Multivariable logistic regression analyses and receiver operator characteristic (ROC) analyses were conducted. Subgroup analyses were performed according to age (< 70/≥70 years), gender (male/female), percutaneous coronary intervention (with/without), and estimated glomerular filtration rate (< 60/≥60 ml/min/1.73m 2 )., Results: Overall, 787 (17.9%) patients were diagnosed with CI-AKI. The median score of NRS-2002, CONUT, PNI, and GNRI was 1.0, 3.0, 45.8, and 98.6, respectively. Nutritional risk was proven to be associated with CI-AKI when four different nutritional tools were employed, including NRS-2002 ([3-7 vs. 0]: odds ratio [95% confidence interval], OR [95%CI] = 4.026 [2.732 to 5.932], P < 0.001), CONUT ([6-12 vs. 0-1]: OR [95%CI] = 2.230 [1.586 to 3.136], P < 0.001), PNI ([< 38 vs. ≥52]: OR [95%CI] = 2.349 [1.529 to 3.610], P < 0.001), and GNRI ([< 90 vs. ≥104]: OR [95%CI] = 1.822 [1.229 to 2.702], P = 0.003). This is consistent when subgroup analyses were performed. Furthermore, nutritional scores were proved to be accurate in predicting CI-AKI (area under ROC curve: NRS-2002, 0.625; CONUT, 0.609; PNI, 0.629; and GNRI, 0.603)., Conclusions: Nutritional risks (high scores of NRS-2002 and CONUT; low scores of PNI and GNRI) were associated with CI-AKI in patients undergoing CAG., (© 2022. The Author(s).)

Background: Asian cotton (Gossypium arboreum L.), as a precious germplasm resource of cotton with insect resistance and stress tolerance, possesses a broad spectrum of phenotypic variation related to pigmentation. Flower color affects insect pollination and the ornamental value of plants. Studying flower color of Asian cotton varieties improves the rate of hybridization and thus enriches the diversity of germplasm resources. Meanwhile, it also impacts the development of the horticultural industry. Unfortunately, there is a clear lack of studies concerning intricate mechanisms of cotton flower-color differentiation. Hereby, we report an integrative approach utilizing transcriptome and metabolome concerning flower color variation in three Gossypium arboreum cultivars., Results: A total of 215 differentially accumulated metabolites (DAMs) were identified, including 83 differentially accumulated flavonoids (DAFs). Colorless kaempferol was more abundant in white flowers, while gossypetin-fer showed specificity in white flowers. Quercetin and gossypetin were the main contributors to yellow petal formation. Pelargonidin 3-O-beta-D-glucoside and cyanidin-3-O-(6''-Malonylglucoside) showed high accumulation levels in purple petals. Quercetin and gossypetin pigments also promoted purple flower coloration. Moreover, 8178 differentially expressed genes (DEGs) were identified by RNA sequencing. The correlation results between total anthocyanins and DEGs were explored, indicating that 10 key structural genes and 29 transcription factors promoted anthocyanin biosynthesis and could be candidates for anthocyanin accumulation. Ultimately, we constructed co-expression networks of key DAFs and DEGs and demonstrated the interactions between specific metabolites and transcripts in different color flowers., Conclusion: This study provides new insights into elucidating the regulatory mechanisms of cotton flower color and lays a potential foundation for generate cotton varieties with highly attractive flowers for pollinators., (© 2022. The Author(s).)

Background: The proliferation ability and autophagy level of pulmonary artery endothelial cells (PAECs) play an important role in promoting the development of pulmonary artery hypertension (PAH), and there is still no effective treatment for PAH. Farnesyl diphosphate synthase (FDPS) is a key enzyme in the mevalonate pathway. The intermediate metabolites of this pathway are closely related to the activity of autophagy-associated small G proteins, including Ras-related C3 botulinum toxin substrate 1 (Rac1). Studies have shown that the mevalonate pathway affects the activation levels of different small G proteins, autophagy signaling pathways, vascular endothelial function, and so on. However, the exact relationship between them is still unclear in PAH., Method: In vitro, western blotting and mRFP-GFP-LC3 puncta formation assays were used to observe the expression of FDPS and the level of autophagy in PAECs treated with monocrotaline pyrrole (MCTP). In addition, cell proliferation and migration assays were used to assess the effect of FDPS on endothelial function, and Rac1 activity assays were used to evaluate the effect of Rac1 activation on PAEC autophagy via the PI3K/AKT/mTOR signaling pathway. In vivo, the right heart catheterization method, hematoxylin and eosin (H&E) staining and western blotting were used to determine the effect of FDPS on PAEC autophagy and monocrotaline (MCT)-induced PAH., Results: We show that the expression of FDPS is increased in the PAH module in vitro and in vivo, concomitant with the induction of autophagy and the activation of Rac1. Our data demonstrate that inhibition of FDPS ameliorates endothelial function and decreases MCT-induced autophagy levels. Mechanistically, we found that FDPS promotes autophagy, Rac1 activity and endothelial disfunction through the PI3K/AKT/mTOR signaling pathway., Conclusion: Our study suggests that FDPS contributes to active small G protein-induced autophagy during MCT-induced PAH, which may serve as a potential therapeutic target against PAH., (© 2022. The Author(s).)

Background: Lung cancer is the leading cause of malignancy-related mortality and lung adenocarcinoma accounts for about 40% of lung malignancies. The aim of this study was to investigate the associations of intraflagellar transport protein 20 (IFT20) and Golgi matrix protein 130 (GM130) expression with clinicopathological features and survival in patients with lung adenocarcinoma., Methods: The expressions of IFT20 and GM130 protein in cancerous and matched adjacent lung tissues of 235 patients with lung adenocarcinoma were assessed by tissue microarray and immunohistochemistry, which were indicated by the mean optical density (IOD/area), the rate of positive staining cells and staining intensity score. The correlation between IFT20 and GM130 protein was assessed by Spearman's rank correlation. Associations of IFT20 and GM130 protein expression with clinicopathological features of patients were analyzed by multivariate logistic regression models. The survival analysis of patients was performed by Cox proportional hazard regression models., Results: With adjustment for multiple potential confounders, each one-point increase in IFT20 protein staining intensity score was significantly associated with 32% and 29% reduced risk for TNM stage in II ~ IV and lymphatic metastasis of patients, respectively (P < 0.05). And each one-point increase in GM130 protein staining intensity score was associated with a significant reduction in the risk of poor differentiation and tumors size > 7 cm by 29% and 38% for lung adenocarcinoma patients, respectively (P < 0.05). In stratified Cox model analysis, enhanced IFT20 staining intensity score was significantly decreased the risk of death by 16% for patients without distant metastasis. And elevated the IOD/area of GM130 expression significantly decreased the death risk of lung adenocarcinoma patients with tumor size > 7 cm or distant metastasis by 54% and 65%, respectively (P < 0.05)., Conclusion: IFT20 and GM130 protein expressions were negatively associated with tumor differentiated types, size, TNM stage and lymphatic metastasis of lung adenocarcinoma. Both IFT20 and GM130 proteins have some protective effects on the survival of lung adenocarcinoma patients with specific clinicopathological features., (© 2022. The Author(s).)

Background: Unintended pregnancies (UIP) among unmarried sexually active college students in mainland China have emerged as a major reproductive health issue with detrimental personal and socioeconomic consequences. This cross-sectional study aimed to determine the prevalence and factors associated with UIP among sexually active undergraduates in mainland China., Methods: Between September 8, 2019 and January 17, 2020, a total of 48,660 participants were recruited across the Chinese mainland to complete the self-administered, structured, online questionnaire. This analysis was restricted to 6347 sexually experienced, never-married 15-26 year old undergraduates. Pearson's Chi square tests and multivariate Logistic regression analyses were performed to identify sociodemographic, familial and individual variables associated with UIP., Results: The overall prevalence of UIP was 17.7%. More specifically, 19.5% of male college students reported they had unintentionally gotten a partner pregnant, while 14.9% of female college students became unintentionally pregnant. Students who experienced UIP were more likely to belong to the older age group (23-26 years), live with only one parent or live without parents at home, report that their family members approve of premarital sex, initiate sexual activity younger than 14 years old and have casual sex partners. Furthermore, females with multiple partners and males who came from low- income households, experienced sexual abuse, perceived difficulties in acquiring condoms and did not know how to use condoms correctly were also at higher risk of experiencing an unintended pregnancy., Conclusion: In order to prevent UIP, a comprehensive intervention measure should be taken to target older students and those engaging in risky sexual behaviors, work with young male students to improve condom use skills, improve the availability of free condoms, optimize the involvement of parents and other family members in their children's sex education., (© 2022. The Author(s).)

Background: Bladder cancer (BCa) shows its potential immunogenity in current immune-checkpoint inhibitor related immunotherapies. However, its therapeutic effects are improvable and could be affected by tumor immune microenvironment. Hence it is interesting to find some more prognostic indicators for BCa patients concerning immunotherapies., Methods: In the present study, we retrospect 129 muscle-invasive BCa (MIBC) patients with radical cystectomy in Shanghai General Hospital during 2007 to 2018. Based on the results of proteomics sequencing from 9 pairs of MIBC tissue from Shanghai General Hospital, we focused on 13 immune-related differential expression proteins and their related genes. An immune-related prognostic signature (IRPS) was constructed according to Cancer Genome Atlas (TCGA) dataset. The IRPS was verified in ArrayExpress (E-MTAB-4321) cohort and Shanghai General Hospital (General) cohort, separately. A total of 1010 BCa patients were involved in the study, including 405 BCa patients in TCGA cohort, 476 BCa patients in E-MTAB-4321 cohort and 129 MIBC patients in General cohort., Result: It can be indicated that high IRPS score was related to poor 5-year overall survival and disease-free survival. The IRPS score was also evaluated its immune infiltration. We found that the IRPS score was adversely associated with GZMB, IFN-γ, PD-1, PD-L1. Additionally, higher IRPS score was significantly associated with more M2 macrophage and resting mast cell infiltration., Conclusion: The study revealed a novel BCa prognostic signature based on IRPS score, which may be useful for BCa immunotherapies., (© 2022. The Author(s).)

Background: Organoids are three-dimensional structures that closely recapitulate tissue architecture and cellular composition, thereby holding great promise for organoid-based drug screening. Although growing in three-dimensional provides the possibility for organoids to recapitulate main features of corresponding tissues, it makes it incommodious for imaging organoids in two-dimensional and identifying surviving organoids from surrounding dead cells after organoids being treated by irradiation or chemotherapy. Therefore, significant work remains to establish high-quality controls to standardize organoid analyses and make organoid models more reproducible., Methods: In this study, the Z-stack imaging technique was used for the imaging of three-dimensional organoids to gather all the organoids' maximum cross sections in one imaging. The combination of live cell staining fluorescent dye Calcein-AM and ImageJ assessment was used to analyze the survival of organoids treated by irradiation or chemotherapy., Results: We have established a novel quantitative high-throughput imaging assay that harnesses the scalability of organoid cultures. Using this assay, we can capture organoid growth over time, measure multiple whole-well organoid readouts, and show the different responses to drug treatments., Conclusions: In summary, combining the Z-stack imaging technique and fluorescent labeling methods, we established an assay for the imaging and analysis of three-dimensional organoids. Our data demonstrated the feasibility of using organoid-based platforms for high-throughput drug screening assays., (© 2022. The Author(s).)

Background: Human granulocytic anaplasmosis is a tick-borne zoonotic disease caused by Anaplasma phagocytophilum. Coinfections with A. phagocytophilum and other tick-borne pathogens are reported frequently, whereas the relationship between A. phagocytophilum and flea-borne Yersnia pestis is rarely concerned., Results: A. phagocytophilum and Yersnia pestis were discovered within a Marmota himalayana found dead in the environment, as determined by 16S ribosomal rRNA sequencing. Comparative genomic analyses of marmot-derived A. phagocytophilum isolate demonstrated its similarities and a geographic isolation from other global strains. The 16S rRNA gene and GroEL amino acid sequence identity rates between marmot-derived A. phagocytophilum (JAHLEX000000000) and reference strain HZ (CP000235.1) are 99.73% (1490/1494) and 99.82% (549/550), respectively. 16S rRNA and groESL gene screenings show that A. phagocytophilum is widely distributed in marmots; the bacterium was more common in marmots found dead (24.59%, 15/61) than in captured marmots (19.21%, 29/151). We found a higher Y. pestis isolation rate in dead marmots harboring A. phagocytophilum than in those without it ( 2  = 4.047, p < 0.05). Marmot-derived A. phagocytophilum was able to live in L929 cells and BALB/c mice but did not propagate well., Conclusions: In this study, A. phagocytophilum was identified for the first time in Marmota himalayana, a predominant Yersinia pestis host. Our results provide initial evidence for M. himalayana being a reservoir for A. phagocytophilum; moreover, we found with the presence of A. phagocytophilum, marmots may be more vulnerable to plague. Humans are at risk for co-infection with both pathogens by exposure to such marmots., (© 2022. The Author(s).)

Background: HIV prevention, diagnosis, treatment and care services might be hampered by inaccurate risk assessment. This study aimed to investigate the extent of and factors associated with the discordance between perceived risk and actual risky sexual behaviors among undergraduates in mainland China, guided by the Anderson's behavioral model., Methods: This study involved a secondary analysis of cross-sectional data collected during the fall semester of 2018-2019 academic year. The present analysis was restricted to 8808 undergraduates with low risk perception. Those who had low perceived risk but actually engaged in risky sexual behaviors were categorized as risk discordance (RD). Univariate and multivariate Logistic regression analyses were conducted to identify factors associated with RD., Results: Overall, the discordance rate between perceived and actual risk was 8.5% (95% CI: 7.9%-9.1%). Multivariate Logistic regression analysis indicated that non-heterosexual women (AOR = 0.41, 95% CI:0.27-0.60), heterosexual men (AOR = 0.45, 95% CI:0.33-0.61) and women (AOR = 0.26, 95% CI:0.19-0.35) were less likely to exhibit RD, when compared with non- heterosexual men. Furthermore, non-freshmen (AOR = 1.57, 95% CI:1.30-1.90), early initiators of sexual intercourse (AOR = 5.82, 95% CI:4.10-8.26), and those who had lower levels of HIV knowledge (AOR = 1.28, 95% CI:1.08-1.51), displayed higher levels of stigma against PLHIV (AOR = 1.50, 95% CI:1.26-1.77) and had ever been tested for HIV (AOR = 1.36, 95% CI:1.04-1.77) were more prone to reporting RD. Those with more enabling resources [i.e., displaying high levels of condom use self-efficacy (AOR = 0.70, 95% CI:0.59-0.84) and being knowledge of local testing center (AOR = 0.71, 95% CI:0.60-0.83)] were less likely to report RD. However, spending more than 2000 Yuan a month on basic needs (AOR = 2.55, 95% CI:2.07-3.14), residing in urban areas (AOR = 1.35, 95% CI:1.15-1.59) and being knowledgeable of the national AIDS policy (AOR = 1.40,95% CI:1.18-1.66) increased the chance of exhibiting RD., Conclusions: Comprehensive interventions, including targeting students with high-risk characteristics, improving the acceptability of PrEP and PEP, conducting health education, enhancing self-efficacy for using condoms and making opt-out HIV testing routine in college campus, should be taken to reduce the discordance between perceived and actual HIV risk and finally to reach the goal of Zero AIDS., (© 2022. The Author(s).)

Background: The unique mechanism of diabetic atherosclerosis has been a central research focus. Previous literature has reported that the inflammatory response mediated by dendritic cells (DCs) plays a vital role in the progression of atherosclerosis. The objective of the study was to explore the role of DCs in diabetes mellitus complicated by atherosclerosis., Methods: ApoE -/- mice and bone marrow-derived DCs were used for in vivo and in vitro experiments, respectively. Masson's staining and Oil-red-O staining were performed for atherosclerotic lesion assessment. The content of macrophages and DCs in plaque was visualized by immunohistochemistry. The expression of CD83 and CD86 were detected by flow cytometry. The fluctuations in the RNA levels of cytokines, chemokines, chemokine receptors and adhesions were analyzed by quantitative RT-PCR. The concentrations of IFN-γ and TNF-α were calculated using ELISA kits and the proteins were detected using western blot. Coimmunoprecipitation was used to detect protein-protein interactions., Results: Compared with the ApoE -/- group, the volume of atherosclerotic plaques in the aortic root of diabetic ApoE -/- mice was significantly increased, numbers of macrophages and DCs were increased, and the collagen content in plaques decreased. The expression of CD83 and CD86 were significantly upregulated in splenic CD11c + DCs derived from mice with hyperglycemia. Increased secretion of cytokines, chemokines, chemokine receptors, intercellular cell adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) also were observed. The stimulation of advanced glycation end products plus oxidized low-density lipoprotein, in cultured BMDCs, further activated toll-like receptor 4, protein kinase C and receptor of AGEs, and induced immune maturation of DCs through the RAGE-TLR4-PKCβ 1 signaling pathway that was bound together by intrinsic structures on the cell membrane. Administering LY333531 significantly increased the body weight of diabetic ApoE -/- mice, inhibited the immune maturation of spleen DCs, and reduced atherosclerotic plaques in diabetic ApoE -/- mice. Furthermore, the number of DCs and macrophages in atherosclerotic plaques was significantly reduced in the LY333531 group, and the collagen content was increased., Conclusions: Diabetes mellitus aggravates chronic inflammation, and promotes atherosclerotic plaques in conjunction with hyperlipidemia, which at least in part through inducing the immune maturation of DCs, and its possible mechanism of action is through the RAGE-TLR4-pPKCβ 1 signaling pathway., (© 2022. The Author(s).)

Background: Blood glucose levels that are too high or too low after traumatic brain injury (TBI) negatively affect patient prognosis. This study aimed to demonstrate the relationship between blood glucose levels and the Glasgow Outcome Score (GOS) in TBI patients., Methods: This study was based on a randomized, dual-center, open-label clinical trial. A total of 208 patients who participated in the randomized controlled trial were followed up for 5 years. Information on the disease, laboratory examination, insulin therapy, and surgery for patients with TBI was collected as candidate variables according to clinical importance. Additionally, data on 5-year and 6-month GOS were collected as primary and secondary outcomes, respectively. For multivariate analysis, a generalized additive model (GAM) was used to investigate relationships between blood glucose levels and GOS. The results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). We further applied a two- piecewise linear regression model to examine the threshold effect of blood glucose level and GOS., Results: A total of 182 patients were included in the final analysis. Multivariate GAM analysis revealed that a bell-shaped relationship existed between average blood glucose level and 5-year GOS score or 6-month GOS score. The inflection points of the average blood glucose level were 8.81 (95% CI: 7.43-9.48) mmol/L considering 5-year GOS as the outcome and were 8.88 (95% CI 7.43-9.74) mmol/L considering 6-month GOS score as the outcome. The same analysis revealed that there was also a bell relationship between average blood glucose levels and the favorable outcome group (GOS score ≥ 4) at 5 years or 6 months., Conclusion: In a population of patients with traumatic brain injury, blood glucose levels were associated with the GOS. There was also a threshold effect between blood glucose levels and the GOS. A blood glucose level that is either too high or too low conveys a poor prognosis., Trial Registration: ClinicalTrials.gov NCT02161055 . Registered on 11 June 2014., (© 2022. The Author(s).)

Background: Great achievements have been achieved by free antiretroviral therapy (ART). A rapid and accurate prediction of survival in people living with HIV/AIDS (PLHIV) is needed for effective management. We aimed to establish an effective prognostic model to forecast the survival of PLHIV after ART., Methods: The participants were enrolled from a follow-up cohort over 2003-2019 in Nanjing AIDS Prevention and Control Information System. A nested case-control study was employed with HIV-related death, and a propensity-score matching (PSM) approach was applied in a ratio of 1:4 to allocate the patients. Univariable and multivariable Cox proportional hazards analyses were performed based on the training set to determine the risk factors. The discrimination was qualified using the area under the curve (AUC) and concordance index (C-Index). The nomogram was calibrated using the calibration curve. The clinical benefit of prognostic nomogram was assessed by decision curve analysis (DCA)., Results: Predictive factors including CD4 cell count (CD4), body mass index (BMI) and hemoglobin (HB) were determined and incorporated into the nomogram. In the training set, AUC and C-index (95% CI) were 0.831 and 0.798 (0.758, 0.839), respectively. The validation set revealed a good discrimination with an AUC of 0.802 and a C-index (95% CI) of 0.786 (0.681, 0.892). The calibration curve also exhibited a high consistency in the predictive power (especially in the first 3 years after ART initiation) of the nomogram. Moreover, DCA demonstrated that the nomogram was clinically beneficial., Conclusion: The nomogram is effective and accurate in forecasting the survival of PLHIV, and beneficial for medical workers in health administration., (© 2021. The Author(s).)

Background: Late presentation to HIV/AIDS care presents serious health concerns, like increased transmission and high healthcare costs, increased mortality, early development of opportunistic infection, increased risk of antiretroviral therapy drug resistance. Despite the effort to contain the HIV/AIDS epidemic, LP has remained an impediment to individual immune reconstitution and public health., Objective: This review aimed to estimate the prevalence and determine the factors associated with late presentation to HIV/AIDS care., Methods: We searched PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Wanfang, and Weipu database for articles published from 2010 to 2020. We utilized I 2 statistics and Q-test to estimate heterogeneity between studies. Random-effects meta-analysis models were used to calculate the aggregate odds ratio of late presentation to HIV/AIDS care., Results: Of 9563 titles and abstracts retrieved, 189 were identified as potentially eligible and 39 fulfilled the inclusion criteria. The pooled prevalence of late presentation to HIV/AIDS care was 43.26%. The major risk factors were patients ≥ 50 years old (OR = 2.19, 95% CI: 1.85-2.58; I 2  = 97.44%), married (OR = 1.50, 95% CI: 1.35-1.68; I 2  = 96.58%), with heterosexual contact as risk factor for infection (OR = 1.91, 95% CI: 1.73-2.11; I 2  = 90.74%) and diagnosed in medical institutions (OR = 2.35,95% CI: 2.11-2.62; I 2  = 96.05%). In middle or low HIV prevalence areas, patients ≥ 50 years old (P = 0.01), married (P < 0.01) and diagnosed in medical institutions (P = 0.01) were more likely to be presented late than in high prevalence areas. From 2016-2020, the OR of patients who were married and diagnosed in medical facilities were significantly lower than before (P < 0.01)., Conclusion: Patients ≥ 50 years old, married, with heterosexual contact as risk factor for infection, and diagnosed in medical institutions were risk factors of LP. Gender had no significant relationship with LP. In middle or low prevalence areas, patients who were ≥ 50 years old, married, and diagnosed in medical institutions were more likely to be presented late than in other areas. Married patients and those diagnosed in medical institutions after 2015 have a lower risk of LP than before., (© 2021. The Author(s).)

Background: HIV counseling and testing (HCT) is provided free of charge on college campuses, but very few studies have examined whether HCT uptake is equitably distributed. This cross-sectional study aimed to compare the relative importance of various determinants of HCT uptake among undergraduates in mainland China so as to assess and subsequently to suggest ways to eliminate inequities in its use, guided by the Andersen's behavioral model., Methods: A total of 10,665 eligible undergraduates were conveniently selected to complete an online survey. Hierarchical logistic regression analyses were performed to identify the factors associated with HCT utilization., Results: Only 7.7% of undergraduates had utilized HCT services. HCT uptake was inequitably distributed, since it was mainly determined by predisposing and enabling factors rather than by need factors. Further analysis indicated that HCT uptake was significantly related to two need factors, one enabling factor and six predisposing factors. Those with a higher need [i.e., perceiving themselves to be at higher risk of acquiring HIV infection (AOR = 2.76, 95% CI:2.02-3.78) and engaging in condomless sex (AOR = 1.29, 95% CI:1.00-1.67)] and those with more resources [i.e., being knowledgeable of local AIDS service organization (AOR = 1.59, 95% CI:1.37-1.85)] were more likely to utilize HCT services. Compared to non-heterosexual men, non-heterosexual women (AOR = 0.51, 95% CI:0.37-0.72), heterosexual men (AOR = 0.44, 95% CI:0.33-0.57) and women (AOR = 0.31, 95%CI: 0.24-0.41) were less likely to utilize HCT service. Furthermore, those with more knowledge (AOR = 0.80, 95% CI:0.69-0.94) and taking a positive attitude towards HCT services [i.e, expressing their willingness to utilize HCT services (AOR = 0.68, 95% CI:0.56-0.81) and having recognized the necessity to provide HTC services in the local university (AOR = 0.46, 95% CI:0.36-0.57)] were less likely to utilize HCT services. However, medical students (AOR = 1.34, 95% CI: 1.15-1.56) and non-freshmen (AOR = 1.22, 95% CI:1.03-1.45) were more likely to utilize HCT services., Conclusions: To increase HCT uptake and simultaneously reduce the remaining inequities, a comprehensive intervention should be continued to target non-heterosexual men and non- freshmen and those with a higher need for HCT services, conduct health education, improve the availability and accessibility of HIV testing services., (© 2021. The Author(s).)

Background: N 6 -methyladenine (m 6 A) is the most common modification of mRNA and IncRNA in higher organisms. m 6 A has been confirmed to be related to the formation and progression of tumors and m 6 A-related genes can be used as prognostic biomarkers in a variety of tumors. However, there have been no similar studies on lung squamous cell carcinoma. The main purpose of this study was aimed to explore the differential expression of m 6 A-related genes in lung squamous cell carcinoma tissues and its relationship with patient clinical prognosis., Methods: We integrated three m 6 A writers that catalyze the methylation of adenine on mRNA molecules. The training set including 501 patients with LUSC was collected from The Cancer Genome Atlas (TCGA) database and the test set including 181 patients with LUSC was collected from the Gene Expression Omnibus (GEO) database. Based on the expression level of the m 6 A methylase gene, we established a tumor subgroup and risk-prognosis model to quantify the risk index and long-term patient prognosis, which were confirmed by principal component analysis (PCA) and receiver operating characteristic (ROC) curve analysis. After lung squamous cell carcinoma tissue specimens were obtained during surgery, immunohistochemistry (IHC) was used to verify the results in vitro., Results: The results of the study showed that the expression of the three m 6 A methylases in tumor tissues and normal tissues was significantly different (P < 0.05). The survival-prognostic model based on METTL3 gene expression showed better predictive performance (AUC: 0.706). Patients in the high-risk and low-risk groups exhibited significant differences in terms of survival time and 5-year and 10-year survival rates. Immunohistochemistry revealed that patients with high METTL3 expression exhibited a longer survival time than those with low METTL3 expression., Conclusions: Our study showed that the molecular phenotype based on the expression of METTL3 may be an independent risk factor affecting the prognosis of lung squamous cell carcinoma. These findings not only prove the important role of m 6 A methylase in lung squamous cell carcinoma, but are also expected to provide more accurate prognostic assessment and individualized treatment for patients with lung squamous cell carcinoma., (© 2021. The Author(s).)