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Abstract Background Many studies have shown that using new technologies and medical equipment contributes to increasing health expenditure. Relatively less empirical studies have measured the impact of medical equipment on rising medical costs in China. Against this backdrop, we aim to examine whether the large-scale medical equipment deployment explains the increase in health expenditure. Methods Quasi-experimental research design with a difference-in-differences approach was adopted to explore whether an increase in the number of large-scale medical equipment impacts on outpatient and inpatient costs. Data were obtained from the 2011–2017 Health Financial Annals in Shaanxi province, China. Results The increase in the number of large-scale medical equipment by 1 — regardless of the initial configuration — resulted in the increase of the average cost per outpatient visit and the average cost per inpatient visit by 10.6% (p

Abstract Background Internal migrants in China have long been at a disadvantage in terms of access to publicly financed services, as well as the utilization of public health services. The aim of the study was to examine inequities in the use of basic public health services between internal migrants and the local population and estimate the factors that contributed to inequity in use. Methods The data for this study was derived from the 2017 wave of the China Migrants Dynamic Survey. Basic public health services utilization was measured by the establishment of health records, health education and chronic disease management. We performed multivariable logistic regressions to examine inequities in the utilization of basic public health services between locals and internal migrants, and Oaxaca-Blinder decomposition was used to explore possible explanations for such inequities between the two groups. Results A total of 27,998 cases were included in the analysis. We found that the utilization rates for establishment of health records, health education and chronic disease management among internal migrants were 71.3%, 49.2% and 65.7% lower than their local counterparts, respectively. The decomposition results indicated that the inequities in the establishment of health records between locals and internal migrants were mainly explained by whether people had heard of the National Basic Public Health Services Program (NBPHSP) (17.67%) and by health insurance (5.99%). The contributors to the inequities in health education between locals and internal migrants were community involvement (14.71%) and whether people had heard of the NBPHSP (13.89%). The main factors contributing to the difference in utilization of chronic disease management between the two groups were whether people had heard of the NBPHSP (14.49%) and community involvement (8.43%). Conclusions To reduce inequities in the utilization of basic public health services between locals and internal migrants, measures need to be taken to improve knowledge about the basic public health services and to help migrants integrate into the local community.

Abstract Objective Ovarian tissue cryopreservation has become a promising alternative for fertility preservation in cancer patients, allowing ovarian tissue to be stored for future autotransplantation. Oxidative stress damage occurring during the cryopreservation process may impact tissue quality and function. This study aims to investigate the protective effects and potential mechanisms of Mitoquinone (MitoQ), a mitochondria-targeted derivative of the antioxidant ubiquinone, during the vitrification of ovarian tissue in mice. Methods KGN cells were treated with various concentrations (0.1, 1, 10, and 50 μM) of MitoQ to determine the optimal concentration. Female ICR mice were divided into three groups: control, conventional vitrification, and MitoQ-supplemented vitrification. Ovarian samples were cryopreserved, thawed, and assessed for tissue morphology using Hematoxylin and Eosin (H&E) staining, and mitochondrial changes using immunofluorescence, transmission electron microscopy, and Western blot analysis. RNA sequencing (RNA-seq) was employed to explore potential protective mechanisms. Autotransplantation experiments were conducted, and the long-term effects of MitoQ on ovarian function were evaluated by counting follicle numbers through H&E staining and measuring serum estradiol and AMH levels using ELISA. Results MitoQ at 1 μM was found to be the optimal concentration for maintaining follicular morphology after vitrification. It effectively reduced mitochondrial oxidative damage, preserved mitochondrial morphology, and regulated the expression of mitochondrial dynamics proteins (Drp1 and Mfn2). RNA-seq and Western blot analyses revealed that MitoQ inhibited the p38 MAPK pathway, thereby reducing apoptosis. Additionally, autotransplantation experiments showed that MitoQ treatment significantly increased follicle counts, estradiol (E2), and anti-Müllerian hormone (AMH) levels compared to conventional vitrification. Conclusions MitoQ effectively mitigates vitrification-induced oxidative damage, maintains mitochondrial homeostasis, and preserves both follicular reserve and endocrine function. These findings suggest that MitoQ is a valuable adjunct in ovarian tissue cryopreservation and could significantly improve fertility preservation outcomes for cancer patients.

Abstract Candida albicans is a common opportunistic pathogen, causing infections ranging from superficial to bloodstream infections. The limited antifungal options and rising drug resistance challenge clinical treatment. We screened 98 essential oils and identified 48 with antifungal activity against Candida albicans at 1% concentration, determining their minimum inhibitory concentrations (MIC). Of these, 14 maintained fungicidal activity at lower concentrations (0.25% and 0.125%). 5 essential oils (Cinnamon, Satureja montana, Palmarosa, Lemon eucalyptus, and Honey myrtle) showed the highest inhibitory effects on stationary-phase Candida albicans and inhibited hyphae elongation. Synergistic effects were observed when combining Palmarosa with amphotericin B (AmB) against growing-phase Candida albicans, while Cinnamon and Satureja montana with AmB showed superior efficacy against stationary-phase infections. We identified the active components of 5 essential oils using gas chromatography-mass spectrometry (GC-MS) and found the following main constituents: Cinnamon primarily contains benzyl benzoate and eugenol, Satureja montana is dominated by carvacrol and cymene, Palmarosa features geraniol and geranyl acetate, Lemon eucalyptus includes dl-Isopulegol and citronellal, and Honey myrtle is characterized by citral and neral. Our results may aid in developing more effective antifungal treatments.

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Abstract Advanced pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Immunotherapy alone offers limited efficacy, but it is still unknown whether its combination with chemotherapy could offer synergistic anti-tumor effects. This phase Ib/II study evaluated the safety and efficacy of combining toripalimab with the gemcitabine plus nab-paclitaxel (GnP) regimen as first-line treatment for locally advanced or metastatic PDAC and explored predictive biomarkers (ChiCTR2000032293). The primary endpoints were safety and overall survival (OS). The secondary outcomes were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Immune-related biomarkers including programmed death-ligand 1 (PD-L1) expression, genetic status, cytokine levels, and spatial features of the tumor immune microenviroment (TIME) were investigated. Neither serious treatment-related adverse events nor grade 4 immune-related adverse events were reported. Among the 72 patients, the median OS was 8.9 months, 12-month OS rate was 31.9%, with median PFS of 5.6 months, ORR of 33.3%, and DCR of 90.3%. Higher PD-L1 expression, without liver metastases were associated with higher ORR, however these factors could not effectively distinguish responders and non-responders. Importantly, dendritic cells - T helper cells - cytotoxic T lymphocytes (DC-Th-CTL) enriched immune niche and their spatial interactions were dominant predictors of response based on TIME analysis using a cyclic multiplex tissue staining assay, with an area under the curve value of 0.8. Overall, GnP plus toripalimab exhibited good safety and differentiated efficacy in selected population, and the spatial interactions of DC-Th-CTL represent promising predictors to efficacy of immunochemotherapy in locally advanced or metastatic PDAC.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA)-caused infections greatly threaten public health. The discovery of natural-product-based anti-MRSA agents for treating infectious diseases has become one of the current research focuses. Objectives: This study aims to identify promising anti-MRSA agents with a clear mechanism based on natural norharmane modified by quaternization or dimerization. Methods: A total of 32 norharmane analogues were prepared and characterized. Their antibacterial activities and resistance development propensity were tested by the broth double-dilution method. Cell counting kit-8 and hemolysis experiments were used to assess their biosafety. The plasma stability, bactericidal mode, and biofilm disruption effects were examined by colony counting and crystal violet staining assays. Fluorescence microscopy, metabolomic analysis, docking simulation and spectra titration revealed its anti-MRSA mechanisms. The mouse skin infection model was used to investigate the in vivo efficacy. Results: Compound 5a was selected as a potential anti-MRSA agent, which exhibited potent anti-MRSA activity in vitro and in vivo, low cytotoxicity and hemolysis under an effective dose. Moreover, compound 5a showed good stability in 50% plasma, a low tendency of resistance development and capabilities to disrupt bacterial biofilms. The mechanism studies revealed that compound 5a could inhibit the biosynthesis of bacteria cell walls, damage the membrane, disturb energy metabolism and amino acid metabolism pathways, and interfere with protein synthesis and nucleic acid function. Conclusions: These results suggested that compound 5a is a promising candidate for combating MRSA infections, providing valuable information for further exploiting a new generation of therapeutic antibiotics.

Abstract Reliable and ultra-fast DNA and RNA sequencing have been achieved with the emergence of high-throughput sequencing technology. When combining the results of DNA and RNA sequencing for tumor cells of cancer patients, neoantigens that potentially stimulate the immune response of either CD4+ or CD8+ T cells can be identified. However, due to the abundance of somatic mutations and the high polymorphic nature of human leukocyte antigen (HLA) it is challenging to accurately predict the neoantigens. Moreover, comparing to HLA-I presented peptides, the HLA-II presented peptides are more variable in length, making the prediction of HLA-II loaded neoantigens even harder. A number of computational approaches have been proposed to address this issue but none of them considers the DNA origin of the neoantigens from the perspective of 3D genome. Here we investigate the DNA origins of the immune-positive and non-negative HLA-II neoantigens in the context of 3D genome and discovered that the chromatin 3D architecture plays an important role in more effective HLA-II neoantigen prediction. We believe that the 3D genome information will help to increase the precision of HLA-II neoantigen discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.

Objective: To evaluate the efficacy of photodynamic therapy (PDT) for vaginal intraepithelial neoplasia grade 1 (VaIN1) related to high-risk (Hr)-human papillomavirus (HPV). Methods: Participants aged 25–65 years treated for VaIN1 between March 2022 and September 2022 were retrospectively analyzed into three groups. The PDT and follow-up groups were matched 1:1 for gravidity, HPV type, and quadrants involved. The PDT and CO2 laser groups were compared without matching. Patients were followed up at 6, 12, and 24 months. Results: After matched, the lesion and Hr-HPV clearance rates of the PDT group (89.5%, 89.5%, 92.1%, and 81.6%, 84.2%, 89.5%) were significantly higher than those of the follow-up group (31.6%, 50.0%, 63.2%, and 21.1%, 26.3%, 31.6%, P < 0.05) at 6, 12, and 24 months. But the lesion clearance rates did not differ significantly between the PDT (68.9%, 82.2%, and 91.1%) and CO2 laser groups (68.7%, 78.3%, and 85.5%, P > 0.05) at 6, 12, and 24 months, and so did Hr-HPV clearance rates (PDT as 62.2% and 77.8%, and CO2 laser 54.2% and 61.4%, respectively, P > 0.05) at 6 and 12 months. However, at 24 months, the Hr-HPV clearance rate was higher in the PDT group than in the CO2 laser group (86.7% vs 71.1%, P = 0.047). In the PDT group, none of the lesions progressed. Conclusions: Compared with CO2 laser, PDT resulted in a higher Hr-HPV clearance, as well as a low risk of complications and disease progression. PDT is an effective and noninvasive treatment for VaIN1.

This systematic review provides a comprehensive analysis of corpus-based instruction (CBI) in English as a foreign language (EFL) classroom. Corpus-based instruction is a teaching method based on actual data from natural language use, representing an important branch of corpus research. It serves as an auxiliary tool for foreign language teaching and is considered an effective instructional method. The researchers aim to thoroughly analyze the empirical studies on corpus-based instruction (CBI) in EFL classrooms, exploring research contexts, theoretical foundations, types of classroom activities, research methods, corpus tools, influencing factors, and the advantages and challenges of implementing CBI. It also proposes effective coping strategies. Following the PRISMA guidelines, the research team conducted an extensive search across four reputable databases—ScienceDirect, Google Scholar, Wiley online Library, and the Web of Science—to identify empirical studies on Data-Driven Learning (DDL) and the use of corpora in language learning contexts from 2011 to 2024. A total of forty-four studies met the inclusion criteria for the final review. This systematic review underscores CBI's effectiveness in developing various English skills and promoting learner autonomy but also identifies key challenges, such as its focus on higher-level learners, the complexity of corpus use, and instructional limitations. The review suggests solutions like comprehensive training, simplified resources and tasks, personalized learning paths, and increased resource allocation. These strategies aim to enhance the effectiveness of CBI in EFL classrooms and improve language learning outcomes.

AimThis study aims to create and validate a novel systematic immune-inflammation-nutrition (SIIN) score to provide a non-invasive and accurate prognostic tool for head and neck squamous cell carcinoma (HNSCC) patients.Methods259 participants diagnosed with HNSCC from the First Affiliated Hospital of Xi’an Jiaotong University between 2008 and 2017 was included in this retrospective study. Patients were assigned to training (n=181) and validation (n=78) sets. A LASSO Cox regression model was employed to identify significant biomarkers for constructing a SIIN nomogram and to create SIIN score from this nomogram. The prognostic accuracy of the SIIN score was assessed by exploiting receiver operating characteristic (ROC) analysis, Kaplan-Meier survival analysis, Cox proportional hazard regression models, calibration and DCA curves.ResultsThe SIIN score was formulated based on six biomarkers-platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), albumin-bilirubin index (ALBI), fibrinogen (FIB) and monocyte count-identified by LASSO regression analysis. (1)The SIIN score demonstrated superior predictive value, achieving area under the ROC curve (AUC) values of 0.736 and 0.700 for 3- and 5-year OS. For recurrence-free survival (RFS), the AUC values were 0.752 for 3-year and 0.701 5-year RFS, as assessed in the training set. Validated as an independent prognostic factor in both cohorts, the SIIN score showed strong correlation with adverse clinicopathological outcomes.ConclusionThe SIIN score is a promising prognostic tool that integrates immune, inflammatory, and nutritional factors for predicting clinical outcomes in HNSCC patients. It offers enhanced predictive accuracy compared to existing markers and has the potential to guide personalized treatment strategies and clinical decision-making.

Abstract Gastric cancer (GC) ranks among the leading causes of cancer‐related mortality globally. Often, its initial stages manifest subtly, and the infrequency of routine screenings contributes to late diagnoses in many cases. Systemic treatments for GC include chemotherapy, targeted therapy, and immunotherapy, among which immunotherapy is the first‐line standard treatment for advanced GC. In recent years, immunotherapy has seen notable advancements, as evidenced by the Food and Drug Administration's approval of drugs such as nivolumab and pembrolizumab for GC treatment. Additionally, several other drugs are currently under rigorous preclinical and clinical investigation. This review aims to shed light on the recent advancements in immunotherapy for GC, particularly emphasizing the insights gained from phase 2/3 clinical trials that assess the efficacy, safety, and promise of various immunotherapeutic modalities, including immune checkpoint inhibitors, CAR‐T‐cell therapies, and cancer vaccines, in enhancing patient outcomes. Moreover, this review delves into the intricate immunological framework of GC, focusing on the tumor microenvironment, interactions among immune cells, and the roles of immune checkpoints such as PD‐L1. We also address the hurdles and prospective paths forward in the realm of immunotherapy for GC, offering fresh viewpoints on potential therapeutic approaches in this evolving domain.

Purpose: To describe a case of serous retinal detachment (SRD) resembling Vogt Koyanagi-Harada (VKH) disease following anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection (IVI) for pachychoroid related choroidal neovascularization (CNV). Observation: A 23-year-old female complained of vision loss in her right eye (OD) one day after receiving an anti-VEGF IVI for CNV. Her best-corrected visual acuity (BCVA) in OD dropped from 20/40 to 20/200, and intraocular pressure (IOP) measured 9 mmHg. The IVI resulted in development of hypotony maculopathy, manifesting as evident chorioretinal folds. Notably, there was significant increase in choroidal thickness and dilation of choroidal vessels. Multiple SRD were observed, and fundus fluorescein angiography (FFA) findings resembled those seen in VKH. Topical and systemic steroids were prescribed to prevent inflammation, resulting in an increase in IOP and improvement in choroidal thickness and SRD. Conclusion: Pachychoroid spectrum diseases (PSD) is associated with alterations in pachyvessel permeability and RPE damage. Hypotony maculopathy following IVI for PSD can manifest as SRD, with FFA findings resemble VKH. Careful monitoring of IOP and vigilance regarding scleral wound integrity at the injection site are imperative after IVI procedures in patients with PSD.

IntroductionSuccinate dehydrogenase subunit B (SDHB)-mutated paragangliomas (PGLs) are rare neuroendocrine tumors characterized by increased malignancy, readily metastasizing, and poorer prognosis. Here we report a case of SDHB-mutated metastatic PGL, wherein the patient showed significant tumor shrinkage and complete symptom remission following chemotherapy. We aim to contribute additional evidence to the existing knowledge associated with SDHB-mutated PGLs.Case reportA 40-year-old male patient presented with recurrent hypoglycemia and hypertension crisis. Imaging revealed a huge left retroperitoneal tumor and multiple diffuse metastases in lungs. Catecholamine was also elevated, aligning with a diagnosis of metastatic PGL. Pathology also confirmed this diagnosis. Additionally, the immunohistochemistry indicated negative expression of SDHB and gene test showed somatic SDHB mutation. Given the SDHB mutation, cyclophosphamide-vincristine-dacarbazine (CVD) chemotherapy was initiated in critical conditions. Subsequently, a significant tumor shrinkage and complete biochemical response were observed after two treatment cycles. In September 2024, CT scan revealed new pulmonary lesions. The progression-free survival (PFS) with CVD chemotherapy was 24 months.ConclusionThis report reviews the distinct clinical and biochemical characteristics and treatment approaches of SDHB-mutated paragangliomas, emphasizing that the significance of incorporating both genetic testing and immunohistochemical analysis in clinical practice.

Abstract Perineural invasion (PNI) is a new approach of cervical cancer invasion and metastasis, involving the cross-talk between tumor and nerve. However, the initiating signals and cellular interaction mechanisms of PNI remain largely elusive. The nerve-sparing radical hysterectomy (NSRH) proposed to improve postoperative quality of life is only applicable to cervical cancer patients without PNI. Therefore, it is important to elucidate the underlying mechanisms initiating PNI, and suggest the effective biomarkers to predict PNI before NSRH surgery. Here, we found that PNI is the characteristic of advanced cervical cancer, and Schwann cells were the antecedent cells that initiating PNI. Further, neuropeptide neuromedin B (NMB) produced by cervical cancer cells was determined to induce PNI by reprogramming Schwann cells, including driving their morphological and transcriptional changes, promoting their proliferation and migration, and initiating PNI by secreting CCL2 and directing axon regeneration. Mechanistically, cervical cancer cells-produced NMB activated its receptor NMBR in Schwann cells, and opened the T-type calcium channels to stimulate Ca2+ influx through PKA signaling, which could be blocked by the inhibitor. Clinically, combined examination of serum NMB and CCL2 levels was suggested to effectively predict PNI in cervical cancer patients. Our data demonstrate that cervical cancer-produced NMB initiates the reprograming of Schwann cells, which then direct axon regeneration, thus causing PNI onset. The elevated serum NMB and CCL2 levels may be useful for the decision-making to nerve sparing during hysterectomy surgery of cervical cancer patients.

Abstract Background and Objective Venlafaxine hydrochloride extended-release (ER) capsules are commonly used to treat depression and anxiety disorders. Evaluation of the bioequivalence of generic formulations with reference products is essential to ensure therapeutic equivalence. The objective of this study was to evaluate the bioequivalence, safety, and tolerability of Chinese-manufactured venlafaxine hydrochloride extended-release capsules compared with USA-manufactured EFFEXOR® XR in healthy Chinese volunteers under fed conditions. Methods A randomized, open-label, single-dose, crossover study was conducted. Subjects were randomly assigned to receive the test formulation (one 150-mg ER capsule manufactured in China) or the reference formulation (one 150-mg ER capsule manufactured in the USA). The bioequivalence of the two drugs was assessed using the area under the plasma concentration–time curve from time zero to the last sampling time (AUC0–t ) and the maximum observed concentration (C max). Results A total of 28 subjects were enrolled and randomly assigned to receive a single dose of either the test or reference capsule. All the subjects completed the study and were included in the pharmacokinetic (PK) and safety analyses. The mean AUC0–t and C max of venlafaxine and its active metabolite O-desmethylvenlafaxine were comparable between the test and reference products with both parameters close to 100% and the corresponding 90% confidence intervals within the specified 80–125% bioequivalence boundary. Safety was also assessed between the two products and all adverse events (AEs) in this study were mild in severity. Conclusions Both the test and reference venlafaxine hydrochloride ER capsules were bioequivalent and showed a similar safety and tolerability profile in the population studied. Clinical Trials Registration This study was registered at the Drug Clinical Trial Registration and Information Publicity Platform ( http://www.chinadrugtrials.org.cn/index.html ) with registration number CTR20211243, date: June 1, 2021.

Abstract The FGFR signaling pathway is integral to cellular activities, including proliferation, differentiation, and survival. Dysregulation of this pathway is implicated in numerous human cancers, positioning FGFR as a prominent therapeutic target. Here, we conduct a comprehensive review of the function, signaling pathways and abnormal alterations of FGFR, as well as its role in tumorigenesis and development. Additionally, we provide an in-depth analysis of pivotal phase 2 and 3 clinical trials evaluating the performance and safety of FGFR inhibitors in oncology, thereby shedding light on the current state of clinical research in this field. Then, we highlight four drugs that have been approved for marketing by the FDA, offering insights into their molecular mechanisms and clinical achievements. Our discussion encompasses the intricate landscape of FGFR-driven tumorigenesis, current techniques for pinpointing FGFR anomalies, and clinical experiences with FGFR inhibitor regimens. Furthermore, we discuss the inherent challenges of targeting the FGFR pathway, encompassing resistance mechanisms such as activation by gatekeeper mutations, alternative pathways, and potential adverse reactions. By synthesizing the current evidence, we underscore the potential of FGFR-centric therapies to enhance patient prognosis, while emphasizing the imperative need for continued research to surmount resistance and optimize treatment modalities.

Methamphetamine (MA) use disorder is a chronic neurotoxic brain disease characterized by a high risk of relapse driven by intense cravings. However, the neurobiological signatures of cravings remain unclear, limiting the effectiveness of various treatment methods. Diffusion MRI (dMRI) scans from 62 MA users and 57 healthy controls (HC) were used in this study. The MA users were longitudinally followed up during their period of long-term abstinence (duration of long-term abstinence: 347.52±99.25 days). We systematically quantified the control ability of each brain region for craving-associated state transitions using network control theory from a causal perspective. Craving-associated structural alterations (CSA) were investigated through multivariate group comparisons and biological relevance analysis. The neural mechanisms underlying CSA were elucidated using transcriptomic and neurochemical analyses. We observed that long-term abstinence-induced structural alterations significantly influenced the state transition energy involved in the cognitive control response to external information, which correlated with changes in craving scores (r ∼ 0.35, P

Chemokines play a crucial role in the pathogenesis of patients with hepatocellular carcinoma (HCC). The expression levels of interferon-γ-induced protein-10 (CXCL10) and macrophage inflammatory protein-3α (MIP-3a) were investigated to clarify their clinical significance in HCC.The protein levels of CXCL10 and MIP-3a in the serum of 105 HBV-associated HCC patients, 50 patients with liver cirrhosis (LC), 50 patients with chronic hepatitis B (CHB) and 50 healthy donors (HC) were detected by liquid chip technology (Luminex) or ELISA. In addition, their mRNA levels were also determined in liver cancer and adjacent cancer tissue (paracancer; ParaCa) from 65 HCC patients. The online database UALCAN was used to analyze the association between CXCL10 and pathological manifestations of liver cancer. In addition, the diagnostic value of CXCL10/MIP-3a and AFP in HCC patients was determined by analyzing the Receiver Operating Characteristic Curve (ROC).The protein concentrations of CXCL10 and MIP-3a were significantly higher in the HCC group than in the LC, CHB and HC groups. CXCL10 in sera and liver cancer tissues is significantly positively correlated with ALT, but no significance between CXCL10 in ParaCa tissues and sera-ALT. Their mRNA is significantly higher in cancer tissues than in ParaCa tissues. The areas under the ROC curve of CXCL10, MIP-3a, CXCL10 and MIP-3a combined and AFP were 0.9169, 0.9261, 0.9299 and 0.7880, respectively. Elevated chemokines CXCL10 and MIP-3a in HCC patients may be associated with the clinical manifestation of HCC and could be a potential molecular marker for prognostic evaluation or a therapeutic target for HCC.

BackgroundRecent studies have yielded conflicting results regarding the relationship between smoking history and the effectiveness of immune checkpoint inhibitors (ICIs) for advanced lung cancer. While some studies have suggested that smoking may enhance the response to immunotherapy in patients with lung cancer, other findings indicate the contrary. Therefore, we conducted a systematic review and meta-analysis to thoroughly examine this association.MethodsWe searched the PubMed, Embase, and Scopus databases for clinical trials comparing immunotherapy with conventional chemotherapy as the primary treatment for advanced lung cancer. A random effects model was used to synthesize hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). We also conducted predefined subgroup analyses to investigate the efficacy disparities between never-smokers and smokers who were administered immunotherapy alone or in combination with chemotherapy, as well as the differences between former and current smokers under similar treatment modalities.ResultsOur analysis included data from 17 Phase III clinical trials involving 10,283 patients. The findings indicate that immunotherapy benefits both smokers and never-smokers with lung cancer or non-small cell lung cancer, yielding pooled HRs for OS of 0.74 (95% CI: 0.59–0.92) and 0.73 (95% CI: 0.67–0.80), respectively. A significant interaction effect was not observed (HR: 0.98, 95% CI: 0.77–1.24, pinteraction = 0.14), and the tumor type, immunotherapy combination, and type of immunotherapy did not differ among the groups in the subgroup analyses. Similarly, both former and current smokers experienced a significant survival benefit from immunotherapy, with pooled HRs for OS of 0.79 (95% CI: 0.68–0.91) and 0.71 (95% CI: 0.59–0.87), respectively. However, a significant interaction effect was also not observed (HR: 0.91, 95% CI: 0.74–1.11, pinteraction = 0.14).ConclusionOur findings suggest that smoking status does not affect the effectiveness of immunotherapy for lung cancer treatment. However, additional high-quality clinical trials are needed to confirm this conclusion.Systematic review registrationhttps://inplasy.com/register/, identifier INPLASY2023110058.

BackgroundThe third-line treatment for refractory colorectal cancer (CRC) has limited efficacy. This study aimed to evaluate the safety and efficacy of SHR-8068 (an anti-CTLA-4 antibody), combined with adebrelimab (an anti-PD-L1 antibody), and bevacizumab in refractory non-microsatellite instability-high (MSI-H) or proficient mismatch repair (pMMR) CRC.MethodThis study is a prospective, open-label, single-center phase Ib/II clinical trial. Patients with pathologically confirmed pMMR/non-MSI-H metastatic colorectal adenocarcinoma who have failed ≥2 lines prior standard systemic treatments will be enrolled (n=36). The Ib phase will evaluate two dosing regimens of SHR-8068 in combination therapy (n=9 each dosage): SHR-8068 (1 mg per kilogram, every six weeks, intravenously) or SHR-8068 (4 mg per kilogram, every twelve weeks, intravenously) combined with adebrelimab (1200 mg, every three weeks, intravenously) and bevacizumab (7.5 mg per kilogram, every three weeks, intravenously). The efficacy and adverse events (AEs) of these regimens will be assessed to determine the recommended phase II dose (RP2D) of SHR-8068. Those of RP2D group from the phase Ib will be included in the phase II. The study will go to include 18 additional patients according to the one-sample log-rank test design in the phase II. The primary endpoint of the Ib phase is safety, with secondary endpoints including the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and quality of life (QOL). The primary endpoint for phase II was PFS, with secondary endpoints including ORR, OS, DCR, safety, and QOL. Identifying biomarkers to predict the efficacy of this regimen is the exploratory study endpoint.DiscussionThis proof-of-concept study would provide safety and efficacy signals of this novel combination treatment for the MSS CRCs in the late-line setting. And it may offer new insights on the clinical application of dual immunotherapy combined with anti-angiogenic therapy in the MSS CRC.

Background: Cholangiocarcinoma is a kind of malignant tumor that originates in the epithelium of the biliary tract. Although there are several options for second-line treatment for patients without specific genetic mutations, the overall treatment efficacy is disappointing. Second-line treatment which is composed of liposomal irinotecan plus fluorouracil and leucovorin significantly improved the treatment efficacy for advanced biliary tract cancer and extended patient survival. This study aims to evaluate the efficacy and safety of the combination of cadonilimab with liposomal irinotecan plus fluorouracil and leucovorin for advanced biliary tract cancer. Objectives: The primary objective of this study is to determine the objective response rate. The second objectives of this study are overall survival, progression-free survival, disease control rate, and adverse event incidence rate. Design: The study is a single-arm, prospective phase II clinical trial. In all, 51 patients who are diagnosed with locally advanced or metastatic bile tract cancer will be enrolled. Methods and analysis: Eligible participants will receive cadonilimab at a dosage of 6 mg/kg on day 1 of each 21-day cycle combined with intravenous liposomal irinotecan at a dosage of 70 mg/m 2 for 90 min on day 1 plus leucovorin at a dosage of 400 mg/m 2 for 30 min on day 1 and fluorouracil at a dosage of 400 mg/m 2 for 46 h every 2 weeks. Discussion: Previous studies have suggested that there is a synergistic effect between the two treatment modalities. However, the potential of cadonilimab in bile tract cancer has not been explored. Hence, this trial is the first to investigate its efficacy and toxicity. In addition, the trial is also willing to explore potential biomarkers in patients with locally advanced and metastatic bile tract cancer. Trial registration: This study was registered on ClinicalTrials.gov with NCT06438822. Ethics: This study protocol and amendments have been approved by the Ethics Committee of West China Hospital (2024(791)).

The tea plant (Camellia sinensis (L.) O. Kuntze) is an important woody economic crop and often attacked by various insect pests such as tea aphids (Toxoptera aurantii Boyer de Fonscolombe). To reveal tea plant responses to tea aphid infestation, tea aphid-resistant cultivar ‘Taicha13’ and -susceptible one ‘Jingfeng’ were first screened, and then widely targeted metabolomics profiling, biochemical parameter and RT-qPCR analyses were performed in three samples, TCN (tea aphid non-infested ‘Taicha13’), JFN (tea aphid non-infested ‘Jingfeng’) and JFA (tea aphid-infested ‘Jingfeng’). The results showed amnio acid (plus proline) and protein content, and amnio acid: sucrose ratio were significantly less abundant in TCN relative to JFN, suggesting TCN is low nutritional quality for tea aphids. Metabolite profiling revealed that flavonoids and JA-isoleucine (JA-Ile) were more enriched in TCN and JFA compared to JFN, proposing effective roles of flavonoids and JA-Ile in tea plant defense against tea aphid infestation. RT-qPCR results demonstrated that five JA biosynthesis genes (CsLOX2, CsLOX3, CsOPR, CsAOC and CsJAR) in exception of CsAOS, and six flavonoid biosynthesis genes (CsPAL, CsC4H, CsCHS1, CsCHS2, CsFL and CsDFR) shared similarly higher abundance in TCN than in JFN, and exhibited elevated expression levels in JFA relative to JFN, further suggesting flavonoids and JA confer tea plant resistance against tea aphid feeding. Overall, our findings uncovered that tea aphid-infestation activated defensive responses and highlighted involvement of nutritional quality, flavonoids and JA-Ile in tea plant resistance against tea aphid infestation.

IntroductionThe identification of risk factors for regional lymph node (r-LN) metastasis in rectal neuroendocrine tumors (R-NETs) remains challenging. Our objective was to investigate the risk factors associated with patients diagnosed with R-NETs exhibiting r-LN metastasis.MethodsPatient information was obtained from the Surveillance, Epidemiology, and End Results (SEER) database, complemented by data from the West China Hospital (WCH) databases. The construction cohort comprised patients diagnosed with R-NETs from the SEER database, while cases from the WCH database were utilized as the validation cohort. A novel nomogram was developed to predict the probability of r-LN metastasis, employing a logistic regression model.ResultsUnivariate analysis identified four independent risk factors associated with poor r-LN metastasis: age (HR = 1.027, p < 0.05), grade (HR = 0.010, p < 0.05), T stage (HR = 0.010, p < 0.05), and tumor size (HR = 0.005, p < 0.05). These factors were selected as predictors for nomogram construction.DiscussionThe novel nomogram serves as a reliable tool for predicting the risk of r-LN metastasis, providing clinicians with valuable assistance in identifying high-risk patients and tailoring individualized treatments.

Micro/nanoplastics (MNPs) are detected in human liver, and pose significant risks to human health. Oral exposure to MNPs derived from non-biodegradable plastics can induce toxicity in mouse liver. Similarly, nasal exposure to non-biodegradable plastics can cause airway dysbiosis in mice. However, the hepatotoxicity induced by foodborne and airborne biodegradable MNPs remains poorly understood. Here we show the hepatotoxic effects of biodegradable polylactic acid (PLA) MNPs through multi-omics analysis of various biological samples from mice, including gut, fecal, nasal, lung, liver, and blood samples. Our results show that both foodborne and airborne PLA MNPs compromise liver function, disrupt serum antioxidant activity, and cause liver pathology. Specifically, foodborne MNPs lead to gut microbial dysbiosis, metabolic alterations in the gut and serum, and liver transcriptomic changes. Airborne MNPs affect nasal and lung microbiota, alter lung and serum metabolites, and disrupt liver transcriptomics. The gut Lachnospiraceae_NK4A136_group is a potential biomarker for foodborne PLA MNP exposure, while nasal unclassified_Muribaculaceae and lung Klebsiella are potential biomarkers for airborne PLA MNP exposure. The relevant results suggest that foodborne PLA MNPs could affect the “gut microbiota-gut-liver” axis and induce hepatoxicity, while airborne PLA MNPs could disrupt the “airway microbiota-lung-liver” axis and cause hepatoxicity. These findings have implications for diagnosing PLA MNPs-induced hepatotoxicity and managing biodegradable materials in the environment. Our current study could be a starting point for biodegradable MNPs-induced hepatotoxicity. More research is needed to verify and inhibit the pathways that are crucial to MNPs-induced hepatotoxicity.

BackgroundOlder patients with advanced cholangiocarcinoma lack systemic therapy standards. These people have a high risk of chemotherapy, accompanied by adverse reactions and even discontinuation of treatment.Case presentationWe report a 78-year-old female subject with advanced intrahepatic cholangiocarcinoma presenting with unresectable lesions involving the hepatic veins, along with extensive metastatic lymph nodes. After the geriatric assessment, capecitabine was utilized for only one cycle owing to adverse events (AEs). Next, a combination of low-dose lenvatinib and tislelizumab was administrated as a second-line treatment, which resulted in remarkable early tumor shrinkage. The following individual lenvatinib taper enabled a manageable safety profile and durable deep response. A near-complete response was achieved, with the primary tumor significantly reducing from 5.6 cm × 4.7 cm to nearly complete disappearance, accompanied by complete regression of lymph nodes, and both progression-free survival and overall survival exceeding 24 months.ConclusionThe case provides valuable insights that could influence future treatment strategies for older patients with advanced cholangiocarcinoma who are unsuitable for chemotherapy. The dose-individualized chemotherapy-free regime of lenvatinib and tislelizumab might be used in similar cases to improve their outcomes.

Abstract Objective Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario. Methods In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People’s Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People’s Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction. Results The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively. Conclusion The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.

Objective:. Real-world diagnostic and treatment data for pancreatic cancer in China are lacking. As such, the present study investigated the clinical characteristics, diagnosis, and treatment of advanced pancreatic cancer (including locally advanced and metastatic disease) in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database. Methods:. A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database. The entire course of real-world pancreatic cancer management was analyzed. Results:. The proportion of patients with advanced pancreatic cancer was higher among males than females (62.4% vs 37.6%, respectively). Patients typically had a history of hypertension (30.8%), diabetes (21.6%), and cholangitis (20.2%). Abdominal pain (51.6%), abdominal distension (27.1%), jaundice (20.1%), and weight loss (16.3%) were the main symptoms observed in patients with advanced pancreatic cancer in this cohort. Serum carbohydrate antigen (CA)19-9 is one of the most common tumor markers. In the present study, 2562 patients underwent first-line therapy. The median progression-free survival (PFS) for patients undergoing first-line therapy was 4.1 months. The major options for first-line therapy included gemcitabine (GEM) plus S-1 (GS/X) (23.4%), nab-paclitaxel plus GEM (AG) (18.1%), oxaliplatin, irinotecan, and leucovorin-modulated fluorouracil (FOLFIRINOX; 11.9%), nab-paclitaxel plus S-1 (AS) (8.9%), and GEM combined with oxaliplatin/cisplatin (GEMOX/GP) (7.6%). The AS and GS/X regimens were associated with the highest PFS rates. Conclusion:. This is the first study to report multicenter, real-world data regarding advanced pancreatic cancer in China. Results revealed that real-world treatment options differed from guideline recommendations, and PFS was shorter than that in previously reported data. Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

IntroductionFengxiangxing Huairang Daqu (FHD) is one of the major types of Daqu in China. However, the relationship between the microbial community structure at different stages, the changes in the sensory characteristics, fermentation characteristics, volatiles, the most critical process point, and the quality formation of FHD is not clear.MethodsBased on microscopic characterization, PacBio SMRT sequencing, and HS-SPME-GC-MS volatile metabolite analysis revealed the relationship between FHD quality formation and the dynamics of Qupi.ResultsThe results showed that the 12th day of the culture was the most critical process point, highlighting the most significant differences in microbial community structure, sensory characteristics, fermentation characteristics, and flavor substances. Bacillus licheniformis (43.25%), Saccharopolyspora rectivirgula (35.05%), Thermoascus aurantiacus (76.51%), Aspergillus amstelodami (10.81%), and Saccharomycopsis fibuligera (8.88%) were the dominant species in FHD. S. fibuligera, A. amstelodami, and T. aurantiacus were associated with the snow-white color of the FHD epidermis, the yellow color of the interior, and the gray-white color, respectively. The abundance of T. aurantiacus, A. amstelodami, B. licheniformis, and S. rectivirgula was positively associated with the esterifying power and liquefying power of FHD. The abundance of T. aurantiacus and A. amstelodami was positively correlated with the saccharifying power of FHD. The abundance of S. fibuligera was positively related to the fermenting power of FHD. A total of 248 volatiles were detected in Qupi, mainly including alcohols, esters, aldehydes, and ketones. Of them, eleven volatiles had a significant effect on the flavor of Qupi, such as 1-butanol-3-methyl-, hydrazinecarboxamide, ethanol, phenylethyl alcohol, ethyl acetate, 2-octanone, 1-octen-3-ol, formic acid-hexyl ester, (E)-2-octen-1-ol, ethyl hexanoate, and 2(3H)-furanone-dihydro-5-pentyl-. The abundance of B. licheniformis, S. rectivirgula, T. aurantiacus, and S. fibuligera was positively correlated with the alcohols, aromatic compounds, and phenols in FHD. The abundance of S. fibuligera was positively correlated with the acids, esters, and hydrocarbons in FHD.DiscussionThese results indicate important theoretical basis and technical support for controllable adjustment of FHD microbial community structure, stable control of FHD quality, and precise, effective, and large-scale guidance of FHD production.

Introduction Patients with pancreatic ductal adenocarcinoma (PDAC) remain a poor prognosis despite the development of chemotherapy. Although programmed cell death 1 (PD-1) blockade has shown great efficacy in various solid tumours, its application in treating PDAC is limited. Recent studies have indicated that chemotherapy or stereotactic body radiotherapy (SBRT) may improve the antitumour effect of PD-1 blockade in patients with PDAC. The objective of this study is to evaluate the efficacy and safety of combined therapy comprising PD-1 blockade, gemcitabine plus nab-paclitaxel chemotherapy and SBRT for patients with metastatic PDAC.Methods and analysis This is a multicentre, single-arm, prospective phase II clinical trial. Forty-three patients diagnosed with metastatic PDAC will be enrolled. The eligible patients will be intravenously administered 1000 mg/m2 gemcitabine and 125 mg/m2 nab-paclitaxel on days 1 and 8 of the 21-day cycle. Serplulimab (200 mg) will be administered intravenously on day 1 of the 21-day cycle. Furthermore, during the second cycle, the patients will undergo SBRT with doses of 33 Gy in five fractions for primary lesions or doses of 24 Gy in three fractions for metastases. The primary endpoint is the 6-month progression-free survival (PFS) rate. The secondary endpoints overall survival, PFS, overall response rate, disease control rate, time to progression, duration of response, duration of disease control and safety. Moreover, this trial seeks to investigate biomarkers such as circulating tumour DNA and circulating hybrid cells in patients diagnosed with metastatic PDAC.Ethics and dissemination The study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. The study results will be presented at international conferences and published in a peer-reviewed journal.Trial registration number ChiCTR2300073237.

Prostate cancer (PC) and Ovarian cancer (OC) are two of the most common types of cancer that affect the reproductive systems of older men and women. These cancers are associated with a poor quality of life among the aged population. Therefore, finding new and innovative ways to detect, treat, and prevent these cancers in older patients is essential. Finding biomarkers for these malignancies will increase the chance of early detection and effective treatment, subsequently improving the survival rate. Studies have shown that the prevalence and health of some illnesses are linked to an impaired immune system. However, the age-associated changes in the immune system during malignancies such as PC and OC are poorly understood. Recent research has suggested that the excessive production of inflammatory immune mediators, such as interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor (TGF), tumor necrosis factor (TNF), CXC motif chemokine ligand 1 (CXCL1), CXC motif chemokine ligand 12 (CXCL12), and CXC motif chemokine ligand 13 (CXCL13), etc., significantly impact the development of PC and OC in elderly patients. Our review focuses on the latest functional studies of pro-inflammatory cytokines (interleukins) and CXC chemokines, which serve as biomarkers in elderly patients with PC and OC. Thus, we aim to shed light on how these biomarkers affect the development of PC and OC in elderly patients. We also examine the current status and future perspective of cytokines (interleukins) and CXC chemokines-based therapeutic targets in OC and PC treatment for elderly patients.

BackgroundThe prognostic value of an effective biomarker, pan-immune-inflammation value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients.MethodsA total of 161 HNSCC patients who underwent radical surgery were enrolled retrospectively for development cohort. The cutoff of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). The concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the nomograms. A cohort composed of 50 patients who received radiotherapy or chemoradiotherapy (RT/CRT) alone was applied for generality testing of PIV and nomograms.ResultsPatients with higher PIV (≥123.3) experienced a worse DFS (HR, 5.01; 95% CI, 3.25–7.72; p

ObjectivesWe evaluated the long-term effects of air pollution controls on health and health inequity among Chinese >45 years of age.MethodsData were derived from the China Health Aging and Retirement Longitudinal Survey and the China National Environmental Monitoring Centre. Decreases in PM2.5 and PM10 were scaled to measure air quality controls. We used a quasi-experimental design to estimate the impact of air quality controls on self-reported health and health inequity. Health disparities were estimated using the concentration index and the horizontal index.ResultsAir pollution controls significantly improved self-reported health by 20% (OR 1.20, 95% CI, 1.02–1.42). The poorest group had a 40% (OR 1.41, 95% CI, 0.96–2.08) higher probability of having excellent self-reported health after air pollution controls. A pro-rich health inequity was observed, and the horizontal index decreased after air pollution controls.ConclusionAir pollution controls have a long-term positive effect on health and health equity. The poorest population are the main beneficiaries of air pollution controls, which suggests policymakers should make efforts to reduce health inequity in air pollution controls.

Pancreatoblastoma (PB), a neoplasm derived from pancreatic follicular cells, primarily affects the pediatric population. Although infrequent in adults, it is associated with a considerably worse prognosis. Approximately one-third of patients are diagnosed with metastatic disease, with liver metastases being the most prevalent. Diagnosis relies on histopathological alterations including squamous vesicles, positive staining for CK8/CK18/CK19, and nuclear displacement of β-catenin. Additionally, liver metastases demonstrate substantial enhancement during the arterial phase of a contrast-enhanced computed tomography (CT) scan. Surgical resection serves as the principal therapeutic approach for addressing primary lesions and liver metastatic PB. In instances where surgical intervention is not viable, patients may derive benefits from systemic therapy and radiotherapy. This particular case report presents the clinical details of a 27-year-old female patient diagnosed with PB, who subsequently developed multiple liver metastases following a pancreaticoduodenectomy. Genomic examinations revealed the presence of ERBB2 amplification, RAD54L deletion, low TMB-L, and MSS in the patient. Despite the patient undergoing chemotherapy and Her-2 targeted therapy in conjunction with immunotherapy, no reduction in lesion size was observed until the administration of surufatinib. Subsequently, a notable outcome ensued, where the metastatic lesions were effectively excised via surgical intervention. Surufatinib has demonstrated a progression-free survival (PFS) of no less than 14 months, and the patient’s survival has endured for a duration of 33 months. This indicates the potential efficacy of surufatinib as a viable therapeutic alternative for adult patients afflicted with PB.

Background: Cervical intraepithelial neoplasia (CIN) encompasses a range of cervical lesions that are closely linked to cervical invasive carcinoma. Early detection and timely treatment of CIN are crucial for preventing the progression of the disease. However, no bibliometric analysis has been conducted in this area. This research aimed to employ bibliometric analysis to summarize the current research hotspots and estimate future research trends in the CIN field. Methods: Publications related to CIN (2013–2023) were retrieved from the Science-Citation-Index-Expanded-of-Web-of-Science-Core-Collection. CiteSpace, VOSviewer, and the bibliometric-Online-Analysis-Platform-of-Literature-Metrology were employed to analyze the yearly research output, collaborating institutions or countries, leading researchers, principal journals, co-referenced sources, and emerging keywords. Results: In total, 4677 articles on CIN that were published from 2013 to 2023 and met our criteria were extracted. Major publishing platforms were predominantly USA until 2017 when China emerged as the leading source of publications about CIN. The USA was the leading nation in international collaborations. The National-Cancer-Institute (NCI) was the institution with the most publications. Schiffman Mark produced the highest number of articles, with a total of 92. Ten major clusters were identified through co-cited keyword clustering, including prevalence, human papillomavirus, DNA methylation, p16, methylation, conization, HPV genotyping tests (VALGENT), deep learning, vaginal microbiome, and immunohistochemistry. Keyword burst analysis showed that photodynamic therapy and deep learning emerged as prominent research focal points with significant impact in resent three years. Conclusion: Global publications on CIN research showed a relatively stable trend over the past eleven years. Current research hotspots are deep learning and photodynamic therapy. This research offered organized data and insightful guidance for future studies, which may help better prevent, screen, and treat CIN.

Abstract Background Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. Methods A total of 3251 hrHPV-positive women aged 30–82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. Results CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 −) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). Conclusions PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. Trial registration ChiCTR2100048972. Registered on 19 July 2021.

Abstract Age-related macular degeneration (AMD) is the leading cause of central vision impairment among the elderly. Effective and accurate AMD screening tools are urgently needed. Indocyanine green angiography (ICGA) is a well-established technique for detecting chorioretinal diseases, but its invasive nature and potential risks impede its routine clinical application. Here, we innovatively developed a deep-learning model capable of generating realistic ICGA images from color fundus photography (CF) using generative adversarial networks (GANs) and evaluated its performance in AMD classification. The model was developed with 99,002 CF-ICGA pairs from a tertiary center. The quality of the generated ICGA images underwent objective evaluation using mean absolute error (MAE), peak signal-to-noise ratio (PSNR), structural similarity measures (SSIM), etc., and subjective evaluation by two experienced ophthalmologists. The model generated realistic early, mid and late-phase ICGA images, with SSIM spanned from 0.57 to 0.65. The subjective quality scores ranged from 1.46 to 2.74 on the five-point scale (1 refers to the real ICGA image quality, Kappa 0.79–0.84). Moreover, we assessed the application of translated ICGA images in AMD screening on an external dataset (n = 13887) by calculating area under the ROC curve (AUC) in classifying AMD. Combining generated ICGA with real CF images improved the accuracy of AMD classification with AUC increased from 0.93 to 0.97 (P

Abstract Cholesterol is an indispensable component in mammalian cells, and cholesterol metabolism performs important roles in various biological activities. In addition to the Warburg effect, dysregulated cholesterol metabolism is one of the metabolic hallmarks of several cancers. It has reported that reprogrammed cholesterol metabolism facilitates carcinogenesis, metastasis, and drug-resistant in various tumors, including hepatocellular carcinoma (HCC). Some literatures have reported that increased cholesterol level leads to lipotoxicity, inflammation, and fibrosis, ultimately promoting the development and progression of HCC. Contrarily, other clinical investigations have demonstrated a link between higher cholesterol level and lower risk of HCC. These incongruent findings suggest that the connection between cholesterol and HCC is much complicated. In this report, we summarize the roles of key cholesterol regulatory genes including cholesterol biosynthesis, uptake, efflux, trafficking and esterification in HCC. In addition, we discuss promising related therapeutic targets for HCC.

Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases. However, a lack of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of these strategies. This review presents the viewpoints from an international conference consisting of several expert working groups. The working groups reviewed a series of questions of particular interest to clinicians taking care of patients with pancreatic neuroendocrine neoplasms with liver metastases by reviewing the existing management strategies and literature, evaluating the evidence on which management decisions were based, developing internationally acceptable recommendations for clinical practice, and making recommendations for clinical and research endeavors. The review for each question will be followed by recommendations from the panel.

In order to accurately evaluate the aroma quality of raw Pu'er tea in Lincang City, the aroma components of 16 raw Pu'er teas were systematically analyzed and comprehensively evaluated by multivariate statistical analysis. A total of 48 aroma components were detected, with 11 aroma components were more than 2.00% content. Among them, linalool was the most abundant component and the content was 24.68%. For the aroma types, the alcohols were accounted for the largest proportion with a mean of 46.55%, followed by aldehydes with a mean of 26.81%, while ketones, esters and other components were responsible for little proportion. Multivariate statistical analysis showed that the raw Pu'er teas obtained form in southern region were clearly distinguished from those in northern region. The concentration of alcohols and esters was significantly higher in southern region than those in northern region, whereas aldehyde, ketones and other components were remarkably lower. Altitude may be an important reason for the difference of aroma components of Pu'er raw tea in the south and north regions. Furthermore, 23 aroma components were identified based on variable importance in projection (VIP) score>1, which might be responsible for the discrimination of raw Pu'er teas in southern and northern region. Linalool, isoflolone, ketones, alcohols, aldehydes, β-cyclocitral, α-cyclocitral, 2,2,6-trimethyl-cyclohexanone, nerol and β-ionone play siginificant role in the differentiation of raw Pu'er tea harvested from different regions. This study would provide some theoretical basis for accurately understanding the aroma quality of Lincang Pu'er raw tea, and also provide ideas and methods for the study on the quality evaluation and origin determination of Lincang Pu'er raw tea.

Abstract Background Extravillous trophoblast cell (EVT) differentiation and its communication with maternal decidua especially the leading immune cell type natural killer (NK) cell are critical events for placentation. However, appropriate in vitro modelling system and regulatory programs of these two events are still lacking. Recent trophoblast organoid (TO) has advanced the molecular and mechanistic research in placentation. Here, we firstly generated the self-renewing TO from human placental villous and differentiated it into EVTs (EVT-TO) for investigating the differentiation events. We then co-cultured EVT-TO with freshly isolated decidual NKs for further study of cell communication. TO modelling of EVT differentiation as well as EVT interaction with dNK might cast new aspect for placentation research. Results Single-cell RNA sequencing (scRNA-seq) was applied for comprehensive characterization and molecular exploration of TOs modelling of EVT differentiation and interaction with dNKs. Multiple distinct trophoblast states and dNK subpopulations were identified, representing CTB, STB, EVT, dNK1/2/3 and dNKp. Lineage trajectory and Seurat mapping analysis identified the close resemblance of TO and EVT-TO with the human placenta characteristic. Transcription factors regulatory network analysis revealed the cell-type specific essential TFs for controlling EVT differentiation. CellphoneDB analysis predicted the ligand-receptor complexes in dNK-EVT-TO co-cultures, which relate to cytokines, immunomodulation and angiogenesis. EVT was known to affect the immune properties of dNK. Our study found out that on the other way around, dNKs could exert effects on EVT causing expression changes which are functionally important. Conclusion Our study documented a single-cell atlas for TO and its applications on EVT differentiation and communications with dNKs, and thus provide methodology and novel research cues for future study of human placentation.

Objective: To investigate public awareness about core information regarding chronic diseases and identify factors influencing that awareness among Anhui Province residents, provide a scientific basis for policy-making, and formulate corresponding intervention measures. Methods: From March to April 2021, 12 provincial-level representative counties and districts of Anhui province in the China Adult Chronic Disease and Nutrition Surveillance were selected as survey sites, and 4790 residents were recruited for the survey using stratified multi-stage cluster random sampling. Basic details about the study participants were collected and their awareness of core information about major chronic diseases was measured through an online survey using WeChat. Results: In 2021, the awareness rate of core information about chronic diseases among residents of Anhui Province was 54.93%. Multivariate logistic regression analysis showed that a higher awareness rate was associated with the following factors: non-housework occupations (agriculture, forestry, animal husbandry, and fishery: OR = 1.309, commercial services and production and transportation: OR = 1.450, institutions, and professional and technical personnel: OR = 1.461), a high education level (high school/junior high school/technical school OR = 1.357, college and above OR = 2.133), and residence in the southern and northern Anhui areas (southern Anhui OR = 1.282, northern Anhui OR = 1.431); whereas in rural areas (by district and country) (OR = 0.863), the awareness rate was low (all P

Abstract Background More than half of neuroendocrine tumor (NET) patients will experience liver metastasis, and interventional therapy represented by transarterial embolization (TAE) is the main local treatment method. Surufatinib is recommended as a standard systemic treatment for advanced NETs. The efficacy and safety of surufatinib combined with TAE in the treatment of liver metastasis are undetermined. This study was conducted to compare the clinical outcome of surufatinib combined with TAE versus surufatinib monotherapy in liver metastatic NETs. Methods This is a prospective, multicenter, open‐label, and randomized controlled trial. Patients diagnosed with liver metastatic NETs will be enrolled. Participants are randomly assigned in a 1:1 ratio to either the experimental group or the control group. Patients will be treated with surufatinib plus TAE in the experimental group, while patients in the control group will receive surufatinib monotherapy. The primary endpoint is progression‐free survival (PFS) assessed by a blinded independent image review committee (BIIRC). The secondary endpoints are investigator‐assessed PFS, liver‐specific objective response rate (ORR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. Discussion This is the first prospective study to investigate the efficacy of surufatinib combined with TAE. We expect this trial to propose a new and effective treatment strategy for liver metastatic NETs.

Purpose: To identify essential oils (EOs) active against non-growing stationary phase Mycobacterium abscessus and multidrug-resistant M. abscessus strains. Methods: The activity of EOs against both stationary and log phase M. abscessus was evaluated by colony forming unit (CFU) assay and minimum inhibitory concentration (MIC) testing. Results: We assessed the activity of 80 EOs against stationary phase M. abscessus and found 12 EOs (Cinnamon, Satureja montana, Palmarosa, Lemon eucalyptus, Honey myrtle, Combava, Health shield, Mandarin, Thyme, Rosewood, Valerian Root and Basil) at 0.5% concentration to be active against both growing and non-growing stationary phase M. abscessus. Among them, Satureja montana essential oil and Palmarosa essential oil could eliminate all stationary phase M. abscessus at 0.125% and Cinnamon essential oil could eliminate stationary phase bacteria at 0.063% after 1-day treatment. Interestingly, these EOs also exhibited promising activity against multidrug-resistant M. abscessus clinical strains. Conclusions: Our study indicates that some EOs display outstanding effectiveness against both drug susceptible M. abscessus and multidrug-resistant M. abscessus isolates. These findings may be significant for the treatment of persistent M. abscessus infections.

ABSTRACT: Objectives: Faropenem has antituberculosis activity in vitro but its utility in treating patients with tuberculosis (TB) is unclear. Methods: We conducted an open-label, randomized trial in China, involving newly diagnosed, drug-susceptible pulmonary TB. The control group was treated with the standard 6-month regimen. The experimental group replaced ethambutol with faropenem for 2 months. The primary outcome was the treatment success rate after 6 months of treatment. Noninferiority was confirmed if the lower limit of a 95% one-sided confidence interval (CI) of the difference was greater than −10%. Results: A total of 227 patients eligible for the study were enrolled in the trial group and the control group in a ratio of 1:1. Baseline characteristics of participants were similar in both groups. In the modified intention-to-treat population, 88.18% of patients in the faropenem group achieved treatment success, and 85.98% of those in the control group were successfully treated, with a difference of 2.2% (95% CI, −6.73-11.13). In the per-protocol population, treatment success was 96.04% in the faropenem group and 95.83% in the control group, with a difference of 2.1% (95% CI, −5.31-5.72). The faropenem group showed noninferiority to the control group in the 6-month treatment success rates. The faropenem group had significantly fewer adverse events (P

Background: Orbitofrontal cortex (OFC) is a promising target for intracranial electrical stimulation (iES) aimed at improving mood states. However, knowledge gaps remain regarding the underlying neural mechanisms of iES effects, such as the effect of the OFC target in comparison with other emotional network targets, the impact of brain state at the time of stimulation, and the neural response induced by iES at both local and network scales. Objective: Our study aims to address the neural mechanisms underlying the effects of iES in improving mood states. Methods: We conducted a study in 24 epilepsy patients who received iES through implanted electrodes in the emotional network and compared the effects of iES on multiple targets in the emotional network. Results: We found that only iES applied to the orbitofrontal cortex (OFC) led to mood improvement and changes in neural activity. We also observed that iES to the OFC suppressed the delta-theta power when the brain was in a low mood state. Moreover, the iES to the OFC decreased delta-theta power and increased gamma power at local regions within the emotional network, and enhanced the information flow through the frequency domain among regions within the emotional network. Conclusions: These findings provide insight into the neural correlates of iES-induced mood improvement and support the potential of iES as a therapeutic intervention for mood disorders.