Postpartum Guillain-Barré Syndrome: A Case Report and Literature Review.

Guillain-Barré syndrome (GBS) is a rare acute-onset neurological disease with significant morbidity and mortality. The risk of GBS increases after delivery. Labor and delivery presents many possible risk factors for GBS. However, risk factors and prognosis of postpartum GBS remain unclear due to its low incidence. Here, we first present a patient with a history of postpartum GBS who returned for an elective repeat cesarean section (C-section). For her previous delivery, the patient received spinal anesthesia for an urgent C-section. She presented postpartum with jaw pain, facial palsy, respiratory difficulty, progressive bilateral lower extremity weakness, and areflexia. The diagnosis of GBS was confirmed by cerebrospinal fluid (CSF) examination, nerve conduction studies (NCS), and electromyography (EMG). Her symptoms of GBS improved after intravenous immunoglobulin (IVIG) treatment. The patient also had an Escherichia coli-positive urinary tract infection (UTI), which was treated with nitrofurantoin. For her repeat elective C-section, we performed a dural puncture epidural (DPE) anesthesia. After delivery, she was discharged to home uneventfully. She did not report any new neurological symptoms at her three-week follow-up. Here, we also review published cases of postpartum GBS and discuss peripartum anesthetic considerations for patients with GBS, aiming to inform clinical management of postpartum GBS in the future.

The State of Systematic Therapies in Clinic for Hepatobiliary Cancers.

Hepatobiliary cancer (HBC) includes hepatocellular carcinoma and biliary tract carcinoma (cholangiocarcinoma and gallbladder carcinoma), and its morbidity and mortality are significantly correlated with disease stage. Surgery is the cornerstone of curative therapy for early stage of HBC. However, a large proportion of patients with HBC are diagnosed with advanced stage and can only receive systemic treatment. According to the results of clinical trials, the first-line and second-line treatment programs are constantly updated with the improvement of therapeutic effectiveness. In order to improve the therapeutic effect, reduce the occurrence of drug resistance, and reduce the adverse reactions of patients, the treatment of HBC has gradually developed from single-agent therapy to combination. The traditional therapeutic philosophy proposed that patients with advanced HBC are only amenable to systematic therapies. With some encouraging clinical trial results, the treatment concept has been revolutionized, and patients with advanced HBC who receive novel systemic combination therapies with multi-modality treatment (including surgery, transplant, TACE, HAIC, RT) have significantly improved survival time. This review summarizes the treatment options and the latest clinical advances of HBC in each stage and discusses future direction, in order to inform the development of more effective treatments for HBC.

Association between coronary artery disease and clinical outcome in cancer patients: A propensity score matching analysis.

Objective: The aim of this study was to evaluate the prognostic value of coronary artery disease (CAD) detected by coronary computed tomography angiography (CTA) to predict the risk of all-cause mortality in cancer patients in a propensity score matching (PSM) analysis. Methods: A total of 331 patients who previously had cancer and underwent coronary CTA from January 2015 to December 2019 were included. Multivariate Cox proportional hazards regression analysis and propensity-score matching analysis were performed. The primary endpoint was all-cause of mortality. Results: In total, 125 with CAD and 206 with no CAD during a median follow-up of 3.3 years were included in this study. After PSM, age (HR, 1.040; 95%CI, 1.001-1.081; p = 0.014) and CAD (HR, 2.164; 95%CI, 1.057-4.430; p = 0.035) remained significant factors for all-cause mortality. Conclusion: CAD evaluated by coronary CTA was found to be at higher risk for all-cause mortality in cancer patients. Due to the retrospective design and lack of information on some medical history and treatments, especially immune checkpoint inhibitors, a large-scale prospective study is needed to further determine the prognostic value of coronary CTA in cancer patients.

All-solid-state ultrafast 2 µm laser with 1.83 W output power.

In this paper, a high-power all-solid-state ultrafast 2 µm mode-locked laser is investigated. The particularity of this laser is the simultaneous utilization of two Tm:YAP crystals in the same resonant cavity, independently pumped by two laser diodes. Using a 20% output coupler, pulses with output power as high as 1.83 W are achieved at a wavelength of 1938 nm with a pulse duration of 1.97 ps and a pulse repetition frequency of 100 MHz. To our knowledge, this mode-locked laser achieves the highest output power of any mode-locked Tm:YAP ultrafast laser reported to date. In addition, this paper provides a new approach to solve the problem of low output power due to multi-mode low-brightness laser diode pumping.

NKUT: Dataset and Benchmark for Pediatric Mandibular Wisdom Teeth Segmentation.

Germectomy is a common surgery in pediatric dentistry to prevent the potential dangers caused by impacted mandibular wisdom teeth. Segmentation of mandibular wisdom teeth is a crucial step in surgery planning. However, manually segmenting teeth and bones from 3D volumes is time-consuming and may cause delays in treatment. Deep learning based medical image segmentation methods have demonstrated the potential to reduce the burden of manual annotations, but they still require a lot of well-annotated data for training. In this paper, we initially curated a Cone Beam Computed Tomography (CBCT) dataset, NKUT, for the segmentation of pediatric mandibular wisdom teeth. This marks the first publicly available dataset in this domain. Second, we propose a semantic separation scale-specific feature fusion network named WTNet, which introduces two branches to address the teeth and bones segmentation tasks. In WTNet, We design a Input Enhancement (IE) block and a Teeth-Bones Feature Separation (TBFS) block to solve the feature confusions and semantic-blur problems in our task. Experimental results suggest that WTNet performs better on NKUT compared to previous state-of-the-art segmentation methods (such as TransUnet), with a maximum DSC lead of nearly 16%. Dataset and codes will be released at https://github.com/nkicsl/NKUT.

Bimetallic nanoparticles as cascade sensitizing amplifiers for low-dose and robust cancer radio-immunotherapy.

Radiotherapy (RT) is one of the most feasible and routinely used therapeutic modalities for treating malignant tumors. In particular, immune responses triggered by RT, known as radio-immunotherapy, can partially inhibit the growth of distantly spreading tumors and recurrent tumors. However, the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immunogenicity of tumor. Herein, we report oxaliplatin (IV)-iron bimetallic nanoparticles (OXA/Fe NPs) as cascade sensitizing amplifiers for low-dose and robust radio-immunotherapy. The OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA (II) and Fe2+ in response to the reductive and acidic microenvironment within tumor cells. The cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage, increasing ROS and O2 levels, and amplifying the immunogenic cell death (ICD) effect after RT to facilitate potent immune activation. As a result, OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal effect. Moreover, a long-term immunological memory effect to protect mice from tumor rechallenging is observed. Overall, the bimetallic NPs-based cascade sensitizing amplifier system offers an efficient radio-immunotherapy regimen that addresses the key challenges.

Ultrasound-Based Predictive Model to Assess the Risk of Orbital Malignancies.

OBJECTIVE: Ultrasound (US) is widely used for evaluating various orbital conditions. However, accurately diagnosing malignant orbital masses using US remains challenging. We aimed to develop an ultrasonic feature-based model to predict the presence of malignant tumors in the orbit. METHODS: A total of 510 patients with orbital masses were enrolled between January 2017 and April 2023. They were divided into a development cohort and a validation cohort. In the development cohort (n = 408), the ultrasonic and clinical features with differential values were identified. Based on these features, a predictive model and nomogram were constructed. The diagnostic performance of the model was compared with that of MRI or observers, and further validated in the validation cohort (n = 102). RESULTS: The involvement of more than two quadrants, irregular shape, extremely low echo of the solid part, presence of echogenic foci, cast-like appearance, and two demographic characteristics (age and sex) were identified as independent features related to malignant tumors of the orbit. The predictive model constructed based on these features exhibited better performance in identifying malignant tumors compared to MRI (AUC = 0.78 [95% CI: 0.73, 0.82] vs. 0.69 [95% CI: 0.64, 0.74], p = 0.03) and observers (AUC = 0.93 [95% CI: 0.90, 0.95] vs. Observer 1, AUC = 0.80 [95% CI: 0.76, 0.84], p < 0.01; vs. Observer 2, AUC = 0.71 [95% CI: 0.66, 0.76], p < 0.01). In the validation cohort, the predictive model achieved an AUC of 0.88 (95% CI: 0.81, 0.94). CONCLUSION: The ultrasonic-clinical feature-based predictive model can accurately identify malignant orbital tumors, offering a convenient approach in clinical practice.

Cesarean section "en caul" in preterm twin pregnancy: experience of a single center.

PURPOSE: The "en caul" cesarean section (CS) is a method to keep the amnion intact during CS. This amnion protection effect may have benefits in preterm twin pregnancy. This study aimed to explore the benefits and risks of this method in preterm twin pregnancy. METHODS: This study is a retrospective analysis of preterm twin pregnancies underwent CS in West China Second University Hospital of Sichuan University from January 2011 to December 2022. Data on maternal and fetal outcomes were collected. Univariable analyses and multivariate logistic regression analyses were applied. The level of significance was set at p < 0.05. RESULTS: A total of 182 patients were included (90 in the "en caul" group, 92 in the conventional group). "en caul" CS was associated with lower incidence for respiratory distress (aOR 0.47, 95% CI 0.25-0.88, for the first fetus; aOR 0.42, 95% CI 0.21-0.82, for the second fetus). This method was proved to have beneficial effects in improving the Apgar scores at 1st minute and reducing the mechanical ventilation rate in the second neonates (aOR 0.41, 95% CI 0.19-0.88). CONCLUSION: "En caul" CS is an easy and safe technique to perform during CS for preterm twin pregnancy. The efficacy and safety of this method could be tested by future studies with larger sample size.

Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3.

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.

cGAS suppresses hepatocellular carcinoma independent of its cGAMP synthase activity.

Cyclic GMP-AMP synthase (cGAS) is a key innate immune sensor that recognizes cytosolic DNA to induce immune responses against invading pathogens. The role of cGAS is conventionally recognized as a nucleotidyltransferase to catalyze the synthesis of cGAMP upon recognition of cytosolic DNA, which leads to the activation of STING and production of type I/III interferon to fight against the pathogen. However, given that hepatocytes are lack of functional STING expression, it is intriguing to define the role of cGAS in hepatocellular carcinoma (HCC), the liver parenchymal cells derived malignancy. In this study, we revealed that cGAS was significantly downregulated in clinical HCC tissues, and its dysregulation contributed to the progression of HCC. We further identified cGAS as an immune tyrosine inhibitory motif (ITIM) containing protein, and demonstrated that cGAS inhibited the progression of HCC and increased the response of HCC to sorafenib treatment by suppressing PI3K/AKT/mTORC1 pathway in cellular and animal models. Mechanistically, cGAS recruits SH2-containing tyrosine phosphatase 1 (SHP1) via ITIM, and dephosphorylates p85 in phosphatidylinositol 3-kinase (PI3K), which leads to the suppression of AKT-mTORC1 pathway. Thus, cGAS is identified as a novel tumor suppressor in HCC via its function independent of its conventional role as cGAMP synthase, which indicates a novel therapeutic strategy for advanced HCC by modulating cGAS signaling.

Preserving Mesoporosity in Type III Porous Liquids through Dual-layer Surface Weaving.

The fundamental limitation for pore preservation in a Type III porous liquid (T3PL) is the need for a small aperture from the porous filler to realize size exclusion of a bulky solvent. We present a dual-layer surface weaving strategy that can disregard this limitation and achieve micro- and mesoporous metal-organic framework (MOF)-based T3PLs even with apertures much larger than the solvent molecules. By first weaving a tight network of poly(tert-butyl methacrylate) on the MOF surface, the poly(dimethylsiloxane) (PDMS) solvent can be effectively excluded from the pores while smaller guest molecules such as CO2, C2H4, and H2O can freely access the interior, as confirmed by low-pressure adsorption isotherms. Further application of a PDMS-containing polymer coating helps lower the viscosity of the PL due to increased particle dispersibility. This strategy has resulted in the successful construction of T3PLs with aperture sizes up to 3.1 nm.

Self-sorting of Interfacial Compatibility in MOF-based Mixed Matrix Membranes.

Metal-organic framework (MOF)-based mixed matrix membranes (MMMs) have shown great promises to overcome the performance upper limit of polymeric membranes for various gas separation processes. However, the gas separation properties of the MMMs largely depend on the MOF-polymer interfacial compatibility which is a metric difficult to quantify. In most cases, whether a MOF filler and a polymer matrix make a good pair is not revealed until the gas transport experiments are performed. This is because there is a lack of characterization techniques to directly probe the MOF-polymer interfacial compatibility. In this work, we demonstrate a self-sorting method to rank the interface compatibility among several MOF-polymer pairs. By mixing one MOF with two polymers in an MMM, the demixing of two polymers will form two polymer domains. The MOF particles will preferably partition into the "preferred" polymer domain due to their higher interfacial affinity. By scanning different polymer pairs, a rank of MOF-polymer interfacial compatibility from high to low can be obtained. Moreover, based on this ranking, it was also found that a highly compatible MOF-polymer pair suggested by this method also corresponds to a more predictable MMM gas separation performance.

Evaluation of the efficacy and safety of immunotherapy in sarcoma: a two-center study.

Background: Sarcoma is a highly heterogeneous malignancy with a poor prognosis. Although chemotherapy and targeted therapy have improved the prognosis to some extent, the efficacy remains unsatisfactory in some patients. The efficacy and safety of immunotherapy in sarcoma need further evaluation. Methods: We conducted a two-center study of sarcoma patients receiving PD-1 immunotherapy at Tianjin Medical University Cancer Institute and Hospital and Henan Provincial Cancer Hospital. The treatment regimens included PD-1 inhibitor monotherapy and combination therapy based on PD-1 inhibitors. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival curves were compared using the Kaplan-Meier method. Results: A total of 43 patients were included from the two centers. The median follow-up time for all patients was 13 months (range, 1-48 months). In the group of 37 patients with advanced or unresectable sarcoma, the mPFS was 6 months (95%CI: 5-12 months), and the mOS was 16 months (95%CI: 10-28 months). The ORR was 10.8% (4/37), and the DCR was 18.9% (7/37). Subgroup analysis showed no significant differences in mPFS (p=0.11) and mOS (p=0.88) between patients with PD-L1 negative/positive expression. There were also no significant differences in mPFS (p=0.13) or mOS (p=0.72) between PD-1 inhibitor monotherapy and combination therapy. Additionally, there were no significant differences in mPFS (p=0.52) or mOS (p=0.49) between osteogenic sarcoma and soft tissue sarcoma. Furthermore, the results showed no significant differences in mPFS (p=0.66) or mOS (p=0.96) between PD-1 inhibitors combined with targeted therapy and PD-1 inhibitors combined with AI chemotherapy. Among the 6 patients receiving adjuvant therapy after surgery, the mPFS was 15 months (95%CI: 6-NA months), and the mOS was not reached. In terms of safety, most adverse events were mild (grade 1-2) and manageable. The most severe grade 4 adverse events were bone marrow suppression, which occurred in 4 patients but resolved after treatment. There was also one case of a grade 4 adverse event related to hypertension. Conclusion: Immunotherapy is an effective treatment modality for sarcoma with manageable safety. Further inclusion of more patients or prospective clinical trials is needed to validate these findings.

Analyzing the changing trend of corneal biomechanical properties under different influencing factors in T2DM patients.

To analyze the changing trend of CH and CRF values under different influencing factors in T2DM patients. A total of 650 patients with T2DM were included. We discovered that the course of T2DM, smoking history, BMI, and FBG, DR, HbA1c, TC, TG, and LDL-C levels were common risk factors for T2DM, while HDL-C levels were a protective factor. Analyzing the CH and CRF values according to the course of diabetes, we discovered that as T2DM continued to persist, the values of CH and CRF gradually decreased. Moreover, with the increase in FBG levels and the accumulation of HbA1c, the values of CH and CRF gradually decreased. In addition, in patients with HbA1c (%) > 12, the values of CH and CRF decreased the most, falling by 1.85 ± 0.33 mmHg and 1.28 ± 0.69 mmHg, respectively. Compared with the non-DR group, the CH and CRF values gradually decreased in the mild-NPDR, moderate-NPDR, severe-NPDR and PDR groups, with the lowest CH and CRF values in the PDR group. In patients with T2DM, early measurement of corneal biomechanical properties to evaluate the change trend of CH and CRF values in different situations will help to identify and prevent diabetic keratopathy in a timely manner.

NCAPH serves as a prognostic factor and promotes the tumor progression in glioma through PI3K/AKT signaling pathway.

Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) has been shown to facilitate progression and predict adverse prognostic outcome in many cancer types. However, the function of NCAPH in gliomas is still unclear. Series of experiments were taken to uncover the function of NCAPH in glioma. The expression of NCAPH and potential mechanism regulating progression of glioma was verified by bioinformatics analysis. Lentiviral transfection was used for establishment of loss-of-function and gain-of-function cell lines. CCK-8 assay and Colony-formation assay were used to evaluate proliferation. Transwell assay and Cell wound healing assay were used to assess migration and invasion. Cell cycle and apoptosis were measured by flow cytometry. Protein and RNA were quantified by WB and RT-PCR, respectively. The nude mice model of glioma was used to evaluate the effect of NCAPH in vivo. The expression of NCAPH increased significantly in glioma tissues and correlated with WHO grade, IDH wild-type and non-1p/19q codeletion. Glioma patients with high expression of NCAPH had an undesirable prognosis. Functionally, upregulated NCAPH promotes the malignant hallmarks of glioma cells in vivo and in vitro. NCAPH correlated with DNA damage repair ability of glioma cells and facilitated the proliferation, invasion, and migration of glioma cells by promoting the PI3K/AKT signaling pathway. This study identifies the important pro-tumor role of NCAPH in glioma and suggests that NCAPH is a potential therapeutic target.

4-phenylbutyric acid improves sepsis-induced cardiac dysfunction by modulating amino acid metabolism and lipid metabolism via Comt/Ptgs2/Ppara.

INTRODUCTION: Cardiac dysfunction after sepsis the most common and severe sepsis-related organ failure. The severity of cardiac damage in sepsis patients was positively associated to mortality. It is important to look for drugs targeting sepsis-induced cardiac damage. Our previous studies found that 4-phenylbutyric acid (PBA) was beneficial to septic shock by improving cardiovascular function and survival, while the specific mechanism is unclear. OBJECTIVES: We aimed to explore the specific mechanism and PBA for protecting cardiac function in sepsis. METHODS: The cecal ligation and puncture-induced septic shock models were used to observe the therapeutic effects of PBA on myocardial contractility and the serum levels of cardiac troponin-T. The mechanisms of PBA against sepsis were explored by metabolomics and network pharmacology. RESULTS: The results showed that PBA alleviated the sepsis-induced cardiac damage. The metabolomics results showed that there were 28 metabolites involving in the therapeutic effects of PBA against sepsis. According to network pharmacology, 11 hub genes were found that were involved in lipid metabolism and amino acid transport following PBA treatment. The further integrated analysis focused on 7 key targets, including Comt, Slc6a4, Maoa, Ppara, Pparg, Ptgs2 and Trpv1, as well as their core metabolites and pathways. In an in vitro assay, PBA effectively inhibited sepsis-induced reductions in Comt, Ptgs2 and Ppara after sepsis. CONCLUSIONS: PBA protects sepsis-induced cardiac injury by targeting Comt/Ptgs2/Ppara, which regulates amino acid metabolism and lipid metabolism. The study reveals the complicated mechanisms of PBA against sepsis.

Exploring the optimal indicator of short-term peridiagnosis weight dynamics to predict cancer survival: A multicentre cohort study.

BACKGROUND: Body weight and its changes have been associated with cancer outcomes. However, the associations of short-term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short-term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. METHODS: This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height-adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight-related indicators and compared their prognostic performance using Harrell's C-index, integrated discrimination improvement, continuous net reclassification improvement and time-dependent C-index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan-Meier analysis and multivariable-adjusted Cox regression models. RESULTS: The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow-up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C-index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P < 0.05). Time-dependent C-index analysis also indicated that peridiagnosis RWC was optimal for predicting OS. The multivariable-adjusted RCS analysis revealed an N-shaped non-linear association between peridiagnosis RWC and OS (PRWC < 0.001, Pnon-linear < 0.001). Univariate survival analysis showed that the peridiagnosis RWC groups could represent distinct mortality risk stratifications (P < 0.001). Multivariable survival analysis showed that, compared with the maintenance group (weight change < 5%), the significant (gain >10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5-10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5-10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. CONCLUSIONS: The prognostic performance of peridiagnosis RWC is superior to other weight-related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change-related premature deaths.

The effect of age, sex, and eastern cooperative oncology group performance status on the efficacy and safety of immune checkpoint inhibitors in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The effect of age, sex, and eastern cooperative oncology group performance status (ECOG PS) on the efficacy and safety of immune checkpoint inhibitor (ICI) therapy among hepatocellular carcinoma (HCC) patients remains elusive. Thus, a meta-analysis was conducted to evaluate whether such effects exist. RESEARCH DESIGN AND METHODS: Eligible studies in PubMed, Embase, and Cochrane Library databases were retrieved. RESULTS: One-hundred-and-eleven studies involving 14,768 HCC patients were included. The findings indicated that the ECOG PS didn't have a significant effect on the ORR and PFS in ICI-treated HCC patients (higher ECOG PS vs. lower ECOG PS: ORR: OR = 0.78, 95%CI = 0.55-1.10; PFS: HR = 1.15, 95%CI = 0.97-1.35), while those patients with a higher ECOG PS may have a worse OS (HR = 1.52, 95% CI = 1.26-1.84). There is no significant evidence of the effect of age (older vs. younger) or sex (males vs. females) on the efficacy of ICI therapy in HCC. CONCLUSION: ICI therapy in HCC should not be restricted strictly to certain patients in age or sex categories, while HCC patients with higher ECOG PS may require closer medication or follow-up strategy during ICI therapy. PROSPERO REGISTRATION: CRD42024518407.

Hydrostatic pressure mediates epithelial-mesenchymal transition of cholangiocytes through RhoA/ROCK and TGF-ß/smad pathways.

Biomechanical cue within the tissue microenvironment is known to play a critical role in regulating cell behaviors and maintaining tissue homeostasis. As hydrostatic pressure often increases in biliary system under pathological states, we investigated the effect of the moderate elevation of the hydrostatic pressure on biliary epithelial cells, especially on the epithelial-mesenchymal transition (EMT). Human intrahepatic biliary epithelial cells were loaded to hydrostatic pressure using a commercial device. We found that loading the cells to 50 mmHg hydrostatic pressure induced obvious morphological changes and significantly upregulated vimentin, ZEB1, and pSmad2/3, fibronectin, and collagen 1α. All changes induced by hydrostatic pressure loading were effectively mitigated by either ROCK inhibitor (Y-27632) or ALK5 inhibitor (SB-431542). Our in vitro experimental data suggests that hydrostatic pressure loading induces EMT of cholangiocytes through RhoA/ROCK and TGF-ß/Smad pathways. Elevated hydrostatic pressure in biliary duct system under pathological states may promote the biliary epithelial cells shifting to profibrotic and mesenchymal characteristics.

Gastric cancer prognosis: unveiling autophagy-related signatures and immune infiltrates.

Background: Autophagy played a crucial regulatory role in tumor initiation and progression. Therefore, we aimed to comprehensively analyze autophagy-related genes (ARGs) in gastric cancer, focusing on their expression, prognostic value, and potential functions. Methods: The gastric cancer gene chip datasets (GSE79973 and GSE54129) were collected from the Gene Expression Omnibus (GEO) database. Subsequently, the Limma package was employed to identify differentially expressed genes (DEGs) between the normal and disease groups. The selected ARGs were further authenticated using the Human Protein Atlas (HPA) database, The Cancer Genome Atlas (TCGA) database, and GSE19826 database. Results: A total of 15 autophagy-related DEGs, eight of which were upregulated [FKBP1A, IL24, PEA15, HSP90AB1, cathepsin B (CTSB), ITGB1, SPHK1, HIF1A], while seven were downregulated (DAPK2, EIF2AK3, FKBP1B, PTK6, NKX2-3, NFE2L2, PRKCD). Analysis revealed that CTSB was specifically associated with the prognosis of gastric cancer patients. Gene set enrichment analysis (GSEA) showcased a significant enrichment of CTSB-related genes within immune-related pathways. Moreover, correlation analysis demonstrated a clear association between the expression of CTSB and immune infiltration. The upregulation of CTSB in gastric cancer was linked to poor survival and increased immune infiltration. Conclusions: We conjectured that CTSB likely played a critical role in regulating immunity and autophagy in gastric cancer.