A complexity evaluation system for mitral valve repair based on preoperative echocardiographic and machine learning.

BACKGROUND: To develop a novel complexity evaluation system for mitral valve repair based on preoperative echocardiographic data and multiple machine learning algorithms. METHODS: From March 2021 to March 2023, 231 consecutive patients underwent mitral valve repair. Clinical and echocardiographic data were included in the analysis. The end points included immediate mitral valve repair failure (mitral replacement secondary to mitral repair failure) and recurrence regurgitation (moderate or greater mitral regurgitation [MR] before discharge). Various machine learning algorithms were used to establish the complexity evaluation system. RESULTS: A total of 231 patients were included in this study; the median ejection fraction was 66% (63-70%), and 159 (68.8%) patients were men. Mitral repair was successful in 90.9% (210 of 231) of patients. The linear support vector classification model has the best prediction results in training and test cohorts and the variables of age, A2 lesions, leaflet height, MR grades, and so on were risk factors for failure of mitral valve repair. CONCLUSION: The linear support vector classification prediction model may allow the evaluation of the complexity of mitral valve repair. Age, A2 lesions, leaflet height, MR grades, and so on may be associated with mitral repair failure.

Gut microbiota-dependent modulation of pre-metastatic niches by Jianpi Yangzheng decoction in the prevention of lung metastasis of gastric cancer.

AIM OF THE STUDY: To evaluate the in vitro and in vivo anti-metastasis efficacy of Jianpi Yangzheng (JPYZ) decoction against gastric cancer (GC) and its potential mechanisms. MATERIALS AND METHODS: The distant metastasis of GC cells administered via tail vein injection was assessed using the pre-metastatic niche (PMN) model. 16S rRNA sequencing and GC-MS/MS were applied to determine the component of the gut microbiota and content of short-chain fatty acids (SCFAs) in feces of mice, respectively. The proportion of myeloid-derived suppressor cells (MDSCs) in the lung was evaluated by flow cytometry and immunofluorescence. Serum or tissue levels of inflammation factors including IL-6, IL-10 and TGF-ß were determined by ELISA or Western blot respectively. RESULTS: Injecting GC cells into the tail vein of mice led to the development of lung metastases and also resulted in alterations in the composition of gut microbiota and the levels of SCFAs produced. Nevertheless, JPYZ treatment robustly impeded the effect of GC cells administration. Mechanically, JPYZ treatment not only prevented the alteration in gut microbiota structure, but also restored the SCFAs content induced by GC cells administration. Specifically, JPYZ treatment recovered the relative abundance of genera Moryella, Helicobacter, Lachnoclostridium, Streptococcus, Tuzzerella, GCA-900066575, uncultured_Lachnospiraceae, Rikenellaceae_RC9_gut_group and uncultured_bacterium_Muribaculaceae to near the normal control levels. In addition, JPYZ abrogated MDSCs accumulation in the lung tissue and blocked inflammation factors overproduction in the serum and lung tissues, which subsequently impede the formation of the immunosuppressive microenvironment. Correlation analysis revealed that the prevalence of Rikenellaceae in the model group exhibited a positive correlation with MDSCs proportion and inflammation factor levels. Conversely, the scarcity of Muribaculaceae in the model group showed a negative correlation with these parameters. This suggests that JPYZ might exert an influence on the gut microbiota and their metabolites, such as SCFAs, potentially regulating the formation of the PMN and consequently impacting the outcome of GC metastasis. CONCLUSION: These findings suggest that GC cells facilitate metastasis by altering the gut microbiota composition, affecting the production of SCFAs, and recruiting MDSCs to create a pro-inflammatory pre-metastatic niche. JPYZ decoction counteracts this process by reshaping the gut microbiota structure, enhancing SCFA production, and inhibiting the formation of the pre-metastatic microenvironment, thereby exerting an anti-metastatic effect.

Collectivism, face concern and Chinese-style lurking among university students: the moderating role of trait mindfulness.

Introduction: This study focuses on understanding the unique causes and mechanisms of "Chinese-style lurking" on WeChat among university students, within a cultural context that emphasizes collectivism and face concern. The research also looks into the moderating role of trait mindfulness. Methods: For the confirmation of these phenomena and to validate the theories, a structural equation model was constructed using the Stress-Strain-Outcome (SSO) theory and mindfulness buffering theory. The model was then tested and validated with data from 1,453 valid online surveys. These data were analyzed using the SmartPLS 4.0 software. Results: The results indicate that collectivism increases face concern, which in turn escalates online social anxiety. Face concern completely mediates between collectivism and online social anxiety, creating a serial mediation effect between face concern, online social anxiety, and lurking behavior. Additionally, trait mindfulness was found to negatively modulate the pathways from collectivism to face concern and from online social anxiety to lurking. Discussion: The findings underscore the influence of traditional Chinese culture on contemporary students' online behavior and provide a new perspective for understanding social media lurking in an Eastern context. The results suggest that a mindfulness-based approach could be used to mitigate the associated silence and anxiety.

PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer.

BACKGROUND: Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. METHODS: We employed LC-MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. RESULTS: There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p < 0.05), a total of 15 potential biomarkers were obtained, including MGDG(43:11)-H, Cer(d18:1/24:0) + HCOO, PI(18:0/18:1)-H, PE(16:1/18:1)-H, PE(36:2) + H, PE(34:2p)-H, Cer(d18:1 + hO/24:0) + HCOO, Cer(d18:1/23:0) + HCOO, PC(34:2e) + H, SM(d34:0) + H, LPC(18:2) + HCOO, PI(18:1/22:5)-H, PG(18:1/18:1)-H, Cer(d18:1/24:0) + H and PC(35:2) + H. Furthermore, we obtained five potential key targets (PLA2G4A, PLA2G3, DGKA, ACHE, and CHKA), and a metabolite-reaction-enzyme-gene interaction network was built to reveal the biological process of how they could disorder the endogenous lipid profile of platinum resistance in GC patients through the glycerophospholipid metabolism pathway. Finally, we further identified PLA2G4A and ACHE as core targets of the process by correlation analysis and tissue microarray immunohistochemical verification. CONCLUSION: PLA2G4A and ACHE regulated endogenous lipid profile in the platinum resistance in GC patients through the glycerophospholipid metabolism pathway. The screening of lipid biomarkers will facilitate earlier precision medicine interventions for chemotherapy-resistant gastric cancer. The development of therapies targeting PLA2G4A and ACHE could enhance platinum chemotherapy effectiveness.

Nobiletin targets SREBP1/ACLY to induce autophagy-dependent cell death of gastric cancer cells through PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Autophagy could sense metabolic conditions and safeguard cells against nutrient deprivation, ultimately supporting the survival of cancer cells. Nobiletin (NOB) is a kind of bioactive component of the traditional Chinese medicine Citri Reticulatae Pericarpium and has been proven to induce GC cell death by reducing de novo fatty acid synthesis in our previous study. Nevertheless, the precise mechanisms by which NOB induces cell death in GC cells still need further elucidation. OBJECTIVES: To examine the mechanism by which NOB inhibits gastric cancer progression through the regulation of autophagy under the condition of lipid metabolism inhibition. METHODS/ STUDY DESIGN: Proliferation was detected by the CCK-8 assay. RNA sequencing (RNA-seq) was used to examine signaling pathway changes. Electron microscopy and mRFP-GFP-LC3 lentiviral transfection were performed to observe autophagy in vitro. Western blot, plasmid transfection, immunofluorescence staining, and CUT & Tag-qPCR techniques were utilized to explore the mechanisms by which NOB affects GC cells. Molecular docking and molecular dynamics simulations were conducted to predict the binding mode of NOB and SREBP1. CETSA was adopted to verify the predicted of binding model. A patient-derived xenograft (PDX) model was employed to verify the therapeutic efficacy of NOB in vivo. RESULTS: We conducted functional studies and discovered that NOB inhibited the protective effect of autophagy via the PI3K/Akt/mTOR axis in GC cells. Based on previous research, we found that the overexpression of ACLY abrogated the NOB-induced autophagy-dependent cell death. In silico analysis predicted the formation of a stable complex between NOB and SREBP1. In vitro assays confirmed that NOB treatment increased the thermal stability of SREBP1 at the same temperature conditions. Moreover, CUT&TAG-qPCR analysis revealed that NOB could inhibit SREBP1 binding to the ACLY promoter. In the PDX model, NOB suppressed tumor growth, causing SREBP1 nuclear translocation inhibition, PI3K/Akt/mTOR inactivation, and autophagy-dependent cell death. CONCLUSION: NOB demonstrated the ability to directly bind to SREBP1, inhibiting its nuclear translocation and binding to the ACLY promoter, thereby inducing autophagy-dependent cell death via PI3K/Akt/mTOR pathway.

Advances in the research and application of neurokinin-1 receptor antagonists. / 神经激肽1å—ä½“æ‹®æŠ—å‰‚çš„ç ”ç©¶ä¸Žåº”ç”¨è¿›å±•.

Recently, the substance P (SP)/neurokinin-1 receptor (NK-1R) system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019 (COVID-19). Besides, studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis. These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy. This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers, as well as the underlying mechanisms. Furthermore, the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized, such as solid dispersion systems, nanonization, and nanoencapsulation. As a radiopharmaceutical therapeutic, the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors. However, combining NK-1R antagonists with other drugs can produce a synergistic effect, thereby enhancing the therapeutic effect, alleviating the symptoms, and improving patients quality of life in several diseases and cancers.

Cell division cycle 42 attenuates high glucose-treated renal tubular epithelial cell apoptosis, fibrosis, and inflammation, but activates the PAK1/AKT pathway.

BACKGROUND: Cell division cycle 42 (CDC42) modulates metabolism, inflammation, and fibrosis to engage in the pathology of diabetic complications. This study intended to further investigate the influence of CDC42 on viability, apoptosis, inflammation, epithelial-mesenchymal transition, and fibrosis in high glucose (HG)-treated renal tubular epithelial cells. METHODS: HK-2 cells were exposed to HG medium (30 mM) to establish the diabetic nephropathy (DN) cellular model, then the cells were transfected with scramble overexpression control (oeNC) or CDC42 overexpression (oeCDC42) vectors. RESULTS: Both the level of CDC42 mRNA and protein were decreased in HG-treated HK-2 cells in a dose- and time-dependent manner. Then HG-treated HK-2 cells were proposed for the following experiments. It was found that CDC42 increased CCK-8 detected viability and EdU positive cells. On the contrary, CDC42 reduced cell apoptosis, which was reflected by decreased TUNEL positive rate, increased BCL2, and reduced BAX. Interestingly, CDC42 inhibited fibrosis, which was reflected by increased E-Cadherin, as well as decreased Vimentin, TGF-ß1, Collagen1, and α-SMA. Apart from these, CDC42 also attenuated proinflammatory cytokine production, including TNF-α, IL-1ß, and IL-6. Moreover, CDC42 activated the PAK1/AKT pathway, which was reflected by increased p-PAK1 and p-AKT. However, CDC42 did not affect p-ERK. CONCLUSION: CDC42 may retard DN progression via its regulation of renal tubular epithelial cell functions, which may be due to its stimulation of the PAK1/AKT pathway.

Insufficient recovery of proprioception in chronic ankle instability after surgical restabilization: A systematic review.

Surgical repair or reconstruction of the lateral ligaments for patients with chronic ankle instability (CAI) could, logically, restore the proprioception of ankle through retensing receptors. To validate this hypothesis, seven databases were systematically searched, and thirteen studies comprising a total of 347 patients with CAI were included. Although five studies reported improved proprioceptive outcomes after surgeries, the other five studies with between-limb/group comparisons reported residual deficits at final follow-up, which does not consistently support proprioceptive recovery after existing surgical restabilization for CAI. More controlled studies are needed to provide evidence-based protocols to improve proprioceptive recovery after ankle restabilization for CAI.

Dehydrocostus lactone suppresses gastric cancer progression by targeting ACLY to inhibit fatty acid synthesis and autophagic flux.

INTRODUCTION: Dehydrocostus lactone (Dehy), a natural sesquiterpene lactone from Saussurea lappa Clarke, displays remarkable efficacy in treating cancer and gastrointestinal disorders. However, its anti-gastric cancer (GC) effect remains poorly understood. OBJECTIVES: Our study aimed to elucidate the anti-GC effect of Dehy and its putative mechanism. METHODS: The anti-GC effect was assessed with MTT, colony formation, wound healing and transwell invasion assays. Cell apoptosis rate was detected by Annexin V-FITC/PI binding assay. Network pharmacology analysis and XF substrate oxidation stress test explored the underlying mechanism and altered metabolic phenotype. Lipogenic enzyme expressions and neutral lipid pool were measured to evaluate cellular lipid synthesis and storage. Biolayer interferometry and molecular docking investigated the direct target of Dehy. Autophagosomes were observed by transmission electron microscopy and MDC staining, while the autophagic flux was detected by mRFP-GFP-LC3 transfection. The clinical significance of ACLY was confirmed by tissue microarrays. Patient-derived xenograft (PDX) models were adopted to detect the clinical therapeutic potential of Dehy. RESULTS: Dehy prominently suppressed GC progression both in vitro and in vivo. Mechanistically, Dehy down-regulated the lipogenic enzyme ACLY, thereby reducing fatty acid synthesis and lipid reservation. Moreover, IKKß was identified as the direct target of Dehy. Dehy inhibited the phosphorylation of IKKß, promoting the ubiquitination and degradation of ACLY, thereby resulting in lipid depletion. Subsequently, GC cells initiated autophagy to replenish the missing lipids, whereas Dehy impeded this cytoprotective mechanism by down-regulating LAMP1 and LAMP2 expressions, which disrupted lysosomal membrane functions, ultimately leading to apoptosis. Additionally, Dehy exhibited potential in GC clinical therapy as it enhanced the efficacy of 5-Fluorouracil in PDX models. CONCLUSIONS: Our work identified Dehy as a desirable agent for blunting abnormal lipid metabolism and highlighted its inhibitory effect on protective autophagy, suggesting the future development of Dehy as a novel therapeutic drug for GC.

Construction of an immune-related risk score signature for gastric cancer based on multi-omics data.

Early identification of gastric cancer (GC) is associated with a superior survival rate compared to advanced GC. However, the poor specificity and sensitivity of traditional biomarkers suggest the importance of identifying more effective biomarkers. This study aimed to identify novel biomarkers for the prognosis of GC and construct a risk score (RS) signature based on these biomarkers, with to validation of its predictive performance. We used multi-omics data from The Cancer Genome Atlas to analyze the significance of differences in each omics data and combined the data using Fisher's method. Hub genes were subsequently subjected to univariate Cox and LASSO regression analyses and used to construct the RS signature. The RS of each patient was calculated, and the patients were divided into two subgroups according to the RS. The RS signature was validated in two independent datasets from the Gene Expression Omnibus and subsequent analyses were subsequently conducted. Five immune-related genes strongly linked to the prognosis of GC patients were obtained, namely CGB5, SLC10A2, THPO, PDGFRB, and APOD. The results revealed significant differences in overall survival between the two subgroups (p < 0.001) and indicated the high accuracy of the RS signature. When validated in two independent datasets, the results were consistent with those in the training dataset (p = 0.003 and p = 0.001). Subsequent analyses revealed that the RS signature is independent and has broad applicability among various GC subtypes. In conclusion, we used multi-omics data to obtain five immune-related genes comprising the RS signature, which can independently and effectively predict the prognosis of GC patients with high accuracy.

The emerging role of glycolysis and immune evasion in gastric cancer.

Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Similar to other types of tumors, GC cells undergo metabolic reprogramming and switch to a "predominantly glycolytic" metabolic pattern to promote its survival and metastasis, also known as "the Warburg effect", which is characterized by enhanced glucose uptake and lactate production. A large number of studies have shown that targeting cancer cells to enhanced glycolysis is a promising strategy, that can make cancer cells more susceptible to other conventional treatment methods of treatment, including chemotherapy, radiotherapy and immunotherapy, and so on. Therefore, this review summarizes the metabolic characteristics of glycolysis in GC cells and focuses on how abnormal lactate concentration can lead to immunosuppression through its effects on the differentiation, metabolism, and function of infiltrating immune cells, and how targeting this phenomenon may be a potential strategy to improve the therapeutic efficacy of GC.

Characterization of site-specific N-glycosylation signatures of isolated uromodulin from human urine.

Uromodulin (Umod, Tamm-Horsfall protein) is the most abundant urinary N-glycoprotein produced exclusively by the kidney. It can form filaments to antagonize the adhesion of uropathogens. However, the site-specific N-glycosylation signatures of Umod in healthy individuals and patients with IgA nephropathy (IgAN) remain poorly understood due to the lack of suitable isolation and analytical methods. In this study, we first presented a simple and fast method based on diatomaceous earth adsorption to isolate Umod. These isolated glycoproteins were digested by trypsin and/or Glu-C. Intact N-glycopeptides with or without HILIC enrichment were analyzed using our developed EThcD-sceHCD-MS/MS. Based on the optimized workflow, we identified a total of 780 unique intact N-glycopeptides (7 N-glycosites and 152 N-glycan compositions) from healthy individuals. As anticipated, these glycosites exhibited glycoform heterogeneity. Almost all N-glycosites were modified completely by the complex type, except for one N-glycosite (N275), which was nearly entirely occupied by the high-mannose type for mediating Umod's antiadhesive activity. Then, we compared the N-glycosylation of Umod between healthy controls (n = 9) and IgAN patients (n = 9). The N-glycosylation of Umod in IgAN patients will drastically decrease and be lost. Finally, we profiled the most comprehensive site-specific N-glycosylation map of Umod and revealed its alterations in IgAN patients. Our method provides a high-throughput workflow for characterizing the N-glycosylation of Umod, which can aid in understanding its roles in physiology and pathology, as well as serving as a potential diagnostic tool for evolution of renal tubular function.

Research progress on extracellular vesicles in the renal tubular injury of diabetic kidney disease.

Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes and is a chronic progressive condition. It is also a common cause of end-stage renal disease (ESRD), which is characterized by proteinuria or a progressive decline in the glomerular filtration rate. Due to their dependence on high-energy and aerobic metabolism, renal tubules are more susceptible to the metabolic disturbances associated with DKD, leading to inflammation and fibrosis. Consequently, tubular injury has become a recent research focus, and significant advancements have been made in studying the role of extracellular vesicles in DKD-associated tubular injury. This review aimed to elucidate the mechanisms and potential applications of different types of extracellular vesicles in tubular injury in DKD to provide new insights for the prevention and treatment of DKD.

Photoswitchable upconversion nanoparticles with excitation-dependent emission for programmed stepwise NIR phototherapy.

Programmable control over therapeutic processes in phototherapy, like photodynamic therapy (PDT), is promising but challenging. This study uses an energy segmentation-based strategy to synthesize core-multi-shell upconversion nanoparticles (UCNPs), which can release three different colors (red, green, and blue) upon exposure to different near-infrared light (1550 nm, 808 nm, and 980 nm). By combining these UCNPs with photosensitizers and nitric oxide (NO) donors, a smart "off-on" PDT nanoplatform is developed. UCNPs enable independent activation of imaging, release of NO, and generation of reactive oxygen species using specific light wavelengths. The results show that sequential NO release before PDT can greatly alleviate tumor hypoxia by reducing oxygen consumption. This stepwise approach shows potential for precise NIR light-activated and imaging-guided phototherapy.

Erratum to "Protein Z modulates the metastasis of lung adenocarcinoma cells".

[This corrects the article DOI: 10.1515/biol-2022-0667.].

Generating a Murine PTEN Null Cell Line to Discover the Key Role of p110ß-PAK1 in Castration-Resistant Prostate Cancer Invasion.

Although androgen deprivation treatment often effectively decreases prostate cancer, incurable metastatic castration-resistant prostate cancer (CRPC) eventually occurs. It is important to understand how CRPC metastasis progresses, which is not clearly defined. The loss of PTEN, a phosphatase to dephosphorylate phosphatidylinositol 3,4,5-trisphosphate in the PI3K pathway, occurs in up to 70% to 80% of CRPC. We generated a mouse androgen-independent prostate cancer cell line (PKO) from PTEN null and Hi-Myc transgenic mice in C57BL/6 background. We confirmed that this PKO cell line has an activated PI3K pathway and can metastasize into the femur and tibia of immunodeficient nude and immunocompetent C57BL/6 mice. In vitro, we found that androgen deprivation significantly enhanced PKO cell migration/invasion via the p110ß isoform-depended PAK1-MAPK activation. Inhibition of the p110ß-PAK1 axis significantly decreased prostate cancer cell migration/invasion. Of note, our analysis using clinical samples showed that PAK1 is more activated in CRPC than in advanced prostate cancer; high PAK1/phosphorylated-PAK1 levels are associated with decreased survival rates in patients with CRPC. All the information suggests that this cell line reflects the characteristics of CRPC cells and can be applied to dissect the mechanism of CRPC initiation and progression. This study also shows that PAK1 is a potential target for CRPC treatment. IMPLICATIONS: This study uses a newly generated PTEN null prostate cancer cell line to define a critical functional role of p110ß-PAK1 in CRPC migration/invasion. This study also shows that the p110ß-PAK1 axis can potentially be a therapeutic target in CRPC metastasis.

Protein Z modulates the metastasis of lung adenocarcinoma cells.

Protein Z (PZ), a vitamin-K-dependent anticoagulant glycoprotein, is reported to be highly expressed in various malignant tissues and correlated with a poor prognosis in patients with lung cancer. This study aimed to investigate the pathological activity of PZ on lung cancer cell migration, invasion, and metastasis. PZ was assessed by Western blot in three non-small-cell lung cancer cell lines (A549, H1299, and H1975). Meanwhile,western blot was used to detect the expression of EMT pathway-related proteins (Slug, Vimentin, and N-cadherin) in the A549 cells knocked down with siRNA. The cellular proliferation, migration, and invasion were detected by Cell Counting Kit (CCK)-8, wound healing, and Transwell assays in the A549 cells. The results showed that PZ expression was higher in A549, H1299, and H1975 cells, according to Western blot. CCK-8, wound healing, and Transwell assays showed that knockdown of PZ significantly decreased cellular proliferation, migration, and invasion, as well as the protein levels of Slug, Vimentin, and N-cadherin in the A549 cells. In conclusion, the pro-metastasis activity of PZ may modulate the epithelial-mesenchymal transition pathway in lung cancer A549 cells.

Association of the CD4+/CD8+ ratio with response to PD-1 inhibitor-based combination therapy and dermatological toxicities in patients with advanced gastric and esophageal cancer.

The host immune system affects the treatment response to immune checkpoint inhibitors and can be reflected by circulating immune cells. This study aimed to evaluate whether circulating T cell subtypes are correlated with clinical response and dermatological toxicities in patients with advanced gastric and esophageal cancer receiving PD-1 inhibitor-based combination therapy (n = 203). In the training cohort, Eastern Cooperative Oncology Group performance status (ECOG PS), PD-L1 expression, antibiotic use, and CD4+/CD8+ ratio were identified as independent prognostic factors in these patients, using a Cox regression model. A nomogram to predict the overall survival (OS) and survival probabilities was constructed using these factors. The nomogram showed good discrimination ability (C-index, 0.767) and was externally confirmed in the validation and test cohorts. Kaplan-Meier analysis showed that median OS in patients with a CD4+/CD8+ ratio ≥1.10 was 6.2 months, which was significantly shorter than that in patients with a CD4+/CD8+ ratio <1.10 (P < 0.001). Patients with a CD4+/CD8+ ratio <1.10 had a superior objective response (43.8% vs. 23.1%) and disease control (72.9% vs. 59.0%) rate, relative to those with ratio ≥ 1.10. In addition, PD-L1 expression, corticosteroid use, and CD4+/CD8+ ratio can independently predict dermatological toxicities. In conclusion, baseline CD4+/CD8+ ratio is a potential prognostic factor for patients with advanced gastric and esophageal cancer treated with PD-1 inhibitor-based combination therapy, and can independently predict dermatological toxicities. In addition, a nomogram incorporating CD4+/CD8+ ratio, ECOG PS, PD-L1 expression, and antibiotic use can predict OS with considerable accuracy.

The effects of group-based cognitive behavioral therapy in the rehabilitation of patients with chronic schizophrenia with more than two years of community-based mental health group rehabilitation.

BACKGROUND: Studies have shown that community-based group rehabilitation activities can have a positive impact on patients. OBJECTIVE: This study attempted to improve schizophrenia patients' social and self-cognition through short-term group-based cognitive behavioral therapy (G-CBT), break negative coping styles, and improve the patients' quality of life. METHODS: The patients with schizophrenia who participated in long-term community-based group rehabilitation were treated with G-CBT. Training on coping styles was conducted to improve their self-cognition and social cognition, and the rehabilitation effects of G-CBT on these patients were evaluated. RESULTS: Compared with the control group, patient scores for self-esteem, self-efficacy, and positive coping in the G-CBT group increased, while patient scores for negative coping decreased. Compared with the control group, the differences in the total scores for mental health and the five dimensions of physical functioning, general health, vitality, social functioning, and emotional role function in the short-form (SF-12) survey were statistically significant. Compared with the baseline data, the differences in self-esteem, self-efficacy, positive coping, negative coping, and quality of life scores were statistically significant. CONCLUSION: Short-term G-CBT had a good effect on patients with chronic schizophrenia who participated in community-based group rehabilitation for the long-term.

DeepSCI: scalable speckle correlation imaging using physics-enhanced deep learning.

In this Letter we present a physics-enhanced deep learning approach for speckle correlation imaging (SCI), i.e., DeepSCI. DeepSCI incorporates the theoretical model of SCI into both the training and test stages of a neural network to achieve interpretable data preprocessing and model-driven fine-tuning, allowing the full use of data and physics priors. It can accurately reconstruct the image from the speckle pattern and is highly scalable to both medium perturbations and domain shifts. Our experimental results demonstrate the suitability and effectiveness of DeepSCI for solving the problem of limited generalization generally encountered in data-driven approaches.