Optimization of Mg-Al Layered Double Hydroxide Film Preparation and Corrosion Resistance Study on AZ91D Mg Alloy by Multivariate Polynomial Regression Fitting.

Layered double hydroxide (LDH) films have received extensive attention for their unique physical barrier function and ion exchange properties, which make them promising candidates for corrosion protection of magnesium alloys. In this paper, we used the multiple polynomial regression fitting method to establish a regression equation for the electrochemical corrosion resistance with the reaction temperature (T), pH, and reaction time (t) of the Mg-Al LDH film on the AZ91D magnesium alloy. The goodness of fit, confidence, and residual analyses confirmed the high accuracy of the model equation. According to the calculation using the fmincon function, the best corrosion resistance of the prepared samples could be achieved when the parameters are T = 135 °C, pH = 12.0, and t = 15 h. Then, the experimental results showed that the corrosion current density (Icorr) of the obtained LDH film under the above conditions could be 1.07 × 10-7 A/cm2, approximately 3 orders of magnitude lower than the magnesium alloy substrate, after immersion in a 3.5 wt % NaCl solution for 180 h, the surface structure of the LDH film did not change significantly, and the Icorr was still 2 orders of magnitude higher than that of the magnesium alloy substrate. Hence, a synergistic effect equation for the reaction temperature, pH, and reaction time on the corrosion resistance of the LDH film on a magnesium alloy surface prepared by the hydrothermal method was obtained. Moreover, using this equation, we obtained an LDH film with good corrosion resistance and durability, providing theoretical guidance for optimizing the process of preparing the LDH film by the hydrothermal method in practical applications.

Nanomaterials Boost CAR-T Therapy for Solid Tumors.

T cell engineering, particularly via chimeric antigen receptor (CAR) modifications for enhancing tumor specificity, has shown efficacy in treating hematologic malignancies. The extension of CAR-T cell therapy to solid tumors, however, is impeded by several challenges: The absence of tumor-specific antigens, antigen heterogeneity, a complex immunosuppressive tumor microenvironment, and physical barriers to cell infiltration. Additionally, limitations in CAR-T cell manufacturing capacity and the high costs associated with these therapies restrict their widespread application. The integration of nanomaterials into CAR-T cell production and application offers a promising avenue to mitigate these challenges. Utilizing nanomaterials in the production of CAR-T cells can decrease product variability and lower production expenses, positively impacting the targeting and persistence of CAR-T cells in treatment and minimizing adverse effects. This review comprehensively evaluates the use of various nanomaterials in the production of CAR-T cells, genetic modification, and in vivo delivery. It discusses their underlying mechanisms and potential for clinical application, with a focus on improving specificity and safety in CAR-T cell therapy.

Unleashing the power of immune checkpoints: Post-translational modification of novel molecules and clinical applications.

Immune checkpoint molecules play a pivotal role in the initiation, regulation, and termination of immune responses. Tumor cells exploit these checkpoints to dampen immune cell function, facilitating immune evasion. Clinical interventions target this mechanism by obstructing the binding of immune checkpoints to their ligands, thereby restoring the anti-tumor capabilities of immune cells. Notably, therapies centered on immune checkpoint inhibitors, particularly PD-1/PD-L1 and CTLA-4 blocking antibodies, have demonstrated significant clinical promise. However, a considerable portion of patients still encounter suboptimal efficacy and develop resistance. Recent years have witnessed an exponential surge in preclinical and clinical trials investigating novel immune checkpoint molecules such as TIM3, LAG3, TIGIT, NKG2D, and CD47, along with their respective ligands. The processes governing immune checkpoint molecules, from their synthesis to transmembrane deployment, interaction with ligands, and eventual degradation, are intricately tied to post-translational modifications. These modifications encompass glycosylation, phosphorylation, ubiquitination, neddylation, SUMOylation, palmitoylation, and ectodomain shedding. This discussion proceeds to provide a concise overview of the structural characteristics of several novel immune checkpoints and their ligands. Additionally, it outlines the regulatory mechanisms governed by post-translational modifications, offering insights into their potential clinical applications in immune checkpoint blockade.

Renal cell carcinoma and venous tumor thrombus: predicting sarcomatoid dedifferentiation through preoperative IVIM-based MR imaging.

PURPOSE: To evaluate the value of preoperative intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and conventional MRI indicators in identifying sarcomatoid dedifferentiation in renal cell carcinoma (RCC) and tumor thrombus. METHODS: From September 2016 to April 2023, consecutive patients with RCC and tumor thrombus who received routine MRI examination and IVIM-DWI before radical resection were enrolled prospectively. Kaplan-Meier method with log-rank test was used to calculate and compare the survival probability. The preoperative imaging features were analyzed. Univariate and multivariable logistic regression analyses were employed to identify independent predictors of sarcomatoid dedifferentiation. The predictive ability was evaluated by receiver operating characteristic (ROC) curves. RESULTS: Twenty-two patients (15.3%) of the 144 patients in the training set (median age, 58.0 years [IQR, 52.0-65.0 years]; 108 men) and 11 patients (22.4%) of the 49 patients in the test set (median age, 58.0 years [IQR, 53.0-63.0 years]; 38 men) had sarcomatoid dedifferentiated tumors. Patients with sarcomatoid-differentiated tumors had poor progress-free survival in the training set and test set (P < 0.001 and P = 0.007). f value (P = 0.011), mN stage (P = 0.007), and necrosis (P = 0.041) were independent predictors for predicting sarcomatoid dedifferentiation in the training set. The model combining conventional MRI features and f value had AUCs of 0.832 (95% CI 0.755-0.909) and 0.825 (95% CI 0.702-0.948) in predicting sarcomatoid dedifferentiation in the training set and test set. CONCLUSION: It is feasible to preoperatively identify sarcomatoid dedifferentiation based on IVIM-DWI and conventional MR imaging indicators.

Assessment of Ki-67 proliferation index in prognosis prediction in patients with nonmetastatic clear cell renal cell carcinoma and tumor thrombus.

PURPOSE: To determine the optimal cut-off value of Ki-67 for predicting the survival of patients with clear cell renal cell carcinoma (ccRCC) and tumor thrombus and to explore the correlation between Ki-67 expression and pathological features. PATIENTS AND METHODS: We retrospectively analyzed Ki-67 immunohistochemical staining of ccRCC and tumor thrombus resected from February 2006 to February 2022. The survival rate was evaluated using the Kaplan-Meier method. The optimal cut-off value of the Ki-67 expression for predicting survival was determined by the minimum P-value method. Clinicopathological data were compared based on Ki-67 status (low versus high expression). Univariate and multivariate Cox regression analysis was used to explore independent predictors. RESULTS: A total of 202 patients (median age, 58 years [IQR, 52-65 years], 147 men) with ccRCC and tumor thrombus were included in the study. The optimal cut-off value of Ki-67 for predicting survival was 30%. 159 (78.7%) and 43 (21.3%) patients were included in the low-expression and high-expression groups. Patients with Ki-67 high expression had significantly worse recurrence-free survival (P < 0.001) and cancer-specific survival (P < 0.001). Ki-67 high expression was associated with adverse pathological features, including tumor necrosis, ISUP nuclear grade, sarcomatoid differentiation, perirenal fat invasion, renal pelvis invasion, and inferior vena cava wall invasion (all P < 0.050). Ki-67 expression ≥ 30% (P = 0.016), tumor side (P = 0.003), diabetes (P = 0.040), blood loss (P = 0.016), inferior vena cava wall invasion (P = 0.016), and sarcomatoid differentiation (P = 0.014) were independent predictors of cancer-specific survival. CONCLUSION: The optimal cut-off level of Ki-67 in predicting the prognosis of ccRCC and tumor thrombus was 30%. The high expression of Ki-67 was associated with the aggressive pathological phenotype and poor prognosis.

The Overlap Subgroup of Functional Dyspepsia Exhibits More Severely Impaired Gastric and Autonomic Functions.

GOALS: A combination of multiple tests was introduced to noninvasively investigate the differences in pathophysiologies among functional dyspepsia (FD) subgroups, including postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlap. BACKGROUND: It has not been extensively evaluated whether different pathophysiologies are involved in FD subgroups. STUDY: This multicenter study included 364 FD patients fulfilling Rome IV criteria and 47 healthy controls. A combined noninvasive gastric and autonomic function test was performed: The electrogastrogram and electrocardiogram were recorded simultaneously in the fasting state and after a drink test. Symptoms after drinking were recorded using visual analog scale. RESULTS: (1) Compared with HC, FD patients showed a decreased maximum tolerable volume (MTV) ( P <0.01) and percentage of normal gastric slow waves [normal gastric slow waves (%NSW)] ( P <0.01), and increased postdrinking symptoms, anxiety ( P <0.01), and depression ( P <0.01). The drink reduced %NSW in both FD patients and HC; however, the effect was more potent in patients. (2) The PDS and overlap groups displayed a reduced MTV ( P <0.05). The overlap group exhibited a higher symptom score at 30 minutes after drinking, and higher anxiety and depression scores, and a higher sympathovagal ratio than the EPS ( P <0.05 for all) and PDS ( P <0.01 for all). (3) In the PDS subgroup, the MTV, postprandial sympathovagal ratio, and depression were associated with the overall dyspepsia symptom scale (DSS, P =0.034, 0.021, 0.043, respectively). No significant associations were found in the other 2 subgroups. CONCLUSIONS: The combination of multiple tests can detect pathophysiological abnormities in FD patients. Overall, patients with overlap symptoms display more severe pathophysiologies.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging and Venous Tumor Thrombus Consistency in Renal Cell Carcinoma.

BACKGROUND: Venous tumor thrombus (VTT) consistency of renal cell carcinoma (RCC) is an important consideration in nephrectomy plus thrombectomy. However, evaluation of VTT consistency through preoperative MR imaging is lacking. PURPOSE: To evaluate VTT consistency of RCC through intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters (Dt , Dp , f, and ADC) and the apparent diffusion coefficient (ADC) value. STUDY TYPE: Retrospective. POPULATION: One hundred and nineteen patients (aged 55.8 ± 11.5 years, 85 male) with histologically-proven RCC and VTT who underwent radical resection. FIELD STRENGTH/SEQUENCES: 3.0-T; two-dimensional single-shot diffusion-weighted echo planar imaging sequence at 9 b-values (0-800 s/mm2 ). ASSESSMENT: IVIM parameters and ADC values of the primary tumor and the VTT were calculated. The VTT consistency (friable vs. solid) was determined through intraoperative findings of two urologists. The accuracy of VTT consistency classification based on the individual IVIM parameters of primary tumors and of VTT, and based on models combining parameters, was assessed. Type of operation, intra-operative blood loss, and operation length were recorded. STATISTICAL TESTS: Shapiro-Wilk test; Mann-Whitney U test; Student's t-test; Chi-square test; Receiver operating characteristic (ROC) analysis. Statistical significance level was P < 0.05. RESULTS: Of the enrolled 119 patients, 33 patients (27.7%) had friable VTT. Patients with friable VTT were significantly more likely to experience open surgery, have significantly more intraoperative blood loss, and significantly longer operative duration. The area under the ROC curve (AUC) values of Dt of the primary tumor and VTT in classifying VTT consistency were 0.758 (95% CI 0.671-0.832) and 0.712 (95% CI 0.622-0.792), respectively. The AUC value of the model combining Dp and Dt of VTT was 0.800 (95% CI 0.717-0.868). Furthermore, the AUC of the model combining Dp and Dt of VTT and Dt of the primary tumor was 0.886 (95% CI 0.814-0.937). CONCLUSION: IVIM-derived parameters had the potential to predict VTT consistency of RCC. EVIDENCE LEVEL: 3 Technical Efficacy: Stage 2.

[Design and practice of the course of "Biochemical Engineering Experiment" under the context of "Emerging Engineering Education"].

"Biochemical Engineering Experiment" is a compulsory curriculum for the concentrated practical teaching of biotechnology majors in Hunan University of Science and Engineering. It is also an experimental curriculum for improving the overall quality of bioengineering students under the context of "Emerging Engineering Education". The course includes comprehensive experiments and designable experiments, and the contents of which are designed by combining the local characteristic resources of Yongzhou, the research platform and the characteristics of the talents with engineering background. In the teaching practice, methods such as heuristic teaching, research cases-embedded teaching and interactive teaching are comprehensively used to boost students' interest in learning and stimulate their innovative thinking and application capability. Through curriculum examination and post-class investigation, it was found that the students' abilities of knowledge transfer and application were significantly improved, and they achieved excellent performances in discipline competitions and approved project proposals. The practice and continuous improvement of this course may facilitate fostering high-level innovative and application-oriented talents of biotechnology majors.

Objective Value of the Apparent Diffusion Coefficient (ADC) Map from Ultrahigh b-value Diffusion-weighted Imaging (DWI) in 3T MRI could be a Non-invasive Specific Biomarker for Prostate Cancer.

OBJECTIVE: This article aims to explore the ADC value of ultrahigh b-value DWI and the diagnostic cutoff point in prostate cancer. METHODS: A total of 78 patients were included in this study. T2 weighted imaging (T2WI), conventional diffusion-weighted imaging (DWI) (1000 s/mm2), and DWI with ultrahigh b-values of 2000 s/mm2 and 3000 s/mm2 were performed in each patient. With reference biopsy as the gold standard, the apparent diffusion coefficient (ADC)s of each b-value DWI image were analyzed. According to different b-value receiver operating characteristic (ROC) curves, the ADC diagnostic cutoff point for prostate cancer was determined. RESULTS: A total of 154 lesions were identified as prostate cancer. The ADC values for conventional DWI and ultrahigh b-value DWI with 2000 s/mm2 and 3000 s/mm2 were 1.097×10-3 mm2/s (1.040-1.153), 0.809×10-3 mm2/s (0.766-0.851) and 0.622×10-3 mm2/s (0.591-0.652), respectively, in the peripheral zone and 1.085×10-3 mm2/s (1.022-1.147), 0.815×10-3 mm2/s (0.770-0.861) and 0.651×10-3 mm2/s (0.617-0.685) in the transition zone. The area under the curve (AUC)s of the ADC values from ultrahigh b-value DWI (2000 s/mm2 and 3000 s/mm2) were 0.824 and 0.852 in the peripheral zone and 0.905 for the ADC values from ultrahigh b-value DWI (3000 s/mm2) in the transition zone. In the peripheral zone, the ADC diagnostic cutoff values for prostate cancer were 0.75×10-3 mm2/s and 0.685×10-3 mm2/s in DWI at 2000 s/mm2 and 3000 s/mm2, respectively, and the diagnosis of transition zone cancer was 0.8×10-3 mm2/s and 0.634×10-3 mm2/s, respectively. CONCLUSION: The ADC values from ultrahigh b-value DWI demonstrated better consistency and diagnostic efficacy in the diagnosis of prostate cancer.

The clinical application value of salivary pepsin in the diagnosis of gastroesophageal reflux diseases.

BACKGROUND: Peptest is a noninvasive and convenient diagnostic kit for gastroesophageal reflux disease (GERD). We aimed to explore the application value of Peptest in the diagnosis of GERD. METHODS: Patients suspected of GERD all completed 24 h pH-impedance monitoring (24 h MII-pH) and then took proton pump inhibitor (PPI) 2 weeks. The postprandial, post-symptom and random salivary samples were taken. Receiver operating characteristic analysis was used to identify the best cutoff value of Peptest, to differentiate GERD patients from non-GERD patients and the optimal sampling time of Peptest was analyzed. Reflux characteristics and esophageal motility between Peptest (+) group and Peptest (-) group were compared in negative 24 h MII-pH patients. Peptest concentration were compared among non-reflux, distal reflux, and proximal reflux groups according to 24 h MII-pH curve. RESULTS: The area under the curve of post-symptom Peptest was highest in three time points and the diagnostic specificity was 81.0% and sensitivity was 53.3% with the diagnostic value of 86 ng/mL. Compared with negative Peptest group, distal mean nocturnal baseline impedance was significantly lower, gastroesophageal junction contractile integral was substantially lower in positive Peptest group in negative 24 h MII-pH patients. The concentration of post-symptom and postprandial Peptest increased gradually in the non-reflux, distal reflux, and proximal reflux groups. CONCLUSIONS & INFERENCES: Peptest has a relatively low diagnostic value for GERD. Post-symptom Peptset is the best sampling time with the optimal value of 86 ng/mL and may have auxiliary diagnostic value for negative 24 h MII-pH patients. Peptest may assist 24 h MII-pH in monitoring proximal reflux.

LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is highly heterogeneous, and stemness signatures are frequently elevated in HCC tumor cells to generate heterogeneous subtypes via multidirectional differentiation. However, the mechanisms affecting the regulation of stemness in HCC remain unclear. In this study, we identified that lysosome-associated protein transmembrane-4ß (LAPTM4B) was significantly overexpressed in stem-like tumor cell populations with multidirectional differentiation potential at the single cell level, and verified that LAPTM4B was closely related to stemness of HCC using in vitro and in vivo experiments. Mechanistically, elevated LAPTM4B suppresses Yes-associated protein (YAP) phosphorylation and ubiquitination degradation. In turn, stabilized YAP localizes to the nucleus and binds to cAMP responsive element binding protein-1 (CREB1), which promotes transcription of LAPTM4B. Overall, our findings suggest that LAPTM4B forms a positive feedback loop with YAP, which maintains the stemness of HCC tumor cells and leads to an unfavorable prognosis for HCC patients.

Clinical significance and related factors of rectal hyposensitivity in patients with functional defecation disorder.

Background: Rectal hyposensitivity (RH) is not uncommon in patients with functional defecation disorder (FDD). FDD patients with RH are usually unsatisfied with their treatment. Aims: The aim of this study was to find the significance of RH in patients with FDD and the related factors of RH. Methods: Patients with FDD first completed clinical questionnaires regarding constipation symptoms, mental state, and quality of life. Then anorectal physiologic tests (anorectal manometry and balloon expulsion test) were performed. Rectal sensory testing (assessing rectal response to balloon distension using anorectal manometry) was applied to obtain three sensory thresholds. Patients were separated into three groups (non-RH, borderline RH, and RH) based on the London Classification. The associations between RH and clinical symptoms, mental state, quality of life, and rectal/anal motility were investigated. Results: Of 331 included patients with FDD, 87 patients (26.3%) had at least one abnormally elevated rectal sensory threshold and 50 patients (15.1%) were diagnosed with RH. Patients with RH were older and mostly men. Defecation symptoms were more severe (p = 0.013), and hard stool (p < 0.001) and manual maneuver (p = 0.003) were more frequently seen in the RH group. No difference in rectal/anal pressure was found among the three groups. Elevated defecatory desire volume (DDV) existed in all patients with RH. With the number of elevated sensory thresholds increasing, defecation symptoms got more severe (r = 0.35, p = 0.001). Gender (male) (6.78 [3.07-15.00], p < 0.001) and hard stool (5.92 [2.28-15.33], p < 0.001) were main related factors of RH. Conclusion: Rectal hyposensitivity plays an important role in the occurrence of FDD and is associated with defecation symptom severity. Older male FDD patients with hard stool are prone to suffer from RH and need more care.

Hydrogel Complex Containing the Antimicrobial Peptide HX-12C Accelerates Healing of Infected Wounds.

Bacterial infections of the wound surface can be painful for patients, and traditional dressings do not effectively address this problem. In this study, an antimicrobial wound dressing is prepared using a novel antimicrobial peptide, HX-12C. This hydrogel system is based on the natural biomaterials sodium alginate and gelatin, utilizing calcium carbonate as a source of Ca2+ , and ionic cross-linking is facilitated by lowering the solution pH. The resulting sodium alginate/gelatin HX-12C-loaded hydrogel (CaAGEAM) has good mechanical and adhesion properties, biocompatibility and in vitro degradability. Its extraordinary antibacterial efficacy (>98%) is verified by an antibacterial experiment. More importantly, in vivo experiments further demonstrate its healing-promotion effect, with a 95% wound healing rate by day 9. Tissue staining demonstrates that the hydrogel containing antimicrobial peptides is effective in suppressing inflammation. The dressing promotes wound healing by stimulating the deposition of skin appendages and collagen. The results of this study suggest that composite hydrogels containing antimicrobial peptides are a promising new type of dressing to promote the healing of infected wounds.

Clinical Characteristics of Adult Functional Constipation Patients with Rectoanal Areflexia and Their Response to Biofeedback Therapy.

Background: The London Classification for anorectal physiological dysfunction specifically proposes rectoanal areflexia (RA), which means the absence of a rectoanal inhibitory reflex (RAIR) based on a manometric diagnosis. Although RA is not observed in healthy people, it can be found in adult patients with functional constipation (FC). This study describes the clinical manifestations of adult patients with FC and RA and their response to biofeedback therapy (BFT). Methods: This retrospective study reviewed the reports of high-resolution anorectal manometry (HR-ARM) and the efficacy of BFT in adult patients with FC. In addition, the Constipation Scoring System (CSS) scale, Patient Assessment of Constipation Symptoms (PAC-SYM) scale, Patient Assessment of Constipation Quality of Life (PAC-QOL) scale, Zung's Self-Rating Anxiety Scale (SAS), Zung's Self-Rating Depression Scale (SDS), balloon expulsion test (BET), and the use of laxatives were assessed. Results: A total of 257 adult patients diagnosed with FC were divided into the RA group (n = 89) and the RAIR group (n = 168). In the RA and RAIR groups, 60 (67.4%) and 117 (69.6%) patients, respectively, had dyssynergic defecation (DD) during simulated defecation. Type II pattern of dyssynergia was most frequently observed in both groups. Compared with the RA group, the RAIR group showed a higher CSS score, physical discomfort score, and prevalence of inadequate relaxation of the anal sphincter (p < 0.001, p = 0.036, and p = 0.017, respectively). The anxiety and depression scores were not different between the two groups. The proportion of patients using volumetric and stimulant laxatives and their combination was significantly higher in FC patients with RA, whereas the efficacy of BFT was significantly lower (p = 0.005, p < 0.001, p = 0.045, and p = 0.010, respectively). Conclusion: Adult FC patients with RA may suffer more severe constipation and have a lower efficacy of BFT compared with those with RAIR.

Preference to Family Doctor Contracted Service of Patients with Chronic Disease in Urban China: A Discrete Choice Experiment.

Objective: Shanghai is one of the pioneers proposing family doctor contract service (FDCS). However, there is no quantitative research focusing on the Shanghai experience from a demand-side perspective. This study investigated Shanghai chronic patients' relative preferences for FDCS using a discrete choice experiment method. Methods: A face-to-face discrete choice experiment (DCE) was performed to elicit the preference with 300 samples. Attributes and levels were extracted from the literature review and focus group consultation with patients. Seven attributes, follow-up frequency, medicine accessibility, family doctor competency, health management, referral convenience, appointment flexibility, and shared decision-making, were decided. Three levels were attached to each attribute. A mixed logit model was used to evaluate the multiple-choice data. Results: A total of 248 patients completed the survey. Patient valued FDCS medicine accessibility (ß=0.57, P < 0.05), and high family doctor competency (ß= 0.43, P < 0.05), regular health management activities (ß=0.36, P < 0.05), high follow-up frequency (ß=0.31, P < 0.05) the most. The good doctor-patient shared decision-making atmosphere (ß=0.12, P < 0.05), high referral convenience (ß=0.06, P < 0.05) and high appointment flexibility (ß=0.04, P < 0.05) are valued as less important. No significant preference heterogeneity was identified for patients with different sociodemographic characteristics. Respondents reported other FDCS needs, including online health consultation, specialist services in local institutes, higher reimbursement rates, free rehabilitation guidance for the disabled and personal health management. Conclusion: This research is the first discrete choice experiment FDCS preference research targeting on Chinese urban population. The results suggested that to increase the quality of FDCS, policy-makers should prioritize follow-up frequency, medicine accessibility, family doctor competency and health management. The service package should consider a higher reimbursement rate and rehabilitation guidance for the disabled if extra health-care resources available. Future FDCS policy should consider stated societal preference and be congruent with it.

Single cell transcriptional diversity and intercellular crosstalk of human liver cancer.

Liver cancer arises from the evolutionary selection of the dynamic tumor microenvironment (TME), in which the tumor cell generally becomes more heterogeneous; however, the mechanisms of TME-mediated transcriptional diversity of liver cancer remain unclear. Here, we assess transcriptional diversity in 15 liver cancer patients by single-cell transcriptome analysis and observe transcriptional diversity of tumor cells is associated with stemness in liver cancer patients. Tumor-associated fibroblast (TAF), as a potential driving force behind the heterogeneity in tumor cells within and between tumors, was predicted to interact with high heterogeneous tumor cells via COL1A1-ITGA2. Moreover, COL1A1-mediated YAP-signaling activation might be the mechanistic link between TAF and tumor cells with increased transcriptional diversity. Strikingly, the levels of COL1A1, ITGA2, and YAP are associated with morphological heterogeneity and poor overall survival of liver cancer patients. Beyond providing a potential mechanistic link between the TME and heterogeneous tumor cells, this study establishes that collagen-stimulated YAP activation is associates with transcriptional diversity in tumor cells by upregulating stemness, providing a theoretical basis for individualized treatment targets.

Effect of peer support on adults with diabetes-related peripheral neuropathy.

OBJECTIVE: To explore the effect of peer support on exercise self-efficacy, physical activity level, and neuropathic symptoms in patients with diabetes-related peripheral neuropathy (DPN). METHODS: A total of 60 adults with DPN were assigned to groups. Patients in the control group received routine education (RE), while patients in the intervention group received peer support (PS) combined with routine diabetes education. Data were collected at baseline and after intervention (12 weeks). RESULTS: At 12 weeks, better outcomes were found in the PS group compared to the RE group for the following aspects: exercise self-efficacy, steps, total physical activity, fasting blood glucose and 2-hour postprandial blood glucose. Decreases in scores on Toronto Clinical Scoring System occurred between baseline and post-intervention in both groups. CONCLUSION: Peer support is an effective way to improve exercise self-efficacy, number of steps, and general physical activity and to reduce blood glucose for patients with DPN. But the effects of peer support on neuropathic symptoms is are obvious. Further research is needed. PRACTICE IMPLICATIONS: As a low-cost, effective education approach, peer support strategies should be integrated into our healthcare system to meet the minimum needs of patients with DPN.

Effects of group psychological counselling on transition shock in newly graduated nurses: A quasi-experimental study.

AIM: This study examined the effects of group psychological counselling on transition shock in newly graduated nurses. BACKGROUND: Newly graduated nurses are often faced with transition shock as they enter the workforce. Helping them adapt to the new work environment and role as quickly as possible is an important goal for nursing managers. METHOD: This prospective, parallel-group, quasi-experimental trial enrolled 71 newly graduated nurses who were randomly assigned to the intervention (n = 38) or control (n = 41) group. In addition to routine hospital training, the intervention group received psychological counselling. Participants were evaluated with the Transition Shock Scale of Newly Graduated Nurses before (pre) and after (post) the training with or without intervention. RESULTS: The total score and score on each dimension of the scale were decreased after the intervention (P < .05); control subjects showed no difference between pre- and post-scores. The total score and score on each dimension were higher in the control group than in the intervention group (P < .05). CONCLUSION: Psychological counselling alleviates transition shock in newly graduated nurses entering the workforce. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers can introduce group psychological counselling into their training programmes to increase the job readiness of newly graduated nurses.

Esophageal Nocturnal Baseline Impedance and Post-reflux Swallow-induced Peristaltic Wave Index in Identifying Proton Pump Inhibitor-refractory Non-erosive Reflux Disease.

BACKGROUND/AIMS: Esophageal mean nocturnal baseline impedance (MNBI) levels and post-reflux swallow-induced peristaltic wave (PSPW) index could increase the diagnostic value of 24-hour multichannel intraluminal impedance and pH monitoring in patients with gastroesophageal reflux disease. This study aims to compare the MNBI and PSPW index in patients with no evidence of erosive reflux disease. METHODS: Impedance-pH monitoring tracings from 70 patients, 50 with non-erosive reflux disease (NERD) and 20 with functional heartburn (FH), were reviewed. According to proton pump inhibitors (PPI) treatment response, NERD patients were divided into NERD/PPI responders and NERD/PPI nonresponders. MNBI, PSPW index, and intercellular spaces were measured and compared among each group. RESULTS: MNBI values and PSPW index were lower in NERD patients than in FH (P < 0.01 and P < 0.05, respectively). MNBI positively correlated with PSPW index (r = 0.525, P < 0.001). NERD/PPI responders had lower MNBI values and PSPW index compared to NERD/PPI nonresponders (both P < 0.01). MNBI and PSPW index distinguished NERD from FH patients with an area under the curve of 0.914 and 0.677, respectively. Wider intercellular space could be identified in patients with NERD (P < 0.01). CONCLUSION: MNBI and PSPW index may differentiate NERD from FH patients and relate to PPI treatment efficacy in patients with NERD.

A Pilot Study of Clinical Evaluation and Formation Mechanism of Irritable Bowel Syndrome-like Symptoms in Inflammatory Bowel Disease Patients in Remission.

BACKGROUND/AIMS: Some inflammatory bowel disease (IBD) patients in remission suffer from irritable bowel syndrome (IBS)-like symptoms (IBD-IBS). The pathogenesis has not yet been elucidated. The study aim is to evaluate relationships among quality of life (QOL), psychological status, and visceral sensitivity, and explore the formation mechanism of IBD-IBS. METHODS: Forty-seven patients with Crohn's disease in remission, 24 ulcerative colitis in remission, 26 IBS, and 20 healthy controls were included in the study. The abdominal pain, QOL, anxiety, and depression were evaluated through questionnaires. Visceral sensitivity was measured by rectal balloon distension. The serum levels of 5-hydroxytryptamine (5-HT) and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay. The expressions of tryptase, 5-HT, NGF, and related receptors in colonic tissues were detected by immunohistochemistry and western blot. RESULTS: Prevalence of IBS-like symptoms in Crohn's disease and ulcerative colitis patients in clinical remission was 29.8% and 50.0%, respectively. The QOL was lower, the anxiety/depression scores were higher in IBD-IBS patients than those without IBS-like symptoms. Additionally, patients with IBD-IBS existed visceral hypersensitivity. Besides, abdominal pain was associated with poor QOL, visceral hypersensitivity, anxiety, and depression in IBD-IBS patients. The number of mast cells (MCs) and expressions of 5-HT, NGF, and related receptors were higher in IBD-IBS patients than those with no such symptoms. The serum levels of 5-HT and NGF positively correlated with abdominal pain and visceral hypersensitivity. CONCLUSION: IBD-IBS patients may have low QOL and psychological abnormalities, as wells as visceral hypersensitivity which may be related to increased 5-HT and NGF levels released from activated mast cells.