Prognostic relevance of prognostic nutritional indices in gastric or gastro-esophageal junction cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

Background: The Prognostic Nutritional Index (PNI) has become an important predictive tool for assessing patients' nutritional status and immune competence. It is widely used in prognostic evaluations for various cancer patients. However, the prognostic relevance of the Prognostic Nutritional Index (PNI) in gastric or gastro-esophageal junction cancer patients (GC/GEJC) undergoing immune checkpoint inhibitors (ICIs) treatment remains unclear. This meta-analysis aimed to determine the prognostic impact of PNI in this specific patient cohort. Methods: We conducted a thorough literature search, covering prominent databases such as PubMed, Embase, Web of Science, SpringerLink, and the Cochrane Library. The search spanned from the inception of these databases up to December 5, 2023. Employing the 95% confidence interval and Hazard Ratio (HR), the study systematically evaluated the relationship between PNI and key prognostic indicators, including the objective remission rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) in GC/GEJC patients undergoing ICI treatment. Results: Eight studies comprising 813 eligible patients were selected. With 7 studies consistently demonstrating superior Overall Survival (OS) in the high-Prognostic Nutritional Index (PNI) group compared to their low-PNI counterparts (HR 0.58, 95% CI: 0.47-0.71, P<0.001). Furthermore, the results derived from 6 studies pointed out that the significant correlation between he low-PNI and poorer progression-free survival (PFS) (HR 0.58, 95% CI: 0.47-0.71, P<0.001). Subgroup analyses were performed to validate the robustness of the results. In addition, we conducted a meta-analysis of three studies examining the correlation between PNI and objective response rate/disease control rate (ORR/DCR) and found that the ORR/DCR was significantly superior in the high PNI group (ORR: RR: 1.24, P=0.002; DCR: RR: 1.43, P=0.008). Conclusion: This meta-analysis indicates that the low-PNI in GC/GEJC patients undergoing ICI treatment is significantly linked to worse OS and PFS. Therefore, PNI can serve as a prognostic indicator of post-treatment outcomes in patients with GC receiving ICIs. Further prospective studies are required to assess the reliability of these findings. Systematic review registration: https://inplasy.com/, identifier INPLASY202450133.

Prognostic relevance of platelet lymphocyte ratio (PLR) in gastric cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

Objectives: The prognostic relevance of the platelet-to-lymphocyte ratio (PLR) in gastric cancer (GC) patients undergoing immune checkpoint inhibitor (ICI) treatment remains unclear. This meta-analysis aimed to determine the prognostic impact of PLR in this specific patient cohort. Methods: We searched the PubMed, Cochrane Library, CNKI, and EMBASE databases, including literature published up to September 2023, to investigate the prognostic implications of PLR in patients with gastric cancer undergoing immune checkpoint inhibitor therapy. Outcome measures encompassed overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rates (DCR). Results: Nine studies from seven articles comprising 948 eligible patients were selected. The results revealed a significant correlation between elevated PLR and poorer OS and progression-free survival (PFS) (OS: HR 1.67, 95% CI 1.39-2.00, p < 0.001; PFS: HR 1.51, 95% CI 1.29-1.76, p < 0.001). Subgroup analyses were performed to validate the robustness of the results. Moreover, a meta-analysis of four studies investigating the correlation between the PLR in gastric cancer (GC) patients and the objective response rate/disease control rate (ORR/DCR), showed no significant association between the PLR and ORR/DCR (ORR: RR = 1.01, p = 0.960; DCR: RR = 0.96, p = 0.319). Conclusions: This meta-analysis indicates that elevated PLR in GC patients undergoing ICI treatment is significantly linked to worse OS and PFS. Therefore, PLR can serve as a prognostic indicator of post-treatment outcomes in patients with GC receiving ICIs. Further prospective studies are required to assess the reliability of these findings. Systematic review registration: https://inplasy.com/, identifier INPLASY2023120103.

Nomogram for predicting overall survival after curative gastrectomy using inflammatory, nutritional and pathological factors / Nomograma para predecir la supervivencia global después de una gastrectomía curativa utilizando factores inflamatorios, nutricionales y patológicos

Purpose: To establish a nomogram for predicting the overall survival (OS) in patients with gastric cancer (GC) based on inflammatory, nutritional and pathological factors. Methods: GC patients underwent curative gastrectomy from January 2012 to June 2017 in our hospital were included, and were classified into training set and validation set with a ratio of 7:3. Then variables associated with OS were analyzed using univariate and multivariate Cox regression analysis. Nomograms predicting OS were built using variables from multivariable Cox models. Finally, Kaplan–Meier curve and Log-rank test were also conducted to analyze the 1-yr, 3-yr and 5-yr OS to validate the efficiency of risk stratification of the nomogram. Results: A total of 366 GC patients were included. After univariate and multivariate Cox regression analysis, age (HR = 1.52, 95% CI = 1.01–2.30, P = 0.044), CA50 (HR = 1.90, 95% CI = 1.12–3.21, P = 0.017), PNI (HR = 1.65, 95% CI = 1.13–2.39, P = 0.009), SII (HR = 1.46, 95% CI = 1.03–2.08, P = 0.036), T stage (HR = 2.26, 95% CI = 1.01–5.05, P = 0.048; HR = 7.24, 95% CI = 3.64–14.40, P < 0.001) were independent influencing factors on the survival time of GC patients. Five factors including CEA, prognostic nutritional index (PNI), systemic immune-inflammation index (SII), ln (tumor size), T stage, and N stage were identified and entered the nomogram, which showed good discrimination and calibration in both sets. On internal validation, 1-yr, 3-yr and 5-yr nomogram demonstrated a good discrimination with an area under the ROC curve (AUC) of 0.77, 0.84 and 0.86, respectively. The AUC for 1-yr, 3-yr and 5-yr nomogram in validation set was 0.77, 0.79 and 0.81, respectively. The OS in low risk group of training cohort and validation cohort was significantly higher than that of intermediate risk group and high risk group, respectively...(AU)

Nomogram for predicting overall survival after curative gastrectomy using inflammatory, nutritional and pathological factors.

PURPOSE: To establish a nomogram for predicting the overall survival (OS) in patients with gastric cancer (GC) based on inflammatory, nutritional and pathological factors. METHODS: GC patients underwent curative gastrectomy from January 2012 to June 2017 in our hospital were included, and were classified into training set and validation set with a ratio of 7:3. Then variables associated with OS were analyzed using univariate and multivariate Cox regression analysis. Nomograms predicting OS were built using variables from multivariable Cox models. Finally, Kaplan-Meier curve and Log-rank test were also conducted to analyze the 1-yr, 3-yr and 5-yr OS to validate the efficiency of risk stratification of the nomogram. RESULTS: A total of 366 GC patients were included. After univariate and multivariate Cox regression analysis, age (HR = 1.52, 95% CI = 1.01-2.30, P = 0.044), CA50 (HR = 1.90, 95% CI = 1.12-3.21, P = 0.017), PNI (HR = 1.65, 95% CI = 1.13-2.39, P = 0.009), SII (HR = 1.46, 95% CI = 1.03-2.08, P = 0.036), T stage (HR = 2.26, 95% CI = 1.01-5.05, P = 0.048; HR = 7.24, 95% CI = 3.64-14.40, P < 0.001) were independent influencing factors on the survival time of GC patients. Five factors including CEA, prognostic nutritional index (PNI), systemic immune-inflammation index (SII), ln (tumor size), T stage, and N stage were identified and entered the nomogram, which showed good discrimination and calibration in both sets. On internal validation, 1-yr, 3-yr and 5-yr nomogram demonstrated a good discrimination with an area under the ROC curve (AUC) of 0.77, 0.84 and 0.86, respectively. The AUC for 1-yr, 3-yr and 5-yr nomogram in validation set was 0.77, 0.79 and 0.81, respectively. The OS in low risk group of training cohort and validation cohort was significantly higher than that of intermediate risk group and high risk group, respectively. CONCLUSIONS: We established a nomogram based on PNI, SII and pathological factors for predicting OS in GC patients. In addition, its efficiency was validated by validation set and stratified analysis.

Transdermal delivery of Protocatechuic aldehyde using hyaluronic acid/gelatin-based microneedles for the prevention and treatment of hypertrophic scars.

The formation of hypertrophic scar (HS) involves many pathological processes, such as reduced apoptosis in fibroblasts, excessive collagen deposition by fibroblasts, over-abundant angiogenesis, etc. The therapeutic effects of current treatments targeting one single pathological process are limited. Due to their diverse biological activities, natural products offer a potential solution to this issue. In this study reported herein, we investigated the effects of Protocatechuic aldehyde (PA) on both hypertrophic scar-derived fibroblasts (HSF) and vascular endothelial growth factor (VEGF)-stimulated human umbilical vein endothelial cells (HUVECs). Microneedles (MN) containing PA and hyaluronic acid (HA) or containing PA, HA, and gelatin were prepared by mixing PA stock solution with HA or HA/gelatin at a ratio of 1:10. The HS prevention and treatment outcomes of these HA-PA-MN and HA/gelatin-PA-MN were tested using a rabbit ear HS model. Our data indicate that PA induces apoptosis and reduces collagen deposition in HSF. In addition, PA attenuates VEGF-stimulated angiogenesis of HUVECs. Furthermore, HA-PA-MN or HA/gelatin-PA-MN are able to effectively penetrate the epidermis of the HS tissues and then quickly dissolve, enabling the fast release of PA directly into the dermis of the HS tissues. HA-PA-MN or HA/Gelatin-PA-MN have also been found to effectively prevent or alleviate HS in a rabbit ear HS model. In conclusion, this study demonstrates that PA can be used to prevent and treat HS by simultaneously regulating HSF and HUVECs, which offers a potential novel reagent for HS management.

Dissolvable hyaluronic acid microneedles loaded with ß-Elemene for the treatment of psoriasis.

The pathology of psoriasis involves the over-proliferation of keratinocytes, exaggerated inflammation of keratinocytes, and infiltration of inflammatory cells such as macrophages (Mø), etc. The therapeutic outcomes of current treatment targeting one single pathological process are less than satisfactory. Based on their diverse biological activities, natural products offer a potential solution to this problem. In this study, we investigated the effects of ß-Elemene (ELE) on both psoriatic keratinocytes and M1-type Mø (M1-Mø) in vitro. Hyaluronic acid (HA) microneedles loaded with ELE (HA-ELE-MN) were also fabricated and tested for the treatment of psoriasis in vivo using an imiquimod (IMQ)-induced psoriatic mice model. Our data suggest that ELE induces apoptosis and inhibits inflammation of psoriatic keratinocytes. In addition, ELE attenuates the expression of inflammatory cytokines secreted from M1-Mø, thus indirectly inhibiting the inflammation of keratinocytes. Furthermore, HA-ELE-MN has been found to significantly alleviate symptoms in an IMQ-induced psoriatic mice model by inducing keratinocytes apoptosis, suppressing keratinocytes proliferation, and inhibiting M1-Mø infiltration. Taken together, this study demonstrates that ELE can be used for the treatment of psoriasis by targeting both keratinocytes and M1-Mø, which provides a potential novel reagent for psoriasis treatment.

Multi-functional wound dressings based on silicate bioactive materials.

Most traditional wound dressings passively offer a protective barrier for the wounds, which lacks the initiative in stimulating tissue regeneration. In addition, cutaneous wound healing is usually accompanied by various complicated conditions, including bacterial infection, skin cancer, and damaged skin appendages, bringing further challenges for wound management in clinic. Therefore, an ideal wound dressing should not only actively stimulate wound healing but also hold multi-functions for solving problems associated with different specific wound conditions. Recent studies have demonstrated that silicate bioceramics and bioglasses are one type of promising materials for the development of wound dressings, as they can actively accelerate wound healing by regulating endothelial cells, dermal fibroblasts, macrophages, and epidermal cells. In particular, silicate-based biomaterials can be further functionalized by specific structural design or doping with functional components, which endow materials with enhanced bioactivities or expanded physicochemical properties such as photothermal, photodynamic, chemodynamic, or imaging properties. The functionalized materials can be used to address wound healing with different demands including but not limited to antibacterial, anticancer, skin appendages regeneration, and wound monitoring. In this review, we summarized the current research on the development of silicate-based multi-functional wound dressings and prospected the development of advanced wound dressings in the future.

Chitosan oligosaccharide regulates AMPK and STAT1 pathways synergistically to mediate PD-L1 expression for cancer chemoimmunotherapy.

After regular chemotherapy, the expression of programmed cell death ligand 1 (PD-L1) in almost all kinds of cancers is significantly increased, leading to reduced efficacy of T cell mediated immune killing in tumors. To solve this, a lot of PD-L1 antibodies were produced and used, but their high cost and serious toxic side effects still limit its usage. Recently, small molecule compounds that could effectively regulate PD-L1 expression possess the edges to solve the problems of PD-L1 antibodies. Chitosan oligosaccharide (COS), a biomaterial derived from the N-deacetylation product of chitin, has a broad spectrum of biological activities in treating tumors. However, the mechanism of its anti-cancer effect is still not well understood. Here, for the first time, we clearly identified that COS could inhibit the upregulated PD-L1 expression induced by interferon γ (IFN-γ) in various tumors via the AMPK activation and STAT1 inhibition. Besides, COS itself significantly restricted the growth of CT26 tumors by enhancing the T cell infiltration in tumors. Furthermore, we observed that combining COS with Gemcitabine (GEM), one of the typical chemotherapeutic drugs, leaded to a more remarkable tumor remission. Therefore, it was demonstrated that COS could be used as a useful way to improve the efficacy of existing chemotherapies by effective PD-L1 downregulation.

The role of text messaging intervention in Inner Mongolia among patients with type 2 diabetes mellitus: a randomized controlled trial.

BACKGROUND: Short messages service (SMS) provides a practical medium for delivering content to address patients to adherence to self-management. The aim of study was to design some patient-centered health education messages, evaluate the feasibility of messages, and explore the effect of this model. METHODS: The messages were designed by a panel of experts, and SMS Quality Evaluation Questionnaire was used to evaluate their quality. A two-arm randomized controlled trial was conducted to evaluate the effectiveness of this management model. Participants were randomly divided into an intervention group (IG) who received evaluated messages and a control group (CG) who received regular education. The primary outcomes were changes in plasma glucose and control rates, and the secondary outcomes were improvements in diet control, physical activities, weight control, etc. RESULTS: A total of 42 messages covering five main domains: health awareness, diet control, physical activities, living habits and weight control were designed, and the average scores of the messages were 8.0 (SD 0.7), 8.5 (SD 0.6), 7.9 (SD 1.0), 8.0 (SD 0.7), and 8.4 (SD 0.9), respectively. In the SMS intervention, 171 patients with an average age of 55.1 years were involved, including 86 in the CG and 85 in the IG. At 12 months, compared with the control group (CG), the decrease of fasting plasma glucose (FPG) (1.5 vs. 0.4, P = 0.011) and control rate (49.4% vs. 33.3%, P = 0.034), the postprandial glucose (PPG) (5.8 vs. 4.2, P = 0.009) and control rate (57.8% vs. 33.7%, P = 0.002) were better in the intervention group (IG). In terms of self-management, improvements in weight control (49.3% vs. 28.2%, P = 0.031), vegetables consumption (87.3% vs. 29.0%, P < 0.001), fruits consumption (27.5% vs. 7.4%, P = 0.022), and physical activities (84.7% vs. 70.0%, P = 0.036) were better in the IG than in the CG. CONCLUSIONS: The overall quality of the messages was high. It was effective and feasible to carry out an SMS intervention to improve the behavioral habits of patients with chronic diseases in remote and undeveloped areas. TRIAL REGISTRATION: Clinicaltrials.gov, ChiCTR1900023445. Registered May 28, 2019--Retrospectively registered.

A rapid and universal method for isolating starch granules in plant tissues.

Starch is the major form of carbohydrate storage in plants and exists as discrete starch granules (SGs). Isolation of high-quality SGs in different plant tissues is a prerequisite for studying the roles of SGs during plant growth, development, and responses to abiotic stress. However, it is difficult to isolate transitory SGs from leaves and storage SGs from pollen grains due to their small sizes and low quantities. Herein, we develop a novel method for isolating SGs by using the aqueous two-phase system (ATS) of ethanol/NaH2 PO4 . The ATS method efficiently separated SGs from contaminants based on their differences in density, solubility, and polarity. Using this method, we first isolated and purified three kinds of SGs from maize seeds, pollen, and leaves. The biochemical, microscopic, and proteomic analyses demonstrated the high purity of the isolated SGs. Proteomic analysis revealed distinct differences in SG-bound proteins between seed SGs and pollen SGs. As a simple, rapid, and low-cost method, the ATS-based method exhibits highly universal and reproducible results for starch-containing tissues in various plant species.

Self-reported hypertension in Northern China: a cross-sectional study of a risk prediction model and age trends.

BACKGROUND: Hypertension is a major risk factor for the global burden of disease, particularly in countries that are not economically developed. This study aimed to evaluate risk factors associated with self-reported hypertension among residents of Inner Mongolia using a cross-sectional study and to explore trends in the rate of self-reported hypertension. METHODS: Multi-stage stratified cluster sampling was used to survey 13,554 participants aged more than 15 years residing in Inner Mongolia for the 2013 Fifth Health Service Survey. Hypertension was self-reported based on a past diagnosis of hypertension and current use of antihypertensive medication. Adjusted odds risks (ORs) of self-reported hypertension were derived for each independent risk factor including basic socio-demographic and clinical factors using multivariable logistic regression. An optimized risk score model was used to assess the risk and determine the predictive power of risk factors on self-reported hypertension among Inner Mongolia residents. RESULTS: During study period, self-reported hypertension prevalence was 19.0% (2571/13,554). In multivariable analyses, both female and minority groups were estimated to be associated with increased risk of self-reported hypertension, adjusted ORs (95% CI) were 1.22 (1.08, 1.37) and 1.66 (1.29, 2.13) for other minority compared with Han, increased risk of self-reported hypertension prevalence was associated with age, marital status, drinking, BMI, and comorbidity. In the analyses calculated risk score by regression coefficients, old age (≥71) had a score of 12, which was highest among all examined factors. The predicted probability of self-reported hypertension was positively associated with risk score. Of 13,421 participants with complete data, 284 had a risk score greater than 20, which corresponded to a high estimated probability of self-reported hypertension (≥67%). CONCLUSIONS: Self-reported hypertension was largely related to multiple clinical and socio-demographic factors. An optimized risk score model can effectively predict self-reported hypertension. Understanding these factors and assessing the risk score model can help to identify the high-risk groups, especially in areas with multi-ethnic populations.

De-escalation techniques for psychosis-induced aggression or agitation.

BACKGROUND: Aggression is a disposition, a willingness to inflict harm, regardless of whether this is behaviourally or verbally expressed and regardless of whether physical harm is sustained.De-escalation is a psychosocial intervention for managing people with disturbed or aggressive behaviour. Secondary management strategies such as rapid tranquillisation, physical intervention and seclusion should only be considered once de-escalation and other strategies have failed to calm the service user. OBJECTIVES: To investigate the effects of de-escalation techniques in the short-term management of aggression or agitation thought or likely to be due to psychosis. SEARCH METHODS: We searched Cochrane Schizophrenia Group's Study-Based Register of Trials (latest search 7 April, 2016). SELECTION CRITERIA: Randomised controlled trials using de-escalation techniques for the short-term management of aggressive or agitated behaviour. We planned to include trials involving adults (at least 18 years) with a potential for aggressive behaviour due to psychosis, from those in a psychiatric setting to those possibly under the influence of alcohol or drugs and/or as part of an acute setting as well. We planned to include trials meeting our inclusion criteria that provided useful data. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Two review authors inspected all abstracts of studies identified by the search process. As we were unable to include any studies, we could not perform data extraction and analysis. MAIN RESULTS: Of the 345 citations that were identified using the search strategies, we found only one reference to be potentially suitable for further inspection. However, after viewing the full text, it was excluded as it was not a randomised controlled trial. AUTHORS' CONCLUSIONS: Using de-escalation techniques for people with psychosis induced aggression or agitation appears to be accepted as good clinical practice but is not supported by evidence from randomised trials. It is unclear why it has remained such an under-researched area. Conducting trials in this area could be influenced by funding flow, ethical concerns - justified or not - anticipated pace of recruitment as well the difficulty in accurately quantifying the effects of de-escalation itself. With supportive funders and ethics committees, imaginative trialists, clinicians and service-user groups and wide collaboration this dearth of randomised research could be addressed.