Prognosis stratification of cancer patients treated with immune checkpoint inhibitors through lung immune prognostic index: a meta-analysis and systematic review.

BACKGROUND: Although numerous studies have reported the prognostic value of the lung immune prognostic index (LIPI) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), the prognostic value of the LIPI in a pancancer setting remains unclear. METHODS: A comprehensive search was conducted until July 2023 across the PubMed, Embase, Web of Science, and Cochrane Library databases to identify relevant studies evaluating the prognostic value of the LIPI in cancer patients treated with ICIs. The outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). We described and compared the pooled outcomes by stratifying the patients based on different groupings of LIPI (good vs. intermediate [0 vs. 1], good vs. poor [0 vs. 2], and good vs. intermediate / poor [0 vs. 1 + 2]). RESULTS: A total of 9959 patients in 35 studies were included. A higher score of LIPI was associated with impaired OS. The pooled HRs were 1.69 (95% CI: 1.55-1.85, p < 0.001; 0 vs. 1), 3.03 (95% CI: 2.53-3.63, p < 0.001; 0 vs. 2), and 2.38 (95% CI: 1.97-2.88, p < 0.001; 0 vs. 1 + 2). A higher LIPI score was associated with shorter PFS. The pooled HRs were 1.41 (95% CI: 1.31-1.52, p < 0.001; 0 vs. 1), 2.23 (95% CI: 1.87-2.66, p < 0.001; 0 vs. 2), and 1.65 (95% CI: 1.46-1.86, p < 0.001; 0 vs. 1 + 2). Similarly, a higher LIPI score was associated with a lower ORR. The pooled ORs were 0.63 (95% CI: 0.54-0.75, p < 0.001; 0 vs. 1) and 0.38 (95% CI: 0.29-0.50, p < 0.001; 0 vs. 2). A higher LIPI score was associated with a lower DCR. The pooled ORs were 0.47 (95% CI: 0.35-0.61, p < 0.001; 0 vs. 1) and 0.19 (95% CI: 0.12-0.30, p < 0.001; 0 vs. 2). CONCLUSION: In patients with NSCLC or other solid tumours, the lung immune prognostic index could robustly stratify the clinical outcomes into three groups among the patients who receive ICIs. LIPI is a low-cost, simple, accessible, and accurate prognostic tool in a pancancer setting and it may contribute to the evaluation of risk stratification in patients treated with ICIs.

Effects of low-tube voltage coronary CT angiography on plaque and pericoronary fat assessment: intraindividual comparison.

OBJECTIVES: To investigate the effects of low tube voltage on coronary plaques and pericoronary fat assessment, and to compare their extent among various levels of low voltage. MATERIALS AND METHODS: Patients were recommended for high-pitch low-tube voltage coronary computed tomography angiography (CCTA), and they were included if they had poor image quality and were referred to a conventional CCTA. The patients were classified into a low-voltage group (with 70-kV, 80-kV, and 90-kV subgroups) and a conventional group (100/120 kV). Their total plaque and subcomponent volumes and pericoronary fat attenuation index (FAI) were measured. RESULTS: A total of 1002 image slices (from 65 patients and 74 plaques) were included, including 21, 31, 13, 4, and 61 patients in the 70-kV, 80-kV, 90-kV, 100-kV, and 120-kV groups respectively. The CT values of noncalcified plaques in the conventional and low-voltage groups were 54.6 ± 21.3 HU and 31.5 ± 22.6 HU, respectively (p < 0.05). Compared with the conventional group, the necrotic core and calcification volume were increased, and the fibrolipid volume, periplaque, and right coronary artery FAI were decreased in the low-voltage group and its subgroups (p < 0.001). The magnitude of changes in fibrous and calcification volumes increased in the 70-kV subgroup compared with that in the 90-kV subgroup (p < 0.05). CONCLUSION: Low tube voltages, particularly of 70 kV, have a significant effect on coronary plaque and FAI. The effect of low voltage on plaque composition is characterized by a polarization pattern, i.e., a decrease in fibrolipid (medium density) and an increase in necrotic core (low density) and calcification (high density). CLINICAL RELEVANCE STATEMENT: Our results highlight the comparability and repeatability of plaque and pericoronary fat assessments facilitated by the same or a similar tube voltage. It is necessary to carry out studies on the specificity threshold of low tube voltage at each level. KEY POINTS: • Low tube voltage had a significant effect on coronary plaque and pericoronary fat, particularly 70 kV. • The effect of low tube voltage on plaque composition shows the shift from medium-density mixed components to low- and high-density components. • It is necessary to correct the specificity threshold or attenuation difference for low tube voltage at each level.

Young Chinese female body skin pigmentation map: A pilot study.

BACKGROUND: Most studies have discussed variations in facial skin colour based on age, gender, and anatomical site within a specific ethnic group. However, skin pigmentation on the body is also a concern for many people. AIM: The aim of this study is to gather baseline data for Chinese young females, conduct a comprehensive assessment of body skin pigmentation, and create a body skin pigmentation map. METHOD: Individual type angle (ITA°) was registered by CL 400 and melanin index (MI) was registered by MX 18 in 100 body points of 20 Chinese females. A total of 12,000 measurements were recorded. RESULT: Our results showed significant differences among the symmetrical points on both sides of the body, including the clavicle, inner wrists, groin, inner ankle, elbow, armpit, waist side, the space between the thumb and index finger, instep, back shoulder, and popliteal space. Of all the points tested on the body, the points with the most severe skin pigmentation were the back of the neck, the heel, the elbow, and the popliteal space. CONCLUSION: This is the first comprehensive study of skin pigmentation conducted on the human body. In young Chinese women, the points with the most severe skin pigmentation were the back of the neck, heels, elbows, and the popliteal space.

Total life expectancy and disability-free life expectancy and differences attributable to cigarettes' smoking among Chinese middle-aged and older adults.

OBJECTIVES: Middle-aged and older adults smoking for years are afflicted by smoking-related diseases and functional limitations; however, little is known about the effect of smoking on nonfatal conditions in middle and later life. This study aims to investigate the impact of smoking on both total life expectancy (TLE) and disability-free life expectancy (DFLE) and the variations in such effects by educational level in China. METHODS: Data were drawn from the China Health and Retirement Longitudinal Study (CHARLS), 2011-2018, with a total sample of 16,859 individuals aged 45 years or older involved in the final analysis. The Activities of Daily Living (ADL) scale was used to measure disability, and the population-based multistate life table method was used to estimate the differences in TLE and DFLE by smoking status and educational attainment. RESULTS: At baseline, 28.9% of participants were current smokers, 8.5% were former smokers, and 62.6% never smoked. Approximately 5.6% were identified with ADL disability. Both current smokers and former smokers experienced lower TLE and DFLE than never smokers, and such differences were particularly prominent among men. Intriguingly, former smokers manifested a lower DFLE for both sexes and a lower TLE among women, though a longer TLE among men, compared with current smokers. Similar differences in TLE and DFLE by smoking status were observed for groups with different levels of education. CONCLUSION: Never smokers live longer and healthier than current smokers and persons who quit smoking. Smoking was associated with greater reductions in TLE and DFLE among men. However, educational attainment might not moderate the adverse effect of smoking on both fatal and nonfatal conditions in the context of China. These findings have implications for disability prevention, aged care provision and informing policies of healthy aging for China and elsewhere.

Development and validation of a prospective questionnaire for assessing oily sensitive skin.

BACKGROUND: Skin type has a strong influence on how sensitive skin develops, with oily skin accounting for a larger proportion of sensitive skin. However, there has not been a scientifically sound questionnaire for determining oily sensitive (OS)-type skin in prior studies. OBJECTIVES: In order to identify OS-type skin in the general population, we therefore intend to create an OS-type skin evaluation questionnaire, develop various thresholds through data analysis and classify skin based on two dimensions of sensitivity and oiliness. METHODS: A questionnaire with questions regarding subjects' basic information, skin oiliness and skin sensitivity was given to each individual who participated in the study (n = 1297). To define the thresholds for OS-type skin, receiver-operating characteristic (ROC) curves were generated. The results of the lactic acid stinging test (LAST) and noninvasive instrument information obtained were compared with the thresholds mentioned above to verify the effectiveness of this tool. RESULTS: According to the ROC curves, questionnaire cut-off values of 11.5, 20.5 and 29.5 can be used to detect mildly, moderately and severely sensitive skin, respectively. In addition, the questionnaire cut-off values of 22.5 and 31.5 can be used to detect moderately and severely oily skin, respectively. According to our study, the four sensitive-skin groups' LAST scores differed significantly from one another, while the skin sebum levels differed significantly between the three oily groups. Additionally, the EI and LAST scores were significantly correlated with skin sensitivity levels, whereas sebum, moisture and EI were positively correlated with skin oiliness levels. CONCLUSIONS: We developed an OS-type skin evaluation questionnaire that has been tested and shown scientifically to be a promising method for evaluating OS-type skin and to completely examine the traits of sensitive and oily skin.

CONTEXTE: Le type de peau a une forte influence sur la sensibilité de la peau, avec une peau grasse représentant une plus grande proportion de peaux sensibles. Cependant, il n'y a pas eu de questionnaire scientifiquement fiable pour déterminer le type de peau sensible grasse (OS) dans les études antérieures. OBJECTIFS: Afin d'identifier la peau grasse et sensible dans la population générale, nous avons donc l'intention de créer un questionnaire d'évaluation de la peau grasse et sensible, d'élaborer différents seuils par l'analyse des données et de catégoriser à partir de deux dimensions de sensibilité et d'état huileux. MÉTHODES: Un questionnaire comprenant des questions sur les informations de base des sujets, la sécrétion de sébum de la peau et la sensibilité cutanée a été distribué à chaque individu ayant participé à l'étude (n = 1297). Pour définir les seuils des peaux grasse et sensible, des courbes sensibilité/spécificité (receiver-operating characteristic, ROC) ont été générées. Les résultats du test de picotement à l'acide lactique (LAST) et les informations obtenues à l'aide d'instruments non invasifs ont été comparés aux seuils mentionnés ci-dessus pour vérifier l'efficacité de cet outil. RÉSULTATS: Selon les courbes ROC, des valeurs limites du questionnaire de 11,5, 20,5 et 29,5 peuvent être utilisées pour détecter une sensibilité cutanée légère, modérée et sévère, respectivement. De plus, les valeurs de seuil du questionnaire de 22,5 et 31,5 peuvent être utilisées pour détecter respectivement une peau modérément et sévèrement grasse. Selon notre étude, les scores LAST des quatre groupes à peau sensible différaient significativement les uns des autres, tandis que les taux de sébum cutané différaient significativement entre les trois groupes à peau grasse. De plus, les scores IE et LAST étaient significativement corrélés avec les taux de sensibilité cutanée, tandis que le sébum, l'humidité et l'IE étaient positivement corrélés avec les taux de graisse cutané. CONCLUSIONS: Nous avons développé un questionnaire d'évaluation de la peau grasse et sensible qui a été testé et qui s'est avéré scientifiquement être une méthode prometteuse pour évaluer la peau grasse et sensible et pour examiner complètement les caractéristiques de la peau sensible et grasse.

Influencing factors and improvement methods of coronary artery plaque evaluation in CT.

Accurate evaluation of the nature and composition of coronary plaque involves clinical follow-up and prognosis. Coronary CT angiography is the most commonly non-invasive method for plaque evaluation, however, the qualitative and quantitative evaluation of plaque based on CT value is inaccurate, due to the influence of luminal attenuation, tube voltage, parameter setting and the subjectivity.

[The efficacy of iRoot BP plus in the treatment of adult carious pulp exposure and its impact on pulp blood flow].

PURPOSE: To explore the efficacy of iRoot BP plus in the treatment of adult carious pulp exposure and its impact on pulp blood flow. METHODS: A total of 126 cases of 156 permanent teeth from adult patients with carious pulp exposure who were treated from January 2020 to January 2022 were selected, the patients were divided into experimental group(63 cases with 79 permanent teeth) and control group(63 cases with 77 permanent teeth) by the envelope method. The experimental group was treated with iRoot BP plus, while the control group was treated with mineral trioxide polymer. The differences in treatment effectiveness, operation time, and tooth discoloration between the two groups were observed. Statistical analysis was performed with SPSS 22.0 software package. RESULTS: There was no significant difference in treatment success rates between the experimental group and the control group at 3, 6, and 12 months after surgery(P＞0.05). The operating time for each capsule in the experimental group was (2.53±0.41) min, which was significantly shorter than that in the control group(P＜0.05). The incidence of tooth discoloration in the experimental group at 12 months after surgery was 3.80%, which was significantly lower than that in the control group (P＜0.05). The bite force quotient and masticatory efficiency of the experimental group 12 months after operation were (16.65±1.14) Ibs and (94.45±5.65)%, which were significantly higher than those of the control group(P＜0.05). CONCLUSIONS: IRoot BP plus has good efficacy in the treatment of adult carious pulp exposure, with advantages such as convenient operation, less tooth discoloration, less inflammatory reactions and stable pulp blood flow after decline.

The role of ventral hippocampal-medial prefrontal glutamatergic pathway on the non-affected side in post-stroke cognitive impairment.

Elucidate the pathogenesis mechanism of post-stroke cognitive impairment (PSCI) can help to develop precision interventions. In this study, we established a mouse model of PSCI using the photochemical method, and behavioral tests including Y-maze and Novel object recognition task for accessing cognitive impairment were observed at week 2 post-stroke. Besides, synaptic plasticity, theta nerve oscillatory and the activity of glutamatergic neurons related to the ventral hippocampal-medial prefrontal glutamatergic neural pathway in the non-affected hemisphere (contralateral hemisphere to the lesion site) were observed. The result indicated the cognitive function declined at week 2 post-stroke. Synaptic plasticity, theta nerve oscillatory synchronization and the activity of glutamatergic neurons of the ventral hippocampal-medial prefrontal glutamatergic neural pathway in the non-affected hemisphere was down-regulated in the PSCI group compared to those of the SHAM group. Therefore we concluded that the declined function of the ventral hippocampal-medial prefrontal glutamatergic pathway in the non-affected hemisphere is a biomarker in the occurrence of cognitive dysfunction after stroke.

Clinical and CT Quantitative Features for Predicting Liver Metastases in Patients with Pancreatic Neuroendocrine Tumors: A Study with Prospective/External Validation.

RATIONALE AND OBJECTIVES: We aimed to evaluate clinical characteristics and quantitative CT imaging features for the prediction of liver metastases (LMs) in patients with pancreatic neuroendocrine tumors (PNETs). METHODS: Patients diagnosed with pathologically confirmed PNETs were included, 133 patients were in the training group, 22 patients in the prospective internal validation group, and 28 patients in the external validation group. Clinical information and quantitative features were collected. The independent variables for predicting LMs were confirmed through the implementation of univariate and multivariate logistic analyses. The diagnostic performance was evaluated by conducting receiver operating characteristic curves for predicting LMs in the training and validation groups. RESULTS: PNETs with LMs demonstrated significantly larger diameter and lower arterial/portal tumor-parenchymal enhancement ratio, arterial/portal absolute enhancement value (AAE/PAE value) (p < 0.05). After multivariate analyses, A high level of tumor marker (odds ratio (OR): 5.32; 95% CI, 1.54-18.35), maximum diameter larger than 24.6 mm (OR: 7.46; 95% CI, 1.70-32.72), and AAE value ≤ 51 HU (OR: 4.99; 95% CI, 0.93-26.95) were independent positive predictors of LMs in patients with PNETs, with area under curve (AUC) of 0.852 (95%CI, 0.781-0.907). The AUCs for prospective internal and external validation groups were 0.883 (95% CI, 0.686-0.977) and 0.789 (95% CI, 0.602-0.916), respectively. CONCLUSION: Tumor marker, maximum diameter and absolute enhancement value in arterial phase were independent predictors with good predictive performance for the prediction of LMs in patients with PNETs. Combining clinical and quantitative features may facilitate the attainment of good predictive precision in predicting LMs.

Tyrosol regulates hepatic lipid metabolism in high-fat diet-induced NAFLD mice.

This study aimed to elucidate the effect of tyrosol (TYR) on the amelioration of nonalcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed a low-fat diet (LFD), a high-fat diet (HFD), or a HFD supplemented with 0.025% (w/w) TYR (TYR) for 16 weeks. Following a 16-week intervention, the TYR cohort exhibited diminished final body weight and hepatic lipid accumulation, compared to HFD fed mice. Liver metabolomics analysis revealed that TYR increased the hepatic levels of spermidine, taurine, linoleic acid, malic acid and eicosapentaenoic acid (EPA), indicating the beneficial effect of TYR on lipid homeostasis. Using molecular docking analysis and the luciferase assay, we found that TYR acts as a ligand and binds with peroxisome proliferator-activated receptor-α (PPARα), which plays a pivotal role in the modulation of hepatic lipid metabolism, thereby activating the transcription of downstream genes. Our results suggest that TYR alleviates NAFLD in HFD-fed mice probably by the modulation of the PPARα signaling pathway.

Mitochondrial dysfunction: mechanisms and advances in therapy.

Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation and disease progression. Particularly, mitochondrial dysfunctions are identified in many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer. However, the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among the most important therapeutic targets. In recent years, strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical trials. Advanced intervention such as using healthy mitochondria to replenish or replace damaged mitochondria, has shown promise in preclinical trials of various diseases. Mitochondrial components, including mtDNA, mitochondria-located microRNA, and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue injuries. Here, we review current knowledge of mitochondrial pathophysiology in concrete examples of common diseases. We also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies, as well as the clinical translational situation of related pharmacology agents. Finally, this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.

Unveiling the role of PYGB in pancreatic cancer: a novel diagnostic biomarker and gene therapy target.

PURPOSE: Pancreatic cancer (PC) is a highly malignant tumor that poses a severe threat to human health. Brain glycogen phosphorylase (PYGB) breaks down glycogen and provides an energy source for tumor cells. Although PYGB has been reported in several tumors, its role in PC remains unclear. METHODS: We constructed a risk diagnostic model of PC-related genes by WGCNA and LASSO regression and found PYGB, an essential gene in PC. Then, we explored the pro-carcinogenic role of PYGB in PC by in vivo and in vitro experiments. RESULTS: We found that PYGB, SCL2A1, and SLC16A3 had a significant effect on the diagnosis and prognosis of PC, but PYGB had the most significant effect on the prognosis. Pan-cancer analysis showed that PYGB was highly expressed in most of the tumors but had the highest correlation with PC. In TCGA and GEO databases, we found that PYGB was highly expressed in PC tissues and correlated with PC's prognostic and pathological features. Through in vivo and in vitro experiments, we found that high expression of PYGB promoted the proliferation, invasion, and metastasis of PC cells. Through enrichment analysis, we found that PYGB is associated with several key cell biological processes and signaling pathways. In experiments, we validated that the MAPK/ERK pathway is involved in the pro-tumorigenic mechanism of PYGB in PC. CONCLUSION: Our results suggest that PYGB promotes PC cell proliferation, invasion, and metastasis, leading to poor patient prognosis. PYGB gene may be a novel diagnostic biomarker and gene therapy target for PC.

A study on the role of Taxifolin in inducing apoptosis of pancreatic cancer cells: screening results using weighted gene co-expression network analysis.

Pancreatic adenocarcinoma (PAAD) is a frequent malignant tumor in the pancreas. The incomplete understanding of cancer etiology and pathogenesis, as well as the limitations in early detection and diagnostic methods, have created an urgent need for the discovery of new therapeutic targets and drugs to control this disease. As a result, the current therapeutic options are limited. In this study, the weighted gene co-expression network analysis (WGCNA) method was employed to identify key genes associated with the progression and prognosis of pancreatic adenocarcinoma (PAAD) patients in the Gene Expression Profiling Interactive Analysis (GEPIA) database. To identify small molecule drugs with potential in the treatment of pancreatic adenocarcinoma (PAAD), we compared key genes to the reference dataset in the CMAP database. First, we analyzed the antitumor properties of small molecule drugs using cell counting kit-8 (CCK-8), AO/EB and Transwell assays. Subsequently, we integrated network pharmacology with molecular docking to explore the potential mechanisms of the identified molecules' anti-tumor effects. Our findings indicated that the progression and prognosis of PAAD patients in pancreatic cancer were associated with 11 genes, namely, DKK1, S100A2, CDA, KRT6A, ITGA3, GPR87, IL20RB, ZBED2, PMEPA1, CST6, and MUC16. These genes were filtered based on their therapeutic potential through comparing them with the reference dataset in the CMAP database. Taxifolin, a natural small molecule drug with the potential for treating PAAD, was screened by comparing it with the reference dataset in the CMAP database. Cell-based experiments have validated the potential of Taxifolin to facilitate apoptosis in pancreatic cancer cells while restraining their invasion and metastasis. This outcome is believed to be achieved via the HIF-1 signaling pathway. In conclusion, this study provided a theoretical basis for screening genes related to the progression of pancreatic cancer and discovered potentially active small molecule drugs. The experimental results confirm that Taxifolin has the ability to promote apoptosis in pancreatic cancer cells.

Determining the Optimal Stimulation Sessions for TMS-Induced Recovery of Upper Extremity Motor Function Post Stroke: A Randomized Controlled Trial.

To find out the optimal treatment sessions of repetitive transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) for upper extremity dysfunction after stroke during the 6-week treatment and to explore its mechanism using motor-evoked potentials (MEPs) and resting-state functional magnetic resonance imaging (rs-fMRI), 72 participants with upper extremity motor dysfunction after ischemic stroke were randomly divided into the control group, 10-session, 20-session, and 30-session rTMS groups. Low-frequency (1 Hz) rTMS over the contralesional M1 was applied in all rTMS groups. The motor function of the upper extremity was assessed before and after treatment. In addition, MEPs and rs-fMRI data were analyzed to detect its effect on brain reorganization. After 6 weeks of treatment, there were significant differences in the Fugl-Meyer Assessment of the upper extremity and the Wolf Motor Function Test scores between the 10-session group and the 30-session group and between the 20- and 30-session groups and the control group, while there was no significant difference between the 20-session group and the 30-session group. Meanwhile, no significant difference was found between the 10-session group and the control group. The 20-session group of rTMS decreased the excitability of the contralesional corticospinal tract represented by the amplitudes of MEPs and enhanced the functional connectivity of the ipsilesional M1 or premotor cortex with the the precentral gyrus, postcentral gyrus, and cingulate gyrus, etc. In conclusion, the 20-session of rTMS protocol is the optimal treatment sessions of TMS for upper extremity dysfunction after stroke during the 6-week treatment. The potential mechanism is related to its influence on the excitability of the corticospinal tract and the remodeling of corticomotor functional networks.