Isolation Techniques, Structural Characteristics, and Pharmacological Effects of Phellinus Polysaccharides: A Review.

Phellinus is a precious perennial medicinal fungus. Its polysaccharides are important bioactive components, and their chemical composition is complex. The polysaccharides are mainly extracted from the fruiting body and mycelium. The yield of the polysaccharides is dependent on the extraction method. They have many pharmacological activities, such as antitumor, immunomodulatory, antioxidant, hypoglycemic, anti-inflammatory, etc. They are also reported to show minor toxic and side effects. Many studies have reported the anticancer activity of Phellinus polysaccharides. This review paper provides a comprehensive examination of the current methodologies for the extraction and purification of Phellinus polysaccharides. Additionally, it delves into the structural characteristics, pharmacological activities, and mechanisms of action of these polysaccharides. The primary aim of this review is to offer a valuable resource for researchers, facilitating further studies on Phellinus polysaccharides and their potential applications.

Disruption of TIGAR-TAK1 alleviates immunopathology in a murine model of sepsis.

Macrophage-orchestrated inflammation contributes to multiple diseases including sepsis. However, the underlying mechanisms remain to be defined clearly. Here, we show that macrophage TP53-induced glycolysis and apoptosis regulator (TIGAR) is up-regulated in murine sepsis models. When myeloid Tigar is ablated, sepsis induced by either lipopolysaccharide treatment or cecal ligation puncture in male mice is attenuated via inflammation inhibition. Mechanistic characterizations indicate that TIGAR directly binds to transforming growth factor ß-activated kinase (TAK1) and promotes tumor necrosis factor receptor-associated factor 6-mediated ubiquitination and auto-phosphorylation of TAK1, in which residues 152-161 of TIGAR constitute crucial motif independent of its phosphatase activity. Interference with the binding of TIGAR to TAK1 by 5Z-7-oxozeaenol exhibits therapeutic effects in male murine model of sepsis. These findings demonstrate a non-canonical function of macrophage TIGAR in promoting inflammation, and confer a potential therapeutic target for sepsis by disruption of TIGAR-TAK1 interaction.

Association between Postmenopausal Osteoporosis and IL-6、TNF-α: A Systematic Review and A Meta-analysis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) greatly increases the risk of bone fracture in postmenopausal women, seriously affects the quality of life of patients, and is an important global public health problem. Persistent chronic systemic inflammation may be involved in the change process of PMOP, and many cytokines, such as TNF-alpha and Interleukin-6, play an important role in the inflammatory response. Therefore, This study takes commonly representative inflammatory factors as indicators to better determine their role in PMOP patients by means of databases from multiple studies for use in Meta-analysis. METHOD: Systematic review of studies on the relationship between PMOP and markers of inflammation: interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). Each effect size was expressed with a 95% confidence interval (CI), and I2 quantified the heterogeneity. The final results were aggregated and evaluated using random or fixed effects models. RESULTS: Twenty-one original studies were identified. There were twenty studies involving IL-6 and eleven involving TNF-α. Overall, The levels of IL-6[MD=23.93, 95%CI (19.65, 28.21)] and TNF-α[MD=2.9, 95%CI (2.37, 3.44)] were increased in PMOP patients compared with postmenopausal women without osteoporosis; The levels of IL-6[MD=42.4, 95%CI (38.62, 46.19)] and TNF-α[MD=0.40, 95%CI (0.36, 0.44)] were significantly higher than those of premenopausal healthy women. CONCLUSIONS: The levels of inflammatory cytokines IL-6 and TNF-α were significantly increased in PMOP patients compared with controls, suggesting that persistent chronic inflammatory reaction exists in PMOP patients, which may be an important cause of aggravated osteoporosis in postmenopausal women. Therefore, the level of IL-6 and TNF-α indexes may be of great significance for the early prevention, diagnosis, treatment and prognosis assessment of PMOP.

The Evolution and Future Trends of Stromal Vascular Fraction: A Bibliometric Analysis.

The heterogeneous population of cells obtained from processed adipose tissue, known as stromal vascular fraction (SVF), exhibits immunomodulatory and angiogenic properties. The therapeutic efficacy of SVF has been substantiated in numerous diseases, instilling hope for its clinical application as a cellular therapy. This study aims to provide a comprehensive analysis of the scholarly literature on SVF, including its worldwide progression, highlighting significant literatures, temporal development, research clusters, current active topics, and emerging trends. The combination of CiteSpace, HistCite Pro, and VOS Viewer tools was used to analyze the SVF literature. The overall panorama of the field is elucidated in terms of publication count, timeline, institutional distribution, journal coverage, and authors' contributions. In addition, this analysis explores the literature and keywords through the lens of co-occurrence, citation, and co-citation frequencies. Clustering algorithms are used to track the trajectory of the literature further, providing insight into its development. The findings offer a comprehensive overview of the progress made in the SVF field, highlighting distinct phases of development: the "Seedling period" from 1980 to 2010, the "Panicle period" from 2011 to 2016, and the "Flowering period" from 2017 to 2023. Within these periods, the evolution of 10 clusters is unraveled, encompassing topics such as vascular disease, CD34 expression, adipose tissue macrophage in 2013, cell-assisted lipotransfer, and knee osteoarthritis. In summary, this bibliometric study, conducting a quantitative analysis of publications in SVF research, encompasses a global overview of research, an analysis of pivotal literature in the field, research hotspots, and emerging frontiers.

[Diagnostic value and interventional treatment of elbow cyst by high frequency ultrasound].

OBJECTIVE: To study and analyze the diagnostic value and interventional treatment value of high-frequency ultrasound for elbow cyst. METHODS: From February 2018 to February 2021, the data of 60 patients with elbow cyst treated by high-frequency ultrasound interventional therapy were retrospectively analyzed, including 30 males and 30 females with an average age of (30.93±5.32) years old ranging from 20 to 54 years old. The course of disease ranged from 1 to 10 years with an average of (3.45±0.25) years. High-frequency ultrasound features of all patients were analyzed. The clinical efficacy, the occurrence of adverse events and the changes of psychological status before and after treatment were analyzed. RESULTS: In 60 cases of elbow cyst, the cyst size was from 6 mm×7 mm to 111 mm×60 mm. The characteristics of ultrasonic images included such as most of the morphology was regular, which was round or oval, and a few were irregular;the boundary was clear, there was a capsule wall, most of the inside of the capsule was good, no echo;when accompanied by bleeding or infection, small dense points can be seen floating;the cystic wall of the patients with long course of disease was coarser, and the internal light bands were separated, showing multilocular shape;no significant blood flow signal was observed. Final results involved olecranon bursa cysts in 19 cases, annular ligament cysts in 10 cases, radial bursa cysts in 9 cases, accessory ligament cysts in 7 cases, epidermoid cysts in 4 cases, ganglion cysts in 6 cases, nerve sheath cysts in 5 cases. After treatment, 33 cases were cured, 16 cases had obvious effect, 11 cases were improved, 0 cases were invalid. After treatment, mild adverse events occurred in 1 case, moderate adverse events in 1 case, and severe adverse events in 0 cases, with a total incidence of 3.33% (2/60). After treatment, positive affect score (38.04±1.74) was higher than that before treatment (35.92±2.34), and negative affect score (24.61±1.51) was lower than that before treatment (30.15±3.46), with statistical significance(P<0.05). CONCLUSION: High-frequency ultrasound has high diagnostic value for elbow cyst, and it has ideal effect in interventional therapy.

The prevalence of osteoporotic fractures in the elderly in China: a systematic review and meta-analysis.

BACKGROUND: Prevalence information is the first step in developing preventive procedures or health services. This study was conducted to systematically evaluate the epidemiology of osteoporotic fractures in Chinese elderly aged ≥ 60 years and to provide evidence-based evidence for the prevention and treatment of osteoporotic fractures. METHODS: We identified relevant studies by searching the literature published in PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang Data, and VIP databases from the establishment of the database until August 2022. We used a random-effects model to obtain prevalence estimates and identified sources of heterogeneity and comparisons of prevalence among different groups through subgroup analysis and sensitivity analysis. RESULTS: A total of 29 articles were included in this study, and the prevalence of osteoporosis fractures in elderly Chinese was high (18.9%). The prevalence has increased significantly over the past decade (from 13.2% in 2000-2010 to 22.7% in 2012-2022). The prevalence of osteoporosis is higher in women than in men (18.5% vs 14.3%) and increases with age. The northern region was higher than the southern region (20.3% vs 18.9%), and the spine, hip, and distal forearm were the most common sites of fracture. CONCLUSION: The prevalence of osteoporotic fractures in the Chinese elderly is 18.9%, and timely prevention and treatment are necessary.

Severe pneumonia induces immunosenescence of T cells in the lung of mice.

Severe pneumonia may induce sequelae and accelerated aging process even after the person has recovered. However, the underline mechanism is not very clear. More research is needed to fully understand the long-term effects of severe pneumonia. In this study, we found that mice recovered from severe pneumonia showed lung immunosenescence, which was characterized by a bias naive-memory balance of T lymphocytes in the lung. The reduction of naïve T cells is associated with the diminished immune response to cancer or external new antigens, which is one of the key changes that occurs with age. Our results also indicate the link between severe pneumonia and aging process, which is mediated by the disrupted T cells homeostasis in the lungs after pneumonia.

Machine learning-based algorithms to predict severe psychological distress among cancer patients with spinal metastatic disease.

BACKGROUND CONTEXT: Metastatic spinal disease is an advanced stage of cancer patients and often suffer from terrible psychological health status; however, the ability to estimate the risk probability of this adverse outcome using current available data is very limited. PURPOSE: The goal of this study was to propose a precise model based on machine learning techniques to predict psychological status among cancer patients with spinal metastatic disease. STUDY DESIGN/SETTING: A prospective cohort study. PATIENT SAMPLE: A total of 1043 cancer patients with spinal metastatic disease were included. OUTCOME MEASURES: The main outcome was severe psychological distress. METHODS: The total of patients was randomly divided into a training dataset and a testing dataset on a ratio of 9:1. Patients' demographics, lifestyle choices, cancer-related features, clinical manifestations, and treatments were collected as potential model predictors in the study. Five machine learning algorithms, including XGBoosting machine, random forest, gradient boosting machine, support vector machine, and ensemble prediction model, as well as a logistic regression model were employed to train and optimize models in the training set, and their predictive performance was assessed in the testing set. RESULTS: Up to 21.48% of all patients who were recruited had severe psychological distress. Elderly patients (p<0.001), female (p =0.045), current smoking (p=0.002) or drinking (p=0.003), a lower level of education (p<0.001), a stronger spiritual desire (p<0.001), visceral metastasis (p=0.005), and a higher Eastern Cooperative Oncology Group (ECOG) score (p<0.001) were significantly associated with worse psychological health. With an area under the curve (AUC) of 0.865 (95% CI: 0.788-0.941) and an accuracy of up to 0.843, the gradient boosting machine algorithm performed best in the prediction of the outcome, followed by the XGBooting machine algorithm (AUC: 0.851, 95% CI: 0.768-0.934; Accuracy: 0.826) and ensemble prediction (AUC: 0.851, 95% CI: 0.770-0.932; Accuracy: 0.809) in the testing set. In contrast, the AUC of the logistic regression model was only 0.836 (95% CI: 0.756-0.916; Accuracy: 0.783). CONCLUSIONS: Machine learning models have greater predictive power and can offer useful tools to identify individuals with spinal metastatic disease who are experiencing severe psychological distress.

Treatment of patients with metastatic epidural spinal cord compression using an enhanced recovery after surgery program.

Purpose: The aims of this study were to introduce a new medical, pathway based on the concept of "enhanced recovery after surgery" (ERAS) for patients with metastatic epidural spinal cord compression (MESCC), and to test whether the ERAS program could improve clinical metrics among such patients. Methods: Data from patients with MESCC (n = 98), collected between December 2016 and December 2019 (Non-ERAS cohort), and from 86 patients with metastatic epidural spinal cord compression collected between January 2020 and December 2022 (ERAS cohort), were retrospectively analyzed. Patients were treated by decompressive surgery combined with transpedicular screw implantation and internal fixation. Patient baseline clinical characteristics were collected and compared between the two cohorts. Surgical outcomes analyzed included operation time; intraoperative blood loss; postoperative length of hospital stay; time to ambulation, regular diet, urinary catheter removal, and radiation therapy; perioperative complications; anxiety; depression; and satisfaction with treatment. Results: No significant differences in clinical characteristics were found between the non-ERAS and enhanced recovery after surgery cohorts (all p > 0.050), indicating that the two cohorts were comparable. Regarding surgical outcomes, the enhanced recovery after surgery cohort had significantly less intraoperative blood loss (p < 0.001); shorter length of postoperative hospital stay (p < 0.001); shorter time to ambulation (p < 0.001), regular diet (p < 0.001), urinary catheter removal (p < 0.001), radiation administration (p < 0.001), and systemic internal therapy (p < 0.001); lower perioperative complication rate (p = 0.024); less postoperative anxiety (p = 0.041); and higher score for satisfaction with treatment (p < 0.001); whereas operation time (p = 0.524) and postoperative depression (p = 0.415) were similar between the two cohorts. Compliance analysis demonstrated that ERAS interventions were successfully conducted in the vast majority of patients. Conclusion: The enhanced recovery after surgery intervention is beneficial to patients with metastatic epidural spinal cord compression, according to data on intraoperative blood loss; length of hospital stay; time to ambulation, regular diet, urinary catheter removal, radiation exposure, and systemic internal therapy; perioperative complication; alleviation of anxiety; and improvement of satisfaction. However, clinical trials to investigate the effect of enhanced recovery after surgery are needed in the future.

A machine learning-Based model to predict early death among bone metastatic breast cancer patients: A large cohort of 16,189 patients.

Purpose: This study aims to develop a prediction model to categorize the risk of early death among breast cancer patients with bone metastases using machine learning models. Methods: This study examined 16,189 bone metastatic breast cancer patients between 2010 and 2019 from a large oncological database in the United States. The patients were divided into two groups at random in a 90:10 ratio. The majority of patients (n = 14,582, 90%) were served as the training group to train and optimize prediction models, whereas patients in the validation group (n = 1,607, 10%) were utilized to validate the prediction models. Four models were introduced in the study: the logistic regression model, gradient boosting tree model, decision tree model, and random forest model. Results: Early death accounted for 17.4% of all included patients. Multivariate analysis demonstrated that older age; a separated, divorced, or widowed marital status; nonmetropolitan counties; brain metastasis; liver metastasis; lung metastasis; and histologic type of unspecified neoplasms were significantly associated with more early death, whereas a lower grade, a positive estrogen receptor (ER) status, cancer-directed surgery, radiation, and chemotherapy were significantly the protective factors. For the purpose of developing prediction models, the 12 variables were used. Among all the four models, the gradient boosting tree had the greatest AUC [0.829, 95% confident interval (CI): 0.802-0.856], and the random forest (0.828, 95% CI: 0.801-0.855) and logistic regression (0.819, 95% CI: 0.791-0.847) models came in second and third, respectively. The discrimination slopes for the three models were 0.258, 0.223, and 0.240, respectively, and the corresponding accuracy rates were 0.801, 0.770, and 0.762, respectively. The Brier score of gradient boosting tree was the lowest (0.109), followed by the random forest (0.111) and logistic regression (0.112) models. Risk stratification showed that patients in the high-risk group (46.31%) had a greater six-fold chance of early death than those in the low-risk group (7.50%). Conclusion: The gradient boosting tree model demonstrates promising performance with favorable discrimination and calibration in the study, and this model can stratify the risk probability of early death among bone metastatic breast cancer patients.

A novel nomogram to stratify quality of life among advanced cancer patients with spinal metastatic disease after examining demographics, dietary habits, therapeutic interventions, and mental health status.

BACKGROUND: It would be very helpful to stratify patients and direct patient selection if risk factors for quality of life were identified in a particular population. Nonetheless, it is still challenging to forecast the health-related quality of life among individuals with spinal metastases. The goal of this study was to stratify patient's populations for whom the assessment of quality of life should be encouraged by developing and validating a nomogram to predict the quality of life among advanced cancer patients with spine metastases. METHODS: This study prospectively analyzed 208 advanced cancer patients with spine metastases, and collected their general characteristics, food preferences, addictions, comorbidities, therapeutic strategies, and mental health status. The functional assessment of cancer therapy-general (FACT-G) and hospital anxiety and depression scale (HADS) were used to assess quality of life and mental health, respectively. The complete cohort of patients was randomly divided into two groups: a training set and a validation set. Patients from the training set were conducted to train and develop a nomogram, while patients in the validation set were performed to internally validate the nomogram. The nomogram contained significant variables discovered using the least absolute shrinkage and selection operator (LASSO) approach in conjunction with 10-fold cross-validation. The nomogram's predictive ability was assessed utilizing discrimination, calibration, and clinical usefulness. Internal validation was also completed using the bootstrap method after applying 500 iterations of procedures. A web calculator was also developed to promote clinical practice. RESULTS: Advance cancer patients with spinal metastases had an extremely low quality of life, as indicated by the average FACT-G score of just 60.32 ± 20.41. According to the LASSO and 10-fold cross-validation, Eastern Cooperative Oncology Group (ECOG) score, having an uncompleted life goal, preference for eating vegetables, chemotherapy, anxiety status, and depression status were selected as nomogram predictors. In the training set, the area under the receiver operating characteristic curve (AUROC) was 0.90 (95% CI: 0.84-0.96), while in the validation set, it was 0.85 (95% CI: 0.78-0.93). They were 0.50 (95% CI: 0.41-0.58) and 0.44 (95% CI: 0.33-0.56), respectively, for the discrimination slopes. The nomogram had favorable capacity to calibrate and was clinically useful, according to the calibration curve and decision curve analysis. When compared to patients in the low-risk group, patients in the high-risk group were above four times more likely to experience a poor quality of life (82.18% vs. 21.50%, P < 0.001). In comparison to patients in the low-risk group, patients in the high-risk group also exhibited significant higher levels of anxiety and depression. The webpage for the web calculator was https://starshiny.shinyapps.io/DynNomapp-lys/ . CONCLUSIONS: This study suggests a nomogram that can be applied as a practical clinical tool to forecast and categorize the quality of life among patients with spine metastases. Additionally, patients with poor quality of life experience more severe anxiety and depression. Effective interventions should be carried out as soon as possible, especially for patients in the high-risk group, to improve their quality of life and mental health condition.

FLASH X-ray spares intestinal crypts from pyroptosis initiated by cGAS-STING activation upon radioimmunotherapy.

DNA-damaging treatments such as radiotherapy (RT) have become promising to improve the efficacy of immune checkpoint inhibitors by enhancing tumor immunogenicity. However, accompanying treatment-related detrimental events in normal tissues have posed a major obstacle to radioimmunotherapy and present new challenges to the dose delivery mode of clinical RT. In the present study, ultrahigh dose rate FLASH X-ray irradiation was applied to counteract the intestinal toxicity in the radioimmunotherapy. In the context of programmed cell death ligand-1 (PD-L1) blockade, FLASH X-ray minimized mouse enteritis by alleviating CD8+ T cell-mediated deleterious immune response compared with conventional dose rate (CONV) irradiation. Mechanistically, FLASH irradiation was less efficient than CONV X-ray in eliciting cytoplasmic double-stranded DNA (dsDNA) and in activating cyclic GMP-AMP synthase (cGAS) in the intestinal crypts, resulting in the suppression of the cascade feedback consisting of CD8+ T cell chemotaxis and gasdermin E-mediated intestinal pyroptosis in the case of PD-L1 blocking. Meanwhile, FLASH X-ray was as competent as CONV RT in boosting the antitumor immune response initiated by cGAS activation and achieved equal tumor control in metastasis burdens when combined with anti-PD-L1 administration. Together, the present study revealed an encouraging protective effect of FLASH X-ray upon the normal tissue without compromising the systemic antitumor response when combined with immunological checkpoint inhibitors, providing the rationale for testing this combination as a clinical application in radioimmunotherapy.

Quality of Life and Mental Health Status Among Cancer Patients With Metastatic Spinal Disease.

This study aimed to investigate the quality of life and mental health status and further to identify relevant risk factors among advanced cancer patients with spine metastases. This study prospectively included and analyzed 103 advanced cancer patients with spine metastases. Patient's basic information, lifestyles, comorbidities, tumor characteristics, therapeutic strategies, economic conditions, quality of life, anxiety, and depression were collected. Patient's quality of life was assessed using the Functional Assessment of Cancer Therapy-General Scale (FACT-G), and anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). Subgroup analysis was performed based on different age groups, and a multivariate analysis was performed to test the ability of 20 potential risk factors to predict quality of life, anxiety, and depression. The mean total FACT-G score was only 61.38 ± 21.26. Of all included patients, 52.43% had skeptical or identified anxiety and 53.40% suffered from skeptical or identified depression. Patients had an age of 60 or more and <70 years had the lowest FACT-G score (54.91 ± 19.22), highest HADS anxiety score (10.25 ± 4.22), and highest HADS depression score (10.13 ± 4.94). After adjusting all other potential risk factors, age was still significantly associated with quality of life (OR = 0.57, 95%CI: 0.38-0.86, p < 0.01) and depression (OR = 1.55, 95%CI: 1.00-2.42, p = 0.05) and almost significantly associated with anxiety (OR = 1.52, 95%CI: 0.94-2.43, p = 0.08). Besides, preference to eating vegetables, time since knowing cancer diagnosis, surgical treatment at primary cancer, hormone endocrine therapy, and economic burden due to cancer treatments were found to be significantly associated with the quality of life. A number of comorbidities and economic burden due to cancer treatments were significantly associated with anxiety. Advanced cancer patients with spine metastases suffer from poor quality of life and severe anxiety and depression, especially among patients with an age of 60 or more and <70 years. Early mental health care and effective measures should be conducted to advanced cancer patients with spine metastases, and more attention should be paid to take care of patients with an age of 60 or more and <70 years in terms of their quality of life and mental health status.

[Experimental study on effect of complement C3 on bone formation observed by cell culture in vitro].

OBJECTIVE: To explore effect of lentivirus-mediated complement C3 silencing vector on the osteogenic ability of human B lymphocyte Raji-osteoblast cell line MG63 co-culture system and its mechanism. METHODS: The lentiviral complement C3 silencing vector was constructed and transfected into human B lymphocyte Raji to establish in vitro Raji-osteoblast cell line MG63 co-culture system. The cells were divided into blank control group (without special treatment), complement C3 silencing group (lentiviral complement C3 silencing vector transfection co-culture system) and model group(lentiviral vector transfection co-culture system). The expression of complement C3 in each group was detected by reverse transcription-polymerase chain reaction(RT-PCR) and Western-Blot at 24 h after culture, proliferation of MG63 cells was detected by CCK-8 at 0, 3, 6, 12, 24, 48 and 72 h, apoptosis of MG63 cells in each group was detected by flow cytometry at 24 h after culture, and alkaline phosphatase(AKP) activity of MG63 cells in each group was detected by AKP detection kit, and osteoprotegerin (OPG ) protein expression of MG63 cells in each group was detected by Western-Blot method. RESULTS: RT-PCR results showed that the expression level of C3 in complement C3 silencing group was lower than that in blank control group and model group, Western-Blot results showed that expression of C3 in complement C3 silencing group was lower than that in blank control group and model group, CCK-8 results showed that there was no difference in proliferation ability of MG63 among complement C3 silencing group and blank control group and model group at 3 and 6 h after culture;at 12 h after culture, proliferation ability of MG63 cells with C3 silencing was higher than that of blank control group and model group;at 24, 48 and 72 h after culture, proliferation ability of MG63 cell line with complement C3 silencing group were higher than that of blank control group and model group. Flow cytometry resluts showed that apoptosis of proliferation ability of MG63 cell line with complement C3 silencing group was lower than that of blank control group and model group;AKP detection kit suggested that AKP activity in complement C3 silencing group was higher than that in blank control group and model group, Western-Blot results showed that expression level of OPG protein in complement C3 silencing groupwas higher than that in blank control groupand model group. CONCLUSION: Silencing of complement C3 could enhance bone formation ability of osteoblast MG63, and it takes time to accumulate this ability. Complement C3 may affect osteogenesis by altering OPG / RANKL / RANK axis.

The effect of QiangGuYin on osteoporosis through the AKT/mTOR/autophagy signaling pathway mediated by CKIP-1.

Osteoporosis is a systemic bone disease characterized by decreased bone mass and deterioration of bone microstructure, which leads to increased bone fragility and increased risk of fractures. Casein kinase 2 interacting protein 1 (CKIP-1, also known as PLEKHO1) is involved in the biological process of bone formation, differentiation and apoptosis, and is a negative regulator of bone formation. QiangGuYin (QGY) is a famous TCM formula that has been widely used in China for the clinical treatment of postmenopausal osteoporosis for decades, but the effect in regulating CKIP-1 on osteoporosis is not fully understood. This study aimed to explore the potential mechanism of CKIP-1 participating in autophagy in bone cells through the AKT/mTOR signaling pathway and the regulatory effect of QGY. The results in vivo showed that QGY treatment can significantly improve the bone quality of osteoporotic rats, down-regulate the expression of CKIP-1, LC3II/I and RANKL, and up-regulated the expression of p62, p-AKT/AKT, p-mTOR/mTOR, RUNX2 and OPG. It is worth noting that the results in vitro confirmed that CKIP-1 interacts with AKT. By up-regulating the expression of Atg5 and down-regulating the p62, the level of LC3 (autophagosome) is increased, and the cells osteogenesis and differentiation are inhibited. QGY inhibits the combination of CKIP-1 and AKT in osteoblasts, activates the AKT/mTOR signaling pathway, inhibits autophagy, and promotes cell differentiation, thereby exerting an anti-osteoporosis effect. Therefore, QGY targeting CKIP-1 to regulate the AKT/mTOR-autophagy signaling pathway may represent a promising drug candidate for the treatment of osteoporosis.

Coupling programmed cell death 1-positive tumor-infiltrating T cells with anti-programmed cell death 1 antibody improves the efficacy of adoptive T-cell therapy.

BACKGROUND AIMS: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has shown great success in clinical trials. Programmed cell death 1 (PD-1)-expressing TILs show high specificity to autologous tumor cells. However, limited therapeutic efficiency is observed as a result of the tumor immune microenvironment (TIME). METHODS: Coupling PD-1+ex vivo-derived TILs with a monoclonal antibody against anti-PD-1 (aPD-1) reinvigorated the anti-tumor response of TILs against solid tumor without altering their high tumor targeting ability. RESULTS: Using a melanoma-bearing mouse model, PD-1+ TILs blocked with aPD-1 (PD-1+ TILs-aPD-1) exhibited a high capability for tumor targeting as well as improved anti-tumor response in TIME. Tumor growth was substantially delayed in the mice treated with PD-1+ TILs-aPD-1. CONCLUSIONS: The strategy utilizing TIL therapy coupled with immune checkpoint antibodies may extend to other therapeutic targets of ACT.