Ethnopharmacological relevance Chemotherapy-induced cardiotoxicity (CIC) is a serious and potentially life-threatening adverse effect associated with various chemotherapeutic agents, which has become the second leading cause of mortality among cancer survivors, following only the malignancy itself. However, effective preventive and therapeutic strategies for CIC remain limited. Accumulating evidence suggests that traditional Chinese Medicine (TCM) holds considerable promise in mitigating CIC through multiple pathways. However, research findings in this field are currently fragmented and lack systematic integration. Aim of the study To provide a comprehensive understanding of the current research status, emerging hotspots, developmental trends, and key challenges in the field of TCM interventions for CIC. Materials and Methods A systematic literature search was conducted using the China National Knowledge Infrastructure and Web of Science databases from January 1, 2000, to December 30, 2024. CiteSpace software was employed for visualization and knowledge mapping, enabling an in-depth analysis of research hotspots and trends in TCM interventions for CIC. Results A total of 532 relevant articles were retrieved, with the number of publications showing an increasing trend over the past two decades. Core authors such as Xie Ming, Ji Xuming, and Fu Chaomei, along with institutions like Beijing University of Chinese Medicine and the Shanghai University of Traditional Chinese Medicine, have played leading roles in this field. Co-occurrence and clustering of keywords revealed several core research domains, including tumor types associated with CIC, chemotherapeutic agents inducing CIC, and pharmacological mechanisms of TCM interventions. Burst keywords and timeline analyses highlighted emerging research hotspots and developmental trends, such as enhancing efficacy, reducing toxicity, and elucidating underlying mechanism, reflecting a shift toward mechanistic exploration and clinical translation. The article further discusses various TCM therapies—including classical TCM formulas, modern TCM formulas, single herbs, active compounds and injections—in alleviating CIC, as well as modern pharmacological insights and the current challenges in this field. Conclusion Over the past two decades, interest in TCM interventions for CIC has grown significantly. Current research hotspots focus on the pathophysiological mechanisms of CIC and emerging evidence supports the potential of multi-target TCM interventions as a strategy to mitigate CIC. However, key challenges remain, future research should prioritize the discovery of novel TCM candidates, in-depth mechanistic investigations, and the implementation of high-quality clinical trials to support evidence-based application of TCM in CIC prevention and treatment.

The lack of a favorable tumor immune microenvironment (TIME) results in limited response rates to immune checkpoint blockade (ICB) across human solid tumors, necessitating the development of novel combination strategies. In this study, we repurposed FK228, an US FDA-approved histone deacetylase inhibitor that is used clinically in non-solid tumor treatment, as a novel ICB sensitizer in solid tumors and revealed the diverse regulatory functions of FK228 in the TIME. FK228 serves as a novel necroptosis inducer in cancer cells by triggering endoplasmic reticulum stress. This in turn enhances the immunogenicity of cancer cells and increases the infiltration of tumor-killing immunocytes, including CD8+ T and natural killer cells, particularly activating tumor-infiltrated CD8+ T cells. Meanwhile, FK228 treatment shifts macrophages toward the pro-inflammatory phenotype. Moreover, the combined use of FK228 and a PD-L1 inhibitor significantly delay tumor growth and extend the survival of tumor bearing mice. Overall, our findings reveal new possibilities for the clinical application of FK228 in solid tumors and underscore the critical role of histone deacetylases in maintaining the immune-unfavorable TIME.

Hepatocellular carcinoma (HCC) accounts for more than 90% of all liver cases and often responds poorly to conventional treatment modalities, including multi-kinase inhibitors and immune checkpoint inhibitors. Therefore, it is urgent to develop novel therapeutic options for HCC. In this study, we conducted high-throughput screening of histone demethylase inhibitors for HCC treatment. Among the inhibitors examined, Corin significantly suppressed the growth and proliferation of two HCC cell lines, HepG2 and Hep3B cells without affecting non-cancerous cells. Based on the targets of Corin, we identified HDAC1/KDM1A dual-positive HCC as a novel subtype of HCC. Transcriptome profiling indicated that this novel subtype possessed rapid proliferation and high DNA damage repair capacity. Additionally, Corin treatment upregulated FDX1 expression to trigger Cuproptosis, which suppressed HCC proliferation. Conclusively, Corin possesses potential application as a novel and effective therapeutic option for HCC that simultaneously inhibits KDM1A and HDAC1 expression.

Less-aggressive lower-grade gliomas (LGGs) frequently transform into glioblastoma (GBM). Most previous studies of gliomas have not focused on LGG-original high-risk subpopulations, which may be one of the most critical hallmarks of glioma progression. In this study, LGG samples are collected to perform single-cell sequencing (scRNA-seq) and identify a unique cell subpopulation marked by CDC20, KIF20A and PTTG1, correlating with poor survival in multiple cohorts. Importantly, the CDC20+KIF20A+PTTG1+ cell subpopulation is strongly associated with transforming LGG to GBM according to scRNA-seq and multiplexed immunofluorescence staining assays. In vitro, ex vivo and in vivo investigations further hint that this cell subpopulation is critical to the proliferation and growth of gliomas, and is associated with the hypoxia core activation. Pharmaceutically and therapeutically, the inhibition of this cell subpopulation showed significant anti-tumor effects and effective enhancement of the Temozolomide treatment efficiency. These findings provide insights into the therapeutic strategies of glioma progression, highlighting promising ways to avoid early-stage gliomas developing into advanced gliomas.

Programmed death ligand 1 (PD-L1) is a protein expressed in hepatocellular carcinoma (HCC) that drives immune evasion by binding to programmed death receptor 1 (PD-1) on activated T cells. Understanding PD-L1 regulation is essential to understand the immunosuppressive microenvironment for antitumor immunity. We screened ribonucleic acid (RNA)-binding motif proteins (RBMs). RBM30 can enhance PD-L1 expression in HCC cells. In this study, we found that high RBM30 expression in tumor tissues can drive HCC tumor immune evasion and accelerate disease progression via increased PD-L1 transcription. We conducted multiple molecular and high-throughput assays to elucidate the intrinsic molecular mechanisms by which RBM30 upregulates PD-L1 expression in HCC. RBM30 binds to DNA near the transcriptional start site of STAT1 and recruits DOT1L to promote H3K79me3 enrichment, enhancing its accessibility to upregulate STAT1 transcription, consequently activating the PD-L1 transcription. This enhances PD-L1 expression to facilitate immune evasion. These findings reveal the vital role of RBM30 in HCC immune evasion.

Hyperactive ribosome biogenesis is a hallmark of tumours. Current ribosome-related studies are concentrated on cancer cells. Ribosomes can regulate both tumour and non-cancer cells within the tumour microenvironment, yet the immunomodulatory effects of cellular ribosome biogenesis blockade remain inadequately understood. We performed ribosome-targeting therapy utilizing CX-5461, an effective and acknowledged selective inhibitor of ribosome biogenesis, in immunocompetent in vivo models and submitted for single-cell RNA sequencing (scRNA-seq). Additional large-scale human scRNA-seq data, in-house clinical samples and assays were used. Ribosome inhibition elevated lymphoid cell cytotoxic granule secretion and macrophage pro-inflammation reprogramming. We uncovered unique immune cell subpopulations that are sensitive to ribosome biogenesis blockade and are associated with adverse clinical outcomes. Impressively, these cells regress during responsive immune checkpoint blockade (ICB) treatment, revealing that they are essential for immunotherapy efficacy. Moreover, targeting ribosomes induces immune checkpoint expression (such as Lag3) and significantly sensitizes tumours to anti-Lag3 immunotherapy, eliciting potent tumour regression and deeper anti-tumour immune responses. These findings unravel previously unrecognized roles of cellular ribosome biogenesis in sustaining immunosuppressive non-cancer cells. Our work unveils that ribosome biogenesis blockade could reinstate immunosurveillance and provide novel strategies to enhance the ICB efficacy in patients with poor immunogenicity.

BACKGROUND:Immune checkpoint blockade, such as monoclonal antibodies targeting programmed cell death protein 1 (PD-1), has been a major breakthrough in the treatment of several cancers, but has limited effect in colorectal cancer (CRC), which is a highly prevalent cancer worldwide. Current chemotherapy-based strategies to boost PD-1 response have many limitations. And the role of peripheral immunity in boosting PD-1 response continues to attract attention. Therefore, candidate combinations of PD-1 blockade need to be drugs with multi-targets and multi-modulatory functions. However, it is still unknown whether traditional Chinese medicines with such property can enhance the applicability and efficacy of PD-1 blockade in colorectal cancer. METHODS:Euphorbia Pekinensis extract (EP) was prepared and the constituents were analyzed by HPLC. CRC cells were used for in vitro experiments, including cell viability assay, colony formation assay, flow cytometry for 7-AAD staining, western blotting for caspase 3 and caspase 7, HMGB1 and ATP detection. An orthotopic CT26 mouse model was subsequently used to investigate the combination of EP and PD-1 blockade therapy. Tumor volume and tumor weight were assessed, tumor tissues were subjected to histopathological HE staining and TUNEL staining, and tumor-infiltrating immune cells were evaluated by immunofluorescence staining. RNA-sequencing, target prediction and pathway analysis were further employed to explore the mechanism. Molecular docking and cellular thermal shift assay (CETSA) were utilized to verify the direct target of the core component of EP. And, loss-of-function analysis was carried to confirm the upstream-downstream relationship. Flow cytometry was employed to analyze CD8+ T cells in the peripheral blood and spleen. RESULTS:The main constituents of EP are diterpenoids and flavonoids. EP dramatically suppresses CRC cell growth and exerts its cytotoxic effect by triggering immunogenic cell death in vitro. Moreover, EP synergizes with PD-1 blockade to inhibit tumorigenesis in tumor-bearing mice. Disruption of ISX nuclear localization by helioscopinolide E is a central mechanism of EP-induced apoptosis in CRC cell. Meanwhile, EP activates immune response by upregulating Phox2b to reshape the immune microenvironment. In addition, EP regulates peripheral immunity by regulating the T cell activation and proliferation, and the ratio of CD8+ T cells in peripheral blood is drastically increased, thereby enhancing the therapeutic efficacy of anti-PD1 immunotherapy. CONCLUSION:EP triggers intra-tumor immunogenic cell death and modulates the immunoregulatory signaling to elicit the tumor immunogenicity. Moreover, EP participates in transcriptional activation of immune response-related pathways. Consequently, multiple stimulating functions of EP on macro- and micro-immune potentiates the anti-tumor effect of PD-1 blockade in CRC.

BACKGROUND:An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer (CRC). However, no work is currently available to synthesize the field through bibliometrics.AIM:To analyze the development in the field of "glucose metabolism" (GM), "amino acid metabolism" (AM), "lipid metabolism" (LM), and "nucleotide metabolism" (NM) in CRC by visualization.METHODS:Articles within the abovementioned areas of GM, AM, LM and NM in CRC, which were published from January 1, 1991, to December 31, 2022, are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS:The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields. Meanwhile, China and the United States were two of the most prominent contributors in these four areas. In addition, Gang Wang, Wei Jia, Maria Notarnicola, and Cornelia Ulrich ranked first in publication numbers, while Jing-Yuan Fang, Senji Hirasawa, Wei Jia, and Charles Fuchs were the most cited authors on average in these four fields, respectively. "Gut microbiota" and "epithelial-mesenchymal transition" emerged as the newest burst words in GM, "gut microbiota" was the latest outburst word in AM, "metastasis", "tumor microenvironment", "fatty acid metabolism", and "metabolic reprogramming" were the up-to-date outbreaking words in LM, while "epithelial-mesenchymal transition" and "apoptosis" were the most recently occurring words in NM.CONCLUSION:Research in "cellular metabolism in CRC" is all the rage at the moment, and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC. Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.

Purpose Major depressive disorder (MDD) is a prevalent and severe mental illness that characterized by high rates of recurrence. One of the primary clinical features of MDD is cognitive impairment. Structural abnormalities such as changes in synaptic density in the related brain regions of MDD patients might be the underlying mechanism of their cognitive dysfunction. Positron emission tomography (PET) scans can be used to measure synaptic density which can impact the efficiency of information transfer between neurons. Here, we firstly attempted to examine synaptic density measured by Vesicle glycoprotein 2A (SV2A) PET to investigate the relationship between synaptic alterations and cognitive function in first-diagnosed, drug-naïve depressed patients. Method s We examined the relationship between synaptic density measured by SV2A PET, using both BPND and standard uptake value ratio (SUVR), and neuropsychological test performance in 6 participants with depression and 9 healthy controls. Cognitive function was measured by repeatable battery for the assessment of neuropsychological status [RBANS] scores.Results MDD exhibit significantly decreased synaptic density in cingulate cortex, prefrontal cortex, parahippocampal gyrus, precuneus and vermis as compared to HCs. The 60-90 min period yielded the most accurate correlation between SUVR-1 and BPND. However, SUVR may lead to an overestimation of the disease burden. Furthermore, there is evidence of a relationship between synaptic density and depression symptoms, as well as cognitive function, including immediate memory, delayed memory, visuospatial and attention.C onclusion Lower synaptic density is associated with impaired cognitive function in first-diagnosed, drug-naïve depressed patients.

药品质量管理及控制是医疗机构药事管理的重要内容,加强医疗机构药品质量管理及控制有助于提升医疗质量,从而为患者的用药安全提供有力的保障.为实施同质化的药品质量管理及控制,编制团队以科学性、通用性、指导性和可操作性为编写原则,通过梳理问题、征集意见、专家论证审议,最终形成国内首部对药品质量管理及控制全过程进行规范的团体标准.该文阐述药品质量管理及控制标准制订过程,并对标准内容进行解析,以期为各级各类医疗机构开展药品质量管理及控制提供建议和指导.

Objective: Deep vein thrombosis (DVT) in the upper extremities caused by a peripherally inserted central venous catheter (PICC) is distinct from the typical DVT. This specific type of mural thrombus might have an effect on the D-dimer levels. In the present study, we aimed to ascertain whether the D-dimer level might be considered an independent diagnostic marker to rule out upper extremity DVT caused by PICCs.Methods: We performed a retrospective case-cohort study of 205 patients who had undergone D-dimer measurement and color Doppler ultrasound within 14 days after placement of a PICC to December 31, 2020, from January 1, 2018. The participants were followed up for 3 months to evaluate for upper extremity DVT. In addition, different D-dimer diagnostic strategies were analyzed. Results: Of the 205 included patients, 53 (25.9%) had had a negative D-dimer level. Of the 53 patients, 10 had had upper extremity DVT attributable to a PICC using color Doppler ultrasound. Of these 10 patients, 3 had developed upper extremity DVT during the 3-month follow-up. Using the various D-dimer diagnostic techniques, the negative predictive value for the D-dimer levels was 81.1%. Conclusions: The present study has shown that the different D-dimer diagnostic strategies are not effective for safely excluding the diagnosis of suspected PICC-related upper extremity DVT. Adding PICC placement as a special factor in the modified Wells score, in addition to the D-dimer level, could securely rule out PICC-related upper extremity DVT; however, the diagnostic efficacy was low. (J Vasc Surg Venous Lymphat Disord 2023;11:565-72.)

Ethnopharmacological relevance: Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance.Aim of the study: This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs).Materials and methods: Based on a mouse constipation model, 2.6 mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image.Results: Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the adminis-tration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus, Romboutsia, Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The compre-hensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration.Conclusion: Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia, Akkermansia and UCG_005 and water channels of AQP1 and AQP3.

BackgroundWe have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels. MethodsWe conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts. ResultsThere were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information. ConclusionsThis guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off.

Chemotherapy is one of the main options in clinical tumor treatment. Although chemotherapy drugs have a good therapeutic effect, they can also cause a series of adverse reactions, such as neurotoxicity. Chemotherapy-induced neurotoxicity is a dose-limi-ting adverse reaction that significantly affects patients' long-term treatment and quality of life. This article reviewed literature from 2000 to the present on chemotherapy-induced neurotoxicity and found that oxaliplatin was the most frequently used chemotherapy drug. Based on the clinical characteristics of oxaliplatin-induced neurotoxicity, this article summarized the understanding of its pathogenesis from both traditional Chinese medicine(TCM) and western medicine perspectives, discussed the role and mechanism of TCM compounds and monomeric components, and explored the research direction of using cutting-edge biotechnology to reveal the mechanism of oxaliplatin-induced neurotoxicity from a temporal-spatial perspective of intercellular communication and the application prospects of an interdisciplinary model combining TCM pathogenesis, western medicine manifestations, and artificial intelligence in precise intervention decision-making for TCM, aiming to provide research ideas for the prevention and treatment of oxaliplatin-induced neurotoxicity and the development of new drugs.

In clinics, sepsis is a critical disease that often develops into shock and multiple organ dysfunction, leading to a serious threat of death. Patients with sepsis are often accompanied by stress hyperglycemia which is an independent risk factor for poor prognosis in sepsis. Thus, the treatment for stress hyperglycemia has attracted more and more attention, among which intensive insulin therapy is widely concerned. However, the benefits and harms of intensive insulin therapy for sepsis patients remain controversial. What the existing literature discusses mostly are the clinical benefit and hypoglycemia risk of intensive insulin therapy, but there is no conclusion on the target range of blood glucose control, the applicable patients, the timing of treatment initiation, and how to avoid the risk. In this study, we have analyzed and summarized the existing literature, hoping to determine the adverse and clinical benefit of intensive insulin therapy in sepsis. And we attempt to assemble better evidence to propose a better recommendation on hyperglycemia intervention for sepsis patients.

Emerging evidence suggests that myo-inositol (MI) has a critical role in reducing renal inflammatory processes and improving podocyte function and preventing diabetes-related renal damage. We aimed to explore the function and underlying workings of MI in renal interstitial fibrosis (RIF). Based on a mouse model, we explored the effect of MI in unilateral ureteral obstruction (UUO) and in transforming growth factor-β1 (TGF-β1)-treated HK-2 cells. Pathological changes of the kidney tissues were examined following staining of the tissues with hematoxylin, eosin, and Masson's trichrome. The mRNA quantities of fibrosis markers, fibronectin, α-smooth muscle actin (α-SMA), and collagen I, were analyzed by means of real-time polymerase chain reaction, whereas those of protein levels were assessed with Western blotting. We also determined the expression of collagen I by immunofluorescence, and the levels of phosphorylated phosphotidylinositol-3-kinase and protein kinase B (PI3K/AKT) by Western blot. In vivo, histopathological examination in the UUO mice revealed renal tubular epithelial cell necrosis, inflammatory cell infiltration, and RIF. UUO mice showed higher expression levels of collagen I, fibronectin, α-SMA, pPI3K, and pAKT compared with sham-operated mice. However, MI treatment diminished the pathological alterations of RIF in UUO mice and downregulated the expression of fibrosis markers and phosphorylated PI3K/AKT. In vitro, TGF-β1 positively influenced the propagation and differentiation of HK-2 cells and upregulated the levels of α-SMA, fibronectin, collagen I, pPI3K, and pAKT, but these became significantly reversed by MI treatment. In conclusion, MI ameliorates RIF, possibly by negatively regulating TGF-β1-induced epithelial transdifferentiation and PI3K/AKT activation.

Failure to achieve target-specific delivery to ischemic brain sites has hampered the clinical efficacy of newly developed therapies for ischemic stroke. Emodin, an active ingredient isolated from traditional Chinese medicine, has been indicated to alleviate ischemic stroke; however, the underlying mechanism remains unclear. In this study, we aimed to achieve brain-targeted delivery of emodin to maximize its therapeutic efficacy and elucidate the mechanisms by which emodin alleviates ischemic stroke. A polyethylene glycol (PEG)/cyclic Arg-Gly-Asp (cRGD)-modified liposome was used to encapsulate emodin. TTC, HE, Nissl staining, and immunofluorescence staining were employed to evaluate the therapeutic efficacy of brain-targeting emodin in MCAO and OGD/R models. Inflammatory cytokine levels were determined using ELISA. Immunoprecipitation, immunoblotting, and RT-qPCR were utilized for clarifying the changes in key downstream signaling. Lentivirus-mediated gene restoration was employed to verify the core effector of emodin for relieving ischemic stroke. Encapsulating emodin in a PEG/cRGD-modified liposome enhanced its accumulation in the infarct region and substantially raised its therapeutic efficacy. Furthermore, we demonstrated that AQP4, the most abundant water transporter subunit expressed in astrocytes, plays a crucial role in mediating the mechanisms by which emodin inhibits astrocyte swelling, neuroinflammatory blood-brain barrier (BBB) breakdown in vivo and in vitro, and brain edema in general. Our study unveiled the critical target of emodin responsible for alleviating ischemic stroke and a localizable drug delivery vehicle in the therapeutic strategy for ischemic stroke and other brain injuries.

There is an increasing evidence suggesting that myo-inositol (MI) may be a renoprotective factor. Our previous study revealed that decreased MI concentrations and increased excretion are often observed in animal models of renal injury and in patients with nephropathy. However, the role of MI supplementation in renal injury remains unclear. In this study, we aimed to explore the role of MI in cisplatin-induced acute kidney injury (AKI). We established a model of acute kidney injury caused by cisplatin (CDDP). Male Kunming mice were randomly divided into six groups: Sham (normal saline), CDDP (15 mg/kg), + MI (150 mg/kg), + MI (300 mg/kg), + MI (600 mg/kg) and MI (600 mg/kg). Human renal tubular epithelial cell line HK-2 cells were likewise separated into six groups at random: Control (normal saline), CDDP (20 µM), + MI (200 µM), + MI (400 µM), + MI (800 µM) and MI (800 µM). After the model was established, renal function indexes were subsequently detected, and experiments such as pathological staining analysis and protein expression analysis were performed. Our results showed that cisplatin administration led to AKI and apoptosis in mice and HK-2 cells, accompanied by markedly increased levels of MIOX, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), whereas exogenous MI significantly attenuated kidney injury and HK-2 cell damage induced by cisplatin both in vivo and in vitro by inhibiting excessive apoptosis. Overall, our findings demonstrate that exogenous MI can reduce excessive apoptosis, thus playing a protective role in cisplatin-induced AKI, indicating that exogenous MI may be used as an adjunctive treatment modality in cisplatin-induced AKI.

RATIONALE:The growing evidence has demonstrated the importance of endoplasmic reticulum stress (ERS) in the pathophysiology of depression. ERS genes were considered to be potential novel therapeutic targets for depression.OBJECTIVES:To clarify the mechanisms of the chronic unpredictable mild stress (CUMS)-induced ERS response and the potential contributing pathways in depression, and further investigate the potential link between N-3 polyunsaturated fatty acids (PUFAs) and stress-induced ERS disturbances.METHODS:This study analyzed the expression of ERS-related genes including GRP78, ATF-4, ATF-6, XBP-1, and CHOP, and sigma-1R with real-time PCR in peripheral blood mononuclear cell (PBMC) RNA samples from participants. All of the rats except for those in the control groups were subjected to 5 consecutive weeks of CUMS to establish the depression model, and the antidepressant effects of N-3 PUFAs were observed by behavior tests. Moreover, the effect of diet and stress on the ERS pathways was also investigated using the western blot.RESULTS:Blood CHOP, ATF-4, and XBP-1 levels were notably elevated in depressed patients relative to healthy individuals. Moreover, increased sigma-1R and decreased ATF-6 implied the protective role of sigma-1R through modulating ERS in patients with depression. Animal studies disclosed the novel findings that supplementary N-3 PUFAs in rats alleviated CUMS-induced disturbance of ERS through the ATF-4/XBP-1/CHOP pathway, implying its potential strategy for depression.CONCLUSION:CUMS-induced depressive-like behaviors are related to the disturbance of ERS. Furthermore, supplementary N-3 PUFAs might be an effective way to alleviate ERS.

ObjectiveThis meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in patients with glioma.MethodsPubMed, EMBASE, Web of Science, and the Cochrane library were searched from inception to January 2023 without language restriction. Primary outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The risk of bias was assessed by subgroup analysis, sensitivity analysis, and publication bias, including funnel plot, Egger’s test, and Begg’s test.ResultsA total of 20 studies involving 2,321 patients were included in this meta-analysis. In the analysis of the included phase III clinical trials, the forest plot showed that PD-1/PD-L1 inhibitors did not improve the OS (HR=1.15, 95% CI: 1.03-1.29, P=0.02, I2 = 14%) and PFS (HR=1.43, 95% CI: 1.03-1.99, P=0.03, I2 = 87%). In the single-arm analysis, the forest plot demonstrated that the 6-month OS was 71% (95% CI: 57%-83%, I2 = 92%), 1-year OS was 43% (95% CI: 33%-54%, I2 = 93%), and the 2-year OS was 27% (95% CI: 13%-44%, I2 = 97%). The pooled estimate of the median OS was 8.85 months (95% CI: 7.33-10.36, I2 = 91%). Furthermore, the result indicated that the 6-month PFS was 28% (95% CI: 18%-40%, I2 = 95%), 1-year PFS was 15% (95% CI: 8%-23%, I2 = 92%), and the 18-month PFS was 10% (95% CI: 3%-20%, I2 = 93%). The pooled estimate of the median PFS was 3.72 months (95% CI: 2.44-5.00, I2 = 99%). For ORR, the pooled estimate of ORR was 10% (95% CI: 2%-20%, I2 = 88%). We further analyzed the incidence of PD-1/PD-L1 inhibitor-related AEs, and the pooled incidence of AEs was 70% (95% CI: 58%-81%, I2 = 94%). The incidence of AEs ≥ grade 3 was 19% (95% CI: 11%-30%, I2 = 94%). The funnel plot for the median PFS and median OS was symmetric with no significant differences in Egger’s test and Begg’s test. The sensitivity analysis revealed that our results were stable and reliable.ConclusionThe results of this meta-analysis suggest that anti-PD-1/PD-L1 therapy is relatively safe but could not prolong survival in glioma. More randomized controlled trials are needed to confirm our results.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023396057.