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Background: This study aimed to assess the overall reporting quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) formulas for patients with diabetes, and to identify factors associated with better reporting quality.Methods: Four databases including PubMed, Embase, Cochrane Library and Web of Science were systematically searched from their inception to December 2022. The reporting quality was assessed based on the Consolidated Standards of Reporting Trials (CONSORT) statement and its CHM formula extension. The overall CONSORT and its CHM formula extension scores were calculated and expressed as proportions separately. We also analyzed the pre-specified study characteristics and performed exploratory regressions to determine their associations with the reporting quality.Results: Seventy-two RCTs were included. Overall reporting quality (mean adherence) were 53.56% and 45.71% on the CONSORT statement and its CHM formula extension, respectively. The strongest associations with reporting quality based on the CONSORT statement were multiple centers and larger author numbers. Compliance with the CHM formula extension, particularly regarding the disclosure of the targeted traditional Chinese medicine (TCM) pattern (s), was generally insufficient.Conclusion: The reporting quality of RCTs in CHM formulas for diabetes remains unsatisfactory, and the adherence to the CHM formula extension is even poorer. In order to ensure transparent and standardized reporting of RCTs, it is essential to advocate for or even mandate adherence of the CONSORT statement and its CHM formula extension when reporting trials in CHM formulas for diabetes by both authors and editors.

Background: Allergic rhinitis is prevalent among children and can cause nasal itching, fatigue, and even hinder growth and development. The main discomfort symptom of allergic rhinitis is nasal itching. Clinical reports suggest that Chinese herbal medicine (CHM) is effective in allergy rhinitis treatment. Therefore, we evaluate the clinical efficacy of Chinese herbal medicine in treating nasal itching caused by allergic rhinitis in children.Methods: Nine databases, including PubMed, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Data, CQVIP, Chinese Biological Medicine, and ClinicalTrials.gov, were systematically searched from their inception until March 2023. Randomized controlled trials (RCTs) comparing the efficacy of Chinese herbal medicine, either alone or in combination with Western medicine, to Western medicine treatment or placebo intervention for treating allergic rhinitis in children were eligible for inclusion. The effectiveness of Chinese herbal medicines for nasal itching was mainly evaluated. The Risk of Bias tool 2.0 assessed the risk of bias. Statistical analysis using RevMan 5.3 and Stata/SE 12. The quality of evidence was evaluated by GRADEpro 3.6. Risk ratios (RR) with corresponding 95% confidence intervals (CI) were utilized to evaluate and present dichotomous data, while mean difference (MD) and standardized mean difference (SMD) were employed for continuous data. A fixed-effects model was applied in cases where the data exhibited homogeneity (p > 0.1, I2 < 50%), whereas a random-effects model was utilized for heterogeneous data. Statistical significance was determined by a p-value

Objective: Autophagy plays an important role in the occurrence and development of chronic obstructive pulmonary disease (COPD). We evaluated the effect of Xuanfei Pingchuan capsule (XFPC) on autophagy-related genes of COPD by a bioinformatics analysis and experimental verification.Methods: The best treatment duration was screened by CCK8 assays. HBE cells were divided into three groups: blank, CSE and XFPC. After intervened by XFPC, HBE cells were collected and sent to Shenzhen Huada Gene Company for transcriptome sequencing. Subsequently, differential expression analyses, target gene prediction, and function enrichment analyses were carried out. Expression changes were verified in HBE cells by real-time Quantitative PCR (RT-qPCR) and western blotting (WB).Results: The result of differential expression analysis displayed that 125 target genes of HBE cells were mainly related to mitogen-activated protein kinase (MKK) binding, interleukin 33 binding, 1-Pyrroline-5-carboxylate dehydrogenase activity, and the mitogen-activated protein kinase (MAPK) signal pathway. Among the target genes, the core genes related to autophagy obtained by maximum neighborhood component algorithm were CSF1, AREG, MAPK9, MAP3K7, and AKT3. RT-qPCR and WB methods were used to verify the result, it showed similar expression changes in CSF1, MAPK9, MAP3K7, and AKT3 in bronchial epithelial cells to those in the bioinformatics analysis.Conclusion: Through transcriptome sequencing and validation analysis, we predicted that CSF1, MAPK9, MAP3K7, and AKT3 may be the potential autophagy-related genes that play an important role in the pathogenesis of COPD. XFPC may regulate autophagy by down-regulating the expression of CSF1, MAPK9, MAP3K7, and AKT3, thus achieving the purpose of treating chronic obstructive pulmonary disease.

Background: Peritoneal metastasis (PM) is an advanced stage of intra-abdominal malignancy with a very poor prognosis. In recent years, hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) has been utilized as an active treatment in the prevention and treatment of PM, with encouraging results. However, compared with CRS alone, the results of the CRS plus HIPEC strategy in the treatment of patients with intra-abdominal malignancies are still controversial. This study sought to determine the impact of HIPEC + CRS on patient survival and adverse events (AEs) by reviewing randomized controlled trials (RCTs) for all types of intra-abdominal malignancies.Methods: A PubMed, Embase, Cochrane Library, Web of Science and Clinical Trials.gov search extracted all RCTs until 12 October 2022, examining the CRS + HIPEC vs. CRS alone strategies in the treatment of various types of intra-abdominal malignancies. The outcomes included overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), progression-free survival (PFS) and AEs. The dichotomous data were pooled and reported as odds ratios (ORs) with 95% confidence intervals (CIs). The survival outcome data were pooled using hazard ratios (HRs) and corresponding 95% CIs. The Cochrane Collaboration’s Risk of Bias Tool was used to assess the risk of bias in the included studies.Results: A total of 12 RCTs were included in this meta-analysis, including 873 patients in the CRS + HIPEC group and 878 patients in the CRS alone group. The studies included 3 (617 patients) on colorectal cancer, 4 (416 patients) on gastric cancer, and 5 (718 patients) on ovarian cancer. Our analysis showed no difference in OS between the CRS + HIPEC and CRS alone groups (HR: 0.79, 95% CI 0.62–1.01). Subgroup analysis showed that CRS + HIPEC improved the OS of gastric cancer patients (HR: 0.49, 95% CI 0.32–0.76) compared with CRS alone. However, CRS + HIPEC did not significantly improve the OS of colorectal cancer (HR: 1.06, 95% CI 0.81–1.38) and ovarian cancer (HR: 0.82, 95% CI 0.62–1.07) patients. In addition, there was no significant difference in DFS/RFS (HR: 0.78, 95% CI 0.57–1.07) or PFS (HR: 1.03, 95% CI 0.77–1.38) between the two groups. Compared with CRS alone, CRS with HIPEC had greater nephrotoxicity (OR: 0.45, 95% CI 0.21–0.98), while other AEs did not differ significantly between the two groups.Conclusion: Our results suggest that CRS + HIPEC may improve OS in gastric cancer patients compared with CRS alone, but we did not observe a benefit for DFS/RFS. For patients with ovarian and colorectal cancers, our results suggest that HIPEC + CRS does not appear to improve survival outcomes. In addition, CRS + HIPEC has higher nephrotoxicity than CRS alone. More evidence from RCTs is needed to evaluate whether the use of CRS + HIPEC is an appropriate option.

Background: S-ketamine (the S-isomer of ketamine) is twice as potent as the racemic mixture of this agent and carries fewer side effects when administered to humans. Information regarding the use of S-ketamine for the prevention of emergence delirium (ED) is limited. Thus, we evaluated the effect of S-ketamine administered at the end of anesthesia on ED in preschool children undergoing tonsillectomy and/or adenoidectomy.Methods: We investigated 108 children aged 3–7 years, who were scheduled for elective tonsillectomy and/or adenoidectomy under general anesthesia. They were randomly assigned to receive either S-ketamine 0.2 mg/kg or an equal volume of normal saline at the end of anesthesia. The primary outcome was the highest score on the pediatric anesthesia ED (PAED) scale during the first 30 min post-surgery. The secondary outcomes included the incidence of ED (defined as a score of ≥ 3 on Aono scale), pain score, time to extubation, and incidences of adverse events. Multivariate analyses were also performed using logistic regression to evaluate the independent factors predictive of ED.Results: The median (interquartile range) PAED score of the S-ketamine group (0 [0, 3]) was significantly lower than that in the control group (1 [0, 7]) (estimate median difference = 0, 95% confidence interval −2 to 0, p = 0.040). Significantly fewer patients in the S-ketamine group had an Aono scale score ≥ 3 (4 [7%] vs. 12 [22%], p = 0.030). Patients in the S-ketamine group also had a lower median pain score than did control subjects (4 [4, 6] vs. 6 [5, 8], p = 0.002). The time to extubation and incidences of adverse events were comparable between the two groups. However, multivariate analyses indicated that except S-ketamine use, pain scores, age and duration of anesthesia were independent factors predictive of ED.Conclusion: S-ketamine (0.2 mg/kg) administered at the end of anesthesia effectively reduced the incidence and severity of ED in preschool children undergoing tonsillectomy and/or adenoidectomy without prolonging the time to extubation or increasing adverse events. However, S-ketamine use was not an independent factor predictive of ED.

Combined with Network Analysis (NA) and in vivo experimental methods, we explored and verified the mechanism of Cepharanthine (CEP) involved in the treatment of acute respiratory distress syndrome (ARDS). Potential targets of CEP were searched using the SwissTargetPrediction database. The pathogenic genes related to ARDS were obtained using the DisGeNET database. A protein-protein interaction network of common target genes of disease-compound was subsequently built and visualised. Functional enrichment analysis was performed through the Enrichr database. Finally, for in vivo experimental verification, we established an oleic acid-induced ARDS rat model, mainly through histological evaluation and the ELISA method to evaluate both the protective effect of CEP on ARDS and its effect on inflammation. A total of 100 genes were found to be CEP targeted genes, while 153 genes were found to be associated with ARDS. The PPI network was used to illustrate the link and purpose of the genes associated with CEP and ARDS, which contained 238 nodes and 2,333 links. GO and KEGG analyses indicated that inflammatory response and its related signalling pathways were closely associated with CEP-mediated ARDS treatment. Thus, a key CEP–gene–pathway-ARDS network was constructed through network analysis, including 152 nodes (5 targets and 6 pathways) and 744 links. The results of in vivo experiments showed that CEP could alleviate histopathological changes and pulmonary edema related to ARDS, in addition to reducing neutrophil infiltration and secretion of inflammatory cytokines, whilst increasing serum contents of ResolvinD1 and ResolvinE1. Thus, these effects enhance the anti-inflammatory responses. Thus, our results show that CEP can treat oleic acid-induced ARDS in rats via ResolvinE1 and ResolvinD1 signalling pathways that promote inflammation resolution, providing a new avenue to explore for the clinical treatment of ARDS.

Background: For localized disease, partial nephrectomy of small tumors continues to be the gold-standard treatment. However, temporary clamping is routinely performed during this process to control renal blood flow, which can cause renal ischemic/reperfusion injury. We evaluated whether dexmedetomidine postconditioning (DPOC) can reduce renal ischemic/reperfusion injury for patients receiving laparoscopic partial nephrectomy (LPN).Methods: This randomized double-blind controlled trial included 77 patients who were scheduled for LPN at our hospital. Patients were randomly allocated to the DPOC or control group. DPOC was performed via intravenous administration of dexmedetomidine at 0.6 μg kg−1 for 10 min immediately after unclamping the renal artery. In the control group, saline was administered in place of dexmedetomidine under the same protocol. All participants underwent a 6-month follow-up. The primary outcome were the values of 99mTc-DTPA-GFR in the affected kidney at one and 6 months post-LPN.Result: The GFR values in the DPOC group (35.65 ± 4.89 ml min−1.1.73 m−2) were significantly higher than those the control group (33.10 ± 5.41 ml min−1.1.73 m−2; p = 0.022) at 1 month after LPN. There was no statistically significant difference in GFR value between the two groups at 6 months after LPN.Conclusion: DPOC provides therapeutic benefits to LPN patients, at least on a short-term basis, by alleviating renal ischemic/reperfusion injury.Clinical Trial Registration: Chinese Clinical Trial Registry, identifier [ChiCTR-TRC-14004766].

Background: Acute kidney injury is the most common complication after liver transplantation. Sodium bicarbonate Ringer’s solution is a new type of crystalloid solution that has been recently used in the clinical setting. Whether sodium bicarbonate Ringer’s solution reduces the occurrence of postoperative AKI and improves the clinical outcomes of liver transplantation patients is not clear.Objective: To compare the effects of sodium bicarbonate Ringer’s solution versus normal saline on acute kidney injury and clinical outcomes following classic orthotopic liver transplantation.Methods: Sixty-four participants were randomly assigned to the sodium bicarbonate Ringers (BRS) group or the normal saline (NS) group. The primary outcomes were the incidence and severity of acute kidney injury after liver transplantation. The secondary outcomes included the rate of renal replacement therapy, length of mechanical ventilation, stay in the ICU, stay in the hospital after surgery and 30-day mortality. Other outcomes included the concentration of sodium, chloride, bicarbonate, anion gap, lactate concentration and changes in chloride preoperatively and postoperatively.Result: Sixty-two patients completed the trial and were analyzed, with 31 patients in each group. There was a significantly lower rate of postoperative acute kidney injury in the BRS group (14/31, 45.2%) than in the NS group (24/31, 77.4%), with a relative risk of 0.58 (95% CI, 0.38–0.90; p = 0.009). The severity of AKI in the BRS group was lower than that in the NS group (Z = -2.932, p = 0.003). There was no significant difference observed in the secondary outcomes. For other outcomes, the concentration of preoperative sodium was lower than postoperative sodium in the NS group (137.2 vs. 140.4, p = 0.009). The concentration of preoperative chloride was lower than that of postoperative chloride in the NS group (102.9 vs. 106.2, p < 0.001). The change in the concentration of chloride in the BRS group was lower than that in the NS group (1.6 vs. 4.7, p = 0.006).Conclusion: Sodium bicarbonate Ringer’s solution reduced the incidence and severity of acute kidney injury after classic orthotopic liver transplantation.

With the aging of the world population and advances in medical and health technology, more and more elderly patients are undergoing anesthesia and surgery, and perioperative neurocognitive dysfunction (PND) is receiving increasing attention. The latest definition of PND, published simultaneously in November 2018 in 6 leading journals in the field of anesthesiology, clarifies that PND includes preoperatively cognitive impairment, postoperative delirium, delayed neurocognitive recovery, and postoperative cognitive dysfunction and meets the diagnostic criteria for neurocognitive impairment in the Diagnostic and Statistical Manual of Mental Disorders -fifth edition (DSM-5). The time frame for PND includes preoperatively and within 12 months postoperatively. Recent studies have shown that gut microbiota regulates central nervous function and behavior through the gut microbiota - gut - brain axis, but the role of the axis in the pathogenesis of PND remains unclear. Therefore, this article reviews the mechanism of the role of gut microbiota-gut-brain axis in PND, so as to help explore reasonable early treatment strategies.

Background: This study aimed to investigate the protective effect of Xuanfei Pingchuan Capsules (XFPC) on autophagy and p38 phosphorylation in human bronchial epithelial (HBE) cells induced by cigarette smoke extract (CSE).Methods: HBE cells were divided into five groups: blank, CSE, low XFPC dose (XFPC-L), medium XFPC dose (XFPC-M), and high XFPC dose (XFPC-H). HBE cells were induced by CSE to establish a cell model for chronic obstructive pulmonary disease, and different doses of XFPC medicated serum were used to treat the cells. The Cell Counting Kit-8 was used to detect cell viability. Flow cytometry was used to detect cell apoptosis. Fluorescence microscopy and the expression level of microtubule-associated protein light chain 3 (LC3)-II in immunohistochemical method were used to observe autophagy in cells. Western blot was used to detect the protein expression level of p38, phospho-p38 (p-p38), LC3-I, LC3-II and Beclin 1. Real-time polymerase chain reaction was used to detect the expression of LC3-I, LC3-II and Beclin 1 on mRNA level.Results: Compared with the blank group, the cell viability of the CSE group was significantly decreased, and apoptosis and the level of autophagy in cells were significantly increased. The mRNA and protein expression of LC3-I, LC3-II, Beclin 1 and the protein level of p-p38 were significantly increased in the CSE-HBE cells. Compared to the CSE group, the different doses of XFPC medicated serum increased cell viability, decreased cell apoptosis, and inhibited mRNA and protein expression of LC3-I, LC3-II, Beclin 1 and protein level of p-p38. These results were especially observed in the group XFPC-H. After adding a p38 agonist, the therapeutic effect of XFPC on cell viability and autophagy was suppressed.Conclusion: XFPC significantly increased cell viability in a CSE-induced HBE cell model for chronic obstructive pulmonary disease through inhibiting the level of autophagy mediated by phosphorylation of p38.

Ischemic/reperfusion (I/R) injury is the primary cause of acute kidney injury (AKI). Gastrin, a gastrointestinal hormone, is involved in the regulation of kidney function of sodium excretion. However, whether gastrin has an effect on kidney I/R injury is unknown. Here we show that cholecystokinin B receptor (CCKBR), the gastrin receptor, was significantly up-regulated in I/R-injured mouse kidneys. While pre-administration of gastrin ameliorated I/R-induced renal pathological damage, as reflected by the levels of serum creatinine and blood urea nitrogen, hematoxylin and eosin staining and periodic acid-Schiff staining. The protective effect could be ascribed to the reduced apoptosis for gastrin reduced tubular cell apoptosis both in vivo and in vitro. In vitro studies also showed gastrin preserved the viability of hypoxia/reoxygenation (H/R)-treated human kidney 2 (HK-2) cells and reduced the lactate dehydrogenase release, which were blocked by CI-988, a specific CCKBR antagonist. Mechanistically, the PI3K/Akt/Bad pathway participates in the pathological process, because gastrin treatment increased phosphorylation of PI3K, Akt and Bad. While in the presence of wortmannin (1 μM), a PI3K inhibitor, the gastrin-induced phosphorylation of Akt after H/R treatment was blocked. Additionally, wortmannin and Akt inhibitor VIII blocked the protective effect of gastrin on viability of HK-2 cells subjected to H/R treatment. These studies reveals that gastrin attenuates kidney I/R injury via a PI3K/Akt/Bad-mediated anti-apoptosis signaling. Thus, gastrin can be considered as a promising drug candidate to prevent AKI.

Understanding the mechanistic basis for temozolomide (TMZ)-induced glioma resistance is an important obstacle in developing an effective form of chemotherapy for this type of tumor. Glycogenolysis is known to play an essential role in cellular proliferation and potassium homeostasis and involves the glycogen phosphorylase isoenzyme BB (GPBB). In this investigation, plasma GPBB was correlated with TMZ-resistance. Elevated plasma GPBB concentrations were found to be more frequent in a TMZ-resistant cohort of patients with poor survival rates. TMZ inhibits cell proliferation and induces TMZ resistance by upregulating the expression of O(6)-methylguanine-DNA methyltransferase (MGMT). This process requires glycogenolysis, which was confirmed herein by treatment with 1,4-dideoxy-1,4-imino-D-arabinitol hydrochloride, a glycogenolysis inhibitor and a special GPBB inhibitor. Acute TMZ treatment leads to upregulation of [Ca2+]i, extracellular-regulated kinase (ERK)1/2 phosphorylation, and chronic TMZ treatment leads to upregulation of the expression of Na,K-ATPase, ERK1/2, and MGMT protein. Upregulation was abolished for each of these by inhibitors of transient receptor potential channel 1 and the inositol trisphosphate receptor. L-channel [Ca2+]i inhibitors and RyR antagonists had no such effect. These results demonstrate that [Ca2+]i-dependent glycogenolysis participates in acquired glioma TMZ-resistance by upregulating MGMT via a Na,K-ATPase/ERK1/2 signaling pathway. GPBB and glycogenolysis may therefore represent novel therapeutic targets for overcoming TMZ-resistant gliomas.

Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products. [ABSTRACT FROM AUTHOR]

Editorial: Targeted cancer therapies, from small molecules to antibodies, volume II [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is one of the main impediments in successful chemotherapy in cancer treatment. Overexpression of ATP-binding cassette (ABC) transporter proteins is one of the most important mechanisms of MDR. Natural products have their unique advantages in reversing MDR, among which diterpenoids have attracted great attention of the researchers around the world. This review article summarizes and discusses the research progress on diterpenoids in reversing MDR.

Cancer is a major global health challenge for our health system, despite the important pharmacological and therapeutic discoveries we have seen since past 5 decades. The increasing prevalence and mortality of cancer may be closely related to smoking, exposure to environmental pollution, dietary and genetic factors. Despite significant promising discoveries and developments such as cell and biotechnological therapies a new breakthrough in the medical field is needed to develop specific and effective drugs for cancer treatment. On the development of cell therapies, anti-tumor vaccines, and new biotechnological drugs that have already shown promising effects in preclinical studies. With the continuous enrichment and development of chromatin immunoprecipitation sequencing (ChIP-seq) and its derivative technologies, epigenetic modification has gradually become a research hotspot. As key ingredients of epigenetic modification, Writers, Readers, Erasers have been gradually unveiled. Cancer has been associated with epigenetic modification especially methylation and therefore different epigenetic drugs have been developed and some of those are already undergoing clinical phase I or phase II trials, and it is believed that these drugs will certainly assist the treatment in the near future. With respect to this, an overview of anti-tumor drugs targeting modified enzymes and de-modified enzymes will be performed in order to contribute to future research.

Loganin is an iridoid glycoside extracted from Cornus officinalis, which is a traditional oriental medicine, and many biological properties of loganin have been reported. Nevertheless, it is not clear whether loganin has therapeutic effect on cardiovascular diseases. Hence, the aim of the present study was to investigate the effect of loganin on Ang II–induced cardiac hypertrophy. In the present study, we reported for the first time that loganin inhibits Ang II–provoked cardiac hypertrophy and cardiac damages in H9C2 cells and in mice. Furthermore, loganin can achieve cardioprotective effects through attenuating cardiac fibrosis, decreasing pro-inflammatory cytokine secretion, and suppressing the phosphorylation of critical proteins such as JAK2, STAT3, p65, and IκBα. Besides, the outstanding findings of the present study were to prove that loganin has no significant toxicity or side effects on normal cells and organs. Based on these results, we conclude that loganin mitigates Ang II–induced cardiac hypertrophy at least partially through inhibiting the JAK2/STAT3 and NF-κB signaling pathways. Accordingly, the natural product, loganin, might be a novel effective agent for the treatment of cardiac hypertrophy and heart failure.

The emergence of multidrug resistance (MDR) has been a major issue for effective cancer chemotherapy as well as targeted therapy. One prominent factor that causes MDR is the overexpression of ABCB1 transporter. In the present study, we revealed that the Aurora kinase inhibitor GSK-1070916 is a substrate of ABCB1. GSK-1070916 is a newly developed inhibitor that is currently under clinical investigation. The cytotoxicity assay showed that overexpression of ABCB1 significantly hindered the anticancer effect of GSK-1070916 and the drug resistance can be abolished by the addition of an ABCB1 inhibitor. GSK-1070916 concentration-dependently stimulated ABCB1 ATPase activity. The HPLC drug accumulation assay suggested that the ABCB1-overexpressing cells had lower levels of intracellular GSK-1070916 compared with the parental cells. GSK-1070916 also showed high binding affinity to ABCB1 substrate-binding site in the computational docking analysis. In conclusion, our study provides strong evidence that ABCB1 can confer resistance to GSK-1070916, which should be taken into consideration in clinical setting.

Integrins are the adhesion molecules and receptors of extracellular matrix (ECM). They mediate the interactions between cells-cells and cells-ECM. The crosstalk between cancer cells and their microenvironment triggers a variety of critical signaling cues and promotes the malignant phenotype of cancer. As a type of transmembrane protein, integrin-mediated cell adhesion is essential in regulating various biological functions of cancer cells. Recent evidence has shown that integrins present on tumor cells or tumor-associated stromal cells are involved in ECM remodeling, and as mechanotransducers sensing changes in the biophysical properties of the ECM, which contribute to cancer metastasis, stemness and drug resistance. In this review, we outline the mechanism of integrin-mediated effects on biological changes of cancers and highlight the current status of clinical treatments by targeting integrins.

Cancer has been a major global health problem due to its high morbidity and mortality. While many chemotherapy agents have been studied and applied in clinical trials or in clinic, their application is limited due to its toxic side effects and poor tolerability. Monoclonal antibodies specific to the PD-1 and PD-L1 immune checkpoints have been approved for the treatment of various tumors. However, the application of PD-1/PD-L1 inhibitors remains suboptimal and thus another strategy comes in to our sight involving the combination of checkpoint inhibitors with other agents, enhancing the therapeutic efficacy. Various novel promising approaches are now in clinical trials, just as icing on the cake. This review summarizes relevant investigations on combinatorial therapeutics based on PD-1/PD-L1 inhibition.