Objective To investigate the role and molecular mechanisms of Exo70 in the metastasis of pancreatic cancer cells. Methods Stable cell lines with Exo70 knockdown or overexpression were established using lentiviral infection. The migration ability of pancreatic cancer cells was assessed by Transwell assay. The morphology, particle size, and secretion levels of exosomes were observed using transmission electron microscopy. Changes in the expression of Exo70 and exosomal marker proteins were detected by Western blot. The localization of multivesicular bodies (MVBs) was examined by immunofluorescence. Results Exo70 knockdown inhibited the migration ability of pancreatic cancer cells and substantially reduced the total amount of exosome secretion. By contrast, Exo70 overexpression enhanced the migration ability of pancreatic cancer cells. Immunofluorescence results showed that Exo70 knockdown induced the perinuclear accumulation of CD63 and LAMP2, leading to an increase in MVB accumulation and lysosomal degradation in pancreatic cancer cells. Conclusion Exo70 promotes the normal transport of MVBs and maintains exosome secretion. Its knockdown enhances the lysosomal degradation of MVBs, resulting in impaired exosome biogenesis and secretion and thereby inhibiting the migration of pancreatic cancer cells.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

As an increasing number of emerging anti-tumor drugs are approved and marketed,the imperative for clinical safety monitoring and risk information management has grown significantly.Drug-induced neuropathy associated with these drugs exhibit characteristics such as insidious onset,rapid progression,and challenging treatment,ultimately leading to treatment failures.Therefore,a comprehensive understanding of the risk of neuropathy induced by emerging anti-tumor drugs,coupled with risk surveillance and early warning,as well as management and reporting,can significantly reduce the incidence and severity of drug-related diseases.This paper provides a review of the neuropathy caused by emerging anti-tumor drugs,introduces the pharmacovigilance system and risk information management measures in clinical usage,aiming to provide a reference for guiding the rational clinical use and minimizing the incidence of drug-induced diseases.

Since the approval of gemtuzumab ozogamicin,an antibody-drug conjugate(ADC)targeting CD33 in 2000,13 ADC drugs have been approved by the FDA.Although these drugs have clearly improved the survival of patients with various types of advanced cancers,their significant toxicity has compromised their therapeutic benefits.The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities,where the payload drug is a determining factor.Antibody and linker may also affect the degree of toxicity.Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency,but treatment-related adverse reactions also increase accordingly.This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies,including but not limited to optimizing linker molecules,upgrading antibody design,and changing drug administration strategies,to improve the overall safety profile of ADC drugs.

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

Objective To explore better methods of ceramic crown design and reduce foreign body sensation of prostheses by digitally replicating the lingual morphology of the original teeth in the patient's aesthetic zone.Methods Patients with anterior tooth defects were collected from July 2022 to December 2023 at Department of Second Clinical Division of the Affiliated Stomatological Hospital,Nanjing Medical University.Patients with crown prostheses designed using automatically matched tooth morphology from the tooth shape database served as the control group.Patients with crown prostheses designed using digital technology to replicate the lingual morpholo-gy of the original teeth were used as the experimental group.Differences in occlusal evaluation and foreign body sensation evaluation of the prostheses in the two groups were compared.Results Results showed that the minimal interocclusal distance of the experimental group was greater than that of the control group,and the difference was statistically significant.The occlusal evaluation of the prostheses in the experimental group was better than that of the control group,and the difference was statistically significant.The foreign body sen-sation of the prostheses in the experimental group was also less than that of the control group.Conclusion Prostheses designed using digital technology to replicate the original lingual morphology of the teeth have a better lingual occlusal relationship with less foreign body sensation and better comfort.

Gastric cancer is one of the most common malignant tumors in China. Currently, the surgery-based procedure is still the most acceptable strategy for treating gastric cancer. As an important part of standardized management, appropriate specimen processing following surgery is receiving more and more attention across the world. With the release of guidelines and consensus on the specimens processing after gastric cancer surgery, several centers in China have started to follow this standard procedure. However, due to differences in understanding the consensus and the degree of surgery practice, the results are variable. This paper will focus on reviewing every aspect of the processing procedure, with the hope that the concept and skill involved can be popularized in clinical operations. Hopefully this will help promote the development of high-quality gastric cancer surgery in China.

Gastric cancer is one of the most common malignant tumors in China. Currently, the surgery-based procedure is still the most acceptable strategy for treating gastric cancer. As an important part of standardized management, appropriate specimen processing following surgery is receiving more and more attention across the world. With the release of guidelines and consensus on the specimens processing after gastric cancer surgery, several centers in China have started to follow this standard procedure. However, due to differences in understanding the consensus and the degree of surgery practice, the results are variable. This paper will focus on reviewing every aspect of the processing procedure, with the hope that the concept and skill involved can be popularized in clinical operations. Hopefully this will help promote the development of high-quality gastric cancer surgery in China.

Objective To analyze the correlation between internal iliac artery calcification and delayed graft function (DGF) and short-term prognosis of kidney transplant recipients. Methods Clinical data of 222 kidney transplant recipients were retrospectively analyzed. According to the recovery of renal function, all recipients were divided into the DGF group (n=50) and immediate graft function (IGF) group (n=172). According to whether the recipients were complicated with severe internal iliac artery calcification, DGF and IGF groups were further divided into the high-risk DGF (n=22), low-risk DGF (n=28), high-risk IGF (n=41) and low-risk IGF(n=131) subgroups, respectively. Clinical data of donors and recipients were statistically compared between two groups. The incidences of postoperative DGF and internal iliac artery calcification were recorded. The risk factors of DGF after kidney transplantation, and the correlation between internal iliac artery calcification and clinical parameters were analyzed. Short-term prognosis of recipients with DGF complicated with severe internal iliac artery calcification was evaluated. Results The incidence of DGF was 22.5% (50/222). Among all recipients, 28.4% (63/222) were complicated with severe internal iliac artery calcification. In the DGF group, 44% (22/50) of the recipients were complicated with severe internal iliac artery calcification, higher than 23.8% (41/172) in the IGF group (P < 0.05). Univariate analysis showed that high serum creatinine (Scr) level of donors, male donor, high triglyceride level and severe internal iliac artery calcification of recipients were the risk factors for DGF after kidney transplantation (all P < 0.05). Multivariate logistic regression analysis revealed that Scr≥143 μmol/L of donors and severe internal iliac artery calcification of recipients were the independent risk factors for DGF after kidney transplantation (both P < 0.05). Correlation analysis indicated that internal iliac artery calcification was weakly correlated with the age of recipients and renal artery anastomosis (both P < 0.05). In the DGF group, the Scr level at postoperative 1 month was significantly higher, whereas the estimated glomerular filtration rate (eGFR) was significantly lower than those in the IGF group (both P < 0.05). The eGFR at postoperative 12 months in the high-risk DGF subgroup was significantly lower than those in the low-risk DGF, high-risk IGF and low-risk IGF subgroups (all P < 0.05). Conclusions Internal iliac artery calcification is not only a risk factor for recovery of renal allograft function, but also negatively affects short-term prognosis of renal allograft function.