Laparoscopic common bile duct exploration(LCBDE), as a safe and feasible surgical procedure for the treatment of choledocholithiasis, has been widely applied in clinical practice.However, due to the generally declined organ function, comorbidities, and polypharmacy associated with elderly patients, there is currently no unified consensus on the application of LCBDE in elderly patients with choledocholithiasis.This review aims to summarize the current status of LCBDE for the treatment of choledocholithiasis in the elderly patients, in order to provide reference for clinicians to select appropriate treatment strategies.

ObjectiveTo investigate the safety and feasibility of intra-biliary drainage tube placement after laparoscopic common bile duct exploration in elderly patients with choledocholithiasis， and to provide more options for surgical procedures in the clinical management of elderly patients with choledocholithiasis. MethodsA retrospective analysis was performed for the clinical data of 52 elderly patients with choledocholithiasis who were admitted to Department of Hepatobiliary Surgery， Affiliated Dalian Friendship Hospital of Dalian Medical University， from November 2021 to October 2024. According to the biliary drainage method after surgery， the patients were divided into internal drainage group with 24 patients and T-tube drainage group with 28 patients， and there were 19 patients in each group after propensity score matching. The two groups were compared in terms of perioperative parameters and postoperative complications. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsCompared with the T-tube drainage group， the internal drainage group had a significantly shorter length of postoperative hospital stay and a significantly lower volume of postoperative bile loss （Z=-2.845 and -5.633， both P<0.05）， while there were no significant differences between the two groups in time of operation， intraoperative blood loss， and drainage tube indwelling time （all P>0.05）. There were no significant differences between the two groups in postoperative bile leak， stone recurrence， biliary stricture， and drainage tube-related complications， and the internal drainage group had a significantly lower total complication rate than the T-tube drainage group ［1 （5.3%） vs 7 （36.8%）， P<0.05］. ConclusionFor elderly patients with choledocholithiasis， intra-biliary drainage tube placement after laparoscopic common bile duct exploration can shorten the length of postoperative hospital stay， reduce bile loss， and lower the incidence rate of postoperative complications， thereby helping to accelerate postoperative recovery.

Laparoscopic common bile duct exploration(LCBDE), as a safe and feasible surgical procedure for the treatment of choledocholithiasis, has been widely applied in clinical practice.However, due to the generally declined organ function, comorbidities, and polypharmacy associated with elderly patients, there is currently no unified consensus on the application of LCBDE in elderly patients with choledocholithiasis.This review aims to summarize the current status of LCBDE for the treatment of choledocholithiasis in the elderly patients, in order to provide reference for clinicians to select appropriate treatment strategies.

Cancer of unknown primary(CUP)refers to a group of histopathologically confirmed malignancies that cannot be identified in terms of their primary origin despite thorough investigations.CUP accounts for approximately 3%-5%of all newly diagnosed cancers worldwide,with an overall survival(OS)ranging from 2.7 to 16.0 months.CUP has long been a significant scientific challenge due to the elusive nature and heterogeneity of the primary sites.In the era of immunohistochemistry(IHC),IHC has been applied to identify the primary site in approximately 70%of CUP cases.However,IHC also has limitations for undifferentiated cancers of unknown primary,and results can be influenced by experimental and human factors.In recent years,with the development of molecular tumor profiling(MTP),techniques such as cytology,histology,gene expression profiling(GEP),genomics and epigenomics have been able to accurately detect the primary site in 90%of cases.Currently,the 90-gene tumor tissue origin test has been proven to have an accuracy rate of 94.4%in diagnosing the primary site of CUP,laying the foundation for precision treatment.In the past,platinum and taxane-based empirical chemotherapy was commonly used for treating CUP.However,these treatments did not yield significant improvements in patient survival and prognosis.Since 2008,there has been a global emergence of clinical studies on MTP-guided first-line therapy for CUP.However,due to study design flaws and result controversies,there is no international consensus on the superiority of organ-specific treatment over empirical chemotherapy in terms of improving progression-free survival(PFS)and OS for CUP.Based on this,our center conducted the world's first phase Ⅲ clinical trial in 2017,and demonstrated improved PFS and favorable OS by GEP-guided site-specific therapy of CUP,which established the primacy of site-specific first-line therapy for CUP.In this review,we detailed the epidemiology,pathogenesis,clinical characteristics and the progression of CUP diagnosis from the era of IHC to MTP.Furthermore,we reviewed the advancements in CUP treatment from empirical chemotherapy to MTP-guided organ-specific treatment.Additionally,this review delved into the exploration of second-line treatment options and the establishment of a clinical stratified management model,which are two topics in future research of CUP.This review aimed to summarize the progress in the diagnosis and treatment of CUP,further explore future research directions for CUP,and improve the survival and prognosis of patients with CUP.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

Cancer of unknown primary(CUP)refers to a group of histopathologically confirmed malignancies that cannot be identified in terms of their primary origin despite thorough investigations.CUP accounts for approximately 3%-5%of all newly diagnosed cancers worldwide,with an overall survival(OS)ranging from 2.7 to 16.0 months.CUP has long been a significant scientific challenge due to the elusive nature and heterogeneity of the primary sites.In the era of immunohistochemistry(IHC),IHC has been applied to identify the primary site in approximately 70%of CUP cases.However,IHC also has limitations for undifferentiated cancers of unknown primary,and results can be influenced by experimental and human factors.In recent years,with the development of molecular tumor profiling(MTP),techniques such as cytology,histology,gene expression profiling(GEP),genomics and epigenomics have been able to accurately detect the primary site in 90%of cases.Currently,the 90-gene tumor tissue origin test has been proven to have an accuracy rate of 94.4%in diagnosing the primary site of CUP,laying the foundation for precision treatment.In the past,platinum and taxane-based empirical chemotherapy was commonly used for treating CUP.However,these treatments did not yield significant improvements in patient survival and prognosis.Since 2008,there has been a global emergence of clinical studies on MTP-guided first-line therapy for CUP.However,due to study design flaws and result controversies,there is no international consensus on the superiority of organ-specific treatment over empirical chemotherapy in terms of improving progression-free survival(PFS)and OS for CUP.Based on this,our center conducted the world's first phase Ⅲ clinical trial in 2017,and demonstrated improved PFS and favorable OS by GEP-guided site-specific therapy of CUP,which established the primacy of site-specific first-line therapy for CUP.In this review,we detailed the epidemiology,pathogenesis,clinical characteristics and the progression of CUP diagnosis from the era of IHC to MTP.Furthermore,we reviewed the advancements in CUP treatment from empirical chemotherapy to MTP-guided organ-specific treatment.Additionally,this review delved into the exploration of second-line treatment options and the establishment of a clinical stratified management model,which are two topics in future research of CUP.This review aimed to summarize the progress in the diagnosis and treatment of CUP,further explore future research directions for CUP,and improve the survival and prognosis of patients with CUP.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

OBJECTIVE To investigate the effects of nasal administration of non-mitogenic acid fibroblast growth factor(NMFGF1) loaded nanoparticles(NMFGF1-NPs) on the improvement of cognitive function in vascular dementia(VD) mice and its mechanism. METHODS Nanoparticles containing NMFGF1(NMFGF1-NPs) were prepared by water-in-water emulsion technique and characterized. The mice were divided into sham group, VD model group, blank-NPs group, NMFGF1 solution group and NMFGF1-NPs group after repeated cerebral ischemia-reperfusion to establish VD test model, and then given the corresponding form of drug intervention by nasal cavity. After drug intervention, Morris water maze was used to evaluate the learning and memory function of the animals in each group from the perspective of behavior. Meanwhile, the morphology, arrangement and apoptosis index(AI) of hippocampal neurons in each group were evaluated by pathological methods such as HE staining, FJB staining and Tunel apoptosis staining. In addition, ELISA and Western blotting were used to investigate the molecular mechanism of NMFGF1-NPs improving VD by nasal administration. RESULTS The morphology of NMFGF1-NPs was round. The encapsulation rate of NMFGF1-NPs respectively was (87.76±5.89)%. Morris water maze results showed that the behavioral indexes of mice in VD model group were significantly different from those in sham operation group(P<0.01). At the same time, the pathological results showed that the neurons in the CA1 region of the hippocampus in the VD model group were disordered, the cells morphology and structure were missing, and the AI was significantly increased compared with that in the sham operation group(P<0.01). Meanwhile, compared with the VD model group, the NMFGF1-NPs treatment group showed significant improvement in various behavioral indexes, and the hippocampal neuron cells were intact and orderly, and the AI index was significantly decreased(P<0.01). ELISA and Western blotting analysis showed that compared with that of VD model group and other intervention groups, the content of MDA in the brain of NMFGF1-NPs treatment group was significantly decreased. While the content of SOD, NO and the expressions of Nrf2, SOD-1 and GSTO1/2 was significantly increased (P<0.01). CONCLUSION Nasal administration of NMFGF1-NPs can play the role of antioxidant stress damage by activating Nrf2/ARE signal pathway, and ultimately improve the learning and cognitive function of VD mice.

Objective:To evaluate the clinical efficacy of intra-biliary drainage versus T-tube drainage following laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis.Methods:The clinical data of 50 patients undergoing LCBDE for choledocholithiasis in Dalian Friendship Hospital of Dalian Medical University from January 2018 to October 2022 were retrospectively analyzed, including 23 males and 27 females, aged (61.3±16.2) years old. Patients were divided into the intra-biliary drainage group and T-tube drainage group. Propensity score matching was used to match the baseline data of the two groups at a 1∶1 ratio. The operation time, intraoperative blood loss, postoperative hospital stay, abdominal drainage tube indwelling time, postoperative bile drainage volume and postoperative complications were compared between the groups.Results:Compared with the T-tube group, the operative time [(155.0±36.5) min vs. (194.4±55.8) min], length of postoperative hospital stay [8.0(7.0, 8.0) d vs. 11.0(8.0, 13.0) d], and abdominal drainage tube indwelling time [5.0(4.0, 6.0) d vs. 6.0(5.0, 8.0) d] were all shorter in the intra-biliary drainage tube group (all P<0.05). The postoperative bile drainage volume was reduced [0 ml vs. 431.4(344.7, 484.3) ml]. No postoperative bile leakage occurred in either group. The intraoperative blood loss, proportion of postoperative residual stone, stone recurrence and biliary stricture were comparable between the two groups (all P>0.05). Conclusion:Intra-biliary tube drainage following LCBDE could be safe and effective for choledocholithiasis. Compared to the classic procedure of T-tube drainage, it may be superior in the operation time, postoperative hospital stay, abdominal drainage tube indwelling time, postoperative bile drainage volume.

Objective:To investigate the clinical effect of hyperbaric oxygen (HBO) combined with platelet-rich plasma (PRP) in the reconstruction of anterior cruciate ligament injury (ACLI).Methods:A total of 100 ACLI patients who were treated in the Department of Joint Trauma Surgery of Qingdao Jiaozhou Central Hospital from January 2018 to May 2019 were randomly divided into two groups according to the random number table: observation group and control group. Each group had 50 cases. The patients in the control group were only treated with PRP, while the patients in the observation group were treated with hyperbaric oxygen combined with PRP. Then the curative effect of the two groups, Lysholm, Tegner, and IDKC scores of knee joint, serum insulin-like growth factor-1 (IGF-1), bone gla protein (BGP), and matrix metalloproteinase-1 (MMP-1) were observed after 3 consecutive courses of treatment.Results:After 3 consecutive courses of treatment, the total effective rate of the observation group (90.0%) was significantly higher than that of the control group (68.0%) ( P<0.05); the difference was statistically significant. The scores of Lysholm, Tegner, and IDKC of the knee joint in the observation group and the control group were significantly higher than those before treatment, and the scores of Lysholm, Tegner, and IDKC of the knee joint in the observation group were significantly higher than those in the control group ( P<0.05). The contents of IGF-1, BGP, and MMP-1 in the two groups were significantly lower than those before treatment, and those contents of observation group were significantly lower than those of the control group ( P<0.05). Conclusion:HBO combined with platelet-rich plasma can effectively improve the therapeutic effect of ACLI reconstruction, improve the serum contents of IGF-1, BGP, and MMP-1. This treatment, therefore, is worthy of popularization and application in clinic.