Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Neoantigens exhibit high immunogenic potential and confer a uniqueness to tumor cells, making them ideal targets for personalized cancer immunotherapy. Neoantigens originate from tumor-specific genetic alterations, abnormal viral infections, or other biological mechanisms, including atypical RNA splicing events and post-translational modifications (PTMs). These neoantigens are recognized as foreign by the immune system, eliciting an immune response that largely bypasses conventional mechanisms of central and peripheral tolerance. Advances in next-generation sequencing (NGS), mass spectrometry (MS), and artificial intelligence (AI) have greatly expedited the rapid detection and forecasting of neoantigens, markedly propelling the development of diverse immunotherapeutic strategies, including cancer vaccines, adoptive cell therapy, and antibody treatment. In this review, we comprehensively explore the discovery and characterization of neoantigens and their clinical use within promising immunotherapeutic frameworks. Additionally, we address the current landscape of neoantigen research, the intrinsic challenges of the field, and potential pathways for clinical application in cancer treatment.
Humans ; Neoplasms/therapy* ; Precision Medicine/methods* ; Immunotherapy/methods* ; Antigens, Neoplasm/genetics* ; Cancer Vaccines/immunology* ; High-Throughput Nucleotide Sequencing

Objective:To compare the therapeutic effect of one-stage versus two-stage percutaneous transhepatic biliary fistulation lithotripsy in treatment of complex hepatolithiasis.Methods:A retrospective study was conducted on 145 patients with complex hepatolithiasis who were treated at the First Affiliated Hospital of Guangzhou Medical University between September 2013 and June 2018. There were 60 males and 85 females, aged 21 to 91 (56.5±14.1) years. According to the method of fistula establishment, patients were divided into the percutaneous transhepatic one-step biliary fistulation (PTOBF) group ( n=94) or the two-stage percutaneous transhepatic choledochoscopic lithotripsy (PTCSL) group ( n=51). The success rates of one-time puncture and fistula dilation, operation time of lithotripsy, operative conversion rate (PTCSL was converted to laparotomy and laparoscopic surgery), postoperative complications (including catheter dislodgement), residual stone rates and stone recurrence rates were compared between groups. Results:In the PTOBF group, operation time (105.8±43.6) min, success rate of one puncture 73.4% (69/94), and success rate of one fistula dilation 93.6% (88/94), the rate of operative conversion 0. All these results were significantly better than the corresponding results of the two-stage PTCSL group of (130.0±70.0) min, 54.9% (28/51), 68.6% (35/51), and 13.7%(7/51) respectively (all P<0.05). There were no significant differences in stone residual rate [17.0%(16/94) vs. 15.7% (8/51)] and stone recurrence rate [14.9%(14/94) vs. 17.6% (9/51)] between groups (both P>0.05). The postoperative complications rate was 7.4%(7/94) in PTOBF group, which was 39.2% (20/51) in two-stage PTCSL group (χ 2=22.02, P<0.001). The catheter dislodgement rate of PTOBF group was 2.1% (2/94), lower than that of two-stage PTCSL group 27.4% (14/51), the difference was statistically significant (χ 2=21.59, P<0.001). Conclusion:One-stage PTOBF and two-stage PTCSL were both safe and effective in treatment of complex hepatolithiasis. However, PTOBF had shorter operative times, lower catheter dislodgement and operative conversion rates than PTCSL.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Objective:To evaluate the clinical value of percutaneous transhepatic one-step biliary fistulation(PTOBF)lithotomy plus laparoscopic cholecystectomy(LC) in the treatment of choledocholithiasis combined with cholecystolithiasis.Methods:From Jul 2012 to Jun 2018, 44 patients with cholecystolithiasis and choledocholithiasis were treated by PTOBF + LC ( n=20) vs laparoscopic common bile duct exploration(LCBDE)+ LC( n=24). Results:The success rate of one-step operation in both groups was 100%.The average intra-operative hemorrhage and the average hospital stay after operation were higher in LCBDE+ LC group (all P<0.05). The post-operative complication rate of PTOBF lithotomy + LC group was 10.0% (2/20), recurrence rate of observation period was 10.0% (2/20), while that of LCBDE+ LC group was 8.3% (2/24), and 12.5% (3/24), the difference was not statistically significant (all P>0.05). Conclusion:PTOBF lithotomy combined with LC is a safe, effective and feasible minimally invasive method for the treatment of choledocholithiasis combined with gall stones.

Objective To study the efficacy and safety of percutaneous transhepatic one-step biliary fistulation (PTOBF) with rigid cholangioscopic lithotripsy for treatment of complicated hepatolithiasis under the ultrasonic navigation technique.Methods In this retrospective study,PTOBF lithotripsy surgery was performed in 94 patients with hepatolithiasis under general anesthesia with tracheal intubation,and with percutaneous transhepatic puncture of targeted bile duct under ultrasonic navigation in The First Affiliated Hospital of Guangzhou Medical University.Biliary expanders were used along a guidewire to expand the sinus gradually until 14Fr to establish a fistulous channel.Lithotripsy was then performed through the channel by rigid cholangioscopy.The operation-related data were collected and analyzed,including puncture and fistula establishment success ratio,complication rate,intraoperative blood loss,residual and recurrence hepatolithiasis rates.Results 94 patients (total 122 patient-times) underwent PTOBF lithotripsy.There was no perioperative mortality.The overall puncture success rate was 100％,and the fistula/puncture rate was 97.5％ (119/122).In 118 patients success was achieved in 2 time (96.7％).The complication rate was 9.6％ (9/94).The average intraoperation blood loss were (24.9 ± 21.3)ml.The residual calculus rate after therapy was 13.8％ (13/94).All patients were followed-up for a period that ranged between 18 and 30 months.The recurrence rate was 14.9％ (14/94).Conclusions Ultrasonic navigation technique plays an important role in bile duct puncture,sinus expansion and rigid cholangioscopic lithotripsy for treatment of complicated hepatolithiasis.PTOBF lithotripsy is a safe and effective procedure,which provides a new way in mini-invasive treatment for hepatolithiasis.It is worth generalizing.

Objective:To compare the clinical efficacy of percutaneous transhepatic choledochoscope lithotomy (PTCSL) with laparoscopic choledocholithotomy (LD) in treatment of choledocholithiasis.Methods:Data of 132 patients with choledocholithiasis treated at the First Affiliated Hospital of Guangzhou Medical University from July 2012 to December 2018 were retrospectively analyzed. There were 75 males and 57 females, with an average age of 62.7 years. For 76 patients underwent PTCSL (the PTCSL group) and 56 underwent LD (the LD group). The data of the patients the success rate of lithotomy, stone residual rate, operation time, postoperative complications and stone recurrence, chronic cholangitis, and acute cholangitis 1 month after operation were compared between the two groups.Results:The ratio of upper abdominal operation history and biliary tract infection in the PTCSL group was higher than that in the LD group, and the difference was statistically significant (both P<0.05). In the PTCSL group, the calculi were successfully removed in 64 patients in one treatment session, while residual calculi were removed through subsequent sinus choledochoscopy in 9 patients. In the remaining 3 patients, the residual calculi were removed with LD or laparotomy operations. Postoperative complications occurred in 14 patients (19.2%, 14/73). In the LD group, the calculi were successfully removed in one session in 46 patients while in 8 patients the residual calculi were removed by choledochoscopy (1 patient still had residual calculi after choledochoscopy). The remaining 2 patients underwent open surgery due to anatomical difficulties. Postoperative complications occurred in 11 patients (20.4%, 11/54). There were no significant differences between the two groups in the one-off stone removal rate, postoperative stone residual rate, final stone removal rate and postoperative complication rate (all P>0.05). The operation time of the PTCSL group was (156±60) min, which was significantly shorter than the LD group (203±59) min ( P<0.05). There was no significant difference between the two groups in the incidence of postoperative chronic cholangitis and recurrence rate of calculi (both P>0.05). The incidence of acute cholangitis in the PTSCL group was significantly higher than that in the LD group ( P<0.05). Conclusion:PTCSL was as safe and effective as LD, with fewer complications and faster recovery. It is especially suitable for patients with previous upper abdominal surgery, recurrence of calculi and repeated biliary tract infection.

Objective To investigate the curative effect on patients with choledocholithiasis by percutaneous transhepatic rigid choledochoscope lithotomy (PTCSL) vs endoscopic retrograde cholangiopancreatography (ERCP) plus EST.Methods From Jan 2010 to Dec 2015,92 cases of choledocholithiasis were treated by one-stage PTCSL (n =23) vs ERCP (n =69).The curative effects and postoperative complications in two groups were observed and analyzed.Results In PTCSL group,the complete stone clearance at one-time achieved in all 23 cases (100％).While in ERCP group stone clearance was achieved in 72.46％ cases at first attempt and the final clearance rate was 82.60％,leaving 12 cases with residual stones and among those 12 cases 5 cases were converted to surgical operation.The average intra-operative hemorrhage in two groups was (20.6 ± 4.6) ml vs (3.0 ± 0.3) ml,and the average hospital stay after operation was 6.8 d and 7 d respectively.The post-operative complications (30.43％) and stone recurrence (13.04％) were similar in the two groups.Conclusions PTCSL is safe,effective,and more suitable to patients with large stones and those with a history of biliary surgeries.

Objective To observe the clinical effect of percutaneous transhepatic one-step biliary fistulation (PTOBF) and percutaneous transhepatic cholangioscopy (PTCS) in the treatment of hepatolithiasis with hepatobiliary surgery history,and to explore the clinical application value of PTOBF.Methods This is retrospective analysis of 68 patients with hepatolithiasis who were admitted to hepatobiliary surgery in the First Affiliated Hospital of Guangzhou Medical University from November 2009 to October 2017.Among these cases,35 patients in the observation group (group PTOBF) were treated with PTOBF,and 33 patients in the control group (group PTCS) received PTCS treatment.The final clearance rate,the postoperative complications rate,the hospitalization time,the operation times within the course of treatment,the recurrence rate and the residual stenosis rate of the two groups were compared.Results Compared with group PTCS,the clearance rate was significantly higher in group PTOBF(82.9％ vs 54.6％,P＜0.05),while the postoperative complications rate between the two groups are similar (14.3 ％ vs 30.3 ％,P＞ 0.05);Besides,the hospitalization time(12.3±5.3 d vs 17.4±7.0 d,P＜0.05),the operation times within the course of treatment (2.2±1.3 vs 2.8±1.0,P＜0.05) and the recurrence rate(17.4％ vs 39.4％,P＜0.05) of group PTOBF were obviously lower.Conclusions PTOBF is a safe and feasible treatment for hepatolithiasis with hepatobiliary surgery history.Compared with PTCS,it has the advantages of short hospitalization time,fewer operations and better recovery.

Many factors contribute to a successful total knee arthroplasty, and postoperative coronal lower limb alignment has always been a focus of joint surgeons. Previous researches have suggested that neutral alignment can bring higher prosthesis survival rate and better knee function. However, the theory has been challenged in recent years.In this article, the author introduces the axis, alignment and osteotomy of total knee arthroplasty briefly and reviews the studies on the neutral alignment and kinematic alignment of recent years in order to provide some advice for the clinical operation.