Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer:A retrospective study

Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.Methods: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.Results: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of patients.Programmed death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of patients.CLDN18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P<0.05). Uterine adnexa metastasis(P<0.001) was more frequent and liver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive group.Conclusions: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

Value of multiple models of diffusion-weighted imaging to predict hepatic lymph node metastases in colorectal liver metastases patients

BACKGROUND About 10%-31% of colorectal liver metastases(CRLM)patients would concomitantly show hepatic lymph node metastases(LNM),which was considered as sign of poor biological behavior and a relative contraindication for liver resection.Up to now,there’s still lack of reliable preoperative methods to assess the status of hepatic lymph nodes in patients with CRLM,except for pathology examination of lymph node after resection.AIM To compare the ability of mono-exponential,bi-exponential,and stretchedexponential diffusion-weighted imaging(DWI)models in distinguishing between benign and malignant hepatic lymph nodes in patients with CRLM who received neoadjuvant chemotherapy prior to surgery.METHODS In this retrospective study,97 CRLM patients with pathologically confirmed hepatic lymph node status underwent magnetic resonance imaging,including DWI with ten b values before and after chemotherapy.Various parameters,such as the apparent diffusion coefficient from the mono-exponential model,and the true diffusion coefficient,the pseudo-diffusion coefficient,and the perfusion fraction derived from the intravoxel incoherent motion model,along with distributed diffusion coefficient(DDC)andαfrom the stretched-exponential model(SEM),were measured.The parameters before and after chemotherapy were compared between positive and negative hepatic lymph node groups.A nomogram was constructed to predict the hepatic lymph node status.The reliability and agreement of the measurements were assessed using the coefficient of variation and intraclass correlation coefficient.RESULTS Multivariate analysis revealed that the pre-treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes.A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients,with an area under the curve of 0.873.Furthermore,parameters from SEM showed substantial repeatability.CONCLUSION The developed nomogram,incorporating the pre-treatment DDC and the short axis of the largest lymph node,can be used to predict the presence of hepatic LNM in CRLM patients undergoing chemotherapy before surgery.This nomogram was proven to be more valuable,exhibiting superior diagnostic performance compared to quantitative parameters derived from multiple b values of DWI.The nomogram can serve as a preoperative assessment tool for determining the status of hepatic lymph nodes and aiding in the decision-making process for surgical treatment in CRLM patients.

Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

Genomic characterization of peritoneal lavage cytology-positive gastric cancer

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.

Laser additive manufacturing of zinc:formation quality,texture,and cell behavior

Laser powder bed fusion(LPBF)makes it possible for biodegradable zinc(Zn)to be used to produce customized orthopedic implants.In this research,we investigate the impact of laser power and scanning speed on the development of surface quality,relative densification,and texture during LPBF of Zn implants.Increasing laser power was able to decrease melt viscosity and surface tension,which improved the metallurgical bonding between adjacent tracks.Uneven and twisted tracks also became continuous and straight.Scanning speed could controlmolten-pool temperature to restrain grain natural orientation,achieving various crystal orientations and a weakened texture.Importantly,it further avoided the thermal expansion and contraction caused by excessive energy storage and accumulation in the matrix,thus reducing the generation of high-dislocation density.As a result,by selecting a reasonable laser power and scanning speed,the LPBF parts exhibited a flat surface morphology and a high density over 99.5%.Their average hardness,mechanical strength,and elongation reached 50.2 HV,127.8 MPa,and 7.6%,respectively.Additionally,the parts displayed a moderate degradation rate and excellent osteogenic properties.All these results provide a basis for selecting process parameters to optimize the comprehensive properties of LPBF-processed Zn parts for biodegradable applications.

High expression of PD-L1 mainly occurs in non-small cell lung cancer patients with squamous cell carcinoma or poor differentiation

Background:Lung cancer is one of the most lethal cancers worldwide,but studies have shown that the higher the expression of programmed cell death protein 1 ligand 1(PD-L1)in non-small cell lung cancer(NSCLC),the more likely it will benefit from anti-PD-L1 immunotherapy.The purpose of our study was to collect and analyze abundant clinical samples in order to provide evidence for clinicians and patients who might consider anti-PD-L1 immunotherapy while jointly formulating treatment plans.Methods:On the one hand,we obtained cases from The Cancer Genome Atlas(TCGA)database,including 498 lung squamous cell cancer(LUSC)patients and 515 lung adenocarcinoma(LUAD)patients.We studied the lung caner driver gene in LUSC and LUAD.On the other hand,PD-L1 expression was detected in lung cancer tissues of 1,008 NSCLC patients with immunohistochemistry staining(IHC),and we studied the correlation between PD-L1 protein expression and clinicopathological characteristics.Results:PD-L1 expression was higher in LUSC than in LUAD at the mRNA level.In univariate analysis,PD-L1 expression at the protein level was higher in patients who were males,were LUSC,were smokers,had a tumor diameter>3 cm,had poor differentiation,or had stages Ⅲ-Ⅳ disease.In multivariate analysis,PD-L1 expression was higher in patients who were LUSC or in poor differentiation.Conclusion:In term of protein level,PD-L1 expression was higher in NSCLC patients who were LUSC or in poor differentiation.We recommend that PD-L1 IHC detection can be routinely performed in such populations that are likely to benefit most from PD-L1 immunotherapy.

In-situ deposition of apatite layer to protect Mg-based composite fabricated via laser additive manufacturing

Biodegradable magnesium(Mg) and its alloy show huge potential as temporary bone substitute due to the favorable biocompatibility and mechanical compatibility. However, one issue deserves attention is the too fast degradation. In this work, mesoporous bioglass(MBG)with high pore volume(0.59 cc/g) and huge specific surface area(110.78 m^(2)/g) was synthesized using improved sol-gel method, and introduced into Mg-based composite via laser additive manufacturing. Immersion tests showed that the incorporated MBG served as powerful adsorption sites, which promoted the in-situ deposition of apatite by successively adsorbing Ca2+and HPO42-. Such dense apatite film acted as an efficient protection layer and enhanced the corrosion resistance of Mg matrix, which was proved by the electrochemical impedance spectroscopy measurements. Thereby, Mg based composite showed a significantly decreased degradation rate of 0.31 mm/year. Furthermore,MBG also improved the mechanical properties as well as cell behavior. This work highlighted the advantages of MBG in the fabrication of Mg-based implant with enhanced overall performance for orthopedic application.

Challenge and future of cancer screening in China: Insights from esophageal cancer screening practice

Cancer stands as a prominent public health concern in China, with elusive intervention targets due to unidentified high-risk causal factors for most cancers. Consequently, emphasis has shifted towards screening, diagnosing, and treating early cancer cases within the general population. However, China faces considerable obstacles in its cancer prevention and control efforts, attributing to the complexity and heterogeneity of the occurrence, progression, and prognosis of malignant tumors across populations, time, and regions. Taking esophageal cancer screening practices as an example, this review outlines the importance and assessment of cancer screening, delineating major challenges in China's cancer prevention and control: 1) limited comprehension of cancer's natural history;2) lack of “China Evidence” supporting screening effectiveness and value;3) compromised efficiency and accuracy in current screening modality;and 4) insufficient sustainability of the current screening practices and translation of relevant scientific research achievements. To address these challenges, we propose potential coping strategies: 1)establishing tailored technologies and pathways for cancer prevention and control based on population-based and clinical epidemiological studies using high-quality designs;2) breaking conventional constraints to establish a novel cancer screening strategy aligned with real-world needs;and 3) establishing enhanced communication platforms among scientific research teams, policymakers, and industrial institutions to foster collaboration and innovation.

Exploration and optimization of surgical techniques for laparoscopic transhiatal lower mediastinal lymph node dissection for adenocarcinoma of esophagogastric junction: A prospective IDEAL 2a study with qualitative design

Objective: To explore the change and feasibility of surgical techniques of laparoscopic transhiatal(TH)-lower mediastinal lymph node dissection(LMLND) for adenocarcinoma of the esophagogastric junction(AEG)according to Idea, Development, Exploration, Assessment, and Long-term follow-up(IDEAL) 2a standards.Methods: Patients diagnosed with AEG who underwent laparoscopic TH-LMLND were prospectively included from April 14, 2020, to March 26, 2021. Clinical and pathological information as well as surgical outcomes were quantitatively analyzed. Semistructured interviews with the surgeon after each operation were qualitatively analyzed.Results: Thirty-five patients were included. There were no cases of transition to open surgery, but three cases involved combination with transthoracic surgery. In qualitative analysis, 108 items under three main themes were detected: explosion, dissection, and reconstruction. Revised instruction was subsequently designed according to the change in surgical technique and the cognitive process behind it. Three patients had anastomotic leaks postoperatively, with one classified as Clavien-Dindo Ⅲa.Conclusions: The surgical technique of laparoscopic TH-LMLND is stable and feasible;further IDEAL 2b research is warranted.

Nonoperative management of gastrointestinal malignancies in era of neoadjuvant treatment

Cancers derived from the gastrointestinal(GI)tract are often treated with radical surgery to achieve a cure.However,recent advances in the management of GI cancers involve the use of a combination of neoadjuvant radiation and chemotherapy followed by surgical intervention to achieve improved local control and cure.Interestingly,a small proportion of patients with highly sensitive tumors achieved a pathological complete response(pCR)(no residual tumor cells in the resected specimen)to neoadjuvant chemoradiation therapy(nCRT).The desire for organ preservation and avoidance of surgical morbidity brings the idea of a nonoperative management(NOM)strategy.Because of the different nature of tumor biology,GI cancers present diverse responses to nCRT,ranging from high sensitivity(anal cancer)to low sensitivity(gastric/esophageal cancer).There is an increasing attention to NOM of localized GI cancers;however,without the use of biomarkers/imaging parameters to select such patients,NOM will remain a challenge.Therefore,this review intends to summarize some of the recent updates from the aspect of current nCRT regimens,criteria for patient selection and active surveillance schedules.We also hope to review significant sequelae of radical surgery and the complications of nCRT to clarify the directions for optimization of nCRT and NOM for oncologic outcomes and quality of life.

GPU-based cross-platform Monte Carlo proton dose calculation engine in the framework of Taichi

In recent years,graphics processing units(GPUs)have been applied to accelerate Monte Carlo(MC)simulations for proton dose calculation in radiotherapy.Nonetheless,current GPU platforms,such as Compute Unified Device Architecture(CUDA)and Open Computing Language(OpenCL),suffer from cross-platform limitation or relatively high programming barrier.However,the Taichi toolkit,which was developed to overcome these difficulties,has been successfully applied to high-performance numerical computations.Based on the class II condensed history simulation scheme with various proton-nucleus interactions,we developed a GPU-accelerated MC engine for proton transport using the Taichi toolkit.Dose distributions in homogeneous and heterogeneous geometries were calculated for 110,160,and 200 MeV protons and were compared with those obtained by full MC simulations using TOPAS.The gamma passing rates were greater than 0.99 and 0.95 with criteria of 2 mm,2%and 1 mm,1%,respectively,in all the benchmark tests.Moreover,the calculation speed was at least 5800 times faster than that of TOPAS,and the number of lines of code was approximately 10 times less than those of CUDA or OpenCL.Our study provides a highly accurate,efficient,and easy-to-use proton dose calculation engine for fast prototyping,beamlet calculation,and education purposes.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Cancer risk in relatives of BRCA1/2 pathogenic variant carriers in a large series of unselected patients with breast cancer

Objective:The spectrum and risk of cancer in relatives of BRCA1/2 pathogenic variant carriers in the Chinese population have not been established.Methods:A family history of cancer in 9903 unselected breast cancer patients was retrospectively analyzed.BRCA1/2 status was determined for all patients and relative risks(RRs)were calculated to evaluate cancer risk in relatives of the patients.Results:The incidences of breast cancer in female relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 33.0%,32.2%,and 7.7%,respectively.The corresponding incidences of ovarian cancer were 11.5%,2.4%,and 0.5%,respectively.The incidences of pancreatic cancer in male relatives of BRCA1 carriers,BRCA2 carriers,and non-carriers were 1.4%,2.7%,and 0.6%,respectively.The corresponding incidences of prostate cancer were 1.0%,2.1%,and 0.4%,respectively.The risks of breast and ovarian cancers in female relatives of BRCA1 and BRCA2 carriers were significantly higher than female relatives of non-carriers(BRCA1:RR=4.29,P<0.001 and RR=21.95,P<0.001;BRCA2:RR=4.19,P<0.001 and RR=4.65,P<0.001,respectively).Additionally,higher risks of pancreatic and prostate cancers were noted in male relatives of BRCA2 carriers than non-carriers(RR=4.34,P=0.001 and RR=4.86,P=0.001,respectively).Conclusions:Female relatives of BRCA1 and BRCA2 carriers are at increased risk for breast and ovarian cancers,and male relatives of BRCA2 carriers are at increased risk for pancreatic and prostate cancers.

PTPRD/PTPRT mutation correlates to treatment outcomes of immunotherapy and immune landscape in pan-cancers

Objective: PTPRD and PTPRT are phosphatases of the JAK-STAT pathway related to immunotherapy.However, the role and mechanism of PTPRD and PTPRT mutations in multiple cancers remains unclear.Methods: Clinical data and PTPRD/PTPRT mutation information from 12 cohorts were collected and classified as a discovery cohort and three validation cohorts. The association between PTPRD/PTPRT mutations and immunotherapeutic efficacy was analyzed. Then, the association between PTPRD/PTPRT mutation and immune profiles was analyzed using The Cancer Genome Atlas(TCGA) cohort.Results: A total of 2,392 patients across 20 cancer types were included in this study. Our results showed that patients harboring PTPRD/PTPRT mutation, especially co-mutations, had a significantly elevated response rate to immunotherapy in multiple cancers. Patients with PTPRD/PTPRT mutation had a higher objective response rate(ORR)(P=0.002), longer overall survival(OS)(P=0.005) and progression-free survival(PFS)(P=0.038).Importantly, the above findings were further verified in validation cohorts. In addition, we found that the PTPRD/PTPRT co-mutations(co-mut) subgroup exhibited an immune-activated phenotype, the wild-type subgroup tended to have an immune-desert phenotype, and the uni-mutation(uni-mut) subgroup might have an immune-mixed phenotype. Our further analyses suggested that combining programmed cell death ligand 1(PDL1) expression and PTPRD/PTPRT mutation can be used to screen patients who may benefit from immunotherapy.Conclusions: PTPRD/PTPRT mutation could serve as a potential predictive biomarker for cancer immunotherapy.

Research progress of minimally invasive surgery for gastric cancer

Since the first laparoscopic radical surgery for early gastric cancer 30 years ago, there has been a gradual shift from“open” to “minimally invasive” surgery for gastric cancer. This transition is due to advancements in refined anatomy, enlarged field of view, faster recovery, and comparable oncological outcomes. Several high-quality clinical studies have demonstrated the safety and effectiveness of laparoscopy in the treatment of both early and locally advanced gastric cancer. The role of perioperative chemotherapy in managing locally advanced gastric cancer has been widely recognized, and there have been continuous breakthroughs in the exploration of targeted therapy and immunotherapy for perioperative treatment. Additionally, the application of indocyanine green near-infrared imaging technology, 3D laparoscopic technology, and robotic surgery systems has further improved the accuracy and minimally invasive nature of gastric cancer surgeries. Looking ahead, the field of minimally invasive surgery for gastric cancer is expected to become more standardized, resulting in a significant enhancement in the quality of life for gastric cancer patients.

Double-tract reconstruction is superior to esophagogastrostomy in controlling reflux esophagitis and enhancing quality of life after proximal gastrectomy:Results from a prospective randomized controlled clinical trial in China

Objective:The aim of this study was to prospectively compare double-tract reconstruction(DTR)and esophagogastrostomy(EG)after proximal gastrectomy(PG)regarding the incidence of reflux esophagitis,quality of life(QOL),nutritional status and surgical safety.Methods:This study was a randomized controlled trial.Patients eligible for PG were enrolled and randomly assigned to the EG group and DTR group.The characteristics of patients,parameters for surgical safety,incidence of reflux esophagitis,nutrition status and QOL were collected and compared between the two groups.Univariate analysis and multivariate analysis were performed to determine the significant factors affecting the incidence of reflux esophagitis after PG.Results:Thirty-seven patients of the EG group and 36 patients of the DTR group were enrolled.The incidence of reflux esophagitis was significantly lower in the DTR group than in the EG group(8.3%vs.32.4%,P=0.019).The DTR group demonstrated a more favorable QOL than the EG group after PG.The nutritional status was balanced within the EG group and the DTR group.The operation time was longer in the DTR group than in the EG group(191 min vs.221 min,P=0.001),while surgical safety was similar in the two groups.Conclusions:Our research demonstrated that DTR is superior to EG after PG in terms of the incidence of reflux esophagitis and provides a more satisfactory QOL without increasing surgical complications or sacrificing nutritional status.

Aqueous-soluble components of sporoderm-removed Ganoderma lucidum spore powder promote ferroptosis in oral squamous cell carcinoma

Objective: Ferroptosis is a novel cell death process which displays a promising role in cancer treatment.However, clinically available drugs targeting ferroptosis are rarely used, and yet there are no studies reporting on inducing ferroptosis via Chinese herbal extracts. Here we explored the tumor inhibition effects of Ganoderma lucidum(G. lucidum) on oral squamous cell carcinoma(OSCC). Specifically, we aimed to clarify the biological mechanism of components in the dietary, aqueous-soluble sporoderm-removed G. lucidum spore powder(A-GSP).Methods: Preliminary transcriptome analysis revealed the significant enrichment of the ferroptosis pathway.Cellular Fe2+, glutathione(GSH), malondialdehyde(MDA), reactive oxygen species(ROS) and lipid peroxide levels were measured to identify ferroptosis occurrence. Western blotting was used to measure ferroptosis-related proteins. Changes in mitochondria morphology and function were observed with transmission electron microscopy(TEM) and ATP detection assays. Ferroptosis inhibitor ferrostatin-1 was then used to verify the anti-tumor effects of A-GSP. Finally, nude mice xenograft models of oral cancer confirmed that A-GSP inhibited tumor growth.Results: A-GSP promoted ferroptosis in oral cancer cells by inducing Fe2+influx, GSH depletion, as well as lipid peroxide and ROS accumulation. Ferroptosis-related proteins exhibited corresponding changes, particularly Acylco A synthetase long chain family member 4(ACSL4) increase and glutathione peroxidase 4(GPX4) decrease. A-GSP considerably lowered mitochondrial volume and ridge number, while significantly decreasing ATP production. Ferrostatin-1 reversed all of these A-GSP-induced changes. In vivo, A-GSP exerted a ferroptosismediated tumor-suppressing effect without observable adverse reactions.Conclusions: Our findings demonstrate the therapeutic potential of A-GSP for treating patients with OSCC by targeting ferroptosis.

Inspired by novel radiopharmaceuticals:Rush hour of nuclear medicine

Nuclear medicine plays an irreplaceable role in the diagnosis and treatment of tumors.Radiopharmaceuticals are important components of nuclear medicine.Among the radiopharmaceuticals approved by the Food and Drug Administration(FDA),radio-tracers targeting prostate-specific membrane antigen(PSMA)and somatostatin receptor(SSTR)have held essential positions in the diagnosis and treatment of prostate cancers and neuroendocrine neoplasms,respectively.In recent years,FDA-approved serials of immune-therapy and targeted therapy drugs targeting programmed death 1(PD-1)/programmed death ligand 1(PD-L1),human epidermal growth factor receptor 2(HER2),and nectin cell adhesion molecule 4(Nectin 4).How to screen patients suitable for these treatments and monitor the therapy?Nuclear medicine with specific radiopharmaceuticals can visualize the expression level of those targets in systemic lesions and evaluate the efficacy of treatment.In addition to radiopharmaceuticals,imaging equipment is also a key step for nuclear medicine.Advanced equipment including total-body positron emission tomography/computed tomography(PET/CT)and positron emission tomography/magnetic resonance imaging(PET/MRI)has been developed,which contribute to the diagnosis and treatment of tumors,as well as the development of new radiopharmaceuticals.Here,we conclude most recently advances of radiopharmaceuticals in nuclear medicine,and they substantially increase the“arsenal”of clinicians for tumor therapy.

Comments on National Health Commission guidelines for diagnosis and treatment of colorectal cancer 2023 in China(English version)

Colorectal cancer(CRC)has always been one of the most common malignant tumors in the world,and the incidence and mortality have been on the rise in China.The Cancer Statistics Report of China in 2020 showed that the incidence and mortality of CRC ranked second and fifth among all malignant tumors,with 555,000 new cases and 286,000 deaths,respectively.Among them,cities were much higher than rural areas,and the incidence of colon cancer had increased significantly.Most patients were already in the advanced stage at the time of diagnosis.