Objective To systematically evaluate the efficacy and safety of proximal gastrectomy (PG) versus total gastrectomy (TG) for the treatment of Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG). Methods PubMed, The Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, and VIP databases were searched for literature comparing the efficacy and safety of PG and TG for the treatment of Siewert type Ⅱ/Ⅲ AEG. The search period was from database inception to March 2023. Meta-analysis was performed using Review Manager 5.4 software. Results A total of 23 articles were included, including 16 retrospective cohort studies, 5 prospective cohort studies, and 2 randomized controlled trials. The total sample size was 2 826 patients, with 1 389 patients undergoing PG and 1 437 patients undergoing TG. Meta-analysis results showed that compared with TG, PG had less intraoperative blood loss [MD=−19.85, 95%CI (−37.20, −2.51), P=0.02] and shorter postoperative hospital stay [MD=−1.23, 95%CI (−2.38, −0.08), P=0.04]. TG had a greater number of lymph nodes dissected [MD=−6.20, 95%CI (−7.68, −4.71), P<0.001] and a lower incidence of reflux esophagitis [MD=3.02, 95%CI (1.24, 7.34), P=0.01]. There were no statistically significant differences between the two surgical approaches in terms of operative time, postoperative survival rate (1-year, 3-year, 5-year), and postoperative overall complications (P>0.05). Conclusion PG has advantages in terms of intraoperative blood loss and postoperative hospital stay, while TG has advantages in terms of the number of lymph nodes dissected and the incidence of reflux esophagitis. There is no significant difference in long-term survival between the two surgical approaches.

Chemotherapy is an important treatment for tumors， but most patients experience varying degrees of chemotherapy- induced myelosuppression. Four properties theory of traditional Chinese medicine （TCM） has unique advantages in improving chemotherapy-induced myelosuppression. The monomers from TCM with different properties and flavors， such as cold-natured （e.g. Scutellaria baicalensis， Rhus chinensis）， cool-natured （e.g. Ligustrum lucidum， Ophiopogon japonicus）， warm-natured （e.g. Panax ginseng， Epimedium brevicornu， Curcuma longa， Angelica sinensis）， hot-natured （e.g. Cinnamomum cassia， Aconitum carmichaeli）， and neutral-natured （e. g. donkey-hide gelatin， Lycium barbarum， Rhodiola rosea， fungi）， can exert anti- myelosuppressive effects by reducing damage to hematopoietic stem/progenitor cells， improving the bone marrow hematopoietic microenvironment， inhibiting the oxidative stress response， regulating signaling pathways， so as to ultimately repaire inflammatory damage and improve hematopoietic function， thereby playing an anti-myelosuppressive role.

Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans ; Gastrointestinal Microbiome/physiology* ; Animals ; Carcinogenesis/metabolism* ; Colitis-Associated Neoplasms/microbiology* ; Fatty Acids, Volatile/metabolism* ; Bile Acids and Salts/metabolism* ; Colitis/microbiology*

This study aims to establish a method for counting the viral particles in adenovirus vector-based vaccines. Nano-flow cytometry was employed to analyze the viral particles in adenovirus-based vector vaccines at the single-particle level. Monodisperse silica nanoparticles with a refractive index close to that of the virus were selected as the particle size standard to calculate the viral particle size, which was then compared with the results obtained from transmission electron microscopy (TEM) to determine the gating strategy. Subsequently, a particle count standard was employed to calculate the viral particle concentration. The established method demonstrated good linearity, accuracy, precision, and specificity. The results of determined viral particle concentration showed a good correlation with the infectious titer. Compared with the conventional OD₂₆₀ method, nano-flow cytometry can directly measure the viral particle concentration and indicate whether the sample has been disassembled according to changes in viral particle concentration and size, thus more accurately reflecting the actual infectious potency of the sample. The novel quantification method established in this study is capable of indicating the efficacy of adenovirus vector-based vaccines and provides effective technical support for the quality control of such products.
Adenoviridae/genetics* ; Genetic Vectors ; Flow Cytometry/methods* ; Virion/isolation & purification* ; Particle Size ; Nanoparticles ; Viral Vaccines

L-phosphinothricin (L-PPT) is an efficient broad-spectrum herbicide. To realize the multi-enzyme catalytic preparation of L-PPT, we constructed an engineered strain Escherichia coli YM-1 for efficient expression of D-amino acid transaminase, which could catalyze the generation of the intermediate 2-oxo-4-[(hydroxymethylphosphonyl)] butyric acid (PPO) from D-phosphinothricin (D-PPT). In addition, E. coli pLS was constructed to co-express glutamate dehydrogenase and glucose dehydrogenase, which not only catalyzed the generation of L-PPT from PPO but also regenerated the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH). A fed-batch fermentation process was then established for E. coli YM-1 and pLS, and the apparent activities of D-amino acid transaminase and glutamate dehydrogenase were increased by 22.68% and 100.82%, respectively, compared with those in shake flasks. The process parameters were optimized for the catalytic preparation of L-PPT by whole-cell cascade of E. coli YM-1 and pLS with D, L-PPT as the substrate. After reaction for 8 h, 91.36% conversion of D-PPT was achieved, and the enantiomeric excess of L-PPT reached 90.22%. The findings underpin the industrial production of L-PPT.
Escherichia coli/enzymology* ; Aminobutyrates/metabolism* ; Glutamate Dehydrogenase/biosynthesis* ; Glucose 1-Dehydrogenase/biosynthesis* ; Herbicides/metabolism* ; Multienzyme Complexes/metabolism* ; Transaminases/metabolism* ; Phosphinic Acids/metabolism*

The objective of this experiment was to investigate the inhibitory effect and mechanism of mammary-derived extracellular vesicles(MmEVs)from mastitis dairy cows on the biofilm for-mation of Staphylococcus aureus SA1.The biofilm-forming ability of Staphylococcus aureus SA1 was confirmed using Congo red staining,and the biofilm growth curve of S.aureus SA1 was plot-ted using the crystal violet staining method.The minimum inhibitory concentration(MIC)and minimum biofilm inhibitory concentration(MBIC)of MmEVs against S.aureus SA1 were deter-mined.After treating S.aureus SA1 with different concentrations of MmEVs,the cell morphology of S.aureus SA1 was observed using transmission electron microscopy.The effects of MmEVs on S.aureus SA1 under low pH(pH value=5)or heat stress(58℃)were investigated.The hydro-phobicity index was explored using the microbial adhesion to hydrocarbons(MATH)assay.Bacte-rial conductivity was measured.The expression levels of biofilm-related genes(SarA,icaB,FnbA,ClfB,CidA,and gyrB)were detected using quantitative real-time PCR(qPCR).The results showed that MIC of MmEVs against the biofilm of S.aureus SA1 was 1 000 mg/L,and the MBIC was 500 mg/L.Under the influence of MmEVs,the internal substances of S.aureus SA1 leaked,the biofilm boundary became blurred,and the cell wall separated.At the MBIC concentration,MmEVs significantly reduced the tolerance of S.aureus SA1 to low pH(P＜0.001)and high tem-perature(P＜0.001),decreased hydrophobicity(P＜0.001),and increased bacterial conductivity(P＜0.001).At the MBIC concentration,MmEVs significantly downregulated the gene expression of Sa rA(P＜0.001),icaB(P＜0.001),FnbA(P＜0.001),ClfB(P＜0.001),and CidA(P＜0.001)in S.aureus SA1,while no significant effect was observed on the expression of the gyrB gene.In summary,MmEVs inhibit the formation of Staphylococcus aureus SA1 biofilms by sup-pressing the gene expression of SarA,icaB,FnbA,ClfB,and CidA within the biofilm.This dis-ruption damages the biofilm's morphological structure,reduces its tolerance to low pH and high temperature,decreases hydrophobicity,and increases bacterial conductivity,thereby ultimately in-hibiting the formation of S.aureus SA1 biofilms.

Malignant intestinal obstruction is one of the common clinical symptoms of peritoneal metastasis of colorectal cancer, and its pathophysiological mechanism involves various factors such as local invasion and compression of tumors, intestinal adhesions caused by the formation of scattered nodules in the abdominal cavity, inflammatory response in the abdominal cavity, and neuromodulation disorders. Patients with traditional intestinal obstruction are generally treated with surgery, but patients with malignant intestinal obstruction associated with peritoneal metastasis of colorectal cancer can present with multi-level obstruction, complex and diverse symptoms. Combined with multiple metastases in the abdominal cavity and even accompanied by cachexia, malignant intestinal obstruction as a major treatment problem in the field of colorectal surgery is often difficult to be treated by surgery. What's more, it is worth noting that new progress and breakthroughs have been made in the diagnosis and treatment of peritoneal metastasis of colorectal cancer, and the treatment of cancerous intestinal obstruction has also begun to receive extensive attention. Therefore, this article summarizes the clinical features of peritoneal metastasis-related malignant intestinal obstruction in colorectal cancer and looks forward to its treatment challenges.

Iron,a vital trace element and redox-active metal in the human body,is pivotal in cellular processes and en-gages in a multitude of biological reactions.Ferroptosis,an emerging form of regulated cell death,is predominantly instiga-ted by the excessive free iron that catalyzes reactive oxygen species(ROS)production via the Fenton reaction.This process results in the peroxidation of polyunsaturated fatty acids within the cellular lipid membrane,compromising the membrane's integrity and thereby inducing ferroptosis.In the context of diabetic retinopathy(DR),ferroptosis plays a sig-nificant role.The disruption of iron metabolism,the excessive accumulation of ROS,and the imbalance of the antioxidant system are key mechanisms contributing to ferroptosis in retinal tissues and the exacerbation of DR's pathological progres-sion.This review provides a systematic summary and in-depth discussion of the advancements in understanding the role of ferroptosis in DR pathogenesis,intending to offer valuable insights for future research endeavors in this field.

Objective:To explore the related risk factors of diaphragmatic hernia after thoraco-laparoscopic minimally invasive Mckeown esophagectomy (MIME).Methods:This is a retrospective controlled study. A retrospective analysis was conducted on the clinical data of patients who underwent MIME at the Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, from January 2016 to December 2023. A total of 619 patients were included. There were 423 males and 196 females, aged (63.7±7.6) years (range: 37 to 87 years). The diagnosis of diaphragmatic hernia after MIME was made based on clinical symptoms and CT scans. Patients were divided into two groups: the diaphragmatic hernia group ( n=16) and the non-diaphragmatic hernia group ( n=603). Clinical data, including age, gender, body mass index (BMI), smoking history, tumor location (upper, middle, and lower thoracic esophagus), preoperative neoadjuvant therapy history, and tumor staging, were collected and analyzed. A BMI of 25 kg/m2 and age of 65 years were used as cutoff values. The χ2 test and Fisher′s exact test were used to compare the data between the two groups, and Logistic regression was employed for risk factor analysis. The diaphragmatic hernia group and non-diaphragmatic hernia group were matched in a 1∶3 ratio with a caliper value of 0.02 by propensity score matching. Kaplan-Meier method was used for survival analysis and compared using the log-rank test for between-group differences. Results:The proportion of patients with diaphragmatic hernia after MIME who underwent surgical treatment was 6/16. Statistically significant differences were observed between the diaphragmatic hernia group and the non-diaphragmatic hernia group in terms of age ( χ2=16.057, P<0.01), BMI ( χ2=16.057, P<0.01), and tumor location ( χ2=12.048, P=0.002). Multivariate logistic regression analysis revealed that age ≥65 years ( OR=1.236, P=0.023) and BMI<25 kg/m2 ( OR=0.810, P<0.01) were independent risk factors for the development of diaphragmatic hernia after MIME. Survival analysis showed no significant difference in long-term survival between patients with and without diaphragmatic hernia after MIME ( P=0.187), and whether patients with diaphragmatic hernia underwent surgery was not associated with long-term prognosis ( P=0.560). Conclusion:Patients with BMI<25 kg/m 2 and age ≥65 years are independent risk factors for diaphragmatic hernia after MIME. The occurrence of diaphragmatic hernia is not associated with prognosis, and whether patients with diaphragmatic hernia undergo surgery does not affect the prognosis.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.