Erratum: Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform.

This corrects the article 10.3791/66058.

Metastable FeSe2 nanosheets as a one-for-all platform for stepwise synergistic tumor therapy.

The urgent need to curb the rampant rise in cancer has impelled the rapid development of nanomedicine. Under the above issue, transition metal compounds have received special attention considering their physicochemical and biochemical properties. However, how to take full advantage of the valuable characteristics of nanomaterials based on their spatial structures and chemical components for synergistic tumor therapy is a worthwhile exploration. In this work, a tailored two-dimensional (2D) FeSe2 nanosheet (NS) platform is proposed, which integrates enzyme activity and drug efficacy through the regulation of itsstability. Specifically, metastable FeSe2 NSs can serve as dual nanozymes in an intact state, depleting GSH and increasing ROS to induce oxidative stress in the tumor microenvironment (TME). With the gradual degradation of the FeSe2 in TME, its degraded products can amplify the Fenton reaction and GSH consumption, enhance the expression of inflammatory factors, and achieve effective near-infrared (NIR)-light irradiation-enhanced synergistic photothermal therapy (PTT) and chemodynamic therapy (CDT). Our exploration further confirmed such a strategy that may integrate carrier activity and drug action into a metastable nanoplatform for tumor synergistic therapy. These results prompt the consideration of the rational design of a one-for-all carrier that can exhibit multifunctional properties and nanomedicine efficacy for versatile therapeutic applications in the future.

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform.

Gastric cancer is a common heterogeneous tumor. Most patients have advanced gastric cancer at the time of diagnosis and often need chemotherapy. Although 5-fluorouracil (5-FU) is widely used for treatment, its therapeutic sensitivity and drug tolerance still need to be determined, which emphasizes the importance of individualized administration. Pharmacogenetics can guide the clinical implementation of individualized treatment. Single nucleotide polymorphisms (SNPs), as a genetic marker, contribute to the selection of appropriate chemotherapy regimens and dosages. Some SNPs are associated with folate metabolism, the therapeutic target of 5-FU. Methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133, dihydrofolate reductase (DHFR) rs1650697 and rs442767, methionine synthase (MTR) rs1805087, gamma-glutamyl hydrolase (GGH) rs11545078 and solute carrier family 19 member 1 (SLC19A1) rs1051298 have been investigated in different kinds of cancers and antifolate antitumor drugs, which have potential forecasting and guiding significance for application of 5-FU. The ion torrent next-generation semiconductor sequencing technology can rapidly detect gastric cancer-related SNPs. Each time a base is extended in a DNA chain, an H+ will be released, causing local pH changes. The ionic sensor detects pH changes and converts chemical signals into digital signals, achieving sequencing by synthesis. This technique has low sample requirement, simple operation, low cost, and fast sequencing speed, which is beneficial for guiding individualized chemotherapy by SNPs.

Effects of positive end-expiratory pressure on regional cerebral oxygen saturation in elderly patients undergoing thoracic surgery during one-lung ventilation: a randomized crossover-controlled trial.

BACKGROUND: A significant reduction in regional cerebral oxygen saturation (rSO2) is commonly observed during one-lung ventilation (OLV), while positive end-expiratory pressure (PEEP) can improve oxygenation. We compared the effects of three different PEEP levels on rSO2, pulmonary oxygenation, and hemodynamics during OLV. METHODS: Forty-three elderly patients who underwent thoracoscopic lobectomy were randomly assigned to one of six PEEP combinations which used a crossover design of 3 levels of PEEP-0 cmH2O, 5 cmH2O, and 10 cmH2O. The primary endpoint was rSO2 in patients receiving OLV 20 min after adjusting the PEEP. The secondary outcomes included hemodynamic and respiratory variables. RESULTS: After exclusion, thirty-six patients (36.11% female; age range: 60-76 year) were assigned to six groups (n = 6 in each group). The rSO2 was highest at OLV(0) than at OLV(10) (difference, 2.889%; [95% CI, 0.573 to 5.204%]; p = 0.008). Arterial oxygen partial pressure (PaO2) was lowest at OLV(0) compared with OLV(5) (difference, -62.639 mmHg; [95% CI, -106.170 to -19.108 mmHg]; p = 0.005) or OLV(10) (difference, -73.389 mmHg; [95% CI, -117.852 to -28.925 mmHg]; p = 0.001), while peak airway pressure (Ppeak) was lower at OLV(0) (difference, -4.222 mmHg; [95% CI, -5.140 to -3.304 mmHg]; p < 0.001) and OLV(5) (difference, -3.139 mmHg; [95% CI, -4.110 to -2.167 mmHg]; p < 0.001) than at OLV(10). CONCLUSIONS: PEEP with 10 cmH2O makes rSO2 decrease compared with 0 cmH2O. Applying PEEP with 5 cmH2O during OLV in elderly patients can improve oxygenation and maintain high rSO2 levels, without significantly increasing peak airway pressure compared to not using PEEP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200060112 on 19 May 2022.

Helicobacter pylori CagA-mediated ether lipid biosynthesis promotes ferroptosis susceptibility in gastric cancer.

Helicobacter pylori, particularly cytotoxin-associated gene A (CagA)-positive strains, plays a key role in the progression of gastric cancer (GC). Ferroptosis, associated with lethal lipid peroxidation, has emerged to play an important role in malignant and infectious diseases, but the role of CagA in ferroptosis in cancer cells has not been determined. Here, we report that CagA confers GC cells sensitivity to ferroptosis both in vitro and in vivo. Mechanistically, CagA promotes the synthesis of polyunsaturated ether phospholipids (PUFA-ePLs), which is mediated by increased expression of alkylglycerone phosphate synthase (AGPS) and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3), leading to susceptibility to ferroptosis. This susceptibility is mediated by activation of the MEK/ERK/SRF pathway. SRF is a crucial transcription factor that increases AGPS transcription by binding to the AGPS promoter region. Moreover, the results demonstrated that CagA-positive cells are more sensitive to apatinib than are CagA-negative cells, suggesting that detecting the H. pylori CagA status may aid patient stratification for treatment with apatinib.

Bacillus subtilis improves antioxidant capacity and optimizes inflammatory state in broilers.

OBJECTIVE: Bacillus subtilis, a kind of probiotic with broad-spectrum antibacterial function, was commonly used in livestock and poultry production. Recent research suggested that Bacillus subtilis may have antioxidant properties and improve immune response. This study aimed to verify the probiotic function of Bacillus subtilis in the production of broiler chickens. METHODS: A total of 324 (1-day-old) Arbor Acres broilers were selected and randomly divided into three groups: basal diet group (Ctr Group), basal diet + antibiotic growth promoter group (Ctr + AGP) and basal diet + 0.5% Bacillus subtilis preparation group (Ctr + Bac). The experiment lasted for 42 days. Muscle, serum and liver samples were collected at 42 days for determination. RESULTS: The results showed that Bacillus subtilis could decrease malondialdehyde content in the serum and liver (p<0.05) and increase superoxide dismutase 1 mRNA expression (p<0.01) and total superoxide dismutase (p<0.05) in the liver. In addition, compared with AGP supplementation, Bacillus subtilis supplementation increased interleukin-10 (IL-10) and decreased tumor necrosis factor-α and IL-1ß level in the serum (p<0.05). At 45 minutes after slaughter Ctr + Bac presented a higher a* value of breast muscle than Ctr Group (p<0.05), while significant change in leg muscle was not identified. Moreover, there was no difference in weight, shear force, cooking loss and drip loss of breast and leg muscle between treatments. CONCLUSION: Our results demonstrate that Bacillus subtilis in diet can enhance antioxidant capacity and optimize immune response of broilers.

Nutritional composition, health-promoting effects, bioavailability, and encapsulation of tree peony seed oil: a review.

Tree peony is cultivated worldwide in large quantities due to its exceptional ornamental and medicinal value. In recent years, the edible value of tree peony seed oil (TPSO) has garnered significant attention for its high content of alpha-linolenic acid (ALA, >40%) and other beneficial minor components, including phytosterols, tocopherols, squalene, and phenolics. This review provides a systematic summary of the nutritional composition and health-promoting effects of TPSO, with a specific focus on its digestion, absorption, bioavailability, and encapsulation status. Additionally, information on techniques for extracting and identifying adulteration of TPSO, as well as its commercial applications and regulated policies, is included. Thanks to its unique nutrients, TPSO offers a wide range of health benefits, such as hypolipidemic, anti-obesity, cholesterol-lowering, antioxidant and hypoglycemic activities, and regulation of the intestinal microbiota. Consequently, TPSO shows promising potential in the food and cosmetic industries and should be cultivated in more countries. However, the application of TPSO is hindered by its low bioavailability, poor stability, and limited water dispersibility. Therefore, it is crucial to develop effective delivery strategies, such as microencapsulation and emulsion, to overcome these limitations. In conclusion, this review provides a comprehensive understanding of the nutritional value of TPSO and emphasizes the need for further research on its nutrition and product development.

Impact of preoperative therapy on surgical outcomes of laparoscopic total gastrectomy for gastric/gastroesophageal junction cancer.

Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer (GC)/gastroesophageal junction cancer (GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy (LTG) for GC/GEJC patients who have received preoperative therapy (PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients. Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405 received LTG (LTG group) and 106 received PT+LTG (PT-LTG group) at Nanfang Hospital between June 2018 and September 2022. The surgical outcomes were compared between the two groups. Results: The surgical duration was significantly longer in the PT-LTG group (P<0.001), while the incidence of intraoperative complications (P=1.000), postoperative complications (LTG group vs. PT-LTG group: 26.2% vs. 23.6%, P=0.587), the classification of complication severity (P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups (LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio (OR)=14.094, 95% confidence interval (95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG (OR=0.945, 95% CI: 0.371-2.408, P=0.905). Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.

Clinical outcomes of conversion surgery following immune checkpoint inhibitors and chemotherapy in stage IV gastric cancer.

BACKGROUND: The clinical benefit of conversion surgery following immunochemotherapy in patients with stage IV gastric cancer (GC) remains uncertain. This study aims to clarify the clinical outcomes of conversion surgery for such patients. METHODS: This retrospective cohort study enroled consecutive patients with stage IV GC treated with a combination of immune checkpoint inhibitors and chemotherapy and/or anti-human epidermal growth factor receptor-2 targeted therapy as first-line therapy. Cumulative survival curves were estimated using Kaplan-Meier method. Logistic regression and Cox regression analyses were conducted to identify factors associated with conversion surgery and survival, respectively. RESULTS: Among the 136 patients included in the study. The disease control rate was 72.1% (98/136), with objective response rate in 58.8% (80/136) and complete response rate in 5.9% (8/136). Among 98 patients with disease control, 56 patients underwent palliative immunochemotherapy with median progression-free survival (PFS) and overall survival at 9.2 and 16.2 months, respectively; the remaining 42 patients underwent conversion surgery, yielding an unreached median PFS over a 19.0-month median follow-up, accompanied by 1-year overall survival and PFS rates of 96.6% and 89.1%, respectively. The R0 resection rate reached 90.5% (38/42). 7 out of 42 patients achieved pathological complete response, of whom three patients demonstrated human epidermal growth factor receptor-2 positivity. No serious complications leading to death were observed during the perioperative period. Multivariate analysis indicated that programmed death ligand 1 combined positive score greater than or equal to 5 (odds ratio, 0.22; 95% CI, 0.08-0.57; P =0.002) favored successful conversion surgery, while signet ring cell carcinoma (hazard ratio, 6.29; 95% CI, 1.56-25.36; P =0.010) was the poor prognostic factor associated with survival in patients who underwent conversion surgery. CONCLUSIONS: Conversion surgery holds the potential for significant survival benefits in stage IV GC patients who have achieved a favourable clinical response to immunochemotherapy. Individuals with signet ring cell carcinoma may experience increased post-conversion surgery recurrence.

Corrigendum: Relationship between programmed death ligand 1 expression and other clinicopathological features in a large cohort of gastric cancer patients.

[This corrects the article DOI: 10.3389/fimmu.2022.783695.].

N4-Acetylcytidine Drives Glycolysis Addiction in Gastric Cancer via NAT10/SEPT9/HIF-1α Positive Feedback Loop.

Anti-angiogenic therapy has long been considered a promising strategy for solid cancers. Intrinsic resistance to hypoxia is a major cause for the failure of anti-angiogenic therapy, but the underlying mechanism remains unclear. Here, it is revealed that N4-acetylcytidine (ac4C), a newly identified mRNA modification, enhances hypoxia tolerance in gastric cancer (GC) cells by promoting glycolysis addiction. Specifically, acetyltransferase NAT10 transcription is regulated by HIF-1α, a key transcription factor of the cellular response to hypoxia. Further, acRIP-sequencing, Ribosome profiling sequencing, RNA-sequencing, and functional studies confirm that NAT10 in turn activates the HIF-1 pathway and subsequent glucose metabolism reprogramming by mediating SEPT9 mRNA ac4C modification. The formation of the NAT10/SEPT9/HIF-1α positive feedback loop leads to excessive activation of the HIF-1 pathway and induces glycolysis addiction. Combined anti-angiogenesis and ac4C inhibition attenuate hypoxia tolerance and inhibit tumor progression in vivo. This study highlights the critical roles of ac4C in the regulation of glycolysis addiction and proposes a promising strategy to overcome resistance to anti-angiogenic therapy by combining apatinib with ac4C inhibition.

SARS-Cov-2 Spike-S1 Antigen Test Strip with High Sensitivity Endowed by High-Affinity Antibodies and Brightly Fluorescent QDs/Silica Nanospheres.

The extensive research into developing novel strategies for detecting respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in clinical specimens, especially the sensitive point-of-care testing method, is still urgently needed to reach rapid screening of viral infections. Herein, a new lateral flow immunoassay (LFIA) platform was reported for the detection of SARS-CoV-2 spike-S1 protein antigens, in which four sensitive and specific SARS-CoV-2 mouse monoclonal antibodies (MmAbs) were tailored by using quantum dot (QD)-loaded dendritic mesoporous silica nanoparticles modified further for achieving the -COOH group surface coating (named Q/S-COOH nanospheres). Importantly, compact QD adsorption was achieved in mesoporous channels of silica nanoparticles on account of highly accessible central-radial pores and electrostatic interactions, leading to significant signal amplification. As such, a limit of detection for SARS-CoV-2 spike-S1 testing was found to be 0.03 ng/mL, which is lower compared with those of AuNPs-LFIA (traditional colloidal gold nanoparticles, Au NPs) and enzyme-linked immunosorbent assay methods. These results show that optimizing the affinity of antibody and the intensity of fluorescent nanospheres simultaneously is of great significance to improve the sensitivity of LFIA.

Enhancing the Stability and Bioaccessibility of Tree Peony Seed Oil Using Layer-by-Layer Self-Assembling Bilayer Emulsions.

Tree peony seed oil (TPSO) is an important plant source of n-3 polyunsaturated fatty acid (α-linolenic acid, ALA > 40%) that is receiving increasing attention for its excellent antioxidant and other activities. However, it has poor stability and bioavailability. In this study, a bilayer emulsion of TPSO was successfully prepared using a layer-by-layer self-assembly technique. Among the proteins and polysaccharides examined, whey protein isolate (WPI) and sodium alginate (SA) were found to be the most suitable wall materials. The prepared bilayer emulsion contained 5% TPSO, 0.45% whey protein isolate (WPI) and 0.5% sodium alginate (SA) under selected conditions and its zeta potential, droplet size, and polydispersity index were -31 mV, 1291 nm, and 27%, respectively. The loading capacity and encapsulation efficiency for TPSO were up to 84% and 90.2%, respectively. It was noteworthy that the bilayer emulsion showed significantly enhanced oxidative stability (peroxide value, thiobarbituric acid reactive substances content) compared to the monolayer emulsion, which was accompanied by a more ordered spatial structure caused by the electrostatic interaction of the WPI with the SA. This bilayer emulsion also exhibited markedly improved environmental stability (pH, metal ion), rheological properties, and physical stability during storage. Furthermore, the bilayer emulsion was more easily digested and absorbed, and had higher fatty acid release rate and ALA bioaccessibility than TPSO alone and the physical mixtures. These results suggest that bilayer emulsion containing WPI and SA is an effective TPSO encapsulation system and has significant potential for future functional food development.

A small pore black TiO2/-large pore Fe3O4 cascade nanoreactor for chemodynamic/photothermal synergetic tumour therapy.

Various unique spatial structures are often found in the enzymes of biological systems. From the consideration of bionics, it is challenging but meaningful to design nanozymes with distinctive structures to enhance their bioactivities. To explore the relationship between the structure and activity of nanozymes, in this work, a special structural nanoreactor, namely small pore black TiO2 coated/doped large pore Fe3O4 (TiO2/-Fe3O4) loaded with lactate oxidase (LOD), was constructed for chemodynamic and photothermal synergistic therapy. Specifically, LOD loaded on the surface of the TiO2/-Fe3O4 nanozyme alleviates the low level of H2O2 in the tumour microenvironment (TME); the black TiO2 shell with multiple pinhole channels and a large specific surface area not only facilitates LOD loading, but also enhances the affinity of the nanozyme for H2O2; H2O2 is continuously enriched on the surface of the TiO2/-Fe3O4 nanozyme and transmitted to mesoporous Fe3O4, in turn efficiently producing abundant toxic hydroxyl radicals (˙OH) for chemodynamic therapy. Meanwhile, the TiO2/-Fe3O4 nanozyme under 1120 nm laser irradiation has excellent photothermal conversion efficiency (η = 41.9%), and further accelerates the production of ˙OH for amplifying the chemodynamic therapy efficiency. This self-cascading, special structure nanozyme provides a novel strategy for application in highly efficient tumour synergetic therapy.

A dandelion-like nanomedicine via hierarchical self-assembly for synergistic chemotherapy and photo-dynamic cancer therapy.

The synergistic effect of chemotherapy and photo-dynamic therapy (PDT) is an effective way to improve the efficiency of tumor treatment. However, most synergistic therapeutic drugs have poor water solubility and stability, so it is difficult to achieve high therapeutic effects while avoiding the severe side effects. Herein, a unique dandelion-like nanomedicine (named as cRGDfk-CCPT-mCe6) was successfully synthesized using Ce6-loaded amphiphilic ß-cyclodextrins (ß-CD) doped lipid-based vesicles as the core (receptacle) and ß-CD modified camptothecin (CPT) pro-drug as the flyable dandelion seeds. The ß-CD modified CPT pro-drug was introduced into the core vesicles in succession via host-guest interaction between inter-molecular ß-CD and CPT, and cRGDfk peptides were further introduced as the outermost layer (stigma) to enhance the internalization into cancer cells. CPT interacted with ß-CD through glutathione (GSH)-cleavable disulfide bonds, which led to drug release in glutathione-rich cancer cells, just as spread of dandelion seeds in the wind. GSH consumption further disrupted the intracellular redox homeostasis of cancer cells through combined action of Ce6 with light irradiation and the synergistic anti-tumor effect was thus achieved, resulting in apoptosis of cancer cells. Therefore, the nanomedicine provides a facile and versatile anti-tumor strategy, as well as a persistent anti-cancer effects.

Association of plasma lipid metabolism profiles with overall survival for patients with gastric cancer undergoing gastrectomy based on 1H-NMR spectroscopy.

BACKGROUND: Lipid metabolism dysregulation is a prominent metabolic alteration in various cancers. The study aimed to explore the association of plasma lipid metabolism profiles with overall survival (OS) for gastric cancer (GC) patients who received gastrectomy. METHODS: GC patients who were treated with gastrectomy and measured with plasma lipid metabolism profiles using proton nuclear magnetic resonance (1H-NMR) spectroscopy in Nanfang Hospital between January 1, 2017, and October 31, 2018, were recruited. The Least Absolute Shrinkage and Selection Operator (LASSO) regression model was used to analyze variables selected by univariate analysis for OS. An index of plasma lipid metabolism profiles, named plasma lipid metabolism index (PLMI), was constructed by variables' coefficients in LASSO regression to explore its association with OS and its role in the prediction model. RESULTS: A total of 158 GC patients were included in this study. Four of the 110 lipid profiles, including LDL-5 Apo-B, LDL-4 Cholesterol, HDL-4 Apo-A2, and HDL-4 Free Cholesterol, were selected to construct the PLMI. The optimal cut-off value of PLMI for OS was used to classify the population into two subgroups, the high PLMI group (≥ - 0.163) and the low PLMI group (< - 0.163). The high PLMI group had a shorter OS (p = 0.0034) and was the independent risk factor for OS (Hazard Ratio = 2.13, 95% Confidence Interval (CI): 1.07-4.22, p = 0.031) after adjusting for perineural invasion and tumor stage. In subsets of the I-III stage and treating postoperative chemotherapy, high PLMI also had an unfavorable correlation with OS (p = 0.016 and p = 0.0086, respectively). The nomogram prediction models of both the training cohort and validation cohort showed good calibration and discrimination with the concordance indexes of 0.806 (95% CI, 0.732-0.880) in the training cohort and 0.794 (95% CI, 0.725-0.862) in the validation cohort. CONCLUSIONS: This study found that the index derived from the LDL-5 Apo-B, LDL-4 Cholesterol, HDL-4 Apo-A2, and HDL-4 Free Cholesterol, was significantly associated with overall survival, suggesting that regulating lipid metabolisms might improve the prognosis for GC patients.

Safety and Efficacy of OGT-Assisted Overlap Oesophagojejunostomy Versus the Traditional Overlap Method in Laparoscopic Total Gastrectomy for Gastric/Gastroesophageal Junction (G/GEJ) Tumours.

INTRODUCTION: Overlap guiding tube (OGT)-assisted overlap oesophagojejunostomy (EJS), which was first designed and reported by our team, has shown feasibility. However, its safety and efficiency have not yet been compared with the conventional overlap approach. METHODS: We retrospectively analysed the data of 155 gastric/gastroesophageal junction (G/GEJ) cancer patients who underwent laparoscopic total gastrectomy by conventional (conventional group, n = 83) or OGT-assisted (OGT group, n = 72) overlap methods at Nanfang Hospital. The anastomotic efficiency and surgical outcomes were compared between the two groups. RESULTS: The success rate of inserting an anvil fork into the oesophageal lumen at the first attempt in the OGT group was much higher than in the conventional group (86.7% vs. 97.2%, P = 0.019). Consistently, the duration of EJS (P < 0.001) in the OGT group was significantly shorter than that in the conventional group. Operatively, there was one case in which oesophageal pseudocanals developed; another case was converted to thoracoscopic surgery in the conventional group, but there were no such cases in the OGT group. In terms of postoperative recovery, the OGT group was superior to the conventional group. The incidence of postoperative complications (28.9% vs. 20.8%, P = 0.247) and the classification of complication severity (P = 0.450) were milder in the OGT group, although the difference was not statistically significant. Notably, the conventional group had four cases (4.8%) of oesophagojejunal anastomotic leakage (EJAL) and one case (1.2%) of anastomotic stenosis. In the OGT group, two patients (2.8%) developed EJAL, but none developed anastomotic stenosis or anastomotic bleeding. Neither group had any cases of unplanned secondary surgery or perioperative deaths. CONCLUSIONS: The OGT-assisted method reduced the surgical difficulty of overlap EJS with good safety. This study provides new perspectives for optimizing EJS.

Medical insurance payment schemes and patient medical expenses: a cross-sectional study of lung cancer patients in urban China.

BACKGROUND: As the main cause of cancer death, lung cancer imposes seriously health and economic burdens on individuals, families, and the health system. In China, there is no national study analyzing the hospitalization expenditures of different payment methods by lung cancer inpatients. Based on the 2010-2016 database of insured urban resident lung cancer inpatients from the China Medical Insurance Research Association (CHIRA), this paper aims to investigate the characteristics and cost of hospitalized lung cancer patient, to examine the differences in hospital expenses and patient out-of-pocket (OOP) expenses under four medical insurance payment methods: fee-for-service (FFS), per-diem payments, capitation payments (CAP) and case-based payments, and to explore the medical insurance payment method that can be conducive to controlling the cost of lung cancer. METHOD: This is a 2010-2016, 7-year cross-sectional study. CHIRA data are not available to researchers after 2016. The Medical Insurance Database of CHIRA was screened using the international disease classification system to yield 28,200 inpatients diagnosed with lung cancer (ICD-10: C34, C34.0, C34.1, C34.2, C34.3, C34.8, C34.9). The study includes descriptive analysis and regression analysis based on generalized linear models (GLM). RESULTS: The average patient age was 63.4 years and the average length of hospital stay (ALOS) was 14.2 day; 60.7% of patients were from tertiary hospitals; and 45% were insured by FFS. The per-diem payment had the lowest hospital expenses (RMB7496.00/US$1176.87), while CAP had the lowest OOP expenses (RMB1328.18/US$208.52). Compared with FFS hospital expenses, per-diem was 21.3% lower (95% CI = -0.265, -0.215) and case-based payment was 8.4% lower (95% CI = -0.151, -0.024). Compared with the FFS, OOP expenses, per-diem payments were 9.2% lower (95% CI = -0.130, -0.063) and CAP was 15.1% lower (95% CI = -0.151, -0.024). CONCLUSION: For lung cancer patients, per-diem payment generated the lowest hospital expenses, while CAP meant patients bore the lowest OOP costs. Policy makers are suggested to give priority to case-based payments to achieve a tripartite balance among medical insurers, hospitals, and insured members. We also recommend future studies comparing the disparities of various diseases for the cause of different medical insurance schemes.

Safety and short-term outcomes of laparoscopic surgery for advanced gastric cancer after neoadjuvant immunotherapy: A retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of advanced gastric cancer (AGC). However, the safety and the short-term outcomes of laparoscopic gastrectomy for patients with AGC after neoadjuvant immunotherapy (NAI) remain unknown. Methods: We retrospectively analyzed the patients with AGC who underwent laparoscopic surgery after neoadjuvant therapy between 1 January 2019 and 31 October 2021. We further compared the differences in postoperative complications, overall response rate, adverse events, surgical parameters, and postoperative recovery between two cohorts: the NAI group (NAI plus chemotherapy) and the neoadjuvant chemotherapy (NAC) group. Multivariable regression analyses were used to determine the risk factors for the overall response rate. Results: Overall, 80 patients were enrolled, of whom 30 cases were included in the NAI cohort and 50 were included in the NAC cohort. The overall rate of postoperative complications was 30.0% in both groups (p = 1.000). The overall response rate was 70.0% in the NAI cohort and 40% in the NAC cohort (p = 0.012). The adverse effects were found in 16 cases (53.3%) of the NAI cohort and 23 cases (46.0%) of the NAC cohort (p = 0.645). There was no statistical difference in intraoperative bleeding (50 ml vs. 50 ml, p = 0.983), operation time (320.9 min vs. 303.5 min, p = 0.382), dissected lymph node count (43.5 vs. 40.0, p = 0.364), first postoperative anal aerofluxus (3 days vs. 3 days, p = 0.091), first liquid diet (4 days vs. 5 days, p = 0.213), and postoperative length of stay in the hospital (8 days vs. 7 days, p = 0.508) between the two groups. NAI was estimated to be the independent protective factor [odds ratio (OR) 4.931, 95% confidence interval (CI) (1.385-17.559), p = 0.014] for odds to overall response rate, whereas vessel invasion was found to be the significant risk factor [OR 0.113, 95% CI (0.027-0.475), p = 0.003]. Conclusions: Laparoscopic surgery after NAI combined with chemotherapy is a safe therapeutic choice for AGC and may bring better short-term outcomes due to a higher overall response rate.

Prognostic characteristics and clinical response to immunotherapy targeting programmed cell death 1 for patients with advanced gastric cancer with liver metastases.

Background: The specific efficacy of immunotherapy for patients with liver metastases of gastric cancer is unclear. This study set out to explore the treatment response and related prognostic factors for patients with liver metastases of gastric cancer treated with immunotherapy. Patients and methods: This retrospective cohort study included 135 patients with unresectable advanced gastric cancer. According to the presence of liver metastases and/or first-line treatment with immunotherapy, patients were divided into the following three groups: I-LM(-) group(patients without liver metastases treated with immunotherapy, n=66), I-LM(+) group(patients with liver metastases treated with immunotherapy, n=36), C-LM(+) group(patients with liver metastases treated with chemotherapy and/or target therapy, n=33). Cox regression analyses were used to identify factors associated with survival in all patients and the three groups, respectively. Results: For the patients with liver metastases treated with immunotherapy, multivariate analysis showed that only the presence of peritoneal metastases was significantly associated with shorter PFS [hazard ratios (HR), 3.23; 95% CI, 1.12-9.32; P=0.030] and the patients with peritoneal metastases had shorter median PFS than patients without peritoneal metastases(3.1 vs 18.4 months; P=0.004), while the objective response rate was 100% in patients with HER2-positive (2 complete radiographic responses and 2 partial responses; 3 of 4 patients were still ongoing benefits [median follow-up time, 15.3 months ; interquartile range(IQR), 6.3-17.9 months]). Conclusions: The findings suggest that patients with various types of gastric cancer liver metastases respond differently to immune checkpoint inhibitors, HER2-positive patients may derive clinical benefits from immune checkpoint inhibitors, while the presence of peritoneal metastases is associated with resistance.