6-week time-restricted eating improves body composition, maintains exercise performance, without exacerbating eating disorder in female DanceSport dancers.

BACKGROUND: Despite the high risk of eating disorder (ED)-related attitudes and behaviors among female dancers, targeted scientific dietary regimens are currently inadequate. Time-restricted eating (TRE), a popular intermittent fasting protocol, has been shown to be effective in enhancing body composition and exercise performance in athletes. In this study, TRE was employed as a dietary regimen to improve body composition and exercise performance and address ED attitudes and behaviors in DanceSport dancers. METHODS: Twenty female DanceSport dancers were recruited and divided into two groups: TRE (n = 10) and normal diet (ND) (n = 10). The TRE group consumed their self-selected necessary energy intake exclusively between 11 a.m. and 7 p.m. (utilizing a 16-hour fasting and 8-hour eating window) for 6 weeks, while the ND group maintained their regular dieting patterns. The consumption of water, black tea, or coffee without added sugar or milk was not restricted. Physical activity and calorie intake were systematically recorded during the TRE intervention. Body composition, aerobic and anaerobic performance, and ED attitudes and behaviors were assessed before and after the TRE intervention. The trial was registered in the Chinese Clinical Trial Registry under the identifier ChiCTR2200063780. RESULTS: The fixed effects tests (p < 0.0001) and estimates for the intercept (p < 0.0001) of hunger level indicated a noticeable effect on the initial state of hunger during TRE. No significant differences were observed in ED attitudes or behaviors (p > 0.05). TRE resulted in a reduction in hip circumference (p = 0.039), fat mass (kg) (p = 0.0004), and body fat percentage (p = 0.0005), with no significant decrease in fat-free mass (p > 0.05). No significant improvement was observed in aerobic performance (p > 0.05). The average power (AP) (p = 0.01) and AP/Body weight ratio (p = 0.003) significantly increased. Additionally, the power drop decreased significantly (p = 0.019). Group-by-time interactions were observed for fat mass (kg) (p = 0.01), body fat percentage (p = 0.035), and AP/Body weight (p = 0.020). CONCLUSION: TRE can be considered a feasible nutritional strategy for DanceSport dancers, facilitating improvements in body composition without compromising aerobic and anaerobic exercise performance or exacerbating ED attitudes and behaviors. Moreover, TRE may facilitate more favorable physiological adaptations, potentially contributing to improved exercise performance.

Longitudinal metabolomics of human plasma reveal metabolic dynamics and predictive markers of antituberculosis drug-induced liver injury.

Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver injury (ATB-DILI). We established a prospective longitudinal cohort of ATB-DILI with multiple timepoint blood sampling and used untargeted metabolomics to analyze the metabolic profiles of 107 plasma samples from healthy controls and newly diagnosed TB patients who either developed ATB-DILI within 2 months of anti-TB treatment (ATB-DILI subjects) or completed their treatment without any adverse drug reaction (ATB-Ctrl subjects). The untargeted metabolome revealed that 77 metabolites (of 895 total) were significantly changed with ATB-DILI progression. Among them, levels of multiple fatty acids and bile acids significantly increased over time in ATB-DILI subjects. Meanwhile, metabolites of the same class were highly correlated with each other and pathway analysis indicated both fatty acids metabolism and bile acids metabolism were up-regulated with ATB-DILI progression. The targeted metabolome further validated that 5 fatty acids had prediction capability at the early stage of the disease and 6 bile acids had a better diagnostic performance when ATB-DILI occurred. These findings provide evidence indicating that fatty acids metabolism and bile acids metabolism play a vital role during ATB-DILI progression. Our report adds a dynamic perspective better to understand the pathological process of ATB-DILI in clinical settings.

Lipidomics and single-cell RNA sequencing reveal lipid and cell dynamics of porcine glycerol-injured skeletal muscle regeneration model.

AIMS: Intramuscular fat (IMF) infiltration and extracellular matrix (ECM) deposition are characteristic features of muscle dysfunction, such as muscular dystrophy and severe muscle injuries. However, the underlying mechanisms of cellular origin, adipocyte formation and fibrosis in skeletal muscle are still unclear. MAIN METHODS: Pigs were injected with 50 % glycerol (GLY) to induce skeletal muscle injury and regeneration. The acyl chain composition was analyzed by lipidomics, and the cell atlas and molecular signatures were revealed via single-cell RNA sequencing (scRNA-seq). Adipogenesis analysis was performed on fibroblast/fibro-adipogenic progenitors (FAPs) isolated from pigs. KEY FINDINGS: The porcine GLY-injured skeletal muscle regeneration model was characterized by IMF infiltration and ECM deposition. Skeletal muscle stem cells (MuSCs) and FAP clusters were analyzed to explore the potential mechanisms of adipogenesis and fibrosis, and it was found that the TGF-ß signaling pathway might be a key switch that regulates differentiation. Consistently, activation of the TGF-ß signaling pathway increased SMAD2/3 phosphorylation and inhibited adipogenesis in FAPs, while inhibition of the TGF-ß signaling pathway increased the expression of PPARγ and promoted adipogenesis. SIGNIFICANCE: GLY-induced muscle injury and regeneration provides comprehensive insights for the development of therapies for human skeletal muscle dysfunction and fatty infiltration-related diseases in which the TGF-ß/SMAD signaling pathway might play a primary regulatory role.

The relationship between gastric microbiome features and responses to neoadjuvant chemotherapy in gastric cancer.

Background: Emerging evidence demonstrates that the gastrointestinal microbiome has the potential to be a biomarker in neoadjuvant chemoradiotherapy for colorectal cancer (CRC). Yet studies on the impact of the gastric microbiome (GM) on the response to neoadjuvant chemotherapy (NACT) are still scarce. Methods: Forty-eight patients with gastric cancer participated in this retrospective study, and 16S rRNA sequencing was performed to evaluate formalin-fixed and paraffin-embedded (FFPE) tissue biospecimens and fresh-frozen tissues. Results: In this study, 16 bacterial taxa at different levels, including Bacillus, Anaerococcus, and Chloroflexi, were identified to be enriched before NACT in response (R) patients in group FFPE. In contrast, 6 bacterial taxa, such as Haemophilus, Veillonellaceae (Veillonella), etc. were enriched after NACT, in which we reported for the first time that the phylum Chloroflexi was enriched before NACT in R patients. Thirty-one bacterial taxa of Coriobacteriaceae, Ruminococcaceae, Veillonellaceae, and Lachnospiraceae were identified in group mucosa as being enriched in R patients. In comparison, 4 bacterial taxa dominated by the phylum Proteobacteria were enriched in NR patients. Notably, the family Veillonellaceae was found in both tissue samples, and the metabolic pathways, including the citrate cycle (TCA cycle) and various amino acids, including alanine, were found to be potentially predictive in both sample species. Conclusion: There are differences in the features of the GM for different NACT response results. The causal relationship deserves to be confirmed by further investigations.

Long term survival outcomes of surgery combined with hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms: A multicenter retrospective study.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.

Effect of preoperative immunonutrition on postoperative short-term clinical outcomes in patients with gastric cancer cachexia: a prospective randomized controlled trial.

BACKGROUND: Although current guidelines(ESPEN guideline: Clinical nutrition in surgery and other guidelines) recommend preoperative immunonutrition for cachectic gastric cancer patients, the strength of the recommendation is weak, and the level of evidence is low. The benefits of preoperative immunonutrition still remain controversial. PATIENTS AND METHODS: 112 patients with gastric cancer cachexia were enrolled in the study and randomly assigned in a 1:1 ratio to receive either preoperative enteral immunonutrition support (IN, n = 56) or standard enteral nutrition support (SEN, n = 56). The primary endpoint was the incidence of infectious complications, and the secondary endpoints included the nutritional indicators, inflammatory markers, immune parameters, postoperative recovery and complications and gastrointestinal intolerance reactions. RESULTS: The incidence of postoperative infectious complications(P = 0.040) and overall complications (P = 0.049)was significantly lower in the IN group compared to the SEN group. In terms of laboratory inflammatory indexes, patients in the IN group demonstrated significantly lower levels of white blood cells (WBC), C-reactive protein (CRP), and interleukin-6 (IL-6), as well as higher levels of lymphocytes (LYMPH) and immunoglobulin A (IgA), compared to patients in the SEN group, with statistically significant differences. In terms of clinical outcomes, the IN group had a shorter duration of antibiotic use (P = 0.048), shorter hospital stay (P = 0.018), and lower total hospital costs (P = 0.034) compared to the SEN group. The IN group also experienced significantly less weight loss after surgery (P = 0.043). CONCLUSION: Preoperative administration of immunonutrition formula has a positive impact on the incidence of infectious complications in patients with gastric cancer cachexia after surgery. It improves patients' inflammatory and immune status, shortens hospital stays, and reduces healthcare costs. Preoperative use of immunonutrition may contribute to the improvement of prognosis in this high-risk population.

Perioperative versus adjuvant S-1 plus oxaliplatin chemotherapy for stage II/III resectable gastric cancer (RESONANCE): a randomized, open-label, phase 3 trial.

Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361).

Deciphering the tumor immune microenvironment of imatinib-resistance in advanced gastrointestinal stromal tumors at single-cell resolution.

The heterogeneous nature of tumors presents a considerable obstacle in addressing imatinib resistance in advanced cases of gastrointestinal stromal tumors (GIST). To address this issue, we conducted single-cell RNA-sequencing in primary tumors as well as peritoneal and liver metastases from patients diagnosed with locally advanced or advanced GIST. Single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. Immunohistochemistry and multiplex immunofluorescence staining were used to further validate it. This analysis revealed unique tumor evolutionary patterns, transcriptome features, dynamic cell-state changes, and different metabolic reprogramming. The findings indicate that in imatinib-resistant TME, tumor cells with activated immune and cytokine-mediated immune responses interacted with a higher proportion of Treg cells via the TIGIT-NECTIN2 axis. Future immunotherapeutic strategies targeting Treg may provide new directions for the treatment of imatinib-resistant patients. In addition, IDO1+ dendritic cells (DC) were highly enriched in imatinib-resistant TME, interacting with various myeloid cells via the BTLA-TNFRSF14 axis, while the interaction was not significant in imatinib-sensitive TME. Our study highlights the transcriptional heterogeneity and distinct immunosuppressive microenvironment of advanced GIST, which provides novel therapeutic strategies and innovative immunotherapeutic agents for imatinib resistance.

Integrative cross-species analysis reveals conserved and unique signatures in fatty skeletal muscles.

Fat infiltration in skeletal muscle is now recognized as a standard feature of aging and is directly related to the decline in muscle function. However, there is still a limited systematic integration and exploration of the mechanisms underlying the occurrence of myosteatosis in aging across species. Here, we re-analyzed bulk RNA-seq datasets to investigate the association between fat infiltration in skeletal muscle and aging. Our integrated analysis of single-nucleus transcriptomics in aged humans and Laiwu pigs with high intramuscular fat content, identified species-preference subclusters and revealed core gene programs associated with myosteatosis. Furthermore, we found that fibro/adipogenic progenitors (FAPs) had potential capacity of differentiating into PDE4D+/PDE7B+ preadipocytes across species. Additionally, cell-cell communication analysis revealed that FAPs may be associated with other adipogenic potential clusters via the COL4A2 and COL6A3 pathways. Our study elucidates the correlation mechanism between aging and fat infiltration in skeletal muscle, and these consensus signatures in both humans and pigs may contribute to increasing reproducibility and reliability in future studies involving in the field of muscle research.

Early enteral nutrition versus early supplemental parenteral nutrition in patients undergoing major abdominal surgery: a secondary analysis of 2 randomized clinical trials.

BACKGROUND: The effect of early isoenergetic feeding routes [early enteral nutrition (E-EN) or early supplemental parenteral nutrition (E-SPN)] on the outcome of patients undergoing major abdominal surgery is controversial. OBJECTIVES: The aim of this study was to investigate the impact of early isoenergetic EN compared with early isoenergetic SPN on nosocomial infections in patients undergoing major abdominal surgery. METHODS: This study is a secondary, post hoc analysis of data from 2 open-label randomized clinical trials. Participants were recruited from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and with Nutritional Risk Screening 2002 score ≥3. All eligible patients were categorized into 2 groups based on their achievement of the 100% energy target on postoperative day (POD) 3: the E-EN group (n = 199) and the E-SPN group (n = 115). The primary outcome was the incidence of nosocomial infections between POD 3 and hospital discharge. RESULTS: In total, 314 patients [mean (SD) age, 59.2 (11.4) y; 113 (36.0%) females] were included. Patients in the E-EN group showed no significant difference in nosocomial infections compared with those in the E-SPN group {17/199 [8.5%] compared with 10/115 [8.7%], risk difference, 0.2% [95% confidence interval (CI): -6.3, 6.6]}. The hematological nutritional status of the E-EN group showed a significant improvement at discharge compared with the E-SPN group (albumin: 38.0 ± 6.0 g/L compared with 35.5 ± 7.6 g/L; mean difference, -2.5 g/L; 95% CI: -4.0, -1.0 g/L; prealbumin: 200.0 ± 8.0 mg/L compared with 158.4 ± 38.1 mg/L; mean difference, -41.6 mg/L; 95% CI: -41.7, -36.1 mg/L). Other indicators were comparable between groups. CONCLUSION: E-EN compared with isoenergetic SPN may not be associated with a reduced rate of nosocomial infection in patients undergoing major abdominal surgery, but may be associated with improved hematological nutritional status. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT03115957 (https://clinicaltrials.gov/ct2/show/NCT03115957) and NCT03117348 (https://clinicaltrials.gov/ct2/show/NCT03117348).

Leucine improves the growth performance, carcass traits, and lipid nutritional quality of pork in Shaziling pigs.

Leucine is involved in promoting fatty acid oxidation and lipolysis, mediating lipid metabolism and energy homeostasis, thus it has been widely used in livestock production. However, the effects of leucine on fat deposition and nutrition in Shaziling pigs remain unclear. A total of 72 Shaziling pigs (150 days old, weight 35.00 ± 1.00 kg) were randomly divided into 2 groups and fed with basal diet (control group) or basal diet containing 1% leucine (leucine group) for 60 days. The results showed that leucine significantly increased the average daily feed intake but decreased the ratio of feed to gain (P < 0.05), increased the loin muscle area and serum glucose content (P < 0.05) of Shaziling pigs. Besides, leucine regulated the re-distribution of fatty acids from adipose tissue to muscle as it significantly increased the contents of C18:1n-9 and C22:6n-3 (DHA) in the longissimus thoracis while decreased the contents of C22:5n-3 (DPA), C20:5n-3 (EPA), and DHA in the adipose tissue of Shaziling pigs (P < 0.05). Lipidomic analysis showed that the contents of phosphatidylethanolamines (PEs), cardiolipins (CLs), and phosphatidylglycerols (PGs) in the longissimus thoracis and the contents of lysophosphatidylethanolamines (LPEs), ceramides (Cers), phosphatidylinositols (PIs) in adipose tissue of Shaziling pigs were decreased in leucine group (P < 0.05). Collectively, this study clarified that dietary addition of 1% leucine have a better effect on growth performance and the deposition of beneficial fatty acids in the muscle of Shaziling pigs, which is conductive to the production of high quality and healthy pork. In addition, leucine altered the lipid composition of muscle and fat in Shaziling pigs. The related results provide a theoretical basis and application guidance for regulating fat deposition in Shaziling pigs, which is important for the healthy breeding of Shaziling pigs.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Single-Cell Sequencing Reveals Functional Alterations in Tuberculosis.

Despite its importance, the functional heterogeneity surrounding the dynamics of interactions between mycobacterium tuberculosis and human immune cells in determining host immune strength and tuberculosis (TB) outcomes, remains far from understood. This work now describes the development of a new technological platform to elucidate the immune function differences in individuals with TB, integrating single-cell RNA sequencing and cell surface antibody sequencing to provide both genomic and phenotypic information from the same samples. Single-cell analysis of 23 990 peripheral blood mononuclear cells from a new cohort of primary TB patients and healthy controls enables to not only show four distinct immune phenotypes (TB, myeloid, and natural killer (NK) cells), but also determine the dynamic changes in cell population abundance, gene expression, developmental trajectory, transcriptomic regulation, and cell-cell signaling. In doing so, TB-related changes in immune cell functions demonstrate that the immune response is mediated through host T cells, myeloid cells, and NK cells, with TB patients showing decreased naive, cytotoxicity, and memory functions of T cells, rather than their immunoregulatory function. The platform also has the potential to identify new targets for immunotherapeutic treatment strategies to restore T cells from dysfunctional or exhausted states.

Short- and long-term comparison of robotic versus laparoscopic gastrectomy for gastric cancer patients with BMI≥30 kg/m2: A propensity score matched analysis.

BACKGROUND: Although minimally invasive surgery (MIS) for gastric patients has gained popularity in recent decades, reports on the comparison of short and long clinical outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer patients with BMI≥30 kg/m2 are still limited. METHODS: A total of 226 obese gastric cancer patients who underwent either RG (n = 81) or LG (n = 145) were enrolled in this study between October 2014 and September 2022. Propensity score matching (PSM) (1:1) was performed to reduce confounding bias. Short-term and long-term outcomes were compared between the RG and LG groups. RESULTS: The clinicopathological characteristics of 156 patients in the RG group (n = 79) and LG group (n = 79) were well balanced after PSM. Compared with the LG group, the RG group had a significantly shorter operation time, less estimated blood loss, more harvested lymph nodes, a faster postoperative recovery course, reduced surgical morbidity, and a shorter postoperative hospital stay. The long-term outcomes were comparable between the two groups. CONCLUSIONS: RG is a safe and feasible approach for gastric cancer with a BMI≥30 kg/m2 and has better short-term clinical outcomes than LG. However, RG is similar to LG in terms of long-term prognosis.

Efficacy and safety of ripretinib vs. sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: A phase 2, multicenter, randomized, open-label study in China.

AIM: A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second-line treatment in Chinese GIST patients. METHODS: This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). RESULTS: Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had primary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0·99, 95 % CI 0·57, 1·69; nominal p = 0·92; median PFS [mPFS] 10·3 vs 8·3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0·46, 95 % CI 0·23, 0·92; nominal p = 0·03; mPFS not reached in ripretinib arm and 4·9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). CONCLUSIONS: Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second-line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation.

Deep Learning Radiomics Nomogram Based on Enhanced CT to Predict the Response of Metastatic Lymph Nodes to Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

BACKGROUND: We aimed to construct and validate a deep learning (DL) radiomics nomogram using baseline and restage enhanced computed tomography (CT) images and clinical characteristics to predict the response of metastatic lymph nodes to neoadjuvant chemotherapy (NACT) in locally advanced gastric cancer (LAGC). METHODS: We prospectively enrolled 112 patients with LAGC who received NACT from January 2021 to August 2022. After applying the inclusion and exclusion criteria, 98 patients were randomized 7:3 to the training cohort (n = 68) and validation cohort (n = 30). We established and compared three radiomics signatures based on three phases of CT images before and after NACT, namely radiomics-baseline, radiomics-delta, and radiomics-restage. Then, we developed a clinical model, DL model, and a nomogram to predict the response of LAGC after NACT. We evaluated the predictive accuracy and clinical validity of each model using the receiver operating characteristic curve and decision curve analysis, respectively. RESULTS: The radiomics-delta signature was the best predictor among the three radiomics signatures. So, we developed and validated a DL delta radiomics nomogram (DLDRN). In the validation cohort, the DLDRN produced an area under the receiver operating curve of 0.94 (95% confidence interval, 0.82-0.96) and demonstrated adequate differentiation of good response to NACT. Furthermore, the DLDRN significantly outperformed the clinical model and DL model (p < 0.001). The clinical utility of the DLDRN was confirmed through decision curve analysis. CONCLUSIONS: In patients with LAGC, the DLDRN effectively predicted a therapeutic response in metastatic lymph nodes, which could provide valuable information for individualized treatment.

Changing inequity in health service utilization and financial burden among patients with hypertension in China: evidence from China Health and Retirement Longitudinal Study (CHARLS), 2011-2018.

BACKGROUND: China initiated a health system reform in 2009 to achieve Universal Health Coverage (UHC) by 2020. While the effectiveness of health-system reforms has been studied, equity in health-service utilization and financial burden remains underexplored. This study evaluated whether the health system reform has improved the equity in utilization and financial burden of health services among patients with hypertension in China. METHODS: We obtained data from four waves of the China Health and Retirement Longitudinal Study (CHARLS) conducted between 2011 and 2018. The main outcome variables were outpatient and inpatient service utilization rates and catastrophic health expenditure (CHE) for patients with hypertension. The Standardized Concentration Index (CI) was used to measure the changing equity in health service utilization and affordability. RESULTS: Outpatient service utilization was relatively equal among patients with varying socioeconomic statuses (SESs) (CI: 0.041 in 2011 and 0.064 in 2018). Inpatient service utilization inequity improved from CI 0.144 in 2011 to CI 0.066 in 2018. CHE incidence increased from 15.6% in 2011 to 24.2% in 2018. CI for CHE declined from -0.069 in 2011 to -0.012 in 2015 but increased to -0.063 in 2018. CONCLUSIONS: Health insurance expansion and poverty alleviation policies promoted equity in inpatient service utilization for hypertensive patients. However, the financial burden for the poor requires further attention through reimbursement policy adjustments for outpatient services in primary care settings.

Lung cancer organoids: models for preclinical research and precision medicine.

Lung cancer is a malignancy with high incidence and mortality rates globally, and it has a 5-year survival rate of only 10%-20%. The significant heterogeneity in clinical presentation, histological features, multi-omics findings, and drug sensitivity among different lung cancer patients necessitate the development of personalized treatment strategies. The current precision medicine for lung cancer, primarily based on pathological and genomic multi-omics testing, fails to meet the needs of patients with clinically refractory lung cancer. Lung cancer organoids (LCOs) are derived from tumor cells within tumor tissues and are generated through three-dimensional tissue culture, enabling them to faithfully recapitulate in vivo tumor characteristics and heterogeneity. The establishment of a series of LCOs biobanks offers promising platforms for efficient screening and identification of novel targets for anti-tumor drug discovery. Moreover, LCOs provide supplementary decision-making factors to enhance the current precision medicine for lung cancer, thereby addressing the limitations associated with pathology-guided approaches in managing refractory lung cancer. This article presents a comprehensive review on the construction methods and potential applications of LCOs in both preclinical and clinical research. It highlights the significance of LCOs in biomarker exploration, drug resistance investigation, target identification, clinical precision drug screening, as well as microfluidic technology-based high-throughput drug screening strategies. Additionally, it discusses the current limitations and future prospects of this field.