Drug screening on digital microfluidics for cancer precision medicine.

Drug screening based on in-vitro primary tumor cell culture has demonstrated potential in personalized cancer diagnosis. However, the limited number of tumor cells, especially from patients with early stage cancer, has hindered the widespread application of this technique. Hence, we developed a digital microfluidic system for drug screening using primary tumor cells and established a working protocol for precision medicine. Smart control logic was developed to increase the throughput of the system and decrease its footprint to parallelly screen three drugs on a 4 × 4 cm2 chip in a device measuring 23 × 16 × 3.5 cm3. We validated this method in an MDA-MB-231 breast cancer xenograft mouse model and liver cancer specimens from patients, demonstrating tumor suppression in mice/patients treated with drugs that were screened to be effective on individual primary tumor cells. Mice treated with drugs screened on-chip as ineffective exhibited similar results to those in the control groups. The effective drug identified through on-chip screening demonstrated consistency with the absence of mutations in their related genes determined via exome sequencing of individual tumors, further validating this protocol. Therefore, this technique and system may promote advances in precision medicine for cancer treatment and, eventually, for any disease.

Platinum-based adjuvant chemoradiotherapy versus adjuvant radiotherapy in patients with head and neck adenoid cystic carcinoma.

PURPOSE: The objective of the study was to assess the effectiveness and toxicity of platinum-based adjuvant chemoradiotherapy (POCRT) in comparison to postoperative radiotherapy (PORT) in patients with head and neck adenoid cystic carcinoma (HNACC). MATERIALS AND METHODS: This retrospective study analyzed patients diagnosed with HNACC at our center between January 2010 and April 2020. A 1:1 propensity score matching method was used to create a matched cohort. RESULTS: In this study, 206 patients were analyzed, with 147 patients (71.4%) receiving postoperative radiotherapy (PORT) and 59 patients (28.6%) receiving POCRT. Twenty-one patients experienced local-regional failure. The 3-, 5-, and 10-yr local-regional control (LRC) rate for the cohort were 92.0%, 90.6%, and 86.9%, respectively. In both the entire cohort and the matched cohort, the POCRT group exhibited superior LRC compared to the PORT group (Gray's test, all P < 0.05*). Multivariate analysis identified adjuvant concurrent chemotherapy as an independent prognostic factor for LRC (Competing risks regression, HR = 0.144, 95% CI 0.026-0.802, P = 0.027*). In addition, the POCRT group had higher incidences of upper gastrointestinal toxicity and hematologic toxicities, including leukopenia, neutropenia, and anemia (all P < 0.05*). CONCLUSION: In terms of reducing locoregional failures in HNACC patients, POCRT may potentially offer a more effective therapeutic approach than using PORT alone, although it also entails an augmented burden of treatment-related toxicity.

Omission of radiotherapy to lymph node level III in patients with cN0 adenoid cystic carcinoma of the major salivary gland: a single center experience.

PURPOSE: Due to the rarity of adenoid cystic carcinoma (ACC) of the major salivary gland, there is no consensus on the extent of prophylactic neck irradiation (PNI) for patients with clinically negative lymph nodes (cN0) disease. MATERIALS AND METHODS: We conducted a retrospective analysis of all patients with ACC of the major salivary gland who received treatment at our center between January 2010 and April 2020. The primary endpoint was regional failure-free survival (RRFS). Secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and acute toxicity. RESULTS: A total of 139 patients were included in the analysis. For cN0 patients, the 5-year RRFS, OS, DMFS, and LRFS were 93.2%, 90.2%, 75.7%, and 91.4%, respectively. Multivariate analysis revealed that PORT was an independent prognostic factor for RRFS and LRFS. No statistically significant differences were observed between the Level III sparing PNI group and the Standard PNI group in terms of RRFS, OS, DMFS, and LRFS. The doses delivered to the larynx and thyroid in the Level III sparing PNI group were significantly lower than those in the Standard PNI group. CONCLUSION: In patients with cN0 ACC of the major salivary gland, PNI improves regional control, and the level III nodal region sparing radiotherapy does not increase the risk of level III recurrence, while potentially reducing toxicity.

The effect of surgical starting time on elective colorectal cancer surgery: A propensity score matching analysis.

The purpose of the current study is to analyze whether surgical starting time affects the short-term outcomes of elective colorectal cancer (CRC) surgery. We retrospectively collected CRC patients who underwent elective surgery from Jan 2008 to Jan 2021 in a single clinical center. The effect of surgical starting time (morning surgery vs afternoon surgery, day surgery vs night surgery) on elective CRC surgery was analyzed using propensity score matching (PSM). A total of 6783 patients were included in the current study. There were 5751 patients in day surgery group and 1032 patients in night surgery group, and there were 2920 patients in morning surgery group and 2831 patients in afternoon surgery group. After 1:1 ratio PSM, there were no significant difference in terms of the baseline information (P > .05). Day surgery group had longer operation time (P = .000) and longer hospital stay (P = .029) than night surgery group after PSM. Morning surgery group had longer operation time than afternoon surgery group before PSM (P = .000) and after PSM (P = .000). Univariate and multivariate analysis of the total of 6783 patients were conducted to find predictors of complications, and found that night surgery was a predictor of major complications (P = .002, OR = 1.763, 95% CI = 1.222-2.543) but not a predictor of overall complications (P = .250, OR = 1.096, 95% CI = 0.938-1.282). Night surgery is a predictor of major complications after elective CRC surgery, therefore, surgeons should be careful when operating at night.

Novel stent-assisted ileal bypass is applied to avoid protective stoma and prevent anastomotic leakage for rectal cancer.

PURPOSE: This study aimed to investigate the safety and feasibility of a novel stent-assisted ileal bypass for rectal cancer patients who received sphincter-preserving surgery. METHODS: Patients who were diagnosed with rectal cancer and received sphincter-preserving surgery plus a novel stent-assisted ileal bypass were respectively included from January 2022 to January 2023. Biofragmentable ileal stent with diaphragm sheet in the cavity was placed in the terminal ileum using absorbable sutures after anastomosis. At the proximal end of the stent, an intestinal diversion tube was placed in the prefabricated purse-string, through which faeces were drained. The stent completely disintegrated in the body after 3-4 weeks, which protected the anastomosis after surgery and avoided protective stoma. Clinical characteristics and surgical outcomes were collected. RESULTS: Eleven patients who successfully received surgery were included. There were seven (63.6%) males and four (36.4%) females. The tumour size was 3.2 ± 1.7 cm and the lower verge of tumour to anal verge was 6.8 ± 1.3 cm. As for surgical outcomes, operation time was 216.4 ± 54.1 min, blood loss was 43.6 ± 64.6 mL, time to first flatus via intestinal diversion tube was 3.2 ± 1.1 days, time to discharge stent was 22.8 ± 3.0 days, and postoperative hospital stay was 21.0 ± 5.4 days. Two patients suffered from postoperative complications including pneumonia and incision infection. CONCLUSION: This novel stent-assisted ileal bypass is safe and feasible, it provides a new choice for rectal cancer patients to avoid protective stoma and secondary surgery.

Clinical application of a novel stent-assisted in situ intestinal bypass in preventing postoperative anastomotic leakage for low-mid rectal cancer: A retrospective study.

This study aimed to investigate the safety and feasibility of a novel stent-assisted in situ intestinal bypass for low-mid rectal cancer patients. Patients who were diagnosed with rectal cancer and received laparoscopic low anterior rectal resection plus a novel stent-assisted in situ intestinal bypass were respectively included from March 2022 to June 2022. Biofragmentable intestinal stent with a protective sleeve was placed in the proximal colon before anastomosis, and feces could be discharged through the protective sleeve without touching the anastomosis, which achieved an in situ bypass of feces. Perioperative characteristics and short-term outcomes were collected. Rectal imaging was performed each week after surgery for the first 3 weeks to surveil the stent and feces delivery. Follow-ups were conducted for more than 3 months. Thirty patients who successfully received surgery were included in this study. There were 18 (60.0%) males and 12 (40.0%) females. As for perioperative characteristics, operation time was 213.8 ± 43.0 minutes, blood loss was 53.3 ± 24.6 mL, time to first flatus via protective sleeve after surgery was 3.2 ± 1.1 days, postoperative hospital stay was 11.8 ± 1.6 days, and time to discharge stent was 22.4 ± 3.2 days. As for short-term outcomes, 6 patients suffered from pneumonia, urinary tract infection or incision infection. During the follow-up, there was no anastomotic leakage or mortality. This novel stent-assisted in situ intestinal bypass is safe and feasible, it might be an applicable way to prevent postoperative anastomotic leakage for patients with low-mid rectal cancer.

Distribution of regional lymph lode metastasis in unilateral nasopharyngeal carcinoma and the suggestions for selective prophylactic irradiation with intensity-modulated radiotherapy.

PURPOSE: To address the regional lymph node (RLN) distribution and the long-term efficacy in unilateral nasopharyngeal carcinoma (NPC), providing elective irradiation for RLN with intensity-modulated radiotherapy (IMRT). METHODS: The involvement of clinical data of 136 patients with unilateral NPC, who underwent IMRT from November 2003 to December 2020 were analyzed retrospectively. The therapeutic effect and failure pattern of RLN metastasis were evaluated. RESULTS: Of 57.1% patients have bilateral RLN metastasis. The rate of contralateral RLNs metastasis is lower than that of ipsilateral RLNs. Contralateral RLN metastasis mainly occurs in level VIIa (39.0%) and II (38.2%). While level IVa is only 0.7%, and none of RLN metastasis was found in level IVb and Va. The median follow-up was 70 months, and the 3-, 5-and 10-year regional recurrence-free survival (RRFS) were 94.1%, 93.1%, and 93.1%, respectively. CONCLUSION: Routine prophylactic irradiation may not include contralateral lower neck LN and level Va for N0-1 unilateral NPC.

Red blood cell distribution width has a prognostic value for gastric cancer patients after gastrectomy: A pooling-up analysis.

Our study aims to investigate whether preoperative red blood cell distribution width (RDW) has a prognostic value for patients after gastric cancer (GC) surgery. We searched articles in 3 databases including PubMed, Embase, and the Cochrane Library on May 16th, 2022. The prognostic indicators included overall survival (OS) and disease-free survival (DFS). RevMan 5.3 (The Cochrane Collaboration, London, United Kingdom) and Stata V16.0 were used for statistical analysis. The Risk Of Bias In Non-randomized Studies-of Interventions tool was used to assess risk of bias of the included studies. Ten articles involving 2740 patients were included. RDW was a prognostic factor for OS (hazard ratio = 1.81, 95% confidence interval [CI] = 1.38-2.37, P < .01) and DFS (hazard ratio = 1.99, I2 = 26%, 95% CI = 1.53-2.58, P < .01) for GC patients. Meanwhile, there were some differences between the high RDW group and the low RDW group. We found more patients older than 60 years old (OR = 2.58, 95% CI = 1.08-6.13, P = .03), larger tumor diameter (OR = 1.95, 95% CI = 1.33-2.85, P < .01) and later T stage (OR = 1.91, 95% CI = 1.07-3.42, P = .03) in the high RDW group than the low RDW group. No statistic difference was found in gender, N stage, tumor node metastasis stage, vascular invasion, differentiation, and adjuvant therapy between the 2 groups (P > .05). RDW was an independent prognostic factor for both OS and DFS of GC patients. High RDW level were strongly associated with poor survival.

Gene co-expression networks unravel the molecular responses of freshwater hydrophytes to combined stress of salinity and cadmium.

Salinization in freshwater lakes is becoming a serious global environmental problem, especially in lakes of plateaus such as south-western plateau of China. However, limited information is available about the molecular response of freshwater hydrophytes to salinity under multiple stress. In the present study, a weighted gene co-expression network (WGCNA) was used to identify the modules of co-expressed genes in the physiological and biochemical indicators of Pistia stratiotes to determine its molecular response to salinity (NaCl) alone and when combined with cadmium (Cd). The physiological and biochemical indicators showed that P. stratiotes improved its salt tolerance by enhancing photosynthetic abilities, reducing oxidative stress, and inducing osmoprotectant generation. Morever, addition of NaCl reduced the Cd accumulation in P. stratiotes. Transcriptome and WGCNA analysis revealed that the pathways of alpha-linolenic acid metabolism, ribosomal, flavonoid biosynthesis, and phenylpropanoid biosynthesis were significantly enriched in both treatments. Genes associated with photosynthesis-antenna proteins, nitrogen metabolism, and the acid cycle pathways were only expressed under salinity stress alone, while the proteasome pathway was only significantly enriched in the combined salinity and Cd treatment. Our findings provide novel insights into the effects of salinization on aquatic plants in freshwater ecosystems and the management of aquatic ecosystems under global change.

Enhanced Oxygen Evolution Reaction Performance on NiSx@Co3O4/Nickel Foam Electrocatalysts with Their Photothermal Property.

Based on the principle of heterogeneous catalysis for water electrolysis, electrocatalysts with appropriate electronic structure and photothermal property are expected to drive the oxygen evolution reaction effectively. Herein, amorphous NiSx-coupled nanourchin-like Co3O4 was prepared on nickel foam (NiSx@Co3O4/NF) and investigated as a electrocatalyst for photothermal-assisted oxygen evolution reaction. The experimental investigations and simulant calculations jointly revealed NiSx@Co3O4/NF to be of suitable electronic structure and high near-infrared photothermal conversion capability to achieve the oxygen evolution reaction advantageously both in thermodynamics and in kinetics. Relative to Co3O4/NF and NiSx/NF, better oxygen evolution reaction activity, kinetics, and stability were achieved on NiSx@Co3O4/NF in 1.0 M KOH owing to the NiSx/Co3O4 synergetic effect. In addition, the oxygen evolution reaction performance of NiSx@Co3O4/NF can be obviously enhanced under near-infrared light irradiation, since NiSx@Co3O4 can absorb the near-infrared light to produce electric and thermal field. For the photothermal-mediated oxygen evolution reaction, the overpotential and Tafel slope of NiSx@Co3O4/NF at 50 mA cm-2 were reduced by 23 mV and 13 mV/dec, respectively. The present work provides an inspiring reference to design and develop photothermal-assisted water electrolysis using abundant solar energy.

Could definitive radiotherapy be a treatment option for lymphoepithelial carcinoma of major salivary gland: Comparison of clinical outcomes of upfront surgery and upfront chemoradiotherapy.

OBJECTIVES: The optimal treatment and associated clinical outcomes for lymphoepithelial carcinoma of the major salivary gland (LECSG) are currently unclear. As such, the purpose of this study was to assess the survival rates of LECSG patients who received either upfront surgery or upfront chemoradiotherapy (CRT). MATERIALS AND METHODS: In this retrospective study, we analyzed cases of LECSG patients treated at our center from January 2010 to April 2021. The cumulative incidences of overall survival rate (OS) and locoregional failure-free survival rate (LRFFS) were evaluated using the Kaplan-Meier method. In order to balance potential risk factors between the treatment groups, we conducted propensity score matching (PSM) at a 1:1 ratio. RESULTS: The study enrolled a total of 107 patients, among whom 24 received surgery alone, 56 underwent surgery combined with postoperative radiotherapy, and 27 underwent definitive radiotherapy. The 5-year LRFFS rate and 5-year OS rate for the entire cohort were 86.6% and 84.4%, respectively. Following PSM, the 5-year LRFFS and OS rates for the upfront CRT cases were comparable to those of upfront surgery, both before and after matching. However, the upfront surgery group showed a tendency toward more de novo facial nerve injury and post-treatment facial nerve injury. CONCLUSION: The results of this study suggest that upfront CRT is as effective as upfront surgery in terms of locoregional control and overall survival for LECSG patients. Therefore, upfront CRT could be considered a viable treatment option, potentially avoiding the risks associated with surgical intervention.

dECM based dusal-responsive vascular graft with enzyme-controlled adenine release for long-term patency.

Rapid occlusion is the culprit leading to implantation failure of biological blood vessels. Although adenosine is a clinical-proven drug to overcome the problem, its short half-life and turbulent burst-release limit its direct application. Thus, a pH/temperature dual-responsive blood vessel possessed controllable long-term adenosine secretion was constructed based on acellular matrix via compact crosslinking by oxidized chondroitin sulfate (OCSA) and functionalized with apyrase and acid phosphatase. These enzymes, as adenosine micro-generators, controlled the adenosine release amount by "real-time-responding" to acidity and temperature of vascular inflammation sites. Additionally, the macrophage phenotype was switched from M1 to M2, and related factors expression proved that adenosine release was effectively regulated with the severity of inflammation. What's more, the ultra-structure for degradation resisting and endothelialization accelerating was also preserved by their "double-crosslinking". Therefore, this work suggested a new feasible strategy providing a bright future of long-term patency for transplanted blood vessels.

Bow-and-arrow sign on point-of-care ultrasound for diagnosis of pacemaker lead-induced heart perforation: A case report and literature review.

BACKGROUND: Pacemaker lead-induced heart perforation is a rare but life-threatening complication of pacemaker implantation, and timely diagnosis remains a challenge for clinicians. Here, we report a case of pacemaker lead-induced cardiac perforation rapidly diagnosed by a "bow-and-arrow" sign on point-of-care ultrasound (POCUS). CASE SUMMARY: A 74-year-old Chinese woman who had undergone permanent pacemaker implantation 26 d before suddenly developed severe dyspnea, chest pain, and hypotension. The patient had received emergency laparotomy for an incarcerated groin hernia and was transferred to the intensive care unit 6 d before. Computed tomography was not available due to unstable hemodynamic status, so POCUS was performed at the bedside and revealed severe pericardial effusion and cardiac tamponade. Subsequent pericardiocentesis yielded a large volume of bloody pericardial fluid. Further POCUS by an ultrasonographist revealed a unique "bow-and-arrow" sign indicating right ventricular (RV) apex perforation by the pacemaker lead, which facilitated the rapid diagnosis of lead perforation. Given the persistent drainage of pericardial bleeding, urgent off-pump open chest surgery was performed to repair the perforation. However, the patient died of shock and multiple organ dysfunction syndrome within 24 h post-surgery. In addition, we also performed a literature review on the sonographic features of RV apex perforation by lead. CONCLUSION: POCUS enables the early diagnosis of pacemaker lead perforation at the bedside. A step-wise ultrasonographic approach and the "bow-and-arrow" sign on POCUS are helpful for rapid diagnosis of lead perforation.

Is red blood cell distribution width a prognostic factor for colorectal cancer? A meta-analysis.

Background: RDW might be an easy and cost-effective pre-operative prognostic factor for cancer patients. The aim of the current study was to analyze whether red blood cell distribution width (RDW) was a prognostic factor for colorectal cancer (CRC) patients who underwent radical surgery. Methods: We conducted the searching strategy in three databases including the PubMed, Embase and Cochrane Library from the inception to May 07, 2022, to find eligible studies. In this meta-analysis, we focused on the prognosis. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). Results: A total of seven studies involving 7,541 patients were included in this meta-analysis. After pooling up the HRs, red blood cell distribution width-coefficient of variation (RDW-CV) was not an independent prognostic factor of OS (HR = 1.48, I 2 = 90%, 95% CI = 0.93 to 2.36, P = 0.10), however, red blood cell distribution width-standard deviation (RDW-SD) was an independent prognostic factor of OS (HR = 1.99, I 2 = 0%, 95% CI = 1.59 to 2.49, P < 0.01). As for DFS, we found that RDW-CV (HR = 1.51, I 2 = 83%, 95% CI = 0.94 to 2.43, P = 0.09 < 0.10) and RDW-SD (HR = 1.77, I 2 = 56%, 95% CI = 0.91 to 3.43, P = 0.09 < 0.10) were both the independent prognostic factors. In terms of CSS, we found that RDW-CV was not an independent prognostic factor (HR = 1.23, I 2 = 95%, 95% CI = 0.72 to 2.10, P = 0.46). Conclusion: RDW-SD was an independent prognostic factor of OS and DFS, and RDW-CV was an independent prognostic factor of DFS.

Discovering common pathogenetic processes between COVID-19 and sepsis by bioinformatics and system biology approach.

Corona Virus Disease 2019 (COVID-19), an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread rapidly worldwide, resulting in a pandemic with a high mortality rate. In clinical practice, we have noted that many critically ill or critically ill patients with COVID-19 present with typical sepsis-related clinical manifestations, including multiple organ dysfunction syndrome, coagulopathy, and septic shock. In addition, it has been demonstrated that severe COVID-19 has some pathological similarities with sepsis, such as cytokine storm, hypercoagulable state after blood balance is disrupted and neutrophil dysfunction. Considering the parallels between COVID-19 and non-SARS-CoV-2 induced sepsis (hereafter referred to as sepsis), the aim of this study was to analyze the underlying molecular mechanisms between these two diseases by bioinformatics and a systems biology approach, providing new insights into the pathogenesis of COVID-19 and the development of new treatments. Specifically, the gene expression profiles of COVID-19 and sepsis patients were obtained from the Gene Expression Omnibus (GEO) database and compared to extract common differentially expressed genes (DEGs). Subsequently, common DEGs were used to investigate the genetic links between COVID-19 and sepsis. Based on enrichment analysis of common DEGs, many pathways closely related to inflammatory response were observed, such as Cytokine-cytokine receptor interaction pathway and NF-kappa B signaling pathway. In addition, protein-protein interaction networks and gene regulatory networks of common DEGs were constructed, and the analysis results showed that ITGAM may be a potential key biomarker base on regulatory analysis. Furthermore, a disease diagnostic model and risk prediction nomogram for COVID-19 were constructed using machine learning methods. Finally, potential therapeutic agents, including progesterone and emetine, were screened through drug-protein interaction networks and molecular docking simulations. We hope to provide new strategies for future research and treatment related to COVID-19 by elucidating the pathogenesis and genetic mechanisms between COVID-19 and sepsis.

Heterogeneity, inherent and acquired drug resistance in patient-derived organoid models of primary liver cancer.

PURPOSE: We aimed to elucidate the applicability of tumor organoids for inherent drug resistance of primary liver cancer (PLC) and mechanisms of acquired drug resistance. METHODS: PLC tissues were used to establish organoids, organoid-derived xenograft (ODX) and patient-derived xenograft (PDX) models. Acquired drug resistance was induced in hepatocellular carcinoma (HCC) organoids. Gene expression profiling was performed by RNA-sequencing. RESULTS: Fifty-two organoids were established from 153 PLC patients. Compared with establishing PDX models, establishing organoids of HCC showed a trend toward a higher success rate (29.0% vs. 23.7%) and took less time (13.0 ± 4.7 vs. 25.1 ± 5.4 days, p = 2.28 × 10-13). Larger tumors, vascular invasion, higher serum AFP levels, advanced stages and upregulation of stemness- and proliferation-related genes were significantly associated with the successful establishment of HCC organoids and PDX. Organoids and ODX recapitulated PLC histopathological features, but were enriched in more aggressive cell types. PLC organoids were mostly resistant to lenvatinib in vitro but sensitive to lenvatinib in ODX models. Stemness- and epithelial-mesenchymal transition (EMT)-related gene sets were found to be upregulated, whereas liver development- and liver specific molecule-related gene sets were downregulated in acquired sorafenib-resistant organoids. Targeting the mTOR signaling pathway was effective in treating acquired sorafenib-resistant HCC organoids, possibly via inducing phosphorylated S6 kinase. Genes upregulated in acquired sorafenib-resistant HCC organoids were associated with an unfavorable prognosis. CONCLUSIONS: HCC organoids perform better than PDX for drug screening. Acquired sorafenib resistance in organoids promotes HCC aggressiveness via facilitating stemness, retro-differentiation and EMT. Phosphorylated S6 kinase may be predictive for drug resistance in HCC.

Does Intraoperative Blood Loss Affect the Short-Term Outcomes and Prognosis of Gastric Cancer Patients After Gastrectomy? A Meta-Analysis.

Purpose: The purpose of the current meta-analysis was to analyze whether intraoperative blood loss (IBL) influenced the complications and prognosis of gastric cancer patients after gastrectomy. Methods: We systematically searched the PubMed, Embase and Cochrane library databases on November 29, 2021. The Newcastle-Ottawa scale was used to evaluate the quality of included studies. This meta-analysis uses RevMan 5.3 for data analysis. Results: A total of nine retrospective studies were included in this meta-analysis, involving 4653 patients. In terms of short-term outcomes, the Larger IBL group has a higher complication rate (OR = 1.94, 95% CI, 1.44 to 2.61, P < 0.0001) and a longer operation time (OR = 77.60, 95% CI, 41.95 to 113.25, P < 0.0001) compared with the smaller IBL group, but the Larger IBL group had higher total retrieved lymph nodes (OR = 3.68, 95% CI, 1.13 to 6.24, P = 0.005). After pooling up all the HRs, the Larger IBL group has worse overall survival (OS) (HR = 1.80, 95% CI, 1.27 to 2.56, P = 0.001) and disease-free survival (DFS) (HR = 1.48, 95% CI, 1.28 to 1.72, P < 0.00001). Conclusion: Larger IBL increased operation time and postoperative complications, and decreased OS and DFS of gastric cancer patients. Therefore, surgeons should be cautious about IBL during operation.

Advancing Prediction of Risk of Intraoperative Massive Blood Transfusion in Liver Transplantation With Machine Learning Models. A Multicenter Retrospective Study.

Background: Liver transplantation surgery is often accompanied by massive blood loss and massive transfusion (MT), while MT can cause many serious complications related to high mortality. Therefore, there is an urgent need for a model that can predict the demand for MT to reduce the waste of blood resources and improve the prognosis of patients. Objective: To develop a model for predicting intraoperative massive blood transfusion in liver transplantation surgery based on machine learning algorithms. Methods: A total of 1,239 patients who underwent liver transplantation surgery in three large grade lll-A general hospitals of China from March 2014 to November 2021 were included and analyzed. A total of 1193 cases were randomly divided into the training set (70%) and test set (30%), and 46 cases were prospectively collected as a validation set. The outcome of this study was an intraoperative massive blood transfusion. A total of 27 candidate risk factors were collected, and recursive feature elimination (RFE) was used to select key features based on the Categorical Boosting (CatBoost) model. A total of ten machine learning models were built, among which the three best performing models and the traditional logistic regression (LR) method were prospectively verified in the validation set. The Area Under the Receiver Operating Characteristic Curve (AUROC) was used for model performance evaluation. The Shapley additive explanation value was applied to explain the complex ensemble learning models. Results: Fifteen key variables were screened out, including age, weight, hemoglobin, platelets, white blood cells count, activated partial thromboplastin time, prothrombin time, thrombin time, direct bilirubin, aspartate aminotransferase, total protein, albumin, globulin, creatinine, urea. Among all algorithms, the predictive performance of the CatBoost model (AUROC: 0.810) was the best. In the prospective validation cohort, LR performed far less well than other algorithms. Conclusion: A prediction model for massive blood transfusion in liver transplantation surgery was successfully established based on the CatBoost algorithm, and a certain degree of generalization verification is carried out in the validation set. The model may be superior to the traditional LR model and other algorithms, and it can more accurately predict the risk of massive blood transfusions and guide clinical decision-making.

Liposomal Co-delivery of PD-L1 siRNA/Anemoside B4 for Enhanced Combinational Immunotherapeutic Effect.

Combination therapy has gained a lot of attention thanks to its superior activity against cancer. In the present study, we report a cRGD-targeted liposomal preparation for co-delivery of programmed cell death ligand 1 (PD-L1) small interfering RNA (siRNA) and anemoside B4 (AB4)─AB4/siP-c-L─and evaluate its anticancer efficiency in mouse models of LLC and 4T1 tumors. AB4/siP-c-L showed a particle size of (180.7 ± 7.3) nm and a ζ-potential of (32.8 ± 1.5) mV, with high drug encapsulation, pH-sensitive release properties, and good stability in serum. AB4/siP-c-L demonstrated prolonged blood circulation and increased tumor accumulation. Elevated cellular uptake was dependent on the targeting ligand cRGD. This combination induced significant tumor inhibition in LLC xenograft tumor-bearing mice by downregulating PD-L1 protein expression and modulating the immunosuppressive microenvironment. Liposomes favored the antitumor T-cell response with long-term memory, without obvious toxicity. A similar tumor growth inhibition was also demonstrated in the 4T1 tumor model. In summary, our results indicate that cRGD-modified and AB4- and PD-L1 siRNA-coloaded liposomes have potential as an antitumor preparation, and this approach may lay a foundation for the development of a new targeted drug delivery system.

Combined Microbiome and Metabolome Analysis Reveals a Novel Interplay Between Intestinal Flora and Serum Metabolites in Lung Cancer.

As the leading cause of cancer death, lung cancer seriously endangers human health and quality of life. Although many studies have reported the intestinal microbial composition of lung cancer, little is known about the interplay between intestinal microbiome and metabolites and how they affect the development of lung cancer. Herein, we combined 16S ribosomal RNA (rRNA) gene sequencing and liquid chromatography-mass spectrometry (LC-MS) technology to analyze intestinal microbiota composition and serum metabolism profile in a cohort of 30 lung cancer patients with different stages and 15 healthy individuals. Compared with healthy people, we found that the structure of intestinal microbiota in lung cancer patients had changed significantly (Adonis, p = 0.021). In order to determine how intestinal flora affects the occurrence and development of lung cancer, the Spearman rank correlation test was used to find the connection between differential microorganisms and differential metabolites. It was found that as thez disease progressed, L-valine decreased. Correspondingly, the abundance of Lachnospiraceae_UCG-006, the genus with the strongest association with L-valine, also decreased in lung cancer groups. Correlation analysis showed that the gut microbiome and serum metabolic profile had a strong synergy, and Lachnospiraceae_UCG-006 was closely related to L-valine. In summary, this study described the characteristics of intestinal flora and serum metabolic profiles of lung cancer patients with different stages. It revealed that lung cancer may be the result of the mutual regulation of L-valine and Lachnospiraceae_UCG-006 through the aminoacyl-tRNA biosynthesis pathway, and proposed that L-valine may be a potential marker for the diagnosis of lung cancer.