Topology and giant circular dichroism of enantiomorphic Kagome bands in a designed covalent organic framework.

Covalent organic frameworks (COFs) are an emerging class of crystalline organic materials that have shown potential to be a new physical platform. In this work, a designed COF named AB-COF, which has novel enantiomorphic Kagome bands, is proposed and a feasible route to synthesize it is given. Via a combination of first-principles calculations and tight-binding analysis, we investigate the electronic structures and the phase interference of the COF. It becomes topologically nontrivial when doping one iodine atom in a unit cell. The Berry curvatures of the valence band (VB) and conduction band (CB) of the iodine-doped AB-COF show opposite values and different distributions. This provides an opportunity to study the new mechanism of circular dichroism from the different Berry curvatures of the VB and CB. Surprisingly, the circular-dichroism dissymmetry factor of AB-COF reaches a theoretical maximum value, and the oscillator strength data are in agreement with this result. When two iodine atoms are doped in a unit cell, the Berry curvatures of the VB and CB also have different values, but with more symmetry and similar distributions. This behavior enhances the circular dichroism with a wider range of dissymmetric absorption, and the circular dichroism dissymmetry factor also reaches its theoretical maximum value.

A real-world analysis of second-line treatment option, Gemcitabine plus Anlotinib and anti-PD1, in advanced pancreatic cancer.

BACKGROUND: In the second-line treatment of advanced pancreatic cancer (APC), there is only one approved regimen based on the phase III NAPOLI-1 trial. However, for patients progressing after Nab-paclitaxel and Gemcitabine (Nab-P/Gem) or Nab-P combinations, second-line treatment were very limited. METHODS: This is a retrospective single-center analysis of patients. Our aim was to determine the effectiveness and tolerability of a novel regimen, gemcitabine plus Anlotinib and anti-PD1, in APC patients and to compare it with oxaliplatin, irinotecan, leucovorin, and fluorouracil (FOLFIRINOX) in the second-line setting who have failed on the first-line Nab-P combinations. RESULTS: In total, twenty-three patients received Gemcitabine plus Anlotinib and anti-PD1 in the second-line, 28 patients were treated with FOLFORINOX. There was no significant difference in overall survival (OS) or progression free survival (PFS) for either of the two sequences (p > 0.05). Patients who received Gemcitabine plus Anlotinib and anti-PD1 had a median PFS of 4.0 months (95% CI: 1.1-6.9) versus 3.5 months (95% CI 1.8-5.2) in FOLFORINOX group (p = 0.953). The median OS of Gemcitabine plus Anlotinib and anti-PD1 was 9.0 months (95% CI: 4.0-13.7) and 8.0 months (95% CI: 5.5-10.5) in FOLFORINOX group (p = 0.373). Grade ≥3 treatment-emergent adverse events (AEs) occurred for 13% of patients with Gemcitabine plus Anlotinib and anti-PD1 and 40% for FOLFORINOX. CONCLUSION: Our data confirms the effectiveness of Gemcitabine plus Anlotinib and anti-PD1 as a well-tolerated regimen in the second-line treatment of APC and extends available data on its use as a second-line treatment option when compared with FOLFIRINOX.

High somatic mutations in circulating tumor DNA predict response of metastatic pancreatic ductal adenocarcinoma to first-line nab-paclitaxel plus S-1: prospective study.

AIMS: We previously showed that the nab-paclitaxel plus S-1 (NPS) regimen had promising effects against metastatic pancreatic ducal adenocarcinoma (mPDAC), whose efficacy however could not be precisely predicted by routine biomarkers. This prospective study aimed to investigate the values of mutations in circulating tumor DNA (ctDNA) and their dynamic changes in predicting response of mPDAC to NPS chemotherapy. METHODS: Paired tumor tissue and blood samples were prospectively collected from patients with mPDAC receiving first-line NPS chemotherapy, and underwent next-generation sequencing with genomic profiling of 425 genes for ctDNA. High mutation allelic frequency (MAF) was defined as ≥ 30% and ≥ 5% in tumor tissue and blood, respectively. Kappa statistics were used to assess agreement between mutant genes in tumor and ctDNA. Associations of mutations in ctDNA and their dynamic changes with tumor response, overall survival (OS), and progression-free survival (PFS) were assessed using the Kaplan-Meier method, multivariable-adjusted Cox proportional hazards regression, and longitudinal data analysis. RESULTS: 147 blood samples and 43 paired tumor specimens from 43 patients with mPDAC were sequenced. The most common driver genes with high MAF were KRAS (tumor, 35%; ctDNA, 37%) and TP53 (tumor, 37%; ctDNA, 33%). Mutation rates of KRAS and TP53 in ctDNA were significantly higher in patients with liver metastasis, with baseline CA19-9 ≥ 2000 U/mL, and/or without an early CA19-9 response. κ values for the 5 most commonly mutated genes between tumor and ctDNA ranged from 0.48 to 0.76. MAFs of the genes mostly decreased sequentially during subsequent measurements, which significantly correlated with objective response, with an increase indicating cancer progression. High mutations of KRAS and ARID1A in both tumor and ctDNA, and of TP53, CDKN2A, and SMAD4 in ctDNA but not in tumor were significantly associated with shorter survival. When predicting 6-month OS, AUCs for the 5 most commonly mutated genes in ctDNA ranged from 0.59 to 0.84, larger than for genes in tumor (0.56 to 0.71) and for clinicopathologic characteristics (0.51 to 0.68). Repeated measurements of mutations in ctDNA significantly differentiated survival and tumor response. Among the 31 patients with ≥ 2 ctDNA tests, longitudinal analysis of changes in gene MAF showed that ctDNA progression was 60 and 58 days ahead of radiologic and CA19-9 progression for 48% and 42% of the patients, respectively. CONCLUSIONS: High mutations of multiple driving genes in ctDNA and their dynamic changes could effectively predict response of mPDAC to NPS chemotherapy, with promising reliable predictive performance superior to routine clinicopathologic parameters. Inspiringly, longitudinal ctDNA tracking could predict disease progression about 2 months ahead of radiologic or CA19-9 evaluations, with the potential to precisely devise individualized therapeutic strategies for mPDAC.

Microbial metabolism of diosgenin by a novel isolated Mycolicibacterium sp. HK-90: A promising biosynthetic platform to produce 19-carbon and 21-carbon steroids.

Green manufacture of steroid precursors from diosgenin by microbial replacing multistep chemical synthesis has been elusive. It is currently limited by the lack of strain and degradation mechanisms. Here, we demonstrated the feasibility of this process using a novel strain Mycolicibacterium sp. HK-90 with efficiency in diosgenin degradation. Diosgenin degradation by strain HK-90 involves the selective removal of 5,6-spiroketal structure, followed by the oxygenolytic cleavage of steroid nuclei. Bioinformatic analyses revealed the presence of two complete steroid catabolic gene clusters, SCG-1 and SCG-2, in the genome of strain HK-90. SCG-1 cluster was found to be involved in classic phytosterols or cholesterol catabolic pathway through the deletion of key kstD1 gene, which promoted the mutant m-∆kstD1 converting phytosterols to intermediate 9α-hydroxyandrostenedione (9-OHAD). Most impressively, global transcriptomics and characterization of key genes suggested SCG-2 as a potential gene cluster encoding diosgenin degradation. The gene inactivation of kstD2 in SCG-2 resulted in the conversion of diosgenin to 9-OHAD and 9,16-dihydroxy-pregn-4-ene-3,20-dione (9,16-(OH)2 -PG) in mutant m-ΔkstD2. Moreover, the engineered strain mHust-ΔkstD1,2,3 with a triple deletion of kstDs was constructed, which can stably accumulate 9-OHAD by metabolizing phytosterols, and accumulate 9-OHAD and 9,16-(OH)2 -PG from diosgenin. Diosgenin catabolism in strain mHust-ΔkstD1,2,3 was revealed as a progression through diosgenone, 9,16-(OH)2 -PG, and 9-OHAD to 9α-hydroxytestosterone (9-OHTS). So far, this work is the first report on genetically engineered strain metabolizing diosgenin to produce 21-carbon and 19-carbon steroids. This study presents a promising biosynthetic platform for the green production of steroid precursors, and provide insights into the complex biochemical mechanism of diosgenin catabolism.

PD-1 inhibitor combined with albumin paclitaxel and apatinib as second-line treatment for patients with metastatic gastric cancer: a single-center, single-arm, phase II study.

BACKGROUND: Immune checkpoint inhibitors have been approved for first- and third-line treatment of advanced gastric cancer. However, pembrolizumab alone in the second line did not improve overall survival compared to chemotherapy in the KEYNOTE-061 study. In this study, we aimed to explore the efficacy and safety of a three-drug regimen of PD-1 inhibitor combined with albumin paclitaxel and apatinib (a VEGFR inhibitor) for the second-line treatment of patients with metastatic gastric cancer (mGC). METHODS: This was a single-center, single-arm, phase II clinical study. Patients with mGC with stable microsatellite and negative HER-2 expression who failed first-line chemotherapy were enrolled. The enrolled patients were treated with PD-1 inhibitor (selected according to patients' requirements) in combination with albumin paclitaxel (125 mg/m2, intravenously, days 1 and 8, or 250 mg/m2, intravenously, day 1) and apatinib (250 or 500 mg, orally, days 1-21) every 3 weeks. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response, and adverse events (AEs). RESULTS: From July 11, 2019, to October 13, 2022, a total of 43 patients were enrolled, of whom 10 were PD-L1 negative, 11 were PD-L1 positive, and 22 had unknown PD-L1 expression. As of the data cutoff on April 1st, 2023, nine patients had partial response, 29 had stable disease, and five experienced progressive disease, with the ORR of 20.9% and DCR of 88.3%. The median PFS was 6.2 months (95% CI, 3.9-9.3), and the median OS was 10.1 months (95% CI, 7.5-14.1). All patients suffered from alopecia and neurotoxicity. The other main AEs of grade 1 or 2 were bone marrow suppression (N = 21, 48.8%), hand-foot reaction (N = 19, 44.2%), hypertension (N = 18, 41.9%), hypothyroidism (N = 11, 25.6%), gastrointestinal bleeding (N = 3, 7.0%), and liver function damage (N = 5, 11.6%). Two patients reported grade 3-4 immune-related liver damage. CONCLUSION: Second-line PD-1 inhibitor combined with albumin paclitaxel and apatinib showed certain efficacy and safety in patients with mGC. TRIAL REGISTRATION: Clinical trials, NCT04182724. Registered 27 November 2019; retrospectively registered, https://clinicaltrials.gov/study/NCT04182724.

Application of percutaneous biliary drainage in the treatment of post-operative bile leakage after liver rupture: A case report.

ABSTRACT: Post-operative bile leakage (POBL) is a serious complication following hepatobiliary surgery, with potentially life-threatening consequences if left untreated. This article presents a successful case of POBL management without surgical intervention. A 31-year-old male, diagnosed with bile leakage before hospitalisation, underwent percutaneous biliary drainage (PTBD) to address bilomas. Follow-up after 3 months indicated biloma atrophy and POBL healing but revealed bile duct stenosis. The patient received a larger biliary drainage tube, and after 1 month, the biloma and tube were removed. A 1-year follow-up confirmed the patient's excellent health. This case underscores the safety and efficacy of PTBD for managing POBL, offering a non-invasive alternative for patients with this complication. PTBD presents a viable treatment option for POBL cases, minimising the need for surgical interventions and their associated risks.

Survival outcome of different treatment sequences in patients with locally advanced and metastatic pancreatic cancer.

BACKGROUND: Despite some therapeutic advances, improvement in survival rates of unresectable and/or metastatic pancreatic ductal adenocarcinoma (PDAC) has been minimal over recent decade. We aimed to evaluate the impact of different treatment sequences on clinical outcomes of advanced PDAC at our academic institution. METHODS: In this single institution retrospective analysis, we assessed characteristics and survival rates of unresectable and/or metastatic pancreatic PDAC patients who started a systemic treatment between 01/2015 and 12/2021. Survival analyses were performed by Kaplan-Meier and Cox proportional hazards model. RESULTS: The number of 285 patients received at least two lines of treatment, but only 137 patients were suitable for third-line treatment. Subgroup analysis showed that thirty-seven patients received A line (gemcitabine/nab-paclitaxel or nab-paclitaxel combined therapy to FOLFIRINOX) therapy, 37 patients received B line (nab-paclitaxel combined therapy to gemcitabine combined therapy to FOLFIRINOX) therapy, 21 patients received C line (nab-paclitaxel combined therapy to gemcitabine combined therapy to oxaliplatin or irinotecan combined therapy) therapy. Survival rates for different treatment lines were significantly different and median overall survival (OS) was 14.00, 18.00, and 14.00 months, respectively (p<0.05). CONCLUSION: Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the treatment sequences on survival outcome when considering the entire management in advanced PDAC.

Enantiomorphic kagome bands in a two-dimensional covalent organic framework with non-trivial magnetic and topological properties.

The kagome lattice is one of the most intriguing topics to study. It has a frustrated flat band touching a set of Dirac bands and can possess various promising properties, such as ferromagnetism, superconductivity, and a non-trivial topology. Covalent organic frameworks (COFs) are a rare type of inorganic material, however, they can provide a platform for generating certain required lattices. Based on first-principles density functional theory calculations, we show that a newly synthesized two-dimensional COF named COF-SH has novel enantiomorphic kagome bands, which include two sets of flat bands touching the Dirac bands around the Fermi level. The Bloch wave of the flat-valence band at the K-point shows the kagome nature of the phase interference. Under charge doping, the COF-SH exhibits a ferromagnetic ground state. Moreover, when COF-SH is doped with iodine atoms, a sizable gap in the system is opened between the flat bands and the Dirac bands due to the spin-orbit coupling (SOC) effect. Meanwhile, the spin degeneracy is lifted since the organic layer loses electrons due to the oxidizing property of iodine. In addition, our tight-binding analysis with the SOC effect shows that the flat valence band separates from the Dirac bands and holds a nonzero Chern number. Consequently, this I-doped COF can give rise to a quantum anomalous Hall effect.

Prognostic value of the Lung Immune Prognostic Index for HER-2-negative metastatic gastric cancer.

Background: The aim of this study was to explore whether the Lung Immune Prognostic Index (LIPI) is associated with clinical outcomes in patients with metastatic gastric cancer (MGC) treated with anti-PD-1 and chemotherapy. Methods: Patients with MGC treated with an anti-PD-1 therapy or chemotherapy were enrolled. This study was composed of two cohorts including 266 patients in the anti-PD-1-treated group and 139 patients in the chemotherapy-treated group. Results: Patients treated with anti-PD-1 therapy that also showed a good LIPI showed a longer median progression-free survival and median overall survival in patients with an intermediate or poor LIPI. These outcomes were not observed in the chemotherapy cohort. Conclusion: Good LIPI correlated with better outcomes for patients with MGC in the anti-PD-1-treated group but not in the chemotherapy-treated group.

Functional identification and prediction of lncRNAs in esophageal cancer.

Esophageal cancer is a highly lethal malignancy with poor prognosis, and the identification of molecular biomarkers is crucial for improving diagnosis and treatment. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the development and progression of esophageal cancer. However, due to the time cost of biological experiments, only a small number of lncRNAs related to esophageal cancer have been discovered. Currently, computational methods have emerged as powerful tools for identifying and characterizing lncRNAs, as well as predicting their potential functions. Therefore, this article proposes a transformer-based method for identifying esophageal cancer-related lncRNAs. Experimental results show that the AUC and AUPR of this method are superior to other comparison methods, with an AUC of 0.87 and an AUPR of 0.83, and the identified lncRNA targets are closely associated with esophageal cancer. We focus on the role of esophageal cancer-related lncRNAs in the immune microenvironment, and fully explore the functions of the target genes regulated by lncRNAs. Enrichment analysis shows that the predicted target genes are related to multiple pathways involved in the occurrence, development, and prognosis of esophageal cancer. This not only demonstrates the effectiveness of the method but also indicates the accuracy of the prediction results.

The influence of dust on extreme precipitation at a large city in North China.

In recent decades, the Beijing-Tianjin-Hebei city cluster is experiencing rapid urbanization along with economic booming. Meanwhile, these cities are suffering the influence of extreme precipitation and dust storms. In this study, the impact of dust aerosol on extreme precipitation that occurred in Beijing during 19-21 July 2016 is investigated using both satellite retrievals and Weather Research and Forecasting model coupled to Chemistry (WRF-Chem) model simulations. Results reveal that the dust particles can increase extreme precipitation by promoting the formation of ice clouds and enhancing convections. The dust is lifted into the upper troposphere (>10 km) via strong convection and affects the physical process of precipitation after long-range transport. It further transforms the supercooled water into the middle and high levels of ice nuclei (IN). These promote the formation of ice clouds according to the decreased effective radius of IN and increased ice water path, respectively. Along with sufficient water vapor transport and strong convergence, the formation of IN could release more latent heat and further strengthen convection development. Thus, the precipitation amount in southern Beijing is almost enhanced by 40 % (>80 mm). This study will provide a deep insight into understanding the causes of urban extreme precipitation.

PD-1 inhibitors-based second-line therapy for metastatic gastric cancer.

Background: Metastatic gastric cancer (MGC) patients with progression on first-line treatment still have poor outcomes on chemotherapy. The KEYNOTE-061 study demonstrated that pembrolizumab, a PD-1inhibitor, was not better than paclitaxel as second-line therapy for MGC. Herein, we explored the efficacy and safety of PD-1inhibitor based treatment for MGC patients in the second line. Methods: In this observational, retrospective study, we enrolled MGC patients treated with anti-PD-1 based therapy as second-line in our hospital. We primarily assessed the treatment's efficacy and safety. We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses. Results: We enrolled 129 patients with an objective response rate (ORR) of 16.3% and a disease control rate (DCR) of 79.1%. Patients treated with PD-1inhibitor combined with chemotherapy and anti-angiogenic agents had ORR of 19.6% and higher DCR of 94.1%. The median progression-free survival (PFS) was 4.10 months, and the median overall survival (OS) was 7.60 months. In univariate analysis, patients treated with PD-1inhibitor combined with chemotherapy and anti-angiogenic agents and with prior anti-PD-1 history were significantly associated with favorable PFS and OS. In the multivariate analysis, different combination therapy and prior anti-PD-1 history were independent prognosis biomarkers for PFS and OS. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 28 (21.7%) patients. Common adverse events (AEs) included fatigue, hyper/hypothyroidism, neutrophil decrease, anemia, skin reactions, proteinuria, and hypertension. We did not observe treatment-related deaths. Conclusion: Our current results indicated that PD-1-inhibitor and chemo-anti-angiogenic agents combination therapy and prior PD-1 treatment history might improve clinical activity for GC immunotherapy as second-line treatment with acceptable safety profiles. Further studies are needed to verify those outcomes for MGC in other centers.

Enhanced photoelectric performance of MoSSe/MoS2 van der Waals heterostructures with tunable multiple band alignment.

Janus MoSSe with mirror asymmetry has recently emerged as a new two-dimensional (2D) material with a sizeable out-of-plane dipole moment. Here, based on first-principles calculations, we theoretically investigate the electronic properties of two patterns of 2D MoSSe/MoS2 van der Waals heterostructures (vdWHs). The electronic properties of MoSSe can be tuned by the intrinsic out-of-plane dipole field. When the Se side of the Janus layer faces the MoS2 layer, the dipole field points from the MoSSe layer towards the MoS2 layer, and the vdWH possesses a type-I band alignment which is desirable for light emission applications. With a reversal of the Janus layer, the intrinsic field inverts accordingly, and the band alignment becomes a typical type-II band alignment, which benefits carrier separation. Moreover, it possesses superior optical absorption (∼105 cm-1), and the calculated photocurrent density under visible-light radiation is up to 0.9 mA cm-2 in the MoSSe/MoS2 vdWH. Meanwhile, an external electric field and vertical strain can remarkably modulate the band alignment to switch it between type-I and type-II. Thus, MoSSe/MoS2 vdWHs have promising applications in next-generation photovoltaic devices.

Construction of a nomogram to predict the survival of metastatic gastric cancer patients that received immunotherapy.

Background: Immunotherapy has shown promising results for metastatic gastric cancer (MGC) patients. Nevertheless, not all patients can benefit from anti-PD-1 treatment. Thus, this study aimed to develop and validate a prognostic nomogram for MGC patients that received immunotherapy. Methods: Herein, MGC patients treated with anti-PD-1 between 1 October 2016 and 1 June 2022 at two separate Chinese PLA General Hospital centers were enrolled and randomly divided into training and validation sets (186 and 80 patients, respectively). The nomogram was constructed based on a multivariable Cox model using baseline variables from the training cohort. Its predictive accuracy was validated by the validation set. The consistency index (C-index) and calibration plots were used to evaluate the discriminative ability and accuracy of the nomogram. The net benefit of the nomogram was evaluated using decision curve analysis (DCA). Finally, we stratified patients by median total nomogram scores and performed Kaplan-Meier survival analyses. Results: We developed the nomogram based on the multivariate analysis of the training cohort, including four parameters: surgery history, treatment line, lung immune prognostic index (LIPI), and platelet-to-lymphocyte ratio (PLR). The C-index of the nomogram was 0.745 in the training set. The calibration curve for 1- and 2-year survival showed good agreement between nomogram predictions and actual observations. In the validation group, the calibration curves demonstrated good performance of the nomogram, with a C-index for overall survival (OS) prediction of 0.713. The OS of patients with a score greater than the median nomogram score was significantly longer than patients with a score lower or equal to the median (p < 0.001). Conclusion: We constructed a nomogram to predict the outcomes of MGC patients that received immunotherapy. This nomogram might facilitate individualized survival predictions and be helpful during clinical decision-making for MGC patients under anti-PD-1 therapy.

Fruquintinib in Combination With PD-1 Inhibitors in Patients With Refractory Non-MSI-H/pMMR Metastatic Colorectal Cancer: A Real-World Study in China.

Background: Fruquintinib, a vascular endothelial growth factor receptor inhibitor, is a new anticancer drug independently developed in China to treat refractory metastatic colorectal cancer (mCRC). In Japan, regorafenib combined with nivolumab has been demonstrated to be promising in patients with refractory mCRC. Here, in a real-world study, we were aimed to evaluate the efficacy of fruquintinib with various programmed death-1 (PD-1) inhibitors after standard treatment in Chinese non-microsatellite instability-high (MSI-H)/mismatch repair proficient mCRC patients. Methods: A total of 45 patients with refractory mCRC were involved in the study. They received fruquintinib (3 or 5 mg, orally administered once a day for 3 weeks followed by 1 week off in 4-week cycles) and a PD-1 inhibitor(200 mg pembrolizumab, 3 mg/kg nivolumab, 200 mg sintilimab or camrelizumab, intravenously administered on D1 once every 3 weeks). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and objective response rate (ORR) were reviewed and evaluated. Results: Among the 45 patients, the median age was 54 years (29-85). The ORR was 11.1% (5/45), DCR 62.2% (28/45), median PFS equal 3.8 months, and median OS was 14.9 months. The response duration was 3.4 months. PFS between left and right primary tumors and PFS with or without lung metastases were both not significantly different (p > 0.05), which was inconsistent with the result of REGONIVO study. The multivariate analysis indicated no association of OS benefit in the specified subgroups. No adverse-effect-related deaths were reported. Conclusions: Fruquintinib, in combination with anti-PD-1, was observed to have clinical activity in a small population of patients with heavily pretreated mCRC in our center. Further studies are needed to verify this outcome in a large population.

S-1 Maintenance Therapy After First-Line Treatment With Nab-Paclitaxel Plus S-1 for Advanced Pancreatic Adenocarcinoma: A Real-World Study.

Background: In our previous phase II study, nab-paclitaxel plus S-1 (NPS) showed encouraging objective response rate (ORR) as first-line treatment for advanced pancreatic adenocarcinoma (APAC). This study aimed to evaluate the effectiveness and safety of S-1 maintenance after NPS in APAC and to explore factors predicting survival benefits when using S-1 maintenance. Methods: Between 2014 and 2018 a total of 182 patients with APAC, who were primarily treated with NPS, were included. For patients without progression or with treatment discontinuation due to any reasons within 4 months during NPS treatment, S-1 monotherapy was administrable as maintenance therapy at the physicians' discretion based on the patients' preference and performance status. Efficacy and safety of S-1 maintenance were investigated. Results: In 123 patients without progression within 4 months during NPS treatment, 74 received S-1 maintenance and had median progression-free survival of 9.6 months and median overall survival of 16.7 months. Multivariable analysis showed that in patients receiving S-1 maintenance after first-line NPS therapy, an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, non-metastatic disease, and complete or partial response as best response to NPS chemotherapy were independently associated with better survival. The most common all-grade hematological and non-hematological adverse events were neutropenia (82.4%) and peripheral neurotoxicity (66.2%), respectively, and the most common ≥Grade 3 hematological and non-hematological adverse events were neutropenia (40.5%) and peripheral neurotoxicity (6.8%), respectively in patients who received S-1 maintenance. Conclusions: Our real-world study showed that S-1 maintenance after tumor response or stable disease induced by first-line NPS treatment was effective and well-tolerated for some patients with APAC, which offers a promising alternative treatment strategy with encouraging survival for APAC.

Identification of Small Nucleolar RNA SNORD60 as a Potential Biomarker and Its Clinical Significance in Lung Adenocarcinoma.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths in the world and often diagnosed at an advanced stage, so it is urgent to explore the pathogenesis and new diagnostic biomarkers. Accumulated evidences suggested that small nucleolar RNAs (snoRNAs) played a key role in the development and progression of NSCLC. To examine differential expression snoRNA profile and identify snoRNAs with clinical significance in lung adenocarcinoma (LUAD), The Cancer Genome Atlas (TCGA) LUAD RNA sequencing dataset was used to investigate differential expression snoRNA signatures and compared with snoRNA PCR array analysis in pair-matched LUAD tissues. The diagnostic ability of SONRD60 was assessed using a receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to plot survival curves. Univariate and multivariate Cox regression analyses were used to investigate the prognostic effect of SNORD60 expression on LUAD. The results showed that SNORD60 was a significantly upregulated snoRNA after intersection analysis in LUAD cases. SNORD60 has 74.2% sensitivity and 75.3% specificity for the diagnosis of LUAD. Increased SNORD60 expression was linked with lymph node metastases and the TNM stage (P < 0.05). Pathological T category and lymph node metastases were independent prognostic factors for overall survival in a multivariate Cox regression study. Our findings demonstrated that SNORD60, a small nucleolar RNA, has an oncogenic function in LUAD and might be used as a new early diagnostic biomarker for LUAD.

Enhancement of lipid accumulation and docosahexaenoic acid synthesis in Schizochytrium sp. H016 by exogenous supplementation of sesamol.

Schizochytrium sp. is one of the most promising marine oleaginous microorganisms for industrial production of docosahexaenoic acid (DHA). In this study, the exogenous supplementation of 1 mM sesamol to the fermentation medium effectively prevented the peroxidation of polyunsaturated fatty acids in the fermentation process, which thereby significantly increasing the lipid and DHA yield by 53.52% and 78.30%, respectively. The addition of sesamol also increased the total antioxidant capacity of cells and induce the gene expression of polyketide synthase and antioxidant enzyme system. Moreover, the supply of nicotinamide adenine dinucleotide phosphate was regulated by sesamol by inhibiting the malic enzyme activity and promoting the glucose-6-phosphate dehydrogenase activity. Finally, fed-batch fermentation showed that the addition of sesamol significantly enhanced the DHA yield by 90.76%. This study provides an important reference for enhancing the DHA productivity of Schizochytrium sp. in industrial fermentation.

Preoperative lung immune prognostic index predicts survival in patients with pancreatic cancer undergoing radical resection.

Background: Lung immune prognostic index (LIPI), a combination of derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH), is currently attracting considerable interest as a potential prognostic indicator in many malignancies. Our study aimed to investigate the prognostic value of preoperative LIPI in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing radical resection. Methods: We retrospectively reviewed PDAC patients treated with radical resection from February 2019 to April 2021 at Chinese People's Liberation Army (PLA) general hospital. Based on the cut-off value of dNLR and LDH identified by X-tile, patients were divided into LIPI good and LIPI intermediate/poor group. Kaplan-Meier curve and log-rank test were used to compare the recurrence-free survival (RFS) and overall survival (OS) of the two groups. Univariate and multivariate Cox regression was used to identify the independent prognostic value of LIPI. Subgroup analysis was performed to identify specific population benefited from radical resection. Results: A total of 205 patients were included and the median RFS and OS was 10.8 and 24.3 months, respectively. Preoperative LIPI intermediate/poor was related to worse RFS and OS (p < 0.05). Preoperative LIPI intermediate/poor, vascular invasion and no adjuvant chemotherapy were indicators of poor OS. Patients with LIPI intermediate/poor had worse OS especially among females and those with adjuvant chemotherapy (p < 0.05). Adjuvant chemotherapy related to better RFS and OS in patients with LIPI good (p < 0.05). Conclusions: Preoperative LIPI intermediate/poor can be an indicator of poor prognosis in patients with PDAC undergoing radical resection. LIPI good could be an effective marker of benefit from adjuvant chemotherapy. Larger studies are warranted for further validation.

The Prognostic Value of Pre-treatment Hemoglobin (Hb) in Patients With Advanced or Metastatic Gastric Cancer Treated With Immunotherapy.

BACKGROUND: Biomarkers such as prevailing PD-L1 expression and TMB have been proposed as a way of predicting the outcome of immunotherapy in patients with advanced gastric cancer (AGC) and metastatic gastric cancer (MGC). Our study aims to investigate whether there is a link between pretreatment hemoglobin (Hb) levels and survival to immunotherapy in patients with AGC and MGC. METHODS: We retrospectively reviewed patients with AGC or MGC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor. The Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) and overall survival (OS) was analyzed among different Hb level (normal Hb group and decreased Hb group). Objective response rate (ORR), disease control rate (DCR) were also analyzed. Univariate analysis and multivariate analysis were performed further to validate the prognostic value of Hb level. RESULTS: We included 137 patients with AGC and MGC who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) in this study. After PSM matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 7.8 months in the normal Hb level group and 4.3 months in the decreased Hb group (HR 95% CI 0.5(0.31, 0.81), P=0.004). The OS was 14.4 months with normal Hb level as compared with 8.2 months with decreased Hb level(HR 95% CI 0.59(0.37, 0.94), P=0.024). The ORR was 40.7% and DCR was 83.0% in the normal Hb group, while the ORR was 25.5% and DCR was 85.1% in the decreased Hb group. No significant differences were found in the ORR and DCR between the two groups (P=0.127, P=0.779). Univariate analysis and multivariate analysis showed that Hb level was only independent predictor for PFS and baseline Hb level was significant prognostic factor influencing the OS. Only when patients had normal Hb level, anti-pd-1 monotherapy or combined with chemotherapy was superior to anti-pd-1 plus anti-angiogenic therapy with respect to PFS (10.3 m vs 2.8 m, HR 95% CI 0.37(0.15, 0.95), P=0.031) and OS(15 m vs 5.7 m, HR 95% CI 0.21 (0.08, 0.58), P=0.001). CONCLUSIONS: Our study have demonstrated that pretreatment Hb level was an independent prognostic biomarker in term of PFS and OS with immunotherapy for AGC and MGC patients. Correction of anemia for GC patients as immunotherapy would be a strategy to improve the survival. More data was warranted to further influence this finding.