Akkermansia muciniphila improves gastric cancer treatment by modulating the immune microenvironment.

Background: Gut microbiota is pivotal in tumor occurrence and development, and there is a close relationship between Akkermansia muciniphila (AKK) and cancer immunotherapy. Methods: The effects of AKK and its outer membrane proteins on gastric cancer (GC) were evaluated in vitro and in vivo using cell counting kit-8 assay, flow cytometry, western blotting, ELISA, immunohistochemistry and immunofluorescence. Results: AKK outer membrane protein facilitated apoptosis of GC cells and exerted an immunostimulatory effect (by promoting M1 polarization of macrophages, enhancing expression of cytotoxic T-lymphocyte-related cytokines and suppressing that of Treg-related cytokines). Additionally, AKK and its formulation could inhibit tumor growth of GC and enhance the infiltration of immune cells in tumor tissues. Conclusion: AKK could improve GC treatment by modulating the immune microenvironment.

Akkermansia muciniphila (AKK) is a type of bacteria found in the human gut that is good for the immune system. We wanted to investigate the effect of AKK on cancer. We extracted a protein from AKK called Amuc. AKK and Amuc inhibited the growth of stomach cancer by encouraging the action of immune cells. AKK may therefore be able to treat stomach cancer.

B7-H3 promotes proliferation and migration of lung cancer cells by modulating PI3K/AKT pathway via ENO1 activity.

Background: B7-H3 (CD276) is overexpressed in diverse malignant tumors and plays critical roles in tumorigenesis and metastasis. However, the mechanism of B7-H3 in lung cancer remains unclear. This study aimed to explore the mechanism of interaction between B7-H3 and α-enolase (ENO1) in lung cancer progression. Methods: Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) databases were used to analyze the B7-H3 messenger RNA (mRNA) expression levels in lung cancer. The Kaplan-Meier (KM) plotter was used to analyze the correlation between B7-H3 and prognosis. Immunoprecipitation and glutathione S-transferase (GST) pull-down were used to verify the B7-H3 and ENO1 interaction. Cell counting kit-8 (CCK-8) and wound healing assays were used to investigate the effect of B7-H3 on the lung cancer growth. Results: Based on the public databases, the analysis showed that B7-H3 mRNA expression levels were up-regulated and correlated with patient prognosis in lung cancer. By using B7-H3 gain and off cell model, we concluded that B7-H3 overexpression promoted proliferation and migration of SBC5 cells. Subsequently, we found that both B7-H3 and ENO1 knockdown could inhibit cell proliferation and migration, in the meanwhile, and the phosphorylation levels of PI3K-p85α, and AKT were significantly reduced. Interestingly, we determined that B7-H3 regulated ENO1 activity rather than changing its expression levels. Furthermore, we used an AP-III-a4 to block ENO1 activity in the experiments, which attenuated the roles of B7-H3 not only on phosphorylation levels of those molecules, but also on cell growth and migration. Conclusions: B7-H3 directly interacts with ENO1 in lung cancer cells. B7-H3 can promote proliferation and migration of lung cancer cells by modulating PI3K/AKT pathway via ENO1 activity.

Enhancing Neuroprotection in Mouse Model of Parkinson's Disease through Protein Nanosystem Conjugation with ApoE Peptide for miR-124 Delivery.

Parkinson's disease (PD) affects millions of people's lives worldwide. The main pathogenesis of PD is dopaminergic neuron necrosis and neuroinflammation mediated by activated microglia cells. In recent years, the anti-inflammatory ability and neuroprotective effects of miR-124 in PD models were well proved, but the in vivo delivery of miR-124 remains challenging. Herein, we report a protein nanosystem modified with a brain-targeting peptide ApoE that could efficiently deliver miR-124 across the blood-brain barrier (BBB). This nanosystem showed good cell viability on brain endothelial cells and microglia cells, and administration of this nanosystem significantly decreased the neuroinflammation and dopaminergic neuron loss, as well as recovered parts of neurobehavioral deficits. This ApoE peptide-based protein nanosystem holds great promise for the delivery of RNA therapeutics to the brain and for realizing neuron protection in PD treatment.

Research on dynamic comfort maintenance by measuring lower limb edema and seat pressure during simulated seated sleep in flight.

Objectives. Seated sleep during flight can bring significant discomfort to passengers. The objective of this research was to study passengers' dynamic comfort maintenance strategies in lower limb postural shifting during seated sleep in flight. Methods. Studies on seated sleep postures and sitting comfort were conducted. First, 40 participants were recruited to the observational research for collecting typical leg postures during seated sleep. Then, an experiment was conducted with the participants simulating seated sleep in the aircraft seat. The changes in lower limb edema and seat pressure in different postures were measured with a bioelectrical impedance device, near-infrared spectroscopy device and pressure mapping device. Results. Six postures were selected through the observational research. The experiment showed that tissues of the thighs and buttocks suffer alternate higher compression by shifting between the six postures. Lower limb edema is higher when the shanks are forward, while the tissue under the ischial tuberosity suffers higher compression when the shanks are neutral. Conclusion. Six motivations for passengers to shift each sitting posture to achieve dynamic comfort were summarized, which helps obtain alternating rest in different body parts. The suggestion of a leg position adjustment system was also proposed.

Integration of mRNA and miRNA analysis reveals the molecular mechanisms of sugar beet (Beta vulgaris L.) response to salt stress.

The continuous increase of saline-alkali areas worldwide has led to the emergence of saline-alkali conditions, which are the primary abiotic stress or hindering the growth of plants. Beet is among the main sources of sugar, and its yield and sugar content are notably affected by saline-alkali stress. Despite sugar beet being known as a salt-tolerant crop, there are few studies on the mechanisms underlying its salt tolerance, and previous studies have mainly delineated the crop's response to stress induced by NaCl. Recently, advancements in miRNA-mRNA network analysis have led to an increased understanding of how plants, including sugar beet, respond to stress. In this study, seedlings of beet variety "N98122" were grown in the laboratory using hydroponics culture and were exposed to salt stress at 40 days of growth. According to the phenotypic adaptation of the seedlings' leaves from a state of turgidity to wilting and then back to turgidity before and after exposure, 18 different time points were selected to collect samples for analysis. Subsequently, based on the data of real-time quantitative PCR (qRT-PCR) of salt-responsive genes, the samples collected at the 0, 2.5, 7.5, and 16 h time points were subjected to further analysis with experimental materials. Next, mRNA-seq data led to the identification of 8455 differentially expressed mRNAs (DEMs) under exposure to salt stress. In addition, miRNA-seq based investigation retrieved 3558 miRNAs under exposure to salt stress, encompassing 887 known miRNAs belonging to 783 families and 2,671 novel miRNAs. With the integrated analysis of miRNA-mRNA network, 57 miRNA-target gene pairs were obtained, consisting of 55 DEMIs and 57 DEMs. Afterwards, we determined the pivotal involvement of aldh2b7, thic, and δ-oat genes in the response of sugar beet to the effect of salt stress. Subsequently, we identified the miRNAs novel-m035-5p and novel-m0365-5p regulating the aldh gene and miRNA novel-m0979-3p regulating the thic gene. The findings of miRNA and mRNA expression were validated by qRT-PCR.

AI-based soundscape analysis: Jointly identifying sound sources and predicting annoyancea).

Soundscape studies typically attempt to capture the perception and understanding of sonic environments by surveying users. However, for long-term monitoring or assessing interventions, sound-signal-based approaches are required. To this end, most previous research focused on psycho-acoustic quantities or automatic sound recognition. Few attempts were made to include appraisal (e.g., in circumplex frameworks). This paper proposes an artificial intelligence (AI)-based dual-branch convolutional neural network with cross-attention-based fusion (DCNN-CaF) to analyze automatic soundscape characterization, including sound recognition and appraisal. Using the DeLTA dataset containing human-annotated sound source labels and perceived annoyance, the DCNN-CaF is proposed to perform sound source classification (SSC) and human-perceived annoyance rating prediction (ARP). Experimental findings indicate that (1) the proposed DCNN-CaF using loudness and Mel features outperforms the DCNN-CaF using only one of them. (2) The proposed DCNN-CaF with cross-attention fusion outperforms other typical AI-based models and soundscape-related traditional machine learning methods on the SSC and ARP tasks. (3) Correlation analysis reveals that the relationship between sound sources and annoyance is similar for humans and the proposed AI-based DCNN-CaF model. (4) Generalization tests show that the proposed model's ARP in the presence of model-unknown sound sources is consistent with expert expectations and can explain previous findings from the literature on soundscape augmentation.

Association analysis of agronomic traits and construction of genetic networks by resequencing of 306 sugar beet (Beta vulgaris L.) lines.

Due to the relatively brief domestication history of sugar beet (Beta vulgaris ssp. vulgaris), our understanding of the genomic diversity and functional genes in its cultivars is limited, resulting in slow breeding progress. To address this issue, a total of 306 germplasm materials of major cultivars and breeding lines from China, the USA, and Europe were selected for genome resequencing. We investigated population structure and genetic diversity and performed selective scanning of genomic regions, identifying six novel genes associated with important agronomic traits: the candidate genes DFAX2 and P5CS for skin roughness; the candidate genes FRO5, GL24, and PPR91 for root yield and sugar yield, and the pleiotropic candidate gene POLX for flourishing growth vigour, plant height, crown size, flesh coarseness, and sugar yield. In addition, we constructed a protein-protein interaction network map and a phenotype-gene network map, which provide valuable information for identifying and characterizing functional genes affecting agronomic traits in sugar beet. Overall, our study sheds light on the future improvement of sugar beet agronomic traits at the molecular level.

The active aging level of the rural older adults with disability in China: a cross-sectional study.

Background: Active aging has been listed as an important indicator to measure the quality of life of the older adults and the construction of the senior care system. There is an imbalance between the supply and demand of senior care services for the disabled older adults in rural areas, and the quality of life needs to be improved. Objectives: We aimed to analyze the current situation of active aging and the influencing factors of the rural disabled older adults, in order to provide a reference basis for improving the quality of life of the rural disabled older adults. Methods: We conducted a multicenter and cross-sectional study, using the Barthel Index Scale and Chinese version of the Active Aging Scale, to facilitate the selection of 304 rural older adults with disability in 26 villages under Henan Province for a questionnaire survey. Results: The mean score for the level of active aging of rural older adults with disability was 1.87 (SD 0.36), with the highest score for the dimension of being self-reliant (Mean2.29, SD 0.61) and lower scores for the dimension of active contribution to society (Mean 1.37, SD 0.55) and building up financial security (Mean 1.37, SD 0.57). The results of the multiple regression analysis showed higher levels of active aging among the disabled older adults with retirement pay, mild disability, and longer time per activity/rehabilitation exercise (p < 0.05). Conclusion: Active aging of the rural disabled older adults is at a low level, with insufficient economic security and social participation. The national government should help improve the quality of primary health care in rural areas, build a friendly environment for senior communities, and improve policies to protect the welfare of the older adults, so as to collaboratively empower the disabled older adults in rural areas at three levels: health, participation, and protection.

Nuclear localization of TET2 requires ß-catenin activation and correlates with favourable prognosis in colorectal cancer.

Mutation-induced malfunction of ten-eleven translocation methylcytosine dioxygenase 2 (TET2) is widely reported in haematological malignancies. However, the role of TET2 in solid cancers, including colorectal cancer (CRC), is unclear. Here, we found that TET2 malfunction in CRC is mostly due to decreased nuclear localization and that nuclear localization of TET2 is correlated with better survival of patients. To explore the underlying mechanisms, 14 immortalized solid tumour cell lines and 12 primary CRC cell lines were used. TET2 was mostly detected in the nucleus, and it induced significant DNA demethylation and suppressed cell growth by demethylating RORA and SPARC in cell lines like SW480. While in cell lines like SW620, TET2 was observed in the cytosol and did not affect DNA methylation or cell growth. Further examination with immunoprecipitation-mass spectrometry illustrated that ß-catenin activation was indispensable for the nuclear localization and tumour suppression effects of TET2. In addition, the ß-catenin pathway activator IM12 and the TET2 activator vitamin C were used simultaneously to enhance the effects of TET2 under low-expression conditions, and synergistic inhibitory effects on the growth of cancer were observed both in vitro and in vivo. Collectively, these data suggest that ß-catenin-mediated nuclear localization of TET2 is an important therapeutic target for solid tumours.

Analysis of the information ability of nurses in county hospitals in northern Henan province: a survey.

OBJECTIVE: To investigate the status quo of nursing information ability of nurses in county-level hospitals and analyze its influencing factors. METHODS: In June 2022, a total of 303 on-the-job clinical nurses from 3 county-level hospitals in Hebi City, Henan Province were selected as subjects by convenience sampling method. General data questionnaire and self-rating nursing information ability scale were used to investigate them. RESULTS: The total score of nursing information ability of 303 nurses in county hospitals of Hebi City, Henan Province was (77.72 ± 18.76). There were statistically significant differences in the scores of nursing information ability among different ages, working years, positions, education, marriage, monthly income, whether they had learned computer-related knowledge and skills, and whether they had participated in the learning or training of nursing information system (all p < 0.05).Multiple linear regression analysis showed that age, years, position, monthly income and whether they had learned computer-related knowledge and skills were the main influencing factors of nursing information ability of county-level nurses (all p < 0.05). CONCLUSIONS: The nursing information ability of nurses in county-level hospitals in northern Henan is at a medium level. The government or society should provide training and guidance on nursing information ability, so as to provide more opportunities for nurses in county-level hospitals to participate in and learn nursing information technology to improve their ability.

Sustainable Development Evaluation on the Landscape Design of Industrial Heritage Park: A Case Study of Tao Sichuan, China.

The sustainable development of the urban environmental landscape is a process that integrates resource utilization, ecological benefit, economy, and society and involves elements of culture, society, politics, economy, and individual residents. Citizen participation is increasingly important for the urban landscape design, and therefore, urban environmental landscape studies must be evaluated objectively by the public to ensure both sustainable development and social justice. In this study, the Tao Sichuan Creative Industry Park (the former "Universe Porcelain Factory") in Jingdezhen, Jiangxi province, China, was taken as example, and the implemented landscape reconstruction was evaluated. The analytical hierarchy process was used to collect both expert and public opinions regarding the cultural landscape; then, the weight coefficient of the value index layer of the industrial heritage park was obtained. A comparison of the two groups (experts and the public) showed that the experts do not exactly agree with the perspective of the public: experts prefer the artistic value far more than any other factors, while the public prefers the artistic value, social value, and economic value. Each group prefers different values of the landscape, suggesting that environmental justice should not be biased toward one of these perspectives. Finally, a design optimization principle is proposed according to the results of this study. This principle strengthens the sustainable development concept in the landscape reconstruction of industrial heritage parks, and suggestions are provided for optimizing the allocation of urban public landscape resources.

Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins.

Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive and heterogeneous tumor composed of adenocarcinoma (ACA) and neuroendocrine carcinoma (NEC). The genomic properties and evolutionary clonal origins of MANEC remain unclear. We conduct whole-exome and multiregional sequencing on 101 samples from 33 patients to elucidate their evolutionary paths. We identify four significantly mutated genes, TP53, RB1, APC, and CTNNB1. MANEC resembles chromosomal instability stomach adenocarcinoma in that whole-genome doubling in MANEC is predominant and occurs earlier than most copy-number losses. All tumors are of monoclonal origin, and NEC components show more aggressive genomic properties than their ACA counterparts. The phylogenetic trees show two tumor divergence patterns, including sequential and parallel divergence. Furthermore, ACA-to-NEC rather than NEC-to-ACA transition is confirmed by immunohistochemistry on 6 biomarkers in ACA- and NEC-dominant regions. These results provide insights into the clonal origin and tumor differentiation of MANEC.

Biomechanical mechanism driving typical postural shifts of lower limbs during sleeping in an aircraft seat.

The purpose of this study was to determine the biomechanical mechanisms driving passengers' lower-limb postural shifts during seated sleep on a flight to prevent negative effects on passengers' physical health. Twenty subjects participated in an observational study and a subsequent experiment on fatigue development and tissue oxygenation changes during seated sleep in an economy-class aircraft seat. Three of the most frequently used postures, which involved four targeted muscles of the legs and the thigh-buttock region, were selected and examined in the experiment with the following measures: muscle electromyogram, tissue oxygenation, and body contact pressure distribution. The results showed that the fatigue of the tibialis anterior and gastrocnemius and the compression of the region under the medial tuberosities were relieved by alternations among the three positions-position 1 (placing the shanks forwards), position 2 (placing the shanks neutrally), and position 3 (placing the shanks backwards). This research reveals the mechanical properties of the biomechanical factors functioning in lower-limb postural shifts during seated sleep and provides design optimization strategies for economy-class aircraft seats to reduce the negative effects on passenger health.

CD5L aggravates rheumatoid arthritis progression via promoting synovial fibroblasts proliferation and activity.

Rheumatoid arthritis (RA) is a chronic inflammatory disease with progressive cartilage erosion and joint destruction. Synovial fibroblasts (SFs) play a crucial role in the pathogenesis of RA. This study aims to explore the function and mechanism of CD5L during RA progression. We examined the levels of CD5L in synovial tissues and SFs. The collagen-induced arthritis (CIA) rat models were used to investigate the effect of CD5L on RA progression. We also investigated the effects of exogenous CD5L on the behavior and activity of RA synovial fibroblasts (RASFs). Our results showed that CD5L expression was significantly upregulated in synovium of RA patients and CIA-rats. Histology and Micro-CT analysis showed that synovial inflammation and bone destruction were more severe in CD5L-treated CIA rats compared with control rats. Correspondingly, CD5L blockade alleviated bone damage and synovial inflammation in CIA-rats. The exogenous CD5L treatment promoted RASFs proliferation invasion and proinflammatory cytokine production. Knockdown of CD5L receptor by siRNA significantly reversed the effect of CD5L treatment on RASFs. Moreover, we observed that CD5L treatment potentiated PI3K/Akt signaling in the RASFs. The promoted effects of CD5L on IL-6 and IL-8 expression were significantly reversed by PI3K/Akt signaling inhibitor. In conclusion, CD5L promote RA disease progression via activating RASFs. CD5L blocking is a potential therapeutic approach for RA patients.

Intratumoral microbiome impacts immune infiltrates in tumor microenvironment and predicts prognosis in esophageal squamous cell carcinoma patients.

Background: Different intratumoral microbiotaexist in different tumors and play a crucial function in carcinogenesis. However, whether they impact clinical outcomes in esophageal squamous cell carcinoma (ESCC) and their mechanism remain unclear. Methods: 16S rDNA amplicon sequencing was performed on surgically resected samples from 98 ESCC patients to analyze intratumoral microbiome abundance and composition. Multiplex fluorescent immunohistochemistry staining was used to profile the phenotypes of immune infiltrates in the tumor microenvironment (TME). Results: Patients with higher intratumoral Shannon index had significantly worse surgical outcomes. When patients were divided into short-term survivors and long-term survivors based on the median survival time, both intratumoral alpha-diversity and beta-diversity were found to be significantly inconsistent, and the relative abundance of Lactobacillus and Leptotrichia emerged as the two microorganisms that probably influenced the survival of ESCC patients. Only Lactobacillus in ESCC was validated to significantly worsen patients' prognoses and to be positively correlated with the Shannon index. Multivariate analysis revealed that the intratumoral Shannon index, the relative abundance of Lactobacillus, and the pathologic tumor-node-metastasis (pTNM) stage were independently associated with patients' overall survival. Furthermore, the relative abundance of both Lactobacillus and Shannon index was positively correlated with the proportions of PD-L1+ epithelial cells (ECs) and tumor-associated macrophages (TAMs). The Shannon index was negatively correlated with the proportions of natural killer (NK) cells in the TME. Conclusions: A high abundance of intratumoral Lactobacillus and bacterial alpha-diversity was associated with the formation of the immunosuppressive TME and predicted poor long-term survival in ESCC patients.

Neoadjuvant PD-1 blockade with sintilimab in mismatch-repair deficient, locally advanced rectal cancer: an open-label, single-centre phase 2 study.

BACKGROUND: The current standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by radical surgery, but this approach can lead to multiple complications. We aimed to investigate the clinical activity and safety of neoadjuvant therapy with sintilimab, a single-agent PD-1 antibody, in patients with mismatch-repair deficient locally advanced rectal cancer. METHODS: This open-label, single-arm, phase 2 study was done at the Sun Yat-sen University Cancer Center, Guangzhou, China. Patients aged 18-75 years with mismatch-repair deficient or microsatellite instability-high locally advanced rectal cancer were enrolled and received neoadjuvant sintilimab monotherapy (200 mg by intravenous infusion) every 21 days. After an initial four cycles of treatment, patients and clinicians could choose one of the following options: total mesorectal excision surgery, followed by four cycles of adjuvant sintilimab with or without CapeOX chemotherapy (capecitabine 1000 mg/m2, orally administered twice daily on days 1-14; oxaliplatin 130 mg/m2, intravenously administered on day 1 every 3 weeks), determined by clinicians; or another four cycles of sintilimab followed by radical surgery or observation (only for patients with a clinical complete response; also known as the watch and wait strategy). The primary endpoint was the complete response rate, which included both a pathological complete response after surgery and a clinical complete response after completion of sintilimab treatment. Clinical response was evaluated by digital rectal examination, MRI, and endoscopy. Response was assessed in all patients who received treatment at least until the first tumour response assessment, after the first two cycles of sintilimab. Safety was analysed in all patients who received at least one dose of treatment. This trial is closed to enrolment and is registered with ClinicalTrials.gov (NCT04304209). FINDINGS: Between Oct 19, 2019, and June 18, 2022, 17 patients were enrolled and received at least one dose of sintilimab. The median age was 50 years (IQR 35-59) and 11 (65%) of 17 patients were male. One patient was excluded from efficacy analyses because they were lost to follow-up after the first sintilimab cycle. Of the remaining 16 patients, six underwent surgery, of whom three had a pathological complete response. Nine other patients had a clinical complete response and chose the watch and wait strategy. One patient had a serious adverse event and discontinued treatment; this patient did not have a complete clinical response and refused to undergo surgery. A complete response was thus noted for 12 (75%; 95% CI 47-92) of 16 patients. One of the three patients who underwent surgery but did not have a pathological complete response showed an increase in tumour volume after the initial four cycles of sintilimab (at which point they underwent surgery); this patient was deemed to have primary resistance to immune checkpoint inhibitors. After a median follow-up of 17·2 (IQR 8·2-28·5) months, all patients were alive and none had disease recurrence. Only one (6%) patient had a grade 3-4 adverse event, which was deemed a serious adverse event (grade 3 encephalitis). INTERPRETATION: The preliminary results of this study suggest that anti-PD-1 monotherapy is effective and tolerable for patients with mismatch-repair deficient locally advanced rectal cancer and could potentially spare some patients from radical surgery. Longer treatment courses might be needed to achieve maximum effects in some patients. Longer follow-up is also needed to observe the duration of response. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, Science and Technology Program of Guangzhou, and Innovent Biologics.

Neoadjuvant Camrelizumab for Non-Small Cell Lung Cancer: A Retrospective Multicenter, Real-World Study (CTONG2004).

BACKGROUND: Camrelizumab has shown encouraging efficacy in advanced non-small cell lung cancer (NSCLC), either as monotherapy or combined with chemotherapy. However, evidence of neoadjuvant camrelizumab for NSCLC remains lacking. METHODS: Patients with NSCLC treated with neoadjuvant camrelizumab-based therapy followed by surgery between December 2020 and September 2021 were retrospectively reviewed. Demographic and clinical data, details of neoadjuvant therapy and surgical information were retrieved. RESULTS: In this multicenter retrospective real-world study, 96 patients were included. Ninety-five patients (99.0%) received neoadjuvant camrelizumab combined with platinum-based chemotherapy, with a median of 2 cycles (range 1-6). The median interval from the last dose to surgery was 33 days (range 13-102 days). Seventy patients (72.9%) underwent minimally invasive surgery. Lobectomy was the most frequent surgical procedure (94 [97.9%]). The median estimated intraoperative blood loss was 100 mL (range 5-1200 mL), and the median operative time was 3.0 h (range 1.5-6.5 h). The R0 resection rate was 93.8%. Twenty-one patients (21.9%) experienced postoperative complications, with the most common being cough and pain (both 6 [6.3%]). The overall response rate was 77.1% (95% CI 67.4-85.0%), and the disease control rate was 93.8% (95% CI 86.9-97.7%). Twenty-six patients (27.1%, 95% CI 18.5-37.1%) had pathological complete response. Neoadjuvant treatment-related adverse events of grade ≥ 3 were reported in seven patients (7.3%), with the most frequent being abnormal liver enzymes (two [2.1%]). No treatment-related deaths were reported. CONCLUSION: The real-world data indicated that camrelizumab-based therapy had promising efficacy for NSCLC in the neoadjuvant setting, with manageable toxicities. Prospective studies investigating neoadjuvant camrelizumab are warranted.

Effectiveness and safety of camrelizumab in inoperable or advanced non-small cell lung cancer patients: a multicenter real-world retrospective observational study (CTONG2004-ADV).

Background: Camrelizumab plus chemotherapy have been approved as standards for the treatment of advanced non-small cell lung cancer (NSCLC) patients based on two phase III trials. However, clinical trial results may not be representative of the general population, as clinical trials often have specific inclusion and exclusion criteria. Our research aims to investigate the real-world effectiveness and safety of camrelizumab in inoperable or advanced NSCLC patients. Methods: This multicenter retrospective observational study included inoperable or advanced pathologically confirmed NSCLC patients who received at least one dose of camrelizumab at 22 hospitals. Clinical and follow-up data of camrelizumab were collected retrospectively from the medical records. The primary outcome was the objective response rate (ORR) and secondary outcomes were disease control rate (DCR), 6-month progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Multivariate logistic and Cox regression analyses were applied to identify potential predictive factors of ORR and PFS, respectively. Results: Between July 2019 and March 2021, 336 patients were included. Adenocarcinoma was seen in 58.4% and stage IV disease in 69.3%. Twenty-nine (8.6%) had liver metastasis at baseline. Most patients received camrelizumab in the first-line setting (74.1%) and in combination with chemotherapy (60.7%). The ORR was 40.2% [95% confidence interval (CI): 34.9-45.6%] and DCR was 85.1% (95% CI: 81.3-88.9%), while the 6-month PFS and OS rates were 73.0% (95% CI: 67.1-78.0%) and 93.1% (95% CI: 89.8-95.4%), respectively. In multivariate analyses, liver metastasis [odds ratio (OR), 0.324; 95% CI: 0.115-0.915; P=0.033] and increasing lines of camrelizumab treatment (vs. first line, second line: OR, 0.347; 95% CI: 0.162-0.741; P=0.006; ≥ third line: OR, 0.126; 95% CI: 0.043-0.367; P<0.001) were negatively associated, while a longer duration of camrelizumab treatment was positively associated with ORR and PFS. TRAEs were recorded in 164 (48.8%) patients, without new safety signal. Conclusions: We conducted a comprehensive overview of the effectiveness and safety profile of camrelizumab in a broader NSCLC population in real world NSCLC patients, and subgroup analysis indicated the presence of liver metastasis was associated with worse outcomes.

Systemic analysis identifying PVT1/DUSP13 axis for microvascular invasion in hepatocellular carcinoma.

BACKGROUND: Microvascular invasion (MVI) is an independent detrimental risk factor for tumor recurrence and poor survival in hepatocellular carcinoma (HCC). Competitive endogenous RNA (ceRNA) networks play a pivotal role in the modulation of carcinogenesis and progression among diverse tumor types. However, whether the ceRNA mechanisms are engaged in promoting the MVI process in patients with HCC remains unknown. METHODS: A ceRNA regulatory network was constructed based on RNA-seq data of patients with HCC from The Cancer Genome Atlas (TCGA) database. In total, 10 hub genes of the ceRNA network were identified using four algorithms: "MCC," "Degree," "Betweenness," and "Stress." Transcriptional expressions were verified by in situ hybridization using clinical samples. Interactions between ceRNA modules were validated by luciferase reporting assay. Logistic regression analysis, correlation analysis, enrichment analysis, promoter region analysis, methylation analysis, and immune infiltration analysis were performed to further investigate the molecular mechanisms and clinical transformation value. RESULTS: The ceRNA regulatory network featuring a tumor invasion phenotype consisting of 3 long noncoding RNAs, 3 microRNAs, and 93 mRNAs was constructed using transcriptional data from the TCGA database. Systemic analysis and experimentally validation identified a ceRNA network (PVT1/miR-1258/DUSP13 axis) characterized by lipid regulatory potential, immune properties, and abnormal methylation states in patients with HCC and MVI. Meanwhile, 28 transcriptional factors were identified as potential promotors of PVT1 with 3 transcriptional factors MXD3, ZNF580, and KDM1A promising as therapeutic targets in patients with HCC and MVI. Furthermore, miR-1258 was an independent predictor for MVI in patients with HCC. CONCLUSION: The PVT1/DUSP13 axis is significantly associated with MVI progression in HCC patients. This study provides new insight into mechanisms related to lipids, immune phenotypes, and abnormal epigenetics in oncology research.

The prognostic value and molecular properties of tertiary lymphoid structures in oesophageal squamous cell carcinoma.

BACKGROUND: Tertiary lymphoid structures (TLSs) play key roles in tumour adaptive immunity. However, the prognostic value and molecular properties of TLSs in oesophageal squamous cell carcinoma (ESCC) patients have not been studied. METHODS: The prognostic values of the presence and maturation status of tumour-associated TLSs were determined in 394 and 256 ESCC patients from Sun Yat-sen University Cancer Center (Centre A) and the Cancer Hospital of Shantou University Medical College (Centre B), respectively. A deep-learning (DL) TLS classifier was established with haematoxylin and eosin (H&E)-stained slides using an inception-resnet-v2 neural network. Digital spatial profiling was performed to determine the cellular and molecular properties of TLSs in ESCC tissues. RESULTS: TLSs were observed in 73.1% of ESCCs from Centre A via pathological examination of H&E-stained primary tumour slides, among which 42.9% were TLS-mature and 30.2% were TLS-immature tumours. The established DL TLS classifier yielded favourable sensitivities and specificities for patient TLS identification and maturation evaluation, with which 55.1%, 39.5% and 5.5% of ESCCs from Centre B were identified as TLS-mature, TLS-immature and TLS-negative tumours. Multivariate analyses proved that the presence of mature TLSs was an independent prognostic factor in both the Centre A and Centre B cohorts (p < .05). Increased proportions of proliferative B, plasma and CD4+ T helper (Th) cells and increased B memory and Th17 signatures were observed in mature TLSs compared to immature ones. Intratumoural CD8+ T infiltration was increased in TLS-mature ESCC tissues compared to mature TLS-absent tissues. The combination of mature TLS presence and high CD8+ T infiltration was associated with the best survival in ESCC patients. CONCLUSIONS: Mature TLSs improve the prognosis of ESCC patients who underwent complete resection. The use of the DL TLS classifier would facilitate precise and efficient evaluation of TLS maturation status and offer a novel probability of ESCC treatment individualization.