Health technology assessment in traditional and complementary medicine: a scoping review of international activity and examples of acupuncture.

BACKGROUND: Traditional therapies are crucial in maintaining and improving human well-being. China's healthcare policymakers are attempting to use health technology assessment (HTA) as a decision-making supportive tool. The value assessment framework for Chinese patent medicine (CPM) has been developed and is being adopted and validated widely by research institutions. Subsequently, the healthcare decision-makers particularly hanker for the value framework of traditional non-pharmacological therapies. METHODS: To construct a practical value framework for traditional non-pharmacological therapies, a scoping review methodology was adopted to identify the evaluation domains and obstacles. A search, screening, and analysis process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Evidence was retrieved from scientific databases and HTA agencies' websites. RESULTS: The search strategy identified 5 guidelines records and 17 acupuncture HTA reports. By synthesizing the valuable reports of CPM and acupuncture evaluation in representative countries, this study found that Mainland China was promoting the comprehensive value assessment of CPM, whereas the United Kingdom, Singapore, Canada, the United States, and Malaysia had carried out the HTA evaluation of acupuncture for various conditions among which chronic pain was the most common. UK and Singapore applied the HTA results to support acupuncture reimbursement decisions. Three domains, including safety, effectiveness, and economy, were commonly adopted. The identified biggest challenge of evaluating traditional non-pharmacological therapies is the scarce high-quality clinical evidence. CONCLUSIONS: This study identified value domains and issues of traditional therapies, and pointed out future research implications, to promote the development value framework of traditional therapies.

Evolution and distribution of antibiotic resistance genes in submerged macrophytes and biofilm systems: From seasonal monitoring to mesocosm experiments.

The aquatic ecosystem has been extensively investigated as a hotspot for the spread of antibiotic resistance genes (ARGs); yet, the evolution and distribution of ARGs profiles in submerged macrophytes biofilms and surrounding water remained unclear. In this study, the dynamic distribution and seasonal variations of microbial communities and ARGs profiles were investigated, alongside their assembly processes and mutual interactions. Bacitracin and multidrug resistance genes were predominant, constituting more than 60% of the total ARGs abundance. The deterministic processes (<65%), influenced by the physicochemical properties of the river environment, governed the assembly and composition of ARGs profiles, exhibiting significant seasonal variation. The peak diversity (21 types) and abundance (0.316 copy ratios) of ARGs were detected during the summer. Proteobacteria and Actinobacteria were the dominant bacterial phyla, accounting for 38.41-85.50% and 4.03-27.09% of the microbial community, respectively. Furthermore, Proteobacteria, especially genera such as Acinetobacter, Burkholderia, and Pseudomonas, with various resistance sequences, were the primary carriers of multiple ARGs. Notably, the genetic exchanges between biofilms and surrounding water facilitated the further propagation of high-risk ARGs, posing greater ecological risks. Redundancy analysis indicated that the total nitrogen and temperature in water determined the fate of pathogenic-resistant species. These findings provided theoretical support for the mitigation of ARGs contamination in aquatic environments.

A modified lung ultrasound score to evaluate short-term clinical outcomes of bronchopulmonary dysplasia.

BACKGROUND: Lung ultrasound (LUS) is a useful tool for assessing the severity of lung disease, without radiation exposure. However, there is little data on the practicality of LUS in assessing the severity of bronchopulmonary dysplasia (BPD) and evaluating short-term clinical outcomes. We adapted a LUS score to evaluate BPD severity and assess the reliability of mLUS score correlated with short-term clinical outcomes. METHODS: Prospective diagnostic accuracy study was designed to enroll preterm infants with gestational age < 34 weeks. Lung ultrasonography was performed at 36 weeks postmenstrual age. The diagnostic and predictive values of new modified lung ultrasound (mLUS) scores based on eight standard sections were compared with classic lung ultrasound (cLUS) scores. RESULTS: A total of 128 infants were enrolled in this cohort, including 30 without BPD; 31 with mild BPD; 23 with moderate BPD and 44 with severe BPD. The mLUS score was significantly correlated with the short-term clinical outcomes, superior to cLUS score. The mLUS score well correlated with moderate and severe BPD (AUC = 0.813, 95% CI 0.739-0.888) and severe BPD (AUC = 0.801, 95% CI 0.728-0.875), which were superior to cLUS score. The ROC analysis of mLUS score to evaluate the other short-term outcomes also showed significant superiority to cLUS score. The optimal cutoff points for mLUS score were 14 for moderate and severe BPD and 16 for severe BPD. CONCLUSIONS: The mLUS score correlates significantly with short-term clinical outcomes and well evaluates these outcomes in preterm infants.

Peri-tumoral infiltrate associates with postoperative prognosis of patients with OSCC: Stronger association in HPV negative patients.

PURPOSE: The current data on the relationship between local inflammatory infiltration and prognosis in oral squamous cell carcinoma (OSCC) are limited and controversial, especially in different HPV status. In this study, we analyzed the relationship between peri-tumoral inflammatory infiltrate (PTI) and HPV status and prognosis of patients with OSCC after surgery. METHODS: A retrospective cohort of 99 primary OSCC patients who underwent surgery was constructed. P16 immunohistochemistry was used to determine HPV status. PTI was determined by hematoxylin-eosin staining and quantified into four levels: none (Score 0), weak (Score 1), moderate (Score 2) and strong (Score 3). The associations of PTI with clinico-pathological characteristics, HPV status and survival were examined. RESULTS: Most OSCC patients had weak to moderate PTI. PTI was significantly associated with lymph node metastasis (P = 0.041), and patients with moderate PTI had significantly better OS (P = 0.009) than those with no PTI. In HPV negative OSCC, patients with moderate PTI also had significantly better OS (P = 0.019) than those with no PTI. However, PTI was not significantly associated with survival in HPV positive OSCC. CONCLUSIONS: In HPV negative OSCC, moderate PTI may suggest a better postoperative prognosis than no PTI.

Coupled effects of redox-active substances and microbial communities on reactive oxygen species in rhizosphere sediments of submerged macrophytes.

Reactive oxygen species (ROS) play crucial roles in element cycling and pollutant dynamics, but their variations and mechanisms in the rhizosphere of submerged macrophytes are poorly investigated. This study investigated the light-dark cycle fluctuations and periodic variations in ROS, redox-active substances, and microbial communities in the rhizosphere of Vallisneria natans. The results showed sustained production and significant diurnal fluctuations in the O2•- and •OH from 27.6 ± 3.7 to 61.7 ± 3.0 µmol/kg FW and 131.0 ± 6.8 to 195.4 ± 8.7 µmol/kg FW, respectively, which simultaneously fluctuated with the redox-active substances. The ROS contents in the rhizosphere were higher than those observed in non-rhizosphere sediments over the V. natans growth period, exhibiting increasing-decreasing trends. According to the redundancy analysis results, water-soluble phenols, fungi, and bacteria were the main factors influencing ROS production in the rhizosphere, showing contribution rates of 74.0, 17.3, and 4.4 %, respectively. The results of partial least squares path modeling highlighted the coupled effects of redox-active substances and microbial metabolism. Our findings also demonstrated the degradation effect of ROS in rhizosphere sediments of submerged macrophytes. This study provides experimental evidence of ROS-related rhizosphere effects and further insights into submerged macrophytes-based ecological restoration.

The coupling effect promotes superoxide radical production in the microalgal-fungal symbiosis systems: Production, mechanisms and implication for Hg(II) reduction.

Redox transformation of mercury (Hg) is critical for Hg exchange at the air-water interface. However, the superoxide radicals (O2•─) contribution of microalgal-fungal symbiotic systems in lake water to Hg(II) reduction is mainly unknown. Here, we studied the enhanced potential for O2•─ production by the coupling effect between microalgae and fungi. The relationships between microenvironment, microorganisms, and O2•─ production were also investigated. Furthermore, the implication of O2•─ for Hg(II) reduction was explored. The results showed that the coupling effect of microalgae and fungi enhanced O2•─ generation in the symbiotic systems, and the O2•─ generation peaked on day 4 in the lake water at 160.51 ± 13.06-173.28 ± 18.21 µmol/kg FW (fresh weight). In addition, O2•- exhibited circadian fluctuations that correlated with changes in dissolved oxygen content and redox potential on the inter-spherical interface of microalgal-fungal consortia. Partial least squares path modeling (PLS-PM) indicates that O2•─ formation was primarily associated with microenvironmental factors and microbial metabolic processes. The experimental results suggest that O2•─ in the microalgal-fungal systems could mediate Hg(II) reduction, promoting Hg conversion and cycling. The findings highlight the importance of microalgae and fungal symbiotic systems in Hg transformation in aquatic environments.

Influence of anionic species on the low temperature pyrolysis performance of heated tobacco sheets catalyzed by sodium salts.

Development of low temperature catalytic pyrolysis technology for heated tobacco sheets is expected to increase the aroma of heated tobacco products and improve their overall smoking quality. In this study, the low temperature pyrolysis performances of heated tobacco sheets catalyzed by various anionic sodium salts were investigated using TG-DTG, Py-GC-MS technology and smoke routine chemical composition analysis. The results showed that the total weight loss between 100°C and 300°C increased by 7.8%-13.15% after adding various anionic sodium salts, among which, sodium acetate and sodium tartrate showed a relatively higher weight loss. The relative content of free hydroxyacetone, furfuryl alcohol, butyrolactone and megastigmatrienone in the pyrolysis gas increased, while the relative content of free nicotine decreased. With the change of anionic species, the catalytic decomposition ability of cellulose, lignin, and other substances may change, resulting in the distribution alteration of compounds in the pyrolysis gas. After adding sodium acetate and sodium citrate, the release of total particulate matter (TPM), glycerol, and nicotine in flue gas increased. Overall, the addition of sodium acetate and sodium citrate showed a higher low temperature pyrolysis performance of heated tobacco sheets. The research results in this paper provide data support for changing the low temperature catalytic pyrolysis performance of heated tobacco sheets by adjusting the type of anions in sodium salts.

[In vitro metabolism of fenbendazole prodrug].

Synthesized fenbendazole prodrug N-methoxycarbonyl-N'-(2-nitro-4-phenylthiophenyl) thiourea (MPT) was analyzed in vitro in artificial gastric juice, intestinal juice and mouse liver homogenate model by using HPLC method, and metabolic curve was then generated. MPT was tested against Echinococcus granulosus protoscolices in vitro. The result showed that MPT could be metabolized in the three biological media, and to the active compound fenbendazole in liver homogenate, with a metabolic rate of 7.92%. Besides, the prodrug showed a weak activity against E. granulosus protoscolices with a mortality of 45.9%.

Hexavalent chromium (Cr(VI)) removal by ball-milled iron-sulfur @biochar based on P-recovery: Enhancement effect and synergy mechanism.

After the biochar recovery of phosphorus (P), its role in eliminating Cr(VI) is uncertain. In this study, the iron-sulfur biochar (Fe/S@BC) was made by grinding Fe0, S0, and biochar with a ball mill. P-loaded iron-sulfur biochar (P-Fe/S@BC) was produced after recovering P from simulated wastewater and then used to remove Cr(VI) contamination in waterbodies. P-Fe/S@BC got a rich pore structure and more reactive sites through P-recovery. The experiments revealed that P-Fe/S@BC had an enhancement effect on Cr(VI) pollution with removal efficiencies of 76.9 % ∼ 99.4 %, all greater than Fe/S@BC (58.2 %). In particular, 25P-Fe/S@BC (with 6.55 mg P/g) had the most significant advantage. The combination of physical adsorption, electrostatic attraction, and precipitation contributed to Cr(VI) removal. This is an efficient strategy for reusing Fe/S@BC followed by P-recovery, intending to improve the Cr(VI) removal effect and achieve the sustainable use of P resources and wastes.

Establishment of induced pluripotent stem cell line SDPHi003-A from a healthy male donor.

Peripheral blood mononuclear cells (PBMCs) were derived from a 67-year-old Chinese male. We used non-integrating episomal vectors containing OCT4, SOX2, KLF4 and c-MYC to reprogram PBMCs into induced pluripotent stem cell (iPSCs). This iPSC line, SDPHi003-A, have a normal karyotype, expressed pluripotent markers and have the potential for trilineage differentiation. This iPSC line can be used as a control for disease modeling studies and contribute to the research exploring disease pathogenesis.

Phosphorus recovery and reuse in water bodies with simple ball-milled Ca-loaded biochar.

The demand to control eutrophication in water bodies and the risk of phosphorus scarcity have prompted the search for treatment technologies for phosphorus recovery. In this study, ball-milled Ca-loaded biochar (BMCa@BC) composites were prepared with CaO and corn stover biochar as raw materials by a new ball-milling method to recover phosphorus from water bodies. Experimental results demonstrated that BMCa@BC could efficiently adsorb phosphorus in water bodies with an excellent sorption capacity of 329 mg P/g. Hydrogen bonding, electrostatic attraction, complexation, and surface precipitation were involved in adsorption process. In addition, phosphorus recovered by BMCa@BC had high bioavailability (86.7 % of TP) and low loss (3.3 % of TP) and was a potential slow-release fertilizer. P-laden BMCa@BC significantly enhanced seed germination and growth in planting experiments, proving that it could be used as a substitute for P-based fertilizer. After five cycles of regeneration, BMCa@BC still showed good adsorption recovery and the P-enriched desorption solution could be recovered as Ca-P products with the fertilizer value. Overall, BMCa@BC has good cost-effectiveness and practical applicability in phosphorus recovery. This provides a new way to recover and reuse phosphorus effectively.

Generation of an induced pluripotent stem cell line SDPHi002-A from a patient with lung cancer.

Here, an induced pluripotent stem cell (iPSC) line from a patient with lung neuroendocrine carcinoma was generated. The iPSCs were developed using nonintegrating episomal vectors carrying OCT4, SOX2, KLF4, BCL-XL and c-MYC. The established iPSCs (SDPHi002-A) had normal karyotype, excellent differentiation potential in vitro, showing pluripotent stem cell morphology and high expression of pluripotent markers.

Co-inhibition of adenosine 2b receptor and programmed death-ligand 1 promotes the recruitment and cytotoxicity of natural killer cells in oral squamous cell carcinoma.

Adenosine promotes anti-tumor immune responses by modulating the functions of T-cells and natural killer (NK) cells in the tumor microenvironment; however, the role of adenosine receptors in the progression of oral squamous cell carcinoma (OSCC) and its effects on immune checkpoint therapy remain unclear. In this study, we obtained the tumor tissues from 80 OSCC patients admitted at the Shandong University Qilu Hospital between February 2014 and December 2016. Thereafter, we detected the expression of adenosine 2b receptor (A2BR) and programmed death-ligand 1 (PD-L1) using immunohistochemical staining and analyzed the association between their expression in different regions of the tumor tissues, such as tumor nest, border, and paracancer stroma. To determine the role of A2BR in PD-L1 expression, CAL-27 (an OSCC cell line) was treated with BAY60-6583 (an A2BR agonist), and PD-L1 expression was determined using western blot and flow cytometry. Furthermore, CAL-27 was treated with a nuclear transcription factor-kappa B (NF-κ B) inhibitor, PDTC, to determine whether A2BR regulates PD-L1 expression via the NF-κ B signaling pathway. Additionally, a transwell assay was performed to verify the effect of A2BR and PD-L1 on NK cell recruitment. The results of our study demonstrated that A2BR and PD-L1 are co-expressed in OSCC. Moreover, treatment with BAY60-6583 induced PD-L1 expression in the CAL-27 cells, which was partially reduced in cells pretreated with PDTC, suggesting that A2BR agonists induce PD-L1 expression via the induction of the NF-κ B signaling pathway. Furthermore, high A2BR expression in OSCC was associated with lower infiltration of NK cells. Additionally, our results demonstrated that treatment with MRS-1706 (an A2BR inverse agonist) and/or CD274 (a PD-L1-neutralizing antibody) promoted NK cell recruitment and cytotoxicity against OSCC cells. Altogether, our findings highlight the synergistic effect of co-inhibition of A2BR and PD-L1 in the treatment of OSCC via the modulation of NK cell recruitment and cytotoxicity.

Enhanced bioavailability and cysticidal effect of three mebendazole-oil preparations in mice infected with secondary cysts of Echinococcus granulosus.

The aim of the present study is to explore the possibility to increase the efficacy of mebendazole (MBZ) against secondary cysts of Echinococcus granulosus harbored in mice by augmenting the solubility and bioavailability of the drug. Firstly, the saturated solubility of MBZ in nine kinds of oil was determined by high performance liquid chromatography (HPLC), and MBZ was found exhibiting the highest, secondary, and lowest solubility in oleic acid (OA), glycerol trioleate (GT), and soybean oil (SB), respectively. Secondly, MBZ-OA suspension, MBZ-GT suspension, MBZ-SB suspension, and MBZ suspended in 1 % tragacanth (MBZ-1 % tragacanth) were selected for further studies on pharmacokinetics and experimental therapy in mice. Four groups of mice were treated orally with one of aforementioned four MBZ preparations at a single dose of 25 mg/kg, and concentrations of MBZ in plasma obtained from each mouse at various intervals within 24 h postadministration were determined by HPLC. The major pharmacokinetic parameters calculated by MBZ plasma concentration-time curve demonstrated that the peak concentration of the drug (C (max) ) values obtained from three MBZ-oil preparation groups was 1.6-2.8 times higher than that of MBZ-1 % tragacanth group. The same was true that the area under the drug concentration-time curve (AUC(0-∞)) values of 19.8 (2.5)-28.2 (2.5) µg/ml × h revealed in the three MBZ-oil preparation groups was significantly higher than that of 11.6 (2.0) µg/ml × h in MBZ-1 % tragacanth group, and the bioavailability of the three MBZ-oil preparation groups was 71-143 % higher than that of MBZ-1 % tragacanth group. In mice infected with secondary cysts of E. granulosus for 8 months treated orally with MBZ-1 % tragacanth at a daily dose of 25 mg/kg for 14 consecutive days, the mean cyst weight was lower than that of untreated control, but the difference was not statistically significant with cyst weight reduction of 48 %. When the infected mice received three MBZ-oil preparations at the same oral dose schedule as aforementioned, the mean cyst weights were significantly lower than those in MBZ-1 % tragacanth group or control group with cyst weight reductions of 71.2-84.7 %. The results indicate that the solubility of MBZ in oils may increase to various degrees according to the kinds of oil used. Meanwhile, three MBZ-oil (OA, GT, and SB) preparations administered orally to mice not only improve the bioavailability of MBZ relative to that of MBZ suspended in 1 % tragacanth, but their effects against hydatid cysts also significantly enhance.

[Progress on hydrolases-targeting antiparasitic prodrugs].

Prodrug strategies have been used for drug optimization to overcome the drawbacks in pharmaceutics, pharmacokinetics and pharmacodynamics. Most enzymes involved in prodrug biotransformation are hydrolases, in which esterase and amidase have been widely researched. This review summarizes the recent progress in antiparasitic prodrugs based on both targets.

Biocontrol yeast T-2 improves the postharvest disease resistance of grape by stimulation of the antioxidant system.

Table grapes are susceptible to external pathogens during postharvest storage. The resulting continuous oxidative stress causes damage and aging, thereby reducing the defense against disease. In this study, the effect of biocontrol yeast T-2 on the storage performance of grapes was evaluated. After T-2 treatment, the grapefruits rot rate and lesion diameter caused by Botrytis cinerea (B. cinerea) were significantly decreased at 2-5 days after inoculation (DAI). Additionally, the browning rate and shedding rate of grapefruit during storage were significantly reduced at 2-5 DAI, and the weight loss rate was significantly reduced at 3-5 DAI. The decreased malondialdehyde (MDA) content in grapefruits at 1-5 DAI with T-2 indicated a reduction in oxidative damage. Furthermore, the activities of antioxidant enzymes such as peroxidase (POD), catalase (CAT), phenylalanin ammonia-lyase (PAL) were significantly increased during most storage time after being treated with T-2. Moreover, the contents of total phenolics and flavonoids and the expression levels of key enzyme genes in metabolic pathways were increased after T-2 treatment during most postharvest storage time, providing evidence that T-2 changed the biological process of phenolic flavonoid metabolism. The increase in enzymatic and nonenzymatic antioxidants after treatment with T-2 reflected the strengthening of the antioxidant system, hence postponing fruit senescence and promoting storage performance under the stress of B. cinerea.

Ball milling sulfur-doped nano zero-valent iron @biochar composite for the efficient removal of phosphorus from water: Performance and mechanisms.

This study successfully prepared a novel sulfur-doped nano zero-valent iron @biochar (BM-SnZVI@BC) by modifying corn stover biochar with Fe0 and S0 using a mechanical ball milling method for effective phosphorus (P) adsorption in the waterbody. Batch experiments revealed that BM-SnZVI@BC (BC/S0/Fe0 = 3:1:1) reached a Qmax of 25.00 mg P/g and followed PFO and Langmuir models. This work had shown that electrostatic attraction, surface chemical precipitation, hydrogen bonding, and ligand effects all contributed to P removal. Since the FeS layer mitigated the oxidation-induced surface passivation of nZVI, sulfidation significantly extended the lifetime of BM-SnZVI@BC, removing 84.4% of P even after 60 d aging in air. The regeneration experiments of composites showed that re-ball milling destroyed the surface iron oxide layer to improve the properties of the recovered material. This is an essential step in the design of P-removal agents to implement anti-aging and commercialization of adsorbents for engineering applications.

Whole transcriptome analysis of trophoblasts under hypoxia.

INTRODUCTION: A physiological hypoxia environment exists at maternal-fetal interface during early pregnancy. In addition, there is a pathological hypoxic microenvironment in patients with preeclampsia. Therefore, investigating the hypoxic adaptation and the effects of hypoxia on trophoblasts transcriptome is helpful to better understand the function and regulatory mechanism of trophoblasts at the maternal-fetal interface. METHODS: Trophoblast cell line HTR-8/SVneo was cultured under normoxia and hypoxia for 24 h, the full transcriptome was analyzed via RNA-Seq. GO and KEGG enrichment were performed on differentially expressed mRNA, adjacent genes of differentially expressed lncRNA, host genes of differentially expressed circRNA and target genes of differential expressed miRNA. RESULTS: The results showed that hypoxia differentially regulated 373 mRNAs, 334 lncRNAs, 71 circRNAs and 33 miRNAs. GO and KEGG enrichment showed that hypoxia negatively regulated TLR3 and PI3K-Akt signaling pathways. Consistently, we found hypoxia significantly inhibited TLR3 agonist-induced cytokines expression and the phosphorylation of Akt and mTOR. DISCUSSION: Our study obtained the full transcriptome data and potential regulatory network of trophoblasts under hypoxia, providing supportive data for revealing the function of trophoblasts.

Identification and validation of a prognostic signature of autophagy, apoptosis and pyroptosis-related genes for head and neck squamous cell carcinoma: to imply therapeutic choices of HPV negative patients.

Introduction: An effective tool is needed to predict the prognosis of head and neck squamous cell carcinoma (HNSCC). Human papillomavirus (HPV) positive HNSCC patients generally have a favorable survival and a promising responsiveness to radiotherapy, chemoradiotherapy and checkpoint blockades. However, HPV negative patients, the majority of HNSCC patients, have been largely overlooked. Cell death has been involved in the therapeutic resistance of cancers. To this end, we aimed to identify the association of autophagy, apoptosis and pyroptosis-related genes with the prognosis of HNSCC, and construct a prognostic signature to predict the prognosis for HNSCC, especially for HPV negative HNSCC. Methods: Autophagy and apoptosis-related genes were obtained from Gene Set Enrichment Analysis (GSEA) website, and pyroptosis-related genes were obtained from GSEA and Gene Ontology (GO) database. We established the cell death index (CDI) based on RNA sequencing (RNA-seq) data and clinicopathological information from The Cancer Genome Atlas (TCGA) dataset. The prognostic value of CDI was verified by Kaplan-Meier, receiver operating characteristic (ROC) and univariate and multivariate Cox regression analyses in TCGA dataset, and validated with the datasets from Gene Expression Omnibus (GEO) and Qilu Hospital of Shandong University. We further assessed the immune microenvironment of patients with high and low CDI scores. Moreover, the expression of the signature genes in HNSCC cell lines were explored. Results: We found that CDI was an independent prognostic indicator for overall survival (hazard ratio 3.80, 95% confidential interval: 2.70-5.40, P < 0.001). Furthermore, HNSCC patients with high CDI scores obtained increased overall survival post radiation indicating benefits from radiotherapy of this subgroup. On the other hand, HPV negative HNSCC patients with low CDI exhibited increased checkpoint gene expressions, an inflamed tumor microenvironment and an enriched immune response-related functions, suggesting the potential benefits from checkpoint immunotherapies of this subgroup. Moreover, we validated the baseline and induced expressions of above 16 genes in two HPV negative HNSCC cell lines, CAL27 and SCC-15. Discussion: We established a prognostic signature and emphasized its implements in the therapeutic choices of HPV negative HNSCC patients, the majority and the poor outcome population of HNSCC.

Dysbiotic tumor microbiota associates with head and neck squamous cell carcinoma outcomes.

BACKGROUND: The need for an effective tool to predict prognosis of head and neck squamous cell carcinoma (HNSCC) patients is critical and unmet. Microbiota has recently been found involved in tumor progression and response to immunotherapy. However, the association of microbiota with the prognosis of HNSCC patients remains obscure. This study aims to investigate the association between tumor microbiota and outcomes of HNSCC patients. METHODS: A retrospective study including 129 primary tumors of HNSCC was conducted. Using 16S rRNA sequencing, the profile and the composition of tumor microbiota were measured and their associations with overall survival (OS) and disease free survival (DFS) were examined. RESULTS: We observed a reduced richness and enriched abundances of genera Schlegelella and Methyloversatilis in tumor microbiota of HNSCC patients with poor prognosis. However, a richer tumor microbiota with greater abundances of genera Bacillus, and Lactobacillus and Sphingomonas was characterized in the patients with favorable prognosis.The ratio of these differentially abundant taxa, microbial dysbiosis index (MDI), was significantly associated with OS (hazard ratio [HR], 4.67, 95% confidence interval [CI], 2.51 to 8.69,P < 0.001) and DFS (HR, 2.89; 95% CI, 1.74 to 4.80, P < 0.001) independently of age, tumor size, lymph node metastasis, differentiation and p16 status. The risk score of multivariate Cox regression exhibited an excellent performance for estimating three-year OS (AUC of 0.826). We also found a richer tumor microbiota was correlated with moderate peritumoral inflammatory infiltration. CONCLUSION: These results indicate that tumor microbiota associates with outcomes of HNSCC patients.