Comparison of learning curves and related postoperative indicators between endoscopic and robotic thyroidectomy: a systematic review and meta-analysis.

BACKGROUD: Endoscopic thyroidectomy (ET) and robotic thyroidectomy (RT) yield similar perioperative outcomes. This study investigated how the learning curve (LC) affects perioperative outcomes between ET and RT, identifying factors that influence the LC. MATERIALS AND METHODS: Two researchers individually searched PubMed, EMBASE, Web of Science, and Cochrane Library for relevant studies published until February 2024. The Newcastle-Ottawa Scale assessed study quality. Random effects model was used to compute the odds ratio and weighted mean difference (WMD). Poisson regression comparison of the number of surgeries (NLC) was required for ET and RT to reach the stable stage of the LC. Heterogeneity was measured using Cochran's Q. Publication bias was tested using funnel plots, and sensitivity analysis assessed findings robustness. Subgroup analysis was done by operation type and patient characteristics. RESULTS: This meta-analysis involved 33 studies. The drainage volume of ET was higher than that of RT (WMD=-17.56 [30.22, -4.49]). After reaching the NLC, the operation time of ET and RT was shortened (ET: WMD=28.15[18.04, 38.26]; RT: WMD=38.53[29.20, 47.86]). Other perioperative outcomes also improved to varying degrees. Notably, RT showed more refined central lymph node resection(5.67 vs. 4.71), less intraoperative bleeding (16.56 mL vs. 42.30 mL), and incidence of transient recurrent laryngeal nerve injury(24.59 vs. 26.77). The NLC of RT was smaller than that of ET(Incidence-rate ratios [IRR]=0.64[0.57, 0.72]). CUSUM analysis (ET: IRR=0.84[0.72, 0.99]; RT: IRR=0.55[0.44, 0.69]) or a smaller number of respondents (ET: IRR=0.26[0.15, 0.46]; RT: IRR=0.51[0.41, 0.63]) was associated with smaller NLC. In RT, transoral approach (IRR=2.73[1.96, 4.50]; IRR=2.48[1.61, 3.84]) and retroauricular approach (RAA) (IRR=2.13[1.26, 3.60]; IRR=1.78[1.04, 3.05]) had smaller NLC compared to bilateral axillo-breast and transaxillary approach (TAA). In ET, the NLC of RAA was smaller than that of TAA (IRR=1.61[1.04, 2.51]), breast approach(IRR=1.67[1.06, 2.64]), and subclavian approach(IRR=1.80[1.03, 3.14]). CONCLUSIONS: Rich surgical experience can improve surgical results of ET and RT. After reaching the NLC, the perioperative outcomes of RT are better than those of ET. Study subjects, surgical approaches, and analysis methods can affect NLC.

Endoscopy-Assisted Thyroglossal Duct Cyst Resection: A Scoping Review.

OBJECTIVES: Thyroglossal duct cysts (TGDCs) are a common congenital mass in the cervical region. As the traditional surgical approach for TGDC removal, the Sistrunk procedure, often leaves a visible neck scar, the demand for improved cosmetic outcomes has increased. Emerging endoscopy-assisted approaches offer promise for addressing cosmetic concerns. We conducted a scoping review to evaluate the feasibility and safety of endoscopy-assisted TGDC surgery. DATA SOURCES: PubMed, Embase, and Cochrane databases. METHODS: Electronic databases were searched from their respective inception dates to January 2023. Data on surgical approach, patient demographics, surgical procedure, and postoperative outcomes were extracted and analyzed. The quality of the studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. RESULTS: The literature search yielded nine articles published between 2011 and 2022. Overall, 85 patients in these studies successfully underwent endoscopy-assisted TGDC surgery using various approaches, including areolar, axillo-breast, transoral-vestibular, and transoral-sublingual. The operative time varied across the studies, ranging from 50 to 480 min. TGDC sizes ranged from 1 to 3 cm in diameter. Complications, including infection, skin bruising, and dysarthria, were reported in seven patients (8%). No cases of conversion to open surgery or postoperative recurrences were reported. CONCLUSION: Endoscopy-assisted surgery is a potential alternative for patients seeking TGDC resection with satisfactory aesthetic results while ensuring safety. However, existing evidence is insufficient to support the superior effectiveness of endoscopy-assisted TGDC surgery over the traditional Sistrunk procedure. Laryngoscope, 134:3038-3043, 2024.

A decision tree model to help treatment decision-making for severe spontaneous intracerebral hemorrhage.

BACKGROUND: Surgical treatment demonstrated a reduction in mortality among patients suffering from severe spontaneous intracerebral hemorrhage (SSICH). However, which SSICH patients could benefit from surgical treatment was unclear. This study aimed to establish and validate a decision tree (DT) model to help determine which SSICH patients could benefit from surgical treatment. MATERIALS AND METHODS: SSICH patients from a prospective, multicenter cohort study were analyzed retrospectively. The primary outcome was the incidence of neurological poor outcome (modified Rankin scale as 4-6) on the 180th day posthemorrhage. Then, surgically-treated SSICH patients were set as the derivation cohort (from a referring hospital) and validation cohort (from multiple hospitals). A DT model to evaluate the risk of 180-day poor outcome was developed within the derivation cohort and validated within the validation cohort. The performance of clinicians in identifying patients with poor outcome before and after the help of the DT model was compared using the area under curve (AUC). RESULTS: One thousand two hundred sixty SSICH patients were included in this study (middle age as 56, and 984 male patients). Surgically-treated patients had a lower incidence of 180-day poor outcome compared to conservatively-treated patients (147/794 vs. 128/466, P <0.001). Based on 794 surgically-treated patients, multivariate logistic analysis revealed the ischemic cerebro-cardiovascular disease history, renal dysfunction, dual antiplatelet therapy, hematoma volume, and Glasgow coma score at admission as poor outcome factors. The DT model, incorporating these above factors, was highly predictive of 180-day poor outcome within the derivation cohort (AUC, 0.94) and validation cohort (AUC, 0.92). Within 794 surgically-treated patients, the DT improved junior clinicians' performance to identify patients at risk for poor outcomes (AUC from 0.81 to 0.89, P <0.001). CONCLUSIONS: This study provided a DT model for predicting the poor outcome of SSICH patients postsurgically, which may serve as a useful tool assisting clinicians in treatment decision-making for SSICH.

Cell-free multi-omics analysis reveals potential biomarkers in gastrointestinal cancer patients' blood.

During cancer progression, tumorigenic and immune signals are spread through circulating molecules, such as cell-free DNA (cfDNA) and cell-free RNA (cfRNA) in the blood. So far, they have not been comprehensively investigated in gastrointestinal cancers. Here, we profile 4 categories of cell-free omics data from patients with colorectal cancer and patients with stomach adenocarcinoma and then assay 15 types of genomic, epigenomic, and transcriptomic variations. We find that multi-omics data are more appropriate for detection of cancer genes compared with single-omics data. In particular, cfRNAs are more sensitive and informative than cfDNAs in terms of detection rate, enriched functional pathways, etc. Moreover, we identify several peripheral immune signatures that are suppressed in patients with cancer. Specifically, we establish a γδ-T cell score and a cancer-associated-fibroblast (CAF) score, providing insights into clinical statuses like cancer stage and survival. Overall, we reveal a cell-free multi-molecular landscape that is useful for blood monitoring in personalized cancer treatment.

The Alleviating Effects and Mechanisms of Betaine on Dextran Sulfate Sodium-Induced Colitis in Mice.

SCOPE: Ulcerative colitis (UC) is an intestinal disease that is becoming increasingly prevalent and is often overlooked in early stages, and its pathogenesis is often closely related to inflammatory processes. Betaine is a natural product with anti-inflammatory effects that exists in a wide range of plants and animals. METHODS AND RESULTS: In this study, the protective effects of betaine are investigated on intestinal barrier function in a mouse model, a dextran sulfate sodium-induced ulcerative colitis and its mechanism of action in the inflammatory context. FITC-dextran 4000 Da (FD-4) flux, disease activity index, histopathological scores, and inflammatory factor levels in sera are determined across different groups. In addition, Caco-2 cell monolayer barrier function is evaluated by transepithelial resistance and FD-4 flux. The expression levels and distribution of tight junction proteins are determined using Western blot and immunofluorescence, respectively. Activation of the NF-κBp65/MLCK/p-MLC signaling pathway is detected by Western blot. Chromatin immunoprecipitation is performed to examine the binding of NF-κB to the MLCK gene promoter. The results indicated that betaine inhibits NF-κB-mediated activation of the MLCK/p-MLC signaling pathway to protect the intestinal barrier function of mice with UC. CONCLUSION: Betaine can be used as a potential candidate drug to improve intestinal barrier dysfunction in patients with UC.

Neoadjuvant Immune Checkpoint Inhibitors for Resectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Resectable hepatocellular carcinoma (HCC) has poor prognosis because of its high recurrence rate. Immunotherapy has been tried for neoadjuvant therapy as it has shown excellent performance in the treatment of advanced HCC. This systematic review and meta-analysis aimed to assess the reported efficacy and safety of neoadjuvant immune checkpoint inhibitors (ICIs) for resectable HCC. Electronic databases, including PubMed (MEDLINE), Embase, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify published and ongoing studies evaluating the efficacy and safety of neoadjuvant ICIs for resectable HCC up to October 2022. The odds ratio (OR) and 95% confidence interval (CI) were calculated. Heterogeneity and subgroup analyses were performed, and data quality was assessed. The study was registered with PROSPERO (registration number: CRD42022371495). A total of 193 patients from 9 studies were included in this meta-analysis. The overall pathological complete response (pCR) rate was 12.9% (95%CI, 6.7-19.1%), and major pathological response (MPR) rate was 27.3% (95%CI, 15.1-39.4%), indicating a favorable association with neoadjuvant ICIs (pCR: OR = 0.17, p < 0.00001; MPR: OR = 0.38, p = 0.001). The pooled OR values for the incidence of grade 3 to 4 treatment-related adverse events and surgical delay rate were 0.26 and 0.05, respectively, which were significantly in favor of neoadjuvant ICIs (p < 0.0001; p < 0.00001, respectively). The subgroup analyses did not demonstrate superiority of one ICI over another ICI or combination therapy. The present study found that neoadjuvant ICIs were well tolerated by patients with resectable HCC and conferred therapeutic benefits in view of histopathological response results.

Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients.

Background: Numerous studies have shown autophagy affects cellular immune responses. This study aims to explore prognosis and immunotherapeutic biomarkers related to autophagy in colon adenocarcinoma (COAD). Methods: Based on R software, we performed the ssGSEA, differential expression analysis, Kaplan-Meier survival analysis, correlation analysis, and enrichment analysis. For wet experiment, we did qRT-PCR, immunohistochemistry and CCK-8 experiments. Results: Using autophagy-related genes (ARGs) and the ssGSEA, COAD patients were divided into low and high autophagy groups. For immune score, stromal score, tumor purity, tumor infiltrating immune cells, co-signaling molecules, tumor mutational burden, microsatellite instability, mismatch repair, immune-related pathways, immune signatures, somatic mutations and subtype analysis, high autophagy group might benefit more from immunotherapy. Among 232 ARGs, IFNG was generally significantly correlated with tumor immunotherapy biomarkers (PD-L1, CD8A and cytotoxic T lymphocytes (CTL)). The disease-free survival of high IFNG group was significantly longer than that of low group. On above-mentioned immune-related research, the high IFNG group reached the same conclusion. The qRT-PCR and IHC analysis confirmed that IFNG was significantly higher expressed in dMMR samples compared to pMMR samples. For chemotherapy, the autophagy and IFNG were significantly negatively related to the chemosensitivity to cisplatin; IFNG inhibitor glucosamine increased cisplatin chemoresistance while IFNG increased cisplatin chemosensitivity; IFNG could reverse glucosamine induced chemoresistance. The functional enrichment analysis of IFNG, PD-L1, CD8A and 20 similar proteins were related to the activation of the immune system. The GSEA and ceRNA network partly described interaction mechanisms of IFNG with PD-L1 and CD8A. Conclusion: Autophagy score and IFNG expression were novel immunotherapy predictive biomarkers, which might play predictive effects through the JAK-STAT signaling pathway. IFNG might be a potential targeted therapy for cisplatin resistant colon cancer. Besides, IFNG was also a prognostic indicator.

Management of Parapharyngeal Space Tumors: Clinical Experience with a Large Sample and Review of the Literature.

Parapharyngeal space (PPS) tumors are rare, and they account for 0.5-1.5% of all head and neck tumors. This study summarized the findings of large-sample clinical studies of PPS tumors and reported the clinical work-up and management of 177 cases of PPS tumors at our center. This retrospective study included patients treated for PPS tumors between 2005 and 2020 at our center. The basic characteristics, symptoms, surgical approach, complications, and recurrence rates were analyzed. A total of 99 male and 78 female patients, with a mean age of 48.3 ± 15.1 years, were enrolled in this study. The most common symptoms were external or intraoral masses (114 patients, 64%). Surgical management leveraging, a cervical approach, was used for 131 cases (74%). The tumors were benign for 92% (160 cases), with pleomorphic adenoma being the most common (88 cases, 50%). Surgical complications were reported for 31 cases (18%); facial and vocal cord paralyses were the most common. Three cases of recurrence were observed during the follow-up. PPS tumors are rare and present with atypical clinical manifestations. The current study, which involved cases in a large single center, demonstrates the importance of surgical interventions for PPS tumors. The use of endoscopic techniques has further expanded the scope of traditional surgical approaches and demonstrated its advantages in selected cases.

Associations Between Physical Activity, Tinnitus, and Tinnitus Severity.

OBJECTIVES: To examine the associations between physical activity and tinnitus development and physical activity and tinnitus severity in a large representative sample of US adults. DESIGN: Data were obtained from 3826 eligible participants (20 to 69 years) in the National Health and Nutrition Examination Survey between 2015 and 2016. Physical activity was assessed using a Global Physical Activity Questionnaire. We used multivariable logistic regression to test the associations of physical activity (without physical activity, with physical activity) and amount of physical activity (min/week, in quartiles) with tinnitus symptoms. Adults with depressive symptoms were excluded, and the models were controlled for relevant sociodemographic, lifestyle, and health-related covariates. A restricted cubic spline was used to explore the dose-response relationship between the amount of physical activity and tinnitus. RESULTS: Overall, 12.8% of the population who engaged in physical activity reported tinnitus, compared with 18.5% of the population who did not ( p = 0.005). Subgroup analysis based on the amount of physical activity showed that participants who performed physical activity (150 to 300, 310 to 540, and 550 to 4800 min/week) had lower risks of tinnitus than those with no physical activity (odds ratio = 0.72, 0.56, and 0.62, respectively), after adjusting for covariates. However, no correlation was observed between physical activity and tinnitus severity in the present study. The dose-response analysis showed a nonlinear relationship (P for nonlinearity = 0.04) between the amount of physical activity and the risk of tinnitus. CONCLUSIONS: Physical activity may be associated with a reduced risk of tinnitus. Further research using a longitudinal design is required to confirm these findings and clarify the direction of causation.

Hydrogen Sulfide Creates a Favorable Immune Microenvironment for Colon Cancer.

Immunotherapy can elicit robust anticancer responses in the clinic. However, a large proportion of patients with colorectal cancer do not benefit from treatment. Although previous studies have shown that hydrogen sulfide (H2S) is involved in colorectal cancer development and immune escape, further insights into the mechanisms and related molecules are needed to identify approaches to reverse the tumor-supportive functions of H2S. Here, we observed significantly increased H2S levels in colorectal cancer tissues. Decreasing H2S levels by using CBS+/- mice or feeding mice a sulfur amino acid-restricted diet (SARD) led to a marked decrease in differentiated CD4+CD25+Foxp3+ Tregs and an increase in the CD8+ T-cell/Treg ratio. Endogenous or exogenous H2S depletion enhanced the efficacy of anti-PD-L1 and anti-CTLA4 treatment. H2S promoted Treg activation through the persulfidation of ENO1 at cysteine 119. Furthermore, H2S inhibited the migration of CD8+ T cells by increasing the expression of AAK-1 via ELK4 persulfidation at cysteine 25. Overall, reducing H2S levels engenders a favorable immune microenvironment in colorectal cancer by decreasing the persulfidation of ENO1 in Tregs and ELK4 in CD8+ T cells. SARD represents a potential dietary approach to promote responses to immunotherapies in colorectal cancer. SIGNIFICANCE: H2S depletion increases the CD8+ T-cell/Treg ratio and enhances the efficacy of anti-PD-L1 and anti-CTLA4 treatment in colon cancer, identifying H2S as an anticancer immunotherapy target.

Different photosynthetic responses of haploid and diploid Emiliania huxleyi (Prymnesiophyceae) to high light and ultraviolet radiation.

Solar radiation varies quantitatively and qualitatively while penetrating through the seawater column and thus is one of the most important environmental factors shaping the vertical distribution pattern of phytoplankton. The haploid and diploid life-cycle phases of coccolithophores might have different vertical distribution preferences. Therefore, the two phases respond differently to high solar photosynthetically active radiation (PAR, 400-700 nm) and ultraviolet radiation (UVR, 280-400 nm). To test this, the haploid and diploid Emiliania huxleyi were exposed to oversaturating irradiance. In the presence of PAR alone, the effective quantum yield was reduced by 10% more due to the higher damage rate of photosystem II in haploid cells than in diploid cells. The addition of UVR resulted in further inhibition of the quantum yield for both haploid and diploid cells in the first 25 min, partly because of the increased damage of photosystem II. Intriguingly, this UVR-induced inhibition of the haploid cells completely recovered half an hour later. This recovery was confirmed by the comparable maximum quantum yields, maximum relative electron transport rates and yields of the haploid cells treated with PAR and PAR + UVR. Our data indicated that photosynthesis of the haploid phase was more sensitive to high visible light than the diploid phase but resistant to UVR-induced inhibition, reflecting the ecological niches to which this species adapts.

Cancer type classification using plasma cell-free RNAs derived from human and microbes.

The utility of cell-free nucleic acids in monitoring cancer has been recognized by both scientists and clinicians. In addition to human transcripts, a fraction of cell-free nucleic acids in human plasma were proven to be derived from microbes and reported to have relevance to cancer. To obtain a better understanding of plasma cell-free RNAs (cfRNAs) in cancer patients, we profiled cfRNAs in ~300 plasma samples of 5 cancer types (colorectal cancer, stomach cancer, liver cancer, lung cancer, and esophageal cancer) and healthy donors (HDs) with RNA-seq. Microbe-derived cfRNAs were consistently detected by different computational methods when potential contaminations were carefully filtered. Clinically relevant signals were identified from human and microbial reads, and enriched Kyoto Encyclopedia of Genes and Genomes pathways of downregulated human genes and higher prevalence torque teno viruses both suggest that a fraction of cancer patients were immunosuppressed. Our data support the diagnostic value of human and microbe-derived plasma cfRNAs for cancer detection, as an area under the ROC curve of approximately 0.9 for distinguishing cancer patients from HDs was achieved. Moreover, human and microbial cfRNAs both have cancer type specificity, and combining two types of features could distinguish tumors of five different primary locations with an average recall of 60.4%. Compared to using human features alone, adding microbial features improved the average recall by approximately 8%. In summary, this work provides evidence for the clinical relevance of human and microbe-derived plasma cfRNAs and their potential utilities in cancer detection as well as the determination of tumor sites.

PD-1 signaling facilitates activation of lymphoid tissue inducer cells by restraining fatty acid oxidation.

Anti-programmed death-1 (PD-1) immunotherapy that aims to restore T cell activity in cancer patients frequently leads to immune-related adverse events such as colitis. However, the underlying mechanism is still elusive. Here, we find that Pdcd1-deficient mice exhibit disrupted gut microbiota and aggravated dextran sulfate sodium (DSS)-induced colitis. In addition to T cells, PD-1 is also substantially expressed in colonic lymphoid tissue inducer (LTi) cells. During DSS-induced colitis, LTi cell activation is accompanied by increased PD-1 expression, whereas PD-1 deficiency results in reduced interleukin-22 (IL-22) production by LTi cells and exacerbated inflammation. Mechanistically, activated LTi cells reprogram their metabolism toward carbohydrate metabolism and fatty acid synthesis, while fatty acid oxidation (FAO) is unchanged. However, PD-1 deficiency leads to significantly elevated FAO in LTi cells, which in turn attenuates their activation and IL-22 production. Consistently, FAO suppression efficiently restores IL-22 production in Pdcd1-/- LTi cells. Thus, our study provides unforeseen mechanistic insight into colitis occurrence during anti-PD-1 immunotherapy through LTi cell metabolic reconfiguration.

Anatomic variations of the anterosuperior pancreaticoduodenal veins encountered during laparoscopic right hemicolectomy: a retrospective single-center analysis.

OBJECTIVE: The vascular anatomic variations of the right colon present a challenge for colorectal surgeons. However, there have been few detailed studies of the variations in the anterosuperior pancreaticoduodenal vein (ASPDV). METHODS: We studied consecutive patients with right colon cancer who underwent laparoscopic right hemicolectomy at Peking University First Hospital (N = 117) between January 2018 and June 2021. RESULTS: The variations in the ASPDV were classified as type I (n = 101, (86.3%)), defined as ASPDVs draining into the gastrocolic trunk of Henle (GCT); type II (n = 10, (8.5%)), defined as ASPDVs draining into the superior mesenteric vein (SMV); or type III, defined as ASPDVs draining into both the GCT and SMV. For type I, subtypes were defined according to the branching of the ASPDVs: subtype a, with one branch (n = 87, (86.1%)); subtype b, with two branches (n = 12, (11.9%)); and subtype c, with more than two branches (n = 2, (2.0%)). Type I was also subtyped according to the confluence of the ASPDV and GCT, with subtype 1 being defined by a proximal site (n = 96, 95%) and subtype 2 by a distal site (n = 5, 5.0%). CONCLUSIONS: We have characterized the variations in ASPDVs encountered during laparoscopic right hemicolectomy, which should provide a reference for colorectal surgeons.

A Novel Coagulation Classification and Postoperative Bleeding in Severe Spontaneous Intracerebral Hemorrhage Patients on Antiplatelet Therapy.

BACKGROUND AND PURPOSE: For patients with severe spontaneous intracerebral hemorrhage on antiplatelet therapy (patients with APT-SICH), postoperative rebleeding (PR) is an important cause of poor outcomes after surgery. As impacted by coagulation disorder caused by APT, patients with APT-SICH are likely to suffer from PR. This study aimed to assess the risk of PR in patients with APT-SICH receiving emergency surgery using a novel coagulation classification. METHODS: This prospective, multicenter cohort study consecutively selected patients with APT-SICH between September 2019 and March 2021. The preoperative coagulation factor function was recorded, and the platelet function was assessed using thrombelastography. Based on platelet and coagulation factor function, a novel four-type coagulation classification, i.e., Type I (severe coagulation disorder), Type IIa (low platelet reserve capacity), Type IIb (normal coagulation), and Type III (hypercoagulation), was presented. The primary outcome was PR, defined as the rebleeding in the operative region or new intracerebral hemorrhage correlated with the operation. RESULTS: Of the included 197 patients with APT-SICH, PR occurred in 40 patients (20.3%). The novel coagulation classification categorized 28, 32, 122, and 15 patients into Type I, Type IIa, Type IIb, and Type III, respectively. The Type I patients had the highest incident rate of PR (39.3 per 100 persons), followed by the Type IIa patients (31.3 per 100 persons). In the PR-related analysis, the large hematoma volume (hazard ratio (HR): 1.02; 95% CI: 1.02-1.03; p < 0.001), Type I (HR: 9.72; 95% CI: 1.19-79.67; p = 0.034), and Type IIa (HR: 8.70; 95% CI: 1.09-69.61; p = 0.041) were correlated with the highest risk of PR. The coagulation classification could discriminate the PR patients from no PR (NPR) patients (p < 0.001), and it outperformed the conventional coagulation assessment (only considering platelet count and coagulation factor function) (c-statistic, 0.72 vs. 0.55). CONCLUSION: The novel coagulation classification could discriminate the patients with APT-SICH with the highest risk of PR preoperatively. For the Type I and Type IIa patients, emergency surgery should be performed carefully.

Overexpression of CBS/H2S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44.

BACKGROUND: The role of hydrogen sulfide (H2S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H2S refers to pro-cancer action at lower doses and anti-cancer effect at higher concentrations. We hypothesized that overexpression of cystathionine-beta-synthase (CBS)/H2S exerts an inhibitory effect on colon cancer cell proliferation and metastasis. METHODS: Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), clone-formation and sphere formation assay. Cell migration was evaluated by transwell migration assay. Intracellular H2S was detected by H2S probe. Chromatin immunoprecipitation (ChIP) analysis was carried out to examine DNA-protein interaction. Cell experiments also included western blotting, flow cytometry, immunohistochemistry (IHC) and immunofluorescence analysis. We further conducted in vivo experiments to confirm our conclusions. RESULTS: Overexpression of CBS and exogenous H2S inhibited colon cancer cell proliferation and migration in vitro. In addition, overexpression of CBS attenuated tumor growth and liver metastasis in vivo. Furthermore, CD44 and the transcription factor SP-1 was probably involved in the inhibitory effect of CBS/H2S axis on colon cancer cells. CONCLUSIONS: Overexpression of CBS and exogenous provision of H2S inhibited colon cancer cell proliferation and migration both in vivo and in vitro. Molecular mechanisms might involve the participation of CD44 and the transcription factor SP-1.

The CBS-H2S axis promotes liver metastasis of colon cancer by upregulating VEGF through AP-1 activation.

BACKGROUND: The main therapy for colon cancer with liver metastasis is chemotherapy based on 5-fluorouracil combined with targeted drugs. However, acquired drug resistance and severe adverse reactions limit patients' benefit from standard chemotherapy. Here, we investigate the involvement of endogenous hydrogen sulfide (H2S) in liver metastasis of colon cancer and its potential value as a novel therapeutic target. METHODS: We used the CRISPR/Cas9 system to knockdown CBS gene expression in colon cancer cell lines. PCR arrays and proteome arrays were applied to detect the transcription and protein expression levels, respectively, of angiogenesis-related genes after knockdown. The molecular mechanism was investigated by western blot analysis, RT-qPCR, immunofluorescence staining, ChIP assays and dual-luciferase reporter assays. A liver metastasis mouse model was adopted to investigate the effect of targeting CBS on tumour metastasis in vivo. RESULTS: Knockdown of CBS decreased the metastasis and invasion of colon cancer cells and inhibited angiogenesis both in vivo and in vitro. Tissue microarray analysis showed a positive correlation between CBS and VEGF expression in colon cancer tissues. Further analysis at the molecular level validated a positive feedback loop between the CBS-H2S axis and VEGF. CONCLUSIONS: Endogenous H2S promotes angiogenesis and metastasis in colon cancer, and targeting the positive feedback loop between the CBS-H2S axis and VEGF can effectively intervene in liver metastasis of colon cancer.

CAF promotes chemoresistance through NRP2 in gastric cancer.

BACKGROUND: Fibroblasts are the predominant cell type in the stroma of tumor, and cancer-associated fibroblasts (CAFs) promote cancer chemoresistance by secreting various bioactive molecules. However, the differential expression between CAFs and normal fibroblasts (NFs) and how can CAFs uniquely impact cancer cells are still unexplored. METHODS: Primary CAFs and NFs were cultured from gastric cancer specimens, and their variant expression was analyzed by RNA-sequencing. Chemoresistance was evaluated by measuring cell viability, apoptosis, and 3D-coculture techniques. RESULTS: CAFs were isolated from gastric cancers and defined by specific cell-surface markers. CAFs decreased the sensitivity of gastric cancer cells to 5-FU. RNA-sequencing showed that CAFs expressed a higher level of NRP2 than NFs. And the high expression of NRP2 was correlated with worse oncological outcomes in gastric cancer patients. Further study showed that the knockdown of NRP2 eradicated the resistance to 5-FU. And the secretion of stromal cell-derived factor-1 (SDF-1) was reduced following NRP2 knockdown. Furthermore, we found that the increased sensitivity to 5-FU was induced by DNA damage. And this process was mediated by predominant effectors of the Hippo pathway, YAP/TAZ. CONCLUSIONS: The present study indicated that CAFs within gastric cancers promote chemoresistance through the expression of NRP2. The secretion of SDF-1 that mediated by VEGF/NRP2 signaling in CAFs and the activation of Hippo pathway in cancer cells in large part participated in this project.

Endoscopic and Robotic Parotidectomy for the Treatment of Parotid Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: The goal of this review was to introduce endoscopic/robotic parotidectomy (EP/RP) and compare EP/RP against conventional parotidectomy (CP) regarding the intraoperative and postoperative parameters in the treatment of parotid tumors. METHODS: A systematic literature search of medical databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) was performed from inception to November 2020 to generate relevant studies. RESULTS: A total of 13 eligible studies (572 patients) were included for systematic review, and 7 out of 13 comparable studies for the quantitative synthesis of outcomes. Patients who underwent EP were characterized by less intraoperative bleeding volume, shorter incision length, and higher satisfaction postoperatively (WMD, 95% CI, -42.80; - 58.23 to -27.37; p < 0.01; WMD, 95% CI, -5.64; -7.88 to -3.39; p < 0.01; SMD, 95% CI, 1.88; 1.46 to 2.31; p < 0.01, respectively). However, operative time and risk of facial palsy exhibited no significant differences (WMD, 95% CI, -11.17; -26.71 to 4.34; p = 0.16; OR, 95% CI,0.71; 0.39 to 1.32; p = 0.28, respectively). CONCLUSIONS: Our findings suggest that the current evidence does not adequately support EP is equally safe and effective as CP. In certain selected cases, endoscopic technology has its unique advantages. For patients with strong cosmetic needs, endoscopic or robotic techniques may be an alternative through adequate preoperative evaluations. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews, identifier CRD42020210299.

Two Similar Signatures for Predicting the Prognosis and Immunotherapy Efficacy of Stomach Adenocarcinoma Patients.

BACKGROUND: Globally, stomach adenocarcinoma (STAD)'s high morbidity and mortality should arouse our urgent attention. How long can STAD patients survive after surgery and whether novel immunotherapy is effective are questions that our clinicians cannot escape. METHODS: Various R packages, GSEA software, Metascape, STRING, Cytoscape, Venn diagram, TIMER2.0 website, TCGA, and GEO databases were used in our study. RESULTS: In the TCGA and GEO, macrophage abundance of STAD tissues was significantly higher than that of adjacent tissues and was an independent prognostic factor, significantly related to the overall survival (OS) of STAD patients. Between the high- and low- macrophage abundance, we conducted differential expression, univariate and multivariate Cox analysis, and obtained 12 candidate genes, and finally constructed a 3-gene signature. Both low macrophage abundance group and group D had higher TMB and PD-L1 expression. Furthermore, top 5 common gene-mutated STAD tissues had lower macrophage abundance. Macrophage abundance and 3 key genes expression were also lower in the Epstein-Barr Virus (EBV) and HM-indel STAD subtypes and significantly correlated with the tumor microenvironment score. The functional enrichment and ssGSEA revealed 2 signatures were similar and closely related to BOQUEST_STEM_CELL_UP, including genes up-regulated in proliferative stromal stem cells. Hsa-miR-335-5p simultaneously regulated 3 key genes and significantly related to the expression of PD-L1, CD8A and PDCD1. CONCLUSION: macrophage abundance and 3-gene signature could simultaneously predict the OS and immunotherapy efficacy, and both 2 signatures had remarkable similarities. Hsa-miR-335-5p and BOQUEST_STEM_CELL_UP might be novel immunotherapy targets.