Morphine promotes non-small cell lung cancer progression by downregulating E-cadherin via the PI3K/AKT/mTOR pathway.

Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro (p < 0.05). It also enhanced the migratory and invasive capacities of these cell lines (p < 0.01). Mechanistically, morphine treatment (10 µM) led to a reduction in the expression of E-cadherin, and an increase in the phosphorylation of PI3K, AKT, and mTOR in A549 and LLC cells (p < 0.01). Morphine treatment (1.5 mg/kg) also reduced E-cadherin expression in xenograft tumours and promoted tumour growth in vivo (p < 0.05). This effect was reversed by naloxone (0.1 mg/kg). The results demonstrated that morphine stimulates the malignant proliferation of A549 and LLC cell lines and promotes xenograft tumour growth. Perhaps by specifically targeting MOR, morphine triggers a signalling cascade that activates the PI3K/AKT/mTOR pathway while inhibiting the EMT marker E-cadherin, which may consequently promote the progression of lung cancer.

A fully digital planning protocol for dynamic computer-assisted zygomatic implant surgery based on virtual surgery simulation: A dental technique.

Dynamic navigation-guided zygomatic implant (ZI) surgery has been a preferred option for achieving optimal prosthetic-driven implant placement. However, during the actual surgical procedure, surgical execution may still be hindered by environmental factors such as mouth opening. A fully digital planning protocol is described that integrated the patient's maxillofacial soft tissue information and virtual surgical handpiece with the drills on the implant planning path to ensure the precise, time-saving, and smooth implementation of dynamic navigation-guided ZI surgery.

Chitinase-3 like-protein-1, a prognostic biomarker in patients with hepatocellular carcinoma and concomitant myosteatosis.

BACKGROUND: Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT). METHODS: This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman's rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. RESULTS: Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p < 0.001). Interestingly, in patients with myosteatosis, Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse OS (p < 0.001) and RFS (p = 0.047). However, in patients without myosteatosis, Kaplan-Meier analysis found elevated serum CHI3L1 levels were not associated with OS (p = 0.070) or RFS (p = 0.104). CONCLUSIONS: Elevated CHI3L1 was negatively correlated with SMRA, and predicted poorer prognosis in Chinese population after LT for HCC, especially in those patients with concomitant myosteatosis. Monitoring serum CHI3L1 can predict prognosis and effectively guide individual nutrition intervention.

Research hotspots and trends of spinal cord stimulation for neuropathic pain: a bibliometric analysis from 2004 to 2023.

The purpose of this study is to systematically analyze the development trend, research hotspots, and future development direction on the treatment of neuropathic pain (NP) with spinal cord stimulation through bibliometric method. We extracted the literature related to the treatment of NP with spinal cord stimulation from January 2004 to December 2023 from the Web of Science database. As a result, a total of 264 articles were retrieved. By analyzing the annual published articles, authors, countries, institutions, journals, co-cited literature, and keywords, we found that the count of publication in this field has been experiencing an overall growth, and the publications within the past 5 years accounted for 42% of the total output. Experts from the United States and the UK have made significant contributions in this field and established a stable collaborative team, initially establishing an international cooperation network. Pain is the frequently cited journal in this field. The study on spinal cord stimulation therapy for NP especially the study on spinal cord stimulation therapy for back surgery failure syndrome (FBSS) and its potential mechanisms are the research hotspots in this field, while the study on novel paradigms such as high-frequency spinal cord stimulation and spinal cord burst stimulation represents the future development directions. In short, spinal cord stimulation has been an effective treatment method for NP. The novel paradigms of spinal cord stimulation are the key point of future research in this field.

Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells.

Inhibiting the death receptor 3 (DR3) signaling pathway in group 3 innate lymphoid cells (ILC3s) presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis (UC). Paeoniflorin, a prominent component of Paeonia lactiflora Pall., has demonstrated the ability to restore barrier function in UC mice, but the precise mechanism remains unclear. In this study, we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s. C57BL/6 mice were subjected to random allocation into 7 distinct groups, namely the control group, the 2 % dextran sodium sulfate (DSS) group, the paeoniflorin groups (25, 50, and 100 mg/kg), the anti-tumor necrosis factor-like ligand 1A (anti-TL1A) antibody group, and the IgG group. We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry, respectively. Meanwhile, DR3-overexpressing MNK-3 cells and 2 % DSS-induced Rag1-/- mice were used for verification. The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier. Simultaneously, paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines (Interleukin-17A, Granulocyte-macrophage colony stimulating factor, and Interleukin-22). Alternatively, paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system. We additionally confirmed that paeoniflorin-conditioned medium (CM) restored the expression of tight junctions in Caco-2 cells via coculture. In conclusion, paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner, and its mechanism is associated with the inhibition of the DR3 signaling pathway.

Tumor­suppressive effects of Smad­ubiquitination regulator 2 in papillary thyroid carcinoma.

Smad-ubiquitination regulator 2 (SMURF2) functions as a homolog of E6AP carboxyl terminus-type E3 ubiquitin ligase to regulate cell cycle progression and tumor growth factor expression. SMURF2 has been revealed to function as a tumor suppressor in a number of cancers; however, its function in papillary thyroid carcinoma (PTC) remains largely unknown. Therefore, the aim of the present study was to investigate the function of SMURF2 in PTC. Reverse transcription-quantitative PCR and western blotting were used to detect cellular expression of SMURF2 in vitro. After increasing or inhibiting the expression of SMURF2, MTT was used to detect the effect on tumor cell proliferation and Transwell assays were used to detect the effect on tumor cell migration and invasion. Finally, ELISA was used to detect the effects on glucose and glutamine metabolism in tumor cells and the findings revealed that SMURF2 was downregulated in PTC tissues. Moreover, SMURF2 inhibited the proliferation, invasion and migration of PTC cells, and promoted their apoptosis. Finally, SMURF2 inhibited cell glycolysis and glutaminolysis and affected metabolism in the PTC cell line, TPC-1. Thus, the findings of the present study suggest that SMURF2 may be a potential target in the treatment of PTC.

Post-transplant hepatitis B virus reactivation impacts the prognosis of patients with hepatitis B-related hepatocellular carcinoma: a dual-centre retrospective cohort study in China.

BACKGROUND: Highly active hepatitis B virus (HBV) is known to be associated with poor outcomes in patients with hepatocellular carcinoma (HCC). This study aims to investigate the relationship between HBV status and HCC recurrence after liver transplantation. METHODS: The study retrospectively analyzed HCC patients undergoing liver transplantation in two centres between January 2015 and December 2020. The authors reviewed post-transplant HBV status and its association with outcomes. RESULTS: The prognosis of recipients with hepatitis B surface antigen (HBsAg) reappearance ( n =58) was poorer than those with HBsAg persistent negative ( n =351) and positive ( n =53). In HBsAg persistent positive group, recipients with HBV DNA reappearance or greater than 10-fold increase above baseline had worse outcomes than those without ( P <0.01). HBV reactivation was defined as (a) HBsAg reappearance or (b) HBV DNA reappearance or greater than 10-fold increase above baseline. After propensity score matching, the 5-year overall survival rate and recurrence-free survival rate after liver transplantation in recipients with HBV reactivation were significantly lower than those without (32.0% vs. 62.3%; P <0.01, and 16.4% vs. 63.1%; P <0.01, respectively). Moreover, HBV reactivation was significantly related to post-transplant HCC recurrence, especially lung metastasis. Cox regression analysis revealed that beyond Milan criteria, microvascular invasion and HBsAg-positive graft were independent risk factors for post-transplant HBV reactivation, and a novel nomogram was established accordingly with a good predictive efficacy (area under the time-dependent receiver operating characteristic curve=0.78, C-index =0.73). CONCLUSIONS: Recipients with HBV reactivation had worse outcomes and higher tumour recurrence rates than those without. The nomogram could be used to evaluate the risk of post-transplant HBV reactivation effectively.

Curcumin alleviates atrazine-induced cardiotoxicity by inhibiting endoplasmic reticulum stress-mediated apoptosis in mice through ATF6/Chop/Bcl-2 signaling pathway.

Atrazine (ATR), a water-soluble herbicide commonly used to control broad-leaf and monocotyledonous weeds, presents a significant risk to environmental soil and water quality. Exposure to ATR adversely affects human and animal health, frequently resulting in cardiac impairment. Curcumin (Cur), an acidic polyphenol derivative from plants acclaimed for its pronounced anti-inflammatory and antioxidant properties, has garnered interest as a potential therapeutic agent. However, whether it has the potential to ameliorate ATR-induced cardiac toxicity via modulation of endoplasmic reticulum stress (ERS) and apoptosis pathways in mice remains unclear. Our results showed that Cur supplementation attenuates ATR-induced cardiotoxicity, evidenced by decrease in creatine kinase and lactate dehydrogenase, key biochemical markers of myocardial injury, which have a more significant protecting effect in high-dose ATR induced injury. Histopathological and electron microscopy examinations further solidified these findings, demonstrating an amelioration in organellar damage, particularly in endoplasmic reticulum swelling and subsequent mitochondrial impairment. Additionally, ATR exposure augments ERS and triggers apoptotic pathways, as indicated by the upregulation of ERS-related gene expression (ATF6, CHOP, IRE1, GRP78) and pro-apoptotic markers (BAX, BAK1, Caspase3, Caspase. Intriguingly, Cur counteracts this detrimental response, significantly reducing ERS and pro-apoptotic signals at both transcriptional and translational levels. Collectively, our findings illuminate Cur's cardioprotective effect against ATR-induced injury, primarily through its anti-ERS and anti-apoptotic activities, underscoring Cur's potential as a therapeutic for ATR-induced cardiotoxicity.

A pan-cancer analysis of prognostic significance and immunological role of lysosomal-associated membrane protein 3.

Lysosomal dysfunction can drive carcinogenesis. Lysosomal-associated membrane protein 3 (LAMP3), is a member of the Lysosome Associated Membrane Proteins and is involved in the malignant phenotype such as tumour metastasis and drug resistance, while the mechanisms that regulate the malignant progression of tumour remain vague. Our study aims to provide a more systematic and comprehensive understanding of the role of LAMP3 in the progression of various cancers by various databases.We explored the role of LAMP3 in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Multiple online web platforms and software were used for data analysis, including HPA, TIMER, TISIDB, GEPIA, UALCAN, Kaplan-Meier plotter, DAVID and TIGER. The immunohistochemistry was used to quantify the LAMP3 and PD-L1 expression levels in cancer.High LAMP3 expression was found in most cancers and differentially expressed across molecular and immune subtypes. The expression of LAMP3 was involved in the immune-associated processes of Antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and the immune-associated pathways of T cell receptor and B cell receptor signalling pathways in most cancers. It also correlated with genetic markers of immunomodulators in various cancers. LAMP3 and PD-L1 expression in BRCA and HNSC tissues was higher than that in corresponding adjacent normal tissues by immunohistochemistry. There is a significant correlation between the expression of LAMP3 and PD-L1.Our study elucidates that LAMP3 has different expression patterns and genetic alteration patterns in different tumours. It is a potential biomarker for immune-related cancer diagnosis, prognosis and efficacy prediction.

Pediatric gliosarcoma, a rare central nervous system tumor in children: Case report and literature review.

Gliosarcoma is a rare and highly malignant central nervous system tumor that accounts for 1%-8% of glioblastomas; it usually occurs in middle-aged and older adults between 40 and 60 years of age and is rare in children. We report an 11-year-old boy with right frontal lobe gliosarcoma who underwent aggressive gross total resection and postoperative radiotherapy, experienced recurrence and subsequently underwent a second operation. To better understand the disease and explore treatment options, we briefly report this case and review the relevant literature.

Insulin-Like Growth Factor 1 Receptor Deficiency Alleviates Angiotensin II-Induced Cardiac Fibrosis Through the Protein Kinase B/Extracellular Signal-Regulated Kinase/Nuclear Factor-κB Pathway.

Background The renin-angiotensin system plays a crucial role in the development of heart failure, and Ang II (angiotensin II) acts as the critical effector of the renin-angiotensin system in regulating cardiac fibrosis. However, the mechanisms of cardiac fibrosis are complex and still not fully understood. IGF1R (insulin-like growth factor 1 receptor) has multiple functions in maintaining cardiovascular homeostasis, and low-dose IGF1 treatment is effective in relieving Ang II-induced cardiac fibrosis. Here, we aimed to investigate the molecular mechanism of IGF1R in Ang II-induced cardiac fibrosis. Methods and Results Using primary mouse cardiac microvascular endothelial cells and fibroblasts, in vitro experiments were performed. Using C57BL/6J mice and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-mediated IGF1R heterozygous knockout (Igf1r+/-) mice, cardiac fibrosis mouse models were induced by Ang II for 2 weeks. The expression of IGF1R was examined by quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot. Mice heart histologic changes were evaluated using Masson and picro sirius red staining. Fibrotic markers and signal molecules indicating the function of the Akt (protein kinase B)/ERK (extracellular signal-regulated kinase)/nuclear factor-κB pathway were detected using quantitative reverse transcription polymerase chain reaction and Western blot. RNA sequencing was used to explore IGF1R-mediated target genes in the hearts of mice, and the association of IGF1R and G-protein-coupled receptor kinase 5 was identified by coimmunoprecipitation. More important, blocking IGF1R signaling significantly suppressed endothelial-mesenchymal transition in primary mouse cardiac microvascular endothelial cells and mice in response to transforming growth factor-ß1 or Ang II, respectively. Deficiency or inhibition of IGF1R signaling remarkably attenuated Ang II-induced cardiac fibrosis in primary mouse cardiac fibroblasts and mice. We further observed that the patients with heart failure exhibited higher blood levels of IGF1 and IGF1R than healthy individuals. Moreover, Ang II treatment significantly increased cardiac IGF1R in wild type mice but led to a slight downregulation in Igf1r+/- mice. Interestingly, IGF1R deficiency significantly alleviated cardiac fibrosis in Ang II-treated mice. Mechanistically, the phosphorylation level of Akt and ERK was upregulated in Ang II-treated mice, whereas blocking IGF1R signaling in mice inhibited these changes of Akt and ERK phosphorylation. Concurrently, phosphorylated p65 of nuclear factor-κB exhibited similar alterations in the corresponding group of mice. Intriguingly, IGF1R directly interacted with G-protein-coupled receptor kinase 5, and this association decreased ≈50% in Igf1r+/- mice. In addition, Grk5 deletion downregulated expression of the Akt/ERK/nuclear factor-κB signaling pathway in primary mouse cardiac fibroblasts. Conclusions IGF1R signaling deficiency alleviates Ang II-induced cardiac fibrosis, at least partially through inhibiting endothelial-mesenchymal transition via the Akt/ERK/nuclear factor-κB pathway. Interestingly, G-protein-coupled receptor kinase 5 associates with IGF1R signaling directly, and it concurrently acts as an IGF1R downstream effector. This study suggests the promising potential of IGF1R as a therapeutic target for cardiac fibrosis.

Upregulation of ubiquitin carboxy­terminal hydrolase 47 (USP47) in papillary thyroid carcinoma ex vivo and reduction of tumor cell malignant behaviors after USP47 knockdown by stabilizing SATB1 expression in vitro.

Aberrant ubiquitination contributes to cancer development, including thyroid carcinoma. The present study assessed the expression of ubiquitin carboxy-terminal hydrolase 47 (USP47) and underlying molecular events in the development of papillary thyroid carcinoma (PTC). The effects of USP47 on PTC cell invasion and migration were analyzed by Transwell assays, while. the effects of USP47 and SATB1on PTC cell gene expression and changes in tumor cell metabolism were assayed by reverse transcription-quantitative PCR, western bolt, or ELISA, respectively. The expression of USP47 mRNA and protein was upregulated in PTC tissue and associated with the PTC tumor size. Knockdown of USP47 expression in PTC cell lines (TPC-1 and K1), decreased the cell proliferation mobility and invasion capacities, whereas USP47 overexpression in these cell lines showed an inverse effect and promoted cell glycolysis and glutamine metabolism. Moreover, expression of special AT-rich sequence-binding protein-1 (SATB1) was high in PTC tissue and was associated with USP47 expression. SATB1 expression promoted tumor cell glycolysis and glutamine metabolism, while USP47 protein bound to and deubiquitinated SATB1 to increase its intracellular levels, thus promoting glycolysis and glutamine metabolism. USP47 promotion of PTC development may be due to its stabilization of SATB1 protein, suggesting that targeting the USP47/SATB1 signaling axis may serve as a therapeutic intervention for PTC.

Postoperative infusion of dexmedetomidine via intravenous patient-controlled analgesia for prevention of postoperative delirium in elderly patients undergoing surgery.

BACKGROUND: Postoperative delirium (POD) is a common clinical complication in elderly patients after surgery and predicts poor outcomes. AIM: We researched whether postoperative infusion of dexmedetomidine (DEX) had prophylactic effect on POD in elderly patients. METHODS: A total of 236 patients over the age of 60 years undergoing thoracoabdominal tumor surgery were enrolled in Zhejiang Cancer Hospital from November 2016 to October 2020. The patients were randomly assigned into DEX group (group D) and control group (Group C). DEX was provided via PCIA pump 1-3 days after surgery, which consisted of 3 ug/kg sufentanil and 3 ug/kg DEX in group D, and 3 ug/kg sufentanil without DEX in group C. The PCIA parameters were programmed as follows: total amount 150 ml, 2 ml bolus dose with a lock-out of 10 min and background infusion rate 2 ml/h. The primary endpoint was the incidence of POD, assessed twice daily within 7 days after surgery by Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). The secondary endpoint was postoperative hospitalization days, ICU stay time, adverse events and non-delirium complications. RESULTS: The incidence of POD in all patients was 7%. The incidence of POD in group C was significantly higher than that in group D (10.1% vs 3.4%, P = 0.042). There were no significant differences in length of hospital stay after operation, ICU stay time, the percentage of patients discharged within 7 days after surgery, non-delirium complications, and 30-day all-cause deaths between the two groups. The incidence of hypertension in group D was lower than that in group C (P = 0.003), and there were no differences in other adverse events. CONCLUSION: Patients aged over 60 years received DEX in addition to intravenous patient-controlled analgesia (PCIA) for major thoracoabdominal surgery experienced less delirium.

Accuracy of immediate dental implant placement with task-autonomous robotic system and navigation system: An in vitro study.

OBJECTIVES: The aim of this study was to compare the accuracy of dental implant placement in a single tooth gap, including the postextraction site and healed site, using a task-autonomous robotic system and a dynamic navigation system. MATERIALS AND METHODS: Forty partially edentulous models requiring both immediate and conventional implant placement were randomly divided into a robotic system group and a navigation system group. The coronal, apical, and angular deviations of the implants were measured and assessed between the groups. RESULTS: The deviations in immediate implant placement were compared between the robotic system and dynamic navigation system groups, showing a mean (±SD) coronal deviation of 0.86 ± 0.36 versus 0.70 ± 0.21 mm (p = .101), a mean apical deviation of 0.77 ± 0.34 versus 0.95 ± 0.38 mm (p = .127), and a mean angular deviation of 1.94 ± 0.66° versus 3.44 ± 1.38° (p < .001). At the healed site, significantly smaller coronal deviation (0.46 ± 0.29 vs. 0.70 ± 0.30 mm, p = .005), apical deviation (0.56 ± 0.30 vs. 0.85 ± 0.25 mm, p < .001), and angular deviation (1.36 ± 0.54 vs. 1.80 ± 0.70 mm, p = .034) were found in the robotic system group than in the dynamic navigation group. CONCLUSIONS: The position in both immediate and conventional implant placement was more precise with the task-autonomous robotic system than with the dynamic navigation system. Its performance in actual clinical applications should be confirmed in further trials.

A cable-driven highly compact single port laparoscopic surgical robot with sequentially inserted arms.

BACKGROUND: The single port surgical robot causes only one incision and brings many benefits to patients. It is very challenging to design a single port surgical robot that causes a smaller incision than current products. METHODS: This paper presents a highly compact single port laparoscopy surgical robot, which makes full use of the space of the port and only needs a 15 mm-diameter port. The robot is composed of a camera manipulator and two operating manipulators. The non-fully cylindrical manipulators enter the port sequentially, and the equivalent diameter of each operating manipulator is 12 mm. An additional 9 mm-diameter channel is left for other surgical tools to pass through after all manipulators entering the port. RESULTS: The kinematics model of the robot is established, including detailed forward kinematics model and inverse kinematics solution based on geometric iteration method. The teleoperation experiment shows that the manipulator can complete the object-grasping, object-transfer and weight-lifting tasks. CONCLUSIONS: The proposed single port surgical robot design concept can also be extended to the field of natural orifice transluminal endoscopic surgical robots.

A novel analytical approach for outcome prediction in newly diagnosed NSCLC based on [18F]FDG PET/CT metabolic parameters, inflammatory markers, and clinical variables.

OBJECTIVES: To develop a novel analytical approach based on 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) metabolic parameters, serum inflammatory markers, and clinical variables to improve the outcome prediction in NSCLC. METHODS: A total of 190 newly diagnosed NSCLC patients who underwent pretreatment [18F]FDG PET/CT were retrospectively enrolled and divided into a training cohort (n = 127) and a test cohort (n = 63). Cox regression analysis was used to investigate the predictive values of PET metabolic parameters, inflammation markers, and clinical variables for progression-free survival (PFS) and overall survival (OS). Based on the results of multivariate analysis, PET-based, clinical, and combined models were constructed. The predictive performance of different models was evaluated using time-dependent ROC curve analysis, Harrell concordance index (C-index), calibration curve, and decision curve analysis. RESULTS: The combined models incorporating SULmax, MTV, NLR, and ECOG PS demonstrated significant prognostic superiority over PET-based models, clinical models, and TNM stage in terms of both PFS (C-index: 0.813 vs. 0.786 vs. 0.776 vs. 0.678, respectively) and OS (C-index: 0.856 vs. 0.792 vs. 0.781 vs. 0.674, respectively) in the training cohort. Similar results were observed in the test cohort for PFS (C-index: 0.808 vs. 0.764 vs. 0.748 vs. 0.679, respectively) and OS (C-index: 0.836 vs. 0.785 vs. 0.726 vs. 0.660, respectively) prediction. The combined model calibrated well in two cohorts. Decision curve analysis supported the clinical utility of the combined model. CONCLUSIONS: We reported a novel analytical approach combining PET metabolic information with inflammatory biomarker and clinical characteristics, which could significantly improve outcome prediction in newly diagnosed NSCLC. KEY POINTS: • The nomogram incorporating SULmax, MTV, NLR, and ECOG PS outperformed the TNM stage for outcome prediction in patients with newly diagnosed NSCLC. • The established nomogram could provide refined prognostic stratification.

Efficacy and safety profile of two-dose SARS-CoV-2 vaccines in cancer patients: An observational study in China.

BACKGROUND: The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced a global pandemic of coronavirus disease 2019 (COVID-19), resulting in modifications to public health policies on a universal scale. SARS-CoV-2 vaccine has evolved as the most effective and secure way for protecting healthy individuals against COVID-19. Patients with cancer were excluded from clinical trials due to their increased COVID-19 risk and current immunosuppressing therapy. Safety and effectiveness evidence is insufficient for SARS-CoV-2 vaccination in cancer patients. AIM: To assess the efficacy and safety of two-dose SARS-CoV-2 vaccines in cancer patients. METHODS: A multicenter observational study was performed at ten Chinese hospitals between January 1, 2021 and December 31, 2021. Each participant in the research received two doses of vaccination. A total of 215 healthy people were screened and 132 eligible patients with cancer were recruited. In order to verify the safety of the second dose of the vaccine, a side-effect report was compiled. Two weeks following the second vaccination dose, subjects underwent an analogous questionnaire survey. Utilizing a magnetic particle-based chemiluminescence immunoassay, serum levels of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies were measured to determine the effectiveness of vaccination. IgG levels ≥ 10 AU/mL were considered seropositive. RESULTS: All the 347 eligible patients completed the follow-up, and anti-SARS-CoV-2 IgG antibodies were detected. Local pain at the injection location was the most common side effect mentioned by all responders, with an increased incidence in cancer patients than the healthy people after the second dose vaccine (17.2% vs 9.1%; P = 0.035). There was no significant difference in headache, urticaria, or other adverse reactions between patients with cancer and healthy people. In the group of cancer patients, the seropositivity incidence was 83.3%, while it was 96.3% in the group of healthy people. In the group of cancer patients, the seropositivity incidence and antibody levels were significantly lower (P < 0.001). This analysis showed a poorer response rate in patients on active immunosuppressive treatment and elderly cancer patients. CONCLUSION: Two-dose Chinese vaccines are effective and safe in cancer patients. However, further research is required on the efficacy in elderly cancer patients and those on active immunosuppressive treatment.

Prognosis and Efficacy of Laparoscopic Surgery on Patients with Endometrial Carcinoma: Systematic Evaluation and Meta-Analysis.

Objective: The prognosis and efficacy of laparoscopic surgery (LPS) and open surgery or robotic surgery (RS) on endometrial carcinoma (EC) patients were compared. Methods: Data as of May 2021 were retrieved from databases like PubMed, Embase, Cochrane Library, and Web of Science. The study involved randomized controlled trials (RCTs), cohort studies, or case-control studies for comparing the effects of LPS and open surgery or robotic surgery (RS) on EC treatment. The primary outcomes included duration of operation, blood loss, length of stay (LOS), postoperative complications, and recurrence rate. Secondary outcomes included 3-year progression-free survival (PFS) rate/disease-free survival (DFS) rate and 3-year overall survival (OS) rate. Results: A total of 24 studies were involved, and all of them were cohort studies except 1 RCT and 1 case-control study. There was no significant difference in duration of operation between LPS and open surgery (MD = -0.06, 95% CI: -0.37 to 0.25) or RS (MD = -0.15, 95% CI: -1.27 to 0.96). In comparison with the open surgery, LPS remarkably reduced blood loss (MD = -0.43, 95% CI: -0.58 to -0.29), LOS (MD = -0.71, 95% CI: -0.92 to -0.50), and the complication occurrence rate (RR = 0.83, 95% CI: 0.73 to 0.95). However, LPS and RS saw no difference in blood loss (MD = 0.01, 95% CI: -0.77 to 0.79). Besides, in comparison with RS, LPS prominently shortened the LOS (MD = 0.26, 95% CI: 0.12 to 0.40) but increased the complication occurrence rate (RR = 1.74, 95% CI: 1.57 to 1.92). In contrast to open surgery or RS, LPS saw no difference in occurrence rate (RR = 0.75, 95% CI: 0.56 to 1.01; RR = 0.97, 95% CI: 0.62 to 1.53), 3-year PFS/DFS (RR = 0.99, 95% CI: 0.90 to 1.09; RR = 1.30, 95% CI: 0.87 to 1.96), and 3-year OS (RR = 0.97, 95% CI: 0.91 to 1.04; RR = 1.21, 95% CI: 0.91 to 1.60). Conclusion: In sum, LPS was better than open surgery, which manifested in the aspects of less blood loss, shorter LOS, and fewer complications. LPS, therefore, was the most suitable option for EC patients. Nevertheless, LPS had no advantage over RS, and sufficient prospective RCTs are needed to further confirm its strengths.

Huang Qin Decoction inhibits the initiation of experimental colitis associated carcinogenesis by controlling the PAD4 dependent NETs.

BACKGROUND: Colorectal cancer is associated with ulcerative colitis (UC). The infiltration of neutrophils is the main cause of DNA damage produced by inflammation in the intestinal epithelium. Under the action of peptidyl arginine deaminase 4 (PAD4), neutrophils dissociate chromatin and form neutrophil extracellular traps (NETs), which can aggravate tissue inflammation and encourage tumor development. Although Huang Qin Decoction (HQD) was found to be useful in treating UC and was used to gradually prevent and treat digestive tract cancers, the underlying reasons were unclear. METHODS: To demonstrate HQD could inhibits the initiation of colitis associated carcinogenesis by controlling NETs related inflammation, we first performed an AOM/DSS-generated colitis-associated carcinogenesis model to assess the efficacy of HQD in reducing neutrophil infiltration and anti-tumor activity. Then, using network pharmacology research, we investigated the potential mechanisms underlying those medicinal effects, as demonstrated by the detection of NETs aggregation and PAD4 expression changes in the colon. RESULTS: HQD substantially reduced the number of colon cancers and the expression of Ki67, restored the level of intestinal tight junction protein occludin and ZO-1, and relieved the intestinal inflammation caused by TNF-α, IL-1ß. At the same time, it inhibited neutrophil infiltration in the colon and improved the immunosurveillance of CD8+T cells. The potential mechanisms of HQD intervention against UC and UC with neoplasia (UCN) were studied using network pharmacology, and 156 conjunct genes as well as numerous inflammation-related pathways were identified. Protein-protein interaction (PPI) analysis indicated that HQD inhibition of intestinal tumors might be related to the deactivation of PAD4, which was verified by the down-regulation of NETs, MPO-DNA complex levels, and PAD4 expression after HQD treatment. CONCLUSION: Huang Qin Decoction inhibits the initiation of colitis associated carcinogenesis by controlling PAD4-dependent neutrophil extracellular traps.

Reconstruction and analysis of potential biomarkers for hypertrophic cardiomyopathy based on a competing endogenous RNA network.

Hypertrophic cardiomyopathy (HCM) is a common heritable cardiomyopath. Although considerable effort has been made to understand the pathogenesis of HCM, the mechanism of how long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network result in HCM remains unknown. In this study, we acquired a total of 520 different expression profiles of lncRNAs (DElncRNAs) and 371 messenger RNAs (mRNA, DEGs) by microarray and 33 microRNAs (DEmiRNAs) by sequencing in plasma of patients with HCM and healthy controls. Then lncRNA-miRNA pairs were predicted using miRcode and starBase and crossed with DEmiRNAs. MiRNA-mRNA pairs were retrieved from miRanda and TargetScan and crossed with DEGs. Combined with these pairs, the ceRNA network with eight lncRNAs, three miRNAs, and 22 mRNAs was constructed. lncRNA RP11-66N24.4 and LINC00310 were among the top 10% nodes. The hub nodes were analyzed to reconstruct a subnetwork. Furthermore, quantitative real-time polymerase chain reaction results showed that LINC00310 was significantly decreased in patients with HCM. For LINC00310, GO analysis revealed that biological processes were enriched in cardiovascular system development, sprouting angiogenesis, circulatory system development, and pathway analysis in the cGMP-PKG signaling pathway. These results indicate that the novel lncRNA-related ceRNA network in HCM and LINC00310 may play a role in the mechanism of HCM pathogenesis, which could provide insight into the pathogenesis of HCM.