Safety and efficacy of delayed completion lobectomy following wedge resection vs. segmentectomy-a retrospective cohort study.

Background: Data regarding the safety and efficacy of delayed completion lobectomy (CL) following sublobar resections remain scant. We evaluated the technical difficulty and short-term outcomes of CL occurring at least 3 months following the anatomical segmentectomy or wedge resection. Methods: Consecutive non-small cell lung cancer (NSCLC) patients who underwent a second resection within the same lobe at least 3 months after their initial resection from January 2013 to December 2019 at the Shanghai Pulmonary Hospital were retrospectively included. The patients were divided into a segmentectomy group (SG group) and a wedge resection group (WR group) based on their initial resection strategy. Baseline characteristics and short-term outcomes after CL between the two groups were compared. Results: Twenty-five patients undergoing CL were included, nine in the SG group and 16 in the WR group. No deaths occurred within 30 days postoperatively, and the rate of overall postoperative complications was 28.0% (7/25). Statistically significant differences were found in rates of postoperative complications between the two groups (SG: 55.6% vs. WR: 12.5%, P=0.03) and in the use of bronchoplasty or angioplasty during the CL (SG: 33.3% vs. WR: 0.0%, P=0.04). After CL, no significant differences were found in 5-year recurrence-free survival (RFS) (WR: 66.7% vs. SG: 61.0%, P=0.31) or overall survival (OS) (WR: 93.8% vs. SG: 66.7%, P=0.06) between two groups. Conclusions: Delayed CL occurring over 3 months after sublobar resection is a safe and effective procedure, with no deaths occurring within 30 days postoperatively. As compared to a segmentectomy at the time of the index operation, a wedge resection may portend less morbidity, with a decreased risk of needing adjunctive bronchoplasty or angioplasty procedures during CL. After CL, 5-year RFS and OS were comparable between WR and SG groups.

Nanozymes with biomimetically designed properties for cancer treatment.

Nanozymes, as a type of nanomaterials with enzymatic catalytic activity, have demonstrated tremendous potential in cancer treatment owing to their unique biomedical properties. However, the heterogeneity of tumors and the complex tumor microenvironment pose significant challenges to the in vivo catalytic efficacy of traditional nanozymes. Drawing inspiration from natural enzymes, scientists are now using biomimetic design to build nanozymes from the ground up. This approach aims to replicate the key characteristics of natural enzymes, including active structures, catalytic processes, and the ability to adapt to the tumor environment. This achieves selective optimization of nanozyme catalytic performance and therapeutic effects. This review takes a deep dive into the use of these biomimetically designed nanozymes in cancer treatment. It explores a range of biomimetic design strategies, from structural and process mimicry to advanced functional biomimicry. A significant focus is on tweaking the nanozyme structures to boost their catalytic performance, integrating them into complex enzyme networks similar to those in biological systems, and adjusting functions like altering tumor metabolism, reshaping the tumor environment, and enhancing drug delivery. The review also covers the applications of specially designed nanozymes in pan-cancer treatment, from catalytic therapy to improved traditional methods like chemotherapy, radiotherapy, and sonodynamic therapy, specifically analyzing the anti-tumor mechanisms of different therapeutic combination systems. Through rational design, these biomimetically designed nanozymes not only deepen the understanding of the regulatory mechanisms of nanozyme structure and performance but also adapt profoundly to tumor physiology, optimizing therapeutic effects and paving new pathways for innovative cancer treatment.

The Metabolomic Characteristics and Dysregulation of Fatty Acid Esters of Hydroxy Fatty Acids in Breast Cancer.

Lipid reprogramming metabolism is crucial for supporting tumor growth in breast cancer and investigating potential tumor biomarkers. Fatty acid esters of hydroxy fatty acids (FAHFAs) are a class of endogenous lipid metabolites with anti-diabetic and anti-inflammatory properties that have been discovered in recent years. Our previous targeted analysis of sera from breast cancer patients revealed a significant down-regulation of several FAHFAs. In this study, we aimed to further explore the relationship between FAHFAs and breast cancer by employing chemical isotope labeling combined with liquid chromatography-mass spectrometry (CIL-LC-MS) for profiling of FAHFAs in tumors and adjacent normal tissues from breast cancer patients. Statistical analysis identified 13 altered isomers in breast cancer. These isomers showed the potential to distinguish breast cancer tissues with an area under the curve (AUC) value above 0.9 in a multivariate receiver operating curve model. Furthermore, the observation of up-regulated 9-oleic acid ester of hydroxy stearic acid (9-OAHSA) and down-regulated 9-hydroxystearic acid (9-HSA) in tumors suggests that breast cancer shares similarities with colorectal cancer, and their potential mechanism is to attenuate the effects of pro-apoptotic 9-HSA by enhancing the synthesis of FAHFAs, thereby promoting tumor survival and progression through this buffering system.

Biomimetic Trachea Engineering via a Modular Ring Strategy Based on Bone-Marrow Stem Cells and Atelocollagen for Use in Extensive Tracheal Reconstruction.

The fabrication of biomimetic tracheas with a architecture of cartilaginous rings alternately interspersed between vascularized fibrous tissue (CRVFT) has the potential to perfectly recapitulate the normal tracheal structure and function. Herein, the development of a customized chondroitin-sulfate-incorporating type-II atelocollagen (COL II/CS) scaffold with excellent chondrogenic capacity and a type-I atelocollagen (COL I) scaffold to facilitate the formation of vascularized fibrous tissue is described. An efficient modular ring strategy is then adopted to develop a CRVFT-based biomimetic trachea. The in vitro engineering of cartilaginous rings is achieved via the recellularization of ring-shaped COL II/CS scaffolds using bone marrow stem cells as a mimetic for native cartilaginous ring tissue. A CRVFT-based trachea with biomimetic mechanical properties, composed of bionic biochemical components, is additionally successfully generated in vivo via the alternating stacking of cartilaginous rings and ring-shaped COL I scaffolds on a silicone pipe. The resultant biomimetic trachea with pedicled muscular flaps is used for extensive tracheal reconstruction and exhibits satisfactory therapeutic outcomes with structural and functional properties similar to those of native trachea. This is the first study to utilize stem cells for long-segmental tracheal cartilaginous regeneration and this represents a promising method for extensive tracheal reconstruction.

Octogenarians may benefit from stage-specific small cell lung cancer treatment.

BACKGROUND: Our study investigates treatment profiles in octogenarian patients with small cell lung cancer (SCLC) and assesses each treatment's role in a stage-specific manner. METHODS: Patient data from individuals with SCLC aged 80 years and older between 1988 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) database were extracted. Cancer-specific survival (CSS) between patients with no treatment and different treatment groups were compared by the Kaplan-Meier method, with stratifications by stage. Cox Proportional Hazard model further identified independent prognostic factors. RESULTS: A total of 7,290 patients were included in this study. Notably, 3,358 (46.1%) patients did not receive active treatment. Compared with the no active treatment group, the CSS of patients who received treatment was significantly improved (median 6 vs. 0 months, P<0.001) and further validated in stage subgroups. Chemotherapy combined with local therapy was associated with the best CSS in regional and distant disease stages, with the hazard ratios (HR) and 95% confidence intervals (CI) being 0.30 (0.26-0.34) and 0.27 (0.25-0.30), respectively. Local therapy only appeared to confer better oncological outcomes (HR =0.33; 95% CI: 0.25-0.42) than chemotherapy only (HR =0.37; 95% CI: 0.29-0.47) in the localized disease stage. CONCLUSIONS: Although nearly half of octogenarians with SCLC did not receive active treatment in the real clinical setting, these patients may benefit from treatment. Chemotherapy combined with local therapy may provide the best treatment choice in octogenarians with advanced SCLC, while local therapy appears to play a more critical role in treating those with early-stage disease.

Growth hormone secretagogue receptor deficiency promotes lung cancer growth by affecting the Th17/Treg balance.

BACKGROUND: Cluster of differentiation 4 (CD4+) T cells plays a prominent role in eliminating cancer cells. The balance between T helper (Th)17 and regulatory T (Treg) cells is crucial for optimal immune response and protection against cancer. Growth hormone secretagogue receptor 1a (GHSR1a), a member of the G protein-coupled protein receptor superfamily, plays a critical role in immune cell function. The aim of our study is to investigate the role of GHSR1a in CD4+ T cell differentiation and lung cancer progression. METHODS: A subcutaneous lung cancer model was used to examine the role of GHSR1a in controlling tumor growth. Lewis lung carcinoma (LLC) cells were subcutaneously implanted into Ghsr1a -/- mice and wild-type (WT) mice. The ratio of Th17 and Treg in the draining lymph node of Ghsr1a -/- mice and WT tumor-bearing mice was detected by fluorescence-activated cell sorting (FACS). The effect of GHSR1a deficiency on Th17 and Treg cell differentiation was examined using an in vitro differentiation assay. The phosphorylation of mammalian target of rapamycin (mTOR), signal transducer, and activator of transcription (STAT)3 and STAT5 signaling was detected with Western blot. RESULTS: We found that the ablation of GHSR1a resulted in impaired anti-tumor immunity to control lung cancer growth in vivo. We also demonstrated that the deficiency of GHSR1a promoted a shift in the Th17/Treg balance toward enhanced Treg differentiation and inhibited Th17 differentiation both in vivo and in vitro, which suggests that GHSR1a regulates T cell lineage choices between Th17 and Treg cell commitment in the tumor microenvironment. Mechanistically, the deficiency of GHSR1a resulted in reduced phosphorylation in mTOR and STAT3, and increased phosphorylation in STAT5. CONCLUSIONS: Our findings showed the important role of GHSR1a in CD4+ T cell differentiation in the context of the lung cancer microenvironment. This research provides a novel molecular target and insights into interventions for the prevention and treatment of lung cancer.

Age at diagnosis is a heterogeneous factor for non-small cell lung cancer patients.

BACKGROUND: The incidence of lung cancer is reported as age dependent. However, the link between survival and age at diagnosis remains controversial. To date, few studies have examined the relationship between age and the clinicopathologic characteristics of patients with non-small cell lung cancer (NSCLC). METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we included in our analysis 151,919 patients diagnosed with NSCLC between 2004 and 2013. Logistic regression was used to evaluate the associations between age and clinicopathological characteristics. N and M stages were separately assessed in each T stage. RESULTS: Of the patients enrolled, 60,271 patients were diagnosed at the M1 stage, 147,263 patients had lymph node metastasis, and 49,862 patients underwent surgery. Younger age was inversely associated with high N stage and M stage (P<0.001, respectively). For each T stage, the inverse associations with M1 stage and lymph node metastasis were also presented (P<0.001, respectively). Age was an independent risk predictor for NSCLC patients by using univariate and multivariate analyses. CONCLUSIONS: Age at diagnosis is a heterogeneous factor for NSCLC patients: younger patients have an increased risk of lymph node and distant metastases, yet have a better prognosis.

Effects of dietary ß-glucan supplementation on growth performance and immunological and metabolic parameters of weaned pigs administered with Escherichia coli lipopolysaccharide.

The objective of this study was to determine the effects of dietary ß-glucan (BG) on growth performance and blood parameters in weaned pigs administered with Escherichia coli lipopolysaccharide (LPS). Twenty four pigs [24 ± 2 days old; 6.60 ± 0.04 kg body weight (BW)] were randomly allocated into two groups (12 pigs per group) with diets supplemented with 0 or BG at 200 mg kg-1 diet (CON vs. BG). These pigs were fed for a 35-day trial. On day 36, six pigs each from CON and BG were intramuscularly administered LPS (50 µg kg-1), while another 6 pigs from CON were intramuscularly administered an equivalent amount of sterile saline. Blood samples were collected at 3 h and rectal temperature data were collected at 0, 4, 8 and 24 h after LPS administration. Results showed that the pigs fed with BG diet had an increased average daily gain in rectal temperature during week 4, week 5 and the overall period, compared with the pigs fed with CON diet (P < 0.05), and resulted in greater final BW (P < 0.05). LPS administration increased the rectal temperature of the pigs fed with CON diet at 4, 8 and 24 h post administration (P < 0.05), and also increased the serum concentrations of pig-major acute phase protein, haptoglobin, tumor necrosis factor-α and interleukine-1 beta (P < 0.05). However, the pigs fed with BG diet had higher concentration of serum complement 3 (P < 0.05) and lower concentration of serum Pig-MAP, HP and interleuking-6 (P = 0.08) compared to that of pigs fed with CON diet after the LPS administration. Moreover, relative to the non-administered pigs, LPS administration increased the concentrations of serum creatinine, direct bilirubin and some of the amino acids in pigs after LPS administration (P < 0.05). In conclusion, the study suggested that feeding BG diet could improve the growth performance and partially alleviate the inflammation response of pigs after LPS administration.

The burdens of lung cancer involved multiple primary cancers and its occurring patterns-SEER Analysis between 1973 and 2006.

The prognosis of malignancies has improved in recent years, subsequent primary cancers (SPCs) have become more frequent. This study investigates the patterns of lung cancer involved multiple primary cancers. We enrolled 206,619 primary lung cancer patients and 2,071,922 patients with other primary malignancies from Surveillance, Epidemiology and End Results (SEER) database. Observed annual risk (OAR) and absolute numbers were used to describe the risk of SPC and observed cases of SPC per 10,000 person-years at risk. Overall, OAR of SPCs following lung cancer was 176.28. At follow-up, 41.26% of SPCs occurred within 12-59 months while the highest OAR appeared after 120 months. The overall OAR of subsequent lung cancer after other malignancies was 27.90. Overall, the highest OAR and the highest absolute numbers of subsequent lung cancers were noticed 60-119 months and over 120 months post-diagnosis, respectively. Ten related cancers were listed. Our findings encourage surveillance for 10 common SPCs in lung cancer survivors during follow-up as well as screening for lung cancer after 10 common malignancies.

Relationship of Lymph Node Micrometastasis and Micropapillary Component and Their Joint Influence on Prognosis of Patients With Stage I Lung Adenocarcinoma.

This study aimed to investigate the relationship between lymph node micrometastasis and histologic patterns of adenocarcinoma, with a particular focus on their joint effect on prognosis. We retrospectively reviewed 235 patients with stage I adenocarcinoma from January 2009 to December 2009. Lymph node micrometastasis was evaluated by immunohistochemical staining for cytokeratin (AE1/AE3) and thyroid transcription factor-1. A logistic regression model was applied to confirm the predictive factors of micrometastasis. Survival analysis was performed to evaluate the effect of micrometastasis on prognosis. Lymph node micrometastasis was observed in 35 patients (15%). Patients with micrometastasis had significantly worse recurrence-free survival (P<0.001) and overall survival (P<0.001) compared with those without micrometastasis. Micropapillary component was confirmed as an independent predictor of increased frequency of micrometastasis (P<0.001). Among 62 patients with adenocarcinoma with a micropapillary component, 23 (37%) had lymph node micrometastasis. Micropapillary-positive/micrometastasis-positive patients had significantly worse survival compared with micropapillary-positive/micrometastasis-negative patients (RFS, P=0.039; OS, P=0.002) and micropapillary-negative patients (recurrence-free survival, P<0.001; overall survival, P<0.001). Moreover, the presence of micrometastasis correlated with a higher risk of locoregional recurrence (P=0.031) rather than distant recurrence (P=0.456) in micropapillary-positive patients. In summary, lymph node micrometastasis was more frequently observed in adenocarcinoma with a micropapillary component. Moreover, lymph node micrometastasis could provide helpful prognostic information in patients with resected stage I lung adenocarcinoma with a micropapillary component; thus, immunohistochemical detection of micrometastatic tumor cells in lymph nodes should be recommended.

Maternal high fat intake affects the development and transcriptional profile of fetal intestine in late gestation using pig model.

BACKGROUND: The objective of this study was to investigate the effects of maternal high fat intake on intestinal development and transcriptional profile. METHODS: Eight gilts with similar age and body weight were randomly allocated into 2 groups receiving the control and high fat diets (HF diet) from d 30 to 90 of gestation, with 4 gilts each group and one gilt each pen. At d 90 of gestation, two fetuses each gilt were removed by cesarean section. Intestinal samples were collected for analysis of morphology, enzyme activities and transcriptional profile. RESULTS: The results showed that feeding HF diet markedly increased the fetal weight and lactase activity, also tended to increase intestinal morphology. Porcine Oligo Microarray analysis indicated that feeding HF diet inhibited 64% of genes (39 genes down-regulated while 22 genes up-regulated),which were related to immune response, cancer and metabolism, also markedly modified 33 signal pathways such as antigen processing and presentation, intestinal immune network for IgA production, Jak-STAT and TGF-ß signaling transductions, pathways in colorectal cancer and glycerolipid metabolism. CONCLUSION: Collectively, it could be concluded that maternal high fat intake was able to increase fetal weight and lactase activity, however, it altered the intestinal immune response, signal transduction and metabolism.

Efficient automated syntheses of high specific activity 6-[18F]fluorodopamine using a diaryliodonium salt precursor.

6-[(18)F]Fluorodopamine (6-[(18) F]F-DA) is a positron emission tomography radiopharmaceutical used to image sympathetic cardiac innervation and neuroendocrine tumors. Imaging with 6-[(18)F]F-DA is constrained, in part, by the bioactivity and neurotoxicity of 6-[(19)F]fluorodopamine. Furthermore, routine access to this radiotracer is limited by the inherent difficulty of incorporation of [(18)F]fluoride into electron-rich aromatic substrates. We describe the simple and direct preparation of high specific activity (SA) 6-[(18)F]F-DA from no-carrier-added (n.c.a.) [(18)F]fluoride. Incorporation of n.c.a. [(18)F]fluoride into a diaryliodonium salt precursor was achieved in 50-75% radiochemical yields (decay corrected to end of bombardment). Synthesis of 6-[(18)F]F-DA on the IBA Synthera® and GE TRACERlab FX-FN automated platforms gave 6-[(18)F]F-DA in >99% chemical and radiochemical purities after HPLC purification. The final non-corrected yields of 6-[(18)F]F-DA were 25 ± 4% (n = 4, 65 min) and 31 ± 6% (n = 3, 75 min) using the Synthera and TRACERlab modules, respectively. Efficient access to high SA 6-[(18)F]F-DA from a diaryliodonium salt precursor and n.c.a. [(18)F]fluoride is provided by a relatively subtle change in reaction conditions - replacement of a polar aprotic solvent (acetonitrile) with a relatively nonpolar solvent (toluene) during the critical radiofluorination reaction. Implementation of this process on common radiochemistry platforms should make 6-[(18)F]F-DA readily available to the wider imaging community.

A Novel Technique of Long-Segment Tracheal Repair With Extended Bronchial Flap of Right Upper and Main Bronchus Plus Tracheoplasty.

Long-segment tracheal resection and repair pose a great challenge. We present a successful case of long-segment tracheal defect repair with extended bronchial flap of the right upper and main bronchus, together with a tracheoplastic method. This is a novel technique for repairing a large tracheal defect with an extended pedicled bronchial flap in specific situations.

[Study the effects of flavonoids of Rhizoma Drynariae on gene level of rats without ovaries by technology of cDNA array].

OBJECTIVE: To study the effects of flavonoids of Rhizoma Drynariae on gene level of rats without ovaries (OP) by technology of cDNA array. METHOD: The models of rats without ovaries were made After. 24 weeks of treatment, put them to death and sampled 6 ml blood from the abdominal aorta and 4cm spinal cord. Take out the total RNA, then separate the mRNA to check. RESULT: There is 70 genes difference between the blank control group and model group, 9 genes difference between the blank control group and flavonoids of Rhizoma Drynariae group. The genes over expression of OP rats models regain normal after the models were fed on flavonoids of Rhizoma Drynariae. There are no differences in the spinal cords genes in the cDNA array analysis of this trail. CONCLUSION: The genes over expression of OP rats models regain normal after the models were fed on flavonoids of Rhizoma Drynariae for 6 months. The result shows that the flavonoids of Rhizoma Drynariae does have certain effects on the gene expression of rats without ovaries.