Surgery for stage IIB-IIIB small cell lung cancer.

PURPOSE: The NCCN guidelines do not recommend surgery for T3-4N0M0/T1-4N1-2M0 small cell lung cancer (SCLC) due to a lack of evidence. METHODS: Data of patients with T3-4N0M0/T1-4N1-2M0 SCLC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to determine the impact of surgery on this population. The Kaplan-Meier method, univariable and multivariable Cox proportional hazard regression, and propensity score matching (PSM) were used to compare the overall survival (OS) between the surgery and non-surgery groups. In addition, we explored whether sublobectomy, lobectomy, and pneumonectomy could provide survival benefits. RESULTS: In total, 8572 patients with SCLC treated without surgery and 342 patients treated with surgery were included in this study. The PSM-adjusted hazard ratio (HR, 95% CI) for surgery vs. no surgery, sublobectomy vs. no surgery, lobectomy vs. no surgery, pneumonectomy vs. no surgery, and lobectomy plus adjuvant chemoradiotherapy vs. chemoradiotherapy were 0.71 (0.61-0.82) (P < 0.001), 0.91 (0.70-1.19) (P = 0.488), 0.60 (0.50-0.73) (P < 0.001), 0.57 (0.28-1.16) (P = 0.124), and 0.73 (0.56-0.96) (P = 0.023), respectively. The subgroup analysis demonstrated consistent results. CONCLUSIONS: Lobectomy improved OS in patients with T3-4N0M0/T1-4N1-2M0 SCLC, while pneumonectomy also demonstrated a tendency to improve OS without statistical significance; however, sublobectomy showed no survival benefit.

Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study.

Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm+. Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological complete response (pCR) rate, pathological downstaging rate, margin-free resection (R0) rate, event-free survival, disease-free survival, progression-free survival, overall survival, treatment-related adverse events (TRAEs). The ORR was 70.2% (95% CI: 56.5% to 84.0%), meeting the pre-specified endpoint. The major pathological response (MPR), pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively. The median survivals were not reached. The most common TRAEs were diarrhea (78.7%) and rash (78.7%). Only three patients experienced grade 3/4 TRAEs. Biomarker analysis and tumor microenvironment dynamics by bulk RNA sequencing were included as predefined exploratory endpoints. CISH expression was a promising marker for Afatinib response (AUC = 0.918). In responders, compared to baseline samples, increasing T-cell- and B-cell-related features were observed in post-treatment tumor and lymph-node samples, respectively. Neoadjuvant Afatinib is feasible for stage III NSCLC+ patients and leads to dynamic changes in the tumor microenvironment.

Does the number of cycles of neoadjuvant therapy affect the efficacy of neoadjuvant chemoimmunotherapy for non-small cell lung cancer in locally advanced stage? Retrospective experience based on a single center.

BACKGROUND: The number of cycles of neoadjuvant therapy programmed cell death 1 (PD-1) inhibitor for locally advanced non-small cell lung cancer (NSCLC) remains controversial. METHODS: From October 2019 to March 2022, neoadjuvant chemoimmunotherapy followed by radical surgery for NSCLC patients with stage II-III were retrospectively reviewed in Shanghai Pulmonary Hospital. The radiologic response was assessed according to the Response Evaluation Criteria for Solid Tumors version 1.1. The major pathological response was defined as no more than 10% residual tumor. Student's t-test, chi-square test, and Mann-Whitney test were used for univariate analysis, logistic regression analysis was used for multivariate analysis. All statistical analyses were calculated by SPSS software (version 26). RESULTS: Among 108 patients, the number of patients who received 2-cycle (2-cycle group) and more than 2-cycle (>2-cycle group) neoadjuvant chemoimmunotherapy were 75 (69.4%) and 33 (30.6%), respectively. Compared with patients in the >2-cycle group, patients in the 2-cycle group had significantly smaller diagnostic radiological tumor size (37.0 mm vs. 49.6 mm, p = 0.022) and radiological tumor regression rate (36% vs. 49%, p = 0.007). However, no significant difference in pathological tumor regression rate was observed between patients in the 2-cycle group and >2-cycle group. Further logistic regression analysis demonstrated that the neoadjuvant chemoimmunotherapy cycle could independently affect the radiographic response (odds ratio [OR]: 0.173, 95% confidence interval [CI]: 0.051-0.584, p = 0.005) but not for pathological response (OR: 0.450, 95% CI: 0.161-1.257, p = 0.127). CONCLUSIONS: For patients diagnosed with stage II-III NSCLC, the number of neoadjuvant cycles administered can significantly influence the radiographic efficacy of chemoimmunotherapy.

The efficacy of neoadjuvant EGFR-TKI therapy combined with radical surgery for stage IIIB lung adenocarcinoma harboring EGFR mutations: A retrospective analysis based on single center.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could provide survival benefits for locally advanced EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC). However, the role of radical surgery for EGFR-TKI treated stage IIIB EGFRm NSCLC remains controversial. This study attempted to assess the feasibility of neoadjuvant EGFR-TKI followed by radical surgery for stage IIIB EGFRm NSCLC. Patients and Methods: Between 2013 and 2020, EGFRm lung adenocarcinoma (LUAD) patients in clinical stage IIIB undergoing neoadjuvant EGFR-TKI followed by surgery (T-S-Arm) and EGFR-TKI alone (T-Arm) were reviewed retrospectively in Shanghai Pulmonary Hospital (SPH). The chi-square test, Student's t-test or Fisher's exact test was performed for analysis of baseline characteristics. Progression-free survival (PFS) was estimated using the Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify independent predictors of progression. Results: A total of 43 patients were divided into T-S-Arm (n = 21) and T-Arm (n = 22). Patients were well-balanced between the two arms. The majority of patients were female (n = 25, 58.1%), non-smokers (n = 35, 81.4%), first-generation of EGFR-TKI treatment (n = 39, 90.7%), and exon 19 deletions (19-DEL) (n = 26, 60.5%). The median diagnostic age was 63.0 years [interquartile range (IQR), 54.0-67.5 years). At the cut-off date with June 30th 2022, median follow-up time was 28 months (IQR, 20-39 months). Neoadjuvant EGFR-TKI treatment followed by radical surgery could significantly improve the median PFS compared with patients underwent EGFR-TKI alone (23.0 months vs 14.5 months, P = 0.002). Multivariate Cox regression analysis demonstrated that radical surgery (T-S-Arm vs. T-Arm, HR: 0.406; 95% CI: 0.207-0.793, P = 0.027) was the only independent predictor for disease progression. The stratified analysis demonstrated patients with N2 disease could benefit from radical surgery (HR, 0.258; 95% CI, 0.107-0.618), especially for patients harboring L858R mutation (HR, 0.188; 95% CI, 0.059-0.604). Conclusions: For stage IIIB EGFRm NSCLC patients, the prognosis might be improved by neoadjuvant EGFR-TKI followed by radical surgery versus EGFR-TKI alone, especially for those with N2 disease and harboring L858R mutation.

Significance of spread through air spaces in small cell lung cancer.

PURPOSE: Tumor spread through air space (STAS) is a novel pattern of invasion related to poor prognosis in non-small cell cancer (NSCLC). Nevertheless, little is known about the role of STAS in small cell lung cancer (SCLC). We sought to determine whether STAS has a significant effect on recurrence among SCLC patients. METHODS: We collected clinical and follow-up information from 181 resected stage I-III SCLC patients and compared overall survival (OS) and disease-free survival (DFS) between the patients with or without STAS using the Kaplan‒Meier method. To explore the effect of STAS on recurrence, a competing-risk analysis was conducted. RESULTS: Among 181 SCLC patients, STAS was observed in 56 (30.94%) patients, and 125 (69.06%) patients did not have STAS. Furthermore, 33 (18.23%) patients had recurrence, including 12 patients with brain metastases. Patients with STAS had worse DFS. The cumulative incidence of any recurrence was higher in patients with STAS than in those without STAS. Univariate and multivariate competing-risk regression analyses revealed that sublobar resection and STAS were independent risk factors for SCLC recurrence (p = 0.009 and p = 0.029 for multivariate analysis, respectively). CONCLUSION: SCLC patients with STAS have worse DFS than SCLC patients without STAS. STAS is an independent prognostic factor in SCLC patients.

Gallium ions incorporated silk fibroin hydrogel with antibacterial efficacy for promoting healing of Pseudomonas aeruginosa-infected wound.

The continual resistance to antibiotics and the generation of a series of bacterial infections has emerged as a global concern, which requires appropriate measures and therapeutics to address such a menace. Herein, we report on Silk fibroin (SF) hydrogel with good biocompatibility and biodegradability fabricated through the crosslinking of the SF of different concentrations with Gallium nitrate (Ga (NO3)3) against Pseudomonas aeruginosa. However, the SF: Ga = 500: 1 (w/w) (SF/Ga) demonstrated a good bactericidal and wound healing effect as a result of the moderate and prolonged release of the Ga3+ following the gradual degradation of the hydrogel. The Ga3+, known for its innovative nature acted as a crosslinked agent and a therapeutic agent employing the "Trojan horse" strategy to effectively deal with the bacteria. Also, the Ga3+, which is positively charged neutralizes the negative potential value of the SF particles to reduce the charge and further induce the ß-sheet formation in the protein structure, a characteristic of gelation in SF. The morphology showed a fabricated homogenous structure with greater storage modulus- G' with low loss modulus- G'' modulus demonstrating the mechanical performance and the ability of the SF/Ga hydrogel to hold their shape, at the same time allowing for the gradual release of Ga3+. A demonstration of biocompatibility, biodegradability, bactericidal effect and wound healing in in vitro and in vivo present the SF/Ga hydrogel as an appropriate platform for therapeutic and for antibacterial wound dressing.

Optimize the Preparation of Novel Pyrite Tailings Based Non-sintered Ceramsite by Plackett-Burman Design Combined With Response Surface Method for Phosphorus Removal.

The large amount of untreated pyrite tailings has caused serious environmental problems, and the recycling of pyrite tailings is considered as an attractive strategy. Here, we reported a novel non-sintered ceramsite prepared with pyrite tailings (PTNC) as the main active raw material for phosphorus control, and the dosage effect of ingredients on total phosphorus (TP) removal ability was investigated. The results from Plackett-Burman Design (PBD) suggested the dosages of dehydrated sludge, sodium bicarbonate, and cement were the factors which significantly affect the TP removal ability. The Box-Behnken Design (BBD) based response surface methodology was further employed, and it indicated the interactions between different factors, and the optimized recipe for PTNC was 84.5 g (pyrite tailings), 10 g (cement), 1 g (calcined lime), 1 g (anhydrous gypsum), 3 g (dehydrated sludge), and 0.5 g (sodium bicarbonate). The optimized PTNC was characterized and which presented much higher specific area (7.21 m2/g) than the standard limitation (0.5 m2/g), as well as a lower wear rate (2.08%) rather than 6%. Additionally, the leaching metal concentrations of PTNC were far below the limitation of Chinese National Standard. The adsorption behavior of TP on PTNC was subsequently investigated with batch and dynamic experiments. It was found that the calculated max adsorption amount (qmax) was about 7 mg/g, and PTNC was able to offer a stable TP removal ability under different hydraulic retention time (HRT). The adsorption mechanism was discussed by model fitting analysis combined with XRD and SEM characterization, and cobalt phosphide sulfide was observed as the newly formed substance through the adsorption process, which suggested the existing of both physical and chemical adsorption effect. Our research not only offered an economic preparation method of ceramsite, but also broadened the recycling pathway of pyrite tailings.

Fully Printed Stretchable and Multifunctional E-Textiles for Aesthetic Wearable Electronic Systems.

Electronic textiles (e-textiles) that combine the wearing comfort of textiles and the functionality of soft electronics are highly demanded in wearable applications. However, fabricating robust high-performance stretchable e-textiles with good abrasion resistance and high-resolution aesthetic patterns for high-throughput manufacturing and practical applications remains challenging. Herein, the authors report a new multifunctional e-textile fabricated via screen printing of the water-based silver fractal dendrites conductive ink. The as-fabricated e-textiles spray-coated with the invisible waterproofing agent exhibit superior flexibility, water resistance, wearing comfort, air permeability, and abrasion resistance, achieving a low sheet resistance of 0.088 Ω sq-1 , high stretchability of up to 154%, and excellent dynamic stability for over 1000 cyclic testing (ε = 100%). The printed e-textiles can be explored as strain sensors and ultralow voltage-driven Joule heaters driven for personalized thermal management. They finally demonstrate an integrated aesthetic smart clothing made of their multifunctional e-textiles for human motion detection and body-temperature management. The printed e-textiles provide new opportunities for developing novel wearable electronics and smart clothing for future commercial applications.

Nitrite removal by Acinetobacter sp.TX: a candidate of curbing N2O emission.

The nitrite removal pathway in Acinetobacter sp. TX5 was explored through the key gene identification and the corresponding enzyme purification, after which the capability to reduce nitrite by immobilized beads was investigated in a fixed-bed reactor. Results revealed that a nosZ gene encoding nitrous oxide reductase (N2OR) exists in TX5 cells, and a N2OR responsible for the reduction of N2O to N2 was purified successfully with a molecular weight of 70.05 kDa, a purification fold of 16.30 and a recovery rate of 5.17%. For TX5 immobilization, the optimal values of polyvinyl alcohol (PVA), spent mushroom substrate (SMS) and Aci (TX5) obtained by response surface methodology (RSM) were 6.32%, 2.92% and 4.57%, respectively. In a fixed-bed reactor packed with immobilized TX5, the removal efficiency (RE) achieved 90% (at 50 h) for NO2--N and 85% (at 96 h) for total nitrogen (TN). On the basis of these results, a nitrite removal pathway in TX5 was proposed. Overall, Acinetobacter sp. TX5 might be a promising candidate for nitrite removal with an ability to suppress N2O accumulation.

[Remediation performance and mechanism of aquatic plants for iron polluted water]. / 水生植物修复铁污染水体的效果及作用机制.

To solve the yellow colorization in water caused by iron ion, we evaluated the remediation performances of six aquatic plant species (Hygroryza aristata, Myriophyllum verticillatum, Hydrocotyle verticillata, Jussiaea stipulacea, Pistia stratiotes and Rotala rotundifolia) using hydroponic experiment. Effects of iron concentration, pH, plant biomass on iron removal were investigated, and the intensification of removing iron incurred by aeration was also discussed. Results showed that all the examined plant species could improve both divalent iron and total iron removal, but with significant difference in their performance. Divalent iron concentrations were decreased by H. aristata and H. verticillata from 5.0 mg·L-1 to 0.23 and 0.26 mg·L-1 within 24 h, respectively, meeting the standard of supplementary items for the drinking water and surface water sources (divalent iron concentration ≤0.3 mg·L-1), while total iron concentrations declined to 0.84 and 1.21 mg·L-1 with removal efficiency of 83.2% and 75.8%, respectively. Concentrations of divalent iron and total iron of plant treatment plots at pH 5, 6, 7, 8 were not significantly different, with removal efficiency of divalent iron and total iron being among 95.4%-98.4% and 92.2%-94.6%, separately. When initial divalent iron concentration was less than 5.0 mg·L-1, removal efficiency of divalent iron and total iron increased with the increases of divalent iron concentration. The growth of H. aristata was inhibited at divalent iron concentration of 10.0 mg·L-1. Total iron removal was not stable during the trial. Removal efficiency of plant treatment rose only by 7.0% compared with the control, which was much lower than other concentration treatments. The divalent iron concentration was decreased to ＜ 0.3 mg·L-1 in 24 h at plant biomass :300 g, with no difference of removal efficiency among biomass treatments. Both intermittent and continuous aeration enhanced iron removal by H. aristata, but continuous aeration was more favorable for the removal of total iron due to stabilization.

Nutrient removal by Rotala rotundifolia: a superior candidate for ecosystem remediation at low temperatures.

Temperature is an extremely important factor affecting the nutrient (mainly nitrogen and phosphorus) removal of aquatic macrophytes. A novel submersed Rotala rotundifolia was separately cultivated at room and low temperatures to investigate its ability for nutrient removal. The physiological metabolism was analyzed to explore the mechanism of removing nutrients under a wide temperature range. The results showed that the removal efficiency (RE) of nutrients at low temperature was competitive with that obtained at normal temperature, demonstrating that temperature exerted no obvious influence on the nutrient removal by R. rotundifolia. The root vitality at 5 °C rose from the initial 0.26 to 1.5 mg g-1 h-1, whereas it fell by 38.66% at 10 °C, 28.74% at 20 °C and 5.15% at 30 °C. The peroxidase (POD) activity at 5 °C showed the maximum value on day 7 followed by a notable decline on day 21. All the peak values of soluble sugar and protein as well as MDA showed up at 5 °C and they were 5.5, 437.9 and 10.1 mg g-1, respectively. Chlorophyll a and b reached 8.4 and 4.4 mg g-1 on day 28, respectively, with a total chlorophyll content (a plus b) of 12.4 mg g-1 at 5 °C, all of which were higher than that at 30 °C. These results validated that R. rotundifolia could be a superior candidate suitable for in situ application.

Subduction of a low-salinity water mass around the Xisha Islands in the South China Sea.

Based on three climatologically observed temperature and salinity datasets (i.e., GDEM-V3, SCSPOD14 and WOA13), this paper reports a low-salinity (~34.32) water mass in the subsurface-to-intermediate layer around the Xisha Islands in the South China Sea. This water mass mainly subducts from the surface layer into the intermediate layer, characterized by a relatively low potential vorticity tongue extending from the bottom of mixed layer to the thermocline, and accompanied by a thermocline ventilation in spring (especially in April). The potential dynamics are the joint effects of negative wind stress curl, and an anticyclonic eddy triggered by the inherent topographic effect of the Xisha Islands, reflecting that downward vertical motion dominates the subduction. Despite lacking of the homogenous temperature and density, the low-salinity water mass is to some extent similar to the classic mode water and can be regarded as a deformed mode water in the South China Sea.

[Study on growth of height among students during their adolescence in Zhongshan, Guangdong].

OBJECTIVE: To discuss characteristics of height growth such as Peak Height Velocity (PHV) and Age at Peak Height Velocity (PHA) during adolescence, and to compare the results with other research findings. METHODS: Primary and middle school students' annual physical examination data of Zhongshan in 2005 - 2010 was used. The height velocity by age, PHV, PHA, height velocity by PHA were calculated. RESULTS: The average peak height velocity boys was (10.03 ± 1.67) cm/yr. and that of the girls was (8.39 ± 1.05) cm/yr. Both findings were close to the results from previous similar findings. The average age at which peak height velocity reached 12.28 ± 1.30 years for boys and 10.78 ± 1.04 years for girls, both lower than the previous findings. The correlation coefficients, between height level and PHA were -0.357 (P < 0.001) for boys and -0.338 (P < 0.001) for girls. CONCLUSION: The height levels were positively related to the height velocity before PHA. The Zhongshan students' PHA was lower than the Beijing, Shanghai and Shenyang students, also lower than American and Britain students', but their PHVs were similar.

Development of new rabbit monoclonal antibody to progesterone receptor (Clone SP2): no heat pretreatment but effective for paraffin section immunohistochemistry.

Evaluation of estrogen and progesterone receptor (ER, PgR) status in breast cancer is widely used for the prediction of the response to endocrine therapy and as a biologic parameter closely related to disease prognosis. The IHC method is considered to be a specific, sensitive, and economical method for determining ER and PgR status. The authors developed the first rabbit anti-PgR mAb (clone SP2) used in IHC on formalin-fixed, paraffin-embedded tissue sections from breast carcinomas. This new antibody, compared with currently available anti-PgR antibodies, has important advantages, including its reactivity even without heat-based antigen retrieval of fixed-embedded tissue sections in IHC and the predominance of nuclear immunostaining with only very low cytoplasmic signal. A comparative study of IHC on 107 histologic specimens from breast cancer cases showed that SP2 yields the same results as the wellknown mouse mAb to PgR (clone 1A6). The antibody affinity of SP2 is 12 times higher than that of 1A6. Thus, SP2 may prove of great value in the assessment of PgR status in human breast cancer.

Development of new rabbit monoclonal antibody to estrogen receptor: immunohistochemical assessment on formalin-fixed, paraffin-embedded tissue sections.

Evaluation of estrogen and progesterone receptors in breast cancer is widely used for the prediction of the response to endocrine therapy and as a biologic parameter closely related to disease prognosis. Immunohistochemistry is considered a specific, sensitive, and economic method for the determination of estrogen receptor/progesterone receptor status. The authors developed the first rabbit antiestrogen receptor monoclonal antibody (clone SP1) used in immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections especially from breast carcinomas. This new antibody, compared with currently available antiestrogen receptor antibodies, has important advantages, including its reactivity even without heat-based antigen retrieval of fixed, embedded tissue sections in immunohistochemistry, and the predominance of nuclear immunostaining with only a very low cytoplasmic signal. A comparative study of immunohistochemistry on 61 histologic specimens from breast cancer cases showed that SP1 yields the same results as the well-known, standardized mouse monoclonal antibody to estrogen receptor (clone 1D5). Antibody affinity of SP1 is 8 times higher than that of 1D5. Thus, SP1 may prove of great value in the assessment of estrogen receptor status in human breast cancer.

[Transforming growth factor beta receptor II mutations in RER positive colorectal cancers].

OBJECTIVE: To detect alterations of microsatellite loci [transforming growth factor beta receptor II (TGF-betaRII)(A)(10), TGF-betaRII(GT)(3), hMSH3(A)(8), hMSH6(C)(8), Bax(G)(8), IGFIIR(G)(8), IGFIIR(CT)(3)] and point mutations of TGF-betaRII (TGF-betaRII 452/454, TGF-betaRII 533). METHODS: PCR-SSLP, microdissection-PCR-SSLP, PCR-SSCP, clone sequencing and immunohistochemistry were used. RESULTS: The mutation rate of TGF-betaRII(A)(10) in RER+ (replication error positive) colorectal carcinomas was 33% (3/9). Similar mutations were also observed in adenomas with severe dysplasia. No mutations at other microsatellite loci were found. RER+ colorectal cancers mainly occurred in male patients at a young age and were more common in the colon than in the rectum (P < 0.05). CONCLUSIONS: RER+ colorectal cancers were found in young males and commonly located in the colon. A one third mutation rate in TGF-betaRII(A)(10) in these patients is lower than that observed in western populations, which may imply diverse pathways of carcinogenesis of RER+ colorectal carcinoma. TGF-betaRII(A)(10) mutation may play a role in the transforming process from an adenoma with severe dysplasia to a full blown carcinoma.