The relative risk of immune checkpoint inhibitor pneumonitis in advanced non-small- cell lung cancer: Meta-analyses of controlled clinical trials.

OBJECTIVE: Immune checkpoint inhibitor pneumonitis (CIP) is a prevalent form of immunotherapy-induced pulmonary toxicity, ranking among the leading causes of mortality associated with immune checkpoint inhibitors (ICIs). Despite its significance, the risk stratification of CIP in advanced non-small cell lung cancer (NSCLC) remains uncertain. In this study, we conducted a comprehensive analysis, comparing various factors such as histological types, treatment regimens, PD-L1 expression levels, and EGFR/ALK negativity in advanced NSCLC. Our investigation extends to evaluating the relative risk of developing CIP based on previous treatment history. This analysis aims to provide valuable insights for the identification of specific patient subgroups at higher risk, facilitating more effective risk management and precision therapy approaches. METHODS: PubMed, Embase, and Cochrane databases were systematically searched up to February 16, 2023. We conducted a screening of randomized controlled trials (RCTs) that compared ICI monotherapy or its combination with chemotherapy in advanced NSCLC. The trials were categorized based on histological type, treatment regimen, PD-L1 expression level, EGFR/ALK-negative status, and prior treatment history. Subsequently, the data were stratified into five subgroups, and the occurrences of all-grades (1-5) and high-grades (3-5) pneumonia events were extracted. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were then calculated for further analysis. RESULTS: Twenty-two RCTs, encompassing 13,725 patients with advanced NSCLC, were included in this analysis. Regardless of histology (OR = 2.47, 95% CI 1.41-4.33, P = 0.002; OR = 1.84, 95% CI 1.10-3.09, P = 0.02), treatment regimen (OR = 3.27, 95% CI 2.00-5.35, P < 0.00001; OR = 2.91, 95% CI 1.98-4.27, P < 0.00001), PD-L1 expression level (OR = 5.11, 95% CI 2.58-10.12, P < 0.00001; OR = 5.15, 95% CI 2.48-10.70, P < 0.0001), negative EGFR/ALK expression (OR = 4.32, 95% CI 2.22-8.41, P < 0.0001; OR = 3.6, 95% CI 1.56-8.28, P = 0.003), whether there is a history of treatment (OR = 3.27, 95% CI 2.00-5.35, P < 0.00001; OR = 2.74, 95% CI 1.75-4.29, P < 0.0001), ICI use was associated with a higher risk of all-grade (1-5) and high-grade (3-5) pneumonia compared to chemotherapy. Subgroup analysis revealed that the squamous group, the ICI vs. combination chemotherapy (CT) group, the PD-L1 > 50% group, and the previously untreated group had a higher risk of developing all-grade and grade 3-5 CIP (P < 0.05). CONCLUSIONS: In advanced NSCLC, ICI treatment was linked to an elevated risk of pneumonitis across all grades (1-5) as well as high-grade occurrences (3-5) compared to chemotherapy. Notably, individuals with squamous histology and high PD-L1 expression, along with those lacking a history of prior treatment, demonstrated a heightened susceptibility to developing immune-related pneumonitis of all grades (1-5) and high grades (3-5). These observations provide valuable insights for clinicians seeking to enhance the management of pulmonary toxicity associated with immunotherapy.

Charge-Shift Bonding Propensity in Halogen-Bonded BXY (B Is a Small Lewis Base H2O or NH3; X and Y Are Halogen Atoms) Complexes: An NBO/NRT/AIM Investigation.

Charge-shift (CS) bonding is a new bonding paradigm in the field of chemical bonds. Our recent study has revealed that certain Cu/Ag/Au-bonds display both CS bonding and ω-bonding characters. In this investigation, we extend our study to halogen bonding. Our focus is on scrutinizing the CS bonding in halogen-bonded BXY (B is a small Lewis base H2O or NH3; X and Y are halogen atoms) complexes by using natural bond orbital (NBO) analysis, natural resonance theory (NRT), and atoms in molecules (AIM) methods. The primary objective is to establish a connection between halogen bonding (B-X) in BXY and CS bonding in free XY (di-halogens). The calculations indicate that the studied BXY can be classified into two types. One type with a weak halogen bond shows closed-shell interaction. The other type with a stronger B-X interaction exhibits both CS bonding and ω-bonding characters (as seen in NH3ClF, NH3BrF, and NH3IF). Another interesting finding is a novel propensity that the CS bonding in free XY tends to carry over the halogen bonding in BXY, and the same propensity is found in Cu/Ag/Au ω-bonded species. The present study may offer an approach to probe CS bonding in many more 3c/4e ω-bonded molecules.

Enhanced Hydrogen Bonds of the (H2O)n (n = 4-8) Clusters Confined in Uranyl Peroxide Cluster Na20(UO2)20(O2)30.

Water is a basic resource and an essential component of living organisms. It often exhibits some novel properties under confinement. The water clusters (H2O)n (n = 4-8) confined in the cavity of uranyl peroxide cluster Na20(UO2)20(O2)30 (U20) have been computationally investigated by using ab initio molecular dynamics (AIMD) simulations and density functional theory (DFT) calculations in this study. The results show that the confined water clusters can form hydrogen bonds with the internal oxygen atoms (Ouranyl) of U20, and their conformations changed significantly. The average lengths (2.553-2.645 Å) of hydrogen bonds in confined (H2O)n are shorter than those (2.731-2.841 Å) in the corresponding free water clusters. Moreover, these confined hydrogen bonds show better hydrogen bond patterns according to the quantified indices. The natural bond orbital (NBO) calculations determine that there is electron transferring from the U20 to its interior (H2O)n. It is the main reason for enhancing hydrogen bond interactions among the confined water molecules because their oxygen atoms are more negatively charged and their hydrogen atoms are more positively charged. The quantum theory of atoms in molecules (QTAIM) and interacting quantum atoms (IQA) analyses indicate that the confined hydrogen bonds are more covalent, based on the significant electron density ρ(r) and local energy density H(r) at the bond critical points (BCPs), and the stronger energies of interatomic exchange interactions (Vxc). These findings may help to promote the communication of confined water clusters and enrich the understating of confined hydrogen bonds.

Ultrafiltration separation of Am(VI)-polyoxometalate from lanthanides.

Partitioning of americium from lanthanides (Ln) present in used nuclear fuel plays a key role in the sustainable development of nuclear energy1-3. This task is extremely challenging because thermodynamically stable Am(III) and Ln(III) ions have nearly identical ionic radii and coordination chemistry. Oxidization of Am(III) to Am(VI) produces AmO22+ ions distinct with Ln(III) ions, which has the potential to facilitate separations in principle. However, the rapid reduction of Am(VI) back to Am(III) by radiolysis products and organic reagents required for the traditional separation protocols including solvent and solid extractions hampers practical redox-based separations. Herein, we report a nanoscale polyoxometalate (POM) cluster with a vacancy site compatible with the selective coordination of hexavalent actinides (238U, 237Np, 242Pu and 243Am) over trivalent lanthanides in nitric acid media. To our knowledge, this cluster is the most stable Am(VI) species in aqueous media observed so far. Ultrafiltration-based separation of nanoscale Am(VI)-POM clusters from hydrated lanthanide ions by commercially available, fine-pored membranes enables the development of a once-through americium/lanthanide separation strategy that is highly efficient and rapid, does not involve any organic components and requires minimal energy input.

An Unusual Case of Systemic Lymphadenopathy - Kimura's Disease.

Background: Kimura's disease (KD) is a rare, chronic inflammatory disease. Clinically, subcutaneous nodules of the head and neck are typical manifestations, often accompanied by local lymphadenopathy or salivary gland enlargement, but there is also systemic damage, such as kidney involvement. Due to the lack of specific markers and imaging examination is not specific, it is difficult to clinically diagnose accurately and can be easy to misdiagnose. The treatment of KD is still not standardized and overtreatment can affect the quality of life. Case Presentation: The case of a 26-year-old man complaining of chest pain with self-conscious progressive lymphadenopathy after receiving Pfizer BioNTech COVID-19 vaccine for more than 1 month is presented. Eosinophil levels were normal and IgE elevated and the final diagnosis of KD was eventually confirmed by lymph node biopsy, which revealed lymphadenopathy with extensive eosinophilic infiltration in the right neck. Treatment was prednisone combined with methotrexate, resulting in satisfactory control. Conclusion: This case demonstrates that that Kimura disease can involve systemic lymphadenopathy, not only in the head and face or regional lymphadenopathy, suggested that KD should be excluded in patients with systemic lymphadenopathy. The current patient's response to treatment suggested that corticosteroid combined with disease-modifying antirheumatic drugs (DENARDs) was a promising treatment for KD patients with systemic damage. It is worth noting that the mechanism of immunity in the pathogenesis of KD still needs to be further studied.

Arteriovenous thrombotic events in a patient with advanced lung cancer following bevacizumab plus chemotherapy: A case report.

BACKGROUND: In driver gene-negative non-small cell lung cancer patients who relapse following radical resection, combination chemotherapy using bevacizumab and platinum-based dual drugs is known to increase both progression-free and overall survival. Treatment initially includes bevacizumab, and if patients are able to tolerate it, bevacizumab can continue to be utilized until disease progression. Bevacizumab is a recombinant humanized monoclonal neutralizing antibody that acts against vascular endothelial growth factor (VEGF). Various anti-VEGF monoclonal antibodies, such as bevacizumab, can increase the risk of arterial thromboembolism. Current data indicate that VEGF-targeted treatment does not significantly increase the risk of venous thromboembolism events, except for bevacizumab. CASE SUMMARY: A 55-year-old man underwent radical resection for cancer of the right lung. Six months following surgery, multiple metastases were observed in his left lung. Subsequently, six cycles of bevacizumab combined with pemetrexed/carboplatin chemotherapy was given. Efficacy evaluation continued to be partial relief according to RECIST 1.1 standards, and no noticeable adverse reactions were noted. After three cycles of maintenance therapy using a combination of bevacizumab and pemetrexed, the patient developed dizziness and dyspnea. The patient was diagnosed with acute cerebral infarction and pulmonary embolism following head magnetic resonance imaging, computed tomography (CT) angiography, and chest enhanced CT. Although the patient received low-molecular-weight heparin anticoagulation and other treatment, the patient eventually died of respiratory failure 1 mo later. This case report may offer some insight into fatal arteriovenous embolism, which has not been previously reported. CONCLUSION: Bevacizumab combined with chemotherapy may also increase the risk of arteriovenous thromboembolism. Accordingly, patients who receive angiogenesis inhibitor therapy should be carefully selected. Furthermore, close monitoring and timely intervention are necessary in order to reduce the risk of such toxicities.

Maintenance treatment of combination with bevacizumab vs single agent for advanced non-squamous non-small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND: When the patients of advanced non-squamous non-small cell lung cancer (NSCLC) have achieved remission by induction therapy, it is controversial that combination with bevacizumab is used as maintenance therapy. Pemetrexed is a classic drug for maintenance therapy, is bevacizumab the superiority to pemetrexed is also unclear. This meta-analysis aims to evaluate the effectiveness and safety of advanced non-squamous NSCLC in the maintenance treatment. METHOD: From the establishment as of December 6, 2020, PubMed, Embase, and Cochrane electronic databases were searched and the American Society of Clinical Oncology, European Society of Medical Oncology, and National Comprehensive Cancer Network databases in the past 10 years. The application of combination with bevacizumab, pemetrexed was studied in clinical trials of maintenance treatment for advanced NSCLC. The extracted data include progression-free survival (PFS), overall survival (OS), and grade 3-4 adverse events (AE). RESULTS: Seven clinical trials we screened, 6 were phase III RCTs, and a cohort trial, including 3298 patients. Compared with bevacizumab and pemetrexed, PFS of combination with bevacizumab was significantly improved (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.65-0.77, P < .00001), but OS was not improved (HR = 0.93, 95% CI = 0.85-1.01, P = .10). Compared with bevacizumab and pemetrexed, no significant difference of PFS (HR = 0.87, 95% CI = 0.69-1.09, P = .21), and OS (HR = 0.87, 95% CI = 0.72-1.05, P = .15) was found. A higher incidence of grade 3-4 AE occurred in combination with bevacizumab (odds ratio = 1.63, 95% CI = 1.35-1.97, P < .00001). CONCLUSIONS: PFS was significantly improved in patients with advanced non-squamous NSCLC who use bevacizumab combination with single-agent as maintenance treatment, but it does not translate into the advantages of OS; compared with bevacizumab, no PFS and OS benefits were found. A higher incidence of grade 3-4 AE occurred in combination with bevacizumab than pemetrexed and bevacizumab.

Ligands enhanced the Ac[triple bond, length as m-dash]Ac triple bond.

The multiple bonds between actinide atoms and their derivatives are computationally investigated extensively and compounds with an unsupported actinide-actinide bond, especially in low oxidation states, have attracted great attention. Herein, high level relativistic quantum chemical methods are used to probe the Ac-Ac bonding in compounds with a general formula LAcAcL (L = AsH3, PH3, NH3, H, CO, NO) at both scalar and spin-orbit coupling relativistic levels. H3AsAcAcAsH3, H3PAcAcPH3 and OCAcAcCO compounds show a type of zero valence Ac[triple bond, length as m-dash]Ac triple bond with a 1σ2g1π4u configuration, and H3AsAcAcAsH3 has been found to have the shortest Ac-Ac bond length of 3.012 Å reported so far. The Ac2 unit is very sensitive to the σ donor ligands and can form triple, double and even single bonds when suitable ligands are introduced, up to 3.652 Å with an Ac-Ac single bond in H3NAcAcNH3.

Meteorological factors, governmental responses and COVID-19: Evidence from four European countries.

With the global lockdown, meteorological factors are highly discussed for COVID-19 transmission. In this study, national-specific and region-specific data sets from Germany, Italy, Spain and the United Kingdom were used to explore the effect of temperature, absolute humidity and diurnal temperature range (DTR) on COVID-19 transmission. From February 1st to November 1st, a 7-day COVID-19 case doubling time (Td), meteorological factors with cumulative 14-day-lagged, government response index and other factors were fitted in the distributed lag nonlinear models. The overall relative risk (RR) of the 10th and the 25th percentiles temperature compared to the median were 0.0074 (95% CI: 0.0023, 0.0237) and 0.1220 (95% CI: 0.0667, 0.2232), respectively. The pooled RR of lower (10th, 25th) and extremely high (90th) absolute humidity were 0.3266 (95% CI: 0.1379, 0.7734), 0.6018 (95% CI: 0.4693, 0.7718) and 0.3438 (95% CI: 0.2254, 0.5242), respectively. While the DTR did not have a significant effect on Td. The total cumulative effect of temperature (10th) and absolute humidity (10th, 90th) on Td increased with the change of lag days. Similarly, a decline in temperature and absolute humidity at cumulative 14-day-lagged corresponded to the lower RR on Td in pooled region-specific effects. In summary, the government responses are important factors in alleviating the spread of COVID-19. After controlling that, our results indicate that both the cold and the dry environment also likely facilitate the COVID-19 transmission.

Potentially Resectable mCRC-treated with Cetuximab Combined with Chemotherapy.

Surgical resection of a potentially resectable metastatic colorectal cancer (mCRC) may lead to additional clinical benefits for the patients. In some cases, patients with initially unresectable lesions can be converted to resectable ones after induction of chemotherapy; and these patients are primarily treated with fluorouracil-based systemic chemotherapy preoperatively. However, the optimal protocol for neoadjuvant therapy has not been determined yet, and it remains a source of controversy about whether systemic chemotherapy combined with cetuximab can increase the surgical resection rate and obtain more clinical benefits. Metastatic CRC patients that received chemotherapy combined with cetuximab were compared with those undergoing chemotherapy alone. The hazard ratio (HR) and odds ratio (OR) were used as the efficacy indicators. The 95% confidence interval (95% CI) was used as interval estimation method. Seven studies including 1,895 patients were selected. Compared with patients undergoing chemotherapy, the patients receiving systemic chemotherapy combined with cetuximab of the R0 resection was not improved (OR=1.25; 95% CI, 0.76-2.06; p=0.08); The progression-free survival (PFS) of the patients received chemotherapy combined with cetuximab was slightly longer than those received chemotherapy alone (HR=0.88; 95% CI, 0.77-1; p=0.005); and the overall survival (OS) of patients undergoing systemic chemotherapy combined with cetuximab was not prolonged relative to that in patients receiving chemotherapy alone (HR=0.98; 95% CI, 0.86-1.11; p=0.04). Compared with patients receiving chemotherapy alone, the surgical resection rate and PFS are not increased in patients undergoing chemotherapy combined with cetuximab, but the OS is slightly prolonged. Key Words: Chemotherapy, Cetuximab, Colorectal cancer, Metastatic tumor, Surgery.

Airborne particulate matter, population mobility and COVID-19: a multi-city study in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, which has caused numerous deaths and health problems worldwide. This study aims to examine the effects of airborne particulate matter (PM) pollution and population mobility on COVID-19 across China. METHODS: We obtained daily confirmed cases of COVID-19, air particulate matter (PM2.5, PM10), weather parameters such as ambient temperature (AT) and absolute humidity (AH), and population mobility scale index (MSI) in 63 cities of China on a daily basis (excluding Wuhan) from January 01 to March 02, 2020. Then, the Generalized additive models (GAM) with a quasi-Poisson distribution were fitted to estimate the effects of PM10, PM2.5 and MSI on daily confirmed COVID-19 cases. RESULTS: We found each 1 unit increase in daily MSI was significantly positively associated with daily confirmed cases of COVID-19 in all lag days and the strongest estimated RR (1.21, 95% CIs:1.14 ~ 1.28) was observed at lag 014. In PM analysis, we found each 10 µg/m3 increase in the concentration of PM10 and PM2.5 was positively associated with the confirmed cases of COVID-19, and the estimated strongest RRs (both at lag 7) were 1.05 (95% CIs: 1.04, 1.07) and 1.06 (95% CIs: 1.04, 1.07), respectively. A similar trend was also found in all cumulative lag periods (from lag 01 to lag 014). The strongest effects for both PM10 and PM2.5 were at lag 014, and the RRs of each 10 µg/m3 increase were 1.18 (95% CIs:1.14, 1.22) and 1.23 (95% CIs:1.18, 1.29), respectively. CONCLUSIONS: Population mobility and airborne particulate matter may be associated with an increased risk of COVID-19 transmission.

The Correlation of Type 2 Diabetes Status with Bone Mineral Density in Middle-Aged Adults.

BACKGROUND: Bone metabolism can be influenced by type 2 diabetes mellitus (T2DM). However, the relationship between T2DM and bone mineral density (BMD) remains inconsistent. This study explored the differences in BMD in middle-aged adults with and without T2DM. METHODS: We conducted a cross-sectional study of 4986 participants aged 40-59 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2018. We performed multivariable logistic regression models to evaluate the associations between T2DM status, serum glucose, glycohemoglobin (HbA1c), disease duration and lumbar BMD. RESULTS: There was a positive association between T2DM status and lumbar BMD in all three models (model 1: ß=0.039, 95% CI: 0.025-0.052; model 2: ß=0.045, 95% CI: 0.031-0.059; model 3: ß=0.035, 95% CI: 0.014-0.055). In the subgroup analysis stratified by gender, this positive association existed in both gender after adjusting for confounders (males: ß=0.033, 95% CI: 0.003-0.062; females: ß=0.035, 95% CI: 0.008-0.062). Besides, there were no significant associations of serum glucose, HbA1c, disease duration with lumbar BMD in both genders with T2DM. CONCLUSION: This study indicated that middle-aged adults with T2DM had significantly higher lumbar BMD compared with those without DM.

Impact of meteorological factors on the COVID-19 transmission: A multi-city study in China.

The purpose of the present study is to explore the associations between novel coronavirus disease 2019 (COVID-19) case counts and meteorological factors in 30 provincial capital cities of China. We compiled a daily dataset including confirmed case counts, ambient temperature (AT), diurnal temperature range (DTR), absolute humidity (AH) and migration scale index (MSI) for each city during the period of January 20th to March 2nd, 2020. First, we explored the associations between COVID-19 confirmed case counts, meteorological factors, and MSI using non-linear regression. Then, we conducted a two-stage analysis for 17 cities with more than 50 confirmed cases. In the first stage, generalized linear models with negative binomial distribution were fitted to estimate city-specific effects of meteorological factors on confirmed case counts. In the second stage, the meta-analysis was conducted to estimate the pooled effects. Our results showed that among 13 cities that have less than 50 confirmed cases, 9 cities locate in the Northern China with average AT below 0 °C, 12 cities had average AH below 4 g/m3, and one city (Haikou) had the highest AH (14.05 g/m3). Those 17 cities with 50 and more cases accounted for 90.6% of all cases in our study. Each 1 °C increase in AT and DTR was related to the decline of daily confirmed case counts, and the corresponding pooled RRs were 0.80 (95% CI: 0.75, 0.85) and 0.90 (95% CI: 0.86, 0.95), respectively. For AH, the association with COVID-19 case counts were statistically significant in lag 07 and lag 014. In addition, we found the all these associations increased with accumulated time duration up to 14 days. In conclusions, meteorological factors play an independent role in the COVID-19 transmission after controlling population migration. Local weather condition with low temperature, mild diurnal temperature range and low humidity likely favor the transmission.

Association of XPD Asp312Asn polymorphism and response to oxaliplatin-based first-line chemotherapy and survival in patients with metastatic colorectal cancer.

BACKGROUND: Identification of biomarkers predicting a response to chemotherapeutic drugs would greatly ease the selection of personalized therapy. The protein xeroderma pigmentosum group D (XPD) functions in nucleotide excision repair (NER) to remove DNA cross-links and in the regulation of transcription. The potential role of the Asp312Asn polymorphism in predicting the response to chemotherapy has not been established. OBJECTIVES: This prospective study was designed to determine the role of the XPD Asp312Asn polymorphism in predicting the response to oxaliplatin-based first-line chemotherapy and survival in patients with metastatic colorectal cancer. MATERIAL AND METHODS: A total of 106 patients treated with 2 cycles of either FOLFOX4 (n = 72) or XELOX (n = 34) regimen as the chemotherapy were enrolled. The genotype of XPD Asp312Asn polymorphism was analyzed using TaqMan probe-based real-time polymerase chain reaction (PCR). Logistic regression was applied to predict the response to treatment protocols. Cox regression models were applied to predict overall survival. RESULTS: The overall response to chemotherapy was 57.6% (61/106). FOLFOX4 and XELOX regimens demonstrated comparable efficacy. The XPD Asp312Asn polymorphism was not associated with the response to either FOLFOX4 or XELOX regimen in univariate and in multivariate logistic regression analyses. Levels of carcinoembryonic antigen (CEA) ≥5 ng/mL and female gender were associated with a lack of response to FOLFOX4, but not to XELOX regimen. In a multivariate survival analysis, XPD Asp312Asn AA genotype, lack of response to chemotherapy, CEA ≥ 5 ng/mL, and age ≥65 were significantly associated with worse overall survival. CONCLUSIONS: The XPD Asp312Asn polymorphism is associated with overall survival, but it is not a biomarker in predicting the response to oxaliplatin-based first-line chemotherapy in patients with metastatic colorectal cancer.

Relationship between the Asp1104His polymorphism of the nucleotide excision repair gene ERCC5 and treatment sensitivity to oxaliplatin in patients with advanced colorectal cancer in China.

OBJECTIVES: To study the relationship between the Asp1104His polymorphism of the nucleotide excision repair gene ERCC5 and treatment sensitivity to oxaliplatin in patients with advanced colorectal cancer (CRC) in China. METHODS: A group of 226 patients in the Department of Gastrointestinal Oncology at Zhejiang Xiaoshan Hospital from July 2011∼December 2016 and a control group of 226 normal healthy individuals were involved in this study. All patients were first diagnosed with advanced CRC and were treated with oxaliplatin-based chemotherapy. The genotype of ERCC5 at the site of amino acid 1104 was determined by a TaqMan probe-based real-time PCR approach. RESULTS: There were no differences in age or gender between the groups, but the percentages of smokers and individuals with a family history of cancer were significantly higher in the patient group than in the control group. Analysis of the G/C polymorphism frequency among the patients and the healthy controls showed that the frequencies of the CC genotype and the CC+GC genotype were significantly related to CRC, but no significant difference in these frequencies was found between genders. The analysis of the relationship between the 5-year survival rate and different genotypes showed that in the total patient group, regardless of gender, the 5-year survival rate was significantly associated with the Asp1104His polymorphism of ERCC5. CONCLUSIONS: The Asp1104His polymorphism of ERCC5 was associated with the risk and 5-year survival rate of CRC as well as treatment sensitivity to oxaliplatin.

Model of lymph node metastasis posterior to the right recurrent laryngeal nerve in papillary thyroid carcinoma.

BACKGROUND: Cervical lymph node metastasis (LNM) is a prognostic factor of papillary thyroid carcinoma (PTC). The way to deal with lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is controversial. Nevertheless, if metastatic lymph nodes are not removed during the first operation, the subsequent salvage surgery of recurrent tumor in this area would entail high risk and complication. The purpose of this study was to develop a preoperative prediction model for LN-prRLN metastasis in PTC patients using clinicopathological characteristics. PATIENTS AND METHODS: We performed a prospective study of 595 patients with PTC who underwent LN-prRLN dissection from March 2014 to June 2017. The clinicopathological data were randomly divided into derivation (n=476) and validation sets (n=119). A predictive model was initially established based upon the data of the derivation set via multivariate analyses, and the accuracy of the model was then examined with data of the validation set. The discriminative power of this model was assessed in both sets. RESULTS: Metastases of the LN-prRLN were identified in 102 (17.14%) of 595 patients. Age (odds ratio [OR] 0.971, 95% CI, 0.949-0.994, p=0.013), tumor size (OR 2.163, 95% CI, 1.431-3.270, p<0.001), capsular invasion (OR 1.934, 95% CI, 1.062-3.522, p=0.031), and right LNM (OR 3.786, 95% CI, 2.012-7.123, p<0.001) were significantly associated with LN-prRLN metastasis. The areas under the curves were 0.790 for the derivation set (sensitivity 71.95%, specificity 78.68%) and 0.878 for the validation set (sensitivity 85.00%, specificity 78.79%). CONCLUSION: We developed and validated the first model to predict LN-prRLN metastases in patients with PTC based on clinicopathological parameters.

Brønsted Basicity in Metal-Organic Framework-808 and Its Application in Base-Free Catalysis.

The Brønsted basicity in activated metal-organic framework-808 (hereinafter denoted as MOF-808a) was confirmed by the analyses of CO2-TPD-MS, in situ DRIFTS, and acid-base titration. MOF-808a exhibited efficient recyclable catalytic activities for Heck coupling and oxidation of alcohol as a one-pot tandem reaction in base-free catalysis. It is the first evidence of the Brønsted basicity in zirconium metal-organic frameworks (Zr-MOFs) and gave rise to a new opportunity to extend the catalytic application of Zr-MOFs.

Relationship between the Asp1104His polymorphism of the nucleotide excision repair gene ERCC5 and treatment sensitivity to oxaliplatin in patients with advanced colorectal cancer in China

OBJECTIVES: To study the relationship between the Asp1104His polymorphism of the nucleotide excision repair gene ERCC5 and treatment sensitivity to oxaliplatin in patients with advanced colorectal cancer (CRC) in China. METHODS: A group of 226 patients in the Department of Gastrointestinal Oncology at Zhejiang Xiaoshan Hospital from July 2011∼December 2016 and a control group of 226 normal healthy individuals were involved in this study. All patients were first diagnosed with advanced CRC and were treated with oxaliplatin-based chemotherapy. The genotype of ERCC5 at the site of amino acid 1104 was determined by a TaqMan probe-based real-time PCR approach. RESULTS: There were no differences in age or gender between the groups, but the percentages of smokers and individuals with a family history of cancer were significantly higher in the patient group than in the control group. Analysis of the G/C polymorphism frequency among the patients and the healthy controls showed that the frequencies of the CC genotype and the CC+GC genotype were significantly related to CRC, but no significant difference in these frequencies was found between genders. The analysis of the relationship between the 5-year survival rate and different genotypes showed that in the total patient group, regardless of gender, the 5-year survival rate was significantly associated with the Asp1104His polymorphism of ERCC5. CONCLUSIONS: The Asp1104His polymorphism of ERCC5 was associated with the risk and 5-year survival rate of CRC as well as treatment sensitivity to oxaliplatin.

Clinical value and indication for the dissection of lymph nodes posterior to the right recurrent laryngeal nerve in papillary thyroid carcinoma.

Lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) are common sites of nodal recurrence after the resection of papillary thyroid carcinoma (PTC). However, the indication for LN-prRLN dissection remains debatable. We therefore studied the relationships between LN-prRLN metastasis and the clinicopathological characteristics in 306 patients with right or bilateral PTC who underwent LN-prRLN dissection. We found that LN-prRLN metastasis occurred in 16.67% of PTC and was associated with a number of the clinicopathological features. The receiver-operator characteristic (ROC) analysis showed that the areas under the ROC curves for the prediction of LN-prRLN metastasis by the risk factors age < 35.5 years, right tumor size > 0.85 cm, lymph node (right cervical central VI-1) number > 1.5, metastatic lymph node (right cervical central VI-1) size > 0.45 cm, and lymph node number in the right cervical lateral compartment > 0.5 were 0.601, 0.815, 0.813, 0.725, and 0.743, respectively. In conclusion, the risk factors for LN-prRLN metastasis in patients suffering right thyroid lobe or bilateral PTC include age ≤ 35.5 years, right tumor size ≥ 0.85 cm, capsular invasion, metastatic lymph node (right cervical central VI-1) number ≥ 2, metastatic lymph node (right cervical central VI-1) size ≥ 0.45 cm, and metastatic lymph node number in the right cervical lateral compartment ≥ 1. In patients whose risk factors can be identified pre-operatively or intraoperatively, the dissection of LN-pr-RLN should be considered during right cervical central compartment dissection.

Cost-utility analysis of rhegmatogenous retinal detachment surgery in Shanghai, China.

PURPOSE: To perform a short-term and a long-term cost-utility analysis of rhegmatogenous retinal detachment (RRD) surgery in Shanghai, China. METHODS: A total of 117 patients who underwent RRD surgery at Shanghai First People's Hospital, Affiliated Shanghai Jiaotong University, and then underwent follow-up for at least 1 year, were included in the study. Costs associated with RRD surgery and time trade-off utility values before and after surgery were recorded. Short-term analysis was made for 1 year. Quality-adjusted life years (QALYs) gained by RRD surgery over the lifetime were calculated at a 3% discount rate in the long-term analysis. This study used the bootstrap method in statistical analysis and one-way sensitivity analyses to test robustness of the results. RESULTS: Compared with no treatment, the mean incremental costs of RRD surgery was 11,384 Chinese yuan (CN¥) (US$1751); the mean additional QALYs gained was 0.05 (95% confidence interval [CI] 0.04-0.06) for 1 year and 0.88 (95% CI 0.64-1.13) for life expectancy; the incremental cost effectiveness ratio (ICER) was CN¥224,921 (US$34,603)/QALY for the short-term, and CN¥13,794 (US$2122)/QALY for the long-term. In short-term analysis, the ICER was CN¥150,087 (US$23,090)/QALY for scleral buckling surgery, and CN¥507,727 (US$78,112)/QALY for vitreous surgery. In the long-term analysis, the ICER was CN¥6280 (US$966)/QALY for scleral buckling, and CN¥30,756 (US$4732)/QALY for vitreous surgery. CONCLUSIONS: For RRD patients, surgery increases QALYs. In a 1-year analysis, surgery is not a cost-effective treatment, however it is cost-effective over the lifetime.