[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer.

BACKGROUND: Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. PATIENTS AND METHODS: A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients' PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. RESULTS: RS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 [95% confidence interval (CI) 0.923-0.993], 0.941 (95% CI 0.904-0.977), 0.928 (95% CI 0.886-0.971), and 0.920 (95% CI 0.862-0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability. CONCLUSION: CT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.

Disulfide-Linked Dendritic Oligomeric Phthalocyanines as Glutathione-Responsive Photosensitizers for Photodynamic Therapy.

A series of disulfide-linked dendritic phthalocyanines were synthesized by using the CuI -catalyzed alkyne-azide cycloaddition reaction as the key step. Whereas these compounds were essentially nonaggregated in N,N-dimethylformamide, they were stacked in citrate solution (pH 7.4, with 1 % Cremophor EL), as shown by the broad appearance of their Q-band absorption. Having two-to-six zinc(II) phthalocyanine units in a molecule, these compounds were significantly self-quenched, particularly in citrate solution. Both the fluorescence intensity and singlet-oxygen generation efficiency were significantly lower than those of the monomeric counterparts, and the self-quenching efficiency increased as the number of phthalocyanine units increased. Upon interaction with 5 mm glutathione (GSH) in citrate solution, the fluorescence intensity of these compounds increased as a result of cleavage of the disulfide linkages and separation of the phthalocyanine units, which thereby reduced the self-quenching effect. The "on/off" ratios were found to be 7, 18, 23, and 21 for the dimeric (PC2), trimeric (PC3), tetrameric (PC4), and hexameric (PC6) systems, respectively. GSH also enhanced the fluorescence emission inside human colon adenocarcinoma HT29 cells and promoted the formation of singlet oxygen of these compounds. Upon irradiation, their half maximal inhibitory concentration (IC50 ) values were found to be in the range of 0.18 to 0.38 µm. Finally, the biodistribution and activation of PC2 and PC6 were also examined in HT29 tumor-bearing nude mice. For both compounds, the fluorescence intensity per unit area at the tumor was found to grow gradually during the first 24 h. Whereas the intensity then dropped for PC2, the intensity for PC6 remained steady over the following 6 d, which might have been a result of the enhanced permeability and retention effect arising from the larger molecular mass of the hexameric system.

Risk of complications of ultrasound-guided renal biopsy for adult and pediatric patients with systemic lupus erythematosus.

Objective The objective of this paper is to identify the risk of complications of real-time ultrasound-guided renal biopsy in adult and pediatric patients with systemic lupus erythematosus (SLE). Materials and methods This retrospective study examined outcomes of 296 renal biopsy procedures in 275 SLE patients. Imaging-confirmed symptomatic hematoma was regarded as a major complication when intervention (blood transfusion, angiographic embolization, or surgery) was required or as a minor complication otherwise. Clinical and laboratory data were compared between groups with or without complications after initial or subsequent renal biopsy. Binary logistic regressions were used to evaluate complication risk of initial renal biopsy. Results Overall complication rate of initial renal biopsy was 8.7% (major: 2.9%, minor: 5.8%). Three patients expired from pulmonary hemorrhage, thrombotic microangiopathy, and pneumonia. Pediatric SLE patients tended to have a higher rate of major complications (12.5%) than adult patients (2.3%). According to multivariable analysis results, elevated serum creatinine (SCr) level (OR 1.45; 95% CI 1.17-1.81 per mg/dl), prolonged prothrombin time (PT) (OR 2.2; 95% CI 1.05-4.62 per second), and thrombocytopenia (OR 4.3; 95% CI 1.56-11.9) increased overall complication risk of initial renal biopsy. Age < 18 years (OR 8.43; 95% CI 1.21-58.8), thrombocytopenia (OR 16.4; 95% CI 2.44-110.5), and elevated SCr level (OR 1.97; 95% CI 1.36-2.86 per md/dl) increased risk of major complications. Thrombocytopenia, prolonged PT, and elevated SCr level were associated with complications after subsequent renal biopsy (all p = 0.01). Conclusions SLE patients, particularly patients under 18 years old or with elevated SCr level, prolonged PT, or thrombocytopenia, have an increased risk of complications after initial or subsequent renal biopsy.

[Application of decision curve on evaluation of MRI predictive model for early assessing pathological complete response to neoadjuvant therapy in breast cancer].

Objective: To construct a dynamic enhanced MR based predictive model for early assessing pathological complete response (pCR) to neoadjuvant therapy in breast cancer, and to evaluate the clinical benefit of the model by using decision curve. Methods: From December 2005 to December 2007, 170 patients with breast cancer treated with neoadjuvant therapy were identified and their MR images before neoadjuvant therapy and at the end of the first cycle of neoadjuvant therapy were collected. Logistic regression model was used to detect independent factors for predicting pCR and construct the predictive model accordingly, then receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive model. Results: ΔArea(max) and Δslope(max) were independent predictive factors for pCR, OR=0.942 (95%CI: 0.918-0.967) and 0.961 (95%CI: 0.940-0.987), respectively. The area under ROC curve (AUC) for the constructed model was 0.886 (95%CI: 0.820-0.951). Decision curve showed that in the range of the threshold probability above 0.4, the predictive model presented increased net benefit as the threshold probability increased. Conclusions: The constructed predictive model for pCR is of potential clinical value, with an AUC>0.85. Meanwhile, decision curve analysis indicates the constructed predictive model has net benefit from 3 to 8 percent in the likely range of probability threshold from 80% to 90%.

Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation.

BACKGROUND AND AIMS: Recent studies have suggested that serum uric acid (SUA) induces oxidative stress and inflammation, which are involved in the mechanism of cardiac hypertrophy. In patients with atrial fibrillation (AF), comorbidity of left ventricular hypertrophy (LVH) exacerbates cardiac function. In this study, we investigated the association between SUA and cardiac hypertrophy in AF patients. METHODS AND RESULTS: Initially, 1296 consecutive elderly patients (age >60) with nonvalvular AF were retrospectively selected from the inpatient clinic between January 2012 and April 2015. Demographic, clinical, and echocardiographic characteristics were carefully recorded. The final study population was 577 patients. The mean SUA level was significantly higher in patients with LVH than those without LVH. Compared with the non-LVH group, the LVH group was older, had a higher percentage of female patients, and had lower hemoglobin levels and estimated glomerular filtration rates. Patients in the LVH group also had a higher rate of coronary heart disease and fewer had history of radiofrequency ablation compared with the non-LVH group. In the hyperuricemia group, B-type natriuretic peptide levels, left atrial diameter, left ventricular mass index, and percentage of NYHA (New York Heart Association) class III/IV were significantly higher than the SUA normal group. Multivariate logistic regression analysis indicated the independent risk factors for LVH in elderly AF patients included SUA, age, male sex, the presence of coronary heart disease, and diuretic therapy. Subgroup analysis identified SUA as a significant risk factor associated with LVH in men. CONCLUSIONS: SUA was independently associated with LVH in elderly male patients with nonvalvular AF.

Practices and thinking of laboratory detection in the aid to West Africa to fight against Ebola.

BACKGROUND: The outbreak of Ebola virus disease in West Africa has brought great disaster to the people's health in affected countries. China dispatched first group of public health experts and medical staff to Sierra Leone in September 2014 to fight Ebola. METHODS: To systematically collect huge amount of primary data, and to make analysis, draw conclusions and lessons in terms of six aspects, respectively as training before departure, local disease information, track of epidemic situation, transformation of temporary laboratory, detection of Ebola virus samples as well as assessment through single blind test. RESULTS: 1) Our team has launched preparatory works in advance before going to Sierra Leone. 2) Malaria is the country's severest infectious disease. 3) Observation centers were overcrowded with large number of suspected cases being inspected, implying high risk of nosocomial infection. 4) A BSL-II laboratory with 3 work areas and 2 buffer areas was built, achieving several major functions within 6 days. 5) Confirmed by South African Raqqa laboratory, our detection accuracy reached 100%. 6) At one week before return, the daily average sample amount of our team reached 66 cases and our detection capability was equivalent to that of USA. CONCLUSIONS: Successful experience from fighting against Ebola in Sierra Leone could be summarized as: 1) Optimized processes and scientific security measures are prerequisite to improving the detection ability. 2) The close collaboration between laboratory and observation center has created a new model of China's foreign aid. 3) Comprehensive information investigation and training lay a solid foundation for the successful completion of tasks.

[Association between ambulatory arterial stiffness index with left ventricular mass index in the elderly hypertensive patients].

Objective: To investigate the relationship between ambulatory arterial stiffness index (AASI) and left ventricular mass index (LVMI) in the elderly hypertensive patients. Methods: This study population consisted of 332 elderly hypertensive patients, who hospitalized in our department from January 2012 to December 2014.AASI was calculated from 24 h ambulatory BP monitoring recordings and LVMI from echocardiography examination.According to the median value of AASI, patients were divided to less than the AASI median group (low AASI group) and equal to or above the AASI median group (high AASI group). Differences between two groups were evaluated using the Student's t-test and Chi-square test.Univariate association was assessed by the Pearson correlation analyses.Multivariate linear regression models were performed to analyze the correlation between AASI and LVMI. Results: LVMI was significantly higher in high AASI group compared with low AASI group ( (115.91±21.36) g/m2 vs.(104.11±17.24) g/m2,P=0.008). Pearson correlation analyses showed that AASI and 24 h pulse pressure were positively correlated to LVMI (r=0.332, P<0.001; r=0.169, P=0.002). In multivariate linear regression model, AASI(ß=44.48, P<0.001), LDL-C(ß=-5.97, P<0.001) and UA (ß=0.02, P=0.045)showed significant association with LVMI. Conclusion: AASI independently associated with LVMI, and AASI might be one predictor of left ventricular hypertrophy in hospitalized elderly hypertensive patients.

Evaluating local lymph node metastasis with magnetic resonance imaging, endoluminal ultrasound and computed tomography in rectal cancer: a meta-analysis.

AIM: Magnetic resonance imaging (MRI), endorectal ultrasound (EUS) and computed tomography (CT) are commonly used to evaluate lymph node (LN) metastasis for rectal cancer, but there is no agreement on which form of imaging is most accurate. The study aimed to review systematically the diagnostic performance of the three imaging modalities. METHOD: The PubMed, Cochrane Library and EMBASE databases were systematically searched for English and Chinese language studies evaluating the diagnostic accuracy of MRI, EUS and/or CT for evaluating LN metastasis. Papers published before 31 December 2013 were included in the search. Subject-level data were included. Diagnostic odds ratios were calculated for each modality and summary receiver operating characteristic curves were constructed using hierarchical regression models. The performance of the three modalities was compared. RESULTS: The analysis included data from 123 studies evaluating LN metastasis. The sensitivity and specificity in patients having no chemoradiotherapy were 0.77 and 0.76 for MRI, 0.57 and 0.80 for EUS and 0.79 and 0.76 for CT. The three modalities showed similar accuracy (P = 0.39). MRI showed higher accuracy than EUS for patients who received neoadjuvant therapy (P = 0.04). MRI at a field strength > 1.5 T yielded better performance than EUS (P = 0.03) and similar performance to CT (P = 0.17). High resolution MRI showed similar diagnostic accuracy to EUS (P = 0.18) and CT (P = 0.16). CONCLUSION: MRI, EUS and CT show similar accuracy but none could provide reliable evaluation for LN metastasis. MRI rather than EUS is recommended for LN evaluation after neoadjuvant therapy. MRI at a field strength of 3.0 T is the recommended method for MRI examination. But high resolution MRI does not improve the diagnostic performance in evaluating LN metastasis.

Evaluating the response of gastric carcinomas to neoadjuvant chemotherapy using iodine concentration on spectral CT: a comparison with pathological regression.

AIM: To investigate the potential of iodine concentration (IC) determined using virtual monochromatic spectral computed tomography (CT) to predict the response of gastric carcinomas to preoperative neoadjuvant chemotherapy (NC). MATERIALS AND METHODS: A total of 20 patients were enrolled who underwent two spectral CT examinations (1 week before and two cycles after NC). The percentage change in tumour thickness (%ΔCWT) and in IC on the arterial phase (%ΔIC-a) and venous phase (%ΔIC-v) after NC were calculated and compared for different histopathological regression grades and response groups. The diagnostic efficacies to discriminate good response (GR) and poor response (PR) of the above three parameters were evaluated using receiver operating characteristic (ROC) curves. RESULTS: The decrease rate of %ΔIC-a for the GR group was higher than that for the PR group (-0.59 [-0.76, -0.20] versus -0.11 [-0.75, 0.92], p=0.012). There was no significant difference in the %ΔIC-v and %ΔCWT values between the GR and PR groups (p=0.076 and p=0.779, respectively). The areas under the ROC curve (AUC) values were 0.857, 0.762, and 0.542 for %ΔIC-a, %ΔIC-v, and %ΔCWT, respectively, in the response prediction. The cut-off value for identifying PR was a decrease rate of <52.9% for %ΔIC-a, and the sensitivity and specificity values were 0.857 and 0.833. CONCLUSION: Changes in the IC for gastric carcinomas following NC were detected using spectral CT and correlated with histopathological regression. The prediction efficacy for IC was better than that for tumour thickness, with IC on the arterial phase being a better predictor than IC on the venous phase.

Parathyroid hormone-related peptide (PTHrP): prokaryotic expression, purification, and preparation of a polyclonal antibody.

Parathyroid hormone-related peptide (PTHrP) plays important roles in promoting cancer occurrence and in the development of bone metastases. To increase our knowledge of the biological functions of PTHrP, the prokaryotic expression vector pET-PTHrP was successfully constructed and the His-PTHrP fusion protein was expressed in Escherichia coli. Anti-PTHrP polyclonal antibody was then prepared from rabbits. Finally, the goat tissue expression profile of PTHrP was analyzed by Western blot with the anti-PTHrP polyclonal antibody. The results showed that the expression of PTHrP in goat mammary glands was significantly higher than that in other organs. This indicates that PTHrP may play important roles in the goat mammary gland. The antibody prepared will be a useful tool for detecting PTHrP and will be valuable in future studies investigating the role of PTHrP in calcium metabolism in the goat model.

Association between dietary intake of folate and MTHFR and MTR genotype with risk of breast cancer.

We investigated the association between dietary intake of folate, vitamin B6, and the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotype with breast cancer. A matched case-control study was conducted, and 413 patients with newly diagnosed and histologically confirmed breast cancer and 436 controls were recruited. Folate intake, vitamin B6, and vitamin B12 levels were calculated, and the MTHFR C677T and A1298C and MTR A2756G polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Breast cancer cases were generally older, older at first live birth, and younger at menarche, had a higher body mass index, were smokers, had higher energy intake, and more first-degree relatives with breast cancer as well as more live births compared to controls. With respect to energy intake, we found that higher energy intake were more likely to increase the risk of breast cancer. The MTHFR 667TT genotype was associated with a moderately increased risk of breast cancer when compared with the CC genotype, and a significant odds ratio (OR; 95% confidence interval, CI) was found (OR = 1.70, 95%CI = 1.06-2.73). Individuals carrying T allele were associated with higher risk of breast cancer when compared with C allele (OR = 1.34, 95%CI = 1.06-1.70). We did not find a significant effect of the MTHFR A1298C and MTR A2756G on the risk of breast cancer. We did not find any association between folate intake and MTHFR C677T polymorphisms. In conclusion, we found that the MTHFR C667T polymorphism is associated with the risk of breast cancer, indicating that this genotype plays a role in breast cancer development.

Magnetically driven metal-insulator transition in NaOsO3.

The metal-insulator transition (MIT) is one of the most dramatic manifestations of electron correlations in materials. Various mechanisms producing MITs have been extensively considered, including the Mott (electron localization via Coulomb repulsion), Anderson (localization via disorder), and Peierls (localization via distortion of a periodic one-dimensional lattice) mechanisms. One additional route to a MIT proposed by Slater, in which long-range magnetic order in a three dimensional system drives the MIT, has received relatively little attention. Using neutron and x-ray scattering we show that the MIT in NaOsO(3) is coincident with the onset of long-range commensurate three dimensional magnetic order. While candidate materials have been suggested, our experimental methodology allows the first definitive demonstration of the long predicted Slater MIT.

[A prediction model of pathological complete response in patients with locally advanced rectal cancer after PD-1 antibody combined with total neoadjuvant chemoradiotherapy based on MRI radiomics].

Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.

[Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors].

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.

[Application of imaging diagnosis in watch and wait strategy for locally advanced rectal cancer patients after neoadjuvant therapy].

After neoadjuvant chemoradiotherapy(nCRT), 15%-40% of rectal cnacers has a pathological complete response (pCR), with non-malignant cells demonstrated in histological assessment of the surgical resection specimen. Since these patients have excellent oncological outcomes, there has been a rapidly growing interest in organ preservation for those who achieve a clinical complete response (cCR), that is "Watch and Wait strategy" (W&W). One of the major challenges in the W&W of rectal cancer is the careful and precise selection of patients suitable for this approach. The published series on W&W has all used different modalities to assess response post nCRT, including the MSKCC's three-tiered evaluation plan and Mercury's mrTRG criteria. Except significant heterogeneous results, the evidence available comes mostly from retrospective cohort studies, furthermore, there is a lack of data of long-term outcomes. How to accurately screen pCR patients preoperatively is an important and difficult issue of clinical concern.

Macromolecular scaffolds for immobilizing small molecule microarrays in label-free detection of protein-ligand interactions on solid support.

We explored two macromolecular scaffolds, bovine serum albumin (BSA) and polyvinyl alcohol (PVA), as chemically complementary platforms for immobilizing small molecule compounds on functionalized glass slides. We conjugated biotin molecules to BSA and amine-derivatized PVA and subsequently immobilized the conjugates on epoxy-functionalized glass slides through reaction of free amine residues on BSA and PVA with surface-bound epoxy groups. We studied binding reactions of such immobilized small molecule targets with solution-phase protein probes using an oblique-incidence reflectivity difference scanning optical microscope. The results showed that both BSA and amine-derivatized PVA were effective and efficient as carriers of small molecules with NHS residues and fluoric residues and for immobilization on epoxy-coated solid surfaces. A significant fraction of the conjugated small molecules retain their innate chemical activity.

Enhanced Cell Response to Zirconia Surface Immobilized with Type I Collagen.

Zirconia (ZrO2) dental implants provide good biocompatibility, have good corrosion resistance, and have a color that is similar to that of natural teeth. Unfortunately, ZrO2 is a bioinert material and therefore achieves osseointegration difficultly. In this study, we sought to enhance osseointegration by producing rough ZrO2 surfaces that contain hydroxyl groups (designated ZSA) through the use of sandblasting in conjunction with alkaline treatment. We immobilized type I collagen on ZSA surfaces using the natural cross-linker, procyanidin. Our results further showed that surfaces produced in ZSA-P/C featured more and steadier type I collagen than surfaces produced in ZSA-C. The ZSA-P/C also presented superior cell responses in terms of adhesion, proliferation, and mineralization of human bone marrow mesenchymal stem cells. The enhanced cell responses in the ZSA-P/C were induced through the prolonged activation of focal adhesion kinase, AKT (the phosphoinositide 3-kinase pathway), and p38 (the mitogen-activated protein kinase pathway). The simple and novel approach to immobilize type I collagen on roughened ZrO2 surfaces presented in this article can likely benefit dental implant applications.

[Application value of colonoscopic assessment in "watch and wait" strategy for mid-lower rectal cancer after neoadjuvant chemoradiotherapy].

Objective: To investigate the value of colonoscopic assessment in "watch and wait" strategy for mid-lower rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods: A single-center retrospective case series study was performed. Database of mid-lower rectal cancer patients at Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute from March 2011 to June 2017 was retrieved. Inclusion criteria: (1) nCRT was completed (50.6 Gy/22 f, plus oral capecitabine); (2) radical surgery was performed within 12 weeks after nCRT treatment; (3) clinical response to nCRT was determined as clinical complete response (cCR) or near-cCR. Patients who did not undergo colonoscopy and MRI in our center during initial assessment and follow-up, or whose colonoscopy data were unable to re-evaluated, were excluded. Initial evaluation of nCRT response was carried out between 6 and 16 weeks after nCRT. The results of endoscopy (eCR, near-eCR and non-eCR) and MRI (mCR, near-mCR and non-mCR) were compared to local lesion relapse during follow-up. The consistency of the results of colonoscopy and MRI was evaluated by Kappa test (Kappa value of 0.21 to 0.40 indicates general consistency, 0.41 to 0.60 moderate consistency, and 0.61 to 0.80 high consistency). The non-regrowth disease-free survival (NR-DFS) curves of the eCR group and the near-eCR group were plotted by Kaplan-Meier method and compared by log-rank test. Clinical significance of colonoscopy examination in the following "watch and wait" strategy during follow-up period was analyzed. Results: A total of 32 patients were enrolled in the study, including 21 (65.6%) males and 11 (34.4%) females with a median age of 57 years old. The differentiated type of rectal cancer included 1 (3.1%) case of well-differentiated, 26 (81.2%) of moderately differentiated and 5 (15.6%) of poorly differentiated. Clinical stage of the patients included 9 (28.1%) cases of T2-3N0 and 23 (71.9%) of T2-3N+. Median follow-up period was 48 (18 to 80) months. The local regrowth rate was 34.4% (11/32) and median interval of local regrowth was 10.0 (4 to 37) months. Initial colonoscopy evaluation was carried out at a median time of 9 (5 to 19) weeks after nCRT was completed. According to endoscopic findings, patients were divided into 3 groups, including 15 cases in eCR group, 15 cases in near-eCR group and 2 cases in non-eCR group. According to the appearance of MRI, patients were divided into 3 groups, including 8 cases in mCR group, 21 cases in near-mCR group and 3 cases in non-mCR group. The regrowth rate of eCR group was lower than that of mCR group (1/15 vs. 1/8) without significant difference (P=1.000). The regrowth rate of near-eCR group was higher than that of near-mCR group [9/15 vs. 42.9% (9/21)] without significant difference as well (P=0.500). The consistency between colonoscopy and MRI in response evaluation of cCR or near-cCR after nCRT was unsatisfactory (Kappa=0.341, P=0.011). After initial evaluation, 31 patients underwent watch and wait strategy, and 1 underwent local resection. The 1- and 3-year NR-DFS in the eCR group was both 100%, which was higher than that in the near-eCR group (53.3% and 38.9%, respectively), and the difference was statistically significant (P=0.001). During watch and wait period, 11 cases developed local regrowth by colonoscopy examination and the biopsy result included 4 case of high-grade intraepithelial neoplasia (HIN), 6 cases of adenocarcinoma and 1 case of chronic mucosal inflammation. Meanwhile lateral developmental tumor of ascending colon in 1 case and of sigmoid in a case was found by colonoscopy and confirmed as HIN by postoperative pathology. Besides, 4 cases developed colonic multiple adenoma and all underwent endoscopic resection. Conclusion: Colonoscopy examination plays an important role in both initial assessment and regrowth monitoring during watch and wait strategy after nCRT treatment.

[Genotype and evolution of hantavirus in Tiantai of Zhejiang province, 2011-2018].

Objective: By investigating the genotype and evolutionary variation of hantavirus (HV) in Tiantai county, a national surveillance site for hemorrhagic fever with renal syndrome (HFRS) was set in Zhejiang province, from 2011 to 2018, to reveal the molecular epidemiological characteristics of hantavirus (HV) in Tiantai. Methods: Total RNA was extracted from ultrasound treated HV antigen- positive rat lung samples in Tiantai from 2011 to 2018. After cDNA was prepared, nested PCR was used to amplify partial sequence of M fragments by using specific primers of HV. The sequences of HV in Tiantai from 2011 to 2018 were compared with other known HV sequences in order to identify the genotype and analyze the evolution and variation of the virus. Results: In 67 HV antigen-positive lung specimens, 31 were positive in nested PCR amplification with type-specific primers, including 30 Hantaan virus (HTNV) positive samples, 1 Seoul virus (SEOV) positive sample, and all the 31 samples were from Apodemus agrarius. The phylogenetic tree based on partial M segment was divided into monophyletic group, 30 strains were distributed in HTNV group and 1 was in SEOV group. The HTNV strain Tiantai T2018-130 was independently in one branch, sharing 84.8%-87.9% homology with other strains both at home and abroad, including 29 strains in HTNV group in Tiantai. The other 29 HTNV strains in Tiantai showed closer relationship. The SEOV strain T2016-31 from Apodemus agrarius showed closer relationship with previous strains of SEOV, Tiantai ZT71, ZT10 and Z37 strains of Wenzhou, Zhejiang province. Conclusions: HTNV, the main genotype of HV in Tiantai of Zhejiang province, showed obvious geographic clustering, but the strain T2018-130 was distinct from the others in Tiantai. Meanwhile, by sequence analysis, we confirmed that The SEOV strain T2016-31 existed in in Apodemus agrarius, indicating there was a phenomenon of "spillover" between virus and host in SEOV evolution.