[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.

[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.

[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.

[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.

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.

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.

Impact of knee varus and valgus deformity on alignment in lower extremities after total knee arthroplasty (TKA).

OBJECTIVE: To investigate the impact of knee varus and valgus in varying degrees on the alignment in lower extremities of patients who received the total knee arthroplasty (TKA). PATIENTS AND METHODS: We retrospectively analyzed the condition of varus and valgus deformity in full-length X-ray films of double lower extremities in weight-bearing position of 120 patients before and after they firstly received the TKA between March 2012 and May 2014 to discover the impact of knee varus and valgus in varying degrees on the alignment in lower extremities of patients who received the total knee arthroplasty (TKA). 120 patients were divided into three groups by the pre-operative hip-knee-ankle angle (HKA), the HKAs of three groups were compared after operation, and linear regression analysis was conducted to identify the correlation between pre- and post-operative HKAs. In addition, comparison between the pre- and post-operative lean of arms and legs (LMAL) was carried out to explore the variations before and after operation as well as the differences in the average variations among three groups. RESULTS: The differences were statistically significant in comparison of the pre- and post-operative HKAs and medial proximal tibia angles (MPTA) of all affected extremities (p<0.05), but no statistically significant difference was shown in comparison between the pre- and post-operative knee physical valgus angles (KPVA) (p>0.05). The post-operative lengths of 86.57% of affected extremities (116/134) were longer than those before operation with statistically significant differences (p<0.05). However, no statistically significant difference was identified in comparison between the pre- and post-operative lengths of extremities that did not receive any operation (p>0.05). The ratios of HKAs between -3° and 3° in normal group, mild-deformity group and severe-deformity group were respectively 90.48%, 81.25%, and 34.69% with a statistically significant difference (p<0.05). Besides, the scatter plot revealed that there was a linear regression relation between pre- and post-operative HKAs (F=51.197, p<0.05). There were statistically significant differences in comparisons of the pre-operative KPVA and MPTAs among three groups (p<0.05). CONCLUSIONS: Severe knee varus and valgus deformity can increase the deviation of alignment in lower extremities after TKA, and most of LMALs after TKA are longer than those before TKA, and the most significant extension is identified in severe varus and valgus deformity.

[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%.

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.

A cell-selective glutathione-responsive tris(phthalocyanine) as a smart photosensitiser for targeted photodynamic therapy.

A biotin-conjugated disulfide-linked tris(phthalocyanine) has been synthesised and characterised. As shown by electronic absorption and steady-state fluorescence spectroscopy methods, the compound remains non-aggregated in N,N-dimethylformamide, but is significantly aggregated in phosphate buffered saline with 1% Cremophor EL. The reduction in fluorescence intensity and singlet oxygen generation efficiency as compared with the monomeric counterpart suggests that the tris(phthalocyanine) exhibits an excellent self-quenching effect, particularly in an aqueous medium. Upon interaction with glutathione, both the fluorescence emission and singlet oxygen production can be restored as a result of the cleavage of the disulfide linkages, thereby releasing the phthalocyanine units and reducing their aggregation and self-quenching effects. With a biotin moiety, this tris(phthalocyanine) is preferentially taken up by the biotin-receptor-positive HeLa cells and activated by the intracellular glutathione, resulting in fluorescence recovery and photocytotoxicity with an IC50 value of 0.68 µM. This compound can therefore act as a dual functional photosensitiser.

Screening and identification of a tumor specific methylation phenotype in the colorectal laterally spreading tumor.

OBJECTIVE: We screened and identified the differential expression of the methylation phenotype in the whole genome of colorectal laterally spreading tumor (LSTs). MATERIALS AND METHODS: 3 tissue samples of colorectal polypoid adenomas (PAs), 3 tissue samples of LSTs and 3 tissue samples of colon cancer were analyzed with a high-density gene chip, and about 450,000 methylation sites were detected covering approximately 95% of the CpG islands. The Delta Data screening was taken through a cluster analysis of methylation phenotype differential expression. 50 tissue samples each of PAs patients, LSTs patients, and colorectal cancer patients were selected. Methylation-specific PCR (MSP) was used to detect RASSF1A and WIF-1 methylation levels. He RT-PCR method was used to detect the relative mRNA expression levels for methylation expression identification. RESULTS: The degree of LST methylation was higher than that of PAs, and 1234 genes were found to have a lower expression when compared to colorectal cancer samples. 764 genes had a higher expression when compared to colorectal cancer, and 559 genes lower expression when compared to PAs. The average methylation level of LSTs was higher than that of PAs, and lower than that of colorectal cancer. The chromosomal location was taken on these 1234 genes, which were higher than that of PAs, and lower than that of colorectal cancer; 518 genes were located on chromosome No. 2 (41.98%), 236 on No. 5 (19.12%), 357 on No. 8 (28.93%), and 123 on No. 10 (9.97%). According to clustering analysis, DNA differentially methylated sites were mainly on genes of cell adhesion molecules regulation, signaling pathways, energy transduction, cell cycle and apoptosis. The positive rate of RASSF1A and WIF-1 methylation in the tissues of LSTs patients were higher than that of PAs, and lower than that of colorectal cancer; differences were statistically significant (p<0.05). The relative expression levels of RASSF1A and WIF-1mRNA in the tissues of LSTs patients were lower than that of PAs, higher than that of colorectal cancer, and the difference was statistically significant (p<0.05). CONCLUSIONS: The administration of high-density gene chip technology has a good application value to screen the differential expression of LSTs gene methylation phenotype. Results are consistent with the identification results.

pH-Responsive Dimeric Zinc(II) Phthalocyanine in Mesoporous Silica Nanoparticles as an Activatable Nanophotosensitizing System for Photodynamic Therapy.

An acid-cleavable acetal-linked zinc(II) phthalocyanine dimer with an azido terminal group (cPc) was prepared and conjugated to alkyne-modified mesoporous silica nanoparticles via copper(I)-catalyzed alkyne-azide cycloaddition reaction. For comparison, an amine-linked analogue (nPc) was also prepared as a non-acid-cleavable counterpart. These dimeric phthalocyanines were significantly self-quenched due to the close proximity of the phthalocyanine units inside the mesopores, resulting in much weaker fluorescence emission and singlet oxygen generation, both in N,N-dimethylformamide and in phosphate-buffered saline (PBS), compared with the free molecular counterparts. Under acidic conditions in PBS, the cPc-encapsulated nanosystem was activated in terms of fluorescence emission and singlet oxygen production. After internalization into human colon adenocarcinoma HT29 cells, it exhibited much higher intracellular fluorescence and photocytotoxicity compared to the nanosystem entrapped with nPc. The activation of this nanosystem was also demonstrated in tumor-bearing nude mice. The intratumoral fluorescence intensity increased gradually over 24 h, while for the nPc counterpart the fluorescence remained very weak. The results suggest that this nanosystem serves as a promising activatable nanophotosensitizing agent for photodynamic therapy.

[Risk factors for central neck lymph node metastases of papillary thyroid carcinoma].

Objective: To investigate the impact factors for central neck lymph node metastases(CLNM) of papillary thyroid carcinoma(PTC). Methods: A total of 498 patients with PTC who underwent total or hemi-thyroidectomy plus central neck lymph node dissection between January 2014 and July 2016 were included. Univariate and multivariate analyses were performed to identify clinicopathological characteristics, thyroid function parameters and US findings that associated with CLNM of PTC. A nomogram was developed to predict the probability of CLNM. The receiver operating characteristic curve(ROC) was used to estimate the efficiency of the nomogram. Results: Among 498 patients, 284 patients were affected by CNLM. The sensitivity and specificity of US in predicting PTC metastasis in the central neck were 31.3% and 88.3%, respectively. Univariate and multivariate analyses showed that gender, age, number and size of suspicious malignant nodules in thyroid, and suspicious lymph node metastasis detected by ultrasonography were independently correlated with CLNM. The ROC showed that the AUC was 0.748, with sensitivity of 80.8%, and specificity of 59.8%. Conclusions: Gender, age, number and size of suspicious malignant nodules in thyroid, suspicious lymph node metastasis were predictive factors for CLNM in patients with PTC. The nomogram developed based on related factors with CLNM is more sensitive than sonographic central neck lymph node features in predicting the probability of CLNM.

[Recombinant expression of hantaan virus protein N with application of Western-blot in detecting anti-hantavirus antibody].

Objective: S gene of hantavirus(HV) was expressed in insect cells by genetic engineering technology. The expression product of S gene was used as antigen to detect anti-HV specific antibody IgG in serum. Methods: Gene encoding NP of the strain HV-Z10 was amplified by PCR and then its eukaryotic expression system rBAC-Z10S-TN was constructed by using the routine genetic engineering method. SDS-PAGE was applied to measure the expression of rNP.Ion-exchange plus Ni-NTA-affinity chromatography was performed to purify the recombinant product. Indirect immuno-fluorescence assay (IFA) was used to determine the specific immune-reactivity of rNP. WB assay was established to detect the serum samples from 95 confirmed HFRS patients. Parameters related to the outcomes of detection were compared with the routine HV-IgG IFA method. Results: rBAC-Z10S-TN was able to express rNP with high efficiency. The purified rNP only showed a single protein fragment in the gel after SDS-PAGE. HV IgG could efficiently recognize rNP and hybridize with the recombinant protein. 97.67% of the serum samples from the HFRS patients were positive confirmed by WB. Conclusions: We successfully constructed a high efficient prokaryotic expression system of NP encoding gene from hantavirus strain HV-Z10. WB assay which was established in this study could be used as a new serological test for HFRS diagnosis, thanks to the simplicity, safety, sensitivity and specificity of this method.

A point-prevalence survey of healthcare-associated infection in fifty-two Chinese hospitals.

BACKGROUND: Healthcare-associated infection (HCAI) represents a major problem for patient safety worldwide. AIM: To demonstrate the prevalence, causative agents, and risk factors for HCAI in Chinese hospitals. METHODS: A one-day point-prevalence survey was conducted in 52 Chinese hospitals between October 2014 and March 2015. A web-based software system was developed for data entry and management. FINDINGS: Among 53,939 patients surveyed, the prevalence of patients with at least one HCAI was 3.7%. Of 2182 HCAI episodes, the most frequently occurring types were lower respiratory tract infections (47.2%), followed by urinary tract infection (12.3%), upper respiratory tract infection (11.0%), and surgical site infection (6.2%). The prevalence of patients with at least one HCAI in critical care units was highest (17.1%). Device-associated infections, including ventilator-associated pneumonia, catheter-associated urinary tract infection, and central catheter-associated bloodstream infection, accounted for only 7.9% of all HCAIs. The most frequently isolated micro-organisms were Pseudomonas aeruginosa [206 infections (9.4%)], Acinetobacter baumannii [172 infections (7.9%)], Klebsiella pneumoniae [160 infections (7.3%)], and Escherichia coli [145 infections (6.6%)]. Of the survey patients (18,206/53,939), 33.8% were receiving at least one antimicrobial agent at the time of the survey. Risk factors for HCAI included older age (≥80 years), male gender, days of hospital admission, admission into a critical care unit, and device utilization. CONCLUSION: Our study suggests that the overall prevalence of HCAI in surveyed Chinese hospitals was lower than that reported from most European countries and the USA. More attention should be given to the surveillance and prevention of non-device-associated HCAI in China.