Role of photobleaching process of indocyanine green for killing neuroblastoma cells.

Indocyanine green (ICG) is an FDA-approved near infrared (NIR) imaging agent for diagnosis and imaging guided surgery. It also exhibits phototoxicity under high-dose NIR irradiation, expanding its application as a photo-therapeutic agent. Since ICG's efficiency as a type II photosensitizer has been controversial due to its low triplet state yield, other mechanisms have been explored. While claims of toxic decomposition products, accompanied by irreversible ICG photobleaching, were proposed as the main mechanism, evidences from systemic studies are lacking. In this work, we aimed to unravel the factors affecting ICG photobleaching and the associated photo-killing effect on neuroblastoma, one of the most common pediatric tumors but often escapes therapy. Specifically, we examined how albumin-induced ICG stabilization affects the ICG photobleaching process, and the effect of photobleached ICG on cell proliferation and viability of neuroblastoma cells. It was found that ICG photobleaching was significant only under aerobic conditions and was more efficient in solutions with higher concentration ICG monomers, which were stabilized from aggregates by the presence of BSA while increasing photobleaching and associated oxygen consumption. Photobleached ICG inhibited cell proliferation, indicating another effect of tumor treatment by ICG. Taken together, while enhanced photobleaching by BSA-bound ICG monomers may reduce the photodynamic effect targeting cellular components, the photoproducts directly contribute to tumor growth inhibition and assist in a secondary mechanism to stop tumor growth.

[Analysis of clinical characteristics of 21 cases of acute fibrinous and organizing pneumonia].

Objective: To summarize the clinical features of 21 cases of acute fibrinous and organizing pneumonia (AFOP) confirmed by pathology, thereby improving clinicians' understanding of this disease and avoiding misdiagnosis in clinical practice. Methods: Twenty-one patients diagnosed pathologically with AFOP from January 2016 to April 2019 were analyzed retrospectively. The clinical symptoms, laboratory examination results, imaging features, treatments and outcomes were analyzed comprehensively. Results: There were 10 males and 11 females, with an average age of (58±10) years. All the cases presented subacute disease onset. The main symptoms were cough, expectoration and fever. The results from laboratory examination showed that the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were significantly higher than the normal levels. The total number of leukocytes, the percentage of neutrophils, and procalcitonin were also higher than the normal levels. Among these patients, 4 cases showed positive sputum bacteriology. Nine patients were found to have probable etiological factors (infections in 4, tumors in 4 cases, and connective tissue disease in 1 case). Twelve patients had no confirmed etiological factors. As to radiological findings, the patterns were multiple patchy infiltrates(16/21), solitary mass (3/21) and multiple nodules in both lungs (2/21). Most lesions were subpleural in distribution (15/21), with air bronchogram sign (11/21), pleural effusion (9/21), and cavity (4/21). Three patients received anti-infective therapy only. The infiltration in lung disappeared within 2 months in one patient, but the lesion still existed in one case after three years of follow-up. However, one patient were lost during the follow-up. Eighteen patients were treated with oral glucocorticoids, and about 50% of the patients showed significant improvement in symptoms and imaging findings within one month. The average follow-up time was (22±10) months, and there was no death. Conclusions: The clinical and imaging findings of AFOP are nonspecific. The exact mechanism of its pathogenesis is not clear. Infection and tumor may be related to the pathogenesis of AFOP. AFOP with subacute onset has a good response to glucocorticoid treatment with a better prognosis.

[Application of p16/Ki-67 immunocytochemistry in triage of patients with atypical squamous cells of undetermined significance].

Objective: To investigate the clinical value of p16/Ki-67 immunocytochemistry in patients with atypical squamous cells of undetermined significance(ASC-US). Methods: One hundred and seventy-one cases of thin-prep cytology test (TCT) diagnosed as ASC-US underwent p16/Ki-67 immunocytochemistry. All patients had colposcopy and biopsy from March 2015 to January 2016. Ninety of the 171 cases underwent high-risk HPV test at the same time. Results: p16/Ki-67 immunocytochemistry was positive in 43.9% (75/171) of the 171 cytology samples; the sensitivity and specificity of p16/Ki-67 immunocytochemistry were 77.6%(52/67) and 77.9%(81/104) in detecting CIN2+ , and the positive and negative predictive value were 69.3%(52/75) and 84.4%(81/96), respectively. The sensitivity and specificity in diagnosing CIN2+ were 100.0%(34/34) and 10.7%(6/56) for HPV test, and the positive and negative predictive value were 40.5%(34/84) and 6/6. p16/Ki-67 immunocytochemistry showed lower sensitivity but obviously higher specificity than high-risk HPV detection. Conclusion: p16/Ki-67 immunocytochemistry is a good triage test for identifying CIN2+ in ASC-US specimens.

[Fine needle aspiration cytology of thyroid nodules: a cytopathologic study of 2 043 cases].

OBJECTIVE: To evaluate the clinical value of thyroid fine needle aspiration cytology(FNAC) and the Bethesda system for reporting thyroid cytopathology(TBSRTC). METHODS: FNAC was performed for 2 043 cases and cytopathological data were retrospectively analyzed. Cytopathological diagnoses according to TBSRTC were classified as non-diagnostic, benign, atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS), follicular neoplasm/suspicious for follicular neoplasm(FN/SFN), suspicious for malignancy(SM) and malignancy. The results of 234 FNAC samples in which surgery was performed were compared with the histological diagnoses. RESULTS: Of the 2 043 FNAC samples, 15.7%(320/2 043)were non-diagnostic, 51.2%(1 047/2 043)were benign, 16.6%(339/2 043) were AUS/FLUS, 2.3%(46/2 043)were FN/SFN, 8.6%(176/2 043)were SM and 5.6%(115/2 043)were malignant. In 234 cases, there was follow-up histology. Rates of malignancy were as follows: non-diagnostic, 18.2%(2/11); benign(2.2%, 1/45); AUS/FLUS(25.6%, 10/29); FN/SFN(12.1%, 10/39); SM(91.8%, 56/61); malignant(100.0%, 45/45). The sensitivity, specificity, false positive rate, false negative rate and overall accuracy of FNAC in the diagnosis of thyroid nodules was 87.1%(101/116), 95.3%(102/107), 4.7%(5/107), 12.9%(15/116), 91.0%(203/223). CONCLUSIONS: FNAC is a reliable diagnostic method for evaluation of thyroid disease. TBSRTC is a accurate and effective reporting system for cytopathological diagnoses, so it is worthy of being widely popularized in clinical application.

PKR and HMGB1 expression and function in rheumatoid arthritis.

The pathogenesis of rheumatoid arthritis (RA) is characterized by inflammation. We aimed to examine the roles of double-stranded RNA-activated protein kinase (PKR) and high-mobility group box chromosomal protein 1 (HMGB1) in a rat model of RA. Male SD rats were divided into three groups: control, RA model, and intervention (RA model plus treatment). The model of RA was made by injecting Freund's adjuvant into the posterior right limb of the rat and the intervention group received a PKR-specific inhibitor C16 after RA modeling. The degree of limb swelling was measured following RA modeling and intervention. In addition, plasma levels of HMGB1 were determined using ELISA. The mRNA and protein levels of PKR and HMGB1 were detected in rat synovium using quantitative PCR and western blot, respectively. The degree of limb swelling in the RA model was increased compared to control, while it was decreased in the intervention model compared to the RA model. Plasma HMGB1 levels in the model group were significantly higher compared to the control group but were lower in the intervention group compared to the model group. PKR and HMGB1 protein and mRNA levels in the rat synovium were elevated in the model group and markedly reduced in the intervention group. Increased levels of PKR and HMGB1 in synovium or blood appear to be involved in the occurrence and development of RA in a rat model. Selective inhibition of PKR improves the symptoms of RA, perhaps by inhibiting the release of HMGB1.

Intraoperative platelet transfusion is associated with increased postoperative sternal wound infections among type A aortic dissection patients after total arch replacement.

BACKGROUND: Blood transfusion and its impact upon clinical outcomes of cardiac surgery have been extensively discussed, especially in the post-aprotinin era. This study compared clinical outcomes and perioperative blood utilisation among acute type A aortic dissection (AAD) patients with or without intraoperative platelet transfusion during total arch replacement, thus intending to investigate prognostic value of platelet transfusion during major aortic surgeries. MATERIALS AND METHODS: Acute AAD patients undergoing total arch replacement and stented elephant trunk procedure under hypothermic circulatory arrest with and without intraoperative platelet transfusion at our institute from January 2008 to December 2012 were retrospectively included. Patients were categorised into PLT (n = 74) and non-PLT (n = 85) groups to compare the in-hospital mortality and complications, as well as blood components utilisation. RESULTS: Baseline characteristics and operational features were all comparable between two groups. In PLT group, in-hospital survival was not improved and intraoperative utilisation of red blood cell RBC, fresh frozen plasma (FFP) and cryoprecipitate was not reduced. Postoperative RBC transfusion [2.0(0-4.0) vs 0(0-4.0) U, p = 0.026; 64.9 vs 43.5%, p = 0.007] was significantly increased in PLT group, parallel with the prolonged postoperative hospitalisation time [(24.0 ± 12.7) vs (20.8 ± 10.9) days, p = 0.093] and elevated incidence of sternal wound infections (16.2 vs 5.9%, p = 0.035). Intraoperative platelet transfusion [odds ratio (OR): 3.10, 95% confidence interval (CI): 1.04-9.25, p = 0.043] was identified as independent risk factor of postoperative sternal wound infections by multivariate logistic regression analysis. CONCLUSION: Intraoperative platelet transfusion did not improve in-hospital prognosis among AAD patients after total arch replacement. The incidence of postoperative sternal wound infections increased among those who received intraoperative platelet transfusion.

The cost-effectiveness analysis of laparoscopic treatment of ectopic pregnancy: a single-center review of a five-year experience.

PURPOSE: The aim of this study was to investigate the cost-effectiveness of laparoscopic treatment for ectopic pregnancy by comparing the medical expenses and time of hospitalization of laparoscopic and open surgery for ectopic pregnancy in partial area of Shanghai, China. MATERIALS AND METHODS: Clinical data of 762 cases with ectopic pregnancy undergoing surgical treatment (307 cases for laparoscopic surgery and 455 cases for open surgery) were analyzed retrospectively. The clinical information including the medical expenses and time of hospitalization was compared. The patients were divided into three groups according to the treatments of different lesions (lesions resection, conservative laparotomy, and exploration group) and were analyzed. RESULTS: The total hospitalization expenses and the top three single costs including surgery, exams, and medicine expenses were higher in laparoscopic group than in open surgery group. There was no significant difference between the two groups on the total time of hospitalization. The hospital days of preoperation were higher but the postoperative hospital days were lower in laparoscopic group than in open surgery group. Compared with the open surgery treatment, the hospitalization expenses of laparoscopic treatment for ectopic pregnancy increased. There was no significant difference on the total hospitalization days. CONCLUSION: The preoperative waiting period of inpatients increased and the post-operative hospital days reduced in laparoscopic group.

Machine learning enabled multiplex detection of periodontal pathogens by surface-enhanced Raman spectroscopy.

Periodontitis is a chronic inflammation of the periodontium caused by a persistent bacterial infection, resulting in destruction of the supporting structures of teeth. Analysis of microbial composition in saliva can inform periodontal status. Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Streptococcus mutans (Sm) are among reported periodontal pathogens, and were used as model systems in this study. Our atomic force microscopic (AFM) study revealed that these pathogens are biological nanorods with dimensions of 0.6-1.1 µm in length and 500-700 nm in width. Current bacterial detection methods often involve complex preparation steps and require labeled reporting motifs. Employing surface-enhanced Raman spectroscopy (SERS), we revealed cell-type specific Raman signatures of these pathogens for label-free detection. It overcame the complexity associated with spectral overlaps among different bacterial species, relying on high signal-to-noise ratio (SNR) spectra carefully collected from pure species samples. To enable simple, rapid, and multiplexed detection, we harnessed advanced machine learning techniques to establish predictive models based on a large set of raw spectra of each bacterial species and their mixtures. Using these models, given a raw spectrum collected from a bacterial suspension, simultaneous identification of all three species in the test sample was achieved at 95.6 % accuracy. This sensing modality can be applied to multiplex detection of a broader range and a larger set of periodontal pathogens, paving the way for hassle-free detection of oral bacteria in saliva with little to no sample preparation.

Gamma-glutamyl transpeptidase level is a novel adverse prognostic indicator in human metastatic colorectal cancer.

AIM: Biomarkers have been utilized for prognosis in colorectal cancer; however, relatively few have been identified. We compared the prognostic value of serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with metastatic colorectal cancer (mCRC). METHOD: Blood samples were collected from 239 patients with mCRC presenting between 2005 and 2010 in the Sun Yat-sen University Cancer Center. RESULTS: CEA (P < 0.001), CA19-9 (P < 0.001), GGT (P < 0.001), ALP (P < 0.001) and LDH (P = 0.001) were statistically significant prognostic factors of overall survival (OS). CEA (P = 0.002) and GGT (P = 0.021) were validated as independent predictors. On univariate analysis, CEA (P = 0.003), CA19-9 (P = 0.006), GGT (P < 0.001) and ALP (P = 0.001) were statistically significant predictive factors of progression-free survival (PFS) in patients having first-line chemotherapy. CEA (P = 0.011) and GGT (P = 0.027) were independent predictors. GGT (P = 0.001), ALP (P = 0.016) and LDH (P = 0.039) levels were correlated with the tumour response rate assessed by CT, whilst CEA (P = 0.724) and CA19-9 (P = 0.822) were not. There was a statistically significant difference in OS (P < 0.001) and PFS (P < 0.001) among patients who had elevations of both CEA and GGT compared with those in whom only one or neither was elevated. CONCLUSION: Among GGT, LDH and ALP, only GGT plays an independent role with CEA in predicting OS and PFS in mCRC. When coupled with CEA, GGT may lead to improved prognostic predictors.

Differential gene expression profiling of primary cutaneous melanoma and sentinel lymph node metastases.

Limited understanding of molecular mechanisms of metastasis in melanoma contributes to the absence of effective treatments. Increased knowledge of alterations in genes that underpin critical molecular events that lead to metastasis is essential. We have investigated the gene expression profiles of primary melanomas and melanoma metastases in sentinel lymph nodes. A total of 19 samples (10 primary melanomas and 9 sentinel lymph node metastases) were evaluated. Melanoma cells were dissected from tissue blocks. Total mRNA was isolated, amplified, and labeled using an Ambion Recover All Total Nucleic Acid Isolation kit, Nu-GEN WT-Ovation formalin-fixed, paraffin-embedded RNA Amplification System, and FL-Ovation cDNA Biotin Module V2, respectively. Samples were hybridized to the Affymetrix Gene Chip Human U133 Plus 2.0 Array. Data were analyzed using Partek Genomics Suite Version 6.4. Genes selected showed ≥2-fold difference in expression and P<5.00E-2. Validation studies used standard immunohistochemical assays. Hierarchical clustering disclosed two distinct groups: 10 primary melanomas and 9 sentinel lymph node metastases. Gene expression analysis identified 576 genes that showed significant differential expression. Most differences reflected decreased gene expression in metastases relative to primaries. Reduced gene expression in primaries was less frequent and less dramatic. Genes significantly increased or decreased in sentinel lymph node metastases were active in cell adhesion/structural integrity, tumor suppression, cell cycle regulation, and apoptosis. Validation studies indicate that MAGEC1 (melanoma antigen family C1) and FCRL1 (Fc receptor-like 1) are involved in melanoma progression. There are striking differential gene expression patterns between primary and nodally metastatic melanomas. Similar findings were seen with autologous paired primary melanomas and sentinel lymph node metastases, supporting involvement of these gene alterations in evolution of metastases. With further study, it may be possible to determine the exact sequence of molecular events that underlie melanoma metastases.

Electrospun Silk Fibroin-CNT Composite Fibers: Characterization and Application in Mediating Fibroblast Stimulation.

Electrospinning is a simple, low-cost, and highly efficient technique to generate desirable nano/microfibers from polymer solutions. Silk fibroin (SF), a biopolymer found in Bombyx mori cocoons, has attracted attention for various biomedical applications. In this study, functionalized CNT was incorporated in SF to generate biocomposite fibers by electrospinning. The electrospun (E-spun) fibers were well aligned with morphology mimicking the locally oriented ECM proteins in connective tissues. While as-spun fibers dissolved in water in just two minutes, ethanol vapor post-treatment promoted ß-sheet formation leading to improved fiber stability in an aqueous environment (>14 days). The addition of a minute amount of CNT effectively improved the E-spun fiber alignment and mechanical strength while retained high biocompatibility and biodegradability. The fibers' electrical conductivity increased by 13.7 folds and 21.8 folds, respectively, in the presence of 0.1 w% and 0.2 w% CNT in SF fibers. With aligned SF-CNT 0.1 % fibers as a cell culture matrix, we found electrical stimulation effectively activated fibroblasts from patients of pelvic organ prolapse (POP), a connective tissue disorder. The stimulation boosted the fibroblasts' productivity of collagen III (COLIII) and collagen I (COLI) by 74 folds and 58 folds, respectively, and reduced the COLI to COLIII ratio favorable for tissue repair. The developed material and method offer a simple, direct, and effective way to remedy the dysfunctional fibroblasts of patients for personalized cell therapeutic treatment of diseases and health conditions associated with collagen disorder.

Distinctive structure, composition and biomechanics of collagen fibrils in vaginal wall connective tissues associated with pelvic organ prolapse.

Collagen is the predominant structural protein within connective tissues. Pelvic organ prolapse (POP) is characterized by weakening of the pelvic floor connective tissues and loss of support for pelvic organs. In this study, we examined the multiscale structure, molecular composition and biomechanics of native collagen fibrils in connective tissues of the posterior vaginal fornix collected from healthy women and POP patients, and established the correlation of these properties with clinical POP quantification (POP-Q) scores. The collagen characteristics, including collagen amount, ratio of Collagen I and Collagen III, collagen fibril d-period, alignment and stiffness, were found to change progressively with the increase of the clinical measurement of Point C, a measure of uterine descent and apical prolapse. The results imply that a severe prolapse is associated with stiffer collagen fibrils, reduced collagen d-period, increased fibril alignment and imbalanced collagen synthesis, degradation and deposition. Additionally, prolapse progression appears to be synchronized with deterioration of the collagen matrix, suggesting that a POP-Q score obtained via a non-invasive clinical test can be potentially used to quantitatively assess collagen abnormality of a patient's local tissue. STATEMENT OF SIGNIFICANCE: Abnormal collagen metabolism and deposition are known to associate with connective tissue disorders, such as pelvic organ prolapse. Quantitative correlation of the biochemical and biophysical characteristics of collagen in a prolapse patient's tissue with the clinical diagnostic measurements is unexplored and unestablished. This study fills the knowledge gap between clinical prolapse quantification and the individual's cellular and molecular disorders leading to connective tissue failure, thus, provides the basis for clinicians to employ personalized treatment that can best manage the patient's condition and to alert pre-symptomatic patients for early management to avoid unwanted surgery.

Levator avulsion using a tomographic ultrasound and magnetic resonance-based model.

OBJECTIVE: Delivery-related levator avulsion can cause pelvic floor dysfunction. We compared agreement between tomographic ultrasound and magnetic resonance-based models for the detection of levator defects. STUDY DESIGN: Sixty-nine Chinese women with pelvic organ prolapse were assessed prospectively by 3-dimensional ultrasound scans and magnetic resonance imaging. Levator-urethra gap (LUG), levator-symphysis gap (LSG), and puborectalis attachment width were measured offline with state-of-the-art software. Interobserver variability and agreement between the 2 methods were determined. RESULTS: Interobserver repeatability was moderate-to-excellent for all parameters that were measured with both methods and agreement between methods in diagnosing levator avulsion. LUG and LSG measurements were significantly higher in women with a levator avulsion. With a diagnosis of complete levator avulsion, receiver operating characteristics analysis suggested a cutoff of 23.65 mm for LUG and 28.7 mm for LSG. CONCLUSION: Levator avulsion can be diagnosed reliably by tomographic ultrasound scanning and magnetic resonance imaging evaluation, and linear measures, such as LSG and LUG, can be proxy measurements for avulsion.

Hyperspectral Imager for the Coastal Ocean: instrument description and first images.

The Hyperspectral Imager for the Coastal Ocean (HICO) is the first spaceborne hyperspectral sensor designed specifically for the coastal ocean and estuarial, riverine, or other shallow-water areas. The HICO generates hyperspectral images, primarily over the 400-900 nm spectral range, with a ground sample distance of ≈90 m (at nadir) and a high signal-to-noise ratio. The HICO is now operating on the International Space Station (ISS). Its cross-track and along-track fields of view are 42 km (at nadir) and 192 km, respectively, for a total scene area of 8000 km(2). The HICO is an innovative prototype sensor that builds on extensive experience with airborne sensors and makes extensive use of commercial off-the-shelf components to build a space sensor at a small fraction of the usual cost and time. Here we describe the instrument's design and characterization and present early images from the ISS.

[Application of Hydrashift 2/4 daratumumab assay in eliminating interference of daratumumab on serum immunofixation electrophoresis].

Objective: To investigate the interference of daratumumab on immunofixation electrophoresis after treating plasma cell diseases and methods to eliminate the interference. Methods: Serum samples of eight patients with plasma cell diseases treated with daratumumab in Peking University People's Hospital from April 2020 to March 2021 were collected for standard immunofixation electrophoresis and Hydrashift 2/4 daratumumab assay. Results: After treatment, 81.3% (13/16) of the samples showed drug-induced monoclonal antibodies (IgG-κ) . The samples without drug-induced monoclonal bands were related to individual differences, administration intervals, and immunoglobulin levels. Among the samples with IgG-κ monoclonal bands, 76.9% (10/13) could be directly identified as endogenous or exogenous monoclonal bands by immunofixation electrophoresis, and the others (3/13) could be identified by Hydrashift 2/4 daratumumab assay. Conclusion: Hydrashift 2/4 daratumumab assay can remove the band of daratumumab on the immunofixation electrophoresis and help with efficacy evaluation.

Aligned Collagen-CNT Nanofibrils and the Modulation Effect on Ovarian Cancer Cells.

Fibrillar collagen is a one-dimensional biopolymer and is the most abundant structural protein in the extracellular matrix (ECM) of connective tissues. Due to the unique properties of carbon nanotubes (CNTs), considerable attention has been given to the application of CNTs in developing biocomposite materials for tissue engineering and drug delivery. When introduced to tissues, CNTs inevitably interact and integrate with collagen and impose a discernible effect on cells in the vicinity. The positive effect of the collagen-CNT (COL-CNT) matrix in tissue regeneration and the cytotoxicity of free CNTs have been investigated extensively. In this study, we aimed to examine the effect of COL-CNT on mediating the interaction between the matrix and SKOV3 ovarian cancer cells. We generated unidirectionally aligned collagen and COL-CNT nanofibrils, mimicking the structure and dimension of collagen fibrils in native tissues. AFM analysis revealed that the one-dimensional structure, high stiffness, and low adhesion of COL-CNT greatly facilitated the polarization of SKOV3 cells by regulating the ß-1 integrin-mediated cell-matrix interaction, cytoskeleton rearrangement, and cell migration. Protein and gene level analyses implied that both collagen and COL-CNT matrices induced the epithelial-mesenchymal transition (EMT), and the COL-CNT matrix prompted a higher level of cell transformation. However, the induced cells expressed CD44 at a reduced level and MMP2 at an increased level, and they were responsive to the chemotherapy drug gemcitabine. The results suggested that the COL-CNT matrix induced the transdifferentiation of the epithelial cancer cells to mature, less aggressive, and less potent cells, which are inapt for tumor metastasis and chemoresistance. Thus, the presence of CNT in a collagen matrix is unlikely to cause an adverse effect on cancer patients if a controlled dose of CNT is used for drug delivery or tissue regeneration.

Maf1 suppression of ATF5-dependent mitochondrial unfolded protein response contributes to rapamycin-induced radio-sensitivity in lung cancer cell line A549.

mTOR is well known to promote tumor growth but its roles in enhancing chemotherapy and radiotherapy have not been well studied. mTOR inhibition by rapamycin can sensitize cancer cells to radiotherapy. Here we show that Maf1 is required for rapamycin to increase radio-sensitivity in A549 lung cancer cells. In response to ionizing radiation (IR), Maf1 is inhibited by Akt-dependent re-phosphorylation, which activates mitochondrial unfolded protein response (UPRmt) through ATF5. Rapamycin suppresses IR-induced Maf1 re-phosphorylation and UPRmt activation in A549 cells, resulting in increased sensitivity to IR-mediated cytotoxicity. Consistently, Maf1 knockdown activates ATF5-transcription of mtHSP70 and HSP60, enhances mitochondrial membrane potential, reduces intracellular ROS levels and dampens rapamycin's effect on increasing IR-mediated cytotoxicity. In addition, Maf1 overexpression suppresses ethidium bromide-induced UPRmt and enhances IR-mediated cytotoxicity. Supporting our cell-based studies, elevated expression of UPRmt makers (mtHSP70 and HSP60) are associated with poor prognosis in patients with lung adenocarcinoma (LAUD). Together, our study reveals a novel role of Maf1-UPRmt axis in mediating rapamycin's enhancing effect on IR sensitivity in A549 lung cancer cells.

Clinical progress and advanced research of red blood cells based drug delivery system.

Red blood cells (RBCs) are biocompatible carriers that can be employed to deliver different bioactive substances. In the past few decades, many strategies have been developed to encapsulate or attach drugs to RBCs. Osmotic-based encapsulation methods have been industrialized recently, and some encapsulated RBC formulations have reached the clinical stage for treating tumors and neurological diseases. Inspired by the intrinsic properties of intact RBCs, some advanced delivery strategies have also been proposed. These delivery systems combine RBCs with other novel systems to further exploit and expand the application of RBCs. This review summarizes the clinical progress of drugs encapsulated into intact RBCs, focusing on the loading and clinical trials. It also introduces the latest advanced research based on developing prospects and limitations of intact RBCs drug delivery system (DDS), hoping to provide a reference for related research fields and further application potential of intact RBCs based drug delivery system.

Hand-assisted laparoscopic donor nephrectomy: a comparative study with conventional open donor nephrectomy in a single Chinese center.

BACKGROUND: Traditional open donor nephrectomy (ODN) is associated with good outcomes and excellent allograft function; nevertheless, it causes too much injury to the donor. Hand-assisted laparoscopic donor nephrectomy (HLDN) may accomplish these goals with less damage. We compared the outcomes of the hand-assisted with the traditional open approach. We also investigated whether the availability of the HLDN approach affected a donor's decision and why he or she selected HLDN versus ODN. MATERIALS AND METHODS: We retrospectively analyzed donor and allograft outcomes for the first 65 patients undergoing HLDN at our institution compared with those of 32 patients undergoing traditional ODN. Patient data were obtained from medical record reviews and telephone interviews. RESULTS: HLDN and ODN were successfully completed in 97 (100%) donors. No conversion to open operation occurred among the HLDN group. The mean (standard deviation) operative durations were 157.92 (23.79) minutes for HLDN and 103.21 (19.63) minutes for ODN (P = .000), and hospital stays were 5.00 (1.54) days for the HLDN group and 6.59 (0.79) days for the ODN group (P = .000). There was no significant difference between the 2 groups in postoperative donor (P = .541) and recipient (P = .337) renal functions. The primary reason encouraging donors was family obligations and bonds (70.1%); the availability of HLDN did encourage the decision (29.9%). Although all renal donors were aware of the option of HLDN, 28 selected ODN because of financial reasons, another 4 patients due to safety concerns. The main reasons for choosing HLDN instead of ODN were less postoperative pain (60%) and cosmetic concerns (29.2%). CONCLUSIONS: HLDN was safe and feasible to procure a normally functional organ for live donor transplantation. The availability of the HLDN approach did affect a donor's decision. The main reason for choosing HLDN instead of ODN was less postoperative pain.