The dilemmas and possible solutions for CAR-T cell therapy application in solid tumors.

Chimeric antigen receptor T (CAR-T) cell therapy, as an adoptive immunotherapy, is playing an increasingly important role in the treatment of malignant tumors. CAR-T cells are referred to as "living drugs" as they not only target tumor cells directly, but also induce long-term immune memory that has the potential to provide long-lasting protection. CD19.CAR-T cells have achieved complete response rates of over 90 % for acute lymphoblastic leukemia and over 60 % for non-Hodgkin's lymphoma. However, the response rate of CAR-T cells in the treatment of solid tumors remains extremely low and the side effects potentially severe. In this review, we discuss the limitations that the solid tumor microenvironment poses for CAR-T application and the solutions that are being developed to address these limitations, in the hope that in the near future, CAR-T cell therapy for solid tumors can attain the same success rates as are now being seen clinically for hematological malignancies.

Enhancing deep vein thrombosis prediction in patients with coronavirus disease 2019 using improved machine learning model.

BACKGROUND: Deep vein thrombosis (DVT) is a significant complication in coronavirus disease 2019 patients, arising from coagulation issues in the deep venous system. Among 424 scheduled patients, 202 developed DVT (47.64%). DVT increases hospitalization risk, and complications, and impacts prognosis. Accurate prognostication and timely intervention are crucial to prevent DVT progression and improve patient outcomes. METHODS: This study introduces an effective DVT prediction model, named bSES-AC-RUN-FKNN, which integrates fuzzy k-nearest neighbor (FKNN) with enhanced Runge-Kutta optimizer (RUN). Recognizing the insufficient effectiveness of RUN in local search capability and its convergence accuracy, spherical evolutionary search (SES) and differential evolution-inspired knowledge adaptive crossover (AC) are incorporated, termed SES-AC-RUN, to enhance its optimization capability. RESULTS: Based on the benchmark set by CEC 2017 and comparative analyses with several peers, it is evident that SES-AC-RUN significantly enhances search performance compared to traditional RUN, even standing comparably against leading championship algorithms. The proposed bSES-AC-RUN-FKNN model was applied to predict a dataset comprising 424 cases of DVT patients, totaling 7208 records. Remarkably, the model demonstrates outstanding accuracy, reaching 91.02%, alongside commendable sensitivity at 91.07%. CONCLUSIONS: The bSES-AC-RUN-FKNN emerges as a robust and efficient predictive tool, significantly enhancing the accuracy of DVT prediction. This model can be used to manage the risk of thrombosis in the care of COVID-19 patients. Nursing staff can combine the model's predictions with clinical judgment to formulate comprehensive treatment approaches.

Feasibility and safety of laparoscopic radical cystectomy for male octogenarians with muscle-invasive bladder cancer.

This study was designed to evaluate the safety and feasibility of laparoscopic radical cystectomy (LRC) for male octogenarian patients with muscle-invasive bladder cancer (MIBC). Briefly, a total of 57 male octogenarian patients (A group) with bladder carcinoma were enrolled and underwent LRC and intracorporeal pelvic lymph node dissection with bilateral cutaneous ureterostomy from May 2016 to December 2022. Besides, 63 male patients (age < 80 years old) with bladder carcinoma undergoing LRC and 17 octogenarian male patients with bladder carcinoma undergoing open radical cystectomy (ORC) were enrolled in B and C groups as control. All perioperative clinical materials and outcomes of long-term follow-up, and complication were collected. The specific results were shown as follows. Compared with C group, the operation time and resected lymph node in A group was increased, and the estimated blood loss, the number of transfusion needed, duration of pelvic drainage and hospital stay after surgery was decreased. The death rate and ileus complication rate were higher in A group (12 cases) than in C group (15 cases). The cases of ureteral stricture in A group (13 cases) was decreased compared with that in C group. Overall, LRC and bilateral cutaneous ureterostomy are safe, feasible and better choices for the treatment of male octogenarian patients with MIBC. The octogenarian receiving cutaneous ureterostomy heals slowly and exists certain incomplete intestinal obstruction after surgery.

A novel microenvironment regulated system CAR-T (MRS.CAR-T) for immunotherapeutic treatment of esophageal squamous carcinoma.

Chimeric antigen receptor T cell immunotherapy has achieved promising therapeutic effects in the treatment of hematological malignancies. However, there are still many obstacles, including on-target off-tumor antigen expression, that prevent successful application to solid tumors. We designed a tumor microenvironment (TME) regulated system chimeric antigen receptor T (MRS.CAR-T) which can only be auto-activated in the solid TME. B7-H3 was selected as the target antigen for esophageal carcinoma. An element comprising a human serum albumin (HSA) binding peptide and a matrix metalloproteases (MMPs) cleavage site was inserted between the 5' terminal signal peptide and single chain fragment variable (scFv) of the CAR skeleton. Upon administration, HSA bound the binding peptide in MRS.B7-H3.CAR-T effectively and promoted proliferation and differentiation into memory cells. MRS.B7-H3.CAR-T was not cytotoxic in normal tissues expressing B7-H3 as the antigen recognition site in the scFv was cloaked by HSA. The anti-tumor function of MRS.B7-H3.CAR-T was recovered once the cleavage site was cleaved by MMPs in the TME. The anti-tumor efficacy associated with MRS.B7-H3.CAR-T cells was improved compared to classic B7-H3.CAR-T cells in vitro and less IFN-γ was released, suggesting a treatment that may induce less extent of cytokine release syndrome-mediated toxicity. In vivo, MRS.B7-H3.CAR-T cells had strong anti-tumor activity and were safe. MRS.CAR-T represents a novel strategy to improve the efficacy and safety of CAR-T therapy in solid tumors.

Comparison of the Effects of Prebiotics and Synbiotics Supplementation on the Immune Function of Male University Football Players.

This study was conducted to compare the effects of long-term prebiotic and synbiotic supplementations on the immunosuppression of male football players after daily high-intensity training and a one-time strenuous exercise. A total of 30 male university student-athletes were recruited and randomly assigned to the prebiotic (PG, n = 15) or synbiotic group (SG, n = 15), receiving a prebiotic or synbiotic once per day for six weeks. Physiological assessments were conducted by a maximal oxygen uptake (VO2max) test and an exhaustive constant load exercise (75% VO2max test). Inflammatory cytokine and secretory immunoglobulin A (SIgA) were measured. VO2max, maximal heart rate (HRmax), and lactic acid elimination rate (ER) were used to evaluate aerobic capacity. Upper respiratory tract infection (URTI) complaints were evaluated using a questionnaire. URTI incidence and duration were significantly lower in the SG group than that in the PG group (p < 0.05). At baseline, SIgA and interleukin-1ß (IL-1ß) levels in the SG group (p < 0.01) as well as IL-1ß and IL-6 in the PG group (p < 0.05) were significantly increased, and IL-4 concentration was markedly reduced in the PG group (p < 0.01). The concentrations of IL-4, IL-10 and transforming growth factor-ß1 (TGF-ß1) were significantly reduced in the PG and SG group immediately after the constant load exercise. Significantly decreased HRmax and enhanced ER (increased by 193.78%) were detected in the SG group, not in the PG group, during the constant load experiment (p < 0.05) and the recovery period (p < 0.01), respectively. However, VO2max value was not changed. These data suggest that synbiotic supplementation for six weeks has a more positive effect than prebiotics on the immune function and athletic performance of male university football players.

Genome-wide identification of GRF gene family and their contribution to abiotic stress response in pitaya (Hylocereus polyrhizus).

Growth-regulating factors (GRFs) are plant-specific transcription factors identified in many land plants. Recently, their indispensable roles in stress response are highlighted. In present work, 11 HpGRFs were cloned in pitaya. Segmental duplication is considered essential for the expansion of HpGRFs. A phylogenetic tree suggested that GRFs could be divided into eight categories, among which G-I was a Caryophyllales-specific one. The categorization was further evidenced by differences in the gene structure, collinearity, protein domain of HpGRFs. Five miR396 hairpins giving rise to two types of matured miR396s were identified in pitaya via sRNA-Seq in combination with bioinformatic analysis. Parallel analysis of RNA ends proved that HpGRFs except HpGRF5 were degraded by miR396-directed cleavages at the regions which code the conserved WRC motifs of HpGRFs. Multiple cis-regulatory elements were discovered in the promoters of HpGRFs. Among the elements, most are involved in stress and phytohormone response as well as plant growth, indicating a crosstalk between them. Expression analysis showed the responsive patterns of the miR396-GRF module under abiotic stresses. To conclude, our work systematically identified the miR396-targeted HpGRFs in pitaya and confirmed their involvement in stress response, providing novel insights into the comprehensive understanding of the stress resistance of pitaya.

Effect of velocity and acceleration in joint angle estimation for an EMG-Based upper-limb exoskeleton control.

Most studies on estimating user's joint angles to control upper-limb exoskeleton have focused on using surface electromyogram (sEMG) signals. However, the variations in limb velocity and acceleration can affect the sEMG data and decrease the angle estimation performance in the practical use of the exoskeleton. This paper demonstrated that the variations in elbow angular velocity (EAV) and elbow angular acceleration (EAA) associated with normal use led to a large effect on the elbow joint angle estimation. To minimize this effect, we proposed two methods: (1) collecting sEMG data of multiple EAVs and EAAs as training data and (2) measuring the values of EAV and EAA with a gyroscope. A self-developed upper-limb exoskeleton with pneumatic muscles was used in the online control phase to verify our methods' effectiveness. The predicted elbow angle from the sEMG-angle models which were trained in the offline estimation phase was transferred to control signal of the pneumatic muscles to actuate the exoskeleton to move to the same angle. In the offline estimation phase, the average root mean square error (RMSE) between predicted elbow angle and actual elbow angle was reduced from 22.54° to 10.01° (using method one) and to 6.45° (using method two), respectively; in the online control phase, method two achieved a best control performance (average RMSE = 6.87°). The results showed that using multi-sensor fusion (sEMG sensors and gyroscope) achieved a better estimation performance than using only sEMG sensor, which was helpful to eliminate the velocity and acceleration effect in real-time joint angle estimation for upper-limb exoskeleton control.

A retrospective analysis on the effect of single-channel minimally invasive percutaneous nephrolithotomy combined with retrograde flexible ureteroscopy using the completely lateral decubitus and semi-lithotomy positions to treat complex kidney stones.

BACKGROUND: Some types of complex kidney stones cannot be broken down and removed through single-channel percutaneous nephroscope or retrograde flexible ureteroscope. In order to be removed, these types of stones require multiple combined methods to be performed. The aim of this study was to retrospectively evaluate the clinical effect of single-channel minimally invasive percutaneous nephrolithotomy (mPCNL) combined with retrograde flexible ureteroscopy using the completely lateral decubitus and semi-lithotomy positions for treating complex renal calculi. METHODS: We selected 117 patients with complex renal calculi who were admitted to Peking University Shougang Hospital and Weifang People's Hospital from January 1, 2017, to January 31, 2021. All patients were treated with single-channel mPCNL combined with retrograde flexible ureteroscopy in the completely lateral decubitus and semi-lithotomy positions. During the operation, the patients were placed in a completely lateral decubitus position, or their lower limbs were placed in a semi-lithotomy position for a single attempt only. RESULTS: An 18-Fr percutaneous channel was successfully established in all patients. The mean operation time was 112±37 minutes, and the average blood loss was 71±31 mL. A 14-Fr renal fistula was maintained for 7 days, a urethral catheter for 2-3 days, and a ureteral stent tube for 2 weeks after each surgery. According to the results of computed tomography (CT) scans performed 3-5 days after the operation, the total lithotripsy success rate reached 100%, with a first-stage lithotripsy rate of 98.29%. Two patients were found to each have 1 residual stone, with a diameter of 4 mm, left in kidney by CT, which then was to be removed under local anesthesia. The average postoperative hospitalized time was 7±2 days, and no severe complications occurred perioperatively. CONCLUSIONS: Single-channel mPCNL combined with retrograde flexible ureteroscopy in the completely lateral decubitus and semi-lithotomy positions is a safe, feasible, and highly effective method of treating complex renal calculi, which is of benefit to save operation time and facilitate operation process, because patient's position could not need to be changed repeatedly during the surgery.

2D atomic crystal molecular superlattices by soft plasma intercalation.

Two-dimensional (2D) atomic crystal superlattices integrate diverse 2D layered materials enabling adjustable electronic and optical properties. However, tunability of the interlayer gap and interactions remain challenging. Here we report a solution based on soft oxygen plasma intercalation. 2D atomic crystal molecular superlattices (ACMSs) are produced by intercalating O2+ ions into the interlayer space using the plasma electric field. Stable molecular oxygen layer is formed by van der Waals interactions with adjacent transition metal dichalcogenide (TMD) monolayers. The resulting interlayer gap expansion can effectively isolate TMD monolayers and impart exotic properties to homo-(MoS2[O2]x) and hetero-(MoS2[O2]x/WS2[O2]x) stacked ACMSs beyond typical capacities of monolayer TMDs, such as 100 times stronger photoluminescence and 100 times higher photocurrent. Our potentially universal approach to tune interlayer stacking and interactions in 2D ACMSs may lead to exotic superlattice properties intrinsic to monolayer materials such as direct bandgap pursued for future optoelectronics.

TGFß regulates NK1R-Tr to affect the proliferation and apoptosis of breast cancer cells.

OBJECTIVES: TGFß promotes cancer aggressiveness in advanced stages. NK1R-Tr expression in advanced breast cancer has a pro-carcinogenic effect. In this study, we aimed to investigate the effect of the association of TGFß with NK1R-Tr expression on the proliferation and apoptosis of breast cancer cells. METHODS: Immunohistochemical staining and Western blot analysis were used to detect TGFß and NK1R-Tr in breast cancer and paracancerous tissue samples. MDA-MB-231 and BT549 cells were stimulated with TGFß after NK1R knockdown or treated with the NK1R antagonist aprepitant, and the effects of TGFß and NK1R-Tr on proliferation and apoptosis were detected by CCK-8, colony formation and flow cytometry assays. In vivo xenograft models were used to further verify the effects of NK1R-Tr and TGFß. The regulatory effects of Smad4 on NK1R promoter activity were confirmed by ChIP and dual-luciferase reporter assays. RESULTS: The expression levels of TGFß and NK1R-Tr were higher in breast cancer tissues than in adjacent tissues and were positively correlated in human breast cancer tissues. NK1R knockdown or aprepitant treatment in MDA-MB-231 and BT549 cells attenuated the effects of TGFß on cell proliferation. The proportion of cells in G2/M phase significantly increased, the expression of cyclin B1 decreased, and the expression of P21 increased; these effects were weakened by TGFß treatment. Apoptosis in breast cancer cells was significantly increased. In vivo xenograft models were used to further verify that NK1R-Tr and TGFß promoted tumour growth. After TGFß treatment, the binding capacity of Smad4 to the NK1R promoter, as well as luciferase activity, was enhanced. CONCLUSIONS: The expression levels of TGFß and NK1R-Tr were higher in breast cancer tissues than in normal tissues, and both were correlated with a poor patient prognosis. TGFß and NK1R-Tr promoted cell proliferation and inhibited apoptosis, and TGFß regulated the expression of NK1R-Tr via Smad4.

miR-206 Promotes Cancer Progression by Targeting Full-Length Neurokinin-1 Receptor in Breast Cancer.

Substance P plays a pivotal role in human cancer development and progression by binding to its receptor, neurokinin-1. Neurokinin-1 has 2 isoforms: full-length neurokinin-1 and truncated neurokinin-1, the latter lacking the cytoplasmic terminal 96-amino acid residues of the full-length protein. We have identified 3 candidate miR-206 target sites within the 3'-untranslated region of the full-length neurokinin-1 gene from bioinformatics database searches. In the present study, real-time quantitative polymerase chain reaction was performed to quantify the expression of miR-206, and the expression of neurokinin-1 and full-length neurokinin-1 was detected by immunohistochemistry in 82 clinical cases of breast cancer and paired adjacent normal tissues. The miR-206 target gene was demonstrated by using a dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and Western blotting. Transwell migration and invasion, colony formation, and proliferation assays were performed to evaluate the effects of miR-206 expression on various aspects of breast cancer cell behavior in vitro. We showed that miR-206 expression is upregulated in breast cancer cell lines and breast cancer tissues when compared to that in adjacent normal tissues, and full-length neurokinin-1 expression inversely correlates with Tumor Lymph Node Metastasis (TNM) stage and lymph node metastasis. Western blotting, quantitative real-time polymerase chain reaction, and dual-luciferase reporter assays demonstrated that miR-206 binds the 3'-untranslated region of full-length neurokinin-1 messenger RNA, regulating protein expression. We showed that the overexpression of miR-206 promotes breast cancer cell invasion, migration, proliferation, and colony formation in vitro. The present study furthers the current understanding of the mechanisms underlying breast cancer pathogenesis and may be useful for the development of novel targeted therapies.

UNC5D, suppressed by promoter hypermethylation, inhibits cell metastasis by activating death-associated protein kinase 1 in prostate cancer.

Prostate cancer (PCa) death primarily occurs due to metastasis of the cells, but little is known about the underlying molecular mechanisms. This study aimed to evaluate the expression of UNC5D, a newly identified tumor suppressor gene, analyze its epigenetic alterations, and elucidate its functional relevance to PCa metastasis. Meta-analysis of publicly available microarray datasets revealed that UNC5D expression was frequently downregulated in PCa tissues and inversely associated with PCa metastasis. These results were verified in clinical specimens by real-time PCR and immunohistochemistry assays. Through methylation analysis, the downregulated expression of UNC5D in PCa tissues and cell lines was found to be attributable to the hypermethylation of the promoter. A negative correlation was observed between methylation and UNC5D mRNA expression in PCa samples. The ectopic expression of UNC5D in PCa cells effectively reduced their ability to migrate and invade both in vitro and in vivo, and siRNA-mediated knockdown of UNC5D yielded consistent results. UNC5D can recruit and activate death-associated protein kinase 1, which remained to be essential for its metastatic suppressor function. In conclusion, these results suggested that UNC5D as a novel putative metastatic suppressor gene that is commonly down-regulated by hypermethylation in PCa.

Soft hydrogen plasma induced phase transition in monolayer and few-layer MoTe2.

Phase transition from the semiconducting hexagonal (2H) phase to the metallic monoclinic (1T') phase in two-dimensional (2D) transition metal dichalcogenides like MoTe2 is not only of great importance in fundamental study but also of technological significance for broad device applications. Here we report a universal, facile, scalable and reversible phase engineering technique (between 2H and 1T' phases) for both monolayer and few-layer MoTe2 based on a soft hydrogen plasma treatment. The 2H â†’ 1T' transition was confirmed by a series of characterizations including Raman spectra and mapping studies, XPS analysis and FET device measurements at varying temperatures. We attribute the phase transition to the warping of Te-Mo bonds and the lateral sliding of the top Te-layer induced by the soft hydrogen ion bombardment according to both the structural and electronic characterizations as well as the horizontal comparison with the cases of Ar or O2 plasma treatment. We have also prepared a 2D heterostructure containing periodical 2H and 1T' MoTe2 and showed that such phase transition can be readily reversed by post annealing. These results thus provide a robust and efficient approach for the phase engineering of monolayer and few-layer MoTe2 and could aid the development of 2D optoelectronic, memory and reconfigurable devices.

MicroRNA-22 inhibits proliferation, invasion and metastasis of breast cancer cells through targeting truncated neurokinin-1 receptor and ERα.

HEADING AIMS: This topic aims to clarify whether miR-22 directly targets and downregulates the expression of ERα and NK1R-Tr to inhibit the malignant behaviors of breast cancer cells. MATERIALS AND METHODS: RT-PCR and Western Blotting were used to detect the expression profile of miR-22, NK1R-Tr and ERα. Luciferase reporter assay and CHIP experiment were conducted to investigate the regulation network between miR-22, NK1R-Tr and ERα. MCF-7-ERαI and MDA-MB-231-ERα cell lines were constructed to study the biological behaviors. The SP-NK1R-ERK1/2 signaling pathway was analyzed using Western Blotting. The subcutaneous and metastases tumor models were employed to study the effects of miR-22 on cell proliferation and metastasis of breast cancer cells in vivo. KEY FINDINGS: MiR-22 expression level was significantly lower in breast cancerous tissues and cell lines than the adjacent normality, while that of NK1R-Tr increased. The ERα could positively regulate NK1R-Tr expression at DNA level. The descent degree of NK1R-Tr in MCF-7-ERαI cells was far less than that in wild MCF-7 cells, while the findings in MDA-MB-231-ERα cells was more apparent than wild MDA-MB-231 cells. The malignant phenotype was decreased in miR-22 overexpressing cells compared with the wild type. The peak of ERK1/2 phosphorylation was delayed and weakened in miR-22 overexpressing MCF-7 cells, which was agreed with the findings using NK1R-Tr antagonist. The size and number of metastatic tumors declined compared to the controls. SIGNIFICANCE: MiR-22 downregulated the expression of NK1R-Tr and ERα to delay and weaken phosphorylation of ERK1/2 to inhibit proliferation and metastasis of breast cancer cells.

MiR-34b/c-5p and the neurokinin-1 receptor regulate breast cancer cell proliferation and apoptosis.

OBJECTIVES: MiR-34 is a tumour suppressor in breast cancer. Neurokinin-1 receptor (NK1R), which is the predicted target of the miR-34 family, is overexpressed in many cancers. This study investigated the correlation and clinical significance of miR-34 and NK1R in breast cancer. MATERIALS AND METHODS: Western blotting, quantitative reverse transcription-PCR (qRT-PCR) and luciferase assays were conducted to analyse the regulation of NK1R by miR-34 in MDA-MB-231, MCF-7, T47D, SK-BR-3 and HEK-293 T cells. MiR-34b/c-5p, full-length NK1R (NK1R-FL) and truncated NK1R (NK1R-Tr) expression in fifty patients were quantified by qRT-PCR and correlated with their clinicopathological parameters. CCK-8 assays, colony formation assays and flow cytometry were used to measure cell proliferation and apoptosis in MDA-MB-231 and MCF-7 cells transfected with miR-34b/c-5p or NK1R-siRNA and before treatment with or without Substance P (SP), an endogenous peptide agonists of NK1R. The effect of NK1R antagonist aprepitant was also investigated. In vivo xenograft models were used to further verify the regulation of NK1R by miR-34b/c-5p. RESULTS: Expression levels of miR-34b/c-5p and NK1R-Tr, but not NK1R-FL, were associated with enhanced malignant potential, such as tumour stage and Ki67 expression. The overexpression of miR-34b/c-5p or NK1R silencing potently suppressed cell proliferation and induced G2/M phase arrest and the apoptosis of MDA-MB-231 and MCF-7 cells. The NK1R antagonist aprepitant had similar effects. In vivo studies confirmed that miR-34b/c-5p overexpression or NK1R silencing reduced the tumorigenicity of breast cancer. In addition, SP rescued the effects of miR-34b/c-5p overexpression or NK1R silencing on cell proliferation and apoptosis in vitro and in vivo assays. CONCLUSIONS: MiR-34b/c-5p and NK1R contribute to breast cancer cell proliferation and apoptosis and are potential targets for breast cancer therapeutics.

Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9 in detecting pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with few biomarkers to guide treatment options. Carbohydrate antigen 19.9 (CA19.9), the most frequently used biomarker for PDAC, is not sensitive and specific enough for the detection of the disease. This study aimed to evaluate serum periostin (POSTN) and CA242 as potential diagnostic biomarkers complementing CA19.9 in detecting pancreatic cancer. Blood samples were from 362 participants, including 213 patients with different stages of PDAC, 75 patients with benign pancreatic disease, and 74 healthy individuals. All samples were randomly divided into a training set and a validation set. Carbohydrate antigen 19.9, CA242, POSTN, as well as carcinoembryonic antigen, were measured by ELISA or automated immunoassay. The receiver operating characteristic curve analysis revealed that the performance of CA19.9 in the validation group were improved by the marker panel composed of CA19.9, POSTN, and CA242, to discriminate early stage PDAC not only from healthy controls (area under the curve [AUC]CA19.9 = 0.94 vs AUCCA19.9 + POSTN + CA242 = 0.98, P < .05) but also from benign conditions (AUCCA19.9 = 0.87 vs AUCCA19.9 + POSTN + CA242 = 0.90, P < .05). In addition, POSTN retained significant diagnostic capabilities to distinguish PDAC CA19.9-negative from healthy controls (AUCPOSTN = 0.87) as well as from benign conditions (AUCPOSTN = 0.84) in the whole set. This study suggested that POSTN and CA242 are potential diagnostic serum biomarkers complementing CA19.9 in detecting early pancreatic cancer.

Identification of Serum Periostin as a Potential Diagnostic and Prognostic Marker for Colorectal Cancer.

BACKGROUND: Periostin (POSTN) plays an important role in numerous cancers, especially in gastrointestinal malignancy. The objective of this study was to investigate the diagnostic and prognostic role of serum POSTN in colorectal cancer (CRC). METHODS: Serum periostin, together with CEA, CA19.9, CA72.4, and CA242 levels were measured in samples from 108 patients with CRC and 56 healthy controls, and their correlation with clinical characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses were used to evaluate diagnostic and prognostic significance. RESULTS: Serum POSTN levels were significantly higher in patients with CRC compared with healthy controls (p < 0.0001) and associated with clinical stages (p < 0.001). ROC analysis revealed that POSTN was a biomarker comparable to CEA, CA19.9, and CA72.4 to distinguish all CRC from healthy controls (AUC = 0.75). Moreover, POSTN retained its diagnostic ability for CEA-negative (AUC = 0.69) and CA19.9-negative CRC patients (AUC = 0.71). Survival analysis revealed that patients with lower serum POSTN had longer overall survival than those with high serum POSTN (p = 0.0146). CONCLUSIONS: Serum POSTN might be a novel diagnostic and prognostic biomarker for patients with CRC.

Inappropriate Use of Antimicrobials for Lower Respiratory Tract Infections in Elderly Patients: Patient- and Community-Related Implications and Possible Interventions.

The elderly are more susceptible to infections, which is reflected in the incidence and mortality of lower respiratory tract infections (LRTIs) increasing with age. Several aspects of antimicrobial use for LRTIs in elderly patients should be considered to determine appropriateness. We discuss possible differences in microbial etiology between elderly and younger adults, definitions of inappropriate antimicrobial use for LRTIs currently found in the literature, along with their results, and the possible negative impact of antimicrobial therapy at both an individual and community level. Finally, we propose that both antimicrobial stewardship interventions and novel rapid diagnostic techniques may optimize antimicrobial use in elderly patients with LRTIs.

Evaluation of Serological Indicators and Glomerular Filtration Rate Equations in Chinese Cancer Patients.

BACKGROUND The performance of estimated glomerular filtration rate (eGFR) have been proved to vary according to the races of the target population. The eGFR equations have not been validated in the Chinese cancer population received chemotherapy. Meanwhile, serum cystatin C (CysC), urea, ß2 microglobulin (ß2-MG), and creatinine (SCr) were also evaluated in a cohort of Chinese cancer patients. MATERIAL AND METHODS A total of 1000 cancer patients undergoing combination chemotherapy and 108 healthy volunteers were included in this study, and their renal function parameters were evaluated. The eGFR values were compared with reference GFR (rGFR) according to correlation, consistency, precision, and accuracy. Receiver operating characteristic (ROC) curves were used to evaluate the discriminating ability of the GFR equations and serological indicators of renal function. RESULTS (1) The equations contained CysC had the same varying tendency as rGFR in relation to the chemotherapeutic cycle. (2) eGFRscr+cysc and eGFRChinese scr+cysc worked better than the other equations, as indicated by a stronger correlation, less bias, improved precision, higher accuracy, and greater AUC. (3) CysC was more sensitive than the other serological indicators for identifying early renal injury. (4) Each parameter showed different characteristics in subgroups of Chinese cancer patients. CONCLUSIONS CysC was the most sensitive marker for early renal injury. Among the 8 most commonly used eGFR equations, the combination equation eGFRscr+cysc and eGFRChinese scr+cysc exhibited the best performance in the assessment of the renal function of Chinese cancer patients.

Nanomechanical clues from morphologically normal cervical squamous cells could improve cervical cancer screening.

Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis.