Impact of air pollutants on influenza-like illness outpatient visits under COVID-19 pandemic in the subcenter of Beijing, China.

This study aimed to explore the association between air pollutants and outpatient visits for influenza-like illnesses (ILI) under the coronavirus disease 2019 (COVID-19) stage in the subcenter of Beijing. The data on ILI in the subcenter of Beijing from January 1, 2018 to December 31, 2020 were obtained from the Beijing Influenza Surveillance Network. A generalized additive Poisson model was applied to examine the associations between the concentrations of air pollutants and daily outpatient visits for ILI when controlling meteorological factors and temporal trend. A total of 171 943 ILI patients were included. In the pre-coronavirus disease 2019 (COVID-19) stage, an increased risk of ILI outpatient visits was associated to a high air quality index (AQI) and the high concentrations of particulate matter less than 2.5 (PM2.5 ), particulate matter 10 (PM10 ), sulphur dioxide (SO2 ), nitrogen dioxide (NO2 ), and carbon monoxide (CO), and a low concentration of ozone (O3 ) on lag0 day and lag1 day, while a higher increased risk of ILI outpatient visits was observed by the air pollutants in the COVID-19 stage on lag0 day. Except for PM10 , the concentrations of other air pollutants on lag1 day were not significantly associated with an increased risk of ILI outpatient visits during the COVID-19 stage. The findings that air pollutants had enhanced immediate effects and diminished lag-effects on the risk of ILI outpatient visits during the COVID-19 pandemic, which is important for the development of public health and environmental governance strategies.

Value of Radiomic Analysis Combined With Diffusion Tensor Imaging in Early Diagnosis of HIV-Associated Neurocognitive Disorders.

BACKGROUND: The combination of radiomics and diffusion tensor imaging (DTI) may have potential clinical value in the early stage of HIV-associated neurocognitive disorders (HAND). PURPOSE: To investigate the value of DTI-based radiomics in the early stage of HAND in people living with HIV (PLWH). STUDY TYPE: Retrospective. POPULATION: A total of 138 male PLWH were included, including 68 with intact cognition (IC) and 70 with asymptomatic neurocognitive impairment (ANI). Seventy healthy controls (HCs) were recruited for tract-based spatial statistics (TBSS) analysis. All PLWHs were randomly divided into training and validation cohorts at a 7:3 ratio. FIELD STRENGTH/SEQUENCE: A 3 T, single-shot spin-echo echo planar imaging (EPI). ASSESSMENT: The differences between the PLWH groups were compared using TBSS and region of interest (ROI) analysis. Radiomic features were extracted from the corpus callosum (CC) on DTI postprocessed images, including fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD). The performance of the radiomic signatures was evaluated by ROC curve analysis. The radiomic signature with the highest area under the curve (AUC) was combined with clinical characteristics to construct a nomogram. Decision curve analysis (DCA) was performed to evaluate the ability of different methods in discriminating ANI. STATISTICAL TESTS: Chi-square test, independent-samples t test, Kruskal-Wallis test, Mann-Whitney U test, threshold-free cluster enhancement (TFCE), ROC curve analysis, DCA, multivariate logistic regression analysis, Hosmer-Lemeshow test. P < 0.05 with TFCE corrected and P < 0.0001 without TFCE corrected were considered statistically significant. RESULTS: The ANI group showed lower FA and higher AD than the IC group. In the validation cohort, the AUCs of the FA-, AD-, MD- and RD-based radiomic signatures and the clinicoradiomic nomogram were 0.829, 0.779, 0.790, 0.864, and 0.874, respectively. DCA revealed that the nomogram was of greater clinical value than TBSS analysis, the clinical models, and the RD-based radiomic signature. DATA CONCLUSION: The combination of DTI and radiomics is correlated with early stage of HAND in PLWH. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

A novel model based on liver/spleen volumes and portal vein diameter on MRI to predict variceal bleeding in HBV cirrhosis.

OBJECTIVE: To develop a novel logistic regression model based on liver/spleen volumes and portal vein diameter measured on magnetic resonance imaging (MRI) for predicting oesophagogastric variceal bleeding (OVB) secondary to HBV cirrhosis. METHODS: One hundred eighty-five consecutive cirrhotic patients with hepatitis B undergoing abdominal contrast-enhanced MRI were randomly divided into training cohort (n = 130) and validation cohort (n = 55). Spleen volume, total liver volume, four liver lobe volumes, and diameters of portal venous system were measured on MRI. Ratios of spleen volume to total liver and to individual liver lobe volumes were calculated. In training cohort, univariate analyses and binary logistic regression analyses were to determine independent predictors. Performance of the model for predicting OVB constructed based on independent predictors from training cohort was evaluated by receiver operating characteristic (ROC) analysis, and was validated by Kappa test in validation cohort. RESULTS: OVB occurred in 42 and 18 individuals in training and validation cohorts during the 2 years' follow-up, respectively. An OVB prediction model was constructed based on the independent predictors including right liver lobe volume (RV), left gastric vein diameter (LGVD) and portal vein diameter (PVD) (odds ratio = 0.993, 2.202 and 1.613, respectively; p-values < 0.001 for all). The logistic regression model equation (-0.007 × RV + 0.79 × LGVD + 0.478 × PVD-6.73) for predicting OVB obtained excellent performance with an area under ROC curve of 0.907. The excellent performance was confirmed by Kappa test with K-value of 0.802 in validation cohort. CONCLUSION: The novel logistic regression model can be reliable for predicting OVB. KEY POINTS: • Patients with oesophagogastric variceal bleeding are mainly characterized by decreased right lobe volume, and increased spleen volume and diameters of portal vein system. • The right liver lobe volume, left gastric vein diameter and portal vein diameter are the independent predictors of oesophagogastric variceal bleeding. • The novel model developed based on the independent predictors performed well in predicting oesophagogastric variceal bleeding with an area under the receiver operating characteristic curve of 0.907.

TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma.

BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

Sodium butyrate improves mitochondrial function and kidney tissue injury in diabetic kidney disease via the AMPK/PGC-1α pathway.

PURPOSE: Investigate the mechanism of how sodium butyrate (NaBut) improves mitochondrial function and kidney tissue injury in diabetic kidney disease (DKD) via the AMPK/PGC-1α pathway. METHODS: Assess the effects of NaBut on glucose and insulin tolerance, urine, and gut microbial composition in db/db and db/m mice. Use flow cytometry and western blotting to detect the effects of NaBut on apoptosis, kidney mitochondrial function, and AMPK/PGC-1α signaling. Use HK-2 cells induced by high glucose (HG) to establish the DKD model in vitro and detect changes in the AMPK/PGC-1α signaling pathway and mitochondrial function after NaBut intervention. RESULTS: NaBut attenuated blood glucose levels and reversed increases in urine and serum levels of glucose, BUN, Ucr, TG, TC, and UAE in db/db mice. NaBut improved insulin tolerance, reversed PGC-1α and p-AMPK expression level in the kidneys of db/db mice, and improved lipid accumulation and mitochondrial function. NaBut was able to reverse the effects of elevated glucose, compound C, and siRNA-PGC on ROS and ATP levels. Additionally, it increased protein expression of PGC-1α and p-AMPK. CONCLUSION: NaBut activates the kidney mitochondrial AMPK/PGC-1α signaling pathway and improves mitochondrial dysfunction in DKD, thus protecting kidney tissue in vitro and in vivo.

Epidemiological characteristics of hand, foot, and mouth disease clusters during 2016-2020 in Beijing, China.

Hand, foot, and mouth disease (HFMD) is an infectious disease that usually occurs in children under 5 years and is caused by a group of enteroviruses. This study aimed to investigate the epidemiological characteristics of HFMD clusters from 2016 to 2020 in Tongzhou, Beijing, and explored the genetic evolution of CV-A6. The HFMD case information came from the Information System of China Center for Disease Control and Prevention (CDC), as well as the clusters information verification and on-site investigation by Tongzhou CDC. ARIMA model was applied to forecast HFMD clusters in 2020. Totally 440 HFMD clusters were reported during 2016-2020. The large peak of the clusters occurred in April-July, followed by a smaller peak in October-November during 2016-2019. However, in 2020, the two peaks disappeared. The main site of HFMD clusters was childcare facilities (65.0%) and mostly occurred in urban areas (46.1%). The detection rate of CV-A6 was the highest (36.1%), and cases with CV-A6 infection had the highest proportion of fever. The phylogenetic analysis based on CV-A6 VP1 gene showed that the predominant strains mainly located in Group F during 2016-2017, while changed into Group A during 2018-2020. HFMD clusters presented seasonality, mainly located in childcare facilities and urban areas, and CV-A6 was the major causative agent. Targeted prevention and control measures should be taken to reduce HFMD clusters.

Dynamics of influenza-like illness under urbanization procedure and COVID-19 pandemic in the subcenter of Beijing during 2013-2021.

Influenza-like illness (ILI) varies in intensity year by year, generally keeping a stable pattern except for great changes of its epidemic pattern. Of the most impacting factors, urbanization has been suggested as shaping the intensity of influenza epidemics. Besides, growing evidence indicates the nonpharmaceutical interventions (NPIs) to severe acute respiratory syndrome coronavirus 2 offer great advantages in controlling infectious diseases. The present study aimed to evaluate the impact of urbanization and NPIs on the dynamic of ILI in Tongzhou, Beijing, during January 2013 to March 2021. ILI epidemiological surveillance data in Tongzhou district were obtained from Beijing Influenza Surveillance Network and separated into three periods of urbanization and four intervals of coronavirus disease 2019 pandemic. Standardized average incidence rates of ILI in each separate stages were calculated and compared by using Wilson method and time series model of seasonal ARIMA. Influenza seasonal outbreaks showed similar epidemic size and intensity before urbanization during 2013-2016. Increased ILI activity was found during the process of Tongzhou's urbanization during 2017-2019, with the rate difference of 2.48 (95% confidence interva [CI]: 2.44, 2.52) and the rate ratio of 1.75 (95% CI: 1.74, 1.76) of ILI incidence between preurbanization and urbanization periods. ILI activity abruptly decreased from the beginning of 2020 and kept at the bottom level almost in every epidemic interval. The top decrease in ILI activity by NPIs was shown in 5-14 years group in 2020-2021 influenza season, as 92.2% (95% CI: 78.3%, 95.2%). The results indicated that both urbanization and NPIs interrupted the epidemic pattern of ILI. We should pay more attention to public health when facing increasing population density, human contact, population mobility, and migration in the process of urbanization. NPIs and influenza vaccination should be implemented as necessary measures to protect people from common infectious diseases like ILI.

Differences in Clinical and Imaging Features between Asymptomatic and Symptomatic COVID-19 Patients.

Objectives: The clinical and imaging features of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 and symptomatic COVID-19 patients. Methods: The clinical and chest computed tomography imaging data of 47 asymptomatic carriers and 36 symptomatic COVID-19 patients were derived. All patients underwent 4-6 CT scans over a period of 2-5 days. Results: The bulk of asymptomatic carriers who developed symptoms and most of the COVID-19 patients were older than 18 years of age with a decreased lymphocyte count, abnormal hepatic and renal function, and increased D-dimer and C-reactive protein. In the early stage, the pulmonary lesion involved mostly 1-2 lobes at the peripheral area in asymptomatic carriers but more than three lobes at both the central and peripheral areas in COVID-19 patients. In the progression stage, the lesion of asymptomatic carriers extended from the peripheral to the central area, and no significant difference was found in the lesion range compared with the symptomatic control group. In early improvement stage, the lesion was rapidly absorbed, and lesions were located primarily at the peripheral area in asymptomatic carriers; contrastingly, lesions were primarily located at both the central and peripheral areas in symptomatic patients. Asymptomatic carriers reflected a significantly shorter duration from disease onset to peak progression stage compared with the symptomatic. Conclusions: Asymptomatic carriers are a potential source of transmission and may become symptomatic COVID-19 patients despite indicating less severe pulmonary damage, earlier improvement, and better prognosis. Early isolation and intervention can eliminate such carriers as potential sources of transmission and improve their prognosis.

Early prediction of putamen imaging features in HIV-associated neurocognitive impairment syndrome.

BACKGROUND: To explore the correlation between the volume of putamen and brain cognitive impairment in patients with HIV and to predict the feasibility of early-stage HIV brain cognitive impairment through radiomics. METHOD: Retrospective selection of 90 patients with HIV infection, including 36 asymptomatic neurocognitive impairment (ANI) patients and 54 pre-clinical ANI patients in Beijing YouAn Hospital. All patients received comprehensive neuropsychological assessment and MRI scanning. 3D Slicer software was used to acquire volume of interest (VOI) and radiomics features. Clinical variables and volume of putamen were compared between patients with ANI and pre-clinical ANI. The Kruskal Wallis test was used to analysis multiple comparisons between groups. The relationship between cognitive scores and VOI was compared using linear regression. For radiomics, principal component analysis (PCA) was used to reduce model overfitting and calculations and then a support vector machine (SVM) was used to build a binary classification model. For model performance evaluation, we used an accuracy, sensitivity, specificity and receiver operating characteristic curve (ROC). RESULT: There were no significant differences in clinical variables between ANI group and pre-clinical-ANI group (P>0.05). The volume of bilateral putamen was significantly different between AHI group and pre-clinical group (P<0.05), but there was only a trend in the left putamen between ANI-treatment group and pre-clinical treatment group(P = 0.063). Reduced cognitive scores in Verbal Fluency, Attention/Working Memory, Executive Functioning, memory and Speed of Information Processing were negatively correlated with the increased VOI (P<0.05), but the correlation was relatively low. In diagnosing the ANI from pre-clinical ANI, the mean area under the ROC curves (AUC) were 0.85 ± 0.22, the mean sensitivity and specificity were 63.12 ± 5.51 and 94.25% ± 3.08%. CONCLUSION: The volumes of putamen in patients with ANI may be larger than patients with pre-clinical ANI, the change of the volume of the putamen may have a certain process; there is a relationship between putamen and cognitive impairment, but the exact mechanism is unclear. Radiomics may be a useful tool for predicting early stage HAND in patients with HIV.

PTGER3 and MMP-2 play potential roles in diabetic nephropathy via competing endogenous RNA mechanisms.

BACKGROUND: Diabetic nephropathy (DN) is a primary complication of diabetes mellitus (DM). The pathology of DN is still vague, and diagnostic accuracy is not enough. This study was performed to identify miRNAs and genes that have possibilities of being used as therapeutic targets for DN in type 2 DM. METHODS: Human miRNA data GSE51674 and gene data GSE111154 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) in the kidney between control and DN patients were screened out. The competing endogenous RNA (ceRNA) network was constructed, and key lncRNA-miRNA-mRNA pairs were selected accordingly. Potential drugs targeting DEGs were screened out and validated using PCR analysis. RESULTS: Totally, 83 DEmiRNAs and 293 DEGs were identified in GSE51674 and GSE111154, respectively. Thirteen of the top 20 DEmiRNAs (10 up and 10 down) targeted to 47 DEGs. In the ceRNA network, RP11-363E7.4/TTN-AS1/HOTAIRM1-hsa-miR-106b-5p-PTGER3 and LINC00960-hsa-miR-1237-3p-MMP-2 interaction pairs were identified as the key ceRNA network. Interestingly, PTGER3 and hsa-miR-1237-3p were downregulated, and MMP-2 and hsa-miR-106b-5p were upregulated in the kidney of patients with DN compared with normal controls, respectively. PTGER3 and MMP-2 were targeted by drugs including iloprost, treprostinil, or captopril, and the deregulation of the two genes was confirmed in the plasma samples from patients with DN as compared with controls. CONCLUSIONS: We speculated that the RP11-363E7.4/TTN-AS1/HOTAIRM1-hsa-miR-106b-5p-PTGER3 and LINC00960-hsa-miR-1237-3p-MMP-2 networks were associated with diabetic renal injury.

Influences of the lncRNA TUG1-miRNA-34a-5p network on fibroblast-like synoviocytes (FLSs) dysfunction in rheumatoid arthritis through targeting the lactate dehydrogenase A (LDHA).

BACKGROUND: Rheumatoid arthritis (RA) is a systemic and chronic inflammatory disease. The cellular glucose metabolism of fibroblast-like synoviocytes (FLSs) of RA has been revealed to be essential to the pathogenesis and development of RA. To date, the precise roles and molecular mechanisms of long noncoding RNA TUG1 in RA have not been elucidated. METHODS: TUG1 and miR-34a-5p were detected by qRT-PCR. Interactions between lncRNA-miRNA and miRNA-mRNA were validated by RNA pull-down assay and luciferase assay. The glucose metabolism was evaluated by glucose uptake and extracellular acidification rate (ECAR). Cell viability was determined by MTT assay and Annexin V assay. RESULTS: TUG1 expression was significantly upregulated in synovial fibroblast-like synoviocytes (FLSs) compared with normal FLSs. Functional assays uncovered that silence of TUG1 suppressed FLSs-RA invasion, migration, glucose metabolism, and increased apoptosis. Bioinformatics analysis indicated that TUG1 interacted with miR-34a-5p. RNA pull-down assay and luciferase assay validated that TUG1 sponged miR-34a-5p in FLSs-RA. Overexpression of miR-34a-5p effectively inhibited glucose metabolism of FLSs-RA. Furthermore, the glucose metabolism of FLSs-RA was significantly elevated compared with normal FLSs. The glucose metabolism enzyme, LDHA, was directly targeted by miR-34a-5p in FLSs. Rescue experiments validated that the miR-34a-5p-inhibited glucose metabolism of FLSs-RA was through targeting LDHA. Finally, we showed restoration of miR-34a-5p in TUG1-overexpressing FLSs-RA successfully overcame the TUG1-promoted glucose metabolism and apoptosis resistance via targeting LDHA. CONCLUSION: The present study uncovered critical roles and molecular mechanisms underlying the TUG1-mediated glucose metabolism and apoptosis of FLSs-RA through modulating the miR-34a-5p-LDHA pathway in fibroblast-like synoviocytes of rheumatoid arthritis.

Programmable Delivery of Immune Adjuvant to Tumor-Infiltrating Dendritic Cells for Cancer Immunotherapy.

Tumor-infiltrating dendritic cells (TIDCs) are mostly immature and immunosuppressive, usually mediating immune inhibition. The utilization of cytosine-guanine oligodeoxynucleotides (CpG ODNs) to stimulate the activation of TIDCs has been demonstrated to be effective for improving antitumor immunity. However, a series of biological barriers has limited the efficacy of previous nanocarriers for delivering CpG to TIDCs. Herein, we developed a dual-sensitive dendrimer cluster-based nanoadjuvant for delivering CpG ODNs into TIDCs. We show that the tumor acidity triggers the rapid release of CpG conjugated polyamidoamine (PAMAM) dendrimers from the nanoadjuvant, thus facilitating its perfusion deep into tumors and phagocytosis by TIDCs. Thereafter, the reductive condition of the endolysosomes led to the subsequent release of CpG, which promotes the DCs activation and enhances antitumor immunotherapies. Programmable delivery of immune adjuvant efficiently overcomes the barriers for targeted delivery to TIDCs and provides a promising strategy for improving cancer immunotherapy.

Application of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver, and its morbidity and mortality have been increasing in recent years. The early diagnosis and prompt treatment of small HCC are crucial to improve the prognosis and quality of life of patients. In China, hepatitis B virus infection is the main cause. HCC with a single tumor nodule of ≤ 3 cm in diameter, or HCC with a number of nodules, in which each nodule is ≤ 2 cm in diameter, with a total diameter of ≤ 3 cm, is considered as small HCC. The MRI liver-specific contrast agent can detect small HCC at the early stage. This has important clinical implications for improving the survival rate of patients. MAIN BODY: Gd-EOB-DTPA-enhanced MRI can significantly improve the sensitivity and specificity of the detection of HBV-related small hepatocellular carcinoma, providing an important basis for the clinical selection of appropriate personalized treatment. Gd-EOB-DTPA-enhanced MRI can reflect the degree of HCC differentiation, and the evaluation of HCC on Gd-EOB-DTPA-enhanced MRI would be helpful for the selection of the treatment and prognosis of HCC patients. The present study reviews the progress of the application of Gd-EOB-DTPA in the early diagnosis of small HCC, its clinical treatment, the prediction of the degree of differentiation, and the assessment of recurrence and prognosis of HCC, including the pharmacoeconomics and application limitations of Gd-EOB-DTPA. The value of the application of HCC with the Gd-EOB-DTPA was summarized to provide information for improving the quality of life and prolonging the survival of patients. CONCLUSION: Gd-EOB-DTPA-enhanced MRI has the diagnostic capability for small HCC with a diameter of ≤ 2 cm. This will have a broader application prospect in the early diagnosis of small liver cancer with a diameter of ≤ 1 cm in the future. The relationship between GD-EOB-DTPA-MRI and the degree of HCC differentiation has a large research space, and Gd-EOB-DTPA is expected to become a potential tool for the preoperative prediction and postoperative evaluation of HCC, which would be beneficial for more appropriate treatments for HCC patients.

The research status and prospect of Periostin in chronic kidney disease.

The continuous accumulation of extracellular matrix will eventually lead to glomerular sclerosis, interstitial fibrosis, tubular atrophy and vascular sclerosis, which are involved in the progression of chronic kidney disease (CKD). If these processes can be discovered early and effective interventions given in time, the progression of kidney disease may be delayed. Therefore, exploring new biomarkers and therapeutic targets that can identify CKD at an early stage is urgently needed. In recent years, studies have shown that urine periostin may be used as a marker of early renal tubular injury. And in an animal model experiment of hypertensive nephropathy, periostin is involved in the progression of kidney injury and reflects its progression. Here we review the current progress on the role of periostin in pathologic pathways of kidney system to explore whether periostin is a potential therapeutic target for the treatment of CKD.

Intratumor Performance and Therapeutic Efficacy of PAMAM Dendrimers Carried by Clustered Nanoparticles.

In recent years, small nanoparticles (NPs) with a diameter of less than 10 nm have aroused considerable interest in biomedical applications. However, their intratumor performance, as well as the antitumor efficacy, has not been well understood due to their size-dependent pharmacokinetics, which presents a formidable challenge for delivering a comparable amount of different small NPs to tumor tissues. Utilizing the multistage delivery strategy, we construct G3-, G5-, and G7-iCluster delivery systems by using poly(amidoamine) (PAMAM) dendrimers of different generations (G3-, G5-, and G7-PAMAM) as building blocks. The iCluster nanoparticles showed comparable pharmacokinetics and similar initial tumor deposition due to their similarity in size and surface chemistry. After accumulating at a tumor site, individual small dendrimers were released, and thus, their intratumor performance was comparatively investigated. Our results indicated that a subtle change in generation markedly affects their intratumor activities. G5-iCluster outperformed G3-iCluster and G7-iCluster in the treatment efficacy in an orthotopic pancreatic tumor model. The mechanistic study revealed that G3-PAMAM showed reduced particle retention in tumor tissue due to its small size and weak cell internalization, while G7-PAMAM was much less penetrative because of its relatively large size and strong particle-cell interaction. In contrast, G5-PAMAM exhibited balanced tumor penetration, cell internalization, and tumor retention. Our finding highlights the huge influence of the subtle difference of small NPs in their intratumor performance.

[Diagnostic clues for knotty andrological diseases].

A most difficult task for andrological clinicians is the diagnosis of knotty diseases, because they are very prevalent, intractable and complicated with unique features. This article systematically analyzes the categorization of knotty andrological disease and provides some elementary protocols and clues for their diagnosis, including three ground rules, six basic clues, two difficult situations and two principal focuses, which are essential for clinical practice.

[Advances in the studies of special biomarkers for the experimental diagnosis of CP/CPPS].

At present, there are no widely accepted specific biomarkers for the experimental diagnosis of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS). Recent studies show that many related biomarkers exist in expressed prostatic secretions (EPS) or semen, urine and blood or serum. The monocyte chemotactic protein-1 (MCP-1/CCL-2), macrophage-inflammatory-protein-1 alpha (MIP-1α/CCL-3), interleukin-6 (IL-6), interleukin-8 (IL-8), nerve growth factor (NGF) and B7-H3 in EPS, prostatic exosomal protein (PSEP) in the urine, and prostate-specific antigen (PSA), mean platelet volume (MPV) and macrophage migration inhibitory factor (MIF) in the serum are believed to be of significant clinical and research value, and expected to become important laboratory biomarkers for the diagnosis of CP/CPPS.

[Prevalence of erectile dysfunction and the associated factors in infertile males].

OBJECTIVE: To investigate the prevalence of ED and the associated factors in infertile males. METHODS: We continuously selected 896 infertile males present at Peking Union Medical College Hospital, Dongzhimen Hospital and the Sixth Medical Center of PLA General Hospital and evaluated the erectile function of the patients using a self-designed questionnaire and IIEF-5. We analyzed the ED-associated factors by multivariate analysis. RESULTS: Based on the results of questionnaire investigation, there were 416 cases of ED in the 896 infertile males (46.43%), including 23 (2.56%) severe, 38 (4.24%) moderate, 109 (12.17%) mild-moderate and 246 (27.46%) mild cases. Multivariate analysis indicated that the prevalence rate of ED was correlated positively with obesity, hypertension and diabetes, and negatively with husband-wife affection and the frequency of sexual intercourse. CONCLUSIONS: The prevalence rate of ED is high in infertile males, mostly mild, and correlated with husband-wife affection, the frequency of sexual intercourse and some diseases.

Metal trabecular bone reconstruction system better improves clinical efficacy and biomechanical repair of osteonecrosis of the femoral head than free vascularized fibular graft: A case-control study.

In this study, we aim to compare and analyze the biomechanical repair and clinical efficacy of osteonecrosis of the femoral head (ONFH) with the use of metal trabecular bone reconstruction system and free vascularized fibular graft. The study enrolled 66 adult patients from medical records of nontraumatic ARCO 2A-3B stage ONFH. A simple ONFH model without surgical treatment was established in 13 cases, 29 cases were treated with metal trabecular bone reconstruction system, and 24 cases were treated with free vascularized fibular graft. Computer-recognized and extracted femur outlines were imported, and three-dimensional reconstructions were performed. The stress concentration and stress peak value were analyzed, and the Harris score, visual analog scale pain score, and operation status of the above patients were compared. Finally, quality of life assessment was performed using SF-36 scale. Metal trabecular bone reconstruction system provided less operation time, blood loss, and the total length of postoperative hospital stay than free vascularized fibular graft. Metal trabecular bone reconstruction system promoted bone reconstruction, increased bone mineral density and Harris score. The total clinical effective rate of young patients (20-40 years) was higher than that of older patients (41-60 years). Metal trabecular bone reconstruction system provided higher physical component summary, mental component summary, and role/social component summary than free vascularized fibular graft. This study demonstrates that both metal trabecular bone reconstruction system and free vascularized fibular graft can prevent or delay the progression of ONFH, while metal trabecular bone reconstruction system is a better choice because of better short-term clinical efficacy.

Tumor-Acidity-Cleavable Maleic Acid Amide (TACMAA): A Powerful Tool for Designing Smart Nanoparticles To Overcome Delivery Barriers in Cancer Nanomedicine.

Over the past few decades, cancer nanomedicine has been under intensive development for applications in drug delivery, cancer therapy, and molecular imaging. However, there exist a series of complex biological barriers in the path of a nanomedicine from the site of administration to the site of action. These barriers considerably prevent a nanomedicine from reaching its targets in a sufficient concentration and thus severely limit its therapeutic benefits. According to the delivery process, these biological delivery barriers can be briefly summarized in the following order: blood circulation, tumor accumulation, tumor penetration, cellular internalization, and intracellular drug release. The therapeutic effect of a nanomedicine is strongly determined by its ability to overcome these barriers. However, advances in cancer biology have revealed that each barrier has its own distinct microenvironment, which imposes different requirements on the optimal design of nanocarriers, thus further complicating the delivery process. For example, the pH of blood is neutral, while the tumor extracellular environment features an acidic pH (pHe ≈ 6.5-7.0) and the endosome and lysosome are more acidic (pH 5.5-4.5). The nanoparticles (NPs) should be able to change their properties to adapt to each individual environment for robust and effective delivery. This demand promotes the design and development of smart delivery carriers that can respond to endogenous and exogenous stimuli. It is well-documented that tumors develop acidic extracellular microenvironments with pH ≈ 6.5-7.0 due to their abnormal metabolism in comparison with normal tissues. This provides a unique tool for designing smart NP drug delivery systems. Our studies have revealed that the NPs' physiochemical properties, such as particle size and surface charge, have profound effects on their systemic transport in the body. In different delivery stages, the NPs should possess different sizes or surface charges for optimal performance. We developed a class of stimuli-responsive NPs by incorporating tumor-acidity-cleavable maleic acid amide (TACMAA) as a design feature. TACMAA is produced by the facile reaction of an amino group with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives and can be cleaved under tumor acidity. By virtue of such characteristics, NPs containing TACMAA enable size or surface charge switching at tumor sites so that they can overcome those delivery barriers for improved drug delivery and cancer therapy. In this Account, we systemically review the development and evolution of TACMAA-based delivery systems and elaborate how TACMAA helps the innovation and design of intelligent nanocarriers for overcoming the delivery barriers. In particular, our Account focuses on five parts: TACMAA chemistry, tumor-acidity-triggered charge reversal, tumor-acidity-triggered shell detachment, tumor-acidity-triggered size transition, and tumor-acidity-triggered ligand reactivation. We provide detailed information on how tumor-acidity-triggered property changes correlate with the ability of NPs to overcome delivery barriers.