Mapping the scientific research on integrated care: a bibliometric and social network analysis.

Background: Integrated care (IC) is the cornerstone of the sustainable development of the medical and health system. A thorough examination of the existing scientific literature on IC is essential for assessing the present state of knowledge on this subject. This review seeks to offer an overview of evidence-based knowledge, pinpoint existing knowledge gaps related to IC, and identify areas requiring further research. Methods: Data were retrieved from the Web of Science Core Collection, from 2010 to 2020. Bibliometrics and social network analysis were used to explore and map the knowledge structure, research hotspots, development status, academic groups and future development trends of IC. Results: A total of 7,501 articles were obtained. The number of publications on IC was rising in general. Healthcare science services were the most common topics. The United States contributed the highest number of articles. The level of collaboration between countries and between authors was found to be relatively low. The keywords were stratified into four clusters: IC, depression, integrative medicine, and primary health care. In recent years, complementary medicine has become a hotspot and will continue to be a focus. Conclusion: The study provides a comprehensive analysis of global research hotspots and trends in IC, and highlights the characteristics, challenges, and potential solutions of IC. To address resource fragmentation, collaboration difficulties, insufficient financial incentives, and poor information sharing, international collaboration needs to be strengthened to promote value co-creation and model innovation in IC. The contribution of this study lies in enhancing people's understanding of the current state of IC research, guiding scholars to discover new research perspectives, and providing valuable references for researchers and policymakers in designing and implementing effective IC strategies.

Milling Stability Prediction: A New Approach Based on a Composited Newton-Cotes Formula.

Based on a composited Newton-Cotes formula, this paper proposes a numerical method to predict milling stability considering regenerative chatter and focusing on rate and prediction accuracy. First, the dynamic model of milling motion is expressed as state-space equations considering regenerative chatter, with the tooth passing period divided into a set of time intervals. Second, a composited Newton-Cotes formula is introduced to calculate the transition function map for each time interval. Third, the state transition matrix is constructed based on the above-mentioned transition function, and the prediction stability boundary is determined by the Floquet theory. Finally, simulation analysis and experimental verification are conducted to verify the effectiveness of the proposed method. The simulation results demonstrate that, for the milling model with a single degree of freedom (DOF), the convergence rate and prediction accuracy of the proposed method are higher than those of the comparison method. The experimental results demonstrate that, for the milling model with two DOFs, the machining parameters below the prediction stability boundary can avoid the chatter as much as possible, ensuring the machined surface quality.

Chalcone Derivatives Suppress Proliferation and Migration of Castration-resistant Prostate Cancer Cells Through FAK-mediated DNA Damage.

BACKGROUND/AIM: Castration-resistant prostate cancer (CRPC) contributes to the deaths of most men from prostate cancer. Focal adhesion kinase (FAK) is abnormally up-regulated in CRPC. Chalcone possesses potent anticancer activity with clinical potential. However, it remains unknown whether its derivatives can be exploited as promising oncotherapeutic agents in CRPC treatment by inhibiting FAK-related signaling pathway. AIM: This study aimed to investigate the anticancer effects and the underlying mechanisms of action of chalcone derivatives against CRPC cells. MATERIALS AND METHODS: Two chalcone derivatives (compounds 1 and 2) were synthesized, and their anti-CRPC activity toward DU145 and PC3 cells was evaluated. The effect of chalcone derivatives on CRPC cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony-formation, 5-ethynyl-2'-deoxyuridine staining, flow cytometric, cell adhesion and transwell assays. The study of mechanisms was conducted through comet, immunofluorescence and western blot assay, analysis of The Cancer Genome Atlas and molecular docking. RESULTS: The results revealed that both compounds exhibited stronger cytotoxicity to CRPC cells along with significant inhibition of colony formation, especially compound 1 Further experimental evidence indicated that 1 significantly inhibited DNA replication, induced cell-cycle arrest and cell apoptosis. Additionally, treatment with 1 inhibited cell-matrix adhesion and migration of CRPC cells. Mechanistically, the results suggest that 1 inhibited FAK expression and phosphorylation, as well as affected its distribution, resulting in intense DNA damage and strong DNA damage response. CONCLUSION: We discovered two chalcone derivatives and collective results indicated that 1 inhibited CRPC cell proliferation and migration through FAK-mediated DNA damage and may be a potential therapeutic drug against CRPC.

A newly defined basement membrane-related gene signature for the prognosis of clear-cell renal cell carcinoma.

Background: Basement membranes (BMs) are associated with cell polarity, differentiation, migration, and survival. Previous studies have shown that BMs play a key role in the progression of cancer, and thus could serve as potential targets for inhibiting the development of cancer. However, the association between basement membrane-related genes (BMRGs) and clear cell renal cell carcinoma (ccRCC) remains unclear. To address that gap, we constructed a novel risk signature utilizing BMRGs to explore the relationship between ccRCC and BMs. Methods: We gathered transcriptome and clinical data from The Cancer Genome Atlas (TCGA) and randomly separated the data into training and test sets to look for new potential biomarkers and create a predictive signature of BMRGs for ccRCC. We applied univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to establish the model. The risk signature was further verified and evaluated through principal component analysis (PCA), the Kaplan-Meier technique, and time-dependent receiver operating characteristics (ROC). A nomogram was constructed to predict the overall survival (OS). The possible biological pathways were investigated through functional enrichment analysis. In this study, we also determined tumor mutation burden (TMB) and performed immunological analysis and immunotherapeutic drug analysis between the high- and low-risk groups. Results: We identified 33 differentially expressed genes and constructed a risk model of eight BMRGs, including COL4A4, FREM1, CSPG4, COL4A5, ITGB6, ADAMTS14, MMP17, and THBS4. The PCA analysis showed that the signature could distinguish the high- and low-risk groups well. The K-M and ROC analysis demonstrated that the model could predict the prognosis well from the areas under the curves (AUCs), which was 0.731. Moreover, the nomogram showed good predictability. Univariate and multivariate Cox regression analysis validated that the model results supported the hypothesis that BMRGs were independent risk factors for ccRCC. Furthermore, immune cell infiltration, immunological checkpoints, TMB, and the half-inhibitory concentration varied considerably between high- and low-risk groups. Conclusion: Employing eight BMRGs to construct a risk model as a prognostic indicator of ccRCC could provide us with a potential progression trajectory as well as predictions of therapeutic response.

circ_NRIP1 is oncogenic in malignant development of esophageal squamous cell carcinoma (ESCC) via miR-595/SEMA4D axis and PI3K/AKT pathway.

BACKGROUND: The hsa_circ_0004771 derived from NRIP1 (called circ_NRIP1) is a recently identified oncogenic circRNA. Here, we intended to investigate the role and mechanism of circ_NRIP1 in esophageal squamous cell carcinoma (ESCC), a prevalent and aggressive type of esophageal cancer. METHODS: Expression of circ_NRIP1, miRNA-595-5p (miR-595) and semaphorin 4D (SEMA4D) was detected by RT-qPCR and western blotting. Cell growth was assessed by colony formation assay, MTS assay, flow cytometry, and xenograft experiment; migration and invasion were evaluated by transwell assay and western blotting. Dual-luciferase reporter assay identified the relationship among circ_NRIP1, miR-595 and SEMA4D. Western blotting measured phosphatidylinositol-3-hydroxykinase (PI3K)/AKT pathway-related proteins. RESULTS: Expression of circ_NRIP1 was upregulated in ESCC tissues and cells. Knockdown of circ_NRIP1 could enhance apoptosis rate and E-cadherin expression, but suppress colony formation, cell viability, migration, invasion, and snail expression in KYSE30 and KYSE450 cells, as well as retarded tumor growth in mice. The suppressive role of circ_NRIP1 knockdown in cell growth, migration and invasion in vitro was abated by blocking miR-595; meanwhile, miR-595 overexpression elicited similar anti-tumor role in KYSE30 and KYSE450 cells, which was abrogated by restoring SEMA4D. Notably, circ_NRIP1 was a sponge for miR-595, and SEMA4D was a target of miR-595. Besides, PI3K/AKT signal was inhibited by circ_NRIP1 knockdown and/or miR-595 overexpression via indirectly or directly regulating SEMA4D. CONCLUSION: circ_NRIP1 functioned as an oncogene in ESCC, and modulated ESCC cell growth, migration and invasion both in vitro and in vivo via targeting miR-595/SEMA4D axis and inhibiting PI3K/AKT signaling pathway.

Prognostic Value of Site-Specific Metastases and Therapeutic Roles of Surgery and Chemotherapy for Patients With Metastatic Renal Pelvis Cancer: A SEER Based Study.

BACKGROUND AND AIMS: There is a lack of research on metastatic renal pelvis cell carcinoma in the current literature. In this study, we aimed to detect distant metastatic patterns in renal pelvis cell carcinoma, and illustrated the affection of different metastatic sites, surgery to primary site and chemotherapy on prognosis outcomes in patients with diverse conditions. METHODS: We collected data between 2010 and 2015 from the Surveillance, Epidemiology and End Results database. Kaplan-Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic sites on overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 424 patients were included in the analysis, the median follow-up time was 5 months (interquartile range (IQR): 2-12) and 391 deaths (92.2%) in all patients were recorded. Among them, 192 (45.3%), 153 (36.1%), 137 (32.3%) and 127 (30.0%) patients were diagnosed with lung, bone, liver and brain metastases, respectively, while only 12 (2.8%) patients had brain metastases. The bi-organ, tri-organ and tetra-organ metastatic pattern was found in 135 (31.8%), 32 (7.5%) and 11 (2.6%) patients, respectively. The multivariate Cox analyses showed that distant lymph nodes (DL) metastases was not an independent prognostic factor for both OS and CSS (OS: Hazard ratios (HR) = 1.1, 95% CI = 0.8-1.4, P = 0.622; CSS: HR = 1.0, 95% CI = 0.8-1.3, P = 0.906). Besides, there was no significant difference of survival in patients with T3-T4 stage (OS: HR = 0.8, 95% CI = 0.5-1.2, P = 0.296; CSS: HR = 0.8, 95% CI = 0.5-1.2, P = 0.224), N2-3 stage (OS: HR = 0.8, 95% CI = 0.5-1.3, P = 0.351; CSS: HR = 0.7, 95% CI = 0.4-1.2, P = 0.259) and multi-organ metastases (OS: HR = 0.8, 95% CI = 0.5-1.3, P = 0.359; CSS: HR = 0.7, 95% CI = 0.4-1.2, P = 0.179) between surgery to primary site group and no-surgery to primary site group. CONCLUSION: we described the metastatic patterns of mRPCC and the prognosis outcomes of DL metastases, surgery to primary site and chemotherapy. Our findings provide more information for clinical therapeutic intervention and translational study designs.

U-shaped relationship of age at diagnosis and cancer-specific mortality in primary urachal adenocarcinoma: a cohort study.

BACKGROUND: To examine the association between age at diagnosis and cancer-specific mortality (CSM) in primary urachal adenocarcinoma. METHODS: The data was obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results program (SEER). A total of 393 patients were included in the study. Smooth curve fitting and two-piecewise Cox proportional hazards models were used to identify the nonlinearity between the age at initial diagnosis and cancer-specific survival rate. Survival time between different groups was compared using Kaplan-Meier survival curves and the log-rank test. RESULTS: Using smooth curve fitting we found that the relationship between age at diagnosis and cancer-specific survival takes on a U-shaped curve. The inflection point that we identified for the age at initial diagnosis was 60 years. The log-likelihood ratio test (P<0.05) indicated that the two-piecewise Cox regression model was more appropriate for fitting the correlation of age at diagnosis and CSM. The two-piecewise Cox regression model showed that when the age was <60 years, reduced risk of CSM was significantly associated with increased age (HR: 0.95, P=0.0002). Conversely, when age was >60 years, increased risk of CSM was significantly associated with increased age (HR: 1.05, P=0.0499). CONCLUSIONS: In summary, our study suggested that the relationship between age at diagnosis and cancer-specific survival is nonlinear, and takes on a U-shaped curve. Both younger and older age at initial diagnosis age were associated with increased CSM.

Mapping the Scientific Research on Healthcare Workers' Occupational Health: A Bibliometric and Social Network Analysis.

In the last few years, the occupational health (OH) of healthcare workers (HCWs) has been shown increasing concern by both health departments and researchers. This study aims to provide academics with quantitative and qualitative analysis of healthcare workers' occupational health (HCWs+OH) field in a joint way. Based on 402 papers published from 1992 to 2019, we adopted the approaches of bibliometric and social network analysis (SNA) to map and quantify publication years, research area distribution, international collaboration, keyword co-occurrence frequency, hierarchical clustering, highly cited articles and cluster timeline visualization. In view of the results, several hotspot clusters were identified, namely: physical injuries, workplace, mental health; occupational hazards and diseases, infectious factors; community health workers and occupational exposure. As for citations, we employed document co-citation analysis to detect trends and identify seven clusters, namely tuberculosis (TB), strength training, influenza, healthcare worker (HCW), occupational exposure, epidemiology and psychological. With the visualization of cluster timeline, we detected that the earliest research cluster was occupational exposure, then followed by epidemiology and psychological; however, TB, strength training and influenza appeared to gain more attention in recent years. These findings are presumed to offer researchers, public health practitioners a comprehensive understanding of HCWs+OH research.

Development and validation of a nomogram to predict survival in patients with metastatic testicular germ cell tumors.

BACKGROUND: To develop a nomogram to predict cancer-specific survival (CSS) in patients with metastatic testicular germ cell tumors (mTGCTs). METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression models were used to identify factors associated with CSS. Survival times between different groups were compared using Kaplan-Meier survival curves and the log-rank test. A nomogram visualization model was established using the R language to predict survival rates. Harrell's concordance index (C-index), the area under the receiver operating characteristic curve (AUC) and calibration plots were used to assess the performance of the model. RESULTS: We analyzed the data of 949 patients. The median follow-up time was 32 months (range 0 to 83 months), and 224 (23.60%) patients died before the last follow-up, of whom 193 (20.33%) died of mTGCTs. The site of distant metastases was an independent prognostic factor for CSS. Compared to patients without involvement of the corresponding organ, patients with bone, brain, liver, and lung involvement had worse CSS. We also found that age, histological type, surgery, radiation therapy, chemotherapy, metastatic site and insurance status affected the CSS of patients with mTGCTs. We used these prognostic factors to construct our nomogram. Harrell's C-index for CSS was 0.739. The AUC and calibration plots indicated good performance of the nomogram. CONCLUSIONS: A nomogram for predicting CSS in patients with mTGCTs has been developed, which can help patients and clinicians accurately predict mortality risk and recommend personalized treatment modalities.

[Low-dose PDE5 inhibitors for erectile dysfunction with subclinical metabolic syndrome].

OBJECTIVE: To investigate the effects of low-dose PDE5 inhibitors on metabolic parameters and erectile function in ED patients with subclinical metabolic syndrome (SCMS). METHODS: Totally, 132 ED patients, aged 21－61 (mean 34.5) years, were treated in the Andrology Clinic of the First Hospital of Wenzhou Medical University from April 2017 to May 2018. According to the diagnostic criteria, we divided the patients into groups A (simple ED, n = 40), B (ED with SCMS, n = 34) and C (ED with MS, n = 58) to receive 3 months of oral administration of tadalafil at 5 mg qd at bedtime, and followed them up for 3 months after drug withdrawal. During the treatment, we advised the patients to keep a healthy diet, change bad habits, participate in regular physical exercise, and maintain psychological balance. Before and right after medication and at 3 months after drug withdrawal, we recorded the changes in the IIEF-5 scores, abdominal circumference, blood pressure and levels of fasting blood sugar (FBS), triglyceride (TG) and high-density lipoprotein (HDL) of the patients. RESULTS: The IIEF-5 scores showed statistically significant differences at different time points between groups A and C (P < 0.01), remarkably higher right after treatment than before treatment and at 3 months after drug withdrawal in group B (19.71 ± 2.40 vs 10.21 ± 3.92 and 16.29 ± 2.41, P < 0.01). At 3 months after drug withdrawal, the abdominal circumference was significantly smaller in group A than in B and C (ï¼»78.10 ± 6.00ï¼½ vs ï¼»84.15 ± 8.17ï¼½ and ï¼»91.53 ± 11.49ï¼½ cm, P < 0.01) and the HDL level lower in group C than in A and B (ï¼»0.96 ± 0.15ï¼½ vs ï¼»1.27 ± 0.14ï¼½ and ï¼»1.16 ± 0.2ï¼½] mmol/L, P < 0.01). Systolic blood pressure exhibited statistically significant differences between any two time points in group C (P < 0.05 or P < 0.01) but not in group A (P > 0.05) or B (P > 0.05). Diastolic blood pressure was markedly lower in group B right after medication and at 3 months after drug withdrawal than before treatment (ï¼»75.62 ± 10.70ï¼½ and ï¼»74.65 ± 9.90ï¼½ vs ï¼»78.00 ± 11.42ï¼½ mmHg, P < 0.05), and so was it in group C (ï¼»82.19 ± 10.36ï¼½ and ï¼»82.40 ± 10.09ï¼½ vs ï¼»86.71 ± 12.32ï¼½ mmHg, P < 0.05), but manifested no significant difference between any two time points in group A (P > 0.05). There were statistically significant differences in the FBS level among different time points in groups A and C (P < 0.05) but not in B between post-treatment and 3 months after drug withdrawal (ï¼»5.34 ± 0.60ï¼½ vs ï¼»5.36 ± 0.40ï¼½ mmol/L, P > 0.05), and so were there in the TG level among different time points in groups A and C (P < 0.05) but not in B between pre- and post-treatment (ï¼»1.80 ± 0.98ï¼½ vs ï¼»1.64 ± 1.19ï¼½ mmol/L, P > 0.05). CONCLUSIONS: Periodic administration of low-dose sustained-release PDE5 inhibitors with health education and lifestyle guidance may reverse ED with SCMS and improve most of the related metabolic parameters.

[Diagnosis and treatment of male urethritis in urology and andrology: A status survey].

OBJECTIVE: To investigate the status quo of the diagnosis and treatment of male urethritis (MU) in urology and andrology. METHODS: According to The Guidelines for Clinical Diagnosis and Treatment of Sexually Transmitted Diseases (2017), we designed 27 questions on the prevalence, diagnosis, treatment, and prognosis of MU. Using these questions, we conducted a questionnaire investigation among urological, andrological and other relevant clinicians with different professional titles, followed by an analysis of the compliance of the doctors to the Guidelines. RESULTS: Totally, 116 valid questionnaires were collected from 86 urological, 28 andrological and 2 other relevant doctors, including 22 professors, 36 associate professors, 40 attending doctors and 16 resident doctors. MU was found mostly in those aged 20－40 years and more than half of the patients had a history of unclean sex, gonococcal urethritis significantly less prevalent than non-gonococcal, with Ureaplasma urealyticum as the most common pathogen of non-gonococcal urethritis. As for the compliance to the Guidelines in the diagnosis of MU, 22.73% of the professors, 16.67% of the associate professors, 15.00% of the attending doctors and 12.50% of the resident doctors examined the eyes, mouth and perianus (P > 0.05), 40.91% of the professors, 58.33% of the associate professors, 40.00% of the attending doctors and 37.50% of the resident doctors conducted HIV and syphilis screening (P > 0.05), and 86.36% of the professors, 77.78% of the associate professors, 70.00% of the attending doctors and 75.00% of the resident doctors performed genital mycoplasma screening (P > 0.05). Concerning the treatment of MU, 50.00% of the professors, 47.22% of the associate professors, 22.50% of the attending doctors and 43.75% of the resident doctors used anti-Chlamydia trachomatis drugs for gonococcal urethritis (P > 0.05), 0.00% of the professors, 11.11% of the associate professors, 5.00% of the attending doctors and 31.25% of the resident doctors prescribed 1g single-dose oral azithromycin for non-gonococcal urethritis (P < 0.05), 13.64% of the professors, 33.33% of the associate professors, 17.50% of the attending doctors and 6.25% of the resident doctors medicated persistent or recurrent non-gonococcal urethritis for >4 weeks (P > 0.05), 63.64% of the professors, 83.33% of the associate professors, 57.50% of the attending doctors and 62.50% of the resident doctors treated asymptomatic trachomatis and mycoplasma infections according to the proposed medication in the Guidelines (P > 0.05). As regards the results of treatment, the cure rate of gonococcal urethritis was 100.00% by professors, 97.22% by associate professors, 95.00% by attending doctors and 81.25% by resident doctors (P > 0.05), and that of non-gonococcal urethritis was 86.36% by professors, 61.11% by associate professors, 62.50% by attending doctors and 37.50% by resident doctors (P < 0.05). CONCLUSIONS: Urological and andrological clinicians do not strictly follow the Guidelines in the diagnosis and treatment of male urethritis. There are significant differences in the dosing of azithromycin and results of treatment of non-gonococcal urethritis among doctors with different professional titles, but not in the other aspects.

Effect of puerarin on melanogenesis in human melanocytes and vitiligo mouse models and the underlying mechanism.

Puerarin is the major bioactive ingredient derived from the root of the Pueraria lobata (Willd.), and its antioxidative stress effects have been demonstrated in several previous studies. Moreover, Puerarin can upregulate melanin synthesis and microphthalmia-associated transcription factor (MITF) transcription by increasing cAMP level of intracellular cyclic adenosine monophosphate. Vitiligo is an acquired cutaneous disorder of pigmentation, and the pathogenesis has remained elusive. Current treatment modalities are directed towards achieving repigmentation. In this study, we found that after treating with puerarin at various concentrations of 40 µmol/L, the melanin content of human melanocytes increased significantly and the apparent level of protein and the RNA levels of MITF, tyrosinase (TYR), and tyrosinase-related protein 1 (TRP-1) were also increased. Further, puerarin was shown to inhibit phosphorylation and activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) without significantly affecting p38 and c-Jun N-terminal kinase phosphorylation. These results demonstrated that puerarin stimulated melanogenesis in human melanocytes via inhibition of ERK1/2 signaling pathways, which leads to upregulation of MITF and TYR as well as TRP-1 subsequently. Additionally, mice vitiligo models with puerarin treatment showed lighter pathological changes. Therefore, we suggested that puerarin might be a potential medicine for vitiligo.

The effect of lentivirus-mediated expression of tumor necrosis factor related apoptosis-inducing ligand and shRNA against Bcl-2 on the growth of lymphoma cells.

It has been well established that tumor necrosis factor related apoptosis-inducing ligand (TRAIL) effectively induces apoptosis in tumor cells. However, tumor resistance to TRAIL, especially of hematological tumor cells, has become a major problem in the potential use of TRAIL in clinical practice. Among many factors that contribute to TRAIL resistance, overexpression of Bcl-2 is commonly seen in many kinds of tumors, particularly in lymphoma. In this study, we developed a lentivirus system that encodes recombinant human TRAIL cDNA for overexpression and Bcl-2 shRNA for down-regulation of Bcl-2 (lenti-TRAIL-shBcl-2) simultaneously. The efficiency of recombinant lentiviruses infecting different lymphoma cell lines was assessed by flow cytometric analysis and fluorescence microscopy. Reverse transcription polymerase chain reaction and Western blot assay were carried out to evaluate the expression of TRAIL and Bcl-2 in lymphoma cells after infection. We also examined the growth inhibition effect of recombinant lentivirus on lymphoma cell proliferation by CCK-8 (Cell Counting Kit-8) assay and its effect on bystander cells by flow cytometric analysis. The results showed that lymphoma cells were effectively infected by recombinant lentivirus and that TRAIL was exogenously expressed and Bcl-2 expression was down-regulated in lymphoma cells simultaneously. Results of this study demonstrated that lenti-TRAIL-shBcl-2 induced apoptosis in bystander cells as well as infected lymphoma cells and inhibited the growth of lymphoma cells.