CCL2 is a key regulator and therapeutic target for periodontitis.

AIM: Our previous study revealed that the C-C motif chemokine receptor 2 (CCR2) is a promising target for periodontitis prevention and treatment. However, CCR2 is a receptor with multiple C-C motif chemokine ligands (CCLs), including CCL2, CCL7, CCL8, CCL13 and CCL16, and which of these ligands plays a key role in periodontitis remains unclear. The aim of the present study was to explore the key functional ligand of CCR2 in periodontitis and to evaluate the potential of the functional ligand as a therapeutic target for periodontitis. MATERIALS AND METHODS: The expression levels and clinical relevance of CCR2, CCL2, CCL7, CCL8, CCL13 and CCL16 were studied using human samples. The role of CCL2 in periodontitis was evaluated by using CCL2 knockout mice and overexpressing CCL2 in the periodontium. The effect of local administration of bindarit in periodontitis was evaluated by preventive and therapeutic medication in a mouse periodontitis model. Microcomputed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, bead-based immunoassays and flow cytometry were used for histomorphology, molecular biology and cytology analysis. RESULTS: Among different ligands of CCR2, only CCL2 was significantly up-regulated in periodontitis gingival tissues and was positively correlated with the severity of periodontitis. Mice lacking CCL2 showed milder inflammation and less bone resorption than wild-type mice, which was accompanied by a reduction in monocyte/macrophage recruitment. Adeno-associated virus-2 vectors overexpressing CCL2 in Ccl2-/- mice gingiva reversed the attenuation of periodontitis in a CCR2-dependent manner. In ligation-induced experimental periodontitis, preventive or therapeutic administration of bindarit, a CCL2 synthesis inhibitor, significantly inhibited the production of CCL2, decreased the osteoclast number and bone loss and reduced the expression levels of proinflammatory cytokines TNF-α, IL-6 and IL-1ß. CONCLUSIONS: CCL2 is a pivotal chemokine that binds to CCR2 during the progression of periodontitis, and targeting CCL2 may be a feasible option for controlling periodontitis.

Vessels encapsulating tumor clusters: a novel efficacy predictor of hepatic arterial infusion chemotherapy in unresectable hepatocellular carcinoma.

PURPOSE: Vessels encapsulating tumor clusters (VETC) is a novel vascular pattern structurally and functionally distinct from microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This study aims to explore the prognostic value of VETC in patients receiving hepatic arterial infusion chemotherapy (HAIC) for unresectable HCC. METHODS: From January 2016 to December 2017, 145 patients receiving HAIC as the initial treatment for unresectable HCC were enrolled and stratified into two groups according to their VETC status. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were evaluated. RESULTS: The patients were divided into two groups: VETC+ (n = 31, 21.8%) and VETC- (n = 114, 78.2%). The patients in the VETC+ group had worse ORR and DCR than those in the VETC- group (RECIST: ORR: 25.8% vs. 47.4%, P = 0.031; DCR: 56.1% vs. 76.3%, P = 0.007; mRECIST: ORR: 41.0% vs. 52.6%, P = 0.008; DCR: 56.1% vs. 76.3%, P = 0.007). Patients with VETC+ had significantly shorter OS and PFS than those with VETC- (median OS: 10.2 vs. 21.6 months, P < 0.001; median PFS: 3.3 vs. 7.2 months, P < 0.001). Multivariate analysis revealed VETC status as an independent prognostic factor for OS (HR: 2.40; 95% CI: 1.46-3.94; P = 0.001) and PFS (HR: 1.97; 95% CI: 1.20-3.22; P = 0.007). CONCLUSION: VETC status correlates remarkably well with the tumor response and long-term survival in patients undergoing HAIC. It may be a promising efficacy predictor and help identify patients who will benefit from HAIC.

Implementation of Integrated Care for the Aged Population in Anhui and Fujian Province of China: A Qualitative Study.

Introduction: Implementing integrated care for the aged population has been regarded as a mechanism to achieve healthy ageing. However, evidence from undeveloped nations has been scant. This study aims to explore the integrated care experience in Anhui and Fujian Province of China based on the Rainbow Model of Integrated Care (RMIC). Methods: The qualitative study was conducted in Anhui (in the middle area) and Fujian Province (in the eastern area) between May and September in 2018. The interviewees included twenty-eight policy makers working at departments of health and civil affairs at different levels and seventeen heads of medical and elderly care institutions. Results: The preliminary progress of integrated care in the sample cities of two provinces are mainly shown at solid policy basis by multiple key government agencies and political commitment achieved (system integration); preliminary coordination mechanism established between medical and elderly care institutions (organizational integration); consolidation of multi-disciplinary collaboration (professional integration); and reinforced role of family doctor teams for community-home dwelling elderly (service integration). Main challenges are also identified at insufficient inter-agency coordination, weak service capacity, lack of sustainable funding schemes, low level of information integration, and shortage of professional supply. Conclusion: Our findings provide a feasible path for other countries to strengthen integrated care for the aged population, particularly for those confronting rapid population ageing but with fragmented health care and elderly care systems.

Primary healthcare professionals' perspective on vertical integration of healthcare system in China: a qualitative study.

OBJECTIVE: This study aims to present the perspectives of primary healthcare professionals (PHPs) on the impacts of implementation of vertical integration and on the underlying interprofessional collaboration process on achievement of the policy goals in China. DESIGN: A qualitative study involving individual interview and group interview was conducted between 2017 and 2018. SETTING: Primary healthcare institutions (PHIs) in five counties/districts of China. PARTICIPANTS: The major participants include 12 heads of PHIs (by 12 individual interviews) and 38 PHPs (by 12 group interviews). We also interviewed other stakeholders including 24 health policy-makers (by 5 group interviews) and 5 hospital leaders (by 5 individual interviews) for triangulation analysis. RESULTS: Our study indicates that PHPs perceived vertical integration has resulted in improved professional competency, better care coordination and stronger capacity to satisfy patients' needs. The positive impacts have varied between integration types. Contributing factors for such progress are identified at administrative, organisational and service delivery levels. Other perceived effects are a loss of autonomy, increased workload and higher turnover of capable PHPs. Higher level hospitals play a dominant role in the interprofessional collaboration, particularly regarding shared goals, vision and leadership. These findings are different from the evidence in high-income countries. Incentive mechanisms and the balance of power with hospitals management are prominent design elements in the future. CONCLUSIONS: Our findings are particularly valuable for other countries with a fragmented health service system and low competency of PHPs as China's experience in integrated care provides a feasible path to strengthen primary care.

Why patients prefer high-level healthcare facilities: a qualitative study using focus groups in rural and urban China.

INTRODUCTION: Despite policy measure to strengthen and promote primary care, Chinese patients increasingly choose to access higher level hospitals. The resulting overcrowding at higher level hospitals and underutilisation of primary care are viewed to diminish the effects of the continuing health system investments on population health. We explore the factors that influence the choice of healthcare facility level in rural and urban China and aim to reveal the underlying choice processes. METHODS: We conducted eight semistructured focus group discussions among the general population and the chronically ill in a rural area in Chongqing and an urban area in Shanghai. Respondents' discussions of (evidence-based) factors and how they influenced their facility choices were analysed using qualitative analysis techniques, from which we elicited choice process maps to capture the partial order in which the factors were considered in the choice process. RESULTS: The factors considered, after initial illness perception, varied over four stages of health service utilisation: initial visit, diagnosis, treatment and treatment continuation. The factors considered per stage differed considerably between the rural and urban respondents, but less so between the general population and the chronically ill. Moreover, the rural respondents considered the township health centres as default and prefer to continue in primary care, yet access higher levels when necessary. Urban respondents chose higher levels by default and seldom moved down to primary care. CONCLUSIONS: Disease severity, medical staff, transportation convenience, equipment and drug availability played important roles when choosing healthcare facilities in China. Strengthening primary care correspondingly may well be effective to increase primary care utilisation by the rural population but insufficient for the urban population. The developed four-stage process maps are general enough to serve as the basis for (partially) ordering factors influencing facility level choices in other contexts.

Factors influencing choice of health system access level in China: A systematic review.

OBJECTIVE: In China, patients increasingly choose to access already severely overcrowded higher level hospitals, leaving lower level facilities with low utilization rates. This situation undermines the effectiveness and efficiency of the health system. The situation tends to worsen despite policy measures aimed at improvement. We systematically review the factors affecting patient choice to synthesize scientific understanding of health system access in China. The review provides an evidence base for measures to direct patient flow towards lower level facilities. METHODS: We screened the peer-reviewed literature published from April 2009 to January 2016 that investigates Chinese patients' choice of health care facilities at different levels and assessed 45 studies in total. We applied two structured forms to extract data on each study's characteristics, methodology, and factors. RESULTS OF DATA SYNTHESIS: The results identified four factor types: 1) patient, 2) provider, 3) context and 4) composite: combined patient, provider, and/or context attributes. Patient factors are mentioned the most, but the evidence on patient factors is often inconclusive. Evidence suggests that the provider factors 'drug variety' and 'equipment', and composite factor 'perceived quality', push patients from lower levels towards higher levels. CONCLUSION: Underuse of primary care facilities and overcrowding of higher level facilities will likely be amplified by current demographic trends. Evidence suggests that improving drug availability, equipment and perceived quality of primary care services can improve the situation. Well-designed research that considers the interactions between factors is called for to better inform future interventions.