China's application of the One Health approach in addressing public health threats at the human-animal-environment interface: Advances and challenges.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

Assessment of integrated patterns of human-animal-environment health: a holistic and stratified analysis.

BACKGROUND: Data-driven research is a very important component of One Health. As the core part of the global One Health index (GOHI), the global One Health Intrinsic Drivers index (IDI) is a framework for evaluating the baseline conditions of human-animal-environment health. This study aims to assess the global performance in terms of GOH-IDI, compare it across different World Bank regions, and analyze the relationships between GOH-IDI and national economic levels. METHODS: The raw data among 146 countries were collected from authoritative databases and official reports in November 2021. Descriptive statistical analysis, data visualization and manipulation, Shapiro normality test and ridge maps were used to evaluate and identify the spatial and classificatory distribution of GOH-IDI. This paper uses the World Bank regional classification and the World Bank income groups to analyse the relationship between GOH-IDI and regional economic levels, and completes the case studies of representative countries. RESULTS: The performance of One Health Intrinsic Driver in 146 countries was evaluated. The mean (standard deviation, SD) score of GOH-IDI is 54.05 (4.95). The values (mean SD) of different regions are North America (60.44, 2.36), Europe and Central Asia (57.73, 3.29), Middle East and North Africa (57.02, 2.56), East Asia and Pacific (53.87, 5.22), Latin America and the Caribbean (53.75, 2.20), South Asia (52.45, 2.61) and sub-Saharan Africa (48.27, 2.48). Gross national income per capita was moderately correlated with GOH-IDI (R2 = 0.651, Deviance explained = 66.6%, P < 0.005). Low income countries have the best performance in some secondary indicators, including Non-communicable Diseases and Mental Health and Health risks. Five indicators are not statistically different at each economic level, including Animal Epidemic Disease, Animal Biodiversity, Air Quality and Climate Change, Land Resources and Environmental Biodiversity. CONCLUSIONS: The GOH-IDI is a crucial tool to evaluate the situation of One Health. There are inter-regional differences in GOH-IDI significantly at the worldwide level. The best performing region for GOH-IDI was North America and the worst was sub-Saharan Africa. There is a positive correlation between the GOH-IDI and country economic status, with high-income countries performing well in most indicators. GOH-IDI facilitates researchers' understanding of the multidimensional situation in each country and invests more attention in scientific questions that need to be addressed urgently.

Towards a global One Health index: a potential assessment tool for One Health performance.

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

Cordycepin induces apoptosis in human pancreatic cancer cells via the mitochondrial-mediated intrinsic pathway and suppresses tumor growth in vivo.

BACKGROUND: Cordycepin, the main active ingredient of a traditional Chinese herbal remedy - extracted from Cordyceps sinensis - has been demonstrated as a very effective anti-inflammatory and antitumor drug. The present study investigated its antitumor effect on pancreatic cancer, a highly aggressive cancer with extremely poor prognosis due to malignancy, and clarified its underlying mechanism both in vitro and in vivo. METHODS: The antitumor viability of cordycepin on human pancreatic cancer MIAPaCa-2 and Capan-1 cells was determined by colony formation assays. Annexin V/PI double staining and flow cytometry assay were used to investigate whether cordycepin induced apoptosis and cell cycle arrest. The mitochondrial membrane potential (ΔΨm) was analyzed by Rhodamine 123 staining, and expression of related proteins evaluated by Western blot and immunohistochemistry, both on pancreatic cancer cells and tumor xenografts to reveal the potential mechanism for the effect of cordycepin. Furthermore, the in vivo efficacy was examined on nude mice bearing MIAPaCa-2 cell tumors treated by intraperitoneal injection of cordycepin (0, 15, and 50 mg/kg/d) for 28 days. RESULTS: Cordycepin inhibited cell viability, proliferation and colony formation ability and induced cell cycle arrest and early apoptosis of human pancreatic cancer cells (MIAPaCa-2 and Capan-1) in a dose- and time-dependent manner. The same effect was also observed in vivo. Decrease of ΔΨm and upregulation of Bax, cleaved caspase-3, cleaved caspase-9, and cleaved PARP as well as downregulation of Bcl-2 both in vitro and in vivo indicated that the mitochondria-mediated intrinsic pathway was involved in cordycepin's antitumor effect. CONCLUSION: Our data showed that cordycepin inhibited the activity of pancreatic cancer both in vitro and in vivo by regulating apoptosis-related protein expression through the mitochondrial pathway and suggest that cordycepin may be a promising therapeutic option for pancreatic cancer.

The Yin and Yang of regulatory T cell and therapy progress in autoimmune disease.

Autoimmune diseases (ADs) are primarily mediated by the failure of immunological self-tolerance. Regulatory T cells (Tregs) play a critical role in the maintenance of induced tolerance to peripheral self-antigens, suppressing immoderate immune responses deleterious to the host and preventing the AD development. Tregs and suppressive cytokines are homeostatic with effective cells plus pro-inflammatory cytokines in healthy hosts which is defined as "Yang", and ADs are usually induced in case of disturbed homeostasis, which is defined as "Yin". Indeed, the Yin-Yang balance could explain the pathogenic mechanism of ADs. Tregs not only suppress CD4+ and CD8+ T cells but also can suppress other immune cells such as B cell, natural killer cell, DC and other antigen-presenting cell through cell-cell contact or secreting suppressive cytokines. In Tregs, Foxp3 as an intracellular protein displays a more specific marker than currently used other cell-surface markers (such as CD25, CD40L, CTLA-4, ICOS and GITR) in defining the naturally occurring CD4+ Tregs. Though the precise mechanism for the opposite effects of Tregs has not been fully elucidated, the importance of Tregs in ADs has been proved to be associated with kinds of immunocytes. At present, the surface marker, frequency and function of Tregs existed conflicts and hence the Tregs therapy in ADs faces challenges. Though some success has been achieved with Tregs therapy in few ADs both in murine models and humans, more effort should paid to meet the future challenges. This review summarizes the progress and discusses the phenotypic, numeric and functional abnormalities of Tregs and is the first time to systematically review the progress of Tregs therapy in kinds of ADs.

Characteristic patterns of normal meridian acupoint temperature.

BACKGROUND: Body temperature is an important indicator of health and illness. However, a single temperature measurement is not always reliable. Such measurements can be made using meridians, which are energy channels with acupoints being the nodes. To date, there is no published reference of meridian acupoint temperatures applicable to human health, and there is no clear digitalized indicator that could be utilized to evaluate human health by way of meridian acupoints up to now. METHODS: Our study recruited 100 healthy medical college students for the measurement of acupoint temperature. The temperatures of 135 acupoints of 14 main meridians were measured using infrared thermometers in order to provide a comprehensive body temperature reading of each study participant. RESULTS: The degree of the acupoint temperature consistently ranged from 34.88°C to 36.14°C. The gross thermograph was concentric, with high degree readings around the heart and low degree readings originating from the feet. The left and right body sides had significant correlation between the degrees of bilateral same name acupoint temperatures of 12 regular meridians (correlation coefficient, 0.367-0.985; p < 0.0001). There was also a significant correlation between the acupoint temperature for the governor vessel and the conception vessel (correlation coefficient, 0.083; p = 0.006). CONCLUSION: These findings indicate that meridian acupoint temperature is characterized by a consistently narrow range, as well as concentricity and symmetry in body temperature degree readings in college students. Meridian acupoint temperature may be a sensitive and valuable indicator to assist in the accurate evaluation of meridian and general human health, and the significance and changes of acupoint temperature in clinical conditions warrants future exploration.

Morning breathing exercises prolong lifespan by improving hyperventilation in people living with respiratory cancer.

Disturbance of oxygen-carbon dioxide homeostasis has an impact on cancer. Little is known about the effect of breath training on cancer patients. Here we report our 10-year experience with morning breathing exercises (MBE) in peer-support programs for cancer survivors.We performed a cohort study to investigate long-term surviving patients with lung cancer (LC) and nasopharyngeal cancer (NPC) who practiced MBE on a daily basis. End-tidal breath holding time (ETBHT) after MBE was measured to reflect improvement in alveolar O2 pressure and alveolar CO2 pressure capacity.Patients (female, 57) with a diagnosis of LC (90 patients) and NPC (32 patients) were included. Seventy-six of them were MBE trainees. Average survival years were higher in MBE trainees (9.8 ±â€Š9.5) than nontrainees (3.3 ±â€Š2.8). The 5-year survival rate was 56.6% for MBE trainees and 19.6% for nontrainees (RR = 5.371, 95% CI = 2.271-12.636, P < 0.001). Survival probability of the trainees further increased 17.9-fold for the 10-year survival rate. Compared with the nontrainees, the MBE trainees shows no significant differences in ETBHT (baseline, P = 0.795; 1-2 years, P = 0.301; 3-4 years, P = 0.059) at baseline and within the first 4 years. From the 5th year onwards, significant improvements were observed in ETBHT, aCO2%, PaCO2, and PaO2 (P = 0.028). In total, 18 trainees (40.9%) and 20 nontrainees (74.1%) developed new metastasis (RR = 0.315, 95% CI = 0.108-0.919, P = 0.031).MBE might benefit for the long-term survival in patients with LC and NPC due to improvement in hyperventilation.

Efficacy of the wen dan decoction, a Chinese herbal formula, for metabolic syndrome.

CONTEXT: Metabolic syndrome (MS) refers to the clustering of metabolic derangements that include hyperglycemia, dyslipidemia, hypertension, and chronic kidney impairment. Those conditions are well known as being synergistically responsible for morbidity from cardiovascular disease as well as for driving the global epidemic of type 2 diabetes. It is still unknown whether an exact unifying pathogenesis of MS exists. OBJECTIVE: The meta-analysis intended to analyze the use of Chinese medicine (CM) as a therapeutic tool to explore indirectly the unifying pathogenesis of MS. METHODS: PubMed, the Chinese National Knowledge Infrastructure (CNKI), and the Wanfang databases were systematically searched from inception to November 2013 for randomized, controlled trials (RCTs) that compared treatment efficacy for MS patients using the Wen Dan decoction (WDD), a CM formula, versus Western conventional therapeutics. OUTCOME MEASURES: Measurements included tests of the overall therapeutic efficacy of WDD for hyperglycemia, hypertension, dyslipidemia, and renal functions, and the study also analyzed adverse events. Data were expressed as weighted mean differences (WMDs), with 95% confidence intervals (95% CIs) and the odds ratio (OR). RESULTS: A total of 31 RCTs were included for meta-analysis, involving 2512 patients and including 1282 participants in the intervention groups. The pooled data favored WDD over the control treatments as follows: (1) hyperglycemia, with a WMD of -0.95 mmol/L (95% CI: -1.19 to -0.71); (2) hypertension, with a WMD of -7.40 mm Hg (95% CI: -9.86 to -4.93); (3) dyslipidemia: (a) total cholesterol (TC), with a WMD of -0.62 mmol/L (95% CI: -0.90 to -0.33); (b) triglycerides (TGs), with a WMD of -0.32 mmol/L (95% CI: -0.52 to -0.13); (c) low-density lipoproteins (LDPs), with a WMD of -0.22 mmol/L (95% CI: -0.41 to -0.02); and (d) high-density lipoproteins (HDPs), with a WMD of 0.10 mmol/L (95% CI: 0.03 to 0.17); and (4) of renal functions: (a) urea, with a WMD of -3.41 mmol/L (95% CI: -5.50 to -1.32) and (b) creatinine, with a WMD of -68.81 µmol/L (95% CI: -132.63 to -4.98). No statistical significance was documented in creatinine clearance between the 2 treatments with a WMD of 15.47 mL/min (95% CI: -7.71 to 38.64). The overall efficacy rate was 91.4% for WDD and 66.9% for the control treatments (OR: 5.33; 95% CI: 4.06 to 6.99). Adverse events were rare and minor. CONCLUSIONS: The consistent improvements found in metabolic profiles by use of the single herbal formula may indirectly imply a common pathogenesis in MS.

Eight-year survival of AIDS patients treated with Chinese herbal medicine.

Treatment of acquired immunodeficiency syndrome (AIDS) currently relies on the use of antiretroviral drugs. Little is known about Chinese herbal medicine (CHM) outcomes in patients living with AIDS. We conducted a cohort study to investigate long-term survival among CHM-treated AIDS patients. Patients were poor farmers who contracted HIV-1 infection when selling blood in the 1990s. Symptoms of AIDS included recurring respiratory tract infections with a clinical diagnosis of pneumonia, swollen lymph nodes and weight loss. 385 patients with AIDS were included and 165 of them used a 16-herb formula for 14 days to 9 months. The eight-year survival rate was 87% for the CHM users and 34% for the non-users (increased survival probability for CHM user, 9.6; 95% CI = 6.0-15.4; p < 0.0001). Survival probability further increased 14.6-fold (95% CI = 8.2-26.1), when excluding the users who received CHM for less than three months. Zero deaths were found in patients who used CHM for six to nine months. All the survivors regained their body weight and none of them experienced a relapse of AIDS or any severe adverse events. After the CHM treatment for an average of 3.6 months, the plasma HIV load was 74.7% lower (paired t-test, p = 0.151) and the number of blood CD4+ lymphocytes increased from 253 to 314 (paired t-test, p = 0.021). Without life-long medication, CHM may be beneficial for long-term survival of AIDS patients.

Immune mechanism and clinical significance of macrophage to medullary hematopoietic injury of immune-related hematocytopenia patients.

BACKGROUND: Immune-related hematocytopenia (IRH) is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to observe the levels of various cytokines in the blood serum and the in situ active state of macrophage (Mφ) in the medullary hematopoietic microenvironment of IRH patients, and to probe into the immune mechanism and clinical significance of Mφ in hematopoietic cell injury. METHODS: ELISA is used to detect the IL-4, IL-6, IL-12, IL-17, and IFN-γ levels in the peripheral blood serum of 376 patients in pre- and post-therapy. Cytochemistry and cell immunochemistry methods are used to observe the peroxidase (POX), nonspecific esterase (NSE), hemosiderin granules, and HLA-DR activity of Mφ in the bone marrow of patients. Immunofluorescence is used to observe the expression of hemocyte antihuman globulin IgG antibody, lymphocytes CD4 molecule, Mφ membrane FcγIIreceptor (FcγIIR), mannitose receptor (MR), IFN-γ, ICAM-1, IL-12, and IL-17A and the formation mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC) hematopoietic cell islands (HI) in the medullary hematopoietic microenvironment of patients. Glucocorticoid is used for treatment on the basis of anti-infection therapy, and gamma globulin stoss therapy is used for the appearance of ADCC-type HI or serious Mφ bloodthirsty phenomenon; if necessary, association of Cyclosporine A (CsA) should be used and chalybeate should be supplemented. RESULTS: In the patient group, the levels of IL-4, IL-6, IL-12, IL-17, and IFN-γ were increased. After treatment, the cytokine levels gradually became normal. The activated Mφ in the marrow highly expressed NSE and POX, and Mφ swallowed more hemosiderin particles, but the iron in the cytoplasm of immature erythrocytes decreased. The activated Mφ expressed HLA-DR, MR, ICAM-1, IFN-γ, and IL-12. For patients with humoral immunity activation and bacterial infection, Mφ weakly expressed IL-17A but highly expressed FcγIIR, and the phenomenon that ADCC-type HI broke pathological blood corpuscles often occurred; for the cellular immune activation along with virus infection, the white blood count (WBC) significantly reduced, Mφ weakly expressed FcγIIR, secretory highly expressed IL-17A, and the phenomena that Mφ adhered to, captured and swallowed blood cell often occurred. After four weeks of anti-infective and immunosuppressive therapy, nuclear apoptosis of Mφ occurred in the bone marrow of patients, HI and bloodthirsty phenomenon disappeared, and the peripheral blood picture started to improve. CONCLUSIONS: Mφ is an important antigen presenting cell in the IRH marrow for hematopoiesis destruction and an immune effector cell of hematopoietic injury; infection can promote the activation of Mφ, upregulate the impression of immune molecule and receptors, form ADCC HI, aggravate hematopoietic injury, and accelerate the destruction on hematopoietic cell.