ObjectiveTo evaluate the public health governance capacity in Jiangsu Province and provide an optimized pathway for the construction of a “strong, rich, beautiful, and high-quality” new Jiangsu. MethodsA total of 806 policy documents, 658 public information reports, and 148 research literatures related to public health governance capacity in Jiangsu Province from January 1995 to December 2023 were collected. The status of current public health goverance was assessed based on the evaluation criteria suitable for public health systems, and the strengths and the weaknesses of the system were identified. ResultsThe public health governance capability of Jiangsu Province was scored at 738.3 points, ranking 3rd nationally. Maternal health care and emergency response capacities achieved leading positions nationwide, both ranking 2nd. Jiangsu had exhibited a standardized guidance in the strategic level, a well-established management mechanism, an extensive coverage in information collection, and a scientifically established health targets setting. However, bottlenecks remained, including an unclear division of responsibilities across organizational departments, an insufficient public-health workforce, the absence of a stable growth mechanism for government funding investment, and difficulties in promptly identifying public needs. ConclusionJiangsu’s public-health system demonstrates leading nationally, yet several components remain underdeveloped. Future efforts should consolidate advantages while addressing weaknesses, further diversify content and forms, establish a stable funding increase mechanism, and clarify departmental functions, thereby providing solid health support for realizing the developmental goals of a “strong, rich, beautiful and high-quality” new Jiangsu.

ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

BACKGROUND Sepsis, a common acute and critical disease, leads to 11 million deaths annually worldwide. Probiotics are living microorganisms that are beneficial to the host and may benefit sepsis outcomes, but their effects are still inconclusive. This study aimed to evaluate the overall effect of probiotics on the prognosis of patients with sepsis. DATA RESOURCES: We searched several sources for published/presented studies, including PubMed, EMBASE, Web of Science, the Cochrane Library and the US National Library of Medicine Clinical Trials Register (www.clinicaltrials.gov) updated through July 30, 2023, to identify all relevant randomized controlled trials (RCTs) or observational studies that assessed the effectiveness of probiotics or synbiotics in patients with sepsis and reported mortality. We focused primarily on mortality during the study period and analyzed secondary outcomes, including 28-day mortality, in-intensive care unit (ICU) mortality and other outcomes. RESULTS: Data from 405 patients in five RCTs and 108 patients in one cohort study were included in the analysis. The overall quality of the studies was satisfactory, but clinical heterogeneity existed. All adult studies reported a tendency for probiotics to reduce the mortality of patients with sepsis, and most studies reported a decreasing trend in the incidence of infectious complications, length of ICU stay and duration of antibiotic use. There was only one RCT involving children. CONCLUSION: Probiotics show promise for improving the prognosis of patients with sepsis, including reducing mortality and the incidence of infectious complications, particularly in adult patients. Despite the limited number of studies, especially in children, these findings will be encouraging for clinical practice in the treatment of sepsis and suggest that gut microbiota-targeted therapy may improve the prognosis of patients with sepsis.

Liver failure is a common severe syndrome of liver diseases with high mortality. The function and structural integrity of the intestinal barrier as an entity are closely associated with the development and progression of liver failure. The cGAS-STING signaling pathway can participate in innate immune response by recognizing DNA produced by pathogen invasion and host cell damage and inducing the production of type I interferon. Numerous studies have shown that activation of the cGAS-STING pathway can significantly impact the cellular structure， mucosal components， and commensal bacteria of the intestinal barrier. This article reviews the interplay between the cGAS-STING signaling pathway and intestinal barrier disruption in liver failure， in order to provide novel insights for the clinical management of liver failure.

To identify and validate the clinical phenotypes of patients with sepsis in the intensive care unit(ICU).

ObjectiveTo systematically evaluate the public health governance capacity of 40 cities in Jiangsu, Zhejiang, and Anhui Provinces, providing a scientific evaluation basis for building a "Healthy Yangtze River Delta". MethodsA comprehensive collection of policy documents, public information reports, and research literature related to public health governance capacity in Jiangsu, Zhejiang, and Anhui Provinces was conducted, totaling 6 920 policy documents, 1 720 information reports, and 1 200 literature pieces. Based on the evaluation standards for an appropriate public health system established by the research team, the basic status of public health governance capacity was assessed to identify the strengths and weaknesses of the 40 cities. ResultsIn 2022, the public health governance capacity score for the 40 cities in Jiangsu, Zhejiang, and Anhui Provinces was (562.5±38.0) points. In terms of specific areas, the emergency response field received the highest score of (791.4±49.7) points, while the chronic disease prevention and control field received the lowest score of (368.2±29.6) points. The Jiangsu-Zhejiang-Anhui region has largely achieved the strategic priority of health, gradually improved public health legal regulations, and established a basic organizational framework with a solid foundation for information and data infrastructure. However, challenges still need to be addressed, such as unstable government funding for public health, unclear departmental responsibilities, and barriers to information interoperability. ConclusionThe public health governance capacity of the 40 cities in Jiangsu, Zhejiang, and Anhui Province has been at a moderate level, but disparities have still existed across regions and fields. In the future, while continuing to deepen existing advantages, it is essential to accurately identify the causes of problems, establish a long-term and stable investment mechanism, enhance information connectivity mechanisms, further clarify departmental responsibilities, and promote the achievement of the "Healthy Yangtze River Delta" goal.

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus