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.

Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

Objective To analyze the effect of the activation rate of peripheral blood monocytes on the recovery of patients after liver transplantation and to initially explore the possible influencing factors for differences in monocyte activation rates. Methods A total of 139 patients who underwent orthotopic liver transplantation from September 2020 to June 2023 at Department of Liver Surgery and Transplantation of Zhongshan Hospital, Fudan University were selected. The proportion of CD14^＋HLA-DR^＋ monocytes in peripheral blood was defined as the monocyte activation rate. The difference in monocyte activation rates between postoperative day 7 (POD7) and postoperative day 1 (POD1) was calculated as Δ, and patients were divided into Δ＞0 group (n＝73) and Δ＜0 group (n＝66). The two groups were compared in terms of complete blood count, liver and kidney function, coagulation indicators, infection indicators, ICU length of stay, total length of hospitalization, and 90-day mortality. Changes in the proportions of different monocytes subsets (Mo0, Mo1, Mo2, and Mo3) and HLA-DR expression in peripheral blood on POD1 and POD7 were detected using flow cytometry. Results The ICU length of stay in the Δ＜0 group was significantly longer than that in the Δ＞0 group (18[12, 26] days vs 14[10, 20.5] days, P＝0.018). On POD1, the proportion of Mo0 in the Δ＞0 group was significantly lower than that in the Δ＜0 group (P＜0.05); on POD7, the proportion of Mo0 in the Δ＞0 group was significantly lower than that in the Δ＜0 group (P＜0.001), while the proportions of Mo1, Mo2, and Mo3 were significantly higher than those in the Δ＜0 group (P＜0.001). Compared to POD1, the HLA-DR expression level of Mo0 in peripheral blood of patients with liver transplantation significantly decreased on POD7 (P＜0.01), while there was no significant difference in HLA-DR expression levels of Mo1, Mo2, and Mo3. Conclusions Increased proportion of Mo0 (CD14^lowCD16⁻HLA-DR^low) among peripheral blood monocyte subsets may be one of the influencing factors for the differences in monocyte activation rates in patients with liver transplantation. The difference in monocyte activation rate can serve as a new clinical indicator for assessing changes in the immune status and postoperative recovery of patients with liver transplantation.

Objective:To study the effects of parenteral nutrition containing ω-3 fish oil fat emulsion on the inflammatory status of patients with intestinal fistula at the early stage.Methods:A retrospective analysis was conducted on 28 patients with intestinal fistula who were admitted to the Sixth Department of General Surgery of Anhui Provincial Second People's Hospital from November 2023 to May 2024.The patients were either divided into control group(n=15,parenteral nutrition alone group)or study group(n=13,parenteral nutrition plus ω-3 fish oil fat emulsion)according to whether ω-3 fish oil fat emulsion was added to parenteral nutrition.Both groups of patients received parenteral nutrition support treatment,and the study group was given ω-3 fish oil fat emulsion during treatment.The general information,inflammatory factors in the blood,nutrition,and immune status of two groups of patients were collected and compared.The feces samples on the first and 14th day of admission were collected and analyzed by 16S rRNA high-throughput sequencing of gut microbiota.Results:There was no statistically significant difference in the general information,inflammation,nutrition,immune status,and gut microbiota between the two groups of patients on the first day of admission(P>0.05),indicating comparability between the two groups.After two weeks of parenteral nutrition support,the counts of red blood cells,white blood cells,platelets,lymphocytes,and levels of C-reactive protein,glutamate-pyruvate transaminase,aspartate aminotransferase,total bilirubin,direct bilirubin,total protein,albumin,and creatinine in the research group were similar to those in the control group without statistically significant differences(P>0.05).However,the counts of neutrophils and levels of blood urea nitrogen in the study group were significantly lower than those in the control group(P=0.03 and P=0.01).In addition,the abundance of intestinal flora in the study group was significantly higher than that in the control group(P<0.05).At the genus level,the abundance of Bacteroides_uniformis,Parabacteroides_merdae,Alistipes_finegoldii,Streptococcus_constellatus,Christensenella_minuta were different between the two groups after two weeks of treatment(P<0.05).Conclusion:Parenteral nutrition containing ω-3 fish oil fat emulsion can reduce the counts of neutrophils,which may alleviate inflammatory responses for patients with intestinal fistula at the early stage.

Oral squamous cell carcinoma(OSCC)is a common malignant tumor.Interleukin-8(IL-8)is an important biomarker of OSCC,and its level can reflect the occurrence and development of OSCC.It is of great significance to detect IL-8 rapidly and sensitively for the purpose of early diagnosis of OSCC.In this study,gold nanoparticles(AuNPs)with uniform particle size were synthesized by reduction of chloroauric acid with trisodium citrate,and the probe(AuNPs@mAb1)was prepared by coupling AuNPs with the murine anti-IL-8 monoclonal antibody mAb1.Cy5-NHS and murine anti-IL-8 monoclonal antibody mAb2 complex(Cy5-mAb2)and sheep anti-mouse IgG antibody were sprayed on nitrocellulose membrane to form test line(T line)and control line(C line)respectively,and reverse fluorescence-enhanced test strips were thus constructed,based on which an immunochromatographic method was established for highly sensitive detection of IL-8 in saliva samples.The experimental results showed that the test strip had good stability,high specificity and high sensitivity.The linear range for fluorescence detection of IL-8 was 0.01-100 ng/mL,and the limit of detection(3σ)was 7.93 pg/mL.The linear range for visualization detection was 6-100 ng/mL,with limit of detection(3σ)of 0.85 ng/mL.The fabricated test trip had good preparation reproducibility,with inter-and intra-batch assay precision of less than 5.5%.The test strip was used for detection of IL-8 in healthy human saliva samples,with spiked recoveries of 93.7% -102.4%,and relative standard deviations of 2.1% -4.3%.The fabricated test strip could be used for early screening of OSCC.

Objectives:To evaluate the efficacies of laminoplasty(LP)and laminectomy and fusion(LF)in the treatment of multi-level ossification of the posterior longitudinal ligament(OPLL)in the cervical spine through meta-analysis.Methods:The databases of CNKI,Wanfang,Pubmed,Cochrane Library,EMBASE were searched by computer from their inceptions to June 2023 and the published clinical studies comparing LP and LF in the treatment of multi-level OPLL in the cervical spine were included.Cochrane risk bias assess-ment tool and Newcastle-Ottawa scale(NOS)were used to evaluate the quality of the included studies.Rele-vant data including operation time,intraoperative blood loss,the improvement rate of Japanese Orthopaedic Association(JOA)score,the change value of visual analogue scale(VAS)score,neck disability index(NDI),cer-vical curvature index(CCI),sagittal vertical axis(SVA)and cervical range of motion(CROM)at the final fol-low-up,the postoperative complication rate and OPLL progression rate were extracted and sorted.Then the meta-analysis was conducted by RevMan 5.4 and StataSE 16.0 softwares.Results:12 literatures(3 randomized controlled studies and 9 cohort studies)were ultimately included,involving a total sample size of 1496 cases,containing 839 cases in the LP group and 657 cases in the LF group.The results of meta-analysis were as follows:the LP group was better than LF group with significant differences in operation time[WMD=-28.01,95％CI(-36.25,-19.77),P＜0.00001],intraoperative blood loss[WMD=-115.09,95％CI(-197.91,-32.27),P=0.006],the change value of CROM[WMD=-7.83,95％CI(-8.10,-7.55),P＜0.00001]compared with those before surgery at final follow-up,the incidence of postoperative C5 nerve root paralysis[OR=0.32,95％CI(0.21,0.50),P＜0.00001]and axial symptoms[OR=0.44,95％CI(0.28,0.71),P=0.0006].The LF group was better than the LP group with significant differences in the change value of the CCI[WMD=-0.75,95％CI(-0.92,-0.58),P＜0.00001]and SVA[WMD=5.49,95％CI(5.30,5.68),P＜0.00001]compared with those before surgery at final follow-up,and the postoperative OPLL progression rate[OR=1.76,95％CI(1.26,2.46),P=0.0009].There were no significant differences between the two groups in the improvement rate of JOA score[WMD=-1.24,95％CI(-4.02,1.54),P=0.38],the change value of VAS[WMD=0.03,95％CI(-0.43,0.49),P=0.89]and NDI[WMD=0.54,95％CI(-0.07,1.14),P=0.08]compared with those before surgery at final follow-up,the incidence of postoperative cerebrospinal fluid leakage[OR=0.58,95％CI(0.24,1.39),P=0.22],incision infection[OR=0.71,95％CI(0.32,1.57),P=0.39]and epidural hematoma[OR=0.37,95％CI(0.06,2.16),P=0.27].Conclusions:Both LF and LP can effectively treat multi-level OPLL in the cervical spine and improve the neurological function of patients.Compared to LF,LP causes less surgical damage,preserves more cervical mobility and additionally,has a lower incidence of the postoperative C5 nerve root paralysis and axial symptoms.In comparison,LF can better maintain the curvature and stability of the cervical spine and delay the progression of ossification.

Ergopeptines or their derivatives are widely used for treating neurodegenerative and cerebrovascular diseases. The nonribosomal peptide synthetase-d-lysergyl peptide synthetase A (LPSA) determines ergopeptine formation but the detailed mechanism remains to be elucidated. Here, we characterized two LPSAs from Claviceps purpurea Cp-1 strain through heterologous expression in Aspergillus nidulans feeding with d-lysergic acid. We proved that Cp-LPSA1 catalyzed the formation of ergocornine, α-ergocryptine, and β-ergocryptine, precisely controlled by the substrate specificity of its three modules. Cp-LPSA2 was initially inactive but could be restored to catalyze α-ergosine formation. Using this platform, we validated that P1-LPSA1 and P1-LPSA2 from the reported C. purpurea P1 strain catalyzed ergotamine and α-ergocryptine formation, respectively. Typically, the non-ribosomal peptide codes implicated in every module of the LPSAs were defined and elucidated, in which certain key residues could play a switched role for substrate specificity and product interconversion. By constructing chimeric LPSAs through module assembly, the production of the desired ergopeptines was achieved. Notably, 1.46 mg/L of α-ergocryptine and 1.09 mg/L of ergotamine were produced respectively by mixed-culture of C. paspali No. 24 (fermentation supernatant) and the recombinants of A. nidulans. Our findings provide insights into the biosynthetic mechanism of ergopeptines and lay a foundation for directed ergopeptine biosynthesis.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Purpose To investigate the predictive value of nomogram based on preoperative CT imaging for predicting programmed cell death receptor ligand 1(PD-L1)expression in patient with lung adenocarcinoma.Materials and Methods A total of 158 patients with lung adenocarcinoma were enrolled in Shenzhen people's Hospital from January 2021 to July 2022,of which 82 were negative for PD-L1 and 76 were positive for PD-L1.They were randomly divided into training set(n=119)and verification set(n=39)according to the proportion of 7:3.The significant characteristics between PD-L1 negative and PD-L1 positive were screened by univariate and multivariate Logistic regression to construct a clinical model.Radiomics features were extracted from preoperative CT images,and then features were screened and modeled.Finally,the combined model was established by clinical factors and radiomics features,which was visualized by nomogram.The diagnostic performance of the model was evaluated using receiver operating characteristic curves and area under the curve(AUC).Results The area under the curve(AUC)of the clinical model composed of carcinoembryonic antigen and vascular convergence sign was 0.774(95%CI 0.687-0.860)and 0.808(95%CI 0.670-0.947)in the training set and validation set,respectively.Through feature screening,the radiomics model was composed of 17 radiomics features,and the AUC of the training and validation sets was 0.837(95%CI 0.764-0.910)and 0.778(95%CI 0.633-0.923).The training set and validation set of the combined model composed of carcinoembryonic antigen,vascular convergence sign and radiomics score were AUC 0.892(95%CI 0.832-0.952)and 0.853(95%CI 0.737-0.968).In the training set,the AUC of the combined model was higher than that of the other two models(Z=-2.640,-2.855,P＜0.05).Conclusion Based on preoperative CT radiomics nomogram,it had high predictive efficacy on the expression of PD-L1 in lung adenocarcinoma and could provide decision-making support for the selection of clinical treatment regimens for lung adenocarcinoma patients.