Objective:To explore the quality improvement in the organization structure and management model of the integrated community child health services.Methods:This was a qualitative study, including two parts: cause analysis and service improvement suggestions. In the analysis part the data mining was conducted to identify valuable patterns and relationships in the comprehensive child health services. Semi-structured interviews were conducted with 12 relevant department heads and health workers of the comprehensive child health service team at Gumei Community Health Service Center in December 2023, and the causes of the key problems were explored. In the service improvement part, focus group discussions were held to propose suggestions, then improvement measures were formulated to address the identified problems.Results:Through data mining and semi-structured interviews, the key problems were identified: information isolation among multiple departments and lack of coordination mechanism in the comprehensive child health service team. A team organizational structure based on the "three definite" principle was established. The organizational structure should include the pediatric family doctor team, general practitioner management team and departments of pediatrics, maternal and child health care, immunization and child rehabilitation; the management model should include a cross-department resource and information sharing mechanism, the pediatric family doctor model, optimization and integration of physical space, and enhancement of publicity activities for the comprehensive child health services.Conclusion:Based on the analysis in Gumei health service center, this study identified key problems in community integrated child health services, and proposes the quality improvement measure in the organizational structure and management model of the service team.

Objective To investigated the effect of stenosis characteristics (vascular elasticity and plaque properties) on myocardial ischemia. Methods An ideal geometric multi-scale coronary stenosis model based on fluid-structure interaction was established, and the fractional flow reserve (FFR) was simulated to evaluate myocardial ischemia. The effects of vascular elastic wall (elastic modulus of 1 MPa) and rigid wall, plaque types (lipid-rich plaque and calcified plaque) and plaque volume on myocardial ischemia were considered separately. Results The FFRCT simulation result of vessels with elastic wall was larger than that with rigid wall under all stenosis situations. The FFRCT of vessels in lipid-rich lesions was higher than that of calcified plaque (P=0.001). The trapezoidal plaque volume was larger than the cosine plaque volume, and the FFRCT of vessels in trapezoidal plaque was smaller than that of cosine plaque (P=0.001). Conclusions Vascular elasticity is a critical factor to simulate vascular hemodynamics. In moderate stenosis, calcified plaques are more likely to induce myocardial ischemia due to the larger luminal deformation and dilation of rich lipid plaque. When the stenosis is constant, the smaller the plaque volume, the higher the FFRCT and the smaller the possibility of myocardial ischemia.

Although NPM1 mutations are frequently found in acute myeloid leukemia patients, therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy. Here we demonstrated that heliangin, a natural sesquiterpene lactone, exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells, with no apparent toxicity to normal hematogenous cells, by inhibiting their proliferation, inducing apoptosis, causing cell cycle arrest, and promoting differentiation. In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2 (RPS2) is the main target of heliangin in treating NPM1 mutant AML. Upon covalent binding to the C222 site of RPS2, the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes, leading to nucleolar stress, which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53. Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation, leading to a poor prognosis. We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target. Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients, especially those with NPM1 mutations.

Objective To evaluate the rupture risk of carotid atherosclerotic plaque under cervical rotatory manipulation. Methods The fluid-structure interaction (FSI) model of carotid atherosclerotic plaque was established, and tensile deformation of the plaque and lumen under cervical rotatory manipulation was simulated.Mechanical parameters such as the maximum flow shear stress(FSS), the maximum wall shear stress (WSS), the maximum plaque wall stress (PWS), wall tensile stress (WTS) and wall pressure (WP) of the plaque and lumen were recorded. Results Under 16% carotid tensile deformation, the maximum WSS of the plaque was 40.54 Pa. The maximum PWS was 66.16 kPa, which was far smaller than the threshold of plaque rupture.The maximum WTS of fiber cap and the maximum strain were 156.75 kPa and 0.56, which were larger than the fracture strain range. The maximum WTS of the lumen was 1 040.30 kPa, which approached the threshold of medial membrane rupture and might cause vascular injury. Conclusions When the cervical spine rotates to the end range of motion, large carotid artery stretch may cause damage to epidermal tissues of the plaque, leading to abscission. Lesions, ulcers, bleeding and vascular damage may form inside the plaque, which will affect stability of the plaque. Cervical rotatory manipulation should be performed cautiously in patients with cervical diseases who also have carotid atherosclerotic plaques.The finite element assessment of plaques before manipulation may be an effective safety screening method.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is widely used for targeted genomic and epigenomic modifications and imaging in cells and organisms, and holds tremendous promise in clinical applications. The efficiency and accuracy of the technology are partly determined by the target binding affinity and residence time of Cas9-single-guide RNA (sgRNA) at a given site. However, little attention has been paid to the effect of target binding affinity and residence duration on the repair of Cas9-induced DNA double-strand breaks (DSBs). We propose that the choice of DSB repair pathway may be altered by variation in the binding affinity and residence duration of Cas9-sgRNA at the cleaved target, contributing to significantly heterogeneous mutations in CRISPR/Cas9 genome editing. Here, we discuss the effect of Cas9-sgRNA target binding and residence on the choice of DSB repair pathway in CRISPR/Cas9 genome editing, and the opportunity this presents to optimize Cas9-based technology.

Four new lanostane triterpenoids, 3β-hydroxy-12α-methoxylanosta-7,9(11),24-triene(1), 3β-hydroxy-12α-methoxy-24-methylene-lanost-7,9(11)-dien(2), 3,7-dioxo-lanosta-8,24-diene(3), and 3,7-dioxo-24-methylene-lanost-8-en(4), were isolated from the latex of Euphorbia resinifera with a variety of chromatography methods. Their structures were elucidated based on spectroscopic data and/or comparison with the data reported in previous research. Compounds 1, 2, and 4 showed moderate inhibition of LPS-induced NO production by RAW264.7, with IC_(50) of 30.4, 37.5, and 28.3 μmol·L~(-1), respectively.
Euphorbia ; Latex ; Molecular Structure ; Steroids ; Triterpenes

Objective:To study the material basis of the drug effect of the raw material of lamb′s tripe and vitamin B12 capsule.Methods:Rennet and pepsin were extracted with 0.9% sodium chloride and were purified by saturated ammonium sulfate precipitation, diethylaminoethyl-cellulose 52 and high pressure chromatography (HPLC) chromatography. Relative molecular weight was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis and liquid chromatography-triple quadrupole mass spectrometer. The amino acid composition and antioxidant activity of raw materials were analyzed with HPLC. The raw materials were completely extracted with water, phosphate buffer and sodium bicarbonate in turn, and in vitro 1, 1-diphenyl-2-picrylhydrazyl radil 2, 2-diphenyl-1-(2, 4, 6-trinitrophenyl)hydrazyl (DPPH) and 2, 2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical activity were measured. Glycoprotein from raw material was extracted with hot water and determined its growth-promoting activity gaginst Bifidobacterium adolescentis , Lactobacillus delbrueckii subsp. Bulgaricus and Enterococcus faecalis was measured. The composition of amino acid and monosaccharide were analyzed by HPLC and gas chromatography-mass spectrometry, respectively. Results:The enzyme activity of two purified rennet F6-2 and F7-2 which had different ionic strengths and pepsin F7-1 were 27 557.10, 17 532.60 and 17 728.15 U/g, respectively. The results of SDS-PAGE indicated that the molecular weights of three enzymes were similar, ranging from 35 000 to 40 000. The raw material contained 16 kinds of amino acids, of which hydrophobic amino acids accounted for 33.03% of the total amino acid content. When the sample concentration was 5 mg/mL, ABTS free radical scavenging activity of the three extracts was (37.80±0.45)%, (23.20±0.78)% and (62.80±0.74)%; DPPH free radical scavenging activity was (57.87±0.55)%, (5.03±0.25)% and (26.67±3.10)%, respectively. Glycoprotein extracts had promoted the growth of Bifidobacterium adolescentis, Lactobacillus delbrueckii subsp. Bulgaricus and Enterococcus faecalis, and there was statistically significant difference in the promotion of Lactobacillus delbrueckii subsp. Bulgaricus and Enterococcus faecalis ( P<0.05). The protein chain of glycoprotein was composed of 15 amino acids and the polysaccharide chain was composed of two monosaccharides, glucose and lactose. Conclusions:Two rennet and one pepsin are isolated and analyzed from raw material of lamb abomasum by various chromatographic methods. The raw material is rich in antioxidant active ingredients. The glycoprotein components of lamb abomasum has the activity of promoting the growth of probiotics.

OBJECTIVE: To establish a clinical prediction model of the mid-term fatality risk after radical resection in patients with primary hepatocellular carcinoma (HCC) based on the albumin-bilirubin (ALBI) grade and to assess its prediction value. METHODS: Clinical data of 533 patients who received HCC radical resection in Jinhua Hospital of Zhejiang University, Jinhua People's Hospital, Jinhua Hospital of Traditional Chinese Medicine and Jinhua Guangfu Hospital from January 2010 to August 2016 were retrospectively reviewed. In the training group ( =407), Cox model was used to screen the clinical risk factors of postoperative death, and a predictive model based on ALBI grade was established and then examined in the validation group ( =126). The value of the prediction model was assessed by ROC curve and calibration curve; the prediction results of the model were visualized by the nomogram for the convenience of clinical use. RESULTS: Cox model showed that ALT ≥ 80 U/L, tumor maximum diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 were independent risk factors for the prognosis of patients with HCC radical resection. The prognosis index (PI) was 0.550×ALT+0.512×ALBI grade+0.872×maximum tumor diameter+1.377×portal vein tumor thrombus. The AUCs for predicting the risk of death in 12, 36 and 60 months were 0.872, 0.814 and 0.810, respectively (all < 0.01), and the goodness of fit ( ) of the established model were 0.953, 0.976 and 0.994. AUC of the established model for predicting risk of death in 36 months after resection was 0.814, which was higher than those of ALBI (AUC=0.683), BCLC (AUC=0.713), CLIP (AUC=0.689), Child-Pugh (AUC=0.645), TNM (AUC=0.612) ( < 0.05 or < 0.01). CONCLUSIONS ALT ≥ 80 U/L, maximum tumor diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 are independent risk factors of patients after HCC resection, and ALBI grade-based prediction model is satisfactory in prediction of mid-term death risk of the patients.
Albumins ; Bilirubin ; Carcinoma, Hepatocellular ; Humans ; Liver Neoplasms ; Prognosis ; Retrospective Studies

Objective To analyze the influence of ligaments surrounding sacroiliac joints (SIJs) on stability of SIJs by finite element method. Methods The finite element lumbar spine-pelvis-femur model was established. Based on this normal model, all SIJ ligaments in both sides were removed in turn, to establish models without iliolumbar ligaments, sacroiliac anterior ligaments, sacroiliac posterior ligament, sacrotuberous ligaments, sacrospinous ligaments, sacroiliac interosseous ligaments, respectively. The models were used to simulate physiological motions of the spine. The range of motion (ROM) and average stress on the left and right SIJs were analyzed and compared with the normal models. Results Compared with the normal SIJ model, no significant differences in the ROM of bilateral SIJs were found in the models without sacrotuberous ligaments, sacrospinous ligaments and sacroiliac posterior ligaments; for the model without acroiliacinterosseous ligaments, there was no significant difference in the ROM of the left SIJs under spinal right rotation and ROM of the right SIJs under spinal extension, but the ROM of bilateral SIJs increased significantly under the other spinal physiological activities. Under the physiological activities of the spine, the average stress of the SIJ surface in the left and right sides of the model without acroiliacinterosseous ligaments significantly decreased. Conclusions Of all the sacroiliac ligaments, the sacroiliac interosseous ligaments showed the maximum influences on the stability of SIJs. The research findings are helpful to investigate the mechanism of SIJ subluxation and provide certain theoretical basis for clinical treatment of SIJ subluxation.

Objective To investigate the expression levels of IFN-γ, IL-4, IL-6 in the plasma of HBV chronic patients.To acknowledge the correlation between the immune function of T-cell with chronic hepatitis B virus.Methods The expression levels of IFN-γ, IL-4, IL-6 in the plasma were determined by ELISA in 42 cases of chronic hepatitis B (CHB group), 30 cases of cirrhosis (LC group), 30 cases of primary liver cancer (HCC group) and 30 cases of health control (NC group).Combine with the load of HBV DNA, HBeAg and ALT, the expression levels of IFN-γ, IL-4, IL-6 were re-analysed.Results The expression levels of IFN-γ, IL-4 and IL-6 in the researched groups were statistically significantly different.The expression levels of IFN-γ, IL-4, IL-6 in CHB, LC and HCC groups were higher than NC group with significance.The expression level of IL-4 in the CHB group was higher than LC and HCC groups with significance.The expression level of IL-6 in the HCC group was higher than CHB and LC groups with significance.Compared with the control group, the ratio of IFN-γ/IL-4 in CHB, LC and HCC groups were decreased with significance.There was significantly positive correlation between the expression level of IL-4 with the load of HBV DNA (r=0.757, P＜0.001).The expression level of IFN-γhad negative correlation between the load of HBV DNA (r=-0.786, P＜0.001) with the level of ALT (r=-0.713, P＜0.001) with significance.There was no significant correlation between HBeAg with the cytokines in the serum of patients with chronic HBV.Conclusion The results showed the immune function of T-cell play important role in chronic HBV patients.That would provide a good basis on CHB treatment.The expression levels of IL-6 were higher in HCC group with significance, which provided the direction for the deep study of liver cancer.