Objective To optimize the preparation technology of transcription activator (TAT) and polyethylene glycols (PEG) co-modified tilianin-loaded composite phospholipid liposome (TAT & PEG tilianin CPL, T&PTCPL) and investigate its protective effect on cardiomyocytes. Methods The composite phospholipid liposome was prepared by thin film-ultrasonic method. A three- factor, three-level Box-Behnken experimental design was employed. The weight ratio of total phospholipid to tilianin (X1), the concentration of DSPE-PEG2000-TAT (X2), and hydration volume (X3) were observed. The encapsulation efficiency (Y1), particle size (Y2), and polydispersion coefficient (Y3) were evaluated to optimize optimal formula. In addition, hypoxia/reoxygenation model was established with Na2S2O4 in H9C2 cells. Superoxide dismutase (SOD) activity, malonaldehyde (MDA) level and release of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were assessed to evaluate the effect of T&PTCPL, meanwhile, the in vitro release rate (dynamic dialysis method) and absorption rate of tilianin and T&PTCPL in Caco-2 cell were examined. Results The optimal formula was as following: X1 = 20, X2 = 1.7%, and X3 = 3.2 mL; The encapsulation efficiency was (86.62 ± 2.51)%, particle size was (149.7 ± 8.2) nm and PDI was 0.15 ± 0.05. Compared with model group, T&PTCPL and tilianin groups increased SOD activity, inhibited level of MDA, LDH and CK-MB leakage (P < 0.05), and the effect of T&PTCPL group was better than tilianin group, meanwhile, T&PTCPL was completely released at 48 h, with a cumulative release of 88.65%, and Caco-2 cells had better absorption of T&PTCPL. Conclusion The Box-Behnken design is suitable for optimizing the formulation of T&PTCPL, and the observed responses are in close agreement with the predicted values of the mathematic models; Moreover, T&PTCPL shows a better sustained release effect in vitro release, which promots the absorption of tilianin in Caco-2 cells and suggests that T&PTCPL may have protective effect on myocardial ischemia reperfusion injury.

OBJECTIVE: To prepare cRGD-modified harmine hydrochloride long circulating liposomes, investigate its characteristics in vitro, and finally establish its best preparation method. METHODS: Firstly the content determination method was established, and secondly harmine hydrochloride liposomes were prepared through reverse phase evaporation method. Both active and passive drug loading methods were investigated to entrap the drug. Thirdly, cRGD-DSPE-2000 was prepared by conjugation method, and then cRGD modified harmine hydrochloride long circulating liposomes were prepared. Finally the particle sizes, Zeta potential and the entrapment efficiency were determined. The release of the liposomes in vitro was measured. RESULTS: The standard curves all had good linearities except for the one using 100% methanol as solvent. The particle sizes of the liposomes prepared by passive loading method, active loading method, and long circulating cRGD modified liposomes were 227.2, 246.3 and 241.9 nm, respectively, and the Zeta potentials were about 20-30 mV. The entrapment efficiency were (36.78 ± 6.82)%, (81.77 ± 7.61)%, and (80.02 ± 1.27)%, respectively. The release of cRGD liposomes was slower than the liposomes without cRGD and HM solution. CONCLUSION: cRGD-modified long circulating harmine hydrochloride liposomes can be made through reverse phase evaporation method and active loading method. KEY

OBJECTIVE: To conduct a comprehensive PRISMA-compliant systematic review and Meta-analysis to evaluate the safety and efficacy of genotype-guided initial dosing of warfarin. METHODS: PubMed, Web of Science, Cochrane library, CNKI, CBM, and Wanfang data were electronically searched, and randomized controlled trials comparing pharmacogenetic dosing of warfarin vursus routine anticoagulant treatment were included. Then two reviewers independently used EndNote X7 software to filter the literatures, extracte data and assess study quality, and Revman 5, 2 software was used to conduct Meta analysis, The primary endpoints were the percentage of time within the therapeutic INR range and adverse events, The secondary endpoints were the time to reach a stable warfarin dose and the propotion of patients reaching stable warfarin dose. RESULTS: Nine trials met the inclusion criteria, in which a total of 1390 patients were randomly assigned to genotype-guided group and control group (traditional dosing) to receive warfarin treatment with a follow-up time ranging from 4 weeks to 3 months, It was discovered that the percentage of time within the therapeutic INR range in genotype-guided group was improved compared with the control group when the initial routine dose was fixed [SMD=0.26, 95% CI (0.11, 0.41), P=0.0006], and a smaller number of patients in genotype-guided group developed adverse events [RR=0.75, 95% CI (0.66, 0.84), P<0.00001], Genotype-guided group reached stable warfarin dose earlier compared with the control group [SMD=-3.49, 95% CI (-6.15, -0.84), P=0.01], but there was statistical heterogeneity among the studies (P<0.00001, I2=99%), The propotion of patients who reached stable dose in genotype-guide group was larger than that in traditional dosing group [RR=1.25, 95% CI (1.15, 1.35), P <0.00001], CONCLUSION: Genotype-guided initial dosing of warfarin can increase the percentage of time within the therapeutic INR range, reduce the incidance of adverse events, shorten the time to reach stable dose, and increase the propotion of patients reaching stable dose.

OBJECTIVE: To observe the effect of Dracocephalum heterophyllum flavonoids(DHBF) of Uygur Medicine on cardiomyocyte hypertrophy, which were induced by angiotensin Ⅱ(AngⅡ), and it could provide a basis for further study to the mechanism. METHODS: SD rats, 0 - 3 d of age, neonatal rat myocardial cells cultured in vitro, the experiment was divided into control group, AngⅡ(1 μmol•L-1) group, different concentrations of DHBF(10, 25, 50 μmol•L-1) + AngⅡ(1 μmol•L-1) groups, cardiomyocyte hypertrophy were induced by AngⅡ 1 μmol•L-1 and was intervened using DHBF respectively, CCK-8 method was used to observe the activity of myocardial cells, RT-PCR technique was used to detect the expression of m RNA of cardiac hypertrophy gene atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP), the internal factor was glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Confocal laser scanning was used to detect the surface area of myocardial cell was [Ca2+]i; the activity of Ca2+-ATP was measured by the enzymatic reaction of fragmentation cell; the concentration of NO and the activity of NOS were determined by colorimetry. RESULTS: Compared with the control group, the activity of myocardial cell was(85% ± 5%) in the AngⅡgroup, which was increased significantly after it was dealed with DHBF and AngⅡ(P < 0.05); RT-PCR results showed the expression of mRNA of ANP and BNP were increased by using AngⅡ, which were lower by using DHBF and AngⅡ. The surface area of myocardial cell were increased by using AngⅡ, which could be reversed by using DHBF and AngⅡ. Confocal laser scanning showed the concentration of [Ca2+]i was increased by using AngⅡ, but which was lower significantly by using DHBF and AngⅡ(P < 0.05). The enzymatic reaction of fragmentation cell results showed the activity of Ca2+-ATP was decreased by using AngⅡ, but which was increased significantly by using DHBF and AngⅡ(P < 0.05). Colorimetry results showed the concentration of NO and the activity of NOS were decreased by using AngⅡ, but which was increased significantly by using DHBF and AngⅡ(P < 0.05). CONCLUSION: DHBF can improve the activity of hypertrophy cardiomyocytes which were induced by angⅡ, downregulate expression of mRNA of ANP and BNP, reduce surface area of cardiomyocytes induced by AngⅡ, the mechanism of action may be related to promoting the release of NO, regulating the concentration of[Ca2+]i and the activity of Ca2+-ATP.

BACKGROUND: In orthodontic treatment, different anchorage controls will make different effects on the maxillary third molar. Whether this can affect the normal eruption of maxillary third molar remains unclear. OBJECTIVE: To explore the effect of Physiologic Anchorage Spee-Wire System (PASS) treatment on impacted maxillary third molars, and to provide reference for clinical application. METHODS: Thirty patients with maxillary third molars were treated with PASS and 30 patients were treated with McLaughlin, Bennett, and Trevisi (MBT). All patients chose the plan of extracting four first premolars. The angles and distances were measured before and after treatment and statistical analysis was performed. The study was in accordance with the ethical requirements of the Fifth Affiliated Hospital of Xinjiang Medical University. All participants and their guardians signed the informed consents. RESULTS AND CONCLUSION: (1) In the PASS group, the ∠UM3-HP, ∠UM2-HP and U-ES were significantly increased (P=0.00), and the UM3-OP was significantly decreased (P=0.00), indicating that the maxillary second molar and third molar became more upright, and larger eruption space contributed to eruption. (2) Compared with the PASS group, the obliquity of the maxillary third molar in the MBT group showed significant change, while the vertical eruption rate in the PASS group was relatively larger. (3) These results imply that both PASS and MBT can improve the eruption angle and space of the third molar, and make it easier to erupt in orthodontic treatment of extraction of the first premolar.

Background Personal protection is crucial for reducing the risk of zoonotic pathogen infection among livestock workers. Investigating the current status of its implementation and associated influencing factors can provide empirical evidence for developing more effective intervention measures. Objective To investigate the current status of personal protection implementation among livestock workers in Xinjiang, China and its influencing factors, providing a reference for formulating targeted intervention measures. Methods This study was conducted in Bayingolin Mongol Autonomous Prefecture, Kashgar region, and the First and Eighth Divisions of Xinjiang Production and Construction Corps. We selected large-scale cattle and sheep farms, cooperatives, individual livestock households, livestock trading markets, slaughterhouses, and retail markets. Using cluster sampling, we recruited all livestock workers (1074 participants) at sampled sites. During the period from April to July 2024, we conducted face-to-face surveys with a self-designed questionnaire among livestock workers, collecting general demographic information, occupational exposure history, and information related to the use of personal protective equipment, resulting in 939 valid questionnaires. EpiData 3.1 was used for data entry and SPSS 26.0 for statistical analysis. We employed logistic regression to compare the implementation of personal protection among workers by selected categories. Results Among the study subjects, there were 300 workers from large-scale farms (31.95%) and 583 self-employed livestock farmers (62.09%). The sample included 600 males (63.90%) and 339 females (36.10%). The majority of the study subjects was farmers, breeders, or aged 18-60 years (87.75%), auxiliary workers (87.97%) and had an education level of junior high school or below (81.36%). The proportion of workers who consistently and correctly implemented all five personal protective measures (washing hands after work, wearing gloves, wearing masks, wearing dedicated work clothes, and using rubber boots) was 35.14% (330/939). The implementation rates for these five protective measures were 93.61% (879/939), 58.68% (551/939), 57.93% (544/939), 46.01% (432/939), and 42.81% (402/939), respectively. There were statistically significant differences in the implementation rates of differen personal protective measures among the workers by occupation and education level (P<0.05). Among them, workers with lower education levels had lower implementation rates for various protective measures. The results of logistic regression indicated that, compared to male workers, female workers (OR=2.26, 95%CI: 1.68, 3.04) showed a higher rate of non-standard implementation of personal protection. Using the age group of 18 to less than 36 years as a reference, those aged 36 to less than 60 years (OR=1.82, 95%CI: 1.33, 2.50) and 60 years or older (OR=4.45, 95%CI: 2.56, 7.73) reported higher rates of non-standard implementation of personal protection. Compared to those with an education level of primary school or below, those with a junior high school education (OR=0.64, 95%CI: 0.47, 0.88) and a high school education or above (OR=0.13, 95%CI: 0.19, 0.29) showed lower rates of non-standard implementation of personal protection. Compared to farmers, veterinarians (OR=0.03, 95%CI: 0.02, 0.07) reported the lowest rate of non-standard implementation of personal protection, followed by auxiliary workers (OR=0.08, 95%CI: 0.05, 0.12), breeders (OR=0.10, 95%CI: 0.07, 0.15), and other occupational groups (OR=0.28, 95%CI: 0.15, 0.52). Using large-scale farms as a reference, self-employed farmers (OR=13.5, 95%CI: 9.65, 18.88) reported a higher rate of non-standard implementation of personal protection, followed by workers from other workplaces (OR=3.63, 95%CI: 2.01, 6.54). Conclusion The implementation of personal protective measures among livestock workers in Xinjiang is generally satisfactory. However, significant disparities in the execution of these measures exist among different types of workers, indicating the need to enhance occupational health promotion to reduce the risk of zoonotic pathogen infection among the workers.

Background Hypertension is influenced by both genes and environment. At present, most studies on the relationship among occupational stress, polymorphisms of ATP binding cassette subfamily A member 1 (ABCA1) or angiotensinogen (AGT) genes, and hypertension focus on single gene or single environmental effects. Objective To investigate the relationship of potential interactions between ABCA1 and AGT gene polymorphisms and occupational stress with the prevalence of hypertension. Methods A total of 198 hypertensive patients were selected as the case group from the 1200 oilfield workers in Karamay Oilfield in 2018 with random cluster sampling method, and the control group was selected as 1∶1 matched subjects for sex, age (±3 years), and ethnicity, after excluding blood samples, questionnaires, or DNA purity (concentration) that did not meet the inclusion criteria. Finally, 153 workers in the hypertension case group and 153 workers in the control group were determined. A questionnaire was used to collect general information of the oilfield workers, and the Occupational Stress Inventory Revised Edition (OSI-R) was used to evaluate occupational stress. Polymerase chain reaction-restriction fragment length polymorphism technology was used to detect the genotypes of V825I and R219K loci of ABCA1 as well as M235T and T174M loci of AGT. The gene-gene interaction of ABCA1 and AGT and the relationship between the interaction of gene-occupational stress and the prevalence of hypertension were analyzed by generalized multi-factor dimensionality reduction method. Results The difference of reported occupational stress between the hypertension case group and the control group was statistically significant (P＝0.001), and the reporting rate of high occupational stress in the case group (65.4%) was higher than that in the control group (47.7%). The genotype and allele distributions of ABCA1 V825I, ABCA1 R219K, and AGT M235T between the hypertension case group and the control group were significantly different (P<0.05). The results of conditional logistic regression analysis showed that VI and II genotypes at V825I locus of ABCA1 (OR_VI=1.682, 95%CI: 1.099-2.573; OR_II=1.708, 95%CI: 1.045-2.790), TT genotype at M235T locus of AGT (OR=1.645, 95%CI: 1.022-2.647), and high occupational stress (OR=2.642, 95%CI: 1.228-5.686) increased the risks for hypertension (P<0.05). There was no significant correlation between ABCA1 R219K or AGT T174M polymorphisms and the prevalence of hypertension (P>0.05). The gene-gene interactions between ABCA1 V825I and R219K loci and AGT M235T locus were associated with hypertension (accuracy on training and test sets was 0.68 and 0.63, respectively, with a cross-validation coefficient of 10/10, P<0.05), and ABCA1 V825I locus positively interacted with AGT M235T locus. The gene-environment interactions among ABCA1 V825I and R219K loci, AGT M235T locus, and occupational stress were associated with hypertension (accuracy on training and test sets was 0.74 and 0.63, respectively, with a cross-validation coefficient of 10/10, P<0.05), and AGT M235T locus negatively interacted with occupational stress. Conclusion Genotype VI and II of V825I locus at ABCA1, genotype TT of M235T locus at AGT, and high occupational stress may be risk factors for oilfield workers’ hypertension in Karamay, and the interactions of gene-gene and gene-environment among ABCA1 and AGT gene polymorphisms and occupational stress may be associated with hypertension.

ObjectiveTo explore the correlation between skeletal muscle mass and metabolic syndrome （MS） disease risk among middle-aged and elderly community residents in Urumqi， and to provide a theoretical basis for understanding the relationship between skeletal muscle mass and MS among middle-aged and elderly community residents in China. MethodsA total of 1 438 community residents ≥ 50 years old were selected as the research subjects from July 2018 to January 2019 in Urumqi. They were selected from a multi-ethnic natural population cohort in Xinjiang. Data were collected through questionnaires， physical examination， bioelectrical impedance analysis （BIA）， laboratory tests， etc. Skeletal muscle mass was evaluated using the limb skeletal muscle mass index （SMI） corrected for body weight； MS was defined as it at least includes three of the following： abdominal obesity， hypertension， hyperglycemia， high triglycerides and low high-density lipoprotein cholesterol. SMI was divided into four quantile arrays of Q₁‒Q₄. Trend χ² test was applied to explore whether there was a correlation between SMI changes and MS. A multivariate logistic regression model was used to analyze whether there is a difference in the risk of MS between the higher SMI group （Q₂， Q₃， Q₄） and the reference group Q₁. ResultA total of 560 MS patients were detected in this study， with a prevalence rate of 38.94%. Among them， the prevalence rate of MS was 39.16% in males and 38.80% in females. The increase in male SMI grading level is not correlated with the prevalence of MS （trend P>0.05）； After adjusting for confounding factors （model 4）， the increase in SMI was still not related to the prevalence of MS （P_trend=0.995）. There was no statistical difference in the risk of MS between the lowest quartile group Q₁ and the highest quartile group Q₄ （OR=1.01， 95%CI： 0.69‒1.78）. The prevalence of MS in women gradually decreased with the increase of SMI grading level （P_trend<0.001）； After adjusting for confounding factors （model 4）， there was still a correlation between the increase of SMI and the prevalence of MS （P_trend=0.005）. With the lowest quartile of SMI Q₁ as the reference group， the risk of MS in Q₂ （OR=0.63， 95%CI： 0.40‒1.00）， Q₃ （OR=0.56， 95%CI： 0.34‒0.94）， Q₄ （OR=0.42， 95%CI： 0.23‒0.76） decreased. ConclusionAn increase in skeletal muscle mass may be beneficial for preventing MS， especially among middle-aged and elderly female residents. Considering the intensification of aging in China and the close relationship between MS and related comorbidities， managing skeletal muscle mass may contribute to potential MS prevention.

Objective: To explore the protective effect and mechanism of total flavonoids of Dracocephalum moldevica (TFDM) on doxorubicin-induced cardiotoxicity. Methods: H9c2 cells were induced with 1 μmol/L doxorubicin for 24 h to establish a cardiotoxicity model. H9c2 cells were randomly divided into control group, model group, and drug intervention group (four subgroups of 5, 25, 50, and 100 μg/mL). After the intervention of TFDM, the doxorubicin cardiotoxicity model was established in the other groups except the control group. The cell counting Kit-8 method was used to determine the viability of H9c2 cells induced by doxorubicin injury after the intervention of TFDM. The effects of lactate dehydrogenase release, intracellular superoxide dismutase and malondialdehyde in each group were determined by kit method. The apoptosis rate of each group was detected by flow cytometry using Annexin-V FITC/PI double staining method. Reactive oxygen species (ROS) and mitochondrial membrane potential in each group were detected by DCFH-DA and JC-1 probes. The expressions of p38MAPK, ERK1/2, and PI3K/Akt pathway-related proteins were detected by Western blotting. Results: Compared with the control group, the cell viability of the model group induced by doxorubicin was decreased, the release of lactate dehydrogenase and the content of malondialdehyde were increased, the activity of superoxide dismutase was decreased, the apoptosis rate was increased, the release of reactive oxygen species was increased significantly, and the mitochondrial membrane potential was decreased significantly. However, TFDM increased H9c2 cell viability, decreased LDH and MDA levels, increased SOD activity, decreased apoptosis rate, significantly decreased ROS release, and significantly increased MMP in a dose-dependent manner. The difference was statistically significant. The results of Western blot showed that the expression levels of p-PI3K, p-Akt, p-ERK1/2, and Bcl-2 were decreased, and the expression levels of p-p38MAPK, Bax and Caspase-3 were significantly increased compared with the control group. However, in the TFDM-treated group, the expression of p-PI3K, p-Akt, p-ERK1/2, and Bcl-2 protein was increased, and the protein expression of p-p38MAPK, Bax, and Caspase-3 protein was decreased. Conclusion: TFDM can protect cardiomyocytes, and its protective mechanism may be related to the resistance to oxidative stress, protection of cardiomyocyte mitochondria, and regulating MAPK enzyme family proteins, and PI3K/Akt signaling pathway and subsequent release of apoptotic cytokines to inhibit apoptosis.

Objective: To design and synthesize a series of 2-aryl-4-(trans-4-hydroxycyclohexanolamine)-7H-pyrrolo[2, 3-d] pyrimidine derivatives and test their inhibitory activity against Mer tyrosine kinase(MerTK)and tumor cell proliferation. Methods: 2, 4-Dichloro-7H-pyrrolo[2, 3-d]pyrimidine(1)was used as starting material to synthesize the target compounds via iodination, protection with p- Tosyl(Ts), nucleophilic substitution, Stille coupling, vinyl reduction, Suzuki coupling and deprotection of Ts. The MerTK inhibitory activity was tested by the Kinase-Glo Plus luminescence method. The antiproliferation activity was assayed using MV- 4-11, A549, MDA-MB-231, KB, and KB-vin tumor cell lines by the CCK8 and SRB methods. Molecular docking of MerTK and 6h was conducted using the DS3.0 software. Results: Nine compounds were synthesized, and their structures were confirmed by 1H NMR and MS. Compound 6h exhibited certain inhibitory effect on MerTK, with the(6.7±0.3)μmol/L of IC50 value, and could selectively inhibit the growth of MV-4-11 tumor cells, with the(6.6±1.1)μmol/L of GI50 value that was approximately 3-fold to 6-fold more potent than the GI50 value of 6h on the other tested tumor cells. Molecular docking showed that 6h could interact with MerTK on the binding site of UNC569 and overlapped well with the original ligand UNC569, but its binding energy was higher than the binding energy of UNC569. Conclusion: Compound 6h showed a selective inhibitory effect on the MV-4-11 cell growth, which might be further investigated via more biological experiments to explore whether the inhibitory effect is related to the inhibition of MerTK by 6h. The molecular docking results in the present study have suggested that further structural modification on the 2 and 5 position of 7H-pyrrolo[2, 3-d] pyrimidine skeleton could likely improve the MerTK inhibitory activity.