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1.
J Eye Mov Res ; 17(1)2024.
Article En | MEDLINE | ID: mdl-38699659

Objectives To find out the prevalence rate of pre-myopia among primary school students in the Mianyang Science City Area, analyze its related risk factors, and thus provide a reference for local authorities to formulate policies on the prevention and control of myopia for primary school students. Methods From September to October 2021, Cluster sampling was adopted by our research group to obtain the vision levels of primary school students employing a diopter test in the Science City Area. In addition, questionnaires were distributed to help us find the risk factors associated with pre-myopia. Through the statistical analysis, we identify the main risk factors for pre-myopia and propose appropriate interventions. Results The prevalence rate of pre-myopia among primary school students in the Science City Area was 45.27% (1020/2253), of which 43.82% were boys and 46.92% were girls, with no statistically significant difference in the prevalence rate of myopia between boys and girls (2 =2.171, P=0.141). The results of the linear trend test showed that the prevalence rate of pre-myopia tends to decrease with increasing age (Z=296.521, P=0.000). Logistic regression analysis demonstrated that the main risk factors for pre-myopia were having at least one parent with myopia, spending less than 2 hours a day outdoors, using the eyes continuously for more than 1 hour, looking at electronic screens for more than 2 hours, and having an improper reading and writing posture. Conclusion The Science City Area has a high prevalence rate of pre-myopia among primary school students. It is proposed that students, schools, families, and local authorities work together to increase the time spent outdoors, reduce digital screens and develop scientific use of eye habits.

2.
ACS Sens ; 2024 May 29.
Article En | MEDLINE | ID: mdl-38807313

Despite the significant potential of protein biosensors, their construction remains a trial-and-error process. The most obvious approach for addressing this is to utilize modular biosensor architectures where specificity-conferring modalities can be readily generated to recognize new targets. Toward this goal, we established a workflow that uses mRNA display-based selection of hyper-stable monobody domains for the target of choice or ribosome display to select equally stable DARPins. These binders were integrated into a two-component allosteric biosensor architecture based on a calmodulin-reporter chimera. This workflow was tested by developing biosensors for liver toxicity markers such as cytosolic aspartate aminotransferase, mitochondrial aspartate aminotransferase, and alanine aminotransferase 1. We demonstrate that our pipeline consistently produced >103 unique binders for each target within a week. Our analysis revealed that the affinity of the binders for their targets was not a direct predictor of the binder's performance in a biosensor context. The interactions between the binding domains and the reporter module affect the biosensor activity and the dynamic range. We conclude that following binding domain selection, the multiplexed biosensor assembly and prototyping appear to be the most promising approach for identifying biosensors with the desired properties.

3.
J Infect Dev Ctries ; 18(3): 464-472, 2024 Mar 31.
Article En | MEDLINE | ID: mdl-38635624

Paragonimiasis is a common zoonotic parasitic disease. The retinoic acid-inducible gene I (RIG-I) signaling is very important for the host to recognize invading pathogens (especially viruses and bacteria). However, the role of RIG-I signaling in the early stages of P. proliferus infection remains unclear. Therefore, in this study, Sprague-Dawley (SD) rat models with lung damage caused by P. proliferus were established. Experimental methods including Enzyme-linked Immuno Sorbent Assay (ELISA), real-time fluorescent quantitative polymerase chain reaction (PCR), western blotting, and hematoxylin and eosin (HE) staining were used to explore the mechanisms of lung injury caused by P. proliferus. As a result, the expression of the mRNA and proteins of RIG-I signal-related key target molecules, including RIG-I, tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), interferon regulatory Factor 7 (IRF7), IPS-1, and downstream C-X-C chemokine ligand 10 (CXCL10), were significantly up-regulated immediately after infection, peaked at 3 or 7 days, and showed a downward trend on after 14 days. The levels of pro-inflammatory cytokines interleukin-1 (IL-1), interferon (IFN)-α, -ß, and -γ, which represent type 1 immune response, gradually increased and reached a peak by 14 days, which was consistent with the changes in the degree of inflammatory damage observed under HE staining of lung tissues. In conclusion, RIG-I signaling is activated in the early stage (before 14 days) of P. proliferus infection, it is inferred that the lung injury of the host may be related to the activation of RIG-I like signaling to induce type I immune response.


Lung Injury , Paragonimiasis , Paragonimus , Animals , Rats , DEAD Box Protein 58 , Rats, Sprague-Dawley , Interferon-alpha , Immunity , Paragonimus/metabolism , RNA Helicases
4.
Quant Imaging Med Surg ; 14(4): 2857-2869, 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38617154

Background: Pressure wire fractional flow reserve (FFR) and its derivatives, such as quantitative flow ratio (QFR), computational pressure flow-derived FFR (caFFR), coronary angiography-derived FFR (FFRangio), and computed tomography-derived FFR (FFRCT), have been validated for identifying functionally significant stenosis and guiding revascularization strategy. The limitations of using these methods include the side effects of hyperemia-induced agents, additional costs, and vulnerability to microvascular resistance. FFR is related both to the degree of a stenotic coronary artery and to its subtended myocardial territory. Coronary Artery Tree Description and Lesion Evaluation (CatLet) score (also known as Hexu) is a product of the degree of a stenosis and the weighting of the affected coronary artery (myocardial territory). Hence, we hypothesized that the CatLet score could predict hemodynamically significant coronary stenosis. Methods: We retrospectively enrolled consecutive patients with stable coronary artery disease. They attended Sichuan Science City Hospital with at least one lesion of 50-90% diameter stenosis in a coronary artery of 2 mm or larger. FFR measurement was obtained during invasive coronary angiography. The CatLet score was obtained by multiplying a fixed value of 2.0 (for non-occlusive lesions) and the weight of the affected coronary artery. The primary endpoint was the CatLet score's diagnostic accuracy in identifying hemodynamically significant coronary stenosis, with a pressure wire FFR of ≤0.80 being used as reference. Results: We analyzed the FFR and CatLet scores from 206 vessels in 175 patients with stable coronary disease and intermediate coronary lesions. The per-vessel analysis revealed an overall good correlation between the CatLet score and the FFR [r=-0.61; 95% confidence interval (95% CI): -0.69 to -0.52; P<0.01]. We also noted a significant CatLet score-FFR correlation for each of the left anterior descending artery (LAD), left circumflex (LCX), and right coronary artery (RCA). With a CatLet score ≥10 as a predictor of FFR ≤0.80, the overall diagnostic accuracy included a sensitivity of 78.80% (95% CI: 67.00-87.90%), a specificity of 85.00% (95% CI: 78.00-90.50%), a positive likelihood ratio of 5.25, a negative likelihood ratio of 0.25, and an area under the curve of 0.90 (95% CI: 0.85-0.94). Equivalent vessel-specific results were also achieved for each of the LAD, LCX, and RCA. Conclusions: The CatLet score, solely based on visual estimation of the results of coronary angiography, demonstrated good diagnostic performance with respect to myocardial ischemia. Its clinical values in guiding revascularization warrant further investigation.

7.
J Colloid Interface Sci ; 665: 554-563, 2024 Jul.
Article En | MEDLINE | ID: mdl-38552572

The achievement of covalent organic frameworks (COFs) with high stability and exceptional proton conductivity is of tremendous practical importance and challenge. Given this, we hope to prepare the highly stable COFs carrying CN connectors and enhance their proton conductivity via a post-modification approach. Herein, one COF, TpTta, was successfully synthesized by employing 1,3,5-triformylphloroglucinol (Tp) and 4,4',4″-(1,3,5-triazine-2,4,6-triyl)-trianiline (Tta) as starting materials, which has a ß-ketoenamine structure bearing a large amount of -NH groups and intramolecular H-bonds. TpTta was then post-modified by inserting imidazole (Im) and histamine (His) molecules, yielding the corresponding COFs, Im@TpTta and His@TpTta, respectively. As a result, their proton conductivities were surveyed under changeable temperatures (30-100 °C) and relative humidities (68-98 %), revealing a degree of temperature and humidity dependence. Impressively, under identical conditions, the optimum proton conductivities of the two post-modified COFs are 1.14 × 10-2 (Im@TpTta) and 3.45 × 10-3 S/cm (His@TpTta), which are significantly greater than that of the pristine COF, TpTta (2.57 × 10-5 S/cm). Finally, their proton conduction mechanisms were hypothesized based on the computed activation energy values, water vapor adsorption values, and structural properties of these COFs. Additionally, the excellent electrochemical stability of the produced COFs was expressed, as well as the prospective application value.

8.
J Affect Disord ; 352: 237-249, 2024 May 01.
Article En | MEDLINE | ID: mdl-38369262

BACKGROUND: Clinical guidelines and some studies recommend cognitive-behavioral therapy (CBT) as the most effective treatment for body dysmorphic disorder (BDD). However, owing to the lack of randomized controlled trials (RCTs), the research evidence is insufficient. This study aimed to explore the effectiveness of CBT in the treatment of BDD using RCTs. This meta-analysis was registered in PROSPERO (CRD42023410577). METHODS: After a literature search and screening, 11 RCTs with 667 patients were included. The ROB 2.0 tool, funnel plots, sensitivity analysis, and meta-regression analysis were used to assess the quality, publication bias, and sources of heterogeneity. RESULTS: After CBT intervention, the severity of BDD (SMD = -1.73, 95 % CI (confidence interval) = [-2.90; -0.57]), depression symptoms (SMD = -1.72, 95 % CI = [-3.16; -0.28]), and anxiety levels were all reduced in the patients of the experimental group; the remission of BDD (OR = 7.37, 95 % CI = [2.17; 24.98]) and the response of BDD (OR = 8.86, 95 % CI = [4.85; 16.18]) were all increased; incorrect beliefs such as disability and BABS were also reduced; the quality of life was improved. The difference between the groups was statistically significant (p < 0.01). Meta-regression analysis showed that age and sample size were the predictive factors of the effectiveness of CBT. LIMITATIONS: The heterogeneity of most meta-analyses was high (I2 > 75 %). CONCLUSIONS: Although CBT is effective in treating BDD, there is insufficient evidence to suggest that it is the best psychological intervention for BDD. More high-quality evidence is still needed in the future.


Body Dysmorphic Disorders , Cognitive Behavioral Therapy , Humans , Body Dysmorphic Disorders/therapy , Body Dysmorphic Disorders/psychology , Psychosocial Intervention , Randomized Controlled Trials as Topic , Treatment Outcome
9.
Front Immunol ; 15: 1344821, 2024.
Article En | MEDLINE | ID: mdl-38298194

Tuberculosis (TB) and tumor, with similarities in immune response and pathogenesis, are diseases that are prone to produce autoimmune stress response to the host immune system. With a symbiotic relationship between the two, TB can facilitate the occurrence and development of tumors, while tumor causes TB reactivation. In this review, we systematically sorted out the incidence trends and influencing factors of TB and tumor, focusing on the potential pathogenesis of TB and tumor, to provide a pathway for the co-pathogenesis of TB comorbid with tumor (TCWT). Based on this, we summarized the latest progress in the diagnosis and treatment of TCWT, and provided ideas for further exploration of clinical trials and new drug development of TCWT.


Neoplasms , Tuberculosis , Humans , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Neoplasms/complications , Neoplasms/diagnosis , Neoplasms/epidemiology
10.
Asian J Surg ; 47(4): 1756-1762, 2024 Apr.
Article En | MEDLINE | ID: mdl-38228457

BACKGROUND: As an innovative treatment, stapled transperineal rectovaginal fistula repair (STR) for rectovaginal fistula (RVF) has demonstrated effectiveness in preliminary reports. This study aims to compare STR with rectal mucosal advancement flap repair (RAF), a widely utilized surgical procedure, for the surgical outcome of the low- and mid-level RVF. METHODS: In this retrospective cohort study, patients with low- and mid-level RVF who underwent STR or RAF were included from both the Sixth Affiliated Hospital of Sun Yat-sen University and Xi'an Daxing Hospital. Among the 99 total patients, 77 underwent STR and 22 underwent RAF. Patient demographics, operative data, and outcomes were collected and analyzed. Recurrence rate and associated risk factors were evaluated. RESULTS: There were no statistically significant differences among patients in terms of clinical characteristics like age, BMI, aetiology, and fistula features. During the follow-up period of 20 months (interquartile range 3.0-41.8 months), a total of 28 patients relapsed, with a significantly lower recurrence rate in the STR group (20.8 %) than in the RAF group (54.6 %) (P = 0.005). In the multivariate Cox analysis, STR was an independent protective factor against recurrence (HR: 0.37, 95%CI: 0.17-0.79, P = 0.01). Logistic regression indicated that there was no statistically significant difference between these two procedures in terms of surgical complications (OR: 0.53, 95%CI: 0.19-1.48, P = 0.23). CONCLUSION: For low- and mid-level RVF, STR may be an alternative option for treatment modality that offers a lower recurrence rate, without observed disadvantage in terms of surgical complication rates.


Rectovaginal Fistula , Rectum , Female , Humans , Rectovaginal Fistula/etiology , Rectovaginal Fistula/surgery , Retrospective Studies , Rectum/surgery , Surgical Flaps , Risk Factors , Treatment Outcome
11.
BMC Anesthesiol ; 24(1): 7, 2024 01 02.
Article En | MEDLINE | ID: mdl-38166634

BACKGROUND: Stellate ganglion block (SGB) has been shown to reduce perioperative complications in various surgeries. Because laparoscopic techniques and instruments have advanced during the past two decades, laparoscopic liver resection is being increasingly adopted worldwide. Lesser blood loss, fewer postoperative complications, and shorter postoperative hospital stays are the advantages of laparoscopic liver resection, as compared to conventional open surgery. There is an urgent need for an effective intervention to reduce perioperative complications and accelerate postoperative recovery. This study investigated the effect of ultrasound-guided SGB on enhanced recovery after laparoscopic partial hepatectomy. METHODS: We compared patients who received SGB with 0.5% ropivacaine (group S) with those who received SGB with 0.9% saline (group N). A total of 58 patients with partial hepatectomy were enrolled (30 S) and (28 N). Before induction of anesthesia, SGB was performed with 0.5% ropivacaine in group S and 0.9% saline in group N. MAIN OUTCOME: Comparison of serum inflammatory cytokines concentration at each time point. RESULTS: Main outcome: When comparing IL-6 and IL-10 concentrations among groups, group S showed less variation over time compared to group N. For comparison between groups, the serum IL-6 concentration in group S was lower than that in group N at 6 and 24 h after operation (P < 0.01), and there was a significant linear relationship between serum IL-6 concentration at 24 h after operation and hospitalization situation. CONCLUSIONS: Ultrasound-guided SGB can stabilize perioperative inflammatory cytokines plays a positive role in the enhanced recovery of patients after laparoscopic partial hepatectomy. The serum IL-6 level within 24 h after surgery may be used as a predictor of hospitalization. TRIAL REGISTRATION: The study was registered at the ClinicalTrials.gov (Registration date: 13/09/2021; Trial ID: NCT05042583).


Cytokines , Hepatectomy , Humans , Ropivacaine/pharmacology , Hepatectomy/methods , Stellate Ganglion , Interleukin-6 , Saline Solution/pharmacology , Ultrasonography, Interventional
12.
Phytochemistry ; 217: 113905, 2024 Jan.
Article En | MEDLINE | ID: mdl-37913836

Three unusual oleanane-derived triterpenoids, stytontriterpenes A-C (1-3), were isolated from the resin of Styrax tonkinensis together with an oleanane-lactone (stytontriterpene D, 4). Their structures and absolute configurations were characterised using a combination of spectroscopic analysis, electronic circular dichroism, and theoretical calculations. 1 and 2 belong to nor-oleanane with rare spiro D/E rings and 3 contains one infrequent C32 scaffold. 1 considerably suppressed the number of adhered leukemic monocytes (THP-1) to human umbilical vein endothelial cells and attenuated the upregulations of mRNA and protein levels of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 at 5 µM, suggesting that 1 might be a promising anti-vascular inflammatory chemical for atherosclerosis therapy. Plausible biosynthetic pathways for 1-4 are also proposed.


Atherosclerosis , Triterpenes , Humans , Styrax/chemistry , Triterpenes/chemistry , Resins, Plant/chemistry , Human Umbilical Vein Endothelial Cells , Atherosclerosis/drug therapy , Atherosclerosis/metabolism
13.
Front Endocrinol (Lausanne) ; 14: 1289004, 2023.
Article En | MEDLINE | ID: mdl-38152126

Background and aims: Wnt/ß-catenin signaling plays an important role in regulating hepatic metabolism. This study is to explore the molecular mechanisms underlying the potential crosstalk between Wnt/ß-catenin and mTOR signaling in hepatic steatosis. Methods: Transgenic mice (overexpress Wnt1 in hepatocytes, Wnt+) mice and wild-type littermates were given high fat diet (HFD) for 12 weeks to induce hepatic steatosis. Mouse hepatocytes cells (AML12) and those transfected to cause constitutive ß-catenin stabilization (S33Y) were treated with oleic acid for lipid accumulation. Results: Wnt+ mice developed more hepatic steatosis in response to HFD. Immunoblot shows a significant increase in the expression of fatty acid synthesis-related genes (SREBP-1 and its downstream targets ACC, AceCS1, and FASN) and a decrease in fatty acid oxidation gene (MCAD) in Wnt+ mice livers under HFD. Wnt+ mice also revealed increased Akt signaling and its downstream target gene mTOR in response to HFD. In vitro, increased lipid accumulation was detected in S33Y cells in response to oleic acid compared to AML12 cells reinforcing the in vivo findings. mTOR inhibition by rapamycin led to a down-regulation of fatty acid synthesis in S33Y cells. In addition, ß-catenin has a physical interaction with mTOR as verified by co-immunoprecipitation in hepatocytes. Conclusions: Taken together, our results demonstrate that ß-catenin stabilization through Wnt signaling serves a central role in lipid metabolism in the steatotic liver through up-regulation of fatty acid synthesis via Akt/mTOR signaling. These findings suggest hepatic Wnt signaling may represent a therapeutic strategy in hepatic steatosis.


Fatty Liver , Lipogenesis , Mice , Animals , Lipogenesis/genetics , Wnt Signaling Pathway , Proto-Oncogene Proteins c-akt/metabolism , Oleic Acid/pharmacology , beta Catenin/metabolism , Fatty Liver/metabolism , TOR Serine-Threonine Kinases/metabolism , Mice, Transgenic
14.
Gut Microbes ; 15(2): 2274125, 2023 12.
Article En | MEDLINE | ID: mdl-37934002

Vibrio cholerae adapts to the host environment by altering gene expression. Because of the complexity of the gut microbiome, current in vivo V. cholerae transcriptome studies have focused on microbiota-undeveloped conditions, neglecting the interaction between the host's commensal gut microbiota and V. cholerae. In this study, we analyzed the transcriptome of fully colonized adult mice in vivo using V. cholerae coated-magnetic chitin beads (vcMCB). This provides a simple yet powerful method for obtaining high-quality RNA from V. cholerae during colonization in mice. The transcriptome of V. cholerae recovered from adult mice infected with vcMCB shows differential expression of several genes when compared to V. cholerae recovered from the infant mouse and infant rabbit model. Some of these genes were also observed to be differentially expressed in previous studies of V. cholera recovered from human infection when compared to V. cholerae grown in vitro. In particular, we confirmed that V. cholerae resists the inhibitory effects of low pH and formic acid from gut microbiota, such as Anaerostipes caccae and Dorea formicigenerans, by downregulating vc1080. We propose that the vc1080 product may protect V. cholerae from formic acid stress through a novel acid tolerance response mechanism. Transcriptomic data obtained using the vcMCB system provide new perspectives on the interaction between V. cholerae and the gut microbiota, and this approach can also be applied to studies of other pathogenic bacteria.


Cholera , Gastrointestinal Microbiome , Vibrio cholerae , Adult , Animals , Humans , Mice , Rabbits , Vibrio cholerae/genetics , Gastrointestinal Microbiome/physiology , Transcriptome , Chitin/metabolism , Cholera/microbiology , Magnetic Phenomena
15.
Front Oncol ; 13: 1248553, 2023.
Article En | MEDLINE | ID: mdl-37916175

Objectives: To develop a scoring system based on independent predictors of the need for ventriculoperitoneal (VP) shunt after brain tumor resection in pediatric patients. Methods: A total of 416 pediatric patients (≤ 14 years old) with brain tumors who underwent surgery were randomly assigned to the training (n = 333) and validation cohorts (n = 83). Based on the implementation of VP shunt, the training cohort was divided into the VP shunt group (n = 35) and the non-VP shunt group (n = 298). Univariate and multivariate logistic analyses were performed. A scoring system was developed based on clinical characteristics and operative data, and scores and corresponding risks were calculated. Results: Age < 3 (p = 0.010, odds ratio [OR] = 3.162), blood loss (BL) (p = 0.005, OR = 1.300), midline tumor location (p < 0.001, OR = 5.750), preoperative hydrocephalus (p = 0.001, OR = 7.044), and total resection (p = 0.025, OR = 0.284) were identified as independent predictors. The area under the curve (AUC) of the scoring system was higher than those of age < 3, BL, midline tumor location, preoperative hydrocephalus, and total resection (0.859 vs. 0.598, 0.717, 0.725, 0.705, and 0.555, respectively; p < 0.001). Furthermore, the scoring system showed good performance in the validation cohort (AUC = 0.971). The cutoff value for predictive scores was 5.5 points, which categorized patients into low risk (0-5 points) and high risk (6-14 points) groups. Conclusions: Our scoring system, integrating age < 3, BL, midline tumor location, preoperative hydrocephalus, and total resection, provides a practical evaluation. Scores ranging from 6 to 14 points indicate high risk.

17.
BMC Gastroenterol ; 23(1): 372, 2023 Oct 31.
Article En | MEDLINE | ID: mdl-37907854

BACKGROUND: Magnetic resonance imaging (MRI) has excellent accuracy in diagnosing preoperative lesions before anal fistula surgery. However, MRI is not good in identifying early recurrent lesions and effective methods for quantitative assessment of fistula healing are still warranted. This retrospective study aimed to develop and validate a specific MRI-based nomogram model to predict fistula healing during the early postoperative period. METHODS: Patients with complex cryptoglandular anal fistulas who underwent surgery between January 2017 and October 2020 were included in this study. MRI features and clinical parameters were analyzed using univariate and multivariate logistic regression analysis. A nomogram for predicting fistula healing was constructed and validated. RESULTS: In total, 200 patients were included, of whom 186 (93%) were male, with a median age of 36 (18-65) years. Of the fistulas, 58.5% were classified as transsphincteric and 19.5% as suprasphincteric. The data were randomly divided into the training cohort and testing cohort at a ratio of 7:3. Logistic analysis revealed that CNR, ADC, alcohol intake history, and suprasphincteric fistula were significantly correlated with fistula healing. These four predictors were used to construct a predictive nomogram model in the training cohort. AUC was 0.880 and 0.847 for the training and testing cohorts, respectively. Moreover, the decision and calibration curves showed high coherence between the predicted and actual probabilities of fistula healing. CONCLUSIONS: We developed a predictive model and constructed a nomogram to predict fistula healing during the early postoperative period. This model showed good performance and may be clinically utilized for the management of anal fistulas.


Anal Canal , Rectal Fistula , Humans , Male , Adult , Middle Aged , Aged , Female , Retrospective Studies , Wound Healing , Rectal Fistula/diagnostic imaging , Rectal Fistula/surgery , Magnetic Resonance Imaging , Treatment Outcome
18.
Nanomicro Lett ; 15(1): 236, 2023 Oct 24.
Article En | MEDLINE | ID: mdl-37874411

Autonomously self-propelled nanoswimmers represent the next-generation nano-devices for bio- and environmental technology. However, current nanoswimmers generate limited energy output and can only move in short distances and duration, thus are struggling to be applied in practical challenges, such as living cell transportation. Here, we describe the construction of biodegradable metal-organic framework based nanobots with chemically driven buoyancy to achieve highly efficient, long-distance, directional vertical motion to "find-and-fetch" target cells. Nanobots surface-functionalized with antibodies against the cell surface marker carcinoembryonic antigen are exploited to impart the nanobots with specific cell targeting capacity to recognize and separate cancer cells. We demonstrate that the self-propelled motility of the nanobots can sufficiently transport the recognized cells autonomously, and the separated cells can be easily collected with a customized glass column, and finally regain their full metabolic potential after the separation. The utilization of nanobots with easy synthetic pathway shows considerable promise in cell recognition, separation, and enrichment.

19.
Chin J Integr Med ; 2023 Oct 20.
Article En | MEDLINE | ID: mdl-37861962

OBJECTIVE: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge., (Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis (AP) using a network pharmacology approach and validate the findings in animal experiments. METHODS: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation. Finally, the results of network pharmacology enrichment analysis were verified by immunohistochemistry, Western blot analysis and real-time quantitative PCR, respectively. RESULTS: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3 (MAPK3), Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), protein c-Fos (FOS) were identified as core targets in the protein interaction (PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone II and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1ß, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation (P<0.01). CONCLUSION: DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues, which would be functioned by regulating Th17 cell differentiation-related mRNA and protein expressions.

20.
J Math Biol ; 87(5): 66, 2023 10 05.
Article En | MEDLINE | ID: mdl-37798450

Since there exists heterogeneity in incubation periods of tuberculosis and a time lag between treatment and recovery. In this study, we develop a tuberculosis model that takes into account age-dependent latency and time delays in treatment to describe the transmission of tuberculosis. We first show that the solution semi-flow of the model is well-posed and has a global attractor [Formula: see text] within an infinite dimensional space [Formula: see text]. Then we define the basic reproduction number [Formula: see text] and prove that it determines the global dynamics of the model. If [Formula: see text], the global attractor [Formula: see text] reduces to the disease-free equilibrium state, indicating that the disease-free equilibrium state is globally asymptotically stable. When [Formula: see text], the semi-flow generated by the model is uniformly persistent, and there exists an interior global attractor [Formula: see text] for this uniformly persistent model. By constructing a suitable Lyapunov function and applying LaSalle's Invariance Principle, we show that the global attractor [Formula: see text] is reduced to the endemic equilibrium state, which means that the endemic equilibrium state is globally asymptotically stable. Based on the tuberculosis data in China from 2007 to 2020, we simulate the parameters and initial values of the proposed model. Furthermore, we calculate the sensitivity of [Formula: see text] to the parameters and find the most sensitive parameters to [Formula: see text]. Finally, we present an improved strategy to achieve the WHO's goal of reducing the incidence of tuberculosis by 90% by 2035 compared to 2015.


Models, Biological , Tuberculosis , Humans , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Tuberculosis/prevention & control , Basic Reproduction Number , Time Factors , Incidence , Computer Simulation
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