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Abstract Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier’s intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy. Graphical Abstract

Abstract Quantum computing, with its superior computational capabilities compared to classical approaches, holds the potential to revolutionize numerous scientific domains, including pharmaceuticals. However, the application of quantum computing for drug discovery has primarily been limited to proof-of-concept studies, which often fail to capture the intricacies of real-world drug development challenges. In this study, we diverge from conventional investigations by developing a hybrid quantum computing pipeline tailored to address genuine drug design problems. Our approach underscores the application of quantum computation in drug discovery and propels it towards more scalable system. We specifically construct our versatile quantum computing pipeline to address two critical tasks in drug discovery: the precise determination of Gibbs free energy profiles for prodrug activation involving covalent bond cleavage, and the accurate simulation of covalent bond interactions. This work serves as a pioneering effort in benchmarking quantum computing against veritable scenarios encountered in drug design, especially the covalent bonding issue present in both of the case studies, thereby transitioning from theoretical models to tangible applications. Our results demonstrate the potential of a quantum computing pipeline for integration into real world drug design workflows.

Abstract Introduction The chemotherapy and immunotherapy combination is currently the primary strategy to treat metastatic esophageal squamous cell carcinoma (ESCC). Neoadjuvant chemoimmunotherapy (NCIT) is being intensively investigated for treating locally advanced ESCC. Objective We compared the efficacy and safety of NCIT and neoadjuvant chemoradiotherapy (NCRT) to treat locally advanced ESCC. Methods We included 214 locally advanced ESCC patients who were administered neoadjuvant therapy from May 2014 to April 2022. The patients were grouped according to two neoadjuvant protocols (NCIT and NCRT) routinely used at our institution. Perioperative findings, pathological results, and survival data were compared between the two groups by conducting unmatched and 1:1 propensity score matching (PSM) analyses. Results Following 1:1 PSM analysis of the confounders, 66 patients were allocated to each of the two groups. Time span between neoadjuvant therapy completion and esophagectomy was significantly longer after NCRT than that after NCIT (47.1 ± 13.2 days vs. 34.7 ± 8.8 days; p 0.05)]. The overall incidence of pneumonia, anastomotic leakage, or postoperative complications did not differ significantly between the two groups. The 2‐year cumulative overall survival rates and the 2‐year disease‐free survival rates of the NCIT and NCRT groups were 80.2% and 62.2%, respectively (p = 0.029) and 70.0% and 50.8%, respectively (p = 0.023). Conclusion In locally advanced ESCC patients, short‐term survival after NCIT is superior to that after NCRT, with similar perioperative and pathological outcomes.

In recent years, the artificial potential field has garnered significant attention in ship route planning and traffic flow simulation. However, the traditional artificial potential field method faces challenges in accurately simulating a ship’s customary route and navigating experience, leading to significant deviations in prediction results. To address these issues, in this study, we propose an innovative method for simulating and predicting ship traffic flow, building upon the artificial potential field approach. We introduce an AIS track heat map based on the kernel density function and enhance the artificial potential field model by incorporating factors, such as ship navigation habits and ship size. Through a comparison of traffic flow changes before and after the construction of a wind farm, the optimized model demonstrates its effectiveness in improving the accuracy of prediction results.

As a clean and abundant unconventional natural gas resource, natural gas hydrate (NGH) holds the characteristics of safety, high efficiency and sustainable exploitation, which helps to alleviate the energy shortage of China, reduce the foreign-trade dependence of oil and gas, and ensure the national energy security. Microwave heating is a significant method that has been used in natural gas hydrate exploration. By using the microwave heating, the NGH in the reservoir formations would be heated, decomposed and stimulated thanks to taking advantage of microwave heating's unique characters: efficiency, high speed, clean and pollution-free. This paper established the temperature under microwave heating gas hydrate distribution theory model, and by using the finite element method for simulating temperature field of microwave heating gas hydrate, this paper analyzed the natural gas hydrate in the microwave field temperature distribution in the influencing factors. Microwave has a significant heating effect on the hydrate reservoir in the immediate vicinity of wellbore, and it is not affected by the initial conditions of reservoir. The temperature can rise to above 50°C within 1 h which is higher than the phase equilibrium temperature at the time of hydrate decomposition and is helpful to improve the decomposition rate of hydrate. The frequency is set at 915 MHz, and the feed port has a spiral arrangement with a length of 10 mm, which greatly expands the microwave heating range.

ABSTRACT Aims/Introduction Sleep problems are important public health concern worldwide. We carried out a meta‐analysis to quantitatively evaluate whether sleep duration was associated with pregnancy outcomes, and the associations were modified by important characteristics of studies. Materials and Methods Based on PubMed, Embase and the Cochrane Central Register of Controlled Trials databases, we searched for published literature related to maternal sleep duration and adverse pregnancy outcomes before 30 June 2021. We carried out risk of bias assessment, subgroup analyses and sensitivity analysis. The relative risks or odds ratios with 95% confidence intervals (CI) were used to estimate the pooled effects. Results A total of 5,246 references were identified through a database search, and 41 studies were included in the study. Pregnant women with short sleep duration had 1.81‐fold (95% CI 1.35–2.44, P 0.05). Furthermore, long sleep duration was significantly correlated with gestational diabetes mellitus (odds ratio1.24. 95% CI 1.12–1.36, P 0.05). Conclusions Short/long sleep duration appeared to be associated with adverse pregnancy outcomes, specifically with an increased risk of gestational diabetes mellitus. Sleep should be systematically screened in the obstetric population.

Abstract Atherosclerosis (AS) is a leading cause of vascular diseases that severely threats the human health due to the lack of efficient therapeutic methods. During the development and progress of AS, macrophages play critical roles, which are polarized into pro-inflammatory M1 phenotype to excrete abundant cytokines and overproduce reactive oxygen species (ROS), and take up excess amount of lipid to form foam cells. In this work, we developed a MnO2-based nanomedicine to re-educate macrophages for targeting AS therapy. The MnO2 was one-pot synthesized under mild condition, showing intrinsic catalase-mimic activity for self-oxygenation by using endogenous H2O2 as substrate. Moreover, the mesoporous structure as well as the abundant metal coordination sites in MnO2 structure facilitated the loading of an anti-AS drug of curcumin (Cur), achieving extraordinarily high drug loading capacity of 54%. Cur displayed a broad spectrum of anti-oxidant and anti-inflammatory capabilities to repolarize M1 macrophages into M2 phenotype, and the catalytic MnO2 recovered the function of lipid efflux transporter to remove lipid from cells by suppressing HIF-1α. Collectively, the nanocarrier and the payload drug functioned as an all-active nanoplatform to synergistically alleviate the syndromes of AS. In ApoE−/− mice model, the nanosystem could significantly prolong the circulation half-life of Cur by sixfold, and enhance drug accumulation in atherosclerotic lesion by 3.5-fold after intravenous injection by virtue of surface hyaluronic acid (HA) modification. As a result, a robust anti-AS efficacy was achieved as evidenced by the decrease of atherosclerotic lesion, plaque area, lipid level. Graphical Abstract

The plant samples of Bidens pilosa were collected from a coal gangue vacant site and its surrounding area, located in central China, to study the remediation effect of the plant species on heavy metal (HM) contamination in both natural and electrokinetic (EK) conditions. The analytical results showed that the effect of phytoextraction and bioconcentration on the heavy metals in the sample of the EK group is more significant than those in the other control group. Compared with the results of natural condition, under the EK condition the concentrations of cadmium (Cd), lead (Pb), copper (Cu) and zinc (Zn) in the stems and leaves of the Bidens pilosa increased to 0.40 mg/kg, 4.23 mg/kg, 7.27 mg/kg, 830.24 mg/kg, respectively, with their increments of 292%, 1731%, 141%, 2076%. For root samples, the Cd, Pb, Cu and Zn concentrations increased to 0.52 mg/kg, 4.36 mg/kg, 10.87 mg/kg, and 98.12 mg/kg and the increase rates were 1034%, 140%, 29%, and 181%, respectively. The phytoextraction efficiency of the Bidens pilosa was significantly higher than that of control group. The removal efficiency of Cd, Pb, Cu and Zn in soil increased to 26%, 72%, 27%, and 79% with the EK applied. In addition, the mechanism of HM migration, extraction and enrichment in Bidens pilosa under the EK condition was discussed.

Abstract Background A nomogram was developed to predict lymph node metastasis (LNM) for patients with early-stage esophageal squamous cell carcinoma (ESCC). Methods We used the clinical data of ESCC patients with pathological T1 stage disease who underwent surgery from January 2011 to June 2018 to develop a nomogram model. Multivariable logistic regression was used to confirm the risk factors for variable selection. The risk of LNM was stratified based on the nomogram model. The nomogram was validated by an independent cohort which included early ESCC patients underwent esophagectomy between July 2018 and December 2019. Results Of the 223 patients, 36 (16.1%) patients had LNM. The following three variables were confirmed as LNM risk factors and were included in the nomogram model: tumor differentiation (odds ratio [OR] = 3.776, 95% confidence interval [CI] 1.515–9.360, p = 0.004), depth of tumor invasion (OR = 3.124, 95% CI 1.146–8.511, p = 0.026), and tumor size (OR = 2.420, 95% CI 1.070–5.473, p = 0.034). The C-index was 0.810 (95% CI 0.742–0.895) in the derivation cohort (223 patients) and 0.830 (95% CI 0.763–0.902) in the validation cohort (80 patients). Conclusions A validated nomogram can predict the risk of LNM via risk stratification. It could be used to assist in the decision-making process to determine which patients should undergo esophagectomy and for which patients with a low risk of LNM, curative endoscopic resection would be sufficient.

BackgroundTo compare the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy (neoCT) versus neoadjuvant chemoradiotherapy (neoCRT) followed by surgery for locally advanced resectable oesophageal squamous cell carcinoma (ESCC).MethodsThis study is a multicentre, prospective, randomized-controlled, phase III clinical study. Eligible ESCC (staging: cT1N2M0 or cT2-3N0-2M0 (stage II/III, high-risk lesions in T2N0M0)) patients will be randomly assigned to either the experimental group (pembrolizumab with neoCT, n = 228) or the control group (neoCRT, n = 114) at a ratio of 2:1. Within 4–6 weeks after preoperative therapy, the McKeown procedure will be performed. Patients in the experimental group will also receive pembrolizumab alone as adjuvant therapy after surgery until 1 year or until the radiographically confirmed PD or other condition indicated for premature termination is observed. The primary endpoint is event-free survival (EFS). The secondary endpoints are 1-, 3-, and 5-year overall survival (OS) and disease-free survival (DFS), short-term outcomes, and quality of life.DiscussionThis is the first prospectively randomized controlled trial designed to compare pembrolizumab plus chemotherapy and chemoradiotherapy as neoadjuvant therapy for resectable ESCC. According to our hypothesis, preoperative pembrolizumab combined with chemotherapy will result in a better tumour response and prolong the survival of patients, with acceptable toxicity. This study started in December 2021, and the enrolment time is estimated to be 2 years.Trial RegistrationThis prospective study has been registered at ClinicalTrials.gov (NCT04807673), March 2021.

Accurately predicting the breakdown pressure in horizontal sections is essential when designing and optimizing fracturing jobs for horizontal wells in tight gas reservoirs. Taking the Sulige block in the Ordos Basin as an example, for different completion methods combined with indoor rock experience data and well data, a new method for predicting breakdown pressure based on a linear regression model is proposed. Based on the Hossain horizontal well stress field model, this paper established a calculation model of breakdown pressure under different completion methods by using experimental and well data. The average error between the calculation results and the actual breakdown pressure at the initiation point is 3.67%. A Pearson correlation analysis was conducted for eight sensitive factors of horizontal well stress, which showed that the maximum horizontal principal stress, minimum horizontal principal stress, tensile strength, and elastic modulus had strong linear correlations with breakdown pressure. In this study, multiple linear regression was used to establish the prediction model of breakdown pressure under different completion conditions, and the calculation method of the prediction model was optimized. The model was verified using the relevant data for four horizontal wells. The average relative error between the prediction model and the actual breakdown pressure was 4.33–6.30%, indicating that the breakdown pressure obtained by the new prediction model was similar to the actual conditions. Thus, the prediction model is reasonable and reliable.

Abstract Background In recent years, diagnosis of early squamous cell carcinoma of the esophagus has been increasingly emphasized. The application of endoscopic submucosal dissection (ESD) has enabled safe resection of esophageal lesions. Minimally invasive esophagectomy (MIE) is also safe and feasible for early stages of the cancer. This study aimed to compare the therapeutic effects of early esophageal carcinoma treatment, and find the best predictive factor for the selection of treatment for T1a patients. Methods We performed a retrospective study of early‐stage patients admitted to Tianjin Medical University Cancer Institute and Hospital between January 2015 and December 2018. A total of 128 patients underwent MIE, while 78 patients underwent ESD. The depth of the tumor invasion, lymph node metastasis, and complications were compared between the two groups. Results In the ESD group, 76.92% of the patients were stage T1a, while 34.38% in the MIE group were stage T1a. The lymph node metastasis rate was 16.41% in the MIE group (6.98% in T1a stage), which related to tumor differentiation, tumor length (≥37.5 mm), depth of invasion, and angiolymphatic invasion. However, the R0 resection rate was only 73.08% in the ESD group. Comprehensive analysis of all T1 patients in the two groups revealed that the positive margin was related to tumor differentiation, tumor width (≥13.5 mm), and depth of invasion (≥3.25 mm). Conclusion For early‐stage cases, lymph node metastasis and positive margins are risk factors affecting long‐term survival. Efficient predictive factors mentioned in our study would provide a proper indication for treatment strategy selection.

Gastroesophageal junction (GEJ) cancer is a tumor that occurs at the junction of stomach and esophagus anatomically. GEJ cancer frequently metastasizes to lymph nodes, however the heterogeneity and clonal evolution process are unclear. This study is the first of this kind to use single cell DNA sequencing to determine genomic variations and clonal evolution related to lymph node metastasis. Multiple Annealing and Looping Based Amplification Cycles (MALBAC) and bulk exome sequencing were performed to detect single cell copy number variations (CNVs) and single nucleotide variations (SNVs) respectively. Four GEJ cancer patients were enrolled with two (Pt.3, Pt.4) having metastatic lymph nodes. The most common mutation we found happened in the TTN gene, which was reported to be related with the tumor mutation burden in cancers. Significant intra-patient heterogeneity in SNVs and CNVs were found. We identified the SNV subclonal architecture in each tumor. To study the heterogeneity of CNVs, the single cells were sequenced. The number of subclones in the primary tumor was larger than that in lymph nodes, indicating the heterogeneity of primary site was higher. We observed two patterns of multi-station lymph node metastasis: one was skip metastasis and the other was to follow the lymphatic drainage. Taken together, our single cell genomic analysis has revealed the heterogeneity and clonal evolution in GEJ cancer.

Split-type steel box girders are widely used in long-span bridges because of their good wind-resistance performance. In the design stage, a simple finite element model is usually established based on the beam element for wind-resistance design. However, since the irregular cross-beams and diaphragms in the split steel box girder cannot be virtually established, the stiffness of the girder will be underestimated. To improve the accuracy in simulating stiffness of the split-type triple-box steel box girder (STSBG) with the beam element model (BEM), a correction is made to the initial beam element model (IBEM) based on the result of a more refined finite element model. ANSYS is adopted to make a refined model (RM) of a bridge with STSBG as its girder and to calculate its aerostatic responses and dynamic characteristics in 3 typical construction states and 1 finished state. With the reference value, an objective function of the overall residual sum of squares is constructed for the torsion angle of the girder and the frequency of the bridge. Then, the beam element is used for conventional modelling of the bridge, and artificial bee colony (ABC) algorithm is adopted for the optimization and correction of structure parameters of the BEM of the girder. Finally, static and dynamic characteristics of the IBEM and the corrected beam element model (CBEM) are compared with values of the corresponding RM to evaluate the validity of the correction of the model. The results show that the aerostatic responses and dynamic characteristics of the CBEM are close to calculated values of the RM. In more detail, the relative error between the torsion angle of the girder in the middle span of the BEM and the corresponding reference value in the finished state is decreased from +61.71% to +4.94%, and the relative error of torsional fundamental frequency is decreased from −17.43% to +3.66%. According to the calculated value of the RM, ABC algorithm would satisfactorily improve the accuracy in simulating torsional stiffness of the STSBG with the IBEM. This research is expected to provide reference for beam element modelling, which is conducive to accurately simulating torsional stiffness of the STSBG.

Background and objective The aim of this study is to investigate the value of pretreatment biopsy for histological diagnosis and induction therapies in the management of locally advanced thymic malignancies. Methods The clinical pathological data of patients with thymic tumors in the Chinese Alliance for Research in Thymomas (ChART) who underwent biopsy before treatment from 1994 to December 2012 were retrospectively reviewed. The application trend of preoperative histological diagnosis and its influence on treatment outcome were analyzed. Results Of 1,902 cases of thymic tumors, 336 (17.1%) had undergone biopsy for histological diagnosis before therapeutic decision was decided. In recent years, percentage of pretreatment histological diagnosis significantly increased in the later ten years than the former during the study period (P=0.008). There was also a significant increase in thoracoscopy/mediastinoscopy/endobronchial ultrasound (E-BUS) biopsy as compared to open biopsy (P=0.029). Survival in Patients with preoperative biopsy for histology had significantly higher stage lesions (P

In this paper, we prepared the nanoparticle drug carrier system between nanoparticles — chitosan and Epigallocatechin-3-O-gallate (EGCG) for breast cancer cell inhibiting application. For this drug carrier system, chitosan acts as a carrier and EGCG as a drug. Which were systematically characterized and thoroughly evaluated in terms of their inhibition rate and biocompatibility. We also did a cell scratch test and the result indicated that the chitosan-EGCG nanoparticles have inhibitory effect on the growth of breast cancer cells. The inhibition rate could reach up to 21.91%. This work revealed that the modification of nanoparticles paved a way for specific biomedical applications.

Background/Aims: To investigate the expression, clinical significance and the cellular effects of miR-497 in non-small cell lung cancer (NSCLC). Methods: NSCLC cells were transiently transfected with miR-497 mimics or siRNA to up-regulate or down-regulate expression. Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA level of miR-497. Luciferase assays, colony formation assays and BrdU incorporation assays were performed to identify the targets and role of miR-497 in NSCLC cells. Finally, the abundance of miR-497 was analyzed in a total of 51 NSCLC specimens. Results: The transcript levels of miR-497 were significantly decreased in NSCLC tissue (25/30; 83.3%). Low miR-497 levels in tumor tissue correlated with advanced pT stage. Additionally, miR-497 transcript levels correlated with overall survival of NSCLC patients (n = 51, p = 0.022). Overexpression of miR-497 inhibited the proliferation of NSCLC cell and down-regulation of miR-497 resulted in elevated NSCLC growth. Exogenous over-expression of YAP1 partially eliminated miR-497-induced cell growth. Conclusion: miR-497 plays an important role in inhibiting the proliferation of NSCLC by targeting YAP1. Our results suggest that miR-497 is a potential therapeutic target in treating patients with NSCLC.

One alpha-hydroxycholecalciferol (1α-OH D3), an analog of cholecalciferol (vitamin D3), improves growth performance and phosphorus retention in broilers. In the present study, we investigate the effects of dietary calcium (Ca) levels on the efficacy of 1α-OH D3 in the phosphorus (P)-deficient corn-soybean meal diets of 1- to 21-d-old broilers. Four hundred female Ross 308 broilers, 1-d-old, were randomly allotted to 10 treatments with 4 cages of 10 birds each. A 5×2 factorial experiment was designed to test 0.40, 0.60, 0.80, 1.00, and 1.20% Ca combined with 0 and 5μg/kg of 1α-OH D3 in a basal diet (0.25% non-phytate phosphorus (NPP), 0.48% total phosphorus (tP)) without vitamin D3. The lowest levels of body weight gain (BWG), feed intake (FI), feed efficiency (FE), tibia quality (except of ash and P), as well as the highest value of mortality, were observed at 0.40% Ca. Additional Ca corrected the Ca deficiency and eventually 1.2% Ca caused a P deficiency. The addition of 1α-OH D3 improved BWG, FI, FE, serum inorganic phosphate concentration, tP retention, tibia weight, length, breaking-strength, and content of ash, Ca, and P, and decreased mortality. However, 1α-OH D3 efficacy responded negatively to dietary Ca level. These results indicate that 1α-OH D3 exerts the highest activities at lower concentration of dietary Ca.

Objective: To investigate the effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease. Methods: In the study conducted at Heping Hospital of Changzhi Medical College from March 2021 to December 2022, 30 cases of patients diagnosed with diabetic nephropathy were meticulously selected as study subjects. Employing a double-blind randomized table method, these patients were randomly allocated into three groups: the control group (n = 10), the Bifidobacterium bifidum tetragonum tablets group (n = 10), and the Jin Gui Ren Qi Pill group (n = 10). The control group received standard western medical treatments for diabetic nephropathy, including serum glucose, blood lipids, blood pressure management, and other conventional therapies. In addition to the standard treatments, the Bifidobacterium bifidum tetragonum tablets group received Bifidobacterium bifidum tetragonum tablets, while the Jin Gui Ren Qi Pill group received Jin Gui Ren Qi Pill. Before and after a 4-week treatment period, various baseline parameters were assessed, including fasting blood glucose, 2-h postprandial blood glucose, triglycerides, serum total cholesterol, serum low-density lipoprotein cholesterol, serum high-density lipoprotein cholesterol, random urine microalbumin/creatinine ratio (ACR), blood creatinine (SCr), and traditional Chinese medicine evidence scores. Stool specimens were collected from all three groups before and after treatment for 16S rDNA high-throughput sequencing, followed by comprehensive analyses including OUT clustering, Alpha diversity, Beta diversity, species composition analysis, LEfSe analysis, and KEGG function prediction. Spearman correlation analysis was employed to explore the relationship between intestinal flora and clinical indicators. Furthermore, fasting peripheral venous blood was collected from patients in the Bifidobacterium tetrapunctate tablets group and the control group before and after intervention to measure the optical density values of tumor necrosis factor-a (TNF-a), interleukin-2 (IL-2), and interleukin-6 (IL-6) using the Beijing Biolite ELISA kit. This study was conducted with the approval of the Ethics Committee of Changzhi Medical College. Results: 1. The 2hPBG, total cholesterol and LDL levels were observed among patients with diabetic kidney disease (DKD) across all groups: the Jin Gui Ren Qi Pill group, the Bifidobacterium bifidum tetragonum tablets group, and the control group (p < 0.05). 2. The Jin Gui Ren Qi Pill demonstrated superior efficacy in alleviating TCM symptoms and reducing the ACR compared to both the Bifidobacterium bifidum tetragonum tablets group and the control group. Conversely, Bifidobacterium bifidum tetragonum tablets exhibited a more pronounced reduction in TC levels compared to both the Jin Gui Ren Qi Pill and control groups. Notably, Bifidobacterium bifidum tetragonum tablets effectively decreased (IL-2) levels in patients with DKD. 3. Bifidobacterium bifidum tetragonum tablets also demonstrated efficacy in reducing IL-2 levels in DKD patients. 4. Analysis of intestinal microorganism abundance and diversity before and after the intervention, as well as among the three groups, revealed no significant alterations. Similarly, comparisons of ACE, Chao, Simpson, and Shannon indices showed no statistically significant differences (p > 0.05). 5. Qualitative analysis of intestinal microorganisms before and after intervention, as well as among the three groups, indicated no significant differences. Anosim test results also did not reveal qualitative distinctions (Anosim test R = 0.021, p = 0.215). 6. LEfSe analysis unveiled a noteworthy increase in Prevotella_ 7 abundance within the Jin Gui Ren Qi Pill group post-intervention (p < 0.05). 7. Furthermore, Chinesemedicine evidence scores, body mass index, TC, and LDL levels correlated positively with the relative abundance of Tyzzerella_3 bacterial flora. Conversely, age, disease duration, and 2hPBG correlated positively with the relative abundance of Christensenellaceae_R_7 flora, while TC and LDL levels displayed a negative correlation with the relative abundance of Christensenellaceae_R_7 flora. Conclusion: The combination of Jin Gui Ren Qi Pill with western medical treatment exhibited superior efficacy in ameliorating clinical symptoms and reducing the ACR in patients with DKD compared to western medical treatment alone. Furthermore, this combination therapy led to an increase in the abundance of Prevotella_7 within the intestinal flora of patients, suggesting a potential enhancement in carbohydrate metabolism by the intestinal microbiota. On the other hand, Bifidobacterium bifidum tetragonum tablets bacterial tablets combined with western medical treatment demonstrated enhanced efficacy in reducing TC levels in DKD patients compared to western medical treatment alone. Additionally, this combination therapy effectively reduced the levels of IL-2 in DKD patients, thus mitigating inflammation in these individuals. [ABSTRACT FROM AUTHOR]

The restart ability of inlets is significant to the robustness of hypersonic airbreathing vehicles. Classic starting theories based on the one-dimensional and inviscid flow assumption cannot predict the restart boundary accurately. To overcome the classic theories, the restart characteristics of two-dimensional contraction ducts in viscous flow are numerically studied. The restart boundaries for different configurations and flow conditions are determined, and the restart similarity laws are discovered. With the proposed dimensionless quantities (the dimensionless cowl length and the effective throat-entrance area ratio), the influences of multiple factors on restart are described simultaneously in a concise self-similar formulation. The restart characteristics can be described with any two variables in cowl angle, dimensionless cowl length, and effective area ratio. The restarts of two-dimensional inlets are classified into three types of the short-cowl, transitional, and long-cowl restarts according to the features of restart boundary lines and the flow structure. The three restart types are dominated by the competition between the cowl shock system and cowl tail expansion waves, the cowl shock system alone, and the complementation between the cowl shock system and throat choke, respectively. The wall pressure criteria for restart are correlated with the dimensionless cowl length and the characteristic separation scale at the restart critical state. It is observed that Kantrowitz limit is not generalizable for restart boundaries. [ABSTRACT FROM AUTHOR]