The impact of CYP3A4 genetic polymorphism on crizotinib metabolism and drug-drug interactions.

To elucidate the impact of CYP3A4 activity inhibition and genetic polymorphism on the metabolism of crizotinib. Enzymatic incubation systems for crizotinib were established, and Sprague-Dawley rats were utilized for in vivo experiments. Analytes were quantified using LC-MS/MS. Upon screening 122 drugs and natural compounds, proanthocyanidins emerged as inhibitor of crizotinib metabolism, exhibiting a relative inhibition rate of 93.7%. The IC50 values were 24.53 ± 0.32 µM in rat liver microsomes and 18.24 ± 0.12 µM in human liver microsomes. In vivo studies revealed that proanthocyanidins markedly affected the pharmacokinetic parameters of crizotinib. Co-administration led to a significant reduction in the AUC(0-t), Cmax of PF-06260182 (the primary metabolite of crizotinib), and the urinary metabolic ratio. This interaction is attributed to the mixed-type inhibition of liver microsome activity by proanthocyanidins. CYP3A4, being the principal metabolic enzyme for crizotinib, has its genetic polymorphisms significantly influencing crizotinib's pharmacokinetics. Kinetic data showed that the relative metabolic rates of crizotinib across 26 CYP3A4 variants ranged from 13.14% (CYP3A4.12, 13) to 188.57% (CYP3A4.33) when compared to the wild-type CYP3A4.1. Additionally, the inhibitory effects of proanthocyanidins varied between CYP3A4.12 and CYP3A4.33, when compared to the wild type. Our findings indicate that proanthocyanidins coadministration and CYP3A4 genetic polymorphism can significantly influence crizotinib metabolism.

A modified nucleoside O6-methyl-2'-deoxyguanosine-5'-triphosphate exhibits anti-glioblastoma activity in a caspase-independent manner.

Resistance to temozolomide (TMZ), the frontline chemotherapeutic agent for glioblastoma (GBM), has emerged as a formidable obstacle, underscoring the imperative to identify alternative therapeutic strategies to improve patient outcomes. In this study, we comprehensively evaluated a novel agent, O6-methyl-2'-deoxyguanosine-5'-triphosphate (O6-methyl-dGTP) for its anti-GBM activity both in vitro and in vivo. Notably, O6-methyl-dGTP exhibited pronounced cytotoxicity against GBM cells, including those resistant to TMZ and overexpressing O6-methylguanine-DNA methyltransferase (MGMT). Mechanistic investigations revealed that O6-methyl-dGTP could be incorporated into genomic DNA, disrupting nucleotide pools balance, and inducing replication stress, resulting in S-phase arrest and DNA damage. The compound exerted its anti-tumor properties through the activation of AIF-mediated apoptosis and the parthanatos pathway. In vivo studies using U251 and Ln229 cell xenografts supported the robust tumor-inhibitory capacity of O6-methyl-dGTP. In an orthotopic transplantation model with U87MG cells, O6-methyl-dGTP showcased marginally superior tumor-suppressive activity compared to TMZ. In summary, our research, for the first time, underscores the potential of O6-methyl-dGTP as an effective candidate against GBM, laying a robust scientific groundwork for its potential clinical adoption in GBM treatment regimens.

High expression of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) associated with Diquat-induced damage.

Diquat (DQ) is a commonly used bipyridine herbicide known for its toxic properties and adverse effects on individuals. However, the mechanism underlying DQ-induced damage remain elusive. Our research aimed to uncover the regulatory network involved in DQ-induced damage. We analyzed publicly accessible gene expression patterns and performed research using a DQ-induced damage animal model. The GSE153959 dataset from the Gene Expression Omnibus collection and the animal model of DQ-induced kidney injury were used to identify differentially expressed genes (DEGs). Pathways including the regulation of DNA-templated transcription in response to stress, RNA polymerase II transcription regulator complex and transcription coregulatory activity were shown to be enriched in 21 DEGs. We used least absolute shrinkage and selection operator (LASSO) regression analysis to find possible diagnostic biomarkers for DQ-induced damage. Then, we used an HK-2 cell model to confirm these results. Additionally, we confirmed that 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) was the major gene associated with DQ-induced damage using multi-omics screening. The sample validation strongly suggested that HMGCS2 has promise as a diagnostic marker and may provide new targets for therapy in the context of DQ-induced damage.

Functional evaluation of CYP2C19 and CYP3A4 gene polymorphism on ibuprofen metabolism.

AIM: Ibuprofen is the most commonly used analgesic. CYP polymorphisms are mainly responsible for the differences in drug metabolism among individuals. Variations in the ability of populations to metabolize ibuprofen can lead to drug exposure events. The aim of this study was to evaluate the effects of CYP2C19 and CYP3A4 polymorphisms on ibuprofen metabolism in a Chinese population. METHODS: First, 31 CYP2C19 and 12 CYP3A4 microsomal enzymes were identified using an insect expression system. Then, variants were evaluated using a mature incubation system. Moreover, ibuprofen metabolite content was determined via ultra-performance liquid chromatography-tandem mass spectrometry analysis. Finally, kinetic parameters of CYP2C19 and CYP3A4 genotypes were determined via Michaelis-Menten curve fitting. RESULTS: Most variants exhibited significantly altered intrinsic clearance compared to the wild type. In the CYP2C19 metabolic pathway, seven variants exhibited no significant alterations in intrinsic clearance (CLint), six variants exhibited significantly high CLint (121-291%), and the remaining 15 variants exhibited substantially reduced CLint (1-71%). In the CYP3A4 metabolic pathway, CYP3A4*30 was not detected in the metabolite content due to the absence of activity, and 10 variants exhibited significantly reduced CLint. CONCLUSION: To the best of our knowledge, this is the first study to assess the kinetic characteristics of 31 CYP2C19 and 12 CYP3A4 genotypes on ibuprofen metabolism. However, further studies are needed on poor metabolizers as they are more susceptible to drug exposure. Our findings suggest that the kinetic characteristics in combination with artificial intelligence to predict the toxicity of ibuprofen and reduce any adverse drug reactions.

228 × 304 200-mW lidar based on a single-point global-depth d-ToF sensor and RGB-guided super-resolution neural network.

The cutting-edge imaging system exhibits low output resolution and high power consumption, presenting challenges for the RGB-D fusion algorithm. In practical scenarios, aligning the depth map resolution with the RGB image sensor is a crucial requirement. In this Letter, the software and hardware co-design is considered to implement a lidar system based on the monocular RGB 3D imaging algorithm. A 6.4 × 6.4-mm2 deep-learning accelerator (DLA) system-on-chip (SoC) manufactured in a 40-nm CMOS is incorporated with a 3.6-mm2 TX-RX integrated chip fabricated in a 180-nm CMOS to employ the customized single-pixel imaging neural network. In comparison to the RGB-only monocular depth estimation technique, the root mean square error is reduced from 0.48 m to 0.3 m on the evaluated dataset, and the output depth map resolution matches the RGB input.

80 × 120 AI-enhanced LiDAR system based on a lightweight intensity-RGB-dToF sensor fusion neural network deployed on an edge device.

Collecting higher-quality three-dimensional points-cloud data in various scenarios practically and robustly has led to a strong demand for such dToF-based LiDAR systems with higher ambient noise rejection ability and limited optical power consumption, which is a sharp conflict. To alleviate such a clash, an idea of utilizing a strong ambient noise rejection ability of intensity and RGB images is proposed, based on which a lightweight CNN is newly, to the best of our knowledge, designed, achieving a state-of-the-art performance even with 90 × less inference time and 480 × fewer FLOPs. With such net deployed on edge devices, a complete AI-LiDAR system is presented, showing a 100 × fewer signal photon demand in simulation experiments when creating depth images of the same quality.

Formation Mechanism of Starch-Based Double Emulsions from the Interfacial Perspective.

Double emulsions are of significant practical value in protecting the core material owing to their multicomponent structure and have thus been applied in various fields, such as food, cosmetics, and drugs. However, the mechanism of double emulsion formation by native starch is not well established. Herein, we demonstrate a facile route to develop type-A, type-B, and type-C double emulsions using native starch and develop an innovative design for a carrier. Interfacial interaction, enthalpy changes of starch, and interfacial properties are key factors governing the formation of double emulsions and controlling the type of double emulsions formed. Therefore, the results of this study provide a better understanding of how and what type of starch-based double emulsions are formed.

Dectin-1 plays a deleterious role in high fat diet-induced NAFLD of mice through enhancing macrophage activation.

The innate immune response and inflammation contribute to hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). Dectin-1 is a pathogen recognition receptor in innate immunity. In this study, we investigated the role of Dectin-1 in the pathogenesis of NAFLD. We first showed that Dectin-1 expression was significantly elevated in liver tissues of patients with NASH. NAFLD was induced in mice by feeding high fat diet (HFD) for 24 weeks. At the end of treatment, mice were sacrificed, and their blood and liver tissues were collected for analyses. We showed HFD feeding also increased liver Dectin-1 levels in mice, associated with macrophage infiltration. Either gene knockout or co-administration of a Dectin-1 antagonist laminarin (150 mg/kg twice a day, ip, from 16th week to 24th week) largely protected the livers from HFD-induced lipid accumulation, fibrosis, and elaboration of inflammatory responses. In primary mouse peritoneal macrophages (MPMs), challenge with palmitate (PA, 200 µM), an abundant saturated fatty acid found in NAFLD, significantly activated Dectin-1 signaling pathway, followed by transcriptionally regulated production of pro-inflammatory cytokines. Dectin-1 was required for hepatic macrophage activation and inflammatory factor induction. Condition media generated from Dectin-1 deficient macrophages failed to cause hepatocyte lipid accumulation and hepatic stellate activation. In conclusion, this study provides the primary evidence supporting a deleterious role for Dectin-1 in NAFLD through enhancing macrophage pro-inflammatory responses and suggests that it can be targeted to prevent inflammatory NAFLD.

The decreased risk of hepatocellular carcinoma in hepatitis B virus-related cirrhotic portal hypertension patients after laparoscopic splenectomy and azygoportal disconnection.

BACKGROUND: Posthepatitic cirrhosis is one of the leading risk factors for hepatocellular carcinoma (HCC) worldwide, among which hepatitis B cirrhosis is the dominant one. This study explored whether laparoscopic splenectomy and azygoportal disconnection (LSD) can reduce the risk of HCC among patients with hepatitis B virus (HBV)-related cirrhotic portal hypertension (CPH). METHODS: A total of 383 patients with HBV-related CPH diagnosed as gastroesophageal variceal bleeding and secondary hypersplenism were identified in our hepatobiliary pancreatic center between April 2012 and April 2022, and conducted an 11-year retrospective follow-up. We used inverse probability of treatment weighting (IPTW) to correct for potential confounders, weighted Kaplan-Meier curves, and logistic regression to estimate survival and risk differences. RESULTS: Patients were divided into two groups based on treatment method: LSD (n = 230) and endoscopic therapy (ET; n = 153) groups. Whether it was processed through IPTW or not, LSD group showed a higher survival benefit than ET group according to Kaplan-Meier analysis (P < 0.001). The incidence density of HCC was higher in the ET group compared to LSD group at the end of follow-up [32.1/1000 vs 8.0/1000 person-years; Rate ratio: 3.998, 95% confidence intervals (CI) 1.928-8.293]. Additionally, in logistic regression analyses weighted by IPTW, LSD was an independent protective predictor of HCC incidence compared to ET (odds ratio 0.516, 95% CI 0.343-0.776; P = 0.002). CONCLUSION: Considering the ability of LSD to improve postoperative survival and prevent HCC in HBV-related CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, it is worth promoting in the context of the shortage of liver donors.

Impact of Regional Collaborative Network on the Rescue of Patients with ST-Elevation Myocardial Infarction First Visit to non-PCI Hospitals.

Objective: To assess the effect of a regional collaborative network on the treatment of ST-elevation myocardial infarction (STEMI) patients first admitted to non- percutaneous coronary intervention (PCI) hospitals. Methods: Using data from Kunshan Hospital of Traditional Chinese Medicine's chest pain center database, patients were grouped based on the establishment of the regional collaborative rescue network. Key timepoints and in-hospital complications were analyzed. Results: A total of 152 ST-elevation myocardial infarction patients were included in the study. Compared to control group, symptom-to-balloon time (S-B), time of first medical contact to balloon and inter-hospital referral time in observation group were significantly shorter [(314.03 ± 209.26) min vs (451.27 ± 290.44) min, P = .001], [(115.32 ± 54.73) min vs (191.67 ± 130.30) min, P = .001], [(55.09 ± 37.23) min vs (112.67 ± 95.90) min, P = .001], but time of symptom to first medical contact were not statistically significant[(210.27±217.07) min vs (239.61 ± 200.92) min, P = .136].The incidence of heart failure and total complications during hospitalization decreased [7 (8.14%) vs 13 (19.70%), P = .037] and [14 (16.28%) vs 24 (36.36%), P = .004]. However no statistically significant difference were observed in rate of death during hospitalization [2 (2.33%) vs 3 (4.55%), P = .450], ventricular fibrillation [2 (2.33%) vs 3 (4.55%), P = .450], left ventricular thrombosis [2 (2.33%) vs 4 (6.06%), P = .244] and recurrent myocardial infarction[1 (1.16%) vs 1 (1.52%), P = .851]. Conclusions: The regional cooperative rescue network notably reduces ischemic and referral times for STEMI patients, lowering the incidence of heart failure during their hospital stay.

Folic Acid Protects Against Kidney Damage in Mice with Diabetic Nephropathy by Inhibiting M1 Macrophage Polarization via Nuclear Factor-k-gene Binding Pathway.

Kidney damage is one of the most common complications of diabetes, and inflammation caused by macrophage infiltration plays an important role. Folic acid (FA), a water-soluble vitamin, was previously found to affect inflammation by regulating macrophage polarization. In our study, we aimed to investigate the effect of FA on renal injury in mice with diabetic nephropathy (DN). We found that FA treatment ameliorated diabetic metabolic parameters in mice with DN, including reducing 24-hour food consumption, 24-hour urine volume and 24-hour water intake and increasing body weight and serum insulin. Of note, FA treatment improved renal functional and structural damage in mice with DN. In addition, FA treatment significantly reduced the number of renal infiltrating M1 macrophages, inflammatory cytokine FA stimulation significantly reduced the increase in F4/80+CD86+ cell ratio, inflammatory factor content and p-p65/p65 protein expression induced by high glucose exposure in RAW264.7 cells. All in all, our results indicated that FA protects against kidney damage in mice with DN by inhibiting M1 macrophage polarization, and its mechanism may be related to the inhibition of nuclear factor-k-gene binding (NF-kB) signaling pathway.

Environmental explanation of prostate cancer progression based on the comprehensive analysis of perfluorinated compounds.

Perfluorinated compounds (PFCs) are man-made chemicals used in the manufacture of many products with water and dirt repellent properties. Many diseases have been proved to be related to the exposure of PFCs, including breast fibroadenoma, hepatocellular carcinoma, breast cancer and leydig cell adenoma. However, whether the PFCs promote the progression of prostate cancer remains unclear. In this work, through comprehensive bioinformatics analysis, we discovered the correlation between the prostate cancer and five PFCs using Comparative Toxicogenomics Database (CTD), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In addition, further analysis showed that several PFCs-related genes demonstrated strong prognostic value for prostate cancer patients. The survival analysis and receiver operating characteristic (ROC) curves revealed that PFCs-related genes based prognostic model held great predictive value for the prognosis of prostate cancer, which could potentially serve as an independent risk factor in the future. In vitro experiments verified the promotive role of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) in the growth of prostate cancer cells. This study provided novel insights into understanding the role of PFCs in prostate cancer and brought attention to the environmental association with cancer risks and progression.

RRGA-Net: Robust Point Cloud Registration Based on Graph Convolutional Attention.

The problem of registering point clouds in scenarios with low overlap is explored in this study. Previous methodologies depended on having a sufficient number of repeatable keypoints to extract correspondences, making them less effective in partially overlapping environments. In this paper, a novel learning network is proposed to optimize correspondences in sparse keypoints. Firstly, a multi-layer channel sampling mechanism is suggested to enhance the information in point clouds, and keypoints were filtered and fused at multi-layer resolutions to form patches through feature weight filtering. Moreover, a template matching module is devised, comprising a self-attention mapping convolutional neural network and a cross-attention network. This module aims to match contextual features and refine the correspondence in overlapping areas of patches, ultimately enhancing correspondence accuracy. Experimental results demonstrate the robustness of our model across various datasets, including ModelNet40, 3DMatch, 3DLoMatch, and KITTI. Notably, our method excels in low-overlap scenarios, showcasing superior performance.

Pre-selection of monitoring stations for marine water quality using affinity propagation: A case study of Xincun Lagoon, hainan, China.

The development, protection, and restoration of bays require works in scientific research and applications, and the success of which depends on a well deployment of monitoring stations for marine water quality. However, for bays without historical data, it is difficult to carry out related research on deployment of the monitoring stations, resulting in very few research works. This paper has introduced the affinity propagation (AP) clustering algorithm and achieved good results by correcting the preferences. The results show that under the given preference, that is, when the value of M is -6800, the number of monitoring stations in the Xincun lagoon area is 24. Simultaneous the sensitivity analysis of preferences shows that the number of exemplars decreases with lower preferences, that is, when M decreased from -4000 to -12000, the number also decreased from 70 to 36. However, some exemplars remain unchanged or being changed to adjacent positioning. This shows the stability of computation results and the rationality of AP. The research results can be well applied to other bays, even open waters.

The regulation of LPCAT3 by miR-124-3p.1 in acute kidney injury suppresses cell proliferation by disrupting phospholipid metabolism.

Sepsis-associated acute renal injury (SA-AKI) is a common critical clinical disease. It is associated with increased mortality and increased risk of progression to chronic kidney disease. However, its pathogenesis is not fully known. We hypothesized that metabolic interactions mediate cell apoptosis and AKI. We found that phosphatidylcholine content in human renal tubular epithelial cells following lipopolysaccharide-induced injury was increased. The activity of lysophosphatidylcholine acyltransferase 3 (LPCAT3), a key enzyme in phospholipid metabolism, was increased, while the expression of miR-124-3p.1, which targets LPCAT3, was decreased. We also found that in the serum of SA-AKI patients, LPCAT3 activity was increased, and miR-124-3p.1 expression was decreased. Further experiments confirmed the specific binding of exocrine miR-124-3p.1 to LPCAT3. Our data reveal the molecular mechanisms of phospholipid metabolic disorder in early SA-AKI as well as the role of the miR-124-3p.1/LPCAT3 pathway in SA-AKI, which leads to ferroptosis. These results could provide the scientific basis for early diagnosis and renal replacement therapy in SA-AKI.

Reclaiming independence in spatial-clustering datasets: A series of data-driven spatial weights matrices.

Most spatial models include a spatial weights matrix (W) derived from the first law of geography to adjust the spatial dependence to fulfill the independence assumption. In various fields such as epidemiological and environmental studies, the spatial dependence often shows clustering (or geographic discontinuity) due to natural or social factors. In such cases, adjustment using the first-law-of-geography-based W might be inappropriate and leads to inaccuracy estimations and loss of statistical power. In this work, we propose a series of data-driven Ws (DDWs) built following the spatial pattern identified by the scan statistic, which can be easily carried out using existing tools such as SaTScan software. The DDWs take both the clustering (or discontinuous) and the intuitive first-law-of-geographic-based spatial dependence into consideration. Aiming at two common purposes in epidemiology studies (ie, estimating the effect value of explanatory variable X and estimating the risk of each spatial unit in disease mapping), the common spatial autoregressive models and the Leroux-prior-based conditional autoregressive (CAR) models were selected to evaluate performance of DDWs, respectively. Both simulation and case studies show that our DDWs achieve considerably better performance than the classic W in datasets with clustering (or discontinuous) spatial dependence. Furthermore, the latest published density-based spatial clustering models, aiming at dealing with such clustering (or discontinuity) spatial dependence in disease mapping, were also compared as references. The DDWs, incorporated into the CAR models, still show considerable advantage, especially in the datasets for common diseases.

Response to the Temperature and Solvent Stimulation of MOF Material in a Single-Crystal to Single-Crystal Manner.

Under solvothermal conditions, a three-dimensional mononuclear crystal AQNU-1, {[Co(H2L)(DPD)(H2O)2]·2DMA}n (H2L = 5-(bis(4-carboxybenzyl)amino)isophthalic acid, DPD = 4,4'-(2,5-diethoxy-1,4-phenylene)dipyridine) has been synthesized. The transformations of AQNU-1 to binuclear {[Co2(L)(DPD)1.5(H2O)3]·DMA·H2O}n (AQNU-2) and pentanuclear {[Co5(L)2(DPD)2(OH)2]·2H2O}n (AQNU-3) were realized by double stimulation of temperature and solvent, which were accomplished by single-crystal to single-crystal (SC-SC) reaction.

Comparative analysis of the association between traditional and lipid-related obesity indicators and isolated systolic hypertension : Association of obesity indicators with ISH.

BACKGROUND: Obesity is a well-known modified risk factor for isolated systolic hypertension (ISH), but evidence is lacking regarding whether the combination of anthropometric and lipid indicators could strengthen their correlation with ISH. Therefore, we compared the association of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), visceral adiposity index (VAI), lipid accumulation product index (LAP), and cardiometabolic index (CMI) with ISH. METHODS: A total of 106,248 adults who received routine health screening and did not have diastolic blood pressure ≥ 90 mmHg were recruited in this cross-sectional study. The associations between these indicators and ISH were evaluated using multivariate regression. RESULTS: Each standard deviation (SD) increase in traditional obesity indicators (especially WHR and WHtR) had significantly higher multivariate-adjusted odds ratios (ORs) than each SD increase in lipid-related obesity indicators. In addition, multivariate-adjusted ORs for ISH in the third (vs. the first) tertile of traditional obesity indicators were also significantly higher than those of lipid-related indicators. Moreover, traditional obesity indicators exhibited a higher area under the ROC curve for discriminating ISH than lipid-related obesity indicators. CONCLUSIONS: Traditional obesity indicators were more strongly associated with ISH than lipid-related obesity indicators among Chinese adults.

Pharmacological inhibition of MyD88 suppresses inflammation in tubular epithelial cells and prevents diabetic nephropathy in experimental mice.

Emerging evidence shows that chronic inflammation mediated by toll-like receptors (TLRs) contributes to diabetic nephropathy. Myeloid differentiation primary-response protein-88 (MyD88) is an essential adapter protein of all TLRs except TLR3 in innate immunity. It is unclear whether MyD88 could be a therapeutic target for diabetic nephropathy. Here, we used a new small-molecule MyD88 inhibitor, LM8, to examine the pharmacological inhibition of MyD88 in protecting kidneys from inflammatory injury in diabetes. We showed that MyD88 was significantly activated in the kidney of STZ-induced type 1 diabetic mice in tubular epithelial cells as well as in high glucose-treated rat tubular epithelial cells NRK-52E. In cultured tubular epithelial cells, we show that LM8 (2.5-10 µM) or MyD88 siRNA attenuated high-concentration glucose-induced inflammatory and fibrogenic responses through inhibition of MyD88-TLR4 interaction and downstream NF-κB activation. Treatment with LM8 (5, 10 mg/kg, i.g.) significantly reduced renal inflammation and fibrosis and preserved renal function in both type 1 and type 2 diabetic mice. These renoprotective effects were associated with reduced MyD88-TLR4 complex formation, suppressed NF-κB signaling, and prevention of inflammatory factor expression. Collectively, our results show that hyperglycemia activates MyD88 signaling cascade to induce renal inflammation, fibrosis, and dysfunction. Pharmacological inhibition of MyD88 may be a therapeutic approach to mitigate diabetic nephropathy and the inhibitor LM8 could be a potential candidate for such therapy.

Clinical effects of cluster technology optimization and innovations on laparoscopic splenectomy and azygoportal disconnection: a single-center retrospective study with 500 consecutive cases.

BACKGROUND: In Asia, laparoscopic splenectomy and azygoportal disconnection (LSD) has been widely regarded as a preferential treatment modality for cirrhotic portal hypertension (PH). However, LSD involves high surgical risk, technical challenges, and many potential postoperative complications. Technology optimization and innovation in LSD aiming to solve to these difficulties has scarcely been reported. In this retrospective study, we aimed to evaluate the clinical therapeutic effect of our cluster technology optimization and innovation on LSD for PH. METHODS: From February 2012 to January 2020, 500 patients with cirrhosis who had esophagogastric variceal bleeding and hypersplenism underwent LSD in our department. According to different operation periods, patients were divided into the early-, intermediate-, and late-period groups. We collected information regarding clinical characteristics of all patients as well as their preoperative and postoperative follow-up data. RESULTS: Compared with the early-period group, operation time and postoperative hospital stay were all significantly different and gradually declined from the intermediate- and late-period groups, respectively (all P < 0.05). Intraoperative blood loss of these three groups was gradually decreased, with significant differences (P < 0.05). The incidences of delayed gastric emptying and diarrhea in the late-period group were all significantly lower than those in the early- and intermediate-period groups, respectively (all P < 0.05). Compared with the early-period group, the incidence of variceal re-bleeding was significantly lower in the intermediate- and late-period groups (all P < 0.05). CONCLUSION: Our cluster technology optimization and innovation of LSD not only contributed to faster recovery and fewer complications but also enhanced surgical safety for patients. It is worth promoting this approach among patients with EVB and hypersplenism secondary to cirrhotic PH.