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Abstract The concept of the Human Digital Twin (HDT) has recently emerged as a new research area within the domain of digital twin technology. HDT refers to the replica of a physical-world human in the digital world. Currently, research on HDT is still in its early stages, with a lack of comprehensive and in-depth analysis from the perspectives of universal frameworks, core technologies, and applications. Therefore, this paper conducts an extensive literature review on HDT research, analyzing the underlying technologies and establishing typical frameworks in which the core HDT functions or components are organized. Based on the findings from the aforementioned work, the paper proposes a generic architecture for the HDT system and describes the core function blocks and corresponding technologies. Subsequently, the paper presents the state of the art of HDT technologies and their applications in the healthcare, industry, and daily life domains. Finally, the paper discusses various issues related to the development of HDT and points out the trends and challenges of future HDT research and development.

Abstract Background Non-small cell lung cancer (NSCLC) is the primary reason for cancer-related deaths globally. Tertiary lymphoid structure (TLS) is an organized collection of immune cells acquired in non-physiological, non-lymphoid tissues. High expression of TLS in tumor tissues is generally associated with better prognosis. This research aimed to investigate the prognostic and clinicopathological significance of TLS in patients with NSCLC. Methods A comprehensive literature search was conducted based on Pubmed, EMBASE, and Cochrane Library databases to identify eligible studies published up to December 8, 2023. The prognostic significance and clinicopathological value of TLS in NSCLC were evaluated by calculating the combined hazard ratios (HRs) and odds ratios (ORs) and their 95% confidence intervals (CIs). Following that, additional analyses, including subgroup analysis and sensitivity analysis, were conducted. Results This meta-analysis evaluated the prognostic and clinicopathological significance of TLS in 10 studies involving 1,451 patients with NSCLC. The results revealed that the high levels of TLS were strongly associated with better overall survival (OS) (HR = 0.48, 95% CI: 0.35–0.66, p

BackgroundThis study aimed to construct a clinical prediction model and nomogram to differentiate invasive from non-invasive pulmonary adenocarcinoma in solitary pulmonary nodules (SPNs).MethodWe analyzed computed tomography and clinical features as well as preoperative biomarkers in 1,106 patients with SPN who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University between January 2020 and December 2021. Clinical parameters and imaging characteristics were analyzed using univariate and multivariate logistic regression analyses. Predictive models and nomograms were developed and their recognition abilities were evaluated using receiver operating characteristic (ROC) curves. The clinical utility of the nomogram was evaluated using decision curve analysis (DCA).ResultThe final regression analysis selected age, carcinoembryonic antigen, bronchus sign, lobulation, pleural adhesion, maximum diameter, and the consolidation-to-tumor ratio as associated factors. The areas under the ROC curves were 0.844 (95% confidence interval [CI], 0.817–0.871) and 0.812 (95% CI, 0.766–0.857) for patients in the training and validation cohorts, respectively. The predictive model calibration curve revealed good calibration for both cohorts. The DCA results confirmed that the clinical prediction model was useful in clinical practice. Bias-corrected C-indices for the training and validation cohorts were 0.844 and 0.814, respectively.ConclusionOur predictive model and nomogram might be useful for guiding clinical decisions regarding personalized surgical intervention and treatment options.

Abstract Objectives In this study, we aimed to develop a multiparameter prediction model to improve the diagnostic accuracy of invasive adenocarcinoma in pulmonary pure glass nodules. Method We included patients with pulmonary pure glass nodules who underwent lung resection and had a clear pathology between January 2020 and January 2022 at the Qilu Hospital of Shandong University. We collected data on the clinical characteristics of the patients as well as their preoperative biomarker results and computed tomography features. Thereafter, we performed univariate and multivariate logistic regression analyses to identify independent risk factors, which were then used to develop a prediction model and nomogram. We then evaluated the recognition ability of the model via receiver operating characteristic (ROC) curve analysis and assessed its calibration ability using the Hosmer-Lemeshow test and calibration curves. Further, to assess the clinical utility of the nomogram, we performed decision curve analysis. Result We included 563 patients, comprising 174 and 389 cases of invasive and non-invasive adenocarcinoma, respectively, and identified seven independent risk factors, namely, maximum tumor diameter, age, serum amyloid level, pleural effusion sign, bronchial sign, tumor location, and lobulation. The area under the ROC curve was 0.839 (95% CI: 0.798–0.879) for the training cohort and 0.782 (95% CI: 0.706–0.858) for the validation cohort, indicating a relatively high predictive accuracy for the nomogram. Calibration curves for the prediction model also showed good calibration for both cohorts, and decision curve analysis showed that the clinical prediction model has clinical utility. Conclusion The novel nomogram thus constructed for identifying invasive adenocarcinoma in patients with isolated pulmonary pure glass nodules exhibited excellent discriminatory power, calibration capacity, and clinical utility.

Abstract Background The prognostic significance of adjuvant chemotherapy (ACT) for patients with stage IA micropapillary non-predominant (MPNP) lung adenocarcinoma (LUAD) remains unknown. This study aimed to investigate the effects of postoperative ACT in patients with stage IA MPNP-LUAD. Methods A total of 149 patients with pathological stage IA MPNP-LUAD who underwent surgery at our center were retrospectively analyzed. Propensity score matching (PSM) analysis was conducted to reduce potential selection bias. Kaplan–Meier analyses were used to assess the impact of ACT on recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS). Subgroup analyses were performed for the survival outcomes based on the percentage of micropapillary components. Cox proportional hazards regression analyses were applied to identify risk factors associated with survival. Results The receipt or non-receipt of postoperative ACT had no significant effect on RFS, OS, and DSS among all enrolled patients with stage IA MPNP-LUAD (P > 0.05). For patients with a micropapillary component > 5%, the 5-year rates of RFS, OS, and DSS were significantly higher in the ACT group compared to the observation group, both before and after PSM (P 0.05). The resection range (HR = 0.071; 95% CI: 0.020–0.251; P

Abstract Background Lymphocyte-activation gene 3 (LAG3) is a recently discovered immune checkpoint molecule that has been linked to immunosuppression and the advancement of cancer in different types of solid tumors. This study aimed to evaluate the prognostic importance of LAG3 and its role in the immune system within solid tumors. Methods Extensive literature searches were conducted using the Pubmed, EMBASE, and Cochrane Library databases to identify relevant studies exploring the effect of LAG3 on survival outcomes. Pooled hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to evaluate the prognostic values of LAG3. Afterwards, subgroup analysis and sensitivity analysis were conducted. Pan-cancer analysis investigated the possible relationships between LAG3 expression and genetic alterations, RNA methylation modification-related genes, genomic instability, immune checkpoint genes, and infiltration of immune cells. Results A total of 43 studies with 7,118 patients were included in this analysis. Higher expression of LAG3 was associated with worse overall survival (HR = 1.10, 95% CI 1.01–1.19, P = 0.023), but not disease-free survival (HR = 1.41, 95% CI 0.96–2.07, P = 0.078), progression-free survival (HR = 1.12, 95% CI 0.90–1.39, P = 0.317) or recurrence-free survival (HR = 0.98, 95% CI 0.81–1.19, P = 0.871). Subgroup analysis showed that LAG3 might play different prognostic roles in different solid tumors. LAG3 expression was positively associated with immune cell infiltration and immune checkpoint genes in all of the cancers included. LAG3 expression was also found to be associated with microsatellite instability (MSI), copy number variation (CNV), simple nucleoside variation (SNV), tumor mutation burden (TMB), and neoantigen in various types of cancers. Conclusions Elevated expression of LAG3 is linked to poorer prognosis among patients diagnosed with solid cancers. LAG3 might play varying prognostic roles in different types of solid tumors. Given its substantial involvement in cancer immunity and tumorigenesis, LAG3 has garnered attention as a promising prognostic biomarker and a potential target for immunotherapy.

Abstract Background DARS2 expression is upregulated in lung adenocarcinoma (LUAD) which correlates with tumor patient stage and prognosis. The mechanism of DARS2 involvement in LUAD still needs to be further explored. Methods In this study, we found that DARS2 expression in LUAD tissue was significantly higher than that in normal tissue. At the same time, the Kaplan–Meier curve showed that the survival prognosis of LUAD patients with high expression of DARS2 was significantly worse than low expression of DARS2. The expression of DARS2 was detected in LUAD and adjacent normal tissues by IHC staining, histochemical scoring and a survival curve was generated. In addition, we demonstrated that the knockdown and overexpression of DARS2 significantly affected the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. Finally, western blot and rescue assay were performed on LUAD cells to further explore and verify the signaling pathway. Results DARS2 expression was significantly upregulated in LUAD tissues and cell lines. What is more, the increased expression of DARS2 was closely related to proliferation, invasion and metastasis. The tumorigenic assay in nude mice further showed that the tumorigenic ability of nude mice was significantly improved with the increase in DARS2 expression. Finally, we determined that DARS2 plays its role in LUAD by targeting the ERK/c‐Myc signaling pathway. Conclusion Our data revealed the oncogenic role of DARS2 in LUAD, indicating that DARS2 may be a predictive biomarker and novel therapeutic target for LUAD.

N6-methyladenosine (m6A) is a crucial RNA modification affecting skeletal muscle development. Rhein, an anti-inflammatory extract, inhibits FTO, a key demethylase in m6A metabolism. Our study showed that during muscle fiber formation, FTO and ALKBH5 expression increased while m6A levels decreased. After muscle injury, FTO and ALKBH5 expression initially rose but later fell, while m6A levels initially dropped and then recovered. Inhibition of FTO by Rhein reduced MyHC and MyoG expression, indicating myoblast differentiation suppression. In a mouse model, Rhein decreased MyHC expression and muscle fiber cross-sectional area, delaying muscle regeneration. Rhein’s ability to increase RNA m6A modification delays skeletal muscle remodeling post-injury, suggesting a new medicinal application for this plant extract.

BackgroundThe progression of early stage non-small cell lung cancer (NSCLC) is closely related to epidermal growth factor receptor (EGFR) mutation status. The purpose of this study was to systematically investigate the relationship between EGFR mutation status and demographic, imaging, and ultimately pathologic features in patients with NSCLC.MethodsA complete literature search was conducted using the PubMed, Web of Science, EMBASE, and Cochrane Library databases to discover articles published by May 15, 2023 that were eligible. The relationship between EGFR mutation status and specific demographic, imaging, and ultimately pathologic features in patients with NSCLC was evaluated using pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The standardized mean difference (SMD) with 95% CIs was the appropriate statistic to summarize standard deviations (SDs) means for continuous variables.ResultsA total of 9 studies with 1789 patients were included in this analysis. The final findings suggested that patients with a greater age, female gender, and non-smoking status would have a relatively higher incidence of EGFR mutations. Additionally, the risk of EGFR mutations increased with larger tumor diameter, tumor imaging presentation of mixed ground glass opacity (mGGO), and tumor pathological findings of minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (IAC). Significantly, malignancies presenting as MIA are more likely to contain L858R point mutations (OR = 1.80; 95% CI: 1.04–3.13; p = 0.04) rather than exon 19 deletions (OR = 1.81; 95% CI: 0.95–3.44; p = 0.07).ConclusionThis meta-analysis showed that imaging parameters and histological classifications of pulmonary nodules may be able to predict stage IA NSCLC genetic changes.

BackgroundAt present, how to identify the benign or malignant nature of small (≤ 2 cm) solitary pulmonary nodules (SPN) are an urgent clinical challenge. This retrospective study aimed to develop a clinical prediction model combining clinical and radiological characteristics for assessing the probability of malignancy in SPNs measuring ≤ 2 cm.MethodIn this study, we included patients with SPNs measuring ≤ 2 cm who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University from January 2020 to December 2021. Clinical features, preoperative biomarker results, and computed tomography characteristics were collected. The enrolled patients were randomized at a ratio of 7:3 into a training cohort of 775 and a validation cohort of 331. The training cohort was used to construct the predictive model, while the validation cohort was used to test the model independently. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The prediction model and nomogram were established based on the independent risk factors. The receiver operating characteristic (ROC) curve was used to evaluate the identification ability of the model. The calibration power was evaluated using the Hosmer–Lemeshow test and calibration curve. The clinical utility of the nomogram was also assessed by decision curve analysis (DCA).ResultA total of 1,106 patients were included in this study. Among them, the malignancy rate of SPNs was 85.08% (941/1,106). We finally identified the following six independent risk factors by logistic regression: age, carcinoembryonic antigen, nodule shape, calcification, maximum diameter, and consolidation-to-tumor ratio. The area under the ROC curve (AUC) for the training cohort was 0.764 (95% confidence interval [CI]: 0.714–0.814), and the AUC for the validation cohort was 0.729 (95% CI: 0.647–0.811), indicating that the prediction accuracy of nomogram was relatively good. The calibration curve of the predictive model also demonstrated a good calibration in both cohorts. DCA proved that the clinical prediction model was useful in clinical practice.ConclusionWe developed and validated a predictive model and nomogram for estimating the probability of malignancy in SPNs measuring ≤ 2 cm. With the application of predictive models, thoracic surgeons can make more rational clinical decisions while avoiding overtreatment and wasting medical resources.

Abstract Background An increasing number of patients are being diagnosed with synchronous multiple primary lung cancer (SMPLC) with the popularization of lung cancer screening programs. However, a strategy for accurate location and suitable surgery therapy is still lacking. The present study aimed to explore the accuracy and feasibility of electromagnetic navigation bronchoscopy (ENB)‐guided thoracoscopic sublobectomy for stage IA SMPLC. Methods Patients with SMPLC who underwent ENB‐guided sublobectomy from January 2020 to June 2022 were enrolled in this study. The analysis of localization accuracy of ENB and surgical outcome was conducted. Results Overall, 138 patients with 353 malignant nodules were enrolled. The tumor size was 0.7 cm (range from 0.5 to 1.1 cm). ENB localization was performed on 162 nodules, and a customized scoring system was developed to evaluate localization accuracy. The success rate of localization was 98.3% (178/181). Notably, localization accuracy was positively correlated with bronchial signs (p

Abstract Background The effectiveness of robotic‐assisted lobectomy (RAL) for patients with non–small‐cell lung cancer (NSCLC) has not been fully evaluated. Methods This retrospective study compared the perioperative outcomes of NSCLC patients who underwent RAL and video‐assisted lobectomy (VAL) using propensity score matching (PSM) analysis. Subgroup analyses were then performed. Results A total of 822 NSCLC patients (359 RAL cases and 463 VAL cases) were included, and there were 292 patients in each group after PSM. Compared with the VAL group, the RAL group had a significantly higher number of lymph nodes (LNs) harvested (10 vs. 8, p

Abstract Background Prolonged air leak (PAL) remains one of the most frequent postoperative complications after pulmonary resection. This study aimed to develop a predictive nomogram to estimate the risk of PAL for individual patients after minimally invasive pulmonary resection. Methods Patients who underwent minimally invasive pulmonary resection for either benign or malignant lung tumors between January 2020 and December 2021 were included. All eligible patients were randomly assigned to the training cohort or validation cohort at a 3:1 ratio. Univariate and multivariate logistic regression were performed to identify independent risk factors. All independent risk factors were incorporated to establish a predictive model and nomogram, and a web-based dynamic nomogram was then built based on the logistic regression model. Nomogram discrimination was assessed using the receiver operating characteristic (ROC) curve. The calibration power was evaluated using the Hosmer-Lemeshow test and calibration curves. The nomogram was also evaluated for clinical utility by the decision curve analysis (DCA). Results A total of 2213 patients were finally enrolled in this study, among whom, 341 cases (15.4%) were confirmed to have PAL. The following eight independent risk factors were identified through logistic regression: age, body mass index (BMI), smoking history, percentage of the predicted value for forced expiratory volume in 1 second (FEV1% predicted), surgical procedure, surgical range, operation side, operation duration. The area under the ROC curve (AUC) was 0.7315 [95% confidence interval (CI): 0.6979–0.7651] for the training cohort and 0.7325 (95% CI: 0.6743–0.7906) for the validation cohort. The P values of the Hosmer-Lemeshow test were 0.388 and 0.577 for the training and validation cohorts, respectively, with well-fitted calibration curves. The DCA demonstrated that the nomogram was clinically useful. An operation interface on a web page ( https://lirongyangql.shinyapps.io/PAL_DynNom/ ) was built to improve the clinical utility of the nomogram. Conclusion The nomogram achieved good predictive performance for PAL after minimally invasive pulmonary resection. Patients at high risk of PAL could be identified using this nomogram, and thus some preventive measures could be adopted in advance.

BackgroundWith the popularity of computed tomography (CT) of the thorax, the rate of diagnosis for patients with early-stage lung cancer has increased. However, distinguishing high-risk pulmonary nodules (HRPNs) from low-risk pulmonary nodules (LRPNs) before surgery remains challenging.MethodsA retrospective analysis was performed on 1064 patients with pulmonary nodules (PNs) admitted to the Qilu Hospital of Shandong University from April to December 2021. Randomization of all eligible patients to either the training or validation cohort was performed in a 3:1 ratio. Eighty-three PNs patients who visited Qianfoshan Hospital in the Shandong Province from January through April of 2022 were included as an external validation. Univariable and multivariable logistic regression (forward stepwise regression) were used to identify independent risk factors, and a predictive model and dynamic web nomogram were constructed by integrating these risk factors.ResultsA total of 895 patients were included, with an incidence of HRPNs of 47.3% (423/895). Logistic regression analysis identified four independent risk factors: the size, consolidation tumor ratio, CT value of PNs, and carcinoembryonic antigen levels in blood. The area under the ROC curves was 0.895, 0.936, and 0.812 for the training, internal validation, and external validation cohorts, respectively. The Hosmer-Lemeshow test demonstrated excellent calibration capability, and the fit of the calibration curve was good. DCA has shown the nomogram to be clinically useful.ConclusionThe nomogram performed well in predicting the likelihood of HRPNs. In addition, it identified HRPNs in patients with PNs, achieved accurate treatment with HRPNs, and is expected to promote their rapid recovery.

BackgroundBladder cancer is the ninth most common malignant tumor worldwide. As an effective evidence-based multidisciplinary protocol, the enhanced recovery after surgery (ERAS) program is practiced in many surgical disciplines. However, the function of ERAS after radical cystectomy remains controversial. This systematic review and meta-analysis aims to research the impact of ERAS on radical cystectomy.MethodsA systematic literature search on PubMed, EMBASE, SCOPUS, and the Cochrane Library databases was conducted in April 2022 to identify the studies that performed the ERAS program in radical cystectomy. Studies were selected, data extraction was performed independently by two reviewers, and quality was assessed using a random effects model to calculate the overall effect size. The odds ratio and standardized mean difference (SMD) with a 95% confidence interval (CI) served as the summary statistics for the meta-analysis. A sensitivity analysis was subsequently performed.ResultsA total of 25 studies with 4,083 patients were enrolled. The meta-analysis showed that the complications (OR = 0.76; 95% CI: 0.63–0.90), transfusion rate (OR = 0.59; 95% CI: 0.39–0.90), readmission rate (OR = 0.79; 95% CI: 0.64–0.96), length of stay (SMD = −0.79; 95% CI: −1.41 to −0.17), and time to first flatus (SMD = −1.16; 95% CI: −1.58 to −0.74) were significantly reduced in the ERAS group. However, no significance was found in 90-day mortality and urine leakage.ConclusionThe ERAS program for radical cystectomy can effectively decrease the risk of overall complications, postoperative ileus, readmission rate, transfusion rate, length of stay, and time to first flatus in patients who underwent radical cystectomy with relative safety.Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY202250075.

ObjectiveTo compare the efficacy of flexible ureteroscopy for single urinary stones with that of multiple urinary stones.MethodsA retrospective study was conducted on patients who underwent flexible ureteroscopy in Qilu Hospital of Shandong University from January 2016 to March 2021. Propensity score matching was used to match patients with no statistical difference in preoperative clinical data, and they were divided into solitary calculi and multiple calculi two groups. The postoperative hospital days, operation time, complications and stone free rate were compared between the two groups. And multiple stones were divided into high group (S-ReSc > 4) and non-high group (S-ReSc ≤ 4) for analysis.Results313 patients were counted. After propensity score matching, 198 patients were finally included in the study. There were 99 cases in the solitary stone group and the multiple stone group. There were no significant differences in postoperative hospital days, complications and stone free rate between the two groups. The operation time of patients with solitary stone group was significantly shorter than that of patients with multiple stones (65.00 min, 45.00 min VS 90.00 min, 50.00 min, P 4.

Esophageal cancer (EC) is one of the most life-threatening malignancies worldwide. Esophageal squamous cell carcinoma (ESCC) is the dominant subtype, accounting for approximately 90% of new incident EC each year. Although multidisciplinary treatment strategies have advanced rapidly, patients with ESCC are often diagnosed at advanced stage and the long-term prognosis remains unsatisfactory. In recent decades, immunotherapy, such as immune checkpoint inhibitors (ICIs), tumor vaccines, and chimeric antigen receptor T-cell (CAR-T) therapy, has been successfully used in clinical practice as a novel therapy for treating tumors, bringing new hope to ESCC patients. However, only a small fraction of patients achieved clinical benefits due to primary or acquired resistance. Immune evasion plays a pivotal role in the initiation and progression of ESCC. Therefore, a thorough understanding of the mechanisms by which ESCC cells escape from anti-tumor immunity is necessary for a more effective multidisciplinary treatment strategy. It has been widely recognized that immune evasion is closely associated with the crosstalk between tumor cells and the tumor microenvironment (TME). TME is a dynamic complex and comprehensive system including not only cellular components but also non-cellular components, which influence hallmarks and fates of tumor cells from the outside. Novel immunotherapy targeting tumor-favorable TME represents a promising strategy to achieve better therapeutic responses for patients with ESCC. In this review, we provide an overview of immune evasion in ESCC, mainly focusing on the molecular mechanisms that underlie the role of TME in immune evasion of ESCC. In addition, we also discuss the challenges and opportunities of precision therapy for ESCC by targeting TME.

Background: N-Alpha-Acetyltransferase 50 (NAA50) has acetyltransferase activity and is important for chromosome segregation. However, the function and mechanism of NAA50 expression in cancer development was still unclear. Here, we systematically researched the function and mechanism of NAA50 in pan-cancer, and further verified the results of NAA50 in lung adenocarcinoma (LUAD).Methods: In this study, using the online databases TIMER2.0, SangerBox3.0, HPA, UCSC, GEPIA, cBioPortal, UALCAN, TISIDB, CancerSEA and LinkedOmics, we focused on the relevance between NAA50 and oncogenesis, progression, methylation, immune infiltration, function and prognosis. In addition, the proliferation of cells was detected by CCK-8 and Edu assay. Finally, we analyzed the relationship between the expression of NAA50 and cell cycle related proteins.Results: Pan-cancer analysis indicated that NAA50 was overexpressed in most cancers. And there was a significant correlation between NAA50 expression and the prognosis of cancer patients. In the meantime, NAA50 gene changes occur in a variety of tumors. Compared with normal tissues, the methylation level of NAA50 promoter increased in most cancer tissues. In addition, the results exhibited that in most cancers, NAA50 was significantly positively correlated with bone myeloid-derived suppressor cell (MDSC) infiltration and negatively correlated with T cell NK infiltration. Moreover, functional enrichment indicated that NAA50 regulates cell cycle and proliferation in LUAD. In vitro experiments testified that knockout of NAA50 could significantly inhibit the proliferation of LUAD.Conclusion: NAA50 may be a potential biomarker and oncogene of pan-cancer, especially LUAD, which may promote the occurrence and development of tumors through different mechanisms. Furthermore, NAA50 was bound up with to immune cell infiltration in pan-cancer, meaning NAA50 may be an important therapeutic target for human cancers.

ObjectiveThis study aims to determine the optimal pelvic lymph node dissection (PLND) template for radical cystectomy (RC).MethodsA systematic search was conducted using the PubMed, Embase and Cochrane Library database in December 2021. Articles comparing recurrence-free survival (RFS), disease-specific survival (DSS), overall survival (OS), and postoperative complications among patients undergoing limited PLND (lPLND), standard PLND (sPLND), extended PLND (ePLND), or super-extended PLND (sePLND) were included. A Bayesian approach was used for network meta-analysis.ResultsWe included 18 studies in this systematic review, and 17 studies met our criteria for network meta-analysis. We performed meta-analyses and network meta-analyses to investigate the associations between four PLND templates and the RFS, DSS, OS, or postoperative complications. We found that the ePLND group and the sePLND group were associated with better RFS than the sPLND group (Hazard Ratio [HR]: 0.65, 95% Credible Interval [CrI]: 0.56 to 0.78) (HR: 0.67, 95% CrI: 0.56 to 0.83) and the lPLND group (HR: 0.67, 95% CrI: 0.50 to 0.91) (HR: 0.70, 95% CrI: 0.49 to 0.99). For RFS, Analysis of the treatment ranking revealed that ePLND had the highest probabilities to be the best template. There was no significant difference between the four templates in DSS, however, analysis of the treatment ranking indicated that sePLND had the highest probabilities to be the best template. And We found that the sePLND group and the ePLND group were associated with better OS than lPLND (HR: 0.58, 95% CrI: 0.36 to 0.95) (HR: 0.63, 95% CrI: 0.41 to 0.94). For OS, analysis of the treatment ranking revealed that sePLND had the highest probabilities to be the best template. The results of meta-analyses and network meta-analyses showed that postoperative complications rates did not differ significantly between any two templates.ConclusionPatients undergoing sePLND and ePLND had better RFS but not better DSS or OS than those undergoing lPLND or sPLND templates, however, RFS did not differ between patients undergoing sePLND or ePLND. Considering that sePLND involves longer operation time, higher risk, and greater degree of difficulty than ePLND, and performing sePLND may not result in better prognosis, so it seems that there is no need for seLPND. We think that ePLND might be the optimal PLND template for RC.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022318475.

BackgroundA novel inflammatory marker called the systemic immune-inflammation index (SII) was applied to predict the prognosis of different cancers. However, the role of SII in prostate cancer (PCa) remains unclear. This systematic review aims to explore the prognostic role of SII in different stage PCa.MethodsWe comprehensively searched three public databases: PubMed, EMBASE, and the Cochrane Library. The hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were extracted to evaluate the association between SII and the prognosis and clinicopathological characteristics in different stage PCa patients.ResultsTen studies and 7,986 patients were enrolled in our meta-analysis, 1,442 patients were diagnosed with metastatic-castration resistant prostate cancer (mCRPC), and 6544 patients were diagnosed with non-metastatic prostate cancer (nmPCa). According to the pooled results, we found that a high SII was associated with worse overall survival (OS) in mCRPC patients (HR = 1.94, 95% CI: 1.26–3.01, p = 0.003), and a high SII was associated with biochemical recurrence-free survival (BFS) in nmPCa patients (HR = 1.85, 95% CI: 1.06–3.24, p = 0.031). But there was no significant association observed between SII and progression-free survival (PFS) in mCRPC patients (HR = 1.90, 95% CI: 0.87–4.14, p = 0.107). And we found that the high SII was associated with advanced tumor stage of PCa (OR = 2.19, 95% CI: 1.11–4.33, p = 0.024), presence of lymph node involvement (OR = 2.72, 95% CI: 1.96–3.76, p < 0.001) and Gleason score (OR = 1.27, 95% CI: 1.13–1.44, p < 0.001).ConclusionHigh SII was associated with bad OS in mCRPC patients, and associated with bad BFS and some adverse pathological features in nmPCa patients. We think SII can be a prognostic predictor for PCa patients. The application of SII will advance the diagnosis and treatment of different stage prostate cancer.

In the Internet of Things (IoT), security and privacy issues of physical objects are crucial to the related applications. In order to clarify the complicated security and privacy issues, the life cycle of a physical object is divided into three stages of pre-working, in-working, and post-working. On this basis, a physical object-based security architecture for the IoT is put forward. According to the security architecture, security and privacy requirements and related protecting technologies for physical objects in different working stages are analyzed in detail. Considering the development of IoT technologies, potential security and privacy challenges that IoT objects may face in the pervasive computing environment are summarized. At the same time, possible directions for dealing with these challenges are also pointed out.

BackgroundIn recent years, an increasing number of thoracic surgeons have attempted to apply no routine chest tube drainage (NT) strategy after thoracoscopic lung resection. However, the safety and feasibility of not routinely placing a chest tube after lung resection remain controversial. This study aimed to investigate the effect of NT strategy after thoracoscopic pulmonary resection on perioperative outcomes.MethodsA comprehensive literature search of PubMed, Embase, and the Cochrane Library databases until 3 January 2022 was performed to identify the studies that implemented NT strategy after thoracoscopic pulmonary resection. Perioperative outcomes were extracted by 2 reviewers independently and then synthesized using a random-effects model. Risk ratio (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. Subgroup analysis and sensitivity analysis were subsequently performed.ResultsA total of 12 studies with 1,381 patients were included. The meta-analysis indicated that patients in the NT group had a significantly reduced postoperative length of stay (LOS) (SMD = -0.91; 95% CI: -1.20 to -0.61; P < 0.001) and pain score on postoperative day (POD) 1 (SMD = -0.95; 95% CI: -1.54 to -0.36; P = 0.002), POD 2 (SMD = -0.37; 95% CI: -0.63 to -0.11; P = 0.005), and POD 3 (SMD = -0.39; 95% CI: -0.71 to -0.06; P = 0.02). Further subgroup analysis showed that the difference of postoperative LOS became statistically insignificant in the lobectomy or segmentectomy subgroup (SMD = -0.30; 95% CI: -0.91 to 0.32; P = 0.34). Although the risk of pneumothorax was significantly higher in the NT group (RR = 1.75; 95% CI: 1.14–2.68; P = 0.01), the reintervention rates were comparable between groups (RR = 1.04; 95% CI: 0.48–2.25; P = 0.92). No significant difference was found in pleural effusion, subcutaneous emphysema, operation time, pain score on POD 7, and wound healing satisfactory (all P > 0.05). The sensitivity analysis suggested that the results of the meta-analysis were stabilized.ConclusionsThis meta-analysis suggested that NT strategy is safe and feasible for selected patients scheduled for video-assisted thoracoscopic pulmonary resection.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-4-0026, identifier INPLASY202240026.

Intermittent fasting is one of the most common clinical treatments for the obesity, a main risk factor of the metabolic syndrome which can lead to a variety of diseases. Fasting-induced fat mobilization alters the metabolic state of lipid in the liver, predisposing to increase the hepatic lipid droplet aggregation and triglyceride levels. However, the underlying mechanisms regarding the lipid droplet aggregation in the liver after fasting remains elusive. Here, we report that a lipid droplet surface binding protein Cidec (cell death inducing DFFA like effector C) is activated by AMPK to regulate the hepatic lipid droplet fusion following fasting in obese mice. Specifically, we found that lipid droplets were significantly aggregated in the liver of high-fat-diet and ob/ob mice after 16 and 24 h of fasting, accompanied by the dramatically up-regulated expression of Cidec. Consistently, overexpression of Cidec in the AML12 cells resulted in the intracellular lipid droplet aggregation. Furthermore, we showed that fasting caused the up-regulated expression of AMPK, which in turn activated the transcription of Cidec through the transcription factor PPARγ. Altogether, our observations reveal that fasting-induced hepatic lipid droplet aggregation is mediated by the AMPK-activated expression of Cidec via PPARγ, extending our understanding about the molecular mechanism of the impact of fasting on the obesity and providing potential targets for the treatment of human obesity.

BackgroundWith the widespread adoption of prostatic-specific antigen (PSA) screening, the detection rates of prostate cancer (PCa) have increased. Due to the low specificity and high false-positive rate of serum PSA levels, it was difficult to diagnose PCa accurately. To improve the diagnosis of PCa and clinically significant prostate cancer (CSPCa), we established novel models on the basis of the prostate health index (PHI) and multiparametric magnetic resonance imaging (mpMRI) in the Asian population.MethodsWe retrospectively collected the clinical indicators of patients with TPSA at 4–20 ng/ml. Furthermore, mpMRI was performed using a 3.0-T scanner and reported in the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS). Univariable and multivariable logistic analyses were performed to construct the models. The performance of different models based on PSA derivatives, PHI derivatives, PI-RADS, and a combination of PHI derivatives and PI-RADS was evaluated.ResultsAmong the 128 patients, 47 (36.72%) patients were diagnosed with CSPCa and 81 (63.28%) patients were diagnosed with non-CSPCa. Of the 81 (63.28%) patients, 8 (6.25%) patients were diagnosed with Gleason Grade 1 PCa and 73 (57.03%) patients were diagnosed with non-PCa. In the analysis of the receiver operator characteristic (ROC) curves in TPSA 4–20 ng/ml, the multivariable model for PCa was significantly larger than that for the model based on the PI-RADS (p = 0.004) and that for the model based on the PHI derivatives (p = 0.031) in diagnostic accuracy. The multivariable model for CSPCa was significantly larger than that for the model based on the PI-RADS (p = 0.003) and was non-significantly larger than that for the model based on the PHI derivatives (p = 0.061) in diagnostic accuracy. For PCa in TPSA 4–20 ng/ml, a multivariable model achieved the optimal diagnostic value at four levels of predictive variables. For CSPCa in TPSA 4–20 ng/ml, the multivariable model achieved the optimal diagnostic value at a sensitivity close to 90% and 80%.ConclusionsThe models combining PHI derivatives and PI-RADS performed better in detecting PCa and CSPCa than the models based on either PHI or PI-RADS.

BackgroundThe effectiveness of robotic-assisted thoracoscopic surgery (RATS) for mediastinal masses has not been fully evaluated. This study aimed to compare the perioperative outcomes between RATS and video-assisted thoracoscopic surgery (VATS) for mediastinal masses, and then explore which group of people would benefit more from RATS.MethodsThis retrospective study compared the perioperative outcomes of patients with mediastinal masses who underwent RATS and VATS from September 2018 to December 2021. Subgroup analysis were performed according to body mass index (BMI) ranges.ResultsA total of 212 patients with mediastinal masses (106 RATS cases and 106 VATS cases) were included. Compared with the VATS group, the RATS group had a significantly reduced incidence of overall postoperative complications (5.7% vs. 14.2%, p = 0.039), complications of grade II or less (3.8% vs. 12.3%, p = 0.023), and pneumonia (2.8% vs. 9.4%, p = 0.045). Hospitalization costs were significantly higher in the RATS group (¥ 49350.0 vs. ¥ 32551.9, p 0.05). Subgroup analysis indicated that the incidence of overall postoperative complications (3.1% vs. 15.2%, p = 0.017), complications of grade II or less (1.5% vs. 12.1%, p = 0.033) and postoperative length of stay (4 days vs. 4.5 days, p = 0.046) were significantly reduced in the RATS group for overweight and obese patients (BMI ≥ 24 kg/m2), while these differences became insignificant in the BMI

BackgroundThe efficacy of sublobar resection and selective lymph node dissection is gradually being accepted by thoracic surgeons for patients within early-stage non-small cell lung cancer (NSCLC). Nevertheless, there are still some NSCLC patients develop lymphatic metastasis at clinical T1 stage. Lung adenocarcinoma with a micropapillary (MP) component poses a higher risk of lymph node metastasis and recurrence even when the MP component is not predominant. Our study aimed to explore the genetic features and occult lymph node metastasis (OLNM) risk factors in patients with a non-predominant micropapillary component (NP-MPC) in a large of patient’s cohort with surgically resected lung adenocarcinoma.MethodsBetween January 2019 and December 2021, 6418 patients who underwent complete resection for primary lung adenocarcinoma at the Qilu Hospital of Shandong University. In our study, 442 patients diagnosed with lung adenocarcinoma with NP-MPC with a tumor size ≤3 cm were included. Genetic alterations were analyzed using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Abnormal protein expression of gene mutations was validated using immunohistochemistry. A nomogram risk model based on clinicopathological parameters was developed to predict OLNM. This model was invalidated using the calibration plot and concordance index.ResultsIn our retrospective cohort, the incidence rate of the micropapillary component was 11.17%, and OLNM was observed in 20.13% of the patients in our study. ARMS-PCR suggested that EGFR exon 19 del was the most frequent alteration in NP-MCP patients compared with other gene mutations (frequency: 21.2%, P

Emerging studies have indicated that long non-coding RNAs (lncRNAs) play important roles in skeletal muscle growth and development. Nevertheless, it remains challenging to understand the function and regulatory mechanisms of these lncRNAs in muscle biology and associated diseases. Here, we identify a novel lncRNA, Mir22hg, that is significantly upregulated during myoblast differentiation and is highly expressed in skeletal muscle. We validated that Mir22hg promotes myoblast differentiation in vitro. Mechanistically, Mir22hg gives rise to mature microRNA (miR)-22-3p, which inhibits its target gene, histone deacetylase 4 (HDAC4), thereby increasing the downstream myocyte enhancer factor 2C (MEF2C) and ultimately promoting myoblast differentiation. Furthermore, in vivo, we documented that Mir22hg knockdown delays repair and regeneration following skeletal muscle injury and further causes a significant decrease in weight following repair of an injured tibialis anterior muscle. Additionally, Mir22hg gives rise to miR-22-3p to restrict HDAC4 expression, thereby promoting the differentiation and regeneration of skeletal muscle. Given the conservation of Mir22hg between mice and humans, Mir22hg might constitute a promising new therapeutic target for skeletal muscle injury, skeletal muscle atrophy, as well as other skeletal muscle diseases.

Abstract DDRGK domain-containing protein 1 (DDRGK1) is an important component of the newly discovered ufmylation system and its absence has been reported to induce extensive endoplasmic reticulum (ER) stress. Recently, emerging evidence indicates that the ufmylation system is correlated with autophagy, although the exact mechanism remains largely unknown. To explore the regulation mechanism of DDRGK1 on autophagy, in this study, we established an immortalized mouse embryonic fibroblast (MEF) cell lines harvested from the DDRGK1F/F:ROSA26-CreERT2 mice, in which DDRGK1 depletion can be induced by 4-hydroxytamoxifen (4-OHT) treatment. Here, we show that DDRGK1 deficiency in MEFs has a dual effect on autophagy, which leads to a significant accumulation of autophagosomes. On one hand, it promotes autophagy induction by impairing mTOR signaling; on the other hand, it blocks autophagy degradation by inhibiting autophagosome–lysosome fusion. This dual effect of DDRGK1 depletion on autophagy ultimately aggravates apoptosis in MEFs. Further studies reveal that DDRGK1 loss is correlated with suppressed lysosomal function, including impaired Cathepsin D (CTSD) expression, aberrant lysosomal pH, and v-ATPase accumulation, which might be a potential trigger for impairment in autophagy process. Hence, this study confirms a crucial role of DDRGK1 as an autophagy regulator by controlling lysosomal function. It may provide a theoretical basis for the treatment strategies of various physiological diseases caused by DDRGK1 deficiency.

(1) Background: The study aimed to construct nomograms to improve the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CSPCa) in the Asian population. (2) Methods: This multicenter prospective study included a group of 293 patients from three hospitals. Univariable and multivariable logistic regression analysis was performed to identify potential risk factors and construct nomograms. Discrimination, calibration, and clinical utility were used to assess the performance of the nomogram. The web-based dynamic nomograms were subsequently built based on multivariable logistic analysis. (3) Results: A total of 293 patients were included in our study with 201 negative and 92 positive results in PCa. Four independent predictive factors (age, prostate health index (PHI), prostate volume, and prostate imaging reporting and data system score (PI-RADS)) for PCa were included, and four factors (age, PHI, PI-RADS, and Log PSA Density) for CSPCa were included. The area under the ROC curve (AUC) for PCa was 0.902 in the training cohort and 0.869 in the validation cohort. The AUC for CSPCa was 0.896 in the training cohort and 0.890 in the validation cohort. (4) Conclusions: The combined diagnosis of PHI and PI-RADS can avoid more unnecessary biopsies and improve the detection rate of PCa and CSPCa. The nomogram with the combination of age, PHI, PV, and PI-RADS could improve the detection of PCa, and the nomogram with the combination of age, PHI, PI-RADS, and Log PSAD could improve the detection of CSPCa.

Dementia is a severe disease threatening ageing societies, which not only causes great harm to patients both physically and psychologically but also places a heavy burden on patients' families. Medications have been used for the treatment of dementia but with little success. However, serious games, as a new form of dementia therapy, stand out from various therapeutic methods and pave the way for dementia treatment. In the field of serious games for dementia care (SGDC) in ageing societies, there exists abundant research related to this topic. While, a detailed review of the development route and a category framework for characteristics of dementia are still needed. Besides, due to the large number of games, it is difficult to select out effective ones. Yet, there is no unified and comprehensive assessment methods for SGDC. So a reliable assessment model is worth studying. In this paper, we review these existing research work on SGDC from two perspectives: (1) the development of SGDC; (2) the different symptoms in different dementia stages. We also propose a comprehensive and professional assessment model of the therapeutic effectiveness of SGDC to compensate for the simplicity of existing assessment methods. Finally, a discussion related to SGDC is presented.

Background: Pneumonectomy is a drastic but sometimes inevitable treatment option for patients with non-small-cell lung cancer (NSCLC) to improve their chances for long-term survival. However, the optimal adjuvant radiotherapy used for patients with N2 NSCLC following pneumonectomy remains unclear in the literature. Methods: T1-4N0-2M0 NSCLC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Propensity score matching was applied to balance the assignment of patients. Cox proportional hazards models and Kaplan–Meier analyses were used to identify the factors related to overall survival rates. Restricted cubic splines were used to detect the possible nonlinear dependency of the relationship between the risk of survival and age. Results: A total of 4308 NSCLC patients were enrolled in this study. In N2 patients, the long-term outcome of the chemotherapy and postoperative radiotherapy groups was the worst (p = 0.014). Subgroup analyses showed that the influence of age on survival outcome was confined to patients who received chemotherapy and neoadjuvant radiotherapy (p = 0.004). Meanwhile, patients >65 years of age who received chemotherapy and neoadjuvant radiotherapy had significantly worse prognoses than those in the chemotherapy group (p = 0.005). Conclusions: Our results show that neoadjuvant radiotherapy may have potential benefits in patients aged ≤ 65 years who are scheduled for pneumonectomy, but not in elderly patients.

Objective As one of the most important metabolic organs, the liver plays vital roles in modulating the lipid metabolism. This study was to compare miRNA expression profiles of the Large White liver between two different developmental periods and to identify candidate miRNAs for lipid metabolism. Methods Eight liver samples were collected from White Large of 70-day fetus (P70) and of 70-day piglets (D70) (with 4 biological repeats at each development period) to construct sRNA libraries. Then the eight prepared sRNA libraries were sequenced using Illumina next-generation sequencing technology on HiSeq 2500 platform. Results As a result, we obtained 346 known and 187 novel miRNAs. Compared with the D70, 55 down- and 61 up-regulated miRNAs were shown to be significantly differentially expressed (DE). Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis indicated that these DE miRNAs were mainly involved in growth, development and diverse metabolic processes. They were predicted to regulate lipid metabolism through adipocytokine signaling pathway, mitogen-activated protein kinase, AMP-activated protein kinase, cyclic adenosine monophosphate, phosphatidylinositol 3 kinase/protein kinase B, and Notch signaling pathway. The four most abundantly expressed miRNAs were miR-122, miR-26a and miR-30a-5p (miR-122 only in P70), which play important roles in lipid metabolism. Integration analysis (details of mRNAs sequencing data were shown in another unpublished paper) revealed that many target genes of the DE miRNAs (miR-181b, miR-145-5p, miR-199a-5p, and miR-98) might be critical regulators in lipid metabolic process, including acyl-CoA synthetase long chain family member 4, ATP-binding casette A4, and stearyl-CoA desaturase. Thus, these miRNAs were the promising candidates for lipid metabolism. Conclusion Our study provides the main differences in the Large White at miRNA level between two different developmental stages. It supplies a valuable database for the further function and mechanism elucidation of miRNAs in porcine liver development and lipid metabolism.

The different skeletal muscle fiber types exhibit distinctively different physiological and metabolic properties, and have been linked to both human metabolic diseases and meat quality traits in livestock. Circular RNAs (circRNAs) are a new class of endogenous RNA regulating gene expression, but regulatory mechanisms of skeletal muscle fibers involved in circRNAs remain poorly understood. Here, we constructed circRNA expression profiles of three fast-twitch biceps femoris (Bf) and three slow-twitch soleus (Sol) muscles in pigs using RNA-seq and identified 16,342 distinct circRNA candidates. Notably, 242 differentially expressed (DE) circRNAs between Bf and Sol muscles were identified, including 105 upregulated and 137 downregulated circRNAs, and are thus potential candidates for the regulation of skeletal muscle fiber conversion. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of host genes of DE circRNAs revealed that host genes were mainly involved in skeletal muscle fiber-related GO terms (e.g., muscle contraction, contractile fiber part, and Z disk) and skeletal muscle fiber-related signaling pathways (e.g., AMPK and cGMP-PKG). We also constructed co-expression networks of DE circRNA-miRNA-mRNA using previously acquired high-throughput sequencing mRNA and miRNA data, from which 112 circRNA-miRNA and 95 miRNA-mRNA interactions were identified. Multiple circRNAs essentially serve as a sponge for miR-499-5p, which is preferentially expressed in slow-twitch muscle and reduces the severity of Duchenne muscular dystrophy (DMD). Taken together, a series of novel candidate circRNAs involved in the growth and development of porcine skeletal muscle was identified. Furthermore, they provide a comprehensive circRNA resource for further in-depth research on the regulatory mechanisms of circRNA in the formation of skeletal muscle fiber, and may provide insights into human skeletal muscle diseases.

The Meishan pig is a traditional Chinese native breed, known for its excellent reproduction performance that is widely used in commercial pig production through two-way or three-way crossbreeding systems. However, the lean meat yield of Meishan crossbred pigs is still very low and cannot meet the market demand. To evaluate the lean meat yield of Meishan crossbred pigs, six wild-type Meishan sows were artificially inseminated by using the MSTN+/− Duroc boar semen in this experiment. Some reproductive performance-related traits of Meishan sows were recorded to ensure that semen from MSTN knockout Duroc boar did not affect offspring production, including total births, live births, sex, and litter weight. In total, 73 piglets were obtained and 63 were alive. Male to female ratio was close to 1: 1. because of factors such as disease, only 43 pigs were utilized, including 28 MSTN mutant pigs (MSTN+/−) and 15 MSTN homozygous pigs (MSTN+/+). We compared the growth performance and carcass performance of these full or half-sib populations and found that there were no differences between MSTN+/− and MSTN+/+ genotypes for live animal measures including average daily gain (ADG), body dimensions, or ultrasonic measurement of fat thickness when pigs were harvested after 120 days of feeding. Conversely, the MSTN+/− pigs had higher dressing percentage and lean meat percentage, lower level of carcass fat, larger longissimus muscle area, less percentage of skin and skeleton, thinner average backfat thickness, and lower intramuscular fat (IMF) content than MSTN+/+ pigs. In conclusion, the production of MSTN+/− mutant progeny from Meishan females resulted in improved carcass composition, providing a feasible solution to improve the lean meat yield of Chinese local fat-type pig breeds.

Prox1 is involved in muscle fiber conversion, adult-onset obesity, and type 2 diabetes. However, information regarding porcine Prox1 and its relationship with meat quality traits is still unknown. In this study, we characterized the full-length cDNA and proximal promoter of two transcript variants of porcine Prox1. Moreover, Prox1 was expressed abundantly in the skeletal muscle and its expression was higher in the soleus muscle than that in the biceps femoris muscle. Its expression pattern in the high and low meat color (redness) value a* groups was similar to that of myoglobin and MyHC I, but opposed to that of MyHC IIB. Importantly, there was a significant positive correlation between Prox1 expression and meat color (redness) value a* (r = 0.3845, p = 0.0394), and a significant negative correlation between Prox1 expression and drip loss (r = −0.4204, p = 0.0232), as well as the ratio of MyHC IIB to MyHC I expression (r = −0.3871, p = 0.0380). In addition, we found that the polymorphisms of three closely linked SNPs in Prox1 promoter 1 were significantly associated with pH24h in a pig population. Taken together, our data provide valuable insights into the characteristics of porcine Prox1 and indicate that Prox1 is a promising candidate gene affecting meat quality traits.

Intramuscular fat (IMF) content is an important indicator for meat quality evaluation. However, the key genes and molecular regulatory mechanisms affecting IMF deposition remain unclear. In the present study, we identified 75 differentially expressed genes (DEGs) between the higher (H) and lower (L) IMF content of pigs using transcriptome analysis, of which 27 were upregulated and 48 were downregulated. Notably, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the DEG perilipin-1 (PLIN1) was significantly enriched in the fat metabolism-related peroxisome proliferator-activated receptor (PPAR) signaling pathway. Furthermore, we determined the expression patterns and functional role of porcine PLIN1. Our results indicate that PLIN1 was highly expressed in porcine adipose tissue, and its expression level was significantly higher in the H IMF content group when compared with the L IMF content group, and expression was increased during adipocyte differentiation. Additionally, our results confirm that PLIN1 knockdown decreases the triglyceride (TG) level and lipid droplet (LD) size in porcine adipocytes. Overall, our data identify novel candidate genes affecting IMF content and provide new insight into PLIN1 in porcine IMF deposition and adipocyte differentiation.