Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To investigate the predictive value of systemic immune inflammation index(SII)scores in long-term survival of patients with stage Ⅲ squamous lung cancer treated with radical radiotherapy.Methods Clinical data of stage Ⅲ squamous lung cancer patients who underwent radical radiotherapy at the Radiotherapy Department of the Fourth Hospital of Hebei Medical University from January 2010 to December 2018 were retrospectively analyzed.The peripheral hematological indexes one week before radiotherapy were collected and recorded.X-Tile software was applied to determine the best cut-off values for continuous variables.Kaplan-Meier method was used to analyze overall survival(OS)and progression-free survival(PFS).Results A total of 453 patients were included in this study.There were 336 patients in the low SII group(＜1 277.3),and other 117 patients were in the high SII group(≥1 277.3).The median OS and median PFS in the high SII group were shorter than those in the low SII group(OS:20.8 months vs.31.0 months,Log-rank χ2=18.015,P＜0.01;PFS:13.0 months vs.21.0 months,Log-rank χ2=15.062,P＜0.01).Multivariate Cox regression analysis showed that high SII was associated with OS(HR=1.628,95%CI:1.294-2.047,P<0.001)and PFS(HR=1.559,95%CI:1.240-1.961,P<0.001).Other influencing factors included late TNM stage,poor radiotherapy efficacy and decreased HALP score.Conclusion SII can be used to evaluate the long-term survival of patients with stage Ⅲ lung squamous cell carcinoma receiving radical radiotherapy,and the increase of SII indicates a poor prognosis.

Objective:To analyze the local recurrence patterns after concurrent chemoradiotherapy (CCRT) for thoracic esophageal squamous cell carcinoma (ESCC) through image fusion, and to explore the risk factors of local recurrence and its relationships with dosimetric indices.Methods:A retrospective analysis was conducted for 209 thoracic ESCC patients who received radical CCRT in Fourth Hospital of Hebei Medical University during 2016-2019. For the patients diagnosed as the local recurrence of esophageal lesions, their CT images were fused with the original planning CT images using image registration software to identify the recurrence sites. Through 1∶1 propensity score matching (PSM) of the clinal data of patients with local recurrence (the recurrence group, nbefore = 81, nafter = 62) and those without local recurrence (the recurrence-free group, nbefore = 128, nafter=62), the dose and volume parameters of the treatment plans for the two groups were compared. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and the Cox regression model to analyze the factors affecting the overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Results:All patients had 1-, 3-, and 5-year OS rates of 80.9%, 42.6%, and 33.0%, respectively, 1-, 3-, and 5-year PFS rates of 67.9%, 34.0%, and 27.9%, respectively, and 1-, 3-, and 5-year RFS rates of 71.3%, 39.2%, and 30.5%, respectively. T stage, N stage, and radiation dose were independent prognostic factors for the OS, PFS, and RFS ( HR = 1.42-1.87, P < 0.05) of the patients, respectively. Among 68 patients with local recurrence, 62 cases (91.2%) suffered recurrence within the gross tumor volume (GTV). The dose and volume parameters of patients with local recurrence, such as GTV- D95%, clinical target volume (CTV)- D95%, GTV- D50%, CTV- D50%, and planning target volume (PTV)- D50%, GTV- V60, CTV- V60, and PTV- V60, were significantly lower than those of patients free from the local recurrence ( t=1.90-2.15, P < 0.05). Conclusions:Local recurrence of patients with thoracic ESCC after radical CCRT occurs mainly within the GTV. Increasing radiation doses may contribute to their survival benefits. The D50% for each target volume in the radiotherapy plan may be related to local recurrence, and it is necessary to conduct further research.

Objective To investigate the efficacy and safety of bivalirudin versus unfractionated heparin during perioperative primary percutaneous coronary intervention(PCI)in elderly patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 423 elderly patients with acute STEMI who underwent primary PCI in our hospital were consecutively en-rolled in this study.According to different perioperative anticoagulant regimens,they were divided into bivalirudin group(187 cases)and unfractionated heparin group(236 cases).Baseline data,characteristics of interventional procedures and complications during hospitalization were ana-lyzed.Primary endpoint was major adverse cardiac or cerebral events(MACCE).Secondary end-points were net adverse clinical events.Other observational indicators included stent thrombosis,acquired thrombocytopenia,BARC types 1-2 bleeding and total bleeding events.Results In-hospital MACCE and all-cause mortality were significantly lower in the bivalirudin group than unfractionated heparin group(3.7％vs 9.7％,P=0.021;3.7％vs 8.9％,P=0.039).Univariate logistic regression analysis showed that perioperative application of bivalirudin significantly reduced all-cause mortality in the patients with Killip grade Ⅰ and creatinine clearance ≥60 ml/min when compared with unfractionated heparin(P＜0.05).Conclusion In elderly patients with acute STEMI,perioperative use of bivalirudin significantly reduces the incidences of MACCE and all-cause death during hospitalization,especially in the patients with Killip grade Ⅰ and creatinine clearance ≥60 ml/min.

Aiming at the problems of individual differences in the asynchrony process of human lower limbs and random changes in stride during walking, this paper proposes a method for gait recognition and prediction using motion posture signals. The research adopts an optimized gated recurrent unit (GRU) network algorithm based on immune particle swarm optimization (IPSO) to establish a network model that takes human body posture change data as the input, and the posture change data and accuracy of the next stage as the output, to realize the prediction of human body posture changes. This paper first clearly outlines the process of IPSO's optimization of the GRU algorithm. It collects human body posture change data of multiple subjects performing flat-land walking, squatting, and sitting leg flexion and extension movements. Then, through comparative analysis of IPSO optimized recurrent neural network (RNN), long short-term memory (LSTM) network, GRU network classification and prediction, the effectiveness of the built model is verified. The test results show that the optimized algorithm can better predict the changes in human posture. Among them, the root mean square error (RMSE) of flat-land walking and squatting can reach the accuracy of 10 ^-3, and the RMSE of sitting leg flexion and extension can reach the accuracy of 10 ^-2. The R ² value of various actions can reach above 0.966. The above research results show that the optimized algorithm can be applied to realize human gait movement evaluation and gait trend prediction in rehabilitation treatment, as well as in the design of artificial limbs and lower limb rehabilitation equipment, which provide a reference for future research to improve patients' limb function, activity level, and life independence ability.
Algorithms ; Gait ; Humans ; Machine Learning ; Neural Networks, Computer ; Walking

The pathogenesis of hepatocellular carcinoma is complex and has not been fully clarified. KLF4, also known as gut-enriched Kruppel-like factor (GKLF), plays the dual regulatory role of tumor suppressor and tumor promoter. KLF4 plays an anti-cancer role in liver cancer. This article introduces the biological function and regulatory mechanism of KLF4 in the progression of liver cancer, and research on the mechanism of action of KLF4 in liver cancer is expected to provide new ideas for targeted therapy and prognosis monitoring of liver cancer.

Objective: To study the relationship between the dose-volume indexes and acute toxicity of intrathoracic stomach in esophageal cancer patients receiving radiotherapy after esophagectomy. Methods: A total of 104 patients treated with postoperative radiotherapy followed by radical esophagectomy were enrolled. The dose-volume indexes of intrathoracic stomach were collected from treatment planning system. The ROC curve and logistic regression were performed to analyze the relationship between acute toxicity of intrathoracic stomach and clinical parameters, dose-volume indexes. Results: A total of 29 patients (27.88 %) suffered from grade 2 or above acute toxicity. The ROC curve analysis showed that the dose-volume indexes including D_max, D_mean, L₅-L₄₅ and V₅-V₅₀were associated with occurrence of grade 2 or above acute toxicity. The univariate analysis showed that location, D_max, D_mean, L₅-L₄₅ and V₅-V₅₀ were significantly correlated with the incidence of grade 2 or above acute toxicity (P<0.05). The multivariate analysis showed that location, L₅ and V₃₅ were independent factors for incidence of grade 2 or above acute toxicity. The ROC curve analysis showed that cut-off values of L₅ and V₃₅ were 14.00 cm and 44.00%, respectively. And the rates of Grade 2 or above acute toxicity were 20.00% for L₅>14.00 cm and 38.64% for L₅≥14.00 cm (χ²=4.473, P<0.05), 14.08% for V₃₅<44.00% and 57.58% for V₃₅≥44.00% (χ²=7.263, P<0.05), respectively. The incidence of grade 2 or above acute toxicity was significantly higher in post-mediastinum stomach group than the other two groups (χ²=12.881, P<0.05). Conclusions Dose-volume index may be indicator to predict acute toxicity of intrathoracic stomach. It is recommended that post-mediastinum stomach should be chosen carefully if esophageal cancer patients require postoperative radiotherapy.

In recent years, the incidence of stroke in young adults, especially ischemic stroke, has been increasing worldwide. Due to its high disability, high mortality, and high recurrence, it has brought a serious burden to society and families. The common causes of ischemic stroke in young adults include large artery atherosclerosis and small vessel occlusion, while the rare causes such as patent foramen ovale, hereditary cerebral small vessel disease, cerebral artery dissection, moyamoya disease, vasculitis, and cryptogenic stroke also account for a high proportion. Its pathogenesis is complex, and diagnosis and treatment are difficult. This article reviews the latest research progress of the pathogenesis of ischemic stroke in young adults.

Objective:To evaluate the recurrence patterns of esophageal squamous cell carcinoma (ESCC) after radical surgery and analyze the predictors of post-recurrence survival (PRS).Methods:A total of 382 ESCC patients who developed recurrence after radical surgery were retrospectively reviewed from January 2007 to December 2011. All of them received salvage treatment after recurrence. The Univariate analysis was determined using the Kaplan-Meier method and log-rank test. Multivariate prognostic analysis was determined using the Cox proportional hazard model.Results:The 1-, 3-, 5-year overall survival (OS) rates were 80.9%, 35.6% and 20.4%, respectively. The median survival time and recurrence time were 29.2 months and 15.0 months. The 1-, 3-, 5-year PRS rates were 37.7%, 14.6% and 11.9%, respectively. The median PRS time was 10.2 months. Locoregional recurrence was noted at 462 sites among 382 patients including 20.5% (95/462) of sites in supraclavicular LN (lymph node), 10.0% (46/462) in anastomosis, 56.1% (259/462) in mediastinal regional LN and 13.4% (62/462) in upper abdominal LN. There were 156, 43, 82 and 101 patients treated with salvage radiotherapy, chemotherapy, chemoradiotherapy and palliative care after recurrence, respectively. The univariate analysis showed that T stage, N stage, TNM stage, recurrence site, number of recurrent regions and treatment regimen after recurrence were significantly correlated with PRS ( χ2=5.336, 4.292, 8.067, 7.482, 4.093, 76.426, P<0.05). Patients receiving salvage radiotherapy with the median dose of 60 Gy, were divided into <60 Gy group and ≥ 60 Gy group. The ≥60 Gy group had a better PRS than <60 Gy group ( χ2=8.320, P<0.05). Multivariate analysis showed that number of recurrent regions and treatment regimen were independent prognostic factors of PRS. Conclusions:Mediastinal and supraclavicular regions were the most common sites of recurrence in ESCC patients after radical surgery. Salvage radiotherapy and chemoradiotherapy could significantly improve PRS in recurrent ESCC patients.

OBJECTIVE： To establish a method for rapid determination of total phenylethanoid glycosides and total iridoid glycosides in the root of Rehmannia glutinosa. METHODS： The contents of total phenylethanoid glycosides and total iridoid glycosides in medicinal material samples were determined by UV spectrophotometry. Quantitative model of total phenylethanoid glycosides and total iridoid glycosides in medicinal samples was established by NIRS-PLS method. The optimal pretreatment spectra were multivariate scattering correction combined with first derivative method， standard normalization combined with first derivative method. The optimum spectral ranged from 6 703.35-11 065.54 cm－1 and 3 999.63-9 102.36 cm－1. The optimum principal factor number were 10 and 7. RESULTS： The content determination of total phenylethanoid glycosides and total iridoid glycosides in medicinal material samples was proved to meet the requirements by methodological experience. The internal cross validation determination coefficients of total phenylethanoid glycosides and total iridoid glycosides were 0.998 2 and 0.980 9. The correction of root mean square error was 0.032 7 and 0.186 0. The root mean square error of prediction were 0.035 5 and 0.035 1. The root mean square error of cross validation were 0.256 9 and 0.574 3. The predicted values of total phenylethanol glycosides and total iridoid glycosides were 0.268％-1.636％ and 3.424％-6.978％， respectively； the determination value of them were 0.299％-1.629％ and 3.431％-6.952％， respectively； the absolute deviations were －0.042％-0.067％ and －0.111％-0.088％， respectively；the relative deviations were －0.819％-0.076％、－2.257％-1.672％， respectively；There was no statistical significance between predicted values and measured values （P＞0.05）. CONCLUSIONS： The method is accurate and simple. The method can be used for the rapid determination of total phenylethanoid glycosides and total iridoid glycosides in different germplasms of R. glutinosa.