Hepatocellular carcinoma(HCC)is one of the most common malignancies with high morbidity and mortality rates worldwide.With the advances in molecular biology and tumor immunology,molecular-targeted agents represented by tyrosine kinase inhibitors(such as sorafenib and lenvatinib)and immunotherapy represented by PD-1/PD-L1 monoclonal antibodies have brought hope for patients with advanced HCC.The combination of immunotherapy and anti-angiogenic therapy can further improve the treatment outcome of patients.In addition,the optimization and integration of stereotactic body radiotherapy,local treatment,and systemic treatment may maximize the benefits of patients.In the future,through a deep understanding of the heterogeneity of HCC,the development of precision molecular subtyping and individualized treatment,and the establishment of a multidisciplinary collaborative diagnosis and treatment system,systemic therapy is expected to achieve long-term management of advanced HCC.This article reviews the current status and advances in systemic therapy for advanced HCC.

Polycystic ovary syndrome (PCOS) is a common disease among women of childbearing age, and hyperandrogenism (HA) is a typical clinical feature of PCOS patients. In recent years, research has found that HA is closely related to the liver function of PCOS patients, in addition to causing reproductive, endocrine, and metabolic disorders. This article provides a review from four aspects: the relationship between PCOS and HA, the impact of HA on liver function in PCOS patients, the mechanism of HA affecting liver function in PCOS, and the intervention of HA on improving liver function in PCOS. The aim is to further raise awareness of the multi system effects of HA on PCOS patients and provide a basis and approach for improving liver function and clinical prognosis in PCOS patients.

Purpose: To intelligently diagnose whether there is bladder outlet obstruction (BOO) in female with decent detrusor contraction ability by focusing on urodynamic study (UDS) data. Materials and Methods: We retrospectively reviewed the UDS data of female patients during urination. Eleven easily accessible urinary flow indicators were calculated according to the UDS data of each patient during voiding period. Eight diagnosis models based on back propagation neural network with different input feature combination were constructed by analyzing the correlations between indicators and lower urinary tract dysfunction labels. Subsequently, the stability of diagnostic models was evaluated by five-fold cross-validation based on training data, while the performance was compared on test dataset. Results: UDS data from 134 female patients with a median age of 51 years (range, 27–78 years) were selected for our study.Among them, 66 patients suffered BOO and the remaining were normal. Applying the 5-fold cross-validation method, the model with the best performance achieved an area under the receiver operating characteristic curve (AUC) value of 0.949±0.060 using 9 UDS input features. The accuracy, sensitivity, and specificity for BOO diagnosis model in the testing process are 94.4%, 100%, and 89.3%, respectively. Conclusions The 9 significant indicators in UDS were employed to construct a diagnostic model of female BOO based on machine learning algorithm, which performs preferable classification accuracy and stability.

ObjectiveTo compare the retest reliability and discriminant validity of dynamic postural stability indices for functional ankle instability (FAI) obtained by different algorithms based on acceleration signals at different positions of human body. MethodsFrom April to June, 2021, 21 subjects with unilateral FAI and 21 subjects with normal ankle were recruited. Three inertial sensors were attached to the waist points, knee and ankle positions. The ground reaction force (GRF) and kinematics data of the subjects in multi-direction single leg landing test were collected synchronously by 3D force plate and inertial sensors. The unbounded third order polynomial (UTOP) fitting method was used to calculate the stability time, and the root mean square was used to caculate the stability index. ResultsMost of the indicators calculated based on acceleration signal correlated with that based on GRF with low coefficient (|r| = 0.116 to 0.368, P < 0.05). The stability time and stability index based on the acceleration signals of different positions of human body showed low to high retest reliability (CMC 0.30 to 0.91). For the females, among the stability time based on acceleration signal, eleven indexes achieved average to very high discriminant validity (AUC = 0.702 to 0.942, P < 0.05); eight of the stability indexes reached general level of discriminant validity (AUC = 0.717 to 0.782, P < 0.05). No algorithms achieved good discriminant effect in male subjects. ConclusionBased on the acceleration signal of waist point in single-leg landing stability test, the stability time calculated by UTOP algorithm can evaluate the dynamic postural stability of female FAI patients with high discriminant validity and medium to high retest reliability.

Objective:To investigate the risk factors of hypoalbuminemia (HA) in patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) after endovascular mechanical thromboectomy (EMT) and impact on outcomes.Methods:Patients first diagnosed with anterior circulation LVO-AIS and underwent emergency EMT at the Department of Acute Stroke, the Affiliated Hospital of Jining Medical University from June 1, 2020 to April 31, 2023 were retrospectively included. According to the first follow-up serum albumin examination after procedure (6-8 d), the patients were divided into HA group (<35 g/L) and non-HA group (≥35 g/L). According to the modified Rankin Scale score at 90 d after EMT, the patients were divided into a good outcome group (0-2) and a poor outcome group (3-6). Univariate and multivariate logistic analysis was used to determine independent risk factors for HA after EMT and their impact on outcomes. Results:A total of 144 patients were enrolled, including 107 males (74.30%) with a median age of 64 years (interquartile range, 56-71 years). There were 50 patients (34.72%) in the HA group and 94 (65.28%) in the non-HA group; 60 (41.67%) in the good outcome group, and 84 (58.33%) in the poor outcome group. Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.061, 95% confidence interval [ CI] 1.014-1.111; P=0.011) and pulmonary infection ( OR 5.136, 95% CI 1.917-13.760; P=0.001) were independent risk factors for HA; HA ( OR 4.345, 95% CI 1.367-13.814; P=0.013), pneumonia ( OR 5.113, 95% CI 1.217-12.528; P=0.026), and onset to reperfusion time ( OR 5.473, 95% CI 1.090-16.05; P=0.038) were independent risk factors for poor outcomes. Conclusions:Age and pulmonary infection are independent risk factors for HA in LVO-ASI patients after EMT, and HA is the independent risk factor for poor outcomes of the patients.

Objective:To explore the effects of miR-451 on glycolysis and apoptosis of breast cancer cells by regulating the Rho/ROCK1 pathway.Methods:Breast cancer MCF7 cells were divided into breast cancer cells (BC) group, breast cancer cells + miR-451-NC (MN) group, breast cancer cells + miR-451 inhibitor (MI) group, breast cancer cells + miR-451 mimic (MM) group, breast cancer cells + lysophosphatidic acid (BL) group, breast cancer cells + fasudil (BF) group, and breast cancer cells + miR-451 mimic + fasudil (MF) group. Glucose uptake detection kit and lactate detection kit were used to detect cell glycolysis, DAPI staining was used to detect cell apoptosis, Western blotting was used to detect Rho/ROCK1 pathway protein expression, and double luciferase reporting assay was used to confirm the interaction between miR-451 and Rho/ROCK1.Results:The glucose intake of cells in the BC group, MN group, MI group and MM group were (14.22±2.36) ×10 5 mg/h, (14.20±2.37) ×10 5 mg/h, (21.55±2.43) ×10 5 mg/h, (6.19±1.34) ×10 5 mg/h ( F=5.30, P<0.001), respectively, and lactic acid production were (1.52±0.21) ×10 5 μg/h, (1.53±0.22) ×10 5 μg/h, (2.05±0.32) ×10 5 μg/h, (0.54±0.12) ×10 5 μg/h ( F=3.28, P=0.008), respectively. The apoptosis rates were (10.13±1.35) %, (10.16±1.37) %, (5.36±1.24) %, (28.47±2.56) % ( F=6.36, P<0.001), respectively. The expressions of Rho protein were 2.31±0.46, 2.32±0.41, 2.95±0.35, 1.05±0.25 ( F=2.86, P=0.017), respectively. The expressions of ROCK1 protein were 2.51±0.41, 2.52±0.42, 3.05±0.33, 1.15±0.13 ( F=2.43, P=0.035), and there were statistically significant differences between the MN and MI groups, MN and MM groups, MI and MM groups (all P<0.05). The glucose intake in the BC group, BL group and BF group were (14.22±2.36) ×10 5 mg/h, (21.54±2.40) ×10 5 mg/h, (6.20±1.35) ×10 5 mg/h ( F=5.33, P<0.001), respectively. Lactic acid production were (1.52±0.21) ×10 5 μg/h, (2.01±0.30) ×10 5 μg/h, (0.55±0.12) ×10 5 μg/h ( F=3.28, P=0.008), respectively. The apoptosis rates were (10.13±1.35) %, (5.34±1.22) %, (28.44±2.54) % ( F=6.45, P<0.001). The expressions of Rho protein were 2.31±0.46, 2.94±0.45, 1.01±0.24 ( F=2.40, P=0.037), respectively, and the expressions of ROCK1 protein were 2.51±0.41, 3.08±0.42 and 1.13±0.12, respectively ( F=2.38, P=0.039). The pairwise comparisons among the three groups were statistically significant (all P<0.05). In the MF group, glucose intake was (3.21±0.89) ×10 5 mg/h, lactic acid production was (0.33±0.04) ×10 5 μg/h, apoptosis rate was (38.01±2.87) %, Rho protein expression was 0.55±0.14, and ROCK1 protein expression was 0.51±0.10. There were statistically significant differences among the MM group, BF group and MF group ( F=4.53, P=0.001; F=4.26, P=0.002; F=6.12, P<0.001; F=4.06, P=0.002; F=9.72, P<0.001), and there were statistically significant differences between the MF group and BF group (all P<0.05). Dual luciferase report showed that miR-451 transfection significantly decreased the luciferase activity of ROCK1-3'-UTR-WT (0.59±0.03 vs. 1.01±0.05, t=17.64, P<0.001), but had no significant effect on mutated genes (1.01±0.07 vs. 1.02±0.04, t=0.30, P=0.767) . Conclusion:Overexpression of miR-451 can significantly inhibit glycolysis of breast cancer cells and promote apoptosis of breast cancer cells, the mechanism of which may be related to inhibition of Rho/ROCK1 pathway.

Objective To explore the relationship between non-high density lipoprotein cholesterol(non-HDL-C)level and leptomeningeal collateral circulation in patients with acute middle cerebral artery occlusion.Methods A total of 85 patients with first-onset acute cerebral infarction with middle cerebral artery M1 segment occlusion were enrolled.According to the results of DSA,LMC circulation was assessed by American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology Collateral Circulation Assess-ment System.All patients were assigned to better LMC circulation group(score 2～4,n = 30)and worse LMC circulation group(score 0～1,n = 55),and the levels of non-HDL-C were compared between the two groups.Results The levels of LDL-C and non-HDL-C in worse LMC circulation group were significantly higher than those of the better LMC circulation group(P = 0.026,P = 0.010).non-HDL-C was an independent risk factor for the worse LMC circulation(OR = 3.019,95%CI:1.053～8.658,P = 0.04).LMC circulatory score of patients was negatively correlated with the levels of non-HDL-C level(r =-0.228,P = 0.036).The AUC of non-HDL-C predicted for the worse LMC circulation was 0.638(95%CI:0.521～0.755,P = 0.036).Conclusions non-HDL-C in patients with acute cerebral infarction was significantly related to worse LMC circulation,and was a risk factor for worse LMC circulation.It is suggested that the higher expression of non-HDL-C could be used to predict worse LMC circulation as a serological indicator.

Objective:To investigate the correlation between serum albumin and hypoalbuminemia (HA) and the outcome after endovascular mechanical thrombectomy (EMT) in patients with stroke caused by acute anterior circulation large vessel occlusion.Methods:Stroke patients caused by acute anterior circulation large vessel occlusion received EMT treatment at the Department of Emergency Stroke, the Affiliated Hospital of Jining Medical University from June 2020 to August 2022 were retrospectively included. The demographic information, baseline clinical data, endovascular treatment parameters, and clinical outcomes of the patients were collected. HA was defined as serum albumin <35 g/L within 24 h of admission, and poor outcome was defined as the modified Rankin Scale score >2 at 90 d after onset. Multivariate logistic regression analysis was used to identify the independent influencing factors for poor outcomes. Results:A total of 177 patients were included, with a median age of 66 years, and 126 (71.19%) were males. Thirty-nine patients (22.03%) had HA, and 119 (67.23%) had poor outcomes. The proportion of pulmonary infection in the HA group was significantly higher than that in the non-HA group ( P<0.05). Multivariate logistic regression analysis showed that lower serum albumin (odds ratio [ OR] 4.102, 95% confidence interval [ CI] 1.316-16.451; P=0.028), postprocedural neurological deterioration ( OR 6.326, 95% CI 1.263-48.318; P=0.042) and pulmonary infection ( OR 5.873, 95% CI 1.028-24.452; P=0.018) were significantly independently associated with the poor outcomes. Conclusions:The HA group has a higher incidence of postprocedural pulmonary infection. Lower serum albumin, postprocedural neurological deterioration and pulmonary infection are the independent risk factors for the poor outcomes in patients with anterior circulation ischemic stroke who had successful recanalization after EMT.

Objective:To investigate the driving effect of prostate cancer associated transcript 4 (PCAT4) on the up-regulation of upregulator of cell proliferation (URGCP) expression in breast cancer progression through sponging miR-508-5p.Methods:The microarray data of lncRNA and miRNA with differential expression in breast cancer tissue were analyzed by Cancer Genome Atlas. The expression of PCAT4 in breast cancer was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was measured by MTT and colony formation, cell apoptosis was analyzed by TUNEL, and cell migration and invasion were analyzed by Transwell. The correlation between PCAT4 and miR-508-5p, and miR-508-5p and URGCP was analyzed by RNA pull-down and double luciferase assay. Tumor xenograft studies were performed to analyze the correlation between PCAT4/miR-508-5p/URGCP axis and breast cancer cell growth in vivo. Measurement data were expressed as mean ± standard deviation ( ± s). T-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. The correlation between PCAT4 and URGCP and miR-508-5p expression was evaluated by Pearson correlation analysis. Results:The expression level of PCAT4 was up-regulated in breast cancer tissues and cells. Knockout of PCAT4 inhibited cell proliferation and metastasis and promoted cell apoptosis. miR-508-5p was the target of PCAT4 and was negatively correlated with PCAT4. Overexpression of miR-508-5p in breast cancer can inhibit cell growth, migration and invasion, and promote cell apoptosis. URGCP is the target of miR-508-5p and induces progression of breast cancer. Tumor xenograft studies showed that PCAT4 drives breast cancer progression by affecting miR-508-5p/URGCP.Conclusion:The expression of PCAT4 is up-regulated in breast cancer tissues and cells, and PCAT4 can act as a molecular sponge of miR-508-5p, and significantly promote breast cancer progression by activating URGCP protein expression.

Objective:To explore the risk stratification value of HEART score combined with cardiac troponin (cTn) in emergency patients with chest pain.Methods:A total of 11 583 patients with chest pain who visited the Emergency Department of Zhongshan Hospital Affiliated to Fudan University from January to December 2019 were retrospectively collected. Patients who unfinished 0 h high-sensitivity cardiac troponin T (hs-cTnT) or electrocardiogram diagnosed ST-segment elevation myocardial infarction (STEMI) or lost to follow-up were excluded, and 7 057 patients were finally included. The final diagnosis of chest pain and the occurrence of major adverse cardiovascular events within 6 mon (6 m MACEs) were followed up by telephone and medical history. The HEART score of each patient was calculated by two attending physicians, and the patients were divided into the low-risk group (0-3 points), intermediate-risk group (4-6 points) and high-risk group (7-10 points) according to the final score. The risk stratification performance and safety of HEART score were observed and analyzed. A total of 1 884 patients who completed serial hs-cTnT tests were divided into groups according to HEART score (≤3 as low-risk group) and HEART score combined with serial hs-cTnT pathway (HEART score ≤3 and two hs-cTnT measurements <0.03 ng/mL as the low-risk group). The sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of each diagnostic method were calculated to compare the diagnostic performance of the two predictive values.Results:The patients were divided into 3 groups by HEART score : 2 765 (39.2%) patients in the low-risk group, 3 438 (48.7%) in the intermediate-risk group, and 854 (12.1%) in the high-risk group. The incidence of 6 m MACEs in each group was 1.2%, 18% and 55.3%, respectively. When the low-risk threshold was 2, 23.1% of patients entered the low-risk group and the incidence of 6 m MACEs was 0.9%. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive performance of the HEART score for 6 m MACEs, and the final AUC was 0.831 ( P=0.006, 95% CI: 0.819-0.843). Regarding the occurrence of NSTEMI at the time of this visit, 4 (0.8%) patients were misdiagnosed by using the HEART score alone. Combined with serial troponin detection, the diagnostic SE and NPV were both 100%; at the same time, the diagnostic SE and NPV of 6 m MACEs in patients increased from 98.1% (95% CI: 96.9%-99.1%), 97.9% (95% CI: 96.2%-99%) to 99.1% (95% CI: 97.9%-99.7%) and 98.9% (95% CI: 97.4%-99.6%), the diagnosis SE and NPV of 6 m myocardial infarction and cardiac death in patients increased from 98% (95% CI: 96%-99.2%), 98.6% (95% CI: 97%-99.4%) to 99.2% (95% CI: 97.6%-99.8%) and 99.3% (95% CI: 98.1%-99.9%). Conclusions:The HEART score can be used for risk assessment in emergency patients with chest pain, and a threshold of 2 is recommended for the low-risk group. The diagnostic performance of HEART score combined with serial cTn is better than that of HEART score alone.