Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

This paper explores the impacts of accelerated rehabilitation protocols following anterior cruciate ligament reconstruction(ACLR)on bone tunnel enlargement(BTE).While accelerated rehabilitation can shorten the recovery time and improve the knee function,it may increase the risk of BTE.In the early rehabilitation phase after ACLR,excessive early weight-bearing and rapid progression of knee flexion angles should be avoided,along with the proper use of braces.Continuous passive motion is not recommended in the early phase post-ACLR to prevent potential effects on BTE.Further research is needed to investigate the mechanisms of BTE and develop more effective rehabilitation strategies.This will help to select appropriate rehabilitation protocols for patients and balance functional recovery with the risk of BTE,thereby reducing the revision rate and improving postoperative outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/rehabilitation*

A 64-year-old woman was treated with Sindillizumab immunotherapy for classic Hodgkin lymphoma.After 7 cycles,the patient developed fever,fatigue,poor appetite,and other symptoms.Auxiliary examination after admission showed that hemoglobin,platelets,white blood cells,and fibrinogen decreased,liver enzymes increased,serum ferritin increased significantly(3 727.56 μg·L-1),and spleen enlargement,which was finally considered to be sindilizumab associated hemophagic cell syndrome.The patient was given methylprednisolone sodium succinate 60 mg·d-1 intravenously for 2 days,40 mg·d-1 intravenously for 4 days,and 30 mg·d-1 intravenously for 1 day,and their symptoms improved significantly,and the temperature,blood count,aminotransferase and other indicators gradually returned to normal.After discharge,she was changed to prednisone 30 mg·d-1 oral therapy,and the dose was reduced by 10 mg per week until withdrawal.The patient did not restart sindilizumab after discharge,and the serum ferritin gradually returned to normal level during follow-up,and no hemophagocytic syndrome-related symptoms appeared again.It was suggested that during the use of immune checkpoint inhibitors,patients with unexplained fever and decreased blood counts,in the absence of improvement in anti-infection,the possibility of hemophagocytic syndrome should be considered and relevant diagnostic tests such as serum ferritin should be improved as soon as possible,and glucocorticoid therapy should be turned on to avoid delay of the disease.

Background Previous research on chlorinated paraffins (CPs) in fine particulate matter (PM_2.5) has predominantly focused on short- and medium-chain chlorinated paraffins (SCCPs and MCCPs), and few studies could simultaneously determine short-, medium-, and long-chain chlorinated paraffins (LCCPs). Simultaneous extraction and determination of SCCPs, MCCPs, and LCCPs in PM_2.5 could provide technical support for their environmental monitoring and human health risk assessment. Objective To establish a method based on QUEChERS pretreatment method in conjunction with ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry for simultaneously determining the levels of SCCPs, MCCPs, and LCCPs in PM_2.5. Methods The extraction solvents, extraction salts, and extraction steps of a QuEChERS method were optimized. The extraction efficiencies of the target substances were compared under 4 extraction solvents [acetonitrile, dichloromethane, and n-hexane solvents in sequence; acetonitrile: dichloromethane: n-hexane = 1: 1: 2 (v/v/v) mixed solvent; 1% acetic acid-acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent; acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent], 2 dehydrated salts (anhydrous MgSO₄+NaCl and anhydrous Na₂SO₄+NaCl), 2 purification salts (C18 and PSA), and 4 vortex time (5, 7.5, 10, and 12.5 min) conditions. Then internal standard was utilized to estimate linear range and detection limit of the refined QuEChERS approach. Results The linearities of SCCPs, MCCPs, and LCCPs were good in the range of 10~1000 ng·mL⁻¹ with the correlation coefficients all greater than 0.96. The method detection limits (MDLs) ranged from 0.01 to 0.29 ng·m⁻³. The spiked recoveries of SCCPs, MCCPs, and LCCPs at the low, medium, and high concentrations were 77.38%-81.64%, 93.11%-99.78%, and 87.41%-101.39%, respectively, and the relative standard deviations (RSDs) were 2.90%-12.84%. This method was used to determine the CPs levels in 11 PM_2.5 samples from Shijiazhuang. The positive rates of ∑SCCPs, ∑MCCPs, and ∑LCCPs were all 100%, the concentration ranges were 0.24-2.18 ng·m⁻³ (mean 0.84 ng·m⁻³), 0.17-1.67 ng·m⁻³ (mean 0.70 ng·m⁻³), and 0.01-0.16 ng·m⁻³ (mean 0.04 ng·m⁻³), respectively, and the percentages to ΣCPs were 52.95%, 44.39%, and 2.66%, respectively. Conclusion The method established in this study is simple, time-saving, solvent saving, and can simultaneously detect SCCPs, MCCPs, and LCCPs in PM_2.5, which is suitable for the determination of PM_2.5 samples in large quantities, and can also provide a reference for the detection methods of other halogenated organic compounds in PM_2.5.

The correspondence between prescription and syndrome is the advantage and characteristic of traditional Chinese medicine(TCM)treatment.However,the pathogenesis of clinical diseases is complex and the condition is changeable,and the clinical application is difficult to achieve the maximum effect under the existing cognition of the correspondence between prescription and syndrome.In this paper,the five categories of physiological characteristics,pathological characteristics,constitution,syndrome,and disease of the longitudinal classification of"TCM state"are introduced into the correspondence of prescription and syndrome.Under the vertical perspective of"TCM state",the theoretical connotation of the correspondence between prescription and syndrome is interpreted as"correspondence between prescription and state",namely correspondence of"prescription-physiological characteristics",correspondence of"prescription-pathological characteristics",correspondence of"prescription-constitution",correspondence of"prescription-syndrome",and correspondence of"prescription-disease".It is hoped to accurately grasp the corresponding connotation of the correspondence between prescription and syndrome,in order to deepen the clinical thinking mode of TCM.

Based on the"You Gu Wu Yun"theory in traditional Chinese medicine(TCM),this paper believes that"Gu"in"You Gu Wu Yun"is extended to"state"from the perspective of"TCM state".In order to avoid the adverse reactions of TCM,the macro,meso,and micro three views should be used together,and macro,meso,and micro parameters should be integrated.We should also carefully identify the physiological characteristics,pathological characteristics,constitution,syndrome,and disease of human body by combining qualitative and quantitative method,highlighting the relationship between the prescription and the"state".The correspondence between prescription and the"state"will reduce the risk of adverse reactions of TCM.In this paper,we hope to focus on the guiding role of the"You Gu Wu Yun"theory in TCM research,to give full play to the characteristics and advantages of TCM,and to dialectically treat the role of TCM.

AIM To compare the in vivo pharmacokinetics of paeoniflorin,paeoniflorin,liquiritin,isoliquiritin,liquiritigenin and glycyrrhizic acid from Shaoyao Gancao Decoction in normal and gastric ulcer rats.METHODS Six rats were randomly assigned into two groups,after which the 75%ethanol-induced gastric ulcer model was established,the gastric tissues were collected.Twelve rats were randomly assigned into two groups and given intragastric administration(9.9 g/kg),after which blood collection was made at different time points,UPLC-MS/MS method was adopted in the determination of plasma concentrations,and main pharmacokinetic parameters were calculated.RESULTS Prolonged Tmax(P＜0.05,P＜0.01)of various active constituents,prolonged T1/2,MRT0-t(P＜0.05,P＜0.01),increased Cmax,AUC(P＜0.05,P＜0.01)and decreased Vd/F,CL/F(P＜0.05,P＜0.01)of paeoniflorin,increased Cmax,AUC(P＜0.05,P＜0.01)and decreased CL/F(P＜0.05)of albiflorin,prolonged MRT(P＜0.05),increased AUC(P＜0.05)and decreased CL/F(P＜0.01)of liquiritin,prolonged MRT(P＜0.05,P＜0.01)and decreased Vd/F(P＜0.05)of isoliquiritin,no obviously changed pharmacokinetic parameters(except for Tmax)of liquiritigenin(P＞0.05),and prolonged T1/2,MRT0-∞(P＜0.05,P＜0.01),increased Cmax,AUC(P＜0.05,P＜0.01)and decreased CL/F(P＜0.01)of glycyrrhizic acid were observable in the model group as compared with those in the normal group.CONCLUSION Gastric ulcer exhibits certain influences on the velocities and degrees of in vivo absorption and metabolism of active constituents from Shaoyao Gancao Decoction.

OBJECTIVE: To investigate the risk factors for depression in middle-aged and elderly Chinese male patients with benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS). METHODS: Based on the data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), we included 8 426 male participants aged ≥ 45 years in this study, and explored the risk factors for depression in patients with BPH/LUTS by logistic regression analysis. RESULTS: Among the total number of participants, there were 1 447 cases of BPH/LUTS, with a prevalence rate of 17.2%, and 36.5% of the patients (529/1 447) were complicated by depression. Logistic regression analysis showed that underlying diseases were the risk factors for depression in patients with BPH/LUTS (OR = 1.29, 95% CI: 1.03－1.62), while the protective factors against the condition included high school education or above (OR = 0.52, 95% CI: 0.36－0.75), urban residence (OR = 0.75, 95% CI: 0.60－0.95), eastern region (OR = 0.61, 95% CI: 0.38－0.97), and 6－9 h/d sleep (OR = 0.52, 95% CI: 0.41－0.66). CONCLUSION Underlying diseases, education level, residential area, geographical region, and sleep duration are influencing factors for depression in middle-aged and elderly male patients with BPH/LUTS in China and deserve the attention of clinicians.
Humans ; Male ; Prostatic Hyperplasia/psychology* ; Risk Factors ; Depression/etiology* ; Aged ; Middle Aged ; Lower Urinary Tract Symptoms/psychology* ; China/epidemiology* ; Logistic Models ; Prevalence ; Longitudinal Studies

OBJECTIVES: To explore the role of the cGAS-STING signaling pathway in the therapeutic mechanism of Liangxue Jiedu Huayu Formula (LXJDHYF) for acute-on-chronic liver failure (ACLF) in mice. METHODS: Thirty C57BL/6 mice were randomly divided into blank control group, model group, low- and high-dose LXJDHYF groups, and H151 (a specific cGAS-STING pathway inhibitor) group (n=6). In all but the control group, the mice were treated with CCl₄ to induce liver cirrhosis followed by intraperitoneal injections of lipopolysaccharide and D-amino galactose to establish mouse models of ACLF. After the treatments, the mouse livers were collected for HE and TUNEL staining, and serum levels of ALT, AST and TBil were determined. In bone marrow-derived macrophages (BMDMs) and liver tissues of ACLF mice, the expressions of cGAS-STING signaling pathway-related mRNAs including IFN‑β, ISG15, IL-6 and TNF-α were determined with RT-qPCR, and the phosphorylation levels of IRF3 and STING proteins were investigated using Western blotting. RESULTS: Compared with the mice in the model group, the LXJDHYF-treated mice exhibited milder hepatocyte necrosis and inflammatory cell infiltration in the liver with significantly reduced hepatocyte apoptosis. LXJDHYF treatment also significantly lowered serum levels of ALT, AST, TBil, IL-6 and TNF-α in ACLF mice and effectively suppressed the expressions of cGAS-STING signaling pathway-related mRNA in both the BMDMs and the liver tissues and the phosphorylation of IRF3 and STING proteins in the BMDMs. CONCLUSIONS LXJDHYF can significantly improve liver function and attenuate inflammation in ACLF mice possibly by inhibiting excessive activation of the cGAS-STING signaling pathway.
Animals ; Signal Transduction/drug effects* ; Mice ; Nucleotidyltransferases/metabolism* ; Mice, Inbred C57BL ; Acute-On-Chronic Liver Failure/etiology* ; Membrane Proteins/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Liver/metabolism* ; Disease Models, Animal ; Interferon Regulatory Factor-3/metabolism* ; Interleukin-6/metabolism* ; Male

Objective: To analyze the characteristics of human papillomavirus (HPV) infection and the distribution of HPV subtypes in Shijiazhuang, Hebei Province, and to explore the application evaluation of multiple PCR capillary electrophoresis fragment analysis for HPV typing test. Methods: A population-based cross-sectional study was conducted among 434 women (age range 17 to 74 years old, 260 patients and 174 physical examinations) included from May to August 2022 in Hebei General Hospital. HPV typing was detected by multiple PCR-capillary electrophoresis fragment analysis. Using the multiple fluorescence quantitative PCR kit as a reference, Chi-square test was used to analyze the diagnostic effect of multiple PCR-capillary electrophoresis fragment analysis, and the consistency was analyzed by Kappa value. Results: The total HPV infection rate was 45.85%(199/434), including 35.48% (154/434) of high-risk HPV (HR-HPV), 3.92% (17/434) of low-risk HPV (LR-HPV), 6.45% (28/434) of HR-HPV and LR-HPV mixed infection, 27.88% (121/434) of single type HPV and 17.97% (78/434) of multi type HPV. HPV52 (9.68%, 42/434), HPV16 (6.91%, 30/434), and HPV58 (6.91%, 30/434) are common HPV subtypes. The positive rate of physical examination was 45.40% (79/174), which was slightly lower than that of patients 46.15% (120/260), there was no significant difference (χ²=0.024,P>0.05). The highest infection rate in the 17-30 age group was 54.76% (46/84), and there was no statistical difference among the age groups(χ²=4.123,P>0.05). The sensitivity and specificity of multiplex PCR capillary electrophoresis fragment analysis were 92.96% and 94.04%, respectively, and Kappa value was 0.870, with the multiplex fluorescent quantitative PCR as the reference. Conclusion: HPV infection may appear younger, and the positive rate of HR-HPV infection is the highest, with HPV52, 16, 58 as the main infection subtypes. The detection results of multiplex PCR capillary electrophoresis fragment analysis method are highly consistent with those of multiplex fluorescent quantitative PCR method, which is suitable for HPV DNA typing.
Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Uterine Cervical Neoplasms ; Multiplex Polymerase Chain Reaction ; Papillomavirus Infections/diagnosis* ; Cross-Sectional Studies ; Genotype ; Papillomaviridae/genetics*