Liver fibrosis is the common pathological process in the progression of various chronic liver diseases to liver cirrhosis， and it greatly affects the prognosis of patients with chronic liver diseases. As a novel adipokine， Chemerin participates in the metabolism of glucose and lipids and inflammation， and various studies have shown that the expression level of Chemerin is correlated with the degree of liver fibrosis， suggesting that Chemerin may be involved in the process of liver fibrosis by regulating metabolism and inflammation. Chemerin has shown certain potential in the auxiliary diagnosis of liver fibrosis and the intervention against the progression of liver fibrosis. This article reviews the potential role and mechanism of action of Chemerin in the process of liver fibrosis， in order to provide new ideas for the diagnosis and treatment of liver fibrosis.

ObjectiveTo improve the efficacy of Astragalus membranaceus (Fisch.) Bunge (A. membranaceus, Huang Qi), and to further develop and utilize it, fermentation technology was applied to the stem and leaf of A. membranaceus to enhance its immune function.MethodsIn this study, we fermented A. membranaceus stem and leaf (ASL) with probiotics and investigated its immune function. Firstly, we screened suitable strains for ASL fermentation and optimized the fermentation process. Secondly, we determined the antioxidant capacity of fermented ASL and its effect on inflammation in mouse monocyte-macrophage cell. Finally, the immunocompromised mice were treated with fermented ASL to investigate the changes in their immune ability.ResultsAmong the 10 selected probiotics, Lactobacillus plantarum was the most suitable strain for ASL fermentation. After optimization of the fermentation process, the content of saponins in fermented ASL was significantly increased. The fermented ASL exhibited strong anti-inflammatory and antioxidant activities in vitro. The in vivo immune efficacy improved by promoting the development of the spleen and thymus, as well as raising the immunoglobulin M, tumor necrosis factor-α, and interleukin-1β levels of in the serum.ConclusionThis study contributes to developing the non-medicinal parts of A. membranaceus, expands its medicinal resources, highlights the potential of fermentation technology to enhance these parts, and provides a reference for further development. Based on this approach, we can promote using non-medicinal parts of herbal medicines, minimize drug waste, and offer a reference for developing non-medicinal components in Chinese herbal medicines.

Objective To establish a qualitative detection method for tulobuterol in dried urine spots(DUS)as derivatives produced after administration of the non-prohibited substance bupropion can inter-fere with the detection of the doping tulobuterol in urine,and further explore the interference in blood samples and find a method for its detection in dried blood spots(DBS).Methods Ten volunteers(5 males and 5 females)were chosen for method validation,and another 2 volunteers(1 male and 1 fe-male)were recruited for the bupropion study.Totally 20 μL samples of DUS and DBS were collected separately.After pretreatment steps such as liquid-liquid extraction with mixed organic solvents and ni-trogen blowing for re-dissolution,the detection and analysis were carried out using liquid chromatogra-phy-high resolution mass spectrometry(LC-HRMS).Results The limits of detection(LOD)for tulobuter-ol in both DUS and DBS samples were 0.13 ng/mL,respectively,while the limit of identification(LOI)were 0.16 ng/mL and 0.90 ng/mL,respectively.Meanwhile,the repeatability and reproducibility relative standard deviation(RSD%)were<20%for different concentrations,with recovery rate of 38.65%～70.01%and the matrix effect of 37.98%～142.13%,and the stability of the samples could reach 30 days in different storage conditions.As to the bupropion study,its derivatives could be effectively sepa-rated from tulobuterol in DUS samples,but were not detected in DBS samples,which directly ex-cludes their interference.Conclusion Detection of tulobuterol in DUS and DBS using LC-HRMS can eliminate interference from bupropion derivatives in the detection of the doping tulobuterol.

Objective To establish a qualitative detection method for tulobuterol in dried urine spots(DUS)as derivatives produced after administration of the non-prohibited substance bupropion can inter-fere with the detection of the doping tulobuterol in urine,and further explore the interference in blood samples and find a method for its detection in dried blood spots(DBS).Methods Ten volunteers(5 males and 5 females)were chosen for method validation,and another 2 volunteers(1 male and 1 fe-male)were recruited for the bupropion study.Totally 20 μL samples of DUS and DBS were collected separately.After pretreatment steps such as liquid-liquid extraction with mixed organic solvents and ni-trogen blowing for re-dissolution,the detection and analysis were carried out using liquid chromatogra-phy-high resolution mass spectrometry(LC-HRMS).Results The limits of detection(LOD)for tulobuter-ol in both DUS and DBS samples were 0.13 ng/mL,respectively,while the limit of identification(LOI)were 0.16 ng/mL and 0.90 ng/mL,respectively.Meanwhile,the repeatability and reproducibility relative standard deviation(RSD%)were<20%for different concentrations,with recovery rate of 38.65%～70.01%and the matrix effect of 37.98%～142.13%,and the stability of the samples could reach 30 days in different storage conditions.As to the bupropion study,its derivatives could be effectively sepa-rated from tulobuterol in DUS samples,but were not detected in DBS samples,which directly ex-cludes their interference.Conclusion Detection of tulobuterol in DUS and DBS using LC-HRMS can eliminate interference from bupropion derivatives in the detection of the doping tulobuterol.

For muscle-invasive bladder cancer (MIBC) patients, preoperative neoadjuvant chemotherapy (NAC) can reduce the tumor stage, treat micrometastases, prolong the median survival, and improve the prognosis.However, NAC is associated with side effects such as renal impairment, thromboembolism and drug toxicity.NAC itself suffers from deficiencies such as renal function impairment, thromboembolism, and drug toxicity.Its therapeutic efficacy is affected by factors such as tumor pathology type, DNA repair gene defects, whether it is primary MIBC, and TNM staging, so there are certain limitations in its use.Based on the cisplatin treatment regimen, more and more studies are exploring the limitations and shortcomings of NAC in MIBC treatment regimen.Therefore, this paper provides an overview and outlook of the application of NAC in MIBC treatment.

Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules,and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers. Methods In this study,210 different structural types of VOCs were selected from the VOCMM penetration enhancer database,and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2),cholesterol(CHL),and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control,Nootkatone,and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments,with three rats in each group.The donor pool solutions were 3%gastrodin,3%gas-trodin+3%nootkatone,and 3%gastrodin+3%3-butylidenephthalide,respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12,μg/cm2). Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA,and hydrogen bonded to the head group of CER2.Among them,sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings,benzene rings,and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis,most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09 μg/cm2,and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5 503.00±1 080.00 μg/cm2,P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98 μg/cm2,P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2. Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers,and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

Objective:To evaluate the efficacy and safety of disitamab vedotin combined with tislelizumab in the neoadjuvant treatment of bladder cancer.Methods:The clinical data of 16 bladder cancer patients who received neoadjuvant therapy with disitamab vedotin combined with tislelizumab from April 2022 to January 2023 at the First Hospital of Chongqing Medical University were retrospectively analyzed. There were 15 males and 1 female, aged (66.12±14.37) years old. The immunohistochemical staining of biopsy pathology showed that HER-2 (0), (+ ), (+ + ), and (+ + + ) were in 1, 6, 6, and 3 cases, respectively. Before neoadjuvant therapy, 5 cases were in T 2N 0M 0 stage, and 11 cases were in T 3N 0M 0 stage. Biopsy pathology showed 3 cases were low-grade uroepithelial carcinoma, and 13 cases were high-grade uroepithelial carcinoma. Neoadjuvant therapy regimens: Disitamab vedotin 120 mg, every 2 weeks for 1 cycle, a total of 4 cycles. Tislelizumab 200 mg, every 3 weeks for 1 cycle, a total of 3 cycles. Surgery was performed at 2-3 weeks after neoadjuvant therapy. The efficacy and adverse effects of neoadjuvant therapy were analyzed. Results:All 16 cases completed neoadjuvant therapy.Five cases achieved complete remission, 7 cases achieved partial remission, 3 cases had stable disease, and 1 case had disease progression.Twelve cases(75.0%) achieved objective remission, 15 cases (93.8%) had disease control, and 14 cases(87.5%) had a reduction in the target lesion from baseline. Complete remission was achieved in 2 (22.2%)of 9 HER-2-positive patients and and 3 (42.9%) of 7 HER-2-negative patients, respectively, and objective remission was achieved in 8 (88.9%) and 4 (57.1%). After neoadjuvant treatments, surgical treatments were refused in 6 cases, and bladder-preserving combination therapy was performed in 2 cases. Radical cystectomy were performed in 8 cases, with negative margins for surgical incision, of which 5 cases (62.5%) had postoperative pathologic stage

Magnetic resonance imaging (MRI) simulator (MRI-Sim) can provide superior images for radiotherapy.Due to the complexity of MRI technology and the safety problem caused by strong magnetic field, the acquisition and implementation of MRI simulation is more complicated than CT simulation.In order to ensure the introduction of MRI-Sim, this paper reviews the selection, installation, and acceptance test of MRI-Sim, including the selection of host and auxiliary equipment, installation site preparation, and safety precautions,as well as MRI-Sim acceptance test and commissioning.

Objective Cardiac HERG potassium channel currents can cause long QT syndrome .The function of the cardiac HERG potassium channel is regulated by tyrosine kinase and phosphatase , and protein tyrosine phosphatase non-receptor type 11 ( PTPN11) negatively regulates the HERG potassium channel .This study aimed to investigate the effect of PTPN 11 on the electrophysio-logical characteristics of the HERG channel . Methods The plasmids of pcDNA3.1-PTPN11-EGFP were constructed by PCR technique and transfected or cotransfected with the pcDNA 3.1-PTPN11-EGFP plasmid into HEK293 cells using Lipofectamine 2000.The patch clamp technique was employed to record the HERG channel currents in the control group ( HEK293 cells transfected with pcDNA3.0-HERG-EGFP), PTPN11 overexpression group (pcDNA3.0-HERG and pcDNA3.1-PTPN6-EGFP cotransfected HEK293 cells), and PTPN11 overexpression with PAO group . Results The pcDNA3.1-PTPN11-EGFP plasmid was successfully constructed .Green fluorescence was observed in the HEK293 cells transfected with pcDNA3.0-HERG-EG-FP or cotransfected with pcDNA3.0-HERG and pcDNA3.1-PTPN11.The maximum densities of pulse and tail currents were significantly decreased in the PTPN11 overexpression group as compared with the control ([31.85 ±5.54] vs [45.92 ±3.18] pApF, P<0.05;[73.82 ±11.31] vs [108.43 ±7.98] pApF, P<0.05) but markedly in-creased in the PTPN11 overexpression with PAO group ([48.08 ±4.32] pApF;[120.06 ±8.02] pApF) (P<0.05).The time con-stant of deactivation was significantly higher in the PTPN 11 overexpression group than in the control ([622.16 ±46.49] vs [440.70 ± 49.49] ms, P<0.05). Conclusion The overexpression of PTPN11 decreases HERG potassium channel currents , which can be re-versed by PAO.This finding provides a theoretical basis for the application of certain regulatory enzymes in the HERG channel as a treat -ment of long QT syndrome .

OBJECTIVETo study the effect of protein tyrosine phosphatase non-receptor type 12 (PTPN12) in regulating cardiac HERG channel currents.

METHODSThe plasmids pcDNA3.1-PTPN12-RFP and herg mutant constructed by PCR technique were transfected into HEK293 cells via Lipofectamine 2000, and the cells stably expressing PTPN12 selected with G418 were identified by Western blotting with anti-PTPN12 antibody. HERG channel current in cells expressing HERG alone (HEK293/HERG cells), cells overexpressing PTPN12 (HEK293/HERG cells transfected with pCDNA3.1-PTPN12-RFP), PAO-treated cells (PTPN12/HERG cells treated with PAO), and herg mutant cells (HEK293/HERGY327A-Y700A-Y845A cells transfected with pcDNA3.1-PTPN12-RFP) were recorded by patch-clamp technique.

RESULTSThe plasmids pcDNA3.1-PTPN12-RFP and herg mutant were successfully constructed, and the stable expressing cell lines were established. Red fluorescence was obversed in HEK293/HERG cells transfected with pcDNA3.1-PTPN12-RFP, and the protein expression of PTPN12 was detected. Overexpression of PTPN12 significantly decreased HERG current density in HEK293/HERG cells, and this change was significantly weakened in the inhibitor group and herg mutant group.

CONCLUSIONPTPN12 negatively regulates cardiac HERG channel cerrent possibly by decreasing the phosphorylation level of HERG tyrosine residues. This finding provides further insight into the regulatory mechanism of HERG channel and the pathogenesis of long QT syndrome.

Ether-A-Go-Go Potassium Channels ; physiology ; HEK293 Cells ; Heart ; Humans ; Long QT Syndrome ; Patch-Clamp Techniques ; Protein Tyrosine Phosphatase, Non-Receptor Type 12 ; physiology ; Transfection