This study aimed to investigate the therapeutic effect of Yindan Pinggan capsules (YDPG) on intrahepatic cholestasis (IHC) through animal experiments, while utilizing network pharmacology and molecular docking techniques to explore its potential mechanisms. Initially, the therapeutic effect of YDPG on an α-naphthylisothiocyanate (ANIT)-induced IHC mouse model was assessed through liver function tests, routine blood tests, and liver pathology analysis. Subsequently, network pharmacology tools were employed to predict the active components, core targets, and signaling pathways of YDPG. Molecular docking technology was employed to verify the binding activity of key active components of YDPG with core targets, followed by protein immunoblotting to validate the key targets. Results showed that YDPG significantly improved liver function abnormalities and hepatocyte damage in IHC mice. Network pharmacology analysis revealed that 94 active components in YDPG were associated with 396 targets for the treatment of IHC, and were significantly enriched in pathways such as the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, lipid metabolism, and bile secretion. Molecular docking results showed good binding activity between key active components of YDPG and core targets of the PI3K-AKT signaling pathway. Further protein immunoblotting confirmed that YDPG could reduce the phosphorylation levels of PI3K and AKT proteins, core targets of the PI3K-AKT pathway in liver tissue. These findings suggest that YDPG may alleviate biological processes such as oxidative stress and inflammatory responses by regulating the PI3K-AKT signaling pathway, thereby improving liver damage in IHC mice and exerting a therapeutic effect on IHC. This experiment has been approved by the Animal Experiment Ethics Committee of Jinan University (ethical approval number: IACUC-20241011-09).

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

OBJECTIVE To explore the effects of CD20 coding gene （MS4A1） polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020， with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software， including rs1051461， rs17155034， rs4939364， and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors（demographic， clinical， and genotypic variables） in patients and the steady-state trough concentration of rituximab during the first course of treatment， followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival （PFS） and overall survival （OS）. Using MS4A1 genotype and tumor stage as independent variables， Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL，which was significantly lower than 21.95 μg/mL in AA+AC carriers （P＜0.05）. The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers， CT+TT carriers had significantly prolonged PFS and OS （P＜0.05）. The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype （HR＝4.406， 95%CI：1.743-11.137， P＜0.05） and tumor Ⅲ&Ⅳ （HR＝3.233， 95%CI： 1.413-7.399， P＜0.05） were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab， and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.

ObjectiveTo explore the impacts of material type and loading volume of rigid containers on the hydrogen peroxide low temperature plasma sterilization of thoracoscopic instruments, to identify the best rigid containers and loading volume of thoracoscopic instruments. MethodsThoracoscopic instruments sterilized by STERRAD^® 100NX hydrogen peroxide low temperature plasma in Shanghai Pulmonary Hospital affiliated to Tongji University from August to September 2024 were selected as the research items. According to the material of rigid containers, the instruments were divided into polyethylene case group (A), stainless steel case group (B) and silicone resin case group (C). In terms of the loading volume, the rigid containers were divided into (loading capacity <80%) groups of 8, 10 and 12 instruments. The results of physical monitoring, the first type of chemical indicator card monitoring, and the five types of card luminal chemical process challenge device (PCD) monitoring of the 9 groups of A8, A10, A12, B8, B10, B12, C8, C10 and C12 were compared and evaluated. ResultsCompared to A8, A10 A12, C8, C10 or C12 groups, the thoracoscope instruments in the stainless steel containers in B8, B10 or B12 group had higher hydrogen peroxide concentrations and shorter elapsed time in the pressure check phases 1 and phases 2, with the differences statistically significant (P<0.05), followed by the silicone resin case group and the polyethylene case group. The nine groups of physical parameter monitoring, the first type of chemical indicator monitoring, and the five types of chemical PCD monitoring for lumen sterilization achieved 100% qualification rates, and there were no significant differences in the qualified rates of sterilization among the 9 groups (P>0.05). ConclusionWhen using hydrogen peroxide low temperature plasma to sterilize thoracoscopic instruments, it is recommended to use stainless steel or silicone resin rigid containers with a controlled loading capacity (≤12) to ensure optimal sterilization quality.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Objective To evaluate the differential diagnostic value of synthetic magnetic resonance imaging(syMRI)and field of view optimized and constrained undistorted single shot diffusion weighted imaging(FOCUS DWI)in patient with breast imaging reporting and data system(BI-RADS)4 breast lesions.Methods A total of 68 patients who underwent breast MRI and were classified as BI-RADS category 4 were prospectively enrolled.Among them,there were 31 cases of benign lesions(benign group)and 37 cases of malignant lesions(malignant group).All patients underwent T1WI,T2WI,FOCUS DWI,dynamic contrast-enhanced magnetic resonance ima-ging(DCE-MRI)and syMRI.Two radiologists delineated the region of interest(ROI)on quantitative parameters images of syMRI and the apparent diffusion coefficient(ADC)images generated from FOCUS DWI and calculated T1,T2,proton density(PD)and ADC values,respectively.The thresholds and diagnostic efficacy of syMRI and FOCUS DWI parameters were evaluated by the receiver op-erating characteristic(ROC)curve.Logistic regression analysis was used to combine the parameters of the two sequences and evalu-ate the diagnostic efficacy.Results The T2,PD,and ADC values in the malignant group were significantly lower than those in the benign group(P＜0.05),but there were no statistically significant difference in T1 values between the groups(P＞0.05).T2 and ADC values could be used as important diagnostic indexes in patient with malignant lesions of BI-RADS 4 breast lesions,and the area under the curve(AUC)of T2 and ADC was 0.833 and 0.867,respec-tively.There was no significant difference in AUC of T2 and ADC between benign and malignant groups(Z=0.485,P=0.627).The AUC of T2 value combined with ADC value was 0.910,and the sensitivity and specificity was 90.3％and 89.2％,respectively.Conclusion T2 value of syMRI and ADC value of FOCUS DWI can be used as quantitative diagnostic indicators in patients with BI-RADS 4 breast lesions.The combination of T2 and ADC values can further improve the differential diagnosis efficiency.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To observe the efficacy of postauricular injection of compound betamethasone injection in the treatment of sudden deafness and its influence on transcranial doppler(TCD)parameters and fibrinolysis-coagulation indicators.Methods Patients with sudden deafness were divided into control group and treatment group according to cohort methed.The control group was given intravenous injection of dexamethasone sodium phosphate for 10 days on the basis of conventional treatment,and the treatment group was given postauricular injection of compound betamethasone injection 0.8 g for once every other day for 5 times in addition to conventional treatment.The clinical efficacy,hearing level,haemodynamics and laboratory indicators[homocysteine(Hcy),platelet(PLT)count]were compared between the two groups of patients,and the adverse drug reactions or complications were counted.Results There were 50 cases in treatment group and 50 cases in control group.After treatment,the total effective rates in treatment group and control group were 94.00％(47 cases/50 cases)and 80.00％(40 cases/50 cases),with significant difference(P＜0.05).After treatment,the acoustic thresholds under 0.5 kHz,1 kHz,2 kHz and 4 kHz in treatment group were(42.48±5.65),(45.35±6.44),(48.67±5.58)and(50.25±6.06)dB,which in control group were(50.64±6.92),(57.66±7.41),(60.24±8.31)and(63.15±8.25)dB,all with significant difference(all P＜0.05).After treatment,the whole blood high-shear viscosities in treatment group and control group were(4.18±0.58)and(4.99±0.76)mpa·s;the whole blood low-shear viscosities were(9.18±1.15)and(10.31±1.28)mpa·s;the plasma viscosities were(1.44±0.32)and(1.76±0.25)mpa·s;the Hcy levels in treatment group and control group were(15.57±4.25)and(21.75±4.93)μmol·L-1;PLT levels were(198.72±21.41)×109·L-1and(212.67±18.46)×109·L-1 respectively,all with significant difference(all P＜0.05).There were no obvious adverse drug reactions in treatment group and control group.Conclusion Postauricular injection of compound betamethasone injection can improve the hearing level and enhance the clinical efficacy in patients with sudden deafness,and it is helpful to improve haemodynamics and reduce serum Hcy level,with good safety.

Objective To investigate the effects of vitamin D mediated mitogen-activated protein kinase(MEK)/extracellular signal-regulated kinase(ERK)pathway on myocardial injury in rats with gestational diabetes mellitus.Methods Fifty SD rats were divided into control group,model group,experimental-L group,experimental-M group and experimental-H group,and the gestational diabetes rat model was established.After successful modeling,experimental-L,experimental-M,experimental-H groups were given intragastric administration of 0.05,0.10 and 0.15 μg·kg-1 concentration of vitamin D,while control group and model group were given intragastric administration of 0.9％NaCl at the same dose once a day for 2 weeks.Fasting blood glucose concentration and insulin level were detected before intervention,1 week and 2 weeks after intervention.Echocardiography was used to detect cardiac function[left ventricular ejection fraction(LVEF),maximum rate of rise(+dp/dtmax)and maximum rate of decline(-dp/dtmax)of left ventricular pressure].Myocardial enzyme indexes[troponin Ⅰ(cTn Ⅰ)kit,creatine kinase isoenzyme(CK-MB)]and inflammatory factors[tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)]in serum and myocardial tissue of rats were detected by enzyme-linked immunosorbent assay(ELISA),and MEK/ERK pathway protein expression was detected by western blot.Results The levels of cTn Ⅰ in cardiac tissue of control group,model group,experimental-L group,experimental-M group,experimental-H group were(10.50±1.08),(42.26±4.30),(31.85±2.44),(23.31±2.15)and(14.85±1.19)ng·mL-1;serum cTn Ⅰ levels were(23.79±3.46),(63.59±5.52),(51.02±4.27),(42.75±3.19)and(29.20±2.11)ng·mL-1;myocardial tissue levels of CK-MB were(8.52±0.90),(17.65±1.75),(15.62±1.27),(13.11±1.24)and(9.85±0.87)ng·mL-1;serum levels of CK-MB were(11.32±0.98),(21.24±1.45),(18.75±1.32),(15.11±1.02)and(12.27±1.11)ng·mL-1;phosphorylated-MEK protein expression were 0.24±0.03,0.85±0.09,0.72±0.06,0.57±0.07 and 0.35±0.04;phosphorylated-ERK1/2 protein expression were 0.18±0.02,0.66±0.07,0.52±0.06,0.40±0.07 and 0.24±0.05,respectively.There were statistically significant differences of above indexes between control group and model group(all P＜0.05);the difference between model group and experimental-L,experimental-M,experimental-H groups were all statistically significant(all P＜0.05).Conclusion Vitamin D may reduce myocardial injury in rats with gestational diabetes by inhibiting the activation of MEK/ERK pathway.