Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective:To explore the feasibility and efficacy for the dissection and ligation of the superior laryngeal artery in endoscopic surgery for hypopharyngeal cancer.Methods:Eight cadaveric heads were selected, and the laryngopharynxes were harvested. The positions of the superior laryngeal arteries entering the larynxes were dissected and observed under endoscopic vision, and their anatomical characteristics were summarized. Twenty-nine patients (all were male, aged 39-74 years old) with hypopharyngeal cancer who underwent transoral endoscopic surgery at the Department of Otorhinolaryngology Head and Neck Surgery of the Second Xiangya Hospital, Central South University from January 2018 to December 2019 were selected, and the patients were randomly divided into two groups by drawing lots, namely, the superior laryngeal artery was actively dissected and occluded during surgery in observation group ( n=15) or not in control group ( n=14). The differences in surgical time, bleeding volume, postoperative complications, and postoperative disease-free survival rate were compared between the two groups. Statistical analysis was conducted using SPSS 25.0 software. Results:The entry point of the superior laryngeal artery into the larynx was approximately at the level of the superior edge of the thyroid cartilage, and entered the larynx at the posterior one-third of the lateral wall of the pyriform fossa. The superior laryngeal artery might be determined through endoscopic exploration in all patients of observation group. The endoscopic surgery time [(40.00±7.56) minutes] and intraoperative bleeding volume [(24.00±8.28) ml] in the observation group were respectively less than those [(48.57±14.06) minutes and (42.86±15.41) ml] in the control group, and the differences were statistically significant ( t=-2.064, P=0.049; t=-4.064, P=0.001). There was no case with postoperative bleeding in the observation group, but with one case of postoperative bleeding in the control group. Total disease free survival rate was 86.2% and there was no significant difference in disease free survival rates between the two groups during a follow-up period of at least 36 months ( P=0.986). Conclusion:Dissection of the superior laryngeal artery during endoscopic surgery for hypopharyngeal cancer is feasible, and pre-management and occlusion of the superior laryngeal artery can effectively reduce intraoperative bleeding.

Objective lo investigate the predictive value of serum growth differentiation factor 11(GDF-11)and calprotectin A4(S100A4)for contrast-induced nephropathy(CIN)after coronary angiography(CAG).Methods A total of 528 patients who underwent CAG in the First Affiliated Hospital of Xi'an Jiao-tong University from December 2020 to November 2023 were selected as the research objects.According to whether the patients had CIN,they were divided into non-nephropathy group(472 cases)and nephropathy group(56 cases).Enzyme-linked immunosorbent assay was used to detect serum levels of GDF-11 and S100A4.Multivariate Logistic regression analysis was used to explore the influencing factors of CIN after CAG.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum GDF-11 and S100A4 for CIN after CAG.Results The serum levels of GDF-11 and S100A4 in nephropathy group were higher than those in non-nephropathy group(P＜0.05).The contrast agent dose and postoperative ser-um creatinine level in the nephropathy group were higher than those in the non-nephropathy group(P＜0.05).Multivariate Logistic regression analysis showed that contrast agent dose ≥131.84 mL(OR=2.158,95％CI 1.284-3.627),postoperative serum creatinine ≥ 87.57 μmol/L(OR=2.445,95％CI 1.533-3.898),GDF-1 1 ≥4 50.84 ng/mL(OR=2.445,95％CI 1.533-3.898)were the influencing factors of CIN af-ter CAG(P＜0.05).The area under the curve(95％CI)of serum GDF-11 and S100A4 for predicting CIN af-ter CAG was 0.861(95％CI 0.810-0.912)and 0.798(95％CI 0.747-0.849),respectively.The optimal cut-off values were 450.84 ng/mL and 86.98 μg/mL,the specificity were 65.89％and 57.62％,and the sensi-tivity were 94.74％and 94.74％,respectively.The area under the curve of the combination of the two was 0.906(95％CI 0.856-0.957),the specificity was 87.09％,and the sensitivity was 84.26％.Conclusion The elevated levels of serum GDF-11 and S100A4 are closely related to the occurrence of CIN in patients after CAG surgery,which can be used as biological indicators to evaluate the occurrence of CIN in patients after CAG surgery,and the combined prediction efficiency of GDF-11 and S100A4 is higher.

Objective To investigate the ocular hemodynamic characteristics before and after treatment of diabetic retinopathy(DR).Methods This study was a case-control study using a non-random sampling method.A total of 86 DR patients(86 eyes)and 43 healthy subjects who were diagnosed and treated in the Affiliated Hospital of Hebei University from December 2021 to April 2022 were selected as the research objects.Among them,86 DR patients were set up as the observation group,and 43 healthy subjects were set up as the control group.The central retinal artery(CRA),peak systolic velocity(PSV),end-diastolic velocity(EDV),and resistance in-dex(RI)were compared between the two groups.And according to the results of fluorescein fundus angiography(FFA)and macular opti-cal coherence tomography(OCT),the observation group was divided into PRP group[treated with panretinal photocoagulation(PRP)]and VEGF group[treated with intravitreal injection of anti-vascular endothlial growth factor(VEGF)],43 cases in each group.The curative effect was observed,the changes of PSV,EDV and RI before and after surgery were compared,and the area under the curve(AUC),sensitivity and specificity of PSV,EDV and RI for predicting curative effect were analyzed by receiver operating characteristic(ROC)curve model.Results PSV and EDV in the observation group were lower than those in the control group,but RI was higher than that in the control group(P＜0.05).All patients in PRP group successfully completed PRP treatment,with a total effective rate of 88.37％;PSV and EDV at 1day and 1 week after operation were higher than those before operation,while RI was lower than before opera-tion(P＜0.05);There was no significant difference in PSV and EDV at 1week after operation compared with 1day after operation(P＞0.05),while RI was lower than that at 1day before operation(P＜0.05).All patients in VEGF group successfully completed intravitreal injection of anti-VEGF therapy,with a total effective rate of 86.04％;PSV and EDV at 1 day and 1 week after operation were higher than those before operation,while RI was lower than before operation(P＜0.05);PSV and EDV at 1 week were lower than those at 1day after operation,while the RI was higher than that at 1day before operation(P＜0.05).ROC curve analysis showed that the AUC values of PSV,EDV and RI for predicting the efficacy of PRP in the treatment of stage Ⅰ-Ⅲ DR were 0.879,0.831,0.894(P＜0.05),re-spectively;the AUC values of PSV,EDV and RI for predicting the efficacy of intravitreal injection of anti-VEGF in the treatment of stageⅣ DR were 0.860,0.881,0.831(P＜0.05).Conclusion Both PRP and intravitreal injection of anti-VEGF have good curative effects in the treatment of stage Ⅰ-Ⅳ DR,which can effectively increase the PSV and EDV of the CRA and reduce the RI.And color Doppler ultrasound was used to observe the changes of ocular hemodynamics in patients with DR before and after operation,which is bene-ficial to provide reference for clinical diagnosis and treatment.

Objective:To analyze the molecular epidemiological characteristics of the Corona virus disease 2019 (COVID-19) cases in Shijiazhuang, which can reveal the origin of the outbreak and provide a scientific basis for COVID-19 prevention and control.Methods:From January 2 to January 8, 2021, a total of 404 samples from 170 COVID-19 cases were collected from the Shijiazhuang Fifth Hospital. The consensus sequence of 2019 novel Coronavirus(2019-nCoV) was obtained through multiplex polymerase chain reaction-based sequencing. The sequences of 170 COVID-19 cases were analyzed by the PANGOLIN, and the data were statistically analyzed by T-test.Results:Among the 404 COVID-19 samples, a total of 356 samples obtained high quality genome sequences (>95%,100×sequencing depth). The whole genome sequences of 170 COVID-19 cases were obtained by eliminating repeated samples. All 170 sequences were recognized as lineage B1.1 using PANGOLIN. The number of single nucleotide polymorphism arrange from 18-22 and most of the single nucleotide polymorphism were synonymous variants. All of 170 genomes could be classified into 48 sub-groups and most of the genomes were classified into 2 sub-groups (66 and 31, respectively).Conclusions:All cases in this study are likely originated from one imported case. The viruses have spread in the community for a long time and have mutated during the community transmission.

A mixed drug self-delivery system(DSDS)with high drug content(＞50％)was developed to regulate pH-triggered drug release,based on two doxorubicin(DOX)-DOX dimmers:D-DOXADH and D-DOXcar con-jugated with acid-labile dynamic covalent bonds(hydrazone and carbamate,respectively)and stabilized with PEGylated D-DOXADH(D-DOXADH-PEG).Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them,pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS.Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios.The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates.The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slow-release mixed DSDS nanoparticles.

Objective:To explore the value of MRI features in predicting the pathological grade of rectal neuroendocrine tumors and to develop a predicting model.Methods:A retrospective analysis was performed on 30 cases of rectal neuroendocrine tumors confirmed by surgery and pathology between 2013 and 2019. All of them underwent plain rectal MRI, DWI and dynamic contrast-enhanced MRI. The clinical features and MRI characteristics (ie. tumor location, maximum tumor diameter, boundary, growth pattern, enhancement of three-staged lesions, and the lymph node metastasis) were analyzed by statistical methods to evaluate the difference between different tumor pathologic grades (G1, G2 and G3). Characteristics with statistical significance were analyzed by collinearity diagnostics, and stepwise regression method was used to select independent predictors. Ordinal logistic regression analysis was then conducted to develop the predicting model.Results:Maximum tumor diameter, tumor boundary, growth pattern, mr-T, mr-N, EMVI, MRF, T2WI signal intensity, tumor enhancement degree in venous phase and distant metastasis were closely correlated with the pathological grade of rectal neuroendocrine tumors ( P<0.001, 0.001, 0.001, <0.001, 0.001, 0.004, 0.024, 0.015, 0.001, and <0.001, respectively). The mr-T and tumor enhancement degree in venous phase were identified as the independent predictors to construct the prediction model. The model got ideal performance in predicting the grades, with the areas under the receiver operating characteristic (ROC) curves (AUCs) of 0.945, 0.624 and 0.896, the sensitivities were 75.0%, 85.7%, and 90.9% and corresponding specificities were 88.9%, 52.6% and 93.3% for G1, G2 and G3 rectal neuroendocrine tumors, respectively. Conclusion:The model based on mr-T and tumor enhancement degree in venous phase can serve as a clinical tool for predicting the pathological grade of rectal neuroendocrine tumors.

Objective:This study was performed to investigate the feasibility of preservation of internal branch of superior laryngeal nerve(ibSLN) during transoral endoscopic surgery for hypopharyngeal squamous cancer(HSCC) and the influence on patient′s swallowing function after operation.Methods:From May 2020 to June 2021, the data of 29 HSCC patients who required for transoral endoscopic surgery in the Department of Otorhinolaryngology Head and Neck Surgery, the Second Xiangya Hospital of Central South University were prospectively included, and the included patients were divided into two groups randomly by lottery. According to whether ibSLN was actively dissected during operation, they were divided into ibSLN preservation group ( n=15) and control group ( n=14, without ibSLN preservation). Operation time, intraoperative hemorrhage, intraoperative neck dissection, postoperative radiotherapy, postoperative recurrence within 1 year, retention and swallowing function, the recovery of oral soft diet and the quality of life were compared between two groups. SPSS 25.0 software was used for statistical analysis. Results:The study included 29 eligible patients, including 25 males and 4 females.The age ranged from 42 to 67 (56.07±5.93) years. There were no significant differences( P>0.05) between 2 groups in the following data,including age( t=-0.56), gender( χ2=0.01), TNM stage(T stage χ2=0.29, N stage χ2=0.02), pathological diagnosis( χ2=0.03), preoperative swallowing function( χ2=0.00) and M. D. Anderson Dysphagia Inventory(MDADI) score(global t=0.55, emotional t=0.16, functional t=0.60, physical t=0.64), operation time( t=1.62) and intraoperative hemorrhage( t=-1.46), intraoperative neck dissection( χ2=0.01), postoperative radiotherapy( χ2=0.32), postoperative recurrence within 1 year( P>0.050). The swallowing function was evaluated by water swallowing test after operation. The swallowing function of ibSLN preservation group was better than control group, and the difference between two groups was statistically significant on the 1st ( χ2=4.44, P=0.035), 5th ( χ2=4.24, P=0.039) and 7th ( χ2=4.55, P=0.033) day after operation. On the 14th day after operation, the MDADI scores of patients in the ibSLN preservation group were higher than those in the control group in global ( t=2.45, P=0.021), functional ( t=2.54, P=0.017) and physical ( t=2.24, P=0.034) dimensions, except for emotional dimension ( t=1.89, P=0.070). The median time of oral soft diet( U=23.00, P<0.001), normal oral diet( U=21.00, P<0.001) and the nasogastric tube removal time ( U=18.50, P<0.001) in ibSLN preservation group was 2 days, 5 days and 6 days respectively, earlier than that in control group, which had statistically significant difference. Conclusion:Our results show that it is feasible to preserve the ibSLN during HSCC transoral endoscopic surgery, which can achieve rapid recovery of postoperative swallowing function.

Objective:To explore the value of MRI features in predicting the pathological grade of rectal neuroendocrine tumors and to develop a predicting model.Methods:A retrospective analysis was performed on 30 cases of rectal neuroendocrine tumors confirmed by surgery and pathology between 2013 and 2019. All of them underwent plain rectal MRI, DWI and dynamic contrast-enhanced MRI. The clinical features and MRI characteristics (ie. tumor location, maximum tumor diameter, boundary, growth pattern, enhancement of three-staged lesions, and the lymph node metastasis) were analyzed by statistical methods to evaluate the difference between different tumor pathologic grades (G1, G2 and G3). Characteristics with statistical significance were analyzed by collinearity diagnostics, and stepwise regression method was used to select independent predictors. Ordinal logistic regression analysis was then conducted to develop the predicting model.Results:Maximum tumor diameter, tumor boundary, growth pattern, mr-T, mr-N, EMVI, MRF, T2WI signal intensity, tumor enhancement degree in venous phase and distant metastasis were closely correlated with the pathological grade of rectal neuroendocrine tumors ( P<0.001, 0.001, 0.001, <0.001, 0.001, 0.004, 0.024, 0.015, 0.001, and <0.001, respectively). The mr-T and tumor enhancement degree in venous phase were identified as the independent predictors to construct the prediction model. The model got ideal performance in predicting the grades, with the areas under the receiver operating characteristic (ROC) curves (AUCs) of 0.945, 0.624 and 0.896, the sensitivities were 75.0%, 85.7%, and 90.9% and corresponding specificities were 88.9%, 52.6% and 93.3% for G1, G2 and G3 rectal neuroendocrine tumors, respectively. Conclusion:The model based on mr-T and tumor enhancement degree in venous phase can serve as a clinical tool for predicting the pathological grade of rectal neuroendocrine tumors.