Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

Objective:To evaluate the efficacy of multimodal prehabilitation in patients with refractory functional constipation undergoing Jinling procedure(modified Duhamel surgery).Methods:In this prospective randomized controlled trial,80 patients with refractory functional constipation scheduled for Jinling procedure at the Department of General Surgery,the General Hospital of Eastern Theater Command between January 2020 and December 2021 were enrolled.Participants were randomly assigned to either the observation group(n=40,multimodal prehabilitation)or control group(n=40,routine nursing care).Outcome measures included:time to first flatus,time to first ambulation,defecation volume on postoperative day 5,length of hospitalization,nutritional markers(hemoglobin,albumin,total protein at postoperative day 7),anxiety/depression scores(Hospital Anxiety and Depression Scale,HADS),and total complication rates.Results:Compared to controls,the first ventilation time(48.02±6.15)h,first ambulation time(49.92±5.58)h,defecation volume on the fifth day(234.50±51.03)mL,hospital stay(13.15±2.64)d,anxiety score(43.68±3.45)points,depression score(43.81±1.58)points,and the total incidence of postoperative complications(15%)were significantly lower in the observation group(all p values<0.05).By contrast,the serum levels of hemoglobin(115.60±11.60)g/l,albumin(41.19±5.79)g/L and total protein(61.64±4.94)g/L on day 7 post-operatively were significantly higher in the observation group than those in the control group(P<0.05).Conclusions:Multimodal prehabilitation enhances postoperative intestinal recovery,reduces complications,improves nutritional status,and shortens hospital stays in refractory functional constipation patients undergoing Jinling procedure,supporting its clinical adoption.

Objective To analyze the relationship between frailty and acute kidney injury(AKI)after hip fracture surgery in the elderly.Methods A total of 405 elderly patients who underwent hip fracture surgery in Jieyang People's Hospital from August 2021 to January 2023 were retrospectively analysed.According to the modified frailty index(mFI),they were divided into frail group(mFI≥0.27,n=112)and non-frail group(mFI<0.27,n=293).Postoperative AKI was defined according to the Kidney Disease:Improving Global Outcomes(KDIGO)criteria.After 1:1 propensity score matching(PSM),100 cases in each group were successfully matched.Univariable and multivariable logistic regression models,propensity score adjustment,PSM,inverse probability of treatment weighting(IPTW),standardized mortality ratio weighting(SMRW),pairwise algorithm(PA)weighting,and overlap weighting(OW)methods were used to analyze the relationship between frailty and postoperative AKI.Stratified analyses were performed according to age(≥80 or<80 years),gender,whether angiotensin-converting enzyme inhibitors(ACEI)/angiotensin Ⅱreceptor antagonists(ARB)were used,and whether intraoperative hypotension occurred.Results After PSM,there were no significant differences between the two groups in age,sex,surgical type,ACEI/ARB,blood urea nitrogen,serum creatinine,intraoperative blood loss,and intraoperative hypotension[standardized mean difference(SMD)<0.1].In both the original cohort and the matched cohort,the incidence of AKI was higher in frail group than in non-frail group(25.9%vs.8.9%,P<0.001;28.0%vs.11.0%,P=0.002).Analysis of the risk of postoperative AKI in elderly hip fracture patients in frail group found that compared with the non-frail group,in the univariate logistic regression model the odds ratio(OR)and a 95%confidence interval(CI)for the frail group was 3.59(2.00-6.43),P<0.001,and in the multivariable logistic regression model,the OR(95%CI)for frail group was 3.04(1.55-5.95),P=0.001.After adjustment for propensity score,the OR(95%CI)for frail group was 2.85(1.52-5.34),P=0.001,and the OR(95%CI)for frail group after PSM was 3.15(1.47-6.75),P=0.003.After IPTW,SMRW,PA weighting,and OW,the OR(95%CI)for frail group were 2.48(1.37-4.50),2.43(1.41-4.19),2.63(1.25-5.54),and 2.69(1.07-6.78),respectively,with P<0.05.The interaction tests were not statistically significant for age,sex,use of ACEI/ARB,and intraoperative hypotension(P>0.05).Conclusion In elderly patients with hip fractures,preoperative frailty may be a risk factor for postoperative AKI.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Objective To investigate the active ingredients of Fuzheng Huaxian Decoction and its main biological processes and signaling pathways acting on idiopathic pulmonary fibrosis(IPF)through network pharmacology,to explore the core targets and mechanisms of Fuzheng Huaxian Decoction for the treatment of IPF,and to validate the results with molecular docking techniques.Methods Active ingredients of drugs,potential targets and target genes of diseases were screened from TCMSP,HERB,Uniport,Genecards,and Swiss Target Prediction databases.Then the screened drug-disease common targets were input into String database to construct target protein-protein interaction(PPI)network,and R language was used to perform gene ontology(GO)biological process and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses.Results A total of 174 active ingredients,333 drug targets and 3 509 disease targets were screened.The topological analysis revealed that serine/threonine kinase 1(AKT1),tumor necrosis factor(TNF),tumor protein 53(TP53),and vascular endothelial growth factor A(VEGFA)might be the core targets of Fuzheng Huaxian Decoction for the treatment of IPF.GO and KEGG functional enrichment analyses revealed that Fuzheng Huaxian Decoction mainly interfered with IPF through advanced glycation end product-receptor for advanced glycation end-product(AGE-RAGE)signaling pathway,phosphatidylinositol 3-kinase(PI3K-AKT)signaling pathway,and interleukin 17(IL-17)signaling pathway.Conclusion The present study based on network pharmacology and molecular docking finds that Fuzheng Huaxian Decoction can alleviate the progression of IPF through multitargets and multi-signaling pathways,which provides a basis for further study of Fuzheng Huaxian Decoction for the treatment of IPF.

Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Nasopharyngeal Carcinoma ; Jugular Foramina ; Neoplasm Recurrence, Local ; Endoscopy/methods* ; Nasopharyngeal Neoplasms/surgery*

Humans ; Endoscopy ; Neurosurgical Procedures ; Skull Base/surgery*

Objective: To summarize the application of temporalis muscle flap in the salvage nasopharyngectomy for advanced recurrent nasopharyngeal carcinoma (rNPC), and to provide guidance for the repair of extensive skull base defects in salvage rNPC. Methods: A total of 54 patients with the application of temporalis muscle flap in the salvage nasopharyngectomy for advanced rNPC were retrospectively analyzed, including 42 males and 12 females, aging from 29 to 71 years. There were 36 patients with rT3 and 18 patients with rT4. The surgical methods of temporalis muscle flap repair were summarized. The general situation, survival time and postoperative complications of patients were recorded, and the advantages and disadvantages of temporalis muscle flap were discussed. Results: The temporal muscle flap could completely cover the defect area of nasopharynx and skull base, without the need for other autologous repair materials. The follow-up period was 2 to 28 months. The survival rate of temporalis flap was 98.1% (53/54). The 1-year overall survival rate was 84.5% while 1-year progression-free survival rate was 49.0%. None of the patients had facial nerve injury. Three patients (5.6%) had necrosis of the cranial membrane required surgical intervention and four patients (7.4%) required a chonoplasty due to severe chonostril stenosis or chonostril atresia. Eleven cases (20.4%) had mouth opening restriction, chewing weakness, dysphagia and other eating difficulties. Conclusions: Temporalis muscle flap is an alternative flap for the salvage nasopharyngectomy for advanced rNPC. Temporal muscle flap shows high survival rate and wide coverage, but the surgeon should apprehend the possible complications and reduce the occurrence of them.
Humans ; Male ; Female ; Nasopharyngeal Carcinoma ; Retrospective Studies ; Surgical Flaps ; Nasopharyngeal Neoplasms/pathology* ; Muscles/pathology*

Objective    To discuss the feasibility of establishment of animal model of "functional" bicuspid aortic valve with swine and observe its effect on the wall shear stress inside the aorta. Methods    Four common Shanghai White Swine with body weight between 50 kg to 55 kg were selected. Under general anesthesia and cardiopulmonary bypass, the aortic transverse incision approach was used, continuous suture with 6-0 polypropylene to align the left and right coronary valve leaflets to create a bicuspid valve morphology. After the operation, echocardiography was used to observe the aortic valve morphology and the hemodynamic changes of the aortic valve orifice. The effect on the wall shear stress inside the aorta was studied with 4D-Flow magnetic resonance imaging (MRI). Results    A total of 4 swine "functional" bicuspid aortic valve models were established, with a success rate of 100.0%. Echocardiography showed that the blood flow velocity of the aortic valve orifice was faster than that before the operation (0.96 m/s vs. 1.80 m/s). 4D-Flow MRI showed abnormally increased wall shear stress and blood flow velocity in the aorta of the animal models. After the surgery, in model animals, the maximal wall shear stress inside the ascending aorta was greater than 1.36 Pa, and the maximum blood flow velocity was greater than 1.4 m/s. Conclusion    Establishment of the animal model of "functional" bicuspid aortic valve in swine is feasible, scientific and reliable. It can be used in researches on evaluating the pathophysiological changes.

Objective: To investigate the depression status of pregnant and perinatal women in early, medium-term, late pregnancy and postpartum period in China and the outcomes of depression in each period, analyze the influential factors of depression status. Methods: By using the pregnant and perinatal women mental health cohort established by National Center for Women and Children's Health of Chinese Center for Disease Control and Prevention, Haidian District Maternal and Child Health Hospital of Beijing, Women Health Center of Shanxi, Jilin Women and Children Health Hospital, Zhuhai Center for Maternal and Child Health Care and Shenzhen Maternity and Child Healthcare Hospital of Guangdong province, a follow up study was conducted at 7 time points during pregnancy and perinatal period in pregnant and perinatal women in Beijing, Shanxi, Jilin and Guangdong from August 1, 2015 to October 31, 2016. The self-filled questionnaire and Edinburgh Postpartum Depression Scale (EPDS) were used to obtain the general demographic information and depression status of the pregnant and perinatal women, and the depression status and natural outcomes of the pregnant and perinatal women were analyzed. Results: A total of 1 284 pregnant and perinatal women were recruited. In this study, a total of 1 210 subjects who completed follow-up at least 6 times and postpartum 42 day follow up were included in the final analysis. The EPDS depression score at the gestation week 13 was used to indicate the depression status in early pregnancy, the average EPDS score of gestation week 17 and 24 were used to indicate the depression status in medium-term pregnancy, and the average EPDS score of gestation week 31 and 37 were used to indicate depression in late pregnancy. The average EPDS score of postpartum day 3 and 42 were used to indicate postpartum depression status. A total of 321 (26.5%), 218 (18.0%), 189 (15.6%) and 219 (18.1%) pregnant and perinatal women were found to have depression, respectively, in early, medium-term and late pregnancy and in postpartum period. The depression status in early, medium-term and late pregnancy and postpartum period were positively correlated (P<0.001), the correlation between early and middle pregnancy was strong (r=0.678), the correlation between medium-term and late pregnancy was strong (r=0.771), and the correlation between postpartum period and late pregnancy was strong (r=0.706). Among the pregnant women with depression in early pregnancy, 26.2% were depressed during the whole study period, 42.7% were depressed during postpartum period, and the results of multifactorial analysis showed that the education level of college or above of the pregnant and perinatal women (OR=0.437, 95%CI: 0.212-0.900, P=0.025), exercise during pregnancy (OR=0.586, 95%CI: 0.348-0.987, P = 0.044), high marital satisfaction (OR = 0.370, 95%CI: 0.221-0.620, P<0.001), normal body mass index (BMI) (OR=0.516, 95%CI: 0.270-0.985, P=0.045) reduced the risk for depression. Unsatisfactory living environment (OR=1.807, 95%CI: 1.074-3.040, P=0.026) increased the risk for depression. Conclusions: In pregnant and perinatal women in China, the detection rate of depression in early pregnancy was highest compared with those in medium-term and late pregnancy. The detection rate of depression increased again in postpartum period. The depression status detected in the early pregnancy remained in the medium-term and late pregnancy and postpartum period. Exercise, BMI, educational level, living environment satisfaction and marital satisfaction can affect the incidence of depression in pregnant and perinatal women.
Child ; Depression/epidemiology* ; Depression, Postpartum/epidemiology* ; Female ; Follow-Up Studies ; Humans ; Postpartum Period ; Pregnancy ; Psychiatric Status Rating Scales