Objective To observe the effect of Bushen Huoxue Decoction(BSHX)on PI3K/Akt/mTOR signaling pathway and explore its possible mechanism in improving synaptic plasticity in a vascular dementia(VD)rat model.Methods Sprague-Dawley rats were randomly divided into sham operation group(Sham group),model group(VD group),Bushenhuoxue decoction group(BSHXD group),nimodipine group(NMDP group),with 10 rats in each group.The VD model of rats was established by two-vessel(2-VO)occlusion method.Rats in BSHXD group were given BSHXD at a weight of 10.14 g·kg-1,while rats in the NMDP group were given nimodipine decoction at 11 mg·kg-1.The SHAM group and the VD group were given saline at a weight of 10 mL·kg-1 once a day for 4 weeks.Morris water maze was used to observe the spatial learning and memory ability of rats in each group.Nissl staining was used to observe the damage of Nissl bodies and neurons in CA1 area of hippocampus of rats.The expression of synaptophysin(SYN)and postsynaptic density protein 95(PSD-95)in hippocampal CA1 region was detected by immunohistochemistry.Golgi-Cox staining method was used to observe the number changes of dendritic branches and spines of hippocampal neurons.Transmission electron microscopy(TEM)observed the ultrastructural change of synapses.The protein and mRNA expressions of phosphatidylinositol 3-kinase(PI3K),serine-threonine kinase(AKT)and mammalian target of rapamycin(mTOR)in rat hippocampus were detected by Western blot and Reverse transcription quantitative PCR(RT-qPCR).Results Compared with the control group,the learning and memory ability of VD rats decreased.These rats showed abnormal synaptic ultrastructure of hippocampal neurons and neuronal cell damage,and this was accompanied by a decrease in the density of dendrite branches and dendritic spines of neurons.The expression of both SYN and PSD-95 proteins in the hippocampus decreased(P<0.05),and synaptic plasticity was damaged.Both mRNA and protein expression of PI3K,Akt,and mTOR in the hippocampus decreased in the VD rats(P<0.05).Also observed in VD rats was that administration of BHSX mitigated the learning and memory impairment observed in these animals,improved the morphology and synaptic ultrastructure of hippocampal neurons,increased the mRNA and protein expression levels of PI3K,Akt,mTOR,and increased the protein levels of SYN and PSD-95(P<0.05).Conclusion BSHX can alleviate the learning and memory impairment of VD rats and increase the protein expression levels of synapse-related proteins.These effects may be related to the promotion of synaptic plasticity by BSHX through activation of PI3K/Akt/mTOR signaling.

Objective Based on the clinical characteristics of refractory epilepsy in traditional Chinese and Western medicine,this study compares the existing animal models of refractory epilepsy,evaluates the effectiveness and limitations of the models,and explores the integration of traditional Chinese and Western medicine theory and optimization of model construction.Our aim is to provide new research directions for elucidating the mechanism and prevention of refractory epilepsy.Methods By reviewing relevant literature and summarizing the available data,we examined current refractory epilepsy animal models,focusing on their replication methods,animal strains,as well as advantages and disadvantages of animal models.Based on the Western medicine diagnostic criteria and traditional Chinese medicine syndrome differentiation criteria for refractory epilepsy,the coincidence of existing animal models and clinical symptoms were analyzed and evaluated.Results Our review of existing refractory epilepsy animal models revealed that electrical and chemical kindling are common modeling methods.The lithium-pilocarpine model and the intrahippocampal kainic acid model show high congruence with the symptom characteristics of traditional Chinese and Western medical clinical diagnosis and are widely used.Existing models mostly focus on simulating the pathological changes of refractory epilepsy,while neglecting the factors such as congenital endowment and emotional disorders,which have been emphasized in traditional Chinese medicine.Therefore,there are still certain limitations in simulating the complexity of etiology,clinical heterogeneity,and drug treatment responsiveness of refractory epilepsy.Conclusion Although replicating animal models can reflect their pathogenesis to some extent,there are still significant differences between them and the natural pathological state and clinical manifestations of the body.The existing animal models of refractory epilepsy mostly use electrical stimulation or chemical drug induction,which has certain advantages in simulating epileptic persistence and drug resistance.However,there are still limitations such as a single induction method and insufficiently complex pathological changes.In the future,efforts can be made to integrate traditional Chinese medicine syndrome differentiation and conventional electrical stimulation or chemical drug induction methods.By simulating multiple pathogenic factors,a refractory epilepsy animal model covering different traditional Chinese medicine syndrome types can be established.At the same time,multi-dimensional indicators such as behavior,electrophysiology,imaging,and histopathology can be used to construct a more comprehensive evaluation system,in order to improve the clinical relevance and translational application value of the model.During the modeling process,liver depression syndrome models can be established through methods such as tail clamping,chronic restraint,and single cage feeding with neck shackle.A model of phlegm coagulation syndrome can be established using high-fat feed feeding method.A model of qi stagnation and blood stasis syndrome can be established using tail clip and adrenaline injection.A model of essence exhaustio due to kidney deficiency syndrome can be established by combining panic induced kidney injury with fatigue swimming.It is also possible to simulate changes of yin-yang in the environment by altering lighting and temperature conditions and study the impact of environmental changes on traditional Chinese medicine animal models.The aim of this study is to provide more ideas for the treatment and research of refractory epilepsy.

Objective Network pharmacology,molecular docking,metabolomics and experimental verification were used to investigate the effect of Gegen Decoction on epileptic seizure under cerebral hypoxia.Methods The core targets of Gegen Decoction,epilepsy and cerebral hypoxia were screened by network pharmacology,and the correlation between ligand and receptor was verified by molecular docking.Further animal experiments were carried out to verify the effect of Gegen Decoction on the rat model with epilepsy accompanied by cerebral hypoxia,which was established by lithium chlorine-pilocarpine method combined with unilateral common carotid artery ligation and placing in a closed chamber with oxygen content of 10%-15%.Sixty rats were randomly divided into blank group,model group,phenytoin sodium(26 g·kg-1)group,high-,medium-and low-dose(10.62,5.31,2.655 g·kg-1)Gegen Decoction groups.After treatment,the number of epileptic seizures rats in each group was counted,and the recovery of nerve function and epileptic seizures were evaluated.HE staining was used to observe the morphological changes of the CA1 region of hippocampus in rats.The expression of interleukin-6(IL-6)and interleukin-17(IL-17)were detected by immunohistochemistry.The changes of brain neurotransmitters were analyzed by targeted metabolomics.Results Network pharmacological results suggested that 128 active components and 228 targets were obtained.A PPI network map of drug-disease was constructed by STRING.The results showed that STAT3,IL-6 and AKT1 were the core targets.GO enrichment for biological processes(BP)involves responses to external irritant,oxygen levels,hypoxia and metabolic processes of reactive oxygen species.Cell components(CC)mainly involve in the impact on cell membrane and protein kinase complex,while molecular function(MF)involves in influence on the binding of ubiquitin-like protein and ubiquitin-like protein ligase.The key pathways of Gegen Decoction in the treatment of hypoxic-induced epilepsy in the brain,which were analyzed by KEGG,involved lipid and atherosclerosis signaling pathway,IL-17 signaling pathway,Th-17 signaling pathway and so on.The experimental results showed that the number of seizures in the Gegen Decoction group was significantly decreased compared with that in the model group(P＜0.01),the morphology and structure of hippocampal cells were improved to varying degrees,and cell vacuolation was reduced.The expression of IL-17A and IL-6 in all treatment groups was lower than those in model group,and there was statistical significance in medium-dose Gegen Decoction group(P＜0.01,P＜0.05).Brain metabolomics test showed that compared with model group,monoamine neurotransmitters including 5-hydroxytryptophan(5-HTP)and norepinephrine(NE)were increased in high-dose Gegen Decoction group,while tryptophan metabolite kynurenine(Kyn)was decreased.Conclusion Gegen Decoction can reduce the levels of serum inflammatory factors IL-6 and IL-17A in epileptic rats under hypoxia.Moreover,Gegen Decoction can reduce epileptic seizures by improving hypoxia-induced inflammatory response,increasing the content of monoamine neurotransmitter(5-HTP and NE),as well as reducing the content of tryptophan metabolite Kyn and the toxin of tryptophan metabolism pathway.

Objectives: . The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods: . The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. Results: . miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion . Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

BACKGROUND: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
Humans ; Mendelian Randomization Analysis ; Irritable Bowel Syndrome ; Colorectal Neoplasms/genetics* ; Cholelithiasis/complications* ; Cholecystectomy/adverse effects* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

With the high-quality development of biotechnology-related industries in China, the demand for talents and training quality in this field have received extensive attention. Several universities in Nanjing have conducted in-depth analysis on the shortcomings of talent training that does not closely match the needs of industries and enterprises. These universities have since effectively leveraged its professional characteristics, deepened university-enterprise cooperation, and encouraged the alignment of professional development with industrial growth. Biotechnology major has always focused on nurturing individuals with "right conduct, good learning, and strong ability", and capitalized on its comparative disciplinary advantages. These universities vigorously promoted and continuously optimized the model of university-enterprise collaborative training, highlighted the integration of science, industry and education, focused on innovative education teaching methods, as well as practical engineering practice to enhance its quality. The preliminary training results show that this model has promoted students' engineering practical abilities and comprehensive qualities, garnering recognition from employers and students alike.
Humans ; Universities ; Students ; Biotechnology ; Curriculum ; Industry

Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.

A retrospective study was conducted on data of 23 patients with pancreatic duct diseases who were underwent peroral pancreatoscopy (POPS) at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from August 2020 to October 2022. The intraoperative observation, postoperative complications, and the diagnosis and treatment of POPS for pancreatic duct diseases were analyzed. All patients underwent POPS and achieved technical success. Among them, 7 patients were diagnosed as having intraductal papillary mucinous neoplasm of pancreas and 3 pancreatic malignant tumor. Eight patients with pancreatolithiasis accepted laser or eletrohydraulic lithotripsy under POPS. Abdominal pain improved in 2 patients with chronic pancreatitis after treatment. Melena disappeared in 2 patients with pancreatic duct hemorrhage or pancreatic enterostomy inflammation after conservative treatment. The symptom of 1 patient with pancreatic enterostomy stenosis improved after balloon dilation. There was no complication in the 23 patients, and the operation time was 35-90 min. The results indicate POPS is safe, effective with distinctive advantages in the diagnosis and treatment for pancreatic duct diseases.

Objective To explore the spatial distribution of microstructural parameters and mechanical properties for trabecular bone in the femoral head with osteonecrosis. Methods Microstructural parameters and mechanical properties of trabecular bone in different regions were analyzed by combined use of imaging measurements and numerical simulation method, and the spatial distribution of biomechanical properties for trabecular bone along coronal, sagittal and vertical directions was investigated. Results Microstructural characteristics and mechanical properties of trabecular bone were Y-shaped distributed along coronal and sagittal directions, and mechanical properties of trabecular bone in Y-shaped region were higher than those in the other regions. Such distribution characteristics was consistent with the location of principle compressive group in the femoral head. Conclusions Necrotic lesions in Y-shaped region had a greater influence on stress distribution of the femoral head and might cause the deterioration of osteonecrosis. The spacial correlation between necrotic lesions and Y-shaped region should be fully considered during clinical diagnosis.

OBJECTIVE To determine the protein binding rates of main effective components in Houpu paiqi mixture as magnolol and honokiol in animal plasma of different species， and compare the differences among species. METHODS The plasma of bovine， rabbit and rat （internal dialysate） was placed in 4.5， 9.0 and 13.5 μg/mL （according to the weight of the decoction pieces of Houpu paiqi mixture） dialysate containing drug for 24 h by equilibrium dialysate method. The concentrations of magnolol and honokiol in dialysis internal and external fluids were determined by ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry， and the plasma protein binding rates were calculated and compared. RESULTS At the concentrations of 4.5， 9.0 and 13.5 μg/mL， the protein binding rates of magnolol were （68.13±4.52）%， （74.34±1.12）% and （86.22±0.50）% in bovine plasma， （59.55±4.62） %， （72.81±4.56）% and （86.40±1.91）% in rabbit plasma， and （56.63± 2.87）%， （77.81±1.83）% and （83.18±0.65）% in rat plasma， respectively. The protein binding rates of honokiol were （34.82± 1.67）%， （40.29±3.28）% and （63.57±0.59）% in bovine plasma， （34.25±5.62）%， （62.12±7.36）% and （80.86±4.01）% in rabbit plasma， and （37.06±3.28）% ， （52.61±1.69）% and （79.83±7.38）% in rat plasma， respectively. There was generally statistical significance among those groups （P＜0.05 or P＜0.01）. CONCLUSIONS There are significant species differences in plasma protein binding rates of magnolol and honokiol， the main effective components of Houpu paiqi mixture， in a certain concentration-dependent trend.