Objective To investigate the mechanism of glycogen synthase kinase-3β（GSK-3β） participating in stroke-induced inflammatory brain injury through endoplasmic reticulum-mitochondria coupling， and to provide a theoretical reference and potential targets for precise treatment. Methods A rat model of middle cerebral artery occlusion was established， and the rats were divided into sham-operation group， model group， and GSK-3β inhibitor（TDZD-8） intervention group. Neurological function score was used to evaluate the degree of brain injury； TTC staining was used to evaluate cerebral infarct area； electron microscopy was used to observe mitochondrial ultrastructure； mitochondrial calcium concentration was measured； ELISA was used to measure the levels of inflammatory factors[tumor necrosis factor-α（TNF-α）and interleukin-1β（IL-1β）]， and Western blot was used to measure the expression levels of related proteins. Results Compared with the sham-operation group， the model group had significant neurological function impairment， an increase in cerebral infarct area， and significant increases in the expression levels of inflammatory factors and GSK-3β，with enhanced endoplasmic reticulum-mitochondria coupling and mitochondrial calcium overload. TDZD-8 significantly improved the above indicators and reduced the levels of inflammatory factors and cerebral infarct area. Conclusion Abnormal activation of GSK-3β damages brain tissue by regulating endoplasmic reticulum-mitochondria coupling and promotes mitochondrial calcium overload and inflammatory response. Inhibiting GSK-3β activity can effectively improve stroke-induced inflammatory brain injury， which provides a new pathway and a molecular target for developing precise treatment strategies.
Stroke

The prevalence of periodontitis in China is as high as 74.2%, making it the leading cause of tooth loss in adults and severely impacting both oral and overall health. The treatment of periodontitis and periodontal tissue regeneration are global challenges of significant concern. GE Shaohua' s group at School and Hospital of Stomatology, Shandong University has focused on the key scientific issue of "remodeling the periodontal inflammatory microenvironment and optimizing tissue repair and regeneration". They have elucidated the mechanisms underlying the persistence of periodontitis, developed bioactive materials to enhance stem cell regenerative properties, and constructed a series of guided tissue regeneration barrier membranes to promote periodontal tissue repair, leading to the establishment of a comprehensive technology system for the treatment of periodontitis. Specific achievements and progress include: (1) Elucidating the mechanism by which key periodontal pathogens evade antimicrobial autophagy, leading to inflammatory damage; developing intelligent antimicrobial hydrogels and nanosystems, and creating metal-polyphenol network microsphere capsules to reshape the periodontal inflammatory microenvironment; (2) Explaining the mechanisms by which nanomaterial structures and electroactive interfaces regulate stem cell behavior, developing optimized nanostructures and electroactive biomaterials, thereby effectively enhancing the regenerative repair capabilities of stem cells; (3) Creating a series of biphasic heterogeneous barrier membranes, refining guided tissue regeneration and in situ tissue engineering techniques, stimulating the body' s intrinsic repair potential, and synergistically promoting the structural regeneration and functional reconstruction of periodontal tissues. The research outcomes of the group have innovated the fundamental theories of periodontal tissue regeneration, broken through foreign technological barriers and patent blockades, established a cascade repair strategy for periodontal regeneration, and enhanced China' s core competitiveness in the field of periodontal tissue regeneration.
Humans ; Stem Cells/physiology* ; Periodontitis/therapy* ; Guided Tissue Regeneration, Periodontal/methods* ; Regeneration ; Biocompatible Materials ; Tissue Engineering/methods*

OBJECTIVES: To investigate the impact of prenatal fear stress on placental amino acid transport and emotion and cognition development in offspring rats. METHODS: Thirty pregnant Wistar rats were randomized equally into control and fear stress (induced using an observational foot shock model) groups. In each group, placental and serum samples were collected from 6 dams on gestational day 20, and the remaining rats delivered naturally and the offspring rats were raised under the same conditions until 8 weeks of age. Emotional and cognitive outcomes of the offspring rats were assessed with behavioral tests, and placental structure was examined using HE staining. Bioinformatics analysis was used to identify differentially expressed placental transporter genes under fear stress. The expressions of system A and system L amino acid transporters, along with other specialized transporters, were detected using qRT-PCR and Western blotting. Fetal serum amino acid concentrations were determined by HPLC. The correlations between fetal amino acid levels and behavioral outcomes of the offspring rats were analyzed. RESULTS: The dams with fear stress showed reduced open-field activity and increased freezing behavior with significantly decreased placental weight, fetal weight, and fetal-to-placental ratio. Bioinformatics analysis revealed 28 differentially expressed transporter genes involved mainly in amino acid transport. In the fear stress group, fetal serum amino acid levels were significantly lowered and Slc38a1, Slc43a1, Slc43a2, Slc7a8, Slc6a6, Slc1a1 and Slc6a9 mRNA and protein expressions were all downregulated. The offspring rats in fear stress group exhibited decreased novel object preference and spontaneous alternation with reduced open arm exploration and increased immobility in emotional tests. Lower early-life amino acid levels was found to correlate with impaired adult cognition. CONCLUSIONS Prenatal fear stress in rats impairs placental amino acid transporter expression and reduces fetal serum amino acid levels, potentially contributing to long-term cognitive deficits in the offspring rats.
Animals ; Female ; Pregnancy ; Placenta/metabolism* ; Fear ; Rats ; Rats, Wistar ; Cognition ; Prenatal Exposure Delayed Effects ; Stress, Psychological ; Amino Acids/blood* ; Amino Acid Transport Systems/metabolism*

OBJECTIVE To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation. METHODS A "component-target-pathway" network was constructed with the help of TCMSP, Pubchem, SwissTargetPrediction and Genecards databases, and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis. KEGG and GO enrichment analysis was performed in the DAVID database, and molecular docking of active ingredients and key targets was docked in AUTODOCK. PDGF-BB was used to induce activation of cells and verify the effects of six compounds, including quercetin, quercetin, chicoric acid, caffeic acid, chlorogenic acid, and isochlorogenic acid, on the proliferation, apoptosis, and liver fibrosis indicators of HSC-T6 cells. Western blotting was used to detect the expression of Ras, ERK1, ERK2, C-fos, and JNK proteins in HSC-T6 cells. RESULTS Network pharmacology screened 239 common targets between the components and liver fibrosis, PPI analysis showed that SRC, STAT3, HSP90AA1 and other targets were key targets, KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways, metabolic pathways, etc. GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction. The molecular docking results showed that the target that could bind well with the components MAPK1, and the components that could bind well with the target aesculetin, caffeic acid and chlorogenic acid. Compared with the model group, the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger, and all 6 compounds had the effects to reverse the index of liver fibrosis, in which aesculetin had the strongest activity(P<0.01). The expression of Ras, ERK1, ERK2, C-fos, and JNK in HSC-T6 cells decreased after the interventions of 6 compounds. CONCLUSION Each component of Cichorium glandulosum has different anti liver fibrosis effects, which are related to the inhibition of ERK/RAS pathway activation.

Objective:To analyze the nutritional status of progeria, and to provide reference for scientific nutritional management of progeria.Methods:This cross-sectional study included 15 children with progeria who were treated at Children′s Hospital, Zhejiang University School of Medicine, between April 2022 and May 2023. Data of medical history, physical examination, laboratory tests, dietary survey and body composition were collected and analyzed.Results:Among 15 patients there were 7 males and 8 females, aged 7.8 (2.3, 10.8) years. Twelve of the 15 patients exhibited signs of malnutrition. A 24-hour dietary survey was carried out in 14 of them. The daily energy intake of 11 cases was below recommended levels. Carbohydrate intake was insufficient in 10 cases, protein intake was insufficient in 7 cases, and fat intake was insufficient in 12 cases. Deficiencies in calcium, magnesium, iron and zinc were noted in 13, 13, 9 and 10 cases, respectively. Body composition was determined by dual-energy X-ray absorptiometry in 8 cases, and the bone mineral density was below average in 5 of them.Conclusions:Malnutrition, characterized by reduced energy intake, micronutrient deficiencies, and alteration in body composition, is prevalent in children with progeria. Regular routine nutritional assessment and proper interventions may benefit their long-term health status.

The incidence of portal vein tumor thrombus (PVTT) in patients with hepato-cellular carcinoma (HCC) is high and the prognosis is poor. The treatment mode of HCC+PVTT is changing to multidisciplinary comprehensive treatment. The authors make a deep investigation on the occurrence basis, classification, surgical treatment indication, postoperative adjuvant treatment and preoperative conversion treatment plan of HCC+PVTT, in order to provide reference for the diagnosis and treatment of this disease.

【Objective】 To investigate the efficacy of flexible ureteroscopic holmium laser lithotripsy combined with cyst wall incision and drainage in the treatment of renal calculi with ipsilateral renal cyst. 【Methods】 A total of 70 patients with renal calculi complicated with ipsilateral renal cyst (cyst diameter >40 mm, maximum diameter of stone <20 mm, distance from renal calyx <2 mm) treated in our hospital during Feb.2015 and Feb.2020 were selected. The patients were divided into cyst wall incision and drainage group (flexible ureteroscopic holmium laser lithotripsy combined with cyst wall incision and drainage) and renal cyst deroof decompression group (flexible ureteroscopic holmium laser lithotripsy combined with retroperitoneal laparoscopic renal cyst unroofing decompression), with 35 cases in either group. The general information, clinical data, complications, stone-clearance rate and 12-month postoperative effective rate were compared between the two groups. 【Results】 All operations were successful. Compared with the renal cyst unroofing decompression group, the cyst wall incision and drainage group had shorter operation time and postoperative hospital stay (P<0.05), lower postoperative Scr[(107.61±16.88) μmol/L vs. (138.25±18.29) μmol/L, P<0.05], higher Hb[(124.33±12.85) g/L vs. (101.36±13.14) g/L, P<0.001], lower incidence of complications (8.6% vs. 28.6%, P=0.031). There were no significant differences in the residual stone rate and effective rate between the two groups 12 months after operation (P>0.05). 【Conclusion】 Flexible ureteroscopic holmium laser lithotripsy combined with cyst incision and drainage has the advantages of short operation time, small trauma, few adverse reactions, good stone clearance effect and satisfactory efficacy. It can be used as a preferred surgical method for renal calculi complicated with ipsilateral renal cyst.

The Chinese Neonatal Network(CHNN) was established in 2018 with the mission of establishing a national collaboration platform, conducting high-quality and collaborative research, and ultimately improving the quality of neonatal-perinatal care and health in China.At present, 112 hospitals across the country have joined CHNN.CHNN has established a national standardized cohort of very premature infants/very low birth weight infants with >10 000 enrollments each year, has been leading data-driven collaborative quality improvement initiatives, conducting multicenter clinical studies, and performing multi-level training programs.Guided by the principles of collaboration and sharing, data-driven, continuous improvement, and international integration, CHNN has become an important platform for clinical and research collaboration in neonatal medicine in China.

Objective:To compare and analyze the perioperative outcomes of jaundiced patients undergoing laparoscopic pancreaticoduodenectomy (LPD) using preoperative percutaneous transhepatic cholangial drainage (PTCD) versus endoscopic nasobiliary drainage (ENBD).Methods:The perioperative data of 173 patients who underwent LPD at the Second Hospital of Hebei Medical University from January 2016 to December 2020 and were treated preoperatively with either PTCD versus ENBD to alleviate jaundiced were retrospectively analyzed. There were 100 males and 73 females, with age of (60.4±10.8) years old. These patients were divided into the PTCD group ( n=126) and the ENBD group ( n=47). Clinical data including operation time, blood loss, transfusion volume, R 0 resection, and postoperative complications were compared. Results:There was no convension to open surgery. There were no significant differences in operation time, blood loss, transfusion volume, R 0 resection rate, pathological results and hospital stay between the two groups ( P>0.05). For the PTCD group, the pancreatic fistula rate was 10.3% (13/126) and the post-operative hemorrhage rate was 8.7% (11/126). They were both significantly lower than those of the ENBD group [25.5% (12/47) and 25.5% (12/47) respectively, P<0.05]. There were also significant differences in the postoperative complications according to the Clavien-Dindo classification system between the two groups ( P=0.008). Conclusion:Compared with ENBD, PTCD had the advantages of lower post-operative pancreatic fistula and post-operative hemorrhage rates, resulting in a better postoperative recovery.

Conventional therapies for hemophilia A (HA) are prophylactic or on-demand intravenous FVIII infusions. However, they are expensive and inconvenient to perform. Thus, better strategies for HA treatment must be developed. In this study, a recombinant FVIII cDNA encoding a human/rat hybrid FVIII with an enhanced procoagulant potential for adeno-associated virus (AAV)-delivered gene therapy was developed. Plasmids containing human FVIII heavy chain (hHC), human light chain (hLC), and rat light chain (rLC) were transfected into cells and hydrodynamically injected into HA mice. Purified AAV viruses were intravenously injected into HA mice at two doses. Results showed that the hHC + rLC protein had a higher activity than the hHC + hLC protein at comparable expression levels. The specific activity of hHC + rLC was about 4- to 8-fold higher than that of their counterparts. Hydrodynamic injection experiments obtained consistent results. Notably, the HA mice undergoing the AAV-delivered hHC + rLC treatment exhibited a visibly higher activity than those treated with hHC + hLC, and the therapeutic effects lasted for up to 40 weeks. In conclusion, the application of the hybrid FVIII (hHC + rLC) via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice. These data might be of help to the development of optimized FVIII expression cassette for HA gene therapy.
Animals ; Dependovirus/genetics* ; Factor VIII/metabolism* ; Genetic Therapy/methods* ; Hemophilia A/therapy* ; Humans ; Mice ; Rats