OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

With the rapid development of implant dentistry, increasing attention has been paid to the long-term stability and aesthetic outcomes of dental implants, among which sufficient volume and quality of soft and hard tissues are considered crucial contributing factors for successful treatment outcomes. Among the various available tissue regeneration strategies, plasmatrix, an autologous biomaterial derived from the patient ' s own peripheral blood, has demonstrated unique and significant clinical value in the regeneration and augmentation of both soft and hard tissues associated with dental implant therapy in recent years. This notable potential is primarily attributed to its rich content of multiple growth factors, viable cells, and a supportive fibrin scaffold, along with its excellent biocompatibility, tunable biodegradation profile, and a relatively simple and rapid preparation process that does not require complex laboratory equipment. As a result, its clinical applications have been continuously expanding across a wide range of indications. Based on a comprehensive review of the existing literature and current research evidence, this article provides an in-depth summary of the advancements in both basic science and clinical applications of plasmatrix in the context of implant dentistry. Particular attention is given to its classification from a materials science perspective, underlying molecular mechanisms, biological effects in promoting tissue regeneration, and its implementation under different clinical scenarios. Furthermore, the article discusses unresolved technical challenges and existing controversies, and outlines potential future directions for research and technological innovation, aiming to provide robust evidence-based guidance for clinical practice as well as a theoretical and methodological reference for future scientific investigations.
Humans ; Biocompatible Materials/therapeutic use* ; Dental Implants ; Tissue Scaffolds ; Fibrin/therapeutic use* ; Tissue Engineering/methods* ; Dental Implantation/methods* ; Dental Implantation, Endosseous/methods*

Metabolic dysfunction-associated fatty liver disease （MAFLD） has a relatively high prevalence rate around the world and is closely associated with the development of various extrahepatic malignancies， among which pancreatic cancer exhibits the highest mortality rate. However， the underlying mechanism between MAFLD and pancreatic cancer remains unclear. This article systematically introduces the latest epidemiological evidence of the association between MAFLD and pancreatic cancer， reviews the research advances in pathogenesis， and evaluates the impact of MAFLD severity and high-risk factors （such as nonalcoholic fatty pancreatic disease and intraductal papillary mucinous neoplasm） on the risk of pancreatic cancer. This article points out that insulin resistance， adipokines， and gut dysbiosis may be the key mechanisms of MAFLD promoting the onset of pancreatic cancer， and it also highlights the presence of heterogeneity in current studies. Large-scale prospective cohort studies are needed in the future to further validate the causal relationship and explore more effective strategies for risk stratification.

Immediate implant placement can reduce the number of treatments and the time without teeth, but it carries a higher aesthetic risk. Soft tissue augmentation can reduce the risk of gingival recession to a certain extent, improve the predictability and long-term stability of immediate implant aesthetics, and is currently a hot research topic. A comprehensive understanding of the evidence-based medicine and surgical techniques using soft tissue augmentation in immediate implant surgery can assist in clinical diagnosis, treatment decisions and improve treatment outcomes. This article elucidates the changes in soft and hard tissues after immediate implant placement, aesthetic risks, and risk factors. It also discusses the advantages, timing, material selection, and commonly used clinical techniques of soft tissue transplantation in immediate implantation, aiming to provide reference for clinical doctors to improve the effectiveness of immediate implantation.

Objective:To investigate the influence of varied oxygen (O 2) concentration environments on the phenotypic transformation of pulmonary artery smooth muscle cells (PASMC) and the mechanism of pulmonary hypertension. Methods:Primary rat PASMC were isolated and cultured through the process of enzymatic digestion. Following identification, the stable passaged PASMC were subjected to a 6-hour incubation in sealed containers with normal O 2 content (group C) and relative O 2 content comprising 55% (group H55), 75% (group H75), and 95% (group H95). mRNA and protein expression of α-Actin (α-SMA), smooth muscle 22α (SM22α), osteopontin (OPN), and matrix metalloproteinase-2 (MMP-2) were measured using real-time quantitative PCR and western blot analysis. Results:The H55 group displayed no significant difference from the C group in terms of mRNA and relative protein expression levels for α-SMA, SM22α, OPN, and MMP-2 (all P>0.05). On the other hand, groups H75 and H95 exhibited a reduction in mRNA and relative protein expression of α-SMA and SM22α, along with an increase in mRNA and relative protein expression of OPN and MMP-2 when compared with both the C and H55 groups (all P<0.05). The H95 group showed a higher relative mRNA expression of MMP-2 as compared to the H75 group ( P<0.05). Conclusions:Oxygen concentration environments of 75% or higher can serve as the foundation for the pathogenesis of pulmonary hypertension, essentially by inducing a phenotypic transformation in PASMC towards adopting a robust secretory function. This induction is contingent upon the concentration of oxygen present.

Objective:To investigate the value of serum vascular endothelial growth factors (VEGF), pepsinogen ratio (PGR) combined with magnifying chromoendoscopy in the diagnosis of Epstein-Barr virus associated gastric carcinoma (EBVaGC).Methods:A retrospective case control study was conducted. The clinical data of 314 patients with gastric cancer who were confirmed by pathological examination in Baoji Central Hospital from January 2018 to January 2023 were retrospectively collected. All patients were divided into EBVaGC group (34 cases) and EB virus negative gastric cancer (EBVnGC) group (280 cases) according to the result of EB virus quantitative real time polymerase chain reaction in serum before treatment, while 50 healthy volunteers who underwent the physical examination in the same period were selected as the control group. The level of VEGF was detected by using enzyme-linked immunosorbent assay (ELISA), and serum levels of pepsinogen (PG) Ⅰ and PGⅡ were detected by using fluorescence immunochromatography. PGR was calculated by PGⅠ-to-PGⅡ ratio. Electronic magnification gastroscopy was performed, suspicious lesions were stained and the pathological state of gastric tissues was observed. Taking the pathological results of living tissues as the gold standard, the diagnostic efficacy of each index alone and the combination detection for EBVaGC was calculated. Multivariate logistic regression model was used to analyze the independent risk factors of the incidence of EBVaGC.Results:The age of patients in EBVaGC group, EBVnGC group and the healthy control group was (61±10) years, (63±12) years and (61±12) years, respectively; and there were 28 males (82.4%), 228 males (81.4%) and 41 males (82.0%), respectively. There were no statistically significant differences in age and gender among the 3 groups (all P>0.05). The serum VEGF level and the proportion of positive patients detected by endochromatography in EBVaGC group were higher than those in the EBVnGC group and the healthy control group [VEGF: (253±48) pg/ml vs. (183±38) pg/ml, (92±25) pg/ml; positive proportion: 94.1% (32/34) vs. 77.9% (218/280), 2.0% (1/50)], and the PGR in EBVaGC group was lower than that in EBVnGC group and the healthy control group (2.1±1.0 vs. 3.1±1.1, 14.1±1.9), and the differences were statistically significant (all P<0.05). The sensitivity of serum VEGF in the diagnosis of EBVaGC was higher than that of PGR [73.5% (25/34) vs. 66.9% (22/34)]. The diagnostic specificity of PGR [78.2% (219/280) vs. 69.3% (194/280)] and accuracy [76.8% (241/314) vs. 69.8% (219/314)] were higher than those of VEGF. The sensitivity [85.3% (29/34)], specificity [82.9% (232/280)] and accuracy [83.1% (261/314)] of magnifying chromoendoscopy in the diagnosis of EBVaGC were higher than those of VEGF and PGR. The sensitivity [94.1% (32/34)], specificity [95.7% (268/280)] and accuracy [95.5% (300/314)] of the 3 combined detection were higher than those of single and pairwise detection. Multivariate logistic regression analysis showed that the independent risk factors for the incidence of EBVaGC included alcoholism ( OR = 2.310, 95% CI: 1.243-3.581, P = 0.007), spicy food preference ( OR = 1.516, 95% CI: 1.084-2.142, P = 0.026), irregular diet ( OR = 1.448, 95% CI: 1.013-2.104, P = 0.043), family history of gastric cancer ( OR = 2.732, 95% CI: 1.312-4.894, P = 0.001). Conclusions:Serum VEGF and PGR combined with magnifying chromoendoscopy can improve the diagnostic efficiency of EBVaGC, and developing good eating will be helpful to prevent or slow down the progression of stomach diseases.

Objective To explore mechanisms of family resilience in children with obstetrical brachial plexus palsy(OBPP)and provide a basis for developing interventions to family resilience.Methods Semi-structured interviews were conduc-ted with 10 primary caregivers,and data were analyzed through content analysis.Results Three themes were distilled,namely,great impact of the injurious event on the family,positive response of the family to the injurious event,and hidden pain that the injurious event brought to the family.Conclusion The overall resilience of families of OBPP children is in a high level.It is es-sential to address the adverse impact of the injurious event on the families,consolidate the positive results of the family's re-sponse to the injury,and promote the restoration and enhancement of the family's function.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.