Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Objective To explore the efficacy and safety of lung recruitment maneuver(LRM)on postoperative hypoxemia in patients with acute type A aortic dissection(ATAAD).Methods A total of 56 ATAAD patients with postoperative hypoxemia in the First Affiliated Hospital of Guangxi Medical University from November 2019 to May 2022 were selected and randomly divided into LRM group(n=36)and conventional treatment group(n=20).Patients in conventional treatment group received routine mechanical ventilation on the basis of lung protective ventilation.The patients in LRM group were treated with incremental positive end expiratory pressure(PEEP).Arterial blood gas analysis,respiratory parameters,hemodynamics parameters and serum interleukin(IL)-6 and IL-10 levels were compared between two groups before and after treatment.Results At 12h and 24h after treatment,arterial partial pressure of oxygen(PaO2),oxygenation index(OI),static compliance(Cstat)and dynamic compliance(Cdyn)in two groups were significantly higher than before treatment,the alveolar-arterial gradient of oxygen[PO2(A-a)],respiratory index(RI),peak inspiratory pressure(Ppeak)and plateau pressure(Pplat)were significantly lower than before treatment(P<0.05).PaO2,OI,Cstat and Cdyn in LRM group were significantly higher than those in conventional treatment group,PO2(A-a),RI,Ppeak and Pplat were significantly lower than those in conventional treatment group(P<0.05).Systolic blood pressure and mean arterial pressure decreased and central venous pressure increased during pulmonary reexpansion in LRM group(P<0.05),and all patients returned to baseline level after pulmonary reexpansion.At 12h after treatment,serum IL-6 and IL-10 levels in both groups were significantly lower than before treatment(P<0.05).Conclusion Incremental PEEP can improve oxygenation and lung compliance in patients with hypoxemia after ATAAD surgery,but it has transient effects on hemodynamics,and should be closely monitored during treatment.

Cadmium is one of the heavy metals with severe reproductive toxicity,whose half-life lasts 20 to 40 years.Cadmium could induce dysfunction of testis and epididymis for its significant accumulation in human testis,and the amount,motility parameters and morphology of sperm change abnormally.The adverse change could also extend to male offspring and cause the impairment of their reproductive system.There has been no clear mecha-nism of how cadmium induces dysfunction of male reproductive system,and treatment for the adverse influence on male reproductive system by cadmium has not yet been found.Therefore,this problem has been discussed in repro-ductive and environmental field for a long time.A number of previous investigations showed that cadmium could damage male fertility by followed pathways,including interfering with hormone secretion,inducing oxidative stress,activating inflammation and apoptosis,and causing energy metabolism disorder,etc.In order to enlighten new ideas for therapeutic targets of male reproductive function damage induced by cadmium,we systematically reviewed and summarized the findings of previous publications in this paper.

Dynamic multi-leaf collimator, which has the function of radiation beam shaping, is a key executive component of tumor precise radiotherapy, and plays a core role in improving the accuracy, efficiency and quality of radiotherapy. A new type of collimator leaf end structure with circular arc and plane combination was studied, and collimator penumbra performance analysis model combining analytical expression and graphic analysis was developed. The influence of leaf end structure on penumbra was analyzed quantitatively, and a set of three-dimensional structure design of dynamic multi-leaf collimator was completed. The feasibility of the structural design and analysis model was verified through experimental measurements.
Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Particle Accelerators ; Neoplasms ; Radiotherapy Dosage

CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors/antagonists & inhibitors* ; G2 Phase Cell Cycle Checkpoints ; Histone Deacetylase Inhibitors/pharmacology* ; Histone Deacetylases/metabolism* ; M Cells ; Multiple Myeloma/drug therapy*

Human sparganosis is a rare parasitic disease. Pleroceroid can infiltrate brain, mammary gland and other organs, with a high misdiagnosis rate. A case of subcutaneous sparganosis disease of thigh was diagnosed and treated in the Burn, Plastic Surgery and wound Repair Department of Longyan First Hospital Affiliated of Fujian Medical University in January 2022. The patient was followed up for lipoma in other hospitals for many times with no clinical treatment. Combined with the medical history and characteristic of the mass, we also treated the mass as "lipoma" and surgical resection was performed in author’s hospital. Live worms were found intraoperatively, and finally confirmed as pleroceroid by pathology and expert consultation. No local recurrence was found in 6 months of follow-up. In order to reduce the misdiagnosis rate of the disease, the diagnosis and treatment methods were reviewed and discussed. This case may provide more clinical experience for the prevention and treatment of the disease.

Human sparganosis is a rare parasitic disease. Pleroceroid can infiltrate brain, mammary gland and other organs, with a high misdiagnosis rate. A case of subcutaneous sparganosis disease of thigh was diagnosed and treated in the Burn, Plastic Surgery and wound Repair Department of Longyan First Hospital Affiliated of Fujian Medical University in January 2022. The patient was followed up for lipoma in other hospitals for many times with no clinical treatment. Combined with the medical history and characteristic of the mass, we also treated the mass as "lipoma" and surgical resection was performed in author’s hospital. Live worms were found intraoperatively, and finally confirmed as pleroceroid by pathology and expert consultation. No local recurrence was found in 6 months of follow-up. In order to reduce the misdiagnosis rate of the disease, the diagnosis and treatment methods were reviewed and discussed. This case may provide more clinical experience for the prevention and treatment of the disease.

AIM: To observe the effects of rapamycin pregnancy intervention on cognitive function of autism model in rat offspring. METHODS: Fourteen pregnant rats were randomly divided into normal group (n = 3), model group (n = 4), rapamycin (RAPA) control group (n =3) and intervention group (n = 4). The model group and intervention group were i.p. injected with sodium valproate 600 mg/kg at embryonic day (E) 12.5 to establish autism model in rat offspring. RAPA control group and intervention group were i.g. given RAPA 4 mg/kg every day from the 13th day of gestation until the offspring rats were weaned at 23 days. After the birth of the above four groups of pregnant rats, 15, 27, 21 and 26 offspring male rats were selected to conduct behavioral tests to identify the model. Then, paw withdrawal mechanical threshold (PWMT), tail flick latency (TFL) evoked under different light intensity and learning and memory function of offspring rats were further detected. RESULTS: Rat offspring in the model group had lower growth and development indexes and exploratory behavior ability, but stronger repetitive stereotyped behavior compared with the normal group (P < 0.05), while the indexes between the intervention group and model group were reversed (P < 0.05). The model group had higher PWMT than normal group (P < 0.01) and the PWMT of intervention group was lower than that of model group (P < 0.01). The TFLs of rats in 4 groups showed a timed dose-response relationship (TDRR, P < 0.01), that is, TFLs were shortened with the increase of light intensity. The TDRR curve of model group shifted to right compared with normal group (P < 0.01) and intervention group shifted to left compared with model group (P < 0.01). At the light intensity of Focus 34, 51 and 76, the TFLs of model group were longer than those of normal group (P < 0.01) and intervention group had shorter TFLs compared with model group (P<0.01). In spatial probing trial of Morris water maze test, the platform crossover number in model group was less than that in normal group (P<0.01) and that in intervention group was more than model group (P < 0.05). CONCLUSION: RAPA intervention during pregnancy may alleviate behavior disorder, pain tolerance and memory function of autism model in rat offspring to some extent.

Objective: To explore a method for macrostomia repairment, in order to to achieve better physiological and aesthetic outcomes. Methods: 23 patients with macrostomia were treated by standard procedure: including orbicularis oris reconstruction, perioral expression muscles fixation, modiolus reconstruction, commissure point shift, and " w" shape incision. Results: 22 cases obtained both static and dynamic symmetrical outcomes. One case developed asymmetrically. Conclusions The macrostomia repairment following present standard procedure, is likely to achieve both static and dynamic satisfactory outcomes, due to balanced perioral muscles.

Objective: To evaluate the differential calretinin immunostaining in different segments of total colonic aganglionosis and its utility in the diagnosis. Methods: Nine specimens including ileum and colon segments were obtained from 9 patients with total colonic aganglionosis (TCA), from 2010 to 2016 year, in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology. Another 9 ganglionic specimens including the same segments from patients with non-Hirschsprung disease (non-HD) patients were collected as control. All cases were immunostained with calretinin. The patterns of calretinin immunostaining were observed, and morphometric analysis of each sample was performed by image analysis program (Image-Pro-Plus). The mean absorbance was evaluated by calculating the areas of the lamina propria occupied by the positively stained area of the calretinin at high power field. Results: The same pattern of calretinin immunostaining was seen in ganglionic ileum and ganglionic colon segments, with staining seen in intrinsic nerves fibers (INF), and in granular aggregates in the lamina propria and muscularis mucosae. There was no significant difference in the numbers of calretinin-positive INF from the ganglionic segments. In contrast, the number of calretinin-positive INF and granular aggregates in aganglionic segments were significantly lower than those in the ganglionic group (P<0.01). In the ileum transitional zone, scattered calretinin staining was observed, and the amount of calretinin-positive INF was significantly lower than those in the proximal segment of ganlionic ileum (P<0.01). Conclusions Since there is significant different expression of calretinin among the different segments from TCA, calretinin immunostaining has potential value in detecting TCA. It could be an important adjunctive method in detecting TCA in the future.