ObjectiveTo investigate the effects of jujuboside A （JuA） on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment （VCI） and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group （n=10）， a blank control group （n=10）， and a modeling group （n=30）. The rats in the modeling group underwent bilateral carotid artery ligation （2-VO） for the modeling of VCI. After stabilization， the VCI rats were randomized into model， JuA （20 mg·kg^-¹）， and donepezil （0.45 mg·kg^-¹） groups. After 4 weeks of gavage， the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β （GSK-3β）， cAMP response element-binding protein （CREB）， B cell lymphoma-2 （Bcl-2）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β， p-GSK-3β， p-CREB， Bcl-2， PI3K， p-PI3K， Akt， and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group， the model group exhibited declines in the learning and memory abilities （P<0.01）， neuronal damage and decreased neurons in the hippocampal CA1 region （P<0.01）， up-regulation in the mRNA level of GSK-3β （P<0.01）， and down-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2， as well as the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.01）. In comparison to the model group， both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities （P<0.05， P<0.01）， with reduced neuronal damage and increased neurons （P<0.05， P<0.01）. In addition， the two groups showed down-regulation in the mRNA level of GSK-3β （P<0.01） and up-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2 and the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.05， P<0.01）. There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities， neuron count， and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway， reducing the apoptosis of hippocampal neurons， and alleviating the hippocampal neuronal damage.

Objective:To build a transcultural self-management objective incentive framework for adolescents with tuberculosis, so as to provide reference for improving the self-management ability of adolescents with tuberculosis.Methods:Based on the theory of transcultural nursing and process motivation, group discussion and literature search, 24 experts from eight ClassⅢ Grade A hospitals across the country were consulted by Delphi method to form a transcultural self-management objective incentive framework for adolescents with tuberculosis. The positive coefficient of experts was evaluated by questionnaire response rate, the degree of coordination was expressed by the Kendall harmony coefficient, and the degree of authority was expressed by the authority coefficient of expert consultation.Results:After two rounds of consultation, the positive coefficients of experts were both 100%, the authoritative coefficients of the experts were 0.965, and the Kendall harmony coefficients of the expert opinions were 0.309 and 0.402, respectively ( P<0.05). Finally, a transcultural self-management objective incentive framework for adolescents with tuberculosis was formed, including six first-level indicators, 24 second-level indicators and 49 third-level indicators. Conclusions:The transcultural self-management objective incentive framework for adolescents with tuberculosis has high enthusiasm and authority for expert consultation, which is helpful to improve the self-management ability of adolescents with tuberculosis.

Objective:To investigate the relationship between clinical indicators of CRAB symptoms and antioxidant enzyme activity in patients with multiple myeloma(MM).Methods:The activity of catalase(CAT),glutathione peroxidase(GPX),and superoxide dismutase(SOD)in the bone marrow supernatants of 44 patients with MM and 12 patients with non-malignant hematological diseases was detected by colorimetric assay,and then the differences in the activity of antioxidant enzymes between the two groups were compared.Furthermore,the relationship between the activity of antioxidant enzymes in the MM group and the levels of serum calcium,serum creatinine(Scr),hemoglobin(Hb),alkaline phosphatase(ALP)as well as bone lesions were analyzed.Results:The antioxidant enzyme activity was lower in MM patients compared with the control group(P＜0.05).When the concentrations of serum calcium and ALP were higher than the normal levels,Hb was lower than 85 g/L,and there were multiple bone lesions,the activity of CAT,SOD and GPX was significantly declined(P＜0.05);When the concentration of Scr≥177 μmol/L,the activity of GPX was significantly declined(P＜0.05).Regression analyses showed that CAT,SOD and GPX were negatively correlated with serum calcium(r=-0.538,r=-0.456,r=-0.431),Scr(r=-0.342,r=-0.384,r=-0.463),and ALP(r=-0.551,r=-0.572,r=-0.482).Conclusion:The activity of antioxidant enzymes,including CAT,SOD and GPX,were decreased in patients with MM and they were negatively correlated with some clinical indicators of CRAB symptoms(such as serum calcium,Scr,and ALP),which suggests that promoting the activity of antioxidant enzymes may be beneficial to treat the CRAB symptoms of the patients with MM.

Objective To explore the optimization for parameters of 5.0T pseudo continuous arterial spin labeling(pCASL)MRI of whole brain.Methods Nine healthy adults were prospectively enrolled,and single-delay pCASL scanning was performed based on a 5.0T MR scanner with 3 sets of labeling gradients:Group A,average gradient(Gavg)=1 mT/m and the ratio of maximum gradient(Gmax)to Gavg(Gratio)=10,group B,Gavg=0.6 mT/m and Gratio=10,group C,Gavg=0.3 mT/m and Gratio=9.The labeling efficiency and cerebral blood flow(CBF)of 3 groups were compared to screen the best labeling gradient group.Results When the marked average blood flow velocity was 40 cm/s,the gradient field tolerance of group C was better than that of group A and B at the situation of reduced B1+and larger B0 offset frequency range.Under the gradient field of group C,the level of labeled artery B1 ranged from 54.19％to 75.36％,with an average of 64.71％.The labeling efficiencies of group C were all ≥85％,and all ≥90％at the average B1 level(64.71％).In the whole gray matter and almost all brain regions,CBF on pCASL under gradient field of group C was significantly higher than that of group A and B(all P＜0.05).Conclusion Low Gavg and low Gmax were the optimal parameters for 5.0T whole brain pCASL MRI.

Objective     To study the correlation of preoperative hemoglobin amount with venous thromboembolism (VTE) after surgical treatment of bronchiectasis and the clinical significance. Methods     A retrospective study was performed on patients with bronchiectasis who underwent surgical treatment in our center from June 2017 to November 2021. The differences in blood parameters between the VTE patients and non-VTE patients were compared. The relationship between preoperative hemoglobin and VTE was confirmed by quartile grouping and receiver operating characteristic (ROC) curve. Results     A total of 122 patients were enrolled, including 50 males and 72 females, with a mean age of 52.52±12.29 years. The overall incidence of VTE after bronchiectasis was 9.02% (11/122). Preoperative hemoglobin amount (OR=0.923, 95%CI 0.870-0.980, P=0.008) and D-dimer amount (OR=1.734, 95%CI 1.087-2.766, P=0.021) were independent influencing factors for VTE after bronchiectasis. The incidence of VTE after bronchiectasis decreased gradually with the increase of preoperative hemoglobin amount. The area under the ROC curve (AUC) of postoperative D-dimer alone was 0.757, whereas the AUC of postoperative D-dimer combined with preoperative hemoglobin amount was 0.878. Conclusion     Low preoperative hemoglobin is an independent risk factor for postoperative VTE. Postoperative D-dimer combined with preoperative hemoglobin amount has a better predictive performance compared with postoperative D-dimer alone for postoperative VTE.

Objective:To explore the influencing factors of residual thyroid clearance with 131I after surgery in patients with differentiated thyroid cancer (DTC). Methods:A retrospective analysis was conducted on the clinical data of 100 DTC patients admitted to the Hunan Provincial People′s Hospital from January 2018 to February 2021 who underwent 131I treatment for the first time. The success rates of first thyroidectomy using different doses of 131I, different pathological types, and different treatment times were compared, and logistic regression analysis was conducted to investigate the influencing factors of the efficacy of first postoperative 131I thyroidectomy in DTC patients. Results:A total of 54 patients successfully cleared residual thyroid, 46 patients failed to clear residual thyroid, and the success rate of clearing residual thyroid was 54%. The success rates of first clearance of residual thyroid in patients with 131I doses of 80 mCi, 90 mCi, and 100 mCi were 37.50%(12/32), 52.78%(19/36), and 71.88%(23/32), respectively, with statistically significant differences among the groups ( P<0.05); The success rates of first removal of residual thyroid in patients with follicular carcinoma, mixed papillary follicular carcinoma, and papillary carcinoma were 65.71%(23/35), 39.13%(9/23), and 52.38%(22/42), respectively. There was no statistically significant difference between the groups ( P>0.05); The success rates of first removal of residual thyroid in the group1 of patients (treatment time<3 months), the group2 of patients (treatment time 3-12 months), and the group3 of patients (treatment time>12 months) were 68.09%(32/47), 44.44%(16/36), and 35.30%(6/17), respectively. There was no statistically significant difference between the groups ( P>0.05); There was no statistically significant difference in the success rate of clearing residual thyroid in DTC patients of different genders, ages, pathological stages, and thyroid stimulating hormone (TSH) levels (all P>0.05); The difference in the success rate of clearing residual thyroid in DTC patients with different metastatic conditions and stimulating thyroid globulin (sTg) was statistically significant (all P<0.05); sTg, postoperative lymph node metastasis, and postoperative distant metastasis were independent risk factors for the efficacy of residual thyroid clearance in DTC patients for the first time after surgery (all P<0.05). Conclusions:The influencing factors for the efficacy of the first 131I in removing residual thyroid include differences in 131I dosage, presence or absence of metastatic lesions during treatment, Tg levels, etc. Reducing Tg levels is an important factor in improving remission rate, and controlling lymph nodes and distant metastasis is a key factor for the successful efficacy of the first 131I in removing residual thyroid.

Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.

OBJECTIVE: To compare the mid-term clinical effect of arthroscopic surgery versus conservative treatment on the middle aged early knee osteoarthritis (EKOA) patients, with the hope to provide clinical evidence for their individual therapy. METHODS: A total of 145 middle aged EKOA patients(182 knees) who received arthroscopic surgery or conservative treatment from January 2015 to December 2016 were retrospectively enrolled, including 35 males and 110 females, aged from 47 to 79 years old with an average of (57.6±6.9) years old, and the duration of disease ranged from 6 to 48 months with an average of(14.6±8.9) months. According to treatment method, patients were divided into arthroscopic surgery group (47 patients, 58 knees) and conservative treatment group(98 patients, 124 knees). Before treatment, patients presented with symptoms of knee joint, such as pain, swelling, locking, limited flexion and extension, and weakness, as well as abnormal findings in knee X-ray (without or suspicious joint space narrow, and a few of osteophyte formation) or in knee MRI (injury or degeneration of articular cartilage or meniscus, loose body in the joint cavity and synovial hyperemia edema, etc). Related data were collected, including duration of knee symptoms, presence of meniscus injury, loose body in the joint cavity or mechanical symptoms such as locking, and visual analogue scale (VAS) and Lysholm knee function score before treatment and at the latest follow-up. Statistical analysis was performed to compare the differences in VAS or Lyshilm score before or after treatment between the low groups and within each group. RESULTS: Patients in the two groups were followed up from 60 to 76 months. In the arthroscopic surgery group, the incision healing was good and no surgical complications occurred. There were no significant differences in age, gender, BMI and follow-up time between the two groups(P>0.05). Before treatment, compared with conservative group, duration of symptoms in the arthroscopic group was longer (P<0.001), comorbidity rates of meniscus injury (P<0.001), free body (P=0.001) and mechanical symptoms (P<0.001) were higher, VAS (P<0.001) and Lysholm score (P<0.001) were worse. At the final follow-up, VAS and Lysholm score in either the conservative group or the arthroscopic group were significantly better than before treatment (P<0.05), while no significant differences between the two groups were found. The VAS was (1.5±1.2) scores in the arthroscopic group and (1.6±1.0)scores in the conservative group(P=0.549), and the Lysholm score was (84.9±12.5) scores in the arthroscopic group and (84.2±9.9) scores in the conservative group (P=0.676). CONCLUSION Both arthroscopic surgery and conservative treatment have satisfactory intermediate clinical effect middle- aged patients with EKOA, without statistically differences. However, most of the patients before surgery in the arthroscopic treatment group had mechanical locking symptoms caused by meniscus injury or loose body. Therefore, for the middle-aged EKOA patients with mechanical locking symptoms or without obtaining satisfactory outcome after conservative treatment, arthroscopic surgery may be considered.
Male ; Middle Aged ; Female ; Humans ; Aged ; Osteoarthritis, Knee/surgery* ; Retrospective Studies ; Arthroscopy/methods* ; Treatment Outcome ; Knee Joint/surgery*

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.
Animals ; Dopaminergic Neurons/physiology* ; GABAergic Neurons/physiology* ; Mice ; Nucleus Accumbens/metabolism* ; Reward ; Ventral Tegmental Area/metabolism*

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*