Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective To investigate the expression of PIK3CA,phosphorylated protein kinase B(p-AKT)and phosphatase and tensin homologue deleted on chromosome 10(PTEN)in sinonasal squamous cell carcinoma(SNSCC).Methods The expressions of PIK3CA and PTEN in head and neck squamous cell carci-noma(HNSCC)were analyzed through the data set of HNSCC in the cancer genome map of UCSC Xena data-base.The immunohistochemical SP method was used to measure the expression of PIK3CA,p-AKT and PTEN in 43 cases of SNSCC tissues,20 cases of normal inferior concha tissues.The relationship between the expressions of PIK3CA,p-AKT and PTEN protein with the clinicopathological features and prognosis of the patients with SNSCC was analyzed.Results The results of bioinformatic analysis showed that PIK3CA mR-NA expression in HNSCC tissues was higher than that in paracancerous tissues(P＜0.01),while the PTEN mRNA expression was lower than that in paracancerous tissues(P＜0.05).The immunohistochemical detec-tion results showed that the positive expressions rates of PIK3CA and p-AKT proteins in normal nasal mucosa tissues were significantly lower than those in SNSCC tissues,while the positive expression rate of PTEN pro-tein in SNSCC tissues was significantly higher than that in normal inferior nasal concha mucosa tissues,and the differences were statistically significant(P＜0.01).The expressions of PIK3CA and p-AKT protein were related to the clinical stage,differentiation degree and primary site(P＜0.05),but were not related to age,gender,smoking and drinking(P＞0.05);the PTEN protein expression was not related with the clinical stage,differentiation degree,primary site,age,smoking and drinking(P＞0.05).The Spearman analysis showed that the expression of PIK3CA in SNSCC tissues was positively correlated with p-AKT protein ex-pression(r=0.664,P＜0.01),and PIK3CA was negatively correlated with PTEN protein(r=-0.414,P＜0.01).The expression of p-AKT was negatively correlated with PTEN protein(r=-0.453,P＜0.01).The Kaplan-Meier analysis showed that the median survival time of the patients with PIK3CA and p-AKT protein positive expression was shorter than that of the patients with negative expression(P＜0.01).There was no statistically significant difference in median survival between the patients with PTEN protein positive expres-sion and those with negative expression.Conclusion The overexpressions of PIK3CA and p-AKT accompa-nied by the loss of PTEN expression participate in the development and progression of SNSCC,moreover the PIK3CA and p-AKT expressions are related to the poor prognosis of the patients.

Objective To observe the relationship between functional connectivity(FC)of frontoparietal network(FPN)and cognitive function in patients with cerebral small vessel disease(CSVD)using resting-state functional MRI(rs-fMRI).Methods rs-fMRI of 50 CSVD patients with cognitive impairment(CI group),65 CSVD patients with normal cognition(NC group)and 60 healthy controls(HC group),as well as outcomes of neuropsychological tests were retrospectively analyzed.Brain regions with different FC of FPN were compared among 3 groups and between each 2 groups.Partial correlation analysis was used to evaluate the correlations of FC of brain regions value being statistically different between CI and NC groups and cognitive scores.Results Significant differences of FC in bilateral cingulate gyrus,left middle frontal gyrus,right supramarginal gyrus,right inferior parietal lobule and right medial superior frontal gyrus were found among groups(FWE correction,all P＜0.05).Compared with NC group,FC of left cingulate gyrus decreased,of right inferior frontal gyrus and right medial superior frontal gyrus increased in CI group(FWE correction,all P＜0.05).The decreased FC value of left cingulate gyrus was negatively correlated with clock drawing test score in CSVD patients(r=-0.159,P=0.049).Conclusion CSVD patients with or without CI had extensive abnormal FC of FPN,and the left cingulate gyrus was associated with patient's cognitive function.

Objective:To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple myeloma.Methods:A total of 96 patients with newly diagnosed multiple myeloma (NDMM) between July 31, 2020, and December 31, 2022, were retrospectively analyzed, of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode. After hematopoietic stem cells were mobilized and collected, melphalan was started immediately for pre-transplant conditioning, and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning. The control group consisted of 55 patients who received traditional transplantation mode. After hematopoietic stem cells were collected, stem cell cryopreservation was performed in liquid nitrogen, and then the transplant plans were started at the right time. All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor.Results:① A total of 34 patients (82.9% ) with VGPR plus CR in the observation group were significantly higher than 33 patients (60.0% ) in the control group ( P=0.016). ②Compared with the control group, the incidence of grade 1 oral mucosal inflammation was higher in the observation group ( P<0.001) ; however, the incidence of grades 2 and 3 oral mucosal inflammation was lower ( P=0.004, P=0.048), and neither group experienced grade 4 or above oral mucosal inflammation. The incidence of grade 1 diarrhea was higher in the observation group ( P=0.002), whereas the incidence of grade 3 diarrhea was lower ( P=0.007). No statistically significant difference was observed in the incidence of grade 4 diarrhea ( P=0.506), and neither group experienced grade 5 diarrhea. ③ The incidence of bacterial infection in the observation group was lower than that in the control group (34.1% vs 65.5%, P=0.002), whereas no statistically significant difference was observed in the incidence of fungal infection (29.3% vs 31.4%, P=0.863) and viral infection (4.88% vs 3.64%, P=0.831). ④No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups [10 (8-20) days vs 11 (8-17) days, P=0.501; 13 (10-21) days vs 15 (10-20) days, P=0.245]. ⑤ All patients did not receive lenalidomide treatment 100 days post-transplantation. At 30 days post-transplantation, the CTL, NK, and Th cell counts in the observation group were lower than those in the control group ( P<0.001, P=0.002, P=0.049), and the NKT cell counts were higher than those in the control group ( P=0.024). At 100 days post-transplantation, the CTL, NKT, and Th cell counts in the observation group were higher than those in the control group ( P=0.025, P=0.011, P=0.007), and no statistically significant difference in NK cell counts was observed between the two groups ( P=0.396). ⑥ The median follow-up was 18 (4-33) months. The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5% and 78.2%, respectively ( P=0.337). The recurrence-free survival rates were 85.3% and 77.6%, respectively ( P=0.386), and the cumulative recurrence rates were 9.8% and 16.9%, respectively ( P=0.373) . Conclusion:In NDMM, the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models, with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.

Objective:To analyze the construction and operation of the 19th Hangzhou Asian Games designated hospitals, and to discuss the medical emergency security work of large-scale sports events, so as to provide references for the planning of designated hospitals in future large-scale sports events.Methods:Retrospective analysis was made on the establishment principles, requirements, selection of medical support personnel, and training exercises of the designated hospitals, focusing on the key links such as organizational system, staffing, designated areas, and drug management.Results:Total of 40 designated hospitals have successfully completed the task of medical security by rebuilding the medical security area of the Asian Games, elevating the process, equipping facilities, and strengthening staff training. During the Asian Games, 349 people were transferred to designated hospitals by ambulance, 54 people were hospitalized, 19 people underwent surgery, and 1022 people went to designated hospitals by themselves.Conclusion:The construction of the designated hospitals during the 19th Hangzhou Asian Games was of high quality, efficient and smooth operation. It is suggested that efforts should be made in the reconstruction of the medical security area for the Asian Games to be "relatively independent". The treatment process of self-visiting patients should be fully considered and the flat urgent emergency response mechanism needs to be established.

Myxomas are the most frequent, cardiac benign cardiac tumors which often present with stroke caused by tumorous orthrombotic emboli. The treatment of embolic stroke due to cardiac myxoma is still a clinical and technical challenge. A 61-year-old man who had an embolic stroke in the left middle cerebral artery was admitted to the Third Poeple′s Hospital of Huizhou. The initial National Institutes of Health Stroke Scale (NIHSS) score was 16. He received endovascular thrombectomy after intravenous recombinant tissue plasminogen activator (rt-PA) one hour after stroke onset. No intracranial hemorrhage developed. Pathological study of embolus showed a myxoma. A cardiac mass was found in the left atrium and removed surgically three weeks after stroke. Pathological study of the tumor showed a myxoma. At the one-month follow-up after excision of myxoma, the NIHSS score was 1 and the modified Rankin scale score was 0. No recurrence of embolism occurred after surgical resection. Endovascular thrombectomy after intravenous rt-PA (bridging therapy) for embolic stroke due to cardiac myxoma is safe and effective, and early resection of atrial myxoma can effectively avoid recurrence of cerebral infarction.

Objective To explore the differential diagnosis of hydrops fetalis and the rare presentations of neonatal congenital hypothyroidism. Methods The data of one congenital hypothyroidism diagnosed neonate with hydrops fetalis leading to birth asphyxia and respiratory failure were retrospectively analyzed. The relevant literatures were reviewed. Results A Uyghur female infant by cesarean delivery at gestational age of 38+5 week for intrauterine distress, presented general edema with cyanosis and dyspnea after birth. Trachea cannula was used to assist ventilation. At one-day old, the thyroid function examination showed that the serum thyroid stimulating hormone was>100 mU/L and the free thyroid was 6 . 56 pmol/L. Moreover, ultrasonographic examination indicated the thyroid aplasia. The clinical symptoms were improved after the treatment with the levothyroxine tablets replacement, and breathing machine was removed at 8-day old. The dosage of drug was adjusted by clinical manifestation and laboratory monitoring. The patient was discharged at 18-day old with the medicine and was followed-up. Conclusions Congenital hypothyroidism can be the pathogenesis of hydrops fetalis and its differential diagnosis should be paid attention.

Objective To explore the value of contrast-enhanced ultrasound in the diagnosis and classification of traumatic spleen rupture , as compared with enhanced CT. Methods The manifestations of contrast-enhanced ultrasound on surgically or clinically confirmed spleen rupture in 40 patients were retrospectively analyzed. The performance of contrast-enhanced ultrasound on diagnosis and classification was compared with that of enhanced CT. Results For 40 patients with traumatic spleen rupture , the of accuracy of enhanced CT and contrast-enhanced imaging in the diagnosis of traumatic spleen rupture was 97.5%, with no significant statistical differences (chi-square = 0, P = 1). On contrast-enhanced ultrasound examination, 14 patients were diagnosed as true splenic rupture , 9 as subcapsular spleen rupture , and 16 as central splenicrupture, with a accuracy rate of 92.5% (37/40); and accuracy rate for enhanced CT was 90.0% (36/40), there was no significant statistical difference (chi-square = 1.97, P > 0.05). Conclusions Contrast-enhanced and enhanced CT have good consistency in the diagnosis and classification of traumatic spleen rupture. Contrast-enhanced ultrasound can accurately determine the scope and degree of spleen damage , resulting in more accurate classification; and it has values in the diagnosis of traumatic spleen rupture and choice of therapies.

Objective To observe the effects of Chinese medicinal herbs with the efficacy of invigorating spleen, upbearing the clear, and tonifying spleen on the obesity degree, fat hormones, and insulin resistance in diet-induced obesity (DIO) rats;To choose better anti-obesity herbs from different Chinese medicinal herbs that can tonify spleen. Methods Among the 130 Wistar rats, 10 were chosen as the blank control group (fed with basal forage), and the remaining 120 were administered with high-fat high-nutrition forage for 13 weeks. According to weight, 50 DIO rats and 10 diet-induced obesity resistance (DIO-R) rats were obtained. DIO rats were divided into model group (normal saline), sibutramine group, invigorating spleen group (Atractylodix Rhizome and Magnoliae Officinalis Cortex), upbearing the clear group (Bupleuri Radix and Aurantii Fructus Immaturus) and medicine for tonifying qi and spleen group (Astragali Radix). All groups received gavage with corresponding drugs. Rats in the blank control group and the DIO-R group received gavage with normal saline. The basal forage was administered to rats in the blank control group, while high-fat forage was continually given to rats in the other six groups. Insulin resistance index (IRI), blood glucose, triglycerides, cholesterol, tumor necrosis factor α (TNF-α) and adiponectin were detected after blood withdrawing. TNF-α and adiponectin in the fat homogenate were examined. Results Compared with the blank control group, body weight, IRI, and cholesterol of rats in the model group significantly increased (P<0.01);adiponectin in homogenate reduced (P<0.01);serum and adipose homogenate TNF-α increased (P<0.01). Compared with model group, body weight, IRI, cholesterol of rats in DIO-R group significantly decreased (P<0.01);adiponectin in fat homogenate increased (P<0.01). Body weight and cholesterol of rats in the sibutramine group significantly decreased (P<0.01), while serum and adipose homogenates TNF-αdecreased (P<0.05, P<0.01). Body weight, IRI and cholesterol of rats in upbearing the clear group decreased (P<0.05, P<0.01);serum and adipose homogenate TNF-α decreased (P<0.05, P<0.01);adiponectin increased in fat homogenate (P<0.05). IRI, cholesterol and serum TNF-αof rats in the invigorating spleen group decreased (P<0.05, P<0.01);adiponectin in serum and adipose homogenate increased (P<0.05). BMI, blood glucose, IRI and cholesterol of rats in Astragali Radix group decreased (P<0.05, P<0.01);TNF-α decreased and adiponectin increased in serum and adipose homogenate (P<0.05, P<0.01). Conclusion Astragali Radix could reduce obesity induced by high-fat forage, and its effects on improving glucose and lipid metabolism disorder and IR are better than the other TCM groups. Its mechanism is related to decreasing TNF-α and increasing adiponectin level.