ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Primary hypertrophic osteoarthropathy(PHO)is a rare disease also known as pachydermo-periostosis.We reported a painless case whose diagnosis was confirmed by genetic test.A 24-year-old male presented a series of symptoms that first began at 14.He suffered from progressive clubbed-fingers accompa-nied by swelling of the wrist and ankle joints.Facial skin concentric thickening and alar nose broadening ap-peared simultaneously and increased progressively.He was also prone to acne and hyperhidrosis.X-rays showed thickening of the metacarpal and phalangeal bones,as well as symmetrical periosteal ossification of both the tibia and fibula.Clinical diagnosis of PHO is difficult because of the variable features.With acromeg-aly excluded,the diagnosis was confirmed by a genetic test.Whole exome sequencing revealed a heterozygous SLCO2A1 c.611C＞T(p.Ser204Lue)and SLCO2A1 c.1602C＞A(p.Asn534Lys)mutation from each par-ent.It suggests that primary hypertrophic osteoarthropathy should be considered for young limb hypertrophic patients especially when periosteal thickening signs were showed in X-ray.A confirmatory diagnosis can be made through the genetic test.

Objective:To summarize the clinical features of reversible posterior encephalopathy syndrome(PRES)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:The clinical data of six children who developed PRES after undergoing allo-HSCT in the Department of Hematology of Wuhan Children's Hospital from June 2016 to December 2022 were retrospectively analyzed,and their clinical characteristics,imaging examination,laboratory examination,and treatment regression were summarized.Results:Among 281 children underwent allo-HSCT,6 cases(2.14％)developed PRES,with a median age of 5.1(1.5-9.7)years old.4 cases underwent related haploidentical donor transplantation,and 2 cases underwent sibling allografting and unrelated donor allografting donor transplantation,respectively.All six children had an acute onset of illness,with clinical manifestations of nausea and vomiting,seizures,psychiatric disorders,visual disturbances.The five cases elevated blood pressure.All children with PRES were treated with oral immunosuppressive drugs during seizures,and 3 cases were combined with different degrees of graft-versus-host disease.Most of the children showed effective improvement in clinical symptoms and imaging after adjusting/discontinuing suspected medications(cyclosporine,etc.)and symptomatic supportive treatments(oral antihypertensive,diazepam for antispasmodic,mannitol to lower cranial blood pressure),and one of them relapsed more than 8 months after the first seizure.Conclusion:PRES is rare after hematopoietic stem cell transplantation in children,and its onset may be related to hypertension,cytotoxic drugs,graft-versus-host disease,etc.Most of them can be recovered after active treatment,but not completely reversible,and the prognosis of those who combined with TMA is poor.

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24⁺), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO₁₅), Gan (CO₁₂) and Shen (CO₁₀). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans ; Depression ; Quarantine ; Serotonin ; Sleep Initiation and Maintenance Disorders ; COVID-19 ; Acupuncture Therapy ; Comorbidity

Objective: To investigate the diagnosis and treatment of Chiari malformation patients with hoarseness and other otorhinolaryngological symptoms. Methods: The clinical data of 18 patients of Chiari malformation with hoarseness were retrospectively collected, which was composed of 5 men and 13 women, aged 3-71 with median age of 52. All the patients were admitted to the Affiliated Hospital of Qingdao University from January 1989 to January 2020. All patients underwent brain MRI and laryngoscopy. The patient's symptoms and first diagnosis department, diagnosis time, total course of disease, hoarseness course, diagnosis and treatment, and postoperative recovery time were summarized. Follow-up time was 3-16 years, with median follow-up time of 6.5 years. Descriptive methods were used for analysis. Results: The first visit departments of 18 patients included neurology (9 cases), otorhinolaryngology head and neck surgery (5 cases), pediatrics (2 cases), orthopedics (1 case) and respiratory department (1 case). Except for the 7 cases in neurology department, the other 11 patients were not diagnosed in time. The disease duration of 18 patients with Chiari malformation ranged from 2 months to 5 years, and hoarseness was present from 20 days to 5 years. After diagnosis, 9 patients underwent posterior fossa decompression surgery, and 1 of them underwent syrinx drainage at the same time. The symptoms of 8 cases improved significantly after operation, with the improvement time from 1 to 30 days. In addition, 9 patients chose conservative treatment, among whom 8 had no improvement in symptoms and 6 progressed. Conclusions: Posterior fossa decompression is an effective treatment for Chiari malformation, and the prognosis is good. Timely diagnosis and treatment can improve the prognosis of patients.
Male ; Humans ; Female ; Child ; Hoarseness/etiology* ; Retrospective Studies ; Conservative Treatment ; Drainage ; Laryngoscopy

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Objective - To analyze the relationship between cobalt level of post shift urine and individual exposure level of ， cobalt and its compounds in cobalt exposed workers and to explore the feasibility of using urine cobalt as a biomarker. Methods - A total of 148 occupational cobalt exposed workers from a new material company were selected as the exposed ， - - group and 44 non occupational cobalt exposed workers from the company were selected as the control group using the typical sampling method. The exposure concentration of time weighted average of cobalt and its compounds in the workplace air of the - two groups was determined by inductively coupled plasma mass spectrometry as the individual exposure level. The cobalt levels - - of pre shift and post shift urinary samples of the two groups were detected by this method. The linear relationship between the - cobalt level of post shift urine and the individual exposure level of cobalt and its compounds in the air of the workplace was Results - 3 analyzed. The individual exposure level of cobalt and its compounds in the exposed group was 1.10 131.71 μg/m with （M） 3 the median of 12.23 μg/m. No cobalt and its compounds were detected in the workplace air in the control group. The cobalt - - levels of pre shift and post shift urines in exposed group were higher than those in the control group at the same time point （M： vs ， vs ， P ） - - 1.54 0.56 μg/L 8.77 0.83 μg/L all <0.01 . The cobalt level of post shift urine was higher than that in pre shift （M： vs ，P ）， urine in the exposed group 8.77 1.54 μg/L <0.01 and it was positively correlated with the individual exposure level （ ，P ） ， of cobalt and its compounds Spearman correlation coefficient=0.86 <0.01 . After common logarithm conversion the linear regression equation of the cobalt level of post shift urine and the common logarithm of individual exposure level of cobalt and （x） ：ŷ x（ ；F ， its compounds in the exposed group was as follows = −0.178 + 0.988 coefficient of determination=0.72 =374.75 P ；t ， P ） Conclusion - <0.01 = - 19.36 <0.01 . There was a linear correlation between cobalt level of post shift urine and occupational cobalt exposure level of cobalt exposed workers. Urinary cobalt can be used as a biomarker of occupational cobalt

The Myh3 (myosin heavy chain 3) gene is a marker gene of muscle cell differentiation and regulates the utilization of energy in muscle cells, but whether it affects the glycolysis process of muscle cells in different states is rarely reported. In this paper, the expression patterns of Myh3 and glycolysis-related genes Pkm (M-type pyruvate kinse), Prkag3 (protein kinase adenosine monophosphate-activated γ3-subunit), and Gsk3β (glycogen synthase kinase-3β) were studied by the qRT-PCR (quantitative-Real-Time-PCR) method using C2C12 cells at different stages of myoblast and adipogenic differentiation as models. It was found that in the process of myoblast differentiation of C2C12 cells, the relative expression trends of Myh3 and glycolysis genes Prkag3 and Pkm were basically the same, and the relative expression levels first increased, reached the peak on the second day of differentiation, and then decreased; glycogen synthase the expression trend of the inhibitory gene Gsk3β was relatively stable. In the process of adipogenic differentiation of C2C12 cells, the relative expression trend of Myh3 and glycolysis genes Prkag3 and Pkm remained basically the same, and the relative expression gradually increased, reaching the highest value on the 8th day of differentiation; glycogen synthase inhibitory gene Gsk3β expression remained stable. In the myogenic differentiation state of C2C12 cells, qRT-PCR and Western blotting were used to detect the effects of interfering Myh3 on the mRNA and protein expressions of glycolysis-related genes Pkm, Prkag3, and Gsk3β. The results showed that after interfering with Myh3, the mRNA expressions of glycolysis genes Pkm and Prkag3 were significantly decreased (P<0.01), while the mRNA expression of glycogen synthase inhibitory gene Gsk3β had no significant change (P > 0.05). The protein levels of Myh3 and Pkm were significantly lower than those in the blank group and NC group. Under the adipogenic differentiation state of C2C12 cells, after interfering with Myh3, the mRNA levels of glycogen synthase inhibitor Gsk3β and glycolysis gene Prkag3 were significantly increased (P<0.01), and the mRNA level of glycolysis gene Pkm was decreased; the protein levels of Myh3 and Pkm in the Myh3 interference group were also lower than those in the blank group and NC group. Based on the above studies, there are significant differences in the levels of glycolysis in C2C12 cells in the myogenic and adipogenic states, and the expression patterns of Myh3 and glycolysis genes are similar. Further results showed that Myh3 suppression could inhibit the glycolysis of C2C12 cells in the myogenic state without affecting the glycogen synthesis. Unlike in the myogenic state, interfering expression of Myh3 in the adipogenic state of C2C12 cells inhibited both glycogen synthesis and glycolysis.