Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Objective:Through the analysis of the detection results of hepatitis B virus (HBV) serological markers in the population admitted to Shengjing Hospital of China Medical University in recent five years, the prevalence and characteristics of HBV infection in our hospital were clarified.Methods:Cross-sectional study was conducted. A total of 1 017 030 patients who underwent HBV serological markers testing in Shengjing Hospital of China Medical University from January 1, 2019 to December 31, 2023 were enrolled as the research objects. The included cases were divided into 14 districts in Liaoning: Shenyang (345 346), Dalian (13 219), Anshan (38 536), Fushun (40 067), Benxi (28 883), Dandong (34 284), Jinzhou (35 827), Yingkou (40 573), Fuxin (30 675), Liaoyang (26 282), Panjin (21 008), Tieling (74 632), Chaoyang (43 858) and Huludao (20 949). The included cases were divided into 7 groups according to age: 0-10 years old (162 457), 11-20 years old (33 657), 21-30 years old (129 791), 31-40 years old (235 378), 41-50 years old (124 925), 51-60 years old (143 361), and≥61 years old (187 461). According to different time points of the implementation of vaccination policies, cases born from January 1, 1992 to December 31, 2023 were divided into three groups: the group from January 1, 1992 to December 31, 2001 (94 194), the group from January 1, 2002 to May 31, 2005 (70 428), and the group from June 1, 2005 to December 31, 2023 (87 057). The general data and HBV serological markers results were collected for statistical analysis. The comparison of intergroup rates was conducted using the Chi-square test, and the trend test was conducted using the Cochran Armitage test. Results:In recent five years, the total positivity of serum hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb) and hepatitis B core antibody (HBcAb) were 6.68% (67 938/1 017 030), 51.69% (485 627/939 498), 2.37% (21 961/926 626), 15.00% (138 853/925 759) and 27.86% (257 344/923 703), respectively. According to gender, the total positivity of HBV serological markers in men was significantly higher than that in women, and the difference was statistically significant (HBsAg: χ 2=5 599.286, P<0.001; HBsAb: χ 2=5.065, P=0.024; HBeAg: χ 2=2 451.420, P<0.001; HBeAb: χ 2=1 066.145, P<0.001; HBcAb: χ 2=4 013.618, P<0.001). According to the age group, the peak of HBsAg positivity was mainly distributed in the age group of 41-50 years old, with a positivity of 10.48% (2 864/27 324). The positivity of HBsAb decreased with age.The positivity of HBsAb decreased with age increase, highest in the 0-10 years old group, and a decrese in the 11-20 years old group ( Z=18 915.453, P<0.001). The positivity of HBcAb increased with age ( Z=27 493.853, P<0.001). According to the regional groups, the positivity of HBsAg and HBeAg in Shenyang City were 5.01% (3 996/76 974) and 1.45% (944/69 117) respectively. The positivity of HBsAb in patients from Liaoyang district was the highest [55.89% (3 362/6 150)]. The highest positivity of HBeAb and HBcAb were in patients from Dandong district, 19.90% (3 362/6 150) and 37.37% (3 119/8 680) respectively. According to the different time points of the implementation of the vaccination policies, the positivity of HBsAg in cases born from June 1, 2005 and December 31, 2023 decreased to 0.30% (259/87 057) compared with cases born before this time point (χ 2=5 777.47, P<0.001). Conclusions:The analysis of HBV serological laboratory characteristics showed that the positivity of contagious HBV serological markers was still high. The positivity of male was higher than that of female. HBsAb levels decreased significantly in the 11-20 years old group, suggesting the necessity to strengthen hepatitis B prevention in this age group. There were regional differences in the prevalence of hepatitis B, suggesting the necessity to optimize and improve HBV prevention and control strategies.

Objective:Through the analysis of the detection results of hepatitis B virus (HBV) serological markers in the population admitted to Shengjing Hospital of China Medical University in recent five years, the prevalence and characteristics of HBV infection in our hospital were clarified.Methods:Cross-sectional study was conducted. A total of 1 017 030 patients who underwent HBV serological markers testing in Shengjing Hospital of China Medical University from January 1, 2019 to December 31, 2023 were enrolled as the research objects. The included cases were divided into 14 districts in Liaoning: Shenyang (345 346), Dalian (13 219), Anshan (38 536), Fushun (40 067), Benxi (28 883), Dandong (34 284), Jinzhou (35 827), Yingkou (40 573), Fuxin (30 675), Liaoyang (26 282), Panjin (21 008), Tieling (74 632), Chaoyang (43 858) and Huludao (20 949). The included cases were divided into 7 groups according to age: 0-10 years old (162 457), 11-20 years old (33 657), 21-30 years old (129 791), 31-40 years old (235 378), 41-50 years old (124 925), 51-60 years old (143 361), and≥61 years old (187 461). According to different time points of the implementation of vaccination policies, cases born from January 1, 1992 to December 31, 2023 were divided into three groups: the group from January 1, 1992 to December 31, 2001 (94 194), the group from January 1, 2002 to May 31, 2005 (70 428), and the group from June 1, 2005 to December 31, 2023 (87 057). The general data and HBV serological markers results were collected for statistical analysis. The comparison of intergroup rates was conducted using the Chi-square test, and the trend test was conducted using the Cochran Armitage test. Results:In recent five years, the total positivity of serum hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb) and hepatitis B core antibody (HBcAb) were 6.68% (67 938/1 017 030), 51.69% (485 627/939 498), 2.37% (21 961/926 626), 15.00% (138 853/925 759) and 27.86% (257 344/923 703), respectively. According to gender, the total positivity of HBV serological markers in men was significantly higher than that in women, and the difference was statistically significant (HBsAg: χ 2=5 599.286, P<0.001; HBsAb: χ 2=5.065, P=0.024; HBeAg: χ 2=2 451.420, P<0.001; HBeAb: χ 2=1 066.145, P<0.001; HBcAb: χ 2=4 013.618, P<0.001). According to the age group, the peak of HBsAg positivity was mainly distributed in the age group of 41-50 years old, with a positivity of 10.48% (2 864/27 324). The positivity of HBsAb decreased with age.The positivity of HBsAb decreased with age increase, highest in the 0-10 years old group, and a decrese in the 11-20 years old group ( Z=18 915.453, P<0.001). The positivity of HBcAb increased with age ( Z=27 493.853, P<0.001). According to the regional groups, the positivity of HBsAg and HBeAg in Shenyang City were 5.01% (3 996/76 974) and 1.45% (944/69 117) respectively. The positivity of HBsAb in patients from Liaoyang district was the highest [55.89% (3 362/6 150)]. The highest positivity of HBeAb and HBcAb were in patients from Dandong district, 19.90% (3 362/6 150) and 37.37% (3 119/8 680) respectively. According to the different time points of the implementation of the vaccination policies, the positivity of HBsAg in cases born from June 1, 2005 and December 31, 2023 decreased to 0.30% (259/87 057) compared with cases born before this time point (χ 2=5 777.47, P<0.001). Conclusions:The analysis of HBV serological laboratory characteristics showed that the positivity of contagious HBV serological markers was still high. The positivity of male was higher than that of female. HBsAb levels decreased significantly in the 11-20 years old group, suggesting the necessity to strengthen hepatitis B prevention in this age group. There were regional differences in the prevalence of hepatitis B, suggesting the necessity to optimize and improve HBV prevention and control strategies.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

Objective:To analyze the clinical characteristics, treatment course and prognosis of children with intermediate-high risk pulmonary embolism.Methods:The clinical data of 48 children with pulmonary embolism treated in Beijing Children′s Hospital, Capital Medical University from January 2017 to December 2021 were analyzed retrospectively.Including 12 intermediate-high risk cases and 36 low-risk cases.The clinical manifestations, laboratory results, treatment and prognosis were compared between groups by the t-test, rank sum test and Chi- square test with the yates continuity correlation or Fisher′ s exact test. Results:There were no significant differences in the sex and age between the intermediate-high risk group and the low-risk group.The proportions of patients with shortness of breath, dyspnea, cyanosis or hypoxemia were higher in the intermediate-high risk group than those of in low-risk group.Twelve children in the low-risk group did not have specific symptoms of pulmonary embolism.There were no significant differences in the D-dimer level, and the distribution of pulmonary embolism between the two groups (all P>0.05). However, the proportion of children with other thromboembolism in the intermediate-high risk group was significantly higher than that of the low-risk group, among which heart thrombosis was the most common (7 cases). There were no significant differences in the underlying diseases and thrombophilia between the two groups (all P>0.05). The treatment of the intermediate-high risk group was more active: 6/12(50.00%) patients in the intermediate-high risk group received reperfusion treatment, including 3 cases of systemic thrombolysis, 1 case of catheter thrombolysis, and 2 cases of thrombectomy.In the low-risk group, only 1 case was treated with systematic thrombolysis.Unfavorable outcomes were reported in 3/48 (6.25%) patients, including 1 death of massive bleeding after catheter-directed thrombolysis in the acute phase, 1 case of recurrent pulmonary embolism after self-decided withdrawal and 1 case of progression of pulmonary embolism that was managed by surgical thrombectomy, all of whom were in the intermediate-high risk group. Conclusions:Shortness of breath, dyspnea, cyanosis or hypoxemia and co-existed venous thromboembolism were more common in intermediate-high risk cases.The treatment regimen of was more aggressive, but the incidence of unfavorable outcomes was higher in intermediate-high risk group; further research is needed to determine the risk factors for intermediate-high risk pulmonary embolism in children.

Objective:To confirm the reuse of mismatched regenerated motor axons of brachial plexus and explore the effect of target organs on their regeneration in a rat model.Methods:This study was carried out between January 2021 and December 2021 at the research laboratory of the Department of Microsurgery, Orthopaedic Trauma and Hand Surgery, the First Affiliated Hospital of Sun Yat-sen University. Animals were randomly assigned into 2 groups, as a regeneration group (RGen) with 5 subgroups and a reuse group (RUs) with 3 subgroups. There were 6 rats per subgroup with 42 rats in total. It was observed that in the groups of RGen1-4, after the transection and suture of the musculocutaneous nerve, the motor axons of the proximal end could accurately grow into the distal corresponding endoneural tube. It was also observed that in the mismatched regenerated group, motor axons were the axons that grew into the endoneurial tube of the lateral forearm cutaneous nerve (LFCN), and other non-target organ contacts were made to the regenerated nerves after mismatch. It was specifically further divided into RGen1, the group without an organ for nerve to make contact with; RGen2, the group with skin as the target organ with nerves contact by neurorrhaphy; RGen3, the group with skin as the target organ with originally reserved natural nerve contact; RGen4, the group with muscle as the target organ with nerves contact by neurorrhaphy and RGen5, a control group. After 8 weeks, the positive area (PA), mean density (MD) and integral optical density (IOD) were measured, with AChE and ChAT fluorescence staining of the medial branch of LFCN, to evaluate the regenerated nerves after mismatch. Of the RUs group, firstly, the innervating branches of the flexor carpi radialis (FCR) were dissected and exposed, then further assigned according to initially innervated FCR (RUs1), contacted with regenerated nerves after mismatch (RUs2) and denervated (RUs3), respectively. After 8 weeks, compound muscle action potential (CMAP) and wet weight ratio of FCR were taken. Masson staining of FCR was also performed to evaluate muscle reinnervation by the regenerated nerves after mismatch. Data analysis with One-Way ANOVA and Bonferroni 0.05 indicated a statistically significant difference.Results:In the RGen groups, after AChE staining, the PA, MD and IOD of RGen3 and RGen4 were higher than that of RGen1 and RGen5, and PA of RGen4 were higher than that of RGen2, with a statistically significant difference ( P<0.05). After ChAT staining, the values of PA and IOD of RGen3 and RGen4 were higher than that of RGen1 and RGen5, and PA of RGen4 were higher than that of RGen2, with a statistically significant difference ( P<0.05). In the RUs, electrophysiological assessment showed that no CMAP was observed in RUs3, there was no significant difference in Latency of RUs1 and RUs2. The difference was statistically significant ( P<0.05). Wet weight rate of muscle of RUs1 (98.91%±3.86%) was higher than that of RUs3 (86.67%±4.68%) with a statistically significant difference ( P<0.01), but no significant difference when compared with RU2 (92.74%±3.88%). Masson staining showed that the CVF value of RUs2 (8.61%±1.16%) was significantly higher than that of RUs1 (3.17%±0.76%), and statistic significantly lower than that of RUs3 (16.44%±2.26%)( P<0.01). Conclusion:Target organ contact can promote the regenerated nerves after mismatched regeneration, and the muscle target organs exhibit greater facilitation than the cutaneous target organs. Besides, regenerated nerves after mismatch can establish effective innervation with muscle target organs, comfirming their effective reuse.

Objective To explore the mechanism of Gusong Yigu Decoction(inchuding Astragali Radix,Codonpsis Radix,Angelicae Sinensis Radix,etc.)in the treatment of postmenopausal osteoporosis(PMOP)based on network pharmacology and animal experiment.Methods The effective ingredients and corresponding targets of Gusong Yigu Decoction were collected by using TCMSP database.GeneCards,TTD,and other databases were used to collect PMOP target proteins.R language was used to obtain the intersection targets and draw Wayne diagram.STRING database was used for the establishment of protein-protein interaction network.At last,GO function enrichment and KEGG pathway enrichment were performed on all common targets.The ovariectomized SD rats were used in the animal experiment.Gusong Yigu Decoction was administered by gavage for 12 weeks.The changes of bone histomorphology were detected by HE staining,the mRNA and protein levels of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(Akt)in bone tissue of proximal tibial were tested by qRT-PCR and Western Blot,respectively.Results A total of 91 effective ingredients of Gusong Yigu Decoction in the treatment of PMOP,70 common targets of drugs-diseases were obtained.GO enrichment analysis mainly included DNA-binding transcription activator activity,RNA polymerase II-specific,ubiquitin protein ligase binding.KEGG pathway enrichment analysis included PI3K/Akt signaling pathway,TNF signaling pathway,and apoptosis.The animal experiment showed that bone histomorphology was significantly improved,meanwhile the mRNA and protein expressions of PI3K and Akt were significantly increased in Gusong Yigu Decoction group(P＜0.01).Conclusion Gusong Yigu Decoction may improve bone microstructure through multiple channels and targets.Gusong Yigu Decoction can increase the number and thickness of bone trabeculae and reduce the separation of bone trabeculae by activating PI3K/Akt signaling pathway,and thus play an anti-osteoporosis role in postmenopausal osteoporosis.

Objective: To describe the status of non-steroidal anti-inflammatory drugs (NSAIDs) use in areas with a high incidence of upper gastrointestinal cancer in China. Methods: This study was based on the National Key Research and Development Program of "National Precision Medicine Cohort of Esophageal Cancer" and "Study on Identification and Prevention of High-risk Populations of Gastrointestinal Malignancies (Esophageal cancer, Gastric cancer and Colorectal cancer)" . From January 2017 to August 2018, 212 villages or communities with a high incidence of esophageal cancer or gastric cancer were selected from 12 regions in 6 provinces. A total of 35 910 residents aged between 40 and 69 years old who met the inclusion criteria and signed the informed consent were investigated and enrolled in this study. The use of NSAIDs, demographic characteristics, health-related habits, height, weight, and blood pressure were collected by the questionnaire and physical examination. The status of main NSAIDs (aspirin, acetaminophen and ibuprofen) use with the difference varying in genders, age groups and regions were analyzed by using χ² test and Cochran-Armitage trend analysis method. Results: Of 35 910 subjects, the mean age was (54.6±7.1) years old and males accounted for 43.42% (15 591). The overall prevalence of NSAIDs intake was 4.56% (1 638), but it significantly varied in different provinces (P<0.001). The overall prevalence of NSAIDs intake was 4.87% (1 750) in females, which was significantly higher than that in males 4.24% (1 524) (P<0.001). The prevalence of NSAIDs intake increased with age (P for trend <0.001). As the frequency of NSAIDs intake increased, the incidence of gastrointestinal symptoms, gastrointestinal ulcers and black stools increased (P for trend <0.05 for all). Conclusion The use of NSAIDs is prevalent in some areas with a high incidence of upper gastrointestinal cancer in China. The increased use of NSAIDs may lead to more adverse effects related to the gastrointestinal tract.

Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10⁹/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10⁹/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10⁹/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10⁹/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.

Objective: To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF). Methods: Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated. Results: Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×10⁹/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT. Conclusions RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.