Hypoxic-ischemic brain damage (HIBD) is one of the main causes of disability in middle-aged and elderly people, as well as high mortality rates and long-term physical impairments in newborns. The pathological manifestations of HIBD include neuronal damage and loss of myelin sheaths. Tau protein is an important microtubule-associated protein in brain, exists in neurons and oligodendrocytes, and regulates various cellular activities such as cell differentiation and maturation, axonal transport, and maintenance of cellular cytoskeleton structure. Phosphorylation is a common chemical modification of Tau. In physiological condition, it maintains normal cell cytoskeleton and biological functions by regulating Tau structure and function. In pathological conditions, it leads to abnormal Tau phosphorylation and influences its structure and functions, resulting in Tauopathies. Studies have shown that brain hypoxia-ischemia could cause abnormal alteration in Tau phosphorylation, then participating in the pathological process of HIBD. Meanwhile, brain hypoxia-ischemia can induce oxidative stress and inflammation, and multiple Tau protein kinases are activated and involved in Tau abnormal phosphorylation. Therefore, exploring specific molecular mechanisms by which HIBD activates Tau protein kinases, and elucidating their relationship with abnormal Tau phosphorylation are crucial for future researches on HIBD related treatments. This review aims to focus on the mechanisms of the role of Tau phosphorylation in HIBD, and the potential relationships between Tau protein kinases and Tau phosphorylation, providing a basis for intervention and treatment of HIBD.
Humans ; tau Proteins/physiology* ; Phosphorylation ; Hypoxia-Ischemia, Brain/physiopathology* ; Animals ; Oxidative Stress

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Introduction: Chinese medicine (CM) external therapy is commonly used to treat rheumatoid arthritis (RA) in combination with conventional drug. This study aims to provide a comprehensive synthesis on the efficacy of CM external therapy combined with conventional drug treatment in RA. Methods: Randomised controlled trials (RCTs) experimenting the efficacy of CM external therapy (acupuncture, moxibustion and CM fumigation) combined with conventional drug in comparison with conventional drug only in RA patients were collected from PubMed, Medline, Cochrane Central of Controlled Trials (CENTRAL), ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), and Wanfang databases. Quality was assessed using the Cochrane Risk of Bias Tool. The outcome measures which include Disease Activity Score-28 (DAS28), Visual Analogue Scale (VAS), Swollen Joint Count (SJC), Tumour Necrosis Factor (TNF-α), serum levels of C-reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) were analysed using Review Manager 5.4.1 and GRADEpro GDT online software. Results: Fifty RCTs fulfilling the criteria were included. Although some level of efficacy was statistically noted on the use of CM external therapies, their certainty levels are mixed, ranging only in between moderate and low. Conclusions Mixed levels of certainty has hindered the drawing of conclusion. The addition of CM external therapies to conventional drug treatment may provide some benefits in RA. Further clinical trials with considerations in minimising the risk of bias are recommended to provide more high-quality evidence in the effect of CM external therapies as a complementary treatment in RA.
Medicine, Chinese Traditional ; Fumigation ; Meta-Analysis [Publication Type] ; Moxibustion ; Arthritis, Rheumatoid ; Systematic Review [Publication Type]

BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Objective To evaluate the efficacy of ultrasound and computed tomography (CT) in diagnosing cervical lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC). Methods The patients with PTC treated by surgery in the Chinese PLA General Hospital from January 2016 to January 2021 were selected for analysis.All the patients underwent preoperative ultrasound and CT examinations,the diagnostic values of which for CLNM were retrospectively analyzed. Results A total of 322 PTC patients were enrolled in this study,including 242 with CLNM and 80 with non-CLNM.The CLNM group and non-CLNM group had significant differences in age,tumor size,and maximum size of lateral CLNM (χ²=20.34,27.34,and 4.30,respectively,all P<0.001).For the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis showed higher sensitivity (χ ²=82.26,P<0.001;χ²=114.01,P<0.001;χ²=82.26,P<0.001) and accuracy (χ²=20.27,P<0.001;χ²=15.56,P<0.001;χ²=44.00,P<0.001) than CT,and had no significant differences from ultrasound combined with CT (all P>0.05).However,ultrasound diagnosis had lower specificity than CT (χ²=17.01,P<0.001;χ²=21.29,P<0.001) in the central compartment and lateral compartment.Receiver operating characteristic curve analysis showed that in the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis had larger AUC than CT (Z=2.99,P=0.003;Z=3.86,P<0.001;Z=4.47,P<0.001) and had no significant difference from ultrasound combined with CT (Z=1.87,P=0.062;Z=1.68,P=0.093;Z=1.61,P=0.107). Conclusions Ultrasound and CT have their own advantages in the diagnosis of central and lateral CLNM.In general,ultrasound has better performance than CT in the diagnosis of CLNM.
Humans ; Lymphatic Metastasis/diagnostic imaging* ; Retrospective Studies ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/surgery* ; Tomography, X-Ray Computed ; Ultrasonography/methods*

Objective: To investigate the clinical manifestation, pathological type, treatment and prognosis of primary lung tumors in children. Methods: We collected and retrospectively analyzed the clinical manifestation, pathological type, therapeutic method and prognosis of 56 primary lung tumors patients who diagnosed from 2009 to 2019 in Guangzhou Women and Children Medical Center. Results: There were 56 patients identified as the primary lung tumors, including pleuropulmonary blastoma (PPB, n=28), pulmonary inflammatory myofibroblastic tumor(IMT, n=20), mucoepidermoid carcinoma(n=6), infantile hemangioma (n=1), pulmonary sclerosing hermangioma(n=1). Respiratory symptoms were the most manifestation at the time of diagnosis including 26 patients with cough, 3 with hemoptysis, and 17 with dyspnea. Others included 15 with fever, 3 with chest pain, and 2 with epigastiric pain. The primary tumor of 18 cases were located in the lower lobe of left lung, 11 cases in the lower lobe of right lung, 10 cases in the upper lobe of left lung, 7 cases in the upper lobe of right lung, 6 cases in the middle lobe of right lung, and 4 cases in pulmonary hilum. Among the 56 patients, 41 patients underwent thoracotomy, 13 thoracoscopy, and 2 fiberoptic bronchoscopy. Five patients with type Ⅰ PPB were still alive at the end of follow-up without chemotherapy. Among 5 patients with type Ⅱ PPB, 2 patients without chemotherapy died after recurrence, 3 patients suffered postoperative chemotherapy were still alive at the end of follow-up. All of the 18 patients with type Ⅲ PPB underwent postoperative chemotherapy with IVADo regimen. Recurrence occurred in 6 cases, distant metastasis occurred in 3 cases, and cancer-related deaths occurred in 8 cases. For 20 patients with IMT, recurrence occurred in 5 of 13 patients experienced wedge resection, 1 of 6 patients experienced lobectomy and 1 of 6 underwent fiberoptic bronchoscopy, respectively. For 6 mucoepidermoid carcinoma patients, lobectomy was carried on 5 patients, wedge resection on 1 patient, all of them were still alive at the end of follow-up. One hermangioma patient underwent fiberoptic bronchoscopy and other 1 sclerosing hermangioma patient underwent wedge resection, both of them were still alive at the end of follow-up. Conclusions: The clinical manifestations of the primary lung tumors in children are nonspecific. Complete resection and achieving negative marginattribute to the excellent outcome. Adjunctive treatment such as chemotherapy is necessary for patients with type Ⅱ and type Ⅲ PPB.
Bronchoscopy ; Child ; Female ; Humans ; Lung/pathology* ; Lung Neoplasms/surgery* ; Pulmonary Blastoma/surgery* ; Retrospective Studies

Carcinoma, Mucoepidermoid/surgery* ; Child ; Humans ; Lung/pathology* ; Lung Neoplasms/surgery*

Aim To preliminarily investigate the effect of brusatol(BRU), the monomer components fromChinese medicines on H1299 cells and its mechanisms.Methods CCK-8 and EdU staining experiment were used to detect the effect of BRU on cell prolifera-tion.Clone formation experiment was performed to measure the effect of drugs on cell clone formation.Hoechst33258 staining experiment and flow cytometry were employed to observe the cell apoptosis.Western blot assay was used to detect the protein expression levels of Bcl-xL, Bax, Bcl-2, cleaved-caspase-3, caspase-3, Gadd45α, PI3K, p-PI3K, Akt, p-Akt and NF-κB-p65.Results CCK-8 assay revealed that the inhibitory effect of H1299 cells gradually increased with the rising of BRU concentration and action time.Compared with control group, the EdU incorporation rate of the BRU treatment group decreased significantly.Treated with different concentrations of BRU for 24 h, the clone formation rate was significantly reduced in a concentration-dependent manner.Hoechst33258 experiment and flow cytometry showed that BRU could induce apoptosis in H1299 cell nucleus and increase its apoptotic rate.Western blot results revealed that BRU could significantly up-regulate the protein levels of Bax, cleaved-caspase-3, Gadd45α, and significantly down-regulate the expression of Bcl-xL, Bcl-2, caspase-3.In addition, BRU could significantly decrease the expression level of p-PI3K, p-Akt, NF-κB-p65 in cell nucleus.Conclusions BRU can inhibit the proliferation and induce apoptosis of H1299 cells in a concentration and time-dependent manner.The mechanism may be related to the inhibition of PI3K/Akt signaling pathway and the nuclear shuttle of NF-κB-p65.

Aim To explore the effect of homoharringtonine (HHT) on the prohferation of liver cancer cell PLCS and its possible mechanism. Methods CCK-8 and EdU were used to detect the effect of HHT on the proliferation of PLCS cells; flow cytometry was employed to assess the effect of HHT on cell cycle of PLCS; Western blot was applied to measure the expression levels of cycle-related proteins cyclinA, CDK 2, p 2 1, p53 and A T M. Results Treated with HHT (0, 5, 10, 20, 40, 80 • L