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

OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

Objective:Quantified MRCP imaging data was used as a reference for design and preparation of a modified percutaneous transhepatic cholangio drainage (PTCD) tube.Methods:3.0 T upper abdominal MR and MRCP imaging data of 2 300 patients treated from July 2015 to July 2020 at the Department of Radiology of the Affiliated Cancer Hospital of Zhengzhou University were screened and a total of 381 patients diagnosed with biliary duct structures were identified. Causative etiologies among these patients included pancreatic adenocarcinoma (pancreatic head), cholangiocarcinoma, ampullary carcinoma, as well as intrahepatic and/or extrahepatic bile duct dilation. An improved PTCD tube was designed based on MRCP quantification of left and right hepatic and common hepatic duct length.Results:In the setting of biliary obstruction caused by malignancy, the distance of the left hepatic duct from its origin to the point of left and right hepatic duct confluence was 15.9±3.8 mm, while the distance of the right hepatic duct from its origin to the point of left and right hepatic duct confluence was 12.4±3.2 mm; the length of the bile duct from its origin to the point of left and right hepatic duct confluence was 34.0±8.1 mm. The improved PTCD tube design incorporated an altered length of the drainage orifice.Conclusion:MRCP imaging of the biliary tract is effective for measuring biliary tract length in the setting of pathological dilation. Based on our biliary tract measurements, a modified PTCD tube was designed to more effectively meet drainage requirements and manage biliary obstruction caused by Bismuth-Corlette type Ⅱ and Ⅲ malignancies.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

The precise localization of pulmonary nodules has become an important technical key point in the treatment of pulmonary nodules by thoracoscopic surgery, which is a guarantee for safe margin and avoiding removal of too much normal lung parenchyma. With the development of medical technology and equipment, the methods of locating pulmonary nodules are also becoming less trauma and convenience. There are currently a number of methods applied to the preoperative or intraoperative localization of pulmonary nodules, including preoperative percutaneous puncture localization, preoperative transbronchial localization, intraoperative palpation localization, intraoperative ultrasound localization, and localization according to anatomy. The most appropriate localization method should be selected according to the location of the nodule, available equipment, and surgeon鈥檚 experience. According to the published literatures, we have sorted out a variety of different theories and methods of localization of pulmonary nodules in this article, summarizing their advantages and disadvantages for references.

It has become an industry consensus that self-assembled nanoparticles (SAN) are formed by molecular recognition of chemical components in traditional Chinese medicine during the decoction process. The insoluble components in the decoction are mostly in the form of nanoparticles, which can improve the problem of poor water solubility. However, the transfer rate of these insoluble components in the decoction is still very low, which limits the efficacy of the drug. This study aimed to refine the traditional decoction self-assembly phenomenon. The self-assembled nanoparticles were constructed by micro-precipitation method (MP-SAN), and characterized by particle size, zeta potential, stability index and morphology. The formation of MP-SAN and alterations in related physicochemical properties were evaluated using modern spectroscopic and thermal analysis techniques. The quality value transmitting pattern of lignan components within the MP-SAN was assessed via high performance liquid chromatography (HPLC). The MP-SAN showed sphere-like structure with uniform morphology, particle size of (245.3 ± 3.2) nm, polydispersity index (PDI) of (0.13 ± 0.03), zeta potential of (-48.9 ± 5.9) mV and stability index (SI) of (86.05% ± 2.27%). Comprehensive analyses using ultraviolet visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and other techniques confirmed molecular recognition between the decoction and ethanol extraction, leading to electron rearrangement under the influence of non-covalent bonding. This resulted in the formation of nanoparticles possessing superior thermal stability. As determined by HPLC, the encapsulation rates of the index components in the MP-SAN were all greater than 75% (dehydrodiconiferyl alcohol: 77.00%; herpetolide A: 78.57%; herpetrione: 94.53%), and the transfer rates were all higher than 65% (dehydrodiconiferyl alcohol: 96.01%; herpetolide A: 67.86%; herpetrione: 65.55%), which were 1.34, 1.38 and 4.81 times compared with those of the traditional decoction. In summary, this study successfully constructed the MP-SAN based on micro-precipitation method to achieve high transfer rate and high encapsulation rate of insoluble components in docoction, which provides a pharmaceutics idea for the efficient utilization of pharmacodynamic substance basis of traditional Chinese medicine.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle frac-tures in children.Methods A systematic search was conducted in PubMed,Embase,the Cochrane library,Web of Science,China National Knowledge Internet(CNKI),Wanfang Datebase from in ception to February 2022.Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included.Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality,their excellent and good rate of fracture healing,malunion,delayed union or nonunion,infection,limitation of elbow flexion or extension(＞10°)were ex-tracted and analyzed using software Rev Man 5.3.Results A total of 9 retrospective studies involving 647 patients were includ-ed,with 255 patients in the screw fixation group(including screw combined with Kirschner wire)and 392 patients in the Kirschner wire fixation group.Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[OR=0.22,95％CI(0.09,0.56),P=0.001].There were no significant differences between the 2 groups in excellent and good rate of fracture healing,malunion rate(P＞0.05).Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[OR=0.18,95％CI(0.05,0.65),P=0.009].Conclusion For lateral humeral condyle fractures,Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation.There were no significant differences in the excellent and good rate of fracture healing,malunion.In terms of postoperative efficacy and safety of internal fixation,orthopaedic surgeons are more like-ly to recommend screws for fixation of lateral humeral condyle fractures in children.

Objective To investigate the dosimetric effects of different calculation grid size(CGS)in helical tomotherapy(HT)planning system on stereotactic body radiation therapy(SBRT)for non-small cell lung cancer(NSCLC).Methods Nine NSCLC patients receiving radiation therapy for the first time at some hospital from March 2019 to December 2022 were selected as the subjects.SBRT planning was carried out through the HT system with three different CGS plans(Fine,Normal,and Coarse)and the same pitch,modulation factor(MF)and optimization conditions,and the target area indexes of the three CGS plans were compared including conformity index(CI),homogeneity index(HI),dosimetric parameters of the organ at risk(OAR),point dose verification pass rate,treatment time,number of monitor units and Sinograms.SPSS 22.0 was used for statistical analysis.Results For target area HI,there weres significant differences between CGS Fine plan and Coarse plan and between CGS Normal plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan(P＞0.05).For target area CI,there were significant differences between CGS Fine plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan and between CGS Normal plan and Coarse plan(P＞0.05).For OAR dosimetric parameters,CGS Fine plan and Coarse plan had significant differences in heart Dmax and Dmean,esophageal Dmax and Dmean,V5,V20,V30 and Dmean of the whole lung and affected lung,V5 and Dmax of the affected lung and heart V10 and V30(P＜0.05),CGS Normal plan and Coarse plan had obvious differences in esophageal Dmax(P＜0.05),and the remained dosimetric parameters were not statistically significant(P＞0.05).Fine,Normal and Coarse plans had the point dose verifica-tion pass rates being 0.96％,1.50％and 1.77％,respectively.In terms of treatment time and number of monitor units,there were significant differences between Fine plan and Coarse plan(P＜0.05)while no statistical differences were found between Fine and Normal plans and between Normal and Coarse plans(P＞0.05).Sinograms analyses showed Fine plan had evenly distributed segment color gradient,Coarse plan had areas of very dark and very light color gradients and Normal plan was somewhere in between.Conclusion Low CGS has to be used as much as possible to obtain accurate dose distribution during SBRT planning for NSCLC patients,which contributes to the execution of the radiation therapy plan and the prevention of ad-verse effects.[Chinese Medical Equipment Journal,2024,45(2):52-57]

Objective To investigate the radiotherapy dose impacts of different jaw widths on stereotactic body radiotherapy(SBRT)for hepatocellular carcinoma(HCC)with the hilical tomotherapy(HT)planning system.Methods Totally 16 HCC patients who received radiotherapy at some hospital from March 2021 to August 2023 were selected,and the planning was carried out with the same pitch,modulation factors and optimization conditions and the jaw widths being 1.0,2.5 and 5.0 cm.The dosimetric differences due to the jaw widths in planned targets and organs at risk(OAR)were compared,and the planned treatment time,monitor unit,gantry rotations and gantry period were evaluated.SPSS 22.0 was used for statistical analysis.Results Better dosimetric parameters and lower doses to OARs could be got with lower jaw widths.The widened jaw widths resulted in reduced planned treatment time,decreased monitor units and gantry rotations,shortened gantry period while enhanced treatment efficiency.Conclusion A 2.5 cm jaw width for HT planning contributes to improving treatment efficiency during HCC SBRT under the premise of ensured target dose distribution and satisfactory dose to OAR for clinical require-ments.[Chinese Medical Equipment Journal,2024,45(7):51-55]