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1.
Biometals ; 37(2): 337-355, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37904075

ABSTRACT

Fe was selected as an alloying element for the first time to prepare a new antibacterial titanium alloy based on micro-area potential difference (MAPD) antibacterial mechanism. The microstructure, the corrosion resistance, the mechanical properties, the antibacterial properties and the cell biocompatibility have been investigated in detail by optical microscopy, scanning electron microscopy, electrochemical testing, mechanical property test, plate count method and cell toxicity measurement. It was demonstrated that heat treatment had a significant on the compressive mechanical properties and the antibacterial properties. Ti-xFe (x = 3,5 and 9) alloys after 850 °C/3 h + 550 °C/62 h heat treatment exhibited strong antimicrobial properties with an antibacterial rate of more than 90% due to the MAPD caused by the redistribution of Fe element during the aging process. In addition, the Fe content and the heat treatment process had a significant influence on the mechanical properties of Ti-xFe alloy but had nearly no effect on the corrosion resistance. All Ti-xFe alloys showed non-toxicity to the MC3T3 cell line in comparison with cp-Ti, indicating that the microzone potential difference had no adverse effect on the corrosion resistance, cell proliferation, adhesion, and spreading. Strong antibacterial properties, good cell compatibility and good corrosion resistance demonstrated that Ti-xFe alloy might be a candidate titanium alloy for medical applications.


Subject(s)
Alloys , Titanium , Titanium/pharmacology , Titanium/chemistry , Alloys/pharmacology , Alloys/chemistry , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Iron/pharmacology , Corrosion , Materials Testing
2.
BMC Cardiovasc Disord ; 23(1): 554, 2023 11 11.
Article in English | MEDLINE | ID: mdl-37951879

ABSTRACT

BACKGROUND: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis has been controversial, which has become a hit of recent research. The study aimed to explore the association between MASLD, cardiovascular and cerebrovascular diseases (CCVD), and the thickness of carotid plaque which was assessed by ultrasound. METHODS: From September 2018 to June 2019, 3543 patients were enrolled. We asked participants to complete questionnaires to obtain information. All patients underwent liver ultrasound and bilateral carotid ultrasound to obtain carotid intima-media thickness (IMT) and maximum carotid plaque thickness (CPT). Hepatic steatosis was quantified during examination according to Hamaguchi's ultrasonographic score, from 0 to 6 points. A score < 2 was defined as without fatty liver, and a score ≥ 2 was defined as fatty liver. Information about blood lipids was collected based on the medical records. RESULTS: We found common risk factors for CCVD events, MASLD, and atherosclerosis. There was a significant correlation between MASLD and carotid plaque, but not with CPT. No association was found between MASLD and CCVD events. CPT and IMT were thicker in CCVD patients than in non-CCVD patients. No significant difference was found between IMT and CPT in MASLD patients and non-MASLD patients. CCVD was independently and consistently associated with higher IMT, and free fatty acid (FFA). CONCLUSIONS: According to our results, we recommend carotid ultrasound examination of the patients when FFA is increased, regardless of the presence of risk factors and MASLD. Due to the distribution of CPT of both CCVD and MASLD patients in the CPT 2-4 mm group, contrast-enhanced ultrasound is necessary to assess the vulnerability of the plaque when CPT ≥ 2 mm. Timely treatment of vulnerable plaques may reduce the incidence of future CCVD events.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Carotid Artery Diseases , Cerebrovascular Disorders , Fatty Liver , Plaque, Atherosclerotic , Humans , Carotid Intima-Media Thickness , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/etiology , Cerebrovascular Disorders/diagnostic imaging , Cerebrovascular Disorders/etiology , Cardiovascular Diseases/epidemiology , Risk Factors , Fatty Liver/complications , Plaque, Atherosclerotic/complications
3.
Sci Rep ; 13(1): 20264, 2023 11 20.
Article in English | MEDLINE | ID: mdl-37985672

ABSTRACT

The efficacy of Mesh optimized versus standard percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures. Grid optimization (102 cases; 38 men, 64 women aged 67.3 ± 8.5) and traditional PVP groups (94 cases) were identified from 196 PVP patients treated from May 2016 to 2019. The optimal puncture site and angle forced bone cement into both groups before surgery. The main indexes were operation time, X-ray fluoroscopy times, bone cement injection volume, leakage, VAS, and injured vertebrae height. Preoperative general data were equivalent between groups (P > 0.05). All patients survived surgery without spinal cord injury, incision infection, pulmonary embolism, or death. The mesh optimization group had improved operation time (34.8 ± 6.5 min), fluoroscopy times (29.5 ± 5.5), bone cement injection volume (5.3 ± 2.1 ml), and bone cement permeability greater (3.9 percent; 4/98) than the standard PVP group (P < 0.05). Similarly, the grid optimization group had superior VAS scores (1.1 ± 0.6; 1.0 ± 0.3; and 0.9 ± 0.2) than the standard PVP group at 3 days, 3 months, and the last follow-up visit (P < 0.05). On day three after surgery, both had similar heights of injured vertebra's anterior and middle edges (P > 0.05). However, in the mesh optimization group, measurements improved to 1.8 ± 0.4 mm and (1.8 ± 0.3) mm by month three and to 1.7 ± 0.3 mm at last follow-up (P < 0.05). Mesh-optimized PVP with a mesh locator treats osteoporotic vertebral compression fractures more safely and effectively than regular PVP.


Subject(s)
Fractures, Compression , Osteoporotic Fractures , Spinal Fractures , Vertebroplasty , Male , Humans , Female , Fractures, Compression/surgery , Spinal Fractures/surgery , Bone Cements/therapeutic use , Conservative Treatment , Retrospective Studies , Treatment Outcome , Spinal Puncture , Osteoporotic Fractures/surgery
4.
Orthop Surg ; 15(12): 3309-3316, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37814482

ABSTRACT

OBJECTIVE: Percutaneous vertebroplasty (PVP) is currently the primary minimally invasive surgical approach for treating vertebral compression fractures caused by senile osteoporosis. The current existing problem is the lack of research on the application of a specific set of intraoperative C-arm fluoroscopy terminologies in PVP. Therefore, the purpose of this study is to explore the use of a specific set of intraoperative C-arm fluoroscopic terminologies in PVP in order to increase fluoroscopy accuracy, decrease fluoroscopy frequencies and ray protection, and minimize operation times through rapid preoperative training of surgeons and radiographers. METHODS: Spine surgeons and radiographers with at least 5 years of experience from nine different hospitals were randomly selected for a series of specialized intraoperative C-arm fluoroscopy terminology training between October 2018 and December 2021. Before and after the training, they were surveyed using a five-point Likert scale to statistically compare their knowledge of the terminology. Simultaneously, 190 PVP cases completed by these surgeons and radiographers before and after the training were chosen for comparison and analysis of fluoroscopy times, effective fluoroscopy rate, fluoroscopy time, repeated puncture rate, and other indicators before and after receiving specialized terminology training. Two-sample tests were mainly used to investigate differences in answers between surgeons and radiographers. RESULTS: After the training, there was a notable improvement in the fluency of intraoperative communication between professional spine surgeons and radiographers. By comparing the indicators of pre-training with post-training, the effective anteroposterior fluoroscopy rate increased from 46.5% to 75.7%; the effective lateral fluoroscopy rate increased from 59.8% to 76.9%. Moreover, a notable decrease in communication barriers, fluoroscopy frequencies, fluoroscopy time, and the rate of repeated punctures, and a notable increase in the effective fluoroscopy rate was observed. CONCLUSION: Smooth intraoperative communication between professional spine surgeons and radiographers can significantly lower the communication barrier, reduce the fluoroscopy frequencies and time, the rate of repeated puncture, and increase the effective fluoroscopy rate, all of which are important in improving the fluoroscopy in PVP.


Subject(s)
Fractures, Compression , Osteoporotic Fractures , Spinal Fractures , Vertebroplasty , Humans , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery , Fractures, Compression/surgery , Osteoporotic Fractures/surgery , Fluoroscopy , Treatment Outcome , Bone Cements
5.
Front Endocrinol (Lausanne) ; 14: 1141645, 2023.
Article in English | MEDLINE | ID: mdl-37152927

ABSTRACT

Background: China has the world's largest diabetic population, and the cost of caring for all these people every day is substantial. Online information exchange and app usage frequency have been demonstrated to play a significant influence in the management of blood glucose and enhancement of diabetes-related quality of life. However, the association between online information exchange and app usage frequency among actual online populations remains unclear and deserves additional study. Therefore, we evaluated the factors affecting the frequency of app usage in the online glucose management population, with a particular emphasis on the connection between online information exchange and app use frequency, contributing to the expansion of the research of diabetes management models. Method: This cross-sectional study was conducted by disseminating questionnaires in blood glucose management-related forums and WeChat groups and included 1586 online users concerned about blood glucose management. Information exchange and app usage frequency were considered as independent and dependent variables, respectively. We performed stratified and single factor analysis, multiple equation regression analysis, smooth curve fitting, and threshold effect and saturation effect analysis. R (version 4.1.3, http://www.Rproject.org) and EmpowerStats were used for data analysis. Result: After adjusting for other covariates, information exchange was independently and positively associated with app use frequency (ß = 8.6, 95% CI: 6.5 to 11.2, p < 0.001). Through interaction analysis, the most significant interaction factors influencing the relationship between information exchange and app usage frequency were identified as health insurance status, whether living with parents, glycated hemoglobin status in the previous month, and self-monitoring of blood glucose (SMBG). The association between information exchange and app usage frequency is U-shaped, with information exchange inflection points of 3.0 and 4.2. Information exchange and app usage frequency are negatively correlated when the average information exchange score is less than 3.0, and for every point increase in the average information exchange score, the likelihood of the app high usage frequency group compared to the app low usage frequency group decreases by 70%. The relationship between information exchange and app usage frequency is strongest when it is greater than or equal to 3.0 and less than or equal to 4.2. The probability of the app high usage frequency group occurring compared to the app low usage frequency group rises 17.3 times for every 1 point increase in the average information exchange score. The probability of the app high usage frequency group occurring in comparison to the app low usage frequency group increased by 1.8 times for every 1 point rise in information exchange when the average information exchange score was higher than 4.2. Conclusion: Age, body mass index, married, living with parents, hemoglobin level, SMBG, and information exchange were positively connected with app usage frequency in our study of online blood glucose management population. The link between information exchange and app use frequency was significantly U-shaped. The app usage frequency changed the most with the rise in information exchange when the information exchange score was greater than or equal to 3.0 and less than or equal to 4.2. Therefore, we ought to offer effort to concentrate on and increase the health-related behaviors and activities of those in this score interval.


Subject(s)
Diabetes Mellitus , Mobile Applications , Prediabetic State , Middle Aged , Humans , Blood Glucose , Cross-Sectional Studies , Quality of Life , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Surveys and Questionnaires , China/epidemiology
6.
Cancer Control ; 29: 10732748221124519, 2022.
Article in English | MEDLINE | ID: mdl-36039467

ABSTRACT

PURPOSE: The aim of the present study was to develop a nomogram for prognostic prediction of patients with lung cancer in hospice. METHODS: The data was collected from 1106 lung cancer patients in hospice between January 2008 and December 2018. The data were split into a training set, which was used to identify the most important prognostic factors by the least absolute shrinkage and selection operator (LASSO) and to build the nomogram, while the testing set was used to validate the nomogram. The performance of the nomogram was assessed by c-index, calibration curve and the decision curve analysis (DCA). RESULTS: A total of 1106 patients, including 835 (75%) from the training set and 271 (25%) from testing set, were retrospectively analyzed in this study. Using the LASSO regression, 5 most important prognostic predictors that included sex, Karnofsky Performance Scale (KPS), quality-of-life (QOL), edema and anorexia, were selected out of 28 variables. Validated c-indexes of training set at 15, 30, and 90 days were .778 [.737-.818], .776 [.743-.809], and .751 [.713-.790], respectively. Similarly, the validated c-indexes of testing set at 15, 30, and 90 days were .789 [.714-.864], .748 [.685-.811], and .757 [.691-.823], respectively. The nomogram-predicted survival was well calibrated, as the predicted probabilities were close to the expected probabilities. Moreover, the DCA curve showed that nomogram received superior standardized net benefit at a broad threshold. CONCLUSIONS: The study built a non-lab nomogram with important predictor to analyze the clinical parameters using LASSO. It may be a useful tool to allow clinicians to easily estimate the prognosis of the patients with lung cancer in hospice.


Subject(s)
Hospice Care , Hospices , Lung Neoplasms , Algorithms , Humans , Lung Neoplasms/therapy , Quality of Life , Retrospective Studies
7.
Comput Math Methods Med ; 2022: 2651062, 2022.
Article in English | MEDLINE | ID: mdl-35924112

ABSTRACT

Objective: To explore the clinical advantages of grid body surface locator combined with preemptive analgesia in the treatment of osteoporotic lumbar fractures in daytime vertebroplasty. Methods: A retrospective study was conducted on 120 patients who underwent lumbar vertebroplasty in the Department of Orthopedics of General Hospital of Northern Theater Command from January 2017 to January 2020. According to the preoperative planning and analgesic mode of treatment, they were divided into the daily operation experimental group and the traditional mode control group. Prone positioning of a patient under anesthetic is safe of ensuring optimum surgical access for many procedures, providing that the risks are fully understood. The general baseline data, intraoperative fluoroscopy times and operation time, bone cement injection volume, bone cement permeability, VAS score before operation, 1 day, and 3 months after operation, and the recovery of anterior vertebral height before and after operation were analyzed. Results: There was no statistically significant difference in the preoperative general data between the two groups. One day after operation, the VAS score of the experimental group was lower than that of the control group, but there was no difference after 3 months. The permeability of bone cement in the experimental group was lower than that in the control group, the height of anterior edge of injured vertebra was better than that in the control group, and the operation time was less than that in the control group. Conclusion: The daytime operation experimental group can significantly alleviate postoperative pain, increase the amount of bone cement injection, and reduce the permeability of bone cement through preoperative planning of puncture path and key puncture points, combined with advanced labor pain, but there is no significant difference in long-term pain relief.


Subject(s)
Analgesia , Fractures, Compression , Osteoporotic Fractures , Spinal Fractures , Vertebroplasty , Bone Cements/therapeutic use , Humans , Osteoporotic Fractures/surgery , Retrospective Studies , Spinal Fractures/surgery , Treatment Outcome , Vertebroplasty/methods
8.
Biometals ; 35(6): 1225-1241, 2022 12.
Article in English | MEDLINE | ID: mdl-35996064

ABSTRACT

Titanium and titanium alloy with low density, high specific strength, good biological, excellent mechanical compatibility and easy to process have been widely used in the medical materials, but their application in orthopedics and dentistry often face bacterial infection, corrosion failure and stress shielding. In this paper, Ti-15Mo-7Cu (TM-7Cu) alloy was prepared by high vacuum non-consumable electric arc melting furnace and then treated by solution and aging treatment. The microstructure, mechanical properties, antibacterial properties and cytocompatibility were studied by X-ray diffraction, microhardness tester, electrochemical working station, antibacterial test and Live/Dead staining technology. The results have shown that the heat treatment significantly influenced the phase transformation, the precipitation of Ti2Cu phase, the elastic modulus and the antibacterial ability. With the extension of the aging time, the elastic modulus slightly increased and the antibacterial rate obviously increased. TM-7Cu alloy with a low elastic modulus of 83GPa and a high antibacterial rate of > 93% was obtained. TM-7Cu alloy showed no cytotoxicity to MC3T3. It was suggested that TM-7Cu might be a highly competitive medical material.


Subject(s)
Alloys , Titanium , Elastic Modulus , Feasibility Studies , Titanium/pharmacology , Alloys/pharmacology , Anti-Bacterial Agents/pharmacology
9.
Ther Adv Chronic Dis ; 13: 20406223221117449, 2022.
Article in English | MEDLINE | ID: mdl-36003287

ABSTRACT

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease. Not only genetics, but the intestinal environment affected by gut microbiota is also the key to pathogenesis. Besides the occurrence of diabetes, gut microbiota dysbiosis may also contribute to the development of diabetes-related complications. Fecal microbiota transplantation (FMT) is an emerging technique that had shown its potential as a treatment for metabolic disease. Here, we report the first case of T1DM with malnutrition and gastrointestinal symptoms treated with FMT. A 24-year-old T1DM patient suffered from poor blood glucose control, recurrent nausea and vomiting, severe malnutrition, and intractable constipation after insulin treatment. The clinical response of the patients after FMT was well, especially nausea and vomiting were significantly relieved. In addition, constipation, nutritional status, and blood glucose control (fasting blood glucose, HbA1c) gradually improved. A degree of similarity was found in gut microbiota composition between the patient and healthy donor after FMT while it was totally different before the treatment. Furthermore, pathway function analysis of MetaCYC database implies that the potential mechanism of the response of FMT may be driven by specific bacteria involved in several metabolic pathways that need further exploration. To sum up, we believe that the reconstruction of intestinal flora by FMT may be a new choice for the treatment of T1DM patients with malnutrition.

10.
Comput Math Methods Med ; 2022: 6762530, 2022.
Article in English | MEDLINE | ID: mdl-35832135

ABSTRACT

Objective: Comparison of the clinical and radiological effects of precise unilateral puncture pathway prepared by preoperative CT data and traditional unilateral puncture pathway in PVP administration for the treatment of osteoporotic vertebral compression fractures. Summary of background data. PVP is a commonly used vertebral augmentation operation for the treatment of painful spinal compression fractures. A percutaneous unilateral approach is routinely used to get access to the vertebral body. PVP has had positive clinical results in a number of prior investigations. Numerous difficulties and issues, including puncture difficulty, radiation exposure, cement leakage, spinal cord or nerve damage, and intraspinal hematoma, have been described in contrast. Methods: This prospective study included 300 patients with single-level lumbar osteoporotic vertebral compression fractures, 180 females and 120 males, with an average age of 71.5 years. PVP was performed on randomized subjects using two distinct puncture procedures. The patients were separated into two groups: Preoperative planning, in which a precise unilateral puncture path was established using preoperative CT data, and Conventional planning, in which multiple puncture procedures were used. The participants were followed up on after surgery and mostly assessed on clinical and radiological results. The visual analogue scale for pain and the 36-item Short Form Health Survey (SF-36) questionnaire for health status were used to assess clinical outcomes. Radiation dosage, bone cement distribution, vertebral body height, and kyphotic angle were used to evaluate radiological results. Results: Participants remained monitored for 12 to 28 months on average. 151 individuals were treated with accurate unilateral puncture paths planned by preoperative CT data percutaneous vertebroplasty and 149 patients were treated with conventional unilateral paths percutaneous vertebroplasty. The Preoperative planning group's operation time and radiation dose were significantly lower than the Conventional group's; nevertheless, the volume of injected cement was significantly higher in the Preoperative steering committee than in the Conventional group. All patients in both groups had much less pain after the operations when compared to their preoperative suffering. There were no statistically significant variations between groups when the visual analogue scale and the 36-Item Short Form Health Survey were compared. Neither group showed a substantial decrease in the kyphotic angle during the follow-ups. In the Preoperative planning group, the kyphotic angle improved much more than in the Conventional group. At 1 month postoperatively, 16 patients in the Conventional group experienced apparent discomfort in the puncture sites because to facet joint violation. At the latest follow-up, all of the patients' discomfort had vanished after receiving local block therapy. Conclusion: Both preoperatively designed precise unilateral puncture pathways and traditional unilateral puncture procedures PVP are reasonably safe and effective for individuals with painful osteoporotic spinal compression fractures. Unilateral puncture courses planned via preoperative PVP, on the other hand, absorbed less radiation and operation time, as well as a good level of deformity correction and amount of injected cement, and caused less complications than traditional unilateral PVP.


Subject(s)
Fractures, Compression , Osteoporotic Fractures , Spinal Fractures , Vertebroplasty , Aged , Bone Cements/therapeutic use , Female , Fractures, Compression/diagnostic imaging , Fractures, Compression/surgery , Humans , Male , Osteoporotic Fractures/drug therapy , Osteoporotic Fractures/surgery , Pain/drug therapy , Prospective Studies , Punctures , Retrospective Studies , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery , Treatment Outcome , Vertebroplasty/methods
11.
Dalton Trans ; 51(23): 9030-9038, 2022 Jun 13.
Article in English | MEDLINE | ID: mdl-35639483

ABSTRACT

Carbon-supported bimetallic NiCo nanoparticles (NPs) have emerged as attractive catalysts and adsorbents for the reduction of 4-nitrophenol (4-NP) and separation of histidine-rich (His-rich) protein recently due to their low cost, high catalytic activity and good affinity for His-rich protein. In this study, new strongly coupled nickel-cobalt alloy/N,P,S co-doped carbon (NPSC) nanocages are rationally designed via chemical etching of the ZIF-67 dodecahedron with Ni2+ under sonication at room temperature, followed by poly(cyclotriphosphazene-co-4,4'-sulfonyldiphenol) (PZS) coating and subsequent carbonization treatment in a nitrogen atmosphere. When evaluated as a catalyst for 4-NP or an adsorbent for His-rich protein, the as-prepared NiCo@NPSC nanocages obtained at 700 °C show better performance than those obtained at other temperatures (500 and 900 °C). This improved catalytic effect is attributed to the controllable size and fine distribution of the NiCo NPs together with the effective contact between the catalysts and the N,P,S co-doped carbon matrix, leading to a superior catalytic effect on the reduction of 4-NP and the adsorption of His-rich protein. This catalyst design principle can be easily extended to other catalysis research fields.


Subject(s)
Nanoparticles , Nickel , Adsorption , Carbon , Catalysis , Cobalt , Proteins
12.
Clin Hemorheol Microcirc ; 80(2): 197-209, 2022.
Article in English | MEDLINE | ID: mdl-34511491

ABSTRACT

BACKGROUND: Conventional ultrasound and contrast-enhanced ultrasound play an important role in the application of carotid plaque. AIMS: To establish carotid artery vulnerable plaques model by conventional ultrasound combined with contrast-enhanced ultrasound, identify high-risk plaques that may lead to cerebrovascular events, and provide clinical risk warning of high-risk plaques of stroke. METHODS: 205 cases of patients selected in 5053 patients with symptoms from 2018 to 2019 who were verified carotid plaques by conventional ultrasound and contrast-enhanced ultrasound image characteristics, 147 cases as a training set, establishing the carotid artery plaque model, analyzing the characteristic of the plaques and the relationship between cerebrovascular event, with 58 cases as a test set, verify the model. Routine carotid ultrasound and contrast-enhanced carotid ultrasound were performed in all enrolled patients. RESULTS: The gray-level characteristics of conventional ultrasound in the training concentration showed statistical differences in plaque morphology, fibrous cap morphology, uniformity and calcification degree in cerebrovascular events. The contrast enhanced ultrasound characteristics of plaques showed statistical differences in neovascularization and perfusion mode in cerebrovascular events. In the test set, there were statistical differences in the above conventional gray scale features and CEUS features. CONCLUSION: The vulnerable plaque model established by conventional ultrasound combined with contrast-enhanced ultrasound has good diagnostic value for the characteristic plaque of carotid artery with cerebrovascular events.


Subject(s)
Carotid Stenosis , Plaque, Atherosclerotic , Carotid Arteries/diagnostic imaging , Carotid Stenosis/diagnostic imaging , Contrast Media , Humans , Neovascularization, Pathologic , Plaque, Atherosclerotic/diagnostic imaging , Ultrasonography/methods
13.
Redox Biol ; 48: 102199, 2021 Nov 26.
Article in English | MEDLINE | ID: mdl-34847508

ABSTRACT

3CLpro is a key proteinase for SARS-CoV-2 replication and serves as an important target for antiviral drug development. However, how its activity is regulated intracellularly is still obscure. In this study, we developed a 3CLpro protease activity reporter system to examine the impact of various factors, including nutrient supplements, ions, pHs, or oxidative stress inducers, on 3CLpro protease activity. We found that oxidative stress could increase the overall activity of 3CLpro. Not altering the expression, oxidative stress decreased the solubility of 3CLpro in the lysis buffer containing 1% Triton-X-100. The Triton-X-100-insoluble 3CLpro was correlated with aggregates' formation and responsible for the increased enzymatic activity. The disulfide bonds formed between Cys85 sites of 3CLpro protomers account for the insolubility and the aggregation of 3CLpro. Besides being regulated by oxidative stress, 3CLpro impaired the cellular antioxidant capacity by regulating the cleavage of GPx1 at its N-terminus. This cleavage could further elevate the 3CLpro-proximate oxidative activity, favor aggregation and activation of 3CLpro, and thus lead to a positive feedback loop. In summary, we reported that oxidative stress transforms 3CLpro into a detergent-insoluble form that is more enzymatically active, leading to increased viral replication/transcription. Our study provided mechanistic evidence that suggests the therapeutic potential of antioxidants in the clinical treatment of COVID-19 patients.

14.
Virol Sin ; 36(5): 913-923, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33999369

ABSTRACT

SARS-CoV-2 causes the pandemic of COVID-19 and no effective drugs for this disease are available thus far. Due to the high infectivity and pathogenicity of this virus, all studies on the live virus are strictly confined in the biosafety level 3 (BSL3) laboratory but this would hinder the basic research and antiviral drug development of SARS-CoV-2 because the BSL3 facility is not commonly available and the work in the containment is costly and laborious. In this study, we constructed a reverse genetics system of SARS-CoV-2 by assembling the viral cDNA in a bacterial artificial chromosome (BAC) vector with deletion of the spike (S) gene. Transfection of the cDNA into cells results in the production of an RNA replicon that keeps the capability of genome or subgenome replication but is deficient in virion assembly and infection due to the absence of S protein. Therefore, such a replicon system is not infectious and can be used in ordinary biological laboratories. We confirmed the efficient replication of the replicon by demonstrating the expression of the subgenomic RNAs which have similar profiles to the wild-type virus. By mutational analysis of nsp12 and nsp14, we showed that the RNA polymerase, exonuclease, and cap N7 methyltransferase play essential roles in genome replication and sgRNA production. We also created a SARS-CoV-2 replicon carrying a luciferase reporter gene and this system was validated by the inhibition assays with known anti-SARS-CoV-2 inhibitors. Thus, such a one-plasmid system is biosafe and convenient to use, which will benefit both fundamental research and development of antiviral drugs.


Subject(s)
Antiviral Agents , COVID-19 , Antiviral Agents/pharmacology , Containment of Biohazards , Humans , Replicon , SARS-CoV-2 , Virus Replication
15.
Aging (Albany NY) ; 13(7): 9522-9541, 2021 02 03.
Article in English | MEDLINE | ID: mdl-33539323

ABSTRACT

Chronic cerebral hypoperfusion (CCH) may lead to the cognitive dysfunction, but the underlying mechanisms are unclear. EGB761, extracted from Ginkgo biloba and as a phytomedicine widely used in the world, has been showed to have various neuroprotective roles and mechanisms, and therapeutic effects in Alzheimer's disease and other cognitive dysfunctions. However, improvements in cognitive function after CCH, following treatment with EGB761, have not been ascertained yet. In this study, we used the behavior test, electrophysiology, neurobiochemistry, and immunohistochemistry to investigate the EGB761's effect on CCH-induced cognitive dysfunction and identify its underlying mechanisms. The results showed that EGB761 ameliorates spatial cognitive dysfunction occurring after CCH. It may also improve impairment of the long-term potentiation, field excitable potential, synaptic transmission, and the transmission synchronization of neural circuit signals between the entorhinal cortex and hippocampal CA1. EGB761 may also reverse the inhibition of neural activity and the degeneration of dendritic spines and synaptic structure after CCH; it also prevents the downregulation of synaptic proteins molecules and pathways related to the formation and stability of dendritic spines structures. EGB761 may inhibit axon demyelination and ameliorate the inhibition of the mTOR signaling pathway after CCH to improve protein synthesis. In conclusion, EGB761 treatment after CCH may improve spatial cognitive function by ameliorating synaptic plasticity impairment, synapse degeneration, and axon demyelination by rectifying the inhibition of the mTOR signaling pathway.


Subject(s)
Brain Ischemia/complications , Cognitive Dysfunction/drug therapy , Ginkgo biloba , Neuronal Plasticity/drug effects , Neuroprotective Agents/therapeutic use , Plant Extracts/therapeutic use , Animals , Brain Ischemia/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Dendritic Spines/drug effects , Dendritic Spines/metabolism , Male , Maze Learning/drug effects , Neurons/drug effects , Neurons/metabolism , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley , Synapses/drug effects , Synapses/metabolism
16.
Dis Markers ; 2021: 6591784, 2021.
Article in English | MEDLINE | ID: mdl-34992694

ABSTRACT

METHODS AND RESULTS: We conducted a retrospective study of 531 patients with ultrasonogram-confirmed NAFLD who underwent percutaneous coronary intervention (PCI). Then, all patients were separated into four categories by Gensini score (0, 0-9, 9-48, and ≥48) for use in ordinal logistic regression analysis to determine whether NAFLD fibrosis was associated with increased Gensini scores. Mediation analysis was used to investigate whether systemic inflammation is a mediating factor in the association between NAFLD fibrosis and CAD severity. FIB - 4 > 2.67 (OR = 5.67, 95% CI 2.59-12.38) and APRI > 1.5 (OR = 14.8, 95% CI 3.24-67.60) remained to be independent risk factors for the severity of CAD after adjusting for conventional risk factors, whereas among the inflammation markers, only neutrophils and neutrophil-to-lymphocyte ratio (NLR) were independently associated with CAD. Multivariable ordinal regression analysis suggested that increasing Gensini score (0, 0-9, 9-48, and ≥48) was associated with advanced NAFLD fibrosis. ROC curve showed that either fibrosis markers or inflammation markers, integrating with traditional risk factors, could increase the predictive capacity for determining CAD. Inflammation markers, especially neutrophils and NLR, were mediators of the relationship between NAFLD fibrosis and CAD severity. CONCLUSIONS: NAFLD patients with advanced fibrosis are at a high risk of severe coronary artery stenosis, and inflammation might mediate the association between NAFLD fibrosis and CAD severity.


Subject(s)
Coronary Artery Disease/complications , Inflammation/complications , Liver Cirrhosis/etiology , Non-alcoholic Fatty Liver Disease/complications , Aged , Coronary Artery Disease/blood , Female , Humans , Inflammation/blood , Liver Cirrhosis/blood , Lymphocytes , Male , Middle Aged , Neutrophils , Non-alcoholic Fatty Liver Disease/blood , Retrospective Studies , Severity of Illness Index
17.
Aging (Albany NY) ; 12(19): 19520-19538, 2020 Oct 11.
Article in English | MEDLINE | ID: mdl-33040050

ABSTRACT

Cognitive dysfunction caused by chronic cerebral hypoperfusion is a common underlying cause of many cognition-related neurodegenerative diseases. The mechanisms of cognitive dysfunction caused by CCH are not clear. Long non-coding RNA is involved in synaptic plasticity and cognitive function, but whether lncRNA is involved in cognitive dysfunction caused by CCH has not yet been reported. In the present study, we identified the altered lncRNAs and mRNAs by deep RNA sequencing. A total of 128 mRNAs and 91 lncRNAs were up-regulated, and 108 mRNAs and 98 lncRNAs were down-regulated. Real-time reverse transcription-polymerase chain reaction verified the reliability of the lncRNA and mRNA sequencing. Gene Ontology and KEGG pathway analyses showed that differentially-expressed mRNAs were related to peptide antigen binding, the extracellular space, the monocarboxylic acid transport, and tryptophan metabolism. The co-expression analysis showed that 161 differentially expressed lncRNAs were correlated with DE mRNAs. By predicting the miRNA in which both DE lncRNAs and DE mRNAs bind together, we constructed a competitive endogenous RNA network. In this lncRNAs-miRNAs-mRNAs network, 559 lncRNA-miRNA-mRNA targeted pairs were identified, including 83 lncRNAs, 67 miRNAs, and 108 mRNAs. Through GO and KEGG pathway analysis, we further analyzed and predicted the regulatory function and potential mechanism of ceRNA network regulation. Our results are helpful for understanding the pathogenesis of cognitive dysfunction caused by CCH and provide direction for further research.

18.
Eur Neurol ; 81(5-6): 231-238, 2019.
Article in English | MEDLINE | ID: mdl-31574518

ABSTRACT

OBJECTIVE: To analyze the clinical phenotypes and features of Guillain-Barré syndrome (GBS) in our hospital and explore the diagnostic value of the Brighton criteria. METHODS: We retrospectively analyzed the clinical data of GBS patients hospitalized in our hospital from January 1, 2013, to September 30, 2016. The patients were affirmatively graded according to the Brighton criteria (highest: level 1, lowest: level 4). RESULT: (1) We enrolled 72 patients with GBS, including 7 with cranial nerve variants, 4 with Miler-Fisher syndrome, and 61 with classic GBS that mainly presented as limb weakness. (2) A total of 56.94% of the included patients had preceding events, of which respiratory tract infections accounted for 63.41%; there was a significant difference in the incidence of GBS across the spring, summer, autumn, and winter. Weakness was the first symptom in 75% of patients, all patients reached peaked within 4 weeks, and 94.44% of the patients presented with decreased or absent deep tendon reflexes. Among the patients who completed a lumbar puncture cerebrospinal fluid (CSF) examination, 73.24% showed proteins dissociated from CSF cells. Demyelinating GBS was found in 54%, and axonal GBS was found in 22% of the patients who completed an electrophysiological examination. All patients with classic GBS were graded according to the Brighton diagnostic criteria as level 1 (60.66%, 37/61), level 2 (34.42%, 21/61), level 3 (4.92%, 3/61), or level 4 (0%). CONCLUSION: In our hospital, the clinical features of patients with GBS were similar to those described in previous studies, but demyelinating GBS was the most important subtype. Most preceding events were upper respiratory tract infections. The Brighton criteria were highly sensitive, and perfect clinical data improved diagnostic grading. In areas where medical resources are relatively scarce, a detailed medical history and physical examination can help improve diagnostic accuracy.


Subject(s)
Guillain-Barre Syndrome/diagnosis , Adult , Aged , Female , Guillain-Barre Syndrome/complications , Humans , Male , Middle Aged , Muscle Weakness/etiology , Phenotype , Retrospective Studies
19.
Front Neurol ; 10: 1031, 2019.
Article in English | MEDLINE | ID: mdl-31632334

ABSTRACT

Objective: To investigate the clinical manifestations, underlying diseases, pathological features, and therapeutic responses in patients with muscular tuberculosis (MT), which is rare and often misdiagnosed in clinical practice. Methods: This study describes a rare MT case that was recently diagnosed in our department. Additionally, 18 other MT cases retrieved from the PubMed database from 2,000 to date are included in this study. The clinical manifestations, areas of residence, underlying diseases, laboratory test results, pathology results, and outcomes of the patients were recorded and analyzed. Results: The MT patients in this study included 13 males and six females with an average age of 34.58 years old. Eight patients were from Asia, and six patients were from Africa, accounting for the majority of patients, at 73.68%. Underlying diseases included flu-like illness in one patient; chronic kidney disease (CKD) in one patient; Sjögren's syndrome in one patient; systemic lupus erythematosus (SLE), lupus nephropathy, and deep vein thrombosis in one patient; and Alzheimer's disease (AD) and Paget's disease in one patient. Two patients had a previous history of tuberculosis, and two patients had contact with suspected tuberculosis patients. All patients presented chronic occult onset, with an average of 3 (1.75, 5) months. Six cases had local masses, and 13 cases had swelling as the main clinical manifestations. Twelve patients (63.2%) presented manifestations at single sites, and seven patients presented manifestations at multiple sites, including the thigh, calf, arm, chest wall, dorsal, psoas, gluteal, and forehead muscles. Of the 19 total patients, 13 (68.4%) reported pain, and only 8 (42.1%) patients presented tuberculosis symptoms. All patients received laboratory results associated with Mycobacterium tuberculosis infection. Fourteen (73.7%) of the 19 patients underwent skeletal muscle biopsy, where granulomatous inflammation was observed. Eighteen patients were treated with anti-tuberculosis therapies. Sixteen patients improved or recovered after anti-tuberculosis treatment, and unfortunately, two patients died. Conclusion: As a kind of systemic disease, MT is mainly characterized by painful or painless muscle masses and swelling at a single site or at multiple sites. Patients with a history of tuberculosis and immune system disease are susceptible to MT. A diagnosis is mainly made on the basis of the results of pathological biopsy and bacteriological culture. Early diagnosis and timely standardized anti-tuberculosis treatment can improve the prognosis.

20.
Australas J Dermatol ; 60(3): e227-e231, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30592019

ABSTRACT

Eosinophilic fasciitis is a rare scleroderma-like syndrome with an unknown aetiology. The characteristics of this disorder include lymphoplasmacytic inflammation involving the subcutaneous fat septa and fascia. Eosinophilic myositis is diagnosed when inflammation extends into the muscles. Here, we describe four patients who developed eosinophilic fasciitis, three of whom developed eosinophilic fasciitis with myositis. Fascial and muscle biopsies were used to confirm the diagnoses. All the patients presented with musculoskeletal symptoms; their electromyographic examinations showed myogenic lesions [short-duration, low-amplitude and polyphasic motor unit action potentials (MUPs), so-called myopathic changes, frequently with abnormal spontaneous activity], in contrast with findings from other reports.


Subject(s)
Eosinophilia/pathology , Fasciitis/pathology , Myositis/pathology , Adolescent , Adult , Biopsy , Electromyography , Female , Humans , Male , Myalgia/etiology , Young Adult
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