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1.
Heliyon ; 10(6): e27219, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38524593

ABSTRACT

Upon confirming an HIV diagnosis, patients need to start life-long antiretroviral therapy (ART) as soon as possible. During HIV treatment, ART drugs can cause intolerable adverse reactions, leading to poor medication compliance, treatment failure, and advancement of the HIV stage. Herein, we report a case of AIDS intolerant to multiple antiviral drugs due to side effects that we finally stabilized with the Albuvirtide (ABT) and Dolutegravir (DTG) combination. A 48 -year-old woman developed intractable nausea, vomiting and abdominal discomfort within one month of starting ART. Over the course of four years, she was switched to four different ART regimens due to her intolerance of severe adverse effects, mainly gastrointestinal symptoms, rash, and lethargy. Over four years, she failed to attain viral suppression due to poor drug compliance. After several ART changes, we started her on the Long-acting antiretroviral therapy (LA ART), Albuvirtide, combined with Dolutegravir, which she tolerated well. The patient's general condition improved significantly and attained marked virologic suppression. The patient's condition has been well controlled for nearly two years with good adherence. This case emphasizes the influence of ART treatment options on medication compliance and the outcome of HIV infection.

2.
Yi Chuan ; 46(1): 34-45, 2024 Jan 20.
Article in English | MEDLINE | ID: mdl-38230455

ABSTRACT

Currently, there are over 170 recognized species of Mycobacterium, the only genus in the family Mycobacteriaceae. Organisms belonging to this genus are quite diverse with respect to their ability to cause disease in humans. The Mycobacterium genus includes human pathogens (Mycobacterium tuberculosis complex and Mycobacterium leprae) and environmental microorganisms known as non-tuberculosis mycobacteria (NTM). A common pathogenic factor of Mycobacterium is the formation of biofilms. Bacterial biofilms are usually defined as bacterial communities attached to the surface, and are also considered as shared spaces of encapsulated microbial cells, including various extracellular polymeric substrates (EPS), such as polysaccharides, proteins, amyloid proteins, lipids, and extracellular DNA (EDNA), as well as membrane vesicles and humic like microorganisms derived refractory substances. The assembly and dynamics of the matrix are mainly coordinated by second messengers, signaling molecules, or small RNAs. Fully deciphering how bacteria provide structure for the matrix, thereby promoting extracellular reactions and benefiting from them, remains a challenge for future biofilm research. This review introduces a five step development model for biofilms and a new model for biofilm formation, analyses the pathogenicity of biofilms, their interactions with bacteriophages and host immune cells, and the key genes and regulatory networks of mycobacterial biofilms, as well as mycobacterial biofilms and drug resistance, in order to provide a basis for clinical treatment of diseases caused by biofilms.


Subject(s)
Mycobacterium , Humans , Biofilms , Proteins , DNA , Anti-Bacterial Agents/pharmacology
3.
Acta Pharmaceutica Sinica ; (12): 503-510, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016630

ABSTRACT

italic>Mycobacterium tuberculosis, responsible for tuberculosis (TB), remains a major health problem worldwide and is one of the infectious diseases causing increased morbidity and mortality worldwide. Biotin, namely vitamin H, is an important cofactor necessary for fatty acid biosynthesis, gluconeogenesis and amino acid metabolism in organisms including Mycobacterium tuberculosis. Due to its inability to ingestion biotin from outside, Mycobacterium tuberculosis can only obtain biotin through biotin biosynthesis. Different from the classical BioC-BioH, BioI-BioW and non-classical BioZ pathways, Mycobacterium tuberculosis synthesized biotin by "BioC-BioH(2)" pathway in the early stage. This review focuses on the unique biotin synthesis pathway of Mycobacterium tuberculosis and its key genes, especially the response of this pathway and biotin-dependent carboxylase to tuberculosis first-and second-line drugs, as well as inhibitors and natural products targeting biotin synthesis.

4.
Sci Total Environ ; 875: 162536, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-36870503

ABSTRACT

In recent years, due to global warming and water eutrophication, cyanobacterial blooms have occurred frequently worldwide, resulting in a series of water quality problems, among which the odor problem in lakes is one of the focuses of attention. In the late stage of the bloom, a large amount of algae accumulated on the surface sediment, which will be a great hidden danger to cause odor pollution in lakes. ß-Cyclocitral is one of the typical algae-derived odor compounds that cause odor in lakes. In this study, an annual survey of 13 eutrophic lakes in the Taihu Lake basin was investigated to assess the effects of abiotic and biotic factors on ß-cyclocitral in water. Our results showed that high concentrations of ß-cyclocitral in the pore water (pore-ß-cyclocitral) were detected in the sediment and far exceeded that in the water column, with an average of about 100.37 times. Structural equation modeling indicated that algal biomass and pore-ß-cyclocitral can directly regulate the concentrations of ß-cyclocitral in the water column, and total phosphorus (TP) and temperature (Temp) promoted the algal biomass which further enhanced the production of ß-cyclocitral both in the water column and pore water. It was worth noting that when Chla ≥30 µg/L, the effects of algae on pore-ß-cyclocitral were significantly enhanced, and pore-ß-cyclocitral played a major role in the regulation of ß-cyclocitral concentrations in water column. Overall, our study facilitated a comprehensive and systematic understanding of the effects of algae on odorants and the dynamic regulatory processes in complex aquatic ecosystems, and revealed a long-neglected process, that was, the important contribution of sediments to ß-cyclocitral in the water column in eutrophic lakes, which would conduce to a more accurate understanding of the evolution of off flavors in lakes and also useful for the management of odors in lakes in the future.


Subject(s)
Lakes , Water Pollutants, Chemical , Lakes/chemistry , Environmental Monitoring , Ecosystem , Geologic Sediments/chemistry , Water Pollutants, Chemical/analysis , Eutrophication , Phosphorus/analysis , China
5.
International Eye Science ; (12): 1887-1890, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-996904

ABSTRACT

AIM: To investigate the effect of peripheral defocus spectacles and orthokeratology lenses on the control of axial length in children and adolescents with myopia.METHODS: Prospective study. A total of 71 cases(134 eyes)of children and adolescents with myopia who visited the Second Hospital of Longyan from June 2019 to June 2021 were selected. They were fitted with peripheral defocus spectacles for 12mo and then switched to orthokeratology lenses. The growth of axial length was observed at 3, 6, and 12mo after wearing peripheral defocus spectacles and orthokeratology lenses.RESULTS: The median axial length growth after wearing peripheral defocus spectacles and orthokeratology lenses for 12mo was 0.35 and 0.14mm, respectively. The axial growth at 3, 6, and 12mo after wearing orthokeratology lenses was lower than those after wearing peripheral defocus spectacles(P<0.001), and the growth rate of axial length was significantly reduced. The patients were divided into a rapid progression group(axial growth ≥0.4 mm, 29 cases, 54 eyes)and a non-rapid progression group(axial growth <0.4mm, 42 cases, 80 eyes)according to the axial growth of peripheral defocus spectacles for 12mo. The median axial growth after wearing peripheral defocus spectacles for 12mo in the two groups was 0.70 and 0.24mm, respectively, while the median axial growth after wearing orthokeratology lenses was 0.31 and 0.09mm, respectively. The growth rate was reduced by 56% and 63% respectively in the two groups after wearing orthokeratology lens. The axial growth of cases wearing orthokeratology lenses for 12mo in the non-rapid progression group was lower than that in the rapid progression group, and it did not change with age or diopter. There was no significant difference among different ages and different diopters in the rapid progression group(P>0.05). In the non-rapid progression group, axial growth of cases aged 7-12 years was higher than those aged 13-16 years(P<0.05), but there was no significant difference among different diopters(P>0.05).CONCLUSION: Orthokeratology lens is more effective than peripheral defocus spectacles in controlling axial growth in children and adolescents with myopia, and the control effect of orthokeratology lens on rapid-progressing myopia is remarkable.

6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-994386

ABSTRACT

Objective:To explore the effect and underlying mechanism of casein kinase 2 interacting protein-1 (CKIP-1) on hepatocyte apoptosis in nonalcoholic fatty liver disease (NAFLD).Methods:Experimental study. An NAFLD cell model was established by inducing human hepatoma cell line, HepG 2 cells, with oleic acid (OA). Flag-CKIP-1 expression vector and shRNA-CKIP-1 were transfected into HepG 2 cells. Flow cytometry was used to detect the effect of CKIP-1 on the activity and apoptosis of NAFLD hepatocytes. The levels of apoptosis-related proteins were detected by Western blot. CKIP-1 knockout mice in C57BL/6 back-ground were fed with either standard or high-fat diet for 8 weeks. Apoptosis-related signal proteins in NAFLD hepatocytes were detected by immunohistochemistry. Results:After CKIP-1 was transfected into HepG 2 cells, the degree of OA induced cell liposis was significantly reduced ( P<0.05). Annexin V-FITC/PI flow cytometry showed that CKIP-1 reduced the apoptosis of steatotic hepatocytes. Overexpression of CKIP-1 could significantly inhibit the expression of caspase-3 and caspase-9 and increase the expression of Bcl-2/Bax ( P<0.05). Knockdown of CKIP-1 could increase the expression of caspase-3 and caspase-9 ( P<0.05). CKIP-1 knockout could further increase the expression of caspase-3 and caspase-9 in NAFLD mice ( P<0.01, P<0.05), and further decrease the expression of Bcl-2/Bax ( P<0.05). Conclusion:CKIP-1 inhibited the apoptosis of steatotic hepatocytes by up-regulating the expression of apoptosis inhibitor gene, Bcl-2/Bax, and affecting the proteases, caspase-3 and caspase-9.

7.
Yi Chuan ; 45(11): 998-1006, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-38764265

ABSTRACT

The transcription of interferon-stimulated gene 15 (isg15) is induced by type I interferons. ISG15 can covalently modify target proteins through the sequential action of enzymesE1, E2, and E3, a process known as ISGylation. The ISGylation of host proteins is widely involved in immune responses, such as host antiviral defence. Ubiquitin-specific protease 18 (USP18), as a deubiquitinase (DUB), can remove ISG15 conjugated to target proteins and inhibit host immune responses by suppressing the type I interferon signaling. The dynamic balance between ISGylation and deISGylation mediated by ISG15 or USP18 respectively plays a significant role in the tuberculosis. Furthermore, similar to ISG15, USP18 is extensively involved in virus-host interaction. In this review, we summarize the roles of ISGylation and deISGylation in tuberculosis and other important diseases mediated by ISG15 and USP18 respectively, underlying regulator network. Further studies in this aspect will inspire new host-targeted strategies to control important diseases such as tuberculosis.


Subject(s)
Cytokines , Tuberculosis , Ubiquitin Thiolesterase , Ubiquitins , Humans , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , Ubiquitins/metabolism , Ubiquitins/genetics , Tuberculosis/metabolism , Tuberculosis/microbiology , Cytokines/metabolism , Animals , Signal Transduction
8.
Yi Chuan ; 45(12): 1100-1113, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38764274

ABSTRACT

Mycobacterium infection can affect the host's immune function by secreting extracellular effector proteins. ESX (or type VII) system plays an important role in the secretion of effector proteins. ESX system is the protein export system in mycobacteria and many actinomycetes. However, how ESX system secretes and underlying mechanism of action remain unclear. In this review, we introduce the components, function, classification of ESX system and the process of substrates transfer to the peripheral space via this system, and discuss the roles of ESX system in antibiotics resistance, persistence, host-phage interaction, new drug targets. We hope to provide insights into the discovery of new drugs and vaccine antigens for tuberculosis.


Subject(s)
Bacterial Proteins , Mycobacterium , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Humans , Type VII Secretion Systems/genetics , Type VII Secretion Systems/metabolism , Type VII Secretion Systems/physiology , Tuberculosis/microbiology
9.
Yi Chuan ; 45(11): 1018-1027, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-38764267

ABSTRACT

Mismatch repair (MMR) is a common repair system after DNA replication, which is critical for maintaining genomic stability. Members of the MutS and MutL protein families are involved in key steps of mismatch repair. Despite the major importance of this repair pathway, MutS-MutL are absent in almost all Actinobacteria and many Archaea. Mycobacteria and others have another non-canonical MMR pathway, in which EndoMS/NucS plays a key role and has no structural homology compared to canonical MMR proteins (MutS/MutL). EndoMS/NucS mediated non-canonical mismatch repair plays an important role in DNA repair, mutation, homologous recombination and antibiotic resistance of Mycobacterium. By comparing the classical and non-canonical MMR pathways, this paper reviews the EndoMS/NucS-mediated non-canonical MMR pathway in Mycobacterium and its recent progress. We hope to bring new insights into the molecular mechanism of mycobacterial mismatch repair as well as to provide new research clues for mycobacterial antibiotic therapy.


Subject(s)
DNA Mismatch Repair , Mycobacterium , Mycobacterium/genetics , Mycobacterium/drug effects , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Drug Resistance, Bacterial/genetics , Drug Resistance, Microbial/genetics , Anti-Bacterial Agents/pharmacology , Humans
10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1008908

ABSTRACT

In order to fully explore the neural oscillatory coupling characteristics of patients with mild cognitive impairment (MCI), this paper analyzed and compared the strength of the coupling characteristics for 28 MCI patients and 21 normal subjects under six different-frequency combinations. The results showed that the difference in the global phase synchronization index of cross-frequency coupling under δ-θ rhythm combination was statistically significant in the MCI group compared with the normal control group ( P = 0.025, d = 0.398). To further validate this coupling feature, this paper proposed an optimized convolutional neural network model that incorporated a time-frequency data enhancement module and batch normalization layers to prevent overfitting while enhancing the robustness of the model. Based on this optimized model, with the phase locking value matrix of δ-θ rhythm combination as the single input feature, the diagnostic accuracy of MCI patients was (95.49 ± 4.15)%, sensitivity and specificity were (93.71 ± 7.21)% and (97.50 ± 5.34)%, respectively. The results showed that the characteristics of the phase locking value matrix under the combination of δ-θ rhythms can adequately reflect the cognitive status of MCI patients, which is helpful to assist the diagnosis of MCI.


Subject(s)
Humans , Electroencephalography/methods , Cognitive Dysfunction/diagnosis , Neural Networks, Computer , Sensitivity and Specificity
11.
J Clin Lab Anal ; 36(12): e24779, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36447427

ABSTRACT

BACKGROUND: In almost every country, cardiovascular diseases are the major cause of death, which are responsible for 17.7 million deaths worldwide, or 54% of all deaths. However, the latest evidence has shown that non-communicable diseases such as obesity, diabetes, and cardiovascular events are significantly influenced by the blood microbiota and circulating metabolites. METHODS: We searched online databases for the most recent related papers through the comprehensive international databases of the Institute of PubMed/ MEDLINE, ISI/WOS, and Scopus up to August 2022, using MESH terms and the related keywords in the English language. Considering the titles and abstracts, unrelated studies were excluded. The full texts of the remained studies were evaluated by authors, independently. Then, the studies' findings were assessed and reported. RESULTS: The study demonstrated that the bacterial profiles of patients with cardiovascular diseases and healthy individuals are significantly different. The diseased patients showed a significantly high abundance of phylum Proteobacteria, an important Proteobacterial component known as lipopolysaccharides that has been linked to the pathogenesis of cardiovascular disease, while phylum Firmicutes were found in healthy individuals. It suggests that Proteobacteria has a direct role in the onset of cardiovascular disease. CONCLUSION: We focused on the blood bacterial composition and circulating microbial metabolites in their relationship with the etiology and onset of cardiovascular disease. However, the various genera and species in the results reported were not always identical. Therefore, the microbial community structure of blood was more complicated and thus required a more in-depth exploration.


Subject(s)
Cardiovascular Diseases , Microbiota , Humans , Cardiovascular Diseases/epidemiology , Bacteria
12.
Front Cell Infect Microbiol ; 12: 943808, 2022.
Article in English | MEDLINE | ID: mdl-36268223

ABSTRACT

Emerging evidence revealed that the blood microbiota plays a role in several non-communicable diseases, including cardiovascular disease. However, the role of circulating microbes in atherosclerosis remains understudied. To test this hypothesis, we performed this study to investigate the microbial profile in the blood of Chines atherosclerosis volunteers. A total of seventy Acute Coronary Syndrome patients, seventy Chronic Coronary Syndrome patients, and seventy healthy individuals were examined using high-throughput Illumina Novaseq targeting the V3-V4 regions of the 16S rRNA gene. The relationship between atherosclerosis and blood microbiome, clinical variables, and their functional pathways were also investigated. Our study observed significantly higher alpha diversity indices (Chao1, p = 0.001, and Shannon, p = 0.004) in the acute coronary syndrome group compared with chronic coronary syndrome and healthy group, although a significantly lower alpha diversity was observed in the chronic coronary syndrome compared to acute coronary syndrome and healthy group. Beta diversity based on principal coordinate analysis demonstrated a major separation among the three groups. In addition, using linear discriminant analysis, a significant distinct taxon such as Actinobacteria _ phylum, and Staphylococcus_ genus in the healthy group; Firmicutes_ phylum, and Lactobacillus_ genus in the chronic coronary syndrome group, and Proteobacteria and Acidobacteriota _ phyla in acute coronary syndrome group were observed among three groups. Clusters of Orthologous Genes grouped and Kyoto Encyclopedia of Genes and Genomes pathways suggested a significant variation among all groups (p < 0.05). The blood microbiota analysis provides potential biomarkers for the detection of coronary syndromes in this population.


Subject(s)
Acute Coronary Syndrome , Atherosclerosis , Humans , RNA, Ribosomal, 16S/genetics , Acute Coronary Syndrome/diagnosis , Bacteria/genetics , Biomarkers
13.
J Tradit Chin Med ; 42(5): 764-772, 2022 10.
Article in English | MEDLINE | ID: mdl-36083484

ABSTRACT

OBJECTIVE: To determine whether Shunxin decoction improves diastolic function in rats with heart failure with preserved ejection fraction (HFpEF) by regulating the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFpEF rat models using the abdominal aorta constriction method. These rats in the HFpEF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin low-dose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, low-dose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the cGMP-PKG pathway. Natriuretic peptide receptor A (NPRA) and guanylate cyclase (GC) were detected by immunohistochemistry, and eNOS, phosphodiesterase 5A (PDE5A), and cGMP-dependent protein kinase 1(PKG I) were determined by Western blotting. RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole (IVSd) and the thickness of the posterior wall at the end of diastole (PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced ( < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased ( < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group ( < 0.01). Compared to the model group, the expressions of eNOS and PKG I increased ( < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group ( < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFpEF. It increases the expression of NPRA, GC, and eNOS in the myocardial cell cGMP-PKG signaling pathway, upregulates cGMP expression, decreases PDE5A expression to reduce the cGMP degradation. Thus, the cGMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFpEF rats.


Subject(s)
Heart Failure , Animals , Aorta, Abdominal/metabolism , Constriction , Cyclic GMP/metabolism , Cyclic GMP-Dependent Protein Kinases/genetics , Cyclic GMP-Dependent Protein Kinases/metabolism , Diastole , Guanosine Monophosphate , Heart Failure/drug therapy , Heart Failure/genetics , Male , Rats , Signal Transduction , Stroke Volume/physiology
14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-957508

ABSTRACT

Objective:To evaluate the efficacy of compound chamomile and lidocaine hydrochloride gel in prevention of complications related to laryngeal mask airway (LMA) insertion.Methods:Ninety American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 18-60 yr, undergoing elective surgery with ventilation using LMA under general anesthesia, were divided into 3 groups ( n=30 each) using a random number table method: paraffin oil group (group A), compound lidocaine cream group (group B), and compound chamomile and lidocaine hydrochloride gel group (group C). The paraffin oil, compound lidocaine cream, and compound chamomile and lidocaine hydrochloride gel were evenly applied on the front, shoulder and back of the LMA before inserting the LMA in A, B and C groups, respectively.The severity of sore throat, oropharyngeal mucositis score, hoarseness score and occurrence in each time period (0-1 h, >1-6 h, >6-24 h, > 24-48 h) were recorded at 1, 6, 24 and 48 h after removal of the laryngeal mask.The stress responses during removal of the LMA and occurrence of drug-related adverse reactions within 48 h after removal of LMA were recorded. Results:Twenty-nine cases in group A, 28 cases in group B and 27 cases in group C completed the trial.Compared with group A, the severity of sore throat at each time point after removal of the LMA and incidence of sore throat in each time period were significantly decreased, the oropharyngeal mucositis score at 6, 24 and 48 h after removal of the LMA and the incidence of oropharyngeal mucositis in the time period >1-48 h were decreased, and the incidence of drug-related adverse reactions was increased in group C ( P<0.05). Compared with group B, the severity of sore throat at 6 h after removal of the LMA and incidence of sore throat > 1-48 h after removal of the LMA were significantly decreased, the oropharyngeal mucositis score at 6, 24 and 48 h after removal of the LMA and incidence of oropharyngeal mucositis in the time period >1-48 h after LMA removal were reduced, and the incidence of drug-related adverse reactions was decreased in group C ( P<0.05). There was no significant difference in the hoarseness score and incidence of hoarseness after removal of the LMA and incidence of stress responses during removal of the LMA among the three groups ( P>0.05). Conclusions:Compound chamomile and lidocaine hydrochloride gel has a certain efficacy in preventing complications related to LMA placement.

15.
Acta Pharmaceutica Sinica ; (12): 2126-2138, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-936572

ABSTRACT

Based on the idea of multi-target drug design, taking p-aminosalicylic acid (PAS) as the parent nucleus, the unreported target molecules TM1 and TM2 were designed with PAS, isonicotinic acid and fluoroquinolone as three structural units conjugated by different linkers. Sixteen target molecules were synthesized by multi-step reaction, and their activities against Mycobacterium tuberculosis and human pathogenic bacteria were evaluated. The results showed that the anti-tuberculosis activity of TM2a was stronger than those of the assayed fluoroquinolones, while TM1a was comparable to that of clinafloxacin, the most active compound of the positive control fluoroquinolones; TM1a showed the strongest inhibitory activity to all almost tested strains, TM1b and TM2a showed very strong inhibitory activity to most strains, and TM1h/2h had strong inhibitory activity to some strains; The inhibitory activities of TM1a/1h on Staphylococcus aureus ATCC14125 are much stronger than those of fluoroquinolones, which eminently deserves further study. The hemolysis test results showed that the highly active molecules TM1a and TM2a exhibited relative safety below the concentrations of 8 and 32 μg·mL-1, respectively. In this study, a new hybrid molecule of three molecular pharmacophores with PAS as the parent nucleus was synthesized for the first time, and some of which have highly strong antibacterial activity, which provides a new idea for the research and development of antibiotics.

16.
Chinese Journal of Pediatrics ; (12): 14-19, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-935632

ABSTRACT

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.


Subject(s)
Child , Female , Humans , Infant , Male , Coronary Aneurysm/etiology , Immunoglobulins, Intravenous/therapeutic use , Infliximab/adverse effects , Mucocutaneous Lymph Node Syndrome/drug therapy , Retrospective Studies
17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-931036

ABSTRACT

Age-related macular degeneration (AMD), the leading cause of central vision loss among people aged 50 years and older, is one of the major eye diseases causing blindness in the world.Clinically, advanced AMD is divided into two types, non-exudative AMD with manifestation of geographic atrophy and exudative AMD with manifestation of choroidal neovascularization.The pathogenesis of AMD is complex, and the para-inflammation is recognized as an important risk factor.Nucleotide-binding oligomerization domain like receptors 3 (NLRP3) inflammasome is a cytoplasmic pattern recognition receptor and is expressed in several kings of cells, including retinal pigment epithelium (RPE) cells, microglial cells, Müller glia cells and retinal vascular endothelial cells.Recent studies have suggested that NLRP3 inflammasome plays an important role in the pathophysiology of both non-exudative and exudative AMD.The role of the NLRP3 inflammasome and its effector cytokines interleukin (IL)-1β and IL-18 in AMD were reviewed in this article to provide guidance on future prevention and therapy of AMD.

18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-930962

ABSTRACT

Objective:To investigate the clinical efficacy of pancreaticoduodenectomy with TRIANGLE operation in the treatment of pancreatic head cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 51 patients with pancreatic head cancer who were admitted to the Sichuan Provincial People′s Hospital, Affiliated Hospital of School of Medicine of University of Electronic Science and Technology of China from January 2017 to July 2018 were collected. There were 33 males and 18 females, aged from 42 to 74 years, with a median age of 56 years. Of the 51 patients, 24 cases undergoing standard pancreaticoduodenectomy, in which No.12, 13 and 17 lymph nodes were dissected, combined with transcatheter arterial infusion chemo-therapy (TAI) were allocated into the standard group, and 27 cases undergoing pancreaticoduo-denectomy with TRIANGLE operation, in which No.7, 8, 9, 12, 13, 16, 17 lymph nodes were dissected, combined with TAI were allocated into the TRIANGLE group, respectively. Observation indicators: (1) intraoperative conditions of the two groups; (2) postoperative conditions of the two groups; (3) follow-up and survival. Follow-up was conducted using outpatient examination and telephone interview once three months to detect tumor recurrence and metastasis and survival of patients up to July 2021 or the death of patient. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the chi-square test or the Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Kaplan‐Meier method was used to calculate the survival rate and median survival time and draw survival curve. Log‐Rank test was used for survival analysis. Results:(1) Comparison of intraoperative conditions between the two groups. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion were (501±61)minutes, (563±278)mL, 4 in the standard group, versus (556±46)minutes, (489±234)mL, 6 in the TRIANGLE group, respectively. There was a significant difference in the operation time between the two groups ( t=3.62, P<0.05) but there was no significant difference in the volume of intraoperative blood loss or cases with intraoperative blood transfusion between the two groups ( t=1.03, χ2=0.25, P>0.05). (2) Comparison of postoperative conditions between the two groups. Of the 51 patients, 30 had 50 times of postoperative complications, including 18 times of grade Ⅰ complications of Clavien-Dindo classification, 29 times of grade Ⅱ complications of Clavien-Dindo classification, 2 times of grade Ⅲa complications of Clavien-Dindo classification, 1 time of grade Ⅲb complications of Clavien-Dindo classification, respectively. Cases with postoperative complications, cases with delayed gastric emptying, cases without or with pancreatic fistula as class A or class B, cases with biliary fistula, cases with bleeding, cases with diarrhea were 15, 4, 13, 7, 4, 4, 2, 2 in the standard group, versus 15, 6, 14, 10, 3, 4, 1, 3 in the TRIANGLE group, respectively. There was no significant difference in cases with postoperative complications, cases with delayed gastric emptying, cases with pancreatic fistula between the two groups ( χ2=0.16, 0.02, Z=-0.04, P>0.05) and there was no significant difference in cases with biliary fistula, cases with bleeding, cases with diarrhea between the two groups ( P>0.05). Cases with complications as Clavien-Dindo grade Ⅰ, grade Ⅱ, grade Ⅲ were 10, 11, 2 in the standard group, versus 8, 18, 1 in the TRIANGLE group, showing no significant difference between the two groups ( Z=-0.67, P>0.05). The duration of postoperative hospital stay was (23±8)days in both of the standard group and the TRIANGLE group, showing no significant difference between the two groups ( t=0.31, P>0.05). (3) Follow-up and survival. All the 51 patients were followed-up for 6 to 54 months, with a median follow-up time of 17 months. The postoperative 1-year overall survival rate was 75.0% and 81.5% in the standard group and the TRIANGLE group, respectively. The postoperative 3-year overall survival rate was 12.5% and 22.2% in the standard group and the TRIANGLE group, respectively. The median postoperative survival time was 15.00 months (95% confidence interval as 12.63 to 17.37 months) and 21.00 months (95% confidence interval as 15.91 to 19.62 months) in the standard group and the TRIANGLE group, respectively. There was a significant difference in survival of patients between the two groups ( χ2=4.30, P<0.05). Cases with tumor recurrence during post-operative 1 year and 3 year were 9 and 20 in the standard group, versus 6 and 15 in the TRIANGLE group, respectively. There was no significant difference in cases with tumor recurrence during postoperative 1 year between the two groups ( P>0.05) and there was a significant difference in cases with tumor recurrence during postoperative 3 year between the two groups ( P<0.05). Conclusion:Compared with standard pancreaticoduodenectomy, pancreaticoduodenectomy with TRIANGLE operation can prolong the median survival time of patients with pancreatic head cancer without increasing surgical related complications.

19.
Journal of Biomedical Engineering ; (6): 1233-1239, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-970662

ABSTRACT

The electroencephalogram (EEG) signal is a general reflection of the neurophysiological activity of the brain, which has the advantages of being safe, efficient, real-time and dynamic. With the development and advancement of machine learning research, automatic diagnosis of Alzheimer's diseases based on deep learning is becoming a research hotspot. Started from feedforward neural networks, this paper compared and analysed the structural properties of neural network models such as recurrent neural networks, convolutional neural networks and deep belief networks and their performance in the diagnosis of Alzheimer's disease. It also discussed the possible challenges and research trends of this research in the future, expecting to provide a valuable reference for the clinical application of neural networks in the EEG diagnosis of Alzheimer's disease.


Subject(s)
Humans , Alzheimer Disease/diagnosis , Neural Networks, Computer , Machine Learning , Brain , Electroencephalography
20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-974568

ABSTRACT

Objective To understand the level of quality control in medical linear accelerator in Guangxi, and to provide technical support for the health administrative department to make related standards. Methods To select medical linear accelerators in Guangxi by random sampling method. Results A total of 118 accelerators were checked in 2017—2019, the initial inspection pass rates of medical linear accelerators were 56.8% and re-inspect pass rate were 96.6%. Conclusion The quality control level of the radiology institutions needs to be improved. The health administrative department should strengthen routine management,it is necessary to implement quality control in medical linear accelerator.

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