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1.
J Gastroenterol Hepatol ; 39(6): 1008-1015, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38326979

RESUMO

BACKGROUND AND AIM: The study aims to evaluate the feasibility of body mass index (BMI)-based individualized small bowel preparation for computed tomography enterography (CTE). METHODS: In this prospective randomized controlled study, patients undergoing CTE were randomly assigned to the individualized group or standardized group. Those in individualized group were given different volumes of mannitol solution based on BMI (1000 mL for patients with BMI < 18.5 kg/m2, 1500 mL for patients with 18.5 kg/m2 ≤ BMI < 25 kg/m2 and 2000 mL for patients with BMI ≥ 25 kg/m2) while patients in the standardized group were all asked to consume 1500-mL mannitol solution. CTE images were reviewed by two experienced radiologists blindly. Each segment of the small bowel was assessed for small bowel image quality and disease detection rates. Patients were invited to record a diary regarding adverse events and acceptance. RESULTS: A total of 203 patients were enrolled and randomly divided into two groups. For patients with BMI < 18.5 kg/m2, 1000-mL mannitol solution permitted a significantly lower rate of flatulence (P = 0.045) and defecating frequency (P = 0.011) as well as higher acceptance score (P = 0.015), but did not affect bowel image quality and diseases detection compared with conventional dosage. For patients with BMI ≥ 25 kg/m2, 2000-mL mannitol solution provided better overall image quality (P = 0.033) but comparable rates of adverse events and patients' acceptance compared with conventional dosage. CONCLUSIONS: Individualized bowel preparation could achieve both satisfactory image quality and patients' acceptance thus might be an acceptable alternative in CTE.


Assuntos
Índice de Massa Corporal , Intestino Delgado , Manitol , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Manitol/administração & dosagem , Manitol/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Intestino Delgado/diagnóstico por imagem , Adulto , Idoso , Estudos de Viabilidade , Catárticos/administração & dosagem , Catárticos/efeitos adversos , Medicina de Precisão
2.
Inflamm Bowel Dis ; 30(1): 114-124, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37454276

RESUMO

BACKGROUND: Mucosal healing is one of the principal therapeutic targets for ulcerative colitis (UC). Mitochondria are dynamic organelles that undergo constant fusion and fission; however, the process that is most conducive to mucosal healing remains unclear. This study investigated the role of mitochondrial fission in mucosal healing in UC patients. METHODS: Quantitative polymerase chain reaction, Western blotting, and immunostaining were used to detect mitochondrial fission in UC patients and a dextran sulfate sodium-induced colitis model. Colonic organoids were used to investigate the role of mitochondrial fission in butyrate metabolism. Enzyme activity assays were performed to identify the key proteins involved in this mechanism. RESULTS: It was found that inhibition of mitochondrial fission promoted mucosal healing in mice and that there was an increase in mitochondrial fission in colonic epithelial cells of UC patients. Excessive fission inhibits stem cell proliferation by impairing butyrate metabolism in colonic organoids. The mitochondrial fission antagonist P110 failed to promote mucosal healing in antibiotic-treated mice, and the addition of exogenous butyrate reversed this effect. Increased butyrate exposure in the colonic stem cell niche has also been observed in UC patients. Mechanistically, enzyme activity assays on colonic organoids revealed that excessive fission inhibits mitochondrial acetoacetyl-CoA thiolase activity via reactive oxygen species. CONCLUSIONS: Collectively, these data indicate that excessive mitochondrial fission suppresses mucosal repair by inhibiting butyrate metabolism and provides a potential target for mucosal healing in patients with ulcerative colitis.


Assuntos
Colite Ulcerativa , Humanos , Animais , Camundongos , Colite Ulcerativa/tratamento farmacológico , Dinâmica Mitocondrial , Mucosa Intestinal/metabolismo , Butiratos/farmacologia , Butiratos/metabolismo
3.
Medicine (Baltimore) ; 102(43): e35781, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37904420

RESUMO

RATIONALE: Among numerous types of nontuberculous mycobacterial infections, Mycobacterium avium complex is a related group of species, which can cause various diseases in humans. Mycobacterium marseillense is a member of the Mycobacterium avium complex, which accounts for only a small proportion of species, but causes rare diseases affecting the lungs, lymph nodes, skin, and tendon sheath. So far, very few cases have been reported. PATIENT CONCERNS: A 76-year-old male of peculiar skin infection. Metagenomic Next Generation Sequencing and bacterial culture of skin secretions revealed M marseillense. To the best of our knowledge, we report the first patient diagnosed with disseminated M marseillense infection. Here, we identified only 8 other reports of patients with M marseillense infection. DIAGNOSES: Disseminated M marseillense infection. INTERVENTIONS: The patient was treated with clarithromycin, rifampicin, moxifloxacin, and ethambutol. OUTCOMES: The skin lesions of the patient showed significant improvement, and his pruritus and limb pain were notably reduced after 7 months of follow-up. LESSONS: Metagenomic Next Generation Sequencing may be a useful tool to diagnose M marseillense infection, but the results should be confirmed by culture and mycobacterial identification.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium , Masculino , Humanos , Idoso , Complexo Mycobacterium avium , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Claritromicina/uso terapêutico
4.
Genome Res ; 33(5): 779-786, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37295844

RESUMO

Tandem duplications are frequent structural variations of the genome and play important roles in genetic disease and cancer. However, interpreting the phenotypic consequences of tandem duplications remains challenging, in part owing to the lack of genetic tools to model such variations. Here, we developed a strategy, tandem duplication via prime editing (TD-PE), to create targeted, programmable, and precise tandem duplication in the mammalian genome. In this strategy, we design a pair of in trans prime editing guide RNAs (pegRNAs) for each targeted tandem duplication, which encode the same edits but prime the single-stranded DNA (ssDNA) extension in opposite directions. The reverse transcriptase (RT) template of each extension is designed homologous to the target region of the other single guide RNA (sgRNA) to promote the reannealing of the edited DNA strands and the duplication of the fragment in between. We showed that TD-PE produced robust and precise in situ tandem duplications of genomic fragments ranging from ∼50 bp to ∼10 kb, with a maximal efficiency up to 28.33%. By fine-tuning the pegRNAs, we achieved simultaneous targeted duplication and fragment insertion. Finally, we successfully produced multiple disease-relevant tandem duplications, showing the general utility of TD-PE in genetic research.


Assuntos
DNA , Genoma , Animais , DNA/genética , Genômica , Sistemas CRISPR-Cas , Mamíferos/genética
5.
Int J Antimicrob Agents ; 62(2): 106872, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37247645

RESUMO

OBJECTIVES: To compare the effectiveness of ceftazidime/avibactam (CAZ/AVI) and polymyxin B against carbapenem-resistant Gram-negative bacteria (CRGNB) infections in western China. METHODS: The medical records of patients with CRGNB infections in this hospital from 2018-2022 were retrospectively reviewed. The data included demographic characteristics, laboratory results, antibiotic strategies and clinical outcomes. RESULTS: A total of 378 patients with CRGNB infections were enrolled, including 112 patients in the CAZ/AVI group and 266 patients in the polymyxin B group. The most common pathogen was carbapenem-resistant Klebsiella pneumoniae (44.44%). The rates of treatment failure at 28 days (65.04% vs. 45.54%; P = 0.000) and 28-day in-hospital mortality (20.30% vs. 9.82%; P = 0.014) in the polymyxin B group were higher than those in the CAZ/AVI group. Multivariable analysis revealed that multiple organ dysfunction syndrome (OR 2.730; P = 0.017), acute renal failure (OR 2.595; P = 0.020), higher Charlson comorbidity index (CCI) (OR 1.184; P = 0.011) and Acute Physiology And Chronic Health Evaluation (APACHE) Ⅱ scores (OR 1.149; P = 0.000) were independent risk factors for treatment failure, whereas CAZ/AVI therapy (OR 0.333; P = 0.002) had a protective effect. Multivariate Cox regression analysis revealed that CCI ≥ 5 and APACHE II score ≥ 15 were associated with a higher 28-day in-hospital mortality rate (P < 0.001). CONCLUSION: CAZ/AVI therapy was associated with treatment success among patients with CRGNB infection. However, CAZ/AVI therapy did not improve 28-day in-hospital survival compared with polymyxin B. The CCI ≥ 5 and APACHE II score ≥ 15 affected 28-day in-hospital mortality of CRGNB-infected patients.


Assuntos
Ceftazidima , Infecções por Bactérias Gram-Negativas , Humanos , Ceftazidima/uso terapêutico , Carbapenêmicos/uso terapêutico , Polimixina B/uso terapêutico , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Combinação de Medicamentos , Testes de Sensibilidade Microbiana
6.
J Gastroenterol Hepatol ; 38(6): 962-969, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37094943

RESUMO

BACKGROUND AND AIM: Lugol chromoendoscopy is the standard technique to detect an esophageal squamous cell carcinoma (ESCC). However, a high concentration of Lugol's solution can induce mucosal injury and adverse events. We aimed to investigate the optimal concentration of Lugol's solution to reduce mucosal injury and adverse events without degrading image quality. METHODS: This was a two-phase double-blind randomized controlled trial. In phase I, 200 eligible patients underwent esophagogastroduodenoscopy and then were randomly (1:1:1:1:1) sprayed with 1.2%, 1.0%, 0.8%, 0.6%, or 0.4% Lugol's solution. Image quality, gastric mucosal injury, adverse events, and operation satisfaction were compared to investigate the minimal effective concentration. In phase II, 42 cases of endoscopic mucosectomy for early ESCC were included. The patients were randomly assigned (1:1) to the minimal effective (0.6%) or conventional (1.2%) concentration of Lugol's solution for further comparison of the effectiveness. RESULTS: In phase I, the gastric mucosal injury was significantly reduced in 0.6% group (P < 0.05). Furthermore, there was no statistical significance in image quality between 0.6% and higher concentrations of Lugol's solution (P > 0.05, respectively). It also showed that the operation satisfaction decreased in 1.2% group compared with the lower concentration groups (P < 0.05). In phase II, the complete resection rate was 100% in both groups, while 0.6% Lugol's solution showed higher operation satisfaction (W = 554.500, P = 0.005). CONCLUSIONS: The study indicates that 0.6% might be the optimal concentration of Lugol's solution for early detection and delineation of ESCC, considering minimal mucosal injury and satisfied image. The registry of clinical trials: ClinicalTrials.gov (NCT03180944).


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/patologia , Esofagoscopia/métodos , Corantes
7.
Parasitology ; 150(3): 240-247, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36529855

RESUMO

Taeniasis and cysticercosis, which are caused by Taenia saginata, Taenia solium and Taenia asiatica, are zoonotic parasitic infections with a significant disease burden worldwide. There is consensus amongst experts that T. saginata is a common tapeworm that causes taeniasis in humans as opposed to cysticercosis. This case study of a middle-aged Tibetan man conducted in 2021 challenges the prevailing notion that T. saginata exclusively causes taeniasis and not cysticercosis by documenting symptoms and laboratory studies related to both taeniasis and multiple cysticercosis. The patient's medical record with the symptoms of taeniasis and cysticercosis was reviewed, and the tapeworm's proglottids and cyst were identified from the patient by morphological evaluation, DNA amplification and sequencing. The patient frequently experienced severe headaches and vomiting. Both routine blood screenings and testing for antibodies against the most common parasites were normal. After anthelmintic treatment, an adult tapeworm was found in feces, and medical imaging examinations suggested multiple focal nodules in the brain and muscles of the patient. The morphological and molecular diagnosis of the proglottids revealed the Cestoda was T. saginata. Despite the challenges presented by the cyst's morphology, the molecular analysis suggested that it was most likely T. saginata. This case study suggests that T. saginata infection in humans has the potential to cause human cysticercosis. However, such a conclusion needs to be vetted by accurate genome-wide analysis in patients with T. saginata taeniasis associated with cysts. Such studies shall provide new insights into the pathogenicity of T. saginata.


Assuntos
Cisticercose , Taenia saginata , Taenia solium , Taenia , Teníase , Masculino , Adulto , Pessoa de Meia-Idade , Animais , Humanos , Taenia saginata/genética , Cisticercose/diagnóstico , Cisticercose/parasitologia , Teníase/diagnóstico , Teníase/parasitologia , Taenia/genética , Taenia solium/genética , Zoonoses
8.
Crit Rev Microbiol ; : 1-11, 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36562731

RESUMO

Cryptococcal meningitis (CM) is an invasive fungal disease that currently poses a threat to human health worldwide, with high morbidity and mortality, particularly in immunocompromised patients. Although CM mainly occurs in HIV-positive patients and other immunocompromised patients, it is also increasingly seen in seemingly immunocompetent hosts. The clinical characteristics of CM between immunocompromised and immunocompetent populations are different. However, few studies have focussed on CM in immunocompetent individuals. This review summarizes the clinical characteristics of apparently immunocompetent CM patients in terms of aetiology, immune pathogenesis, clinical presentation, laboratory data, imaging findings, treatment strategies and prognosis. It is of great significance to further understand the disease characteristics of CM, explore new treatment strategies and improve the prognosis of CM in immunocompetent individuals.

9.
Front Public Health ; 10: 972619, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091563

RESUMO

Background: Alveolar echinococcosis (AE) is a parasitic zoonosis with high mortality and disability rates. Diverse clinical manifestations and mimicking of differential diagnoses such as tuberculosis and malignancy pose a diagnostic dilemma. With the rapid development of molecular diagnostic techniques in recent years, metagenomic next-generation sequencing (mNGS) has become an attractive approach for the etiological diagnosis of infectious diseases. Case presentation: we report a case of 51-year-old Chinese Tibetan male presented with 3-year low-back pain and 4-month discomfort in the right upper quadrant of the abdomen. He had been in good health. He was diagnosed with tuberculosis and was given anti-tuberculosis treatment a month prior to the visit, but the symptoms were not relieved. Abdominal computerized tomography (CT) revealed a hypodense lesion with uneven enhancement in the liver, and two ring-enhancing cystic lesions in the right abdominal wall. Lumbar spine enhanced MRI showed lesions of mixed density with uneven enhancement in the L1 vertebra and paraspinal tissue. The pathological results of the liver biopsy revealed parasitic infection and possibly echinococcosis. The metagenomic next-generation sequencing (mNGS) of the puncture fluid of abdominal cysts using Illumina X10 sequencer revealed 585 sequence reads matching Echinococcus multilocularis. Disseminated AE was diagnosed. Albendazole (400 mg, twice daily) was used, and the patient was in stable condition during follow-up. Conclusions: mNGS may be a useful tool for the diagnosis of AE. The case would help clinicians to improve their diagnostic skills.


Assuntos
Equinococose , Echinococcus multilocularis , Animais , Equinococose/diagnóstico , Equinococose/parasitologia , Equinococose/patologia , Echinococcus multilocularis/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
10.
Front Oncol ; 12: 945904, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992850

RESUMO

Background and aim: Magnifying image-enhanced endoscopy was demonstrated to have higher diagnostic accuracy than white-light endoscopy. However, differentiating early gastric cancers (EGCs) from benign lesions is difficult for beginners. We aimed to determine whether the computer-aided model for the diagnosis of gastric lesions can be applied to videos rather than still images. Methods: A total of 719 magnifying optical enhancement images of EGCs, 1,490 optical enhancement images of the benign gastric lesions, and 1,514 images of background mucosa were retrospectively collected to train and develop a computer-aided diagnostic model. Subsequently, 101 video segments and 671 independent images were used for validation, and error frames were labeled to retrain the model. Finally, a total of 117 unaltered full-length videos were utilized to test the model and compared with those diagnostic results made by independent endoscopists. Results: Except for atrophy combined with intestinal metaplasia (IM) and low-grade neoplasia, the diagnostic accuracy was 0.90 (85/94). The sensitivity, specificity, PLR, NLR, and overall accuracy of the model to distinguish EGC from non-cancerous lesions were 0.91 (48/53), 0.78 (50/64), 4.14, 0.12, and 0.84 (98/117), respectively. No significant difference was observed in the overall diagnostic accuracy between the computer-aided model and experts. A good level of kappa values was found between the model and experts, which meant that the kappa value was 0.63. Conclusions: The performance of the computer-aided model for the diagnosis of EGC is comparable to that of experts. Magnifying the optical enhancement model alone may not be able to deal with all lesions in the stomach, especially when near the focus on severe atrophy with IM. These results warrant further validation in prospective studies with more patients. A ClinicalTrials.gov registration was obtained (identifier number: NCT04563416). Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04563416.

11.
Chin Med J (Engl) ; 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35861304

RESUMO

BACKGROUND: Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-ß-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. METHODS: Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. RESULTS: The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ2  = 19.83, P   <  0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ2  = 24.65, P  < 0.001), and fungal culture (33% [84/253]) ( χ2  = 29.38, P  < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher's exact P  = 1.000) to and slightly lower specificity (87% [77/89]) ( χ2  = 5.52, P  = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) ( P  = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ2  = 0.89, P  = 0.345) to and lower sensitivity (63% [24/38]) ( χ2  = 4.14, P  = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ2  = 6.95, P  = 0.008), BDG ( χ2  = 10.43, P  = 0.001), and fungal culture ( χ2  = 12.70, P  < 0.001). CONCLUSIONS: Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

12.
Nucleic Acids Res ; 50(11): 6423-6434, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35687127

RESUMO

Prime editors consisting of Cas9-nickase and reverse transcriptase enable targeted precise editing of small DNA pieces, including all 12 kinds of base substitutions, insertions and deletions, while without requiring double-strand breaks or donor templates. Current optimized prime editing strategy (PE3) uses two guide RNAs to guide the performance of prime editor. One guide RNA carrying both spacer and templating sequences (pegRNA) guides prime editor to produce ssDNA break and subsequent extension, and the other one produces a nick in the complementary strand. Here, we demonstrated that positioning the nick sgRNA nearby the templating sequences of the pegRNA facilitated targeted large fragment deletion and that engineering both guide RNAs to be pegRNAs to achieve bi-direction prime editing (Bi-PE) further increase the efficiency by up to 16 times and improved the accuracy of editing products by 60 times. In addition, we showed that Bi-PE strategy also increased the efficiency of simultaneous conversion of multiple bases but not single base conversion over PE3. In conclusion, Bi-PE strategy expanded the editing scope and improved the efficiency and the accuracy of prime editing system, which might have a wide range of potential applications.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Pequeno RNA não Traduzido , Animais , Sistemas CRISPR-Cas/genética , Desoxirribonuclease I/metabolismo , Quebras de DNA de Cadeia Dupla , Mamíferos/genética , DNA Polimerase Dirigida por RNA/metabolismo , Pequeno RNA não Traduzido/genética
13.
BMC Infect Dis ; 22(1): 557, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35717143

RESUMO

BACKGROUND: Splenic cyst complicated by non-typhoid Salmonella infection is rare in healthy individuals in the era of antibiotics. Salmonella enterica subsp. enterica serovar Livingstone causing infection of giant splenic cyst has not been previously reported. CASE PRESENTATION: We report a case of giant splenic cyst (maximum diameter, 21 cm) complicated with Salmonella Livingstone infection, which resulted in splenic abscess, in a 16-year-old previously healthy adolescent male. The splenic abscess was successfully treated with ultrasonography-guided percutaneous drainage and antimicrobial therapy. CONCLUSION: Infection of splenic cyst may be caused by S. Livingstone in immunocompetent individuals. This case may help clinicians to raise awareness towards splenic abscess and highlights the importance of drainage and antimicrobial agents to avoid splenectomy.


Assuntos
Abscesso Abdominal , Cistos , Infecções Intra-Abdominais , Infecções por Salmonella , Salmonella enterica , Esplenopatias , Abscesso Abdominal/tratamento farmacológico , Abscesso/tratamento farmacológico , Adolescente , Antibacterianos/uso terapêutico , Drenagem/métodos , Humanos , Infecções Intra-Abdominais/tratamento farmacológico , Masculino , Salmonella , Infecções por Salmonella/complicações , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/tratamento farmacológico , Sorogrupo , Esplenopatias/complicações , Esplenopatias/diagnóstico , Esplenopatias/cirurgia
14.
Viral Immunol ; 35(5): 381-385, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35605096

RESUMO

Coxsackievirus B3 (CVB3) is one of the major viruses associated with human viral myocarditis, in members of the Picornaviridae order. Cellular localization depends on the activity of nuclear pore complexes, which are composed of nucleoporins (Nups), including Nup62. To better understand interactions between Nup62 and CVB3, we investigated the impact of CVB3 infection on Nup62 levels and the impact of Nup62 production on CVB3 replication in cultured cells. We found that CVB3 infection correlated with decreased Nup62 expression in vitro and that lower levels of Nup62 led to inhibition of CVB3 replication and to decreased activation of AKT and extracellular signal-related kinase. Our study reveals that Nup62 regulates the CVB3 replication during infection.


Assuntos
Infecções por Coxsackievirus , Miocardite , Enterovirus Humano B/fisiologia , Células HeLa , Humanos , Poro Nuclear/metabolismo , Replicação Viral
15.
Front Med (Lausanne) ; 9: 835252, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463003

RESUMO

Background: Strongylodiasis may be asymptomatic or cause mild gastrointestinal symptoms, and may be a fatal disseminated disease or Strongyloides hyperinfection syndrome. Non-specific clinical manifestations, such as pneumonia and gastroenteritis, pose a diagnostic dilemma. Case Presentation: We report a case of a 67-year-old Chinese male who presented with abdominal pain, fever, headache, vomiting, constipation, and slight cough with sputum for nearly 2 months. He had been in good health and had no history of glucocorticoid use. He was diagnosed with enterococcal meningitis and intestinal obstruction at a local hospital and improved after treatment with vancomycin, but symptoms of headache and abdominal pain soon recurred. The metagenomic next-generation sequencing (mNGS) of the cerebrospinal fluid using Illumina X10 sequencer revealed seven sequence reads matching Strongyloides stercoralis. Strongyloidiasis was suspected. Microscopic examination of gastric fluid revealed the presence of S. stercoralis larvae, which was confirmed by PCR to amplify both S. stercoralis ribosomal DNA gene and mitochondrial cytochrome c oxidase subunit 1 gene and sequencing amplicons. Strongyloidiasis was diagnosed. Albendazole (400 mg, twice daily) was used, and the patient recovered gradually. Conclusion: mNGS may be a useful tool for detecting uncommon infectious disease. The case would help clinicians to raise awareness of strongyloidiasis in non-endemic areas and reduce fatality.

16.
Medicine (Baltimore) ; 101(7): e28656, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35363160

RESUMO

RATIONALE: The clinical manifestations in patients with disseminated tuberculosis (TB) are nonspecific and may present challenges for early diagnosis. PATIENT CONCERNS AND DIAGNOSES: We describe the case of a 44-year-old man who presented with abdominal pain and discomfort for more than a month. He had undergone surgery for a chest wall abscess 9 months ago. Computed tomography scans showed a miliary pattern in the lung and multiple abscesses in the liver, spleen, left psoas major muscle, skin, and soft tissue, with rim enhancement. Mycobacterium tuberculosis was detected in the drainage fluid of the abscesses and surgical slices, and disseminated TB was diagnosed. INTERVENTIONS AND OUTCOMES: With anti-tuberculosis therapy, the abscesses were gradually absorbed and all cultures were negative. LESSONS: The patient exemplifies the difficulty of the early diagnosis of disseminated TB. Disseminated TB should be considered first in patients with multisystem illness, and then evidence should be pursued relentlessly to establish a diagnosis.


Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Miliar , Abscesso , Adulto , Diagnóstico Tardio , Humanos , Masculino , Tuberculose Miliar/diagnóstico , Tuberculose Miliar/tratamento farmacológico
17.
FEBS J ; 289(19): 5899-5913, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35411720

RESUMO

The recognition of protospacer adjacent motif (PAM) is a key factor for the CRISPR (i.e. clustered regularly interspaced short palindromic repeats)/CRISPR-associated 9 (Cas9) system to distinguish foreign DNAs from the host genome, and also significantly restricts the targeting scope of the system during genome-editing applications. Structurally, the PAM interacting (PI) domain, which usually is located in the C-terminus of Cas9 proteins, directly binds to PAM and plays a key role in determining the recognition specificity. However, several lines of evidence showed that other regions of Cas9 protein beyond the PI domain might also play roles in PAM interaction. Here, we constructed a mosaic SpCas9 protein (xCas9-NG) by fusing the PI domain of SpCas9 PAM variant, Cas9-NG with the non-PI fragment of xCas9 protein that contains multiple amino acid substitutions. We found that non-PI fragment of xCas9 expanded PAM recognition of the Cas9-NG PI domain. In addition, xCas9-NG showed an improved editing efficiency in the majority of targets harboring xCas9 and Cas9-NG PAMs. Importantly, this finding was also successfully extended to other Cas9 variants, including SpRY and the non-G SpCas9 series. Together, our work expands the target scope of SpCas9 editing system and demonstrates the notion that the non-PI domain fragment plays an important role in PAM restriction.


Assuntos
Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Substituição de Aminoácidos , Proteína 9 Associada à CRISPR/genética , Proteína 9 Associada à CRISPR/metabolismo , Edição de Genes , Mutação
18.
Helicobacter ; 27(2): e12880, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35150600

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) infections are of serious concern due to the associated risk of gastric cancer. However, many patients have poor medication and therapy compliance, which makes it difficult to eradicate their infections. This points to the need for stronger educational interventions aimed at enhancing compliance, thus increasing the potential for treatment success. As such, this study conducted a meta-analysis to clarify the effects of enhanced patient education (EPE) programs for H. pylori. MATERIALS AND METHODS: We searched electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library) for randomized controlled trials (RCTs) on health education for patients infected with H. pylori from inception to June 2021. The primary outcome was the eradication rate of H. pylori, while the secondary outcomes included the incidence of individual adverse symptoms, treatment compliance, clinical symptom remission after treatment, and patient satisfaction. We used the fixed or random-effects model to pool the risk ratio (RR), with 95% confidence interval. We also conducted sensitivity and subgroup analyses. RESULTS: Our search returned seven relevant studies across a total of 1,433 patients. Compared with controls, EPE was significantly associated with improved H. pylori eradication rates (RR = 1.16, 95%CI: 1.04-1.29, p = 0.006) and patient compliance (RR = 1.48, 95%CI: 1.14-1.93, p = 0.003). A subgroup analysis also showed that EPE benefits were consistent across patients with different eradication programs, WeChat intervention plans, and intervention frequencies (p < 0.05). However, there were no significant differences in the total adverse effects, common side effects (diarrhea, nausea, abdominal pain, taste disorder, and skin rash), or discontinuation rate (p > 0.05). CONCLUSIONS: Patient education is inexpensive, safe, and convenient. In this context, our findings suggest that enhanced educational interventions have positive effects on both the H. pylori eradication rate and adherence among infected patients, and thus constitute promising complements to clinical treatment regimens.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Antibacterianos/farmacologia , Quimioterapia Combinada , Infecções por Helicobacter/diagnóstico , Humanos , Neoplasias Gástricas/tratamento farmacológico
19.
Front Microbiol ; 13: 758073, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35197947

RESUMO

Emergent viruses (namely, HSV-1, CMV, and EBV) reactivation were common in critically ill patients and/or immunosuppressed patients. This study aimed to understand the clinical manifestations and reactivation of the emergent viruses in SARS-CoV-2-Negative community acquired pneumonia (CAP) patients during the COVID-19 pandemic. We retrospectively reviewed the medical records of CAP patients from January to March 2020, in our university hospital in China. The patients were divided into two groups based on the presence or absence of emergent viruses. In all patients, the positive rates of EBV, HSV, and CMV were 23.43% (15/64), 22.06% (15/68), and 12.50% (8/64), respectively. The most common presenting symptoms were fever (98, 57.99%) and dry cough (55, 32.54%). The levels of albumin, hemoglobin, lymphocyte count, and CD4 + T lymphocyte count in emergent viruses positive group were lower than those of viruses negative group (P < 0.05). The initial chest CT features of these patients were diverse. The most common manifestations were ground-glass opacity (91/169, 53.85%) and pulmonary nodule (88/169, 52.07%). More emergent viruses positive patients have bilateral upper lobes involvement than emergent viruses negative patients (P < 0.05). A total of 80.47% patients (136/169) received empirical antimicrobial treatment. The most commonly used antibiotic regimen was fluoroquinolone monotherapy (80/169, 47.34%). The emergent viruses positive patients have poorer clinical outcome (P < 0.05). In conclusion, emergent viruses reactivation was common in SARS-CoV-2-Negative CAP patients. Emergent viruses positive patients have poorer cellular immune function, more severer conditions and poorer prognosis. Fluoroquinolones may be a therapeutic option for CAP patients.

20.
Front Med (Lausanne) ; 9: 1067548, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36643845

RESUMO

Objective: Polymyxins are currently the last line of defense in the treatment of carbapenem-resistant organisms (CRO). As a kind of polymyxin available for clinical use in China, we aim to explore the efficacy and safety of colistin sulfate (Polymyxin E sulfate, PES) in this study. Methods: This real-world retrospective study included 119 patients diagnosed with CRO infection and treated with PES for more than 72 h, from May 2020 to July 2022 at West China Hospital. The primary outcome was clinical efficacy at the end of treatment, and secondary outcomes included microbial response, in-hospital mortality and incidence of nephrotoxicity. Results: The effective clinical and microbiological responses were 53.8% and 49.1%, respectively. And the in-hospital mortality was 27.7%. Only 9.2% of patients occurred with PES-related nephrotoxicity. Multivariate analysis revealed that duration of PES was an independent predictor of effective therapy, while age-adjusted Charlson comorbidity index (aCCI) and post-treatment PCT(p-PCT) were independent risk factors for poor outcome. Conclusions: PES can be a salvage treatment for CRO-induced infections with favorable efficacy and low nephrotoxicity. The treatment duration of PES, aCCI and p-PCT were factors related to the clinical effectiveness of PES.

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