Metagenomic Next-Generation Sequencing for Accurate Diagnosis of Pneumocystis jirovecii Pneumonia: A Comparative Study with Traditional Methods.

Background: Metagenomic next-generation sequencing (mNGS) is a high-throughput sequencing technique that identifies a wide array of pathogens directly from clinical specimens. This study evaluates the diagnostic value of mNGS in Pneumocystis jirovecii pneumonia (PJP) and compares its efficacy with traditional detection methods, including Grocott's Methenamine Silver (GMS) staining, serum (1-3)-ß-D-Glucan (BDG) testing, and Lactate Dehydrogenase (LDH) testing. Methods: Seventy-eight patients hospitalized between January 2022 and March 2023 with suspected pulmonary infections were included. Patients were eligible for mNGS if they exhibited symptoms such as fever, cough, dyspnea, or progressive hypoxemia, and met specific clinical criteria for PJP. Specimens obtained included bronchoalveolar lavage fluid, sputum, and peripheral blood. Positive rates and pathogen distributions detected by mNGS and traditional methods were compared. Results: In the PJP group, 25%, 37.5%, and 9.38% of patients had solid organ tumors, corticosteroid use, and skin diseases, respectively, significantly higher than in the non-PJP group. The sensitivity and specificity of mNGS were both 100%, significantly higher than those of serum BDG (sensitivity 50%, specificity 81.8%) and LDH (sensitivity 9.3%, specificity 91.3%). Significant differences in microbial composition between the PJP and Non-PJP groups were observed. mNGS detected multiple mixed pathogens in 96.88% of PJP cases, with 68.75% exhibiting mixed bacterial and viral infections. Notably, 71% of patients improved following antibacterial treatment based on mNGS results. Conclusion: mNGS technology shows superior sensitivity and specificity in diagnosing PJP and guides precise treatment for complex pulmonary infections.

Comparison between MRI-negative and positive results and the predictors for a poor prognosis in patients with idiopathic acute transverse myelitis.

BACKGROUND: Idiopathic acute transverse myelitis (IATM) is a focal inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. However, the comparative analysis of MRI-negative and MRI-positive in IATM patients were rarely reported. OBJECTIVES: The purpose of this study was to compare MRI-negative with MRI-positive groups in IATM patients, analyze the predictors for a poor prognosis, thus explore the relationship between MRI-negative and prognosis. METHODS: We selected 132 patients with first-attack IATM at the First Affiliated Hospital of Nanchang University from May 2018 to May 2022. Patients were divided into MRI-positive and MRI-negative group according to whether there were responsible spinal MRI lesions, and good prognosis and poor prognosis based on whether the EDSS score ≥ 4 at follow-up. The predictive factors of poor prognosis in IATM patients was analyzed by logistic regression models. RESULTS: Of the 132 patients, 107 first-attack patients who fulfilled the criteria for IATM were included in the study. We showed that 43 (40%) patients had a negative spinal cord MRI, while 27 (25%) patients were identified as having a poor prognosis (EDSS score at follow-up ≥ 4). Compared with MRI-negative patients, the MRI-positive group was more likely to have back/neck pain, spinal cord shock and poor prognosis, and the EDSS score at follow-up was higher. We also identified three risk factors for a poor outcome: absence of second-line therapies, high EDSS score at nadir and a positive MRI result. CONCLUSIONS: Compared with MRI-negative group, MRI-positive patients were more likely to have back/neck pain, spinal cord shock and poor prognosis, with a higher EDSS score at follow-up. The absence of second-line therapies, high EDSS score at nadir, and a positive MRI were risk factors for poor outcomes in patients with first-attack IATM. MRI-negative patients may have better prognosis, an active second-line immunotherapy for IATM patients may improve clinical outcome.

Practical recommendations for antihypertensive therapy during the primary aldosteronism screening test.

BACKGROUND: The aldosterone-to-renin activity ratio (ARR) is recommended as a screening test for primary aldosteronism (PA). The use of antihypertensive medication is one of the most important factors to take into account when interpreting the ARR. OBJECTIVES: The goal of this study was to compare the effect of various antihypertensive drug classes on biochemical testing and provide practical recommendations for antihypertensive medication regimens in patients suspected of having PA. METHODS: We retrospectively investigated 4218 hypertensive patients who underwent PA detection between January 2020 and February 2023. Finally, 25 patients with essential hypertension (EH) and 39 with PA were involved. The enrolled EH patients were selected from EH patients with at least two screening tests with interfering medication changes for at least 4 weeks. RESULTS: A total of 2/18 (11.1%) EH patients had opposite screening results after angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), dihydropyridine-calcium channel blockers (DHP-CCBs) and diuretics were withdrawn. A total of 3/3 (100%) of the patients were initially screened as positive but had results that tested negative after ß-blockers withdrawal. A total of 3/39 (7.7%) PA patients were misdiagnosed with EH with drug effects. Only plasma renin activity was markedly reduced after antihypertensive medication washout (P = 0.0173). CONCLUSIONS: Not every patient receiving ß-blockers, ACEIs, ARBs and DHP-CCBs with negative reports needed withdrawal or switching antihypertensive drugs. We recommend that patients be left on a regimen that includes ß-blockers, ACEIs, ARBs, DHP-CCBs and spironolactone when determining the ARR during the initial test.

Accuracy of implant placement using CAD-CAM tooth-supported surgical guides for an auricular prosthesis in vitro.

PURPOSE: To evaluate the accuracy of tooth-supported surgical guides used to place implants in auricular prostheses. The accuracy (trueness and precision) of the implant positions was evaluated, and the difference between the surgical guide with and without retention of the external auditory canal (EAC) was compared. MATERIALS AND METHODS: This study simulated implant placement in vitro for the treatment of right auricle malformation. Surgical guides and other casts were fabricated using additive manufacturing technology. The casts were divided into 2 groups according to the surgical guide, with 10 bone blocks in each group (with or without the EAC plug (Guides 1 and 2)). Three implant positions (Implants 1-3) were prepared for each bone block using surgical guides. Implant positions were registered using light-body silicone impressions combined with optical surface scans to measure the coronal, apical, depth, and angular deviations. Four deviations of trueness and precision were reported as the mean ± standard deviation, which was analyzed by Student's t-test. RESULTS: Each group of 10 bone blocks with 30 implant positions was successfully prepared and digitally reproduced as implants. The accuracies of implant position with surgical guides were acceptable when compared with the preoperatively planned implant positions. Compared with the Guide 2 group, there was a significant difference in the apical, depth, and angular deviations of Guide 1 group in terms of precision (p = 0.001). There was a significant difference in the depth deviation of Implant 1 (p = 0.028) and apical deviation of Implant 2 (p < 0.001) compared two groups in terms of trueness. In terms of precision, there was a significant difference in the coronal (p = 0.002), apical (p = 0.001), and depth (p < 0.001) deviation of Implant 1; apical (p = 0.036) and angular (p < 0.001) deviation of Implant 2 also existed significant difference; the coronal deviation of Implant 3 (p = 0.018) also existed significant difference. Moreover, the group with the EAC plug showed lower deviation in precision and a smaller volume in the 95% confidence ellipsoid. CONCLUSION: Both types of tooth-supported surgical guides can provide acceptable accuracy. A surgical guide with an EAC plug was considered to be more precise.

A syndrome featuring developmental disorder of the nervous system induced by a novel mutation in the TCF20 gene, rarely concurrent immune disorders: a case report.

Background: The expression of TCF20 is the most widespread in brain tissue. TCF20 depletion or mutation can affect the proliferation and differentiation of embryonic neurons, leading to developmental disorder of the central nervous system and subsequent rare syndrome featuring. Case presentation: Here, we report a 3-year-old boy carrying a novel frameshift mutation in TCF20, c.1839_1872del (p.Met613IlefsTer159), resulting in multisystem disease. In addition to symptoms of neurodevelopmental disorder, a large head circumference, special appearance, overgrowth, abnormal testicular descent. Remarkably, previously infrequently reported symptoms of the immune system such as hyperimmunoglobulinemia E (hyper-IgE), immune thrombocytopenic purpura, cows milk protein allergy, and wheezy bronchitis, were observed. Conclusion: This study broadens the mutation spectrum of the TCF20 and the phenotypic spectrum of TCF20-associated disease.

[EGF/PI3K signaling pathway regulates the expression of osteopontin in liver cancer HepG2 cells].

OBJECTIVE: To investigate the effect of epidermal growth factor (EGF) on the expression of osteopontin (OPN) in liver cancer HepG2 cells. METHODS: Human liver caner cells of HepG2 line were cultured in medium without bovine serum. EGF was added. Another cells were pretreated with specific phosphatidylinositol 3 (PI3) inhibitor Wortmannin and then added with EGF. HepG2 cell were collected. RNase prote4ction assay and Western blotting were used to examine the expression of OPN in the HepG2 cells. RESULTS: HepG2 cells cultured in the bovine serum free medium expressed very low level of OPN. EGF increased the expression of OPN mRNA and protein in a dose- and time-dependent manners. Pretreatment of Wortmannin significantly reduced the EGF-induced OPN expression. CONCLUSION: EGF increases the OPN expression, possibly through PI3 signaling pathway. It is possible to block the synthesis of OPN through manipulating several target genes, thus inhibiting the metastasis of liver cancer.