[A case of disseminated nocardiosis in a non-immunosuppressed host].

Nocardia is an opportunistic pathogen that most commonly affects immunosuppressed hosts, while disseminated infections in healthy hosts are rare. In this paper, we described a case of disseminated Nocardia infection in a non-immunosuppressed host whose initial imaging was strikingly similar to systemic metastasis from a tumor. Since no tumor cells were found in any of the numerous biopsies taken, we considered infection by specific pathogens before metagenomic next-generation sequencing of a lumbar spine tissue biopsy finally confirmed the diagnosis of Nocardia infection. To help doctors better understand this condition and avoid misdiagnosis a, this article provided a summary of the clinical characteristics, diagnostic techniques, and therapeutic options for disseminated nocardiosis.

[Clinical characteristics analysis of patients with severe immune checkpoint inhibitors related myocarditis].

Objective: To analyze the clinical characteristics of patients with severe immune checkpoint inhibitors (ICIs) related myocarditis. Methods: A retrospective study was conducted on the 50 patients with ICIs-related myocarditis in the multidisciplinary cardio-oncology clinic of Zhongshan Hospital affiliated to Fudan University from April 2020 to April 2022. The age of patients was (63.7±10.8) years old, including 37 males and 13 females. The patients were divided into the mild group (n=37) and the severe group (n=13) according to severity. The differences of basic characteristics, clinical manifestations, laboratory tests, auxiliary examination, combined irAEs, treatment and outcomes between the two groups of patients were analyzed. Results: The immunotherapy time [M(Q1,Q3)] of patients in the mild group and severe group were 81 (49, 134) and 24 (20, 116) days, respectively (P<0.05). In the severe group, the levels of cTnT [0.605 (0.317, 1.072) µg/L], NT-proBNP [1 126 (386, 1 744) ng/L], CK-MB [78 (48, 238) U/L], and CK-MM [240 (45, 6 543) U/L] were higher than those in the mild group [0.104 (0.045, 0.189) µg/L, 237 (39, 785) ng/L, 24 (20, 33) U/L, 108 (72, 168) U/L, respectively] (all P<0.05). The left ventricular ejection fraction of the severe group [64% (57%, 65%)] was lower than that of the mild group [66% (63%, 69%)] (P<0.05), and the incidence of conduction block (n=4, 4/13) and abnormal ventricular wall motion (n=4, 4/13), the incidence of ICIs-related myositis (n=10, 10/13), ICIs-related hepatitis (n=4, 4/13) and ICIs-related neurotoxicity (n=4, 4/13) were higher than those in the mild group (n=1, 2.7%; n=2, 5.4%; n=16, 43.2%; n=2, 5.4%; n=1, 2.7%, respectively) (all P<0.05). The proportion of patients receiving intensified immunosuppressive therapy and mortality rate in the severe group were 12/13 (n=12) and 4/13 (n=4), which were both higher than those in the mild group [10.8% (n=4) and 0] (both P<0.05). Conclusions: The incidence of ICIs-related myocarditis is not high, but the severe rate and mortality are high. The differential diagnosis of severe ICIs related myocarditis should be combined with myocardial markers, electrocardiogram and echocardiogram, and early diagnosis and treatment can improve the prognosis of patients.

[Investigate the role of neutrophil extracellular traps in immune checkpoint inhibitor-associated myocarditis with programmed death protein-1 inhibitors involvement].

Objective: To investigate the role of neutrophil extracellular traps (NETs) in immune checkpoint inhibitor-associated myocarditis (ICIAM) with programmed death protein-1 (PD-1) inhibitors involvement, and to explore the therapeutic potential of targeting NETs in the treatment of ICIAM. Methods: Thirty 6-week-old male BALB/c mice were randomly divided into control group (n=10), myocarditis group (n=10), and treatment group (n=10). Apart from the control group, each mouse was subcutaneously injected with 100 µl of complete Freund's adjuvant containing 250 µg of mouse cardiac troponin I peptide on the 1st and 7th day. Starting on the 8th day, PD-1 inhibitor (15 µg/per mouse) was intraperitoneally injected every other day for a total of 5 times. Since 1 day before the beginning of PD-1+TnI injection, the treatment group was injected with PF-1355 (50 mg·kg-1·d-1) for 16 consecutive days. The mice's general state was observed during the whole process. Real-time fluorescence quantitative PCR (RTFQ-PCR) was carried out to evaluate the transcriptional regulation of neutrophil related chemokines, NETs, pyronecrosis related factors and proinflammatory cytokines. Immunohistochemistry, immunofluorescence and western blot were applied to determine the changes of pyrosis related molecules. Echocardiography showed the differences of main cardiac indexes while cardiac pathology compared the degree of inflammatory infiltration in 3 gruops. Results: The immunofluorescence intensity of myocardial NETs in the myocarditis group was significantly increased compared to the control group mice (2.49±0.08 and 0.99±0.26, P<0.001). The protein expression levels of pyroptosis-related NLRP3, cleaved-Caspase 1, Caspase 1, cleaved-GSDMD, GSDMD, IL-1ß and IL-18 in myocardial tissue of the model group were higher than those of the control group (all P<0.05). After treatment with PF-1355, compared to the myocarditis group, the left ventricular ejection fraction (LVEF) (73.58%±5.31% and 58.12%±3.19%, P<0.001) and left ventricular fraction shortening (LVFS) (39.78%±4.31% and 33.89%±2.19%, P<0.001) increased. H-E staining showed a reduction in inflammatory infiltration area in the treatment group compared to the myocarditis group (30.12%±3.57% and 14.92%±2.46%, P<0.001). The immunofluorescence intensity of NETs decreased in the treatment group compared to the myocarditis group (2.52±0.04 and 1.03±0.05, P<0.001). The levels of NLRP3 and other pyroptosis-related molecules were downregulated in the treatment group compared to the myocarditis group (all P<0.05). Conclusions: NETs lead to myocardial cell pyroptosis by activating the NLRP3 inflammasome in PD-1 inhibitor-associated myocarditis. The specific MPO inhibitor PF-1355 shows a therapeutic potential by regulating the formation of NETs, decreasing NLRP3 level and relieving myocardial pyroptosis, thus reducing myocardial damage.

[New characteristics of COVID-19 caused by the Omicron variant in Guangzhou].

We investigated the types of novel coronavirus strains present during the Omicron epidemic from late 2022 to early 2023, COVID-19 co-infections with other pathogens, and clinical characteristics of patients with novel coronavirus infections. Adult patients hospitalized due to SARS CoV-2 infection in six hospitals in Guangzhou city were included in the study from November 2022 to February 2023. Clinical information was collected and analyzed, and bronchoalveolar lavage fluid was obtained for pathogen detection using a variety of techniques, including standard methods and mNGS, tNGS. The results showed that the main strain circulating in Guangzhou was Omicron BA.5.2, and the overall detection rate of potentially pathogenic pathogens combined with Omicron COVID-19 infection was 49.8%. In patients with severe COVID-19 infection, special attention should be paid to aspergillosis and combined Mycobacterium tuberculosis infection. In additon, Omicron strain infection could cause viral sepsis, which led to a worse prognosis for COVID-19 patients. Diabetic patients with SARS-CoV-2 infection did not benefit from glucocorticoid treatment, and caution was necessary when using glucocorticoids. These findings highlighted some new features of severe Omicron coronavirus infection that should be noted.

[Evaluation of left ventricular function with left atrio-ventricular longitudinal strain in patients with lymphoma underwent anthracycline therapy].

Objective: To analyze the value of 3-dimensional speckle tracking echocardiograghy (3D-STE) derived strain parameters on the detection of subclinical myocardial deformation alterations in patients with lymphoma treated with anthracycline agents. Methods: This study was a retrospective study. A total of 37 patients with newly diagnosed diffuse large B cell non-Hodgkin lymphoma between December 2012 and December 2014 in Cancer Center, Fudan university were included. 3D-STE strain measurements were performed at baseline (T0),after the completion of two therapy circles (T1) and at the end of anthracycline regimen chemotherapy (Te). Echocardiography images were analyzed on the TTA workstation, and the indexes included left atrial minimum volume (LAVmin), left atrial emptying index (LAEF), left atrial active emptying index (LAAEF), as well as the left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left atrial global longitudinal strain (LAGLS). The overall left atrioventricular longitudinal strain (LAVGLS) was calculated, which was the sum of the absolute values of LVGLS and LAGLS. The changes of left ventricular strain indexes measured by 3D-STE at different time points of patients were evaluated. Results: Thirty-seven patients with DLBCL, aged (48.3±12.1)years, including 23 males (63.9%), were enrolled. Compared with baseline, LVGLS (T1: (-18.63±4.73)% vs. (-22.13±4.40)%, P=0.001; Te:(-18.26±4.64)% vs. (-22.13±4.40)%, P<0.001), LAGLS (T1: (20.41±5.56)% vs. (23.98±5.59)%, P=0.003; Te: (17.60±3.96)% vs. (23.98±5.59)%, P<0.001) and LAVGLS (T1: (39.05±7.60)% vs. (46.11±7.77)%, P<0.001; Te: (40.34±8.55)% vs. (46.11±7.77)%, P<0.001) were all deteriorated at the T1 and Te. While LVGCS ((-21.98±5.82)% vs. (-26.15±7.51)%, P=0.010), LAVmin ((23.93±7.29)ml vs. (20.33±7.03)ml, P=0.029), LAEF ((28.94±11.16)% vs. (35.79±11.12)%, P=0.002) and LAAEF ((11.93±10.00)% vs. (18.10±9.96)%, P=0.013) were decreased only until Te. Conclusions: 3D-STE strain measurements could detect early myocaridial function alteration in patients receiving anthracycline regimen chemotherapy, thus may provide a novel approach to monitor anthracycline caused myocardial toxicity.

Frequency Characteristics of AEPs in Normal Young Adults and Comparison of Their Response Threshold and Pure Tone Audiometry Threshold.

ABSTRACT: Objective The tests of three types of auditory evoked potentials （AEPs） were performed on normal young adults, to understand the frequency characteristics of different testing methods and the relationship between response threshold and pure tone audiometry threshold of different methods, and to discuss the forensic value of 3 types of AEPs to evaluate hearing function. Methods Twenty normal young adults were selected, their standard pure tone audiometry threshold, short-term pure tone audiometry threshold and the response threshold of 3 types of AEPs （tone burst-auditory brainstem response, 40 Hz auditory event-related potential and slow vertex response） at 0.5 kHz, 1.0 kHz, 2.0 kHz and 4.0 kHz were recorded. The relationship between the response threshold and standard pure tone audiometry threshold, short-term pure tone audiometry threshold of 3 types of AEPs at different frequencies as well as the differences between different types of AEPs were analyzed. Results The short-term pure tone audiometry threshold was higher than the standard pure tone audiometry threshold at each frequency. The response threshold and standard pure tone audiometry threshold of the 3 types of AEPs all had a certain correlation, and the response threshold of the 3 types of AEPs was higher than short-term pure tone audiometry threshold and standard pure tone audiometry threshold at each frequency. The differences in the differences between the response threshold and standard pure tone audiometry threshold of the 3 types of AEPs at different frequencies had statistical significance. Linear regression mathematical models were established to infer the standard pure tone audiometry threshold （hearing level） from response threshold （sound pressure level） of 3 types of AEPs of normal young adults. Conclusion When using response threshold of different types of AEPs to estimate pure tone audiometry threshold, conversion and correction are needed. Combined use of different types of AEPs could improve the accuracy of hearing function evaluation.

[Research progress of alpha-fetoprotein vaccine in hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is the fifth world's largest malignant tumor, which seriously endangers human health. The commonly used treatment effects are not satisfactory and the mortality rate is still high. Therefore, there is an urgent need for effective adjuvant treatment to improve patient survival. Alpha-fetoprotein (AFP) acts as the most common tumor marker used for HCC diagnosis. Studies have shown that alpha-fetoprotein can self-induce T cells in patients with hepatocellular carcinoma, and its immunogenic antigenic epitopes provide new ideas for the study of AFP vaccine. Presently, a variety of AFP vaccines have been developed, such as DC vaccine, DNA vaccine, and peptide vaccine, which have been successfully applied to HCC mouse model and phase I /II clinical trials, with evident results. This article discusses the molecular mechanism, categories and application prospects of AFP vaccine in HCC.

[Analysis of bronchoscope-guided tracheal intubation in 12 cases with coronavirus disease 2019 under the personal protective equipment with positive pressure protective hood].

Endotracheal intubation is an independent risk factor for respiratory infectious diseases. We conducted a retrospective study in 12 cases with COVID-19 who underwent endotracheal intubation at ICU of the Guangzhou eighth hospital from January 20 to February 10, 2020. The intubation procedure, anesthetic regimen, and complication were collected and analyzed. The 9 healthcare workers who involved in intubation received virus nucleic acid test and 14 days temperature monitoring. All 12 patients were successfully intubated under the guidance of bronchoscope, without any complications. Midazolam, Propofol and Morphine or fentanyl were used for sedation and analgesia, avoiding patients cough and agitated during the procedure. The 9 healthcare workers were protected under the Personal Protective Equipment(PPE) with positive pressure protective hood. The detection of oropharyngeal swab virus nucleic acid were negative in all 9 healthcare workers, none of them had fever or any respiratory symptoms. The PPE with positive pressure protective hood should be needed to perform bronchoscope-guided endotracheal intubation in patients with COVID-19, it could strengthen to protect healthcare workers from virus exposure.

[Prevention for glucocorticoid-induced osteonecrosis of femoral head: a long-term clinical follow-up trail].

Objective: To evaluated the outcome of prevention and treatment for glucocorticoid-induced osteonecrosis of femoral head with anticoagulant and vasodilator drugs. Methods: A prospective, randomized, double-blind study was performed. From August 2003 to August 2006, 58 patients with large amounts of hormone therapy in the Zhongshan Hospital Affiliated Dalian University were enrolled and randomly assigned to the control group (placebo) or preventive group (anticoagulant and vasodilator drugs). And we prospectively analyzed the clinical outcomes of 24 patients with glucocorticoid-induced osteonecrosis of femoral head early stage (treatment group)treated by anticoagulant and vasodilator drugsat the same time. Disease incidence rate and progression were evaluated by radiography and magnetic resonance imaging (MRI), Follow-up of patients with femoral head survival curve was drawn. The Harris Hip Score and the Short Form 36 health survey were used to rate hip function and quality of life, respectively. Results: Thus, a total of 80 patients were assessed in this study, 24 cases in control group[follow up from 7.5 to 13.0(10.7±1.6)years], 22 cases in preventive group and 24 cases in treatment group. There was significant difference in theincidence rate of Osteonecrosis of femoral head, survive rate of femoral head and HHS score between the control groupand preventive group(41.7% vs 13.6%, 66.7% vs 70.8% , P<0.01). Conclusion: Anticoagulant and vasodilator drugs could effect on preventing theglucocorticoid-induced osteonecrosis of femoral head, reducing disease progression, or improving life quality.

[Expression of sal-like 4 in primary hepatocellular carcinoma and its association with epithelial-mesenchymal transition].

Objective: To investigate the expression of sal-like 4 (SALL4) in tissues of primary hepatocellular carcinoma (HCC) and its association with epithelial-mesenchymal transition (EMT) and clinicopathological characteristics. Methods: Immunohistochemistry and nucleic acid in situ hybridization were used to measure the mRNA expression of SALL4, epithelial cadherin (E-cadherin), vimentin, and Snail in 72 HCC samples, 2 fetal liver samples, and 2 normal adult liver tissue samples. Results: Strong expression of SALL4 was observed in hepatoblasts in fetal liver, but SALL4 expression was not observed in primitive hematopoietic cells and normal adult hepatocytes or biliary epithelial cells. In the HCC samples, the positive rate of SALL4 was 47.2% (34/72), showing focal positive nuclear staining. The HCC patients with microscopic microvascular tumor thrombus and portal vein tumor thrombus, a serum alpha-fetoprotein level of≥ 350 ng/ml, International Union Against Cancer (UICC) stage III+IV, and an age of < 46 years showed higher positive expression of SALL4 than those with no microscopic microvascular tumor thrombus or portal vein tumor thrombus, a serum alpha-fetoprotein level of < 350 ng/ml, UICC stage I+II, and an age of≥46 years. The HCC patients with positive SALL4 showed lower postoperative disease-free survival rate and overall survival rate than those with negative SALL4 (P < 0.05). Sixty percent of the patients with microvascular tumor thrombus (21/35) showed positive expression of SALL4. The positive rate of SALL4 was negatively correlated with E-cadherin (r = -0.434, P < 0.01), but positively correlated with vimentin and Snail (vimentin: r = 0.516, P < 0.01; Snail: r = 0.571, P < 0.01). Conclusion: In patients with primary HCC, the expression of SALL4 greatly affects EMT, which helps with the research on invasion and metastasis of liver cancer and prognostic evaluation.

[Application of DNA-image cytometry in the diagnosis of lung cancer].

OBJECTIVE: To explore the value of DNA-image cytometry (DNA-ICM) in diagnosis of lung cancer. METHODS: 532 cases of bronchoalveolar lavage fluid (BALF) and (or) bronchial brushing cytology (216 cases from lung cancer patients and 209 cases from benign lung disease patients) were detected by DNA-ICM and liquid-based cytology (LBC), respectively. The sensitivity and specificity of the two methods were compared. RESULTS: The sensitivity and specificity of DNA-ICM were 69.2% and 100.0%, and which of LBC were 46.7% and 97.9%, respectively. The sensitivity of DNA-ICM was significantly higher than that of LBC method in the diagnosis of lung cancer (P<0.05). The sensitivity and specificity of DNA-ICM of BALF were 71.9% and 100.0%, while those of LBC were 48.2% and 98.5%. The sensitivity and specificity of DNA-ICM of bronchial brushing cytology were 62.8% and 100.0%, while those of LBC were 43.0% and 95.3%. The sensitivity of DNA-ICM of BALF and bronchial brushing cytology were higher than that of LBC method (P<0.05). There were 107 patients who underwent BALF and bronchial brushing cytology simultaneously, the sensitivity of DNA-ICM of BALF was higher than that of bronchial brushing cytology (P<0.05). Among different histologic types of the lung cancers, the sensitivity of squamous carcinoma was higher that of adenocarcinoma. CONCLUSIONS: DNA-ICM has great application value in the diagnosis of lung cancer. DNA-ICM in combination with LBC can increase the detection rate of lung cancer. DNA-ICM of BALF is worthy of application in clinical practice.

Assessing prostate cancer growth with citrate measured by intact tissue proton magnetic resonance spectroscopy.

BACKGROUND: Annual PSA tests have led to a significant increase in the number of prostate cancer (PCa) cases diagnosed. This increased incidence has led to overtreatment of many patients, as current pathology often cannot distinguish latent from aggressive PCa. Studies have shown that the depletion of zinc in prostate cells correlated with cell-line growth rates, and may therefore relate to the progression of PCa. Furthermore, as zinc is normally an inhibitor of citrate oxidation, the reduction of zinc in PCa may cause a decrease in citrate secretion levels in the glandular epithelia of PCa patients. METHODS: Using high-resolution magic angle spinning proton magnetic resonance spectroscopy followed by quantitative histopathology, we investigate unit histo-benign prostate epithelial citrate concentrations in intact tissue samples obtained from 18 patients with pre-surgical PSA values less than 20 ng/ml. Using these data, we evaluate correlations between citrate concentrations and PSA velocities, densities and blood percent-free PSA. RESULTS: We observe different linear patterns between citrate concentrations and histo-benign glandular epithelia from patients of different PSA velocities. More importantly, we obtain a significant correlation between PSA velocity, density and percent-free PSA, and citrate concentrations in unit volume of histo-benign epithelial glands of the peripheral zone. CONCLUSIONS: Low levels of citrate in unit volume represent rapidly increasing PSA values, and, therefore, may be used as an indicator of fast-growing PCa. Thus, tissue samples obtained at the time of biopsy may be evaluated for their citrate concentrations for the prediction of PCa growth rates, allowing for the implementation of alternative treatment options and reducing overtreatment.