Neglected Right Hemidiaphragmatic Angle Soft Tissue Shadow in a Renal Transplant Recipient Diagnosed as Lymphoma.

BACKGROUND: Post-transplant lymphoproliferative disorders are characterized by atypical clinical manifestations, high mortality, and missed diagnosis rates. METHODS: We report a case of renal transplantation in a patient with unexplained soft-tissue nodular shadows, and the type of the post-transplant abnormal soft-tissue shadows was clarified by puncture biopsy. RESULTS: The pathologic returns were consistent with the post-transplant lymphoproliferative disease, and the immunohistochemical returns supported a diffuse large B-cell lymphoma (non-growth center origin). CONCLUSIONS: In organ transplant patients, when unexplained soft tissue nodular shadows are present, the possibility of post-transplant lymphoproliferative disorders should be considered, and an aggressive puncture biopsy should be performed to clarify the diagnosis.

Organizing Pneumonia due to Secondary Invasive Pulmonary Mycosis and Cytomegalovirus Infection in a Patient with Lymphoma.

BACKGROUND: Reactivation of cytomegalovirus is more common in lymphoma patients undergoing hematopoietic stem cell transplantation, but reactivation of cytomegalovirus due to chemotherapy for lymphoma has rarely been reported. We report a case of a lymphoma patient with secondary pulmonary fungal infection and cytomegalovirus infection after chemotherapy, which ultimately led to organizing pneumonia. METHODS: Percutaneous lung biopsy, Next Generation Sequencing (NGS). RESULTS: NGS examination suggestive of cytomegalovirus infection, percutaneous lung biopsy suggests the presence of organizing pneumonia. The patient was discharged after a combination of antifungal and antiviral treatment with posaconazole, ganciclovir, and anti-inflammatory treatment with methylprednisolone. CONCLUSIONS: In patients with lymphoma, one should be alert for fungal and viral infections of the lungs when lung related clinical manifestations occur. Patients with persistent unrelieved symptoms after treatment should undergo lung biopsy or bronchoscopy to obtain pathologic tissue for definitive diagnosis.

Initial Misdiagnosis of Lung Cancer due to Elevated Carcinoembryonic Antigen in a Patient with Tuberculosis.

BACKGROUND: Tuberculosis often presents on imaging in the form of a solitary nodule, sometimes accompanied by elevated CEA, which is clinically difficult to differentiate from lung cancer and prone to misdiagnosis. METHODS: Lung tissue taken by lung biopsy and sent for NGS and Xpert MTB/RIF finally led to the definitive diag-nosis of nodular foci in the upper lobe of the left lung caused by tuberculosis. RESULTS: Enhanced CT of the chest showed nodular foci in the upper lobe of the left lung. Initially the nodules were thought to be malignant, but after a series of tests, were finally confirmed to be tuberculosis. CONCLUSIONS: In patients with lung disease, when chest imaging reveals a space-occupying lesion accompanied by an elevated CEA level, a comprehensive analysis of the type of lung disease, the patient's age, and comorbidities should be performed before final diagnosis to avoid misdiagnosis and delay in appropriate treatment.

Complication of Intrapulmonary Cavitary Lesions after COVID-19 Finally Proved as Pulmonary Aspergillosis.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus type 2, which is characterized by high infectiousness and diverse clinical manifestations. They are more likely to become critical in people who have underlying diseases or are immunocompromised. In the daunting task of treating patients with COVID-19, those with comorbid fungal infections are susceptible to underdiagnosis or misdiagnosis, which can ultimately lead to increased morbidity and mortality in this group of patients. We report a case of intrapulmonary cavitary lesions after COVID-19, which was eventually diagnosed as pulmonary aspergillosis (PA) by metagenomic Next Generation Sequencing (mNGS) to improve our understanding of the disease. METHODS: Appropriate laboratory tests, chest computed tomography (CT), mNGS, and serologic tests were performed for diagnosis. RESULTS: Laboratory tests showed Glactomannan (GM) of 1.41, multiple cavitary lesions in both lungs on chest CT and the presence of aspergillus infection was confirmed by sputum sent for mNGS. CONCLUSIONS: In the case of cavitary lesions after COVID-19, we should be alert to the possibility of combined fungi and should promptly perform mNGS to clarify whether there is a combination of specific pathogenic fungal infections.

Neglected Mycobacterium Avium Complex Infection in a Patient with Prolonged Pneumonia.

BACKGROUND: Non-tuberculous mycobacterial pulmonary infections (NTM-PD) are becoming increasingly common in clinical practice, and early detection and accurate determination of the infecting pathogen is crucial for subsequent treatment. We report a case of NTM-PD in a healthy middle-aged female with Mycobacterium tuberculosis complex group (MAC) infection confirmed by mNGS examination. METHODS: Appropriate laboratory tests, chest CT scan, bronchoscopic alveolar lavage fluid (BALF) examination, and macrogenomic next-generation sequencing (mNGS) were performed to establish the diagnosis. RESULTS: Chest CT showed multiple inflammatory lesions in the right middle lobe, and BALF sent for mNGS finally confirmed the diagnosis of MAC infection. After symptomatic treatment with azithromycin combined with ethambutol and rifampicin, the patient improved and was discharged from the hospital. CONCLUSIONS: In patients with pulmonary infections, pathogens should be clarified early to determine the diagnosis. mNGS of BALF samples have high specificity in detecting pathogens of infectious diseases, especially complex mixed infectious disease pathogens.

Multiple Postoperative Lung Infections after Thymoma Surgery Diagnosed as Nontuberculous Mycobacterial Infection.

BACKGROUND: Thymomas are thymic epithelial-derived, most common primary anterior mediastinal masses. Non-tuberculous mycobacteria (NTM) are species that do not cause leprosy and belong to species outside the Mycobacterium tuberculosis complex. METHODS: With the clinical application of targeted next-generation sequencing (tNGS), we promptly confirmed a case of NTM infection combined with NTM infection after thymoma surgery, and we performed a joint literature analysis of the two diseases to improve clinicians' understanding and recognition of lung infections after thymoma surgery. RESULTS: Chest CT of both lungs showed multiple hyperdense shadows. Sputum bacterial culture and characterization detected Neisseria Dryad and Streptococcus Grass Green. The presence of Mycobacterium abscessus infection was confirmed by alveolar lavage fluid sent for second-generation macro gene sequencing. CONCLUSIONS: The body's immune function decreases after thymoma surgery. When empirical anti-infection treatment for recurrent pneumonia in the lungs is ineffective, we should be alerted to the possibility of the presence of pulmonary non-tuberculous mycobacterial infection, and next-generation sequencing should be performed promptly to arrive quickly at a diagnosis.

[The study of the protection function of the sphingosine kinase 1 in the nerve cell damage caused by acrylamide].

Objective: To study the protective effect and effect of SphK1 overexpression on the injury of nerve cells induced by acrylamide. Methods: ACR with 99% purity was prepared into 1.25 mmol/L and 2.5 mmol/L solutions. SH-SY5Y cells were divided into control group (NC group) , experimental group and SphK1 activator group. The experimental group was given ACR solution with final concentration of 1.25 mmol/L and 2.5 mmol/L respectively for 24 h. In the SphK1 activator group, on the basis of the exposure concentration of the experimental group, the SphK1 specific activator (12-) phorbol tetradecanoate (-13-) acetate (PMA) solution[prepared by dimethyl sulfoxide (DMSO) , the final concentration was 100 nmol/l], and other treatments were the same as the experimental group. Control group (NC group) added PMA solution into normal cells. Western blot was used to detect the expression of SphK1 protein; CCK-8 was used to detect the proliferation of SH-SY5Y cells; hoechst33342 method was used to observe the morphological changes of nerve cells; flow cytometry was used to analyze the apoptosis of cells. Results: Compared with NC group, the expression of SphK1 protein in the experimental group and the SphK1 activator group was significantly lower (P<0.05) . Compared with the experimental group, the expression of SphK1 protein in each concentration of SphK1 activator group was increased, and the difference was statistically significant (P<0.05) . In addition to 1.25 mmol/L SphK1 activator group, compared with NC group, the relative growth survival rate of experimental group and 2.5 mmol/L SphK1 activator group were lower, the difference was statistically significant (P<0.05) . Compared with the experimental group, the relative survival rate of cells in the SphK1 activator group was higher, and the difference was statistically significant (P<0.05) . With the increase of exposure concentration, the cells in the experimental group showed the morphological characteristics of early apoptosis at ACR 1.25 mmol/L and late apoptosis at ACR 2.5 mmol/L. Compared with NC group, the apoptosis rate of experimental group and SphK1 activator group at ACR 2.5 mmol/L was significantly different (P<0.05) ; compared with experimental group, the apoptosis rate of SphK1 activator group at ACR 2.5 mmol/L was lower, the difference was statistically significant (P<0.05) . Conclusion: The SphK1 excessive expression plays the protective function to the nerve cell damage caused by acrylamide.

[The relationship between acid reflux and esophageal motility, esophagitis and cardiac morphology in gastroesophageal reflux disease].

Objective: To analyze the relationship between the severity of esophageal acid reflux and esophageal motility, esophageal mucosal injury and morphological anatomy of gastroesophageal junction (GEJ) in patients with gastroesophageal reflux disease (GERD). Methods: The clinicaldata of GERD patients who underwent 24 h pH-impedance monitoring, gastroscopy and high-resolution manometry (HRM) from January 2016 to January 2019 in the Gastroesophageal Surgery Department of PLA Rocket Force Characteristic Medical Center were retrospectively analyzed. The patients were divided into non-pathological acid reflux group, mild pathological acid reflux group and moderate to severe pathological acid reflux group according to the DeMeester score. The gender and age of each group were matched, with 60 cases in each group. Statistical analysiswas performed to analyze thedifferences in upper esophageal sphincter pressure, lower esophageal sphincter pressure (LES), LES length, length of ventral LES, percentage of ineffective swallowing, esophagitis, Hill grade of GEJ, and hiatus hernia (HH) in each group. The comparison and correlation analysis are also carried out between the groups. Results: The male-female ratio was 33/27, and the age was (57±13) years in each group. Non-parametric analysis showed that the LES pressure and the length of the ventral LES decreased with the severity of acid reflux, and there was a statistical difference (P= 0.033, P=0.015). The detection rate of HH by HRM increased significantly (χ(2)=0.001) as well. Esophagitis score increased with the severity of acid reflux and there was statistical difference (P<0.001).The detection rate of esophagitis increased significantly (χ(2)<0.001) as well. Hill grading score of GEJ increased with the severity of acid reflux, and there was statistical difference (P<0.001).The detection rate of HH by endoscopy increased significantly (χ(2)<0.001) as well. The correlation between DeMeester score and LES pressure, length of ventral LES, percentage of ineffective swallowing, esophagitis score, and Hill grade score were statistically significant (P<0.05). Conclusions: The esophageal low motility (such as low LES pressure) and anatomical abnormalities (abdominal esophageal shortening, GEJ flabbiness, and even HH formation) of the GEJ regionare significantly associated with the severity of acid reflux. These factors may be important causes of increased acid reflux. In addition, the aggravation of acid reflux can also increase the incidence and severity of esophagitis.

Chirped-pulse-amplification seed source through direct phase modulation.

This work presents integration of a directly chirped laser source (DCLS) into a high-energy optical parametric chirped-pulse-amplification (OPCPA) system. DCLS is an all-fiber, chirped laser source that produces nanosecond, linearly chirped laser pulses at 1053 nm for seeding high-energy chirped-pulse-amplification systems. DCLS produces a frequency chirp on an optical pulse through direct temporal phase modulation. A 1-ns, linearly chirped pulse with a 3-nm bandwidth is produced by applying an ~1000-rad (300π) quadratic temporal phase. The chirped pulse is amplified to 76 mJ in an OPCPA system and compressed to close to its Fourier transform limit, producing an intensity autocorrelation trace with a 1.5-ps width.

Prevalence of transmitted drug resistance among HIV-1 treatment-naive patients in Beijing.

To optimise patients' outcomes and gain insight into transmitted drug resistance (TDR) among human immunodeficiency virus (HIV)-1 treatment-naive patients in Beijing, the prevalence of TDR was assessed. Demographic and clinical data of 1241 treatment-naive patients diagnosed between April 2014 and February 2015 were collected. TDR was defined using the Stanford University HIV drug resistance mutations database. The risk factors were evaluated by multi-logistic regression analysis. Among 932 successfully amplified cases, most were male (96.78%) and infected through men having sex with men (91.74%). Genotype were CRF01_AE (56.44%), B (20.60%), CRF07_BC (19.96%), C (1.61%) and other genotypes (1.39%). The overall prevalence of TDR was 6.12%. Most frequent mutations occurred in non-nucleoside reverse transcriptase inhibitors (NNRTIs) (3.11%), followed by protease inhibitors (PIs) (2.25%) and nucleoside reverse transcriptase inhibitors (NRTIs) (1.32%). Furthermore, HIV-1 genotype was associated with high risk of resistance, in which genotype C and other genotype may have higher risk for resistance. The prevalence among treatment-naive patients in Beijing was low. Resistance to NNRTIs was higher than with PIs or NRTIs. Continuous monitoring of regional levels of HIV-1 TDRs would contribute to improve treatment outcomes and prevent failures.

[Relationship between the severity of reflux esophagitis and the esophageal motility features on high resolution manometry].

Objective: To analyze esophageal motility dysfunction in gastroesophageal reflux disease (GERD) with different severity of esophagitis, and the relationship between the esophageal motility dysfunction and the severity of esophagitis. Methods: GERD patients simultaneously undergone endoscopy and high-resolution manometry were divided into four groups: Non-esophagitis (Non-erosive gastroesophageal reflux disease, NERD) group, mild esophagitis group, moderate esophagitis group and severe esophagitis group. The gender and age were matched for each group, and every group consisted of 80 cases. Nonparametric test was used to analyze the differences in HRM parameters, such as upper esophageal sphincter (UES) pressure, lower esophageal sphincter (LES) pressure, LES length, LES-CD (crural diaphragm) separation distance, and the percentage of failed peristalsis of the four groups, and the differences between each two of the groups were also analyzed. Results: Nonparametric test showed that the LES pressure and length decreased with the severity of esophagitis, and there were statistical differences (P<0.001, P=0.030). The failed peristalsis percentage increased with the severity of esophagitis and the difference was statistically significant (P<0.001). The LES-CD separation distance was increased with the severity of esophagitis and had statistically significance (P<0.001). When comparing the differences between each two of the groups, there were significant differences (P<0.001, P=0.012, P<0.001, P<0.001) between NERD group and severe esophagitis group in the HRM parameters of the lower esophageal sphincter pressure, the LES length, the LES-CD separation distance, and the percentage of ineffective swallowing in the NERD and severe esophagitis group. The detection rate of HH was significantly increased from NERD to severe esophagitis, the detection rate of HH was 6.3% to 82.5% in gastoracopy and 16.3% to 45.0% in HRM, and the diagnostic consistency was fair (Kappa Value: 0.31). Conclusions: Hypo-dynamic state of esophageal and HH are the main motility characteristics of erosive gastroesophageal reflux disease, Esophageal motility abnormalities increase in parallel with the severity of GERD from NERD to severe esophagitis, these motility disorders may also play important roles in causing esophagitis.

Treatment of aging oily wastewater by demulsification/flocculation.

The aging oily wastewater (AOW) from Tarim oilfield in China was treated by demulsification/flocculation. A novel sewage treatment agent (YL-7) was developed using a cationic surfactant (LY) and flocculants (polydimethyl diallyl ammonium chloride (PDMDAAC)/polyaluminum chloride (PAC)). At an YL-7 dosage of 320 mg L(-1) at 323 K for 90 min, the oil content of AOW was reduced from 728.8 mg L(-1) to 23.7 mg L(-1), and oil removal efficiency reached 96.7%. Microorganism flocs (extracted from AOW) with high negative zeta potential enhanced the stability of oil/water emulsion. LY and PDMDAAC neutralized the negative charge on the oil droplet surface. PDMDAAC and PAC mainly bridged and swept flocs during the flocculation process. YL-7 was found to be a suitable sewage treatment agent in removing oil from AOW.

LED-based interferometric reflectance imaging sensor for the detection of amyloid-ß aggregation.

Self-aggregation of amyloid-ß (Aß) plays an important role in the pathogenesis of Alzheimer's disease (AD). Small molecule inhibitors of Aß fibril formation reduce the Aß-mediated neurotocixity. In this report, the interaction of amyloid-ß (Aß) with well-described modulators, (-)epigallocatechin-3-gallate (EGCG) and Zn(ii), was detected using a LED-based interferometric reflectance imaging sensor (LED-IRIS) in a high-throughput and real-time format. Nucleation-based fibril growth strategy was employed, as the "seeds" of Aß were prepared in the presence of EGCG and Zn(ii). The seeds were then covalently immobilized on the chip surface. Using microfluidics, Aß oligomers were exposed onto the seeds resulting in the elongation of fibrils, which was detected as the increase in the spot height. Monitoring the changes on the chip surface enabled to detect the efficacy of modulators to inhibit or facilitate the growth of Aß fibrils. The proof-of-concept study reported here introduces a novel platform to facilitate the screening of small molecules towards the discovery of promising AD therapeutics.

CD28 Costimulation Augments CAR Signaling in NK Cells via the LCK/CD3ζ/ZAP70 Signaling Axis.

Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being a key component. Yet, the impact of costimulatory domains on the downstream signaling and subsequent functionality of CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated the impact of various costimulatory domains on CAR-NK cell activity, using a CD70-targeting CAR. We found that CD28, a costimulatory molecule not inherently present in mature NK cells, significantly enhanced the antitumor efficacy and long-term cytotoxicity of CAR-NK cells both in vitro and in multiple xenograft models of hematologic and solid tumors. Mechanistically, we showed that CD28 linked to CD3ζ creates a platform that recruits critical kinases, such as lymphocyte-specific protein tyrosine kinase (LCK) and zeta-chain-associated protein kinase 70 (ZAP70), initiating a signaling cascade that enhances CAR-NK cell function. Our study provides insights into how CD28 costimulation enhances CAR-NK cell function and supports its incorporation in NK-based CARs for cancer immunotherapy. Significance: We demonstrated that incorporation of the T-cell-centric costimulatory molecule CD28, which is normally absent in mature natural killer (NK) cells, into the chimeric antigen receptor (CAR) construct recruits key kinases including lymphocyte-specific protein tyrosine kinase and zeta-chain-associated protein kinase 70 and results in enhanced CAR-NK cell persistence and sustained antitumor cytotoxicity.

Surface plasmon resonance imaging of amyloid-ß aggregation kinetics in the presence of epigallocatechin gallate and metals.

A number of human protein misfolding disorders, including Alzheimer's disease (AD), are closely related to the accumulation of ß-sheet-rich amyloid fibrils or aggregates. Neuronal toxicity in AD has been linked to the interactions of amyloid-ß (Aß) with metals, especially Zn(2+), Cu(2+), and Fe(3+), which leads to the production of reactive oxygen species. Nucleation-dependent Aß aggregation, or "seeding", is thought to propagate fibril formation. In this surface plasmon resonance imaging (SPRi) study, we have shown that the fibril seeds formed with the incubation of Aß in the presence of metals are better at promoting monomer elongation compared to Aß alone or in the presence of a well-described polyphenol, (-)-epigallocatechin-3-gallate (EGCG). This is a novel attempt to simultaneously monitor the effects of multiple modulators on fibril elongation using a single chip. EGCG was shown in transmission electron microscopy (TEM) and thioflavin T (ThT) studies to promote the formation of off-pathway, highly stable unstructured oligomers, supporting the SPRi results. These findings suggest that SPRi provides a promising platform as a screening tool for small molecules that can affect the aggregation pathways in neurodegenerative diseases.

[Calcification distributional density of the aortic-valvular complex is an independent risk factor for conduction block following self-expanding transcatheter aortic valve replacement].

OBJECTIVE: To evaluate the effect of calcification distributional density in different regions of aortic-valvular complex (AVC) on postoperative new-onset conduction block (CB) following transcatheter aortic valve replacement (TAVR) using self-expandable valves (SEV) made in China. METHODS: From January, 2016 to December, 2022, 73 patients with severe aortic valve stenosis received Venus-A prosthetic valve replacement using SEV made in China, and postoperative new-onset CB occurred in 18 (24.7%) of the patients. The baseline data, imaging and intervention- related data were compared were between the patients with CB and those without CB. Univariate and multivariate logistic regression analysis was used for investigating the independent risk factors for new- onset CB after TAVR, and the predictive performance of these risk factors was evaluated using receiver operating characteristic (ROC) curve and DeLong test. RESULTS: Compared with those with CB, the patients experiencing postoperative new-onset CB had a greater implantation depth (6.77±2.45 mm vs 5.11±3.28 mm, P=0.027), a smaller difference between the membranous septum length and the implantation depth (MSID) (0.68±3.49 mm vs 2.82±3.88 mm, P= 0.036), and a higher calcification distributional density of the left coronary sinus (LCS) in the device landing zone (DLZ) (P= 0.026). Multivariate logistic analysis revealed that DLZ-LCS calcification distributional density and MSID were independent risk (protective) factors for new-onset CB following TAVR. ROC curve analysis showed that the AUC of MSID and DLZ-LCS calcification distributional density was 0.775 and 0.716, respectively, and their combination had had a significantly higher AUC of 0.890 (P=0.041 and 0.027, respectively). CONCLUSION: The DLZ-LCS calcification distributional density is an independent risk factor for new-onset CB following TAVR using SEV. The conduction complications following TAVR can be effectively predicted using this calcification indicator combined with MSID.

Disposable immunochips for the detection of Legionella pneumophila using electrochemical impedance spectroscopy.

The rapid diagnosis of Legionellosis is crucial for the effective treatment of this disease. Currently, most clinical laboratories utilize rapid immunoassays that are sufficient for the detection of Legionella serogroup 1, but not other clinically relevant serogroups. In this report, the development of a disposable immunochip system is described in connection with electrochemical impedance spectroscopy and fluorescence microscopy. The immunochips were prepared by covalently immobilizing fluorophore-conjugated L. pneumophilaantibodies on Au chips. The analytical performance of the immunochips was optimized as a prescreening tool for L. pneumophila. The versatile immunochips described here can be easily adapted for the monitoring of all Legionella serogroups in clinical and environmental samples.

[Anythink for CT-based aorta root measurements before transcatheter aortic valve replacement: measurement consistency with 3mensio and impact on short-term prognosis].

OBJECTIVE: To evaluate the consistency and reproducibility of aortic root measurements by Anythink, a semi-automated preoperative CT analysis software, with those of 3mensio. METHODS: Sixty-seven patients undergoing transcatheter aortic valve replacement (TAVR) in the First Medical Center of Chinese PLA General Hospital from December, 2016 to February, 2022 were retrospectively enrolled in this study. A cardiology resident who completed his professional training used both the software Anythink and 3mensio (as the gold standard) to reconstruct the aortic root model and analyze the parameters of the aortic annulus and the surrounding structures. The correlation and consistency of the measurement results of two software were analyzed. Two independent residents also used Anythink software to repeat the measurements for the same patient for assessment of the reproducibility of Anythink measurements. The valve models were selected based on the measurements by Anythink and 3mensio, and similarities and differences of the two software in clinical valve selection were assessed. RESULTS: The measurements of the distances from the anulus plane to the left and right coronary ostium, average diameter of the anulus, anulus area, anulus perimeter, and the angle between the annulus and horizontal plane did not differ significantly between the two software (P > 0.05), and their measurements showed positive correlations (r= 0.884-0.981, P < 0.01). The intra-group and inter-group correlation coefficients of the anulus parameters measured by Anythink ranged from 0.894 to 0.992 and from 0.651 to 0.954, respectively. The Kappa-test values of valve models selected by Anythink and 3mensio based on the average diameter, area diameter and perimeter diameter were 0.886, 0.796 and 0.775, respectively. The intra-group Kappa values for the valve models selected based on Anythink measurements were 0.819, 0.841, and 0.795, and the inter-group Kappa values were 0.812, 0.812, and 0.768, respectively. Compared with the measurements by 3mensio, the recommended area diameter measured by Anythink was slightly greater in patients with postoperative paravalvular leakage, but slightly smaller in patients with postoperative new-onset conduction block. CONCLUSION: Anythink has excellent measurement consistency and high reproducibility for aortic root measurements, and trained cardiologists can use Anythink to obtain accurate aortic root parameters before TAVR.