Clinical values of different specimen preparation methods for the diagnosis of lung cancer by EBUS-TBNA.

BACKGROUND AND OBJECTIVE: EBUS-TBNA has emerged as an important minimally invasive procedure for the diagnosis and staging of lung cancer. Our objective was to evaluate the effect of different specimen preparation from aspirates on the diagnosis of lung cancer. METHODS: 181 consecutive patients with known or suspected lung cancer accompanied by hilar / mediastinal lymphadenopathy underwent EBUS-TBNA from January 2019 to December 2022. Specimens obtained by EBUS-TBNA were processed by three methods: Traditional smear cytology of aspirates (TSC), liquid-based cytology of aspirates (LBC) and histopathology of core biopsies. RESULTS: EBUS-TBNA was performed in 181 patients on 213 lymph nodes, the total positive rate of the combination of three specimen preparation methods was 80.7%. The diagnostic positive rate of histopathology was 72.3%, TSC was 68.1%, and LBC was 65.3%, no significant differences was observed (p = 0.29); however, statistically significant difference was noted between the combination of three preparation methods and any single specimen preparation methods (p = 0.002). The diagnostic sensitivity of histopathology combined with TSC and histopathology combined with LBC were 96.5 and 94.8%, the specificity was 95.0% and 97.5%, the PPV was 98.8% and 99.4%, the NPV was 86.4% and 81.2%, the diagnostic accuracy was 96.2% and 95.3%, respectively; The sensitivity and accuracy of above methods were higher than that of single specimen preparation, but lower than that of combination of three preparation methods. CONCLUSION: When EBUS-TBNA is used for the diagnosis and staging of lung cancer, histopathology combined with TSC can achieve enough diagnostic efficiency and better cost-effectiveness.

Postreperfusion Renal Allograft Biopsy Predicts Outcome of Single-Kidney Transplantation: A 10-Year Observational Study in China.

Introduction: Biopsy findings often lead to the discard of many donor kidneys although their clinical value is not fully understood. We investigated the predictive value of postreperfusion biopsy on long-term allograft outcome after single-kidney transplantation. Methods: We retrospectively evaluated the significance of histologic findings, read by experienced renal pathologists, in 461 postreperfusion biopsy specimens collected from 2010 to 2017 after deceased donor renal transplant; and performed time-to-event analyses to determine the association between histology and hazard of death-censored graft failure. Recipients were followed-up with over a median time of 6.8 (range, 0.2-11.9) years. We assessed specimens using the Remuzzi score (scale of 0-12) and categorized them into low-score (≤3) and high-score (>3) groups. Kappa coefficients were calculated to assess agreement in procurement versus reperfusion biopsies. Results: High Remuzzi score kidneys came from older donors with a higher incidence of hypertension, higher final creatinine, death from cerebrovascular disease, expanded criteria donor, and a higher kidney donor risk index (KDRI) (all P < 0.001). In adjusted analyses, Remuzzi score was independently associated with death-censored graft failure (hazard ratio [HR] 1.389 for each 1 score rise in Remuzzi score, 95% confidence interval 1.181-1.633, P < 0.001). Overall histologic agreement (procurement biopsy versus reperfusion biopsy) was kappa = 0.137. Conclusion: Our findings suggest that postreperfusion biopsy is associated with long-time graft outcomes after transplant from a deceased donor. Agreement between procurement and reperfusion biopsy was found to be low. Prospective trials are necessary to optimize procurement biopsy practices.

Multiple pulmonary cavernous haemangiomas with concurrent primary pulmonary adenocarcinoma: a case report and literature review.

Background: Cavernous haemangiomas (CHs) commonly occurred in the skin, subcutaneous tissue, muscles, and liver. Pulmonary cavernous haemangiomas (PCHs) are quite rare and usually present with nonspecific clinical symptoms. When lung cancer patients are complicated with pulmonary cavernous haemangiomas, radiologically, these haemangioma lesions can be easily misinterpreted as intrapulmonary metastases, potentially resulting in misdiagnosis, or missed diagnosis. Case presentation: The present study reported the case of a 53-year-old female patient with pulmonary adenocarcinoma coexisting with multiple PCHs. 18F-FDG-Positron emission tomography-computed tomography (PET-CT) showed an elevated glucose metabolism in the apicoposterior segment of the left upper lobe; however, the other nodules were not hypermetabolic. Percutaneous lung biopsy was performed on the nodule in the apicoposterior segment of the left upper lobe, which were diagnosed as primary adenocarcinoma. Some nodules in the upper left lobe underwent wedge resection by video-assisted thoracic surgery (VATS) and intraoperative frozen section identified as PCHs. Finally, the patient underwent lobectomy of the left upper lobe via VATS, cancerous nodule in the apicoposterior segment of the left upper lobe underwent genetic molecular testing of PCR-Sanger sequencing, suggested EGFR mutation, and patient received treatment with Osimertinib. During the 4-months follow-up, contrast-enhanced CT showed no recurrence of either disease. PCHs are rare benign tumours of the lung, which can lead to misdiagnosis due to their non-specific clinical symptoms and radiological features, especially when they coexist with lung cancer. PCHs is easily misunderstood as metastatic lung cancer, in this case, PET-CT can assist in differentiating benign from malignant. For the cases of early lung cancer complicated with PCHs, lung cancer can be surgically resected, and whether PCHs should be removed or not should be determined according to the size and distribution of the lesions.

[Short-term Effect of Venetoclax Combined with Azacitidine and "7+3" Regimen in the Treatment of Newly Diagnosed Elder Patients with Acute Myeloid Leukemia].

OBJECTIVE: To compare the short-term effect and adverse reaction of venetoclax (VEN) combined with azacitidine (AZA) versus "7+3" regimen in newly diagnosed elder patients with acute myeloid leukemia (AML). METHODS: From January 2021 to January 2022, the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed, including VEN+AZA group (41 cases) and "7+3" group (38 cases). The propensity score matching(PSM) method was used to balance confounding factors， then response， overall survival(OS), progressionfree survival(PFS) and adverse reactions between the two groups were compared. RESULTS: The ORR of VEN+AZA group and "7+3" group was 68% and 84%, respectively, and the CRc was 64% and 72%, respectively, the differents were not statistically significant (P >0.05). In the VEN+AZA group, there were 5 non-remission (NR) patients, 4 with chromosome 7 abnormality (7q-/-7), and 1 with ETV6 gene mutation. Median followed-up time between the two groups was 8 months and 12 months, respectively, and the 6-months OS was 84% vs 92% (P =0.389), while 6-months PFS was 84% vs 92% (P =0.258). The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳ myelosuppression, and the incidence rate was not statistically different(P >0.05). The median time of neutrophil recovery in two groups was 27(11-70) d, 25(14-61) d （P =0.161）, and platelet recovery was 27(11-75) d, 25(16-50) d （P =0.270）, respectively. The infection rate of VEN+AZA group was lower than that of "7+3" group (56% vs 88%, P =0.012）. The rate of lung infections of two groups was 36% and 64%, respectively, the difference was statistically significant (P =0.048). CONCLUSION: The short-term effect of VEN+AZA group and "7+3" regimens in eldrly AML patients are similar， but the VEN+AZA regimen had a lower incidence of infection. The presence of chromosome 7 abnormality（7q-/-7） may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.

Urinary C4d and progression of kidney disease in IgA vasculitis.

BACKGROUND: IgA vasculitis nephritis is the most common secondary IgA nephropathy. Urinary C4d have been identified associated with the development and progression in primary IgA nephropathy. However, its role in kidney disease progression of IgA vasculitis nephritis is still unclear. METHODS: This study enrolled 139 patients with IgA vasculitis nephritis (IgAVN), 18 healthy subjects, 23 Focal segmental glomerulosclerosis patients and 38 IgA nephropathy (IgAN) patients. Urinary C4d levels at kidney biopsy were measured using enzyme-linked immunosorbent assay. The association between urinary C4d/creatinine and kidney disease progression event, defined as 40% eGFR decline or ESKD, was assessed using Cox proportional hazards models and restricted cubic splines. RESULTS: The levels of urinary C4d/creatinine in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/creatinine were associated with higher proteinuria and severe Oxford C lesions and glomerular C4d deposition. After a median follow-up of 52.79 months, 18 (12.95%) participants reached composite kidney disease progression event. The risk of kidney disease progression event was higher with higher levels of ln (urinary C4d/creatinine). After adjustment for clinical data, higher levels of urinary C4d/creatinine were associated with kidney disease progression in IgA vasculitis nephritis (per ln transformed urinary C4d/creatinine, hazard ratio (HR) =1.573, 95% confidence interval (CI) 1.101-2.245; P = 0.013). Compared to the lower C4d/creatinine group, hazard ratio was 5.539(95%CI, 1.135-27.035; P = 0.034) for the higher levels group. CONCLUSIONS: Higher levels of urinary C4d/creatinine were associated with kidney disease progression event in patients IgAVN.

Glutathione Induced In situ Synthesis of Cu Single-Atom Nanozymes with Anaerobic Glycolysis Metabolism Interference for Boosting Cuproptosis.

Single-atom nanozyme (SAzyme) has sparked increasing interest for catalytic antitumor treatment due to their more tunable and diverse active sites than natural metalloenzymes in complex physiological conditions. However, it is usually a hard task to precisely conduct catalysis at tumor sites after intravenous injection of those SAzyme with high reactivity. Moreover, the explorations of SAzymes in the anticancer application are still in its infancy and need to be developed. Herein, an in situ synthesis strategy for Cu SAzyme was constructed to convert adsorbed copper ions into isolated atoms anchored by oxygen atoms (Cu-O2/Cu-O4) via GSH-responsive deformability of supports. Our results suggest that the in situ activation process could further facilitate the dissociation of copper ions and the consumption of glutathione, thereby leading to copper deposition in cytoplasm and triggering cuproptosis. Moreover, the in situ synthesis of Cu SAzyme with peroxidase-like activity enabled the intracellular reactive oxygen species production, resulting in specifically disturbance of copper metabolism pathway. Meanwhile, the in situ exposed glucose transporter (GLUT) inhibitor phloretin (Ph) can block the glycose uptake to boost cuproptosis efficacy. Overall, this in situ activation strategy effectively diminished the off-target effects of SACs-induced catalytic therapies and introduced a promising treatment paradigm for advancing cuproptosis-associated therapies.

NADPH Oxidase-Like Nanozyme for High-Efficiency Tumor Therapy Through Increasing Glutathione Consumption and Blocking Glutathione Regeneration.

To counteract the high level of reactive oxygen species (ROS) caused by rapid growth, tumor cells resist oxidative stress by accelerating the production and regeneration of intracellular glutathione (GSH). Numerous studies focus on the consumption of GSH, but the regeneration of GSH will enhance the reduction level of tumor cells to resist oxidative stress. Therefore, inhibiting the regeneration of GSH; while, consuming GSH is of great significance for breaking the redox balance of tumor cells. Herein, a simple termed MnOx-coated Au (AMO) nanoflower, as a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) nanoenzyme, is reported for efficient tumor therapy. Au nanoparticles exhibit the capability to catalyze the oxidation of NADPH, hindering GSH regeneration; while, concurrently functioning as a photothermal agent. During the process of eliminating intracellular GSH, MnOx releases Mn2+ that subsequently engages in Fenton-like reactions, ultimately facilitating the implementation of chemodynamic therapy (CDT). Overall, this NOX enzyme-based nanoplatform enhances ROS generation and disrupts the state of reduction equilibrium, inducing apoptosis and ferroptosis by blocking GSH regeneration and increasing GSH consumption, thereby achieving collaborative treatments involving photothermal therapy (PTT), CDT, and catalytic therapy. This research contributes to NADPH and GSH targeted tumor therapy and showcases the potential of nanozymes.

Oxygen-Vacancy-Engineered W18 O49-x Nanobrush with a Suitable Band Structure for Highly Efficient Sonodynamic Therapy.

With the rapid development of external minimally invasive or noninvasive therapeutic modalities, ultrasound-based sonodynamic therapy (SDT) is a new alternative for treating deep tumors. However, inadequate sonosensitizer efficiency and poor biosecurity limit clinical applications. In this study, we prepared an oxygen-vacancy-engineered W18 O49-x nanobrush with a band gap of 2.79 eV for highly efficient SDT using a simple solvothermal method. The suitable band structures of the W18 O49-x nanobrush endows it with the potential to simultaneously produce singlet oxygen (1 O2 ), superoxide anions (⋅O2 - ), and hydroxyl radicals (⋅OH) under ultrasound irradiation. Additionally, abundant oxygen vacancies that serve as further charge traps that inhibit electron-hole recombination are incidentally introduced through one-step thermal reduction. Collectively, the in vitro and in vivo results demonstrate that the oxygen-vacancy-engineered W18 O49-x nanobrush delivers highly efficient reactive oxygen species (ROS) for SDT in a very biosafe manner. Overall, this study provides a new avenue for discovering and designing inorganic nanosonosensitizers with enhanced therapeutic efficiencies for use in SDT.

Cepharanthine synergizes with photodynamic therapy for boosting ROS-driven DNA damage and suppressing MTH1 as a potential anti-cancer strategy.

OBJECTIVE: Photodynamic therapy (PDT) primarily treats skin diseases or cancer by generating reactive oxygen species (ROS) to damage cellular DNA, yet drug resistance limits its application. To tackle this problem, the present study was carried out to improve the efficacy of chlorin e6 (Ce6)-PDT using Cepharanthine (CEP) as well as to reveal the potential molecular mechanism. MATERIALS AND METHODS: Lewis lung cancer cell line (LLC) was utilized as the cancer cell model. chlorin e6 (Ce6) acted as the photosensitizer to induce PDT. The in vitro anti-cancer efficacy was measured by CCK-8, Annexin-V/PI staining, and migration assay. The Ce6 uptake was observed using flow cytometry and confocal microscopy. The ROS generation was detected by the DCFH-DA probe. The analysis of MutT Homolog 1 (MTH1) expression, correlation, and prognosis in databases was conducted by bioinformatic. The MTH1 expression was detected through western blots (WB). DNA damage was assayed by WB, immunofluorescent staining, and comet assay. RESULTS: Ce6-PDT showed robust resistance in lung cancer cells under certain conditions, as evidenced by the unchanged cell viability and apoptosis. The subsequent findings confirmed that the uptake of Ce6 and MTH1 expression was enhanced, but ROS generation with laser irradiation was not increased in LLC, which indicated that the ROS scavenge may be the critical reason for resistance. Surprisingly, bioinformatic and in vitro experiments identified that MTH1, which could prevent the DNA from damage of ROS, was highly expressed in lung cancer and thereby led to the poor prognosis and could be further up-regulated by Ce6 PDT. CEP exhibited a dose-dependent suppressive effect on the lung cancer cells. Further investigations presented that CEP treatment boosted ROS production, thereby resulting in DNA double-strand breakage (DDSB) with activation of MTH1, indicating that CEP facilitated Ce6-PDT-mediated DNA damage. Finally, the combination of CEP and Ce6-PDT exhibited prominent ROS accumulation, MTH1 inhibition, and anti-lung cancer efficacy, which had synergistic pro-DNA damage properties. CONCLUSION: Collectively, highly expressed MTH1 and the failure of ROS generation lead to PDT resistance in lung cancer cells. CEP facilitates ROS generation of PDT, thereby promoting vigorous DNA damage, inactivating MTH1, alleviating PDT resistance, and ameliorating the anti-cancer efficacy of Ce6-PDT, provides a novel approach for augmented PDT.

NIR-Activatable Heterostructured Nanoadjuvant CoP/NiCoP Executing Lactate Metabolism Interventions for Boosted Photocatalytic Hydrogen Therapy and Photoimmunotherapy.

Near-infrared (NIR) laser-induced photoimmunotherapy has aroused great interest due to its intrinsic noninvasiveness and spatiotemporal precision, while immune evasion evoked by lactic acid (LA) accumulation severely limits its clinical outcomes. Although several metabolic interventions have been devoted to ameliorate immunosuppression, intracellular residual LA still remains a potential energy source for oncocyte proliferation. Herein, an immunomodulatory nanoadjuvant based on a yolk-shell CoP/NiCoP (CNCP) heterostructure loaded with the monocarboxylate transporter 4 inhibitor fluvastatin sodium (Flu) is constructed to concurrently relieve immunosuppression and elicit robust antitumor immunity. Under NIR irradiation, CNCP heterojunctions exhibit superior photothermal performance and photocatalytic production of reactive oxygen species and hydrogen. The continuous heat then facilitates Flu release to restrain LA exudation from tumor cells, whereas cumulative LA can be depleted as a hole scavenger to improve photocatalytic efficiency. Subsequently, potentiated photocatalytic therapy can not only initiate systematic immunoreaction, but also provoke severe mitochondrial dysfunction and disrupt the energy supply for heat shock protein synthesis, in turn realizing mild photothermal therapy. Consequently, LA metabolic remodeling endows an intensive cascade treatment with an optimal safety profile to effectually suppress tumor proliferation and metastasis, which offers a new paradigm for the development of metabolism-regulated immunotherapy.

Pulmonary cryptococcosis coexisting with lung adenocarcinoma: A case report and review of the literature.

Pulmonary cryptococcosis (PC) is an invasive pulmonary fungal disease caused by Cryptococcus neoformans or Cryptococcus gattii. It often presents as a single nodule or mass on radiology, which is easily misdiagnosed as lung cancer or metastases. However, cases of PC coexisting with lung cancer are rare and when this scenario is encountered in clinical practice, it is easy to be misdiagnosed as metastatic lung cancer. The present study reported the case of a 65-year-old immunocompetent patient with PC coexisting with lung adenocarcinoma. Percutaneous lung biopsy was performed on the nodule in the anterior segment of the left upper lobe and the nodule in the posterior basal segment of the left lower lobe, which were diagnosed as primary adenocarcinoma and cryptococcus, respectively. Lung cancer was treated by surgery and PC was treated successfully by antifungal treatment. During the 5-year follow-up, contrast-enhanced CT showed no recurrence of either disease. This case reminds us of the possibility of dualism in the diagnosis of multiple pulmonary nodules based on CT examination, such as the coexistence of lung carcinoma and PC. In addition, early diagnosis and treatment contribute to good prognosis.

Endobronchial pigmented mass in a patient with primary malignant melanoma of the lung: A case report.

Malignant melanoma (MM) commonly presents as a primary skin tumor and respiratory MM cases are almost all metastatic. Primary lung MM (PMML) is quite rare, especially when manifested as an endobronchial pigmented mass, its diagnosis is relatively difficult and MM has a poor prognosis. Only a few cases have been described previously and the pathologic features, clinical behavior and therapeutic options are not well established. The present study reports the case of a 72-year-old female patient with PMML who denied any history of tumors. The patient complained of chest pain and coughing for 2 weeks. Chest computed tomography (CT) revealed a mass in the right upper lobe and an enlarged mediastinal lymph node. Positron emission tomogram-CT suggested a hypermetabolic tumor. To confirm the diagnosis, the patient underwent a transbronchial forceps biopsy and endobronchial ultrasound-guided transbronchial needle aspiration, which confirmed the diagnosis of PMML. Genetic testing identified a BRAF V600E mutation, so the patient received treatment with dabrafenib plus trametinib. PMML is extremely rare and is easily misdiagnosed as lung cancer due to its nonspecific clinical manifestations and imaging features. The diagnosis of PMML remains challenging due to its morphologic and immunophenotypic variability. Targeted therapy is a good option for advanced PMML patients with BRAF V600E mutations.

Tumor Microenvironment-Activated Nanocomposite for Self-Amplifying Chemodynamic/Starvation Therapy Enhanced IDO-Blockade Tumor Immunotherapy.

Disrupting intracellular redox homeostasis combined with immune checkpoint blockade therapy is considered as an effective way to accelerate tumor cell death. However, suppressed tumor immune microenvironment and lower cargo delivery restrict the efficiency of tumor therapy. In this study, a multifunctional tumor microenvironment (TME)-responsive nanocomposite is constructed using manganese tetroxide (Mn3 O4 )-decorated disulfide-bond-incorporated dendritic mesoporous organosilica nanoparticles (DMONs) to co-deliver indoleamine 2,3-dioxygenase (IDO) inhibitor Epacadostat (IDOi) and glucose oxidase (GOx) following modification with polyethylene glycol. Owing to the responsiveness of Mn3 O4 -decorated DMONs to the mildly acidic and glutathione (GSH) overexpressed TME, the nanocomposite can rapidly decompose and release inner contents, thus substantially improving the cargo release ability. Mn3 O4 can effectively catalyze hydrogen peroxide (H2 O2 ) decomposition to generate oxygen, enhance the ability of GOx to consume glucose to produce H2 O2 , and further promote the generation of hydroxyl radicals (•OH) by Mn2+ . Furthermore, Mn2+ -mediated GSH depletion and the production of •OH can disrupt intracellular redox homeostasis, contributing to immunogenic cell death. Simultaneously, IDOi can inhibit IDO to reverse inhibited immune response. The results show that self-amplifying chemodynamic/starvation therapy combined IDO-blockade immunotherapy synergistically inhibits tumor growth and metastasis in vivo.

[Risk Factors of Multiple Myeloma Complicated with Venous Thromboembolism].

OBJECTIVE: To analyze the clinical characteristics of venous thromboembolism (VTE) in patients with multiple myeloma (MM) and to identify the risk factors of VTE in MM patients. METHODS: 179 newly diagnosed MM (NDMM) patients admitted to The Second Hospital of Shanxi Medical University from January 2014 to December 2020 who were followed up for more than 6 months were collected, and they were divided into VTE group and control group according to whether combined with VTE. The clinical and laboratory data were compared between the two groups. Mann-whitney U test was used for inter-group comparison of measurement data, Chi-square test or Fisher's exact test was used for inter-group comparison of count data, and multivariate logistic regression analysis was performed to explore the risk factors of VTE in MM patients. RESULTS: Compared with control group, the serum albumin (ALB) level in VTE group was significantly lower (P =0.033), the fibrinogen (FIB) level was significantly higher (P =0.016), and the proportion of patients with D-dimer≥2 000 ng/ml was significantly higher than that in the control group (26.3% vs 4.4%, P =0.002). There was a significant difference in M-component type between the two groups (P =0.028), and the proportion of IgG type in VTE group was higher. There were no statistically significant differences between two groups in age, sex, body mass index (BMI), the proportions of patients with hypertension, diabetes, coronary heart disease and cerebral infarction, white blood cell (WBC) count, platelet (PLT) count, liver and kidney function, plasma cells ratio in bone marrow, serum globulin (GLO), lactate dehydrogenase (LDH), ß2-microglobulin (ß2-MG) level, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), prothrombin time (PT), activated partial thromboplastin time (APTT), disease stage, thrombosis prevention and the use of immunomodulators (P >0.05). Multivariate logistic regression analysis showed that FIB level (OR=1.578, 95%CI:1.035-2.407, P =0.034), D-dimer≥2 000 ng/ml (OR=5.467, 95%CI:1.265-23.621, P =0.023) and IgG type (OR=4.780, 95%CI: 1.221-18.712, P =0.025) were independent risk factors for VTE in MM patients. CONCLUSION: MM patients are prone to VTE, and FIB level, D-dimer≥2 000 ng/ ml and IgG type are independent risk factors for VTE in MM patients.

Exudative pleural effusion caused by lung fluke infection: A practical diagnostic approach.

OBJECTIVES: Pleural effusion caused by lung fluke is a rare etiology of exudative pleural effusion (EPE), which is often misdiagnosed or delayed. We aim to summarize the diagnosis and treatment course of EPE caused by lung fluke infection and put forward a practical diagnosis approach. METHODS: We retrospectively analyzed the diagnosis and treatment of 14 cases of EPE caused by lung fluke infection diagnosed by enzyme-linked immunosorbent assay of serum antibodies or egg detection. RESULTS: All patients (100%) with an absolute count of eosinophils in peripheral blood exceeded 0.5 × 109/l, and 10 patients (71.4%) had a history of special ingestion. Eosinophilic PE occurred in 11 patients (78.6%), pleural biopsy of medical thoracoscopic demonstrated eosinophils infiltration in nine patients (64.3%), and parasite eggs in one patient. All patients showed positive intradermal tests for Paragonimus-specific antigens and enzyme-linked immunosorbent assay of serum antibodies to Paragonimus. CONCLUSION: For patients with unexplained PE, lung fluke infection should be highly suspected when pleural fluid or pleural biopsy shows eosinophilic PE or eosinophils infiltration, especially for patients with certain diet history.

Helicobacter pylori infection selectively attenuates endothelial function in male mice via exosomes-mediated ROS production.

Background: Substantial sex differences exist in atherosclerosis. Excessive reactive oxygen species (ROS) formation could lead to endothelial dysfunction which is critical to atherosclerosis development and progression. Helicobacter pylori (H. pylori) infection has been shown to attenuate endothelial function via exosomes-mediated ROS formation. We have demonstrated that H. pylori infection selectively increases atherosclerosis risk in males with unknown mechanism(s). The present study was to test the hypothesis that H. pylori infection impaired endothelial function selectively in male mice through exosome-mediated ROS formation. Methods and results: Age-matched male and female C57BL/6 mice were infected with CagA+ H. pylori to investigate sex differences in H. pylori infection-induced endothelial dysfunction. H. pylori infection attenuated acetylcholine (ACh)-induced endothelium-dependent aortic relaxation without changing nitroglycerine-induced endothelium-independent relaxation in male but not female mice, associated with increased ROS formation in aorta compared with controls, which could be reversed by N-acetylcysteine treatment. Treatment of cultured mouse brain microvascular endothelial cells with exosomes from H. pylori infected male, not female, mice significantly increased intracellular ROS production and impaired endothelial function with decreased migration, tube formation, and proliferation, which could be prevented with N-acetylcysteine treatment. Conclusions: H. pylori infection selectively impairs endothelial function in male mice due to exosome-mediated ROS formation.

Ultrathin Carbon Nitride Nanosheets Exfoliated and In Situ Modified with a Nickel Bis(Chelate) Complex for Boosting Photocatalytic Performances.

Exfoliation and interfacial modification of two-dimensional (2D) polymeric carbon nitride (CN) are considerably vital for applications in photo/electrocatalysis fields. Here, a grinding-ultrasonic route was designed to construct nickel bis(chelate) complex (Ni(abt)2, abt = 2-aminobenzenethiolate)-modified CN ultrathin nanosheets. Under the assistance of the shear force derived from the grinding process, Ni(abt)2 was implanted into the interlamination of bulk CN, resulting in the formation of ultrathin CN (UCN) nanosheets. Simultaneously, Ni(abt)2 molecules were anchored on the surfaces of as-formed UCN nanosheets due to the π-π stacking interaction. Interestingly, compared with single Ni(abt)2 and UCN, the as-obtained Ni(abt)2/UCN nanosheets exhibited excellent photocatalytic hydrogen evolution capability. A molecule-semiconductor internal electron transmission mechanism was suggested for explaining the separation and transfer of electron-hole pairs. Density functional theory (DFT) calculations demonstrated that the interface-induced electron redistribution tuned the electron density and hydrogen adsorption of the active centers, thus enhancing the photocatalytic performance of the hybrid catalyst. In addition, the as-obtained Ni(abt)2/UCN nanosheets could also catalyze the reduction of nitroaromatics in the presence of NaBH4. It was found that under the simulated sunlight irradiation, the conversion efficiency of nitroaromatic compounds to amino aromatic ones was up to 97.3%, far higher than that under the condition without light irradiation (51.7%), suggesting that the photocatalytic-produced hydrogen took part in the reduction of nitroaromatic compounds.

Rapid on-site evaluation of touch imprints of medical thoracoscopy biopsy tissue for the management of pleural disease.

Background and objective: Medical thoracoscopy (MT) plays an important role in the diagnosis and treatment of pleural diseases, and rapid on-site evaluation (ROSE) has long been used for transbronchial needle aspiration or fine-needle aspiration to evaluate the adequacy of biopsy materials for the diagnosis of peripheral lung lesions. However, research on ROSE combined with MT for the management of pleural disease has been rarely reported. We aimed to evaluate the diagnostic performance of ROSE for pleura biopsies and visual diagnosis by thoracoscopists for gross thoracoscopic appearance. The secondary objective was to assess the intermodality agreement between ROSE and the final histopathologic diagnosis. Methods: A total of 579 patients with exudative pleural effusion (EPE) who underwent MT combined with ROSE from February 2017 to December 2020 at Taihe Hospital were included in the study. Thoracoscopists' visual diagnosis of gross thoracoscopic appearance, ROSE results, histopathologic findings, and the final diagnosis was recorded. Results: Thoracoscopic pleural biopsies were performed in 565 patients (97.6%); 183 patients were confirmed to have malignant pleural effusion (MPE), and 382 patients were confirmed to have benign pleural effusion (BPE). The area under the curve of ROSE for the diagnosis of MPE was 0.96 (95% CI: 0.94-0.98, p < 0.001), with a sensitivity of 98.7%, a specificity of 97.2%, a diagnostic accuracy of 97.1%, a positive predictive value of 97.2%, and a negative predictive value of 97.2%. Diagnostic consistency between ROSE and histopathology was good (κ ± SE = 0.93 ± 0.02, p < 0.001). The area under the curve of the thoracoscopists' visual diagnosis of gross thoracoscopic appearance was 0.79 (95% CI: 0.75-0.83, p < 0.01), with a sensitivity of 76.7%, a specificity of 80.9%, a positive predictive value of 62.4%, and a negative predictive value of 89.3%. Conclusion: ROSE of touch imprints of MT biopsy tissue during MT showed high accuracy for distinguishing between benign and malignant lesions. In addition, ROSE was in good agreement with the histopathological diagnosis, which may help thoracoscopists perform pleurodesis (talc poudrage) directly during the procedure, especially in patients with malignant results.

[Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. METHODS: A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ï¼»66 cases of them were screened by propensity score matching (PSM), as control groupï¼½. The early efficacy and survival between the two groups were compared. RESULTS: The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. CONCLUSION: Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Magnetic tubular nickel@silica-graphene nanocomposites with high preconcentration capacity for organothiophosphate pesticide removal in environmental water: Fabrication, magnetic solid-phase extraction, and trace detection.

Organothiophosphate pesticides (OPPs) are the most common water contaminants, significantly endangering human health and bringing serious public safety issues. Thus, developing effective technologies for the removal or trace detection of OPPs from water is urgent. Herein, a novel graphene-based silica-coated core-shell tubular magnetic nanocomposite (Ni@SiO2-G) was fabricated for the first time and used for the efficient magnetic solid-phase extraction (MSPE) of the OPPs chlorpyrifos, diazinon, and fenitrothion from environmental water. The experimental factors affecting extraction efficiency such as adsorbent dosage, extraction time, desorption solvent, desorption mode, desorption time, and adsorbent type were evaluated. The synthesized Ni@SiO2-G nanocomposites showed a higher preconcentration capacity than the Ni nanotubes, Ni@SiO2 nanotubes, and graphene. Under the optimized conditions, 5 mg of tubular nano-adsorbent displayed good linearity within the range of 0.1-1 µg·mL-1, low limits of detection (0.04-0.25 pg·mL-1), low limits of quantification (0.132-0.834 pg·mL-1), good reusability (n = 5; relative standard deviations between 1.46% and 9.65%), low dosage (5 mg), and low real detection concentration (< 3.0 ng·mL-1). Moreover, the possible interaction mechanism was investigated by density functional theory calculation. Results showed that Ni@SiO2-G was a potential magnetic material for the preconcentration and extraction of formed OPPs at ultra-trace levels from environmental water.