[Clinical efficacy and safety of liposomal amphotericin B in the salvage treatment of invasive fungal disease in patients with hematological diseases].

Objective: To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases. Methods: Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated. Results: Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg(-1)·d(-1) and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status (OR=4.337, 95% CI 1.167-16.122, P=0.029) and duration of medication (OR=1.127, 95% CI 1.029-1.234, P=0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion: L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.

A systematic review of the gut microbiome, metabolites, and multi-omics biomarkers across the colorectal cancer care continuum.

The gut microbiome and the microbial metabolome contribute to treatment efficacy and treatment outcomes across the cancer care spectrum. This study systematically reviewed the existing literature between 2007 to March 2022 to elucidate the role of gut microbiota-metabolite biomarkers in colorectal cancer (CRC) care and treatment-related outcomes. Using Covidence, all studies identified were screened by title and abstract, followed by a full-text review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and data extraction. We analysed 13 non-experimental and 9 experimental CRC studies and found that, usually, the α-diversity of the gut microbiome and short-chain fatty acids decreased in CRC patients, while amino acids (e.g. glutamate) increased in CRC patients. Correlations between specific gut microbial taxa and metabolites were identified, with amino acids, fatty acids, and glycerol positively associated with certain gut microbes. Interventions promoting gut microbes and microbial metabolites associated with better health outcomes (e.g. Bifidobacterium, Lactobacillus, butyric acid, and bile acid) can potentially promote treatment efficacy and improve cancer care outcomes. Gut microbial metabolism should be integrated into targeted cancer interventions for CRC patients, given the confirmed role of the gut microbiome and metabolome pathways across the CRC care continuum.

[Cytoplasmic light-chain immunofluorescence combined with FISH in bone marrow smears to detect cytogenetic abnormalities in multiple myeloma].

Objective: To analyze the sensitivity of cytoplasmic light-chain immunofluorescence with fluorescence in situ hybridization in bone marrow smears (new FISH) for detecting cytogenetic abnormalities in multiple myeloma (MM) . Methods: 42 MM patients admitted to the First Affiliated Hospital of Nanjing Medical University from April 2022 to October 2023 were enrolled. The patients with MM were detected by new FISH and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) or cytoplasmic immunoglobulin FISH (cIg-FISH) to analyze cytogenetic detection results using combination probes which included 1q21/1p32, p53, IgH, IgH/FGFR3 [t (4;14) ], and IgH/MAF [t (14;16) ]. Results: In 23 patients with MM, the abnormality detection rates of cIg-FISH and new FISH were 95.7% and 100.0%, respectively (P>0.05). The detection rates of 1q21+, 1p32-, p53 deletion, and IgH abnormalities by cIg-FISH and new FISH were consistent, which were 52.2%, 8.7%, 17.4%, and 65.2%, respectively. The results of the two methods further performed with t (4;14) and t (14;16) in patients with IgH abnormalities were identical. The positive rate of t (4;14) was 26.7%, whereas t (14;16) was not detected. In 19 patients with MM, the abnormality detection rates of MACS-FISH and new FISH were 73.7% and 63.2%, respectively (P>0.05). The positivity rate of 1q21+, 1p32- and IgH abnormalities detected by MACS-FISH were slightly higher than those detected by new FISH; however, the differences were not statistically significant (all P values >0.05) . Conclusion: The new FISH method has a higher detection rate of cytogenetic abnormalities in patients with MM and has good consistency with MACS-FISH and cIg-FISH.

A comprehensive molecular phylogeny of Cephalotrichum and Microascus provides novel insights into their systematics and evolutionary history.

The genera Cephalotrichum and Microascus contain ecologically, morphologically and lifestyle diverse fungi in Microascaceae (Microascales, Sordariomycetes) with a world-wide distribution. Despite previous studies having elucidated that Cephalotrichum and Microascus are highly polyphyletic, the DNA phylogeny of many traditionally morphology-defined species is still poorly resolved, and a comprehensive taxonomic overview of the two genera is lacking. To resolve this issue, we integrate broad taxon sampling strategies and the most comprehensive multi-gene (ITS, LSU, tef1 and tub2) datasets to date, with fossil calibrations to address the phylogenetic relationships and divergence times among major lineages of Microascaceae. Two previously recognised main clades, Cephalotrichum (24 species) and Microascus (49 species), were re-affirmed based on our phylogenetic analyses, as well as the phylogenetic position of 15 genera within Microascaceae. In this study, we provide an up-to-date overview on the taxonomy and phylogeny of species belonging to Cephalotrichum and Microascus, as well as detailed descriptions and illustrations of 21 species of which eight are newly described. Furthermore, the divergence time estimates indicate that the crown age of Microascaceae was around 210.37 Mya (95 % HPD: 177.18-246.96 Mya) in the Late Triassic, and that Cephalotrichum and Microascus began to diversify approximately 27.07 Mya (95 % HPD: 20.47-34.37 Mya) and 70.46 Mya (95 % HPD: 56.96-86.24 Mya), respectively. Our results also demonstrate that multigene sequence data coupled with broad taxon sampling can help elucidate previously unresolved clade relationships. Citation: Wei TP, Wu YM, Zhang X, et al. 2024. A comprehensive molecular phylogeny of Cephalotrichum and Microascus provides novel insights into their systematics and evolutionary history. Persoonia 52: 119-160. https://doi.org/10.3767/persoonia.2024.52.05 .

Evaluation indicators for access to cancer screening services: a scoping review.

OBJECTIVES: Access to health services has received increasing attention, and the International Agency for Research on Cancer (IARC) includes 'availability' as one of the indicators to evaluate cancer screening. Evaluating, monitoring, and decision-making on cancer screening depends on systematic quantitative evidence on access to cancer screening, but indicators are currently inconsistently, if they are reported at all. This can be improved by developing systematic indicators for evaluating and reporting access to cancer screening. This requires a thorough understanding of current indicators of access to cancer screening. STUDY DESIGN: Scoping review. METHODS: We completed a scoping review of studies on access to cancer screening services from 2013 to 2022. The relevant indicators were extracted, quantified, and then matched to two widely used frameworks: a universal five-dimensional conceptual framework for access to healthcare ('U5D') and a cancer-specific framework/list on the availability/use of screening indicators endorsed by the IARC. RESULTS: A total of 331 studies on access to cancer screening services were included. Based on the U5D framework, publications from supply side reported approachability (number of publications = 16), acceptability (6), availability and accommodation (44), affordability (30), and appropriateness (11); among this process, 17 sub-indicators were identified. Correspondingly, publications from demand side reported ability to perceive (170), ability to seek (85), ability to reach (58), ability to pay (59), and ability to engage (2); 26 sub-indicators were identified. More macroscopically, the publications of the IARC-endorsed indicators reported availability of policies and guidelines for screening (13), type of screening provided (3), extent of population coverage and participation rates (76), and demographic/behavioural related considerations (167). By integrating the universal and cancer-specific frameworks, a new adapted framework was proposed. CONCLUSIONS: This study identified and collated indicators for evaluating access to cancer screening services, and determined the gaps in the current application of various indicators. The findings are anticipated to facilitate further development of an evaluation indicator system for access to cancer screening services.

[Analysis of clinical characteristics and causes of death in 38 patients with pneumoconiosis].

Objective: To analyze the clinical characteristics and causes of death of patients with pneumoconiosis, and to provide evidence for the prevention and management of pneumoconiosis. Methods: From June 2022 to July 2023, 38 dead patients with pneumoconiosis confirmed by Shandong Academy of Occupational Health and Occupational Medicine were selected as the research objects. The clinical data of patients were collected through hospital information system (HIS) and laboratory information management system (LIS) to analyze the basic situation of patients with pneumoconiosis who died, the distribution of industry types, the course of disease, the nature of work, the type of reimbursement, complications/comorbidities, and the direct causes of death. Univariate analysis of variance was used to compare the course of pneumoconiosis death in patients with different age of exposure to dust. Results: Among the 38 patients with pneumoconiosis, there were 37 males and 1 female. The age of exposure to dust was 5-37 (19.29±8.17) years, the duration of disease was 5-41 (20.26±8.53) years, and the age of death was 27-86 (70.42±12.26) years old. There were 10 cases of stage Ⅰ pneumoconiosis, 18 cases of stage Ⅱ, 10 cases of stage Ⅲ pneumoconiosis and 32 cases (84.21%) of silicosis. There were 30 (78.95%) people aged ≥65 years and 8 (21.05%) people aged <65 years. The industry was mainly metal products (18 workers, 47.37%), and the distribution of work was mainly excavation workers (11 workers, 28.95%). The death course of pneumoconiosis patients with 10-<30 years of exposure to dust accounted for 76.32% (29/38). The average course of pneumoconiosis patients with 20-<30 years of exposure to dust was the longest[ (24.00±9.39) years], and there was no statistically significant difference in the average course of disease among different age of exposure to dust groups (F=1.81, P=0.165). The working units of the deceased patients were private enterprises or factories, and the hospitalization expenses were borne by individuals for 21 people (55.26%). The working unit was a state-owned enterprise, and 17 people (44.74%) were reimbursed for hospitalization expenses and work-related injuries. The main comorbidities/complications of pneumoconiosis patients were respiratory infection in 18 cases (47.37%) and chronic pulmonary heart disease (47.37%). The top 3 direct causes of death were pneumoconiosis in 13 cases (34.21%), pulmonary infection in 10 cases (26.32%) and lung cancer in 7 cases (18.42%) . Conclusion: Most of 38 cases of pneumoconiosis patients death diseases such as multiple combination of respiratory system, cardiovascular system, respiratory system disease is a major cause of death in pneumoconiosis patients.

Analysis of postoperative recurrence-free survival in non-small cell lung cancer patients based on consensus clustering.

AIMS: This study aims to assess whether consensus clustering, based on computed tomography (CT) radiomics from both intratumoral and peritumoral regions, can effectively stratify the risk of non-small cell lung cancer (NSCLC) patients and predict their postoperative recurrence-free survival (RFS). MATERIALS AND METHODS: A retrospective analysis was conducted on the data of surgical patients diagnosed with NSCLC between December 2014 and April 2020. After preprocessing CT images, radiomic features were extracted from a 9-mm region encompassing both the tumor and its peritumoral area. Consensus clustering was utilized to analyze the radiomics features and categorize patients into distinct clusters. A comparison of the differences in clinical pathological characteristics was conducted among the clusters. Kaplan-Meier survival analysis was employed to investigate differences in survival among the clusters. RESULTS: A total of 266 patients were included in this study, and consensus clustering identified three clusters (Cluster 1: n=111, Cluster 2: n=61, Cluster 3: n=94). Multiple clinical risk factors, including pathological TNM staging, programmed cell death ligand 1 (PD-L1), and epidermal growth factor receptor (EGFR) expression status exhibit significant differences among the three clusters. Kaplan-Meier survival analysis demonstrated significant variations in RFS across the clusters (P<0.001). The 3-year cumulative recurrence-free survival rates were 76.5% (95% CI: 68.6-84.4) for Cluster 1, 45.9% (95% CI: 33.4-58.4) for Cluster 2, and 41.5% (95% CI: 31.6-51.5) for Cluster 3. CONCLUSIONS: Consensus clustering of CT radiomics based on intratumoral and peritumoral regions can stratify the risk of postoperative recurrence in patients with NSCLC.

[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

[Investigation of the inhibitory potential of caffeic acid phenethyl ester on prion replication, amplification, and fibril formation in vitro].

Objective: To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrPSc). Methods: The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrPSc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrPSc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results: CCK8 cell viability assay results demonstrated that treatment with 1 µmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 µmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 µmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrPSc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrPSc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10-6 mol/L. Conclusions: CAPE inhibits PrPSc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

[Analysis of myopia status and related factors among primary school students in a certain district of Beijing City in 2022].

Objective: To analyze the current situation of myopia and its related factors among primary school students in a certain district of Beijing City in 2022, and provide a basis for the risk assessment of myopia among primary school students. Method: In June 2022, a cluster sampling method was used to include 376 third-grade students from a primary school in a certain district of Beijing. A questionnaire survey was conducted to collect basic information about students, including eye usage habits, reading and writing postures, and parents' myopia conditions. The examination of students' distant visual acuity and refractive status was performed. A multivariate logistic regression model was used to analyze the related factors of myopia occurrence. Results: The age of 376 primary school students was (8.87±0.417) years old, with 48.40% (182) being male. A total of 196 myopia cases were identified, with a myopia rate of 52.13%. The results of the multivariate logistic regression model analysis showed that students who sometimes read while lying down (OR=2.003, 95%CI: 1.128-3.555), often read while lying down (OR=18.853, 95%CI: 4.512-78.778), had outdoor activity time less than 120 minutes per day (OR=4.937, 95%CI: 2.4464-9.892), were engaged in indoor break activities (OR=4.995, 95%CI: 2.773-8.996), performed eye exercises less than once per day (OR=8.710, 95%CI: 4.464-16.995), had a reading distance from the book less than 30 cm (OR=5.098, 95%CI: 2.410-10.787), occasionally maintained a fist distance from the edge of the desk (OR=1.918, 95%CI: 1.086-3.385), and had high school desks and tables (OR=5.325, 95%CI: 1.465-19.359) could have a higher risk of myopia occurrence, compared with those who never read while lying down, had outdoor activity time more than 120 minutes per day, maintained outdoor break activities, performed eye exercises more than once per day, had a reading distance from the book more than 30 cm, always maintained a fist distance from the edge of the desk, and had short school desks and tables. Conclusion: The incidence rate of myopia among primary school students in a certain district of Beijing City. in 2022 is relatively high. The occurrence of myopia is related to insufficient outdoor activity time and poor eye usage habits.

[Efficacy of venetoclax-based induction regimen in newly diagnosed pediatric acute myeloid leukemia].

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

[Clinical management of thrombocytopenia in cirrhosis].

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

[Clinical characteristics and prognostic analysis of 34 patients with primary thyroid lymphoma].

Objective: To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) . Methods: A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors. Results: All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis (P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion: PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.