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Yi-Lun Ge,1,&ast; Si-Yi Gong,1,&ast; Pu-Zhi Wang,1 Jia-Hui Yan,1 Wen Li,1 Jin-Ru Zhang,1 Hong Jin,1 Sheng Zhuang,1 Lei Hu,2 Chang-Wei Ding,2 Ya-Ping Yang,1 Fen Wang,3 Dan Li,4 Jing Chen,1 Cheng-Jie Mao,1,4 Ying-Chun Zhang,2 Kai Li,1 Chun-Feng Liu1,3,4 1Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Ultrasound, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 4Department of Neurology, Suqian First Hospital, Suqian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Li, Department of Neurology, the Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, Jiangsu, 215004, People’s Republic of China, Tel +86-512-6778-4179, Fax +86-512-6828-4303, Email liskai@126.comPurpose: Cognitive impairment (CI) is a common but debilitating non-motor symptom in Parkinson’s disease (PD). Although cerebrovascular functions are related to cognitive performance in healthy individuals, such a relation in PD remains elusive. This study aims to assess the association between cerebrovascular function and cognitive performance in PD individuals.Patients and Methods: Two-hundred-and-one PD individuals were retrospectively included. They were subsequently divided into two groups: PD with normal cognition (PD-NC) and PD with CI (PD-CI). Cerebral hemodynamic characteristics of the middle cerebral arteries were assessed by transcranial ultrasound. The association between scores in each cognitive domain and cerebral hemodynamic parameters was further analyzed using regression analyses. Additionally, a binary logistic regression model with backward stepwise procedure was applied to build the model for discriminating CI in PD individuals. An independent dataset of additional 46 PD individuals was used further.Results: The PD-CI group showed a relatively lower end-diastolic blood flow velocity (EDV, p < 0.05) and a higher resistive index (RI, p < 0.05) compared to the PD-NC group. RI showed significant associations with the memory item score of Montreal Cognitive Assessment (p < 0.05). A model combining clinical and hemodynamic variables was established with optimal efficiency (area under the curve, AUC = 0.651). Further replication of the model in an independent dataset yielded a great consistency (AUC = 0.704).Conclusion: In our study, cerebrovascular functions were significantly associated with the cognitive performance in PD individuals, especially with the memory task. The established model was effective in identifying CI in PD individuals, which might be a potentially useful tool to screen the cognitive decline in PD individuals at an early stage of the disease. Further studies with larger sample sizes in different populations are warranted.Keywords: Parkinson’s disease, cognitive impairment, transcranial ultrasound, resistive index

Xiao-Xia Yu,1,* Ke-Li Ge,2,* Ning Liu,3 Jin-Yu Zhang,1 Mei-Lan Xue,1 Yin-Lin Ge1 1Department of Biochemistry and Molecular Biology, Basic Medical College, Qingdao University, Qingdao, Shandong Province 266071, People’s Republic of China; 2Integrative Medicine Research Center, Medical College, Qingdao University, Qingdao 266021, Shandong Province, People’s Republic of China; 3Department of Dermatology, Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yin-Lin GeDepartment of Biochemistry and Molecular Biology, Basic Medical College, Qingdao University, 308 Ningxia Road, Qingdao 266071, People’s Republic of ChinaEmail geyinlin@126.comBackground: The efficacy of traditional therapeutic methods for liver cancer is unsatisfying because of the poor targeting, and inefficient drug delivery system. A recent study has proven that aptamers, developed through cell-SELEX, could specifically recognize cancer cells and show great potential in the development of a delivery system for anticancer drugs.Purpose: To develop a hepatocellular carcinoma specific aptamer using two kinds of hepatocellular carcinoma cell lines, HepG2 and SMMC-7721, as double targets and a normal hepatocyte, L02, as a negative control cell.Methods: Hepatocellular carcinoma specific aptamer was developed via cell-SELEX. The enrichment of the library was monitored by flow cytometric analysis. The specificity, affinity, and distribution of the candidate aptamer were explored. Further study was carried to assess its potential in drug delivery.Results: The library was enriched after 14 rounds of screening. Candidate aptamer Apt-07S can recognize four kinds of hepatocellular carcinoma cells and show little cell-binding ability to normal cells and four cell lines of different cancer types, revealing a high specificity of Apt-07S. Confocal imaging showed that Apt-07S distributed both on the surface and in the cytoplasm of the two target cells. Moreover, an anti-sense nucleotide to gene Plk1 (ASO-Plk1) was connected at the 3ʹ end of Apt-07S to form an integrated molecule (Apt-07S-ASO-Plk1); the functional analysis indicated that the structure of Apt-07S may help ASO-Plk1 enter the cancer cells.Conclusion: The study indicates that Apt-07S can specifically target HCC and may have potential in the delivery of anticancer drugs.Keywords: aptamer, cell-SELEX, hepatocellular carcinoma, double target

Background: Thyroid gland metastasis from distant primary tumors is uncommon, with liver cancer being a particularly rare source. This case report describes the clinical challenges and diagnostic journey of a thyroid mass in a patient with chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma, underscoring the rarity and complexity of such metastatic relationships., Case Presentation: A 63-year-old male with a long-standing history of hepatitis B-related liver cirrhosis and a recent diagnosis of hepatocellular carcinoma presented with a rapidly enlarging painful right-sided thyroid mass associated with swelling but no systemic symptoms such as fever or dysphonia. This prompted a thorough diagnostic workup. Enhanced neck scans indicated a mass potentially originating from the thyroid with tracheal compression, yet crucially, there was no evidence of lung involvement based on the chest CT. Despite the rarity of liver-to-thyroid metastasis, the patient's multifaceted medical history warranted a broad differential diagnosis., Intervention and Outcome: Surgical intervention included a right-sided thyroidectomy and partial left thyroidectomy under general anesthesia. Histopathological examination unexpectedly confirmed the presence of metastatic thyroid cancer originating from the primary liver tumor. This led to further extensive surgical management, including lymph node dissection in the central neck area. The postoperative regimen was adapted to include thyroid hormone replacement and ongoing treatment for hepatocellular carcinoma. The patient's postoperative recovery was closely monitored, reflecting stable disease with no immediate complications., Conclusion: This case highlights the clinical rarity and diagnostic challenges of liver cancer metastasizing to the thyroid. It emphasizes the need for vigilance in patients with known primary malignancies, especially hepatocellular carcinoma, presenting with new thyroid abnormalities. This advocates for a comprehensive diagnostic approach in such atypical presentations., Competing Interests: The authors declare that they have no conflicts of interest., (© 2024 Ge et al.)

Background: Tuberculous pleurisy (TP) is one of the most common types of extrapulmonary tuberculosis, often secondary to tuberculosis (TB). Clinical and imaging manifestations of non-tuberculous mycobacterial pulmonary diseases (NTM-PD) are usually similar to those of tuberculosis. Because of their similarity and the high incidence of tuberculosis, non-tuberculous mycobacterial infections are often overlooked for a long time. Especially in people without immunodeficiency., Methods: Mycobacterium tuberculosis (MTB) in pleural effusion was found by metagenomic next-generation sequencing (mNGS). During anti-tuberculosis treatment, mNGS of lung tissue by ultrasound-guided percutaneous lung puncture revealed that this patient had combined NTM-PD., Results: Mycobacterium chelonae (M. chelonae) was detected by mNGS, and after anti-NTM treatment, the patient's chest CT showed that the inflammation was absorbed more than before, and the patient's symptoms improved., Conclusions: When TB is poorly treated with standardized anti-tuberculosis therapy, comorbid non-tuberculous mycobacterial infections may be considered, and mNGS may complement traditional pathogenetic testing.

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE., (© 2024. The Author(s).)

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.

Background: As an opportunistic pathogenic fungus, Schizophyllum has been rarely reported to infect humans. By reporting a case of definite diagnosis of Schizophyllum infection, we aim to improve clinicians' understanding of this bacterium., Methods: By reporting a case with cough and sputum as the main manifestations, after empirical antiinfective chest CT suggesting a more progressive inflammatory lesion and a mass-like lesion in the paratracheal area of the main airways, a diagnosis of Schizophyllum infection was finally made by bronchoscopy with the delivery of metagenomic next-generation sequencing (mNGS)., Results: The patient was finally diagnosed with rare Schizophyllum infection. After antifungal treatment, the symptoms improved, and the patient was discharged., Conclusions: Although Schizophyllum is a rare fungal infection, it should be taken seriously in patients with diabetes or who are immunocompromised. At the same time, mNGS plays a key role in the detection of rare and emerging pathogens, which is worthy of clinical interest.

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.

Background: Pulmonary mucormycosis is most common in patients with hematologic malignancies and transplant recipients. This article describes a case of mucormycosis in the lungs secondary to a hematologic disorder with suspected lung cancer., Methods: Rhizopus (Rhizopus microspores) was detected by blood NGS and bronchoalveolar lavage fluid NGS, and pulmonary mucormycosis was confirmed., Results: Secondary to hematologic disease, pulmonary pneumonia, mycosis, and symptoms improved after comprehensive treatment., Conclusions: Clinical data and radiologic knowledge are combined to diagnose invasive pulmonary mycoses; early empirical medicine is very important.

Background: Respiratory syncytial virus (RSV) is a single-stranded RNA virus that commonly causes symptoms of upper respiratory tract infections in humans, with a clear seasonal trend. However, in immunocompromised and elderly patients, RSV infections still result in high rates of hospitalization and even risk of death., Methods: We report a case of RSV infection in an adult with immunodeficiency, which initially showed only mild symptoms of upper respiratory tract infection, which did not improve after receiving empirical anti-infective treatment, and the foci of infection in the lungs continued to expand, which led to the aggravation of the disease. The diagnosis of RSV infection was finally confirmed by electron bronchoscopy and pathogenetic examination of the bronchoalveolar lavage fluid. The patient was given intravenous ribavirin treatment for one week. After one week of intravenous ribavirin treatment, the patient's symptoms improved significantly. A repeat chest CT suggested that the lung lesions were smaller than before. In order to improve clinicians' awareness of this disease, we jointly conducted a literature analysis., Results: The final diagnosis of RSV was made by analyzing the patient's history, symptoms, and signs and performing relevant examinations., Conclusions: For patients with poor results of empirical application of antibiotics, electronic bronchoscopy and pathogenetic examination should be carried out at an early stage to clarify the nature of the lesions and to avoid rapid deterioration of the condition leading to life-threatening conditions in the patients. More consideration should be given to the possibility of disease diagnosis to avoid misdiagnosis and underdiagnosis, and appropriate treatment should be given at an early stage.

The fermentation process has a significant impact on the aromatic profile of wines, particularly in relation to the difference in fermentation matrix caused by grape varieties. This study investigates the leaching and evolution patterns of aroma compounds in Vitis vinifera L. Marselan and Merlot during an industrial-scale vinification process, including the stages of cold soak, alcohol fermentation, malolactic fermentation, and one-year bottle storage. The emphasis is on the differences between the two varieties. The results indicated that most alcohols were rapidly leached during the cold soak stage. Certain C6 alcohols, terpenes, and norisoprenoids showed faster leaching rates in 'Marselan', compared to 'Merlot'. Some branched chain fatty-acid esters, such as ethyl 3-methylbutyrate, ethyl 2-methylbutyrate, and ethyl lactate, consistently increased during the fermentation and bottling stages, with faster accumulation observed in 'Marselan'. The study combines the Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) model based on odor activity values to elucidate the accumulation of these ethyl esters during bottle storage, compensating for the reduction in fruity aroma resulting from decreased levels of ( E )- β -damascenone. The 'Marselan' wine exhibited a more pronounced floral aroma due to its higher level of linalool, compared to the 'Merlot' wine. The study unveils the distinctive variation patterns of aroma compounds from grapes to wine across grape varieties. This provides a theoretical framework for the precise regulation of wine aroma and flavor, and holds significant production value.

To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of Streptococcus agalactia e from respiratory specimen sources. A total of 35 strains of S.agalactiae meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients≥60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly erm B, with a carrying rate of 74.2%; tetracycline resistance genes were mainly tet M, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants gyr A and par C were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, alpha , alp 1, rib , srr , and r df &#95;0594, and seven virulence factors, cba, cfb, cyl E, fbs A, hyl B, l mb , and pav A. Overall, S.agalactiae isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by S. agalactiae from respiratory tract speciments of elderly patients.

Aiming for clarifying the potential distribution characteristics of canopy rainfall partitioning of the loess area, we explored the process of rainfall partitioning across eight typical forest stands ( Pinus tabuliformis forest, Robinia pseudoacacia forest, Platycladus orientalis forest, mixed forest of Robinia pseudoacacia - Pinus tabuliformis , mixed forest of Platycladus orientalis - Robinia pseudoacacia , Quercus wutaishanica forest, Populus davidiana forest, mixed forest of Quercus wutaishanica - Populus davidiana ), and used boosted regression trees (BRT) to quantify the relative influences of stand structures and meteorological environment factors. We established multiple regression relationships according to the most influential factors extracted by BRT, and applied to the dataset of mining to verify the performance of the BRT-derived predictive model. The results showed that the percentages of throughfall (TF), stemflow (SF), and canopy interception ( I c ) in total precipitation were 24.5%-95.1%, 0-13.6%, and 0.7%-55.7% among eight typical forest stands, respectively. For the individual rainfall threshold of TF, coniferous forest (3.06±1.21 mm) was significantly higher than broad-leaved forest (1.97±0.52 mm), but there was no significant difference between coniferous forest and broad-leaved mixed forest (3.01±0.98 mm). There was no significant difference in the individual rainfall threshold of SF among different composition stands. BRT analysis showed that stand structure factors accounted for a relatively small proportion for TF and SF, respectively. By contrast, stand structure factors dominated the I c . Rainfall was the most important factor in determining TF and SF. Tree height was the most important factor in determining I c , followed by rainfall, canopy area, diameter at breast height, and stand density. Compared with the general linear function and the power function, the prediction effect of BRT prediction model constructed here on TF and SF had been further improved, and the prediction of canopy interception still needed to explore. In conclusion, the BRT model could better quantitatively evaluate the effects of stand structure and meteorological environmental factors on rainfall partitioning components, and the performance of the BRT predictive model could satisfy and lay the foundation for the optimization strategy for stand configuration.

Background: IgG4-related disease (IgG4-RD) is an immune-mediated systemic inflammatory fibrotic disease, which is a relatively rare and novel disease that can involve multiple organs or tissues, with variable clinical manifestations, and for which pulmonary involvement has been reported relatively infrequently., Methods: Here we report a case of pulmonary infection that was initially suspected and received anti-inflammatory treatment, but the symptoms did not improve. CT examination indicated progression of the pulmonary lesion, and the nature of the lesion could not be determined by tracheoscopy and bronchoalveolar lavage. The diagnosis of IgG4 related lung disease (IgG4-RLD) was confirmed by percutaneous lung biopsy. A joint literature analysis was conducted to improve clinicians' understanding of this disease., Results: The patient's history, symptoms, signs and relevant examination results were analyzed. The final diagnosis was IgG4-RLD., Conclusions: When the clinical symptoms and imaging manifestations of the patients are consistent with IgG4-RLD, pathological examination can be appropriately performed to clarify the nature of the lesions. More consideration should be given to the possibility of disease diagnosis to avoid misdiagnosis and underdiagnosis, and proper treatment should be given at an early stage.

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.

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.

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.

Background: Invasive pulmonary aspergillosis (IPA) is a deep fungal infection caused by invasion of Aspergillus mycelium into the lung parenchyma resulting in tissue destruction and necrosis, which occurs more often in im-munosuppressed populations. The severity of the disease and the rapid progression of the lung lesions puts pa¬tients at high risk of death and poor prognosis if the correct therapeutic intervention is not given as early as possible., Methods: Here we report a case of IPA, which was initially diagnosed as community-acquired pneumonia in a local hospital. The symptoms did not improve after receiving anti-infective treatment. The patient was diagnosed with IPA after completing a chest CT examination and an electronic bronchoscopy, as well as pathogenetic examination of the bronchoalveolar lavage fluid and pathological examination of the left bronchial mass in the respiratory department of our hospital, which was finally diagnosed as IPA. After one week of administration of voriconazole for anti-fungal infection treatment, the patient's symptoms improved significantly, and a repeat chest CT suggested that the lung lesions were better than before. In order to raise clinicians' awareness of this disease, we also conducted a literature analysis., Results: The final diagnosis of IPA was made by analyzing the patient's history, symptoms, signs, and relevant findings., Conclusions: When the patient's clinical symptoms and imaging manifestations are consistent with IPA, electronic bronchoscopy and pathogenetic and pathological examinations may be appropriately performed to clarify the na-ture of the lesion. More consideration should be given to the possibility of disease diagnosis to avoid misdiagnosis and underdiagnosis. Appropriate treatment should be given at an early stage.

Background: Organizing pneumonia (OP) is a pathologic diagnosis with clinical and imaging manifestations that often resemble other diseases, such as infections and cancers, which can lead to delays in diagnosis and inappropriate management of the underlying disease. In this article, we present a case of organized pneumonia that resembles lung cancer., Methods: We report a case of initial suspicion of pulmonary malignancy, treated with anti-inflammatory medication and then reviewed with CT suggesting no improvement, and finally confirmed to be OP by pathological biopsy taken via transbronchoscopy. A joint literature analysis was performed to raise clinicians' awareness of the diagnosis and treatment of OP., Results: Initially, because of the atypical auxiliary findings, we thought that the disease turned out to be a lung tumor, which was eventually confirmed as OP by pathological diagnosis., Conclusions: The diagnosis and treatment of OP requires a combination of clinical information and radiological expertise, as well as biopsy to obtain histopathological evidence. That is, clinical-imaging-pathological tripartite cooperation and comprehensive analysis.

Background: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the normalization of COVID-19 globally, it is crucial to construct a prediction model that enables clinicians to identify patients at risk for ProLOS based on demographics and serum inflammatory biomarkers., Methods: The study included hospitalized patients with a confirmed diagnosis of COVID-19. These patients were randomly grouped into a training (80%) and a test (20%) cohort. The LASSO regression and ten-fold cross-validation method were applied to filter variables. The training cohort utilized multifactorial logistic regression analyses to identify the independent factors of ProLOS in COVID-19 patients. A 4-variable nomogram was created for clinical use. ROC curves were plotted, and the area under the curve (AUC) was calculated to evaluate the model's discrimination; calibration analysis was planned to assess the validity of the nomogram, and decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model., Results: The results showed that among 310 patients with COVID-19, 80 had extended hospitalization (80/310). Four independent risk factors for COVID-19 patients were identified: age, coexisting chronic respiratory diseases, white blood cell count (WBC), and serum albumin (ALB). A nomogram based on these variables was created. The AUC in the training cohort was 0.808 (95% CI: 0.75 - 0.8671), and the AUC in the test cohort was 0.815 (95% CI: 0.7031 - 0.9282). The model demonstrates good calibration and can be used with threshold probabilities ranging from 0% to 100% to obtain clinical net benefits., Conclusions: A predictive model has been created to accurately predict whether the hospitalization duration of COVID-19 patients will be prolonged. This model incorporates serum WBC, ALB levels, age, and the presence of chronic respiratory system diseases.

Aims: Parkinson's disease (PD), as the second most common neurodegenerative disorder, often presents diagnostic challenges in differentiation from other forms of Parkinsonism. Recent studies have reported an association between plasma glycoprotein nonmetastatic melanoma protein B (pGPNMB) and PD., Methods: A retrospective study was conducted, comprising 401 PD patients, 111 multiple system atrophy (MSA) patients, 13 progressive supranuclear palsy (PSP) patients and 461 healthy controls from the Chinese Han population, with an assessment of pGPNMB levels., Results: The study revealed that pGPNMB concentrations were significantly lower in PD and MSA patients compared to controls (area under the receiver operating characteristics curve (AUC) 0.62 and 0.74, respectively, P < 0.0001 for both), but no difference was found in PSP patients compared to controls (P > 0.05). Interestingly, the level of pGPNMB was significantly higher in PD patients than in MSA patients (AUC = 0.63, P < 0.0001). Furthermore, the study explored the association between pGPNMB levels and disease severity in PD and MSA patients, revealing a positive correlation in PD patients but not in MSA patients with both disease severity and cognitive impairment., Conclusion: This study successfully replicated prior findings, demonstrating an association between pGPNMB levels and disease severity, and also identified a correlation with cognitive impairment in PD patients of the Chinese Han population. Additionally, this study is the first to identify a significant difference in pGPNMB levels between MSA, PD, and normal controls. The data provide new evidence supporting the potential role of pGPNMB in the diagnosis and differential diagnosis of Parkinsonism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As the representative item of environmental chemical carcinogen, MNNG was closely associated with the onset of Gastric cancer (GC), while the underlying mechanisms remain largely unknown. Here, we comprehensively analyzed the potential clinical significance of METTL3 in multiple GC patient cohorts. Additionally, we demonstrated that long-term exposure to MNNG elevated METTL3 and EMT marker expression by in vitro and in vivo models. Furthermore, the depletion of METTL3 impacted the proliferation, migration, invasion, and tumorigenesis of MNNG malignant transformation cells and GC cells. By me-RIP sequencing, we identified a panel of vital miRNAs potentially regulated by METTL3 that aberrantly expressed in MNNG-induced GC cells. Mechanistically, we showed that METTL3 meditated miR-1184/TRPM2 axis by regulating the process of miRNA-118. Our results provide novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Sympatric distribution and temporal overlap of cryptic zooplankton species pose a challenge to the framework of the niche differentiation theory and the mechanisms allowing competitor coexistence. We applied the methods of phylogenetic analysis, DNA taxonomy, and statistical analysis to study the temporal distribution patterns of the cryptic B. calyciflorus species, an excellent model, in three lakes, and to explore the putative mechanisms for their seasonal succession and temporal overlap. The results showed that in the warm-temperate Lake Yunlong, B . fernandoi and B . calyciflorus s.s. underwent a seasonal succession, which was largely attributed to their differential adaptation to water temperature. In the subtropical Lake Jinghu, B . fernandoi , B . calyciflorus s.s., and B. dorcas exhibited both seasonal succession and temporal overlap. Seasonal successions were largely attributed to their differential adaptation to temperature, and temporal overlap resulted from their differential responses to algal food concentration. In the tropical Lake Jinniu, B . calyciflorus s.s. persisted throughout the year and overlapped with B. dorcas for 5 months. The temporal overlap resulted from their differential responses to copepod predation. These results indicated that the temporal distribution pattern of the cryptic B. calyciforus species and the mechanism that allows competitor coexistence vary with different climate zones.

Microcystins (MCs) can cause reproductive and developmental toxicity and disrupt endocrine homeostasis in mammals. In the present study, male, Sprague-Dawley (SD) rats were administrated 3 or 30 μg MC-LR/kg, body mass (bm) per day via intraperitoneal (i.p.) injections for 6 weeks. Effects of MC-LR on histology, hormone concentrations, gene transcriptional profiles and protein expressions along the hypothalamic-pituitary-adrenal (HPA), -gonad (HPG) and -thyroid (HPT) axes were assessed. Sub-chronic administration with MC-LR caused histological damage to hypothalamus, pituitary, adrenal, testes and thyroid and affected relative masses of pituitary, adrenal and testes. The HPA axis was activated and serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were significantly augmented. Along the HPG axis, serum concentrations of gonadotropin-releasing hormone (GnRH) and dihydrotestosterone (DHT) were diminished, while concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and estradiol (E2) were augmented. For the HPT axis, only concentrations of free tetra-iodothyronine (fT4) were significantly diminished, while concentrations of thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH) or free tri-iodothyronine (fT3) were not significantly changed. Also, several genes and proteins related to synthesis of steroid hormones were significantly altered. Findings of the present study illustrate that MC-LR can cause endocrine-disrupting effects through the disruption of synthesis and secretion of hormones along the HPA, HPG and HPT axes and negative feedback regulation. Also, there could be crosstalk among HPA, HPG and HPT axes. These findings elucidate mechanisms of endocrine-disrupting effects of MCs., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Dietary restriction (DR) is cited as the most reliable means of extending life span in a wide range of taxa, yet the evolutionary basis of the DR effect on life span remains unclear. The resource reallocation hypothesis proposes that the longevity-extending response of DR is adaptive and stems from the reallocation of resources from reproduction to somatic maintenance under food-limited conditions. However, if DR continues for multiple generations, such a response becomes maladaptive, and genotypes with higher fecundity should be selectively favored over genotypes with longer longevity. To test this prediction, we exposed replicate populations of the rotifer Brachionus dorcas, a model organism for aging and experimental evolution studies, to DR and ad-libitum (AL) diets for 100 days. During the selection experiment, AL-selected populations showed higher growth rates and mictic ratios than DR-selected populations. After approximately 27 asexual generations of selection, populations with a DR selection history had a higher net reproductive rate but lower body volume and ingestion rate in the absence of survival costs than populations with an AL selection history when they were assayed on an AL diet. Our results are inconsistent with the prediction that evolution on sustained DR increases reproduction and reduces life span, and show for the first time that sustained DR selects for clones with higher energy investment in reproduction but lower investment in somatic growth., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: PLA2G6-associated neurodegeneration (PLAN) can be categorized into infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (aNAD), neurodegeneration with brain iron accumulation (NBIA), and early-onset parkinsonism (EOP)., Objectives: To determine the genotype-phenotype association in PLAN., Methods: "PLA2G6" or "PARK14" or "phospholipase A2 group VI" or "iPLA2β" were searched across MEDLINE from June 23, 1997, to March 1, 2023. A total of 391 patients were identified, and 340 patients of them were finally included in the assessment., Results: The loss of function (LOF) mutation ratios were significantly different (p < 0.001), highest in INAD, followed by NBIA, aNAD, and EOP. Four ensemble scores (i.e., BayesDel, VARITY, ClinPred, and MetaRNN) were assessed to predict the deleteriousness of missense mutations and demonstrated significant differences (p < 0.001). Binary logistic regression analyses demonstrated that LOF mutations were independently associated with brain iron accumulation (p = 0.006) and ataxia (p = 0.025)., Conclusions: LOF or more deleterious missense mutations are more likely to promote the development of serious phenotype of PLAN, and LOF mutations are independently associated with brain iron accumulation and ataxia., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: In general, cerebral blood flow accounts for 10-15% of cardiac output (CO), of which about 75% is delivered through the carotid arteries. Hence, if carotid blood flow (CBF) is constantly proportional to CO with high reproducibility and reliability, it would be of great value to measure CBF as an alternative to CO. The aim of this study was to investigate the direct correlation between CBF and CO. We hypothesized that measurement of CBF could be a good substitute for CO, even under more extreme hemodynamic conditions, for a wider range of critically ill patients., Methods: Patients aged 65-80 years, undergoing elective cardiac surgery were included in this study. CBF in different cardiac cycles were measured by ultrasound: systolic carotid blood flow (SCF), diastolic carotid blood flow (DCF), and total (systolic and diastolic) carotid blood flow (TCF). CO simultaneously was measured by transesophageal echocardiography., Results: For all patients, the correlation coefficients between SCF and CO, TCF and CO were 0.45 and 0.30, respectively, which were statistically significant, but not between DCF and CO. There was no significant correlation between either SCF, TCF or DCF and CO, when CO was <3.5 L/min., Conclusions: Systolic carotid blood flow may be used as a better index to replace CO. However, the method of direct measurement of CO is essential when the patient's heart function is poor.

Introduction: Levodopa-induced dyskinesia (LID) is a common motor complication in Parkinson's disease (PD). Several genes in the levodopa metabolic pathway, such as COMT, DRDx and MAO-B, were reported associated with LID. However, there has been no systematic analyses between common variants in levodopa metabolic pathway genes and LID in a large sample of the Chinese population., Methods: Through the whole exome sequencing (WES) and target region sequencing, we aimed to explore the potential associations between common single nucleotide polymorphisms (SNPs) in the levodopa metabolic pathway and LID in Chinese PD individuals. Five hundred and two PD individuals were enrolled in our study, among them, 348 individuals underwent WES, and 154 individuals underwent target region sequencing. We acquired the genetic profile of 11 genes including COMT, DDC, DRD1-5, SLC6A3, TH and MAO-A/B. We established a stepwise strategy to filter SNPs, which finally included 34 SNPs in our analyses. And we used a two-stage study, with discovery (348 individuals with WES) and the replication (all 502 individuals) to confirm our findings., Results: Among the 502 PD individuals, 104 (20.7%) were diagnosed with LID. In the discovery stage, we found that COMT rs6269, DRD2 rs6275 and DRD2 rs1076560 were associated with LID. In the replication stage, associations between the three above-mentioned SNPs and LID were still present in all 502 individuals., Conclusion: We demonstrated that in the Chinese population, COMT rs6269, DRD2 rs6275 and rs1076560 were significantly associated with LID. And rs6275 was reported associated with LID for the first time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Nutritionally unhealthy obesity is a newly introduced phenotype characterized by a combined condition of malnutrition and obesity. This study aims to explore the combined influence of obesity and nutritional status on the prevalence and outcome of hypertension., Methods: Participants collected from the National Health and Nutrition Examination Survey (NHANES) database were divided into four subgroups according to their obesity and nutritional conditions, as defined by waist circumference and serum albumin concentration. The lean-well-nourished was set as the reference group. Logistic regression models were applied to evaluate the hypertension risk. Kaplan-Meier analysis and Cox proportional hazard regression models were used to assess the survival curve and outcome risk of participants with hypertension., Results: A total of 28,554 participants with 10,625 hypertension patients were included in the analysis. The lean-malnourished group showed a lower hypertension risk (odds ratio [OR] 0.85, 95% confidence interval [CI]: 0.77-0.94), while the obese-well-nourished condition elevated the risk (OR 1.47, 95% CI: 1.3-1.67). Two malnourished groups had higher mortality risks (HR 1.42, 95% CI: 1.12-1.80 and HR 1.31, 95% CI: 1.03-1.69 for the lean and obese, respectively) than the reference group. The outcome risk of the obese-well-nourished group (HR 1.02, 95% CI: 0.76-1.36) was similar to the lean-well-nourished., Conclusion: Malnutrition was associated with a lower risk of developing hypertension in both lean and obese participants, but it was associated with a worse outcome once the hypertension is present. The lean-malnourished hypertension patients had the highest all-cause mortality risk followed by the obese-malnourished. The obese-well-nourished hypertension patients showed a similar mortality risk to the lean-well-nourished hypertension patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Wang, Ge, Wang, Sun, Chen, Su and Sun.)

Background: Community-acquired pneumonia (CAP) is a common cause of hospitalization, characterized by high mortality, morbidity, and cost and has serious human health implications. Various scoring criteria have been used to predict the severity of pneumonia, including the CURB-65 score, Pneumonia Severity Index (PSI) score, and Severe Community-Acquired Pneumonia (SCAP) score. However, these scoring criteria have shortcomings such as low sensitivity, cumbersome clinical application, and limited application. This study aimed to construct a nomogram model to predict the severity of CAP patients by blood indicators., Methods: This is a retrospective study. Patients with CAP were enrolled and then tested by routine blood, coagulation series, biochemical and inflammatory indicators, and general information such as imaging findings and disease history of the patients were recorded. The main observation was the progression of the patients' disease. Univariate analysis and binary logistic regression analysis were used to explore the independent risk factors for the severity of CAP patients, followed by plotting a nomogram to obtain the prediction model and constructing calibration curves to assess the authenticity and accuracy of the prediction model. Finally, the sensitivity, specificity, and other evaluation indexes were calculated by the receiver operating characteristic curve (ROC) to evaluate the clinical application value of the nomogram prediction model., Results: Univariate analysis and binary logistic regression analysis of 277 hospitalized patients yielded platelet to lymphocyte ratio (PLR) and serum amyloid A (SAA) as independent risk factors for the severity of CAP patients. The AUC of the nomogram model for PLR and SAA was 0.889 (95% CI 0.845 - 0.932). The sensitivity was 77.3%, and the specificity was 85.3%, which had an excellent predictive value., Conclusions: The nomogram model based on PLR and SAA to predict the severity of CAP patients has a high specificity and sensitivity.

Background: The study aimed at investigating the effectiveness of the BAP-65 score combined with D-dimer and procalcitonin (PCT) in predicting admission of acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients to the intensive care unit (ICU)., Methods: We conducted a retrospective study. We analyzed data from 369 patients over the age of 40 years ad-mitted to our hospital with AECOPD. All patients received blood routine measurements and BAP-65 score calculation on admission. Receiver operating characteristic curves (ROC) were used to assess the sensitivity and specificity of D-dimer, PCT, and BAP-65 scores and combined metrics in predicting the risk of admissions to the ICU of AECOPD patients., Results: We found that the percentage of patients with AECOPD admitted to the ICU was 32.25% (119/369). The area under the curve (AUC) of D-dimer, PCT, and BAP-65 score in individually predicting the probability of entering the ICU of AECOPD patients were 0.74 (95% CI 0.68 - 0.80), 0.83 (95% CI 0.78 - 0.88), and 0.72 (95% CI 0.66 - 0.79), respectively. The sensitivities of D-dimer, PCT, and BAP-65 score were 0.51, 0.65, and 0.52, respectively. The specificities of D-dimer, PCT, and BAP-65 score were 0.90, 0.91, and 0.92, respectively. The AUC of D-dimer and PCT combined with BAP-65 score was 0.90 (95% CI 0.86 - 0.94), the sensitivity and specificity were 0.90 and 0.80, respectively., Conclusions: D-dimer and procalcitonin improve the sensitivity of the BAP-65 score in predicting the probability of AECOPD patients entering the ICU while having a good specificity.