Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition,nutritional status,and quality of life,and to develop a corresponding risk prediction model.Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023,and categorized into high(n=94)and low energy metabolism group(n=38)based on their metabolic status.Differences in clinical data,body composition,Patient Generated Subjective Global Assessment(PG-SGA)scores,and European Organization for Research and treatment of Cancer(EORTC)Quality of Life Questionnaire-Core 30(QLQ-C30)scores were compared between the two groups.Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients,and a risk prediction model was established accordingly;the Hosmer-Lemeshow test was used to assess the model fit,and the ROC curve was used to test the predictive efficacy of the model.Results Of the 132 patients with primary lung cancer,94(71.2%)exhibited high energy metabolism.Compared with low energy metabolism group,patients in high-energy metabolism group had a smoking index of 400 or higher,advanced disease staging of stage Ⅲ or Ⅳ,and higher levels of IL-6 level,low adiposity index,low skeletal muscle index,and malnutrition(P<0.05),and lower levels of total protein,albumin,hemoglobin level,and prognostic nutritional index(PNI)(P<0.05).There was no significant difference in age,gender,height,weight,BMI and disease type between the two groups(P>0.05).Logistic regression analysis showed that smoking index≥400,advanced disease stage,IL-6≥3.775 ng/L,and PNI<46.43 were independent risk factors for high energy metabolism in lung cancer patients.The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904).Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).
Humans ; Antineoplastic Agents/adverse effects* ; Maximum Tolerated Dose ; Neoplasms/drug therapy* ; Neutropenia/chemically induced* ; Prospective Studies

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

ObjectiveTo summarize the clinical features and prognosis of pulmonary mucormycosis （PM） in southern China， and to explore the diagnostic value of metagenomic next generation sequencing （mNGS） in PM. MethodsThe clinical manifestations， diagnosis， treatment and prognosis of patients diagnosed with PM in The First Affiliated Hospital of Sun Yat-sen University from January 1， 2019 to January 31， 2022 who had undergone mNGS detection in lung tissue or alveolar lavage fluid were collected retrospectively. A total of 14 patients with PM were included， including 4 patients with confirmed diagnosis and 10 patients with clinical diagnosis. ResultsAll patients had underlying medical conditions， with hematological malignancies and diabetes being the most common. The most common symptoms were fever （n = 10）， cough （n = 9） and shortness of breath （n = 9）. Consolidation was the most common sign of chest CT， followed by mass， mostly with cavity. On laboratory tests， decreased CD4+T lymphocytes， elevated CD8+T lymphocytes， and decreased CD4+/CD8+ ratio， and presentation with pleural effusion indicate poor prognosis. The positive rate of mNGS diagnosis was 78.5%， which was significantly higher than that of histopathology （50%）， fungus rapid fluorescence staining （61.5%） and fungal culture （23.1%） of bronchoalveolar lavage fluid. ConclusionsPulmonary mucormycosis is more likely to occur in patients with underlying diseases or who are immunocompromised. The clinical manifestations lack specificity. The low CD4/CD8 ratio and presentation of pleural effusion on CT imaging indicate poor prognosis of patients. mNGS is a rapid， convenient and sensitive method for the diagnosis of PM， which has advantages in the diagnosis of pulmonary mucormycosis.

ObjectiveTo construct a neural network-like tissue with the potential of synaptic formation in vitro by seeding human induced pluripotent stem cell-derived neural precursor cells （hiPSC-NPCs） on decellularized optic nerve （DON）， so as to provide a promising approach for repair of nerve tissue injury. MethodsThrough directional induction and tissue engineering technology， human induced pluripotent stem cells （hiPSCs） and 3D DON scaffolds were combined to construct neural network-like tissues. Then the hiPSCs were directionally induced into human neural precursor cells （hNPCs） and neurons. Immunofluorescence staining was used to identify cell differentiation efficiency. 3D DON scaffolds were prepared. Morphology and cytocompatibility of scaffolds were identified by scanning electron microscopy and Tunnel staining. Induced hiPSC-NPCs were seeded on DON scaffolds. Immunofluorescence staining， scanning electron microscopy， transmission electron microscopy and patch clamp were used to observe the morphology and functional identification of constructed neural network tissues. Results①The results of immunofluorescence staining suggested that most of hiPSC-NPCs differentiated into neurons in vitro. We had successfully constructed a neural network dominated by neurons. ② The results of scanning electron microscopy and immunohistochemistry suggested that a neural network-like tissue with predominating excitatory neurons in vitro was successfully constructed. ③The results of immunohistochemical staining， transmission electron microscopy and patch clamp indicated that the neural network-like tissue had synaptic transmission function. ConclusionA neural network-like tissue mainly composed of excitatory neurons has been constructed by the combination of natural uniform-channel DON scaffold and hiPSC-NPCs， which has the function of synaptic transmission. This neural network plays a significant role in stem cell derived replacement therapy， and offers a promising prospect for repair of spinal cord injury （SCI） and other neural tissue injuries.

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.
Humans ; Male ; Female ; Adult ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Middle Aged ; Retrospective Studies ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Recurrence ; Graft vs Host Disease/etiology* ; Chronic Disease

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

This study investigated whether free prostate-specific antigen (fPSA) performs better than total PSA (tPSA) in predicting prostate volume (PV) in Chinese men with different PSA levels. A total of 5463 men with PSA levels of <10 ng ml^-1 and without prostate cancer diagnosis were included in this study. Patients were classified into four groups: PSA <2.5 ng ml^-1, 2.5-3.9 ng ml^-1, 4.0-9.9 ng ml^-1, and 2.5-9.9 ng ml^-1. Pearson/Spearman's correlation coefficient (r) and receiver operating characteristic (ROC) curves were used to evaluate the ability of tPSA and fPSA to predict PV. The correlation coefficient between tPSA and PV in the PSA <2.5 ng ml^-1 cohort (r = 0.422; P < 0.001) was markedly higher than those of the cohorts with PSA levels of 2.5-3.9 ng ml^-1, 4.0-9.9 ng ml^-1, and 2.5-9.9 ng ml^-1 (r = 0.114, 0.167, and 0.264, respectively; all P ≤ 0.001), while fPSA levels did not differ significantly among different PSA groups. Area under ROC curve (AUC) analyses revealed that the performance of fPSA in predicting PV ≥40 ml (AUC: 0.694, 0.714, and 0.727) was better than that of tPSA (AUC = 0.545, 0.561, and 0.611) in men with PSA levels of 2.5-3.9 ng ml^-1, 4.0-9.9 ng ml^-1, and 2.5-9.9 ng ml^-1, respectively, but not at PSA levels of <2.5 ng ml^-1 (AUC: 0.713 vs 0.720). These findings suggest that the relationship between tPSA and PV may vary with PSA level and that fPSA is more powerful at predicting PV only in the ''gray zone'' (PSA levels of 2.5-9.9 ng ml^-1), but its performance was similar to that of tPSA at PSA levels of <2.5 ng ml^-1.
Male ; Humans ; Prostate-Specific Antigen ; Prostate ; East Asian People ; Prostatic Neoplasms/diagnosis* ; ROC Curve