The integration of multi-omics technologies and artificial intelligence is jointly promoting the application of more precise and dynamic novel tumor markers in cancer diagnosis and treatment. In terms of genomics, high-throughput sequencing technologies have promoted in-depth research into tumor driver genes, epigenetic reprogramming, and circulating cell-free DNA fragmentomics, providing actionable biomarkers for early cancer screening, molecular subtyping, and targeted therapy. Examples include the use of mismatch repair (MMR) deficiency to predict the efficacy of programmed death-1 (PD-1) inhibitors, and the combination of methylation markers with protein markers for the early detection of hepatocellular carcinoma. Transcriptomics, by analyzing mRNA and non-coding RNA combined with single-cell sequencing technologies, reveals tumor heterogeneity and identifies biomarkers for efficacy evaluation. Proteomics utilizes mass spectrometry to analyze protein expression levels and post-translational modifications (phosphorylation, glycosylation, acetylation), overco-ming the sensitivity bottleneck in early detection and providing new approaches for tumor subtyping and the discovery of therapeutic targets. Metabolomics systematically quantifies metabolic reprogramming processes, including glucose metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism, providing a basis for tumor diagnosis and intervention strategies. Microbiomics confirms that the intratumoral microbiota can serve as functional biomarkers to aid in tumor diagnosis and prognosis assessment. Despite challenges such as biological interference, technical standardization, and the risk of false positives, artificial intelligence technologies, particularly machine learning algorithms, provide powerful computational capabilities for multi-omics data mining and pathological image assessment. This is driving the development of tumor markers towards high sensitivity and high specificity, and facilitating a comprehensive breakthrough in precision oncology.
Objective This study aims to analyze the incidence and mortality of lung cancer in Shanghai from 2002 to 2019 and their variation trends. Methods Data on lung cancer incidence and mortality in Shanghai from 2002 to 2019 were obtained from the population-based cancer registry management system and all-cause mortality registration system established by the Shanghai Municipal Center for Disease Control and Prevention. Stratified analyses were conducted by factors including year of diagnosis or death, sex, and age group, and indicators such as number of cases, constituent ratio, crude rate, age-specific rate, and age-standardized rate (ASR) were calculated. ASRs were calculated using Segi's 1960 world standard population. Joinpoint software was used to analyze annual percentage variation trends in ASRs, age-specific rates, and the constituent ratios of selected diagnostic characteristics of new cases across different groups. Results Annual new lung cancer cases in Shanghai increased from 8 005 in 2002 to 21 835 in 2019, and the age-standardized incidence rate increased from 33.73/10⁵ to 63.82/10⁵. Annual deaths increased from 6 871 to 9 573, while the age-standardized mortality rate decreased from 27.90/10⁵ to 21.75/10⁵. In 2019, the age-standardized incidence rate of lung cancer in Shanghai was 63.82/10⁵, including 66.37/10⁵ in males and 62.09/10⁵ in females, and the sex difference was statistically significant (P<0.001). The age-standardized mortality rate was 21.75/10⁵, with 33.50/10⁵ in males and 10.95/10⁵ in females, and the sex difference was statistically significant (P<0.001). Age-specific numbers and rates of lung cancer incidence and mortality generally increased with age. Sex-stratified trend analysis showed that from 2002 to 2019, the age-standardized incidence rate of lung cancer in males in Shanghai increased at an average annual rate of 1.39% (P=0.006), while the age-standardized mortality rate decreased at an average annual rate of 0.98% (P<0.001). In females, the age-standardized incidence rate showed no significant change from 2002 to 2011 (P=0.717), but increased at an average annual rate of 15.57% from 2011 to 2019 (P<0.001). The age-standardized mortality rate showed no statistically significant change from 2002 to 2012 (P=0.779), but decreased at an average annual rate of 2.95% from 2012 to 2019 (P=0.011). Among newly diagnosed lung cancer cases in Shanghai from 2002 to 2019, the proportion confirmed by pathology increased from 44.28% to 61.88%, while the proportion confirmed by imaging examination decreased from 41.50% to 7.99%. The proportion of adenocarcinoma increased from 19.66% to 41.20%, while that of squamous-cell carcinoma decreased from 14.13% to 6.29%. The proportion of stage Ⅰ patients increased from 3.76% to 22.60%, whereas the combined proportion of stage Ⅱ to stage Ⅳ patients decreased. However, the proportions of cases with unspecified anatomic site, unspecified histological type, and unknown stage at diagnosis remained high, and in 2019, the proportions were 75.65%, 45.89%, and 54.05%, respectively. Conclusions In 2019, compared with the global level, the age-standardized incidence rate of lung cancer in Shanghai, China, was relatively high, and mortality showed distinct epidemiological characteristics across sex and age groups. The incidence rate of lung cancer in females showed an overall upward trend from 2002 to 2019. In 2019, the age-standardized incidence rate of lung cancer in females increased with age. These findings suggest that there is still substantial room for improvement in lung cancer screening, diagnosis, and survival. This study provides a basis for further research and prevention and control strategies for lung cancer.
Non-tuberculous mycobacteria (NTM) are a group of opportunistic pathogens widely present in the environment. The global incidence of NTM infections and associated drug resistance rates are increasing. Although unified global surveillance data are lacking, studies based on national surveillance or large-scale databases from multiple countries have consistently reported a significant increasing trend in the incidence of NTM infections. In Japan, the incidence of pulmonary disease caused by NTM infections increased from 15.8 to 19.2 cases per 100 000 population between 2013 and 2017, representing an increase of 17.7%. In Denmark, a national registry study covering 1991 to 2022 shows that the incidence of NTM-related pulmonary diseases has continuously increased over the 30-year period, with an average annual growth rate of 2.3%. The clinical manifestations of non-tuberculous mycobacterial pulmonary disease are non-specific and highly similar to those of pulmonary tuberculosis, but the treatment strategies are markedly different. Moreover, treatment schemes vary greatly among different NTM species. Therefore, rapid and accurate laboratory identification and species differentiation are essential. Conventional diagnostic methods such as smear microscopy and culture have technical limitations including low sensitivity and long turnaround time, making it difficult to meet the requirements of early and precise clinical diagnosis and treatment. Molecular diagnostic techniques, represented by real-time fluorescent PCR, have greatly shorte-ned detection duration and enabled rapid screening and differentiation of NTM. Genomic technologies, represented by next-generation sequencing and nanopore sequencing, can achieve integrated and precise identification of bacterial species to the subspecies level and detect drug resistance genes directly from clinical specimens, thereby guiding early clinical medication. Artificial intelligence technology demonstrates strong potential in integrating imaging features, clinical data, and even genomic information, and can assist in auxiliary diagnosis, optimize treatment schemes, and predict prognosis. The development of these novel NTM laboratory diagnostic techniques is driving the transformation of NTM diagnosis and treatment from an empirical model to an efficient, precise, and individualized model.
Objective This study aims to investigate the expression characteristics of serum soluble CD206 (sCD206) in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AGN) and its value in assessing disease activity. Methods A total of 54 AGN patients hospitalized in the Department of Nephrology of Ruijin Hospital from January 2020 to December 2022 were consecutively enrolled, and 38 active-phase serum specimens and 29 remission-phase specimens for each were collected. Among them, 13 patients provided both active-phase and remission-phase serum specimens. Additionally, 14 age- and sex-matched healthy volunteers were recruited as controls. Serum sCD206 levels of all subjects were measured using double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Comparisons were made among healthy controls, active-phase AGN patients, and remission-phase AGN patients. Paired analysis was performed on active-phase and remission-phase specimens from the 13 patients who achieved clinical remission during the study period. Correlations between serum sCD206 levels and AGN-related clinical indicators [serum creatinine, estimated glomerular filtration rate (eGFR), 24-hour urinary protein, Birmingham Vasculitis Activity Score (BVAS), erythrocyte sedimentation rate, etc.] were analyzed. The efficacy of serum sCD206 levels on assessing disease remission in AGN was evaluated using receiver operating characteristic (ROC) curve. Results Serum sCD206 levels in active-phase AGN patients [(2.359±0.827) AU] were significantly higher than those in remission-phase patients [(0.989±0.230) AU] and healthy controls [(1.074±0.528) AU] (all P<0.000 1). The serum sCD206 levels of the same patients during the remission phase were significantly lower than those during the active phase (ΔsCD206=1.439±0.873 AU, P<0.01). There was no significant difference in serum sCD206 levels between remission-phase AGN patients and healthy controls (P>0.05). Correlation analysis showed that serum sCD206 levels in active-phase AGN patients were positively correlated with BVAS (r=0.577, P<0.001). ROC curve analysis showed that the area under the curve (AUC) of serum sCD206 levels for assessing clinical remission in AGN patients was 0.876. The optimal cutoff value was 1.547 AU, with a sensitivity of 86.21% and a specificity of 78.95%. Conclusions Serum sCD206 levels decrease significantly as disease activity declines, and can serve as a potential biomarker for evaluating clinical remission in AGN patients.
Objective This study aims to investigate the value of 31P magnetic resonance spectroscopy imaging (31P MRSI) in evaluating the therapeutic efficacy of the first cycle of hepatic arterial infusion chemotherapy (HAIC) for patients with hepatocellular carcinoma (HCC). Methods A total of 13 male patients (mean age: 54±14 years) with Barcelona Clinic Liver Cancer-C stage HCC intended to receive HAIC at Ruijin Hospital were prospectively and consecutively enrolled from November 2023 to August 2024. Each patient underwent 31P MRSI before the first cycle [mean (1±1) d] and after the first HAIC cycle [mean (24±6) d]. After the 6th HAIC [median 151 d since the first HAIC (interquartile range, 123-179 d)] or after conversion surgery [median 94 d since the first HAIC (interquartile range, 66-106 d)], patients were divided into response group (n=6) and nonresponse group (n=7) according to modified response evaluation criteria in solid tumor (mRECIST) or pathological assessment criteria. The phosphomonoester (PME)/phosphodiester (PDE) and phosphoethanolamine (PE)/PDE ratios in patients with HCC, as well as their changes and change amplitude (ΔPME/PDE and ΔPE/PDE), were analyzed. Differences in these indicators before and after the first cycle of HAIC were compared between the response and nonresponse groups. The area under the receiver operating characteristic (ROC) curve was used to evaluate the value of these indicators derived from 31P MRSI in predicting HAIC efficacy. Results In the response group, the PME/PDE and PE/PDE ratios showed no change before and after HAIC, whereas it significantly increased in the nonresponse group. Before the first cycle of HAIC, the ratios of PME/PDE (0.97 vs. 1.91, P=0.027) and PE/PDE (0.55 vs. 1.23, P=0.014) in the nonresponse group were lower than those in the response group. In the nonresponse group, the mean ratios of PME/PDE (3.04 vs. 0.97, P=0.006) and PE/PDE (2.03 vs. 0.55, P=0.014) increased significantly after HAIC compared with those before treatment. After the first cycle of HAIC, ΔPME/PDE and ΔPE/PDE (1.69 vs. 0.40, P=0.029; 1.80 vs. 0.47, P=0.032) were significantly greater in the nonresponse group than in the response group. The area under the curve (AUC) values for predicting nonresponders were 0.83, 0.91, 0.86, and 0.83, for the PME/PDE ratio <0.91, and PE/PDE ratio <0.74 before the HAIC, ΔPME/PDE≥0.4 and ΔPE/PDE≥2.2, respectively. Conclusions In patients who do not respond to HAIC, the PME/PDE and PE/PDE ratios increase after the first cycle of HAIC. Baseline PME/PDE and PE/PDE ratios or after the first cycle of HAIC may be useful for predicting the efficacy of HAIC.
Objective This study aims to investigate the effects of low-concentration caffeine on calcium homeostasis and apoptosis in rat cardiomyocytes with ryanodine receptor 2 (RyR2) knockdown. Methods Neonatal Sprague-Dawley (SD) rats of specific pathogen-free (SPF) grade were used, and neonatal rat ventricular myocytes (NRVMs) were isolated and extracted. Synthetic small interfering RNA (siRNA) targeting RyR2 and the negative control (NC) were transfected into NRVMs, and the cells were divided into four groups: NC group (transfected with siRNA NC), siRyR2 group (transfected with RyR2 siRNA), NC+caffeine group (0.2 mmol/L caffeine added after siRNA NC transfection), and siRyR2+caffeine group (0.2 mmol/L caffeine added after RyR2 siRNA transfection). The mRNA and protein expression levels of RyR2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Cell apoptosis and calcium ions were detected by flow cytometry, and free calcium ion concentration was detected by confocal calcium ion imaging. Data from the NC, siRyR2, NC+caffeine, and siRyR2+caffeine groups were analyzed by one-way analysis of variance. Results Compared with the NC group, the mRNA and protein expression levels of RyR2 in the siRyR2 group were significantly decreased (mRNA: 0.41±0.04 vs 1.00±0.09, P=0.000 3; protein: 0.34±0.04 vs 0.72±0.02, P=0.000 1), calcium ion concentration was significantly decreased (flow cytometry: 0.80±0.02 vs 1.00±0.02, P<0.000 1; confocal: 61.08%±0.75% vs 100.00%±2.33%, P<0.000 1), and the apoptosis rate was significantly increased (9.21%±0.07% vs 4.19%±0.07%, P<0.000 1). In the NC+caffeine group, the mRNA and protein expression levels of RyR2 were significantly increased (mRNA: 1.27±0.15 vs 1.00±0.09, P=0.033 6; protein: 0.92±0.10 vs 0.72±0.02, P=0.006 5), calcium ion concentration was significantly increased (flow cytometry: 01.33±0.04 vs 1.00±0.02, P<0.000 1; confocal: 116.21%±1.51% vs 100.00%±2.33%, P=0.000 6), and the apoptosis rate was significantly decreased (2.97%±0.13% vs 4.19%±0.07%, P<0.000 1). Compared with the siRyR2 group, the mRNA and protein expression levels of RyR2 in the siRyR2+caffeine group were significantly increased (mRNA: 0.67±0.08 vs 0.41±0.04, P=0.044 7; protein: 0.54±0.01 vs 0.34±0.04, P=0.009 1), calcium ion concentration was significantly increased (flow cytometry: 0.87±0.02 vs 0.80±0.02, P=0.026 3; confocal: 79.14%±5.02% vs 61.08%±0.75%, P=0.000 3), and the apoptosis rate was significantly decreased (7.59%±0.10% vs 9.21%±0.07%, P<0.000 1). Compared with the NC+caffeine group, the mRNA and protein expression levels of RyR2 in the siRyR2+caffeine group were significantly decreased (mRNA: 0.67±0.08 vs 1.27±0.15, P=0.000 2; protein: 0.54±0.01 vs 0.92±0.10, P<0.000 1), calcium ion concentration was significantly decreased (flow cytometry: 0.87±0.02 vs 1.33±0.04, P<0.000 1; confocal: 79.14%±5.02% vs 116.21%±1.51%, P<0.000 1), and the apoptosis rate was significantly increased (7.59%±0.10% vs 2.97%±0.13%, P<0.000 1). Conclusions Low-concentration caffeine can promote calcium ion release, restore calcium homeostasis, and reduce apoptosis by upregulating RyR2 in cardiomyocytes. This interaction mechanism between caffeine and RyR2 can provide a reference for the development of therapeutic drugs for heart diseases such as arrhythmias caused by decreased RyR2 expression.
为了解情景模拟结合虚拟仿真模式在心脏内科住院医师出科考核中的应用效果,本教研团队对2023年3月至2024年12月在上海交通大学医学院附属瑞金医院心脏内科轮转的240名住院医师,采用轮转月混合区组随机的方法分为试验组和对照组.试验组采用情景模拟结合虚拟仿真模式进行出科考核,考核内容包括临床情境问诊、心音与呼吸音听诊、心电图分析及电除颤操作、诊疗方案制定等;对照组采用笔试与面试传统考核.比较2组医师的出科和年度考核成绩及结业考核通过率,并进行Mini-CEX形成性评价指标评估和满意度问卷调查.结果显示,来自内科基地及非内科基地的试验组医师的出科考核成绩显著均优于对照组[(内科基地(82.3±3.8)分比(77.4±3.7)分,非内科基地(80.8±4.1)分比(76.7±3.2)分,P均<0.01].内科基地住院医师中,试验组的年度考核成绩更高[(82.1±3.9)分比(74.9±3.0分),P<0.01],主要表现在病例分析和病史采集[(85.3±4.2)分比(69.2±5.3)分;(83.1±4.5)分比(74.5±5.3)分,P均<0.01]方面;且试验组的结业考核通过率更高(98.1%比92.0%,P<0.001).Mini-CEX考核整体评分上,试验组显著高于对照组[(6.8±1.2)分比(5.9±1.2)分,P<0.01];考核方式整体满意度方面,试验组更高[(非内科基地3.9±0.8)分比(3.0±0.8分;内科基地(4.3±0.7)分比(3.0±0.6)分,P均<0.01].证实了,在心脏内科住院医师出科考核中开展情景模拟结合虚拟仿真模式,更能真实检验住院医师的临床能力和岗位胜任力,可作为一种新的出科考核方式应用于内科住培的教学考核工作中.
Objective Prototheca is a unicellular microalga belonging to the family Chlorellaceae that has lost its chlorophyll and the ability to perform photosynthesis, exhibiting biological characteristics intermediate between algae and fungi. Protothecosis is predominantly an exogenous infection, with pathogens commonly invading through damaged skin or mucous membranes via contact with contaminated soil, water, or organic matter. Clinical manifestations primarily include cutaneous and subcutaneous infections and olecranon bursitis. This study investigates the epidemiological characteristics and antimicrobial susceptibility distribution of protothecosis in China from 2015 to 2025, aiming to bridge the gap in domestic epidemiological data and clinical management guidelines of protothecosis, and to provide a scientific basis for its clinical diagnosis, treatment, and prevention strategies. Methods A total of 84 clinical Prototheca isolates collected by the Protothecosis Science Popularization and Monitoring Consortium (PSPMC) between 2015 and 2025 were retrospectively analyzed. In vitro susceptibility testing was performed for all isolates using the broth microdilution method. The tested agents included five azoles, three echinocandins, 5-flucytosine, and amphotericin B. Additionally, CYTB gene sequencing was conducted, followed by phylogenetic analysis. Results Among the isolates obtained from patients with protothecosis in China between 2015 and 2025, Prototheca wickerhamii was the predominant species (79.8%), followed by Prototheca bovis (11.9%). The highest number of isolates was found in East China (45.2%). The infections predominantly affected middle-aged and elderly individuals, with 82.1% of patients aged between 41 and 80 years. Skin tissue was the most common isolation source, accounting for 59.5% of all clinical isolates. Non-cutaneous sources included cerebrospinal fluid, blood, ascitic fluid, and bronchoalveolar lavage fluid. Azole antifungal agents, such as itraconazole, posaconazole, and voriconazole, demonstrated strong antimicrobial activity against Prototheca, with the minimum inhibitory concentration (MIC) required to inhibit 50% of isolates (MIC50) being 1.000 μg/mL. Isavuconazole exhibited superior activity, with MICs ranging from 0.015 to 1.000 μg/mL. Amphotericin B also showed strong antimicrobial activity (MIC50 = 0.500 μg/mL). Conversely, fluconazole, 5-flucytosine, and echinocandins showed no significant antimicrobial activity against Prototheca. The antimicrobial activity of isavuconazole against P. wickerhamii was significantly higher than against P. bovis and Prototheca zopfii. Phylogenetic analysis indicated that P. wickerhamii constituted the major evolutionary clade with a highly complex structure, suggesting significant intraspecific genetic heterogeneity. Conclusions Prototheca wickerhamii is the predominant species among isolates obtained from patients with protothecosis in China. The infected population mainly consists of middle-aged and elderly individuals. While skin is the main site of infection, non-cutaneous sites are widely distributed. Amphotericin B and isavuconazole demonstrate strong in vitro antimicrobial activity against these clinical Prototheca isolates, although susceptibility varies among different species.
The in-hospital mortality rate of methicillin-resistant Staphylococcus aureus (MRSA) can reach 20%-30%, which has attracted global attention. However, the clinical treatment options for MRSA infections are still very limited. The drug resistance mechanisms of MRSA can be divided into intrinsic and acquired types. Intrinsic drug resistance is mainly achieved through the secretion of β-lactamase and the activation of efflux pumps. MRSA can acquire drug resistance through gene mutations or plasmid transformation involving drug-resistant genes. Additionally, the formation of biofilms and the emergence of small colony variants are also important mechanisms for acquired drug resistance. In clinical practice, traditional antibiotics are still the main approach for treating MRSA bacteremia. As MRSA tolerance to traditional antibiotics gradually increases, research on new therapeutic methods has also made great progress. Among these, quorum-sensing system (QS) inhibitors, antimicrobial peptides, small-molecule compounds, antimicrobial photodynamic therapy, phage therapy, and combination therapy have shown great potential in the treatment of MRSA infections. These novel approaches not only provide more effective, low-toxicity, and sustainable solutions for clinical practice but also offer new ideas for the exploration of new antibiotics with mechanisms of action different from those of traditional antibiotics.
Pseudohypoparathyroidism (PHP) is a group of clinical syndromes caused by peripheral target tissue resistance to parathyroid hormone (PTH). Its main clinical features are hypocalcemia, hyperphosphatemia, and resulting tetany, convulsions, or epileptoid seizures. Patients with PHP 1b often present no specific signs and have diverse clinical manifestations, and if biochemical tests and PTH measurements are not performed in time, the diagnosis is likely to be delayed. This paper reports a 11-year-old boy with episodic convulsion as the main manifestation. The boy had low serum calcium and ionized calcium, significantly increased PTH, elevated serum phosphorus, and low urinary calcium and phosphorus. Genetic testing revealed heterozygous deletion of exons 5-7 of STX16 gene and loss of maternal methylation at GNAS-A/B. Parental testing for copy number changes and methylation status of STX16/GNAS-AS1/GNAS genes/regions showed no abnormalities. The patient was definitively diagnosed as a male pediatric case of autosomal dominant PHP 1b (AD-PHP 1b) caused by a new mutation of STX16. After oral treatment with calcitriol and calcium supplements, the patient's serum calcium gradually returned to normal, and no further convulsive seizures occurred. The patient is currently under follow-up. At present, no cases of male AD-PHP 1b caused by a new mutation of STX16 have been reported in China.
Objective This study aims to analyze the risk factors for the occurrence of neonatal candidemia and those associated with poor prognosis, thereby providing evidence for clinical diagnosis and treatment. Methods This retrospective study enrolled consecutive 57 cases of neonatal candidemia diagnosed by blood culture in the neonatal ward of Shanghai Children's Hospital between January 2017 and December 2024. All included neonates aged ≤28 days at the time of infection. The clinical features, laboratory findings, and treatment outcomes were analyzed. According to outcomes, the neonates were divided into death group (5 cases) and improved group (52 cases), and the risk factors for poor prognosis were analyzed. Results Among the 57 neonates with candidemia, 30 were male and 27 were female. The median postnatal age at the onset of candidemia was 14 days (interquartile range, 10, 20). Forty-eight cases (84.21%) were preterm infants (<37 weeks), 46 cases (80.7%) were low birth weight infants (<2 500 g), 54 cases (94.7%) had a history of invasive examination and treatment procedures before the onset of candidiasis, and 55 cases (96.5%) had a history of antimicrobial agent use prior to candidiasis. Etiological analysis showed that the predominant Candida species infecting the neonates was Candida parapsilosis (46 cases, 80.7%), follower by Candida albicans (6 cases, 10.53%), Candida glabrata (3 cases, 5.26%), and Candida guilliermondii (2 cases, 3.51%). Drug susceptibility test results indicated there was no antifungal drug-resistant strains. The time from the onset of clinical symptoms to confirmed diagnosis and initiation of antifungal therapy was (2.3±1.2) days, and the duration of antifungal treatment was 29 days (interquartile range, 23, 37). Univariate analysis showed that septic shock, tracheal intubation/mechanical ventilation, decreased platelet (PLT) count, and elevated procalcitonin (PCT) were risk factors for poor prognosis of neonatal candidemia (P<0.05). Conclusions The risk factors for neonatal candidemia include prematurity, low birth weight, a history of invasive examination and treatment procedures, and a history of antimicrobial drug use. The predominant pathogenic Candida species is Candida parapsilosis. Septic shock and endotracheal intubation/mechanical ventilation are risk factors for poor prognosis of neonatal candidemia. PLT and PCT can serve as important reference indicators for evaluating the prognosis of neonatal candidemia.
To establish a scientific, standardized, and operable clinical laboratory pathway for infectious fever, and to address current problems such as blind selection of testing items, inappropriate testing timing, and inadequate multidisciplinary collaboration in clinical testing for infectious fever, the Clinical Microbiology Committee of the Shanghai Society for Microbiology and the Laboratory Medicine Branch and Molecular Diagnosis Branch of the Shanghai Medical Association jointly organized an expert panel. The panel integrated the current status of clinical diagnosis and treatment of infectious fever across different medical institutions, combined evidence-based medical evidence with the characteristics of clinical practice in China, and referred to existing consensuses and guidelines (such as the 2017 Expert Consensus on the Diagnosis and Treatment of Fever of Unknown Origin), as well as relevant domestic and international regulations and standards, to formulate the Expert Consensus on the Clinical Testing Pathway for Infectious Fever. The revision of this consensus unified the standards for the clinical testing pathway for infectious fever, standardized diagnosis and treatment behaviors, optimized allocation of medical resources, improved the quality of diagnosis and treatment, and addressed practical problems such as coexistence of overuse and underuse of testing items, poor multidisciplinary collaboration, and disconnection of testing services among medical institutions at different levels. This article interprets the revision background, implementation difficulties, and clinical significance of the consensus. It focuses on newly added contents such as the differential diagnosis and clinical feature definition of infectious fever, precise testing strategies for high-risk populations, hierarchical testing strategies, and application of novel laboratory diagnostic technologies. Additionally, it highlights core topics including hierarchical testing strategies, optimal selection of special pathogen detection technologies, individualized diagnosis and treatment for high-risk populations, and multidisciplinary collaboration mechanisms. Meanwhile, this article discusses current challenges in the implementation of the consensus, including unbalanced allocation of medical resources, inadequate multidisciplinary collaboration, and limitations in the application of new technologies. It also provides an outlook on the continuous improvement of the consensus with advances in testing technologies and promotion of progress in the diagnosis and treatment of infectious diseases, aiming to provide practical guidance for clinicians and laboratory personnel in medical institutions at all levels, further improve the diagnostic efficiency and accuracy of infectious fever, and promote standardized development of clinical diagnosis and treatment.
Chronic hepatitis B (CHB) remains a major global health challenge. Functional cure represents the ideal therapeutic endpoint for CHB. The pathogenesis of CHB is complex, including hepatitis B virus (HBV) DNA integration, persistent covalently closed circular DNA, and impaired specific immune response against HBV, which poses significant challenges to achieving functional cure in CHB. Current therapeutic drugs have limited efficacy in achieving functional cure. After 10 years of nucleos(t)ide analogs (NAs) monotherapy, less than 5% of patients achieve functional cure, while less than 15% of patients achieve functional cure after 48 weeks of pegylated interferon (Peg-IFN) monotherapy. For the favorable population that achieves HBV e antigen (HBeAg) negativity with NAs treatment and has baseline HBV surface antigen (HBsAg) <1 500 IU/mL, the functional cure rate with sequential Peg-IFN therapy is over 20%, with a functional cure rate of over 30% for patients with baseline HBsAg between 500 and 1 500 IU/mL and over 60% for those with baseline HBsAg <100 IU/mL. For non-cirrhotic patients who meet the recommended drug discontinuation criteria in the guidelines, NAs cessation may accelerate HBsAg clearance and facilitate functional cure. However, close monitoring of hepatitis flares and hepatocellular carcinoma is required. To overcome the low functional cure rate of current drugs for CHB, researchers are exploring novel drugs, including direct-acting antivirals targeting different stages of HBV life cycle, and immunomodulatory drugs aimed at restoring immune function against HBV. Based on current research results, no new drug has achieved a functional cure rate of CHB above 30% through monotherapy. Therefore, combination therapy strategies based on new drugs are currently a research focus.
Objective This study aims to summarize the clinical characteristics of patients with scrub typhus in atypical epidemic areas, and explore the application value of metagenomic next-generation sequencing (mNGS) and targeted next-generation sequencing (tNGS) in etiological diagnosis. Methods A retrospective analysis was conducted on the clinical data of seven patients with scrub typhus diagnosed by next-generation sequencing (NGS) at Ji'an Central People's Hospital from May 2025 to January 2026. Among them, three patients with respiratory symptoms or lung infection as the main manifestation underwent tNGS testing, while four patients with sepsis or systemic infection as the main manifestation underwent mNGS testing. Data on the patients' clinical manifestations, laboratory tests, NGS results, diagnosis time, and treatment outcomes were collected. Results Among the seven patients, four were male and three were female, with a median age of 69 years. All patients presented with high fever as the initial symptom, and only one patient exhibited typical eschar. All seven patients had elevated C-reactive protein levels, five of whom also had thrombocytopenia, and all seven had abnormal liver function. NGS detected Orientia tsutsugamushi sequences within 24 to 72 hours after sample submission. The duration from patient admission to obtaining etiological results ranged from 2 to 4 days, with a median of 3 days. After treatment with doxycycline or minocycline adjusted based on NGS results, the patients' temperatures returned to normal within 1 to 3 days, with a median fever reduction time of 2 days. All patients were cured and discharged. Conclusions Patients with scrub typhus in atypical epidemic areas often exhibit nonspecific clinical manifestations, making them prone to misdiagnosis and missed diagnoses. For high-risk febrile patients who fail to respond to empirical anti-infective treatment and have unidentified causes, NGS can serve as an important supplementary diagnostic tool. Timely NGS testing can facilitate rapid and precise identification of pathogens, providing crucial evidence for subsequent adjustments to targeted anti-infective regimens.
本文以置信职业行为(entrustable professional activities,EPAs)为理论框架,探索医学影像技术本科教育的创新路径.本文首先介绍EPAs理论及其在医学教育中的应用,随后提出基于EPAs的医学影像技术本科核心胜任力培养体系设计,并详细阐述培养体系的实施与评估方法,最后总结其创新性及未来发展方向.通过将EPAs引入本科教育,构建了以任务为导向、以胜任力为核心的培养体系,旨在为影像技师胜任力培养提供科学、可行的解决方案.
Objective Using data from the Global Burden of Disease Study 2023 (GBD 2023), this study aims to systematically analyze the burden and changing trends of mental disorders among adolescents aged 10-19 years globally and in China from 1990 to 2023, to explore the effects of gender, age, sociodemographic index (SDI), and disease subtype composition, and to predict the incidence trends of adolescent mental disorders up to 2050. Methods Data on the incidence, prevalence, and disability-adjusted life years (DALYs) of mental disorders and their subtypes among adolescents aged 10-19 years globally and in China were extracted from the GBD 2023 database. The trends and differences by age, gender, and were analyzed, and the autoregressive integrated moving average (ARIMA) model was used to predict the incidence of adolescent mental disorders up to 2050. Results From 1990 to 2023, the global prevalence and DALYs of mental disorders in adolescents increased by 31.43% and 39.61%, and by 21.00% and 26.39% in China, respectively. The incidence peaked in 2021 (9 641/100 000 globally and 6 265/100 000 in China). Although it declined thereafter, it remained at a relatively high level. Due to demographic shifts, the absolute number of Chinese adolescents with mental disorders decreased by 10.75% from 1990 to 2023. However, the prevalence and incidence rates showed an upward trend, rising from 14 401.99/100 000 and 4 473.53/100 000 in 1990 to 17 425.46/100 000 and 5 716.24/100 000 in 2023 in China, representing increases of 21.00% and 27.78%, respectively. Moreover, the burden of disease among females aged 15-19 years was much higher than that among males of the same age in China. Globally, anxiety disorders and depressive disorders were the main contributors to the burden of mental disorders, together accounting for more than two-thirds of DALYs. The proportions of anxiety disorders (43.5% in China vs. 42.2% globally) and ADHD (9.0% vs. 4.5%) among all mental disorders were higher in China than the global average. The ARIMA model predicted that by 2050, the incidence of adolescent mental disorders would enter a new high-level plateau with potential risks of fluctuation. The global incidence was predicted to remain at approximately 6 300/100 000 [95% UI: (4 500-8 000)/100 000], and the incidence in China was predicted to be approximately 5 700/100 000 [95% UI: (4 000-7 000)/100 000]. Conclusions Over the past three decades, the burden of mental disorders among adolescents has experienced substantial growth both globally and in China, with China exhibiting a higher increase than the global average. The burdens of anxiety disorders and ADHD are particularly prominent in China, and females in mid-to-late adolescence represent the core population for risk prevention. Notably, although the burden of adolescent mental disorders has declined somewhat after 2021, it remains at a high plateau. There is an urgent need to develop precise prevention and intervention strategies based on gender, age, and disease subtype characteristics in China.
Objective To investigate the distribution of targetable mutations and clinical benefits of targeted therapy in Chinese patients with pulmonary large cell neuroendocrine carcinoma (LCNEC). Methods Retrospective data were collected from 44 consecutive treatment-naive LCNEC patients at the North Campus of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between January 2021 and December 2023. PD-L1 expression in pathological tissues was detected by immunohistochemistry, and mutations in 11 driver genes (ALK, ROS1, RET, NTRK1-3, MET, EGFR, BRAF, KRAS, HER2) were detected by quantitative real-time PCR. All patients were followed up for a median duration of 24 months. Results Among the 44 LCNEC patients, with a median age of 70.5 years, and males were predominant (93.2%, 41/44). Stage Ⅲ and Ⅳ disease accounted for 77.2% (34/44). The rates of lymph node metastasis and distant metastasis were 68.2% and 47.7%, respectively. Targetable mutations were identified in 11.4% (5/44) of the patients, including EGFR 19Del (1 case), ALK rearrangement (1 case), MET ex14 skipping mutation (1 case), and KRAS G12C mutation (2 cases). In the LCNEC pathological tissues, programmed death-ligand 1 (PD-L1) was negative in 79.5% (35/44) of the patients, while only 6.8% (3/44) demonstrated high PD-L1 expression (≥ 50%). Among the 34 Ⅲ-Ⅳ patients, the median progression-free survival (PFS) was 6.6 months in the three patients who received targeted therapy, which was significantly longer than the 4.8 months in the 31 patients who received non-targeted therapy (P < 0.05). The PFS reached 7 months and 11 months in patients with EGFR mutations and ALK rearrangements, respectively, whereas the patient with MET ex14 mutation responded poorly to targeted therapy, with a PFS of 2 months. Conclusions In the real-world Chinese population, LCNEC is highly aggressive, with over 70% of patients presenting at stage Ⅲ or Ⅳ. The low PD-L1 expression (negative rate of 79.5%) in pathological tissues indicates a limited population that may potentially benefit from immunotherapy. Additionally, 11.4% of patients have targetable mutations, among whom those with EGFR mutations or ALK rearrangements show favorable responses to targeted therapy. Molecular subtyping may have important guiding value for identifying the patient population who benefit from treatment for LCNEC.
在病理住院医师规范化培训(简称住培)中如何培养高质量的临床病理住院医师,是目前培训中的热点和难点.本文结合我院病理专业住培基地的实践工作,从临床技能、科研技能、人文素养和师资力量四方面进行深入探索与思考.接受"分层递进和分层整合式"模式教学的医师在取材和阅片技能培训中取得的成绩明显高于接受传统示教式教学的医师;其英文文献学习以及从临床问题出发的科研思维能力的培养初见成效,发表SCI论文1篇.培养住培医师病理诊断技能的同时注重医德、医患沟通等综合能力提升,医患满意度调查问卷中总体满意度达95%以上.导师激励和考核制度相结合,提高了带教师资能力.经过不断探索新的住培教学模式,本住培基地在2023年和2024年的上海市住培年度综合评估中获得第1名和第3名的好成绩,希望为优化完善临床病理专业人才的培训提供经验.
Objective To construct a causal artificial intelligence (AI) framework model embedded with medical knowledge for AI-assisted diagnosis of bone marrow morphology in acute leukemia based on medical diagnostic logic. Methods A stage-by-stage causal AI diagnostic framework guided by medical knowledge was constructed using a dataset of 20 089 microscopic images of bone marrow and peripheral blood smears of 93 cases(69 patients with other diseases exhibiting normal bone marrow and peripheral blood; 24 patients with hematological diseases, including 14 cases of acute leukemia ) from Ruijin Hospital (2020-2023). Multiple specialized modules including bone marrow hyperplasia assessment module(M1), bone marrow cell classification module(M2), AKP score calculation module(M3), POX-stained leukaemic cell feature extraction module(M4), and CE -stained leukaemic cell feature extraction module(M5), were trained and tested in a 7∶3 ratio to extract key morphological features, including bone marrow hyperplasia status, the constituent ratio of bone marrow cells, and cytochemical staining patterns in both bone marrow and peripheral blood. Based on morphological characteristics of the peripheral blood and bone marrow of hematological diseases, the aforementioned specific AI recognition models were combined step by step according to medical diagnostic logic, integrating multi-dimensional morphological characteristics of bone marrow cells, and a two-stage process sequential diagnosis and prediction was carried(stage 1: integrating M1, M2, and M3;stage2: integrating modules 4 and 5). The first stage involved distinguishing between normal and abnormal bone marrow cases, while simultaneously identifying chronic myeloid leukemia. The second stage focused on the diagnosis of acute leukemia and the differentiation of its subtypes. An end-to-end AI diagnostic framework model was also established as a control and compared with the medical knowledge-embedded causal AI diagnostic framework model in real-case diagnostic testing. Results The medical knowledge-embedded causal AI diagnostic framework model achieved higher accuracy than the end-to-end AI framework model in real-case diagnostic testing at both stages (Stage 1 accuracy: 90.00% vs. 70.00%; Stage 2 accuracy: 83.33% vs. 66.67%). Conclusions Medical expertise and diagnostic logic play a crucial role in AI-assisted diagnosis of bone marrow cell morphology for hematological diseases. The application of the medical knowledge-embedded causal AI diagnostic framework model improves the accuracy and interpretability of AI-assisted diagnosis, providing a novel and generalizable paradigm for intelligent diagnosis of hematological diseases.
This study reports a case of a 44-year-old female patient with multiple myeloma (MM). Her condition was initially relieved after treatment with bortezomib combined with dexamethasone. However, due to the patient's failure to adhere to the treatment schedule, the disease progressed. After switching to CD38 monoclonal antibody therapy, the di-sease again achieved remission. After 5 months of treatment, the patient suddenly experienced abdominal distension accompanied by cessation of anal gas and stool passage. Abdominal CT indicated intestinal obstruction. The patient underwent exploratory laparotomy, intestinal resection and anastomosis, and abdominal drainage. Postoperative T-cell spot test (T-SPOT) and pathological results confirmed the diagnosis of isolated intestinal tuberculosis complicated by incomplete intestinal obstruction. The patient received six months of quadruple anti-tuberculosis therapy (rifampicin 450 mg once daily orally, isoniazid 300 mg once daily orally, pyrazinamide 500 mg three times daily orally, streptomycin 750 mg once daily intramuscularly), after which her tuberculosis condition improved. However, due to the suspension of anti-tumor therapy, the MM progressed. The patient discontinued treatment for financial reasons and ultimately passed away 19 months after surgery due to MM progression. A review of relevant cases in the database shows that one patient who developed intestinal tuberculosis after heart transplantation was diagnosed with MM during anti-tuberculosis treatment, which later progressed to aggressive plasma cell leukemia. Although induction chemotherapy was administered, the patient experienced retroperitoneal hemorrhage and pancytopenia, and ultimately transitioned to palliative care. This case highlights that patients in an immunosuppressed state (such as MM) have a significantly increased risk of tuberculosis infection, among which extrapulmonary manifestations, such as intestinal tuberculosis, are relatively rare. Due to its atypical clinical manifestations, it is prone to being missed or misdiagnosed. Such infections may interfere with the course of antitumor therapy and affect patient prognosis. Clinicians should remain vigilant and strengthen differential diagnosis.
