中华预防医学杂志最新文献

Objective: Profiling tumor cell heterogeneity before and after chemotherapy in breast cancer patients to delineate the cellular evolutionary trajectory at single-cell resolution, thereby identifying potential targets for intervention. Methods: Using a case-control study design, a female patient with breast cancer admitted to the Department of Breast Surgery, The First Affiliated Hospital of Hunan University of Chinese Medicine in September 2020 was enrolled as the subject. Fresh tumor tissue samples, collected both before and after chemotherapy, were subjected to single-cell RNA sequencing to assess transcriptomic profiles and observe the impact of chemotherapy on the intratumoral microenvironment. Specifically, a pre-chemotherapy biopsy sample was obtained in June 2020, and a post-chemotherapy surgical resection sample was obtained in September 2020. Pathological diagnosis confirmed Grade Ⅲ invasive ductal carcinoma for both samples, with a molecular subtype of Luminal B. Results: A significance threshold of |log₂FC|>2 and a P-value <0.05 were set to define statistically significant differences for subsequent bioinformatic analysis. Sequencing data revealed that a total of 8 599 cells were profiled in this study, with 4 180 (48.6%) and 4 419 (51.4%) cells derived from pre- and post-chemotherapy tumor tissues, respectively. It characterized the cellular composition of the tumor microenvironment and identified 13 distinct cell clusters. These included basal cells, pericytes, plasma cells, T cells, B cells, fibroblasts, endothelial cells, NK cells, mast cells, epithelial cells, macrophages, cycling cells, and plasmacytoid dendritic cells. Signaling pathways and transcription factors associated with these cell clusters were subsequently analyzed and subjected to enrichment analysis. Furthermore, this study delineated the precise cellular architecture and developmental trajectories of breast cancer before and after chemotherapy. It also predicted that the APOD, ELN, and F2R genes may play pivotal roles in disease progression. Conclusion: This study utilized single-cell RNA sequencing to analyze intra-tumoral cellular heterogeneity in a breast cancer patient before and after chemotherapy. The findings may provide a clinically informative direction for identifying novel potential therapeutic targets during chemotherapy, prior to primary tumor resection.

The impact of circadian rhythm disruption on immune system function has been widely studied; however, the precise mechanisms by which it modulates immune system structure and function at the single-cell level remain poorly understood. This study was conducted from April to November 2024 in the Department of Pediatrics, the Third Xiangya Hospital, Central South University. In this study, a zebrafish model of circadian rhythm disruption was established by exposing larvae to constant light (24 h LL) for three days, while control groups were maintained under a standard 14-hour light/10-hour dark (14∶10 h LD) cycle. Single-cell RNA sequencing was performed to comprehensively profile the immune cells from both groups. Immune cell subpopulations, their proportional shifts, and developmental trajectories were characterized through UMAP-based clustering, marker gene annotation, and Monocle pseudotime trajectory analysis. A total of seven immune-related cell subtypes were identified, including hematopoietic progenitors, T cell progenitor-like cells, activated T cell-like cells, macrophages, neutrophils, NK cells, and migratory/repair-associated cells. Notably, the proportion of activated T cells was increased in the circadian rhythm-disrupted group (18.11%) compared with the control group (7.61%), accompanied by enhanced expression of immune activation markers such as cd40lg, il2rb,tnfrsf9b (log₂FC=7.49, 5.58, 3.76, adjusted P<0.01). Pseudotime analysis revealed bifurcated differentiation paths along myeloid and lymphoid lineages. Although the core developmental trajectories remained intact under circadian rhythm disturbance, alterations were observed in the distribution and maturation pace of terminal lymphoid cells. Overall, the findings demonstrate that circadian rhythm disruption induces structural and functional remodeling of the zebrafish immune system, characterized by enhanced activation of T and NK cells and a shift in immune response status. These results provide single-cell-level insights into the immunological mechanisms underlying sleep-related disorders.

Objective: To investigate the genotype and epidemiological characteristics of Human Coronavirus NL63 (HCoV-NL63) epidemic strains in Shanghai, China. Methods: Whole genome sequencing of HCoV-NL63 was performed with the nucleic acid-positive specimens collected from the acute respiratory infection surveillance system in Shanghai from 2019 to 2024. Phylogenetic, homology, and key mutation site analysis of the S gene were conducted in combination with international reference sequences. Results: Seven whole genome sequences of HCoV-NL63 were obtained, including five (2020-2022) of subtype B2 and two (2024) of subtype C3. The B2 subtype sequences were highly homologous to the Guangzhou 2018 strain, while the C3 subtype sequences were highly homologous to the Japanese 2023 strain. There were 44 amino acid mutation sites located on the S gene of five B2 strains, with E572A in the receptor binding domain (RBD) region. There were 15 amino acid mutation sites in the S gene of C3 subtype, with I507L and E572A in the RBD region, and I507L as the signature mutation of C3 subtype, closely related to viral virulence. Conclusion: The B2 and C3 subtypes coexist among the prevalent strains in Shanghai, and the related strains are highly homologous to the domestic and international strains causing severe infections, indicating the need to strengthen continuous monitoring and functional research on HCoV-NL63 variants in Shanghai.

Vaccination is widely acknowledged as one of the most successful and cost-effective health interventions. Vaccines play a critical role in addressing common diseases among the elderly. Promoting vaccination in this demographic helps realize the full potential and value of immunization. Currently, China offers a diverse range of vaccines for older adults; however, vaccination rates remain low, and vaccination services are not adequately tailored to their needs. Against the backdrop of population aging, it is essential to adopt a scientific, systematic, and application-oriented approach to comprehensively optimize vaccination service models. Efforts should be made to further integrate healthcare and preventive services, enhance the accessibility of vaccination services, improve support mechanisms for elderly vaccination, strengthen the development of public health infrastructure, foster a health-conducive environment for vaccination among older adults, and explore a vaccination service system suited to their needs.

To analyze the changes in the pathogen spectrum of hand, foot, and mouth disease (HFMD) in Guangzhou City from 2015 to 2023, and to investigate the time trends of pathogen detection rates by gender and age stratification using Joinpoint regression. Pathogen surveillance data from sentinel hospitals for HFMD in Guangzhou were collected. A total of 9 677 cases were included in the study, among which 7 036 tested positive for enterovirus, yielding a positivity rate of 72.71%. During the study period, statistically significant differences were observed in the overall positive detection rates among different pathogens (χ²=12 988.49, P<0.001). CV-A6 consistently maintained a high detection rate throughout the monitoring period, with an overall positive detection rate of 37.05%, becoming the dominant pathogen. Trend analysis showed that both EV-U (APC=-4.89, P<0.001) and CV-A16 (APC=-20.98, P=0.032) had a significant declining trend, whereas the trend for CV-A6 was not statistically significant (APC=-9.63, P=0.116). Age stratification revealed that only the detection rate of EV-U in the ≤3-year-old group had a declining trend (APC=-5.01, P=0.006). In summary, from 2015 to 2023, the pathogen spectrum of HFMD in Guangzhou City has undergone significant changes, with CV-A6 replacing traditional pathogens as the dominant strain. Although the overall detection rate of EV-U has shown a downward trend, this decline was only evident among children aged ≤3 years. It is recommended to focus on strengthening prevention and control measures for children aged over 3 years old, accelerating the development of multivalent vaccines, and consistently strengthening pathogen surveillance and the construction of medical resources to cope with pathogen variations and changes in epidemiological features.

Objective: To investigate the genomic characteristics, virulence genes, and drug resistance features of Group A Streptococcus (GAS) isolates in Huairou District, Beijing, from 2012 to 2024. Methods: Throat swab specimens were collected from pediatric outpatients and emergency cases clinically diagnosed with scarlet fever or pharyngeal infections in maternal and child health hospitals in Huairou District between May and July each year from 2012 to 2024. GAS isolates were identified and subjected to whole-genome sequencing to analyze M protein gene types (emm) and multilocus sequence typing (MLST). A phylogenetic tree was constructed based on core genomes. Antimicrobial resistance genes and virulence genes were identified and analyzed, and antibiotic susceptibility testing was performed. Results: A total of 1 776 throat swab specimens were collected, and 121 GAS isolates were obtained (6.81%, 121/1 776). Four emm genotypes were identified: emm1, emm3, emm6, and emm12. The most prevalent type was emm12 (54.55%, 66/121). From 2012 to 2019, the predominant type was emm1 (61.18%, 52/85), while from 2023 to 2024, the predominant type was emm12 (97.22%, 35/36). Among the 121 GAS isolates, five ST types were identified: ST36 (54.55%, 66/121), ST1274 (24.79%, 30/121), ST28 (19.01%, 23/121), one isolate of ST15, and one isolate of ST382. Phylogenetic analysis showed a strong consistency between the emm types and ST types. Besides emm genes, 56 virulence genes were detected in the 121 GAS isolates, with an average of 44.42 and 42.53 virulence genes carried by emm12 and emm1 GAS isolates, respectively (Z=-3.691, P<0.001). Nine streptococcal superantigen genes were identified, among which speA and speJ showed statistically significant differences in the carriage rates of GAS in emm1 (26.42%, 24.53%, respectively) and emm12 (59.09%, 57.58%, respectively) (χ²=11.60 and χ²=13.11, respectively; both P<0.05). Among the 121 GAS isolates, 120 exhibited drug resistance, with high resistance rates of erythromycin (99.17%, 120/121), tetracycline (97.52%, 118/121), and clindamycin (99.17%, 120/121). Additionally, 97.52% (118/121) of GAS isolates showed triple resistance to erythromycin, tetracycline, and clindamycin. Four resistance genes were detected: lmrP (100%, 121/121), ermB (99.17%, 120/121), mef(E) (99.17%, 120/121), and tet(M) (97.52%, 118/121). The genotype and phenotype of drug resistance were closely aligned. Conclusion: The predominant GAS types in children in this district of Beijing from 2012 to 2024 are emm12 and emm1, with strong concordance between emm and ST types. GAS isolates demonstrate high resistance to erythromycin, tetracycline, and clindamycin, and resistance genotypes align well with their phenotypes.

To explore the influence of gender and age on the cutoff values of initial high-sensitivity cardiac troponin T (hs-cTnT) elevation in patients and identify optimal diagnostic cutoff values that better meet clinical needs, providing an objective basis for early diagnosis and intervention of acute myocardial infarction (AMI). This cross-sectional retrospective study included 622 patients with suspected AMI who were initially diagnosed and entered the Chest Pain Center treatment pathway emergency departments of Jinan Fourth People's Hospital from December 2022 to August 2023. Patients were categorized by gender, age, and clinical diagnosis. Receiver Operating Characteristic (ROC) curves and Youden indices were used to determine the optimal diagnostic cutoff points for hs-cTnT, evaluating the impact of gender and age on cut-off values and screening cutoff values with the best diagnostic performance under the clinical emergency requirement of positive predictive value (PPV)>85%. The results showed that no significant differences were observed between the AMI group (n=172) and non-AMI group (n=450) in gender, conduction block, atrial fibrillation, hypertension, diabetes, or chronic heart failure (all P>0.05). However, significant differences were found in age [73 (65, 81) years vs. 69 (60, 79) years, Z=-2.55, P=0.011], smoking status [77 (17.11%) vs. 42 (24.42%), χ²=4.93, P=0.038], and ST-T segment changes [224 (49.78%) vs. 108 (62.79%), χ²=8.48, P=0.040]. In the AMI group, age and gender had no significant effect on hs-cTnT concentrations (P>0.05). Binary logistic regression indicated that age was an independent factor associated with AMI diagnosis in this high-risk cohort [OR<1, Exp(b)=0.983]. ROC analysis under PPV>85% identified the following cut-off values: overall (51.60 ng/L), younger group (50.51 ng/L), older group (54.33 ng/L), female group (54.22 ng/L), and male group (49.32 ng/L). At the overall cut-off value of 51.60 ng/L, sensitivity was 0.59, specificity 0.96, PPV 85.0%, and NPV 86.1%, showing higher diagnostic efficacy than other cut-offs. In conclusion,among high-risk patients with initial hs-cTnT elevation, gender-and age-specific diagnostic cut-off values differ under the requirement of PPV>85%, with age having a greater influence on cut-off values. Adopting population-specific cut-off values reduces false-positive cases, conserves medical resources, and optimizes clinical workflows.