OBJECTIVES: To elucidate the underlying mechanisms of macrophage-mediated inflammation and tissue injury in diabetic foot ulcer (DFU). METHODS: Skin tissue samples were collected from patients with DFU and with non-DFU. A total of 79 272 high-quality cell transcriptomes were obtained using single-cell RNA sequencing. An unbiased clustering approach was employed to identify cell subpopulations. Seurat functions were used to identify differentially expressed genes between DFU and non-DFU groups, and gene ontology (GO) enrichment analysis was used to reveal gene function. Furthermore, cell-cell communication network construction and ligand-receptor interaction analysis were performed to reveal the mechanisms underlying cellular interactions and signaling regulation in the DFU microenvironment from multiple perspectives. RESULTS: The results revealed a significant expansion of myeloid cells in DFU tissues, alongside a marked reduction in structural cells such as endothelial cells, epithelial cells, and smooth muscle cells. Major cell types underwent functional reprogramming, characterized by immune activation and impaired tissue remodeling. Specifically, macrophages in DFU skin tissues exhibited a shift toward a pro-inflammatory M1 phenotype, with upregulation of genes associated with inflammation and oxidative stress. Cell communication analysis further demonstrated that M1 macrophages served as both primary signal receivers and influencers in the COMPLEMENT pathway mediated communication network, and as key signal senders and mediators in the secreted phosphoprotein 1 (SPP1) pathway mediated communication network, actively shaping the inflammatory microenvironment. Key ligand-receptor interactions driving macrophage signaling were identified, including C3-(ITGAM+ITGB2) and SPP1-CD44. CONCLUSIONS This study establishes a comprehensive single-cell atlas of DFU, revealing the role of macrophage-driven cellular networks in chronic inflammation and impaired healing. These findings may offer potential novel therapeutic targets for DFU treatment.
Humans ; Macrophages/immunology* ; Diabetic Foot/pathology* ; Single-Cell Analysis ; Transcriptome ; Gene Expression Profiling ; Inflammation ; Skin ; Cell Communication ; Signal Transduction ; Cellular Reprogramming

OBJECTIVE: Serological and molecular biological analysis of a B(A) subtype family was carried out to explore the underlying mechanism of B(A) subtype and clinical safe blood transfusion strategies. METHODS: The ABO blood type of the proband and her four family members were identified by serological methods, and serological experiments such as anti-H, anti-A1 and absorption-elution tests was added. In addition, the exons 6 and 7 of the ABO gene were sequenced by PCR-SSP (polymerase chain reaction - sequence specific primer). RESULTS: The serological results showed that the agglutination intensity of the proband, her mother and her maternal grandmother was imbalanced during forward typing, showing weak A and strong B antigens, and there were strong H antigens and their intensity were higher than that of normal B type. The results of reverse typing indicated the presence of weak anti-A1 antibodies, and human anti-A was positive in the absorption-elution test. Genetic sequencing revealed a characteristic mutation of c.700 C>G in all three individuals. The sequencing results showed that the proband was B(A)02/B01, her mother was B(A)02/O02, and her maternal grandmother was B(A)02/O01 . According to the compatibility principle, 1.5 units of type O washed red blood cells were transfused intraoperatively, resulting in no adverse reactions. CONCLUSION The c.700 C > G mutation on exon 7 is the molecular basis for the formation of B(A)02, and pedigree analysis shows that the B(A)02 allele was inherited from the proband's maternal grandmother to the proband's mother and then to the proband, showing a stable cis-inheritance pattern rather than a spontaneous mutation. For patients with B(A)02 subtype, type O washed red blood cells and type AB plasma can be transfused according to the principle of compatibility.
Humans ; ABO Blood-Group System/genetics* ; Female ; Blood Transfusion ; Blood Grouping and Crossmatching ; Pedigree ; Male ; Mutation ; Adult ; Exons

Objective To explore the mediating role of activities of daily living (ADL) in pain and depressive symptoms in the elderly in China. Methods Utilizing the data from 2020 China Health and Retirement Longitudinal Study, 4403 Chinese elderly individuals aged ≥ 60 years old were selected as the research subjects. Depression Scale (CES-D 10) of the Center for Epidemiological Survey and ADL scale were used in the study. The PROCESS4.1 macro was used to test the mediating effect of daily living activities between pain and depressive symptoms, and the Bootstrap method was applied for verification of the mediating variables. Results A total of 2368 cases of depressive symptoms were detected in the elderly in China, with a detection rate of 53.78%. Pain was positively correlated with depressive symptoms (r=0.27, P<0.01), and activities of daily living were negatively correlated with pain and depressive symptoms (r=-0.27, -0.337, P<0.01). The results showed that the total effect value of pain on depressive symptoms was 0.33, the direct effect value was 0.24, and the mediating effect value of daily living activities was 0.09, accounting for 27.27%. Conclusion Pain and activities of daily living are important factors influencing depressive symptoms in the elderly, and activities of daily living play a partial mediating role in the relationship between pain and depressive symptoms in the elderly.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

Objective To investigate the changing trend and epidemiological characteristics of the incidence and mortality of chronic kidney disease (CKD) with age, period and birth cohort in Chinese population. Methods Based on the data of incidence and mortality of CKD in Chinese population aged 20-80 years from 1990 to 2019 in GHDx database, joinpoint regression model was used to analyze the incidence and mortality trend of CKD. An age-period-cohort model was constructed to analyze the effects of age, period, and birth cohort on the trend of CKD incidence and mortality. Results Joinpoint regression analysis showed that the standardized incidence rate of chronic kidney disease in Chinese population increased from 146.37/100 000 in 1990 to 161.52/100 000 in 2019, while the standardized mortality rate decreased from 12.98/100 000 in 1990 to 11.23/100 000 in 2019. The APC model analysis showed that the risk of CKD incidence and death in the Chinese population increased with age, while the risk of CKD incidence increased with the increase of period. The risk of death did not change significantly with the increase of period. The cohort born later had a lower risk of CKD incidence and death compared to the cohort born earlier. Conclusion At present, the age effect and period effect of the incidence and death risk of chronic kidney disease in China are dominant. It is important to take effective measures and intervene in a timely manner, especially to strengthen the protection of older high-risk groups born earlier.

【Objective】 To study the molecular mechanism of 95 samples of serological ABO subtypes. 【Methods】 A total of 95 samples with discrepancy between forward and reverse blood grouping were subjected to serological confirmation, and genotyped by polymerase chain reaction with sequence-specific primers (PCR-SSP). For those subtype alleles could not be detected by PCR-SSP, ABO gene exon 1-7 sequencing and gene single strand sequencing were performed successively to determine the mutation site and the gene location. 【Results】 A total of 34 ABO alleles were detected in 95 samples. Five common ABO alleles (ABO^*A1.01, ABO^*A1.02, ABO^*B.01, ABO^*O.01.01 and ABO^*O.01.02) and 29 rare ABO alleles were identified, including 16 named alleles by ISBT (ABO^*A2.01, ABO^*A2.05, ABO^*A2.13, ABO^*A3.07, ABO^*AW.37, ABO^*AEL.05, ABO^*B3.01, ABO^*B3.05, ABO^*BW.03, ABO^*BW.07, ABO^*BW.27, ABO^*BEL.03, ABO^*cisAB.01, ABO^*cisAB.05, ABO^*BA.02, ABO^*BA.04) and 5 named alleles by dbRBC(A223, B309, Bw37, Bel09, Bw40)and eight unnamed alleles [ABO^*B.01+ 978C>A, ABO^*A1.02+ 248A>T, ABO^*B.01+ 125dupT, ABO^*B.01+ (98+ 1G>A), ABO^*A1.02/ABO^*B.01+ 1A>G, ABO^*A1.02/ABO^*O.01.01+ 28G>T, ABO^*A1.02/ABO^*B.01+ 538C>T, ABO^*A1.02/ABO^*O.01.01+ 797insT] .The last four samples could not be verified by single strand because of insufficient samples. In 95 samples, 76 samples (21 named alleles of ISBT and dbRBC) were identified by PCR-SSP, and the remaining 19 samples were identified by exon 1-7 sequencing of ABO gene, of which 8 were identified as unnamed alleles, and the remaining 11 samples were not identified as subtype alleles. 【Conclusion】 The molecular genetic mechanism of 95 serological ABO subtypes was revealed, and 8 rare novel alleles were identified. The detection of ambiguous blood groups is influenced by factors such as patient pathology and physiology, therefore the combination of serological testing and genetic testing is suggested for the identification of ABO subtype.

Objective　To explore the mediating role of cognitive function in the association between literacy level and depressive symptoms in middle-aged and elderly people in China. Methods　 Using the fourth national follow-up data of the China Health and Elderly Care Tracking Survey 2018, 8 124 middle-aged and elderly people aged 45 years and above were included as the study subjects. The PROCESS 4.0 program was used to test the mediating effect of cognitive function between literacy level and depressive symptoms, and the Bootstrap method was used for the mediator variable validation. Results The detection rate of depressive symptoms among middle-aged and elderly people in China was 38.10%. After controlling for gender, place of residence, marital status, smoking, alcohol consumption, and exercise, literacy level was a negative predictor of depressive symptoms in middle-aged and elderly people (β =－0.480, t =－11.248, P<0.001). Cognitive function accounted for 58.75% of the amount of mediating effect between literacy level and depressive symptoms. Conclusion 　Literacy level and cognitive function are associated with depressive symptoms in middle-aged and elderly people. Literacy level can influence depressive symptoms directly or indirectly through the mediation of cognitive dysfunction.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Diquat is a kind of conductive contact-killing herbicides. The damage of central nervous system is relatively common, but the peripheral neuropathy caused by diquat has not been reported yet. In September 2021, we treated a patient with diquat poisoning. During the hospitalization, the patient was diagnosed with peripheral neuropathy. Therapy for peripheral nerve injury was given on the basis of conventional treatment of poisoning. The patient was discharged after his condition was stable. The follow-up showed that the peripheral neuropathy of patient was better than before. According to the condition of this patient, it is suggested that we should not only protect the function of gastrointestinal tract, liver, kidney, and central nervous system early, but should also pay attention to the damage of peripheral nervous system in clinical work. We should intervene earlier to improve the prognosis of patients.
Humans ; Diquat ; Herbicides ; Kidney ; Liver ; Peripheral Nerve Injuries ; Poisoning