A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Objective To evaluate cardiac involvement in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) using echocardiography combined with electrocardiography. Methods A retrospective analysis was performed on the detailed medical records of AAV patients treated in Jining First People’s Hospital between January 2020 and December 2024. Eighty patients were enrolled in the AAV group, and the risk of heart disease was compared between the AAV group and a control group with 80 subjects matched for age, sex, and cardiovascular disease risk factors. Results Electrocardiographic abnormalities were observed in 78.75% of patients in the AAV group, while significant electrocardiographic abnormalities only occurred in symptomatic patients in the control group. There were no differences in left atrial enlargement or interventricular septal thickening between the AAV group and the control group. The overall left ventricular systolic function in the AAV group was lower than that in the control group (8.75% vs. 0). The incidence of reduced diastolic function in the AAV group was significantly higher than that in the control group (37.5% vs. 15%). The incidence rates of tricuspid regurgitation, mitral regurgitation, aortic regurgitation, and pericardial effusion in the AAV group were significantly higher than those in the control group. Pericardial thickening, aortic stenosis, pulmonary hypertension, and rare periaortic granulomas were found in the AAV group, but not in the control group. Conclusion Echocardiography and electrocardiography are important examination methods for evaluating cardiac involvement in AAV. These methods have key roles in disease screening, diagnosis and treatment, follow-up, and prognosis judgment.

OBJECTIVE: To investigate the risk factors, clinical characteristics, and bacterial resistance of bloodstream infections caused by Streptococcus mitis in children with hematological disease, so as to provide a reference for infection control. METHODS: The clinical information and laboratory findings of pediatric patients complicated with blood cultures positive for Streptococcus mitis from January 2018 to December 2020 in the Institute of Hematology & Blood Diseases Hospital were searched and collected. The clinical characteristics, susceptibility factors, and antibiotic resistance of the children were retrospectively analyzed. RESULTS: Data analysis from 2018 to 2020 showed that the proportion of Streptococcus mitis isolated from bloodstream infections in children (≤14 years old) with hematological diseases was the highest (19.91%) and significantly higher than other bacteria, accounting for 38.64% of Gram-positive cocci, and presented as an increasing trend year by year. A total of 427 children tested positive blood cultures, including 85 children with bloodstream infections caused by Streptococcus mitis who tested after fever. Most children experienced a recurrent high fever in the early and middle stages (≤6 d) of neutropenia and persistent fever for more than 3 days. After adjusting the antibiotics according to the preliminary drug susceptibility results, the body temperature of most children (63.5%) returned to normal within 4 days. The 85 children were mainly diagnosed with acute myeloid leukemia (AML), accounting for 84.7%. The proportion of children in the neutropenia stage was 97.7%. The incidence of oral mucosal damage, lung infection, and gastrointestinal injury symptoms was 40%, 31.8%, and 27.1%, respectively. The ratio of elevated C-reactive protein (CRP) and procalcitonin was 65.9% and 9.4%, respectively. All isolated strains of Streptococcus mitis were not resistant to vancomycin and linezolid, and the resistance rate to penicillin, cefotaxime, levofloxacin, and quinupristin-dalfopristin was 10.6%, 8.2%, 9.4%, and 14.1%, respectively. None of children died due to bloodstream infection caused by Streptococcus mitis. CONCLUSION The infection rate of Streptococcus mitis is increasing year by year in children with hematological diseases, especially in children with AML. Among them, neutropenia and oral mucosal damage after chemotherapy are high-risk infection factors. The common clinical symptoms include persistent high fever, oral mucosal damage, and elevated CRP. Penicillin and cephalosporins have good sensitivity. Linezolid, as a highly sensitive antibiotic, can effectively control infection and shorten the course of disease.
Humans ; Child ; Streptococcal Infections/microbiology* ; Retrospective Studies ; Hematologic Diseases/complications* ; Streptococcus mitis ; Drug Resistance, Bacterial ; Risk Factors ; Microbial Sensitivity Tests ; Anti-Bacterial Agents ; Female ; Male ; Bacteremia/microbiology* ; Child, Preschool ; Adolescent

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

OBJECTIVE: To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis. METHODS: A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks. Cardiac function was detected by echocardiography and myocardial pathological changes were observed by Van Gieson (VG) staining. Myocardial injury serum markers, including creatine kinase (CK), lactate dehydrogenase (LDH), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and growth differentiation factor-15 (GDF-15) were detected by enzyme linked immunosorbent assay (ELISA). Cardiomyocyte apoptosis was observed by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP triphosphate nick end labeling (TUNEL) and transmission electron microscopy, and the expressions of target proteins and mRNA were detected by Western blot and quantitative real time polymerase chain reaction (qRT-RCR), respectively. RESULTS: The treatment with different doses of SMI reduced rat heart mass index and left ventricular mass index (P<0.05), significantly improved the left ventricular ejection fraction (P<0.05), decreased the levels of serum CK, LDH, cTnT, and NT-proBNP (P<0.05 or P<0.01), reduced the levels of serum sST2 and GDF-15 (P<0.05 or P<0.01), decreased the collagen volume fraction, reduced the expressions of rat myocardial type I and type III collagen (P<0.05 or P<0.01), and effectively alleviated myocardial fibrosis. And the study found that SMI promoted the expression levels of miR-30a and Bcl-2 in myocardium, and down-regulated the expression of Bax, which inhibited the activation of Caspase-3 and Caspase-9 (P<0.05 or P<0.01), and improved myocardial cell apoptosis. CONCLUSIONS SMI can alleviate myocardial injury and apoptosis caused by DOX, and its mechanism possibly by promoting the targeted expression of myocardial Bcl-2 protein through miR-30a.
Animals ; Myocytes, Cardiac/metabolism* ; Apoptosis/drug effects* ; MicroRNAs/genetics* ; Rats, Sprague-Dawley ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Doxorubicin/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Drug Combinations ; Injections ; Rats

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Objective:To investigate the prevalence of enterovirus 71 (EV71) and the genetic characteristics of VP1 region in common hand, foot and mouth disease (HFMD) cases in Shenzhen from 2016 to 2022.Methods:Throat swabs from mild HFMD in Shenzhen sentinel hospitals were collected from 2016 to 2022. A total of 38 EV71-positive samples were screened from these throat swabs and were sequenced. Then, the VP1 sequence of these EV71-positive samples were analyzed for their phylogenetic evolution by bioimformatics software DNAStar and MEGA 6.Results:From 2016 to 2022, the number of EV71 infections among HFMD patients in Shenzhen sentinel hospitals decreased from 136 in 2016 to 0 in 2022. The mumber of EV71 infections in 2018 and 2019 decreased by 96.3%(257/267) compared to that in 2016 and 2017. From 2020 to 2022, the number of EV71 infections decreased to 0. During this period, the EV71 vaccination rate among HFMD patients increased from 6.4% to 39.6%; Evolutionary analysis showed that the nucleotide homology and amino acid homology between 38 EV71 sample strains in Shenzhen from 2016 to 2022 were 91.8%-99.9% and 98.3%-100.0%, all belonging to the C4a subgenotype; Among them, 26 strains wene local epidemic strains, and 11 strains were imported from other provinces, with a close genetic relationship with epidemic strains in Hainan, Yunnan, Sichuan, Tianjin, Henan, Jilin, and other places. One strain from 2017 had the closest genetic relationship with the US epidemic strain OP207969-USA-2017. Further comparing the EV71 epidemic strains in Shenzhen from 2016 to 2022 and EV71 severe strains, it was found that the EV71 strains in Shenzhen carried four amino acid mutation sites related to severe condition, named R22H, K43R, I249V and T289A.Conclusions:The EV71 epidemic strains in Shenzhen from 2016 to 2022 all belong to the C4a subgenotype, and the number of EV71 infection shows a downward trend with the increase of vaccine coverage rate. At the same time, the distribution of EV71 virus strains in Shenzhen shows a significant decrease in local strains and a predominance of imported strains. There are a total of four amino acid mutation sites associated with severe cases in the EV71 sample strains in Shenzhen from 2016 to 2022. Among them, 22R and 289T are located at the N and C ends of VP1, which are related to EV71 adsorption and targeting cells. The 43R site is associated with binding ability to Annexin2 protein, which enhances cell binding ability.

Quinic acid(QA)has antioxidant,anticancer and anti-inflammatory effects,but its pro-tective effect against bovine mastitis remains to be further investigated.The aim of this study was to investigate the inhibitory effects and mechanisms of quinic acid(QA)on lipopolysaccharide(LPS)-induced inflammation and pyroptosis in bovine mammary epithelial cells(MAC-T)and mouse mammary tissues.The CCK-8 method was applied to screen the treatment concentration of QA in MAC-T cells.The ELISA method was used to detect the expression levels of inflammatory factors,oxidative stress factors and pyroptosis indicators.The distribution of CD3 in mouse mam-mary tissues was detected by the immunohistochemical method.p65 nuclear translocation was measured by immunofluorescence.Western blot was performed to test the protein and phosphoryl-ation levels of NF-κB,the inflammasome of NOD-like receptor(NLRP3),Caspase-11 and gasder-min D(GSDMD).The results showed that QA(20,40 and 60 mg/L)significantly increased the activity of MAC-T cells(P＜0.05).QA treatment significantly reduced LPS-induced expression of inflammatory factors(TNF-α,IL-1β and IL 6),oxidative stress indicators(COX-2 and iNOS)and pyroptosis indicators(ROS,LDH and IL-18)in both MAC-T cells and mouse mammary tissues in a manner of dose-dependence(P＜0.05).Moreover,after intraperitoneal injection of QA at 5,10 and 20 mg/kg,respectively,the expression of T-lymphocyte marker CD3 induced by LPS was sig-nificantly downregulated in mouse breast tissues(P＜0.05).In addition,QA significantly de-creased the LPS-induced expression of NF-κB(IκBα,p65,p-IκBα and p-p65),inflammasome(NL-RP3,ASC and Caspase-1),Caspase-11 and DSDMD in both MAC-T cells and mouse mammary tis-sues,and inhibited p65 nuclear transfer in MAC-T cells(P＜0.05).Overall,the above results indi-cate that QA inhibits inflammatory response and pyroptosis through NF-κB and NLRP3 inflamma-some in both MAC-T cells and mouse mammary tissues.The results of this study provide novel da-ta on the prevention and treatment of mastitis by plant active ingredients.

Objective To detect the expression profile of heme oxygenase-1(HO-1)during the process of wound repair in radiation-wound combined injury(R-W-CI),and evaluate its wound healing improving effects of R-W-CI by HO-1 knockdown with siRNA.Methods A total of 36 male C57BL/6J mice(8 weeks old)were randomly and equally divided into a simple skin wound group(W group)and a skin wound group combined with whole-body radiation(6 Gy)injury(R-W-CI group).During the wound healing process,the wounds were photographed and recorded,and the residual areas were quantified by Image J.Wound tissues were sampled and stained with HE staining for pathological and histological observation,and the damage to the hematopoietic system was assessed by dynamic examination of the peripheral blood.The expression and changes of HO-1 in wound tissues were detected by q-PCR and Western blotting.Then,26 male C57BL/6J mice(8 weeks old)were randomly and equally divided into siRNA knockdown HO-1 group(si-HO-1 group)and siRNA negative control group(si-NC group).After radiation combined injury was inflicted,60 μL of F127 gel loaded with si-HO-1(5 μm/L)was applied to each wound in the si-HO-1 group,and an equal amount of F127 gel loaded with negative control si-NC was applied to the wound in the si-NC group.The knockdown of HO-1 in wound tissues was detected by Western blotting,and the changes in wound area were observed.In the wound tissues harvested in 3 d after wounding,the expression of cytokines IL-1β,IL-6 and TNF-α was examined by q-PCR and the proliferation of granulation tissues was evaluated by Ki67 immunohistochemical staining.HE staining was performed on wound tissues on day 3 and day 9 post-injury to assess the improvement effect of knockdown of HO-1 on wound healing of radiation combined injuries.Results Compared with the W group,semi-quantitative analysis of the residual wound area showed that healing was significantly delayed in the R-W-CI group on days 7 and 10 post-injury(P＜0.01).HE staining on day 7 showed that in the R-W-CI group,the re-epithelialization was delayed,and the growth of granulation tissues was poor;and at the same time,peripheral blood leukocytes and their classified counts showed a significant decrease in the early period after injury(P＜0.05).Further tests indicated that the expression of HO-1 protein was slightly higher in the wound of the R-W-CI group than that of the W group in 3 and 7 d after injury,though no significant difference(P＞0.05),whereas statistical difference was seen in 10 d(P＜0.05),accompanied by the distribution of the full-length and truncated forms of HO-1 protein.Quantitative PCR obtained similar results in the mRNA expression of HO-1 in wounds in both 7 and 10 d after injury(P＜0.05).siRNA intervention could effectively knock down the HO-1 protein level of the wounds(P＜0.05),promote wound contraction(P＜0.05),reduce the width of the wound(P＜0.01),up-regulate the inflammatory cytokines IL-6 and TNF-α in 3 d,enhance the proliferation of repair cells in wound margin,and improve the growth of the granulation tissue in the R-W-CI model when compared with the conditions after si-NC intervention.Conclusion There exists a sustained high expression level of HO-1 during wound repair,and wound knockdown of HO-1 by siRNA can improve the lack of inflammation status and promote wound healing in R-W-CI mice.