This study aims to investigate the ameliorating effect of Corni Fructus(CF) on the myocardial ischemic injury and the pharmacokinetic properties of characteristic components of CF. The mouse model of isoproterenol-induced myocardial ischemia was established and administrated with the aqueous extract of CF. The general efficacy of CF in ameliorating the myocardial ischemic injury was evaluated based on the cardiac histopathology and the levels of myocardial injury markers: creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTn-I). The metabolomics analysis was carried out for the heart and serum samples of mice to screen the biomarkers of CF in ameliorating the myocardial ischemic injury and then the predicted biomarkers were submitted to metabolic pathway enrichment. The pharmacokinetic analysis was performed for morroniside, loganin, and cornuside Ⅰ in mouse heart and serum samples to obtain the pharmacokinetic parameters of these components. The pharmacokinetic parameters were then integrated on the basis of self-defined weighting coefficients to simulate an integrated pharmacokinetic profile of CF iridoid glycosides in the heart and serum of the mouse model of myocardial ischemia. The results indicated that CF reduced the pathological damage to cardiac cells and tissue(hematoxylin-eosin staining) and lowered the levels of CK-MB and cTn-I in the serum of the mouse model of myocardial ischemia(P<0.01). Metabolomics analysis screed out 31 endogenous metabolites in the heart and 35 in the serum as biomarkers of CF in ameliorating the myocardial ischemic injury. These biomarkers were altered by modeling and restored by CF. Six metabolic pathways in the heart and 5 in the serum were enriched based on these metabolic markers. The main integrated pharmacokinetic parameters of CF iridoid glycosides were T_(max)=1 h, t_(1/2)=(1.52±0.05) h in the heart and T_(max)=1 h, t_(1/2)=(1.56±0.50) h in the serum. Both concentration-time curves showed a double-peak phenomenon. In conclusion, CF demonstrated the cardioprotective effect by regulating metabolic pathways such as taurine and hypotaurine metabolism, and pantothenic acid and coenzyme A biosynthesis. The integrated pharmacokinetics reflect the general pharmacokinetic properties of characteristic components in CF.
Animals ; Cornus/chemistry* ; Mice ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Myocardial Ischemia/metabolism* ; Humans ; Troponin I/metabolism* ; Myocardium/pathology* ; Disease Models, Animal ; Biomarkers/metabolism* ; Creatine Kinase, MB Form/metabolism*

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

Objective:To investigate the clinicopathological features of advanced-stage mycosis fungoides (MF).Methods:A retrospective case-series study was conducted. The clinical data of 5 cases diagnosed with advanced-stage MF in Chengdu Second People's Hospital between January 2015 and July 2023 were analyzed. The clinicopathological features of patients were summarized.Results:There were 2 males and 3 females in 5 MF patients, with the median age of 55 years (45-86 years) and the medical history of 2-16 years. The main symptoms were pruritus and erythema. The lesions were presented by erythema, scales, plaques, blisters, erosion, ulcers, pigmentation, nodules, and erythroderma. Histopathological examination showed different skin lesion patterns such as psoriasis-like, interfacial dermatitis, non-infectious granuloma, deep and shallow perivascular dermatitis, tumors. Among 5 patients, 1 case was mycosis fungoides bullosa, 2 cases were erythrodermic MF, 1 case was granulomatous MF, and 1 case was classical MF. Lymphocyte epidermis was found in 4 cases, cytoplasmic halos cells lined up along the basal layer of the epidermis and Pautrier microabscess were found in 3 cases, large-cell transformation was found in 1 case. Tumor cells were positive for CD3, CD4 and negative for CD8, CD56, ALK and CD20; EBER 1/2 hybridization in situ was negative. CD30 was positive in transformed large cells and T cell receptor gene rearrangement was positive. The tumor cells were detected in bone marrow and peripheral blood of 2 cases and in cerebrospinal fluid of 1 case. Head magnetic resonance imaging of 1 case indicated abnormal signal nodules in the right temporal region and the normal architecture of the lymph nodes in 2 cases was completed destroyed by malignant cells. TNMB stage: 2 cases were in stage Ⅱ B, 2 cases were in stage Ⅳ A2, and 1 case was in stage Ⅳ B. Interferon α-based systemic therapy was performed in 1 case, 2 cases received chemotherapy or combined with intrathecal injection and radiotherapy, and other 2 cases were not treated. All of them just achieved partial remission. Finally, 1 case died of sudden cardiac death, 2 cases died of lung infection, and 2 cases survived with tumors. Conclusions:Advanced-stage MF is presented with different skin lesion manifestations and histopathologic changes. Multidisciplinary combined management helps the diagnosis and treatment of MF.

OBJECTIVES: To explore the efficacy and adverse reactions of nusinersen combined with risdiplam in the treatment of spinal muscular atrophy (SMA). METHODS: A retrospective analysis was conducted on the clinical data of 10 pediatric SMA patients treated with nusinersen combined with risdiplam at the Children's Medical Center of Xiangya Hospital, Central South University. RESULTS: Among the 10 SMA patients, there were 4 with type I, 4 with type II, and 2 with type III. Nine patients initially received nusinersen monotherapy, while 1 patient received nusinersen combined with risdiplam. The median duration of combination therapy with nusinersen and risdiplam for the 10 patients was 10.5 months (range: 0.5-20.0 months), with 6 patients undergoing combination therapy for more than 6 months, showing improvements in motor and/or respiratory function. The remaining 4 patients had combination treatment durations of 0.5, 1.0, 1.3, and 4.0 months, respectively, with no significant overall improvement. After combined treatment, 5 patients experienced skin hyperpigmentation, 2 had lumbar puncture site pain, 1 experienced vomiting, 1 had increased sputum production, and 1 had reduced total sleep time. All adverse reactions were mild and did not require medical intervention. CONCLUSIONS Nusinersen combined with risdiplam demonstrates efficacy in the treatment of SMA, and no significant adverse reactions have been observed.
Humans ; Oligonucleotides/adverse effects* ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Infant ; Muscular Atrophy, Spinal/drug therapy* ; Drug Therapy, Combination ; Child ; Azo Compounds ; Pyrimidines

The patient was a girl, aged 10 years, who was admitted due to fever for 5 days and pancytopenia in peripheral blood for 2 days. Bone marrow examination showed the presence of phagocytic activity, and peripheral blood tests showed pancytopenia, an increase in ferritin, a reduction in fibrinogen, increases in triglyceride and sCD25, and a reduction in natural killer cell activity, which led to the diagnosis of hemophagocytic lymphohistiocytosis (HLH). On the day of admission, the child developed convulsions and rapidly progressed to refractory status epilepticus, which was consistent with the manifestations of febrile infection-related epilepsy syndrome. HLH was controlled after active immunotherapy, with the sequela of refractory epilepsy, and her cognitive function was essentially within normal limits. This article reports the condition of febrile infection-related epilepsy syndrome caused by HLH for the first time in China, in order to improve the awareness of this disease among clinicians.
Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Female ; Child ; Epilepsy/etiology* ; Fever/etiology* ; Epileptic Syndromes/etiology*

OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

An efficient analytical method was developed for simultaneous detection of alkylamines and alkylamides in food packaging plastics using liquid chromatography-high resolution mass spectrometry(LC-HRMS).Based on the physicochemical properties of alkylamines and alkylamides,as well as the complexity of plastic samples,sample pretreatment and chromatographic-mass spectrometric parameters were optimized.The samples were extracted by vortex-ultrasonic extraction with a methanol-acetonitrile mixture for 15 min,followed by nitrogen evaporation to concentrate the extract,reconstitution,and analysis.The chromatographic mobile phase consisted of 0.1%formic acid aqueous solution and acetonitrile,and a gradient elution was used.The electrospray ionization(ESI)source was operated in positive ion mode,and mass spectrometry data were collected in full scan and data-dependent acquisition modes.Quantification was performed using an isotope-labeled internal standard method.The results showed that within the quantification range of 1-1000 ng/mL,the calibration curves exhibited good linearity(R2>0.99).Some compounds interfered with the validation experiments at higher concentrations,so only 10 kinds of target analytes were validated.Using a mixed food packaging plastic matrix,the recoveries at spiking levels of 40,400,and 4000 ng/g were mostly between 66.0%and 117.1%,with relative standard deviations ranging from 0.6%to 10.6%.The method was applied to detect 14 food packaging plastic samples,and the results showed that the concentrations of alkylamines and alkylamides ranged from not detected to 8924 ng/g.This method offered high sensitivity and accuracy,and was suitable for the screening and quantitative determination of alkylamines and alkylamides in plastics.

A retrospective analysis was conducted on the clinical characteristics, renal pathology, genetic testing, and treatment of five patients —two males and three females—diagnosed with primary atypical hemolytic uremic syndrome (aHUS) in the Department of Nephrology at the Affiliated Hospital of Qingdao University from February 2022 to June 2024. The patients′ ages at disease onset ranged from 14 to 29 years. Four patients experienced prodromal infection symptoms. At disease onset, serum creatinine levels ranged from 168.5 to 1 230.2 μmol/L. All patients presented with hematuria, proteinuria, hypertension, non-immune hemolytic anemia, thrombocytopenia, elevated lactate dehydrogenase (LDH), and fragmented red blood cells in peripheral blood (0.5%-6.0%). Serum haptoglobin levels were below the normal lower limit in all cases. Four patients demonstrated decreased serum complement C3, while one maintained normal serum complement C3 throughout the course of the disease. One patient exhibited serum factor H concentrations below the normal lower limit. Another patient tested positive for anti-factor H antibodies. Renal biopsies were performed on four patients. Electron microscopy revealed typical acute-phase pathological features of aHUS in three cases, including glomerular endothelial cell swelling and widened subendothelial spaces. One patient demonstrated ischemic and atrophic changes in the glomerular capillaries, while another had concurrent membranous nephropathy. Whole-exome high-throughput sequencing related to aHUS was performed in all five patients, revealing heterozygous gene mutations in each case. Complement-related gene mutations, typically occurring in a heterozygous state, are prevalent in aHUS patients. The eight heterozygous gene variations identified in this study were absent from existing databases of known aHUS-associated pathogenic mutations. Four patients received eculizumab treatment at varying time points following diagnosis, resulting in differing clinical outcomes. The patient positive for anti-factor H antibodies was treated with rituximab. The patient with membranous nephropathy initiated combination therapy with rituximab and eculizumab after six months of eculizumab monotherapy. Following treatment, all five patients achieved complete cessation of intravascular mechanical hemolysis, with normalization of LDH and platelet levels, as well as varying degrees of renal function recovery. From a pathophysiological perspective, the timely administration of the complement C5 inhibitor eculizumab can rapidly induce clinical remission, reduce the incidence of end-stage renal disease, and improve prognosis in patients with aHUS.

Objective To analyse the efficacy of Gao Mo therapy in the treatment of aromatase inhibitor-related osteoarticular symptoms in breast cancer patients.Methods A total of 80 breast cancer patients with aromatase inhibitor-related osteoarticular symptoms were selected from the breast clinic of a Tier-IIIA hospital in Guangdong Province between January and August 2024.The patients were divided into an intervention group and a control group according to the random number table,with 40 patients per group.Patients in the control group received routine nursing care,while the patients in the intervention group received Gao Mo therapy for 4 weeks based on the intervention of the control group.The two groups were compared with in terms of pain level,index of knee osteoarthritis,and quality of life of the patients with breast cancer before intervention and at 1st,2nd and 4th weeks after intervention.Results Before the intervention,the two groups presented no significant differences in scores of pain assessment,knee osteoarthritis index and quality of life(P>0.05).Analysis of variance for repeated measures showed that the main effects of time and group as well as the interaction effect,were statistically significant in scores of pain assessments in both groups(both P<0.05).The main effects of time and the interaction effect were statistically significant in scores of knee osteoarthritis index and quality of life assessments at different time points(both P<0.05),but there was no statistically significant difference in the main effect between groups(both P>0.05).After 4 weeks of intervention,the intervention group demonstrated significantly lower scores in knee function and pain assessments with a significantly higher scores in the total quality of life assessment in comparison with those of the control group(all P<0.05).Conclusion Gao Mo therapy can mitigate the aromatase inhibitor-related osteoarticular symptoms in breast cancer patients,enhance the function of knees,and improve the quality of life of the patients with breast cancer.

Objective·To analyze the molecular epidemiological characteristics of Klebsiella pneumoniae isolated from children,including the distribution of serotypes,resistance genes,and virulence genes,to provide a scientific basis for the prevention and treatment strategies of Klebsiella pneumoniae infections in children.Methods·A total of 133 non-duplicate strains of Klebsiella pneumoniae clinically isolated from Shanghai Children's Hospital,Shanghai Jiao Tong University School of Medicine,from April 2023 to April 2024,were collected.Antimicrobial susceptibility testing was performed by using the Vitek-2 Compact system.Capsular polysaccharide K antigen serotypes(K types)were determined by wzy-dependent initiator(wzi)gene sequencing.Resistance genes were detected by the colloidal gold method.Virulence genes and lipopolysaccharide O antigen serotypes(O types)were identified by PCR method.Results·Among the 133 strains of Klebsiella pneumoniae,a total of 50 strains of carbapenem-resistant Klebsiella pneumoniae(CRKP)were detected,mainly distributed in the neonatal ward and intensive care unit(ICU).CRKP exhibited high resistance to most antimicrobial agents,and the main type of carbapenemase gene was blaNDM(34/50,68.00%),followed by co-carriage of blaNDM+blaOXA-48(10/50,20.00%)and blaKPC(6/50,12.00%).Serotype analysis revealed that the 50 CRKP strains could be divided into 8 K types and 6 O types.The most common K type was KL17(30/50,60.00%),followed by KL105(10/50,20.00%)and KL47(5/50,10.00%).The most common O type was O4(30/50,60.00%),followed by O3b(7/50,14.00%,),O3/O3a(6/50,12.00%),and OL101(5/50,10.00%).Significant correlations were identified between KL47 and OL101 serotypes(KL47:OL101),between KL17 and O4 serotypes(KL17:O4),and between KL1/KL2 and O1 serotypes(KL1/KL2:O1).Conclusion·The CRKP strains infecting children primarily carry blaNDM-type carbapenemase genes,showing a significant difference compared to CRKP-infected adults.The detection rate of CRKP in the neonatal ward is significantly higher than those in other departments,suggesting that infection prevention and control measures in this ward need to be strengthened.