OBJECTIVE To explore the improvement effect and mechanism of salidroside on radiation-induced parotid gland injury in rats. METHODS Rats were randomly assigned into normal group， radiation group， salidroside low-dose （salidroside-L， 50 mg/kg） group， salidroside high-dose （salidroside-H， 100 mg/kg） group， and salidroside-H+inhibitor （100 mg/kg salidroside+0.1 µmol/kg H-89） group， with 10 rats in each group. Except for the normal group， rats in the other groups were subjected to radiation exposure to establish a model of radiation-induced parotid gland injury. Rats in each group were intraperitoneally injected with the corresponding drug or normal saline， once a day， for 40 consecutive days. After the last administration， the levels of reactive oxygen species （ROS）， cyclic adenosine monophosphate （cAMP）， superoxide dismutase （SOD）， and amylase in serum were detected； the pathological changes of parotid gland tissue were observed； the apoptosis rate of parotid gland tissue cells， the expression levels of B-cell lymphoma-2 （Bcl-2） and its associated X protein （Bax）， mRNA expression levels of interleukin-6 （IL- 6） and tumor necrosis factor-α （TNF-α）， the protein expression levels of type Ⅲ collagen （Col Ⅲ）， vasoactive intestinal peptide （VIP）， and the phosphorylation level of protein kinase A （PKA） in parotid gland tissue were determined. RESULTS Compared with normal group， the levels of ROS， amylase， apoptosis rate， Bax expression level， mRNA expression levels of IL-6 and TNF- α， and protein expression level of Col Ⅲ in the radiation group were significantly increased， while the levels of cAMP， SOD， Bcl-2 expression level， VIP protein expression level and PKA phosphorylation level were significantly decreased （P＜0.05）. Compared with radiation group， the above indicators in the salidroside-L group and salidroside-H group were significantly improved （P＜0.05）， and the improvement in the salidroside-H group was more significant （P＜0.05）； inhibitor H-89 significantly reversed the changes in the above indicators of the salidroside-H group （P＜0.05）. CONCLUSIONS Salidroside can effectively alleviate radiation-induced parotid gland injury in rats， and its mechanism may be related to the activation of the VIP-cAMP pathway.

The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans ; Male ; Infant ; Disorder of Sex Development, 46,XY/etiology* ; Protein Phosphatase 1/genetics*

OBJECTIVE: To explore the clinical characteristics, diagnosis, and treatment methods of one patient with idiopathic multicentric Castleman disease (iMCD), in order to strengthen the understanding of this rare disease. METHODS: The clinical manifestations, diagnosis and treatment process, and prognosis of one patient with iMCD admitted to our hospital were retrospectively analyzed. RESULTS: The patient was a 45-year-old female with swollen bilateral orbit, edema of lower limbs, multiple serosal cavity effusion, thrombocytopenia, renal insufficiency, and multiple lymph node enlargement. Lymph node biopsy suggested mixed type of Castleman disease. Combined with pathology, imaging and laboratory examination, the patient was finally diagnosed with mixed type of iMCD. After six cycles of R-COP regimen chemotherapy, the patient achieved complete remission. CONCLUSIONS Castleman disease with renal and orbit involvement is rare in clinic and easy to be misdiagnosed. It should be distinguished from lymphoma. The patient has been treated with R-COP regimen, and obtained good short-term efficacy.
Humans ; Castleman Disease/diagnosis* ; Middle Aged ; Female ; Retrospective Studies ; Orbit/pathology* ; Kidney/pathology*

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

The focus of green analytical chemistry (GAC) is to minimize the negative impacts of analytical procedures on human safety, human health, and the environment. Several factors, such as the reagents used, sample collection, sample processing, instruments, energy consumed, and the quantities of hazardous materials and waste generated during analytical procedures, need to be considered in the evaluation of the greenness of analytical assays. In this study, we propose a greenness evaluation metric for analytical methods (GEMAM). The new greenness metric is simple, flexible, and comprehensive. The evaluation criteria are based on both the 12 principles of GAC (SIGNIFICANCE) and the 10 factors of sample preparation, and the results are presented on a 0-10 scale. The GEMAM calculation process is easy to perform, and its results are easy to interpret. The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number.

Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins.Lysosome is an important organelle in eukaryotic cells,containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules.It is closely related to intracellular transport and autophagy,and is important for maintaining cellular homeostasis.This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes.Lysosomal dysfunction can lead to neurodegenerative diseases such as AD.Modulation of lysosomal function is a promising treatment strategy for AD.It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.

Objective To investigate the predictive value of serum uric acid(UA),homocysteine(Hcy)and the product index of UA and Hcy in patients with stable coronary artery disease(SCAD).Methods A total of 783 patients with suspected coronary heart disease were collected,all of whom underwent coronary angiography.Patients were divided into coronary heart disease(CHD)group and non-coronary heart disease(NCHD)group.The CHD group was further divided into low score group(≤35 points)and high score group(>35 points)according to Gensini scores.Baseline data,blood lipids,Hcy,UA,left ventricular function ultrasound indicators,and comorbidities were collected.Logistic regression analysis was used to evaluate the risk factors associated with the onset of SCAD and severe coronary artery disease,while the Receiver Operating Characteristic(ROC)curve was conducted to assess the predictive efficacy of the product index of UA and Hcy,and related risk factors,for SCAD onset and severe coronary artery disease.Results 1.In CHD group,UA,Hcy and the product index of UA and Hcy were all higher than in the NCHD group(P<0.001);the high-score group had higher UA,Hcy and the product index of UA and Hcy than the low Gensini score group(P<0.001).2.Multivariate logistic regression analysis showed that female age,sex,body mass index(BMI),product index of UA and Hcy,high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),type 2 diabetes mellitus(T2DM)and hypertension(HTN)were independent risk factors for SCAD(P<0.05).BMI,the product index of UA and Hcy,HDL-C,LDL-C and LVEF were independent risk factors for severe coronary artery disease(P<0.05).3.There was a positive correlation between UA and Hcy product index and Gensini scores(r=0.433,P<0.05).4.Receiver operating characteristic curve analysis showed that the product index of UA and Hcy and combined detection of coronary heart disease risk factors had predictive value for the occurrence of SCAD(P<0.05),and the predictive value of combined detection was higher(area under the curve 0.808);both the product index of UA and Hcy and the combined detection of coronary heart disease risk factors had predictive value for severe coronary artery lesions(P<0.05),with a higher predictive value for combined detection(area under the curve 0.771).Conclusion As an independent predictor of the risk of SCAD and severe coronary stenosis,the product index of UA and Hcy has a high predictive efficacy regarding disease risk and the severity of coronary artery in patients with SCAD.

Objective To explore the risk signals of niraparib and provide references for rational and safe clinical medication.Methods Niraparib-related adverse drug events(ADEs)reports from Q1 2017 to Q2 2023 were extracted from the US FDA Adverse Event Reporting System(FAERS)database.Risk signals were identified using the reporting odds ratio(ROR),proportional reporting ratio(PRR),Bayesian confidence propagation neural network(BCPNN),and multi-item gamma Poisson shrinker(MGPS)methods.The Risk signals were described and classified by preferred system organ classes(SOCs)and preferred terms(PTs)from the Medical Dictionary for Regulatory Activities(MedDRA)version 26.1,and the occurrence of niraparib-related ADEs was also analyzed.Results A total of 16,961 ADE reports with niraparib as the primary suspected drug were extracted.Through screening and analysis,32 PTs were identified involving 11 SOCs,which were largely consistent with the information in the drug label.However,suspicious signals not mentioned in the label,including neuropathy peripheral,decreased red blood cell count,reduced hematocrit,dehydration,and hot flashes,require further attention.The median occurrence time was 22 days(IQR 2-98 days),and the Weibull distribution test indicated an early failure-type curve.Conclusion When using niraparib,particularly in early stages of treatment,it is essential to monitor not only the ADEs mentioned in the drug instructions,such as decreased platelet count,nausea and fatigue,but also to pay close attention to the ADEs not included in the instructions,such as peripheral neuropathy and decreased red blood cell count,which exhibit strong signal values,to ensure patient medication safety.

Objective To evaluate the predictive value of changes in serum homocysteine(Hcy),high-density lipoprotein cholesterol(HDL-C),and the homocysteine-to-HDL-C ratio(HHR)for the incidence and short-term prognosis of patients with premature coronary heart disease(PCHD).Methods Between January 2022 and December 2023,301 patients with the suspected coronary heart disease(males≤55 years,females≤65 years)were retrospectively selected from the Department of Cardiology at the Third People's Hospital of Yunnan Province.All patients who underwent coronary angiography(CAG)were divided into the premature coronary heart disease(PCHD)group(n=98)and the non-coronary heart disease(NCHD)group(n=203).Patients with PCHD were followed up six months after the discharge and were further classified into the good prognosis group(n=55)and the poor prognosis group(n=43)based on the presence of worsening clinical symptoms such as chest tightness,chest pain,arrhythmias,heart failure,or death.Data collected included general patient information,blood lipid levels,Hcy levels,left ventricular function ultrasound indicators,and the presence of hypertension and type 2 diabetes.Results Hcy and HHR levels were significantly higher in the PCHD group compared to the NCHD group,while HDL-C levels were lower(P<0.001).In the poor prognosis group,Hcy and HHR levels were elevated,and HDL-C levels were reduced compared to the good prognosis group(P<0.001).The Hcy and HHR levels in the severe coronary artery stenosis group were markedly higher than those in the normal coronary artery group and the mild to the moderate stenosis group,with HDL-C levels being lower(P<0.001).Multivariate logistic regression analysis identified that male sex,HHR,Hcy,low-density lipoprotein cholesterol(LDL-C),and left ventricular ejection fraction(LVEF)were independent factors influencing premature coronary heart disease(P<0.05).HHR was found to be an independent risk factor for the poor short-term prognosis in PCHD.The analysis of the operating characteristic curve of the subjects showed that serum Hcy and HHR had the predictive value for the occurrence of PCHD(P<0.05),with HHR showing higher predictive value(area under the curve[AUC]=0.713).HHR also had the substantial predictive value for the short-term prognosis of PCHD(AUC=0.715).Conclusion Elevated HHR levels are associated with the severe coronary artery disease in patients with PCHD.HHR serves as a significant predictor for both the occurrence and short-term prognosis of PCHD.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors