OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To observe the correlation between retinal capillary density and retinal thickness in the macula and spherical equivalent (SE) in school-age children.Methods:A cross-sectional study. From May to December 2022, 182 school-age children who visited the ophthalmology department of the First Affiliated Hospital of Zhengzhou University were included. There were 95 males and 87 females. The age ranged from 6 to 12 years, and the spherical equivalent (SE) was +0.50 to -6.00 D. They were divided into three groups based on the SE of the right eyes: 54 eyes in emmetropia group (+0.50≤SE<-0.50 D), 71 eyes in low myopia group (-0.50≤SE<-3.00 D), and 57 eyes in moderate myopia group (-3.00≤SE≤-6.00 D). The macular area of 6 mm×6 mm was scanned using swept-source optical coherence tomography angiography and was divided into three concentric rings centered on the fovea, including the macular central fovea (0-1 mm diameter), inner ring (1-3 mm diameter) and outer ring (3-6 mm diameter). The retinal thickness and blood flow density of superficial vascular plexus (SVP) and deep vascular plexus (DVP) in different zones within 6 mm of the macular area were measured. The relationships between SE and SVP, DVP and retinal thickness in each ring region were investigated by univariate and multivariate linear regression analyses, smooth curve fitting, and threshold effects.Results:There were significant differences in the SVP ( F=6.64, 26.06, 22.69) and DVP ( F=7.97, 25.01, 5.09) of macular central fovea, inner ring and outer ring among the emmetropia, low myopia and moderate myopia groups ( P<0.05). Univariate linear regression analysis showed that the SVP ( β=-0.56,-1.17, -0.79) and DVP ( β=-1.03, -0.93, -0.45) of the three regions were positively correlated with SE ( P<0.05). After smooth curve fitting, threshold effect analysis and multivariate linear regression analysis, the SVP and DVP in the macular central fovea were linearly positively correlated with SE ( β=-0.91, -1.40; P<0.05), and SVP and DVP in the inner ring and outer ring showed an inverted U-shaped curve relationship with SE with the inflection (<3.00 D). When the SE was less than <3.00 D, the SVP and DVP in the inner ring and outer ring were positively correlated with SE ( P<0.05). When the SE was higher than -3.00 D, except for the DVP in the inner ring region, the other parameters were negatively correlated with SE ( P<0.05). There were significant differences in retinal thickness of the inner ring and outer ring ( F=5.47, 16.36; P<0.05), and no significant difference in the macular central fovea among the emmetropia, low and moderate myopia groups ( F=2.16, P>0.05). By using univariate and multivariate linear regression analyses, the retinal thickness in the inner ring and outer ring were negatively correlated with SE ( β =1.99, 3.05; P<0.05). However, no correlation was found between retinal thickness and SE in the macular central fovea ( β=-1.65, P>0.05). Conclusions:In school-age children with SE between +0.50 D and -6.00 D, the retinal capillaries density of the macular central fovea gradually increase, and increase first and then decrease in the inner ring and outer ring with increasing SE. The retinal thickness of inner ring and outer ring gradually decrease and not change significantly in the macular central fovea.

The conventional noninvasive biological current detection such as electrocardiogram, electroencephalography and surface electromyography can provide electrical reference for diseases diagnosis. Because the bioelectrical signals are the mixed result of the common discharge of sell populations, the spatial resolution of the above bioelectrical detection is relatively limited. In recent years, the acoustoelectric imaging (AEI) has been introduced to spatially code biological current through noninvasive focused ultrasound. Then the electrical signal with precise focus position can be obtained. It can achieve noninvasive detection of biological electrical signals with millimeter-level spatial resolution and millisecond-level temporal resolution which is expected to develop into a new imaging technology for accurately detecting deep electrical activities of living organisms. We firstly describe AEI principle, including acoustoelectric effect and the derivation of acoustoelectric signal equation. Then we briefly introduce characteristics of acoustoelectric signal. It can be seen from the equation of acoustoelectric signal that the acoustoelectric signal depends on the current field and the ultrasonic field. Furtherly, the typical studies of AEI are introduced including acoustoelectric coupling mechanism, AEI methods, acoustoelectric brain imaging (ABI) and acoustoelectric cardiac imaging (ACI). In terms of the acoustoelectric coupling mechanism, the researchers found that the acoustoelectric effect of electrolyte solution is caused by the change of ion molar concentration, ion migration rate and ion viscosity with pressure and temperature, and the acoustoelectric effect coefficient of normal saline is accurate to (0.034±0.003)% MPa^–1. In terms of AEI methods, researchers improved the detection sensitivity, spatial resolution, signal to noise ratio and other performance indicators by improving AEI methods and optimizing AEI systems. In terms of ABI, it can utilize the acoustoelectric coupling mechanism to endow the target area with spatial features of ultrasound, and achieve noninvasive high resolution EEG detection. We review the important research achievements and significance layer by layer from the perspectives of feasibility verification, method system optimization, and clinical application exploration in acoustoelectric imaging. In terms of ACI, it can be used to quantitatively evaluate the spatial distribution and dynamic changes of cardiac current field, providing a new idea for real-time monitoring of cardiac electrophysiological state before and after surgery. We summarize and review the important research achievements and significance of ACI at each stage: in phantom, in vitro and in vivo. Finally, we discuss the future research direction by focusing on the challenges faced by key technical links such as focused ultrasound targeting, ultrasonic spatial coding and decoding, acoustoelectric sensing detection, and imaging system integration, in order to provide basis and inspiration for AEI technology system and clinical transformation.

Due to the prominent unhealthy lifestyle of residents,accelerated population aging,and urbanization processes in our country,the impact of cardiovascular disease(CVD)risk factors on public health is becoming increasingly significant.The prevalence of cardiovascular disease(CVD)in China is still on the rise.It is estimated that there are 330 million people with CVD,including 13 million cases of stroke,11.39 million cases of coronary heart disease,8.9 million cases of heart failure,5 million cases of pulmonary heart disease,4.87 million atrial fibrillation,2.5 million cases of rheumatic heart disease,2 million cases of congenital heart disease,45.3 million cases of peripheral arterial disease,and 245 million cases of hypertension.The economic burden of CVD on residents and society is increasingly heavy,making it a significant public health issue.The turning point for the prevention and control of CVD has not yet arrived,and it is urgent to strengthen government-led efforts in CVD prevention and control.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To investigate the efficacy and safety of Guihuang Formula(GHF)in the treatment of type Ⅲ prostatitis with the syndrome of damp-heat stasis in the essence chamber.Methods:This study included 120 cases of type Ⅲ prostatitis with damp-heat stasis syndrome in the essence chamber,which were randomly and equally divided into a GHF and a control group,the for-mer treated with GHF and the latter with Tamsulosin Hydrochloride Sustained-Release Capsules,both for 6 successive weeks.We fol-lowed up the patients for 4 weeks,recorded the NIH-CPSI,TCM symptom scores,and results of prostatic fluid routine,blood and u-rine routine,liver and kidney function and electrocardiogram examinations,and compared them between the two groups of patients be-fore and after treatment.Results:Compared with the baseline,the total NIH-CPSI scores were significantly decreased in both the GHF and control groups after 6 weeks of treatment,even more significantly in the former group(28.34±9.23 vs 6.78±3.53,P＜0.05)than in the latter(27.81±8.28 vs 14.48±4.27,P＜0.05),so were the scores on pain,voiding symptoms,quality of life(QOL)impact,TCM symptoms and WBC count(all P＜0.05),while the number of lecithin bodies remarkably increased(P＜0.05).There were statically significant differences in the above parameters at 4,6 and 10 weeks of medication(P＜0.05),but not at 2 weeks(P＞0.05).No obvious abnormalities or adverse reactions were observed in either of the two groups during the treatment.Conclusion:Guihuang Formula is safe and effective in the treatment of type Ⅲ prostatitis with the syndrome of damp-heat stasis in the essence chamber.

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

The present study aimed to investigate the protective effect of S-propargyl-cysteine (SPRC) on atherosclerosis progression in mice. A mouse model of vulnerable atherosclerotic plaque was created in ApoE^-/- mice by carotid artery tandem stenosis (TS) combined with a Western diet. Macrophotography, lipid profiles, and inflammatory markers were measured to evaluate the antiatherosclerotic effects of SPRC compared to atorvastatin as a control. Histopathological analysis was performed to assess the plaque stability. To explore the protective mechanism of SPRC, human umbilical vein endothelial cells (HUVECs) were cultured in vitro and challenged with oxidized low-density lipoprotein (ox-LDL). Cell viability was determined with a Cell Counting Kit-8 (CCK-8). Endothelial nitric oxide synthase (eNOS) phosphorylation and mRNA expression were detected by Western blot and RT-qPCR respectively. The results showed that the lesion area quantified by en face photographs of the aortic arch and carotid artery was significantly less, plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced, plaque collagen content was increased and matrix metalloproteinase-9 (MMP-9) was decreased in 80 mg/kg per day SPRC-treated mice compared with model mice. These findings support the role of SPRC in plaque stabilization. In vitro studies revealed that 100 μmol/L SPRC increased the cell viability and the phosphorylation level of eNOS after ox-LDL challenge. These results suggest that SPRC delays the progression of atherosclerosis and enhances plaque stability. The protective effect may be at least partially related to the increased phosphorylation of eNOS in endothelial cells.
Animals ; Humans ; Mice ; Atherosclerosis ; Cholesterol/metabolism* ; Cysteine/pharmacology* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Lipoproteins, LDL/pharmacology* ; Nitric Oxide Synthase Type III/metabolism* ; Phosphorylation ; Plaque, Atherosclerotic/pathology*

With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.
Humans ; Consensus ; Chemical and Drug Induced Liver Injury/etiology* ; Risk Factors ; Dietary Supplements/adverse effects*