Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.
Female ; Humans ; Retrospective Studies ; Gonadal Dysgenesis, 46,XY/surgery* ; Gonadoblastoma/surgery* ; Neoplasms, Germ Cell and Embryonal/surgery* ; Ovarian Neoplasms/pathology*

AIM To investigate the purification process for esculin,fraxin,esculetin and fraxetin in Fraxini Cortex by macroporous resin.METHODS Static adsorption experiment was applied to screening resin model,single factor test was adopted in the optimization of purification process,UPLC-QTOF-MS/MS was used for identifying main components,after which heatmap was drawn.RESULTS The optimal resin model was ADS-5.The optimal purification process was determined to be 1.1 BV for loading amount,0.75 g/mL for loading concentration,2 BV pure water for washing impurity,and 4 BV 25%ethanol for eluting effective constituents,coumarins demonstrated the total transfer rate,purity and yield of 84.42%,53.28%and 4.79%,respectively.Total 37 constituents were identified,among which coumarins and phenylethanol glycosides were mainly concentrated in 25%ethanol eluent,organic acids,iridoids and flavonoids were mainly concentrated in 95%ethanol eluent.CONCLUSION This stable,feasible and accurate method can characterize the distribution patterns of coumarins in Fraxini Cortex in different eluents of macroporous resin,which provides guidance for further related pharmaceutical research.

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.
Rats ; Animals ; Diabetic Nephropathies/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Abelmoschus/chemistry* ; Podocytes ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition ; Flavones/pharmacology* ; Insulin Resistance ; Reactive Oxygen Species ; Diabetes Mellitus

Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.
Rats ; Animals ; Abelmoschus ; Reactive Oxygen Species/metabolism* ; Flavones/pharmacology* ; Endoplasmic Reticulum Stress ; Diabetic Nephropathies/drug therapy* ; Apoptosis ; Diabetes Mellitus

Objective: To investigate the predictive value of glycosylated hemoglobin A1c/apolipoprotein A-1 (HbA1c/ApoA-1) ratio for major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). Methods: The present study is a retrospective cohort study. ACS patients who were hospitalized and underwent coronary angiography at Beijing Hospital from March 2017 to March 2019 were enrolled. Baseline information such as sex, age, previous history, Gensini score, HbA1c and ApoA-1 were analyzed. Patients were divided into two groups according to presence or absence of MACEs and the difference on HbA1c/ApoA-1 ratio was compared between the two groups. According to the tertiles of HbA1c/ApoA-1 levels, patients were divided into high (5.87-16.12), medium (4.50-5.83) and low (2.11-4.48) HbA1c/ApoA-1 groups. Cox proportional risk model was used to evaluate the differences in MACEs and all-cause mortality among the three groups. Kaplan-Meier survival analysis was used to compare the differences of MACEs between the various HbA1c/ApoA-1 groups. Results: A total of 366 ACS patients were included in this study. The mean age of the patients was (65.9±10.3) years. There were 59 MACEs and 10 all-cause deaths during the mean of (22.3±4.4) months follow-up. After adjusting for age, systolic blood pressure, history of diabetes and Gensini score, the incidence of MACEs was 2.45 times higher in the high HbA1c/ApoA-1 group than in the low HbA1c/ApoA-1 group (95%CI 1.16-5.18, P=0.019). There was no significant difference in all-cause mortality between the high and low HbA1c/ApoA-1 groups (P=1.000). Kaplan-Meier survival analysis showed that patients in the high HbA1c/ApoA-1 group had the highest risk of MACEs, while patients in the low HbA1c/ApoA-1 group had the lowest risk of MACEs (P<0.01). Spearman rank correlation analysis showed that HbA1/ApoA-1 ratio was positively correlated with Gensini score in ACS patients (r=0.274, P<0.01). Conclusion: High HbA1c/ApoA-1 ratio was an independent risk factor for MACEs in ACS patients. Patients with high HbA1c/ApoA-1 ratio had more severe coronary artery disease lesions. HbA1c/ApoA-1 ratio may be used as a potential risk stratification biomarker for ACS patients, it might be useful for the early identification of high-risk population and for predicting the incidence of MACEs among ACS patients.
Aged ; Humans ; Middle Aged ; Acute Coronary Syndrome/diagnosis* ; Apolipoprotein A-I/analysis* ; Biomarkers/analysis* ; Glycated Hemoglobin/analysis* ; Percutaneous Coronary Intervention ; Retrospective Studies ; Risk Factors ; Predictive Value of Tests

Humans ; Endovascular Aneurysm Repair ; Endovascular Procedures ; Blood Vessel Prosthesis Implantation ; Aortic Aneurysm, Abdominal/surgery* ; Treatment Outcome ; Postoperative Complications ; Risk Factors ; Aortic Rupture/surgery* ; Retrospective Studies

Objective: Subthreshold attention-deficit/hyperactivity disorder (ADHD) has been suggested to be a “morbid condition” which also needs medical attention. Methods: The present study recruited 89 children with subthreshold ADHD (sADHD), 115 children with diagnosed ADHD (cADHD), and 79 healthy controls (HC) to explore the clinical manifestation, executive functions (EFs) of sADHD, and the caregiver strain. The clinical manifestation was evaluated through clinical interviews and parent-reports. Executive functions were assessed both experimentally and ecologically. Caregiver strain was measured by a parent-reported questionnaire. Results: For the clinical manifestation, both sADHD and cADHD indicated impairments when compared with HC. The comorbidities and the scaled symptoms indicated that the externalizing behaviors were relatively less serious in sADHD than cADHD, whereas the internalizing behaviors between two groups were comparable. For ecological EFs, sADHD scored between cADHD and HC in inhibition and working memory. For experimental EFs, sADHD was comparable to cADHD in inhibition, shifting, and was worse than cADHD in verbal working memory. For the caregiver strain, all scores of sADHD were between that in cADHD and that in HC. Conclusion Our present findings supported the suggestion of subthreshold ADHD as “morbid condition,” which should be treated with caution in clinical practice, especially for the internalizing behaviors and some key components of EFs.

The coronavirus disease 2019 (COVID-19) has been a global epidemic for more than three years, causing more than 6.9 million deaths. COVID-19 has the clinical characteristics of strong infectivity and long incubation period, and can cause multi-system damage, mainly lung damage, clinical symptoms of acute respiratory distress syndrome (ARDS) and systemic multiple organ damage. The SARS-CoV-2 virus is still constantly mutating. At present, there is no global consensus on the pathological changes of COVID-19 associated deaths and even no consensus on the criteria for determining the cause of death. The investigation of the basic pathological changes and progression of the disease is helpful to guide the clinical treatment and the development of therapeutic drugs. This paper reviews the autopsy reports and related literature published worldwide from February 2020 to June 2023, with a clear number of autopsy cases and corresponding pathological changes of vital organs as the inclusion criteria. A total of 1 111 autopsy cases from 65 papers in 18 countries are included. Pathological manifestations and causes of death are classified and statistically analyzed, common pathological changes of COVID-19 are summarized, and analytical conclusions are drawn, suggesting that COVID-19 infection can cause life-threatening pathological changes in vital organs. On the basis of different health levels of infected groups, the direct cause of death is mainly severe lung damage and secondary systemic multiple organ failure.
Humans ; SARS-CoV-2 ; COVID-19/pathology* ; Cause of Death ; Lung/pathology* ; Autopsy

Objective:To investigate the expression of adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation in corneal epithelial cells and the effects of fungus on AMPK phosphorylation and interleukin-6 (IL-6) production in corneal epithelial cells.Methods:The human immortalized corneal epithelial cell line was selected.The safe concentration range of AMPK agonist 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) (100, 300, 500, 1 000 μmol/L) and inhibitor Compound C (10.0, 12.5, 15.0, 17.5, 20.0 μmol/L) on corneal epithelial cells was screened by multi-function real-time unlabeled cell analyzer.Corneal epithelial cells without any treatment were used as the normal control group, and those co-cultured with spores were used as the spore control group.Corneal epithelial cells co-cultured with spores were treated with AICAR and Compound C for 4 hours in the AICAR group and Compound C group, respectively.The expression of phosphorylated AMPK (p-AMPK) and AMPK in corneal epithelial cells was detected by Western blot, and the concentration of IL-6 in the culture supernatant was determined by enzyme-linked immunosorbent assay (ELISA).Results:After treatment with different concentrations of AICAR for different periods, there was no statistical significance in the cell index of corneal epithelial cells (all at P>0.05). The cell index of corneal epithelial cells was increased with 10.0 μmol/L and 12.5 μmol/L Compound C treatment compared with that of the normal control group.The expression levels of p-AMPK were 0.67±0.15, 2.57±0.12, 3.67±0.58 and 1.50±0.50, respectively, in the normal control group, spore control group, AICAR group and Compound C group, showing a statistically significant difference among them ( F=32.820, P<0.001). The expression level of p-AMPK was significantly higher in the spore control group compared with the normal control group ( P<0.001). The expression level of p-AMPK in the AICAR group was higher than that in the spore control group, and the expression level of p-AMPK in the Compound C group was lower than that in the spore control group, and the differences were statistically significant (both at P=0.010). There was no significant difference in the relative expression level of AMPK among the four groups ( F=0.120, P=0.950). The expression levels of IL-6 concentration in the normal control group, spore control group, AICAR group and Compound C group were (107.81±17.15), (156.32±9.94), (167.96±14.16) and (127.42±19.75)pg/ml, respectively, showing a statistically significant difference among them ( F=15.210, P<0.001). The IL-6 concentration of the spore control group was higher than that of the normal control group, and the difference was statistically significant ( P<0.001). The IL-6 concentration of the AICAR group was higher than that of the spore control group, but the difference was not statistically significant ( P=0.260). The IL-6 concentration of the Compound C group was lower than that of the spore control group, and the difference was statistically significant ( P=0.010). Conclusions:In corneal epithelial cells, AMPK phosphorylation is found, which is enhanced after fungal spores stimulation, and the secretion of IL-6 increases.

Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.
Artificial Intelligence ; Endoscopy/methods* ; Esophageal Neoplasms/pathology* ; Esophageal Squamous Cell Carcinoma/diagnostic imaging* ; Humans ; Narrow Band Imaging ; Precancerous Conditions/diagnostic imaging* ; Sensitivity and Specificity