The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objectives To analyze the risk factors and their predictive value for postoperative hypoxemia in Type-A aortic dissection(TAAD).Methods A single-center retrospective study was conducted among 146 consecutive patients diagnosed as TAAD and undergone aortic arch surgery from January 2018 to June 2021 in Nanfang Hospital of Southern Medical University.According to the lowest postoperative PaO2/FiO2 ratio within 24 hours,the patients were classified into two groups:hypoxemia group(PaO2/FiO2≤200 mmHg)and non-hypoxemia group(PaO2/FiO2>200 mmHg).The difference of preoperative oxygen index,duration of mechanical ventilation and mortality in hospital were analyzed between the two groups.The independent risk factors for postoperative hypoxemia were evaluated by multivariate logistic regression and the predictive value was analyzed by receiver operator character(ROC)curves.Results For TAAD patients,the incidence of postoperative hypoxemia was 45.9%.Compared to non-hypoxemia group,hypoxemia group exhibited longer duration of mechanical ventilation(P<0.001)and longer intensive care unit(ICU)length of stay(P<0.05).Moreover,patients with hypoxemia presented higher mortality during hospital(P=0.011).Multivariate regression analysis identified BMI as independent risk factor(OR=1.701,P<0.001)and preoperation PaO2/FiO2 ratio as protective factors for postoperative hypoxemia in patients with TAAD(OR=0.987,P=0.004).Area under the ROC curve of BMI was 0.848,the optimal cut-off point of BMI was 25.8 kg/m2.Area under the ROC curve of pre-operation PaO2/FiO2 ratio was 0.808,the optimal cut-off point of preoperation PaO2/FiO2 ratio was 265 mmHg.Conclusions BMI higher than 25.8 kg/m2 is an independent risk factor and preoperation PaO2/FiO2 ratio higher than 265 mmHg is a protective factor for postoperative hypoxemia in patients with TAAD.Subjects with hypoxemia had longer duration of mechanical ventilation,ICU stay and higher mortality.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

OBJECTIVE: To investigate the expression of fibroblast growth factor receptor 2 (FGFR2) in clear cell renal cell carcinoma (ccRCC; or kidney renal clear cell carcinoma, KIRC), to analyze the relationship between the expression of FGFR2 and the clinical pathological features and prognosis of ccRCC, to study the relationship between the expression of FGFR2 and other molecules, and to explore its role in the development of ccRCC. METHODS: Gene expressional and clinical information of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus(GEO) database. Next, the data were transformed and collated. In the study, 104 clinical ccRCC samples and corresponding paracancerous normal tissue samples were collected from Department of Urology, Peking University First Hospital. Immunohistochemistry (IHC) was performed and the staining results were scored, so as to compare the expression of FGFR2 in ccRCC and paracancerous normal tissues. Besides, quantify real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of FGFR2 in normal renal epithelial cell lines (293) and ccRCC cell lines (786-O, 769-P, OSRC-2, Caki-1, ACHN, and A498). In addition, the relationship between FGFR2 expression and clinical pathological characteristics (including TNM staging and pathological grading) and survival prognosis in ccRCC patients was further analyzed. Furthermore, the relationship between FGFR2 expression and B cells, T cells, natural killer (NK) cells and neutrophil infiltration in the ccRCC patients was analyzed, and the Biological General Repository for Interactionh Datasets (BioGRID) was used to builds protein-protein interaction (PPI) networks to study molecules that interacted with the FGFR2 protein. RESULTS: In the TCGA database, the expression of FGFR2 was down-regulated in ccRCC tissue samples compared with normal tissue samples, and the expression in the GEO database also showed this differences. Furthermore, FGFR2 expression was downregulated in ccRCC clinical samples and ccRCC cell lines, compared with corresponding paracancerous normal tissue or normal renal epithelial cell lines. In addition, FGFR2 high expression was associated with earlier, lower-level ccRCC and was associated with a better prognosis in the patients with ccRCC. Moreover, FGFR2 expression was not significantly related to B cells, T cells, NK cells and neutrophil infiltration, and the PPI network showed that FGFR2 protein interacted with certain molecules. CONCLUSION Our work sheds light on the potential role of FGFR2 in the development of ccRCC, suggesting that FGFR2 may serve as a prognostic marker and potential therapeutic target for patients with ccRCC.
Biomarkers, Tumor/analysis* ; Carcinoma, Renal Cell/pathology* ; Humans ; Kidney Neoplasms/pathology* ; Prognosis ; Receptor, Fibroblast Growth Factor, Type 2/genetics*

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Disease Outbreaks ; HIV Infections/prevention & control* ; Humans ; Prevalence

The pathological mechanism of allergic rhinitis (AR) involves hierarchically acute and chronic reactions among antigens, immunocytes, immunoglobulins and inflammatory factors. AR, which is characterized by heterogeneity, reacts differently to the current treatment on diverse individuals. Some patients receive unsatisfying clinical outcomes after the treatment. Chinese herbal medicine has become a frequent option to treat AR because it can improve clinical symptoms with excellent safety. The description of Biqiu in ancient Chinese medical literatures is very similar to the clinical manifestation of AR. The major pathogeneses of Biqiu included infection of wind-cold pathogens, deficiency and cold in the lung, and evil depression into heat and wind. Therefore, in modern traditional Chinese medicine （TCM）, Biqiu is considered as an integration of AR, allergic sinusitis and vasomotor rhinitis. According to the pathogenesis and clinical manifestations of Biqiu (including AR), this disease belongs to wind disease in TCM. But modern TCM focuses on deficiency of internal organs and ignores wind evil in syndrome differentiation, contrary to the fact that wind medicine is always used in treating AR. This even leads to an abnormal phenomenon that clinical studies attach little importance to syndrome differentiation. In this paper, we started from the phenomenon that wind medicine is always used in TCM for AR, considering TCM literatures and the study results of modern therapy for wind diseases, and put forward the ideas as follows: AR belongs to exogenous wind disease in TCM, and wind pathogen is the major pathogen, in clinical syndrome differentiation, we should attach more importance to wind evil, and dispelling wind and eliminating dampness is the key to treatment. Meanwhile, based on the fact that most of the classical prescriptions with good effectiveness for AR originated from Treatise on Febrile Disease, mainly including the wind medicines for treating exogenous diseases, it can be inferred that the wind-dispelling and itch-arresting effects of wind medicines are helpful to alleviate or block the allergic reaction of nasal mucus and achieve the goal of relieving itching and sneezing, and the wind-dispelling and dampness-eliminating effects are helpful to alleviate the edema of nasal mucus and achieve the goal of relieving running nose and nasal obstruction. In modern researches, it is also found that classical prescriptions which take wind medicine as a principle component and wind medicine used in AR treatment have good anti-inflammatory, anti-allergic and immune function adjusting effects. This indicates that dispelling wind and eliminating dampness and the wind medicine treatment under its instruction not only correspond to TCM theory, but also have modern science evidences.

Leukemia inhibitory factor (LIF) contributes to the neuroprotection by neural stem cells (NSCs) after ischemic stroke. Our aim was to explore whether LIF-transfected NSCs (LIF-NSCs) can ameliorate brain injury and promote neuroprotection in a rat model of cerebral ischemia. To accomplish this goal, we transfected NSCs with a lentivirus carrying the LIF gene to stably overexpress LIF. The LIF-NSCs reduced caspase 3 activation under conditions of oxygen-glucose deprivation in vitro. Transient cerebral ischemia was induced in rats by 2 h of middle cerebral artery occlusion (MCAo), and LIF-NSCs were intravenously injected at 6 h post-ischemia. LIF-NSC treatment reduced the infarction volume and improved neurological recovery. Moreover, LIF-NSCs improved glial cell regeneration and ameliorated white matter injury in the MCAo rats. The NSCs acted as carriers and increased the expression of LIF in the lesions to protect against cerebral infarction, suggesting that LIF-NSCs could be a potential treatment for cerebral infarction.

Endodermal Sinus Tumor/surgery* ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Orchiectomy/methods* ; Teratoma/surgery* ; Testicular Neoplasms/surgery* ; Testis/surgery* ; Treatment Outcome

This article has been retracted at the request of first author, corresponding author and the editor-in-chief of the journal. The authors have plagiarized some parts of the figures and results which are similar to Yuan Gong's doctoral dissertation ‘Experimental study on the effects of bone marrow mesenchymal stem cells in the model of gastric precancerous lesion’ published in the China National Knowledge Infrastructure (http://www.cnki.net). One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents an abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.