ObjectiveTo explore the mechanism by which the ethanol extract of Epimedium brevicornu （EEBM） intervenes in mesenchymal adipose-derived stem cells （ADSCs） to delay aging in castrated rats. MethodsForty-five 3-month-old SPF female SD rats were ovariectomized and randomly divided into model group， ADSCs treatment group， and ADSCs groups treated with low， medium， and high concentrations of EEBM （1， 50， 100 μg·L^-1）， referred to as the AE low， medium， and high concentration groups， with 9 rats in each group. After tail vein injection of 200 μL of the corresponding stem cell suspension， aging-related indicators including cyclin-dependent kinase inhibitor （p21）， tumor suppressor gene （p53）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， superoxide dismutase （SOD）， malondialdehyde （MDA）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cysteine-aspartic acid protease-3 （Caspase-3）， and lipofuscin were measured using enzyme-linked immunosorbent assay （ELISA） and Western blot. ResultsCompared with the model group， the IL-6 content in the AE low， medium， and high concentration groups was significantly decreased （P<0.05）. Lipofuscin， MDA， and IL-8 levels in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.01）， while SOD content was significantly increased （P<0.05， P<0.01）. Compared with the ADSCs treatment group， lipofuscin and IL-8 levels in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）. The MDA content was significantly decreased in the AE medium concentration group （P<0.01）. Compared with the model group， protein levels of p21， p53， Bax， and Caspase-3 in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， while the Bcl-2 protein level was significantly increased （P<0.01）. Compared with the ADSCs treatment group， protein levels of p21， p53， Bax， and Caspase-3 in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， and the Bcl-2 protein level in the AE low concentration group was significantly increased （P<0.01）. ConclusionThe results of this experiment show that EEBM-treated ADSCs or ADSCs may delay aging in castrated rats by inhibiting cell apoptosis， reducing cell cycle inhibitors and pro-inflammatory factors， enhancing antioxidant capacity， and reducing oxidative reactions. Moreover， EEBM-treated ADSCs demonstrate stronger anti-aging effects than ADSCs alone. This study provides experimental evidence supporting the clinical use of EEBM to intervene in ADSCs and delay aging.

Objective To analyze the quality of 19 batches of Ginseng Formula Granules from 11 different manufacturers by using Ginseng water Extract reference substance(GWERS)as references.Methods Thin layer chromatography(TLC)identification and feature map detection were carried out according to the identification items and characteristic maps of Ginseng Formula Granules standard(YBZ-PFKL-2021186)issued by the National Medical Products Administration.Results The results of TLC analysis showed that the 19 batches of Ginseng Formula Granules-labeled samples could be divided into three categories.The overall pattern of the first type of samples was consistent with that of GWERS,and the similarity was high.Pseudoginsenoside F11,a unique component of American ginseng,was detected in the second type of samples.Four blue fluorescent spots were observed in the third type of samples compared to GWERS.HPLC results indicated that all 19 batches of Ginseng Formula Granules showed eight characteristic peaks at the same retention time as that of GWERS chromatogram.Two more chromatographic peaks were found in the chromatogram of three batches of samples from one manufacturer compared to the chromatogram of other samples,whose similarity to the GWERS chromatogram was less than 0.65.The similarity between the chromatogram of the remaining 16 sample and GWERS chromatogram was higher than 0.94.Conclusion At present,the quality of Ginseng Formula Granules on the market varies greatly.It was suspected that American ginseng might appear among them.The application of GWERS for quality analysis of Ginseng Formula Granules has better applicability to the control medicinal materials.

As an important intracellular genetic and regulatory center, the nucleus is not only a terminal effector of intracellular biochemical signals, but also has a significant impact on cell function and phenotype through direct or indirect regulation of nuclear mechanistic cues after the cell senses and responds to mechanical stimuli. The nucleus relies on chromatin-nuclear membrane-cytoskeleton infrastructure to couple signal transduction, and responds to these mechanical stimuli in the intracellular and extracellular physical microenvironments. Changes in the morphological structure of the nucleus are the most intuitive manifestation of this mechanical response cascades and are the basis for the direct response of the nucleus to mechanical stimuli. Based on such relationships of the nucleus with cell behavior and phenotype, abnormal nuclear morphological changes are widely used in clinical practice as disease diagnostic tools. This review article highlights the latest advances in how nuclear morphology responds and adapts to mechanical stimuli. Additionally, this article will shed light on the factors that mechanically regulate nuclear morphology as well as the tumor physio-pathological processes involved in nuclear morphology and the underlying mechanobiological mechanisms. It provides new insights into the mechanisms that nuclear mechanics regulates disease development and its use as a potential target for diagnosis and treatment.
Cell Nucleus ; Biophysics ; Cytoskeleton ; Phenotype ; Signal Transduction

Objective:To investigate the characteristics and change law of influenza in Fuling District of Chongqing in 2010-2019, and to provide a scientific basis for the pre-control of influenza.Methods:We performed an epidemiological analysis on the data of influenza-like illness reported by Fuling District influenza surveillance sentinel hospitals in Chongqing in 2010-2019.Results:In 2010-2019, a total of 42 169 cases of influenza-like illness were reported in Fuling District, with an average treatment rate of 1.22%. The activity of influenza-like illness peaked in winter, spring, and summer. There were 22 788 cases in the group of cases aged < 5 years, accounting for 50.4%. In 2010-2019, a total of 8049 pharyngeal swabs were collected to screen for influenza-like illness, with a positive rate of 14.52%. Influenza virus A H3 positive rate was highest, accounting for 37.98%, followed by influenza virus B BV positive rate, accounting for 30.80%. The highest influenza virus-positive rate was reported in January (26.34%), followed by November (24.85%).Conclusion:Influenza in the Fuling district of Chongqing mainly occurs in winter, spring, and summer. Influenza virus A H3 is the dominant strain. Children and school students are prone to develop influenza-like illnesses. We should continue to strengthen the monitoring of influenza strains, greatly promote vaccination, and strengthen the monitoring and prevention of influenza-like illness among susceptible populations.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global health threat.This raises an urgent need for the devel-opment of effective drugs against the deadly disease.SARS-CoV-2 non-structural protein 14 (NSP14)carrying RNA cap guanine N7-methyltransferase and 3'-5'exoribonuclease activities could be a potential drug target for intervention.NSP14 of SARS-CoV-2 shares 98.7％ of similarity with the one (PDB 5NFY) of acute respiratory syndrome (SARS) by ClustalW.Then,the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14 (PDB 5NFY) as template for virtual screening.Based on the docking score from AutoDock Vina1.1.2,18 small molecule drugs were selected for further evaluation.Based on the 5 ns MD simulation trajectory,binding free energy (AG) was calculated by MM/GBSA method.The calculated binding free energies of Saquinavir,Hypericin,Baicalein and Bromocriptine for the N-terminus of the homology model were-37.2711 ± 3.2160,-30.1746 ± 3.1914,-23.8953 ± 4.4800,and-34.1350 ± 4.3683 kcal/mol,respectively,while the calculated binding free energies were-60.2757 ± 4.7708,-30.9955 ± 2.9975,-46.3099 ± 3.5689,and-59.8104 ± 3.5389 kcal/mol,respectively,when binding to the C-terminus.Thus,the compounds including Saquinavir,Hypericin,Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14,providing a candidate drug against SARS-CoV-2 for further study.

Objective:To evaluate the pathologic findings from biopsy samples to predict the status of nodal metastasis for patients with usual cervical adenocarcinoma.Methods:The 32-pair samples of cervical adenocarcinoma specimens (32 cervical biopsies and 32 hysterectomies with staging) from 2013 to 2019 were selected for retrospective study in Shanghai first Maternal and infant Health Care Hospital Affiliated to Tongji University. The correlation between histopathologic features including necrotic tumor debris (NTD), nuclear grade, mitotic count and pattern-based classification system and the status of lymph node metastasis was evaluated.Results:Tumor invasive patterns of cervical adenocarcinoma, as described previously, could be discerned in hysterectomy/staging specimens, but not in cervical biopsies. Because the biopsy tissues were small, only 14(14/32, 43.8%) cases could be classified according to pattern of invasion, and the concordance rate with resected specimens was 37.5%. NTD (9/19) and grade 3 nuclei (11/19) were positively correlated with invasive pattern C and nodal metastases ( P<0.05). Moreover, when NTD and (or) nuclear grade were evaluated at the same time, the sensitivity for type C infiltration was higher. Conclusions:Evaluation of NTD and nuclear grade in biopsies for cervical adenocarcinoma provides good predictive value for lymph node metastasis. It is helpful for patient stratification and management andto avoid unnecessary staging procedures. However, multicenter studies and prospective clinical trials are necessary to confirm the findings before clinical application can be considered.

Purpose: The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC. Materials and Methods: From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI’s optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram’s clinical utility. Results: One hundred twenty-four patients were included. The SIRI’s optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649). Conclusion The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.

Objective To explore the effect of angiogenesis in carotid atherosclerotic plaque.Methods From Jan 2016 to Aug 2016,Carotid artery plaque was abtained in 52 cases after carotid endarterectomy at the Department of Cardiovascular Surgery of China-Japan Friendship Hospital.Patients were divided into symptomatic group and asymptomatic group.Specimens were stained with HE and Movat,and the density,size,distribution and morphology of neovascularization were counted.Results The density of neovascularization in the symptomatic group and the asymptomatic group were 5.27 ± 0.46 and 2.30 ±0.29,respectively (P ＜ 0.001),the average cross-sectional area of neovascularization in the symptomatic group was (2.26±0.21) mm2 and (1.00 ±0.48) mm2 in the asymptomatic group (P=0.02).In the distribution,the symptomatic group and the asymptomatic group were 3.37 ± 0.46/ mm2,1.32 ±0.16/mm2 in basal part,3.71 ±0.42/mm2,1.56 ±0.20/mm2 in the shoulder part,3.48 ±0.44/mm2,1.55 ± 0.21/ mm2 in the fibrous cap,respectively (P ＜ 0.001).Conclusion The density and cross-sectional area of neovascularization in the symptomatic group were larger than those in the asymptomatic group,irregular branching vessels were dominant.

Objective To summarize the pathological survey of time-zero renal biopsy (T0-RBx ) . Methods The material qualities and pathological features were analyzed retrospectively for T 0-RBx (n=176) between March 2008 and May 2016 .According to the source of donor kidney ,T0-RBx specimens were divided into living donors (LD) group (n=137) and Deceased donation (DD) group (n=39) .Furthermore , the DD group was divided into cerebral hemorrhage group (n= 10) and brain trauma group (n= 29) according to the causes of death .The inter-group differences of pathological characteristics and the effects of abnormal pathological lesions on allograft function were observed .Results All T0-RBx specimens contained cortical kidney tissue .The average microscopic length of renal tissue was (0 .39 ± 0 .23) cm and the median glomerular number 11 . The abnormal pathological lesions included glomerulosclerosis (GS ,30 .7 ％ ) , segmental glomerulosclerosis (1 .1 ％ ) ,mesangial increase (MI ,19 .3 ％ ) ,tubular atrophy (TA ,35 .2 ％ ) , acute tubular necrosis (ATN ,9 .1 ％ ) ,vacuolar degeneration of tubular epithelium (27 .3 ％ ) ,losses in tubule epithelial brush border (97 .7 ％ ) , protein cast (25 ％ ) , interstitial fibrosis (IF ,34 .1 ％ ) , inflammation (I ,42 .6 ％ ) ,arteriolar hyalinosis (AH) (26 .1 ％ ) and vascular fibrous intimal thickening (CV ,23 .3 ％ ) .Among them ,23 .9 ％ ,1 .1 ％ ,0 .55 ％ and 0 .55 ％ cases were diagnosed as IgA nephropathy ,immune complex associated with glomerular disease and focal segmental glomerulosclerosis diabetic nephropathy respectively .And the reminders were of ischemic injury .The incidence rates of TA ,IF and I were lower in DD group than those in LD group ( P< 0 .05 ) . However , ATN and vacuolar degeneration of tubular epithelium were higher (P<0 .001) .The incidence of GS was significantly higher in cerebral hemorrhage group than that in brain trauma group (P<0 .01) .No statistical difference existed in other lesions or disease constitution among the groups (P>0 .05) .Further analysis showed GS was related with allograft function at 6/12 months post-transplantation in both LD and DD groups (P<0 .05) .IF and AH were also related to short-term renal function of recipients post-transplantation in LD and DD groups (P>0 .05) .Conclusions T0-RBx may detect the abnormal lesions of donor kidney .Some differences exist in types and degree of abnormal lesions among different donor kidneys .LD group has a higher risk for chronic histological injury such as TA and IF while DD group is more susceptible to acute renal tubular interstitial injury .Thus it is valuable for predicting allograft function post-transplantation .Material quality is essential for ensuring the reliability of T 0-RBx .

Objective To investigate the detailed molecular mechanism of matrix stiffness regulating cell drug resistance. Methods Polyacrylamide hydrogels of soft substrate (10 kPa), hard substrate (38 kPa) and rigid substrate (57 kPa) with different matrix stiffness were configured to simulate the physical matrix stiffness at different stages of breast cancer in vivo. Results The cell proliferation rate of the hard substrate was significantly higher than that of the soft and rigid substrates. The intracellular endocytosis was significantly lower on the hard substrate. The YAP nucleus translocation increased significantly on the hard substrate, compared with the soft and the rigid substrates, indicating that YAP was a key molecule involved in drug resistance of tumor cells. Conclusions Matrix stiffness could regulate the drug resistance of breast cancer cells through YAP activation. This study not only provides a new direction for elucidating the mechanism of drug resistance, but also lays a new foundation for the drug delivery system of breast cancer treatment.