ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

Objective: To evaluate the effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant. Methods: A total of 1 403 Omicron-infected patients admitted to 20 designated hospitals in Guangdong Province from January 1 to May 31, 2022, were selected as subjects in this study. A case-control study was conducted to collect the demographic data, underlying disease, vaccination status, last exposure date, gene sequencing of infected strains and clinical outcomes from the China Disease Prevention and Control Information System and Guangdong telemedicine platform. Pneumonia (common, severe and critical) and non-pneumonia (asymptomatic and mild) were selected as the case group and control group. The effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant was analyzed. Results: The median age [M (Q₁, Q₃)] of the subjects was 36 (27-47) years old, with males accounting for 52.25% (733 cases). The main outcome of the infection was non-pneumonia, accounting for 92.09% (1 292 cases), and the duration [M (Q₁, Q₃)] of the disease was 18 (14-22) days. There were 134 (9.55%), 39 (2.78%), 403 (28.72%), 437 (31.15%) and 390 (27.80%) cases with no or partial vaccination, within 90 days of primary vaccination, over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination, respectively. Multivariate logistic regression analysis showed that after adjusting for gender, age, underlying disease, and location of the report, compared with those with no or partial vaccination, the risk of developing pneumonia was lower in those with over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination [OR (95%CI) values were 0.52 (0.28-0.98), 0.39 (0.21-0.73) and 0.40 (0.21-0.77), respectively]. Cox proportional hazard regression model analysis showed that after adjusting for gender, age, underlying disease and location of the report, the duration of the disease was shorter in those who received booster vaccinated for more than 90 days compared with that in those who had no or partial vaccination [HR (95%CI): 1.26 (1.03-1.55)]. Conclusion: The inactivated SARS-CoV-2 vaccine affects the clinical outcomes of patients infected with the Omicron variant.
Adult ; Humans ; Male ; Middle Aged ; Case-Control Studies ; China/epidemiology* ; COVID-19/prevention & control* ; COVID-19 Vaccines ; SARS-CoV-2 ; Female

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Objective To investigate the indications of optic canal decompression in the patients with front-orbital fibrous dysplasia and the methods of intraoperative optic canal localization and decompression. Methods We collected 30 cases of fibrous dysplasia. All patients had sufficient images assessment. Patients with symptoms underwent surgery, including front-orbital cranioplasty and optic canal decompression. The frontotemporal epidural approaches were used. If there was a proptosis, the approach was extended with the removal of superior orbital ridge. Six patients undertook intraoperative CT and MRI fusion navigation, assisting in confirming the trunk, orbital and cranial orifice of optic nerve. During the operation, the optic canals were decompressed by three-bits method, to confirm the position of optic nerve. Results There were 30 cases of optic canal decompression and one case of vision loss. The visual acuity and vision field of the remaining patients improved to varying degrees. The proptosis disappeared or alleviated after the operation. Thirteen cases were reconstructed with normal internal plate, five cases with titanium plate, nine cases without reconstruction, and two cases were paved with proliferative broken bone on the orbital top; one case recurred with exophthalmos again after five years, but the visual acuity did not decline. Conclusion For the patients with front-orbital fibrous dysplasia, active surgical treatment should be taken, optic canal decompression should be chosen for diminution of vision, craniofacial anaplasty and orbital decompression should be performed in patients with facial deformity. The epidural approach is a good option to locate the optic nerve from the orbital orifice or cranial orifice. Combined with the three-bits method, we can achieve safe and meticulous optic nerve decompression.

Objective To explore the role of the pyrin domain-containing 3 ( NLRP3) inflammasome in advanced glycation end products ( AGEs )-induced mice pancreatic β-cell damage. Methods AGEs were administered intraperitoneally for 6 weeks in NLRP3 knockout mice or C57BL/6J mice. Intraperitoneal glucose tolerance test and insulin releasing test were performed. Pancreatic sections were stained with haematoxylin and eosin, or with F4/80 and NLRP3 antibodies. Insulin and pancreatic tissue monocyte chemotactic protein 1 ( MCP-1) as well as interleukin-1β( IL-1β) levels were measured with ELISA kits. Expression of MCP-1 protein was determined by western blot. MIN6 cells and mouse peritoneal macrophages cells were treated with AGEs and different interventions (antioxidant NAC, adenovirus NLRP3 shRNA or NLRP3 knockout). Reactive oxygen species production, NLRP3 mRNA expression, IL-1β secretion, caspase 1 activity, apoptosis and glucose stimulated insulin release were determined. Results Injection of AGEs induced an abnormal response to glucose, enhanced the insulitis score, and increased the levels of pancreatic tissue MCP-1 and IL-1β, as well as raised the expression of NLRP3 and F4/80 in pancreatic islet. Remarkably, co-localization of NLRP3 and macrophage marker F4/80 was observed in islet. The damages were improved in NLRP3 knockout mice. After incubation with AGEs, reactive oxygen species production and cell apoptosis was enhanced, NLRP3 inflammasome activated, with glucose-stimulated insulin release impaired in MIN6 cells. NAC treatment alliviated the above damages, but NLRP3 gene silencing had no effect on ROS level, apoptosis, and insulin secretion. Finally NAC treatment and NLRP3 gene knockout inhibited activation of NLRP3 inflammasome induced by AGEs in mouse peritoneal macrophages cells. Conclusion NLRP3 knockout ameliorates the islet β-cell damage induced by AGEs. These effects were associated with AGEs-induced islets macrophage infiltrating by up-regulation of MCP-1 expression, and AGEs-induced activation of NLRP3 inflammasome in macrophage through ROS pathway, which results in the release of active IL-1βand leads to the lesions of β-cell.

Aim To investigate the effect of curcumin against high-fat-diet induced C57BL/6J mice bone changes and the correlation between the expression of cathepsin K and curcumin.Methods Curcumin treated C57BL/6J mice had been on high fat diet for 12 weeks.The HE, Alizarin red S staining and Safranin O/fast green staining of femur were employed to evaluate bone microstructure, bone metabolism and bone development.The expressions of cathepsin K were assessed by Western blot and immunohistochemical staining.Results Histopathological results showed that curcumin could improve the destruction of trabecular bone structure, cartilage development and bone calcification.Biomechanical results proved that curcumin could improve the bone strength of the type 2 diabetic mice induced by high fat.The results of immunohistochemistry and Western blot assay indicated that curcumin could significantly inhibit the expression of cathepsin K in bone tissues of mice.Conclusion Curcumin can increase bone strength, improve bone microstructure, and enhance the degree of bone calcification, which may be achieved by inhibiting the expression of cathepsin K.

Objective To investigate the effect of pretreatment serum hemoglobin (Hb) level on the prognosis of early-stage extranodal nasal-type NK/T-cell lymphoma.Methods A retrospective analysis was performed on the clinical data of 175 patients with stage Ⅰ or Ⅱ extranodal nasal-type NK/T-cell lymphoma who were admitted to The Tumor Hospital Affiliated to Shanxi Medical University from 2000 to 2015.The inclusion criteria included Ann Arbor Ⅰ/Ⅱ stage, the primary tumor located in the upper aerodigestive tract, without other malignant diseases, and complete clinical information and follow-up data.Of the 175 patients, 67 received chemotherapy alone, 8 received radiotherapy alone,100 received radiotherapy and chemotherapyed.The survival rate was calculated using the Kaplan-Meier method.The log-rank test was used for univariate prognostic analysis.The Cox regression model was used for multivariate prognostic analysis.Results The univariate analysis showed that pretreatment serum Hb level (≥120 g/L), lactate dehydrogenase (LDH) level (normal), Eastern Cooperative Oncology Group (ECOG) score (0-1), Ann Arbor stage (IE), and radiotherapy were associated with significantly improved progression-free survival (PFS) and overall survival (OS)(P=0.000-0.046).The multivariate analysis showed that pretreatment serum Hb level, LDH level, ECOG score, and Ann Arbor stage were independent prognostic factors for PFS and OS (P=0.000-0.040).Conclusion Patients with a high pretreatment serum Hb level (≥120 g/L) have a better prognosis than those with a low pretreatment serum Hb level (<120 g/L).

Objective To investigate the effect and clinical significance of neoadjuvant radiotherapy for the expression of CD44v6 in lung squamous cell carcinoma tissues. Methods Fifty cases lung squamous cell carcinoma patients confirmed by aspiration biopsy from May 2013 to January 2015 were collected in Yangquan Coal Mine Group Genernal Hospital,including 20 cases of patients with stageⅢA were treated with neoadjuvant radiotherapy before surgery,and then performed surgery after neoadjuvant therapy. The expression of CD44v6 was detected by immunohistochemistry. The correlation between CD44v6 and clinicopathological features was analyzed by chi?square test. Results Immunohistochemical staining of CD44v6 was performed in tumor tissue of puncture biopsy, the positive rate expression of CD44v6 was 72%( 36/50 ) , it was associated with lymphatic metastasis(χ2 =3. 964, P=0. 046 ) and advanced TNM stage (Ⅲ+Ⅳstage ) (χ2 =4. 276, P=0. 039 ) . The positive expression of CD44v6 protein in tumor tissue was significantly decreased in 20 patients with neoadjuvant radiotherapy compared with before radiotherapy(7. 23±1. 45 vs. 11. 42±1. 31,t=2. 524,P=0. 025). Conclusion Positive expression of CD44v6 in human lung squamous cell carcinoma is related to the malignant clinicopathological features. Neoadjuvant radiotherapy before operation may improve prognosis via down?regulating CD44v6 expression.

Humans ; Ki-67 Antigen ; metabolism ; Lymphoma, Extranodal NK-T-Cell ; diagnosis ; Predictive Value of Tests ; Prognosis

Objective To observe the change of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression during 3T3-L1 adipocyte differentiation as well as other reference gene expressions.Methods The mRNA expressions of several common reference genes were detected by real time-PCR on day 0,1,3,5,and 7 of 3T3-L1 adipocyte differentiation.Western blot was used to confirm the protein expressions of three common reference genes.Results (1) GAPDH and transferrin receptor(TFRC) mRNA expressions were significantly increased during adipocyte differentiation.GAPDH mRNA level was increased by 5.7,7.6,22.0,and 24.5 folds on day 1,3,5,and 7 after induction of adipocyte differentiation,but no apparent changes of β-actin,α-tubulin,peptidylprolyl isomerase A (PIPA),and 18S mRNA expressions were detected.The expression changes of key transcript factors for adipocyte differentiation such as PPARγ2,C/EBPα,and C/EBPβ were under-estimated by real time-PCR if GAPDH was chosen as the reference gene.Western blotting results showed that the GAPDH protein level increased gradually during adipocyte differentiation,especially on day 5 and 7 after adipocyte differentiation.There were no obvious changes of β-actin and α-tubulin protein expressions.(2) Berberine significantly inhibited mRNA and protein expressions of GAPDH in the process of adipocyte differentiation.GAPDH mRNA levels were reduced by 68.1％ and 66.3％ on day 5 and 7 after induction of adipocyte differentiation,but with no significant change in other reference genes.Conclusion It is not suitable for GAPDH to be used as an endogenous reference gene during 3T3-L1 adipocyte differentiation.