ObjectiveTo multidimensionally analyze the clinical effects of Qianyang Yuyin granules on elderly hypertensive patients through an "energy-inflammation-aging" network. MethodsRelevant datasets were retrieved from the GEO database. Gene set enrichment analysis （GSEA） was performed on the gene expression profiles of peripheral blood cells from patients with essential hypertension in dataset GSE24752. The GSEA referenced "GO gene sets" and "KEGG gene sets" to identify significantly enriched gene sets. A clinical trial was conducted using a randomized controlled study design. A total of 40 patients meeting the inclusion criteria were enrolled. The control group received standard antihypertensive treatment with angiotensin receptor blockers （ARBs） or combined calcium channel blockers （CCBs）. In contrast，the treatment group received Qianyang Yuyin Granules in addition to the standard treatment for 12 weeks. Blood pressure levels and clinical efficacy were observed，and changes in energy metabolism indicators，DNA damage markers，and senescence-associated secretory phenotype （SASP） in blood were measured using ELISA before and after treatment. ResultsGSEA results indicated significant energy metabolism dysregulation in hypertensive patients. Clinical findings showed that both groups achieved blood pressure control without significant intergroup differences. In terms of clinical efficacy，the treatment group had a significantly higher effective rate compared to the control group （95% vs 65%，P0.05）. After treatment，the treatment group showed a significant increase in NAD⁺ levels （P0.01），with higher levels compared to the control group （P0.05）. The treatment group also exhibited a greater reduction in DNA damage marker 8-OHdG （P0.01） and cell adhesion factors ICAM-1 and VCAM-1 （P0.01） compared to the control group. Pro-inflammatory cytokines IL-1β and IL-6 were significantly reduced in the treatment group （P0.01），with greater reductions compared to the control group （P0.05，P0.01）. Anti-inflammatory cytokines IFN-α，IL-4，and IL-10 were significantly elevated in the treatment group （P0.01），with higher levels compared to the control group （P0.01）. No significant adverse reactions were reported in either group. ConclusionThe "energy- inflammation- aging" network plays an important role in the pathological mechanism of hypertension patients. Qianyang Yuyin granules may delay the aging process by increasing patients' energy metabolism levels，reducing DNA oxidative damage，and maintaining the balance of inflammatory factors.

Objective: To observe the effect of Xipayimaizibizi oral liquid (XP) in an overactive bladder (OAB) experimental rat model and to explore its pharmacological mechanisms. Methods: Network pharmacology was used to explore the potential mechanisms of action of XP. The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks. The study observed the body weight, water intake, bladder and kidney indices (to evaluate their general status), urination behavior pattern (to observe frequency and urgency), and urodynamics (to measure bladder parameters). Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure. Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor, brain-derived neurotrophic factor, and acetylcholine in the urine. The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and western blot in vivo/vitro experiments. Result: Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways. XP treatment significantly reduced the bladder index, improved urine behavior and urodynamic parameters, decreased the neurotransmitters in urine, and reduced the thickness of the bladder wall and collagen ratio. These results indicate that XP can alleviate OAB symptoms and improve the bladder structure. In vivo/vitro experiments further demonstrated that XP can inhibit targets, such as muscarinic acetylcholine receptor 2, and participate in cholinergic synapses to further regulate the parasympathetic nervous system. It can also reduce the overexpression of Ca2+ caused by agonists, inhibit targets such as transient receptor potential vanilloid type 1, and participate in calcium signaling pathways to maintain Ca2+ homeostasis. Conclusion These results suggest that XP inhibited bladder overactivity by maintaining Ca2+ homeostasis and regulating the parasympathetic nervous system.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L^-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L^-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot. ResultCompared with the blank group， 200 μmol·L^-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L^-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L^-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L^-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）. ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.

ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 （T2DM） rats， and the mechanism based on liver peroxidase proliferators activate receptors-α （PPAR-α） and carnitine palmityl transferase-1 （CPT-1） proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet （HFD） + streptozocin（STZ）method. Rats with blood glucose ≥ 11.1 mmol·L^-1 were divided into three administration groups with the high dose （300 mg·kg^-1）， medium dose （150 mg·kg^-1）， and low dose （75 mg·kg^-1） of total flavonoids of mulberry leaves for 8 weeks， respectively， to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin （HE） staining. Biochemical method was used to detect the levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein-cholesterol （LDL-C）， and high density lipoprotein-cholesterol （HDL-C） of blood lipid metabolism in rats. The messenger ribonucleic acid （mRNA） and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves， compared with the control group， the food intake， liver index， and fasting blood glucose of rats in the model group increased significantly （P<0.01）. Compared with the model group， the food intake， fasting blood glucose， and liver index of rats in the administration groups decreased significantly （P<0.01）. The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group， the levels of TC， TG， and LDL-C increased significantly （P<0.01）， but the level of HDL-C decreased significantly （P<0.01） in the model group. Compared with the model group， the levels of TC， TG， and LDL-C decreased significantly （P<0.05， P<0.01）， whereas the level of HDL-C increased significantly （P<0.01） in the administration groups. The results of Real-time PCR showed that compared with the control group， the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.01）. The results of Western blot showed that compared with the control group， the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.05， P<0.01）. ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.

Objective To identify prognostic factors ofmotorfunctionafter surgery of metastatic spinal cord compression (MSCC).Methods The clinical data of 681 patients with spinal metastases from January 2008 to December 2017 were retrospectively analyzed.According to inclusion and exclusion criteria,a total of 206 patients with spinal metastatic were included.Postoperative neurological function was assessed using Frankel classification.The influence of age,gender,preoperative status,number of spine metastases,location of spinal metastases,visceral metastases,bone metastases,primary tumor type,interval from symptom to surgery,time of developing motor deficits,interval from primary tumor diagnosis to MSCC,preoperativethe Eastern Cooperative Oncology Group performance status (ECOG-PS),Karnofsky Performance score (KPS) and surgical procedures on postoperative function outcomes were explored.Results 140 (68.0％) patients were able to walk postoperatively compared with 88 (42.7％) patients preoperatively.Moreover,in 89.8％ of all patients,79 ambulatory patients maintained ambulation after treatment.The univariate analysis according to Ordered-logit model showed thatnumber of spine metastases,location of spinal metastases,preoperative ECOG-PS,preoperative KPS,interval from symptom to surgery and time of developing motor deficits were related with posttreatment motor functions.The multivariable analysis showed that number of spine metastases (OR=2.03;95％CI:1.12-3.33;P=0.04),preoperative ECOG-PS (OR=4.84;95％CI:2.42-8.15;P=0.038),interval from symptom to surgery (OR=3.78;95％CI:3.12-9.15;P=0.024),time of developing motor deficits(OR=2.75;95％CI:1.22-3.89;P=0.01) were independent prognostic factors for function outcomes.Conclusion 1-2 levels of metastasis,Interval from symptom to treatment ≥ 48 h,time of developing motor deficits ≥7 d,and ECOG-PS 1-2 can be considered as the most significant positive prognosticfactors for post-treatment ambulatory status.Spinal metastasis should have a higher priority,and immediate intervention should be started before the development of irreversible neurologic deficits.Increasing awareness of early symptoms and earlier screeningwith regular outpatient review might make a difference for patients with MSCC.Consequently,the identified prognostic factors can be considered as apreoperative assessment tool to predict the neurologic outcomeand guide clinical treatment for individual patients with MSCC.

Objective To assess the clinical value of cross raft screws technique in preventing postoperative collapse of tibial plateau fracture.Methods From September 2014 to November 2017,data of 14 patients with tibial plateau fracture who were treated by cross raft screws technique were retrospectively analyzed.There were 9 males and 5 females aged from 30-65 years old (average,44.4± 1.7 years).There were 8 patients that the thickness of subchondral cancellous bone measured preoperatively by CT data was less than 4 mm,and 6 patients that the thickness of subchondral cancellous bone measured intraoperatively was less than 4 mm.1/4 tubular plate was placed along the anterior rim of lateral tibial plateau,and the 3.5 mm cortical bone screws were fixed as bamboo raft from anterior to posterior through the plate.The collapse of tibial plateau after surgery were measured by CT scan after union of the fracture.The function of knee was evaluated by Rasmussen Anatomical and Functional Grading.Results The time of tubular plate procedure was 18 to 35 min (average,24.1±5.4 min).All 14 patients were successfully followed-up for 13.8±5.1 months.The height of collapse preoperatively by CT scan was 5-21 mm (average,8.00± 1.40 mm).3 days after the operation,the height between articular line and lateral articular surface was 0-2 mm (average,0.80±0.06 mm).Compared with CT data preoperatively,the collapse was corrected postoperatively that was proved by CT scan (P＜ 0.05).After the fracture was healed,according to CT data,the height between articular line and lateral articular surface was 0-2 mm (average,0.70±0.08 mm).Compared with CT data postoperatively,there was no postoperative collapse happened (P=0.466).The position and length of nails were placed appropriately.The average healing time of fracture was 3.6 months.There were no infection,nonunion and pain of tendon happened.The plate could be touched subcutaneously in 2 patients,who had no discomfort feelings.The patient's postoperative Rasmussen Anatomical Grading were 13-18 (average,16.7),including 8 cases excellent and 6 cases good.The postoperative Rasmussen Functional Grading was 18-28 (average,25.7),including 11 cases excellent and 3 cases good.Conclusion The cross raft screws technique is a good way to prevent the postoperative collapse of the lateral articular surface of tibial plateau.

Ebola virus (EBOV) is an extremely contagious pathogen first discovered in Africa associated with severe hemorrhagic disease in humans and nonhuman primates, which has resulted in at least 28 500 suspected cases and 11 300 confirmed deaths in 2014-2016 Ebola epidemic in West Africa. Rapid and sensitive detection of EBOV is the key to increasing the probability of survival and reducing infection rates in pandemic regions. Here, we report an ultrasensitive and instrument-free EBOV detection assay based on colloidal carbon immunochromatography. Carbon nanoparticle-labeled rabbit anti-EBOV-VP40 IgG were concentrated in the conjugate pad, monoclonal antibody (McAb, 4B7F9) against EBOV-VP40 and goat anti-rabbit IgG were immobilized on the nitrocellulose membrane with 2 μL/cm at a concentration of 1 mg/mL as test and control lines, respectively. Then the sample application pad, conjugate release pad, nitrocellulose membrane and absorbent pad were assembled into a lateral flow test strip. The test strip shows strong specificity against related viruses that share similar clinical symptoms and geographic range with EBOV, including marburg virus, influenza virus, yellow fever virus and dengue virus. In addition, 1 500 negative serums were tested with false-positive rate of 1.3‰ which significantly lower than that of ReEBOV™ colloidal gold test kit recommended by World Health Organization (WHO). The sensitivity of this strip was analyzed using inactivated EBOV with detection limit of 100 ng/mL (10⁶ copies/mL) which clearly higher than that of ReEBOV™ dipstick (10⁸ copies/mL). Furthermore, the strip showed excellent thermal stability characteristics in room temperature and could be as a point-of-care (POC), ultra-sensitive and specific promising candidate for EBOV serological screening in rural Africa or entry/exit ports.
Animals ; Carbon ; Ebolavirus ; Hemorrhagic Fever, Ebola ; Humans ; Nanoparticles ; Rabbits

Objective To study the effects of Jaridonin, a novel diterpenoid from isodon rubescens, on the cell cycle of human gastric cancer cells and its molecular mechanism of action. Methods Flow cytometry was used to analyze the cell cycle distribution and expression of ataxia telangiectasia mutated kinase ( ATM) after Jaridonin treatment. Western blot was performed to detect the expression of cell cycle?related proteins. Results The results of flow cytometry showed that the percentages of MGC?803 cells in G2/M phase at 6 hours after 0, 10, 20 μmol/L Jaridonin?treatment were (10.8±2.2)%, (18.2±2.5)%, (27.3±3.2)%, respectively;those at 12 hours after Jaridonin?treatment were (12.0±1.5)%, (24.1±2.0)%and (39.7±5.2)%, respectively, indicating a G2/M phase arrest of MGC?803 cells was resulted in a time?and dose?dependent manner. The expressions of ATM, Chk1, Chk2, phosphorylated Cdc2 and CDK2 were up?regulated in the MGC?803 cells after Jaridonin treatment, while the levels of Cdc2 and CDK2 were decreased. KU?55933, an inhibitor of ATM, reversed the expression of relevant proteins and G2/M phase arrest induced by Jaridonin. Conclusions Jaridonin can significantly induce G2/M arrest in gastric cancer MGC?803 cells. Its mechanism may be related to the activation of ATM and Chk1/2, and inactivation of Cdc2 and CDK2 phosphorylation.

Objective To study the effects of Jaridonin, a novel diterpenoid from isodon rubescens, on the cell cycle of human gastric cancer cells and its molecular mechanism of action. Methods Flow cytometry was used to analyze the cell cycle distribution and expression of ataxia telangiectasia mutated kinase ( ATM) after Jaridonin treatment. Western blot was performed to detect the expression of cell cycle?related proteins. Results The results of flow cytometry showed that the percentages of MGC?803 cells in G2/M phase at 6 hours after 0, 10, 20 μmol/L Jaridonin?treatment were (10.8±2.2)%, (18.2±2.5)%, (27.3±3.2)%, respectively;those at 12 hours after Jaridonin?treatment were (12.0±1.5)%, (24.1±2.0)%and (39.7±5.2)%, respectively, indicating a G2/M phase arrest of MGC?803 cells was resulted in a time?and dose?dependent manner. The expressions of ATM, Chk1, Chk2, phosphorylated Cdc2 and CDK2 were up?regulated in the MGC?803 cells after Jaridonin treatment, while the levels of Cdc2 and CDK2 were decreased. KU?55933, an inhibitor of ATM, reversed the expression of relevant proteins and G2/M phase arrest induced by Jaridonin. Conclusions Jaridonin can significantly induce G2/M arrest in gastric cancer MGC?803 cells. Its mechanism may be related to the activation of ATM and Chk1/2, and inactivation of Cdc2 and CDK2 phosphorylation.