Cellular senescence, an irreversible state of cell cycle arrest characterized by phenotypic changes and a specific secretory profile, plays a dual role in liver health and disease. Under physiological conditions, senescence aids organ repair and regeneration, but its accumulation due to aging or pathological stress significantly contributes to chronic liver diseases, including alcoholic liver disease, metabolic dysfunction-associated steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Senescence is identified by a range of cellular and molecular changes, such as morphological alterations, expression of cell cycle inhibitors, senescence-associated β-galactosidase activity, and nuclear membrane changes. The onset of senescence in organ cells can affect the entire organism, primarily through the senescence-associated secretory phenotype, which has autocrine, paracrine, and endocrine effects on tissue microenvironments. The objective of this review is to offer a contemporary overview of the pathophysiological events involving hepatic senescent cells and to elucidate their role in the onset and progression of liver diseases, particularly through mechanisms like telomere shortening, genomic and mitochondrial DNA damage, and inflammation. Additionally, this review discusses the emerging senolytic therapies aimed at targeting senescent cells to delay or mitigate liver disease progression. The therapeutic potential of these interventions, alongside their safety and effectiveness, highlights the need for further research to refine these approaches and address unresolved problems in the field of hepatic cellular senescence.
Humans ; Cellular Senescence/physiology* ; Liver Diseases ; Animals ; DNA Damage ; Telomere Shortening/physiology*

【Objective】 To compare the current standards and explore the influencing factors for hemolysis rate of leukocyte-reduced red blood cells at the end of the preservation period, in order to formulate reasonable internal control indicators. 【Methods】 A retrospective analysis was performed on hemolysis rate of 427 samples of leukocyte-reduced red blood cells at the end of the preservation period in Nanning Blood Center from 2015 to 2022. Compared with the current standard for hemolysis rate at the end of the preservation period (GB 18469-2012 Quality Requirements for Whole Blood and Component Blood), the differences were analyzed, and the factors influncing the hemolysis rate were analyzed in terms of different blood donor groups. 【Results】 1) Among the 427 samples, the hemolysis rate of 418 (97.89%) did not exceed 0.4%, all lower than 0.8%; 2)the hemolysis rate of the male group was higher than that of the female group; 3) the hemolysis rate of the 18-29 years old group was lower than that of the 30-39 year old group and the 40-60 year old group, with statistically significant difference; 4) in terms of occupation, the hemolysis rate of students was the lowest, and the differences between groups were statistically significant; 5) no statistical significance was found in ethnicity and blood type. 【Conclusion】 Statistics indicated that gender, age, blood donation volume and occupation of blood donors were the influencing factors of hemolysis rate. The current standard is obviously higher in the qualified range of blood quality control in Nanning. It is advisable to formulate a reasonable quality control strategy with internal control index of hemolysis rate set <0.4%, which is conducive to making accurate evaluation of internal quality control and ensuring blood safety.

Objective: To prepare the total saponins from Paris Polyphylla self-microemulsifying drug delivery system (SMEDDSs) and its solid fied granule, and investigate the in vitro release.Methods: The solubility of the total saponins from Paris Polyphylla in different excipients was investigated.The pseudo-ternary phase diagram composed of different oil phase, emulsifier and co-emulsifier was used to define the self-emulsifying area.The optimal formula of the total saponins from Paris Polyphylla SMEDDSs was prepared into granule.The appearance, morphology, particle size distribution, PdI and zeta potential of the microemulsion and the granule were determined by a dilution method.The drug release profile of the total saponins from Paris Polyphylla SMEDDSs and SMEDDSs granule were compared.Results: The optimal formula of SMEDDSs was as follows: propylene glycol monocaprylate as the oil phase, Tween-80 as the emulsifier and propylene glycol as the co-emulsifier with the optimum ratio of 7.0∶1.5∶1.5.After diluted by water,the total saponins from Paris PolyphyllaSMEDDSs and the granule formed a clear and transparent microemulsion solution with small homogeneous spheres as seen under a transmission electron microscope.The average particle size of the total saponins from Paris Polyphylla SMEDDSs and the granule was (58.6±16.4) nm and (68.1±12.1) nm with PdI of (0.183±0.04) and (0.209±0.05), respectively, and the zeta potential was (-20.2±1.9) mV and (-18.9±1.5) mV, respectively.The results of transmission electron microscopy showed the microemulsion was round, regular and spherical distribution.The in vitro release profile indicated that the accumulated release of the total saponins from Paris Polyphylla SMEDDSs and SMEDDSs granule was more than 85% in 45 min.Conclusion: The self-microemulsifying granule can significantly improve the in vitro dissolution rate of the total saponins from Paris Polyphylla, and the preparation process is simple and feasible.

Objective To observe the effect of polydatin on nerve cell apoptosis and the influence of the caspase-8 and FLIP protein expression after ischemia reperfusion injury. Methods Thirty rats were randomly divided into sham operation group, model group and polydatin group. The middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia was established by the method of thread embolism. Rats were subjected to adaptive feeding for the first 7 days and then recieved the treatment for another 10 days. The model of ischemia reperfusion injury was established at the 14th day. The polydatin group received 15 mg/kg of polydatin, and the sham operation group and the model group with the same volume of saline once a day for 15 days. The expression of caspase-8 and FLIP protein in the hippocampus of rats were observed by immunohistochemical staining. The expression of caspase-8 and FLIP protein in the hippocampus of rats were observed by TUNEL method at 72 h after cerebral ischemia-reperfusion. Results Compared with the model group, the number of apoptotic cells of polydatin group significantly decreased in hippocampus CA1 region (P<0.01); The expression of caspase-8 (148.78 ± 6.82 vs. 89.61 ± 7.76) in the polydatin group significantly decreased and the expression of FLIP (127.60 ± 8.52 vs. 150.22 ± 8.53) in the polydatin group was increased significantly in hippocampus CA1 region(P<0.01). Conclusions Polydatin have a protection effect on ischemia reperfusion injury in rats and its mechanism may be inhibition of caspase-8 protein expression, promote the FLIP protein expression.

Objective:To design and develop a formula of solid lipid nanoparticles containing the total saponins of Paris Polyphylla using a quality by design ( QbD) method. Methods:The target product profile of solid lipid nanoparticles was determined according to the properties of dosage form and administration. The risk assessment was carried out according to the theoretical knowledge and experi-ence to define the critical variables influencing the properties of solid lipid nanoparticles. Firstly, Plackett-Burman test was used to screen out the key variables significantly affecting the pharmacological properties of solid lipid nanoparticles, and then the Box-Behnken effect surface method was use to further optimize the selected variables. The physicochemical properties of solid lipid nanoparticles con-taining the total saponins of Paris Polyphylla were studied, such as the particle size distribution, polydispersity index ( PdI) , zeta po-tential, morphology and in vitro drug release behavior. Results: The optimum formula and preparation process were as follows: the concentration of glycerol monostearate was 5. 5％, the concentration of soybean phospholipid was 8. 0％, the number of homogenization was 6 times, the concentration of drug was 5. 0％, the surfactant was Tween 80, the mass pressure was 600 bar and the homogeneous temperature was 65℃. The mean particle size, PdI and zeta potential of the optimized solid lipid nanoparticles was (116. 5 ± 32. 1) nm, (0. 198 ± 0. 018) and ( -23. 6. 5 ± 0. 9) mV, respectively. Transmission electron microscopy showed that the solid lipid nanop-articles were spherical. The results of in vitro release showed a sustained release property, and the cumulative release was 63. 5％ in 24 h. Conclusion:It is feasible to design and develop solid lipid nanoparticles containing the total saponins of Paris Polyphylla by using the QbD method, which can ensure the product quality to meet the requirements.

AIM:To explore the expression level of microRNA-140 ( miR-140 ) in human gastric cancer and normal gastric tissues, and the regulatory effect of miR-140 expression on the function of SGC-7901 cells.METHODS:The expression levels of miR-140 in human gastric cancer and normal gastric tissues were detected by real-time PCR.miR-140 mimics ( miR-140 up-regulated expression) and miR-140 inhibitors ( miR-140 down-regulated expression) were trans-fected into human gastric cancer SGC-7901 cells by liposome method.At the same time, the untransfected control group ( control group) and miRNA nonsense sequence transfection group ( NC group) were set up .The expression of miR-140 in the cells after transfection was detected by real-time PCR.The cell viability and growth inhibition rate with DDP were meas-ured by MTT assay.The cell cycle and apoptotic rate of SGC-7901 cells were analyzed by flow cytometry.The invasion a-bility of SGC-7901 cells was measured by Transwell assay.The protein expression of histone deacetylase 4(HDAC4) in the cells was determined by Western blot.RESULTS:The expression level of miR-140 in human gastric cancer tissues was significantly lower than that in normal gastric tissues (P<0.05).Compared with control group and NC group, the viability and invasion ability of the SGC-7901 cells were decreased, the cell cycle was arrested, the cell growth inhibition rate and apoptotic rate with DDP treatment were increased, and the protein expression of HDAC4 was down-regulated ( P<0.05) in miR-140 mimics group.However, in miR-140 inhibitors group, the viability and invasion ability of the SGC-7901 cells were increased, the cell cycle was promoted, the cell growth inhibition rate and apoptotic rate with DDP treatment were de-creased, and the protein expression of HDAC4 was up-regulated ( P<0.05 ) .CONCLUSION:The expression level of miR-140 in the gastric cancer tissues is low.miR-140 serves as a tumor suppressor to regulate the viability, apoptosis and invasion ability of gastric cancer cells, and to play a role by down-regulating HDAC4 protein.miR-140 may serve as a new target for diagnosis and treatment of gastric cancer.

Objective:To prepare and characterize the PEGylated liposomes containing total saponins of Paris Polyphylla. Meth-ods:Using the size, PDI, zeta potential and encapsulation efficiency of the liposomes as the indicators, the influencing factors in the preparation were optimized. The particle size, PDI and zeta potential were studied by a Malvern Zetasizer, the morphology was ob-served under a TEM, and the stability was studied as well. Results:The particle size, PDI, zeta potential and encapsulation efficiency of the PEGylated liposomes was (109. 4 ± 32. 7) nm, (0. 171 ± 0. 036), ( -36. 7 ± 4. 5) mV and (93. 5 ± 3. 2) %, respectively. The liposomes were small spheres with smooth surface under the TEM. The long term stability studies showed that the liposomes were stable in 3 months after stored at 4℃. Conclusion:The preparation technology of the PEGylated liposomes containing total saponins of Paris Polyphylla is feasible, which can obtain liposomal preparations with high entrapment efficiency and good stability.

To study the effect and mechanism of Qingdu granules on the tumor growth of 7, 12-dimethyl-benz[ a] an-thracene ( DMBA)-induced breast cancer in Sprague-Dawley rats. Methods: DMBA was used to induce breast cancer in rats. The tumor inhibition of Qingdu granules was observed. Pathological features were observed after hematoxylin-eosin staining, the distribution and content of Ki-67 in tumor were tested by IHC and the content of IL-12, IFN-γ, IL-4 and IL-10 in serum was determined by ELISA. Results:The inhibitory rate of Qingdu granules at low, middle and high dose and saikosaponin a was 30. 93%,43. 84% and 44. 17% and 43. 48%, respectively. The expression of Ki-67 was reduced in Qingdu granules groups and saikosaponin a group, the content of IL-12 and IFN-γ in serum was increased and the level of IL-4 and IL-10 was reduced in the above groups. Conclusion:Qingdu granules can inhibit breast cancer obviously, and the mechanism is probably related to the ability of immune system adjustment, which can enhance the antitumor effect.

Objective To investigate the curative effect of cisplatin combined with gemcitabine and cisplatin plus pacli-taxel in the treatment of advanced non-small cell lung cancer. Methods All 100 patients with non-small cell lung can-cer in our hospital from January 2012 to January 2014 in our hospital, randomly divided into observation group (gemc-itabine+cisplatin, GP group) and control group (paclitaxel+cisplatin, TP group), each group had 50 cases, two groups of patients every 21 days for a cycle, observed curative effect after 2 cycles, toxic and adverse reaction were compared between the two groups. Results The effective rate of the observation group after treatment was 42.0%(21/50),was higher than that of the control group 40% (20/50), but there was no significant difference (P>0.05). Conclusion Cura-tive effect of cisplatin combined with gemcitabine and cisplatin plus paclitaxel in the treatment of advanced non-small cell lung cancer is similar, the poisonous side effect is different and can be tolerated, for the treatment of advanced non-small cell lung cancer treatment plan better.

Objective To discuss the effectiveness of standardized management of hypertension and its significance of economics.Methods Taking prospective,randomized and controlled trial design to screen hypertension in four communities of Changping Town.The patients in the four communities were randomly divided into an intervention group and a control group.The intervention group was taken the standardized management and the control group was taken conventional management.Results The treatment rate and control rate of the intervention group was higher than the control group.Necessary inputs of per capita administration costs for every 1％ increase of treatment or control rate in the intervention group were less than the control groups by 1.08 and 1.36 Yuan respectively.The per capita administrative costs of intervention group were higher than control group,while the per capita comprehensive costs of intervention group were lower than control group.Compared with the control group,every 1 Yuan of per capita administrative costs increases,the comprehensive costs would be reduced 7.58 Yuan in the intervention group.Conclusion Standardized management of hypertension in community can significantly improve the prevention and treatment effects.Moreover,it has good cost-effective value and saving social resources.