Objective:To investigate the impact of High Alcohol-Producing Klebsiella pneumoniae (HiAlc Kpn) on hepatocyte function and explore its regulatory mechanism from the perspective of epigenetic modifications. Methods:Using the HepG2 cell line as the research model, the study involved exposing the cells to alcohol and three different HiAlc Kpn strains in vitro, dividing them into a control group, alcohol-treated group, W8 group, 3-24 group, and 4-26 group. The effect of HiAlc Kpn on liver cell proliferation was investigated using the Incucyte live cell imaging system, and the apoptotic level of liver cells was determined using flow cytometry. The fluorescence confocal microscopy combined with live cell probes was used to detect lipid accumulation and intracellular ROS levels in liver cells. The amount of mitochondrial damage was determined using flow cytometry combined with the seahorse cell metabolism analyzer, and changes in protein levels undergoing global lactylation modification were investigated using Western blotting. Results:Compared with the control group, HiAlc Kpn strains W8, 3-24 and 4-26 could decrease the proliferation rate and increase the ratio of apoptosis of hepatocyte HepG2 cells. The results of high-content cell imaging showed that the fluorescence points of ROS enrichment in HepG2 cells were increased after HiAlc Kpn treatment. The lipid accumulation was significantly increased by oil red O and BODIPY staining. The number of oil droplets and fluorescence points was higher than those in the control group and alcohol treatment group. The results of flow cytometry showed that the ratio of JC-1 monomer/polymer was significantly increased after alcohol and three kinds of HiAlc Kpn were treated and the W8 treatment group was about six times higher than the control group ( P<0.05). Seahorse Energy Metabolism System′s mitochondrial pressure test results showed that the extracellular acidification degree and oxygen consumption rate were significantly reduced by the HiAlc Kpn 4-26 strain. Western blot analysis showed that the pan-lactylation modification level increased after high-concentration alcohol treatment and the increased rate of pan-lactylation modification in the 1 000 mmol/L alcohol group was about three times that of the control group. HiAlc Kpn W8 and 3-24 strains resulted in four or two-times pan-lactylation modification increases compared with the control group, and the differences were statistically significant ( P<0.05). Conclusion:HiAlc Kpn can induce lipid peroxidation in hepatic cells by regulating the increase in histone pan-lactylation modification levels, leading to mitochondrial damage, impaired cell proliferation capacity and increased apoptosis levels.

Objective:To investigate the impact of High Alcohol-Producing Klebsiella pneumoniae (HiAlc Kpn) on hepatocyte function and explore its regulatory mechanism from the perspective of epigenetic modifications. Methods:Using the HepG2 cell line as the research model, the study involved exposing the cells to alcohol and three different HiAlc Kpn strains in vitro, dividing them into a control group, alcohol-treated group, W8 group, 3-24 group, and 4-26 group. The effect of HiAlc Kpn on liver cell proliferation was investigated using the Incucyte live cell imaging system, and the apoptotic level of liver cells was determined using flow cytometry. The fluorescence confocal microscopy combined with live cell probes was used to detect lipid accumulation and intracellular ROS levels in liver cells. The amount of mitochondrial damage was determined using flow cytometry combined with the seahorse cell metabolism analyzer, and changes in protein levels undergoing global lactylation modification were investigated using Western blotting. Results:Compared with the control group, HiAlc Kpn strains W8, 3-24 and 4-26 could decrease the proliferation rate and increase the ratio of apoptosis of hepatocyte HepG2 cells. The results of high-content cell imaging showed that the fluorescence points of ROS enrichment in HepG2 cells were increased after HiAlc Kpn treatment. The lipid accumulation was significantly increased by oil red O and BODIPY staining. The number of oil droplets and fluorescence points was higher than those in the control group and alcohol treatment group. The results of flow cytometry showed that the ratio of JC-1 monomer/polymer was significantly increased after alcohol and three kinds of HiAlc Kpn were treated and the W8 treatment group was about six times higher than the control group ( P<0.05). Seahorse Energy Metabolism System′s mitochondrial pressure test results showed that the extracellular acidification degree and oxygen consumption rate were significantly reduced by the HiAlc Kpn 4-26 strain. Western blot analysis showed that the pan-lactylation modification level increased after high-concentration alcohol treatment and the increased rate of pan-lactylation modification in the 1 000 mmol/L alcohol group was about three times that of the control group. HiAlc Kpn W8 and 3-24 strains resulted in four or two-times pan-lactylation modification increases compared with the control group, and the differences were statistically significant ( P<0.05). Conclusion:HiAlc Kpn can induce lipid peroxidation in hepatic cells by regulating the increase in histone pan-lactylation modification levels, leading to mitochondrial damage, impaired cell proliferation capacity and increased apoptosis levels.

Objective:To study the difference in dissolution behavior of clozapine tablets in four different media between the do-mestic preparations and original preparation to compare the internal quality of the tablets from various manufacturers and provide refer-ence for the drug control. Methods:Referring to the methods of in vitro dissolution test, the dissolution profiles of 46 batches of sam-ples from 18 pharmaceutical enterprises were determined in four kinds of dissolution media with different pH values, and the results were compared with that of the original drug by the method of f2 similarity factor. Results: Totally 46 dissolution profiles were drawn out. The profiles of two batches of samples from one pharmaceutical enterprise were similar to that of the original drug, which account-ing for 4%, and that of the other samples showed notable difference from that of the original drug. Conclusion:The preparation tech-nology of the tablets from domestic has great difference, which leads to significant difference in dissolution behavior. The screening and optimization of the production process in domestic pharmaceutical enterprises should be strengthened to improve the preparation technol-ogy of clozapine tablets.

Objective In this retrospective study, we analyzed the magnetic resonance imaging (MRI)and computed tomography(CT)scans of patients with prostate cancer to investigate the relationship between the apex of prostate and the anatomic structures visible in CT, and to provide evidence for localizing the prostatic apex in radiation treatment planning. Methods MRI and CT scans from 108 patients with prostate cancer were analyzed to measure the distance between the prostatic apex and the bottom of ischial tuberosities,the bottom of obturator foramen, the bottom of pubic symphysis and the bulb of the penis. The volume of prostate was calculated and the relationship between the size of the prostate and the localization of the prostatic apex was analyzed. Results The prostatic apex is located 13. 1 mm ±3. 3 mm superior to the bulb of the penis, 11.0 mm ± 5.4 mm superior to the bottom of obturator foramen, 31.3 mm ± 5.5 mm superior to the bottom of ischial tuberosities, and 7. 1 mm ± 4. 7 mm superior to the bottom of obturator foramen. There was no correlation between the size of prostate and the localization of the prostatic apex(R =0. 07、-0. 33, all P ＞ 0. 05). Conclusions Ninety-five percent of patients had a prostatic apex that is above the bulb of the penis 6 mm, and 100% of patients had a prostatic apex that is above the bottom of obturator foramen.