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.

Ulcerative colitis(UC)is a chronic,recurrent intestinal inflammatory disorder.In recent years,the role of vitamin D in the treatment of UC has attracted widespread attention.Studies have demonstrated that vitamin D exerts therapeutic effects through multiple mechanisms including maintaining intestinal barrier,regulating immune cells and inflammatory factors,modulating gut microbiota,and regulating gene expression.Clinical studies have found that vitamin D supplementation can improve UC symptoms,alleviate inflammatory response,and enhance patients'quality of life.Additionally,there are differences in efficacies when vitamin D is combined with different drugs.This article reviewed the research progress on the mechanism and supplementation dosage of vitamin D in the treatment of UC,as well as its role in disease assessment and clinical significance.

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.

Ulcerative colitis(UC)is a chronic,recurrent intestinal inflammatory disorder.In recent years,the role of vitamin D in the treatment of UC has attracted widespread attention.Studies have demonstrated that vitamin D exerts therapeutic effects through multiple mechanisms including maintaining intestinal barrier,regulating immune cells and inflammatory factors,modulating gut microbiota,and regulating gene expression.Clinical studies have found that vitamin D supplementation can improve UC symptoms,alleviate inflammatory response,and enhance patients'quality of life.Additionally,there are differences in efficacies when vitamin D is combined with different drugs.This article reviewed the research progress on the mechanism and supplementation dosage of vitamin D in the treatment of UC,as well as its role in disease assessment and clinical significance.

OBJECTIVE To explore the effects of Yueju Pill on depression and gastrointestinal function in depressed co-morbid functional dyspepsia mice.METHODS C57BL/6J mice were randomly divided into control group,model group,Yueju Pill low-dose group,Yueju Pill high-dose group and positive drug group.A co-morbidity model was constructed using chronic unpredictable mild stress(CUMS),and the mice were assessed for depression-like behaviour and neuronal damage by behavioural tests and Nissl staining;gastrointestinal function was assessed by HE staining of gastric and intestinal tissues,gastric emptying rate,and small intestinal propul-sive rate;PACAP,VIP,IL-6,TNF-α,and BDNF expression were detected by ELISA;PAC1-R,Vipr1,and Vipr2 protein expres-sion were detected by protein immunoblotting.RESULTS Mice in the model group showed depression-like behaviour,reduced num-ber of hippocampal nidus,slowed gastrointestinal motility,elevated serum inflammatory factors IL-6 and TNF-α(P＜0.05,P＜0.01),and reduced expression of PACAP,VIP,and BDNF(P＜0.05,P＜0.01),The PAC1-R,VPAC1-R,VPAC2-R expression de-creased in the hippocampus and gastric sinus,duodenal tissue(P＜0.05,P＜0.01).Compared with the model group,the low and high dose groups of Yueju Pill improved the above indexes except for Vipr1 and Vipr2(P＜0.05,P＜0.01).CONCLUSION Yueju Pill can reduce inflammatory factors through PACAP/PAC1-R,increase the level of BDNF,and improve the depression-like behaviour and gastrointestinal dysfunction in CUMS mice.

ObjectiveTo evaluate the clinical efficacy and safety of Ganjie Bingmei Tablet （甘桔冰梅片， GBT） in treating acute pharyngitis with wind-heat invading the lung syndrome. MethodsUsing multi-center， rando-mized， double-blind， double-dummy， positive and parallel controlled clinical trial design， 144 acute pharyngitis patients with wind-heat invading the lung syndrome from October 8th， 2022 to March 31st， 2023 were collected and randomly assigned to the treatment group and the control group， with 72 cases in each group. The treatment group was treated by GBT （0.4 g each time， 4 times a day） combined with Ganjie Qingyan Granules （甘桔清咽颗粒， GQG） placebo （10 g each time， 3 times a day）， while the control group was treated by GQG （10 g each time， 3 times a day） combined with GBT placebo （0.4 g each time， 4 times a day）， both for 5 days. The clinical efficacy of the two groups was observed， and the disappearance rate of pharyngalgia and the efficacy regarding TCM syndromes were compared between groups after treatment. The visual analog scale （VAS） score before and after treatment was assessed， and the safety was evaluated. ResultsThe disappearance rate of pharyngalgia in the treatment group was 98.61%（71/72）， significantly higher than 80.56%（58/72） in the control group （P＜0.01）. The VAS scores in both groups significantly decreased after treatment （P＜0.05）， and lower score was found in the treatment group than the control group （P＜0.05）. The total effective rate regarding TCM syndromes was 100% in both groups， but the curative rate was significantly higher in the treatment group（73.61%， 53/72） than the control group （62.50%， 45/72， P＜0.05）. There were no obvious adverse reactions in the both groups. ConclusionGBT is effective and safe in treating acute pharyngitis with wind-heat affecting the lung syndrome.

Many sensitizers have not only photodynamic effects, but also sonodynamic effects. Therefore, the combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT) using sensitizers for sono-photodynamic therapy (SPDT) provides alternative opportunities for clinical cancer therapy. Although significant advances have been made in synthesizing new sensitizers for SPDT, few of them are successfully applied in clinical settings. The anti-tumor effects of the sensitizers are restricted by the lack of tumor-targeting specificity, incapability in deep intratumoral delivery, and the deteriorating tumor microenvironment. The application of nanotechnology-based drug delivery systems (NDDSs) can solve the above shortcomings, thereby improving the SPDT efficacy. This review summarizes various sensitizers as sono/photosensitizers that can be further used in SPDT, and describes different strategies for enhancing tumor treatment by NDDSs, such as overcoming biological barriers, improving tumor-targeted delivery and intratumoral delivery, providing stimuli-responsive controlled-release characteristics, stimulating anti-tumor immunity, increasing oxygen supply, employing different therapeutic modalities, and combining diagnosis and treatment. The challenges and prospects for further development of intelligent sensitizers and translational NDDSs for SPDT are also discussed.

Objective: To investigate the diagnostic value of ultrasound-guided fine-needle aspiration cytology (FNAC) and fine-needle aspiration washout fluid thyroglobulin (FNA-Tg) detection for neck lymph nodes metastasis in patients with papillary thyroid carcinoma (PTC). Methods: A total of 214 PTC patients confirmed by pathology biopsy in Baoji Central Hospital from August 2015 to October 2018 were collected, and they all underwent ultrasound-guided FNAC, and FNA-Tg was measured by using electrochemiluminescence immunoassay. The histopathologic detection was performed for all suspicious lymph nodes after lymphadenectomy, and the results were analyzed by using statistics. Results: There were 282 suspicious enlarged lymph nodes detected from 214 PTC patients. Histopathological examination showed 220 lymph node metastases were positive, 62 were negative. FNAC examination showed 193 lymph nodes were positive and 89 were negative. The sensitivity, specificity, Youden index, positive predictive value, negative predictive value, accuracy of FNAC for diagnosing the lymph nodes of metastasis PTC was 84.55%, 88.71%, 73.26%, 96.37%, 61.80%, 85.46%, respectively. FNA-Tg test showed that 198 lymph nodes were diagnosed as positive metastasis and 84 were negative metastasis. The sensitivity, specificity, Youden index, positive predictive value, negative predictive value, accuracy of FNA-Tg for diagnosing the lymph nodes of metastasis PTC was 88.64%, 95.16%, 83.80%, 98.48%, 70.24%, 90.07%, respectively. Both FNAC and FNA-Tg test showed 215 lymph nodes were diagnosed as positive metastasis and 76 were negative metastasis. The sensitivity, specificity, Youden index, positive predictive value, negative predictive value, accuracy of combined treatments were 97.63%, 87.32%, 84.95%, 95.81%, 92.54%, 96.81%, respectively. The sensitivity and accuracy of combined detection were higher than those of single detection, and there were statistically significant differences (all P < 0.05). Conclusions FNAC and FNA-Tg detection are simple, safe and accurate. The combined detection of FNAC and FNA-Tg can improve the sensitivity and accuracy for the diagnosis of PTC lymph node metastasis.

Objective Intrauterine growth retardation (IUGR) is characterized by low birth weight of neonates. The aim of this study was to provide a reference for the establishment of IUGR models in scientific research, by comparing the experimental data of different rat models of IUGR established by three commonly-used methods. Methods A total of 20 pregnant rats on the day 0 of gestation were divided into 4 groups, with 5 rats in each group (n=5). Among them, 3 groups of rats were treated with alcohol intervention (group A), uterine artery ligation (group U), and low protein diet (LP group), respectively, to establish rat models of IUGR, and the fourth group served as the normal control group (CON group). Fetal rats were taken through cesarean section on the 20th day of gestation. The body mass, brain mass, placental mass, two-kidney mass, body length and tail length of the fetal rats were measured, and the incidence rate of IUGR, stillbirth rate and their brain to placenta ratio were calculated. The fetal rats in each group were continuously raised and the body mass, perirenal fat pad mass and some organ masses were determined at the 3rd, 6th and 12th weeks. Results The average body mass of the fetal rats in the groups A, U and LP group was significantly lower than that of the normal control group (P＜ 0. 05), and the incidence rate of IUGR of the fetal rats was significantly higher than that of the normal control group (P＜ 0. 05). In addition, the stillbirth rate of pregnant rats in the group U was significantly higher than those of the group A and LP group (P ＜ 0. 05). After raising the rats for 3 weeks, the average body mass of rats in the three experimental groups was significantly lower than that of the normal control group (P ＜ 0. 05), and after raising for 6 weeks, the average body mass in the three experimental groups was still lower than that of the normal control group, but with a non-significant difference (P＞ 0. 05). However, after raising for 12 weeks, the average body mass of the rats in the group A and LP group was significantly higher than that of the normal control group (P ＜ 0. 05). Conclusions Rat models of IUGR can be successfully established either by alcohol intervention, uterine artery ligation or low protein diet. The IUGR model established by low protein diet has the advantages of a higher incidence rate of IUGR and lower stillbirth rate, being more suitable for animal model research. As regards the catch-up growth, the average body mass of the rats during the postpartum period and lactation period after delivered by cesarean section in the group A and LP group is lower than that of the normal control group, but after lactation the rats grow faster than those in the normal control group, indicating the existence of a catch-up growth in the group A and LP group.

Objective To evaluate the changes of serum total prostate specific antigen (TPSA) with age and its significance in differential diagnosis of prostate cancer (PCa) and prostatic hyperplasia (BPH). Methods TPSA and free prostate specific antigen (FPSA) in 146 cases of PCa, 108 cases of BPH and 210 cases of healthy subjects were detected by electrochemiluminescence. Results There was a positive correlation between age and serum TPSA level (r=0.265, P<0.01). The levels of TPSA in PCa and BPH groups were (85.40 ±56.70) μg/L and (7.90 ±7.00) μg/L, and the difference was statistically significant (t=8.310, P= 0.001); FPSA levels were (5.16±4.90) μg/L, (1.50±1.36) μg/L, and the difference was statistically significant (t= 3.152, P= 0.030). In patients with TPSA levels ranging from 4.0 to 20.0 μg / L (diagnostic gray zone), the levels of TPSA in PCa and BPH groups were (8.82±4.01)μg/L and (8.41±3.95)μg/L, and the difference had no statistical significance (t= 0.198, P= 0.256); The levels of FPSA were (1.18 ±0.91) μg/L and (2.32±1.20) μg/L, the ratio of FPSA/TPSA were 0.12±0.08 and 0.24±0.23, and the differences were statistically significant (t= 23.56, P= 0.020; t= 32.45, P= 0.006). When FPSA/TPSA ratio was 0.16, its sensitivity and specificity for PCa were 84.4%and 79.8%, respectively. Conclusions Serum TPSA levels vary with age, and 95 % of all age groups should be used as the medical criterion to improve the specificity and accuracy of PSA in diagnosing with PCa. The ratio of FPSA/TPSA has a significant clinical value in differential diagnosis of PCa and BPH in patients with TPSA indiagnostic gray zone.