OBJECTIVE: To explore the specific mechanism of histone deacetylase 2 (HDAC2) mediated histone H3 lysine 27 acetylation (H3K27ac) modification in promoting the proliferation and migration of hepatocellular carcinoma cells. METHODS: Samples of 40 cases of hepatocellular carcinoma and paracancerous tissues resected from January 2021 to January 2023 were collected. The expressions of HDAC2 and H3K27ac in hepatocellular carcinoma, paracancerous tissues and cell lines were detected by immunohistochemistry and Western blotting. The correlation between the expression levels of HDAC2 and H3K27ac and the relationship between HDAC2 expression and clinicopathological characteristics of patients with hepatocellular carcinoma were analyzed. The proliferation, migration and invasion of Hep3B and HepG2 cells were determined by MTS, clone formation, scratch and Transwell experiments. The acetylation of H3K27 mediated by HDAC2 was verified by Western blotting, real-time fluorescence quantitative PCR (qRT-PCR) and chromatin immunoprecipitation high-throughput sequencing (ChIP-seq). In vivo xenotransplantation experiment, the tumorigenicity of cells in each group was measured, and the expression of proteins related to phosphoinositide 3-kinases/phosphatase and tensin homolog deleted on chromosome ten/protein kinase B/mammalian target of rapamycin (PI3K/PTEN/AKT/mTOR) signal pathway was detected. RESULTS: High expression of HDAC2 and low expression of H3K27ac were found in hepatocellular carcinoma tissues and cell lines (P < 0.05), and there was a negative correlation between them (r=-0.477, P=0.002). The expression of HDAC2 was related to tumor size, hepatitis B virus infection, TNM stage and portal vein tumor thrombus (P < 0.05). Compared with the sh-NC group of Hep3B and HepG2 cells, the proliferation, clone formation, migration and invasion ability of sh-HDAC2 group were decreased (P < 0.05). Compared with the Empty group, the HDAC2 group exhibited increased expression levels and activity of HDAC2, as well as enhanced cell proliferation, clone formation, migration, invasion ability, tumor volume and mass in vivo, and elevated expression levels of p-PI3K, p-AKT, and p-mTOR (P < 0.05). Conversely, the enrichment and expression levels of H3K27ac, along with the expression level of PTEN, were decreased (P < 0.05). In the iHDAC2 group, the expression levels and activity of HDAC2, as well as the proliferation, clone formation, migration, invasion ability, tumor volume and mass in vivo, and expression levels of p-PI3K, p-AKT, and p-mTOR were reduced (P < 0.05). Additionally, the expression levels of H3K27ac and PTEN were increased (P < 0.05). To validate the involvement of the PI3K/PTEN/AKT/mTOR signaling pathway in HDAC2-mediated regulation of malignant behaviors in liver cancer cells through H3K27ac, the PI3K activator 740Y-P was introduced. Compared with the iHDAC2 group, the iHDAC2+740Y-P group exhibited increased proliferation, clone formation, migration, invasion ability, tumor volume and mass in vivo, and elevated expression levels of p-PI3K, p-AKT, and p-mTOR (P < 0.05). Conversely, the expression level of PTEN was decreased (P < 0.05). CONCLUSION HDAC2 initiates PI3K/PTEN/AKT/mTOR signal pathway by mediating H3K27 acetylation, which promotes the occurrence and development of hepatocellular carcinoma.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Histone Deacetylase 2/physiology* ; Cell Proliferation ; Acetylation ; Cell Movement ; Histones/metabolism* ; Animals ; Hep G2 Cells ; Male ; Female ; Mice ; Cell Line, Tumor ; Signal Transduction ; Mice, Nude ; PTEN Phosphohydrolase/metabolism* ; Lysine/metabolism* ; Middle Aged

Objective To investigate the value of L3 skeletal muscle index(L3-SMI)combined with interleukin-6(IL-6)and activin A in predicting early-stage pancreatic cancer cachexia.Methods A total of 74 patients with pancreatic cancer who were diagnosed in Hebei Medical University Forth Hospital from July 2020 to July 2023 were enrolled,and according to the presence or absence of cachexia after admission,the patient were divided into cachexia group with 58 patients and non-cachexia group with 16 patients.The levels of L3-SMI,IL-6,and activin A were observed within 48 hours after admission.The independent-samples t test was used for comparison of normally distributed continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.A multivariate Logistic regression analysis was used to investigate the influencing factors for pancreatic cancer cachexia;the receiver operating characteristic(ROC)curve was used to analyze the value of L3-SMI,IL-6,and activin A alone or in combination in predicting pancreatic cancer cachexia,and the Z test was used for comparison of the area under the ROC curve(AUC).Results Compared with the non-cachexia group,the cachexia group had a significantly higher level of L3-SMI and significantly lower serum levels of IL-6 and activin A(t=8.649,3.049,and 8.100,all P＜0.05).The multivariate logistic analysis showed that L3-SMI(odds ratio[OR]=0.266,95%confidence interval[CI]:0.103-0.683,P＜0.05),serum IL-6(OR=4.158,95%CI:1.368-12.333,P＜0.05),and activin A(OR=5.124,95%CI:1.550-16.939,P＜0.05)were influencing factors for pancreatic cancer cachexia.L3-SMI,IL-6,and activin A alone had a significantly lower AUC than the combination of the three indicators in predicting pancreatic cancer cachexia(0.851/0.752/0.791 vs 0.946,Z=-2.841,-2.552,and-2.647,all P＜0.001),and the combination of the three indicators had the highest sensitivity(90.9%),specificity(87.8%)and Youden index(0.788).Conclusion L3-SMI combined with serum IL-6 and activin A has a good value in predicting early-stage pancreatic cancer cachexia.

Objective:To summarize the genetic and phenotypic features of MORC family CW-type zinc finger 2 (MORC2) gene-related neuropathy in Chinese patients. Methods:The clinical and whole exome sequencing data of MORC2 gene-related neuropathy families with a definitive genetic diagnosis were collected from the Third Xiangya Hospital of Central South University between 2010 and 2023. Literature involving Chinese families with MORC2 gene-related neuropathy was extensively reviewed to provide a comprehensive summary of the genetic and phenotypic spectrum of the disease. Results:A total of 10 families with MORC2 gene-related neuropathy were identified and analyzed. Six different heterozygous pathogenic variants in the MORC2 gene were observed among these families, including the novel variant c.1330G>C (p.G444R) that had not been previously reported. Six families presented as axonal Charcot-Marie-Tooth disease caused by variants in the MORC2 gene (CMT2Z) phenotype with childhood or adult onset, and carried variants c.754C>T (p.R252W), c.1199A>G (p.Q400R), c.1330G>C (p.G444R), or c.1396G>A (p. D466N); 3 families manifested as severe spinal muscular atrophy (SMA)-like phenotype with infantile onset, all carried c.260C>T (p.S87L); 1 family carried c.1181A>G (p.Y394C), presented as DIGFAN syndrome phenotype with infantile onset combined with mental and motor retardation. Systematic review showed 8 Chinese families carried pathogenic variants of the MORC2 gene, among which 5 families were associated with the CMT2Z phenotype, carrying c.754C>T (p.R252W), c.1079A>G (p.E360G), c.1220G>A (p.C407Y), or c.1397A>G (p.D466G); 1 family was associated with SMA-like phenotype, carrying c.260C>T (p.S87L); and 2 families were associated with DIGFAN syndrome, carrying c.79G>A (p.E27K) and c.292G>A (p.G98R). Conclusions:A novel pathogenic variant c.1330G>C (p.G444R) of the MORC2 gene associated with the CMT2 phenotype is reported. Eleven pathogenic variants of the MORC2 gene have been reported in the Chinese patients to date, and c.754C>T(p.R252W) may be the most common. Patients with MORC2 gene-related neuropathy carrying different variants present with significant clinical heterogeneity, manifesting as CMT2Z, early-onset severe SMA-like myasthenia, or DIGFAN syndrome.

Objective:To study the clinicopathological features, diagnosis, treatment and prognosis of patients with solid pseudopapillary neoplasm of the pancreas (SPN).Methods:From Jan 2008 to Dec 2017, 112 pathology confirmed SPN patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University were followed up. The clinicopathological characteristics and diagnosis were analyzed.Results:Most SPN patients were young women, the ratio of male to female is 1∶7. SPN patients have no typical clinical symptoms. The preoperative diagnostic accuracy of SPN was 57.14% with imaging examination. Pathological diagnosis depends mainly on immunohistochemical staining. All patients underwent surgical resection. Follow-up ranged from 4 to 123 months. The mean follow-up time was 49 months. All patients were doing well and no recurrence or metastasis was found.Conclusions:SPN is a rare tumor with low malignant potential. Surgical resection is effective.

Objective: To investigate the factors associated with CD4⁺ /CD8⁺ T lymphocyte ratio normalization in acquired immunodeficiency syndrome (AIDS) patients after antiretroviral therapy (ART). Methods: The data of 1 188 human immunodeficiency virus (HIV)/AIDS patients from the national ART reporting system in Yuxi City, Yunnan Province between January 1, 2006 and December 31, 2016 were retrospectively collected and analyzed. The rate of CD4⁺ /CD8⁺ T lymphocyte ratio normalization after ART was calculated by lifetable. Cox proportional hazard models were used to analyze the factors associated with CD4⁺ /CD8⁺ T lymphocyte normalization in AIDS patients after ART. The Wilcoxon rank sum test was used for comparison between groups. Results: The follow-up time was 3.8 (1.0-10.8) years. CD4⁺ /CD8⁺ T lymphocyte ratio normalization was documented in 95 patients with the rate of 1.89 per 100 person-years (95% confidence interval(CI) 1.52-2.27) after ART. The average time from ART to CD4⁺ /CD8⁺ T lymphocyte ratio normalized was 9.4 years. The cumulative normalization rate was 0.02 for the first year, 0.06 for the third year, 0.11 for the fifth year, 0.19 for the seventh year and 0.37 for the ninth year. By Cox proportional hazard models, the probability of CD4⁺ /CD8⁺ T lymphocyte ratio normalization in patients infected HIV by heterosexual contacts was 3.709 (95%CI 1.781-7.726) times higher than those by intravenous injection. The probability of CD4⁺ /CD8⁺ T lymphocyte ratio normalization in patients with baseline CD4⁺ T lymphocytes of 350-499 and more than 500 cell/μL groups were 2.792 (95%CI 1.196-6.519) and 3.832 (95%CI 1.648-8.913) times higher than those with baseline CD4⁺ T lymphocytes less than 200 cell/μL, respectively. The probability of normalization after ART in patients with higher baseline CD4⁺ /CD8⁺ T lymphocyte ratio was higher than those with baseline CD4⁺ /CD8⁺ T lymphocyte ratio≤ 0.20 (hazard ratio>1, all P<0.01). Conclusion The CD4⁺ /CD8⁺ T lymphocyte ratio normalization in AIDS patients after ART is associated with baseline CD4⁺ T lymphocyte counts, baseline CD4⁺ /CD8⁺ T lymphocyte ratio and HIV transmission mode.

Objective To evaluate the molluscicidal effect of suspension concentrate of niclosamide ethanolamine salt(SC-NE)against Oncomelania hupensis snails in laboratory and field. Methods The experiment of SCNE against the snails by using the immersing and spraying methods was performed in laboratory and field,with control groups of wettable powder of ni-closamide ethanolamine salt(WPN). Results In the laboratory,LC50(s) of SCNE for 24,48 h and 72 h by using the immersion method were 0.0926,0.0629 mg/L and 0.0549 mg/L,respectively. The mortality rates of snails for 24,48 h and 72 h by using the immersion method were all 100％ with the concentrations of 0.25 mg/L. The mortality rates of snails were all 100％ while spraying SCNE for 3 d in the laboratory with the concentrations of 0.25 g/m2. In Jiangling County,except 0.5 g/m3 SCNE immers-ing the snails for 24 h,the mortality rates of snails by using SCNE with the immersing method were all 100％. While the concen-tration of SCNE was 0.5 g/m3 or above,the mortality rates were all 100％after the use of it with the immersion method for 2 d in Gong'an County. In Jiangling County,the mortality rates of snails by using SCNE 0.5 g/m3 for 1 d,3 d,and 7 d with the spray-ing method were 87.5％,92.82％and 97.40％respectively. While the concentration of SCNE was 0.5 g/m3,the mortality rates were 85.94％,86.78％and 94.21％respectively after the use of it with the spraying method for 1 d,3 d,7 d in Gong'an Coun-ty,and the molluscicidal effect of SCNE(1.0 g/m2)was higher than that of WPN. Conclusion SCNE has a high molluscicidal effect in the laboratory and field,and it is a novel and simple formulation of niclosamide.

Objective Less surveys on the economic burden of hepatitis B (HB)-related diseases have been conducted in China,so the socioeconomic harm caused by the diseases is not clear and the key parameters for economic evaluation of hepatitis B prevention and treatment are lacking.This study aimed to analyze the direct,indirect and intangible expenditures of hospitalized patients with HB-related diseases during hospitalization and during a year in different areas of China.Methods The hospitals for infectious diseases and the large general hospitals in 12 areas in China were selected in the study.All the inpatients with HB-related diseases were surveyed by cluster sampling of consecutive cases.The direct expenditure included direct medical cost and direct non-medical cost.The indirect expenditure,including work loss of patients and caregivers,were calculated by using human capital method for urban and rural populations in 12 areas.The intangible expenditure were reflected by willing to pay and stochastic tournament.The influencing factors of direct and indirect costs were identified by stepwise linear multi-variation regression analysis.Results A total of 27 hospitals in 12 areas were included in the survey.A total of 4 718 cases were surveyed,the overall response rate was 77.7％.The average hospital stay was 29.2 days (27-34) and the hospitalization expenditure was averagely 16 832.80 yuan (RMB) per case,in which the highest proportion (61.2％)was medicine fees [10 365.10 yuan (RMB)].The average direct expenditure and indirect expenditure were consistent with the severity of illness,which were 18 336.10 yuan (RMB) and 4 759.60 yuan (RMB) respectively,with the ratio of 3.85:1.The direct medical expenditure [17 434.70 yuan (RMB)] were substantially higher than the direct non-medical expenditure [901.40 yuan (RMB)].It was found that the hospitalization expenses was highest in direct medical expenditure and the transportation expenses was highest in direct non-medical expenditures.Among the average indirect expenditure,the loss of income for the patients [3 832.50 yuan (RMB)] was higher than that for the caregivers [927.20 yuan (RMB)],The total direct and indirect expenditure was highest for liver transplantation,followed by severe hepatitis,hepatocellular carcinoma and decompensated cirrhosis,acute hepatitis B,compensated cirrhosis and chronic hepatitis B.The influencing factors for both direct and indirect expenditure were high hospital level,severity of hepatitis B,living in urban area,antiviral therapy,long hospitalization and monthly income of family.For average 3.74 outpatient visits and 1.51 hospitalization,the average annual direct,indirect and intangible expenditure for HB-related diseases were 30 135.30,6 253.80 and 44 729.90 yuan (RMB) [totally 81 119.00 yuan (RMB)],accounting for 37.3％,7.7％ and 55.0％,respectively.Of the annual direct medical expenditure [28 402.80 yuan (RMB)],which were much higher than non-medical expenditure [1 732.50 yuan (RMB)],hospitalization expenditure [26 074.20 yuan (RMB)] was higher than outpatient visit expenditure [4 061.10 yuan (RMB)].The annual indirect expenditures for outpatient visit and hospitalization were 763.60 and 5 490.10 yuan (RMB),respectively.Of the annual intangible expenditure,the highest was that for/primary hepatocellular carcinoma,followed by cirrhosis,chronic hepatitis B,severe hepatitis B,liver transplantation and acute hepatitis B.Conclusions A heavy economic burden has been caused by HB-related diseases in China,and patients are more likely to rely on medical service rather than non-medical service.It is necessary to take effective treatment measures to prevent the adverse outcome of HB related diseases and achieve significant economic benefits.The influence of HB related diseases on mental health of the people can be reflected by an economics term,intangible expenditure.

This study aimed at identifying pig-hide gelatin from tortoise shell glue using ultra-performance liquid chromatography-electrospray-time of flight mass spectrometry(UPLC-ESI-QTOF-MS/MS).The samples of tortoise shell glue were digested by trypsin before the analysis on UPLC coupled with QTOF mass spectrometry.The ions at m/z 925.4 were selected as the marker peptides of pig-hide gelatin.It was found that the test results of the ions at m/z 925.4 were positive in the samples with low contents of the marker peptides of tortoise shell glue,indicating the existence of pig-hide gelatin.However,the result of bovine-hide gelatinordonkey-hide gelatin was negative,while negative results were detected in tortoiseglue standard.The finding was in conformity with previous references over the fragmentation regularity of MS/MS.In conclusion,the method can be adopted to identifying the pig-hide gelatin from tortoise shell glue and applied to the quality control of tortoise shell glue with high specificity and sensibility.