HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective:To analyze the expression of silent information regulator 2-related enzyme 1 (SIRT1) and its relationship with chondrocyte apoptosis in patients with Kashin-Beck disease (KBD).Methods:Twenty patients with KBD were selected as the KBD group from Guide County, Qinghai Province, and 40 healthy subjects matched by age and sex were selected as the control group. Fasting elbow venous blood of the study subjects was collected, and peripheral blood mRNA levels of SIRT1 and selenoprotein genes [glutathione peroxidase (GPX) 2, GPX3, thioredoxin reductase (TXNRD) 1, TXNRD3, iodothyronine deiodinase Ⅰ (DIO1), and selenophosphate synthetase 2 (SPS2)] were detected by real-time PCR. The correlation between SIRT1 expression and selenoprotein genes in peripheral blood of KBD patients was analyzed by curve fitting method. Meanwhile, normal human chondrocytes cultured in vitro were divided into control group (without any treatment), resveratrol (RES) group (to verify the activation effect of RES on SIRT1), tert-butyl hydroperoxide (tBHP) injury group (oxidative injury model of chondrocyte), and RES protection group (tBHP injury after RES pre protection). The mRNA levels of SIRT1, selenoprotein genes, and apoptosis-related genes [B lymphoblastoma-2 gene (BCL2), BCL2-associated X protein (BAX), nuclear transcription factor κB (NF-κB) p65, and tumor suppressor gene P53] in each group of cells were detected by real-time PCR. Results:In the population study, the peripheral blood SIRT1 mRNA level in the KBD group (1.12 ± 0.38) was lower than that of control group (1.87 ± 0.97), and the difference was statistically significant ( t = 3.31, P = 0.002). According to curve fitting analysis, the mRNA levels of GPX3, TXNRD1, and TXNRD3 in peripheral blood of KBD group increased with the increase of SIRT1 mRNA level ( R2 = 0.48, 0.66, 0.95, P < 0.001). The level of DIO1 mRNA showed a trend of decreased first and then increased with the increase of SIRT1 mRNA level ( R2 = 0.51, P = 0.024). The mRNA levels of GPX2 and SPS2 showed no significant change trend with the increase of SIRT1 mRNA level ( R2 = 0.16, 0.12, P = 0.064, 0.114). In cell studies, compared with the control group (1.00 ± 0.10), the SIRT1 mRNA level in the RES group (1.79 ± 0.07) was higher ( P < 0.05). Compared with tBHP injury group, the RES protection group had higher mRNA levels of selenoprotein genes GPX3, TXNRD1, TXNRD3, and DIO1 ( P < 0.05); the mRNA levels of apoptosis-related genes BAX, P53 and the ratio of BAX/BCL2 were lower, while the mRNA levels of BCL2 and NF-κB p65 were higher ( P < 0.05). Conclusions:KBD patients have low expression of SIRT1. And RES activation of SIRT1 may enhance the antioxidant capacity of chondrocyte by up-regulating the expression of selenoprotein genes, thus inhibiting chondrocyte apoptosis.

ObjectiveTo explore the protective effect of Salviae Miltiorrhizae Radix et Rhizoma and Puerariae Lobatae Radix （SP） extract on oxygen-glucose deprivation/reoxygenation （OGD/R）-injured SH-SY5Y cells based on oxidative stress and apoptosis. MethodThe extracts of the two medicinal materials mixed in different ratios were prepared. Human neuroblastoma SH-SY5Y cells were cultured in vitro and the injury was induced by OGD/R. Cell counting kit-8 （CCK-8） assay was used to screen the optimal ratio of the two medicinals and then the extract was used for further experiment. SH-SY5Y cells were classified into normal control group， OGD/R group， and low-， medium-， and high-dose SP （2∶1） extract groups （10， 30， 100 mg·L^-1， respectively）. Cells in the groups， except the normal control group， were rapidly reoxygenated for 12 h after 4 h OGD for modeling. Then cell viability was detected by CCK-8 and cell morphology was observed under the microscope. The release rate of lactate dehydrogenase （LDH）， superoxide dismutase （SOD） activity， and content of glutathione （GSH） and malondialdehyde （MDA） were determined by spectrophotometry. The level of reactive oxygen species （ROS） was detected with 2，7-dichlorodihydrofluorescein diacetate （DCFH-DA） and mitochondrial membrane potential with JC-1 assay. The nuclear morphology was observed based on Hoechst 33342 staining， and apoptosis was examined by flow cytometry combined with Annexin V-FITC/PI staining. ResultThe viability of the cells was highest in the presence of the extract of the two medicinals mixed at the ratio of 2∶1. Compared with normal control group， OGD/R group showed damaged cell morphology， high release rate of LDH and levels of ROS and MDA （P<0.01）， low SOD activity and GSH level （P<0.01）， low mitochondrial membrane potential， and high apoptosis rate （P<0.01）. Compared with OGD/R group， SP extract improved cell viability and cell morphology and reduce cell LDH release rate in a concentration-dependent manner （P<0.01）. In addition， SP extract at 30， 100 mg·L^-1 reduced the level of intracellular ROS and increased SOD activity and GSH level （P<0.05， P<0.01）， and SP extract at 100 mg·L^-1 decreased the content of MDA （P <0.05）. Moreover， SP extract increased mitochondrial membrane potential， and SP extract at 30， 100 mg·L^-1 lowered the apoptosis rate （P<0.01）. ConclusionThe extract of Salvia miltiorrhiza Bunge and Radix Puerariae mixed at 2∶1 shows better protective effect on OGD/R-injured SH-SY5Y cells. The mechanism is the likelihood that it alleviates oxidative damage of cells and inhibits cell apoptosis.

Objective    To explore the relation of preoperative red blood cell distribution width (RDW) with prognosis in esophageal cancer. Methods    The PubMed, EMbase, Web of Science, Cochrane Library, VIP, Wanfang, CNKI and SinoMed databases were searched to identify potential studies assessing the correlation between preoperative RDW and prognosis of esophageal cancer patients from establishment of databases to February 2019. The endpoint events included the overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). The Stata 12.0 software was applied for the meta-analysis and the hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results    A total of 10 retrospective studies involving 4 260 esophageal cancer patients from China or Japan were included. The score of Newcastle-Ottawa scale (NOS) of the included studies was more than 6 points. The results demonstrated that elevated preoperative RDW was significantly associated with poor CSS (HR=1.50, 95% CI 1.14 to 1.99, P=0.004) and DFS (HR=1.45, 95% CI 1.14 to 1.85, P=0.002), while no significant association between preoperative RDW and OS in esophageal cancer was observed (HR=1.17, 95% CI 0.95 to 1.45, P=0.143). Subgroup analysis based on the pathology revealed that preoperative RDW had high prognostic value in esophageal squamous carcinoma (ESCC) (HR=1.37, 95% CI 1.05 to 1.77, P=0.018). Conclusion    Preoperative RDW may be an independent prognostic factor for Chinese and  Japanese esophageal cancer patients, especially for ESCC patients. However, more prospective studies with bigger sample sizes from other countries are still needed to verify our findings.

Objective    To investigate the status quo and influencing factors of depression and anxiety in postoperative patients with thoracic neoplasms. Methods    The general information questionnaire and Huaxi emotional-distress index scale (HEI) were adopted to survey 70 patients after surgery of thoracic neoplasms at the thoracic nursing outpatients from September to November 2016. There were 43 males and 27 females with age of 18-78 (56.20±11.34) years. Results    The prevalence rate of depression and anxiety among postoperative patients with thoracic neoplasms was 50.0%, and moderate to severe negative emotions predominated. There was significant difference in educational levels, postoperative hospitalization and postoperative complications (P<0.05), while no significant difference in age, gender, disease types, complicated diseases, surgical procedures, pathological stages and hospitalization expenditures between patients with unhealthy emotions and normal emotions (P>0.05). Conclusion    There is a high prevalence rate of negative emotion among postoperative patients with thoracic neoplasms. Educational levels, postoperative hospitalization and postoperative complications are important factors for negative emotion.

Objective To test red cells of bone marrow and hematopoietic cells of rats with liver depression and spleen deficiency syndrome in different time period;To discuss the change rules in the blood system. Methods Rat models with liver depression and spleen deficiency syndrome were made by composite method of anger by restraint stress, clipping tails, over fatigue, and abnormal diet. The hemogram, red cells of bone marrow, marrow nucleated red blood cells, stem cell factor, and erythropoietin of male rats in normal group and model group were detected at 2nd, 6th and 9th weeks. Results Compared with normal group, hematokrit and metarubricyte in model group of 2 weeks was higher in the model group (P<0.05);erythropoietin in model group of 6 weeks decreased (P<0.01);red cell counts, red protein level, hemoglobin, hematokrit, and erythropoietin in model group of 9 weeks were lower (P<0.05);red cell counts, hemoglobin, hematokrit, prorubricyte, metarubricyte, and erythropoietin in model group of 6 and 9 weeks were significantly lower than those in model group of 2 weeks (P<0.05, P<0.01). The number of marrow nucleated red blood cells in model group of 2 weeks decreased (P<0.05). Stem cell factor showed no significant difference. Conclusion The rats with liver depression and spleen deficiency syndrome can increase the number of red blood cells in a short time when they suffer from stress stimulation, so that they can fight the damage factors. But long-term stress stimulation will lead the rats to anemia, which may be associated with the reduction of erythropoietin.

Human diphyllobothriasis is a widespread fish-borne zoonosis caused by the infection with broad tapeworms belonging to the genus Diphyllobothrium. In mainland China, so far 20 human cases of Diphyllobothrium infections have been reported, and the etiologic species were identified as D. latum and D. nihonkaiense based on morphological characteristics or molecular analysis. In the present study, proglottids of diphyllobothriid tapeworms from 3 human cases that occurred in Heilongjiang Province, China were identified as D. nihonkaiense by sequencing mitochondrial cytochrome c oxidase subunit I (cox1) and NADH dehydrogenase subunit 5 (nad5) genes. Two different cox1 gene sequences were obtained. One sequence showed 100% homology with those from humans in Japan. The remaining cox1 gene sequence and 2 different nad5 gene sequences obtained were not described previously, and might reflect endemic genetic characterizations. D. nihonkaiense might also be a major causative species of human diphyllobothriasis in China. Meanwhile, the finding of the first pediatric case of D. nihonkaiense infection in China suggests that infants infected with D. nihonkaiense should not be ignored.
Adult ; Animals ; China ; Diphyllobothriasis/*parasitology ; Diphyllobothrium/classification/enzymology/*genetics/*isolation & purification ; Electron Transport Complex IV/genetics ; Female ; Helminth Proteins/genetics ; Humans ; Infant

Objective To investigate the associations of alcohol consumption with the outcome of three-year pre-dia?betes. Methods The objects of this study were selected from the epidemiological study of cancer risk of Chinese patients with type 2 diabetes mellitus (T2DM) in Luzhou area. A total of 1 125 cases with pre-diabetes were selected from the base?line survey. Patients divided into four groups including non-alcohol drinking group, small alcohol drinking group, moderate alcohol drinking group, and large alcohol drinking group. Patients also were divided into two groups according to body mass index (BMI, more than 24 kg/m2). The patients were followed up for three years. The incidence rates of diabetes mellitus were compared between different drinking groups and different BMI groups. Results A total of 1 116 cases were completed the follow-up , 9 cases were lost to follow-up. The incidence rates of DM were 18.81%, 8.80%, 16.51%and 26.53%for non-al?cohol drinking group, small alcohol drinking group, moderate alcohol drinking group, and large alcohol drinking group. Cox proportional hazard regression analysis showed that the relative risk ratios and 95%CI of the gender, age, BMI, calorie, base?line blood glucose were 0.49 (0.31-0.79), 1.15 (0.69-1.92) and 1.95 (1.25-3.04) for small alcohol drinking group, moderate alcohol drinking group, and large alcohol drinking group. In the group of BMI<24 kg/m2,the relative risks and 95%CI were 0.40 (0.20-0.80),0.77 (0.30-1.97) and 1.10 (0.46-2.64) for small alcohol drinking group, moderate alcohol drinking group, and large alcohol drinking group. In the group of BMI≥24 kg/m2, the relative risks and 95%CI were 0.62 (0.33-1.66),1.49 (0.80-2.80) and 2.64 (1.55-4.47). Conclusion Small amount of alcohol drinking can reduce the incidence of DM in predia?betes people with BMI<24 kg/m2. Large amount of alcohol drinking is the risk factor of incidence of DM in people with BMI≥24 kg/m2.

Objective:To investigate the expression status of Sonic Hedgehog signaling genes and molecules in human hepatocellular carcinomas(HCC),and to explore the relationship between these genes and clinical prognosis.Methods:HCC tissue and adjacent normal tissue from 29 HCC patients were assayed for the expression of hedgehog signaling genes by reverse transcription-polymerase chain reaction chain reaction(RT-PCR) techniques and for the expression of hedgehog signaling molecules by immunohistochemistry.The expressions of Shh,Ptch,Smoh,Gli-1 mRNA were assayed as well as Shh,Ptch proteins in 29 cases of HCC and in 29 liver tissues adjacent to the tumor.Results:Expression of Shh mRNA was detectable in about 51% of HCCs examined.Consistent with this,hedgehog target genes Ptch,Smoh and Gli-1 mRNA were expressed in over 68%,48% and 62% of the tumors,respectively,and the expressions of Shh and Ptch proteins in HCC tumor tissues correlated with those of Shh and Ptch mRNA in tumor tissues(P=0.041 and P=0.035).This suggested that the hedgehog pathway was frequently activated in HCCs.The simultaneous expression of Gli-1 in HCC and liver tissues adjacent to the tumor had significantly relationship with poor prognosis.Conclusion:Hedgehog signaling activation is an important event for development of human HCCs.It also suggests that markers for hedgehog signaling activation may be useful for the determination of prognosis.