Objective To investigate the efficacy of histone deacetylase (HDAC) inhibitor chidamide combined with the PD-1 inhibitor on CD8⁺ T cells anti-cancer function in OVA-expressing MC38 (MC38-OVA) colorectal-bearing mice. Methods Animal experiments: C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice. We randomized mice into control group, chidamide group, anti-PD-1 group and chidamide+anti-PD-1 group (20 each group). We monitored the tumor growth and animal survival rate of each group; we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8⁺ T cells, CD8⁺IFN-γ⁺ T cells, OVA antigen-specific CD8⁺ T cells, and the expression changes of regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM). Cell experiments: We used a flow-based method to detect the apoptosis of CD8⁺ T cells and MC38-OVA tumor cells after 0, 10, 25, 50, 100, or 200 nmol/L chidamide treatment. The proliferation of CD8⁺ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting. To evaluate CD8⁺ T cell killing ability, we treated CD8⁺ T cells with various conditions (control group, chidamide group, anti-PD-1 group and chidamide+anti-PD-1 group) followed by co-culture with MC38-OVA tumor cells, using the flow-based method. In the condition that CD8⁺ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells, the expression of CD107a was detected by flow cytometry. Results Compared with control group, the tumor growth was inhibited (P<0.05) while the survival rate was improved (P<0.01) in chidamide+anti-PD-1 group. The number of tumor-infiltrating CD8⁺ T cells was significantly higher in chidamide group, anti-PD-1 group and chidamide+anti-PD-1 group than that in control group (P<0.05). Nonetheless, the ratio and levels of CD8⁺IFN-γ⁺ and OVA antigen-specific CD8⁺ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups (P<0.05). The in vitro experiment results showed that chidamide could enhance the killing ability of CD8⁺ T cells and the expression of CD107a. Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8⁺ T cells and increased antigen-specific CD8⁺ T cells, which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.

Objective To investigate the effect of antinuclear antibodies (ANAs) on hormone response in patients with autoimmune hepatitis (AIH)-primary biliary cholangitis (PBC) overlap syndrome (AIH-PBC OS) and AIH-only within half a year. Methods A retrospective analysis of 77 patients with autoimmune liver disease (AILD) admitted to First Clinical Medical College of Lanzhou University from January 2018 to December 2021, all of whom were confirmed by liver biopsy and receiving glucocorticoid treatment. Among them, 46 patients were in AIH-PBC OS group and 31 were in AIH-only group. The general clinical characteristics, liver puncture-related indexes, autoantibodies and immunoglobulin indexes of patients in each group at the time of diagnosis were collected and compared, and the biochemical and immunoglobulin indexes of patients at the time of hormone use and at the time of review within 6 months were also collected, and the hormone response within 6 months was evaluated according to the levels of glutamic transaminase (AST), glutamic alanine transaminase (ALT) and immunoglobulin G (IgG), and the effect of ANAs on hormone response outcomes in both groups over a six-month period was analyzed. Multifactorial ordered logistic analysis was performed to evaluate the effect of ANAs on hormone response between two groups. Results There was no statistically significant difference in the percentage of AIH-PBC OS and AIH-only patients among both ANAs-positive and -negative AILD patients (55.6% vs. 44.4% and 65.6% vs. 34.4%, P>0.05). Among 46 patients with AIH-PBC OS, there were 25 in ANAs-positive group and 21 in ANAs-negative group. The rate of complete hormone response within 6 months was lower than that of ANAs-negative group (44.0% vs. 76.2%), while the rate of hormone non-response was higher than that of ANAs-negative group (20.0% vs. 0), and the difference was statistically significant (P<0.05). There were 20 cases of ANAs-positive and 11 cases of ANAs-negative in the 31 AIH-only patients. There was no statistically significant difference in the results of hormone response within 6 months between the two groups (P>0.05). Multifactorial ordered logistic analysis showed that AIH-PBC OS patients were more likely to have a higher likelihood of 6-month hormone non-response rate in ANAs-positive patients, and the difference was statistically different (P<0.05). And there was no significant effect of ANAs type on hormone response outcome in AIH-only patients (P>0.05). Conclusion AIH-PBC OS ANAs-positive patients have a poor hormone response within half a year. In AIH-only patients, ANAs have no significant effect on hormone response results.

Objective To investigate the effect and mechanism of pomalidomide (POM) on airway inflammation and mucus hypersecretion in rats with chronic obstructive pulmonary disease (COPD). Methods Thirty-six SD rats were randomly divided into control group, model group and POM group, with 12 in each group, half male and half female. The COPD model was established by smoke exposure combined with Klebsiella pneumoniae infection in model group and POM group. The rats in POM group were treated with POM (0.5 mg/kg, once a day for 1 week). The lung function, lung tissue pathology, the proportion of inflammatory cells in bronchoalveolar lavage fluid (BALF) and the levels of serum inflammatory factors tumor necrosis factor-α (TNF‑α), interleukin (IL)‑1β, IL-6 and IL‑13 were observed and detected in each group. AB-PAS staining and immunohistochemistry were used to analyze the proliferation of goblet cells and the secretion of mucin (MUC) 5AC and MUC5B in airway epithelium of rats. The expression levels of TNF‑α receptor 1 (TNFR1), IκB kinase (IKK), phosphorylated IKK (p-IKK) and P65 protein in lung tissue were detected by Western blotting. Results Compared with control group, model group showed significant decreased of tidal volume (TV), minute ventilation (MV), forced expiratory vital capacity (FVC), 0.1s forced expiratory volume (FEV0.1) and 0.3 s forced expiratory volume (FEV0.3) (P<0.05), increased of the mean linear intercept (MLI) of the alveoli (P<0.01), decreased of the mean alveolar number (MAN) (P<0.01), increased of the proportion of neutrophils and lymphocytes in BALF sediment (P<0.05), and decreased of the proportion of macrophages in BALF sediment (P<0.01);increased of the levels of serum inflammatory factors TNF-α, IL-1β, IL-13 and IL-6 (P<0.05), the proportion of goblet cells in airway epithelium (P<0.01), the secretion of MUC5AC and MUC5B in lung tissue (P<0.01), the content of TNFR1 and the ratio of p-IKK / IKK (P<0.01), the content of P65 in nucleus (P<0.01); and decreased of the content of P65 in cytoplasm (P<0.05). Compared with model group, after one week of POM treatment, POM group showed significant improved of the TV, MV, FVC, FEV0.1, FEV0.3, MLI and MAN of rats (P<0.05); decreased of the proportion of neutrophils and lymphocytes in BALF (P<0.05); increased of the proportion of macrophages (P<0.01); decreased of the levels of serum TNF-α, IL-1β, IL-6 and IL-13 (P<0.05), the proportion of goblet cells in airway (P<0.01), the secretion of MUC5AC and MUC5B (P<0.01), and the expression of TNFR1, P-IKK and P65 (nucleus) (P<0.05); and increased of the level of P65 (cytoplasm) (P<0.01). Conclusions POM can improve airway inflammation and mucus hypersecretion in COPD rats, which may be achieved by inhibiting TNF-α/NF-κB signaling pathway.

Objective To observe the effects of amyloid-β (Aβ) receptor PirB on mouse astrocyte proliferation and reactive astrogliosis in vitro. Methods Mouse primary astrocytes were cultured, and divided into control group, Aβ group, Aβ+0.2 μmol/L PEP group, Aβ+0.4 μmol/L PEP group, Aβ+Fluspirilene group, Aβ+GFP-LV group, and Aβ+mPirB-LV group. The mouse astrocytes were treated with soluble PirB extracellular peptide PEP or PirB inhibitor Fluspirilene, respectively, to inhibit endogenous PirB receptor, or overexpressed PirB gene via lentivirus transfection and then treated with Aβ_1-42 oligomers. The proliferation of astrocytes was observed by RTCA and EdU methods, and the mRNA expression levels of S-100 calcium-binding protein B (S-100β), Vimentin, Nestin and amyloid precursor protein (APP) associated with reactive astrogliosis of astrocytes were observed by real-time PCR, and the expression level of glial fibrillary acid protein (GFAP) was detected by Western-blotting. Results The results of RTCA monitoring showed that normalized cell index (NCI) values of each group decreased sharply after treatment, and then increased gradually and tended to be stable. The results of EdU staining showed that the proliferative activity of astrocytes was significantly enhanced in the Aβ group (P<0.05) compared with control group; Compared with Aβ group, cell proliferation activity in Aβ+0.2 μmol/L PEP group, Aβ+0.4 μmol/L PEP group and Aβ+Fluspirilene group were significantly decreased (P<0.01 or P<0.001). The results of real-time PCR showed that compared with control group, mRNA expressions of GFAP, S-100β, Vimentin, Nestin, APP and PirB in Aβ group were significantly increased (P<0.05); Compared with Aβ group, mRNA expressions of GFAP, S-100β, Vimentin, Nestin, APP and PirB in Aβ+0.4 μmol/L PEP group were significantly decreased (P<0.01); Compared with Aβ+GFP-LV group, mRNA expressions of GFAP, S-100β, Vimentin, Nestin, APP and PirB in Aβ+mPirB-LV group were significantly increased(P<0.05). The results of Western blotting showed that compared with control group, the expression of GFAP in Aβ group was significantly increased (P<0.05); Compared with Aβ group, the expression of GFAP in Aβ+0.4 μmol/L PEP group was significantly decreased (P<0.05). Conclusions PirB is an upstream molecule which could regulate astrocyte proliferation and reactive astrogliosis, and inhibiting PirB receptor in astrocytes may be a potential treatment for Alzheimer's disease.

Helicobacter pylori (HP) infection is a Class Ⅰ carcinogen in gastric cancer, closely related to the occurrence of gastric cancer. Many studies have shown that HP eradication has a preventive effect on gastric cancer. However, 2.7%-6.1% of patients with early gastric cancer who have been eradicated after endoscopic submucosal dissection (ESD) can still develop metachronous gastric cancer (MGC), and the mechanism of its occurrence is still unclear. In this review, the atrophy of gastric mucosa and intestinal metaplasia cannot be completely reversed after HP eradication, the excessive proliferation of gastric mucosa epithelial cells, the accumulation of genetic abnormalities, the homeostasis imbalance of the epigenetic group, changes in immune microenvironment, the abnormality of stem cells in gastric mucosa, chromatin accessibility, and changes in chromosome remodeling were discussed in the mechanism of carcinogenesis caused by the above molecular changes after ESD and HP eradication in early gastric cancer.

Corona virus disease 2019 (COVID-19) epidemic has been effectively controlled, but its related complications still cannot be ignored, especially the cardiovascular circulatory system is the active site of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is a type Ⅰ transmembrane glycoprotein that is highly expressed in heart, kidney and testis. Spike protein of SARS-CoV-2 invades host cells by binding to the cell surface receptor ACE2. However, there are still many deficiencies in the clinical application of vaccines and drugs developed based on this target. As a molecular chaperone, cyclophilin A (CypA) promotes protein folding and T cell activation. CD147 is one of the most widely studied CypA receptors, and the interaction of CypA/CD147 plays an important role in the entry of SARS-CoV-2 into host cells. However, there are few reports on the invasion of SARS-CoV-2 into the cardiovascular system through the CypA/CD147 signaling pathway. Based on this, this article summarizes the previous research evidence and the research basis of the research group, and reviews the structure and function of CypA/CD147, the role of CypA/CD147 in cardiovascular disease, and the cardiovascular disease caused by SARS-CoV-2 targeting CypA/CD147 signal pathway, in order to provide reference for the diagnosis and treatment of the COVID-19 complicated with cardiovascular system diseases.

Objective To evaluate the application value of hydrogel in image guided radiotherapy (IGRT) for prostate cancer (PCa). Methods Eighty PCa patients in the First Affiliated Hospital of Hebei North University from October 2022 to February 2023 were collected. The patients were divided into experiment group injected with hydrogel (n=33) and control group without hydrogel (n=47) by central random system allocation. The acute and advanced radiation proctitis (RP) incidence rate of the two groups were compared. Patients in experimental group were divided into RP group (n=5) and non-RP group (n=28). The independent risk factors leading to RP were analyzed by using logistic regression for PCa patients. Results In experiment group, 12.1% (4/33) of the patients developed acute grade Ⅰ RP, and 3.0% (1/33) developed advanced grade Ⅰ RP. In control group, 31.9% (15/47) of the patients developed acute grade Ⅰ RP, and 12.8% (6/47) developed acute grade Ⅱ RP; 19.1% (9/47) of patients developed advanced grade Ⅰ RP, 4.3% (2/47) developed advanced grade Ⅱ RP, and 2.1% (1/47) developed advanced grade Ⅲ RP. The incidence of acute and advanced RP in experiment group was lower than that in control group (P<0.05). The application of hydrogel effectively reduced rectal toxicity. Age, rectal volume, V₇₀ and V₇₈ were independent risk factors for the incidence of RP in PCa patients (P<0.05). The characteristics of hydrogel injection were not related to the incidence of RP for PCa patients. Conclusions Hydrogel can effectively reduce the rectal toxicity for PCa patients in IGRT and has little impact on the overall treatment. Hydrogel has certain clinical application and promotion value.

Objective To analyze the relationship between MyD88L265P and CD79B mutations in tumor tissue and the prognosis of primary central nervous system lymphoma (PCNSL). Methods 18 PCNSL patients with normal immune function (no history of HIV infection and immunosuppressants administration) who were diagnosed by craniotomy or stereotaxic biopsy in the Second Hospital of Lanzhou University from August 2018 to November 2020 were retrospectively analyzed. Real-time quantitative PCR and first-generation sequencing techniques were respectively used to detect MyD88L265P and CD79B mutations in tumor tissues of 18 PCNSL patients. Univariate analysis and Cox regression multivariate analysis were performed for indicators that may be associated with first progression-free survival (PFS) and overall survival in PCNSL. Results The mutation rate of MyD88L265P was 38.9%, the mutation rate of CD79B was 33.3%, and the co-mutation rate of MyD88L265P/CD79B was 27.8% in PCNSL tissue of 18 patients. Univariate analysis showed that the PCNSL patients with multiple lesions, deep involvement of lesions, and tissue CD79B mutation had a statistically significant shorter time of PFS (P<0.05). Multivariate analysis showed that deep lesion involvement(HR=0.135, 95%CI 0.023-0.799, P<0.05) and CD79B mutation (HR=0.149, 95%CI 0.028-0.800, P<0.05) in PCNSL tissue were independent prognostic factors for PCNSL patients. Conclusion The frequency of MyD88L265P and CD79B mutations was high in tumor tissues of 18 PCNSL patients, and these two gene mutations may be associated with poor prognosis of PCNSL, especially CD79B mutation.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019, including 153 males and 147 females, aged>65 years old. All the patients received PCI, and all had double antiplatelet therapy (DAPT) scores ≥2 and a new DAPT (PRECISE-DAPT) score of ≥25. All patients were divided into two groups by random number table method before operation: ticagrelor group(n=146, ticagrelor 180 mg load dose followed by PCI, and ticagrelor 90 mg bid after surgery) and ticagrelor de-escalation + nicorandil group (n=154, ticagrelor 180 mg load dose followed by PCI, ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery, changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later). Follow-up was 12 months. The composite end points of cardiovascular death, myocardial infarction and stroke, the composite end points of mild hemorrhage, minor hemorrhage, other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study, and the composite end points of cardiovascular death, myocardial infarction, stroke and bleeding within 12 months in the two groups were observed. Results The comparison of general baseline data between the two groups showed no statistically significant difference (P>0.05). There was also no significant difference in the composite end points of cardiovascular death, myocardial infarction and stroke between the two groups (P>0.05). The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group (P<0.05), while the composite end points of cardiovascular death, myocardial infarction, stroke and bleeding were also significantly lower than those in tecagrelor group (P<0.05). Conclusion In elderly patients with ACS, the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death, myocardial infarction or stroke, and it may reduce the incidence of hemorrhagic events.

Objective To investigate the association between body mass index (BMI), sex hormone and single nucleotide polymorphisms (SNPs) of follicle-stimulating hormone receptor (FSHR) gene rs2268361 and rs2349415 and its correlation with the risk of polycystic ovary syndrome (PCOS). Methods Peripheral blood was collected from 213 PCOS patients and 207 healthy controls, attending the Department of Reproductive Medicine at the First Hospital of Shanxi Medical University, and 32 follicular fluids were randomly collected from each of the PCOS and control groups from March to August 2021. Calculation of BMI of the PCOS and control groups; The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂), testosterone (T), progesterone (P) and prolactin (PRL) in peripheral blood of the two groups were detected by immunochemiluminescence method. Polymerase chain reaction (PCR) and high-resolution melting curve (HRM) were used to analyze the polymorphisms of rs2268361 and rs2349415 in FSHR of the two groups. Quantitative real-time PCR was used to detect the expression of FSHR gene mRNA in peripheral blood and ovarian granulosa cells. Results There was a strong positive correlation between LH and LH/FSH(r=0.88, P<0.05); The levels of BMI, E₂, LH, LH/FSH and T in PCOS group were significantly higher than those in control group(P<0.05); FSH level was significantly lower than that of control group (P<0.001). HRM analysis showed the frequencies of CC, CT and TT genotypes at rs2349415 were 55.9%, 34.3% and 9.8% in PCOS group and 68.6%, 23.2% and 8.2% in control group, respectively. The frequencies of C and T alleles were 73.0% and 27.0% in PCOS group and 80.2% and 19.8% in control group, respectively. There were significant differences in genotype frequencies and allele frequencies between the two groups (P<0.05); The expression level of FSHR mRNA was higher in ovarian granulosa cells in PCOS group than in control group (P=0.004), the expression level of FSHR mRNA in rs2349415 TT genotype was higher than that in CC (P=0.002) and CT (P=0.035) genotype. Conclusion High levels of BMI, LH, E₂ and T allele of rs2349415 increased the risk of PCOS.