p62/sequestosome-1(SQSTM1)is an important selective autophagy adaptor protein, which contains six functional regions:ubiquitin-binding domain,Keap1 interacting region,LC3 interaction region,tumor necrosis factor receptor-associated factor 6 binding domain,Phox and Bem1p and ZZ-type zinc finger domain. p62/SQSTM1 plays an important role in the removal of ubiquitin proteins. It also regulates the signaling pathway of nuclear factor erythroid 2 related factor 2-antioxidant respose element, NF-κB and the caspase-8 mediated apoptosis. The abnormal expression of p62/SQSTM 8 is closely related to neurodegenerative diseases (such as Huntington disease,Alzheimer disease,Parkinson disease),cancer,infective diseases,genetic diseases and chronic diseases. So far many researchers have shed light on the structure function and mechanism of p62/SQSTM1. This paper reviews the role of p62/SQSTM1 in the metabolism of proteins,the regulation of multiple signaling pathways and in the occurrence of diseases in order to provide a new theoretical basis for the treatment of autophagy targets.

Survivin has been identified recently as a unique member of the inhibitor of apoptosis protein family. It is expressed during fetal development and in all common human cancers, but not in normal tissues. It can inhibit apoptosis induced by a variety of factors and play an important role during angiogenesis. Being a universal tumor-specific antiapoptosis inhibitor, survivin may serve as a potential target for gene-protein-based therapy of tumor.

Objective:To study the anti-proliferation effects of thiazolidinedione compounds-troglitazone, which is a high affinity ligand of PPAR-? , on rat pituitary adenoma GH3 cell line and explore the related mechanisms.Methods: GH3 cells were separately treated with troglitazone (10-7,10-6 and 10-5 mol/L), dimethyl sulfoxide (DMSO) (DMSO control group) and phenol red- and serum-free F-12 medium (blank group). MTT was used to examine the cell growth in each group and FACS was used to detect the distribution of cell cycle. Semi-quantitative RT-PCR method was utilized to determine the expression of CyclinD1 mRNA. ANOVA was used for statistical analysis.Results:The 72 h treatment with troglitazone inhibited GH3 cell proliferation in a dose-Dependent manner. The treatment also induced cell cycle arrest in G1/S phase and significantly decreased the expression of CyclinD1 mRNA as compared to the other 2 groups (P

OBJECTIVE: To investigate the enhancement of macrophage chemotaxis in patients with knee osteoarthritis (KOA) and its correlation with the disease severity. METHODS: Eighty patients with KOA admitted from July 2019 to June 2022 were enrolled as the observation group and divided into 29 cases of moderate group, 30 cases of severe group and 21 cases of extremely severe group. At the same time, 30 healthy subjects were included as the control group. The gene expressions of NF-κB, CXC chemokine receptor 7 (CXCR7) and CXC chemokine ligand 12 (CXCL12) in macrophages of each group were analyzed. Visual analogue scale(VAS) was used to evaluate the degree of joint pain. Joint function was evaluated by knee Joint Society Scoring system(KSS). Finally, data analysis was carried out. RESULTS: The expression levels of NF-κB, CXCR7 and CXCL12 in moderate group, severe group and extreme recombination group were higher than those in control group. The VAS, the expression of NF-κB, CXCR7 and CXCL12 in the severe group and the extreme recombination group were higher than those in the moderate group, whereas KSS was lower than that in the moderate group. The VAS, expression levels of NF-κB, CXCR7 and CXCL12 in the extremely severe group were higher than those in the severe group, and KSS was lower than that in the severe group (all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with VAS score, but negatively correlated with KSS(all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with the severity of disease. After excluding the influence of traditional factors (gender, age and disease duration), multiple linear regression analysis further showed that the expression levels of NF-κB, CXCR7 and CXCL12 were still positively correlated with the severity of disease(all P<0.01). CONCLUSION The chemotaxis of macrophages in patients with KOA increased with the aggravation of the disease, and was related to the degree of pain and function impairment.
Humans ; Osteoarthritis, Knee/genetics* ; Chemotaxis/genetics* ; NF-kappa B/metabolism* ; Macrophages/metabolism* ; Receptors, CXCR/metabolism* ; Patient Acuity

OBJECTIVE: To investigate the effect of n-hexane on the level of sex hormones and expression of estrogen receptor(ER) in rats and the protective effect of Lyciumbarbarum polysaccharide(LBP) on n-hexane-induced reproductive toxicity. METHODS: Based on factorial design model of 4×2, specific pathogen free adult female SD rats were divided into control group and low-, medium-and high-n-hexane exposure groups, and each group was divided into non-LBP intervention and LBP intervention sub-group. There were 8 subgroups with 6 rats in each group. On the first day, the rats in the 4 groups were given intraperitoneal injection of n-hexane at 0, 675, 1 350 and 2 700 mg/kg body weight, respectively. On day 2-4, the rats in the non-LBP intervention subgroup were given intragastric administration of 0.9% sodium chloride solution, and the rats in the LBP intervention subgroup were given intragastric administration of LBP at 50 mg/kg body weight once a day. On the fifth day, all animals were sacrificed, and the levels of follicle stimulating hormone(FSH), luteinizing hormone(LH), estradiol, progesterone were detected by enzyme linked immunosorbent assay. The mRNA expression of Erα, Erβ and G protein coupled estrogen receptor 1(Gper1) was detected by real time fluorescence polymerase chain reaction, and the expression of ERα, ERβ and GPER1 protein was detected by Western blotting. RESULTS: i) In the absence of LBP intervention(i.e. simple n-hexane exposure), there was no significant difference in the level of serum FSH, LH, estradiol and progesterone in the 4 groups(P>0.05). The relative expression of Erβ mRNA in ovary of low dose group decreased, while the relative expression of proteins of ERα and GPER1 increased(P<0.05) when compared with the control group. The relative expression of Erα mRNA and GPER1 protein in the ovary of medium-and high-dose groups increased(P<0.05), while the relative expression of Erβ, Gper1 mRNA and ERβ protein decreased(P<0.05). The relative expression of ERα protein in ovary of high-dose group increased(P<0.05). ii) At the same dose of n-hexane exposure, the relative expression of Erα mRNA in ovary of rats in low dose group increased(P<0.05), while the relative expression of ERβ and GPER1 protein decreased in LBP intervention group compared with the no LBP intervention group(P<0.05). The relative expression of ERα and GPER1 protein in ovary of medium dose group increased(P<0.05), while the relative expression of Gper1 mRNA and GPER1 protein in ovary of high dose group decreased in LBP intervention group compared with the no LBP intervention group(P<0.05). CONCLUSION: n-Hexane can up-regulate the expression of ERα and GPER1 in rat ovary, but has no significant effect on female endocrine system. LBP may play a protective role in female reproductive system by up-regulating the expression of ERα and GPER1.

Objective To evaluate the effects of 3-dimensional conformal radiation therapy(3DCRT) in form of local control and survival of rectal cancer patients. Methods Forty-two patients with rectal cancer were irradiation by 3DCRT. They first received 40 Gy with larger field, at 1.8-2.0 Gy/f, 1 fraction qd, then followed by a boost of 24-27 Gy with reduced field, at 3.0-4.0 Gy/f, 1 fraction qod, to a total dose of 0,64-67 Gy. Results The 1-,2-,3-year survival rates were 83.3% ,64.3% and 45.2% .The 1-,2-,3-year local recurrence rates were 2.4%,11.9% and 23.9%. Conclusion Three-dimensional conformal radiotherapy is able to prolong the survival and improve the life quality of patients with rectal cancer.

Objective To investigate the related factors of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia complicating cerebrovascular disease in order to reduce the incidence of surgical complications. Methods The clinical data in patients with trigeminal neuralgia complicating cerebrovascular disease treated with PBC in the People's Hospital of Liaoning Province from December 2000 to December 2010 were analyzed retrospectively. The reasons for its occurrence were investigated. Results Of the 6 759 patients with trigeminal neuralgia who received PBC treatment, 10 (0. 15％ ) developed cerebrovascular disease,and 2 of them had arteriovenous fistula; 5 patients developed intracranial hemorrhage: 2 acute subdural hemorrhage, 2 intraventricular hemorrhage with subarachnoid hemorrhage, and 1 small amount of bleeding in brain stem; 1 patient developed internal carotid hemorrhage during the intraoperative puncture and the operation was stopped temporarily, and he was reoperated successfully after 2 weeks; 2 patients had cerebral infarction, they were all in the risk population of cerebrovascular disease, and 3 weeks after treatment, their disease conditions were improved. One of them left severe paralysis of limbs at discharge. Condusions The treatment of trigeminal neuralgia with PBC is safe and the incidence of cerebrovascular complications is lower. The surgical operations and blood pressure changes are the important causes of cerebrovascular complications.

OBJECTIVE:To systematically review the efficacy of Compound danshen dripping pill or Compound danshen tablets for chronic hepatitis B complicated with hepatic fibrosis,and to provide evidence-based reference for clinical treatment.METHODS:Retrieved from PubMed,Cochrane Library,EMBase,Medline,Wanfang database,VIP,CJFD and CBM database,randomized controlled trials (RCTs) about Compound danshen dripping pills or tablets combined with entecavir(trial group) vs.entecavir alone (control group) for chronic hepatitis B complicated with hepatic fibrosis were collected.Meta-analysis was performed by using Rev Man 5.3 statistical software after data extraction and quality evaluation according to Cochrane systematic evaluation manual 5.1.0.RESULTS:A total of 9 RCTs were enrolled,including 714 patients.The results of Meta-analysis showed that ALT [SMD=-0.44,95％CI(-0.86,-0.01),P=0.04],HA [SMD=-1.53,95％CI(-2.28,-0.79),P＜0.001],LN [SMD=-0.93,95％CI(-1.41,-0.46),P＜0.001],CⅣ [SMD=-1.38,95％CI(-2.13,-0.63),P＜0.001] and PCⅢ [SMD=-1.42,95％ CI (-1.60,-1.23),P＜0.001] of trial group were significantly lower than those of control group;HBV-DNA negative rate [OR=3.73,95 ％ CI (2.14,6.49),P ＜ 0.001] was significantly higher than control group,with statistical significance.CONCLUSIONS:Compound danshen dripping pills or tablets can not only improve liver function and liver fibrosis in chronic hepatitis B patients with hepatic fibrosis,but also improve the antiviral effect.

This study was aimed to investigate the effects of Shen-Y uan Y i-Qi Huo-Xue (SYYQHX) capsule com-bined with early percutaneous coronary intervention (PCI) on near-term quality of life (QOL) in unstable angina (UA) patients. Seventy-eight patients diagnosed with UA were selected and randomly divided into the treatment group and control group, with 39 patients in each group. Early PCI was undergone after coronary angiography. Before PCI, the control group was given routine western medication. The treatment group was given routine western medication plus SYYQHX capsule, three pills once, three times daily. The treatment lasted for 30 days. The QOL scores were evalu-ated among patients from both groups before and after treatment in order to determine the efficacy on angina, electro-cardiogram (ECG) and traditional Chinese medicine (TCM) main symptom. The results showed that compared to pre-treatment, the scores of physical limitation (PL), angina stability (AS), angina frequency (AF), and treatment satisfac-tion ( TS ) were significantly increased after treatment ( P < 0 . 05 ) . Compared with the control group , after treat-ment with SYYQHX capsule, the AF, duration time and symptoms of palpitation, fatigue and shortness of breath were obviously improved (P< 0.05). The scores of AS, AF and TS in the treatment group were significantly increased (P < 0.05). It was concluded that SYYQHX capsule combined with early PCI can improve the near-term QOL and TCM main symptoms among UA patients.

Objective:To investigate the specific method, efficacy and safety of intrathecal baclofen (ITB) in the treatment of moderate and severe spasticity.Methods:The clinical features, response to ITB trial, clinical outcomes and treatment-related complications after baclofen pump implantation surgery were retrospectively analyzed in patients with moderate to severe spasticity who received ITB treatment in Hong Kong University Shenzhen Hospital from August 2022 to August 2023.Results:The study included 22 patients with moderate to severe spasticity, of whom 18 patients (81.8%) were effective in ITB trial. For these patients with effective trial, the lowest mean Modified Ashworth Scale (MAS) score of lower extremity muscle groups after ITB bolus injection was decreased significantly compared with the baseline mean value before injection (1.29±0.81 vs 3.31±1.18 , t=11.364, P<0.001), and the M/H amplitude ratio of soleus H-reflex at 4 hours after ITB bolus injection was significantly higher than the baseline value (9.61±4.66 vs 3.83±2.69, t=7.780, P<0.001). Among the 18 patients with effective ITB trial, 10 patients received baclofen pump implantation surgery with the informed consent of the patients or their guardians. Compared with the 8 patients without surgery, the baseline mean MAS score of lower extremity muscle groups of the 10 patients who received surgery was higher (3.71±1.06 vs 2.83±1.16, F=5.645, P<0.05), the maximum reduction of mean MAS score of lower extremity muscle groups of the 10 patients who received surgery was greater (2.61±0.99 vs 1.30±0.64, F=20.696, P<0.001). In 10 patients who received baclofen pump implantation surgery, the mean MAS score of lower limb muscle groups was significantly decreased in the first and sixth months after surgery compared with the baseline mean value before surgery (1.64±0.91, 1.16±0.89 and 3.71±1.06, F=39.946, P<0.001). Among them, 2 patients were followed up to 12 months after surgery, 2 patients were followed up to 18 months after surgery, and the mean MAS score of their lower limb muscle groups showed continuous improvement, and 1 patient with cerebral palsy combined with lower urinary tract hyperactive syndrome also showed significant improvement of urgent urinary incontinence after surgery. Up to the last follow-up, the daily dose of baclofen in 10 patients receiving baclofen pump implantation was (143.60±96.24) μg, and no treatment-related complications occurred. Conclusions:ITB can effectively relieve spasticity symptoms and other related neurological dysfunction in patients with moderate and severe spasticity, and the efficacy can be maintained for a long time, and treatment-related complications are rare. Preoperative ITB trial is helpful to screen out patients more suitable for baclofen pump implantation. Patients with higher grade of spasticity at baseline and better efficacy of ITB trial are more suitable for baclofen pump implantation. The soleus H reflex can effectively reflect the change of stretch reflex of lower limb muscle groups in patients with spasticity treated by ITB, and can be used to evaluate the treatment effect of ITB.