BACKGROUND:Acupotomy is an effective method for the clinical treatment of osteoarthritis,with affirmed clinical outcomes,but the specific mechanisms remain unclear OBJECTIVE:To investigate the role of acupotomy in modulating chondrocyte autophagy to promote chondrocyte homeostasis in osteoarthritis. METHODS:Twenty-eight New Zealand rabbits were randomly divided into control group,osteoarthritis group,acupotomy group,and hyaluronic acid group,with seven rabbits in each group.The knee osteoarthritis rabbit model was prepared using the Videman method in the latter three groups.After modeling,the control group and osteoarthritis group received no interventions.The acupotomy group received acupotomy treatment 15 minutes per time,once a week,while the hyaluronic acid group received intra-articular injection of hyaluronic acid once a week,with a continuous treatment duration of 5 weeks.The day after the final intervention,knee joint macrostructure was observed using DR imaging,chondrocyte ultrastructure was examined through transmission electron microscopy,apoptosis of chondrocytes was assessed using Tunel staining,and western blot analysis was used to detect the expression of proteins related to the PI3K/Akt/mTOR pathway. RESULTS AND CONCLUSION:The DR imaging results revealed that the osteoarthritis group exhibited narrowed knee joint spaces and the formation of periarticular osteophytes,while the hyaluronic acid group and acupotomy group showed widened knee joint spaces with a reduction in periarticular osteophytes.Transmission electron microscopy results demonstrated a decreased number of autophagosomes in chondrocytes in the osteoarthritis group,along with nuclear shrinkage,nuclear membrane rupture,incomplete organelle morphology,and a clear tendency towards cell death.In contrast,both the hyaluronic acid group and acupotomy group exhibited a significant increase in autophagosomes,intact nuclear membranes,and a well-preserved cellular state.Tunel staining results indicated a considerable decrease in the number of apoptotic cells in the hyaluronic acid group and acupotomy group compared with the osteoarthritis group.Western blot results revealed that,compared with the control group,the expression levels of Beclin1,Cath D,and LC3II/LC3I were significantly decreased in the osteoarthritis group(P<0.05),while the expression levels of p-Akt/Akt and p-mTOR/mTOR were significantly increased(P<0.05);compared with the osteoarthritis group,the expression levels of Beclin1,Cath D,and LC3II/LC3I were significantly increased in both the hyaluronic acid group and acupotomy group(P<0.05),while the expression levels of p-Akt/Akt and p-mTOR/mTOR were significantly decreased(P<0.05).To conclude,acupotomy intervention can modulate the PI3K/Akt/mTOR signaling pathway to enhance the autophagic level in chondrocytes,thereby maintaining chondrocyte homeostasis.This ultimately leads to a slowdown in cartilage degeneration.

Objective:To investigate the effects of platycodon D on proliferation, apoptosis, migration and glycolysis of colorectal cancer HT-29 cell.Methods:Human HT-29 cells were selected and randomly divided into the control group and platycodon D 25, 50, and 100 μmol/L groups. The HT-29 cells in the platycodon D 25, 50, and 100 μmol/L groups were treated with 25, 50, and 100 μmol/L platycodon D for 48 h. The cell proliferation of the cells was examined by cell counting Kit-8 (CCK-8) and colony formation assay. The apoptosis of the cells was investigated using flow cytometry and Western Blot assays were used to examine the expression of apoptosis and apoptosis-related proteins, including B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and cleaved cystein-asparate protease-3 (cleaved Caspase-3). Transwell and Western Blot assays were used to examine cell migration, glucose consumption, and lactic acid production, as well as the expression levels of pyruvate kinase M2 (PKM2) and phosphorylated PKM2 (p-PKM2) in HT-29 cells.Results:With the increase in treatment time, the proliferation rate of HT-29 cells in the control group and platycodon D 25, 50, and 100 μmol/L groups decreased gradually. Compared with the control group, the viability of HT-29 cells in the platycodon D 25, 50, and 100 μmol/L groups was decreased (all P < 0.001). Compared with the control group, the colony number of HT-29 cells in the platycodon D 25 μmol/L (36 vs. 50), 50 μmol/L (34 vs. 50), and 100 μmol/L (16 vs. 50) groups was decreased (all P < 0.001), after treatment with platycodon D for 24 h. Compared with the control group, the apoptosis rate of HT-29 cells in the platycodon D 100 μmol/L group was increased (62% vs. 39%), the relative expression of Bax was increased (0.9 vs. 0.1), the cleaved Caspase-3 was increased (1.25 vs. 0.15), and the Bcl-2 decreased (0.12 vs. 0.75) (all P < 0.001). Compared with the control group, the per unit vision number of HT-29 cells in the platycodon D 100 μmol/L group decreased (16 vs. 48), the relative expression of Snail decreased (0.5 vs. 1.3), the relative expression of E-cadherin increased (1.2 vs. 0.1), the relative expression of glucose transporter 1 (GLUT1) decreased (0.2 vs. 1.1), the relative expression of lactate dehydrogenase A (LDHA) decreased (0.2 vs. 1.2), and the relative expression of hexokinase 2 (HK2) decreased (0.15 vs. 1.00) (all P < 0.001). Compared with the control group, glucose consumption of HT-29 cells in platycodon D 100 μmol/L group was decreased (1.9 mmol/L vs. 4.8 mmol/L), and lactic acid production was decreased (3.8 mmol/L vs. 9.2 mmol/L) (both P < 0.001). Compared with the control group, the relative expression of PKM2 in the platycodon D 100 μmol/L group was decreased (0.1 vs. 1.0), and the relative level of p-PKM2 was decreased (0.08 vs. 0.75) (both P < 0.001). Conclusions:Platycodon D can inhibit the proliferation of HT-29 cells, promote cell apoptosis, and inhibit cell migration and glycolysis.

Nonsense-mediated mRNA decay(NMD)is a highly conserved post-transcriptional regulatory mechanism in eukaryotic cells.NMD can recognize and degrade abnormal transcripts con-taining premature termination codons(PTC)to pre-vent the translation of C-terminal truncated pro-teins.Furthermore,NMD could degrade a subset of normal gene transcripts and thus fine-tune gene ex-pression.NMD is essential for cell fate determina-tion,stress response,as well as animal develop-ment.In this review,we briefly discussed the func-tional and molecular mechanisms of NMD pathway activation and inhibition in tumorigenesis,cancer progression and therapy.Current studies indicate that NMD factor mutations can lead to a variety of human tumors.Interestingly,inhibition of NMD fac-tors can activate DNA damage response and inhibit the expression of oncogenic factors,thereby killing cancer cells.This review may provide new perspec-tives for the biological mechanism and therapeutic strategy of human tumors.

Objective To investigate the protective effect and mechanism of J147 on the injury of human neuroblastoma cells(SH-SY5Y)induced by high glucose(HG).Methods We established HG-induced SH-SY5Y cell injury model.Then SH-SY5Y cells were divided into blank control(Con)group HG group,HG+J147 0.5 μmol/L(HG+J147 0.5)group,HG+J147 1 μmol/L(HG+J147 1)group,HG+J147 2 μmol/L(HG+J147 2)group,HG+PI3K/AKT inhibitor LY294002(LY)10 μmol/L(HG+LY)group,HG+ERK1/2 inhibitor U0126(U0)5 μmol/L(HG+U0)group,HG+J147 2 μmol/L+LY 10 μmol/L(HG+J147 2+LY)group,HG+J147 2 μmol/L+U0 5 μmol/L(HG+J147 2+U0)group.Cell viability was detected by MTS cell proliferation and toxicity detection kit;LDH activity was tested by lactate dehydrogenase kit;morphological changes of SH-SY5Y cells were evaluated by microscope;cell apoptosis was detected by flow cytometry;and apoptosis-related proteins(Bcl-2,Bax)and signaling pathway-related proteins(p-AKT,AKT,p-ERK1/2,ERK1/2,p-CREB,CREB,BDNF)were detected by Western blot.Results Compared with Con group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT,p-ERK/ERK,p-CREB/CREB and BDNF protein expressions decreased(P<0.01),while LDH activity and apoptosis rate increased in HG group(P<0.01).Compared with HG group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT,p-ERK/ERK,p-CREB/CREB and BDNF protein expressions increased(P<0.01),while LDH activity and apoptosis rate decreased in HG+J147 2 group(P<0.01).Compared with HG+J147 2 group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT and BDNF protein expression decreased(P<0.05 or P<0.01),while LDH activity and apoptosis rate increased(P<0.05 or P<0.01),the expression of p-ERK/ERK protein in HG+J147 2+LY group decreased(P<0.05),and the expression of p-CREB/CREB protein in HG+J147 2+U0 group decreased in HG+J147 2+LY and HG+J147 2+U0 groups(P<0.05).Conclusions J147 can alleviate HG-induced SH-SY5Y cell damage,and the mechanism may be related to the activation of PI3K/AKT and ERK1/2 signaling and the reduction of apoptosis.

Objective: : Ischemia and hemorrhage of pituitary adenomas (PA) caused important clinical syndrome. However, the differences on clinical characteristics and surgical outcomes between these two kinds apoplexy were less reported. Methods: : A retrospective analysis was made of patients with pituitary apoplexy between January 2013 and June 2018. Baseline and clinical characteristics before surgery were reviewed. All patients underwent transsphenoidal surgery and were followed up at least 1 year. Results: : Total 67 cases (5.8%) among 1147 pituitary tumor patients were enrolled, which consisted of 28 (~2.4%) ischemic PA and 39 (~3.4%) hemorrhagic PA. There were more male patients in the ischemic group compared with hemorrhagic group (78.6% vs 53.8%, p=0.043). However, the mean age, tumor size and functional tumor ratio were significant higher in the hemorrhagic group. Headache was more common in ischemic PA (82.1%) than that of hemorrhagic PA (51.3%, p=0.011). Magnetic resonance imaging findings found that mucosal thickening and enhancement of the sphenoid sinus was observed in 15 ischemic PA patients (n=27, 55.6%), but none in patients with hemorrhagic PA (n=38, p<0.0001). It was worth noting that the rate of pre-surgical hypopituitarism in ischemic PA patients were seemed higher than that in hemorrhagic PA patients, but not significant. The two groups got a total tumor resection rate at 94.1% and 92.9%, independently. No significant difference on the operative time, blood loss in operation and complications in perioperative period was observed in two groups. After operation, cranial nerve symptoms recovered to normal at 81.8% of ischemic PA patients and 82.6% of hemorrhagic PA patients. Importantly, the incidence of postoperative hypopituitarism partially decreased in both groups, among which the rate of hypothyroidism in ischemic PA patients significantly decreased from 46.4% to 18.5% (p=0.044). Conclusion : Patients with ischemic PA presented different clinical characteristics to the hemorrhagic ones. Transsphenoidal surgery should be considered for the patients with neuro-ophthalmic deficits and might benefit for pituitary function recovery of the apoplectic adenoma patients, especially pituitary thyroid axis in ischemic PA patients.

Objective:To analyze the risk factors and prognosis of endoleak after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm.Methods:The clinical data of patients with infrarenal abdominal aortic aneurysms treated by endovascular repair at the Department of Vascular Surgery,the First Affiliated Hospital of Guangxi Medical University from Jun 2012 to Nov 2021 were retrospectively analyzed.Results:During the first follow-up CTA after surgery,136 out of 299 patients had endoleak.A total of 186 patients had at least one CTA reexamination after discharge. Statistical analysis showed that excessive neck angulation was an independent risk factor for type Ⅰa endoleak ( t=-6.108, P<0.001), wider common iliac artery diameter (left Z=-2.787, P=0.005, Right Z=-2.381, P=0.017) and iliac aneurysm ( χ2=6.398, P=0.011) were risk factors for type Ⅰb endoleak. The survival time of patients in endoleak group was similar to no endoleak group. Conclusions:Excessive neck angulation is an independent risk factor for type Ⅰa endoleak. Most leaks resolve spontaneously ,the prognosis is fair.

Objective:To investigate the expression and clinical significance of thymidine kinase 1 (TK1), carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA15-3 and CA72-4 in colorectal tumors.Methods:Enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immuno assay (ECLIA) were used to determine the serum TK1 levels and serum CEA, CA19-9, CA15-3, CA72-4 levels in 124 patients with colorectal cancer, 52 patients with colorectal precancerous lesions, 154 patients with benign colorectal lesions, and 106 health subjects. The relationship between serum TK1 and its clinicopathological characteristics in patients with colorectal cancer were analyzed. The diagnostic efficacy of TK1, CEA, CA19-9, CA15-3 and CA72-4 alone and combined detection for colorectal cancer was investigated.Results:The serum expression level of TK1 in patients with colorectal cancer was related to tumor stage, degree of differentiation, lymph node metastasis, distant metastasis and age (all P<0.05), but not related to the patient's gender ( P>0.05). The serum TK1 level decreased sequentially in colorectal cancer patients, precancerous lesions patients, benign lesions patients and healthy subjects. Colorectal cancer patients with high TK1 expression have a shorter survival time. The sensitivity, specificity and accuracy of the combined detection of TK1, CEA, CA19-9, CA15-3 and CA72-4 were 93.5%, 93.0%, and 93.1%, respectively. Conclusions:Serum TK1 is expected to become an independent marker for the diagnosis and prognosis of colorectal cancer. The combined detection of TK1, CEA, CA19-9, CA15-3 and CA72-4 has clinical significance in the diagnosis of colorectal cancer.

The incidence of colorectal cancer is high threatening human health. About 60％～70％cases of CRC are derived from colorectal polyps, which can be treated by endoscopic electrotomy to prevent the possibility of canceration. Therefore, in the prevention and treatment of CRC, the role of screening is of great significance. CRC screening methods include the most commonly used fecal occult blood test ( FOBT ) and the more sensitive fecal immunochemical test (FIT), cost-effective fiber sigmoidoscopy and colonoscopy, CT colonoscopy (CTC), and fecal DNA testing and immature CRC hematology screening. In this paper, the CRC screening technologies were reviewed, including the principles, characteristics and the latest research progress to provide a theoretical basis for the application and development of CRC screening technology.

Objective To investigate the mechanism of MDM2-p53 signaling pathway in the development of colorectal cancer and correlation between p53 with clinicopathological parameters, so as to further analyze the effect of p53 on prognosis. Methods The colorectal cancer tissues and the adjacent normal tissues from 86 cases of patients with colorectal cancer were collected . The expression of p53 and murine double minute 2 (MDM2) in colorectal cancer and adjacent normal tissues were detected by immunohistochemistry, Western Blot and real-time fluorescence quantitative polymerase chain reaction (RT-PCR). The prognosis of the patients was analyzed by the Kaplan-Meier survival curves. Results The protein expression and the mRNA expression of p53 and MDM2 in colorectal cancer tissues were significantly higher than that in the adjacent non-cancerous tissues (all P<0.01). A positive correlation was observed between the expression of p53 and MDM2 (r=0.785). The expression of p53 in colorectal cancer tissues were correlated well with the degree of tumor differentiation, TNM stage, lymph node metastasis and infiltration depth (all P<0.05). Survival analysis demonstrated that the mean overall survival time in p53 high expression group was (53.92±1.56) months which was significantly lower than that in p53 low expression group of (69.16±3.72) months, and the difference was statistically significant (χ2=14.78, P<0.01). Conclusions The risk and prognosis of colorectal cancer are closely related to the MDM2-p53 signaling pathway. p53 can be used as a potential target for the prognosis and treatment of colorectal cancer.

In the original publication the PDB numbers were not cited.