Objective To investigate the autophagy activation effect of hernandezine (HER) on hepatocellular carcinoma (HCC) cells and its role in inducing autophagic cell death. Methods The inhibitory effects of HER on the proliferation of HCC cell lines Hep 3B and Huh-7 were assessed using CCK-8 assay. HCC cells were treated with HER at different concentrations and time points gradient. Western blot analysis was performed to evaluate the conversion of autophagy marker LC3 from type Ⅰ to type Ⅱ and the levels of SQSTM1/p62. Stable red fluorescent protein(RFP)-LC3-expressing cell lines were established through lentiviral infection, and the accumulation of RFP-LC3 puncta following HER treatment was observed under confocal microscope. Autophagosomes in HER-treated cells were visualized using transmission electron microscopy. The effects of autophagy inhibitors, bafilomycin A1 (BafA1) or hydroxychloroquine (HCQ), in combination with HER were investigated by analyzing cell death rates via flow cytometry. The phosphorylation levels of adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK) and mammalian target of rapamycin(mTOR) were assessed by Western blot.Results HER inhibited the proliferation of HCC cells Hep 3B and Huh-7, promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, and activated autophagy in a dose- and time-dependent manner. Confocal microscopy and transmission electron microscopy revealed a significant increase in autophagic vesicles in HER-treated cells. HER-induced cell death was attenuated by the autophagy inhibitors BafA1 or HCQ. HER treatment increased AMPK phosphorylation levels while decreasing mTOR phosphorylation levels.Conclusions HER induces autophagy and promotes autophagic cell death in HCC cells via the AMPK/mTOR signaling pathway.

Objective To investigate the expression of kinesin family member 15(KIF15), epidermal growth factor receptor(EGFR), and human epidermal growth factor receptor 2(HER2) in gallbladder cancer(GBC) and their clinical and pathological significance. Methods Immunohistochemical staining was employed to detect the expression of KIF15, EGFR, and HER2 proteins in GBC tissue microarrays. The correlation between protein expression levels and various clinical and pathological characteristics of GBC patients was analyzed. Results The positive expression rates of KIF15, EGFR, and HER2 proteins in GBC tissues were 71.6%, 62.2%, and 51.4% respectively, compared to 16.7%, 0, and 0 in para-carcinoma tissues (all P=0.000). KIF15 expression was correlated with cancer differentiation grade (P=0.006), while EGFR expression was associated with lymph node metastasis(P=0.026) and the number of metastatic lymph nodes(P=0.012). HER2 expression was correlated with cancer differentiation grade(P=0.018), tumor size(P=0.005), and T stage(P=0.032). GBC patients with co-positive expression of KIF15 and HER2 had significantly lower overall survival compared to those with negative expression. Positive HER2 expression, lymph node metastasis, and the number of metastatic lymph nodes were identified as independent risk factors for overall survival in GBC patients. Conclusions Positive expression of KIF15, EGFR, and HER2 in GBC tissues are correlated with various clinical indicators and poorer prognosis. These proteins may serve as potential factors for predicting prognosis and evaluating therapeutic efficacy in GBC.

Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.

Objective:To study the photoneutron radiation field caused by photonuclear reaction during the operation of high energy medical linac.Methods:Monte Carlo was used to simulate the photoneutron pollution of Clinic 2300CD medical electron accelerator in 15 MV X-ray mode. The photoneutron spectrum at different positions of the head and the variation in neutron ambient dose equivalent in different irradiation fields were investigated, and the dose distribution of photoneutron on the isocenter plane and the dose attenuation in the water model were analyzed.Results:When the collimator was closed, the average photoneutron energy at the lower surface of target, primary collimator, flattening filter and multi-leaf collimator was 1.08, 1.20, 0.35 and 0.30 MeV, respectively. The neutron ambient dose equivalent at the isocenter first increased and then decreased with the irradiation field expanding, reaching the maximum in about 30 cm × 30 cm irradiation field. With the increase in the depth of the measuring point in water phantom, the neutron fluent first increased and then decreased, while the neutron dose gradually decreased. In different irradiation fields, the photoneutron dose rate was almost close to the background when the depth of the water was 20 cm.Conclusions:By exploring the photoneutron spectrum and dose distribution characteristics of the high energy medical linac head, as well as the dose deposition mechanism of photoneutron in water phantom, this study provides data support for further research on the additional dose and secondary cancer effects on patients caused by photoneutron pollution from the high energy medical linac.

Objective:To detect the expression and methylation of TIA1 in breast cancer and to study its correlation with multi-slice spiral CT signs.Methods:50 patients with breast cancer were collected from Feb.2019 to Mar. 2020. The expression levels of TIA1 in breast cancer tissues and in peritumoral tissues were estimated by quantitative real-time polymerase chain reaction. Bioinformatics software MethPrimer was used for predicting TIA1 promotor and confirmed the existence of cPG island. Methylation-specific PCR (MSP) was performed to detect TIA1 DNA promoter methylation. All patients were examined by multi-slice CT. CT images were analyzed through observing the tumor size, shape, calcification area, lymph node metastasis and margin. The correlation between CT signs and TIA1 methylation status was further analyzed.Results:The expression levels of TIA1 in breast cancer tissues were lower than in peritumoral tissues (0.50±0.12, 0.95±0.10, P=0.00) , while TIA1 DNA promoter methylation rate was higher than in peritumoral tissues (64%, 42%, χ2=4.86, P<0.05) .There were no significant differences in TIA1 DNA promoter methylation rate among patients with different tumor shape and micro calcifications. TIA1 DNA promoter methylation rate in patients with mass diameter≥2 cm were significantly higher than those in patients with mass diameter<2 cm (78.57%, 45.45%, P<0.05) , and TIA1 DNA promoter methylation rate in patients with lymph node metastasis was higher than those without lymph node metastasis (79.17%, 50%, P<0.05) . TIA1 DNA promoter methylation rate in patients with burr at edge of mass was higher than those without burr at edge of mass (80.77%, 45.83%, P<0.05) . Conclusion:There is a correlation between CT imaging signs and TIA1 DNA promoter methylation rate in patients with breast cancer, which can provide more reference for the judgment of malignant degree and prognosis of patients with breast cancer.

Objective To analyze the clinical value of X ray examination, CT examination and MRI examination in the diagnosis of giant cell tumor of bone.Methods 50 patients with giant cell tumor of bone confirmed by postoperative pathology were selected.The patients' X ray, CT scan and MRI imaging examination data were retrospectively analyzed, and the imaging features of giant cell tumor of bone were discussed and summarized.Results The rate of CT examination and MRI examination in the diagnosis of bone destruction was higher than X ray examination, but the difference was not statistically significant (x2=4.181,P>0.05).CT examination and MRI examination in the soap bubble sign, bone crest, liquid plane and soft tissue mass in the diagnostic rate compared with X ray examination was significantly higher, the difference was statistically significant (x2=5.333,22.941,30.000,38.400,64.000,14.166,6.102,all P<0.05).Conclusion The diagnostic accuracy of CT and MRI in giant cell tumor of bone is higher than X ray, but the value of MRI examination in the diagnosis of edema near the tumor is better.

Objective To explore the influence of type 2 diabetes mellitus combined with subclinical hypothyroidism on diabetic vascular complications.Methods One hundred and two patients with type 2 diabetes mellitus were selected.The serum free triiodothyronine (FT3),free thyroxine (FT4),thyroid stimulating hormone (TSH),anti-thyroid peroxidase antibody (TPO-Ab),thyroglobulin antibody (TG-Ab) levels were measured by chemiluminescence method.The patients were divided into type 2 diabctes mellitus combined with subclinical hypothyroidism group (47 cases) and type 2 diabetes mellitus with normal thyroid function group (55 cases) according to the thyroid function.The glycated hemoglobin (HbA1c),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),triacylglycerol (TG),high-density lipoprotein cholesterol (HDL-C),urea nitrogen,creatinine and albumin levels were measured.The estimated glomerular filtration rate (eGFR) was calculated according to the formula of modification of diet in renal disease (MDRD).The presence of diabetic retinopathy was examined by fundus examination,and the presence of lower limb artery lesions was measured by vascular ultrasound.All indicators were compared between 2 groups.Results There were no statistical differences in age,disease course,HbA1c,body mass index (BMI),TC,TG,HDL-C,LDL-C,incidence of lower limb artery lesions and incidence of diabetic retinopathy between 2 groups (P＞ 0.05).TheeGRF in type 2 diabetes mellitus combined with subclinical hypothyroidism group was significantly lower than that in type 2 diabetes mellitus with normal thyroid function group:(83.74 ± 21.55) ml/(min· 1.73 m2) vs.(115.02 ± 12.29) ml/(min· 1.73 m2),and there was statistical difference (t =4.274,P ＜ 0.01).The incidence of diabetic nephropathy in type 2 diabetes mellitus combined with subclinical hypothyroidism group was significanlty higher than that in type 2 diabetes mellitus with normal thyroid function group:48.9％ (23/47) vs.23.6％(13/55),and there was statistical difference (x2 =7.103,P＜ 0.01).Logistic regression analysis showed that subclinical hypothyroidism was a risk factor for diabetic nephropathy (OR =0.524,95％ CI 0.12-0.93,P ＜ 0.05),but it was not the risk factor for diabetic retinopathy (OR =0.618,95％ CI0.19-2.16,P =0.475) and lower limb artery lesions (OR =0.485,95％ CI 0.32-2.13,P =0.689).Conclusion Subclinical hypothyroidism in patients with type 2 diabetes mellitus has no obvious effect on lower limb arterial complications and diabetic retinopathy,but may increase the risk of diabetic nephropathy.

BACKGROUND:Autologous peroneus brevis and alogeneic tendon are often used for reconstruction of lateral colateral ligament of the ankle joint, but these two kinds of materials have different histological and biomechanical properties. OBJECTIVE:To compare the clinical effects of autologous peroneus brevis and alogeneic tendon to reconstruct lateral colateral ligament of the ankle joint. METHODS: Sixty-six patients with chronic external ankle instability caused by old injury to lateral colateral ligament of the ankle joint were enroled, aged 15-63 years. The 34 of 66 patients underwent lateral ligament reconstruction using autologous peroneus brevis and the rest 32 patients received lateral ligament reconstruction using alogeneic tendon. After reconstruction, reaction time of the peroneous brevis, talar tilt angle and anterior talar translation, visual analog scale score and the American Orthopaedic Foot and Ankle Society (AOFAS) score were compared between the two groups. RESULTS AND CONCLUSION:At the last folow-up, the visual analog scale score, tilt angle and anterior talar translation were lowered in the two groups compared with the previous (P < 0.05), and the AOFAS scores were increased significantly in the two groups (P < 0.05); the reaction time of the peroneous brevis was increased inthe autologous peroneus brevis group (P < 0.05) and decreased in the alogeneic tendon group (P < 0.05); the above-mentioned indexes had no difference between the two groups. These findings indicate that autologous peroneus brevis and alogeneic tendon have similar effects on the lateral ligament reconstruction in terms of postoperative ankle function, stability and activity levels, but the alogeneic tendon shows advantages on less trauma and shorter operation time.

The chemokine CXCL12 and its receptor CXCR4 played a very important role in the gastric carcinoma,which promoted the growth,invasion,and metastasis of the gastric carcinoma through various of signal pathways.In this paper,the literatures related CXCL12,signal pathways and gastric carcinoma were retrieved and explored.And the authors present the research progress concerning the roles of CXCL12 and its regulating mechanism in neoplasm,especially in gastric cancer.

Objective:To explore the clinical significance of the level and dynamic changes of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in the diagnosis and prediction of long‐term prognosis for patients with chronic obstructive pulmonary disease (COPD) combined with pulmonary heart disease among Han Chinese in Yunnan district .Methods:A total of 234 patients with COPD who were treated in The Second People′s Hospital of Qujing in Yunnan province during Jan .2013 and Dec .2013 ,were selected .Among them ,there were 98 patients with COPD combined with pulmonary heart disease ,80 patients with acute exacerbation of COPD ,and 56 patients with stable COPD .The clinical data ,results of blood gas analysis and echocardiography were recorded on admission and the levels of NT‐proBNP were measured .Results:The distances of 6 minute walk test(6MWT) in acute exacerbation of COPD and COPD combined with pulmonary heart disease groups were significantly less than that in stable COPD group(P< 0 .01) .The level of NT‐proBNP in COPD combined with pulmonary heart disease group was significantly higher than those in stable COPD and acute exacerbation of COPD group(P< 0 .01) .Kaplan‐Meier survival analysis showed that there was no significant difference regarding the rate of readmission and death during 12 months between the NT‐proBNP<1 000 pg/mL group and the NT‐proBNP≥1 000 pg/mL group(P>0 .05) .The rate of readmission and death during 12 months in the group with NT‐proBNP level decreasing ratio after treatment ≥30% was significantly higher than that in the group with decreasing ratio < 30% (P< 0 .05) .Conclusions: The detection of NT‐proBNP is of great significance to the early diagnosis of COPD combined with pulmonary heart disease .The dynamic changes of NT‐proBNP levels before and after the treatment are superior to single detection of NT‐proBNP level in predicting readmission rate and mortality risk for patients with COPD combined with pulmonary heart disease .