Objective To establish a mouse pancreatic exocrine secretion system,in order to study the effect of secretagogues,such as cholecystokinin (CCK) and carbachol (CCH),on the exocrine secretion of mouse pancreas,and use a protein kinase C (PKC) antagonist-chelerythrine(Che) to research the possible mechanism.Methods Prospective control study.Results CCK and CCH increased the secretion of amylase from the mouse pancreatic acini about two fold of that of the control (7.02%vs14.29%),and,CCK or CCH added Che,could increase the secretion of amylase to a level of about three fold(19.02%).Conclusion CCK or CCH stimulate the pancreatic secretion concerning the PKC cellular signal system;surprisingly,a PKC antagonist,chelerythrine,can reinforces their stimulation.

The present paper is aimedto investigate the effect of basic fibroblast growth factor (bFGF) on proliferation, migration and differentiation of endogenous neural stem cell in rat cerebral cortex with global brain ischemia-reperfusion. A global brain ischemia-reperfusion model was established. Immunohistochemistry was used to observe the pathological changes and the expression of BrdU and Nestin in cerebral cortex. RT-PCR was used to measure the NSE mRNA in brain tissue. The results of measurements indicated that in sham operation group, there was no positive cell in cerebral cortex, and the content of NSE mRNA did not change. In the operation group, the expression of BrdU and Nestin increased significantly at the end of the 3rd day, and peaked on the 7th day. NSE mRNA expression did not significantly increase. In bFGF group, compared with sham operation group and model group, the number of BrdU-positive and Nestin-positive cells increased significantly at each time point (P<0. 05), and peaked at the end of the 11th day, and the content of NSE mRNA increased significantly (P<0. 05). This research demonstrated that the proliferation of endogenous neural stem cells in situ could be induced by global cerebral ischemia and reperfu- sion, and could be promoted and extended by bFGF. In additiion, bFGF might promote endogenous neural stem cells differentiated into neurons.
Animals ; Brain Ischemia ; pathology ; Cell Differentiation ; Cell Movement ; Cell Proliferation ; Cerebral Cortex ; cytology ; metabolism ; pathology ; Fibroblast Growth Factor 2 ; pharmacology ; Nestin ; metabolism ; Neural Stem Cells ; drug effects ; Rats ; Reperfusion Injury

Objective:To investigate the frequency of metabolic syndrome (MS) in patients with psoriatic arthritis (PsA) and further analyze the correlation of MS and its components with clinical features of PsA.Methods:Data including demographics, clinical manifestations, laboratory tests, MS-associated features (height, weight, waist circumference, blood pressure, serum lipid spectrum, and so on) and history of complications (hypertension, diabetes mellitus, atherosclerosis, coronary heart disease, and cerebral vascular disease) were collected from PsA patients in our hospital from Jan 2017 to Sep 2019. The frequency of MS in PsA patients was calculated and the association between PsA clinical manifestations and MS as well as its components was investigated.Results:One hundred and sixty-two PsA patients who fulfilled the Classification Criteria for Psoriatic Arthritis (CASPAR) were recruited. Hypertension was identified in 36 (22.2%) patients, diabetes mellitus in 28(17.2%) patients, coronary heart disease in 11(6.7%) patients, and cerebral vascular disease in 7 (4.3%) patients. Based on the criteria of the International Diabetes Federation (IDF), 58(35.8%) patients were diagnosed as MS. Compared with MS-free patients, patients with MS, hypertension or diabetes mellitus were older [(54±10 vs 44±13; 56±11 vs 45±12; 54±11 vs 44±13, respectively, t=5.058 , 4.450, 5.150, P<0.01 for all], with higher disease activity [DAPSA scores 16.75(11.25, 26.7) vs 8.8(4.8, 16.4), 16.3(9.6, 27.8) vs 10.0 (5.1, 18.0), 14.4 (9, 25.7) vs 9.5 (5, 17.7), Z=4.539 , 3.046, 3.063, P<0.01]. There was a positive correlation between the sum of components of MS and DAPSA score ( r=0.27 , P<0.01), but multiple linear regression showed no correlation between each component with DAPSA score ( P>0.05) except for hypertension ( P<0.01, standard coefficient=0.334) and elevated fasting blood glucose ( P=0.023, standard coefficient=0.247). PsA patients with hypertension had higher ESR [16.5 (9.5, 34.25) mm/1 h vs 10 (5, 24.5) mm/1 h, Z=2.127, P=0.012]. CRP level was higher in patients with dyslipidemia [5.6(2.1, 17.8) mg/L vs 3.7(1.5, 6.5) mg/L, Z=2.543, P<0.01]. Prevalence of inflammatory back pain was also higher in dyslipidemia patients (41.3% vs 22.4%, χ2=5.901, P=0.016). DAPSA score was higher in dyslipidemia patients (14.1 vs9.9, P=0.031). Conclusion:MS and its components are not rare comorbidities in PsA patients. PsA patients with MS tend to be older with higher disease activity, which calls for more attention.

Objective:To explore the expressions of serum N-terminal osteocalcin (N-MID) and cytokeratin (CK) 5/6 in primary lung cancer patients with bone metastasis and their clinical significances.Methods:The clinical data of 96 patients with primary lung cancer admitted to Chengdu Second People's Hospital between February 2019 to February 2022 were retrospectively analyzed. All patients were divided into the bone metastasis group (38 cases) and the non-bone metastasis group (58 cases) according to whether bone metastasis occurred, and 45 healthy people who underwent physical examination during the same period were treated as the healthy control group. The expression levels of serum N-MID and CK5/6 in the bone metastasis group, the non-bone metastasis group and the healthy control group were compared. Logistic regression was used to analyze the factors affecting bone metastasis in patients with primary lung cancer; receiver operating characteristic (ROC) curve analysis was used to analyze the value of the expression levels of serum N-MID and CK5/6 in predicting bone metastasis in patients with primary lung cancer.Results:The composition ratio of patients with pathological stage Ⅲ-Ⅳ, serum bone-derived alkaline phosphatase and N-MID expression levels in the bone metastasis group were higher than those in the non-bone metastasis group (all P < 0.05). The expression level of serum N-MID in the bone metastasis group and non-bone metastasis group was higher than that in the healthy control group [(26.0±5.3) ng/ml, (15.3±3.1) ng/ml vs. (9.9±1.7) ng/ml, F = 224.27, P < 0.001], and there were statistically significant differences in the serum N-MID expression level of the pairwise comparison among the three groups (all P < 0.05). The expression level of serum CK5/6 in the bone metastasis group and the non-bone metastasis group was lower than that in the healthy control group [(3.6±0.7) ng/ml, (7.3±1.4) ng/ml vs. (10.6±2.4) ng/ml, F = 178.11, P < 0.001], and there were statistically significant differences in the serum CK5/6 expression level of the pairwise comparison among the three groups (all P < 0.05). Multivariate analysis showed that CK5/6, N-MID and bone-derived alkaline phosphatase were independent affecting factors for bone metastasis in patients with primary lung cancer ( OR = 4.088, 3.615, 2.892, all P < 0.05). ROC curve analysis showed that the optimal cut-off values of serum N-MID and CK5/6 expression levels for predicting bone metastasis in patients with primary lung cancer were 18.59 ng/ml and 4.71 ng/ml; the corresponding the area under the curve (AUC) was 0.881 and 0.862, respectively; and the specificity and AUC of the combination of serum N-MID and CK5/6 in predicting the bone metastasis in patients with primary lung cancer was 98.28% and 0.937 (95% CI 0.869-0.977), respectively; the AUC predicted by the combination of both was higher than that by serum N-MID or CK5/6 single (all P < 0.001). Conclusions:The expression levels of serum N-MID and CK5/6 in primary lung cancer patients with bone metastasis are abnormally changed. Clinical detection of serum N-MID and CK5/6 expression levels may be used as sensitive indicators for predicting the bone metastasis in patients with primary lung cancer.

BACKGROUND: Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). METHODS: A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. RESULTS: A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment ( P  = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. CONCLUSIONS COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.
Humans ; Arthritis, Rheumatoid ; Cohort Studies ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; East Asian People ; Prospective Studies ; Vaccination/adverse effects*

Objective To comparatively analyze the SD rat chloasma model established by using the two methods of progesterone injection and ultraviolet radiation.Methods The rat chloasma model was established by adopting the high and low doses of progesterone injection and ultraviolet irradiation.The plaque area was observed and the skin section was observed by light microscope.The SOD and MDA levels closely related with chloasma melanin deposition were detected.Results The significant pigment deposition on the back skin in the high dose progesterone group was seen by naked eye and the scattered pigment deposition was seen in the low dose progesterone group;significant pigment deposition could be found in the ultraviolet group.Compared with the control group,the MDA level of various tissues in the high dose progesterone group was increased,while the SOD level was decreased,serum and skin SOD level in the low dose progesterone group was decreased,the difference was statistically significant(P＜0.05).Serum and skin SOD level in the high dose ultraviolet group was decreased,while the MDA level was increased,the skin SOD level in the low dose ultraviolet group was decreased(P＜0.05),but the difference between the two groups was not statistically significant (P＞0.05).The melanin grains were heaped up as the small black body under light microscope,which in the progesterone group showed the clutter distribution,the difference between the high dose group and low dose group was significant;which in the ultraviolet group showed the linear dense arrangement and the intergroup had no significant difference.Conclusion Progesterone injection and ultraviolet irradiation all can successfully establish the SD rat chloasma model,and the constructing model effect and stability of ultraviolet irradiation are better.

OBJECTIVETo synthesize compounds based on imidazo-fused heterocycles and evaluate their anti-tumor activity against breast cancer.

METHODSThe compounds 1a-1e, 2a and 2b were synthesized by aerobic copper-catalyzed halocyclization of methyl N-heteroaromatics with aliphatic amines; 3a and 3b were generated by sonogashira reaction and Suzuki reaction, respectively; the compounds 4a-4c were obtained by Buchwald-Hartwig reaction of the corresponding amines and 1e. The effects of these compounds against breast cancer cells and their nephrotoxicity were determined using MTT assay. Annexin VFITC/PI apoptosis detection kit was used to assess the apoptosis-inducing effects of these compounds in breast cancer cells. With normal saline as the control, the safety and anti-tumor activity of the compound 2a (daily dose of 10 mg/kg for 14 days) was tested in a mouse model bearing human breast cancer xenografts.

RESULTSThe compounds 2a, 4a, 4b and 4c all showed obvious anti-tumor activities. Among these compounds, 2a showed the most potent anti-tumor effect against breast cancer cells with an IC of 9.77 ± 2.32 μmol/L, similar to that of cisplatin (IC=8.96 ± 2.35 μmol/L); 2a also showed a slightly lower nephrotoxicity than cisplatin, and their CC was 10.79±0.87 μmol/L and 8.45±0.68 μmol/L, respectively. 2a obviously promoted apoptosis of breast cancer cells and caused a moderate suppression of the breast cancer growth in the tumor-bearing mouse models without producing serious adverse effects.

CONCLUSIONSFour compounds synthesized based on imidazo-fused heterocycles have anti-tumor activities against breast cancer. The compound 2a is capable of dose-dependently promoting apoptosis of breast cancer cells and has a good safety and a moderate efficacy for suppressing tumor growth in mouse models bearing human breast cancer xenografts.