Leukemia is a kind of cloning disease from malignant hematopoietic stem cells. Its patho-genesis may have relationship with proliferation out of control,dysdiffreentiation and inhibition of apoptosis about leukemia cells. The study confirms that CD44 is expressed in leukemia cells,promoting the occurrence and development of leukemia through participation in cell adhension,proliferation,migration and invasion behavior. In vitro experiment shows that CD44 targeted therapies can effectively kill leukemia cells,and reduce the toxicity to normal tissue cells. Therefore,aiming at the design of the anticancer drugs targeted for CD44 is expected to be used in clinical treatment of leukemia.

Objective To explore the significance in judging the different clinical stages of relapsing polychondritis (RP) patients through examining the changes of aggrecanase and metabolic fragments of aggrecan.MethodsIn comparison with the control group (20 cases),40 patients were divided into the stable stage group (22 cases) and the active stage group (18 cases).The aggrecanase-generated neoeptitopes in cartilage matrix were analysed by immunohistochemistry and Western blot(WB) respectively.The mRNA and protein levels of aggrecanase-1,2 expressed in cartilage cells were measured by real-time reverse transcriptional polymerase chain reaction(RT-PCR) and WB respectively.The difference of these results among these three groups was analyzed accordingly.ResultsThe expression of aggrecanase-1,2 in mRNA level was measured by real-time RT-PCR.The values of aggrecanase-1,2 mRNA 2 -ΔΔC1 were 1.00 ± 0.26 and 1.00 ± 0.27 in control group,1.47 ± 0.11 and 1.57 ± 0.13 in stable stage group,2.09 ±0.12 and 2.09 ± 0.19 in active stage group respectively.By one-way ANOVA analysis,the difference between every two groups was statistically significant (F was 299.113 and 459.013,P ＜ 0.01 ).In comparison with control group,aggrecanase-1,2 increased significantly in both stable and active stage group (P ＜ 0.01 ) and aggrecanase-1,2 increased more significantly in active stage group than in stable stage group (P ＜ 0.01 ).The results from WB analysis indicated that aggrecanase-1,2 could not be detected in control group,and they were detectable in stable stage group and increased in active stage group at the relative molecular of 68 000 Da or 73 000 Da respectively.The aggrecanase-generated neoeptitopes were analyzed by WB as well.The results indicated that NITEGE and ARGSV could be detected in stable stage group and increased in active stage group at the relative molecular of 70 000 Da or 48 000 Da respectively,but there were no signals in control group.Similar with the previous WB results,no signals of NITEGE or ARGSV eptitopes were detected in normal cartilage matrix ( no red staining) by use of immunohistochemical staining.However,in stable stage group and active stage group,these eptitopes were apparently detected (obviously red staining).ConclusionWith the progression of the RP,the activity of the aggrecanase is enhanced,and the degradation of the aggrecan is increased,associated with the severity of the disease.

Objective To evaluate the clinical value of determination of composition of kidney stones by shap and density and of prediction of the efficacy of extracorporeal shock-wave lithotripsy (ESWL) by X-rays. Methods The data of 358 patients were analyzed,with 204 male and 154 female and with 276 cases of solitary stones and 82 cases of multiple stones.Determine the composition of kidney stones by shap and density,predict the efficacy of ESWL by X-rays,and choose the appropriate method of treatment.Analyze stone chemical property by Infrared stone composition automatic analyzer to checkout the prediction results before surgeries. Results 339 cases were successful to remove stones after treatment.The prediction results of 308 cases (86.0％) were consistent in stone chemical property,and the preperative prediction results of 339 cases (94.7％) were consistent in ESWL efficacy. Conclusions Determination of composition of kidney stones and prediction of the efficacy of ESWL by X-rays were feasible.

Objective: To evaluate the effects of vascular endothelial growthfactor A (VEGFA) and vascular endothelial growth factor receptor2 (VEGFR2) on disease-free survival (DFS) of patients with lungadenocarcinoma receiving surgery.Methods: Immunohistochemistry (IHC) was performed to detect theexpressions of VEGFA and VEGFR2 proteins in adenocarcinoma tissues from 114 patients after surgery. The information on clinical characteristics includinggender, age, smoking status, tumor size, number of positive lymph nodes (PLNs), clinicalstage and treatment after surgery was collected, and the associations of VEGFA and VEGFR2expressions with the clinical characteristics were analyzed. The COX proportional hazardsregression model was used to identify the independent prognostic factors for DFS.Results: The IHC result showed that the positive rates of VEGFA and VEGFR2 expressions inadenocarcinoma tissue samples were 46.49% (53/114) and 46.49% (53/114), respectively.There was no evidence indicating that VEGFA expression was significantly associated withthe clinical characteristics of patients with lung adenocarcinoma, but VEGFR2 expression wassignificantly correlated with the tumor size (P = 0.03). COX proportional hazards regressionmodel revealed that VEGFA and VEGFR2 expressions had no significant effects on patients'DFS; the tumor size > 4 cm (relative risk: 2.29; 95% confidence interval: 1.32-3.97; P = 0.003)and the number of PLNs ≥ 2 (relative risk: 2.15; 95% confidence interval: 1.27-3.64; P = 0.005)were independent factors to predict DFS of patients with lung adenocarcinoma after surgery.Conclusion: For patients with lung adenocarcinoma receiving surgery, VEGFA and VEGFR2expressions have no significant correlation with DFS; the tumor size > 4 cm and the numberof PLNs ≥ 2 may be the independent factors affecting DFS.

OBJECTIVEIn this research, we have observed changes of PHF8、H3K9me2、BDNF, and their regulatory roles in changing the amplitude value of LTP in hippocampus due to aluminum exposure so that we can discuss the impact on the learning and memory that caused by chronic aluminum exposure.

METHODSForty healthy SPF grade SD male rats were randomly divided into four groups by weight, including control group and low, medium, high dose aluminum exposed group, each group had 10 rats. The exposed rats drank water containing different doses of aluminum chloride (AlCl3) (2、12、72 mg/kg Al(3+)) for 90 d. We measured LTP in hippocampus by electrophysiological grapier and detected the expression of PHF8、H3K9me2、BDNF by western-blot.

RESULTSElectrophysiological measurements shows that compared with that of control group, the average of fEPSPs was decreased at different time points in all exposed groups (P<0.01) . The results of western-bolt test demonstrated that the expression of PHF8 in the exposed groups were significantly lower than those of control group (P<0.01) . And the expression the of H3K9me2 of medium and high dose groups were significantly higher than control group (P<0.05) . While the expression of BDNF of medium and high dose groups were decreased compared with the control group (P<0.05) .

CONCLUSIONChronic aluminum exposure can reduce the LTP via the route of PHF8-H3K9me2-BDNF in the hippocampus of rats, which then may impair the ability of learning and memory.

Aluminum ; toxicity ; Aluminum Compounds ; toxicity ; Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Chlorides ; toxicity ; Hippocampus ; drug effects ; metabolism ; Histone Demethylases ; metabolism ; Learning ; drug effects ; Long-Term Potentiation ; drug effects ; Male ; Memory ; drug effects ; Pilot Projects ; Rats ; Rats, Sprague-Dawley ; Transcription Factors ; metabolism

Objective: To evaluate the clinical indications of CD151 in patients with lung adenocarcinoma with positive expressions of vascular endothelial growth factor A (VEGFA) or vascular endothelial growth factor receptor (VEGFR). Methods: The expressions of VEGFA, VEGFR1, VEGFR2 and CD151 in 116 specimens of patients with lung adenocarcinoma after surgery were detected by immunohistochemistry. The association of CD151 expression with the clinical features of patients with lung adenocarcinoma with positive expression of VEGFA or VEGFR was analyzed. The effect of CD151 expression on the disease-free survival (DFS) of patients with lung adenocarcinoma with positive expression of VEGFA or VEGFR was evaluated. Results: The positive rates of VEGFA, VEGFR1, VEGFR2 and CD151 in lung adenocarcinoma tissues were 69.83% (81/116), 69.83% (81/116), 44.83% (52/116), and 42.24% (49/116), respectively. For patients with lung adenocarcinoma with positive expression of VEGFA, positive expression of CD151 was positively correlated with clinical TNM stage (r = 0.24, P = 0.04) as well as lymph node metastasis (r = 0.26, P = 0.02). CD151 was an independent factor predicting DFS of patients with lung adenocarcinoma with positive expression of VEGFA [hazard ratio (HR) = 1.80, 95% confidence interval (CI): 1.00 - 3.19, P = 0.048]. The median DFS of CD151-positive patients with positive expression of VEGFA was significantly shorter than that of CD151-negative patients (20 vs 34 months, P < 0.05). For patients with lung adenocarcinoma with positive expression of VEGFR1, positive expression of CD151 was positively correlated with TNM stage (r = 0.28, P = 0.01) and lymph node metastasis (r = 0.31, P < 0.01). Moreover, CD151 was an independent factor predicting DFS of patients with lung adenocarcinoma with positive expression of VEGFR2 (HR = 2.10 C95% CI: 1.02 - 4.33, P = 0.044), and the median DFS of CD151-positive patients with positive expression of VEGFR2 was significantly shorter than that of CD151-negative patients (21 vs 42 months, P < 0.05). Conclusion: CD151 is an independent factor predicting DFS of patients with lung adenocarcinoma with positive expression of VEGFA or VEGFR2.

Objective:To analyze the expression levels of urinary interleukin-6 (IL-6), signal transducer and activator of transcription 3 (STAT3) and heparin-binding protein (HBP) in urinary tract infection and its correlation with infection prognosis.Methods:The clinical data of 100 patients with urinary tract infection (urinary tract infection group) from January 2021 to December 2022 in the Affiliated Hospital of Jining Medical College were retrospectively analyzed. Among them, simple urinary tract infection was in 62 cases, and complex urinary tract infection was in 38 cases; after treatment, 25 cases were not cured, and 75 cases were cured. Another 50 healthy examinees were selected as the health control group. The level of urine IL-6 was detected by luminescence assay method, the level of urine STAT3 was detected by enzyme-linked immunosorbent assay method, and the level of urine HBP was detected by fluorescence immunochromatography method. The blood routine was detected by fully automated blood cell analyzer, and the blood cell count was recorded. The levels of serum C-reactive protein (CRP) and procalcitonin (PCT) were detected by radioimmunoassay. The correlation between urine IL-6, STAT3, HBP and blood routine inflammatory response markers was analyzed by Pearson method. The receiver operating characteristic (ROC) curve was used to evaluate the predictive effectiveness of urine IL-6, STAT3, HBP and blood routine inflammatory response markers in infection prognosis.Results:The urine IL-6, STAT3, HBP, and blood CRP, PCT, white blood cell count in urinary tract infection group were significantly higher than those in healthy control group: (33.19 ± 11.02) μg/L vs. (16.84 ± 3.57) μg/L, (66.77 ± 19.58) μg/L vs. (38.69 ± 11.04) μg/L, (151.98 ± 42.00) μg/L vs. (28.55 ± 9.16) μg/L, (12.57 ± 4.19) mg/L vs. (5.23 ± 1.80) mg/L, (0.58 ± 0.19) μg/L vs. (0.22 ± 0.07) μg/L and (9.86 ± 3.20) × 10 9/L vs. (6.44 ± 2.13) ×10 9/L, and there were statistical differences ( P<0.01). The urine IL-6, STAT3, HBP, and blood CRP, PCT, white blood cell count in patients with complex urinary tract infection were significantly higher than those in patients with simple urinary tract infection: (40.25 ± 10.34) μg/L vs. (28.87 ± 8.55) μg/L, (79.50 ± 17.92) μg/L vs. (58.96 ± 13.43) μg/L, (186.51 ± 35.92) μg/L vs. (130.82 ± 39.74) μg/L, (14.09 ± 4.18) mg/L vs. (11.64 ± 3.55) mg/L, (0.64 ± 0.20) μg/L vs. (0.55 ± 0.13) μg/L and (11.27 ± 3.08) × 10 9/L vs. (8.99 ± 2.36) × 10 9/L, and there were statistical differences ( P<0.01). The urine IL-6, STAT3, HBP, and blood CRP, PCT, white blood cell count in patients with untreated urinary tract infection were significantly higher than those in patients with cured urinary tract infection: (42.97 ± 11.51) μg/L vs. (29.93 ± 8.66) μg/L, (86.81 ± 20.35) μg/L vs. (60.09 ± 17.43) μg/L, (264.27 ± 28.76) μg/L vs. (114.55 ± 21.38) μg/L, (19.11 ± 3.28) mg/L vs. (10.39 ± 2.40) mg/L, (0.85 ± 0.14) μg/L vs. (0.49 ± 0.11) μg/L and (12.26 ± 2.77) × 10 9/L vs. (9.06 ± 2.34) ×10 9/L, and there were statistical differences ( P<0.01). Pearson correlation analysis result showed that urine IL-6, STAT3, HBP were positively correlated with blood CRP, PCT, white blood cell count ( P<0.01). The ROC curve analysis result showed that the area under curve (AUC) of urine IL-6, STAT3 and HBP in predicting the infection prognosis in patients with urinary tract infection was greater than that of blood CRP, PCT and white blood cell count; moreover, the AUC and sensitivity of the combined of urine IL-6, STAT3 and HBP in predicting the infection prognosis in patients with urinary tract infection were significantly higher than the combined of blood CRP, PCT and white blood cell count (0.937 vs. 0.898 and 96.00% vs. 76.00%), but with lower specificity (81.33% vs. 98.67%). Conclusions:Urinary tract infections can cause elevated urine IL-6, STAT3 and HBP, and the degree of elevation is related to the types of simple or complicated infection and the infection prognosis. The combined detection of the urine IL-6, STAT3 and HBP is expected to be a method to predict the infection prognosis, and it provides reference information for clinical diagnosis and treatment.

Objective:To explore the experience of self-management dilemma ofadults with emerging ankylosing spondylitis, and to provide reference for the construction of self-management intervention strategies for emerging adults with ankylosing spondylitis.Methods:Descriptive phenomenology was used to conduct in-depth interviews with 14 adults with emerging ankylosing spondylitis in the Rheumatology and Immunology Department of Drum Tower Hospital Affiliated to Medical College of Nanjing University from August 2022 to March 2023. The interview data were analyzed by Colaizzi′s seven-step analysis method.Results:A total of 14 patients completed the interview,10 males, 4 females, aged 21-30 years. In adults with emerging ankylosing spondylitis, there were dilemmas of role maladjustment and disease management disorder, including role maladjustment of disease management and social role maladjustment. Barriers to disease management included weak self-management awareness, insufficient support for self-management information, inadequate self-management skills, and poor compliance with self-management behaviors.Conclusions:The role adaptation and self-management ability of adults with emerging ankylosing spondylitis are seriously inadequate. It is urgent to construct health management strategies for adults with emerging ankylosing spondylitis to help them improve the level of role adaptation and disease management.

This paper reports the diagnosis and treatment of a case of lymphocytic hypophysitis in pregnancy complicated by intrahepatic cholestasis of pregnancy. The 32-year-old patient had regular menstrual cycles and conceived naturally. Around 24 weeks of gestation, she developed a headache without abnormalities in the visual field. Skin itching occurred at 32 weeks of gestation, but her headache was significantly relieved. By 33 +1 weeks of pregnancy, the patient experienced elevated total bile acid, transaminase, and hypoglycemia, leading to a diagnosis of intrahepatic cholestasis of gestation (mild). Subsequently, at 33 +6 weeks of gestation, her total bile acid increased substantially, and the disease progressed rapidly into intrahepatic cholestasis of pregnancy (severe). As a result, an emergency cesarean section was performed to terminate the pregnancy. The Apgar score of the newborn was five points at one minute and ten points at five minutes. Following the surgery, the patient showed no lactation and had symptoms such as nausea, vomiting, fatigue, and refractory hyponatremia. Blood hormone measurement showed hypopituitarism. An enhanced intracranial MRI showed pituitary enlargement and uniform enhancement. Consequently, the clinical diagnosis was lymphocytic hypophysitis. Treatment with glucocorticoids effectively alleviated the symptoms. Menstruation resumed after more than one month of delivery. The intracranial MRI in postpartum reexamination after six months of delivery revealed a disappearance of the lesion. The patient continued with oral glucocorticoid therapy.

Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C18 col-umn(4.6 mm×50 mm,5 μm)under gradient conditions with eluents of methanol:acetonitrile(1∶1,V/V)and 5mM ammonium formate:methanol(9∶1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30 → 437.30 for RA and m/z 256.10 → 227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40 mg/kg)and intravenous(10 mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20 mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1％to 19.4％.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.