OBJECTIVE To explore the effects of the water extract of Morinda officinalis on the expressions of sex hormones and receptors in bisphenol A （BPA）-contaminated mice. METHODS Totally 60 male Kunming mice were randomly divided into control group， model group， and low-dose， medium-dose and high-dose groups of M. officinalis water extract （20， 40， 60 mg/kg）， with 12 mice in each group. The model group and M. officinalis water extract groups were given BPA intragastrically [50 mg/（kg·d）， once a day， for 4 consecutive weeks] to establish the BPA-contamination model of mice. After modeling， each drug group was gavaged with the corresponding drug solution， once a day， for 4 consecutive weeks. After the last medication， the body weight and testicular weight of the mice in each group were weighed， the histopathological changes in the testis were observed， and the serum sex hormones [luteinizing hormone （LH）， follicle-stimulating hormone （FSH）] contents and the mRNA and protein expressions of LH receptor （LHR） and FSH receptor （FSHR） in the testicular tissues were detected. RESULTS Compared with the control group， the testicular tissues of mice in the model group had structural degeneration， loose connections between spermatogenic cells and Sertoli cells， obvious lacunae and reduced number of spermatogenic cells； the mRNA and protein expressions of LHR and FSHR in testicular tissues were significantly down-regulated （P＜0.01）， but there were no significant changes in their body weights， testicular weights， and serum contents of LH and FSH （P＞0.05）. Compared with the model group， the histopathological changes of testicular tissues of mice in each dose group of M. officinalis water extract were improved to different degrees， and the mRNA and protein expressions of LHR and FSHR in testicular tissues were up-regulated to different degrees （P＜0.05 or P＜ 0.01）， and some indicator levels were similar to those of the control group （P＞0.05）. However， there were no significant changes in their body weights， testicular weights， and serum contents of LH and FSH （P＞0.05）. CONCLUSIONS The water extract of M. officinalis has a certain improvement effect on testicular injury in BPA-contaminated mice， which might be related to its increase in the mRNA and protein expressions of LHR and FSHR.

BACKGROUND:In recent years,the incidence of hyperuricemia caused by purine metabolism disorders has been increasing,which can induce inflammatory responses and lead to renal injury. OBJECTIVE:To explore the role and mechanism of solute carrier family 2 member 12(SLC2A12)in hyperuricemia-related renal injury. METHODS:Renal tubular cells(HK2 cells)were divided into five groups:HK2 group,HK2+uric acid group,HK2+uric acid+NC group,HK2+uric acid+siSLC2A12 group,and HK2+uric acid+siSLC2A12+MK-2206 group.HK2 cells were treated with uric acid and transfected with siRNA SLC2A12,followed by MK-2206 treatment to inhibit AKT expression.Cell proliferation was detected by CCK-8 assay.Apoptosis was detected by TUNEL assay.qRT-PCR and western blot assay were used to detect fibrogenic factors as well as activation of the AKT/FOXO3a pathway.The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION:(1)Uric acid treatment inhibited cell proliferation and promoted cell apoptosis in the HK2+uric acid group compared with the HK2 group.The proliferative ability of cells in the HK2+uric acid+siSLC2A12 group was further decreased and apoptotic cells were further increased compared with the HK2 group.Compared with the HK2+uric acid+siSLC2A12 group,the HK2+uric acid+siSLC2A12+MK-2206 group showed an increase in cell proliferation and a decrease in apoptotic cells.(2)Compared with the HK2 group,the connective tissue growth factor(CTGF),α-smooth muscle actin(α-SMA)and transforming growth factor beta(TGF-β)expressions increased in the HK2+uric acid group;CTGF,α-SMA and TGF-β expression further increased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,the CTGF,α-SMA and TGF-β expressions decreased.(3)Compared with the HK2 group,the expression of p-AKT,FOXO3a,and p-FOXO3a elevated in the HK2+uric acid group;the expression of p-AKT further increased,while the expression of FOXO3a and p-FOXO3a decreased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,p-AKT expression decreased;FOXO3a and p-FOXO3a expression increased in the HK2+uric acid+siSLC2A12+MK-2206 group.(4)Compared with the HK2 group,interleukin-6,interleukin-1 β,and tumor necrosis factor α levels increased in the HK2+uric acid group;interleukin-6,interleukin-1 β,and tumor necrosis factor α levels further increased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,interleukin-6,interleukin-1 β,and tumor necrosis factor α levels diminished in the HK2+uric acid+siSLC2A12+MK-2206 group.(5)These findings indicate that SLC2A12 may protect against hyperuricemia-induced renal injury by counteracting uric acid-induced tubular fibrosis and inflammation through activation of the FOXO3a pathway.

Objective To investigate the expression of circular RNA(Circ RNAS)Actinin α 4(ACTN4)and platelet thrombin protein 1(THBS1)in intrahepatic cholangiocarcinoma(ICC)and their relationship with clinicopathological characteristics and prognosis,and provide reference for clinical diagnosis and treatment.Method A retrospective analysis was conducted on 84 ICC patients diagnosed and treated in the Second Affiliated Hospital of Xian Jiaotong University from May 2017 to June 2020.The expressions of CircACTN4 mRNA,THBS1 mRNA and protein were detected by real-time fluorescent quantitative PCR and immunohistochemistry.Pearson correlation analysis was used to analyze the correlation between CircACTN4 mRNA and THBS1 mRNA in ICC cancer tissue.The prognostic differences of ICC patients with different CircACTN4 mRNA and THBS1 mRNA expressions were compared by the Kaplan-Meier method(log rank test).COX regression analysis was performed to identify prognostic factors in ICC patients.The prognostic value of CircACTN4 mRNA and THBS1 mRNA in evaluating the risk of death in ICC patients was assessed by receiver operating characteristic(ROC)curve analysis.Results The expression of CircACTN4 mRNA in ICC tissues(3.14±0.42)was higher than that in adjacent tissues(0.76±0.25),with significant difference(t=44.094,P＜0.001).The positive rates of THBS1 mRNA(2.82±0.36)and protein positive rate(92.86％)in ICC tissues were higher than those in adjacent tissues(0.81±0.24,7.14％),and the differences were statistically significant(t/x2=42.068,123.429,all P＜0.001).CircACTN4 mRNA was positively correlated with THBS1 mRNA in ICC cancer tissue(r=0.669,P＜0.001).The expressions of CircACTN4 mRNA,THBS1 mRNA in ICC cancer tissues with TNM stage Ⅲ,low differentiation,and lymph node metastasis were higher than those in TNM stage Ⅰ～Ⅱ,high differentiation,and non-lymph node metastasis cancer tissues,and the differences were statistically significant(x2=7.949,9.164,12.207;23.270,18.625,19.828,all P＜0.001).The 3-year cumulative survival rates of the high expression group of CircACTN4 mRNA and THBS1 mRNA were lower than those of the low expression group of CircACTN4 mRNA(25.00％vs 56.82％)and THBS1 mRNA(19.51％vs 62.79％),and the differences were statistically significant(Log rank x2=13.601,24.310,all P＜0.001).CircACTN4 mRNA(OR=1.839,95％CI:1.228～2.753),THBS1 mRNA(OR=1.744,95％CI:1.245～2.443),lymph node metastasis(OR=1.925,95％CI:1.316～2.816),TNM staging(OR=1.613,95％CI:1.223～2.126),and tumor differentiation(OR=1.510,95％CI:1.205～1.892)were independent factors affecting the prognosis of ICC.The area under the curve of the combination detection of circACTN4 and THBS1 mRNA on the prognosis of death in patients with ICC was 0.868,which was greater than that of the single index(0.812 and 0.784),with significant differences(Z=3.348,3.847,all P＜0.001).Conclusion The expressions of CircACTN4 mRNA and THBS1 mRNA were increased in ICC,and they were associated with TNM stage,differentiation,and lymph node metastasis.These markers may serve as novel indicators to evaluate the poor prognosis of ICC patients.

Objective: To optimize the determination of pentachlorophenol in wooden chopping boards through pretreatment of miniaturized samples. Methods: The pretreated wooden chopping board samples were subjected to ultrasound extraction (1 mL of 0.5 mol/L K2CO3 added in 5 mL extraction solution) in 8 mL acetone and 2 mL water, followed by derivatization with 0.3 mL acetic anhydride, extraction with n-hexane and separation with DB-5ms column (30 m×0.25 mm, 0.25 μm). Gas chromatography tandem mass spectrometry (GC-MS/MS) was performed in multiple reaction monitoring (MRM) mode with quantitative analysis using the internal standard method. Results: The GC-MS/MS assay showed a good linear relationship within the range of 0.01 to 0.2 µg/mL (R2>0.999), with a 0.003 mg/kg limit of detection and 0.01 mg/kg limit of quantitation. The mean recovery rates were 84.2% to 96.7% at spiked concentrations of 0.003, 0.01 and 0.03 mg/kg, with relative standard deviation of 2.2% to 6.1%. Conclusions The established GC-MS/MS assay is easy to perform, environment-friendly, highly accurate and sensitivity, which is feasible for determination of pentachlorophenol in wooden chopping boards.

Objective:To explore the method and effect in repairing the defect of fingertip with lateral V-Y advancement flap with one side palmar proper digital artery.Methods:From October 2014 to May 2019, Department of the Hand and Foot Surgery, the Third People's Hospital of Jining(Yanzhou District People's Hospital of Jining City) treated 34 digits of 27 cases with a defect area of 0.5 cm×0.5 cm-1.5 cm×2.0 cm. A lateral V-Y advancement flap with one side palmar proper artery was used to repair the fingertip defect, and the flap size was 1.7 cm×1.0 cm-4.5 cm×1.5 cm. Twenty cases entered long-time follow-up after operation, with 7 cases lost in follow-up, 16 cases were reviewed at outpatient and 4 by WeChat.Results:All the flaps of 34 digits of 27 cases survived. The color of the flaps were close to or completely normal to the surrounding tissue, the texture was soft and the appearance was good. The TPD of the flap was 2.0-6.0 mm. The follow-up time ranged from 22 to 77 months, with an average of 31.45 months. The flexion and extension function of the digits were good with total range of motion(ROM) of the thumb was > 90 °; total active motion (TAM) of the fingers was 260 °-200 °. The fingers of 1 case had hook nail or hook finger deformity. According to the Evaluation Trial Standard of Upper Limb Partial Function of Hand Surgery of Chinese Medical Association, 18 cases were excellent and 2 cases were good.Conclusion:The lateral V-Y advancement flap with one side palmar proper digital artery is easy to operate. The blood supply of the flap is reliable, with good sensation. The flexion and extension of the digits are good, and the appearance and texture of the flap are good.

Objective:To observe the effect of sodium fluoride (NaF) on the expression of phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signal and apoptosis in human osteosarcoma Saos-2 cells.Methods:Saos-2 cells were divided into 0 (control), 5, 10, 20 and 40 mg/L fluoride groups ( n= 3) according to the dose of NaF. The cells were collected after 24 and 48 h of culture in vitro. Western blotting was used to detect the expressions of PI3K/Akt signal and Forkhead transcription factor (FoxO) 1, and the apoptosis level of Saos-2 cells was detected by flow cytometry. Results:There were no significants differences in the expressions of PI3K and Akt in Saos-2 cells at 24 and 48 h ( P > 0.05). At 24 h, the expressions of phosphorylated PI3K (p-PI3K) in 5, 10, 20 and 40 mg/L fluoride groups (0.40 ± 0.06, 0.45 ± 0.02, 0.37 ± 0.06, 0.32 ± 0.06) were higher than that in the control group (0.28 ± 0.04, P < 0.05); at 48 h, the expressions of p-PI3K in 5 and 10 mg/L fluoride groups (0.46 ± 0.06, 0.58 ± 0.03) were higher than that in the control group (0.29 ± 0.04, P < 0.05), and that in the 40 mg/L fluoride group (0.21 ± 0.03) was lower than that in the control group ( P < 0.05). At 24 h, the expressions of phosphorylated Akt (p-Akt) in 5, 10 and 20 mg/L fluoride groups (0.27 ± 0.01, 0.30 ± 0.03, 0.27 ± 0.03) were higher than that in the control group (0.20 ± 0.02, P < 0.05); at 48 h, the expressions of p-Akt in 5 and 10 mg/L fluoride groups (0.42 ± 0.04, 0.60 ± 0.02) were higher than that in the control group (0.27 ± 0.01, P < 0.05), and that in the 40 mg/L fluoride group (0.18 ± 0.02) was lower than that in the control group ( P < 0.05). The expressions of FoxO1 in 10, 20 and 40 mg/L fluoride groups at 24 h (0.38 ± 0.07, 0.41 ± 0.06, 0.47 ± 0.08) were higher than that in the control group (0.34 ± 0.04, P < 0.05). At 48 h, the expressions of FoxO1 in 5, 10, 20 and 40 mg/L fluoride groups (0.36 ± 0.08, 0.37 ± 0.10, 0.54 ± 0.04, 0.73 ± 0.04) were higher than that in the control group (0.28 ± 0.04, P < 0.05). At 24 and 48 h, the apoptosis rates of control group and 5, 10, 20 and 40 mg/L fluoride groups were (2.867 ± 0.583)%, (3.647 ± 0.035)%, (3.773 ± 0.095)%, (5.440 ± 0.325)%, (7.203 ± 0.476)%; (3.707 ± 0.286)%, (4.023 ± 0.241)%, (4.970 ± 0.368)%, (12.473 ± 0.949)%, (19.387 ± 1.892)%, respectively. The apoptosis level of 40 mg/L fluoride group was higher than that of control group at 24 h ( P < 0.05), and that of 20 and 40 mg/L fluoride groups were higher than that of control group at 48 h ( P < 0.05). Conclusion:Fluoride can directly activate the PI3K/Akt signaling pathway in osteoblasts, and then has anti-apoptotic effect.

Objective:To investigate the effect of enhanced external counterpulsation(EECP)on heart failure with preserved ejection fraction(HFpEF)and hemodynamics in elderly patients.Methods:Clinical data of 66 elderly HFpEF patients admitted to the enhanced external counterpulsation center of our hospital from January 2018 to December 2019 were retrospectively analyzed.The primary assessment parameter was the six-minute walk distance, and the secondary parameters included the Minnesota Living with Heart Failure Questionnaire(MLHFQ). Noninvasive hemodynamic parameters including the cardiac index(CI), stroke volume(SV), isovolumic relaxation period(A2-mitral valve opening, A2-O), pulmonary capillary wedge pressure(PCWP)and total peripheral resistance(TPR)were monitored and mean arterial blood pressure(MAP)was calculated.Results:After EECP treatment, the six-minute walk distance increased(372±87 m vs.341±85 m, P<0.05), the score of MLHFQ decreased(47.0±16.0 vs.50.0±17.0, P<0.05), CI increased(2.8±0.7)L·min -1·m -2vs.(2.6±0.6)L·min -1·m -2( P<0.05), SV, PCWP and A2-O did not show significant change(73.3±16.4 ml vs.71.5±17.1 ml, 10.0±3.3 mmHg vs.11.0±3.6 mmHg, 1 mmHg=0.133 kPa, 98.0±29.5 ms vs.91.0±29.1 ms, P>0.05), TPR decreased(1 719.0±427.0 DS/cm 5vs.1 821.0±508.0 DS/cm 5, P<0.05), and there was no significant change in MAP(96.9±10.7 mmHg vs.98.8±13.1 mmHg, P>0.05), compared with pre-EECP treatment levels.Compared with patients without hypertension, MAP decreased in patients with hypertension(14 cases), when stratified by the initial MAP( P<0.05). Conclusions:For elderly patients with HFpEF, EECP can increase the six-minute walk distance, improve the quality of life and hemodynamic parameters, and is a safe adjuvant treatment.

Objective:To explore the effect of diabetes specialist nurse sharing management in diabetic patients in primary medical institutions under the medical alliance model.Methods:From January 2018 to December 2019, convenience sampling was used to select type 2 diabetes patients in the First Affiliated Hospital of Xinxiang Medical University as the research object. A total of 147 patients with type 2 diabetes who were enrolled from January to December 2018 were set as the control group, and 162 patients with type 2 diabetes who were enrolled from January to December 2019 were set as the observation group. Control group adopted routine diabetes management, and observation group conducted the diabetes specialist nurse sharing management under the medical alliance model. Both groups of management lasted for 6 months. Morisky Medication Adherence Scale and Scale of the Diabetes Self-care Activities (SDSCA) were used to evaluate medication adherence and self-management behavior scores of the two groups of patients. The fasting blood glucose and glycosylated hemoglobin of the two groups of patients before and after the intervention were compared, and the readmission rate and the incidence of hypoglycemia of the two groups of patients during the intervention were evaluated.Results:After the intervention, the observation group's medication adherence was better than that of control group, and the difference was statistically significant ( P<0.05) . After the intervention, the fasting blood glucose and glycosylated hemoglobin of observation group were lower than those before intervention and of control group, and the SDSCA score was higher than that before intervention and of control group, and the differences were statistically significant ( P<0.05) . The readmission rate and the incidence of hypoglycemia in observation group were 8.02% and 5.56%, respectively, which were lower than 19.73% and 25.17% in control group, and the differences were statistically significant ( P<0.05) . Conclusions:The diabetes specialist nurse sharing management under the medical alliance model can effectively improve the medication adherence, self-management behavior and blood glucose of diabetic patients in primary medical institutions, and reduce the readmission rate and the incidence of hypoglycemia.

Objective To investigate the comprehensive improvement of multi-system diseases in elderly patients treated with enhanced external counterpulsation(EECP).Methods Clinical data of an elderly patient with multiple systemic diseases were collected and analyzed.The therapeutic effect of EECP was assessed and EECP-related literatures were reviewed.Results The 62-year-old male patient was diagnosed with coronary atherosclerotic heart disease,unstable angina,New York Heart Association(NYHA)functional class Ⅱ,hypertension(grade 3,very high risk),type 2 diabetes,acute cerebral infarction (recovery period)and benign prostatic hyperplasia.After two courses of EECP treatment,angina in the patient was significantly relieved,cardiac systolic and diastolic function was improved,activity tolerance was increased and the corresponding dosage of therapeutic drugs was reduced.In addition,the patient's blood pressure and blood glucose levels were decreased after versus before treatment and the retinal superficial blood flow was enhanced in both eyes assessed by optical coherence tomography.The frequency and volume of nocturia were reduced.The symptoms of numbness on the left side were improved.Conclusions EECP treatment has shown significant therapeutic effects on multi-system diseases in the elderly patient.EECP is safe,effective and simple and has a broad application prospect in geriatrics.

Objective To evaluate the risk factors for diabetic foot in patients with type 2 diabetic mellitus (T2DM).Methods One hundred and forty-three patients with T2DM including 63 cases with diabetic foot(DF) and 80 cases with non-diabetic foot (NDF) were recruited.All possible risk factors for diabetic foot were documented,including low density lipoprotein-cholesterol (LDL-C),homocysteine (Hcy),diabetic polyneuropathy(DPN),diabetic retinopathy(DR),peripheral vascular disease(PVD) and so on.Results (1) There were significant differences between DF group and NDF group in terms of general clinical data,including age(65.38±11.58) years old and (60.12±9.92) years old,precious history of foot ulcer(28.6％ (18/63) and 3.8％(3/80)),serum homocysteine(Hcy) ((23.24± 11.77) μmol/L and (18.62±7.74) μmol/L)),glycosylated hemoglobin(HbA1c) ((10.22±2.81) ％ and (8.67±2.30) ％),blood albumin (Alb) ((32.45±5.83) g/L and (38.58±4.71) g/L),LDL-C ((2.15±0.72) mmol/L and (2.60±0.78) mmol/L),diabetic nephropathy (DN) (77.8％ (49/63) and 45.0％ (36/80)),diabetic retinopathy (DR) ((73.0％ (46/63) and 33.8％ (27/80)),diabetic peripheral vascular disease (PVD) (93.7％ (59/63) and 65.0％ (52/80)) and diabetic peripheral neuropathy (DPN) (77.8％ (46/63) and 60.0％ (48/80)) (P ＜0.05).(2) Logistic regression analysis showed that the development of diabetic foot was significantly correlated with age(OR =1.09,95％ CI:1.02-1.16,P =0.01),Hcy (OR =1.12,95％ CI:1.03-1.22,P =0.01),DR(OR=8.47,95％CI:1.85-38.87,P=0.01),PVD(OR=8.73,95％CI:1.07-70.92,P =0.04) and precious history of foot ulcer (OR =12.28,95％ CI:1.57-96.28,P =0.02).Conclusion Complications due to multiple factors of Diabetic foot,and Hcy is another risk factor for that.