Objective To observe the effects of amyloid-β(Aβ)receptor PirB on mouse astrocyte proliferation and reactive astrogliosis in vitro.Methods Mouse primary astrocytes were cultured,and divided into control group,Aβ group,Aβ+0.2 μmol/L PEP group,Aβ+0.4 μmol/L PEP group,Aβ+Fluspirilene group,Aβ+GFP-LV group,and Aβ+mPirB-LV group.The mouse astrocytes were treated with soluble PirB extracellular peptide PEP or PirB inhibitor Fluspirilene,respectively,to inhibit endogenous PirB receptor,or overexpressed PirB gene via lentivirus transfection and then treated with Aβ1-42 oligomers.The proliferation of astrocytes was observed by RTCA and EdU methods,and the mRNA expression levels of S-100 calcium-binding protein B(S-100β),Vimentin,Nestin and amyloid precursor protein(APP)associated with reactive astrogliosis of astrocytes were observed by real-time PCR,and the expression level of glial fibrillary acid protein(GFAP)was detected by Western-blotting.Results The results of RTCA monitoring showed that normalized cell index(NCI)values of each group decreased sharply after treatment,and then increased gradually and tended to be stable.The results of EdU staining showed that the proliferative activity of astrocytes was significantly enhanced in the Aβ group(P<0.05)compared with control group;Compared with Aβ group,cell proliferation activity in Aβ + 0.2 μmol/L PEP group,Aβ+0.4 μmol/L PEP group and Aβ+Fluspirilene group were significantly decreased(P<0.01 or P<0.001).The results of real-time PCR showed that compared with control group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ group were significantly increased(P<0.05);Compared with Aβ group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ+0.4 μmol/L PEP group were significantly decreased(P<0.01);Compared with Aβ+GFP-LV group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ +mPirB-LV group were significantly increased(P<0.05).The results of Western blotting showed that compared with control group,the expression of GFAP in Aβ group was significantly increased(P<0.05);Compared with Aβ group,the expression of GFAP in Aβ+0.4 μmol/L PEP group was significantly decreased(P<0.05).Conclusions PirB is an upstream molecule which could regulate astrocyte proliferation and reactive astrogliosis,and inhibiting PirB receptor in astrocytes may be a potential treatment for Alzheimer's disease.

Objective: To examine the associations between metabolic syndrome (MS) and the risks for impaired activities of daily living (ADL) in the middle-aged and elderly population in China and provide basis for improving healthy life expectancy. Methods: Prospective cohort study design was used in this study. Based the data of China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018 and the baseline data in 2011, the follow up for ADL outcomes was conducted in 2013, 2015 and 2018 respectively, and the participants recruited in 2013 and 2015 were new baseline populations. The participants with impaired ADL in three baseline populations were excluded. Cox proportional hazard model was used to estimate the effect of different components and number of MS components on the risk for ADL impairment in the middle-aged and elderly population in China. Results: In 59 795 person-years of follow-up, a total of 1 011 cases of ADL impairments were recorded. The incidence density of ADL impairment was 16.91 per 1 000 person-year; The findings of Cox regression analysis showed that compared with the middle aged and elderly people without MS, the risk for ADL impairments was 1.29 times higher (95%CI: 1.12-1.50) for those with one component of MS, 1.32 times higher (95%CI:1.07-1.64) for those with hyperlipemia complicated with diabetes, 1.78 times higher (95%CI: 1.22-2.59) for those with obesity and one component of MS, 2.48 times higher (95%CI:1.59-3.85) for those with hypertension complicated with hyperlipemia, 3.51 times higher (95%CI:1.66-7.43) for those with hypertension complicated with diabetes, 1.80 times higher (95%CI: 1.40-2.32) for those with ≥3 MS, respectively. Compared with the middle-aged and elderly population without MS, the risk for impaired ADL increased by 30% (HR=1.30, 95%CI: 1.13-1.51), 54% (HR=1.54, 95%CI: 1.28-1.85) and 87% (HR=1.87, 95%CI:1.45-2.41), respectively, in the middle-aged and elderly with one, two, and more than three components of MS, with a significant dose-response relationship that ADL impaired risks increased as the number of MS components increased (P<0.001). Conclusions: Our findings suggested that MS is a risk factor for ADL impairment in middle-aged and elderly population in China. Prevention and early intervention of obesity, hypertension, hyperlipemia, diabetes and metabolic syndrome could help to reduce or delay the incidence of ADL impairment.
Activities of Daily Living ; Aged ; China/epidemiology* ; Humans ; Longitudinal Studies ; Metabolic Syndrome/epidemiology* ; Middle Aged ; Prospective Studies

OBJECTIVE: To observe the efficacy of chimeric antigen receptor T cell (CAR-T) in the treatment of children with refractory/recurrent B acute lymphocytic leukemia (B-ALL). METHODS: Thirty-two patients with r/r B-ALL were treated by CAR-T, the recurrence and death respectively were the end point events to evaluate the efficacy and safety of CAR-T. RESULTS: The median age of the patients was 7.5 (2-17.5) years old; 40 times CAR-T were received in all patients and the median number of CAR-T was 0.9×107/kg; efficacy evaluation showed that 2 cases died before the first evaluation. Thirty patients showed that 3, 6, and 9-moth RFS was (96.3±3.6)%, (81.4±8.6)% and (65.3±12.5)%, respectively, while 3, 6, and 9-month OS was all 100%, and 12, 24-month OS was (94.7±5.1)% and (76±12.8)%. BM blasts≥36% before reinfusion and ferritin peak≥2 500 ng/ml within two weeks of CAR-T cell reinfusion were associated with recurrence. Adverse reactions mainly included cytokine release syndrome (CRS) and CART-cell-related encephalopathy syndrome (CRES), CRS appeared in 26 patients within a week of CAR-T cell reinfusion. CRES reaction was detected in 12 patients. Eighteen patients received intravenous drip of tocilizumab, among them, 12 combined with glucocorticoid. CRS and CRES reactions were relieved within one week after treatment. Hormone dosage was related to the duration of remission in patients, and the cumulative dose of methylprednisolone≥8 mg/kg showed a poor prognosis. CONCLUSION CAR-T is a safe and effective treatment for r/r B-ALL, most CRS and CRES reactions are reversible. BM blasts ≥36% before reinfusion and cumulative dose of methylprednisolone ≥8 mg/kg after reinfusion both affect the therapeutic effect. Ferritin≥2 500 ng/ml within two weeks after reinfusion is related to disease recurrence and is an independent prognostic risk factor.
Adolescent ; Antigens, CD19 ; Child ; Child, Preschool ; Chronic Disease ; Ferritins ; Humans ; Immunotherapy, Adoptive ; Methylprednisolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen/metabolism* ; Recurrence ; T-Lymphocytes

Objective: To identify the risk factors related to perinatal complications in patients with pulmonary hypertension underwent cesarean section. Methods: We retrospectively analyzed the medical records of all pregnant women with pulmonary hypertension hospitalized in 4 different hospitals in Shandong province and underwent cesarean section between May 2010 and May 2020. Patients were divided into perinatal complication group and control group according to the presence or absence of perinatal complications. Perinatal complications included aggravated heart function, new onset arrythmias, sudden cardiac arrest, all-cause death within 42 days post cesarean section, postpartum bleeding and thrombotic events. Risk factors of perinatal complications were analyzed. Results: A total of 167 patients (47 cases in the perinatal complication group and 120 cases in the control group) were included in this study. The average age of this cohort was 28(24, 32) years, and 75(44.9%) patients suffered newly diagnosed pulmonary hypertension during pregnancy. The main cause of pulmonary hypertension was congenital heart disease (137(82.0%)). Age, pregnant weeks, percent of primipara, intra-cardiac shunt, and receiving targeted medication therapy, cardiac dimensions were similar between the two groups. A total of 62 complications were recorded in the complication group including 28 cases of aggravated heart function, 4 cases of new onset arrythmias, 2 cases of cardiac arrest, 11 cases of bleeding or thrombotic events and 17 patients were dead. Prevalence of idiopathic pulmonary hypertension and general anesthesia was significantly higher, functional capacity was significantly lower in perinatal complication group than in control group (all P<0.05). The estimated systolic pulmonary artery pressure, serum N-terminal pro-B type natriuretic peptide and total bilirubin (TBIL) levels were significantly higher in perinatal complication group than in control group (all P<0.05). Logistic analysis demonstrated WHO Function Class(FC) Ⅲ/Ⅳ (OR=2.416,95%CI 1.016-5.743, P=0.046) and TBIL level (OR=6.874,95%CI 1.643-28.757, P=0.008) were the independent risk factors of perinatal complications. Conclusion: TBIL and WHO FC are independent risk factors of perinatal complications in pregnant women with pulmonary hypertension underwent cesarean section.
Cesarean Section/adverse effects* ; China/epidemiology* ; Female ; Humans ; Hypertension, Pulmonary/epidemiology* ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies ; Risk Factors

Objective:To explore the optimal local treatment pattern of supraclavicular lymph node in breast cancer patients with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM).Methods:Clinical data of 128 breast cancer patients with sISLM admitted to the Fourth Hospital of Hebei Medical University from 2010 to 2015 were retrospectively analyzed. Among them, 68 cases were treated with supraclavicular lymph node dissection combined with radiotherapy, and 60 cases received radiotherapy alone. The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were statistically compared between two groups.Results:Univariate analysis demonstrated that the 5-year LRFS, DMFS, PFS and OS did not significantly differ between two groups (all P>0.05). Multivariate analysis revealed that the local treatment pattern of supraclavicular lymph node was an independent prognostic factor for the 5-year DMFS, PFS and OS (all P<0.05). Subgroup analysis showed that when radiotherapy alone was performed, the 5-year OS of patients in the supraclavicular region radiation dose of>50 Gy group were significantly better than that in the 50 Gy group ( P=0.047). When supraclavicular lymph node dissection combined with radiotherapy was delivered, if the number of dissection was less than 10, the 5-year LRFS, DMFS, PFS, OS of patients in the>50 Gy group were all better than those in the 50 Gy group numerically without statistical significance (all P>0.05). If the number of dissection was ≥10, the 5-year LRFS, DMFS, PFS, OS in the 50 Gy group were better than those in the>50 Gy group numerically, whereas significant difference was only found in the 5-year DMFS ( P=0.028). Conclusions:Supraclavicular lymph node dissection combined with radiotherapy may be the optimal local treatment pattern for supraclavicular lymph node. When radiotherapy alone is performed, a radiation boost to the supraclavicular region may improve OS. When supraclavicular lymph node dissection combined with radiotherapy is performed, if the degree of dissection is low, a radiation boost to the supraclavicular region may bring clinical benefits. However, if the degree of dissection is high, a radiation boost to the supraclavicular region may not bring significant clinical benefits.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective:To explore the change of serum 25-hydroxyvitamin D [25(OH)D] and prediction for outcome of acute ischemic stroke in emergency. Methods:From October, 2017 to September, 2019, 224 patients with acute ischemic stroke in emergency and 240 healthy controls were detected serum 25(OH)D within 24 hours after enrollment. The patients were assessed with National Institute of Health Stroke Scale (NIHSS) and Nutritional Risk Screening 2002 (NRS2002), and measured biochemics within 24 hours after admission. They were assessed with modified Rankin Scale (mRS) 180 days after stroke, and divided into favourable group (mRS ≤ 2, n = 106) and unfavourable group (mRS > 2, n = 118). The factors related with the outcome were analyzed with Logistic regression, and the prediction of 25(OH)D for the outcome were analyzed with receiver operator characteristic (ROC) curve. Results:Serum 25(OH)D was less in the patients than in the controls (Z = 4.296, P < 0.001), and less in the unfavourable group than in the favourable group (Z = 5.876, P < 0.001). Serum 25(OH)D (OR = 0.925, P < 0.05) was related with the outcome even controlling the impacts of age, sex, nutritional risk, infarct volume, scores of NIHSS, etc. The area under curve for serum 25(OH)D predicting outcome was 0.795 (P < 0.001). The cut-off point of prediction was 13.17 ng/ml, with the Yoden index of 0.548, which yielded a sensitivity of 0.746 and a specificity of 0.802. Conclusion:Serum 25-hydroxyvitamin D may predict the outcome 180 days after acute ischemic stroke, which may help for risk stratification in emergency.

Objective:To explore the efficacy of different unipolar electrocoagulation power on pathological injury of porcine kidney suffering suture-free partial nephrectomy (SFPN).Methods:From April 2018 to July 2018, nine Guizhou pigs were selected, with an average age of 3 years and an average weight of 48 kg. According to different hemostatic power of unipolar electrocoagulation during open partial nephrectomy, they were divided into three groups(60W group, 80W group, and 100W group), with 3 in each group. The left kidney was exposed with a surgical incision, parallel to the lumbosacral muscle.The left renal artery was clamped and about 2 cm renal tissue was excised at the middle pole of the left kidney. 60W, 80W and 100W were used by unipolar electrocoagulation for hemostasis until no bleeding occurred after the artery clamp was released. The total ischemia time was controlled within 20 min. Temperature was measured by a multi-channel thermometer probe which was inserted into the healthy kidney tissue at a distance of 2 mm, 5 mm, and 10 mm away from the unipolar electrocoagulation hook, and the upper pole of the kidney far away from the operation area. The time of operation, the volume of renal bleeding, the time of hemostasis and the temperature were recorded. On the 7th day after operation, the left kidneys were taken and the pathological changes were observed by toluidine blue staining.Results:All operations were completed safely and successfully. The operation time in 60W group, 80W group, and 100W group was (41.2±5.5)min, (35.1±3.7)min, (31.3±2.2)min , respectively. There was no significant difference of operation time among those group ( P>0.05). The blood loss of renal was (35.3±4.1)ml, (21.4±4.7)ml, (15.3±4.1)ml, respectively. The blood loss in the 100W group and 80W group was less than that in the 60W group ( P<0.05). And the blood loss in the 100W group was less than that in the 80W group ( P<0.05). The hemostasis time was (15.2±1.9)min, (10.1±1.4)min, (6.4±0.8)min. The hemostasis time in the 100W and 80W groups was less than that in the 60W group ( P<0.05). And the hemostasis time in the 100W group was less than that in the 80W group ( P<0.05). At the place of 10 mm away from the electrocoagulation hook, the temperature in the three groups were (33.1±1.1)℃, (34.0±1.0)℃, (34.3±0.6)℃, which was not significantly different from that of the respective upper poles. And there was no significant difference between the three groups( P>0.05). At the place of 5 mm and 2 mm away from the electrocoagulation hook, the temperature in the 100W group (41.7±1.3)℃, (61.4±6.4)℃ and the 80W group (38.6±2.4)℃, (50.3±6.0)℃ was higher than that in the 60W group (36.9±4.1)℃, (42.0±4.7)℃, and the temperature in 100W group is higher than that in 80W group ( P<0.05). When the power was 60W, 80W or 100W, the temperature in the place 10 mm away from the electrocoagulation hook was less than that in the place 5 mm away from the electrocoagulation hook ( P<0.05), and the temperature of the place 5 mm away from the electrocoagulation hook was lower than that of the place 2 mm away from the electrocoagulation hook ( P<0.05). The total pathological injury depth of wounds in 60W, 80W, 100W group was (7 323±50)μm, (8 119±100)μm, (8 896±40)μm, respectively. The depth in 100W group and 80W group was deeper than that in 60W group ( P<0.05), and the depth in 100W group was deeper than that in 80W group ( P<0.05). Conclusions:In SFPN, the hemostatic effect of three different monopolar electrocoagulation output power is satisfactory. With the increase of power, the hemostasis speed is faster. However, the temperature of surrounding healthy renal tissue would be higher, and the total pathological injury depth would be deeper.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective: To study the effects of muskolibanum combination on the proliferation and differentiation of prostate stem cells. METHODS: We cultured prostate epithelial cells and urogenital sinus mesenchymal (UGSM) cells from 7－10 d old C57BL/6 mice and 16－18 d old pregnant C57BL/6 mice, transplanted the mixed suspension of the two types of cells under the kidney envelope of SCIDCB.17 male mice, and harvested the transplants 30 days later. We randomly divided the SCIDCB.17 mice into four groups to be treated intragastrically with musk (n = 8), olibanum (n = 8), musk+olibanum (n = 7), and normal saline (blank control, n = 8)) respectively, all for 14 days. Then we collected the kidney tissue for observation of the morphology of the glandular tubes and differentiation of different subsets of stem cells by HE staining and determination of the expressions and distribution of P63, CD133, CD117 and Sca1 by immunohistochemistry and Western blot. RESULTS: A system was successfully established for the isolation and mixed culture of Sca1 Lin+ CD49f+ (LSC) cells of prostate stem cells and UGSM cells of the mouse embryonic prostate. Immunohistochemistry showed positive expressions of P63, CD133, Sca1, and CD117 in the prostatic acinar epithelia and proved the presence of prostatic acinar epithelial structure in the transplants. Compared with the blank control group, the expressions of CD133, Sca1 and CD117 were significantly increased in the musk, olibanum, and musk+olibanum groups (P< 0.05), higher in the musk+olibanum than in the musk or olibanum group (P< 0.05), and their protein expressions were even more elevated in the musk+olibanum group (P< 0.01), with statistically significant difference from the olibanum group (P< 0.05). CONCLUSIONS The combination of musk and olibanum can improve the proliferation and differentiation of prostate stem cells.
Animals ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Drug Therapy, Combination ; Epithelial Cells ; cytology ; drug effects ; Fatty Acids, Monounsaturated ; pharmacology ; Female ; Frankincense ; pharmacology ; Male ; Mesenchymal Stem Cells ; cytology ; drug effects ; Mice ; Mice, Inbred C57BL ; Mice, SCID ; Pregnancy ; Prostate ; cytology ; Random Allocation ; Receptor Protein-Tyrosine Kinases ; Receptors, Cholinergic ; Stem Cells ; cytology ; drug effects