AIM: To study the role of protein kinase B (PKB) in tryptase-induced gene expression on ECV304 cells. METHODS: The expression of PKB, transcript factor AP-1 and NF-?B P65, IL-8, JNK, p38MAPK, and the activity of PKB were measured using RT-PCR and Western blotting. RESULTS: Tryptase at concentration of 1 ?g/L increased the activity of PKB by promoting PKB phosphorylation, promoted the expression of PKB, chemokine IL-8, transcription factor AP-1 and NF-?B P65, however, no changes of JNK and p38MAPK was observed. PI3K specific inhibitor (LY294002) abolished the augment of PKB, NF-?B P65 and IL-8 expression. Antisense PKB cDNA transfection also abolished the augment of PKB, AP-1, NF-?B P65 and IL-8 expression. Though PAR2 antibody did not inhibit PKB expression, it did inhibit the phosphorylation by tryptase in ECV304 cells. CONCLUSION: These results indicate that tryptase can activate PKB through PAR2 receptor and subsequently NF-?B, AP1, IL-8 and PKB expression.

Pituitary tumors are clinically common neoplasms involved in the central nervous system. The endoscopic endonasal approach is a safe and feasible technique for managing pituitary tumors. Endoscopic technology has been increasingly used in clinical practice because it results in limited nasal injury, decreased operating time and postoperative complications, and quick postoperative re-covery. This study aims to evaluate the advantages and effectiveness of the endoscopic endonasal transsphenoidal approach for the re-moval of pituitary tumors. This approach should be further modified and optimized in clinical trials and practices.

Objective:To clarify the significance of the fractional anisotropy(FA) value and apparent diffusion coefficient(ADC) value of diffusion tensor imaging(DTI) applied in the glioma grading with Meta-analysis, and to provide a reference for selecting the treatment program and judging the prognosis of glioma.Methods:Computer search was performed in PubMed database, EMBASE database,CBM, CNKI, Wanfang database, and VIP database.The relevant neurosurgery magazines and neuroimaging magazines, the proceedings of academic meeting were retrieved by hand and the references of related reviews were retrospectively retrieved.Then the case-series studies according to inclusion and exclusion criteria were screened,and the qualities of included studies were evaluated.Meta-analysis was carried out by Review Manager 5.2 software.Results:Nine studies were included.The FA value of low-grade glioma(LGG) in tumor centre was lower than that of high-grade glioma(HGG) (χ2=11.94,df=8,P=0.15;I2=33%,Z=2.78,P=0.005;WMDFA=-0.02,95%CI:-0.03--0.01),and the ADC value of LGG in tumor centre was higher than that of HGG (χ2=5.26,df=4,P=0.26;I2=24%,Z=2.19,P=0.03;WMDADC=0.15,95%CI:0.02-0.28).Conclusion:When the FA value in tumor centre of the glioma is increasd,the ADC value is decreased,and the grade of glioma is increasd.The FA value and ADC value of DTI can help determine the grade of gliomas.

MicroRNAs (miRNAs) are a class of small, single-stranded non-coding RNAs that act as important regulators of gene expression and are involved in a number of important processes in life. A large number of studies have suggested that dysregulation of miRNA expression may be an important part of the mechanism of human tumorigenesis and progression. MiR-155-5p is mainly regarded as an oncomiR that acts on multiple target genes to participate in tumor progression, although it has been suggested to possess cancer growth suppressor effects. In this paper, we summarize the effects of miR-155-5p on cancer cell proliferation, invasion, migration, and drug resistance in various tumor types and elucidate its value as a possible potential marker in assisting diagnosis.

Objective:To explore the efficacy of single-plane bi-parameter magnetic resonance imaging (bpMRI) in the diagnosis of prostate cancer.Methods:The clinical data of 343 patients who underwent transperineal template prostate magnetic resonance-transrectal ultrasound (MRI-TRUS) cognitive fusion biopsy at the First Affiliated Hospital of Nanjing Medical University from January 2020 to July 2021 were retrospectively analyzed, with median age of [65.0(59.0, 72.0)] years, median body mass index (BMI) of [24.1(22.2, 25.6)]kg/m 2, median prostate volume (PV) of [41.7(29.1, 53.3)]ml, median PSA[6.9 (5.5, 8.4) ng/ml], median PSAD of[0.17(0.12, 0.22) ng/ml 2], and abnormal rate of digital rectal examination (DRE) [6.4%(22/343)]. All patients underwent initial biopsy and bi-parameter magnetic resonance imaging (bpMRI) examination before biopsy, and the images were interpreted using prostate image reporting and data system version 2.1 (PI-RADS v2.1). The detection rates of prostate cancer and clinically significant prostate cancer (csPCa) were compared between single-plane bpMRI and bpMRI. When PI-RADS≥3 score, MRI results were positive; when PI-RADS ≤2 score, MRI results were negative. Results:In the single-plane bpMRI group, 121 MRI results were negative and 222 were positive. Positive patients included 95 with PI-RADS 3 score, 94 with PI-RADS 4 score, and 33 with PI-RADS 5 score. In bpMRI group, 141 MRI results were negative and 202 were positive. Among the positive patients, 67 patients with PI-RADS 3 score, 102 patients with PI-RADS 4 score, and 33 patients with PI-RADS 5 score. The detection rates of single-plane bpMRI and bpMRI for prostate cancer were 22.3% (27/121) and 15.6% (22/141) in MRI negative cases[22.3% (27/121) and 15.6% (22/141), P=0.17], and PI-RADS scores with 3 points [35.8% (34/95) vs. 44.8% (30/67), P=0.25], 4 points [89.4% (84/94)vs. 90.2% (92/102), P=0.85] and 5 points [90.9% (30/33) vs. 93.9% (31/33), P=1.00] showed no significant difference in stratification. The detection rate of csPCa in the single-plane bpMRI group and bpMRI group was significantly different in the MRI negative cases [7.4% (9/121) and 2.1% (3/141), P=0.04]. PI-RADS scores with 3 points [22.1% (21/95) vs. 29.9% (20/67), P=0.27], 4 points [80.9% (76/94) vs. 79.4% (81/102), P=0.80] and 5 points [84.9% (28/33) vs. 90.9% (30/33), P=0.71] showed no significant difference in stratification. Conclusions:For those suspected of prostate cancer patients with PSA 4-10 ng/ml and PI-RADS score ≥3, single-plane bpMRI or bpMRI examination has the same efficacy in term of the detection rate of prostate cancer and csPCa.

Objective: To explore physical health status and influencing factors of preschool children in Tibet, so as to provide a scientific reference and theoretical basis for the healthy development of physical fitness. Methods: Data were collected from children (3-6 years old) of Xizang national physical fitness monitoring, and a total of 1 521 preschool children were recruited who received questionnaire survey and physical fitness test. Independent sample t-test and one-way ANOVA were used to compare the differences in physical fitness indexes of preschool children in different groups. Chi square test and binary Logistic regression model were used to analyze the factors affecting physical health of preschool children. Results: The total qualified rate of physical fitness was 79.75%, among which the excellent rate was 3.16%, the good rate was 15.12%, the qualified rate was 61.47% and the unqualified was 20.25%. From the perspective of BMI, the excellent physical fitness rate (3.74%) and good physical fitness rate ( 17.47% ) were highest in healthy weight preschool children, and the qualified physical fitness rate of overweight preschool children (69.03%) was higher than that of obese (55.88%) and healthy weight preschool children (60.68%)( χ 2=53.56, P <0.01). From the perspective of ethnic, Tibetan children s physique proficiency (3.69%), good rate ( 17.13% ) than with the elevation of the Han nationality (0.74%, 5.88%), fraction defective (16.97%), lower than that of Han nationality (35.29%) ( χ 2=53.71, P <0.01); The results of chest circumference, skinfold thickness, body fat percentage, tennis throw distance, continuous jump of both feet, sitting forward bend and balance beam walking of Tibetan children were higher than those of Han children, and the results of quiet heart rate and standing long jump were lower than those of Han children ( t = 2.72 , 10.95, 9.66, 3.68, 3.88, 8.04, 3.56, 8.70, -4.39 , -4.40, P <0.01). Binary Logistic regression analysis showed that Tibetans ( OR =2.29), breastfeeding ( OR =1.51), body dynamics outdoor daily exercise duration 30-90 min (30-<60 min ;OR = 2.03 ; 60-90 min: OR =2.22) were positively correlated with physical health of preschool children ( P <0.05). Conclusions The total physical qualification rate of preschool children aged 3-6 years old in Tibet is lower than the national average. Ethnic group, feeding pattern during infancy, and physical activity are all factors that affected the physical fitness of preschool children in Tibet. It is of great significance to improve the physique of preschool children in Tibet to promote their sustainable and healthy development.

Objective To investigate the effects of Zhoufei Pingchuan Capsules on the balance of peripheral blood helper T lymphocyte 17 cell/regulatory T lymphocyte cell(Th17/Treg)and related inflammatory factors in peripheral blood of patients with stable chronic obstructive pulmonary disease(COPD)with lung-kidney qi deficiency syndrome.Methods Totally 40 COPD patients were randomly divided into the study group and the control group,with 20 cases in each group.Another 20 cases were in the healthy group.The control group was given tiotropium bromide powder inhalation,18 μg/time,1 time/d,inhalation;on the basis of the control group,the study group was given Zhoufei Pingchuan Capsules,3 pills/time,3 times/d,orally.All patients were treated for 8 weeks.The healthy group was not given any intervention.Forced expiratory volume in one second(FEV1),FEV1/forced vital capacity(FEV1/FVC),maximum mid-expiratory flow(MMEF),carbon monoxide diffusing capacity/alveolar ventilation(DLCO/VA),arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),COPD assessment test(CAT)score,Th17/Treg ratio,cytokines interleukin(IL)-17,IL-22,IL-10,and transforming growth factor-β1(TGF-β1)were compared before and after treatment.Results Compared with before treatment,the lung function indexes(FEV1,FEV1/FVC,MMEF,DLCO/VA),blood gas indexes(PaO2,PaCO2)and CAT score in the study group after treatment were significantly improved(P<0.05).After treatment,the mean values of MMEF,DLCO/VA,PaCO2 and CAT score in the study group were better than those in the control group(P<0.05).Compared with before treatment,the levels of Th17,IL-17 and IL-22 in the study group were significantly lower,and the levels of Treg,IL-10 and TGF-β1 were significantly higher(P<0.05).After treatment,there were significant differences in Th17,Treg,IL-17,IL-22,IL-10 and TGF-β1 among the three groups(P<0.01).Further pairwise comparison showed that Th17 ranked in the order of high and low was control group>study group>healthy group,Treg in the order of high and low was healthy group>study group>control group,the levels of IL-17 and IL-22 in the order of high and low were control group>study group>healthy group,and the levels of IL-10 and TGF-β1 in the order of high and low were healthy group>study group>control group,with statistical significance(P<0.05).Conclusion Zhoufei Pingchuan Capsules can improve the lung function,arterial blood gas and symptom score of patients with lung-kidney qi deficiency syndrome in stable stage of COPD.Its mechanism may be related to regulating the balance of Th17/Treg,down-regulating the levels of Th17,IL-17 and IL-22,and up-regulating the levels of Treg,IL-10 and TGF-β1,in order to reduce airway inflammation and regulate immune homeostasis.

Objective:To analyze the clinical features and magnetic resonance imaging of non-malignant patients assigned to Prostate Imaging Reporting And Data System (PI-RADS) 5 score.Methods:We performed a retrospective review of 289 patients who underwent magnetic resonance ultrasound targeted combined system biopsy with PI-RADS 5 lesions in the First Affiliated Hospital of Nanjing Medical University between May 2019 and July 2021. The median age 72 (66, 77)years, median body mass index 24.4(22.3, 27.1)kg/m 2, median prostate volume (PV) 37.39(29.39, 48.86) ml, median PSA 22.24(10.91, 62.69) ng/ml, and median PSAD 0.53(0.30, 1.52)ng/ml 2 were recorded. According to the biopsy pathological results, all patients were divided into benign lesion group and prostate cancer group. PSA, PSAD, PV, and apparent diffusion coefficient (ADC) values were compared, and magnetic resonance imaging and clinical characteristics of patients with biopsy benign lesions were analyzed. Results:There were 11 cases (3.8%) with benign lesion and 278 cases (96.2%) with prostate cancer. The characters of 11 negative biopsy cases were displayed as follows: median age 69(66, 79)years, median body mass index 22.0(21.0, 25.5)kg/m 2, median PV 62.90(38.48, 71.96)ml, median PSA 5.55(2.99, 20.52)ng/ml, median PSAD 0.16(0.07, 0.24) ng/ml 2, median ADC 714.47(701.91, 801.26)×10 -6 mm 2/s, abnormal digital rectal and amination in 5 cases, smoking in 7 cases, and alcohol consumption in 4 cases. The median PV [62.90(38.48, 71.96) vs. 37.21(29.22, 47.82)ml, P<0.01], the PSA value [5.55(2.99, 20.52) vs. 23.53(11.14, 65.98)ng/ml, P<0.01], and the PSAD value [0.16(0.07, 0.24) vs. 0.58(0.31, 1.57)ng/ml 2, P<0.01] were significantly different between benign condition group and prostate carcinoma group. Benign condition group included 5 chronic prostatitis, 2 acute prostatitis (1 with focal adenocarcinoma), 2 granulomatous inflammation, and 2 tuberculous granulomatous inflammation. In 7 benign cases, PSA was less than 10 ng/ml, combined with frequent urination, urgency of urination and incontinence were founded. In 8 benign cases, the area of lesion was more than 50% of the total prostate area in the axial position and the imaging of magnetic resonance were diffused, with regular shape and uniform signal. The imaging of symmetrical distribution was in 6 cases. Conclusions:The benign condition with PI-RADS 5 lesions included chronic prostatitis, acute prostatitis, granulomatous inflammation and tuberculous granulomatous inflammation, among which prostatitis was the most common cause. The PSA value were less than 10 ng/ml in most benign cases, with symptoms such as frequent urination, urgency of urination and incontinence. The imaging of magnetic resonance were diffused, symmetrically distributed, with regular shape and uniform signal.

Objective:To examine the physical health status and factors affecting individuals aged 60-69 years in certain regions of Tibet.Methods:The study analyzed data collected from 824 individuals aged 60-69 from the Xizang national physique monitoring.Chi-square test and binary logistic regression were used to identify factors that affect the physical health of this age group.Results:The study evaluated the physical fitness of elderly individuals aged 60 to 69 years old in three regions of Tibet.The results indicated that only 11 cases(1.3%)of participants had excellent physical fitness, while 47 cases(5.7%) had good physical fitness, 394 cases(47.8%)were qualified, and 372 cases(45.1%)were unqualified.The study also found significant differences in physical fitness based on age( χ2=8.367, P=0.039), sex( χ2=22.168, P<0.001), urban/rural location( χ2=12.282, P=0.006), region( χ2=60.358, P<0.001), and body mass index(BMI)( χ2=105.134, P<0.001). Specifically, individuals aged 60-64 years old had a higher proportion of qualified physique than those aged 65-69 years old.Women had better physical fitness than men, and individuals living in urban areas had better physical fitness than those in rural areas.Moreover, participants from Lhasa and Nagqu regions had better physical fitness than those from Nyingchi.Obese elderly individuals had worse physical fitness than those with normal weight(all P<0.05 for all). The study found that female gender( OR=1.765, 95% CI: 1.284-2.425), being a Lhasa( OR=2.799, 95% CI: 1.677-4.672)or Naqu resident( OR=2.730, 95% CI: 1.677-4.445), and engaging in regular exercise( OR=1.845, 95% CI: 1.078-3.160)were protective factors for physical health among individuals aged 60-69 years old.However, not working( OR=0.503, 95% CI: 0.289~0.876)and obesity( OR=0.108, 95% CI: 0.066-0.177)were identified as risk factors for physical health in this age group.Additionally, the analysis revealed significant differences in fitness ratios based on exercise frequency( χ2=18.760, P<0.001)and exercise time( χ2=15.485, P<0.001). Specifically, the fitness ratio of individuals who exercised 1-2 times and 3-4 times a week was significantly higher than that of non-exercisers.The fitness ratio of elderly individuals who exercised for 30 to 60 minutes per session was significantly higher than those who exercised for less than 30 minutes.Furthermore, those who exercised 3-4 times per week had a fitness ratio 2.58 times higher than those who did not exercise at all( P<0.05). Conclusions:This study conducted in Nyingchi, Lhasa, and Nagqu of Tibet found that 45.1% of individuals aged 60-69 years had an unqualified physique.There was a negative correlation between non-employment and BMI≥28 kg/m 2 with physical health, whereas female gender, residing in Lhasa or Nagqu, and engaging in regular physical exercise showed a positive correlation.The study suggests that physical exercise for 30-60 minutes, 3-4 times a week, can significantly improve the proportion of qualified physical fitness among the elderly.

Biological rhythms controlled by the circadian clock are absent in embryonic stem cells (ESCs). However, they start to develop during the differentiation of pluripotent ESCs to downstream cells. Conversely, biological rhythms in adult somatic cells disappear when they are reprogrammed into induced pluripotent stem cells (iPSCs). These studies indicated that the development of biological rhythms in ESCs might be closely associated with the maintenance and differentiation of ESCs. The core circadian gene Clock is essential for regulation of biological rhythms. Its role in the development of biological rhythms of ESCs is totally unknown. Here, we used CRISPR/CAS9-mediated genetic editing techniques, to completely knock out the Clock expression in mouse ESCs. By AP, teratoma formation, quantitative real-time PCR and Immunofluorescent staining, we did not find any difference between Clock knockout mESCs and wild type mESCs in morphology and pluripotent capability under the pluripotent state. In brief, these data indicated Clock did not influence the maintaining of pluripotent state. However, they exhibited decreased proliferation and increased apoptosis. Furthermore, the biological rhythms failed to develop in Clock knockout mESCs after spontaneous differentiation, which indicated that there was no compensational factor in most peripheral tissues as described in mice models before (DeBruyne et al., 2007b). After spontaneous differentiation, loss of CLOCK protein due to Clock gene silencing induced spontaneous differentiation of mESCs, indicating an exit from the pluripotent state, or its differentiating ability. Our findings indicate that the core circadian gene Clock may be essential during normal mESCs differentiation by regulating mESCs proliferation, apoptosis and activity.
Animals ; Apoptosis ; Base Sequence ; CLOCK Proteins ; genetics ; metabolism ; CRISPR-Cas Systems ; Cell Differentiation ; Cell Proliferation ; Cellular Reprogramming ; Circadian Clocks ; genetics ; Gene Editing ; Gene Expression Regulation ; Gene Knockout Techniques ; Hepatocyte Nuclear Factor 3-beta ; genetics ; metabolism ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Mice ; Mouse Embryonic Stem Cells ; cytology ; metabolism ; SOXB1 Transcription Factors ; genetics ; metabolism