Objective To study the repeatability and consistency of normal female pelvic floor structure using transperineal real‐time three‐dimensional ultrasound .Methods Forty‐two cases of normal adult female were evaluated by two different experience operator ,using the real‐time three‐dimensional ultrasound diagnostic apparatus .The bladder neck movement degrees and the levator hiatus area were observed after Valsalva condition .Differences between the groups were compared .Intraclass correlation coefficient (ICC) ,the coefficient of variation (CV) and Bland‐Altman analysis of consistency were evaluated . Results The bladder neck movement degrees and the levator hiatus area measured by the experienced operator (operator 1) and less experienced operator(operator 2) were (18 4.8 ± 5 8.4)cm and (17 7.9 ± 5 4.8) cm ,(17 5.3 ± 3 9.5)cm2 and (17 3.1 ± 4 3.2)cm2 ,respectively .There was no significant difference between the two operators ( P > 0 0.5) .The intra‐ICC were 0 8.9 and 0 9.0 ,CV were 7 2.6% and 3 0.3% .Experienced operator repeatability (ICC= 0 9.9 ,0 9.4) was slightly higher than the less experienced researchers (ICC 0 9.2 ,0 8.1) .The analysis results of Bland‐Altman image showed good consistency between two different operators .Conclusions The current study proves real‐time three‐dimensional ultrasound is a reproducible method for female pelvic floor structure assessment ,and the reproducibility is very well .The detection performance of experienced operator slightly better than the one with less experience ,strengthen the training of junior doctors may further improve the accuracy of measurement .

Objective To investigate the application value of transperineal ultrasound in female patients with cystocele.Methods Transperineal ultrasound were performed in 36 female patients with cystocele and the bladder neck movement degrees (BND),retrovesical angle and the degree of urethral rotation were observed at maximum Valsalva.The ultrasonic manifestation of 36 female patients with cystocele were summarized.Results On maximal Valsalva bladder neck mobility all increased in 36 patients,32 patients with open retrovesical angle (≥140°) and 30 female patients with urethral rotation ≥ 45°.There were 6 cases with type Ⅰ,bladder neck was lower than inferoposterior margin of the symphysis pubis,cystocele with open retrovesical angle (≥140°) and urethral rotation ＜45°.There were 26 cases with type Ⅱ,bladder neck was lower than inferoposterior margin of the symphysis pubis,cystocele with open retrovesical angle (≥140°) and urethral rotation ≥45°.There were 4 cases with type Ⅲ,bladder was lower than inferoposterior margin of the symphysis pubis,cystocele with intact retrovesical angle (＜ 140°) and urethral rotation ≥45°.Conclusions The transperineal ultrasound can be used for classification of cystocele in female patients and which may provide more reliable information for clinical diagnosis.

Objective To explore the effects of Qingshen Granules(QSG)on adenine-induced renal fibrosis in mice and in uric acid(UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes,miR-330-3p and CREBBP.Methods A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks.An adeno-associated virus vector was injected into the tail vein,and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9,Hsp70,and TSG101 and expressions of Col-Ⅲ,α-SMA,FN,and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining.In the cell experiment,NRK-49F cells were stimulated with uric acid(400 μmol/L)followed by treatment with QSG-medicated serum from SD rats,and the changes in expressions of the exosomal markers and Col-Ⅲ,α-SMA,FN,and E-cad were analyzed.Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP,whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells.Results The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9,Hsp70,and TSG101,which were decreased by treatment with QSG.The expressions of Col-Ⅲ,α-SMA,and FN increased and E-cad decreased in the mouse models but these changes were reversed by QSG treatment.QSG treatment obviously alleviated renal fibrosis in the mouse models.Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p,increased CREBBP levels,and reduced fibrosis in the mouse models.Dual luciferase assay confirmed CREBBP as a target of miR-330-3p,which was consistent with the results of the cell experiments.Conclusion QSG inhibits renal fibrosis in mice by regulating the exosomes,reducing miR-330-3p levels,and increasing CREBBP expression.

Objective To explore the effects of Qingshen Granules(QSG)on adenine-induced renal fibrosis in mice and in uric acid(UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes,miR-330-3p and CREBBP.Methods A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks.An adeno-associated virus vector was injected into the tail vein,and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9,Hsp70,and TSG101 and expressions of Col-Ⅲ,α-SMA,FN,and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining.In the cell experiment,NRK-49F cells were stimulated with uric acid(400 μmol/L)followed by treatment with QSG-medicated serum from SD rats,and the changes in expressions of the exosomal markers and Col-Ⅲ,α-SMA,FN,and E-cad were analyzed.Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP,whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells.Results The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9,Hsp70,and TSG101,which were decreased by treatment with QSG.The expressions of Col-Ⅲ,α-SMA,and FN increased and E-cad decreased in the mouse models but these changes were reversed by QSG treatment.QSG treatment obviously alleviated renal fibrosis in the mouse models.Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p,increased CREBBP levels,and reduced fibrosis in the mouse models.Dual luciferase assay confirmed CREBBP as a target of miR-330-3p,which was consistent with the results of the cell experiments.Conclusion QSG inhibits renal fibrosis in mice by regulating the exosomes,reducing miR-330-3p levels,and increasing CREBBP expression.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Objective:To explore the relationship between lower respiratory tract microflora and type of anti-tuberculosis immune response, clinical characteristics in patients with pulmonary tuberculosis (PT).Methods:The clinical data of 80 patients with PT and 80 patients with non-PT from January 2018 to March 2020 in the Second Hospital of Zhejiang Medical School of Changxing District were retrospectively analyzed. All patients were treated with bronchoalveolar lavage, the bronchoalveolar lavage fluid counts of Haemophilus, Neisser coccus, Streptococcus and Veillonella were detected by germiculture, and the bronchoalveolar lavage fluid expression levels of T-bet mRNA (Th1 immune response) and GATA-3 mRNA (Th2 immune response) was detected by real-time polymerase chain reaction. The clinical symptoms of PT were recorded. The correlation was analyzed by Pearson correlation analysis.Results:There were no statistical differences in bronchoalveolar lavage fluid Neisser coccus, Veillonella and Haemophilus between patients with PT and patients with non-PT ( P>0.05); the bronchoalveolar lavage fluid Streptococcus in patients with PT was significantly lower than that in patients with non-PT (630 ± 120 vs. 1 000 ± 330), and there was statistical difference ( P<0.05). There was no statistical difference in expression level of T-bet mRNA between patients with PT and patients with non-PT ( P>0.05); the expression level of GATA-3 mRNA in patients with PT was significantly lower that in patients with non-PT: (5.883 ± 1.864) ×10 4 vs. (3.997 ± 1.186) ×10 6, and there was statistical difference ( P<0.05). Pearson correlation analysis result showed that fever was positively correlated with bronchoalveolar lavage fluid Neisser coccus and Veillonella ( r = 0.402 and 0.566, P<0.01 or <0.05); proportion of tuberculosis foci to lung area was positively correlated with T-bet and GATA-3 mRNA ( r = 0.024 and 0.442, P<0.05), the body weight loss was positively correlated with T-bet mRNA ( r = 0.112, P<0.05); GATA-3 mRNA was positively correlated with bronchoalveolar lavage fluid Neisser coccus ( r =0.332, P<0.05), T-bet mRNA was positively correlated with bronchoalveolar lavage fluid Haemophilus ( r = 0.162, P<0.05). Conclusions:There is a significant correlation between the Th1/Th2 immune response type and the bronchoalveolar lavage fluid Haemophilus and Neisser coccus in patients with PT, and the fever symptoms is also significantly related to Neisser coccus and Veillonella. There is a certain correlation between weight loss and the quantitative results of proportion of tuberculosis foci to lung area and the type of immune response.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

The correct differentiation of oligodendrocyte precursor cells (OPCs) is essential for the myelination and remyelination processes in the central nervous system. Determining the regulatory mechanism is fundamental to the treatment of demyelinating diseases. By analyzing the RNA sequencing data of different neural cells, we found that cyclin-dependent kinase 18 (CDK18) is exclusively expressed in oligodendrocytes. In vivo studies showed that the expression level of CDK18 gradually increased along with myelin formation during development and in the remyelination phase in a lysophosphatidylcholine-induced demyelination model, and was distinctively highly expressed in oligodendrocytes. In vitro overexpression and interference experiments revealed that CDK18 directly promotes the differentiation of OPCs, without affecting their proliferation or apoptosis. Mechanistically, CDK18 activated the RAS/mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase pathway, thus promoting OPC differentiation. The results of the present study suggest that CDK18 is a promising cell-type specific target to treat demyelinating disease.