ABSTRACT Purpose: To compare the effectiveness and safety of marketed oral drugs for overactive bladder based on a systematic review and network meta-analysis approach. Methods: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. Result: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. Conclusion: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

ABSTRACT Purpose: To investigate the Shikonin (SHI) induce autophagy of hypertrophic scar-derived fibroblasts (HSFs) and the mechanism of which in repairing hypertrophic scar. Methods: This study showed that SHI induced autophagy from HSFs and repaired skin scars through the AMPK/mTOR pathway. Alamar Blue and Sirius red were used to identify cell activity and collagen. Electron microscopy, label-free quantitative proteomic analysis, fluorescence and other methods were used to identify autophagy. The differences in the expression of autophagy and AMPK/mTOR pathway-related proteins after SHI treatment were quantitatively analyzed by Western blots. A quantitative real-time polymerase chain reaction assay was used to detect the expression of LC3, AMPK and ULK after adding chloroquine (CQ) autophagy inhibitor. Results: After treatment with SHI for 24 hours, it was found that the viability of HSFs was significantly reduced, the protein expression of LC3-II/LC3-I and Beclin1 increased, while the protein expression of P62 decreased. The expression of phosphorylated AMPK increased and expression of phosphorylated mTOR decreased. After the use of CQ, the cell autophagy caused by SHI was blocked. The key genes LC3 and P62 were then reexamined by immunohistochemistry using a porcine full-thickness burn hypertrophic scar model, and the results verified that SHI could induce autophagy in vivo. Conclusions: These findings suggested that SHI promoted autophagy of HSFs cells, and the potential mechanism may be related to the AMPK/mTOR signal pathway, which provided new insights for the treatment of hypertrophic scars.

ABSTRACT Due to their tiny size, soil nematodes and plant-parasitic nematodes are challenging to homogenize and collect using traditional mortar and pestle methods. To overcome this, we developed a reliable and efficient nematode preparation and grinding method using the BioPulverizer. The method involves creating a modified sample ‘sandwich’ with liquid nitrogen-frozen nematode samples placed between two layers of aluminum foil. This ‘sandwich’ facilitates complete homogenization through cryogenic grinding without any sample loss during transfer. The powerful nematode grinding yields high-quality and high-quantity samples, suitable for nucleic acid release and subsequent molecular identification and other downstream applications. size plantparasitic plant parasitic methods this BioPulverizer ‘sandwich sandwich nitrogenfrozen nitrogen frozen foil transfer highquality high quality highquantity quantity applications

Abstract Qilian Huaji Decoction (QLHJD) is a mixture of 13 herbs. The aim of this study is to observe the efficacy of QLHJD against hepatocellular carcinoma (HCC). The H22 transplanted mouse models were established to explore the effect of QLHJD on HCC in vivo. QLHJD-containing serum (QCS) was prepared using traditional Chinese medicine serum pharmacology methods. After QCS treatment, cell proliferation, cell cycle and apoptosis in HepG2 cells were assessed by MTT and flow cytometry, respectively. miRNA expression profiles were determined using qPCR arrays. miR-122 was examined by qPCR in HCC tissue samples and cells. AKT3 protein expression was detected by Western blot. We found that QLHJD significantly inhibited the growth of H22 tumor and improve immune function in vivo. In vitro, QLHJD inhibited proliferation by inducing cell cycle arrest at the S phase, and induced apoptosis in HepG2 cells. The miRNA expression profiles were altered and the reduced miR-122 levels in HepG2 cell lines were up-regulated compared with control group, accompanied by a decrease in WNT1 expression. In conclusion, QLHJD could inhibit the growth of HCC by restoring the aberrant expression of miR-122, which may be one of the mechanisms whereby QLHJD exerts its effect on HCC.

Abstract The Clerodendranthus spicatus (Thunb.) C. Y. Wu extract (CSTCYWE) was administered to D-galactose-induced aging mice to investigate the effect and mechanism of CSTCYWE on exercise endurance in aging mice. The effect of CSTCYWE on the improvement of exercise capacity in aging mice was evaluated by detecting serum biochemical indicators, pathological changes in tissues, and expression by qPCR. The composition of CSTCYWE was analyzed by HPLC. The experiment showed that CSTCYWE increased the running time and the exhaustive swimming time of aging mice to improve their exercise endurance. CSTCYWE also reduced the levels of BUN, BLA, and MDA and increased the levels of HG, MG, SOD, and GSH-Px in the serum of aging mice. Pathological observation found that CSTCYWE alleviated the liver and kidney tissue lesions and damage caused by aging. Meanwhile, CSTCYWE could down-regulate the relative mRNA expressions of nNOS, iNOS, TNF-α, and syncytin-1 and up-regulate the relative mRNA expressions of Cu/Zn-SOD, Mn-SOD, and CAT in the mouse liver tissue and skeletal muscle tissue. The results of component analysis showed that CSTCYWE contained caffeic acid, hypericin, isoquercetin, dihydroquercetin, rosmarinic acid, baicalin, luteolin, and baicalein. These active ingredients enable CSTCYWE to act on aging mice and improve their exercise capacity.

Children's dictionaries have existed for more than one thousand years in China, and play an important role in children's learning. However, many of those produced in China are deficient in the selection of the wordlist, in exemplification, and in definition. This paper aims at improving the compilation of English-Chinese children's dictionaries (ECCDs) from a children's cognitive perspective. Children's dictionaries should not only be an abridgement or simplification of dictionaries for adults, because their target user group is immature, uninformed and untrained children. Informed by some innovations in current English learner's dictionaries, this paper proposes that the making of ECCDs needs to be improved in the following aspects. Firstly, instead of lexicographers' intuition, the selection of headwords should be based on an English corpus for Chinese children. Secondly, the words used in examples should be congruent with children's limited cognitive and learning abilities. Thirdly, a multifaceted method of explanation should be provided in order to assist children in understanding the meaning of headwords.

ABSTRACT Purpose: To investigate the active ingredients of walnut ointment (WO) and its mechanism in repairing wounds. Methods: The ingredients of WO were detected by gas chromatography–mass spectrometry. The effect of linoleic acid (LA) was tested by in vitro Alamar Blue (AB) reagent. Image J software, histological and immunohistochemical analysis were used to confirm the healing effect of LA in the porcine skin model. The animals were euthanized after the experiment by injection of pentobarbital sodium. Results: LA, 24% in WO, promotes keratinocytes and fibroblasts proliferation, which were 50.09% and 15.07% respectively higher than control (p < 0.05). The healing rate of the LA group (96.02% ± 2%, 98.58% ± 0.78%) was higher than the saline group (82.11% ± 3.37%, 88.72% ± 1.73%) at week 3 and week 4 (p < 0.05). The epidermal thickness of the LA was 0.16 ± 0.04 mm greater and the expression of the P63 and CK10 proteins was stronger in the LA group than the control (p < 0.05). Conclusions: LA, which is the main components in WO can promote full-thickness burning wounds (FBWs) by stimulating cell proliferation and differentiation.

Although estrogen has crucial functions for endometrium growth, the specific dose and underlying molecular mechanism in intrauterine adhesion (IUA) remain unclear. In this study, we aimed to investigate the effects of estrogen on epithelial-mesenchymal transition (EMT) in normal and fibrotic endometrium, and the role of estrogen and Wnt/β-catenin signaling in the formation of endometrial fibrosis. CCK-8 and immunofluorescence assay were performed to access the proliferation of different concentrations of estrogen on normal human endometrial epithelial cells (hEECs). qRT-PCR and western blot assay were utilized to explore the effect of estrogen on EMT in normal and fibrotic endometrium, and main components of Wnt/β-catenin signaling pathway in vitro. Hematoxylin and eosin and Masson staining were used to evaluate the effect of estrogen on endometrial morphology and fibrosis in vivo. Our results indicated that the proliferation of normal hEECs was inhibited by estrogen at a concentration of 30 nM accompanied by upregulation of mesenchymal markers and downregulation of epithelial markers. Interestingly, in the model of transforming growth factor β1 (TGF-β1)-induced endometrial fibrosis, the same concentration of estrogen inhibited the process of EMT, which might be partially mediated by regulation of the Wnt/β-catenin pathway. In addition, relatively high doses of estrogen efficiently increased the number of endometrial glands and reduced the area of fibrosis as determined by the reduction of EMT in IUA animal models. Taken together, our results demonstrated that an appropriate concentration of estrogen may prevent the occurrence and development of IUA by inhibiting the TGF-β1-induced EMT and activating the Wnt/β-catenin pathway.

The objective of this study was to explore the role of the SULF2-mediated ERK/AKT signaling pathway in cervical cancer. SULF2 expression was detected in tumor tissues and tumor-adjacent normal tissues from cervical cancer patients. HeLa cells were divided into six groups: control group, NC group, SULF2 siRNA group, SULF2 group, SULF2 + LY294002 group, and SULF2 + U0125 group. In each group, HeLa cells received the corresponding treatment, followed by measurement of the cellular biological characteristics and expression of the ERK/AKT signaling pathway. We also confirmed the effect of SULF2 in vivo using a xenograft model in nude mice. SULF2 was upregulated in cervical cancer tissues, which was specifically associated with the clinical stage, histological differentiation, and lymphatic metastasis. Compared to the control group, the SULF2 siRNA group displayed decreased expression of SULF2, concomitant with reduced proliferation, migration, and invasion, but there was an increase in the apoptosis rate of HeLa cells, as well as downregulation of the p-Akt/Akt, p-ERK/ERK, and Bax/Bcl-2 ratios and cyclin D1. Additionally, tumor growth was significantly inhibited in the xenograft model of nude mice. The results in the SULF2 group were quite the opposite in which SULF2 facilitated the growth of cervical cancer cells, which was reversed by LY294002 or U0126. SULF2 is highly expressed in cervical cancer, and thus, downregulation of SULF2 can inhibit the ERK1/2 and AKT signaling pathways to suppress the proliferation, invasion, and migration of cervical cancer cells while facilitating apoptosis.

OBJECTIVES: To explore the clinical significance and correlation of microRNA-21 (miR-21) and the neutrophil-lymphocyte ratio (NLR) in patients with acute myocardial infarction (AMI). METHODS: The observation group contained 184 patients, while the control group contained 150 patients. The expression of miR-21 in the serum of each group was detected by qRT-PCR. RESULTS: A total of 184 patients and their family members were followed-up for 30 days, among which 35 patients died and 149 patients survived, resulting in a survival rate of 80.97%. According to univariate analysis, there were significant differences in age, cardiac troponin (cTn), heart rate, Killip grade, percutaneous coronary intervention (PCI) operation rate, miR-21 and NLR. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) values of miR-21 and NLR for the diagnosis of AMI were 0.909 and 0.868, respectively, and the area under the combined detection curve was 0.960. In the Kaplan-Meier survival analysis, the survival of patients with high miR-21 expression and NLR was significantly higher than that of patients with low miR-21 expression and NLR (p=0.027; p=0.001). The correlation showed that miR-21 expression in serum was positively correlated with the NLR in the observation group (r=0.528, p<0.05). cTn, heart rate, Killip classification, PCI operation rate, miR-21, NLR are independent risk factors for AMI. CONCLUSION: miR-21 and NLR play a role in the diagnosis of AMI and can be used as predictors for the survival of AMI.

Hormones regulate hepatic gene expressions to maintain metabolic homeostasis. Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been thought to interfere with insulin signaling. To determine its potential role in the regulation of metabolism, we analyzed its gene (Enpp1) expression in the liver of rats experiencing fasting and refeeding cycles, and in primary rat hepatocytes and human hepatoma HepG2 cells treated with insulin and dexamethasone using northern blot and real-time PCR techniques. Hepatic Enpp1 expression was induced by fasting and reduced by refeeding in the rat liver. In primary rat hepatocytes and HepG2 hepatoma cells, insulin reduced Enpp1 mRNA abundance, whereas dexamethasone induced it. Dexamethasone disrupted the insulin-reduced Enpp1 expression in primary hepatocytes. This is in contrast to the responses of the expression of the cytosolic form of phosphoenolpyruvate carboxykinase gene to the same hormones, where insulin reduced it significantly in the process. In addition, the dexamethasone-induced Enpp1 gene expression was attenuated in the presence of 8-Br-cAMP. In conclusion, we demonstrated for the first time that hepatic Enpp1 is regulated in the cycle of fasting and refeeding, a process that might be attributed to insulin-reduced Enpp1 expression. This insulin-reduced Enpp1 expression might play a role in the development of complications in diabetic patients.

A new sodium europium carbonate hydrate, Na3Eu(CO3)3•6H2O, has been prepared using the hydrothermal method, and its structure was determined by single crystal X-Ray diffraction analysis for the first time. It crystallizes in the polar hexagonal space group P6(3) with a = 11.382(9) Å, c = 5.989(5) Å, V = 672.06(9) ų, Z = 2, Mr = 509.06, Dc = 2.516 g/cm³, F(000) = 492, μ(MoKα) = 4.84 mm-1, R1 = 0.015 and wR = 0.038. The structure features a three-dimensional (3D) framework composed of planar (CO3)2- triangles, Eu3+ ions and Na+ ions, which delimits 1D infinite chains with a hexangular star appearance along the c-axis. The IR spectrum and the self-activated photoluminescence properties were studied. Under the excitation of near UV light (395nm), it shows strong red emission at 618 nm with a lifetime of 348.7 μs. Present research indicates that Na3Eu(CO3)3•6H2O is a promising red phosphor for white light-emitting diodes.

Single crystal of rare-earth polyphosphate Tm(PO3)3 has been grown under high temperature molten-salt method and structurally characterized by single crystal X-ray diffraction analysis. Using the four-dimensional superspace formalism for aperiodic structures, we performed the crystal structure refinement of Tm(PO3)3 as (3+1)-dimensional incommensurately modulated structure with monoclinic superspace group C2/c(0, 0.358, 0)s0 and α = 14.0620 (12) Å, b = 6.6612 (6) Å, c = 10.0191 (9) Å, β = 127.6043 (9)°, V = 743.51 (11) ų, Z = 4, Mr = 405.8, Dc = 3.626 g/cm³, F(000) = 744, μ(MoKα) = 12.60 mm'¹, R = 0.048 and ωR = 0.050. The structure features infinite chains of corner-sharing PO4 tetrahedra which are affected by positional modulation running along the b-axis. The final structure model was reasonable and did not show any unusual features.

Dois novos diterpenos com esqueleto caurano, 3a,16b-17-tri-hidróxi-ent-caurano 3-O-β-D-glucopiranosídeo e ácido 2β,3α-di-hidróxi-ent-caur-15-eno-17-óico 3-O-β-D-glucopiranosídeo, foram isolados das cascas de Albizia mollis (Wall.) Boiv. As estruturas destes dois cauranos foram elucidadas por métodos espectroscópicos uni e bidimensionais e por espectrometria de massas.

Two new kaurane diterpenoids, 3α, 16β, 17-trihydroxy-ent-kaurane 3-O-β-D-glucopyranoside and 2β,3α-dihydroxy-ent-kaur-15-en-17-oic acid 3-O-β-D-glucopyranoside, were isolated from the bark of Albizia mollis (Wall.) Boiv. The structures of two new compounds were elucidated by extensive 1D- and 2D-NMR spectroscopic methods in combination with MS experiments.