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Fetuin-B (FETUB) is a glycoprotein mainly synthesized and secreted by the liver. It is involved in many physiological and pathological processes including glucose metabolism, inflammatory response, nonalcoholic fatty liver disease, myocardial infarction, tumor and so on. In recent years, FETUB has also been confirmed to play roles in the female reproductive system. FETUB may affect follicular development and play an important role in in vivo and in vitro fertilization. In addition, serum FETUB level is elevated significantly during pregnancy and labor. FETUB expression is changed in a variety of reproductive diseases (polycystic ovary syndrome, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy). In this review, we summarize FETUB related studies in female reproduction, and focus on the roles of FETUB in female reproductive physiology and pathology, in order to provide information for the pathogenesis of reproductive disorders.

Osteoblast-mediated bone formation and osteoclast-mediated bone resorption are critical processes in bone metabolism. Annexin A, a calcium-phospholipid binding protein, regulates the proliferation and differentiation of bone cells, including bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts, and has gradually become a marker gene for the diagnosis of osteoporosis. As calcium channel proteins, the annexin A family members are closely associated with mechanical stress, which can target annexins A1, A5, and A6 to promote bone cell differentiation. Despite the significant clinical potential of annexin A family members in bone metabolism, few studies have reported on these mechanisms. Therefore, based on a review of relevant literature, this article elaborates on the specific functions and possible mechanisms of annexin A family members in bone metabolism to provide new ideas for their application in the prevention and treatment of bone diseases, such as osteoporosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Uterine fibroids are common benign gynecological conditions. Patients who experience excessive menstruation, anemia, and pressure symptoms should be administered medication, and severe cases require a total hysterectomy. This procedure is invasive and causes severe postoperative pain, which can affect the patient's postoperative sleep quality and, thus, the recovery process., Aim: To evaluate use of dezocine in patient-controlled epidural analgesia (PCEA) for postoperative pain management in patients undergoing total myomectomy., Methods: We selected 100 patients undergoing total abdominal hysterectomy for uterine fibroids and randomized them into two groups: A control group receiving 0.2% ropivacaine plus 0.06 mg/mL of morphine and an observation group receiving 0.2% ropivacaine plus 0.3 mg/mL of diazoxide in their PCEA. Outcomes assessed included pain levels, sedation, recovery indices, PCEA usage, stress factors, and sleep quality., Results: The observation group showed lower visual analog scale scores, shorter postoperative recovery indices, fewer mean PCEA compressions, lower cortisol and blood glucose levels, and better polysomnographic parameters compared to the control group ( P < 0.05). The cumulative incidence of adverse reactions was lower in the observation group than in the control group ( P < 0.05)., Conclusion: Dezocine PCEA can effectively control the pain associated with total myomectomy, reduce the negative impact of stress factors, and have less impact on patients' sleep, consequently resulting in fewer adverse effects., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

A widely used type II pyrethroid pesticide cypermethrin (CYP) is one of endocrine disrupting chemicals (EDCs) with anti-androgenic activity to induce male reproductive toxicology. However, the mechanisms have not been fully elucidated. This study was to explore the effects of CYP on apoptosis of mouse Sertoli cells (TM4) and the roles of endoplasmic reticulum (ER)-mitochondria coupling involving 1,4,5-trisphosphate receptor type1-glucose-regulated protein 75-voltage-dependent anion channel 1 (IP3R1-GRP75-VDAC1). TM4 were cultured with different concentrations of CYP. Flow cytometry, calcium (Ca 2+ ) fluorescent probe, transmission electron microscopy and confocal microscopy, and western blot were to examine apoptosis of TM4, mitochondrial Ca 2+ , ER-mitochondria coupling, and expressions of related proteins. CYP was found to increase apoptotic rates of TM4 significantly. CYP was shown to significantly increase expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP). Concentration of mitochondrial Ca 2+ was increased by CYP treatment significantly. CYP significantly enhanced ER-mitochondria coupling. CYP was shown to increase expressions of IP3R, Grp75 and VDAC1 significantly. We suggest that CYP induces apoptosis in TM4 cells by facilitating mitochondrial Ca 2+ overload regulated by ER-mitochondria coupling involving IP3R1-GRP75-VDAC1. This study identifies a novel mechanism of CYP-induced apoptosis in Sertoli cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The nursing model of establishing a chemotherapy safety management supervisory group has guaranteed the safety and effectiveness of intravenous chemotherapy while reducing the adverse effects of chemotherapy and improving patient satisfaction and quality of life., Objective: To explore the impact of establishing a nursing supervision group on improving the safety management of patients receiving chemotherapy in the oncology department., Methods: We selected a total of 60 patients who underwent chemotherapy at the oncology department between January and June 2021 and assigned them to the control group. They received conventional chemotherapy safety management nursing care. We selected another 60 patients undergoing chemotherapy in the oncology department between July and December 2021 and assigned them to the observation group. They received a nursing intervention model facilitated by the chemotherapy safety supervision team. We compared the intervention effects in the two groups., Results: Patient satisfaction was significantly higher in the observation group than in the control group (P< 0.05); the incidence of post-chemotherapy nausea and vomiting was significantly lower in the observation group than in the control group (P< 0.05); and the self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores of patients in the observation group were reduced (P< 0.05) and significantly lower than in the control group (P< 0.05). We used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC-QLQ-C30) and found a statistically significant difference in the quality of life of patients before the nursing intervention and on the day of discharge (P< 0.05)., Conclusion: The establishment of a chemotherapy safety management supervisory group was effective in reducing the incidence of post-chemotherapy nausea and vomiting as well as the patient's psychological burden; it could also improve the quality of life of patients and their satisfaction with nursing care.

Background: Ovarian remnant syndrome (ORS) is a rare complication that occurs after oophorectomy, characterized by residual ovarian tissue causing pelvic pain, masses, and various symptoms. The clinical manifestations of ORS are nonspecific, and its diagnosis relies on histological examination. Since ORS typically represents a benign ovarian lesion, there have been few reported cases of malignant transformation. In this report, we presented a unique case of ovarian clear cell carcinoma (OCCC) arising from an ovarian remnant following salpingo-oophorectomy., Case Presentation: Our patient was a 47-year-old female initially diagnosed with uterine myoma. She had previously undergone cesarean section and unilateral salpingo-oophorectomy. Transvaginal ultrasound and computed tomography (CT) scans revealed a soft tissue mass adjacent to the right lateral wall of the myometrium. The patient opted for transabdominal hysterectomy, left adnexal resection, laparoscopic omentectomy, appendectomy, and pelvic and abdominal lymphadenectomy. The final pathology results confirmed the diagnosis of OCCC, consistent with ORS. The patient subsequently received six cycles of intravenous chemotherapy using the carboplatin/paclitaxel (TC) regimen (paclitaxel liposomes 175 mg/m², carboplatin AUC 5). After 3 years of follow-up, the patient's condition remained normal., Conclusion: ORS can significantly impact patients' quality of life and pose challenges for clinicians. Complete excision of ovarian tissue during the initial surgery is crucial in preventing ORS recurrence and potential malignant transformation of ovarian remnants., (© 2023. The Author(s).)

Pt catalyst has been considered as the state-of-the-art catalyst for hydrogen evolution reaction (HER) under acid condition. However, its catalytic kinetics under alkaline conditions is not well-understood. Herein, we report a Ni-Pt(SAs) (SAs = single atoms) catalyst with Pt atomically dispersed in a Ni matrix, and it possesses an impressive HER performance with an overpotential as low as 210 mV at 500 mA cm -2 in strong alkaline electrolyte (7 M KOH), which is much higher than Pt nanoparticle-modified Ni catalyst (Ni-Pt(NPs)). Kinetics analysis reveals that Pt doping in the Ni matrix can accelerate the Volmer step on the Ni-Pt surface. Moreover, Ni-Pt(SAs) displays a more favorable kinetics for H 2 formation reaction at high current density than Ni-Pt(NPs). Theoretical calculations reveal that atomically dispersed Pt weakens the adsorption of both H and OH on the surface of Ni-Pt electrode and promotes H 2 formation from surface H on Ni-Pt(SAs).

Cypermethrin (CYP) has been identified as one kind of endocrine-disrupting chemicals (EDCs) to induce male reproduction damage. This study aimed to investigate the effects and mechanisms of miR-30a-5p on CYP induced apoptosis of TM4 mouse Sertoli cells in vitro. In the present study, 0 μM, 10 μM, 20 μM, 40 μM and 80 μM CYP were used to treat TM4 cells for 24 h. The apoptosis of TM4 cells, the expression level of miR-30a-5p, the protein expressions and the interaction between miR-30a-5p and KLF9 were detected by flow cytometry, quantitative Real-Time PCR, Western blot and luciferase reporter assays. CYP induced apoptosis of TM4 cells, inhibited expression of miR-30a-5p in TM4 cells, and overexpression of miR-30a-5p partially recovered CYP induced cells apoptosis. Furthermore, KLF9 was a potential downstream target of miR-30a-5p predicted by publicly available databases. KLF9 expression level in TM4 cells was significantly elevated after treatment with CYP, and the induction was inhibited by miR-30a-5p mimics transfection. Meanwhile, dual-luciferase reporter assay demonstrated that miR-30a-5p directly targeted KLF9-3'UTR. Moreover, in the presence of CYP, the apoptosis regulator p53 expression was also increased in TM4 cells. Overexpression miR-30a-5p or down-regulation of KLF9 both attenuated the induction of CYP on p53 expression. Overall, the present study demonstrated that miR-30a-5p regulated CYP induced TM4 cells apoptosis by targeting KLF9/p53 axis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects., Methods: Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS)., Results: In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05)., Conclusion: BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objective: Acute lung injury (ALI) is a life-threatening disease which has high mortality and lacks effective pharmacological treatments. Excessive inflammation and oxidative stress are the key pathogenesis of ALI. Mefunidone (MFD), a novel small molecule compound, displayed anti-inflammation and anti-oxidative stress effects on streptozocin (STZ) and db/db mice in our previous studies. In this study, we aimed to investigate the effects of MFD on lipopolysaccharide (LPS)-induced ALI and explore the potential molecular mechanisms., Methods: We investigated the effects of MFD on LPS-induced ALI mouse model and LPS-stimulated immortalized mouse bone marrow-derived macrophages (iBMDMs)., Results: MFD could alleviate pulmonary structure disorder and attenuate pulmonary neutrophils infiltration induced by LPS. MFD could also decreased proinflammatory cytokines release and reduce reactive oxygen species (ROS) generation stimulated by LPS. Further, MFD could significantly reduce LPS-induced phosphorylation levels of mitogen-activated protein kinase (MAPK), increase expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and restore the expressions of antioxidant enzymes., Conclusion: Our results firstly supported that MFD effectively protected LPS-induced ALI against inflammation and oxidative stress through inhibiting MAPK signaling pathway and activating Nrf2 pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Cypermethrin (CP) exhibits anti-androgenic effects through antagonism on androgen receptor (AR) activation. This study was to identify whether AR-mediated disabled 2 interacting protein (DAB2IP)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway was involved in CP-induced mouse Sertoli cells (TM4) proliferation disorder. Real-Time Cell Analysis-iCELLigence system was to measure cell proliferation. Bioinformatic analyses were performed to identify AR-regulated genes. Quantitative Real-Time PCR and western blot were to detect the genes and proteins levels in AR-mediated DAB2IP/PI3K/AKT pathway. Results showed CP suppressed TM4 proliferation and the expression of AR. Activation of AR restored the inhibition efficacy of CP on TM4 proliferation. AR regulated DAB2IP expression and phosphorylation levels of PI3K and AKT in CP-exposed TM4 cells. In addition, knockdown of DAB2IP alleviated the inhibition efficacy of CP on cell proliferation and phosphorylation of PI3K and AKT. Taken together, AR was a modulator in CP-induced inhibition of Sertoli cells proliferation by negatively regulating DAB2IP/PI3K/AKT signaling pathway. The study may provide a new insight for the mechanisms of male reproductive toxicity induced by CP., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Myocardial fibrosis is the main morphological change of ventricular remodelling caused by cardiovascular diseases, mainly manifested due to the excessive production of collagen proteins. SRY-related high mobility group-box gene 9 (SOX9) is a new target regulating myocardial fibrosis. Bellidifolin (BEL), the active component of G. acuta , can prevent heart damage. However, it is unclear whether BEL can regulate SOX9 to alleviate myocardial fibrosis. The mice were subjected to isoproterenol (ISO) to establish myocardial fibrosis, and human myocardial fibroblasts (HCFs) were activated by TGF- β 1 in the present study. The pathological changes of cardiac tissue were observed by HE staining. Masson staining was applied to reveal the collagen deposition in the heart. The measurement for expression of fibrosis-related proteins, SOX9, and TGF- β 1 signalling molecules adopted Western blot and immunohistochemistry. The effects of BEL on HCFs, activity were detected by CCK-8. The result showed that BEL did not affect cell viability. And, the data indicated that BEL inhibited the elevations in α -SMA, Collagen I, and Collagen III by decreasing SOX9 expression. Additionally, SOX9 suppression by siRNA downregulated the TGF- β 1 expression and prevented Smad3 phosphorylation, as supported by reducing the expression of α -SMA, Collagen I, and Collagen III. In vivo study verified that BEL ameliorated myocardial fibrosis by inhibiting SOX9. Therefore, BEL inhibited SOX9 to block TGF- β 1 signalling activation to ameliorate myocardial fibrosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Ting-Ting Yao et al.)

Background: Neoadjuvant chemotherapy (NACT) is an important treatment option for patients with ovarian cancer. Although intravenous NACT can improve optimal resection rates and decrease surgical morbidity and mortality, these advantages do not translate into a survival benefit. Ovarian carcinoma is mainly confined to the peritoneal cavity, which makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Our previous study showed that HIPEC could be used in the neoadjuvant setting, which was named neoadjuvant HIPEC (NHIPEC). Since hyperthermia is an excellent chemosensitiser, we hypothesised that the combination of NHIPEC and intravenous NACT could show superior efficacy to intravenous NACT alone., Methods: This study is a single-centre, open-label, randomised (1:1 allocation ratio) phase 2 trial. A total of 80 patients will be randomly assigned into an experimental group (NHIPEC+intravenous NACT) or a control group (intravenous NACT). Patients in the experimental group will receive NHIPEC following laparoscopic evaluation, and four tubes will be placed via the laparoscopic ports, which will be used to administer NHIPEC. Then, perfusion with docetaxel (60-75 mg/m 2 ) will be performed (43°C for 60 min, Day 0) followed by cisplatin (75 mg/m 2 , Day 1) infusion (43°C for 60 min) 24 hours later. After NHIPEC, two cycles of intravenous NACT will be given. Patients in the control group will receive three cycles of intravenous NACT. The primary endpoint is the proportion of patients who achieve a Chemotherapy Response Score (CRS) of 3 according to the CRS system. The secondary endpoints include progression-free survival, overall survival and the rates of complete resection and NHIPEC-related adverse events., Ethics Approval and Dissemination: This study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital (approval number: 2020-ky-050). Results will be submitted to peer-reviewed journals and presented at national and international conferences., Trial Registration Number: ChiCTR2000038173., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Gut microbiota dysbiosis can contribute to the progression of atherosclerosis. We investigated the association of the gut microbiota and the severity of coronary artery lesions and prognosis of patients with ACS., Methods: In this case-control study, 402 ACS patients and 100 controls were enrolled from June 2017 to December 2018. The number of bacterial species was determined by real-time PCR. A SYNTAX score was calculated for all ACS patients based on their coronary angiography results., Results: Compared with the healthy controls, the gut microbial levels in Escherichia coli , Streptococcus , and Enterobacteriaceae were significantly increased in ACS patients, while the Lactobacillus level was significantly decreased. Lactobacillus level was as an independent predictor of disease severity on the coronary angiography [high vs. low SYNTAX score: adjusted odds ratio (aOR) = 0.024, 95% confidence interval (CI): 0.004-0.155] and myocardial necrosis [high vs. low cardiac troponin T (cTNT): aOR = 0.317, 95% CI: 0.099-0.914]. Subsequently, a higher Lactobacillus level was associated with a lower risk of an all-cause death [adjusted hazard ratio (aHR) = 0.239; 95% CI: 0.093-0.617] and major adverse cardiac events (MACE) in ACS patients (aHR = 0.208; 95% CI: 0.081-0.531). After stratifying by the type of ACS, a higher Lactobacillus level was significantly associated with the decreased risks of high SYNTAX score, all-cause death, and MACE in the STEMI subgroup but not in the NSTEMI and UAP subgroups., Conclusions: Lower Lactobacillus levels may indicate a higher risk of a more severe coronary atherosclerotic lesions and myocardial necrosis and worse prognosis for patients with ACS, particularly in the STEMI subgroup., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gao, Wang, Zhao, Yao, Chen, Ma, Zhang, Wang, Wang, Cui and Liu.)

Myocardial fibrosis is closely related to high morbidity and mortality. In Inner Mongolia, Gentianella amarella subsp. acuta (Michx.) J.M.Gillett ( G. acuta ) is a kind of tea used to prevent cardiovascular diseases. Bellidifolin (BEL) is an active xanthone molecule from G. acuta that protects against myocardial damage. However, the effects and mechanisms of BEL on myocardial fibrosis have not been reported. In vivo , BEL dampened isoprenaline (ISO)-induced cardiac structure disturbance and collagen deposition. In vitro, BEL inhibited transforming growth factor (TGF)-β1-induced cardiac fibroblast (CF) proliferation. In vivo and in vitro , BEL decreased the expression of α-smooth muscle actin (α-SMA), collagen Ⅰ and Ⅲ, and inhibited TGF-β1/Smads signaling. Additionally, BEL impeded p38 activation and NR4A1 (an endogenous inhibitor for pro-fibrogenic activities of TGF-β1) phosphorylation and inactivation in vitro . In CFs, inhibition of p38 by SB203580 inhibited the phosphorylation of NR4A1 and did not limit Smad3 phosphorylation, and blocking TGF-β signaling by LY2157299 and SB203580 could decrease the expression of α-SMA, collagen I and III. Overall, both cell and animal studies provide a potential role for BEL against myocardial fibrosis by inhibiting the proliferation and phenotypic transformation of CFs. These inhibitory effects might be related to regulating TGF-β1/Smads pathway and p38 signaling and preventing NR4A1 cytoplasmic localization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Sun, Yao, Li, Xu, Zhang, Liu, Zhou, Song, Zhang and Li.)

Professor ZHANG Qing - ping 's clinical experience and characteristics of acupuncture for peripheral facial paralysis were introduced from three aspects: differentiation of meridians and tendons, treatment by stages, and examples of proven cases. In the treatment of peripheral facial paralysis, Professor ZHANG carefully examines the situation of pathogenic factors and health. In the acute stage, the treatment focuses on eliminating pathogenic factors and supporting the health; in the recovery stage, penetrating needling is recommended with strengthening the health and eliminating pathogenic factors as main purpose; in the sequelae stage, wheat-grain moxibustion is recommended with strengthening the health as main purpose. This treatment plan shows superior clinical efficacy.

Gentianella acuta (G. acuta), as a folk medicine, was used to treat heart disease by the Ewenki people in Inner Mongolia. However, the effect of G. acuta on acute myocardial infarction (AMI) is not clear. To explore the mechanisms of G. acuta on isoproterenol (ISO)-induced AMI, rats were administered G. acuta for 28 days, then injected intraperitoneally with ISO (85 mg/kg) on days 29 and 30. An electrocardiogram helped to evaluate the myocardial injury. Serum lactate dehydrogenase (LDH), creatinine kinase (CK) and aspartate aminotransferase (AST) levels were evaluated, and haematoxylin eosin, Masson's trichrome staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining were used to detect myocardial histological changes. Radioimmunoassay was used to measure serum tumour necrosis factor alpha (TNFα) and interleukin (IL)-6. An enzyme-linked immunosorbent assay kit was used to analyse serum galectin-3 (Gal-3) levels. Immunohistochemistry, Western blotting and reverse transcription polymerase chain reaction were used to examine relevant molecular events. The results revealed that pre-treatment with G. acuta decreased the elevation in the ST segment; reduced serum LDH, CK and AST levels; alleviated cardiac structure disorder; and reduced inflammatory infiltration, abnormal collagen deposition and cardiomyocyte apoptosis that were induced by ISO. Furthermore, pre-treatment with G. acuta inhibited serum Gal-3 levels and Gal-3 expression in heart tissue, and also impeded TLR4/MyD88/NF-кB signalling activation, which ultimately prevented the expression of inflammatory cytokines. The study indicated that pre-treatment with G. acuta protects against ISO-induced AMI, and the protective role may be related to inhibiting Gal-3/TLR4/MyD88/NF-кB inflammatory signalling.

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. To date, therapies to treat any forms of TBI are still limited. Recent studies have demonstrated the potential neuroprotective effects of molecular hydrogen on TBI. Although it has been demonstrated that hydrogen inhalation (HI) for about 5 hrs immediately after TBI has a beneficial effect on brain injury, the most effective intervention procedure in the treatment of TBI remains unknown. The mechanism underlying the neuroprotective effects of HI on TBI also needs to be further investigated. Our results showed that inhalation of 4% hydrogen during the first day after TBI was the most effective hydrogen intervention procedure in the treatment of TBI. Pathological examination showed that HI could attenuate TBI-induced reactive astrocytosis and microglial activation. Nissl staining demonstrated a significant decrease in the number of nissl-stained dark neurons (N-DNs) in HI group compared to TBI group at 2 h post-TBI, and the TBI-induced neuronal loss was attenuated by HI at day 3 post-TBI. IHC staining showed that HI resulted a decrease in CD16-positive cells and a further increase in CD206-positive cells as compared to TBI group. Multiplex cytokine assay demonstrated the most profound regulatory effects induced by HI on the levels of IL-12, IFN-γ, and GM-CSF at 24 h post-TBI, which confirmed the inhibitory effect of hydrogen on microglia activation. We concluded that inhalation of 4% hydrogen during the first day after TBI was the most effective intervention procedure in the treatment of TBI. Our results also showed that hydrogen may exert its protective effects on TBI via inhibition of microglia activation and neuroinflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

The potential therapeutic effects of molecular hydrogen (H 2 ) have now been confirmed in various human and animal-disease models. However, the effects of H 2 on the physiological function in a normal state have been largely neglected. Hydrogen-rich water (HRW) intake and hydrogen inhalation (HI) are the most common used methods for hydrogen administration, the difference in the effects between HRW intake and HI remains elusive. In the present study, the body weight and 13 serum biochemical parameters were monitored during the six-month hydrogen intervention, all these parameters were significantly altered by oral intake of HRW or HI. Among the 13 parameters, the most striking alterations induced by hydrogen treatment were observed in serum myocardial enzymes spectrum. The results also showed that the changes in these parameters occurred at different time points, and the alterations in most of the parameters were much more significant in HI than HRW. The results of this study provides the basic data for the mechanism research and application of molecular hydrogen in the future.

Objective: Our study aimed to investigate the effect of anti-differentiation noncoding RNA ( ANCR ) on hepatocellular carcinoma (HCC) and its potential molecular mechanisms., Methods: The expression of ANCR was detected by qRT-RCR in both HCC tissues and HCC cells. Moreover, the relationship between ANCR expression and clinical parameters in HCC patients was investigated. The proliferation, cell clones, migration, invasion and apoptosis of MHCC97H and HCCLM3 cells were measured by MTT assay, colony formation assay, transwell assay and flow cytometry, respectively. The expressions of N-cadherin, vimentin, E-cadherin, cleaved caspase-3, Bax, Bcl-2, Wnt1, β-catenin and GSK-3β in MHCC97H and HCCLM3 cells were measured by Western blot., Results: Our results showed that ANCR was lowly expressed in both HCC tissues and HCC cells. ANCR expression was closely associated with tumor size, tumor-node-metastasis (TNM) stages and vascular invasion in HCC. ANCR could dramatically inhibit cell proliferation, migration and invasion, as well as promote apoptosis in MHCC97H and HCCLM3 cells. ANCR could significantly increase the expression of cleaved caspase-3, Bax, E-cadherin and GSK-3β but reduce the expression of Bcl-2, N-cadherin, vimentin, Wnt1 and β-catenin in MHCC97H and HCCLM3 cells. In addition, Wnt/β-catenin pathway inhibitor (IWP-2) partially reversed the effects of silencing ANCR on the proliferation, migration, invasion and apoptosis of HCCLM3 cells., Conclusion: Our study demonstrated that ANCR can suppress cell proliferation, migration and invasion, as well as promote apoptosis of HCC cells via modulation of the Wnt/β-catenin signaling pathway., Competing Interests: The authors report no potential conflicts of interest for this work., (© 2020 Song et al.)

Myocardial fibrosis (MF) plays a key role in the development and progression of heart failure (HF) with limited effective therapies. Galectin-3 (Gal-3) is a biomarker associated with fibrosis and inflammation in patients with HF. The Gal-3 inhibitor modified citrus pectin (MCP) protects against cardiac dysfunction, though the underlying mechanism remains unclear. The aim of this study was to investigate the effect and mechanism of MCP on MF using an isoproterenol (ISO)-induced rat model of HF. Cardiac function was analyzed by echocardiography and electrocardiography. Histopathological changes in the heart tissue were assessed by hematoxylin-eosin and Masson trichrome staining. The mRNA and protein expression levels of signaling molecules and pro-inflammatory cytokines were monitored by immunohistochemistry, western blot, qRT-PCR and ELISA analyses. The results demonstrated that MCP ameliorated cardiac dysfunction, decreased myocardial injury and reduced collagen deposition. Furthermore, MCP downregulated the expression of Gal-3, TLR4 and MyD88, thereby inhibiting NF-κB-p65 activation. MCP also decreased the expression of IL-1β, IL-18 and TNF-α, which have been implicated in the pathogenesis of HF. These inhibitory effects were observed on day 15 and continued until day 22. Taken together, these results suggest that MCP ameliorates cardiac dysfunction through inhibiting inflammation and MF. These effects may be through downregulating Gal-3 expression and suppressing activation of the TLR4/MyD88/NF-κB signaling pathway. The present study supports the use of Gal-3 as a therapeutic target for the treatment of MF after myocardial infarction., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To study the effects of acute and chronic exercise on phosphatidylinositol 3-hydroxy kinase(PI3K)/protein kinase B(AKT)/glucose transporter 4(GLUT4)signaling pathway in adipose tissue of rats with type 2 diabetes mellitus (T2DM) induced by high-fat diet and low-dose streptozotocin (STZ)., Methods: A total of 52 SD male rats aged 15 months were randomly divided into normal control group (13) and high-fat group (39), and fed normal and high fat diets. After 8 weeks, the body weight of the high-fat group was higher 20% than that of the normal control group. After a small dose of STZ, the blood glucose level was ＞16.7 mmol/l, and the model was successfully established. The diabetic model group was randomly divided into a diabetic control group (DC, n=13), a diabetic chronic exercise group (DCE, n=13), and a diabetic acute exercise group (DAE, n=13). The DCE group underwent an 8-week swimming exercise and the DAE group performed a one-time swimming exercise. Blood lipids, blood glucose and serum insulin levels were measured, and the contents of fat PI3K, AKT and GLUT4 proteins were determined by Western blot method., Results: The levels of body weight, blood lipids, blood glucose and insulin in the diabetic group were significantly higher than those in the normal control group (P＜0.01); high density liptein cholesterol(HDL-C) levels were decreased (P＜0.05), and the expressions of PI3K, AKT and GLUT4 protein in adipose tissue were decreased (P＜0.01). After 8 weeks of swimming training, the levels of body weight, blood lipids, blood glucose and insulin all were decreased significantly (P＜0.01); while the level of HDL-C was increased (P＜0.05), and the expressions of PI3K, AKT and GLUT4 protein were increased (P＜0.01). After acute exercise, the levels of blood lipids, blood glucose and insulin were decreased (P＜0.05); the level of HDL-C was increased (P＜0.05), and the expression levels of fat PI3K, AKT and GLUT4 were increased significantly (P＜0.05)., Conclusion: ①High fat diet combined with low-dose STZ induced damage to the PI3K/AKT pathway in adipose tissue of T2DM rats reduced insulin sensitivity. ②Acute and chronic aerobic exercise can improve the disorder of glucose and lipid metabolism through PI3K/AKT pathway, and the chronic exercise is better than acute exercise.

Hepatocellular carcinoma (HCC) is a severe disease with high mortality in the world. Emerging evidence has suggested that lncRNAs play an important role in cancer progression, including HCC. This study aimed to comprehensively investigate the effect of lncRNA RHPN1 antisense RNA 1 (RHPN1-AS1) on HCC and its underlying molecular mechanism. In this study, we evaluated the expressions of lncRNA RHPN1-AS1 and miR-7-5p by qRT-RCR in both HCC tissue and HCC cells. Our findings showed that lncRNA RHPN1-AS1 was upregulated in HCC tissue and HCC cells, while miR-7-5p was downregulated. LncRNA RHPN1-AS1 expression in HCC patients was closely related to vascular invasion, tumor-node-metastasis (TNM) stage and barcelona clinic liver cancer (BCLC) stage. Furthermore, we quantified cell clone-formation ability, proliferation, migration and invasion of HCCLM3 and MHCC97 H cells using several assays (colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay and transwell assay, respectively). Functional experiments confirmed that silencing lncRNA RHPN1-AS1 inhibited cell proliferation, migration and invasion in HCCLM3 and MHCC97 H cells. After that, bioinformatics analysis, dual luciferase reporter gene assay, qRT-PCR and western blot were used to investigate the molecular mechanism of lncRNA RHPN1-AS1 on HCC. Mechanistically, the rescue experiments demonstrated that miR-7-5p inhibitor reversed the inhibition effect of silencing lncRNA RHPN1-AS1 on HCCLM3 cells proliferation, migration and invasion. Moreover, silencing lncRNA RHPN1-AS1 also inhibited the activation of PI3K/AKT/mTOR pathway. Taken together our findings demonstrated that lncRNA RHPN1-AS1 could facilitate cell proliferation, migration and invasion via targeting miR-7-5p and activating PI3K/AKT/mTOR pathway in HCC.

Diffusion kurtosis imaging can be used to assess pathophysiological changes in tissue structure and to diagnose central nervous system diseases. However, its sensitivity in assessing hippocampal differences between patients with Alzheimer's disease and those with amnestic mild cognitive impairment has not been characterized. Here, we examined 20 individuals with Alzheimer's disease (11 men and 9 women, mean 73.2 ± 4.49 years), 20 with amnestic mild cognitive impairment (10 men and 10 women, mean 71.55 ± 4.77 years), and 20 normal controls (11 men and 9 women, mean 70.45 ± 5.04 years). We conducted diffusion kurtosis imaging, using a 3.0 T magnetic resonance scanner, to compare hippocampal differences among the three groups. The results demonstrated that the right hippocampal volume and bilateral mean kurtosis were remarkably smaller in individuals with Alzheimer's disease compared with those with amnestic mild cognitive impairment and normal controls. Further, the mean kurtosis was lower in the amnestic mild cognitive impairment group compared with the normal control group. The mean diffusion in the left hippocampus was lower in the Alzheimer's disease group than in the amnestic mild cognitive impairment and normal control groups, while the mean diffusion in the right hippocampus was lower in the Alzheimer's disease group than in the normal control group. Fractional anisotropy was similar among the three groups. These results verify that bilateral mean kurtosis and mean diffusion are sensitive to the diagnosis of Alzheimer's disease and amnestic mild cognitive impairment. This study was approved by the Ethics Review Board of Affiliated Sixth People's Hospital of Shanghai Jiao Tong University, China on May 4, 2010 (approval No. 2010(C)-6)., Competing Interests: None

A set of ninety-eight B-Raf V600E inhibitors was used for the development of a molecular docking based QSAR model using linear and non-linear regression models. The integration of docking scores and key interaction profiles significantly improved the accuracy of the QSAR models, providing reasonable statistical parameters ( R train 2 = 0.935, R test 2 = 0.728 and Q CV 2 = 0.905). The established MD-SVR (molecular docking based SMV regression) model as well as model screening of a natural product database was carried out and two natural products (quercetin and myricetin) with good prediction activities were biologically evaluated. Both compounds exhibited promising B-Raf V600E inhibitory activities (ICQuercetin50 = 7.59 μM and ICMyricetin50 = 1.56 μM), suggesting a high reliability and good applicability of the established MD-SVR model in the future development of B-Raf V600E inhibitors with high efficacy.

The identification of novel succinate dehydrogenase (SDH) inhibitors represents one of the most attractive directions in the field of fungicide research and development. During our continuous efforts to pursue inhibitors belonging to this class, some structurally novel pyrazole-furan carboxamide and pyrazole-pyrrole carboxamide derivatives have been discovered via the introduction of scaffold hopping and bioisosterism to compound 1, a remarkably potent lead obtained by pharmacophore-based virtual screening. As a result of the evaluation against three destructive fungi, including Sclerotinia sclerotiorum, Rhizoctonia solani, and Pyricularia grisea, a majority of them displayed potent fungicidal activities. In particular, compounds 12I-i, 12III-f, and 12III-o exhibited excellent fungicidal activity against S. sclerotiorum and R. solani comparable to that of commercial SDHI thifluzamide and 1.

Succinate dehydrogenase (SDH) has been demonstrated as a promising target for fungicide discovery. Crystal structure data have indicated that the carboxyl "core" of current SDH inhibitors contributed largely to their binding affinity. Thus, identifying novel carboxyl "core" SDH inhibitors would remarkably improve the biological potency of current SDHI fungicides. Herein, we report the discovery and optimization of novel carboxyl scaffold SDH inhibitor via the integration of in silico library design and a highly specific amide feature-based pharmacophore model. To our delight, a promising SDH inhibitor, A16c (IC 50 = 1.07 μM), with a novel pyrazol-benzoic scaffold was identified, which displayed excellent activity against Rhizoctonia solani (EC 50 = 11.0 μM) and improved potency against Sclerotinia sclerotiorum (EC 50 = 5.5 μM) and Phyricularia grisea (EC 50 = 12.0 μM) in comparison with the positive control thifluzamide, with EC 50 values of 0.09, 33.2, and 33.4 μM, respectively. The results showed that our virtual screening strategy could serve as a powerful tool to accelerate the discovery of novel SDH inhibitors.

BACKGROUND The aim of the study was to assess whether HIF-1α polymorphisms have an effect on the response to chemotherapy of locally advanced cervical cancer (LACC) patients treated with platinum-based neoadjuvant chemotherapy (NACT) and radical surgery. MATERIAL AND METHODS We conducted a retrospective study in 162 LACC patients. Hypoxia-inducible factor 1α C1772T and G1790A genetic polymorphisms were ascertained using direct sequencing methods. RESULTS The C1772T polymorphism was significantly related to response to chemotherapy (P=0.002), and there was an increased chance of treatment response in patients with the C/C genotype (OR=4.7; 95% CI: 1.67-13.49; P=0.004). The C1772T polymorphism was also associated with poor tumor grade (adjusted OR, 2.98; 95% CI: 1.08-8.13; P=0.037). However, The G1790A polymorphism was not associated with response (P>0.05). CONCLUSIONS The C1772T polymorphism was significantly related to response to chemotherapy and poor tumor grade. Our results may help to better manage individual patients and to improve clinical decision making regarding use of NACT.

In an attempt to discover more potential antifungal agents, in this study, 21 novel trichodermin derivatives containing conjugated oxime ester (5a-5u) were designed and synthesized and were screened for in vitro antifungal activity. The bioassay tests showed that some of them exhibited good inhibitory activity against the tested pathogenic fungi. Compound 5a exhibited better activity against Pyricularia oryzae and Sclerotonia sclerotiorum than trichodermin, and compound 5j showed particular activity against P.oryzae and Botrytis cinerea. The quantitative structure-activity relationship (QSAR) indicated that log P and hardness were two critical parameters for the biological activities. The result suggested that these would be potential lead compounds for the development of fungicides with further structure modification.

To discover more potential antifungal agents, 17 novel trichodermin derivatives were designed and synthesized by modification of 3 and 4a. The structures of all the synthesized compounds were confirmed by (1)H NMR, ESI-MS and HRMS. Their antifungal activities against Ustilaginoidea oryzae and Pyricularia oryzae were evaluated. Most of the target compounds showed potent inhibitory activity, in which 4g showed superior inhibitory effects than 4a and commercial fungicide prochloraz. Furthermore, 4h demonstrated comparable inhibitory activity to 4a. Moreover, 4i and 4l exhibited excellent inhibitory activity for Pyricularia oryzae. Additionally, compound 9 was found to be more active against all tested fungal strains than 3, with EC50 values of 0.47 and 3.71 mg L(-1), respectively., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Tumor formation and growth is dictated by a very small number of tumor cells, called cancer stem cells, which are capable of self-renewal. The genesis of cancer stem cells and their resistance to conventional chemotherapy and radiotherapy via mechanisms such as multidrug resistance, quiescence, enhanced DNA repair abilities and anti-apoptotic mechanisms, make it imperative to develop methods to identify and use these cells as diagnostic or therapeutic targets. Aldehyde dehydrogenase 1 (ALDH1) is used as a cancer stem cell marker. In this study, we evaluated ALDH1 expression in CaSki, HeLa and SiHa cervical cancer cells using the Aldefluor method to isolate ALDH1-positive cells. We showed that higher ALDH1 expression correlated with significantly higher rates of cell proliferation, microsphere formation and migration. We also could demonstrate that SiHa-ALDH1- positive cells were significantly more tumorigenic compared to SiHa-ALDH1-negative cells. Similarly, SiHa cells overexpressing ALDH1 were significantly more tumorigenic and showed higher rates of cell proliferation and migration compared to SiHa cells where ALDH1 expression was knocked down using a lentivirus vector. Our data suggested that ALDH1 is a marker of cervical cancer stem cells and expand our understanding of its functional role.

This study has explored the use of lipid-based formulations to enhance the oral bioavailability of the poorly water-soluble drug anethol trithione (ATT), and compared the performance of different formulations. Two groups of lipid-based formulations, sub-microemulsion (SME) and oil solution, were prepared using short (SCT), medium (MCT) and long (LCT) chain triglycerides respectively; aqueous suspension was used as the reference formulation. In vitro and in vivo studies were conducted to investigate the impact of lipid composition and formulation on drug absorption. In vitro digestion was used to analyze lipid digestion rates and drug distribution/solubilization. After in vitro digestion, the performance rank order for drug solubilization was SCT

Objective: To investigate the extent of exposure of non-smoking pregnant women to passive smoking; to undertake interventions on the knowledge, attitudes and behaviors of those women toward passive smoking; and to evaluate the effectiveness of the interventions., Methods: A total of 128 non-smoking pregnant women participated in the survey. Their knowledge, attitudes and behaviors towards passive smoking were measured by a self-administered questionnaire. A sixteen-week intervention was undertaken., Results: The knowledge and attitudes of the non-smoking pregnant women towards passive smoking improved significantly, as well as their attempts to avoid exposure to the passive smoking brought by their smoking husbands or other family members. Telephone counseling, booklets and doctors' advices were the most acceptable approaches of health education., Conclusion: The comprehensive interventions are effective for improving the knowledge, attitudes and behaviors of non-smoking women toward passive smoking.

Little is known about the characteristics of particulate matter emissions from vehicles in China, although such information is critical in source apportionment modeling, emission inventories, and health effect studies. In this paper, we report a comprehensive characterization of PM2.5 emissions in the Zhujiang Tunnel in the Pearl River Delta region of China. The chemical speciation included elemental carbon, organic carbon, inorganic ions, trace elements, and organic compounds. The emission factors of individual species and their relative distributions were obtained for a mixed fleet of heavy-duty vehicles (19.8%) and light-duty vehicles (80.2%). In addition, separate emission factors of PM2.5 mass, elemental carbon, and organic matter for heavy-duty vehicles and light-duty vehicles also were derived. As compared to the results of other tunnel studies previously conducted, we found that the abundances and distributions of the trace elements in PM2.5 emissions were more varied. In contrast, the characteristics of the trace organic compounds in the PM2.5 emissions in our study were consistent with characteristics found in other tunnel studies and dynamometer tests. Our results suggested that vehicular PM2.5 emissions of organic compounds are less influenced by the geographic area and fleet composition and thereby are more suitable for use in aerosol source apportionment modeling implemented across extensive regions.

Background & Objective: Phosphatidylinositol 3-kinase /protein kinase B (PI3K/Akt) signaling pathway is involved in a variety of important cellular functions, including genesis and progression of neoplasms. However, its role in cervical cancer is unclear. This study was to detect the expression of PI3K and Akt proteins in different cervical lesions, and to investigate the correlation of PI3K/Akt signal transduction pathway to biological behaviors of cervical carcinoma., Methods: The expression of PI3K and Akt in 76 specimens of cervical carcinoma,21 specimens of cervical intraepithelial neoplasia and 10 specimens of normal cervical epithelium were detected by SP immunohistochemistry. Their correlations to clinicopathologic features of cervical carcinoma were analyzed., Results: The positive rates of PI3K and Akt were significantly lower in normal cervical epithelium and cervical intraepithelial neoplasia than in cervical carcinoma (0.0% and 42.9% vs. 69.7%, P<0.01;10.0% and 52.4% vs. 75.0%,P<0.01). The expression of PI3K and Akt proteins were correlated to clinical stage, pathologic grade and lymph node metastasis(P<0.01), but not to age, the size of primary focus, and histological type(P>0.05).The expression of PI3K protein was positively correlated to the expression of Akt protein(r=0.425,P<0.01)., Conclusion: High expression of PI3K and Akt are involved in proliferation, malignant transformation, invasion and metastasis of cervical carcinoma, both of which may play important roles in the occurrence and development of human cervical carcinoma.

The validation study of the prediction method for indoor air pollution was carried out by comparing the results of emission models based on data obtained in a large and a small emission chamber, with actual measured concentrations. A new decorated room was studied as a case. Emissions of complicated objects and simple surface layer materials were studied respectively in the large and small chamber and emission models were developed. Those models were based on the assumptions regarding mass conservation of substances and the hypothesis that pollutants were well mixed. The emissions of formaldehyde and TVOC (total volatile organic compounds) in the studied room were predicted by the method. The predicted concentration trend of pollutants was in accordance with the measured trend when some air exchange (0.03 ACH, air change per hour) was taken into account. The normalized standard errors of formaldehyde and TVOC pollution prediction were respectively 2.8% and 1.6%. Modeling analysis shows that the contribution to total formaldehyde pollution of the studied room was: furniture > paint > floor; the contribution to total TVOC pollution was: paint > floor > furniture. The results lead to the conclusion that this prediction method can well describe the pollution trend, can assess the contribution of different sources, can guide the choice of building materials and is an effective tool for indoor air pollution assessment and control.

The glucoamylase gene (glaA) of Aspergillus niger CICIM F0410 was cloned, sequenced and expressed. The integrated plasmid pBC-Hygro-glaA carrying the glaA was constructed and transformed into A. niger F0410. Transformants with multiple copies of glaA integrated in the chromosome were selected by 150 microg/mL hygromycin B and identified by real-time PCR. Two to three multiples of glaA in the chromosome were found to be optimal for higher expression of glucoamylase. Shake-flask fermentation under optimal conditions showed that glucoamylase secreted by the transformant GB0506 was 17.5% higher than parental strain F0410 at the end of fermentation. In conclusion, increasing copy number of glaA by chromosomal integration significantly improves the yield of glucoamylase in the industrial strain of A. niger.