Abstract Objectives Nasopharyngeal carcinoma (NPC) is an aggressive epithelial cancer. The expression of miR-186 is decreased in a variety of malignancies and can promote the invasion and metastasis of cancer cells. This study aimed to explore the role and possible mechanism of miR-186 in the metastasis and epithelial-mesenchymal transformation (EMT) of NPC. Methods The expression of miR-186 in NPC tissues and cells was detected by RT-PCR. Then, miR-186 mimic was used to transfect NPC cell lines C666-1 and CNE-2, and cell activity, invasion and migration were detected by CCK8, transwell and scratch assay, respectively. The expression of EMT-related proteins was analyzed by western blotting analysis. The binding relationship between miR-186 and target gene Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was confirmed by double luciferase assay. Results The expression of miR-186 in NPC was significantly decreased, and transfection of miR-186 mimic could significantly inhibit the cell activity, invasion, and migration, and regulate the protein expressions of E-cadherin, N-cadherin and vimentin in C666-1 and CNE-2 cells. Further experiments confirmed that miR-186 could directly target ZEB1 and negatively regulate its expression. In addition, ZEB1 has been confirmed to be highly expressed in NPC, and inhibition of ZEB1 could inhibit the activity, invasion, metastasis and EMT of NPC cells. And co-transfection of miR-186 mimic and si-ZEB1 could further inhibit the proliferation and metastasis of NPC. Conclusion miR-186 may inhibit the proliferation, metastasis and EMT of NPC by targeting ZEB1, and the miR-186/ZEB1 axis plays an important role in NPC. (NPC miR186 miR 186 miR-18 epithelialmesenchymal mesenchymal (EMT RTPCR. RTPCR RT PCR. PCR RT-PCR Then C6661 C C666 C666- CNE2, CNE2 CNE 2, 2 activity CCK8 CCK assay respectively EMTrelated related analysis EBox E Box ZEB (ZEB1 Ecadherin, Ecadherin cadherin, cadherin E-cadherin Ncadherin N CNE- addition cotransfection co siZEB1 siZEB si si-ZEB miR186/ZEB1 miR186ZEB1 miRZEB 186/ZEB1 miR-186/ZEB miR18 18 miR-1 C66 (ZEB miR186/ZEB miR186ZEB 186ZEB1 186/ZEB miR1 miR- C6 186ZEB

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy. proinflammatory pro inflammatory M antiinflammatory anti sepsisinduced sepsis induced . (ALI) proliferatoractivated proliferator 1alpha alpha 1 PGC1α PGCα PGC 1α α (PGC-1α activity (PGZ CLP. CLP (CLP) MHS MH S LPS. LPS (LPS) qRTPCR qRT PCR MHCII MHC II Arg CD CD20 PPARγ (PPARγ PGC1α, 1α, NRF1 NRF NRF2 mtTFA function staining qRTPCR. PCR. CLPinduced wettodry wet dry ratio tumor factorα, factorα factor α, factor-α interleukin1β, interleukin1β interleukinβ interleukin 1β, 1β β interleukin-1β interleukin6, interleukin6 6 , interleukin-6) PPARγ/PGC1α/mitochondrial PPARγPGC1αmitochondrial PPARγPGCαmitochondrial PPARγ/PGC 1α/mitochondrial therapy (ALI (CLP (LPS CD2 interleukin-6 PPARγPGC αmitochondrial 1αmitochondrial interleukin-

Abstract Objective To analyze the effect of mast cells (MCs) in neurogenic inflammation and the neuroimmune response of trigeminal ganglia (TG) due to pulpitis and detect the regulatory effect of curcumin (Cur) on neuroimmune responses induced by pulpitis. Methodology Immunohistochemistry, toluidine blue staining (TB), and other methods were used to detect the dynamic changes of MCs, as well as tryptase expression changes and protease activated receptor 2 (PAR2) and calcitonin gene-related peptide (CGRP) levels in the neuroimmune response induced by pulpitis. After administering Cur by intraperitoneal injection, the expression levels of Toll-like receptor 4 (TLR4), CGRP, glial fibrillary acidic protein (GFAP), fractalkine (CX3CL1), Tumor necrosis factor (TNF-α), and other factors were examined in the TG of pulpitis-induced rats. Results After pulpitis induction, the expression of CGRP-positive neurons and GFAP-positive soluble guanylate cyclase (SGC) in the TG significantly increased. A large number of MCs underwent degranulation. MCs were scattered between the CGRP-positive nerve fibers. MCs showing a typical degranulated state within the TG significantly increased and tryptase-positive MCs surrounded the TG nerve fibers and neurons. After treatment with Cur, the inflammatory response in the periodontal bone induced by pulpitis decreased and promoted early tissue repair. The expression of TNF-α significantly decreased as did degranulation of MCs. In contrast, the expression of CGRP, TLR4-positive neurons, activated SGCs, and PAR2-positive TG neurons significantly decreased. MCs could participate in the neuroimmune response induced by pulpitis by the tryptase signaling pathway. Conclusion Importantly, Cur inhibited the degranulation of MCs, downregulated the expression of tryptase and PAR2 in the TG, and attenuated the activation response of osteoclasts in the apical periodontium. (MCs (TG (Cur Immunohistochemistry TB, TB , (TB) PAR (PAR2 generelated gene related CGRP (CGRP injection Tolllike Toll like TLR4, TLR4 TLR (TLR4) GFAP, GFAP (GFAP) CX3CL1, CX3CL1 CXCL CX CL (CX3CL1) TNFα, TNFα TNF α (TNF-α) pulpitisinduced rats induction CGRPpositive positive GFAPpositive SGC (SGC tryptasepositive repair contrast TLR4positive TLRpositive SGCs PAR2positive PARpositive pathway Importantly periodontium (TB (PAR (TLR4 (GFAP CX3CL (CX3CL1 (TNF-α (TLR (CX3CL

Abstract Background Stroke is a leading cause of death worldwide, with oxidative stress and calcium overload playing significant roles in the pathophysiology of the disease. Ozone, renowned for its potent antioxidant properties, is commonly employed as an adjuvant therapy in clinical settings. Nevertheless, it remains unclear whether ozone therapy on parthanatos in cerebral ischemia-reperfusion injury (CIRI). This study aims to investigate the impact of ozone therapy on reducing parthanatos during CIRI and to elucidate the underlying mechanism. Methods Hydrogen peroxide (H2O2) was utilized to mimic the generation of reactive oxygen species (ROS) in SHSY5Y cell reperfusion injury in vitro, and an in vivo ischemic stroke model was established. Ozone saline was introduced for co-culture or intravenously administered to mice. Apoptosis and oxidative stress were assessed using flow cytometry and immunofluorescence. Western blotting was utilized to examine the expression of parthanatos signature proteins. The mechanism by which ozone inhibits parthanatos was elucidated through inhibiting PPARg or Nrf2 activity. Results The findings demonstrated that ozone mitigated H2O2-induced parthanatos by either upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) or activating peroxisome proliferator-activated receptorg (PPARg). Furthermore, through the use of calcium chelators and ROS inhibitors, it was discovered that ROS directly induced parthanatos and facilitated intracellular calcium elevation. Notably, a malignant feedback loop between ROS and calcium was identified, further amplifying the induction of parthanatos. Ozone therapy exhibited its efficacy by increasing PPARg activity or enhancing the Nrf2 translation, thereby inhibiting ROS production induced by H2O2. Concurrently, our study demonstrated that ozone treatment markedly inhibited parthanatos in stroke-afflicted mice. Additionally, ozone therapy demonstrated significant neuroprotective effects on cortical neurons, effectively suppressing parthanatos. Conclusions These findings contribute valuable insights into the potential of ozone therapy as a therapeutic strategy for reducing parthanatos during CIRI, highlighting its impact on key molecular pathways associated with oxidative stress and calcium regulation.

SUMMARY: This study is to investigate the effect of home-based cardiac rehabilitation (HBCR) on quality of life, functional capacity, and readmission rates in patients with heart failure. Randomized controlled trials (RCTs) were screened from Cochrane Library, CINAHL, EMBASE, and MEDLINE. The intervention group received a standardized HBCR or a comprehensive rehabilitation strategy that included HBCR. The participants in the control group received CR at a medical center or usual care without CR intervention. The main outcome measurements included quality of life, exercise capacity, mortality and re-hospitalization. This meta-analysis included 20 RCTs, in which 16 studies compared HBCR with usual care, and 4 studies compared HBCR with center-based CR. In comparison with the usual care, HBCR improved the total quality of life score [MD=-5.85, 95 % CI (-9.76, - 1.94), P=0.003, I2=75 %]. Patients with HBCR and usual care were significantly different in VO2max [MD=1.05 mL/kg/min, 95 % CI (0.35, 1.75), P=0.003, I2=46 %]. However, VO2max of patients with HBCR was not significantly different from those with center-based CR [MD=0.08 mL/kg/min, 95 % CI (-1.29, 1.44), P=0.91, I2=0 %]. There was statistically significant difference in the 6-min Walk Distance between usual care and HBCR (for distance [MD=11.84, 95 % CI (7.41, 16.28), P<0.00001, I2=0 %]; and for feet [MD=98.93, 95 % CI (26.79, 171.08), P=0.007, I2=56 %]). However, there was no significant difference in 6-min Walk Distance between patients with HBCR and center-based CR [MD=12.45, 95 % CI (-9.81, 34.72), P=0.27, I2=0 %] , or in anxiety and depression between patients with usual care and HBCR (for anxiety, [MD=-0.25, 95 % CI (-0.56, 0.05), P=0.11, I2=0 %]; for depression, [MD=-0.18, 95 % CI (-0.51, 0.16), P=0.30, I2=0 %] . No significant difference was found in death number [RR=1.04, 95 % CI (0.55, 1.98), P=0.90, I2=0 %] or in the number of re-hospitalization [RR=0.88, 95 % CI (0.66, 1.18), P=0.40, I2=0 %] between usual care and HBCR. For patients with heart failure, compare with usual care and center-based CR, HBCR can improve the total quality of life. Compare with usual care, HBCR can improve VO2max and 6-min Walk Distance, but compare with center- based CR, there are no differences in mortality, re-hospitalization rate or incidence of anxiety and depression. Additionally, center- based CR and HBCR showed similar outcomes and medical costs.

RESUMEN: El objetivo de este estudio fue investigar el efecto de la rehabilitación cardíaca domiciliaria (HBCR) sobre la calidad de vida, la capacidad funcional y las tasas de reingreso en pacientes con insuficiencia cardíaca. Se seleccionaron ensayos controlados aleatorios (ECA) de la Biblioteca Cochrane, CINAHL, EMBASE y MEDLINE. El grupo de intervención recibió un HBCR estandarizado o una estrategia de rehabilitación integral que incluía HBCR. Los participantes del grupo de control recibieron RC en un centro médico o atención habitual sin intervención de RC. Las principales medidas de resultado incluyeron la calidad de vida, la capacidad de ejercicio, la mortalidad y la rehospitalización. Este metanálisis incluyó 20 ECA, en los que 16 estudios compararon HBCR con la atención habitual y 4 estudios compararon que mejoró la puntuación total de calidad de vida [DM=-5,85, IC del 95 % (-9,76, -1,94), P=0,003, I2=75 %]. Los pacientes con HBCR y atención habitual fueron significativamente diferentes en el VO2máx [DM = 1,05 ml/kg/ min, IC del 95 % (0,35, 1,75), P = 0,003, I2 = 46 %]. Sin embargo, el VO2max de los pacientes con HBCR no fue significativamente diferente de aquellos con CR basada en el centro [DM = 0,08 ml/kg/min, IC del 95 % (-1,29, 1,44), P = 0,91, I2 = 0 %]. Hubo una diferencia estadísticamente significativa en la distancia de caminata de 6 minutos entre la atención habitual y HBCR (para la distancia [DM=11,84, IC del 95 % (7,41, 16,28), P<0,00001, I2=0 %]; y para los pies [DM= 98,93, IC 95 % (26,79, 171,08), P=0,007, I2=56 %]). Sin embargo, no hubo una diferencia significativa en la distancia de caminata de 6 minutos entre los pacientes con HBCR y CR basada en el cen- tro [DM = 12,45, IC del 95 % (-9,81, 34,72), P = 0,27, I2 = 0 %], o en la ansiedad y depresión entre pacientes con atención habitual y HBCR (para ansiedad, [DM=-0,25, IC del 95 % (-0,56, 0,05), P=0,11, I2=0 %]; para depresión, [DM=-0,18, 95 % IC (- 0,51, 0,16), P=0,30, I2=0 %] No se encontraron diferencias significativas en el número de muertes [RR=1,04, IC del 95 % (0,55, 1,98), P=0,90, I2=0 %] o en el número de reingresos [RR=0,88, IC 95 % (0,66, 1,18), P=0,40, I2=0 %] entre atención habitual y HBCR. Para los pacientes con insuficiencia cardíaca, en comparación con la atención habitual y la CR en un centro, la HBCR puede mejorar la calidad de vida total. En comparación con la atención habitual, la HBCR puede mejorar el VO2máx y la distancia recorrida en 6 minutos, pero en comparación con la CR basada en un centro, no hay diferencias en la mortalidad, la tasa de rehospitalización o la incidencia de ansiedad y depresión. Además, CR y HBCR basados en el centro mostraron resultados y costos médicos similares.

Resumo Fundamento A trombose completa da falsa luz facilita a remodelação da dissecção aórtica tipo B (DATB). As características morfológicas afetam a trombose na falsa luz. Objetivos Discutir os fatores pré-admissão presentes, que influenciam a trombose da falsa luz em pacientes com DATB. Metodologia Ao todo, 282 pacientes diagnosticados com DATB em nosso hospital foram estudados, no período entre janeiro de 2008 e dezembro de 2017. Os indivíduos foram divididos em um grupo trombótico e um grupo não trombótico, com base na detecção de qualquer trombo na falsa luz. Analisamos as diferenças entre os dois grupos com relação aos dados clínicos, o comprimento vertical da dissecção e o diâmetro da aorta. Valores de p < 0,05 foram considerados estatisticamente diferentes de modo significativo. Resultados Diferenças significativas entre o grupo trombótico e o grupo não trombótico foram encontradas com relação à idade (53,92 ± 11,40 vs. 50,36 ± 10,71, p = 0,009) e proporção de pacientes com insuficiência renal (7,83% vs. 16,38%, p = 0,026). Nas zonas 3–9, o diâmetro da luz verdadeira do grupo trombótico foi significativamente maior do que no grupo não trombótico (p < 0,05). A análise de regressão logística binária mostrou que o diâmetro da luz verdadeira na zona 5 e a insuficiência renal foram preditores independentes de trombose da falsa luz. Conclusões A idade e a função renal estiveram associadas à trombose na falsa luz. Potencialmente, a diferença entre o diâmetro da luz verdadeira e o da falsa luz pode influenciar na trombose da falsa luz. . (DATB) préadmissão pré admissão presentes todo 28 estudados 200 2017 clínicos aorta 005 0 05 0,0 significativo 53,92 5392 53 92 (53,9 1140 11 40 11,4 vs 5036 50 36 50,3 1071 10 71 10,71 0,009 0009 009 7,83% 783 7 83 (7,83 1638 16 38 16,38% 0,026. 0026 0,026 026 0,026) 39 3 9 3–9 0,05. 0,05) Potencialmente (DATB 2 20 201 00 0, 53,9 539 (53, 114 1 4 11, 503 50, 107 10,7 0,00 000 7,83 78 8 (7,8 163 16,38 002 0,02 02 3– 53, (53 10, 7,8 (7, 16,3 (5 7, (7 16, (

Abstract Background Complete thrombosis of the false lumen facilitates remodeling of type B aortic dissection (TBAD). Morphological characteristics affect thrombosis in the false lumen. Objectives Discuss the factors present before admission that influence false lumen thrombosis in patients with TBAD. Methods We studied 282 patients diagnosed with TBAD in our hospital between January 2008 and December 2017. We divided the subjects into a thrombotic group and a non-thrombotic group based on whether any thrombus was detectable in the false lumen. We analyzed the differences between the two groups with respect to clinical data, the vertical length of the dissection, and the diameter of the aorta. P values < 0.05 were considered statistically significantly different. Results Significant differences between the thrombotic group and non-thrombotic group were found with respect to age (53.92 ± 11.40 vs. 50.36 ± 10.71, p = 0.009) and proportion of patients with renal insufficiency (7.83% vs. 16.38%, p = 0.026). In zones 3–9, the true lumen diameter of the thrombotic group was significantly larger than in the non-thrombotic group (p < 0.05). Binary logistic regression analysis showed that true lumen diameter in zone 5 and renal insufficiency were independent predictors of false lumen thrombosis. Conclusions Age and renal function were associated with thrombosis in the false lumen. Potentially, the difference between the diameter of the true lumen diameter and that of the false lumen may influence the thrombosis of the false lumen. . (TBAD) 28 200 2017 nonthrombotic non data aorta 005 0 05 0.0 different 53.92 5392 53 92 (53.9 1140 11 40 11.4 vs 5036 50 36 50.3 1071 10 71 10.71 0.009 0009 009 7.83% 783 7 83 (7.83 1638 16 38 16.38% 0.026. 0026 0.026 026 0.026) 39 3 9 3–9 0.05. 0.05) Potentially (TBAD 2 20 201 00 0. 53.9 539 (53. 114 1 4 11. 503 50. 107 10.7 0.00 000 7.83 78 8 (7.8 163 16.38 002 0.02 02 3– 53. (53 10. 7.8 (7. 16.3 (5 7. (7 16. (

Abstract Background Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. Methods Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. Results In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. Conclusions Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis. Highlights Microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs) exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes. Microvesicles from propofol post-treated HUVECs ((HR + P)-EMVs) induced diminished oxidative stress and apoptosis in IR-injured cardiomyocytes compared with microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs). lncCCT4-2 was significantly highly expressed in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs, and reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. lncCCT4-2 inhibited HR-EMVs induced oxidative stress and apoptosis in HR-injured AC16 cells by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in AC16 cells.

Abstract Background The main features of polycystic ovary syndrome (PCOS) are abnormal follicular development and ovulatory dysfunction, which are caused by excessive apoptosis of ovarian granulosa cells. Acupuncture has been shown to improve follicular development abnormalities in patients with PCOS, but its mechanism is unknown. This study hypothesized that the mechanism of acupuncture on follicular development abnormalities in PCOS patients is the inhibition of granulosa cell apoptosis through LncMEG3-mediated regulation of miR-21-3p. Methods A PCOS-like rat model was established using subcutaneous injection of dehydroepiandrosterone (DHEA). Acupuncture was performed on rats for 15 d (CV-4, RN-3, CV-6, SP-6 and EX-CA 1). Ovarian morphology was observed by HE staining, and sex hormone and AMH levels were detected by ELISA. Primary granulosa cells were isolated from each group of rats to assess the association of acupuncture treatment, LncMEG3, miR-21-3p, and granulosa cell apoptosis in rats with PCOS. Results LncMEG3 and miR-21-3p were highly expressed in the ovarian granulosa cells of rats with PCOS, and LncMEG3-mediated regulation of miR-21-3p was involved in the development of PCOS in rats. Silencing of MEG3 attenuated sex hormone dysregulation and ovarian histopathological changes in PCOS rats and promoted follicle cell development and maturation. In addition, silencing MEG3 increased the viability and number of granulosa cells. In addition, silencing MEG3 further inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats. Acupuncture improved polycystic ovarian morphology and sex hormone levels in PCOS rats. Acupuncture intervention increased the viability and number of granulosa cells. Acupuncture intervention inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats by targeting miR-21-3p via LncMEG3. Conclusion These results suggest that acupuncture can downregulate LncMEG3, thereby targeting and regulating miR-21-3p to suppress early and late granulosa cell apoptosis and normalize their proliferation. These factors ultimately compensate for abnormal follicular development. These findings shed light on the clinical potential of acupuncture as a safe treatment for follicular developmental abnormalities in PCOS. Highlights LncMEG3-mediated inhibition of miR-21-3p regulates ovarian granulosa cell apoptosis. LncMEG3 and miR-21-3p are involved in the occurrence and development of PCOS-related abnormal follicular development. CuONPs induce co-occurrence of autophagy activation and autophagic flux blockade. Acupuncture can improve the sex hormone levels and follicular development in the context of PCOS. The underlying mechanism of acupuncture in the treatment of PCOS abnormal follicular development was revealed.

Abstract To investigate the safety and efficacy of intraoperative intraperitoneal chemotherapy in treating advanced gastric cancer. A randomized controlled trial (RCT) of gastric cancer surgery combined with intraoperative intraperitoneal chemotherapy for the efficacy and safety were screened by computer search PubMed, Medline, Springer, Elsevier Science Direct, Weipu, Wanfang and China National Knowledge Infrastructure (CNKI) with the last report up to October 2019. The control group underwent radical gastrectomy, and the experimental group underwent intraoperative intraperitoneal chemotherapy and radical gastrectomy. A total of 997 (Experimental group 453; Control group 544) participants were considered in this meta-analysis. Compared with the control group, the experimental group has higher 1-year survival rate [OR=2.40, 95%CI (1.34, 4.33), P=0.003], 2-year survival rate [OR=3.45, 95%CI (2.08, 5.75), P<0.00001], 3-year survival rate [OR=2.70, 95%CI (2.05, 3.54), P<0.00001] and 5-year survival rate [OR=2.90, 95%CI (1.93, 4.37), P<0.00001]. There is no significant difference in postoperative bleeding (P=0.95), postoperative infection (P=0.26), postoperative anastomotic leakage (P=0.41), and postoperative intestinal obstruction (P=0.11). Intraoperative intraperitoneal chemotherapy with advanced gastric cancer in the Chinese population can improve patients’ survival rate after surgery and does not increase the incidence of postoperative complications, so it is clinically significant and safe.

ABSTRACT Purpose: Spontaneous intracerebral hemorrhage (ICH) is a major public health problem with a huge economic burden worldwide. Ulinastatin (UTI), a serine protease inhibitor, has been reported to be anti-inflammatory, immune regulation, and organ protection by reducing reactive oxygen species production, and inflammation. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced EBI in a C57BL/6 mouse model. Methods: The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The anti-inflammation effectiveness of UTI in ICH patients also was evaluated. Results: UTI treatment markedly increased the neurological score, alleviate the brain edema, decreased the inflammatory cytokine TNF-α, interleukin‑1β (IL‑1β), IL‑6, NF‑κB levels, and RIP1/RIP3, which indicated that UTI-mediated inhibition of neuroinflammation, and necroptosis alleviated neuronal damage after ICH. UTI also can decrease the inflammatory cytokine of ICH patients. The neuroprotective capacity of UTI is partly dependent on the MAPK/NF-κB signaling pathway. Conclusions: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation, and necroptosis.

RESUMO Introdução: A dificuldade em adormecer está ligada ao mau funcionamento do mecanismo do ciclo sono-vigília no corpo humano e é causada por diversos motivos. Existe uma serie de reações adversas que resultam da má qualidade – ou qualidade anormal - do sono, especificamente durante o sono. Esses sintomas afetam seriamente a condição física e a saúde mental das pessoas. Objetivo: Explorar o efeito de exercícios físicos em pacientes com dificuldade em adormecer. Métodos: Estatísticas matemáticas foram usadas para analisar 60 pacientes com dificuldade em adormecer. Dividimos os pacientes em um grupo de esportes e outro de controle. Os pacientes no grupo de esportes tiveram treinamento esportivo, enquanto o grupo de controle não. Após duas semanas de intervenção e comparação, usamos estatísticas matemáticas para avaliar a função cognitiva dos grupos. Resultados: Após o exercício físico, houve melhora na qualidade de sono dos pacientes e os transtornos do sono diminuíram. Conclusão: A atividade física é uma forma simples e popular de se exercitar. É eficaz na melhora da função cognitiva de pacientes com dificuldade de adormecer. Nível de evidência II; Estudos terapêuticos – investigação de resultados de tratamento.

ABSTRACT Introduction: Difficulty falling asleep is connected to the malfunctioning of the sleep and wakefulness mechanism of the human body caused by various reasons. There are a series of adverse reactions resulting from abnormal or poor quality of sleep during sleep per se. This symptom severely affects an individual's physical condition and mental health. Objective: To explore the effect of physical exercise on patients with difficulty falling asleep. Methods: Mathematical statistics were used to analyze 60 patients with difficulty falling asleep. We divided the patients into a sports group and a control group. The patients in the sports group took sports training, while the control group did not. After two weeks of intervention and comparison, we used mathematical statistics to evaluate the groups’ cognitive function. Results: After physical exercise, the patient's sleep quality was higher and sleep disorders were reduced. Conclusion: Physical activity is a simple and popular way of exercising. It is effective in improving the cognitive function of patients with difficulty falling asleep. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMEN Introducción: La dificultad en dormirse se relaciona al mal funcionamiento del mecanismo del ciclo sueño-vigilia en el cuerpo humano y es causada por diversos motivos. Existe una serie de reacciones adversas que resultan de la mala calidad o calidad anormal del sueño, durante el sueño en sí. Esos síntomas afectan seriamente la condición física y la salud mental de las personas. Objetivo: Explorar el efecto de ejercicios físicos en pacientes con dificultad en dormirse. Métodos: Dividimos los pacientes en un grupo de deportes y otro de control. Los pacientes en el grupo de deportes tuvieron entrenamiento deportivo, mientras el grupo de control no. Tras dos semanas de intervención y comparación, usamos estadísticas matemáticas para evaluar la función cognitiva de los grupos. Resultados: Tras el ejercicio físico, hubo mejoría en la calidad del sueño de los pacientes y los trastornos del sueño disminuyeron. Conclusión: La actividad física es una forma simple y popular de ejercitarse. Es eficaz en la mejoría de la función cognitiva de pacientes con dificultad de dormirse. Nivel de evidencia II; Estudios terapéuticos – investigación de resultados de tratamiento.

Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.

ABSTRACT A novel inclusion complexes nanofibrous membrane fluorescent sensor was prepared for recognizing F- via electrospinning and host–guest interaction. The host α-cyclodextrin on the surface of the electrospun nanofiber membrane is assembled into the guest azobenzene molecule which modified with F- fluorescent probe, and the formation of the inclusion complex is fixed on the surface of the nanofibrous membrane without external force, to prepare a novel surface controllable composite nanofiber membrane for F- detection. The inclusion complexes nanofibrous membrane exhibited favourable sensitivity and selectivity for F-. The introduction of F- would result in notable fluorescent decreasing of the membrane, but the other most common anions would not disturb the detection of F-. Moreover, this nanofibrous membrane was not only a fluorescent sensor for detecting F-, but also a good adsorbent for F- in solution.

ABSTRACT Background: the esophagogastric junction contractile integral (EGJ-CI) is a novel high-resolution manometry (HRM) tool designed to assess EGJ barrier function. This study assessed whether changes in EGJ-CI values reflect a disruption of the EGJ in achalasia patients undergoing per-oral endoscopic myotomy (POEM). Methods: patients with HRM performed both before and after POEM were identified over a three year period and were compared to healthy controls. EGJ-CI was calculated using the St Louis method, where EGJ vigor is assessed independently of respiration and referenced to the gastric baseline. It is reported as mmHg.cm. Pre- and post-POEM EGJ-CI, conventional lower esophageal sphincter pressure (LESP) metrics (end expiratory LESP and mean basal LESP) and integrated relaxation pressure (IRP) were compared between groups. The correlation between EGJ-CI and conventional LESP metrics was also assessed and compared to controls. Results: fifteen achalasia patients (35.2 ± 2.5 years, 73% female) fulfilled the inclusion criteria and were compared to 20 healthy volunteers (26.6 ± 1.1 years, 50% female). The Eckardt score was significant lower after POEM (1.5 ± 0.3 vs 7.0 ± 0.5, p < 0.001). Baseline conventional LESP metrics, EGJ-CI and IRP were higher in achalasia cases compared to controls (p < 0.001). Both conventional LESP metrics and EGJ-CI decreased significantly following POEM (p < 0.001) and approximated the values recorded in controls (p ≥ 0.1). However, IRP remained higher post-POEM compared to controls (p = 0.011). EGJ-CI correlated with conventional LESP metrics at baseline (Pearson's r = 0.75-0.79; Spearman's rho = 0.84-0.85, p < 0.001) and following POEM (0.55-0.70 and 0.5-0.77, respectively; p ≤ 0.03). Conclusions: EGJ-CI complements the assessment of the EGJ barrier and may be a useful metric to follow barrier function after per-oral myotomy.

Resumo Introdução Atualmente, são limitadas as informações acerca da relação entre o polimorfismo C47T de superóxido dismutase 2 (SOD2) dependente de manganês e suscetibilidade à perda auditiva induzida pelo ruído (PAIR). Objetivo O objetivo desta metanálise foi esclarecer a associação entre o polimorfismo C47T de SOD2 e PAIR. Método Foram feitas buscas no PubMed e Web of Science para coleta de dados. Foram incluídos todos os estudos no idioma inglês, com dados suficientes e completos de casos e controles sobre a relação entre o polimorfismo C47T de SOD2 e PAIR. Foram identificados três estudos qualificados, que abrangeram 1.094 indivíduos. Foram calculadas as razões das chances (odds ratio, OR) acumuladas e intervalos de confiança (IC) de 95% para que fosse avaliada a potência da associação entre o polimorfismo C47T de SOD2 e PAIR. Resultados Não foi encontrada uma associação significativa entre o polimorfismo C47T de SOD2 e risco de PAIR com as seguintes combinações: T vs. C (OR = 0,83, IC 95% = 0,63-1,09); TT vs. CC (OR = 0,49, IC 95% = 0,22-1,09); CT vs. CC (OR = 0,54, IC 95% = 0,25-1,17); TT vs. CC + CT (OR = 0,82, IC 95% = 0,50-1,32); CC vs. TT + TC (OR = 0,49, IC 95% = 0,23-1,04). Contudo, na análise de subgrupo, foi encontrada uma associação significativa para TT vs. CC + CT (OR = 0,77, 95% CI = 0,42-1.41) na população chinesa. Conclusão A presente metanálise sugere que o polimorfismo C47T de SOD2 demonstra associação significativa com maior risco de PAIR na população chinesa. Há necessidade de novos estudos de grande porte bem concebidos, para confirmação dessa associação.

Abstract Introduction Currently, there is limited information about the relationship between manganese superoxide dismutase (sod2) c47t polymorphism and susceptibility to noise-induced hearing loss (NIHL). Objective The aim of this meta-analysis was to clarify the association between SOD2 C47T polymorphism and NIHL. Methods A search in PubMed and Web of Science was performed to collect data. All full-text, English-written studies containing sufficient and complete case-and-control data about the relationship between SOD2 C47T polymorphism and NIHL were included. Three eligible studies, comprising 1094 subjects, were identified. pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated to evaluate the strength of the association between SOD2 C47T polymorphism and NIHL. Results No significant association between C47T polymorphism and risk of NIHL was found with the following combinations: T vs. C (OR = 0.83; 95% CI = 0.63–1.09); TT vs. CC (OR = 0.49; 95% CI = 0.22–1.09); CT vs. CC (OR = 0.54; 95% CI = 0.25–1.17); TT vs. CC + CT (OR = 0.82; 95% CI = 0.50–1.32); CC vs. TT + TC (OR = 0.49; 95% CI = 0.23–1.04). However, in subgroup analysis, a significant association was found for TT vs. CC + CT (OR = 0.77; 95% CI = 0.42–1.41) in the Chinese population. Conclusion The present meta-analysis suggests that SOD2 C47T polymorphism is significantly associated with increased risk of NIHL in the Chinese population. Further large and well-designed studies are needed to confirm this association.