Poly(I:C) Exacerbates Airway Goblet Cell Hyperplasia and Lung Inflammation in HDM-Exposed Balb/C Mice by YAP/FOXM1 Pathway.

INTRODUCTION: Respiratory viral infection in childhood is closely associated with asthmatic attacks. Of all predisposing factors, viral infection is the primary contributor to acute childhood asthma exacerbations. However, the mechanisms involved in viral asthma are unclear. This study attempted to provide insights into molecular mechanisms in respiratory virus-induced acute asthma exacerbations. METHODS: House dust mite (HDM) was given by intranasal administration to induce asthma in mice. Poly(I:C) was used to mimic the viral infection. A selective YAP inhibitor, verteporfin (VP), was used to investigate the role of the YAP/FOXM1 pathway. The expression of YAP, FOXM1, cytokines, and inflammatory cells in lung tissue, and bronchoalveolar lavage fluid (BALF) was determined using RT-PCR, immunohistochemical, ELISA, and flow cytometry studies. The methacholine challenge assesses airway hyperresponsiveness. In 16HBE cell experiments, we selectively inhibited YAP and FOXM1 by VP and RCM1, respectively, and detected the expression of YAP and FOXM1. RESULTS: The experimental studies have confirmed the YAP/FOXM1 pathway plays a vital role in the differentiation and proliferation of airway club cells into goblet cells and lung inflammation. Poly(I:C) upregulated the expression of FOXM1 by activating transcription factor YAP in mice airway epithelial cells and then promoted the expression of downstream transcription factors SPDEF/MUC5AC, resulting in airway mucus hypersecretion and hyperresponsiveness. In addition, Poly(I:C) facilitates the expression of inflammatory factors in lung tissue. All of these events induce asthma exacerbations. The in vitro studies have confirmed that YAP positively regulates FOXM1 in airway epithelial cells. CONCLUSION: Poly(I:C) promotes airway epithelial goblet cell hyperplasia, mucus hypersecretion, and airway hyperresponsiveness. It also upregulates the expression of inflammatory factors in lung tissue and BALF in asthmatic mice by the YAP/FOXM1 pathway, resulting in asthma attacks.

Synthesis of 7-Amido Indolines by Cp*Co(III)-Catalyzed C-H Bond Amidation.

An efficient Cp*Co(III)-catalyzed C-H bond amidation of indolines at the C7-position using dioxazolone as amidating reagents was first reported. N-Methyl-N-(pyrimidin-2-yl)aniline was also found to be a competent coupling partner. This protocol exhibits several unique characteristics, including excellent isolated yields, good functional group tolerance, and operational convenience. Derivatization reactions revealed this method has great potential for applications in synthesis.

[Relationship of pelvic clinic-pathological features and the pain symptoms in ovarian endometrioma].

OBJECTIVE: To study the relationship between the clinic-pathological features and pain symptoms in patients with endometriotic cyst (EM). METHODS: The medical data of symptoms, laparoscopy and pathology examination in 416 patients with endometriosis were studied retrospectively. All cases were divided into two groups on the existence of ovarian endometrioma, including 338 patients in cyst group and 78 cases in non-cyst group. The relationship between clinical symptoms and location and type of endometrioma was studied. RESULTS: (1) Serum CA125 level: the level of CA125 were (61 ± 39) kU/L in cyst group (28 ± 24) kU/L in non-cyst group, which reached statistical difference (P < 0.01). (2) Pathological features: among 338 cases, 34.0% of cyst were on left side (115/338), 26.3% were right side (89/338), and 39.6% were on both side (134/338). And 95.8% (324/338) of cases were combined with the other type of endometriosis, which were 48.5% (164/338) with peritoneal endometriosis, 47.3% (160/338) with deep infiltrating endometriosis (DIE). In cystic patients, the incidences of endometriosis lesion were 13.9% (47/338) on the uterine surface, 38.5% (130/338) on obstruction of cul-de sac, 40.5% (137/338) on utero-sacral ligament of DIE, which were significantly higher than 5.1%, (4/78), 9.0% (7/78) and 28.2% (22/78) in noncyst group. (3) Pain symptom: the incidence and degree of dysmenorrhea and dyschezia had no statistical difference between two groups (P > 0.05), and the incidence of chronic pelvic pain (CPP) of 24.6% (83/338) and dyspareunia of 29.9% (101/338) in the cyst group were significantly lower than 35.9% (28/78) and 44.9% (35/78) in non-cyst group (P < 0.05). The incidence of dysmenorrheal was 85.1% (114/134) in cases with bilateral cyst, which was higher than 74.0% (151/204) in cases with single cyst. The incidence of dysmenorrheal and dyschezia in moderate-severe adhesion was 89.0% (138/155) and 18.7% (29/155), which was significantly higher than 68.8% (126/183) and 8.2% (15/183) in mild adhesion. In the patients cyst existed with DIE, the risk of dysmenorrheal, CPP, dyspareunia, and dyschezia were obviously raised (OR respectively was 5.17, 3.01, 3.05, 2.75). CONCLUSIONS: The endometriotic cyst often co-exists with other type of endometriotic lesions. Ovarian endometrioma was associated with lesion localized on uterine surface, cul-de-sac, sacrum ligament. The risk of all the pain symptoms would be raised when the endometriotic cyst co-exit with the DIE lesions. So the treatment for DIE lesions was as same important as the endometriotic lesions in order to relieve pain symptoms and delay the relapse.

[Pollution Characteristics of Water-soluble Ions in PM2.5 During the Lantern Festival of 2021 in Zibo City].

Based on the online ion data, we have analyzed the cause of a PM2.5 pollution episode, which happened during the Lantern Festival in Zibo in 2021. The pollution characteristics of water-soluble ion components were analyzed, the formation mechanism of secondary inorganic ions (SNA) was discussed, and the changes in the liquid water content (LWC) and pH value of particulate matter before and after pollution were comparatively analyzed. The results showed that the pollution period before the Lantern Festival (T1) and the pollution period at night (T2) ρ(WSIIs) during the Lantern Festival were 46.83 µg·m-3 and 71.18 µg·m-3, respectively, which were 2.3 times and 3.6 times that of the cleaning period, respectively. Among them, the growth multiple of SNA during the T1 period was greater[ρ(NO3-) was 2.9 times, ρ(SO42-) was 2.8 times, and ρ(NH4+) was 2.4 times] than the growth multiple of PM2.5 (2.1 times), which showed that the increase in SNA concentration during the T1 period was the main reason for the increase in PM2.5 concentration. Furthermore, the Cl-, K+, and Mg2+ concentrations, which were 4.0, 14.8, and 16.5 times that of the cleaning period, respectively, increased significantly during the T2 period, indicating that the fireworks and firecrackers caused the rapid increase in the PM2.5 concentration during the T2 period. The LWC during the pollution period was 49.37 µg·m-3, which was 2.9 times that of the cleaning period. LWC was mainly affected by RH and NH4+ during the T1 period and was also affected by Mg2+ during the T2 period. The average pH during the pollution period in Zibo was 4.79±1.54, which was 0.14 lower than that during the cleaning period. The pH during the T1 period was affected by the combined effects of SO42- and NH4+, which made it decrease 0.53 compared to that during the cleaning period. The pH value during the T2 period may be affected by the K+, Cl-, and Mg2+ emitted from the fireworks and firecrackers, causing the pH to increase 0.65 compared to that during the cleaning period. The formation mechanism showed that SO42- was mainly generated by heterogeneous hydrolysis during the pollution episode, whereas NO3- was mainly generated by homogeneous reactions. On the whole, during the pollution episode, the increase in PM2.5 concentration before the Lantern Festival was mainly caused by the increase in SNA concentration, and the increase the night of the Lantern Festival was mainly caused by setting off fireworks and firecrackers.

[Comparison of postoperative residue, recurrence and pregnancy outcome between laparoscopic and transabdominal myomectomy].

OBJECTIVES: To compare operative characteristics, postoperative residue, recurrence, and pregnancy outcome between laparoscopic myomectomy (LM) and transabdominal myomectomy (TAM), and investigate the favourable surgical approach in women with uterine myomas. METHODS: From Jan 2008 to Dec 2008, 313 women undergoing LM and 148 women undergoing TAM were studied retrospectively in Peking Union Medical College Hospital. The patients' general information, including the largest diameter, mean numbers and weights of excised myomas, peri-operative characteristics (operating time, blood loss, and hemoglobin decrease), and residue, recurrence of myoma, and pregnancy outcome were compared and analyzed. RESULTS: The largest diameter, mean numbers and mean weight of myomas removed were larger in TAM group [(7.6 ± 3.0) cm, (5.6 ± 5.5), (308 ± 364) g, respectively] than those in LM group [(6.8 ± 2.0) cm, (2.4 ± 2.1), (140 ± 109) g, respectively; P < 0.01]. While the extension of operating time [(89 ± 32) versus (74 ± 35) min], increased blood loss [(239 ± 251) versus (149 ± 252) ml] and hemoglobin decrease [(22 ± 14) versus (15 ± 12) g/L], and longer hospital stay [(6.4 ± 1.6) versus (4.4 ± 1.3) d] were observed in TAM group when compared with those in LM group (P < 0.01). However, the residue rate of LM and TAM was 2.6% versus 1.4% respectively (P = 0.5130); the recurrence rate of LM and TAM was 11.1% versus 12.3% (P > 0.05); the pregnancy rate of LM and TAM was 49.2% versus 9/13 separately, the difference was not statistically significant (P = 0.2330). The number of myomas removed was the significant risk factors associated with recurrence (OR = 2.805, 95%CI: 1.192 - 6.601, P = 0.0180). No uterine rupture occurred during pregnancy. CONCLUSIONS: Both LM and TAM are effective surgical approaches for the patients with leiomyoma who desire to pregnancy, or to retain the integrity of their uteruses. Most of uterine myoma could be treated through laparoscopy. The residue rate of LM is higher than that of TAM. However, the short term recurrence rates of LM and TAM are similar. Multiple myomas is the risk factor associated with recurrence after myomectomy. The pregnancy rates are comparable between LM and TAM groups.

[Expressions and roles of TGFß/Smad signal pathway in peritoneum of endometriosis].

OBJECTIVE: To investigate the expression of transforming growth factor (TGF)-ß and Smad pathway expressed in adhesion peritoneums in patients with endometriosis (EM). METHODS: From Dec. 2009 to Mar. 2010, 11 patients with EM [including 3 patients treated by gonadotropin releasing hormone agonist (GnRH-a) treatment] underwent laparoscopy surgery in Peking Union Medical College Hospital. In the mean time, 9 patients with benign ovarian tumor without EM and peritoneum adhesion were chosen as control. Peritoneum from lateral peritoneal cavity, adjacent from lesion and grossly normal was obtained during surgery. Microstructure of peritoneums was observed by HE staining and Masson staining. The expression of TGF-ß1, TGF-ß3, Smad 3 and Smad 7 in peritoneums were measured by immunohistochemistry staining and real-time PCR. The effect of GnRH-a on expressions of these markers were also analyzed. RESULTS: (1) Microstructures of peritoneum: enlargement of nucleus of peritoneal mesothelial cells, thickening of connective tissue, distributive disorder of fiber, increasing numbers of fibroblast and inflammatory cells in EM were significantly different from those in control group. (2) The expression of TGF-ß1 and 3 in peritoneum were 0.170 ± 0.020 and 0.110 ± 0.010 in EM group, which were significantly higher than 0.070 ± 0.010 and 0.050 ± 0.020 in control group. TGF-ß1 was downregulated to 0.130 ± 0.030 and TGF-ß3 was upregulated to 0.490 ± 0.090 by GnRH-a. (3) The expression of Smad 3 and 7 were 0.140 ± 0.020 and 0.110 ± 0.020 in peritoneum in EM group, which were significantly higher than 0.024 ± 0.004 and 0.014 ± 0.007 in control group. GnRH-a could upregualted the expression of smad 7 (0.040 ± 0.020), however, but no significant effect was observed on regulating Smad3 expression. CONCLUSIONS: The changes of microstructure and the alteration of TGF-ß/Smad expression in peritoneum of endometriosis were observed. GnRH-a could regulate the expression of TGF-ß and Smad.

Thoracic endometriosis presented as catamental hemoptysis: a case series of a rare disease.

OBJECTIVE: Thoracic endometriosis syndrome (TES) is a rare disease in which a functioning endometrial tissue is observed in the pleura, lung, parenchyma, airways, and/or diaphragm. The optimal management of this disease remains a matter of debate. We aimed to report TES cases and their effective hormonal treatment and management. METHODS: In this retrospective study, women presented as catamenial hemoptysis (CH) diagnosed with thoracic endometriosis were included. The main outcome of measure was cessation or recurrence of the clinical manifestations of thoracic endometriosis. RESULTS: The mean onset age of the 14 patients was 30.21 ± 5.40 years. CH was characteristic symptom of these patients. All patients underwent chest computed tomography (CT) scan during menstruation and 2 or 3 weeks after menstruation, which showed the obvious shrinking or disappearance of the lesions. All of the patients were given Gonadotropin releasing hormone agonists (GnRHa) for 3 to 6 months, eleven of them were administered with combined oral contraceptives (COC) cyclically after GnRHa. The median follow-up duration was 24 months. Hemoptysis recurrence was observed in one patient. CONCLUSIONS: CH is a rare clinical entity of thoracic endometriosis, the change of CT images during and after menstruation or the response to GnRHa were helpful for accurate diagnosis. Hormonal treatment with GnRHa followed by COCs cyclically could be employed for efficient management of thoracic endometriosis.

Directed Cobalt-Catalyzed C-H Activation to Form C-C and C-O Bonds in One Pot via Three-Component Coupling.

Herein, we disclose an efficient cobalt-catalyzed three-component coupling of benzamides, diazo compounds, and tert-butyl hydroperoxide, which provides an efficient approach to construct C(sp2)-C(sp3) and C-O bonds in one-pot accompanied with C-H activation. This protocol features low catalyst loading (4 mol %), the avoidance of additives, and excellent functional group compatibility, providing three-component coupling adducts with high yields under mild conditions (up to 88%). Mechanism studies show that the reaction may involve a radical process.

A phase conversion headspace technique for the determination of anti-anaerobic activity of drug candidate based on the metabolic acidity change in culture medium.

Screening for anti-anaerobic drug candidates is still challenging although the anaerobic bacteria are important sources for human infections, because the method for anti-anaerobic activity testing is not readily available with low-cost and -expertise. We report a novel method for the determination of the anti-anaerobic activity of drug candidates by automated headspace-gas chromatography (HS-GC). Anaerobic bacteria were inoculated in an anaerobic atmosphere or rapidly using sterile syringe in an air-tight manner, and incubated with and without drugs for 48 h. The metabolic acidities of the cultured media were used as an indicator of cell activities and measured as end-products in place by HS-GC after being completely converted to CO2 with sodium bicarbonate. The present method is precise (relative standard deviation is below 5%) and validated by excellent agreements with a reference method on the determinations of the inhibition rates (root-mean-square error = 10%, n = 48) and half maximal inhibitory concentrations (R2 = 0.996, n = 8) of both pure drug compounds and plant extracts. Advantageously, the present method is sensitive in response to cell activity, safe with regard to cross contamination, and suitable for routine screening of diversified drug candidates for anti-anaerobic activity.

Directed Cobalt-Catalyzed anti-Markovnikov Hydroalkylation of Unactivated Alkenes Enabled by "Co-H" Catalysis.

The earth-abundant cobalt-catalyzed anti-Markovnikov hydroalkylation of unactivated alkenes with oxime esters was achieved by introducing an 8-aminoquinoline directing group on the alkenes. The catalytic system, consisting of commercially available Co(acac)3 and PhMeSiH2, enables the construction of unfunctionalized C(sp3)-C(sp3) bonds and features exclusive anti-Markovnikov selectivity, good functional group tolerance, and the avoidance of an extra ligand, oxidant, or base. Mechanistic insight into this new catalytic system indicates the involvement of both alkyl radical and cobalt hydride intermediates.

In-situ headspace analysis of metabolic carbon dioxide of aerobic bacteria for assessing antimicrobial activity of natural products.

Headspace analysis of the volatile metabolites has been used as a good strategy for monitoring the microbial growth in several applications, but never been established for the evaluation of the activity of microbial inhibitor in the field of drug screening from natural products. We report on a new method for the determination of antimicrobial activity of drug compounds or crude extracts from natural products by measuring the amount of metabolic carbon dioxide produced in the drug-bacteria incubation system. 2 mL of medium containing bacteria and drug of interest was incubated at 37 °C for 24 h. The amount of metabolic carbon dioxide partitioned in the headspace was measured to evaluate the drug antimicrobial activity using headspace gas chromatography (HS-GC) coupled with thermal conductive detector (TCD). The principle and the standard procedure of the present method have been developed and verified. As a result, the precision of the present method was less than 4% (expressed as relative standard deviation), and an excellent agreement was found on both inhibition rate (R2 = 0.935) and the half inhibition concentration (R2 = 0.994) between the present method and a reference method (optical density method). By comparison, the present method is simpler and safer regarding the microorganism contamination due to the in-situ incubation and detection in the closed system, and suitable for the routine analysis of antimicrobial activity of natural products with high flexibility in both bacterial strains and sample properties.

Melatonin Reduces Androgen Production and Upregulates Heme Oxygenase-1 Expression in Granulosa Cells from PCOS Patients with Hypoestrogenia and Hyperandrogenia.

BACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by abnormal hormone levels in peripheral blood and poor-quality oocytes. PCOS is a pathophysiological syndrome caused by chronic inflammation and oxidative stress. The aim of this study was to investigate the mechanism of melatonin regulation on androgen production and antioxidative damage in granulosa cells from PCOS patients with hypoestrogenia and hyperandrogenia. METHODS: Cumulus-oocyte complexes were collected from PCOS patients who had low levels of estrogen in follicular fluids. RESULTS: Melatonin triggered upregulation of cytochrome P450 family 19 subfamily A member 1 (CYP19A1) expression via the extracellular signal-regulated kinase pathway in luteinized granulosa cells. As a result, conversion of androgen to 17ß-estradiol was accelerated. We also found that melatonin significantly reduced the levels of inducible nitric oxide (NO) synthetase and NO in luteinized granulosa cells. Levels of transcripts encoding NF-E2-related factor-2 and its downstream target heme oxygenase-1 were also increased, leading to anti-inflammatory and antioxidant effects. We also found that melatonin could improve oocyte development potential. CONCLUSION: Our preliminary results showed that melatonin had a positive impact on oocyte quality in PCOS patients with hypoestrogenia and hyperandrogenia.

Abdominal wall lump after cesarean delivery.

BACKGROUND: An abdominal wall desmoid tumor is a rare event, has a strong tendency for local invasion and recurrence, and usually presents as an abdominal lump. CASE: A 35-year-old multiparous woman presented with a painful abdominal lump that had been slowly increasing in size. The pain was not associated with menstruation. Clinical examination, ultrasonography, and abdominal magnetic resonance imaging were performed and suggested a large, sharply defined mass measuring approximately 11 × 7.1 cm in the right anterolateral abdominal wall. There was no family history of familial adenomatous polyposis. The mass was excised and sent for histopathologic examination, which indicated abdominal wall desmoid tumor. CONCLUSION: Abdominal wall desmoid tumors can be diagnostic dilemmas and should be considered in the differential diagnosis for lumps in the abdomen in women.

Homonymous Quadrantanopsia as the First Manifestation of Cerebral Metastasis of Invasive Mole: a case report.

INTRODUCTION: Homonymous quadrantanopsia results from retrochiasmal lesions in the visual pathway. Invasive mole is a benign tumor that arises from myometrial invasion of a hydatidiform mole via direct extension through tissue or venous channels. Cerebral metastasis of invasive mole is rare and there has been no report demonstrating homonymous quadrantanopsia as the first manifestation of metastasis in any trophoblastic neoplasms. CASE PRESENTATION: We report the case of a 31-year-old Asian woman who presented with right homonymous inferior quadrantanopsia from the mass effect of a solitary cerebral metastasis from an invasive mole. A magnetic resonance image (MRI) of the brain showed a metastatic tumor in the left occipital lobe. The visual field improved slightly after chemotherapy. There was a reduction in the tumor size and the surrounding edema. This is the first case report demonstrating that homonymous quadrantanopsia should be included in the manifestations of the metastasis of an invasive mole. CONCLUSIONS: The presentation of homonymous quadrantanopsia must alert ophthalmologists to conduct a complete medical history and arrange specialist consultation.