Radical Deoxygenative Three-Component Reaction of Alcohols, Aryl Alkenes, and Cyanopyridines.

We report herein a deoxygenative radical multicomponent reaction involving alcohols, aryl alkenes, and cyanopyridine under photoredox conditions. This method is photoredox-neutral, suitable for late-stage modification, and compatible with a wide array of alcohols as alkyl radical sources, including primary, secondary, and tertiary alcohols. This reaction comprises a radical relay mechanism encompassing the Giese addition of aryl alkenes by alkyl radicals, followed by the decyanative pyridination of benzyl radicals.

Corrigendum: Potential Mechanisms of Action of Chinese Patent Medicines for COVID-19: A Review.

[This corrects the article DOI: 10.3389/fphar.2021.668407.].

Potential Mechanisms of Action of Chinese Patent Medicines for COVID-19: A Review.

Coronavirus disease 2019 (COVID-19) is an emergent infectious pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is highly contagious and pathogenic. COVID-19 has rapidly swept across the world since it was first discovered in December 2019 and has drawn significant attention worldwide. During the early stages of the outbreak in China, traditional Chinese medicines (TCMs) were involved in the whole treatment process. As an indispensable part of TCM, Chinese patent medicines (CPMs) played an irreplaceable role in the prevention and treatment of this epidemic. Their use has achieved remarkable therapeutic efficacy during the period of medical observation and clinical treatment of mild, moderate, severe, and critical cases and during convalescence. In order to better propagate and make full use of the benefits of TCM in the treatment of COVID-19, this review will summarize the potential target of SARS-CoV-2 as well as the theoretical basis and clinical efficacy of recommended 22 CPMs by the National Health Commission and the Administration of TCM and local provinces or cities in the treatment of COVID-19. Additionally, the study will further analyze the drug composition, potential active ingredients, potential targets, regulated signaling pathways, and possible mechanisms for COVID-19 through anti-inflammatory and immunoregulation, antiviral, improve lung injury, antipyretic and organ protection to provide meaningful information about the clinical application of CPMs.

The outcomes of pregnant and postpartum patients with cerebral venous sinus thrombosis after anticoagulant therapy.

BACKGROUND: To describe the outcome of the patients with cerebral venous sinus thrombosis (CVST) during pregnancy and postpartum treated with anticoagulant therapy. METHODS: This is a retrospective cohort study and patients with CVST were collected from October 2009 to March 2018. Patients were divided into pregnancy-related (occurred during pregnancy and postpartum) group and non-pregnancy-related. Recovery rate at 12 months after anticoagulant therapy, adverse events, characteristics of patients with poor outcomes were statistically analyzed. RESULTS: Fifty-eight pregnancy-related CVST patients (17 pregnancy and 41 postpartum) as study group and 76 non-pregnancy-related CVST women as control group were enrolled. Study group was statistically different to control group in several baseline variables. More pregnancy-related patients had modified rankin scale (mRS) = 5 (15.5% vs 11.8%, P = 8.1×10-3) before anticoagulant therapy. At 12 months heparinization, difference in recovery rate was not statistically significant (80% vs 87.5%, P = .29) between 2 groups. No differences were found of adverse events between 2 groups. Patients with poor outcomes had less sigmoid sinus thrombosis (16.7% vs 61.5%, P = .14), more coma (41.2% vs 17.2%, P = 5.2×10-7), more mRS = 4 (33.3% vs 19.2%, P = 1.63 × 10-4), more mRS = 5 (66.7% vs 9.6%, P = 1.63 × 10-4) before treatment. CONCLUSION: Pregnancy-related CVST patients had severer condition before treatment, but can achieve comparable recovery rate at 12 months after anticoagulant therapy with non-pregnancy-related women. Pregnancy-related patients with poor prognosis had less sinus sigmoid occlusion, more coma, high mRS at admission.

Clinical characteristics and outcomes in pregnant women with epilepsy.

BACKGROUND: Epilepsy in pregnancy can lead to substantial maternal and neonatal morbidity and mortality. Early intervention in pregnant women with epilepsy (WWE), accurate assessment of the severity of their condition, and effective treatment are required to improve maternal and neonatal prognosis. Many obstetricians lack experience in monitoring and treating pregnant WWE. AIMS: The aim of this study was to describe the demographic and clinical characteristics of pregnant WWE and examine maternal and neonatal outcomes. METHODS: Medical records of 75 pregnant women with a history of epilepsy who delivered at Beijing Tiantan Hospital, China between January 2006 and December 2019 were retrospectively reviewed. Pregnant women with a history of epilepsy were matched 1:2 with a control group of 150 pregnant women without epilepsy who delivered at Beijing Tiantan Hospital during the same time period. Information including type and frequency of epilepsy and seizures, maternal complications, medication, delivery mode, newborn weight, and newborn Apgar score were recorded. In subgroup analyses, pregnant WWE were stratified according to presence or absence of seizures during pregnancy and generalized seizure vs. nongeneralized seizure. RESULTS: The incidence of anemia, hypertensive disorder of pregnancy, premature rupture of membranes (PROM), cesarean section, and postpartum hemorrhage was significantly higher (p < 0.05), and mean newborn weight and newborn Apgar score were significantly lower (p < 0.05) in pregnant WWE compared with pregnant women without epilepsy. The incidence of premature delivery was significantly higher (p < 0.05), and mean newborn weight was significantly lower (p < 0.05) in pregnant WWE with seizures vs. without seizures. Mean newborn weight was significantly lower (p = 0.01) in pregnant WWE with nongeneralized seizures vs. generalized seizures. CONCLUSION: Pregnant WWE are at high risk of anemia, gestational hypertension, PROM, cesarean section, postpartum hemorrhage, and low newborn weight and Apgar score. Women with epilepsy who experience seizures during pregnancy are at high risk of preterm birth and having low birth weight infants. Pregnant WWE who experience nongeneralized seizures are at high risk of having low birth weight infants. These data emphasize the need to routinely monitor fetal weight on ultrasound and offer appropriate intervention. These findings highlight the need for healthcare providers to take a multidisciplinary approach to the management of pregnant WWE. SYNOPSIS: Pregnant WWE are at high risk of obstetric complications. Women with epilepsy who experience seizures during pregnancy are at high risk of preterm birth and having low birth weight infants. Pregnant WWE who experience nongeneralized seizures are at high risk of having low birth weight infants. These data highlight the need for healthcare providers to take a multidisciplinary approach to the management of pregnant WWE.

The clinical characteristics of pregnant women with epilepsy in China.

BACKGROUND: Epilepsy during pregnancy and puerperium is infrequent, and it can induce severe complications and poor prognosis. Pregnancy in women with epilepsy (WWE) is usually uneventful. Previous studies have mainly focused on the effects of different treatments on prognosis. However, few articles have addressed if different epilepsy types were associated with a higher incidence of seizure breakthrough/recurrence and pregnancy outcomes. METHODS: In the present study, based on a unique sample with a low incidence of epilepsy, we evaluated the main clinical characteristics of epilepsy patients. RESULTS: Mean age of pregnant WWE was 29.95±4.65 (range, 21-42) years. Pregnancies were at a mean gestational age of 33.80±9.14 (range, 7-41) weeks, and 88.24% (52/61) of WWE were in their third trimester. There was 9.84% (6/61) of pregnant WWE underwent abortion or induced labor in midpregnancy to ensure maternal safety. There was 75.41% (46/61) of pregnant WWE using antiepileptic drugs (AEDs), of which 52.46% (32/61) were taking a single AED and 22.95% (14/61) were using multiple AEDs. There was 47.54% (29/61) of WWE experiencing seizures during their pregnancy. We found that the type of epilepsy did not affect seizures during pregnancy or the prognosis. However, more pregnant WWE with hypertensive disorder had seizures compared with pregnant WWE without hypertensive disorder. CONCLUSIONS: The study highlighted a novel direction for effectively improving seizures during pregnancy and the prognosis of pregnancy-associated epilepsy.

The incidence of placenta related disease after the hysteroscopic adhesiolysis in patients with intrauterine adhesions.

OBJECTIVE: To analyze the correlation between placenta related disease of pregnant women with antecedent hysteroscopic adhesiolysis due to intrauterine adhesions (IUA). MATERIALS AND METHODS: This is a single center, non-randomized, open-label, retrospective cohort Study. 74 patients who had adhesiolysis and hormone therapy for IUA and progressed into the third trimester were group A and 296 without IUA were group B. The main outcome measure is the incidence of placenta related disease including placenta accreta spectrum, placenta previa, placental abruption, intrauterine growth restriction (IUGR), and pregnancy-induced hypertension (PIH). The second outcome is the perinatal, and intrapartum complications. RESULTS: Patients in group A had a higher frequency of prior pregnancy times (2.51 ± 1.56 vs.1.84 ± 1.06, p = 0.001) and lower frequency of prior delivery times (0.20 ± 0.41 vs. 1.30 ± 0.51, p < 0.05) than group B at baseline. At delivery, there is no difference between the incidence of PIH and IUGR between two groups. However, a significantly higher frequency of placenta accreta (17.6% vs. 1.4%, OR = 15.56, 95% CI 4.91-49.34), placenta increta (5.4% vs. 0.7%, OR = 8.4, 95% CI 1.51-46.78), placenta previa (8.1% vs. 2.0%, OR = 4.265, 95%CI1.33-13.63) and postpartum hemorrhage (21.6% vs. 3.4%, OR = 7.890, 95% CI 3.41-18.26) were observed in group A than in group B. CONCLUSIONS: Compared to general population, the rates of placenta accreta, placenta increta, placenta previa, postpartum hemorrhage are higher among the IUA patients after hysteroscopic adhesiolysis, and special attention is needed at the termination of the pregnancy.

Thymoquinone induces cytotoxicity and reprogramming of EMT in gastric cancer cells by targeting PI3K/Akt/mTOR pathway.

Gastric cancer is one of the lethal causes of cancer-related deaths worldwide. The incidence and mortality rates of this disease is comparatively higher in China. In the current study, we evaluated the anticancer effects of Thymoquinone (TQ) against gastric cancer cells (MGC80-3 and SGC-7901) and normal noncancerous GES-1 cells and attempted to investigate the underlying mechanism. Our results indicated that TQ exhibited significant growth inhibitory effects on gastric cancer cells (MGC80-3 and SGC-7901). However, lower cytotoxicity was observed against normal GES-1 cells. Moreover, TQ could inhibit the colony formation potential of MGC80-3 and SGC-7901 cells in a dose-dependent manner. TQ also inhibited cell migration ability of the gastric cancer cells and down-regulated the expression of the mesenchymal genes such as N-cadherin, Vimentin, and TWIST. However, the epithelial markers such as E-cadherin and cytokeratin-19 were distinctly up-regulated in TQ-treated gastric cancer cells. Since PI3K/Akt/ mTOR plays an important role in progression and tumorigenesis, we also investigated the effect of TQ on PI3K/Akt/mTOR signalling pathway in gastric cancer cells. It was observed that TQ down-regulated the expression of some of the key proteins of this pathway. Taken together, we conclude that TQ may prove lead molecule for the treatment of gastric cancer.

Low concentrations of bisphenol A promote human ovarian cancer cell proliferation and glycolysis-based metabolism through the estrogen receptor-α pathway.

Bisphenol A (BPA) is one of the most prevalent chemicals in many products used on a daily basis, making human exposure to it incredibly pervasive and raising concerns about its health consequences. One area of research focus has been the role of BPA exposure in promoting the development of ovarian cancer; however, the doses used in most of previous studies are relatively high and most likely exceed physiologically relevant levels. At the same time, few studies have described potential mechanisms underlying the link between BPA and increased cancer risk. To address these concerns we investigated the mechanism(s) by which low concentrations of BPA promote proliferation and energy metabolism in the human ovarian cancer cell line OVCAR-3. We found that even sub-toxic BPA concentrations not only drove increased OVCAR-3 cell proliferation but also promoted glycolysis-based metabolism, as evidenced by elevated cell viability, accelerated cell proliferation, increased levels of intracellular ATP, lactate, and pyruvic acid. Importantly, all of these effects were estrogen receptor α (ERα) dependent, as siRNA-mediated ERα silencing decreased BPA-induced proliferation, pinpointing the crucial role of ERα-conducted signaling in BPA-induced biological effects. Together, our findings revealed a new mechanism through which BPA promoted cell proliferation by reinforcing glycolysis-based energy production dependent on ER signaling. This study would thus open a new path to understand BPA-induced biological effects on tumor cells.

Clerosterol from vinegar-baked radix bupleuri modifies drug transport.

Vinegar-baked Radix Bupleuri (VBRB) is reportedly used to treat liver cancer when combined with traditional chemotherapy and data show that this combination may modify drug transport. We isolated clerosterol from VBRB and studied its effect on drug transporters in normal or transporter-overexpressing cells. Transporter activity was assayed using cellular substrate concentration and transporter expression with Western blot and RT-qPCR. Clerosterol decreased cisplatin uptake in BRL cells mainly through increasing Mrp2 gene expression. Clerosterol also decreased the uptake of colchicine in HEK 293 cells by increasing both Pgp and Mrp1 activity; in detail, it could increase Pgp protein but had marginal effects on Mrp1 protein and gene expression. Further study showed clerosterol increased OCT2 activity in HEK293-Pgp cells by increasing OCT2 protein and mRNA. Clerosterol could suppress Pgp overexpression but not by regulating protein and gene expression. And clerosterol had marginal effects on Mrp2 and Mrp1 activity in Mrp2- and Mrp1-overexpressing HEK293 cells. Thus, Clerosterol may be an active constituent of VBRB and may work against cancer multidrug resistance by inhibiting Pgp activity.

Clinical characteristics and prognosis of cerebral venous thrombosis in Chinese women during pregnancy and puerperium.

Due to the specific physiology associated with pregnancy and puerperium, cerebral venous sinus thrombosis (CVT) may manifest different characteristics. This study aimed to identify the clinical manifestations and prognosis of pregnancy-associated CVT. A total of 43 pregnancy-associated CVT patients were enrolled. We analysed the clinical presentations of the disease and performed a multivariate logistic regression analysis to determine which variables were associated with prognosis. Our descriptive results showed the following: 1) the incidence was 202 per 100,000 deliveries, and the mortality rate was 11.63%; 2) the most frequent symptom was headache; 3) the most frequent abnormal laboratory findings were increased levels of fibrinogen and several serum lipoproteins (including triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, apolipoprotein A1, and apolipoprotein B); and 4) the superior sagittal sinus and transverse sinus were the most frequently affected locations. Moreover, an increased modified Rankin Scale score was positively associated with infection, seizure, intracerebral haemorrhage (ICH) and hypertensive disorders of pregnancy (HDP). Comparably, the occurrence of death was positively and significantly associated with infection, seizure and ICH. Consequently, timely diagnosis and treatment of pregnancy-associated CVT patients with infection, seizure, ICH or HDP are needed. Patients with infection, seizure or ICH have a greater risk of death.

E2F1-directed activation of nc886 mediates drug resistance in cervical cancer cells via regulation of major vault protein.

Non-coding RNAs are critical regulators of tumor biology. nc886, a recently identified non-coding RNA, is overexpressed in some tumors, but undetected in others. However, the precise role of nc886 remains unclear in cervical cancers. In this study, we found that nc886, major vault protein (MVP), and E2F1 exhibited coordinate expression as they were silenced in normal tissues but overexpressed in cervical cancer tissues. We subsequently demonstrate that nc886 upregulation was a critical response to chemotherapy treatment of cervical cancer cells. Mechanistically, inhibition of nc886 increased chemosensitivity, induced apoptosis, and suppressed the protein expression of MVP, a critical regulator of drug resistance. Furthermore, we identify E2F1 as a key transcription regulator of nc886 that directly interacts and modulates promoter activity. Taken together, we demonstrate that E2F1 sufficiently promotes nc886 transcription and in turn MVP expression to drive drug resistance in cervical cancer cells.

Hysteroscopic treatment of Robert's uterus with laparoscopy.

Herein is described the case of a 26-year-old woman whose Robert's uterus was treated with hysteroscopy and who then successfully became pregnant and gave birth. The uterus anomaly was diagnosed on combined hysteroscopy and ultrasonography, which showed an asymmetric septate uterus with one blind cavity, causing menstrual retention. The surgery was uncomplicated, with satisfactory results. The patient underwent successful cesarean section delivery of a baby boy weighing 3250 g on 24 March 2014.

A clinical characteristic analysis of pregnancy-associated intracranial haemorrhage in China.

Intracerebral haemorrhage (ICH) occurring during pregnancy and the puerperium is an infrequent but severe complication with a high mortality and poor prognosis. Until recently, previous studies have mainly focused on the effect of different treatments on prognosis. However, few studies have provided solid evidence to clarify the key predisposing factors affecting the prognosis of ICH. In the present study, based on a unique sample with a high ICH incidence and mortality rate, we described the main clinical characteristics of ICH patients and found that the prognosis of patients who underwent surgical intervention was not better than that of patients who received other treatment modalities. However, pre-eclampsia patients had higher maternal and neonatal mortality rates than other aetiology groups. Furthermore, univariate regression analysis identified onset to diagnosis time (O-D time) and pre-eclampsia as the only factors showing independent correlation with poor maternal outcomes (modified Rankin Scale, mRS ≥ 3), and only O-D time was identified as a predictor of maternal mortality. These results revealed that the aetiology of ICH and O-D time might be crucial predisposing factors to prognosis, especially for patients with pre-eclampsia. The study highlighted a novel direction to effectively improve the prognosis of pregnancy-associated ICH.

Bisphenol A and hormone-associated cancers: current progress and perspectives.

Bisphenol A (BPA), a carbon-based synthetic compound, exhibits hormone-like properties and is present ubiquitously in the environment and in human tissues due to its widespread use and biological accumulation. BPA can mimic estrogen to interact with estrogen receptors α and ß, leading to changes in cell proliferation, apoptosis, or migration and thereby, contributing to cancer development and progression. At the genetic level, BPA has been shown to be involved in multiple oncogenic signaling pathways, such as the STAT3, MAPK, and PI3K/AKT pathways. Moreover, BPA may also interact with other steroid receptors (such as androgen receptor) and plays a role in prostate cancer development. This review summarizes the current literature regarding human exposure to BPA, the endocrine-disrupting effects of BPA, and the role of BPA in hormone-associated cancers of the breast, ovary, and prostate.

[Pharmacokinetic study on peoniflorin, astilbin, rosmarinic acid, isofraxidin and liquiritin in rat blood after oral administration of shaolin xiaoyin tablets].

To establish a method for the determination of astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin contained in Shaolin Xiaoyin tablets, in order to lay a foundation for designing late-stage dosage forms and clinical medication schemes. In this paper, efforts were made to establish a method for the determination of the blood concentration of the five components and study the in vivo pharmacokinetics in rats. The blood concentration was determined by HPLC. Phenomenex C18 column (4.6 mm x 250 mm, 5 microm) was adopted and eluted with methanol-acetonitrile-0.05% formic acid, the flow rate was 0.8 mL x min(-1), and the wavelength was 275 nm. The samples were processed by the solid phase extraction method. After oral administration of Shaoling Xiaoyin tablets, the rat bloods were collected at different time points to determine the blood concentrations. The experimental results showed that the baseline separation could be adopted for the five components, and astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin showed good linear relations within ranges of 2.48-248, 0.213 6-21.36, 0.531-53.1, 0.704-70.4, 0.253-25.3 mg x L(-1). All the five components could be absorbed in blood and excreted quickly. The method established in this paper is rapid and accurate, and could be used for in vivo analysis on preparations containing similar components. The main components in Shaoling Xiaoyin tablets could be absorbed and excreted quickly, and thus suitable to be made into sustained release tablets. Common preparations are required to be taken for 4-6 times a day.

Evaluation of lipoprotein-associated phospholipase A2 in healthy Chinese Han adult serum.

OBJECTIVE: The aim of this study is to establish lipoprotein-associated phospholipase A2 (Lp-PLA2) reference intervals (RIs) in healthy Chinese Han adults as a clinical diagnostic indicator according to the Clinical and Laboratory Standards Institute (CLSI) C28-A3 guidelines. DESIGN AND METHODS: Lp-PLA2 levels in 763 healthy Chinese Han subjects (392 males and 371 females) were determined by colorimetric analysis and the central 95th percentile RIs were determined using non-parametric statistical methods. The correlations between serum Lp-PLA2 and blood markers were analyzed by Spearman correlation analyses. RESULTS: The Lp-PLA2 levels showed a Gaussian distribution with a statistically significant difference between females and males (t = 4.866, P < 0.001). The RIs of serum Lp-PLA2 were 194-640 U/L (18-49 years) and 208-698 U/L (50-88 years) for females, and 230-728 U/L for males. There was a positive correlation between Lp-PLA2 levels and age, Body Mass Index (BMI), as well as with levels of alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), triglyceride (TG), total cholesterol (Tch), low density lipoprotein cholesterol (LDL-c), apolipoprotein B (apoB), glucose (Glu), high sensitivity C reactive protein (Hs-CRP), white blood cell (WBC), hemoglobin (HGB) and red blood cell (RBC) (P < 0.05). A negative correlation was found with high density lipoprotein cholesterol (HDL-c) and Apolipoprotein AI (apoAI), and no correlation was found with platelet (Plt) levels. CONCLUSION: Our results establish the RIs of serum Lp-PLA2 in healthy Chinese Han adults and demonstrate correlations between serum Lp-PLA2 and age, BMI, ALT, GGT, TBIL, TG, Tch, HDL-c, LDL-c, apoAI, apoB, Glu, Hs-CRP, WBC, RBC, and HGB levels.

[Clinical analysis of 25 gastric cancer cases undergoing totally laparoscopic distal gastrectomy].

OBJECTIVE: To investigate the feasibility and safety of totally laparoscopic distal gastrectomy. METHODS: Clinical data of 25 patients with distal gastric cancer undergoing totally laparoscopic distal gastrectomy between December 2011 and January 2013 were analyzed retrospectively. Only laparoscopic linear stapler was used in intracorporeal delta-shaped or Roux-en-Y anastomosis for reconstruction. RESULTS: No patient required conversion to laparoscopy-assisted or open surgery. The mean total operative time and anastomotic time were (256±23.6) min and (35.7±8.4) min respectively in patients with delta-shaped anastomosis, and (287±11.5) min and (46.4±12.1) min in those with Roux-en-Y anastomosis. The mean blood loss was(109.6±42.3) ml, and the mean number of stapler used was 5.6. The mean time to the first flatus was (2.8±1.2) d, and mean time liquid diet to resume was (3.5±0.9) d. Postoperative complication occurred in 3 patients(12.0%). CONCLUSION: Totally laparoscopic distal gastrectomy with intracorporeal anastomosis using laparoscopic linear stapler is safe and feasible.

Mitochondrial DNA haplogroup associated with sperm motility in the Han population.

In this study, we aimed to determine whether the main mitochondrial DNA (mtDNA) haplogroups of the Han people have an impact on spermatozoa motility. We recruited 312 men who were consecutively admitted to two affiliated hospitals of College of Medicine, Zhejiang University from May 2011 to April 2012 as part of fertility investigations. Semen and whole blood samples were collected from the men. We determined the mtDNA haplogroups by analysing the sequences of mtDNA hypervariable segment I and testing diagnostic polymorphisms in the mtDNA coding region with DNA probes. No significant differences were found in the clinical characteristics of the mtDNA haplogroup R and non-R (P>0.05). Our results suggest that mtDNA haplogroup R is a strong independent predictor of sperm motility in the Han population, conferring a 2.97-fold (95% confidence interval: 1.74-4.48, P<0.001) decreased chance of asthenozoospermia compared with those without haplogroup R.