Down-regulated Wnt7a and GPR124 in early-onset preeclampsia placentas reduce invasion and migration of trophoblast cells.

OBJECTIVES: Preeclampsia (PE) is a disease specific to pregnancy that causes 9-10 % of maternal deaths. Early-onset PE (<34 weeks' gestation) is the most dangerous category of PE. Wnt7a and GPR124 (G protein-coupled receptor 124) are widely expressed in the human reproductive process. Especially during embryogenesis and tumorigenesis, Wnt7a plays a crucial role. However, few studies have examined the association between Wnt7a-GPR124 and early-onset PE. The aim of this study was to examine the significance of Wnt7a and GPR124 in early-onset PE as well as Wnt7a's role in trophoblast cells. METHODS: Immunohistochemistry (IHC), real-time PCR, and western blotting (WB) were used to investigate Wnt7a and GPR124 expression in normal and early-onset PE placentas. Additionally, FACS, Transwell, and CCK-8 assays were used to diagnose Wnt7a involvement in migration, invasion, and proliferation. RESULTS: In the early-onset PE group, Wnt7a and GPR124 expression was significantly lower than in the normal group, especially in the area of syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). A negative correlation was found between Wnt7a RNA and GPR124 expression (r=-0.42, p<0.01). However, the Wnt7a RNA expression level was positive correlated with PE severity. In further cellular functional experiments, knockdown of Wnt7a inhibits HTR8/SVeno cells invasion and migration but has little effect on proliferation and apoptosis. CONCLUSIONS: Through the Wnt pathway, Wnt7a regulates trophoblast cell invasion and migration, and may contribute to early-onset preeclampsia pathogenesis. A molecular level study of Wnt7a will be needed to find downstream proteins and mechanisms of interaction.

Breaking through the Separation Barrier of Zr(IV) and Hf(IV): Magical Effect of the Bisamide Ligand.

The fundamental safety improvement of the nuclear industry depends on two important elements: Zr(IV) and Hf(IV). However, the elementary knowledge is that separation processes of the two are difficult, so there are few existing methods to meet the requirement. Furthermore, the process is highly contaminated. The development of green and efficient ligands for the separation of Zr(IV) and Hf(IV) is beneficial to the stable development of the nuclear industry. A bisamide ligand D001 was reported for the extraction and separation of Zr(IV) and Hf(IV). D001 utilizes an anionic association mechanism to extract Zr(IV) and Hf(IV) by coordinating amide groups with metals to form complexes H2ZrCl6·2 D001 and H2HfCl6·2 D001. Using quantum chemical calculations, we illuminate the extraction mechanism of bisamide ligands and the reasons for their better coordination ability than monoamide ligands and carboxylic acid ligands. A process of bisamide extraction and separation of Zr(IV) and Hf(IV) was established, and the thermodynamic parameters of the process were investigated.

Different Doses of Ropivacaine either with Sufentanil or with Dexmedetomidine for Labor Epidural Anesthesia regarding Painless Childbirth: A Retrospective, Multicenter Study.

INTRODUCTION: Sufentanil is used with ropivacaine in labor pain management but it can have respiratory depression. Dexmedetomidine is effective to maintain hemodynamic stability in parturient women and allow awake intubation. However, dexmedetomidine is suggested only in patients with major cardiovascular disease that mandates stable hemodynamics (Reference ID: 3987541-USFDA). The objective of the study was to compare different doses of ropivacaine either with sufentanil or with dexmedetomidine for epidural anesthesia regarding labor pain management. METHODS: Parturient women have received 0.125% ropivacaine with 0.5-µg/mL sufentanil (SR1 cohort, n = 115), or 0.08% ropivacaine with 0.5-µg/mL sufentanil (SR2 cohort, n = 109), or 0.125% ropivacaine with 0.5-µg/mL dexmedetomidine (DR1 cohort, n = 124), or 0.08% ropivacaine with 0.5-µg/mL dexmedetomidine (DR2 cohort, n = 135) for epidural anesthesia during vaginal delivery or cesarean section. RESULTS: At 2-h postpartum, the visual analog scale score of parturient women of the DR2 cohort was fewer than that of parturient women of the SR1 (p < 0.0001, q = 4.162) and the SR2 (p < 0.0001, q = 7.568) cohorts and statistically the same as that of parturient women of the DR1 cohort (p < 0.0001, q = 3.087). Bradycardia and itching were reported in parturient women of the DR2 and the DR1 cohorts while nausea, vomiting, and urinary retention at 6 h were reported in parturient women of the SR1 and the SR2 cohorts. In the DR2 cohort, there were fewer numbers of parturient women with bradycardia (4 vs. 19, p < 0.0001, q = 6.613) and hypotension (2% vs. 1%) than those in the DR1 cohort. The child born by women of the DR2 cohort had high partial arterial pressure of oxygen than those born by women of the DR1 (p < 0.0001, q = 18.663), the SR1 (p < 0.0001, q = 29.366), and the SR2 (p < 0.0001, q = 24.039) cohorts. DISCUSSION/CONCLUSION: Epidural 0.08% ropivacaine with 0.5-µg/mL dexmedetomidine is an effective and safe anesthetic regimen for hypertensive parturient women and their newborns. LEVEL OF EVIDENCE: III. Technical Efficacy Stage: 4.

Labor epidural analgesia versus without labor epidural analgesia for multiparous women: a retrospective case control study.

BACKGROUND: Labor epidural analgesia (LEA) effectively relieves the labor pain, but it is still not available consistently for multiparous women in many institutions because of their obviously shortened labor length. METHODS: A total of 811 multiprous women were retrospective enrolled and firstly divided into two groups: LEA group or non-LEA group. And then they were divided into seven subgroups and analyzed according to the use of LEA and cervical dilation. The primary outcomes (time intervals, blood loss and Apgar scores) and secondary outcomes (maternal demographic characteristics and birth weight) were collected by checking electronic medical records. RESULTS: The prevalence of using LEA in multiprous women was 54.5 %. Using LEA significantly lengthened the duration of labor stage by 56 min (P < 0.001), increased the blood loss (P < 0.001) and lowered Apgar scores (P = 0.001). In the comparison of sub-group analysis, using LEA can obviously prolong the duration of first-second stage in women with 2 cm cervical dilation (P < 0.001) and 3 cm cervical dilation (P = 0.014), while there was no significant difference with 4 cm or more cervical dilation (P = 0.69). Using LEA can significantly increased the blood loss when the initiation of LEA in the women with 2 cm cervical dilation (P < 0.001) and 3 cm cervical dilation (P = 0.035), meanwhile there were no significantly differences in the women with 4 cm or more cervical dilation (P = 0.524). Using LEA can significantly lower the Apgar scores when the initiation of LEA in the women with 2 cm cervical dilation (P = 0.001) and 4 cm or more cervical dilation (P = 0.025), while there were no significantly differences in the women with 3 cm cervical dilation (P = 0.839). CONCLUSIONS: Labor epidural analgesia for the multiparous woman may alter progress of labor, increase postpartum blood loss and lower Apgar scores. Early or late initiation of LEA should be defined as with cervical dilatation of less or more than 3 cm and the different effect should be understand. TRIAL REGISTRATION: ChiCTR2100042746. Registered 27 January 2021-Prospectively registered, http://www.chictr.org.cn .

Utility of 360° Real-time Endoanal Sonography for Evaluation of Perianal Fistulas.

OBJECTIVES: To assess the diagnostic accuracy and performance of 360° endoanal sonography for preoperative evaluation of perianal fistulas using surgical results as a reference standard. METHODS: Between January 2012 and May 2016, 122 patients with suspicious anal fistulas and perianal abnormalities had real-time endoanal sonographic examinations using a 360° cross-sectional endoanal transducer (5-13 MHz) for preoperative evaluation of the disease. All patients underwent surgical interventions. The sonographic findings, including the fistulas and other inflammatory lesions, were correlated with surgical results. The types of fistulas on endoanal sonography were compared with the surgical classification of Parks et al (Br J Surg 1976; 63:1-2), and the internal opening of the fistula on endoanal sonography was confirmed by surgical results as a reference standard. RESULTS: The 122 patients studied included 111 male and 11 female patients. Endoanal sonography was able to show and track hypoechoic lesions, their locations, and internal openings of the fistulas. Compared with surgical results, endoanal sonography had sensitivity of 92.2%, specificity of 100%, and accuracy of 93.4% for the diagnosis of perianal fistulas. Also, endoanal sonography had accuracy of 87.4% for determining fistula types based on the Parks classification and 94.6% for identifying internal openings of the fistulas. CONCLUSIONS: Endoanal sonography is an accurate and noninvasive imaging modality for evaluation of fistulas. It is a very useful tool for preoperative management and surgical planning by providing precise and detailed information on fistulas.

Preparation of microgels loaded with lycopene/NMN and their protective mechanism against acute liver injury.

This study aimed to enhance the stability and bioavailability of lycopene (LYC) and nicotinamide mononucleotide (NMN) by incorporating them into porous microgels after loading LYC into liposomes. The particle size, zeta potential, encapsulation rate (%), scanning electron microscopy images, and stability and release kinetics characteristics in simulating digestion confirmed that the microgels had high LYC and NMN encapsulation rates (99.11% ± 0.12% and 68.98% ± 0.26%, respectively) and good stability and release characteristics. The protective effect and potential mechanism of microgels loaded with LYC and NMN on lipopolysaccharide (LPS)-induced acute liver injury in C57BL/6 mice were investigated by intragastric administration for 28 days prior to LPS exposure. The results showed that the microgels loaded with LYC and NMN significantly ameliorated LPS-induced liver injury and reduced the inflammatory response and oxidative stress. In addition, LYC and NMN can not only act on the Toll-like receptor 4 (TLR4)/MD2 complex but also regulate TLR4-related miRNAs (miR-145a-5p and miR-217-5p) in serum extracellular vesicles, thereby synergistically inhibiting the TLR4/NF-κB signaling pathway. In addition, the microgels loaded with LYC and NMN were able to enrich beneficial bacteria that produced short-chain fatty acids and reduce harmful bacteria. In conclusion, LYC and NMN protected against LPS-induced acute liver injury via inhibition of oxidative stress and inflammation, as well as regulating the gut microbiota.

Kaempferol and nicotiflorin ameliorated alcohol-induced liver injury in mice by miR-138-5p/SIRT1/FXR and gut microbiota.

Aims: Excessive alcohol consumption can lead to alcoholic liver diseases (ALDs). Tetrastigma hemsleyanum Diels et Gilg is a rare Chinese medicinal herb. Tetrastigma hemsleyanum Diels et Gilg has been validated to be highly effective for treating hepatitis. Kaempferol and nicotiflorin are two highly representative flavonoids, which have exhibit therapeutic effects on liver disease. Therefore, the protective mechanism of kaempferol and nicotiflorin on alcohol-induced liver injury were investigated. Main methods: Forty mice were used in this study. After treatment of Kaempferol and nicotiflorin, serum and liver were collected and used for determination of biochemical indicators, H&E staining, and molecular detection. The interaction of miRNAs from serum extracellular vehicles (EVs) with mRNAs and 16S rRNA sequencing of gut microbiota were also investigated. Key findings: The results showed that kaempferol and nicotiflorins significantly ameliorated alcohol-induced liver damage and observably regulated gut microbiota. Specifically, the levels of malondialdehyde (MDA) and CYP2E1 in the liver significantly reduced, and the activity of superoxide dismutase (SOD) and glutathione (GSH) in the liver evidently increased. They also significantly relieved liver oxidative stress and lipid accumulation by suppressing miR-138-5p expression, inversely enhancing deacetylase silencing information regulator 2 related enzyme-1 (SIRT1) levels and then decreasing farnesoid X receptor (FXR) acetylation, which then modulated Nrf2 and SREBP-1c signaling pathways to regulate oxidative stress and lipid metabolism induced by alcohol. Significance: Kaempferol and nicotiflorin reduced alcohol-induced liver damage by enhancing alcohol metabolism and reducing oxidative stress and lipid metabolism. The intestinal microorganism disorder was also ameliorated after oral kaempferol and nicotiflorin.

Proton Pump Inhibitors Versus Histamine-2 Receptor Blockers for Stress Ulcer Prophylaxis on In-hospital Mortality Among Intensive Care Unit Patients Hospitalized for Major Adverse Cardiovascular and Cerebrovascular Events: Retrospective Cohort Study.

PURPOSE: Patients in the intensive care unit (ICU) commonly receive stress ulcer prophylaxis drugs, either proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs). The goal of this research was to evaluate the impact of these drugs on mortality among ICU patients hospitalized for major adverse cardiovascular and cerebrovascular events (MACCEs). METHODS: ICU patients hospitalized for MACCEs were sourced from the Medical Information Mart for Intensive Care-III database. We performed a propensity score matching analysis to match patients treated with PPIs to those treated with H2RBs for stress ulcer prophylaxis. The outcome was 90-day mortality. We used multivariable Cox regression analyses to compare the effect. Hazard ratio (HR), 95% CIs, and P values were reported from the model. FINDINGS: From 2001 to 2012, a total of 3577 patients hospitalized for MACCEs (1997 received PPIs and 1580 received H2RBs) were admitted. The 90-day mortality was 23.7% (848/3577); it was 27% (540/1997) and 19.5% (308/1580) for PPIs and H2RBs users, respectively. The PPI group exhibited a greater 90­day mortality in comparison to the H2RBs group (relative risk = 1.17; P = 0.036), after conditioning on potential confounder. The results remained robust in propensity score matching, sensitivity analyses, and subgroup analyses. IMPLICATIONS: PPIs for stress ulcer prophylaxis were linked to an increased risk of in-hospital mortality than H2RBs in patients hospitalized for MACCEs. Further investigation of this association and validation of its clinical significance is needed.

Bio-based microplastic polylactic acid exerts the similar toxic effects to traditional petroleum-based microplastic polystyrene in mussels.

Microplastics (MPs) have accumulated in the oceans, causing adverse effects on marine organisms and the environment. Biodegradable polylactic acid (PLA) is considered as an excellent substitute for traditional petroleum-based plastics, but it is difficult to degrade completely and easily become MPs in the marine environment. To test the ecological risk of bio-based PLA, we exposed thick-shelled mussels (Mytilus coruscus) to bio-based PLA and petroleum-based polystyrene (PS) (at 102, 104, and 106 particles/L) for 14 days. The significant increase in enzyme activities related to oxidative stress and immune response showed that mussels were under physiological stress after MP ingestion. While enzyme activities of nerve conduction and energy metabolism were significantly disturbed after exposure. Meanwhile, normal physiological activities in respiration, ingestion and assimilation were also suppressed in association with enzyme changes. The negative effects of PS and PLA in mussels were not differentiated, and further integration analysis of integrated biomarker response (IBR) and principal component analysis (PCA) also showed that PLA would induce adverse effects in mussels and ecological risks as PS, especially at environmental concentrations. Therefore, it is necessary to pay more attention to the environmental and ecological risk of bio-based MP PLA accumulating in the marine environment.

Tris(1-chloro-2-propyl) phosphate enhances the adverse effects of biodegradable polylactic acid microplastics on the mussel Mytilus coruscus.

Microplastics (MPs) and organophosphate flame retardants (OPFRs) have recently become ubiquitous and cumulative pollutants in the oceans. Since OPFRs are added to or adsorbed onto MPs as additives, it is necessary to study the composite contamination of OPFRs and MPs, with less focus on bio-based PLA. Therefore, this study focused on the ecotoxicity of the biodegradable MP polylactic acid (PLA) (5 µm, irregular fragments, 102 and 106 particles/L), and a representative OPFRs tris(1-chloro-2-propyl) phosphate (TCPP, 0.5 and 50 µg/L) at environmental and high concentrations. The mussel Mytilus coruscus was used as a standardised bioindicator for exposure experiments. The focus was on examining oxidative stress (catalase, CAT, superoxide dismutase, SOD, malondialdehyde, MDA), immune responses acid (phosphatase, ACP, alkaline phosphatase, AKP, lysozyme, LZM), neurotoxicity (acetylcholinesterase, AChE), energy metabolism (lactate dehydrogenase, LDH, succinate dehydrogenase, SDH, hexokinase, HK), and physiological indices (absorption efficiency, AE, excretion rate, ER, respiration rate, RR, condition index, CI) after 14 days exposure. The results of significantly increased oxidative stress and immune responses, and significantly disturbed energy metabolism and physiological activities, together with an integrated biomarker response (IBR) analysis, indicate that bio-based PLA MPs and TCPP could cause adverse effects on mussels. Meanwhile, TCPP interacted significantly with PLA, especially at environmental concentrations, resulting in more severe negative impacts on oxidative and immune stress, and neurotoxicity. The more severe adverse effects at environmental concentrations indicate higher ecological risks of PLA, TCPP and their combination in the real marine environment. Our study presents reliable data on the complex effects of bio-based MP PLA, TCPP and their combination on marine organisms and the environment.

In vitro and in vivo activity of meropenem+avibactam against MBL-producing carbapenem-resistant Klebsiella pneumoniae.

BACKGROUND: Antibiotic resistance has become a public health problem to be solved worldwide and metallo-ß-lactamase (MBL)-producing bacteria make this problem even more challenging. METHODS: The interactions of meropenem (MEM) in combination with avibactam (AVI) in growth inhibition on MBL-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were tested. In vitro interactions of MEM+AVI were tested using the microdilution checkerboard assay and time-kill curves. In vivo interactions of MEM+AVI were tested using the Galleria mellonella model. RESULTS: All strains were multi-drug resistant strains and six of them were proved to produce MBLs. We show that the combination of MEM+AVI generates profound synergistic effects on growth inhibition of all strains, which was better than that of MEM+vaborbactam or imipenem+relebactam. The time-kill curves further confirmed the potent synergistic antibacterial effects of MEM+AVI against MBL-producing CRKP strains. Galleria mellonella studies were consistent with in vitro analysis. Combining MEM with AVI improved survival rates and mean survival days were obviously prolonged compared to the drug alone and the untreated controls. CONCLUSIONS: To our knowledge, this study is the first report of MEM+AVI collaborating against MBL-producing CRKP strains. Our findings showed that the combination of MEM+AVI has the potential for antibiotic drug development to combat MBL-producing pathogens.

Male reproductive system and simulated high-altitude environment: preliminary results in rats.

This study assessed the effects of a simulated high-altitude environment on the reproductive system of prepubertal male rats and the reversibility of these effects upon return to a normal environment. Three-week-old male Wistar rats were randomly allocated to 4 groups that were exposed to different conditions: a normal environment for 6 weeks and 12 weeks, respectively, hypobaric hypoxia for 6 weeks, and hypobaric hypoxia for 6 weeks followed by a normal environment for 6 weeks. Multiple pathophysiological parameters were evaluated at the histological, endocrine, and molecular levels. Hypobaric hypoxia exposure for 6 weeks during the prepubertal phase significantly altered physiological parameters, body functions, blood indices, and reproductive potential. Six weeks after returning to a normal environment, the damaged reproductive functions partially recovered due to compensatory mechanisms. However, several changes were not reversed after returning to a normal environment for 6 weeks, including disorders of body development and metabolism, increased red blood cells, increased fasting blood glucose, abnormal blood lipid metabolism, decreased testicular and epididymis weights, abnormal reproductive hormone levels, excessive apoptosis of reproductive cells, and decreased sperm concentration. In summary, a hypobaric hypoxic environment significantly impaired the reproductive function of prepubertal male rats, and a return to normal conditions during the postpubertal phase did not fully recover these impairments.

Iron deficiency and overload in men and woman of reproductive age, and pregnant women.

Iron is an essential micronutrient for human biology and health, but high iron levels can be dangerous. Both iron deficiency and iron overload have been linked to reproductive health. This review summarizes the effects of iron deficiency and overload on omen of reproductive age (including pregnant women) and adult men. In addition, appropriate iron levels and the need for iron and nutritional supplements at different stages of life and pregnancy are discussed. In general, men should be aware of the risk of iron overload at any stage of life; women should take appropriate iron supplements before menopause; postmenopausal women should pay attention to the risk of iron overload; and pregnant women should receive reasonable iron supplementation in middle and late pregnancy. By summarizing evidence on the relationship between iron and reproductive health, this review aims to promote the development of strategies to optimize reproductive capacity from the perspective of nutrition. However, additional detailed experimental investigations and clinical studies are needed to assess the underlying causes and mechanisms of the observed associations between iron and reproductive health.

The Microbiome, an Important Factor That Is Easily Overlooked in Male Infertility.

Humankind has been interested in reproduction for millennia. Infertility, in which male factors contribute to approximately 50%, is estimated to concern over 72 million people worldwide. Despite advances in the diagnosis, medical treatment, and psychosocial management of male infertility over the past few decades, approximately 30% of male infertility is still thought to be idiopathic. Despite emerging advances in the microbiome associated with male infertility have indicated that the microbiome may be a key factor to the management of male infertility, roles, and mechanisms of the microbiome remain ambiguous. Here, we mainly discussed the association between microbial infection in the genital tract and male infertility, effect of antimicrobial therapy on male reproduction, association between microbial dysbiosis and male infertility, and effect of probiotic intervention on male reproduction. This review made progress toward establishing a relationship between the microbiome and male infertility, and explored the role of the microbiome in male infertility. We call for more high-quality studies to focus on the relationship between microbes and male infertility, and strongly suggest increasing awareness among sterile males with microbial infection and/or microbial dysbiosis when they seek fertility help.

[Comparison of the efficacy and safety of compound carraghenates cream and compound carraghenates suppository in the treatment of mixed hemorrhoids].

OBJECTIVE: To evaluate and compare the efficacy and safety of titanoreine cream with compound carraghenates suppository in the treatment of mixed hemorrhoids. METHODS: Two hundred and fifty-two patients with mixed hemorrhoids were enrolled in this randomized,open, multicentral trial. Patients applied titanoreine cream (study group, n=133) or compound carraghenates suppository (control group, n=119). The symptomatic relief including pain,bleeding and edema was evaluated by scoring system at 30 minutes, 3 hours, 6 hours, 1 day, 2 days, 3 days, 4 days, 6 days after administration. RESULTS: Symptoms were significantly improved in both groups (87.3%, 94.8%, respectively) excepting symptom of pain relief, but there was no significant difference between two groups (P > 0.05). The pain scores were lower at every observing point in the study group than those in the control group (P< 0.05). The proportions of the patients with pain relief and all symptoms relief were both higher in the study group than that in the control group at 30 min, 3 h after drug used (both P< 0.01). No side effect was found during the triad. CONCLUSION: Titanoreine cream has predominance of relieving pain and response time compared with compound carraghenates suppository, but other effects on mixed hemorrhoid are similar between the two groups.