[Extracellular Signal-regulated Kinase 1/2 Signaling Regulates Cell Invasion:a Review].

Extracellular signal-regulated kinase 1/2 (ERK1/2) is a serine/threoninekinase involved in the signal transduction cascade of Ras-Raf-mitogen-activated protein kinase (MEK)-ERK.It participates in the cell growth,proliferation and even invasion by regulating gene transcription and expression.The occurrence of a variety of diseases such as lung cancer,liver cancer,ovarian cancer,cervical cancer,endometriosis,and preeclampsia,as well the metastasis and disease progression,is closely associated with the regulation of cell invasion by ERK1/2 signaling pathway.Therefore,exploring the regulation of ERK1/2 signaling on cell invasion and its role in pathogenesis of diseases may help to develop more effective treatment schemes.This article introduces recent progress in the regulation of ERK1/2 signaling on cell invasion and the role of such regulation in diseases,with a view to give new insights into the clinical treatment of ERK 1/2-related diseases.

Lifestyle is associated with thyroid function in subclinical hypothyroidism: a cross-sectional study.

BACKGROUND: Few studies have focused on the association between lifestyle and subclinical hypothyroidism (SCH). The purpose of this study was to investigate the association between lifestyle and thyroid function in SCH. METHODS: This study was a part of a community-based and cross-sectional study, the Epidemiological Survey of Thyroid Diseases in Fujian Province, China. A total of 159 participants with SCH (81 males and 78 females) and 159 euthyroid (87 males and 72 females) participants without any missing data were included in the analysis. General information and lifestyle information including sleep, exercise, diet and smoking habits of the participants was collected by questionnaire and Pittsburgh sleep quality index scale (PSQI) was collected. Thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid globulin antibody (TgAb) and urine iodine concentration (UIC) were tested. Thyroid homeostasis parameter thyroid' s secretory capacity (SPINA-GT), Jostel's TSH index (TSHI), thyrotroph T4 sensitivity index (TTSI) were calculated. Logistic regression and multiple linear regression were performed to assess associations. RESULTS: Compared with euthyroid subjects, patients with SCH were more likely to have poor overall sleep quality (15.1 vs.25.8 %, P = 0.018) and l less likely to stay up late on weekdays (54.7 vs. 23.9 % P < 0.001). In SCH group, exercise was the influencing factor of TSH (ß= -0.224, P = 0.004), thyroid secretory capacity (ß = 0.244, P = 0.006) and thyrotropin resistance (ß = 0.206, P = 0.009). Iodine excess was the influencing factor of thyroid secretory capacity (ß = 0.209, P = 0.001) and pituitary thyroid stimulating function (ß = 0.167, P = 0.034). Smoking was the influencing factor of pituitary thyroid stimulating function (ß = 0.161, P = 0.040). Staying up late on weekends was the influencing factor of thyroid secretory capacity (ß = 0.151, P = 0.047). After adjusting for possible confounders, logistic regression showed that those with poor overall sleep quality assessed by PSQI and iodine excess had an increased risk of SCH (OR 2.159, 95 %CI 1.186-3.928, P = 0.012 and OR 2.119, 95 %CI 1.008-4.456, P = 0.048, respectively). CONCLUSIONS: Lifestyle including sleep, smoking, diet and exercise was closely related to thyroid function especially thyroid homeostasis in SCH.

Polydatin protects against carbon tetrachloride-induced liver fibrosis in mice.

Reactive oxygen species (ROS) play a key role in chronic liver injury and fibrosis. Polydatin, a glucoside of resveratrol, has been shown to possess anti-oxidative bioactivity. It has been demonstrated that resveratrol has many therapeutic effects on liver disorders including liver fibrosis. Recent study showed that polydatin prevented acute liver injury after carbon tetrachloride (CCl4) induction. However, the protective effects of polydatin on chronic liver injury and fibrosis has not been understood. Thus, we aimed to determine the roles of polydatin in chronic liver injury and fibrosis. Mice were induced by CCl4 for 6 weeks to develop chronic liver injury and fibrosis. Mice were treated with polydatin for 3 and 6 weeks, respectively. After 6 week injection of CCl4, the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly increased. The hepatic expression of α-SMA, collagen deposition and macrophage filtration were also increased. Furthermore, hepatic 4-HNE production and NOX4 expression were also increased in CCl4-induced mice. In contrast, polydatin ameliorated impaired liver function and histology. Moreover, polydatin attenuated liver fibrosis and inflammation in mice induced by CCl4. Additionally, polydatin suppressed hepatic 4-HNE production and NOX4 expression. In conclusion, polydatin ameliorate chronic liver injury and fibrosis through inhibition of oxidative stress and inflammation.

Original endomorphin-1 analogues exhibit good analgesic effects.

A new class of endomorphin-1 analogues was synthesized by combining successful chemical modifications including N-terminal guanidino modification, Phe4 was chlorinated, D-Ala-Gly Substituted L-Pro2. Their bioactivities were measured by radioligand binding assay, metabolic stability and the tail-flick test. In radioligand binding assays, analogue GAGPC (Nα-Amidino-Tyr-D-Ala-Gly-Trp-p-Cl-Phe-NH2), shown a µ-opioid receptor affinity about 1.42-fold higher and a 2.51-fold higher δ-opioid receptor affinity than EM-1. In the metabolic stability assays, GAGPC had the longest half-lives which was 284min and 53-fold higher than that of EM-1. In the tail-flick test in mice, GAGPC chloride modification increases the lipid content of the drug, thus increases the permeability of the blood brain barrier, and has a higher analgesic activity. It might be of importance in potential application as drug candidates as analgesic.

Original endomorphin-1 analogues exhibit good analgesic effects with minimal implications for human sperm motility.

To search a novel analgesic characterizes the effects on human sperm motility as minimal as possible. A new class of endomorphin-1 (EM-1) analogues was synthesized by combining successful chemical modifications including N-terminal guanidino modification, Phe4 was chlorinated, replaced of l-Pro2-Trp3 by d-Ala2-Gly3 or d-Pro2-Gly3 at position 2 and 3. Their bioactivities were measured by radioligand binding assay, metabolic stability, antinociception activity and sperm motility effects. In radioligand binding assays, analogue GAGP shown a µ-opioid receptor affinity about 17.7-fold higher and a 57.3-fold higher δ-opioid receptor affinity than EM-1. In the metabolic stability assays, GAGP had the longest half-lives and 16.6-fold higher than EM-1. In the tail-flick test in mice, GAGP showed the best analgesia. In sperm motility assays, the group of GAGP (10-5, 10-7mol/L) decreased of the percentage of a+b grade, and no significant when compared with initial value. In GAGP (10-6mol/L) group, sperm motility was progressively increased, although it was not statistically significant. But at the groups of morphine (10-7mol/L) and GAGD (10-7mol/L), these caused significant reduction between 0 and 90 min. We found that analogues GAGP, activating µ-opioid receptor and partial δ-opioid receptor, exhibit good analgesic effects with minimal implications for human sperm motility. It might be important in potential application as drug candidates of analgesic without implications for human sperm motility.

The optimal dosage of aspirin for preventing preeclampsia in high-risk pregnant women: A network meta-analysis of 23 randomized controlled trials.

This study aimed to assess the effectiveness and optimal dosage of aspirin in preventing preeclampsia in high-risk pregnant women. Traditional and network meta-analyses were conducted on data from 23 randomized controlled trials involving 10 547 pregnant women. The findings demonstrated that aspirin significantly reduced the incidence of preeclampsia (OR = 0.66, 95%CI [0.58, 0.75]), with the best preventive effect observed at a dosage of 80-100 mg/day (OR = 0.51, 95%CI [0.36, 0.72]). No significant differences were found in the occurrence of postpartum hemorrhage (OR = 1.03, 95%CI [0.79, 1.33]), small for gestational age (OR = 0.83, 95%CI [0.50, 1.35]), placental abruption (OR = 0.96, 95%CI [0.53, 1.73]), and intrauterine growth restriction (OR = 0.63, 95%CI [0.45, 1.86]) between women taking aspirin and those taking placebos. Different doses of aspirin showed a reduction in preeclampsia incidence, but there was no significant difference in efficacy between the dosage groups. Side effects did not significantly differ between placebo and different aspirin dosage groups. SUCRA analysis suggested that 80-100 mg/day may be the optimal dosage, prioritizing both effectiveness and minimizing side effects. Sensitivity analysis confirmed the robustness of the findings. However, improvements are needed in addressing issues like loss to follow-up, reporting bias, and publication bias. In conclusion, a dosage of 80-100 mg/day is recommended for preventing preeclampsia in high-risk pregnant women, although individual circumstances should be considered for optimizing the balance between effectiveness and safety.

Percutaneous nephroscopy combined with the laser used for right kidney bullet extraction: A case report.

RATIONALE: Wounds caused by firearms are intractable problems in treating war traumas and clinical management. Conventional open surgery inflicts large injury and leads to slow recovery. At the same time, most patients suffer from compound injuries with the critical condition and poor operation tolerance. Thus, it is crucial to probe into the minimally invasive surgical removal of residual kidney bullets. PATIENT CONCERNS: We report a case where a bullet remained in the right renal parenchyma on the patient, with penetrating injury in his liver. DIAGNOSIS: Obviously the patient has suffered gunshot wound with a bullet stuck in his kidney, while his liver function was impacted. INTERVENTIONS: Six months after the injury, we performed the minimally-invasive procedures on the patient with percutaneous nephroscope technology and laser technology under the guidance of ultrasound localization. The bullet and ammunition granulation and scar surrounding tissue were fully removed. Intraoperative bleeding was little, while the incision was small. The patient could leave the bed and walk on the 1st postoperative day. The drainage tube was removed on the 3rd postoperative day, after which the patient was discharged on the 4th postoperative day. OUTCOMES: The patient recovered well after surgery and was followed up for 5 years. The latest examination of his liver and kidney function was as follows: alanine aminotransferase 61IU/L, aspartate aminotransferase 33 IU/L, albumin/globulin 46.6/26.0, total bilirubin 19.1µmol/L, direct bilirubin 4.9µmol/L, indirect bilirubin 14.2µmol/L, alkaline phosphatase 111 IU/L, creatinine 57µmol/L, urea 5.16mmol/L, cystatin 0.73mg/L. The plain computed tomography scan showed a few calcifications in the liver and a patchy low-density shadow in the right kidney. It was proved that the liver and kidney function of the patient recovered well, and his living qualify has come back to the track, with no postoperative complications. LESSONS: Innovative integration of percutaneous nephroscopy technology and laser was used to remove kidney foreign bodies and developed the optimal surgical plan, small trauma, fast recovery, and the treatment of kidney foreign bodies was newly explored.

Correlation between Thyroid Homeostasis and Obesity in Subclinical Hypothyroidism: Community-Based Cross-Sectional Research.

OBJECTIVE: It remains unknown whether obesity has an effect on the pituitary-thyroid feedback control axis in subclinical hypothyroidism (SCH). We aimed to investigate the association of thyroid homeostasis with obesity in a SCH population. METHODS: Our study consisted of a community-based and cross-sectional study from the Epidemiological Survey of Thyroid Diseases in Fujian Province, China. A total of 193 subjects with SCH (90 males and 103 females) without a history of treatment of thyroid disease, such as surgery, radiation, and thyroid hormone or antithyroid medication, were included in the present study. Indices of obesity, including body mass index (BMI), waist circumference (WC), and waist-height ratio (WHtR) were measured. RESULTS: Our results showed that the secretory capacity of the thyroid gland (SPINA-GT) and Jostel's thyrotropin index (TSHI) were negatively correlated with BMI, WC, and WHtR, whereas the reciprocal of the thyrotroph thyroid hormone resistance index (TTSI-1) was positively correlated with BMI (all p < 0.05). After adjustment for age, sex, smoking, iodine status, and glucolipid metabolism, the associations between TSHI, TTSI (reciprocal transformation), and BMI still persisted (all p < 0.05). CONCLUSIONS: These results suggest that low levels of thyroid homeostasis indexes may be associated with overall obesity in SCH, rather than central adiposity.

Establishment and internal validation of preoperative nomograms for predicting the possibility of testicular salvage in patients with testicular torsion.

This study aimed to establish nomograms to preoperatively predict the possibility of testicular salvage (TS) in patients with testicular torsion. The clinical data of 204 patients with testicular torsion diagnosed at Xijing Hospital and Tangdu Hospital (Xi'an, China) between August 2008 and November 2019 were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of TS. Based on multivariate regression coefficients, nomograms to predict possibility of TS were established. The predictive ability of the nomograms was internally validated by receiver operating characteristic (ROC) curves and calibration plots. The duration of symptoms ranged from 2 h to 1 month, with a median of 3.5 days. Thirty (14.7%) patients underwent surgical reduction and contralateral orchiopexy, while the remaining 174 (85.3%) underwent orchiectomy and contralateral orchiopexy. Finally, long symptom duration was an independent risk predictor for TS, while visible intratesticular blood flow and homogeneous testicular echotexture under color Doppler ultrasound were independent protective predictors. Internal validation showed that the nomograms, which were established by integrating these three predictive factors, had good discrimination ability in predicting the possibility of TS (areas under the ROC curves were 0.851 and 0.828, respectively). The calibration plots showed good agreement between the nomogram-predicted possibility of TS and the actual situation. In conclusion, this brief preoperative prediction tool will help clinicians to quickly determine the urgency of surgical exploration.

The first competing risk survival nomogram in patients with papillary renal cell carcinoma.

There is still a lack of competing risk analysis of patients with papillary renal cell carcinoma (pRCC) following surgery. We performed the cumulative incidence function (CIF) to estimate the absolute risks of cancer-specific mortality (CSM) and other-cause mortality (OCM) of pRCC over time, and constructed a nomogram predicting the probability of 2-, 3- and 5-year CSM based on competing risk regression. A total of 5993 pRCC patients who underwent nephrectomy between 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The 2-, 3-, 5-year CSM rates were 3.2%, 4.4% and 6.5%, respectively, and that of OCM were 3.2%, 5.0% and 9.3%, respectively. The estimates of 5-year cumulative mortality were most pronounced among patients aged > 75 years in OCM (17.0%). On multivariable analyses, age, tumor grade, T stage, N stage, and with or without bone, liver and lung metastases were identified as independent predictors of CSM following surgery and were integrated to generate the nomogram. The nomogram achieved a satisfactory discrimination with the AUCt of 0.730 at 5-year, and the calibration curves presented impressive agreements. Taken together, age-related OCM is a significant portion of all-cause mortality in elderly patients and our nomogram can be used for decision-making and patient counselling.

The Potential Role of Serum Exosomes in Preeclampsia.

Preeclampsia is a serious pregnancy-specific disease that affects about 5%-8% of pregnant women and is the main reason for the increase in maternal and perinatal mortality. Due to unknown etiology, preeclampsia is still the main cause of increased mortality in maternal and perinatal infants, which is mainly manifested by new hypertension after 20 weeks of pregnancy. As the pathogenesis has not been fully elucidated, early diagnosis and full treatment are lacking. Exosomes secreted from the placenta to the peripheral circulation may be involved in the pathogenesis of preeclampsia and can be detected from the plasma of pregnant women after 6 weeks of pregnancy. Related studies have shown that the levels of exosomes in preeclampsia have changed, and the protein and miRNA expression profiles are also different. Therefore, monitoring changes in plasma exosomes and expression profiles may provide new ideas and new perspectives for the prediction, diagnosis and treatment of preeclampsia.