Intermittent spontaneous ovulation in patients with premature ovarian failure:Three case reports and review of literature

BACKGROUND Premature ovarian failure(POF)is the end-stage of a decline in ovarian function prior to the age of 40 years that involves symptoms associated with low estradiol(E2)levels and a minimal probability of pregnancy.This increases the physical and psychological burden experienced by young women of reproductive age,particularly with regards to over-diagnosis.CASE SUMMARY Here,we report three cases(29,22,and 33 years-of-age)diagnosed with POF after experiencing secondary amenorrhea for more than one year,serum levels of follicle-stimulating hormone(FSH)>40 IU/L on two occasions with an interval of more than 4 wk,and negative progesterone withdrawal tests.All three patients were intermittently administered with drugs to create an artificial cycle.During the subsequent discontinuation period,the patients experienced intermittent follicular growth and spontaneous ovulation.One patient experienced two natural pregnancies(both with embryo arrest).CONCLUSION Our findings suggest that young patients with POF can experience unpredictable and intermittent spontaneous follicular development,ovulation,and even natural pregnancy.Clinicians should provide appropriate medical guidance and individualized treatments according to fertility requirements,genetic risks and hypoestrogenic symptoms as soon as possible.

Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation

Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.

The Role of Nitric Oxide in Hyperoxic Lung Injury in Premature Rats

To investigate the role of nitric oxide (NO) in hyperoxic lung injury, the 3 day old preterm rats were randomly assigned to four groups: group I (hyperoxia group), group Ⅱ (hyperoxia+N w nitro L arginine methyl ester (L NAME) group), group Ⅲ (air group), and group Ⅳ (air+L NAME) group. Group Ⅰ and Ⅱ were exposed to ≥90 % O 2 for 3 or 7 days. Group Ⅱ and Ⅳ received subcutaneous L NAMEy on daily basis (20 mg/kg). After 3 day or 7 day exposure, the lung wet weight/dry weight ratio (W/D), total protein and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) and lung pathology were examined in all groups. NO content, expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in lungs were measured in group Ⅰ and Ⅲ. Our results showed that after 3 day exposure, group Ⅰ appeared acute lung injury characterized by the increase of MDA content ( P <0.01) and the presence of hyperaemia, red cell extravasation and inflammatory infiltration; after 7 day exposure, except MDA, total protein and W/D were also increased in comparison with group Ⅲ ( P <0.01, 0.05), pathological changes were more severe than those after 3 day exposure. After 3 and 7 day exposure, total protein in group Ⅱ was significantly increased as compared with group Ⅰ ( P <0.01 for both). The pulmonary acute inflammatory changes were more obvious in group Ⅱ than in group Ⅰ. Occasionally, mild hemorrhage was detected in the lungs of group Ⅳ. BALF protein content in group IV was higher than that in group Ⅲ after 7 day exposure ( P <0.01). After 3 and 7 day exposure, NO content in BALF were all significantly elevated in group Ⅰ as compared with group Ⅲ ( P <0.01 for all). In the lungs of group Ⅰ, strong immunostaining for iNOS was observed in airway and alveolar epithelia, inflammatory cells, which were stronger than those in group Ⅲ. Expression of iNOS in rats after 7 day hyperoxic exposure was stronger than that after 3 day exposure. Shortly after 7 day exposure, stronger immunostaining for eNOS in airway epithelia in group Ⅰ than that in group Ⅲ was seen. Our study suggested that treatment with L NAME worsened acute hyperoxic lung injury in preterm rats and also had a deleterious effect on the rats exposed to air, indicating that endogenous nitric oxide may play a protective role in rats under both physiological and hyperoxic status. Hyperoxia can significantly upregulate the expression of iNOS and eNOS in inflammatory cells, epithelia in the lungs of preterm rats, promote NO generation, which suggests that endogenous NO may mediate the hyperoxic pulmonary damage. Over stimulation of iNOS may contribute to the pathogenesis of hyperoxic lung injury. NO may have dual roles in pulmonary oxygen toxicity.

The Use of Caudal/Epidural Catheter as the Primary Anesthetic with Dexmedetomidine Secondary to High Risk of Post-Operative Apnea in Premature Infants

Life threatening post-operative apnea is a known complication of general anesthesia in premature infants. Neuraxial anesthesia has been associated with reduced risk of post-operative apnea. We report two cases, presenting for bilateral inguinal hernia repair, where we used a caudal/epidural catheter for the neuraxial block combined with dexmedetomidine for sedation in preterm infants at high risk for postoperative respiratory complications. Dexmedetomidine assisted in providing both favorable surgical conditions via its well proven sedative effects without respiratory comprised and decreased the discomfort and stress to the child during placement of the epidural catheter and the neuraxial anesthesia provided excellent analgesia and surgical conditions.

Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

Effect of blood transfusion therapy on oxygen saturation in brain and intestinal tissues of children with premature anaemia

Objective: To study the effect of blood transfusion therapy on oxygen saturation in brain and intestinal tissues of children with premature anaemia. Methods: Ninety-five children with premature anaemia in our hospital from August 2016 to July 2018 were selected and divided into three groups according to the different degrees of anemia, namely, mild group (n=30), moderate group (n=30) and severe group (n=35), meanwhile, another 35 premature without anemia were set as control group. Then the basal vital signs, levels of hemoglobin (Hb) and hematocrit (Hct), as well as the oxygen saturation in brain and intestinal tissue were compared among the four groups. Results: The SBP and DBP between the four groups after treatment had no difference. The HR and RR after treatment in the control group and the mild group were significantly higher than those in the severe group. The RR of the mild group was significantly lower than that of the control group, with statistical difference. The Hb in the control group and the mild group was significantly higher than that in the moderate group and the severe group. The Hb in the moderate group was significantly higher than that in the severe group. Hct in the control group and the mild group was significantly higher than that in the severe group. The Hct in the moderate group had no statistic difference with that of the mild group and severe group. The cerebral oxygen saturation after treatment in the control group and the mild group was significantly higher than that in the severe group, meanwhile the intestinal tissue oxygen saturation after treatment of the control group was significantly higher than that in the severe group. Cerebral oxygen saturation after treatment showed no difference between the severe group and the moderate group, and the intestinal tissue oxygen saturation after treatment either had no difference among the severe group, the moderate group and the mild group. Conclusion: Blood transfusion therapy can significantly improve the oxygen saturation of brain and intestinal tissues in children with premature anaemia without affecting blood pressure, and improve the degree of anemia, which can be used reasonably under the strict control of clinical indications.

A Novel Genetic Algorithm Preventing Premature Convergence by Chaos Operator

An improved genetic algorithm (GA) is proposed based on the analysis of population diversity within the framework of Markov chain. The chaos operator to combat premature convergence concerning two goals of maintaining diversity in the population and sustaining the convergence capacity of the GA is introduced. In the CHaos Genetic Algorithm (CHGA), the population is recycled dynamically whereas the most highly fit chromosome is intact so as to restore diversity and reserve the best schemata which may belong to the optimal solution. The characters of chaos as well as advanced operators and parameter settings can improve both exploration and exploitation capacities of the algorithm. The results of multimodal function optimization show that CHGA performs simple genetic algorithms and effectively alleviates the problem of premature convergence.

Effects of Hyperoxia on the Dynamic Expression of Aquaporin5 in Premature Rats Lung Development

To explore the dynamic expression and role of Aquaporin5 ( AQP5) in lung development and hyperoxia lung injury, gestation 21-day Sprague-Dawley (SD) rats (term=22 days) were ran- domly assigned to air group and hyperoxia group within 12-24 h after birth. The rats in hypreoxia group were continuously exposed to about 85% oxygen and those in air group to room air. After 1 to 14 days of exposure, total lung RNA was extracted and the expression of AQP5 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry and west- ern-blot were used to detect the expression of AQP5 protein. The results showed that the expression of AQP5 in premature rats lung could be detected at various time points after birth, and the positive staining was restricted to the type Ⅰ alveolar epithelial cells. In air group, the AQP5 expression was detected in a very low level at day 1, but exhibited a persistent increase after birth. Compared with the air group, the expression of AQP5 in hyperoxia group was increased at day 1, and had significant difference in mRNA level (P<0.05), but decreased significantly in mRNA and protein levels after 4 to 14 days (P<0.01 or P<0.05 respectively). It was concluded that AQP5 might play a key role in the alveolar period of premature rats by regulating the lung water balance. Hyperoxia exposure leads to a down-regulation of the AQP5 expression, which may be an important factor for the development of hyperoxia lung injury.

Comparative study of on-demand and daily use of sertraline in treatment of premature ejaculation:A randomized clinical trial

Objective:The intravaginal ejaculatory latency time(IELT)may increase less in on-demand compared to daily intake,but may fulfill a suitable treatment for specific patients.We decided to compare the efficacy and safety of on-demand and daily use of sertraline in order to find the most effective and least complicated method in treatment of premature ejaculation(PE).Methods:This study was parallel or concurrent control randomized clinical trial.Two hundred and forty patients with PE diagnosed by urologist in the two groups of 120 from July 2017 to February 2019 enrolled in the study.In the first group,it is prescribed 50 mg sertraline each 12 h daily and the second group received 50 mg 4 h before coitus for 4 and 8 weeks.The IELT before treatment and during all coitus after treatment were recorded by the patient’s wife with a stopwatch.Results:Mean IELT before,4 and 8 weeks after treatment in two groups were:On-demand group 101.62±65.44 s,208.75±128.02 s and 265.87±145.70 s;daily use group 102.50-81.22 s,276.87±181.08 s and 353.75±176.45 s,respectively.The ejaculation time increased significantly in both groups(p<0.05).However,increase in ejaculation time in daily use group was significantly higher than the on-demand group in 4 weeks(p=0.036),especially in 8 weeks(p=0.009).The percent of side effects in daily use group(26.7%)was higher than on-demand group(20%)(p<0.05).Drowsiness,diarrhea and vertigo were significantly higher in the daily use than on-demand(p<0.05).Conclusions:On-demand and daily use of sertraline are effective and usually have no serious complications,but the on-demand method is considerably more tolerable.In patients who did not tolerate to daily use of this drug,on-demand could be used as a salvage therapy.

Retinoic Aacid Diminished the Expression of MMP-2 in Hyperoxia-exposed Premature Rat Lung Fibroblasts through Regulating Mitogen-activated Protein Kinases

This study examined the effects of retinoic acid (RA), PD98059, SP600125 and SB203580 on the hyperoxia-induced expression and regulation of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-2 (TIMP-2) in premature rat lung fibroblasts (LFs). LFs were exposed to hyperoxia or room air for 12 h in the presence of RA and the kinase inhibitors PD98059 (ERK1/2), SP600125 (JNK1/2) and SB203580 (p38) respectively. The expression levels of MMP-2 and TIMP-2 mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). MMP-2 activity was measured by zymography. The amount of p-ERK1/2, REK1/2, p-JNK1/2, JNK1/2, p-p38 and p38 was determined by Western blotting. The results showed that: (1) PD98059, SP600125 and SB203580 significantly inhibited p-ERK1/2, p-JNK1/2 and p-p38 respectively in LFs; (2) The expression of MMP-2 mRNA in LFs exposed to hyperoxia was decreased after treatment with RA, SP600125 and SB203580 respectively (P<0.01 or 0.05), but did not change after treatment with PD98059 (P>0.05). Meanwhile, RA, PD98059, SP600125 and SB203580 had no effect on the expression of TIMP-2 mRNA in LFs exposed to room air or hyperoxia (P>0.05); (3) The expression of pro- and active MMP-2 experienced no change after treatment with RA or SP600125 in LFs exposed to room air (P>0.05), but decreased remarkably after hyperoxia (P<0.01 or 0.05). SB203580 inhibited the expression of pro- and active MMP-2 either in room air or under hyperoxia (P<0.01). PD98059 exerted no effect on the expression of pro- and active MMP-2 (P<0.05). It was suggested that RA had a protective effect on hyperoxia-induced lung injury by down-regulating the expression of MMP-2 through decreasing the JNK and p38 activation in hyperoxia.

International Comparison of Intercity Differences in Premature Deaths: Pyll-Rates in Canada, Finland and Russia 2010

Background: Potential years of life lost (PYLL) rate describes the number of years lost due to pre-ventable premature death in a population. This is equal to the loss of human capital. Cause-specific PYLL-rates provide information for public health policy. Methods: PYLL-rate is calculated as an absolute difference between the age at death and the assumed length of life. Causes of preventable deaths are defined and classified according to International Classification of Diseases version 10 (ICD-10) as determined by World Health Organization. PYLL rate is age-standardized and expressed per 100,000 persons. Organization for Economic Cooperation and Development (OECD) standard of 70 years was applied as the expected length of life in Saint Petersburg (Russia), Edmonton (Canada), and Helsinki (Finland). Results: There were very big differences in PYLL rates of all causes of death between the countries compared. Total PYLL-rates were the lowest in Helsinki, slightly higher in Edmonton, and the highest in Saint Petersburg. The intercity differences in the total of PYLL-rates were considerably smaller among women than men. In each city, the three most prevalent causes of premature death were injuries, cancer and cardiovascular diseases. Magnitudes of these causes varied between the three cities. Conclusions: PYLL rate provides comparable and sensitive information about the health related well-being of a population concerning all preventable causes of death as well as cause-specific premature deaths. The study demonstrates that the reduction of cause-specific PYLL-rates is possible. It provides supplementary information for planning of health policies and evaluation of effectiveness of past interventions. Results demonstrate that these actions need to differ between countries and localities.

Clinical Study on Huangku Qingxin Mixture Combined with Metoprolol Tartrate Tablets for Treatment of Ventricular Premature Beat

[Objectives] To observe the clinical effect and safety of Huangku Qingxin Mixture combined with Metoprolol Tartrate Tablets for patients with ventricular premature beat.[Methods] 126 patients were divided randomly into the control group (62 cases) and the treatment group (64 cases). The control group was treated with routine western medicine, and the treatment group was treated with routine western medicine combined with Huangku Qingxin Mixture, both for one month. Then, observed the changes of Myerburg score, SAS score, symptom score and dynamic electrocardiogram in the two groups before and after treatment.[Results] The total effective rate of clinical symptoms was 82.81% in the treatment group and 64.52% in the control group. Through comparison of two groups, the difference was statistically significant ( P <0.05). The total effective rate of dynamic electrocardiogram was 84.38% in the treatment group and 58.06% in the control group. Through comparison of two groups, the difference was statistically significant ( P <0.05). Before treatment, there was no significant difference being found in the comparison of the scores of Myerburg and SAS in the two groups ( P >0.05). After treatment, Myerburg score and SAS score in the two groups were lower than those before treatment ( P <0.05);Myerburg score and SAS score in the treatment group were both better than those in the control group ( P <0.05). Before treatment, there was no significant difference in the comparison of the QT interval dispersion (QTd) and the corrected QT interval dispersion (QTcd) by Bazette formula ( P >0.05). After treatment, the results of QTd and QTcd in the two groups were lower than those before treatment ( P <0.05);the results of QTd and QTcd in the treatment group were better than those in the control group ( P <0.05).[Conclusions] The application of Huangku Qingxin Mixture combined with Metoprolol Tartrate Tablets can effectively reduce Myerburg scores and SAS scores in patients with ventricular premature beat, shorten QTd and QTcd, and improve the life quality of patients. It has no adverse clinical reaction.

Current therapeutic strategies for premature ejaculation and future perspectives

早泄(PE ) 是在被骚乱在外部、中央的神经系统调停的人的普通性混乱。尽管为 PE 的所有药品的治疗是，当前使用 &#x02018； off-label' ，一些新奇口头的代理人和药管理的一些更新的方法现在提供重要地势给 PE 病人。然而，这个条件的原因论没被统一，首先因为为基本研究和为在有 PE 的病人的基于证据的临床的研究的一个广泛地接受的定义和评价工具的缺席的一个标准动物模型的缺乏。在这评论，我们为 PE 集中于当前的治疗学的策略和未来治疗观点。

Effects of Hyperoxia on Cytoplasmic Thioredoxin System in Alveolar Type Epithelial Cells of Premature Rats

This study investigated the effects of hyperoxia on dynamic changes of thioredoxin-1 (Trx1) and thioredoxin reductase-1 (TrxR1) in alveolar type Ⅱ epithelial cells (AECⅡ) of premature rats. Pregnant Sprague-Dawley rats were sacrificed on day 19 of gestation. AECⅡ were isolated and purified from the lungs of premature rats. When cultured to 80% confluence, in vitro cells were randomly divided into air group and hyperoxia group. Cells in the hyperoxia group were continuously exposed to 95% O2/5% CO2 and those in the air group to 95% air/5% CO2. After 12, 24 and 48 h, cells in the two groups were harvested to detect their reactive oxygen species (ROS), apoptosis, TrxR1 activity and the expressions of Trx1 and TrxR1 by corresponding protocols, respectively. The results showed that AECⅡ exposed to hyperoxia generated excessive ROS and the apoptosis percentage in the hyperoxia group was increased significantly at each time points as compared with that in the air group (P<0.001). Moreover, TrxR1 activity was found to be markedly depressed in the hyperoxia group in comparison to that in the air group (P<0.001). RT-PCR showed the expressions of both Trx1 and TrxR1 mRNA were significantly increased in AECⅡ exposed to hyperoxia for 12 and 24 h (P<0.01), respectively. At 48 h, the level of Trx1 mRNA as well as that of TrxR1 mRNA in the hyperoxia group was reduced and showed no significant difference from that in the air group (P>0.05). Western blotting showed the changes of Trx1 protein expressions in the hyperoxia group paralleled those of Trx1 mRNA expressions revealed by RT-PCR. It was concluded that hyperoxia can up-regulate the protective Trx1/TrxR1 expressed by AECⅡ in a certain period, however, also cause dysfunction of the cytoplasmic thioredoxin system by decreasing TrxR1 activity, which may contribute to the progression of oxidative stress and cell apoptosis and finally result in lung injury.

Effects of Hyperoxia on Mitochondrial Multienzyme Complex Ⅲ and Ⅴ in Premature Newborn Rat Lung

To investigate the effects of hyperoxia on mitochondrial multienzyme complex Ⅲ(cytochrome,Cytb) and Ⅴ(ATPase6,8) in premature newborn rat lung,the 1-day-old preterm SD rats were randomly assigned to hyperoxia group and air group.The rats in hyperoxia group were con-tinuously exposed to 85% oxygen and those in air group to room air.After 1,4,7,10,14 day(s) of exposure,these rats were killed,total lung RNA was extracted and Cytb,ATPase6,8 mRNA were detected by reverse transcription polymerase chain reaction(RT-PCR).Western blotting was used to detect the expression of Cytb protein in lung tissue.The results showed that compared with air group,Cytb mRNA expression was significantly increased(P>0.05) after 1,4 day(s) of exposure.The gen-eral tendency decreased after 7 days,and its expression became weak but difference in mRNA ex-pression between the two groups was not significant(P>0.05).ATPase6 mRNA expression was sig-nificantly increased 1 day after the exposure(P<0.05) and did not show any significant change 4,7,10 days after the exposure(P>0.05).At the 14th day,ATPase6 mRNA expression was significantly increased(P<0.05).ATPase8 mRNA expression did not show any significant change 1,4,10 day(s) after the exposure(P>0.05).At the 7th and 14th day,ATPase8 mRNA expression was significantly increased(P<0.05).Western blotting showed that Cytb protein expression was increased 1,4 day(s) after the exposure,but the difference between the two groups was not significant(P>0.05).The gen-eral tendency was decreased after 7 days,and its expression became weak but difference was not sig-nificant 7,10 days after the exposure(P>0.05).At day 14 its expression became significantly weak(P<0.05).We are led to conclude that exposure to high concentrations of oxygen can significantly change the expression of Cytb and ATPase6,8,which results in uncoupling of oxidative phosphoryla-tion in mitochondrial respiration chain,and plays an important role in the mechanism of hyper-oxia-induced lung injury.

Long Term Administration of Lannea acida Rich. (Anacardiaceae) Reverses the Imidacloprid-Induced Fertility Impairments in Adult Male Rat through Androgenic and Antioxidant Properties

Aim: The harmful effects of pesticides have been largely documented in recent times. But effective therapeutic solutions to pesticide related male infertility are yet to be established. This study investigated the curative effects of Lannea acida on imidacloprid (IMI)-induced hypofertility in male Wistar rats. Methods: Rats of 150 – 200 g were administered IMI (22.5 mg/kg) for two weeks and partitioned into control (distilled water, vitamin E, clomiphene citrate) or test (aqueous (340 mg/kg), methanol (170 mg/kg) extract) groups for eight weeks treatment. Animals were sacrificed at the end of the treatment and samples were collected for sperm, antioxidant and hormonal analysis. Fertility tests were performed from treatment day 47 for fertility indices estimation. Results were expressed as mean ± SEM and one way ANOVA was applied using STATISTICA Software. Results: Exposition to IMI resulted in a significant decrease in sperm count, motility, viability and normality, testosterone and LH, coupled to an increase in oxidative stress markers. Moreover, IMI impaired male fertility evidenced by a significant drop in fertility index and litter size. Similar to clomiphene citrate and vitamin E, plant extracts significantly improved the sperm parameters, sexual hormones and decreased the oxidative stress markers. More importantly, the fertility index and litter size were restored, especially with the aqueous extract. Conclusion: Present results indicate that L. acida possesses curative potentials against IMI-induced hypofertility through its androgenic and antioxidant properties. However, the effects the extract on spermatozoa DNA structure and the fertility of offsprings from exposed parents are yet to be studied to conclude on total recovery from IMI toxicity.

Underlying anti-hypertensive mechanism of the Mizuhopecten yessoensis derived peptide NCW in spontaneously hypertensive rats via widely targeted kidney metabolomics

The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.

Long-Term Impact of Acute Retinoic Acid Supplementation at the Young Age on Testicular Architecture of Wistar Albino Rats

Introduction: Inappropriate and excess vitamin supplementation, particularly for vitamin A, is increasingly recognized as a public health problem in developed countries. On the other hand, blind supplementation of vitamin A, for children in developing countries is a subject of controversy in the literature. The crucial role of vitamin A in the process of spermatogenesis in adult rodents is well established, but only a few publications are consecrated to the long-term effect of vitamin A intake at a young age on testicular development and differentiation. Objectives: Our study aimed to evaluate the long-term effects of acute supplementation at an early age, in the post-natal period, on spermatogenesis and testicular trophicity at adult age. Material and Methods: Young Wistar Albinos rats of 22 days received an acute high dose of supplementation of vitamin A (retinyl palmitate). The control group, group 1, received only extra virgin olive oil, Group 2 a dose of 7000 IU/kg of retinyl palmitate, group 3, 14,000 IU/kg, and Group 4 a dose of 28,000 IU/kg. At 10 weeks of age, the testes’ testosterone levels were measured by ELISA. For histological assessment, sections were stained with Hematoxylin eosin, and the Johnsen score was used to evaluate spermatogenesis in the seminiferous tubules. Results: The average testicular weights of rats were significantly lower in group 4 (p < 0.05), and so was the testosterone level in the testis compared to the control group (p .01). Most of the seminiferous tubules were concerned by an arrest of spermatogenesis and the Johnsen score was decreased with a mean score of 5.96 ± 1.60 (p .001) in that Group. In Group 3, Johnsen’s score was significantly better than the one obtained with the control. Conclusion: We observed a negative effect in the long term with a high acute dose of supplementation of retinyl palmitate at a young age, on testicular development and differentiation. Despite a return to normal diet after that supplementation, during childhood, impaired spermatogenesis was identified at the adult age with an arrest of spermatogenesis. The reversibility of that lack of differentiation by a return to a normal diet is questionable and would need more investigation.

Dry environment on the expression of lacrimal gland S100A9,Anxa1,and Clu in rats via proteomics

●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-related diseases for further studies.

Preliminary exploration of animal models of congenital choledochal cysts

BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing results.Current surgical techniques can achieve satisfactory outcomes for treatment of CCs.Consequently,recent studies have focused more on clinical issues rather than basic research.Therefore,we need appropriate animal models to further basic research.AIM To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs.METHODS Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group,sham surgical group,or control group.A rat model of CC was established by partial ligation of the bile duct.The reliability of the model was confirmed by measurements of serum biochemical indices,morpho-logy of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues.RESULTS Dilation classified as mild(diameter,≥1 mm to<3 mm),moderate(≥3 mm to<10 mm),and severe(≥10 mm)was observed in 17,17,and 2 rats in the surgical group,respectively,while no dilation was observed in the control and sham surgical groups.Serum levels of alanine aminotransferase,aspartate aminotrans-ferase,total bilirubin,direct bilirubin,and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery,while direct bilirubin,total bilirubin,and gamma-glutamyltransferase were further increased 14 d after surgery.Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery.The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues.CONCLUSION The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC,which may contribute to investigating the pathogenesis of CC.