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As a leading complication of sepsis, sepsis-induced cardiac dysfunction (SICD) contributed to the high mortality of patients with sepsis. Long non-coding RNA (LncRNA) LINC00472 has been reported to be in sepsis-induced disease. Nonetheless, its biological function and underlying molecular in SICD remain largely unknown. In this study, in vivo and in vitro SICD models were established via LPS treatment. H&E staining was employed for the evaluation of myocardial injury. ELISA assay was performed to detect cardiac Troponin I (cTnI), creatine kinase-MB (CK-MB), interleukin (IL)-1β, and tumor necrosis factor-α (TNF-α) levels. Cardiomyocyte viability and apoptosis were assessed via CCK-8 and flow cytometry assays. The transcriptional regulation of YY1 on LINC00472 was demonstrated via ChIP assay. Besides, the interaction between YY1 and LINC00472, as well as the association between miR-335-3p and LINC00472 or MAOA were verified via luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Herein, highly expressed LINC00472 was observed in both in vivo and in vitro SICD models. LINC00472 knockdown substantially attenuated LPS-induced inhibition on cardiomyocyte viability and reversed cardiomyocyte apoptosis and inflammatory response mediated by LPS treatment. YY1 induced LINC00472 upregulation, thereby promoting cardiomyocyte dysfunction induced by LPS. In addition, MAOA upregulation or miR-335-3p inhibition could partly reverse the suppressive effect on LPS-induced cardiomyocyte dysfunction mediated by LINC00472 knockdown. Based on our results, it seemed that YY1-activated LINC00472 might contribute to SICD progression via the miR-335-3p/MAOA pathway.

Sorafenib is an anti-tumor drug widely used in clinical treatment, which can inhibit tyrosine kinase receptor on cell surface and serine/threonine kinase in downstream Ras/MAPK cascade signaling pathway of cells. Tyrosine kinase phosphorylation plays an important role in inflammatory mechanism, such as TLR4 tyrosine phosphorylation, MAPK pathway protein activation, and activation of downstream NF-кB. However, the effects of sorafenib on LPS-induced inflammatory reaction and its specific mechanism have still remained unknown. We found that sorafenib inhibited the phosphorylation of tyrosine kinase Lyn induced by LPS, thereby reducing the phosphorylation level of p38 and JNK, inhibiting the activation of c-Jun and NF-κB, and then inhibiting the expression of inflammatory factors IL-6, IL-1β, and TNF-α. Furthermore, sorafenib also decreased the expression of TLR4 on the macrophage membrane to inhibit the expression of inflammatory factors latterly, which may be related to the inactivation of Lyn. These results provide a new perspective and direction for the clinical treatment of sepsis.

Among the investigated mechanisms of chemotherapy-induced damage to human primordial follicle reserve are induction of DNA double-strand breaks (DSBs) and resultant apoptotic death, stromal–microvascular damage and follicle activation. Accumulating basic and translational evidence suggests that acute exposure to gonadotoxic chemotherapeutics, such as cyclophosphamide or doxorubicin, induces DNA DSBs and triggers apoptotic death of primordial follicle oocytes within 12–24 h, resulting in the massive loss of ovarian reserve. Evidence also indicates that chemotherapeutic agents can cause microvascular and stromal damage, induce hypoxia and indirectly affect ovarian reserve. While it is possible that the acute reduction of the primordial follicle reserve by massive apoptotic losses may result in delayed activation of some primordial follicles, this is unlikely to be a predominant mechanism of loss in humans. Here, we review these mechanisms of chemotherapy-induced ovarian reserve depletion and the potential reasons for the discrepancies among the studies. Based on the current literature, we propose an integrated hypothesis that explains both the acute and delayed chemotherapy-induced loss of primordial follicle reserve in the human ovary.

China is in the process of rapid urbanization and rapid economic development. The demand for infrastructure construction is getting higher and higher, but government funds are limited and cannot meet its needs. With the decline of government investment in the construction of public infrastructure, and the role of private capital enterprises in the construction of public infrastructure has begun to play an increasingly important role, and the continuous development of marketization of investment and financing models, a new financing model has been introduced—Public-Private-Partnership (PPP) model, that is, the cooperation model between public government departments and private enterprises. At the present stage of the development of China’s PPP model, there are many problems: inadequate legal systems, inadequate supervision and management, insufficient understanding of the PPP model in various regions, inadequate risk taking and benefit distribution, and large government credit risks. In view of this, we should start to improve the legal and regulatory system related to the PPP model, establish a sound supervision and management mechanism, establish a specialized PPP management agency, establish a reasonable risk sharing and benefit sharing mechanism, and establish an information sharing platform. Therefore, this article starts from the deep meaning of the PPP model, the current status of development in China, the problems that arise, and better solutions to study it in depth.

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Background: To compare the efficacy and safety of different compatibility schemes in the prevention of visceral pain after gynecological laparoscopic surgery. Methods: from April 2019 to April 2020, patients undergoing elective gynecological laparoscopic surgery in our hospital were randomly divided into four groups: group A: sufentanil 3 μ g / kg; group B: low-dose nalbuphine group: 0.1 mg / kg of nabufen + 3 μ g / kg of sufentanil; group C: medium dose of nabufen group: 1 mg / kg of nabufen + 2 μ g / kg of sufentanil; group D: high-dose nabufen 2 There were 30 cases in each group. The degree of pain and the number of adverse reactions at 2, 4, 8, 12, 24 and 48 hours after operation were observed and recorded. The number and dosage of morphine used as a remedial analgesic were recorded. The pain degree was assessed by visual analogue scale (VAS). The total amount of analgesic pump used, the total number of times of pressing and the effective times of pressing were recorded. The adverse reactions included respiratory depression, nausea and vomiting, drowsiness, restlessness and skin The skin itches. Results: the analgesic effect of group B was similar to that of group A, and there was no significant difference in the number of invalid pressing, total pressing times and rescue analgesia rate (P > 0.05), while the invalid pressing times, total pressing times and remedial analgesia rate of group C and group D were significantly lower than those of group A (P < 0.05). There was no significant difference between group C and group D in the number of invalid compressions, the total number of compressions and the rate of remedial analgesia (P > 0.05), suggesting that increasing the dose of nalbuphine could not significantly increase the analgesic effect. The incidence of postoperative nausea and vomiting, skin pruritus, lethargy and Ramsay Sedation score in group B and group C were significantly lower than those in group A (P < 0.05). Ramsay Sedation score and incidence of drowsiness were lower than those in group D, which indicated that the incidence of adverse reactions was higher in group D than group B and group C.Conclusion: the combination of 1 mg / kg nabufen and 2 μ g / kg sufentanil is a safe and effective combination scheme for the prevention of visceral pain after gynecological laparoscopic surgery with small adverse reactions.Trial registration: http://www.chictr.org.cn/showproj.aspx?proj=40635Registration number：ChiCTR1900025076 . Prospectively registered on 10 August 2019.

Background A nomogram(arthro-MAP) predict major complications after Hip and Knee Arthroplasty has been establish by England people. The goal of this study is to externally validate the nomogram whether suitable for Chinese people or not. Methods A total of 414 elderly patients with Hip and Knee Arthroplasty underwent surgical treatment in the Affiliated Hospital of Guangdong Medical University from March 1, 2017 to August 31, 2019 were included into this study. Variables assessed were lowest intraoperative HR, EBL, preoperative BUN, procedure type, race, ASA score, comorbidities, presence of fracture. Receiver-operator characteristics (ROC) curve analysis, calibration (HL) and DCA were used to evaluate predictive properties of the nomogram. Results A total of 414 patients were consecutively enrolled. 47 patients (11.35%) presented a major complications after Hip and Knee Arthroplasty. The arthro-MAP nomogram presented an AUC of 0.816; 95%CI: 0.757–0.875 to predict major complications. At the calibration plot x2 = 17.13, P > 0.05, means the arthro-MAP nomogram appears to be well-calibrated in Chinese population, with predicted outcome rates closely reflecting the observed rates. Conclusions Although further studies are needed to confirm our results, the arthro-MAP nomogram was, in our experience, an excellent tool to predict major complications after Hip and Knee Arthroplasty, can be perform well in the Chinese population.

Background: By analyzing the risk factors of postoperative complications in elderly patients with hip replacement, We aimed to develop a nomogram model based on preoperative and intraoperative variables and verified the sensitivity and specificity for risk stratification of postoperative complications in elderly with total hip replacement patients.Methods: A total of 414 elderly patients who underwent surgical treatment for total hip replacement hospitalized at the Affiliated Hospital of Guangdong Medical University from March 1, 2017 to August 31, 2019 were included into this study. Univariate and multivariate logistic regression were conducted to identify independent risk factors of postoperative complication in the 414 patients. A nomogram was developed by R software and validated to predict the risk of postoperative complications.Results: Multivariate logistic regression analysis revealed that age (OR=1.05, 95%CI: 1.00-1.09) , renal failure(OR=0.90, 95% CI: 0.83～0.97) , Type2 diabetes (OR=1.05, 95% CI: 1.00～1.09) , ALB (OR=0.91, 95% CI: 0.83～0.99) were independent risk factors of postoperative complication in elderly patients with hip replacement (P＜0.05) . For validation of the nomogram, ROC curve revealed that the model predicting postoperative complication in elderly patients with hip replacement was the area under the curve of 0.8254(95% CI: 0.78～0.87) , the slope of the calibration plot was close to 1 and the model passed Hosmer-Lemeshow goodness of fit test (x2 = 10.16, P=0.4264), calibration in R Emax=0.176, Eavg=0.027, which all demonstrated that the model was of good accuracy. Conclusion: The nomogram predicting postoperative complications in patients with total hip replacement constructed based on age, type 2 diabetes, renal failure and ALB is of good discrimination and accuracy, which was of clinical significance.

Background To investigate the effect of intravenous injection of dexmedetomidine combined with parecoxib sodium on sedation and anxiety and stress response of tracheal intubation in patients undergoing functional endoscopic sinus surgery. Methods One hundred twenty patients undergoing endoscopic sinus surgery were randomly divided into four groups: group DP, group D, group P and group N. The blood pressure (BP), heart rate (HR), blood oxygen saturation (SPO2), EEG, bispectral index (BIS), Ramsay sedation score and state anxiety questionnaire (SAI) were recorded before administration (T0), 10 min (T1), 20 min (T2) and 30 min (T3) after administration. After 30 min, endotracheal intubation was performed after anesthesia induction. The BP, HR, SPO2 were recorded 1 min before intubation (T4), intubation (T5), 3 min (T6) after intubation, 5 min (T7) after intubation, and blood samples were collected from patients before administration and after intubation 2 min to detect serum cortisol (Cor), adrenalin (E) norepinephrine (NE) and blood glucose (BS). Results There was no significant difference in Ramsay sedation score before anesthesia, but the Ramsay sedation score in group D、DP was significantly higher than that in group P and group N, the BIS, BP, HR and anxiety scores were significantly lower than those in the group P and group N (p 0.05). Compared with T4, there was no significant difference in BIS and BP, HR in group D, group DP and group P (p > 0.05), but the BIS, BP and HR in group N were significantly higher than T4, (p 0.05), but the changes of Cor, E, NE and BS values were significantly lower than that in group N (p

Controlled ovarian hyperstimulation (COH) is widely used for the treatment of infertility, while the long-term effects of COH on the reproductive function in female offspring are currently unknown. Based on the fact that COH could cause high E2 levels in women throughout pregnancy and excess estrogenic exposure during fetal development is harmful to subsequent adult ovarian function, we assumed the hypothesis that COH disrupts reproductive function in female offspring. To test this hypothesis, COH was induced in mice to obtain female offspring by pregnant mare serum gonadotropin (PMSG) and HCG, and then we evaluated pubertal transition, serum levels of E2, anti-Mullerian hormone (AMH), FSH and LH, mRNA expressions ofEsr1,Amhr2,FshrandLhcgrin ovaries, number of follicles and ovarian histology. We also investigated the apoptosis of follicles by TUNEL; the mRNA expressions ofFas,FasL,Bax,Bcl2, and caspase 3, 8 and 9 by quantitative real-time PCR; and the protein expressions of cleaved-caspase (CASP) 3, 8 and 9 by Western blot. Moreover, we further observed estrous cyclicity in young adult offspring, performed follicle counting and measured the level of AMH in both serum and ovary. COH could induce detrimental pregnancy outcomes, as well as delayed pubertal transition and irregular estrous cycle due to the aberrant growth and maturation of follicles in female offspring. Our novel findings add new evidence to better understand the potential risks of COH on the reproductive function in female offspring, raising the awareness that COH could exert adverse effects on female offspring, rather than just obtain more oocytes for fertilization.

The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation (COH) implantation dysfunction were studied. The COH implantation dysfunction model in mice was established by intraperitoneal injection of 7.5 IU pregnant mare's serum gonadotrophin (PMSG), followed by 7.5 IU human chorionic gonadotrophin (HCG) 48 h later. Then the female mice were mated with male at a ratio of 2:1 in the same cage at 6:00 p.m. The female mice from normal group were injected intraperitoneally with normal saline and mated at the corresponding time. Day 1 of pregnancy was recorded by examining its vaginal smears at 8:00 a.m. of the next day. Fifty successfully pregnant mice were equally randomly divided into 5 groups: normal control pregnant group (NC), COH implantation dysfunction model group (COH), low dosage of Bu-Shen-An-Tai recipe group (LOW), middle dosage of Bu-Shen-An-Tai recipe group (MID) and high dosage of Bu-Shen-An-Tai recipe group (HIGH). Then from day 1, the mice in different groups were respectively intragastrically given corresponding treatments at 9:00 a.m. for 5 consecutive days. The concentrations of 17β-estradiol (E2) and progesterone (P4) were determined by radioimmunoassay (RIA). The ultrastructural changes of ovarian tissues were observed by transmission electron microscope (TEM). The histopathological changes of ovarian tissues were observed by HE staining. The number of atretic follicles and pregnant corpus luteum were also recorded. TUNEL was applied to measure apoptotic cells of ovarian tissues. Western blotting was used to detect the protein expression of apoptosis- related factors like Bax, Bcl-2 and cleaved-caspase-3 in ovarian tissue of mice. The results showed that ovarian weight, the concentrations of E2 and P4, the number of atretic follicles and pregnant corpus luteum, as well as the apoptosis of granulosa cells were significantly increased in the COH group. The ultrastructures of ovarian tissues in the COH group showed that chromatin in granulosa cells was increased, agglutinated, aggregated or crescent-shaped. The focal cavitation and the typical apoptotic bodies could be seen in granulosa cells in the late stage of apoptosis. After the treatment with different doses of Bu-Shen-An-Tai recipe, the ultrastructural changes of ovarian granulosa cells apoptosis were dramatically improved and even disappeared under TEM. Visible mitochondria and mitochondrial cristae were increased and vacuoles were significantly reduced. The lipid dropltes were shown in a circluar or oval shape. The protein expression levels of Bax and cleaved-caspase-3 were decreased, and the expression of Bcl-2 protein was increased after treatment. It was concluded that Bu-Shen-An-Tai recipe can inhibit the apoptosis of ovarian granulosa cells, probably by up-regulating the protein expression of Bcl-2 and down-regulating Bax and cleaved-caspase-3, which contributes to the formation and maintenance of ovarian corpus luteum. It's helpful to promote the embryonic implantation, to reduce embryo loss and ultimately to improve the success rate of pregnancy.