Kisspeptin-13 enhances memory and mitigates memory impairment induced by Aß1-42 in mice novel object and object location recognition tasks.

Kisspeptin (KP), the endogenous ligand of GPR54, is a recently discovered neuropeptide shown to be involved in regulating reproductive system, anxiety-related behavior, locomotion, food intake, and suppression of metastasis across a range of cancers. KP is transcribed within the hippocampus, and GPR54 has been found in the amygdala and hippocampus, suggesting that KP might be involved in mediating learning and memory. However, the role of KP in cognition was largely unclear. Here, we investigated the role of KP-13, one of the endogenous active isoforms, in memory processes, and determined whether KP-13 could mitigate memory impairment induced by Aß1-42 in mice, using novel object recognition (NOR) and object location recognition (OLR) tasks. Intracerebroventricular (i.c.v.) infusion of KP-13 (2µg) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-improving effects of KP-13 could be blocked by the GPR54 receptor antagonist, kisspeptin-234 (234), and GnRH receptors antagonist, Cetrorelix, suggesting pharmacological specificity. Then the memory-enhancing effects were also presented after infusion of KP-13 into the hippocampus. Moreover, we found that i.c.v. injection of KP-13 was able to reverse the memory impairment induced by Aß1-42, which was inhibited by 234. To sum up, the results of our work indicate that KP-13 could facilitate memory formation and prolong memory retention through activation of the GPR54 and GnRH receptors, and suppress memory-impairing effect of Aß1-42 through activation of the GPR54, suggesting that KP-13 may be a potential drug for enhancing memory and treating Alzheimer's disease.

[Investigation and factor analysis of postoperative surgical site infections in emergency abdominal surgery in China from 2018 to 2021 based on Chinese SSI Surveillance].

Objective: We investigated the incidence of surgical site infection (SSI) following emergency abdominal surgery (EAS) in China and further explored its risk factors, providing a reference for preventing and controlling SSI after EAS. Methods: This was an observational study. Data of patients who had undergone EAS and been enrolled in the Chinese SSI Surveillance Program during 2018-2021were retrospectively analyzed. All included patients had been followed up for 30 days after surgery. The analyzed data consisted of relevant patient characteristics and perioperative clinical data, including preoperative hemoglobin, albumin, and blood glucose concentrations, American Society of Anesthesiologists (ASA) score, grade of surgical incision, intestinal preparation, skin preparation, location of surgical site, approach, and duration. The primary outcome was the incidence of SSI occurring within 30 days following EAS. SSI was defined as both superficial and deep incisional infections and organ/space infections, diagnoses being supported by results of microbiological culture of secretions and pus. Secondary outcomes included 30-day postoperative mortality rates, length of stay in the intensive care unit (ICU), duration of postoperative hospitalization, and associated costs. The patients were classified into two groups, SSI and non-SSI, based on whether an infection had been diagnosed. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with SSI following EAS. Results: The study cohort comprised 5491 patients who had undergone EAS, comprising 3169 male and 2322 female patients. SSIs were diagnosed in 168 (3.1%) patients after EAS (SSI group); thus, the non-SSI group consisted of 5323 patients. The SSIs comprised superficial incision infections in 69 (41.1%), deep incision infections in 51 (30.4%), and organ or space infections in 48 (28.6%). Cultures of secretions and pus were positive in 115 (68.5%) cases. The most frequently detected organism was Escherichia coli (47/115; 40.9%). There were no significant differences in sex or body mass index between the SSI and non-SSI groups (both P>0.05). However, the proportion of individuals aged 60 years or older was significantly greater in the SSI than in the non-SSI group (49.4% [83/168] vs. 27.5% [1464/5323), χ2=38.604, P<0.001). Compared with the non-SSI group, the SSI group had greater proportions of patients with diabetes (11.9% [20/168] vs. 4.8% [258/5323], χ2=16.878, P<0.001), hypertension (25.6% [43/168] vs. 12.2% [649/5323], χ2=26.562, P<0.001); hemoglobin <110 g/L (27.4% [46/168] vs. 13.1% [697/5323], χ2=28.411, P<0.001), and albuminemia <30 g/L (24.4% [41/168] vs. 5.9% [316/5323], χ2=91.352, P<0.001), and a reduced rate of preoperative skin preparation (66.7% [112/168] vs. 75.9% [4039/5323], χ2=7.491, P=0.006). Furthermore, fewer patients in the SSI group had preoperative ASA scores of between one and two (56.0% [94/168] vs. 88.7% [4724/5323], χ2=162.869, P<0.001) in the non-SSI group. The incidences of contaminated and infected incisions were greater in the SSI group (63.1% [106/168] vs. 38.6% [2056/5323], χ2=40.854, P<0.001). There was a significant difference in surgical site distribution between the SSI and non-SSI groups (small intestine 29.8% [50/168] vs. 10.6% [565/5323], colorectal 26.2% [44/168] vs. 5.6% [298/5 323], and appendix 24.4% [41/168] vs. 65.1% [3465/5323]) χ2=167.897, P<0.001), respectively. There was a significantly lower proportion of laparoscope or robotic surgery in the non-SSI group (24.4 % [41/168] vs. 74.2% [3949/5323], χ2=203.199, P<0.001); the percentage of operations of duration less than 2 hours was significantly lower in the SSI than non-SSI group (35.7% [60/168] vs. 77.4% [4119/5323], χ2=155.487, P<0.001). As to clinical outcomes, there was a higher 30-day postoperative mortality rate (3.0%[5/168] vs. 0.2%[10/5323], χ2=36.807, P<0.001) and higher postoperative ICU occupancy rate (41.7% [70/168] vs. 19.7% [1046/5323], χ2=48.748, P<0.001) in the SSI group. The median length of stay in the ICU (0[2] vs. 0[0] days, U=328597.000, P<0.001), median total length of stay after surgery (16[13] vs. 6[5] days, U=128146.000, P<0.001), and median hospitalization cost (ten thousand yuan, 4.7[4.4] vs. 1.7[1.8], U=175965.000, P<0.001) were all significantly greater in the SSI group. Multivariate logistic regression analysis revealed that the absence of skin preparation before surgery (OR=2.435,95%CI: 1.690-3.508, P<0.001), preoperative albuminemia <30 g/L (OR=1.680, 95%CI: 1.081-2.610, P=0.021), contaminated or infected incisions (OR=3.031, 95%CI: 2.151-4.271, P<0.001), and laparotomy (OR=3.436, 95% CI: 2.123-5.564, P<0.001) were independent risk factors of SSI. Operative duration less than 2 hours (OR=0.465, 95%CI: 0.312-0.695, P<0.001) and ASA score of 1-2 (OR=0.416, 95% CI: 0.289-0.601, P<0.001) were identified as independent protective factors for SSI. Conclusions: It is important to consider the nutritional status in the perioperative period of patients undergoing EAS. Preoperative skin preparation should be conducted and, whenever possible, laparoscope or robot-assisted surgery. Duration of surgery should be as short as possible while maintaining surgery quality and improving patient care.

A suppository kit for metronomic photodynamic therapy: The elimination of rectal cancer in situ.

Metronomic photodynamic therapy (mPDT) was developed to improve tumor-specific responses through cell death by apoptosis. We developed an mPDT suppository kit including ALA and LED suppositories and analyzed its killing effect on rectal tumors in rabbits. METHODS: The ALA (10 wt%) suppository was prepared using ALA powder, type 36 semi-synthetic fatty acid glyceride, and azone. The LED suppository was constructed by encapsulating LED units and a circuit in transparent epoxy resin. VX2 cells were injected into the rectal submucosa of rabbits to establish a carcinoma model in situ. The ALA suppository was inserted into the rectal cavity for 30 min of uptake and activated for 1 h by the LED suppository at a power density of 20 mW/cm2. The mPDT process was repeated three times once a day. MRI was used to monitor tumor growth, histopathology and TUNEL staining were performed at 14 days after mPDT. RESULTS: The overall response rate was 60% in the mPDT group using the kit in which the tumor size was decreased up to about 50% at 7 days post-mPDT and almost eliminated at 14 days. HE staining showed that only 6.16% of the tumor tissue remained after mPDT treatment. TUNEL detection showed that the apoptosis rate was 18.9%. CONCLUSION: We verified the killing effect of the mPDT suppository kit on rectal tumors in rabbits based on mPDT that induced tumor cell apoptosis.

Characterization of a corticotropin-releasing hormone-responsive element in the rat proopiomelanocortin gene promoter and molecular cloning of its binding protein.

A corticotropin-releasing hormone (CRH) and cAMP-responsive region (-236/-133) in the rat POMC gene promoter previously reported to confer CRH/cAMP responsiveness to heterologous reporter constructs has been characterized. DNAse footprint analysis revealed that multiple elements in this region were bound by nuclear proteins from the POMC expressing AtT20 cells. When these individual DNA elements were separately tested in heterologous reporter constructs for CRH induction, only one element, designated PCRH-RE (POMC CRH responsive element, -171/-160) was found to give strong CRH stimulation (5- to 7-fold). This element appears novel as to the possible binding factors, although it has homology to the mouse metallothionein metal regulatory element. Gel shift analyses of the PCRH-RE with AtT20 cell nuclear extracts showed marked stimulation of retarded nucleoproteins following CRH stimulation, suggesting that the possible binding factor(s) may mediate transcriptional regulation at this site. The activity of PCRH-RE binding protein was inhibited by divalent cations, with Cu2+ and Cd2+ being most effective; Zn2+ had no effect, indicating that this binding factor(s) is functionally distinct from the metallothionein metal regulatory element binding protein. A 2.6 kilobase cDNA clone encoding a protein (PCRH-REB-1) binding to this element was isolated by Southwestern screening of an AtT20 expression library with radiolabeled PCRH-RE oligonucleotides. This clone was used to isolate several other cDNA clones to determine the sequence corresponding to the entire coding region of the protein (PCRH-REB), which proved to be identical to a recently described DNA binding protein of the replication factor C complex, mRFC140/Mouse Southwestern. Primer extension and Northern blot analysis revealed that the size of the full length mRNA is about 4.9 kilobases. PCRH-REB mRNA expression is not restricted to corticotrophs but is present in a broad tissue distribution as evaluated by reverse transcription polymerase chain reaction analysis. A bacterially expressed beta-galactosidase-PCRH-REB-1 fusion protein was shown to bind PCRH-RE efficiently. Furthermore, binding of the PCRH-REB-1 fusion protein to the POMC CRH-responsive element was inhibited by divalent cations with similar sensitivities to those observed using AtT20 nuclear extracts. The predicted PCHR-REB protein sequence presents several interesting motifs: one p-Loop motif (ATP binding site), nine protein kinase A phosphorylation sites (implying a possible role in responding to the CRH-induced cAMP signal), and regions of homology to proteins involved in DNA replication and repair. PCRH-REB is, therefore, a potential transacting factor binding to a major CRH-responsive element in the POMC promoter.

Phoenixin-14 enhances memory and mitigates memory impairment induced by Aß1-42 and scopolamine in mice.

Phoenixin (PNX) is a recently discovered neuropeptide shown to be involved in regulating the reproductive system, anxiety-related behaviors and pain though its receptor is still unknown. PNX-14, one of the endogenous active isoforms, is reported to regulate gonadotropin releasing hormone (GnRH) receptor expression and GnRH secretion. Because GnRH system is thought to be involved in the regulation of learning and memory processes, we hypothesized that PNX-14 might be mediate learning and memory. Here, we investigated the effects of PNX-14 in memory processes, using novel object recognition (NOR) and object location recognition (OLR) tasks. Our results revealed that intracerebroventricular (i.c.v.) injection of PNX-14 (25nmol) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-enhancing effects of PNX-14 were also seen when it was infused into the hippocampus. Moreover, these memory-improving effects of PNX-14 could be blocked by a GnRH receptor antagonist (Cetrorelix). The memory-improving effects of PNX-14 were not related to any effects on locomotor activity. Additionally, the results suggested that i.c.v. injection of PNX-14 mitigate the memory impairment induced by the amyloid-ß1-42 (Aß1-42) peptide and scopolamine. The present results indicate that PNX-14 facilitates memory formation and prolongs memory retention through activation of the GnRH receptor, and mitigates the memory-impairing effects of Aß1-42 and scopolamine, suggesting that PNX-14 may be effective as a drug for enhancing memory and treating Alzheimer׳s disease.

Effects of Phoenixin-14 on anxiolytic-like behavior in mice.

Phoenixin is an amidated neuropeptide, which is widely distributed in brain and periphery regions and is known for its key role in reproduction. Phoenixin-14 (PNX-14), one of the endogenous active isoforms, was reported to regulate pituitary gonadotrophin secretion by increasing the expression of the GnRH receptor mRNA. Studies showed that GnRH could regulate brain responses to anxiety. However, the role of PNX-14 in anxiety was largely unclear. Here, we investigated that the effects of PNX-14 in anxiety-related behavior in adult mice via the open field and elevated plus maze. PNX-14 was administered intracerebroventricularly (i.c.v.) in different doses (5, 10, 25 and 50 nmol), and dose-dependently induced anxiolytic effects. Then this anxiolytic action was presented after PNX-14 injected into the anterior hypothalamic area (AHA), while PNX-14 infused into the amygdala did not exert anxiolytic effects. GnRH receptor antagonist (Cetrorelix) could significantly antagonize the anxiolytic effects of PNX-14, while Atosiban, a competitive vasopressin/oxytocin receptor antagonist could not. Moreover, PNX-14 could significantly lower the core temperature and Cetrorelix could block this effect of PNX-14. Additionally, the AHA infusion of PNX-14 (5 nmol) increased the expression level of the GnRH mRNA in the hypothalamus and plasma concentrations of GnRH. Similarly, i.c.v. injection of PNX-20 also reduced the core temperature and exerted anxiolytic effects. Taken together, centrally injected PNX-14 generates anxiolytic effects in mice, via the activation of the AHA GnRH system.

[Digital noninvasive microwave thermography in the diagnosis of breast disease].

Thermography is a noninvasive technic of examination. Liquid-Crystal Thermography and Infrared Thermography have provided great help in the general survey of breast diseases during the past twenty years but not without some limitations. Recently, by applying the microwave technic clinically, progress has been made to measure minute temperature changes in the deeper tissues. Differential diagnosis of breast disease is possible by statistical calculating the temperature difference of the two breasts. A prospective study was done in 96 women who had both X ray mammography and digital noninvasive microwave thermography. 70/96 were proved by pathology. In this group of patients, the accuracy rate was 70.00% for digital microwave thermography, 81.82% for X ray mammography and 95.50% for the two combined. The false positive rates and false negative rates, advantages, disadvantages and the for general survey of breast disease of the digital microwave thermography discussed.

Mucopolysaccharidosis type VI: identification of three mutations in the arylsulfatase B gene of patients with the severe and mild phenotypes provides molecular evidence for genetic heterogeneity.

Mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy disease) results from the deficient activity of the lysosomal enzyme, arylsulfatase B (ASB; N-acetylgalactosamine-4-sulfatase E.C.3.1.6.1). The enzymatic defect leads to the accumulation of the glycosaminoglycan, dermatan sulfate, primarily in connective tissue and reticuloendothelial cell lysosomes. Although MPS VI patients have normal intelligence and no neurologic abnormalities, the disease is clinically heterogeneous: severely affected individuals expire in childhood or early adolescence while those with the mild or intermediate phenotypes have a slower, milder disease course and a longer life span. The recent isolation of the full-length cDNA-encoding human ASB permitted an investigation of the molecular lesions underlying the phenotypic heterogeneity in MPS VI. The ASB cDNA-coding sequences were determined from two unrelated MPS VI patients with the severe (proband 1) and mild (proband 2) phenotypes. These patients had about 2% and 7% of normal ASB activity in cultured fibroblasts, respectively. Proband 1 was homoallelic for a T-to-C transition in nucleotide (nt) 349, which predicted a cysteine-to-arginine substitution in the ASB polypeptide at residue 117 (C117R). Proband 2 was heteroallelic, having a T-to-C transition in nt 707, which predicted a leucine-to-proline replacement at ASB residue 236 (L236P), and having a G-to-A transition in nt 1214, which predicted a cysteine-to-tyrosine substitution at ASB residue 405 (C405Y). These mutations did not occur in three other unrelated MPS VI patients or in 120 ASB alleles from normal individuals, indicating that they were not polymorphisms. The identification of these three ASB mutations documents the first evidence of molecular heterogeneity in MPS VI and provides an initial basis for genotype/phenotype correlations in this lysosomal storage disease.