In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Objective: Schizophrenia (SCZ) is a severe psychiatric disorder with unknown etiology and lacking specific biomarkers. Herein, we aimed to explore plasma biomarkers relevant to SCZ using targeted metabolomics. Methods: Sixty drug-naïve SCZ patients and 36 healthy controls were recruited. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. We analyzed the levels of 271 metabolites in plasma samples from all subjects using targeted metabolomics, and identified metabolites that differed significantly between the two groups. Then we evaluated the diagnostic power of the metabolites based on receiver operating characteristic curves, and explored metabolites associated with the psychotic symptoms in SCZ patients. Results: Twenty-six metabolites showed significant differences between SCZ patients and healthy controls. Among them, 12 metabolites were phosphatidylcholines and cortisol, ceramide (d18:1/22:0), acetylcarnitine, and γ-aminobutyric acid, which could significantly distinguish SCZ from healthy controls with the area under the curve (AUC) above 0.7. Further, a panel consisting of the above 4 metabolites had an excellent performance with an AUC of 0.867. In SCZ patients, phosphatidylcholines were positively related with positive symptoms, and cholic acid was positively associated with negative symptoms. Conclusion Our study provides insights into the metabolite alterations associated with SCZ and potential biomarkers for its diagnosis and symptom severity assessment.

Objective:To report 2 young infants of sodium channel related epilepsy with SCN2A gene mutation, and to discuss the clinical characteristics of the disease and the efficacy and safety of lacosamide combined with the literature.Methods:Corresponding information of 2 children hospitalized in the Department of Neurology of Hunan Children′s Hospital in July 2021 and October 2021 was collected, including the symptoms, comprehensive physical examination, blood, cerebrospinal fluid, imaging, electrophysiological examination, diagnosis and treatment process, response to treatment and other clinical data, as well as the sequencing results of the whole exome of the children. The efficacy and safety of lacosamide were analyzed, and the related literatures of the Biomedical Literature Database, Wanfang Data Knowledge Service Platform and Chinese Knowledge Infrastructure Database were searched and reviewed.Results:Both of the 2 cases were girl. Their onset age was within 3 months. The initial symptoms were frequent convulsions and backward development. There was no structural abnormality in the head image. The convulsions could not be controlled according to conventional multidrug treatment. The seizures were quickly controlled with lacosamide. Now they have been followed up for 6 months. No obvious adverse reactions were found. Case 1 gene test results showed the SCN2A gene (chr2:166152333-166246334) heterozygous deletion, SCN1A gene (chr2:166847754-16693013) heterozygous deletion, the deletion size being about 5.72 Mb. Case 2 gene test results showed new missense mutation of SCN2A (c.1285G>A, p.Glu429Lys). There were dozens of seizures every day. They were treated with valproic acid, oxcarbazepine and levetiracetam successively. The seizures could not be controlled. Three focal seizures originated in the left temporal region were detected by electroencephalogram. There was no recurrence on the third day after adding lacosamide, and there was no attack after 5 months of follow-up. No obvious adverse reactions were found during follow-up.Conclusions:Sodium channel related epileptic encephalopathy often starts early, has frequent seizures, and can be accompanied by backward psychomotor development at the same time. The slow sodium channel blocker lacosamide has good efficacy and safety in the treatment of sodium channel-related epilepsy with SCN2A gene mutation or combined SCN1A gene mutation.

Objective:To implement PRECEDE-PROCEED based intervention in community patients with type 2 diabetes mellitus (T2DM) and explore its effects on patients' diabetes knowledge and self-efficacy.Methods:Totally 86 T2DM patients treated in a community health service center in Hangzhou between May and October 2014 were selected using convenient sampling and divided into intervention group ( n=43) and control group ( n=43) . Patients in the intervention group received 6-month intervention based on PRECEDE-PROCEED, while patients in the control group received a regular community health education course once during the same period. The diabetes knowledge and self-efficacy scores were evaluated between the two groups before and 3 and 6 months after intervention. At last, a total of 40 patients in the intervention group and 42 patients in the control group completed the study. Results:Repeated measures analysis of variance showed that there were time-dependent, between-group and combined effects in diabetes knowledge and self-efficacy scores in the two groups ( P<0.05) . Pairwise comparison between the two groups revealed that there was no statistically significant difference in diabetes knowledge and self-efficacy scores between the two groups before intervention ( P>0.05) , but there were statistically significant differences in diabetes knowledge and self-efficacy scores between the two groups 3 and 6 months after intervention ( P<0.05) . Conclusions:The PRECEDE-PROCEED based intervention can effectively improve the diabetes knowledge and self-efficacy of T2DM patients, which is worth promoting in clinical practice.

Objective To construct a knowledge system of cultural competence education among undergraduate nursing students, so as to enhance the cultural capacity of undergraduate nursing students. Methods From September 2015 to January 2016, a two-round expert consultation was conducted among 11 nursing experts who engaged in multicultural related work in Shanghai, Hangzhou and other places by Delphi method. Results The active coefficient of the two rounds of the expert consultation were both 100%. The expert authority (Cr) was 0.89, and the coordination coefficients of the first and second round of consultation were 0.227 and 0.236 respectively (P<0.01). Finally, the knowledge system of cultural competence education in undergraduate nursing students was constructed, including 5 first-level indicators, 10 second-level indicators and 39 third-level indicators. Conclusions The primarily constructed knowledge system of cultural competence education among undergraduate nursing students is a scientific and reasonable frame work system, which provides content references and evaluation basis for the cultural competence education among undergraduate nursing students in our country.

Objective To investigate the value of procalcitonin (PCT ) and high sensitive C reactive protein (Hs-CRP) in the diagnosis of hyperbilirubinemia premature infant complicating infection .Methods A total of 192 cases of hyperbilirubinemia premature infants in our hospital were selected as the research subjects and divided into the infection group and non-infection group ac-cording to the clinical diagnostic results .The levels of WBC ,Hs-CRP ,PCT and total bilirubin(TB) were measured and performed the comparative analysis .Results The Hs-CRP ,PCT and TB levels in the infection group were significantly higher than those in the non-infected group ,the difference was statistically significant (P＜0 .05);while there was no significant difference in WBC count between the two groups(P＞0 .05) .PCT had higher sensitivity and specificity than Hs-CRP in the diagnosis of infection .The positive rates of PCT and Hs-CRP in the infection group were significantly higher than those in the non-infection group ,the difference was statistically significant (P＜0 .05) .Conclusion PCT and Hs-CRP can guide the early diagnosis of hyperbilirubinemia premature infant complicating infection and are conducive to early treatment and rehabilitation of the neonatal patients .

Obej ctive To inev stigate the situation of hands only cardiopulmonary resuscitation ( CPR) and training effectiveness of CPR in middle school students.Methods By the principle of random stratified cluster sampling,7 687 middle school students in Changsha city were trained on hands only CPR through the scene theoyr teaching and anthropom orphic dummy in this study.The training content icn lued d who was rescued by CPR, whne pait ne ts require CPR,h ow logn cna causei rreversible brain damage, the stna dardized process fo CPR,the position of CP R,the depth of CPR,and the ratios of breath-to-compression. We analyzed the middle school students′awareness of hands only CPR know ledge before and after the train-ing,investigated the middle school studne ts′willign ness and way to accept knowledge of first aid.Re sulst All of 7 687 middle scoh ol students inC hangsha cti y received questionnaire us rvey and trained on hands only CPR,including 3 778(49.15%) boys and 3 909 girls(50.48%).The knowledge of hands only CPR was mainly derived from the book,television,network,and education from schools.Before training,the awareness rates of the knowledge on who was rescued by CPR and the position of CPR were more than 50%,and the awareness rates on the rest of know ledge were less than 50%.The awareness rates on hands only CPR were more than 75% by training, which were significantly increased compared with tho se before training ( P <0.01).Conclusion The knowledge on hands only CPR is very scarce in middle school students in Changsha city,and the awareness on hands only CPR can be significantly improved by the scene theory teaching and an-thropomorphic dummy.

Objective To explore the impact of berberine on serum levels of insulin resistance and cytokines in schizophrenia patients treated with risperidone. Methods Sixty-four schizophrenia patients treated with risperidone were randomized to berberine group (n=31) and control group (n=33). The fasting plasma blood glucose (FBG) and fasting insulin (Fins) were detected before and after treatment in two groups. The homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. The serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α) were evaluated by enzyme linked immunosorbent assay before and after the treatment. Results Compared with control group and pre-treatment group, the levels of FBG, Fins, HOMA-IR, IL-1β, IL-6 and TNF-α were significantly decreased after treatment in berberine group (P<0.05). The FBG level was significantly higher, the levels of IL-1β, IL-6 and TNF-αwere significantly lower, after treatment in control group (P < 0.01). There were no significant changes in Fins and HOMA-IR after treatment (P > 0.05). There was positive correlation between HOMA-IR and IL-1β, IL-6 and TNF-α in berberine group (r=0.316, 0.351 and 0.401, P<0.01). Conclusion Berberine can significantly decrease FBG, Fins, HOMA-IR, IL-
1β, IL-6 and TNF-α levels in schizophrenia patients treated with risperidone. The HOMA-IR level is closely correlated with IL-1β, IL-6 and TNF-αlevels.

Objective To investigate the distribution and drug resistance of major pathogens for urinary tract infections in the First Affiliated Hospital of Nanjing Medical University.Methods Strains from midstream urine culture of patients with urinary tract infections were collected during January 1 and December 31,2011.All strains were identified by API system,and disk diffusion method was used for drug sensitivity test.Results Totally 1129 strains were isolated,in which 667 (59.1％ ) were Gram-negative strains,266 (23.5％) were Gram-positive strains,and 196 (17.4) were Candida.Among Gram-negative strains,Escherichia coli,Klebsiella pneumoniae and Proteus mirabilis were highly sensitive to carbapenem antibiotics; while Acinetobacter baumannii and Pseudomonas aeruginosa were highly resistant to most antibiotics including cephalosporins and penicillinase inhibitor,and the resistance rates were over 50％.Among Gram-positive strains,the major strains Enterococcus avium and Enterococcusfaecalis were completely sensitive to vancomycin and teicoplanin,and highly sensitive to linezolid (resistance rate below 10％ ).Candida albicans and Candida glabrata were highly resistant to voriconazole and fluconazole (with the resistance rates of 47.2％ - 60.0％ ), but were completely sensitive to amphotericin and nystatin.Conclusion Gram-negative strains account for most urinary tract infections in the First Affiliated Hospital of Nanjing Medical University with high drug resistance rates.