Objective To research the mechanism or pathway through which Substance P(SP) inhibits r-aminobutyric acid(GABA) activated currents in bullfrog dorsal root ganglion(DRG) neurons.Method The experiment was conducted on freshly isolated bullfrog dorsal root ganglion neurons using a whole-cell patch-clamp technique.Results SP could caused a slow inward current when SP was applied to DRG neurons;SP could inhibits GABA-activated currents;The inhibition could be reduced largely when protein kinase C(PKC) inhibiter,1-(5-isoquinolinesulphorry)-2-methylpiperazine(H-7), was dialyzed in cell body.Conclusion The SP ton inhibit GABA-activated currents through protein kinase C.

BACKGROUND: Revascularization is a challenge for the tissue-engineered bone carrying cells after implanted into human body. Previous studies have found that tanshinol can improve the functions of endothelial progenitor cells and exert vascular protective effects.OBJECTIVE: To prepare the β-calcium phosphate (β-TCP) scaffold with tanshinol coating, and to observe its cytocompatibility.METHODS: The β-TCP scaffolds coated with 10-7, 10-6 and 10-5 mol of tanshinol were constructed by negative pressure absorption method. The distribution of tanshinol coating on the scaffold was observed using scanning electron microscopy,and the inner ingredients were analyzed by infrared spectrum. Human endothelial progenitor cells (hEPCs) were cultured in the extracts of β-TCP and β-TCP scaffolds with 10-7, 10-6, 10-5 mol of tanshinol coatings, respectively. The cell proliferation was detected at 2, 4, 6, 8 and 10 days of culture; the levels of nitric oxide and vascular endothelial growth factor in the supernatants were detected at 1, 7 and 14 days of culture; the lumen formation on the matrigel was observed after 14-day culture. hEPCs were respectively seeded onto the β-TCP and β-TCP scaffolds with different dosages of tanshinol coating,and then the cell growth was observed under scanning electron microscope at 7 days.RESULTS AND CONCLUSION: The tanshinol coating evenly distributed on the inner surface of the pores, and its crystalline structure became dense with dosage increasing. Infrared spectrum analysis revealed no changes in the characteristic absorption peak of tanshinol and TCP in the scaffold. The β-TCP scaffolds with tanshinol coating could promote the proliferation of hEPCs, especially the scaffolds with 10-6 and 10-5 mol tanshinol coating. Compared with the β-TCP scaffold, the scaffolds with 10-6 and 10-5 mol tanshinol coating significantly upregulated the nitric oxide level at 14 days of culture, and significantly increased the level of vascular endothelial growth factor at 7 and 14 days of culture (P <0.05). Although it could be found in all β-TCP scaffolds with tanshinol coating, the lumen formation was the maturest in the scaffold with 10-5 mol tanshinol coating. These results suggest the β-TCP scaffolds with tanshinol coating can promote the proliferation and endothelial differentiation of hEPCs, and hold a good cytocompatibility.

Objective To explore the perception of clinical learning environment,career maturity,and professional identity as well as their associations among 3+2 nursing undergraduates.Method Totally 198 3+2 nursing undergraduate students from two provincial medical colleges in Shandong province were enrolled.Results Mean scores for clinical learning environment,career maturity and professional identity were (3.44 ± 0.54),(3.31 ± 0.37) and (3.63 ± 0.62),respectively.Clinical learning environment and career maturity (P＜0.001) were positivelyassociated with 3+2 nursing undergraduates' professional identity.Conclusions Clinical learning environment,career maturity and professional identity of 3 +2 nursing undergraduates areat a moderate level.Interventions to facilitate clinical learning environments and career maturity will foster the growth of professional identity.

Objective: We investigated the clinical characteristics and the most important risk factors of urinary calculi in children. Methods: Using Cochrane Library, PubMed, ProQuest, ELEVIER Science Direct, Embase, Springerlink, China National Knowledge Infrastructure (CNKI), and Wanfang database, we reviewed literature on clinical characteristics of urinary calculi in children from January 2003 to September 2018, and data was analyzed using STATA 14.0. Results: Incidence of calculi in male children was 62.1% [95% CI (57.2%, 67.1%)]. 39.4% [95% CI (26.5%, 52.2%)] children with urolithiasis had a family history of positive stones, 25.3% [95% CI (19.2%, 31.3%)] had a history of urinary infection, and 16.6% [95% CI (12.3%, 20.9%)] had abnormal urinary anatomy. In addition, urinary calculi were most commonly found in the kidney [63.6%, 95% CI (49.9%, 77.3%)], followed by ureter [17.2%, 95% CI (13.4%, 21.0%)], and bladder [12.4%, 95% CI (6.9%, 18.7%)]. The single component of urinary calculi in children accounted for 58.8% [95% CI(48.7%, 68.9%)], the most common component was calcium oxalate [49.4%, 95% CI (36.7%, 62.1%)], followed by uric acid [7.9%, 95% CI (4.1%, 11.6%)]. The most common urinary metabolic disorders were hypernatremia [38.8%, 95% CI (27.9%, 49.7%)], followed by hypercalciuria [33.4%, 95% CI (27.3%, 39.4%)]. Conclusions Heredity metabolic abnormalities, urinary tract infection, and anatomical structural abnormalities are important risk factors of urinary calculi in children. Stone recurrence could be reduced and prevented by regulating metabolic disorders, managing urinary tract infection, and correcting anatomical abnormality.

Objective:To investigate the role of a simple Nomogram model in evaluating the severity of mycoplasma pneumoniae pneumonia (MPP) in adults.Methods:The clinical data of 162 patients with MPP who received treatment in Wenzhou Central Hospital from March 2015 to October 2022 were retrospectively analyzed. These patients were divided into a severe group ( n = 67) and a common group ( n = 95) according to whether they were diagnosed with severe MPP. The clinical data of patients were recorded. Fourteen clinical variables were screened, including age, sex, onset season, fever, heat peak, fever duration, cough duration, white blood cell count, percentage of neutrophils, percentage of lymphocytes, hemoglobin, platelet count, C-reactive protein, and procalcitonin. Multivariate logistic regression analysis of statistically significant variables in univariate analysis was performed. The Nomogram model was constructed with the R language software package (version 3.6.2). The model was verified with a calibration curve and receiver operating characteristic curve. Results:Univariate analysis results showed that in the severe group, the fever peak ( Z = 5.03, P < 0.001) was higher, fever duration ( χ2 = 27.55, P < 0.001), and cough duration ( χ2 = 28.72, P < 0.001) were longer, white cell count ( t = 2.93, P = 0.004), percentage of neutrophils ( t = 9.08, P < 0.001), C-reactive protein ( t = 35.05, P < 0.001), and procalcitonin level ( t = 15.09, P < 0.001) were greater compared with the common group. The percentage of lymphocytes ( t = 1.16, P < 0.001), hemoglobin level ( t = 1.22, P < 0.001), and platelet count ( t = 2.82, P < 0.001) in the severe group were significantly lower than those in the common group. Multivariate logistic regression analysis results showed that heat peak, cough duration, and C-reactive protein were positively correlated with the severity of MPP (all P < 0.05). The percentage of lymphocytes, hemoglobin concentration, and platelet count were negatively correlated with the severity of MPP (all P < 0.05). The establishment and validation results of the Nomogram model showed that the accuracy of the model was good, with a sensitivity of 88.73%, a specificity of 77.61%, and a C-index of 0.904. Conclusion:Heat peak, cough duration, percentage of lymphocytes, platelet count, and C-reactive protein are closely related to the severity of early MPP. A simple Nomogram model can be one of the tools for early assessment of the severity of MPP.

Chloroquine and hydroxychloroquine are both classic 4-aminoquinoline antimalarial drugs with similar chemical structures and mechanisms of action. As the toxicity and side effects of hydroxychloroquine are lower than those of chloroquine, hydroxychloroquine is the main clinical application at present, with good efficacy and safety. Chloroquine and hydroxychloroquine are widely used in the clinic because of their immunosuppressive, anti-inflammatory, antiviral, antitumor and photoprotective effects. The main mechanisms by which chloroquine/hydroxychloroquine inhibits immunity include inhibiting lysosome activity, autophagy, immune response signaling pathways production of proinflammatory cytokines. Chloroquine stabilizes the lysosomal membrane and reduces the release of lysosomal enzymes. As a prostaglandin antagonist, chloroquine can reduce the production of prostaglandins and leukotrienes, thus playing an anti-inflammatory role. Chloroquine/hydroxychloroquine can inhibit virus proliferation in the early stage of virus replication by inhibiting the glycosylation of the angiotensin converting enzyme 2 receptor. At present, hydroxychloroquine has been found to have significant efficacy in discoid lupus erythematosus, oral lichen planus, chronic cheilitis, pemphigus foliaceus, Sjögren’s syndrome and other stomatological diseases. However, eye damage is the most important adverse reaction of hydroxychloroquine, and its occurrence is related to the cumulative dose of drugs.

Objective To construct sensitive, scientific and practical breast nursing quality evaluation indicators, and provide evidence for hospital breast nursing quality evaluation and monitoring. Methods Potential sensitive indicators of nursing quality were initially built by referencing the development process of the nursing quality indicators national database system of United States, by retrieving the domestic and foreign documents, by combining with breast cancer diagnosis and treatment guidelines, nursing textbooks, and nursing negative events, by clinical investigation and group discussion. An expert survey paper was prepared and three rounds surveys were conducted to revise and fix the sensitive indicators of breast nursing quality. Results The positive coefficients of the three rounds of expert consultation were 100％ , the authoritative coefficients of the three rounds were 0.847,0.851,0.849, respectively. The coordination coefficient of the three rounds of experts was 0.371-0.476、0.597-0.736、0.739-0.873, P<0.01, and finally 4 sensitive indicators of breast specialist care quality were established. Conclusions The nursing quality sensitive indicators were constructed by Delphi method. They comply with the principles of scientificity and rigorousness, and have the characteristics of breast nursing. They can be verified by clinical practices in the role of nursing quality control and evaluation, and gradually achieve effective data sharing to clinical guidelines to help the development of specialist care.

OBJECTIVE: To explore the genetic basis for a child featuring congenital insensitivity to pain (CIP). METHODS: Targeted capture and next generation sequencing (NGS) was carried out for the proband. Suspected pathogenic variants were confirmed by Sanger sequencing of the proband and his parents. RESULTS: The proband was found to harbor compound heterozygous variants of SCN9A gene, namely c.1598delA (p.N533Ifs*31) and c.295_296delCGinsAT (p.R99I), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic, and neither was reported previously. CONCLUSION The compound heterozygous variants of the SCN9A gene probably underlay the CIP in this child. Above finding has enabled genetic counseling for this family.
Channelopathies ; Child ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; NAV1.7 Voltage-Gated Sodium Channel/genetics* ; Pain Insensitivity, Congenital/genetics*

Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Objective:To examine the impact of sleep quality on cognitive function in older adults with mild cognitive impairment(MCI)and explore the potential mediating role of depression.Methods:Using a cross-sectional design, we conducted an on-site questionnaire survey among 310 elderly individuals with MCI in Haishu District, Ningbo City from April to June 2021.Out of the 310 questionnaires collected, 299 were deemed valid.The survey encompassed gathering basic demographic information of the participants, as well as administering the Montreal Cognitive Assessment Scale, Patient Health Questionnaire Depression Scale, and Pittsburgh Sleep Quality Index Scale.Results:The cognitive functions of patients with MCI were found to be positively related to their education level( F=3.89, P<0.05).The correlation analysis indicated that sleep quality was positively correlated with depression( r=0.40, P<0.01)and negatively correlated with cognitive function( r=-0.22, P<0.01).Furthermore, a significant negative correlation was observed between depression and cognitive function( r=-0.20, P<0.01).The mediation analysis revealed that depression played a role in mediating the influence of sleep quality on cognitive function, with a mediation effect of -0.02(95% CI: -0.03--0.01). Conclusions:The cognitive function of elderly individuals with MCI can be significantly affected by sleep quality, with depression playing a mediating role.