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Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective To provide reference for the subsequent clinical application of WBV,based on the impacts of whole body vibration(WBV)with different frequencies on gross motor function and walking function in children with dyskinetic cerebral palsy.Methods 60 children aged 6～12 with dyskinetic cerebral palsy,who had been treated at the department of rehabilitation medicine in the Affiliated Southwest Medical University from October 2021 to November 2022,were selected.They were randomly divided into a control group(n = 20),(25±5)Hz group(n = 20),and(35±5)Hz group(n = 20).All the three groups received conventional rehabilitation,while the(25±5)Hz group received additional WBV with(25±5)Hz and the(35±5)Hz group received WBV with(35±5)Hz.They were treated for eight weeks.The scores on D and E domains of GMFM-88,TUGT,the score on Berg Balance Scale,and footprint analysis were used for assessment of the efficacy after treatment.Results As compared with the baselines,the scores were improved in the three groups after treatment(P＜0.001).BBS(F = 12.502),TUGT(F = 8.211),scores on D and E domains of GMFM-88(F = 12.802 and 8.505),stride length(F = 12.279),1MWT distance(F = 12.619),and step width(F = 13.582)were better in the(35±5)Hz group than in the(25±5)Hz group and the control group(P＜0.05 and P＜0.01);and the efficacy was better in the(25±5)Hz group than in the control group,the difference was statistically significant(P＜0.05 and P＜0.01).Conclusion WBV can improve trunk control,lower limb gross motor function,and walking function in children with involuntary motor type cerebral palsy.(35±5)Hz is better than(25±5)Hz for the efficacy of WBV.

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.

Objective To explore the mechanism of Tongyangxiao Lotion(TYX)for promoting wound healing following surgery for anal fistula.Methods The active ingredients and drug targets of TYX were explored using TCMSP and BATMAN databases,and the targets associated with wound healing were screened using GeneCards and OMIM databases;the intersecting drug and wound-related targets were analyzed with protein-protein interaction(PPI)analysis and GO and KEGG enrichment analyses.In 25 SD rat models with simulated anal fistula surgery,the effect of wound dressing with TYX at low,medium and high doses(once daily for 14 days)on wound healing were assessed in comparison with potassium permanganate(PP)solution.The granulation tissues collected from the wounds were examined for pathological changes with HE staining and for TNF-α expression using immunohistochemistry.The expressions of 1β,TNF-α,IL-6 mRNA and proteins in the granulation tissue were detected using RT-qPCR,Western blotting or ELISA.Results Network pharmacology analysis yielded 156 common targets between TYX and wound healing,and among them IL-1β,TNF-α,and IL-6 were identified as potential targets of TYX for promoting wound healing.Six core components of TYX were capable of binding to IL-1β,TNF-α,and IL-6 with binding energies all below-6.0 Kcal/mol.In the rat models,the wounds with TYX and PP solution dressing showed significantly reduced inflammatory cell infiltration and increased fibroblasts and collagen deposition.TYX at the 3 doses and PP solution all significantly reduced the expressions of IL-6,IL-1β,TNF-α mRNA and IL-6 protein in the granulation tissues,but TYX at the medium and high doses produced significantly stronger effects than PP solution for lowering TNF-α protein expression and mRNA expressions of TNF-α and IL-6.Conclusion TYX accelerates wound healing by down-regulating the inflammatory factors and reducing inflammation in the wounds.

Objective To explore the mechanism of Tongyangxiao Lotion(TYX)for promoting wound healing following surgery for anal fistula.Methods The active ingredients and drug targets of TYX were explored using TCMSP and BATMAN databases,and the targets associated with wound healing were screened using GeneCards and OMIM databases;the intersecting drug and wound-related targets were analyzed with protein-protein interaction(PPI)analysis and GO and KEGG enrichment analyses.In 25 SD rat models with simulated anal fistula surgery,the effect of wound dressing with TYX at low,medium and high doses(once daily for 14 days)on wound healing were assessed in comparison with potassium permanganate(PP)solution.The granulation tissues collected from the wounds were examined for pathological changes with HE staining and for TNF-α expression using immunohistochemistry.The expressions of 1β,TNF-α,IL-6 mRNA and proteins in the granulation tissue were detected using RT-qPCR,Western blotting or ELISA.Results Network pharmacology analysis yielded 156 common targets between TYX and wound healing,and among them IL-1β,TNF-α,and IL-6 were identified as potential targets of TYX for promoting wound healing.Six core components of TYX were capable of binding to IL-1β,TNF-α,and IL-6 with binding energies all below-6.0 Kcal/mol.In the rat models,the wounds with TYX and PP solution dressing showed significantly reduced inflammatory cell infiltration and increased fibroblasts and collagen deposition.TYX at the 3 doses and PP solution all significantly reduced the expressions of IL-6,IL-1β,TNF-α mRNA and IL-6 protein in the granulation tissues,but TYX at the medium and high doses produced significantly stronger effects than PP solution for lowering TNF-α protein expression and mRNA expressions of TNF-α and IL-6.Conclusion TYX accelerates wound healing by down-regulating the inflammatory factors and reducing inflammation in the wounds.

Objective To explore the effects of long non-coding RNA(lncRNA)small nucleolar molecule RNA host gene 12(SNHG12)targeting inhibition of miR-495-3p/phospholipinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling pathway on the proliferation,migration and invasion of prostate cancer cells.Methods The expressions of SNHG12 and miR-495-3p in prostate cancer tissues and cells(LNCaP,C4-2,DU145)were detected with real-time fluorescence quantitative PCR(qRT-PCR).After DU145 cells were divided into si-NC,si-SNHG12,si-SNHG12+anti-miR-NC and si-SNHG12+anti-miR-495-3p groups,the expressions of SNHG12 and miR-495-3p were detected with qRT-PCR;the targeting relationship between SNHG12 and miR-495-3p was determined with dual luciferase assay;cell proliferation was assessed with MTT assay;cell migration and invasion were evaluated with Transwell assay;the protein expressions of proliferating cell nuclear antigen(PCNA),N-cadherin,and E-cadherin were detected with Western blot.Results The expressions of SNHG12 were significantly increased,while the expression of miR-495-3P was significantly decreased in prostate cancer tissues and cells(LNCaP,C4-2,DU145)(P＜0.05).Knockdown of SNHG12 decreased DU145 cell activity,lowered the protein expressions of PCNA and N-cadherin,reduced the number of migrating and invading cells,but increased the protein expression of E-cadherin(P＜0.05).SNHG12 targeted and negatively regulated miR-495-3p,and down-regulation of miR-495-3p reversed the effects of SNHG12 knockdown on the proliferation,migration and invasion of prostate cancer cells.Compared with the si-NC group,the si-SNHG12 group had significantly decreased expressions of p-PI3K and p-Akt(P＜0.05).Compared with the si-SNHG12+anti-miR-NC group,the si-SNHG12+anti-miR-495-3p group had significantly increased protein expressions of p-PI3K and p-Akt(P＜0.05).Conclusion lncRNA SNHG12 can promote the proliferation,migration and invasion of prostate cancer cells through targeted inhibition of miR-495-3p/PI3K/Akt signaling pathway.

Objective:To compare the characteristics of background mucosa, lesion features, and the efficiency of endoscopic submucosal dissection(ESD)between elderly and non-elderly patients with early gastric cancer(EGC).Methods:This study retrospectively collected data on patients with EGC who underwent ESD treatment at Beijing Hospital from April 2020 to December 2022.The clinical characteristics, background mucosa, lesion features, ESD outcomes, and pathological results of the patients were analyzed to compare the differences between elderly and non-elderly patients.Results:A total of 100 patients with EGC were selected, comprising 57 patients in the elderly group and 43 patients in the non-elderly group, with a total of 111 lesions identified(64 lesions in the elderly group and 47 lesions in the non-elderly group).The proportion of patients with a history of chronic atrophic gastritis was significantly higher in the elderly group(89.5%、51/57)compared to the non-elderly group(74.4%、32/43), with a statistically significant difference( P=0.047).Additionally, the difference in the extent of atrophy between elderly patients with EGC and their non-elderly counterparts was statistically significant( P=0.022).Among these patients, the proportion of those classified as Kimura-Takemoto C0 to C1 in the elderly group(15.6%、10/64)was lower than that in the non-elderly group(40.4%、19/47).In contrast, the proportion of patients classified as C2 to C3 in the elderly group(65.6%、42/64)was higher than that in the non-elderly group(51.1%、24/47), and the proportion of those classified as O1 to O3 in elderly patients(12.5%、8/64)was also higher than in the non-elderly group(4.3%、2/47).Furthermore, the difference in the extent of intestinal metaplasia between elderly and non-elderly patients with early gastric cancer was statistically significant( P=0.007).The overall proportion of total intestinal metaplasia in elderly patients(85.9%、55/64)was significantly higher than that in non-elderly patients(61.7%、29/47).Notably, the proportion of patients exhibiting extensive intestinal metaplasia(intestinal metaplasia present in both the gastric antrum and gastric body)was greater in the elderly group(43.8%、28/64)compared to the non-elderly group(23.4%、11/47).The Kyoto gastric cancer risk endoscopic score for elderly patients with EGC was(2.43±1.28)points, significantly higher than that of the non-elderly group(1.72±1.41)points, with a statistically significant difference observed( t=2.778, P=0.006).No statistically significant differences were observed in the proportions of total resection rates, R0 resections, curative resections, or postoperative complications following ESD when comparing elderly patients with EGC to their non-elderly counterparts. Conclusions:The proportion of extensive atrophy and intestinal metaplasia was higher in the background mucosa of elderly patients with EGC, and correspondingly, the Kyoto endoscopic gastric cancer risk score was elevated.Therefore, endoscopic examinations for elderly patients with chronic atrophic gastritis should be conducted with greater care and comprehensiveness.

Objective To investigate the reasons for the inconsistent results between the vertical auto profile(VAP)method and bio-chemical homogeneous phase(BHP)method in detecting plasma low-density lipoprotein cholesterol(LDL-C),and provide experimen-tal basis for the accurate and quantitative detection of plasma LDL-C levels.Methods A total of 360 plasma samples from diabetes mellitus patients combined with carotid plaque admitted to the Department of Endocrinology of Ningbo Yinzhou Hospital of Traditional Chinese Medicine during January,2022 and January,2023 were collected.The LDL-C levels of these samples were detected by the VAP method and BHP method,respectively.The VAP method uses software to automatically calculate the area under the LDL-C curve after centrifugation of the sample as the LDL-C level(LDL-CVAP)and the BHP method directly detects the LDL-C level(LDL-CBHP)by the special surfactant method.360 samples were divided into the consistent group(group A)and inconsistent group(group B)ac-cording to the relative deviation between the LDL-CBHP and LDL-CVAP methods.Group B was further divided into the LDL-CBHP on the high side group(Group B1)and LDL-CBHP on the low side group(Group B2).Groups B1 and B2 were divided into B1-1,B1-2,B1-3 and B2-1 groups based on the degree of relative deviation.The percentages of samples and levels of lipoprotein a cholesterol[Lp(a)-C],intermediate-density lipoprotein cholesterol(IDL-C),Lp(a)-C and IDL-C[Lp(a)-C+IDL-C],very low-density lipo-protein cholesterol(VLDL-C),total cholesterol(TC)and total triglyceride(TG)in each group were compared.Results The LDL-CBHP levels of 360 samples were significantly higher than that of LDL-CVAP(P＜0.01).The percentage of samples in group B was significantly higher than that in group A,and that of group B1 was significantly higher than that of group B2(P＜0.05).The levels of Lp(a)-C,IDL-C and Lp(a)-C+IDL-C in groups B1-1,B1-2,and B1-3 were significantly higher than those in group A(P＜0.01).The relative deviation between LDL-CBHP and LDL-CVAP in 360 samples was significantly positively correlated with the levels of Lp(a)-C,IDL-C,and Lp(a)-C+IDL-C(P＜0.01).The maximum correlation coefficient was found in Lp(a)-C+IDL-C.Conclusion The results of plasma LDL-C in diabetes mellitus patients combined with carotid plaque detected by the BHP method are significantly different from those detected by the VAP method,which mainly shows that the results of the BHP method are on the high side.The higher the level of plasma Lp(a)-C+IDL-C,the greater the relative deviation between the BHP method and VAP method.The reason for the high results of LDL-C detected by the BHP method may be related to the fact that LDL-CBHP contains irremovable Lp(a)-C and cholesterol carried by IDL-C.The VAP method can be used as an accurate method for detecting real LDL-C without Lp(a)-C and IDL-C.

Objective:To construct the evaluation index system of the core competence of neonatal specialist nurses, so as to provide reference for clinical training of neonatal specialist nurses.Methods:From January 2020, through literature review, theoretical analysis, interview, Delphi method and superiority chart, the evaluation index and weight of core competence of neonatal specialist nurses were determined.Results:Totally 28 experts in China were invited for 3 rounds of consultation. The effective recovery rate of the questionnaires was 93.33%(28/30) in the first round. The effective recovery rate of the questionnaires was 100.00%(28/28) in the second and third rounds. The authority coefficient of the experts was 0.85 in the third round. The Kendall′s coefficients of concordance of the first-level indexes, second-level indexes and third-level indexes were 0.150, 0.221 and 0.161, respectively. The final evaluation index system of the core competence of neonatal specialist nurses included 5 first-level indicators, 17 second-level indicators and 58 third-level indicators.Conclusions:The evaluation index system of the core competence of neonatal specialist nurses constructed in this study has certain scientific, reliable and clinical application value, which is conducive to the training of newborn specialized nurses in China.