Identification of candidate genes and residues for improving nitrogen use efficiency in the N-sensitive medicinal plant Panax notoginseng.

BACKGROUND: Nitrogen (N) metabolism-related key genes and conserved amino acid sites in key enzymes play a crucial role in improving N use efficiency (NUE) under N stress. However, it is not clearly known about the molecular mechanism of N deficiency-induced improvement of NUE in the N-sensitive rhizomatous medicinal plant Panax notoginseng (Burk.) F. H. Chen. To explore the potential regulatory mechanism, the transcriptome and proteome were analyzed and the three-dimensional (3D) information and molecular docking models of key genes were compared in the roots of P. notoginseng grown under N regimes. RESULTS: Total N uptake and the proportion of N distribution to roots were significantly reduced, but the NUE, N use efficiency in biomass production (NUEb), the recovery of N fertilizer (RNF) and the proportion of N distribution to shoot were increased in the N0-treated (without N addition) plants. The expression of N uptake- and transport-related genes NPF1.2, NRT2.4, NPF8.1, NPF4.6, AVP, proteins AMT and NRT2 were obviously up-regulated in the N0-grown plants. Meanwhile, the expression of CIPK23, PLC2, NLP6, TCP20, and BT1 related to the nitrate signal-sensing and transduction were up-regulated under the N0 condition. Glutamine synthetase (GS) activity was decreased in the N-deficient plants, while the activity of glutamate dehydrogenase (GDH) increased. The expression of genes GS1-1 and GDH1, and proteins GDH1 and GDH2 were up-regulated in the N0-grown plants, there was a significantly positive correlation between the expression of protein GDH1 and of gene GDH1. Glu192, Glu199 and Glu400 in PnGS1 and PnGDH1were the key amino acid residues that affect the NUE and lead to the differences in GDH enzyme activity. The 3D structure, docking model, and residues of Solanum tuberosum and P. notoginseng was similar. CONCLUSIONS: N deficiency might promote the expression of key genes for N uptake (genes NPF8.1, NPF4.6, AMT, AVP and NRT2), transport (NPF1.2 and NRT2.4), assimilation (proteins GS1 and GDH1), signaling and transduction (genes CIPK23, PLC2, NLP6, TCP20, and BT1) to enhance NUE in the rhizomatous species. N deficiency might induce Glu192, Glu199 and Glu400 to improve the biological activity of GS1 and GDH, this has been hypothesized to be the main reason for the enhanced ability of N assimilation in N-deficient rhizomatous species. The key genes and residues involved in improving NUE provide excellent candidates for the breeding of medicinal plants.

Prevalence, clinical characteristics and treatment outcomes of oxyntic gland neoplasm: a single-center retrospective study.

BACKGROUND: Oxyntic gland neoplasm (OGN) is a rare subtype of gastric cancer. The aim of this study is to evaluate the prevalence, clinicopathological features, effectiveness and safety of endoscopic treatment, as well as the prognosis of OGN. METHODS: We retrospectively analyzed the data of patients pathologically diagnosed with OGN at our hospital from November 1, 2019 to May 1, 2023. RESULTS: A total of 36 patients with 45 lesions were identified, resulting in a disease frequency of 0.047% (36/76,832). The mean age was 55.0 ± 7.5 years, with a male-to-female ratio of about 1:1.12. Most lesions were ≤10 mm in size (84.4%), located in the upper third of the stomach (73.3%), exhibited slight elevation (75.5%), appeared whitish (55%), had dilated blood vessels on the surface (75.5%). 16 and 21 lesions were treated by precutting endoscopic mucosal resection (EMR-P) and endoscopic submucosal dissection (ESD), respectively. No significant differences were found between EMR-P and ESD in terms of en bloc resection rate (100% vs 100%, p = 1.000), complete resection rate (100% vs 90.5%, p = 0.495), and curative resection rate (93.8% vs 90.5%, p = 1.000). No complications such as bleeding and perforation were observed. No recurrence or metastasis was observed during the follow-up period. CONCLUSIONS: OGN is a rare tumor with unique clinical, endoscopic, and pathological characteristics. EMR-P and ESD are deemed safe and effective for treating OGNs. The relatively faster and easier EMR-P seems at least non-inferior to ESD, especially for removal of smaller OGNs. The overall prognosis is favorable.

Efficacy and Safety of Endoscopic Resection for Gastric Gastrointestinal Stromal Tumors Originating from the Muscularis Propria.

BACKGROUND: The role of endoscopic resection (ER) in gastric gastrointestinal stromal tumors (GISTs) has not been fully elucidated. AIMS: The purpose of this work was to evaluate the clinical effectiveness and safety of ER in patients with GISTs originating from the muscularis propria (MP). METHODS: A total of 233 consecutive patients with gastric GISTs originating from the MP layer, who underwent ER between February 2012 and May 2023, were included in this study. Clinical characteristics, tumor features, and outcomes were recorded and compared between patients who underwent en bloc resection and piecemeal resection. RESULTS: Among the 233 patients, the median size of GISTs was 12 mm (range 5-60 mm). Risk assessment categorized 190 patients as very low risk, 26 as low risk, 10 as moderate risk, and 7 as high risk. The procedures performed included endoscopic submucosal excavation (127 cases), endoscopic full-thickness resection (103 cases), and submucosal tunneling endoscopic resection (3 cases). The complete and R0 resection rate was 93.1%. Complications occurred in 4.7% of cases (perioperative perforations 1.7%, perioperative bleeding 1.3%, both 0.9%), resulting in conversion to surgery in 1.3% of cases. Risk factors associated with piecemeal resection were tumor size [odds ratio (OR) 0.402, 95% confidence interval (CI) 0.207-0.783; P = 0.007] and shape (OR 0.045, 95% CI 0.009-0.235; P < 0.001). CONCLUSIONS: ER is proven to be an effective and reasonably safe approach for gastric GISTs originating from the MP. Notably, larger tumor size and irregular shape are identified as risk factors for piecemeal resection during ER procedures.

Clinical outcomes after endoscopic resection and the risk of lymph node metastasis in rectal neuroendocrine tumors: a single-center retrospective study.

BACKGROUND AND AIM: The incidence of rectal neuroendocrine tumors (R-NETs) has increased in recent years. However, the predictors of lymph node (LN) metastasis and clinical outcomes, particularly following endoscopic treatment, remain unclear. Our study aims to elucidate the potential risk factors for LN metastasis and the clinical outcomes of patients undergoing endoscopic resection in R-NETs. METHODS: A total of 128 patients with R-NETs were retrospectively identified from a single center between June 2012 and December 2021. Risk factors for LN metastasis in R-NETs were analyzed using multivariate analysis. Additionally, the clinical outcomes of endoscopic resections in patients with R-NETs were assessed. RESULTS: In our study, 128 patients with R-NETs were retrospectively analyzed. The risk factors for LN metastasis determined by multivariate analysis were tumor size and patient age at diagnosis. Among the 111 patients treated with endoscopic resection and with tumor margin records available, 92 underwent endoscopic submucosal dissection (ESD) and 19 underwent conventional endoscopic mucosal resection (EMR). There was no significant difference between the two groups regarding the positive rates of basal tumor margin and lateral tumor margin. Furthermore, 64 patients who underwent endoscopic resection for R-NETs were successfully followed up (range, 1.64-76.71 months), during which only one patient developed local recurrence. CONCLUSION: Tumor size and age at diagnosis were predictors for LN metastasis of R-NETs. Both ESD and EMR are alternative techniques with a favorable prognosis for R-NETs, even in cases with positive resection margins. However, due to the relatively small number of patients undergoing EMR and missing data in follow-up protocols, definitive conclusions require further large-scale studies.

Xanchryones I-N, Six Unusual Phloroglucinol-Amino Acid Hybrids from the Leaves of Xanthostemon chrysanthus.

Six new phloroglucinol derivatives, xanchryones I-N (1-6), were isolated from the leaves of Xanthostemon chrysanthus. Compounds 1-6 are unusual phloroglucinol-amino acid hybrids constructed through C2 -N and O-C1 ' bonds forming a peculiar oxazole ring. The structures and absolute configurations of compounds 1-6 were determined by MS, NMR, and single-crystal X-ray diffraction. Moreover, the anti-inflammatory and antibacterial activities of these compounds were evaluated.

An unusual cause of diarrhea and colorectal ulcers.

Good syndrome (GS) is a rare entity that associates the existence of thymoma with immunodeficiency. Gastrointestinal symptoms is one of the most common clinical manifestations. However, colorectal ulcers in GS were extremely rare. Herein, we present a case of GS presenting with diarrhea and colorectal ulcers to inform readers.

Primary rectal mucosa-associated lymphoid tissue lymphoma masquerading as proctitis.

A 29-year-old male presented with recurrent mucous bloody stools for more than a year. Colonoscopy revealed ill-defined, mildly congested and edematous mucosa with scattered erosion spots in the lower rectum, highly suspicious for proctitis. Histopathology showed diffuse infiltration of small to medium-sized lymphoid cells in the lamina propria. Immunohistochemistry indicated these cells were positive for CD20, CD79a, CD19, kappa and lambda light chains (partial), and negative for CD3, CD5, CD10, cyclin D and BCL-6. These results were consistent with mucosa-associated lymphoid tissue (MALT) lymphoma. Further investigations consisting of upper endoscopy, bone marrow biopsy, and whole-body PET/CT scan did not detect any extrarectal lesions. Based on these findings, the diagnosis of stage I primary rectal MALT lymphoma was made. The patient underwent 15 fractions of radiotherapy with a total dose of 30 Gy. His symptoms were alleviated following the treatment. A follow-up colonoscopy performed 3 months later showed complete resolution of the lesion.

High nitrogen inhibits photosynthetic performance in a shade-tolerant and N-sensitive species Panax notoginseng.

Nitrogen (N) is a primary factor limiting leaf photosynthesis. However, the mechanism of high-N-driven inhibition on photosynthetic efficiency and photoprotection is still unclear in the shade-tolerant and N-sensitive species such as Panax notoginseng. Leaf chlorophyll (Chl) content, Ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco) activity and content, N allocation in the photosynthetic apparatus, photosynthetic performance and Chl fluorescence were comparatively analyzed in a shade-tolerant and N-sensitive species P. notoginseng grown under the levels of moderate nitrogen (MN) and high nitrogen (HN). The results showed that Rubisco content, Chl content and specific leaf nitrogen (SLN) were greater in the HN individuals. Rubisco activity, net photosynthetic rate (Anet), photosynthetic N use efficiency (PNUE), maximum carboxylation rate (Vcmax) and maximum electron transport rate (Jmax) were lower when plants were exposed to HN as compared with ones to MN. A large proportion of leaf N was allocated to the carboxylation component under the levels of MN. More N was only served as a form of N storage and not contributed to photosynthesis in HN individuals. Compared with the MN plants, the maximum quantum yield of photosystem II (Fv/Fm), non-photochemical quenching of PSII (NPQ), effective quantum yield and electron transport rate were obviously reduced in the HN plants. Cycle electron flow (CEF) was considerably enhanced in the MN individuals. There was not a significant difference in maximum photo-oxidation P700+ (Pm) between the HN and MN individuals. Most importantly, the HN individuals showed higher K phase in the fast chlorophyll fluorescence induction kinetic curve (OJIP kinetic curve) than the MN ones. The results obtained suggest that photosynthetic capacity might be primarily inhibited by the inactivated Rubisco in the HN individuals, and HN-induced depression of photoprotection might be caused by the photodamage to the donor side of PSII oxygen-evolving complex.

[Correlation of B-type Natriuretic Peptide Level with Hemodynamic Parameters and Inflammatory Cytokines in Patients with Gram-negative Sepsis].

Objective To study the correlation of B-type natriuretic peptide(BNP)level with hemodynamic parameters and inflammatory cytokines in patients with Gram-negative sepsis,and further determine the main factors for the significant increase of BNP level. Methods The prospective study method was applied,and septic patients infected with Gram-negative bacteria from May 2017 to October 2019 were enrolled.The patients were divided into the BNP<2400 ng/L group and the BNP≥2400 ng/L group by taking the average value of BNP as the dividing point.The independent predictors of BNP≥2400 ng/L were analyzed by Logistic regression.Pearson correlation analysis was used to analyze the correlation between BNP and various indicators. Results A total of 106 patients with Gram-negative sepsis were included,among which 60 cases present with higher serum BNP levels than the average of(2398.45 ± 421.45)ng/L.Thus BNP≥2400 ng/L was considered as a significantly increased BNP level.Multiple logistic regression analysis showed that cardiac index(CI)[odds ratio (OR)=0.428,95% confidence interval (95%CI)=0.743-0.965,P=0.011],left ventricular ejection fraction(LVEF) (OR=0.394,95%CI=0.182-0.549,P=0.013),lactic acid (OR=1.983,95%CI=1.264-3.420,P=0.023),endotoxin (OR=6.146,95%CI=4.091-8.226,P=0.001),procalcitonin(PCT) (OR=6.513,95%CI=4.365-8.210,P=0.005) and cardiac troponin I(cTnI) (OR=1.144,95%CI=1.001-2.150,P=0.047) were independent predictors of BNP≥2400 ng/L in patients with Gram-negative sepsis.Pearson correlation analysis showed that BNP was negatively correlated with CI(R=-0.514,P<0.001)and LVEF (R=-0.552,P<0.001),whereas positively correlated with lactic acid (R=0.265,P=0.032),cTnI (R=0.204, P=0.036),PCT(R=0.801,P<0.001),and endotoxin(R=0.765,P<0.001). Conclusions In septic patients with Gram-negative bacterial infection,LVEF,CI,lactic acid,cTnI,endotoxin and PCT are all independent risk factors for the significant increase of BNP,and endotoxin and PCT were more significantly correlated with BNP increase.Endotoxin and inflammatory reaction may be the more important stimulators of BNP increase in septic patients with Gram-negative bacterial infection.

Photosynthetic performance and photosynthesis-related gene expression coordinated in a shade-tolerant species Panax notoginseng under nitrogen regimes.

BACKGROUND: Nitrogen (N) is an essential component of photosynthetic apparatus. However, the mechanism that photosynthetic capacity is suppressed by N is not completely understood. Photosynthetic capacity and photosynthesis-related genes were comparatively analyzed in a shade-tolerant species Panax notoginseng grown under the levels of low N (LN), moderate N (MN) and high N (HN). RESULTS: Photosynthetic assimilation was significantly suppressed in the LN- and HN-grown plants. Compared with the MN-grown plants, the HN-grown plants showed thicker anatomic structure and larger chloroplast accompanied with decreased ratio of mesophyll conductance (gm) to Rubisco content (gm/Rubisco) and lower Rubisco activity. Meanwhile, LN-grown plants displayed smaller chloroplast and accordingly lower internal conductance (gi). LN- and HN-grown individuals allocated less N to light-harvesting system (NL) and carboxylation system (NC), respectively. N surplus negatively affected the expression of genes in Car biosynthesis (GGPS, DXR, PSY, IPI and DXS). The LN individuals outperformed others with respect to non-photochemical quenching. The expression of genes (FBA, PGK, RAF2, GAPC, CAB, PsbA and PsbH) encoding enzymes of Calvin cycle and structural protein of light reaction were obviously repressed in the LN individuals, accompanying with a reduction in Rubisco content and activity. Correspondingly, the expression of genes encoding RAF2, RPI4, CAB and PetE were repressed in the HN-grown plants. CONCLUSIONS: LN-induced depression of photosynthetic capacity might be caused by the deceleration on Calvin cycle and light reaction of photosynthesis, and HN-induced depression of ones might derive from an increase in the form of inactivated Rubisco.

[Effect of paeonol on blood pressure and blood flow in artery of spontaneously hypertensive rats and its mechanisms related on vasomotion].

Previous studies have shown that paeonol can antagonize acute myocardial ischemia and infarction in rat. This study further researched the effects of paeonol on blood pressure and blood flow in the artery of spontaneously hypertensive rats and its mechanisms related on vasomotion. Firstly, thirty spontaneously hypertensive rats were randomly divided into spontaneously hypertensive control group and paeonol-treating groups of high dose and low dose, and also, the other ten Wistar rats as healthy control group. Before and after the intraduodenal administration of the drug, arterial blood pressure was measured by carotid artery and blood flow through the renal artery and carotid artery in vivo were measured by animal flowmeter. The same volume of solvent was given to the spontaneously hypertensive control group and the healthy control group, and the other operations were same. In order to further study the effect of paeonol on vasomotor function, the superior mesenteric artery, renal artery and coronary artery of the spontaneously hypertensive rat were removed and separated, precontracted by a certain concentration of potassium chloride (KCl) and 5-serotonin (5-HT) respectively, and dilatory responses were assessed by cumulative addition of paeonol. Results showed that after duodenal one-time delivery of paeonol, the blood pressure significantly lowered, the renal arterial blood flow and the carotid arterial blood flow significantly increased in spontaneously hypertensive rat. And also, paeonol relaxed the mesenteric artery, renal artery and the coronary artery of spontaneously hypertensive rat in a concentration-dependent manner. These results indicated that the effect of paeonol on decreasing arterial blood pressure and increasing the arterial blood flow was related to its vasodilative effect.

Diabetic Retinopathy and Brain Structure, Cognition Function, and Dementia: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Accumulating evidence has demonstrated that hyperglycemia is a possible risk factor for mild cognitive impairment or Alzheimer's disease. Diabetic retinopathy (DR) has been identified as a risk factor for dementia in patients with diabetes. OBJECTIVE: This study aimed to investigate the causal relationships between DR and brain structure, cognitive function, and dementia. METHODS: We performed bidirectional two-sample Mendelian randomization for DR, brain structure, cognitive function, and dementia using the inverse-variance weighted method. RESULTS: Inverse-variance weighted analysis showed the association of DR with vascular dementia (OR = 1.68, 95% CI: 1.01-2.82), and dementia was significantly associated with the increased risk of non-proliferative DR (NPDR) (OR = 1.76, 95% CI: 1.04-2.98). Furthermore, better cognitive performance was significantly associated with a reduced risk of NPDR (OR = 0.85, 95% CI: 0.74-0.98). No association was observed between DR and brain structure. CONCLUSIONS: These findings suggest that the association of DR with vascular dementia. The reciprocal effect of cognitive performance and dementia on NPDR risk highlights the potential benefits of dementia prevention for reducing the burden of DR.

Gastric schwannoma: A retrospective analysis of clinical characteristics, treatments, and outcomes.

BACKGROUND: This study aimed to investigate the clinical characteristics, treatment options, and prognosis of patients with gastric schwannoma (GS). METHODS: Patients who were pathologically diagnosed with GS between April 2011 and October 2022 were enrolled. The data of clinical characteristics, pathological features, treatment options, and clinical outcomes were collected and compared between GS patients who underwent endoscopic resection (ER) and surgical resection (SR). RESULTS: Of the 32 cases, 23 underwent SR and nine underwent ER. The median tumor size was significantly smaller in ER group than in SR group (12.0 vs. 40.0 mm, P < 0.001), while patients in SR group were older than those in ER group (54.5 ± 10.6 vs. 45.3 ± 10.9 years, P = 0.036). Moreover, tumors in ER group were more likely to exhibit an intraluminal pattern (100% vs. 26.1%, P < 0.001). Patients in ER group had significantly lower hospitalization cost (25859.2 ± 8623.9 vs. 44953.0 ± 13083.8 RMB, P = 0.011) than those in SR group. No differences were found between the two groups in terms of R0 resection rate, operative time, estimated blood loss, adverse events, and recurrence rate. All patients were followed up for 4-96 months (mean: 35 months; median: 23 months), during which no evidence of recurrence or metastasis was observed. CONCLUSIONS: Both ER and SR are safe and effective treatment modalities for the management of GS, with ER being associated with lower medical costs compared to SR. The majority of GS are benign and do not recur, with little possibility of malignant transformation.

Integrated metabolome and transcriptome analysis reveals the regulatory mechanism of low nitrogen-driven biosynthesis of saponins and flavonoids in Panax notoginseng.

BACKGROUND: Nitrogen (N) is an important macronutrient involved in the biosynthesis of primary and secondary metabolites in plants. However, the metabolic regulatory mechanism of low-N-induced triterpenoid saponin and flavonoid accumulation in rhizomatous medicinal Panax notoginseng (Burk.) F. H. Chen remains unclear. METHODS: To explore the potential regulatory mechanism and metabolic basis controlling the response of P. notoginseng to N deficiency, the transcriptome and metabolome were analysed in the roots. RESULTS: The N content was significantly reduced in roots of N0-treated P. notoginseng (0 kg·N·667 m-2). The C/N ratio was enhanced in the N-deficient P. notoginseng. N deficiency promotes the accumulation of amino acids (L-proline, L-leucine, L-isoleucine, L-norleucine, L-arginine, and L-citrulline) and sugar (arabinose, xylose, glucose, fructose, and mannose), thus providing precursor metabolites for the biosynthesis of flavonoids and triterpenoid saponins. Downregulation of key structural genes (PAL, PAL3, ACC1, CHS2, PPO, CHI3, F3H, DFR, and FGT), in particular with the key genes of F3H, involved in the flavonoid biosynthesis pathway possibly induced the decrease in flavonoid content with increased N supply. Notoginsenoside R1, ginsenoside Re, Rg1, Rd, F1, R1 + Rg1 + Rb1 and total triterpenoid saponins were enhanced in the N0 groups than in the N15 (15 kg·N·667 m-2) plants. Higher phosphoenolpyruvate (an intermediate of glycolyticwith pathway metabolism) and serine (an intermediate of photorespiration) levels induced by N deficiency possibly promote saponin biosynthesis through mevalonic acid (MVA) and methylerythritol (MEP) pathways. Genes (MVD2, HMGS, HMGR1, HMGR2, DXR, and HMGR1) encoding the primary enzymes HMGS, HMGR, DXR, and MVD in the MVA and MEP pathways were significantly upregulated in the N0-treated P. notoginseng. The saponin biosynthesis genes DDS, DDS, CYP716A52, CYP716A47, UGT74AE2, and FPS were upregulated in the N-deficient plants. Upregulation of genes involved in saponin biosynthesis promotes the accumulation of triterpenoid saponins in the N0-grown P. notoginseng. CONCLUSIONS: N deficiency enhances primary metabolisms, such as amino acids and sugar accumulation, laying the foundation for the synthesis of flavonoids and triterpenoid saponins in P. notoginseng. F3H, DDS, FPS, HMGR, HMGS and UGT74AE2 can be considered as candidates for functional characterisation of the N-regulated accumulation of triterpenoid saponins and flavonoids in future.

Relationship Between Mindfulness and Affiliate Stigma in Parents of Children with Autism Spectrum Disorder in China: The Mediating Role of Coping Styles.

PURPOSE: This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China. METHOD: Between February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. RESULTS: (1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = -0.38, -0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = -0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. CONCLUSIONS: Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.

A fully biodegradable spherical nucleic acid nanoplatform for self-codelivery of doxorubicin and miR122 for innate and adaptive immunity activation.

Facile construction of a fully biodegradable spherical nucleic acid (SNA) nanoplatform is highly desirable for clinical translations but remains rarely explored. We developed herein the first polycarbonate-based biodegradable SNA nanoplatform for self-codelivery of a chemotherapeutic drug, doxorubicin (DOX), and a human liver-specific miR122 for synergistic chemo-gene therapy of hepatocellular carcinoma (HCC). Ring-opening polymerization (ROP) of a carbonate monomer leads to a well-defined polycarbonate backbone for subsequent DOX conjugation to the pendant side chains via acidic pH-cleavage Schiff base links and miR122 incorporation to the chain termini via click coupling, affording an amphiphilic polycarbonate-DOX-miR122 conjugate, PBis-Mpa30-DOX-miR122 that can self-assemble into stabilized SNA. Besides the desired biodegradability, another notable merit of this nanoplatform is the use of miR122 not only for gene therapy but also for enhanced innate immune response. Together with the ICD-triggering effect of DOX, PBis-Mpa30-DOX-miR122 SNA-mediated DOX and miR122 codelivery leads to synergistic immunogenicity enhancement, resulting in tumor growth inhibition value (TGI) of 98.1 % significantly higher than those of the groups treated with only drug or gene in a Hepa1-6-tumor-bearing mice model. Overall, this study develops a useful strategy toward biodegradable SNA construction, and presents a drug and gene-based self-codelivery SNA with synergistic immunogenicity enhancement for efficient HCC therapy. STATEMENT OF SIGNIFICANCE: Facile construction of a fully biodegradable SNA nanoplatform is useful for in vivo applications but remains relatively unexplored likely due to the synthetic challenge. We report herein construction of a polycarbonate-based SNA nanoplatform for co-delivering a chemotherapeutic drug, DOX, and a human liver-specific miR-122 for synergistic HCC treatment. In addition to the desired biodegradability properties, this SNA nanoplatform integrates DOX-triggered ICD and miR-122-enhanced innate immunity for simultaneously activating adaptive and innate immunities, which leads to potent antitumor efficiency with a TGI value of 98.1 % in a Hepa1-6-tumor-bearing mice model.

[Comparative on acute myocardial infarction models in beagle dogs and mongrel dogs].

OBJECTIVE: To compare the acute myocardial infarction models in Beagle dogs and mongrel dogs, and study whether the Beagle dog model is sensitive to drug intervention. METHOD: The acute myocardial infarction model of dog was set up through ligation of anterior descending branch of coronary artery in dogs, in order to observe morphological changes of the heart and determine artery length and heart coefficient of exposed anterior descending branch of coronary artery. The epicardium electrocardiogram (sigmaST, N-ST) was used to measure the degree of myocardial ischemia. The quantitative histological assay (nitroblue tetrazolium, N-BT stain) was adopted to determine the area of myocardial infarction. RESULT: There was no significant difference between Beagle dogs and mongrel dogs in terms of sigmaST, N-ST and ischemia area. The diltiazem group of Beagle dogs showed obvious reduction in the ischemia area (P < 0.05 and P < 0.01), with notable decline in sigmaST and N-ST, however, it had no statistical difference compared with the Beagle dog model group. Beagle dogs had clear coronary branches, longer exposed arteries and less difference in organ coefficient, which were suitable for the preparation of the myocardial infarction model, whereas mongrel dogs had irregular coronary branches and exposed arteries, with greater individual difference. CONCLUSION: Beagle dogs are superior to mongrel dogs in the preparation of the acute myocardial infarction model, which is sensitive to for drug intervention.