Oropharyngeal administration of colostrum targeting gut microbiota and metabolites in very preterm infants: protocol for a multicenter randomized controlled trial.

BACKGROUND: Oropharyngeal administration of colostrum (OAC) has an immune-stimulating effect on oropharyngeal-associated lymphoid tissue, and can promote the maturation of the gastrointestinal tract. However, how OAC promotes intestinal maturation in preterm infants by altering gut microbiota remains unclear. We aim to assess changes in gut microbiota and metabolites after OAC in very preterm infants. METHODS: A multicenter, double-blind, randomized controlled trial will be conducted in three large neonatal intensive care units in Shenzhen, China, with preterm infants with gestational age less than 32 weeks at birth and birth weight less than 1500 g. It is estimated that 320 preterm infants will be enrolled in this study within one year. The intervention group will receive oropharyngeal administration of 0.2 ml colostrum every 3 h, starting between the first 48 to 72 h and continued for 5 consecutive days. Following a similar administration scheme, the control group will receive oropharyngeal administration of sterile water. Stool samples will be collected at the first defecation, as well as on the 7th, 14th, 21st and 28th days after birth for analysis of effect of OAC on gut microbiota and metabolites through 16sRNA gene sequencing and liquid chromatography-mass spectrometry. DISCUSSION: This proposal advocates for the promotion of OAC as a safe and relatively beneficial protocol in neonatal intensive care units, which may contribute to the establishment of a dominant intestinal flora. Findings of this study may help improve the health outcomes of preterm infants by establishment of targeted gut microbiota in future studies. TRIAL REGISTRATION: NCT05481866 (registered July 30, 2022 on ClinicalTrials.gov).

[Therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in treatment of gastric ulcer based on network pharmacology and animal experiment].

The present study aimed to explore the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in the treatment of gastric ulcer by network pharmacology and animal experiments. UPLC-Q-TOF-MS/MS was employed to chara-cterize the chemical components of non-polysaccharide fraction of Bletillae Rhizoma, and the common targets of Bletillae Rhizoma and gastric ulcer were screened out by network pharmacology. The "drug-component-target-disease" network was constructed. Protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed based on Matescape database to predict the therapeutic effect and mechanism of Bletillae Rhizoma. Finally, the gastric ulcer model was induced in mice by alcohol to verify the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma on gastric ulcer. Forty-seven chemical components were identified from non-polysaccharide fraction of Bletillae Rhizoma, among which gymnoside Ⅰ, gymnoside Ⅱ, militarine, bletilloside A, and shancigusin I might be the main active components of non-polysaccharide fraction of Bletillae Rhizoma against gastric ulcer. PPI network analysis revealed core targets such as albumin(ALB), serine/threonine kinase 1(AKT1), tumor necrosis factor(TNF), and epidermal growth factor receptor(EGFR). The KEGG enrichment analysis showed that non-polysaccharide fraction of Bletillae Rhizoma mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, and Ras signaling pathway. The results of animal experiments showed that non-polysaccharide fraction of Bletillae Rhizoma could significantly improve alcohol-induced ulceration in mice to increase ulcer inhibition rate, decrease the levels of TNF-α, interleukin(IL)-1ß, IL-6, vasoactive intestinal peptide(VIP), and thromboxane B2(TXB2), elevated the le-vels of IL-10, prostaglandin E2(PGE2), epidermal growth factor(EGF), and vascular endothelial growth factor(VEGF), down-re-gulate the protein levels of PI3K and AKT, and up-regulate the protein levels of p-PI3K and p-AKT. This study indicates that Bletillae Rhizoma may play a role in the treatment of gastric ulcer through multiple components, targets, and pathways and verifies partial prediction results of network pharmacology. The findings of this study provide a scientific and experimental basis for clinical application.

Higher ETCOc predicts longer phototherapy treatment in neonatal hyperbilirubinemia.

Objective: This study aimed to evaluate the predictive performance of end-tidal carbon monoxide corrected to ambient carbon monoxide (ETCOc) values phototherapy in neonates with significant hyperbilirubinemia. Methods: A prospective study was conducted on neonates with significant hyperbilirubinemia who received phototherapy between 3 and 7 days of life. The breath ETCOc and serum total bilirubin of the recruited infants were measured on admission. Results: The mean ETCOc at admission in 103 neonates with significant hyperbilirubinemia was 1.70 ppm. The neonates were categorized into two groups: phototherapy duration ≤72 h (n = 87) and >72 h (n = 16) groups. Infants who received phototherapy for >72 h had significantly higher ETCOc (2.45 vs. 1.60, P = 0.001). The cutoff value of ETCOc on admission for predicting longer phototherapy duration was 2.4 ppm, with a sensitivity of 62.5% and specificity of 88.5%, yielding a 50% positive predictive value and a 92.7% negative predictive value. Conclusion: ETCOc on admission can help predict the duration of phototherapy in neonates with hyperbilirubinemia, facilitate clinicians to judge disease severity, and make clinical communication easier and more efficient.

Kinetically and thermodynamically controlled one-pot growth of gold nanoshells with NIR-II absorption for multimodal imaging-guided photothermal therapy.

Since the successful clinical trial of AuroShell for photothermal therapy, there is currently intense interest in developing gold-based core-shell structures with near-infrared (NIR) absorption ranging from NIR-I (650-900 nm) to NIR-II (900-1700 nm). Here, we propose a seed-mediated successive growth approach to produce gold nanoshells on the surface of the nanoscale metal-organic framework (NMOF) of UiO-66-NH2 (UiO = the University of Oslo) in one pot. The key to this strategy is to modulate the proportion of the formaldehyde (reductant) and its regulator / oxidative product of formic acid to harness the particle nucleation and growth rate within the same system. The gold nanoshells propagate through a well-oriented and controllable diffusion growth pattern (points → facets → octahedron), which has not been identified. Most strikingly, the gold nanoshells prepared hereby exhibit an exceedingly broad and strong absorption in NIR-II with a peak beyond 1300 nm and outstanding photothermal conversion efficiency of 74.0%. Owing to such superior performance, these gold nanoshells show promising outcomes in photoacoustic (PA), computed tomography (CT), and photothermal imaging-guided photothermal therapy (PTT) for breast cancer, as demonstrated both in vitro and in vivo.

The clinical efficacy of Zuqing Xu "Wuduling" powder for snake injury on the swelling of the affected limb bitten by Agkistrodon halys.

To determine the clinical efficacy of Zuqing Xu 'Wuduling' powder for snake injury on the swelling of the affected limb bitten by Agkistrodon halys. Sixty-five patients with Agkistrodon halys bite were assigned to a treatment group (n = 35) or control group (n = 30). The treatment group was additionally given 'Wuduling' powder dressing locally based on the therapy to the control group with conventional Western medicine. Clinical efficacy and improvement of traditional Chinese medicine symptoms and signs in the two groups were evaluated. The treatment group showed a notably higher cure rate than the control group. After 3 days of therapy, the swelling and pain of the affected limb in the treatment group were greatly alleviated. Additionally, after 7 days of therapy, the swelling and pain of the affected limb in the treatment group were more greatly alleviated, and those in the control group were also alleviated. The comparison of the two groups during the same period showed more obvious alleviation of swelling and pain in the treatment group than that in the other. Moreover, the treatment group experienced notably shorter disappearing time of swelling and pain than the control group. After treatment, the levels of CRP, TBIL, Cr, ALT, AST, BUN, CK, LDH and CK-MB in both groups declined notably, with notably lower levels of them in the treatment group than those in the other. Zuqing Xu 'Wuduling' powder for snake injury can substantially alleviate the swelling and local pain of affected limbs bitten by Agkistrodon halys.

Identification of the anti-inflammatory quality markers of Chrysanthemi Flos (Juhua) using spectrum-effect relationships combined with bioactivity re-evaluation.

Chrysanthemi Flos (Juhua), an edible herbal medicine that possesses efficacies of dispersing wind, clearing heat and detoxifying. Studies have demonstrated that the health benefits of Chrysanthemi Flos are largely attributable to its anti-inflammatory effects. However, the correlation between the compounds monitored by the current quality control methods and the anti-inflammatory effects of Chrysanthemi Flos is unclear. In order to better control the quality of Chrysanthemi Flos, the identification of anti-inflammatory quality markers (Q-markers) of Chrysanthemi Flos was performed. The chemical components of Chrysanthemi Flos were profiled by HPLC fingerprints combined with chemometrics methods. Simultaneously, the anti-inflammatory activities of 10 batches of water extracts of Chrysanthemi Flos were evaluated in lipopolysaccharide-activated RAW 264.7 macrophages cells. Gray correlation analysis was performed to assess the relationship between the anti-inflammatory activity and chemical properties. The results showed that 13 common peaks were closely correlated with the anti-inflammatory effect, and further bioactivity re-evaluation confirmed that 10 known compounds exerted a strong anti-inflammatory effect. The quantitative analysis of the 10 Q-markers showed that the 25 batches of samples could be discriminated into different zones according to their producing areas. Conclusively, the present work identified 10 anti-inflammatory Q-markers of Chrysanthemi Flos using spectrum-effect relationships combined with bioactivity re-evaluation.

Allium vegetable intake associated with the risk of incident gastric cancer: a continuous follow-up study of a randomized intervention trial.

BACKGROUND: Allium vegetable components have antibacterial, antioxidative, and immune modulation properties, thus potentially exhibiting antitumor effects. Despite evidence from case-control studies, prospective studies linking allium vegetables with gastric cancer (GC) have been sparse. OBJECTIVE: In a prospective study, we examined whether allium vegetable intake would change the risk of GC occurrence and whether the associations would be modified by vitamin supplementation, garlic supplementation, and Helicobacter pylori (H. pylori) treatment. METHODS: The study was conducted on the basis of the Shandong Intervention Trial, a randomized, placebo-controlled, factorial-designed trial (1995-2003) in a well-recognized high-risk area for GC in China. Participants were continuously followed up to December 2017 for 22.3 y (1995-2017). A total of 3229 subjects were included, with information on the intake of allium vegetables (garlic vegetables and scallions), collected by structured questionnaires in 1994. The associations of total and individual allium vegetable intake with the risk of GC were examined, respectively. RESULTS: During the follow-up, 144 incident cases of GC were identified. Garlic vegetable intake was associated with a decreased risk of incident GC (P-trend = 0.02; OR: 0.83; 95% CI: 0.70, 0.98, per 1 kg/y increment), whereas scallion intake showed no association (P-trend = 0.80). An inverse association of the risk of GC with total allium vegetable and garlic vegetable intake was particularly stronger among those receiving the placebo for vitamin supplementation or garlic supplementation, indicating potential effect modifications by nutritional supplementation on allium vegetable intake and the risk of developing GC. Similar findings were found for analyses of the combined prevalence of dysplasia or GC. CONCLUSIONS: We found a significant reduction in the risk of developing GC with increasing dietary intake of allium vegetables, particularly garlic vegetables. The findings add to the literature on the potential inverse association of garlic vegetable intake with the risk of GC, therefore holding public health implications for dietary recommendations. This trial was registered at clinicaltrials.gov as NCT00339768.

Feasibility and basic acoustic characteristics of intelligent long-term bowel sound analysis in term neonates.

Objective: Bowel dysfunction continues to be a serious issue in neonates. Traditional auscultation of bowel sounds as a diagnostic tool in neonatal gastrointestinal problems is limited by skill and inability to document and reassess. Consequently, in order to objectively and noninvasively examine the viability of continuous assessment of bowel sounds, we utilized an acoustic recording and analysis system to capture bowel sounds and extract acoustic features in term neonates. Methods: From May 1, 2020 to September 30, 2020, 82 neonates who were hospitalized because of hyperbilirubinemia were included. For 20 h, a convolutional neural network-based acoustic recorder that offers real-time, wireless, continuous auscultation was employed to track the bowel sounds of these neonates. Results: (1) Usable data on five acoustic parameters of bowel sound was recorded for 68 neonates, and the median values were as follows: The rate was 25.80 times/min [interquartile range (IQR): 15.63-36.20]; the duration was 8.00 s/min (IQR: 4.2-13.20); the amplitude was 0.46 (IQR: 0.27-0.68); the frequency was 944.05 Hz (IQR: 848.78-1,034.90); and the interval time was 2.12 s (IQR: 1.3-3.5). (2) In comparison to the parameters of the bowel sounds recorded from the right lower abdomen in 68 infants, the acoustic parameters of the 10 out of 68 infants from chest controls and blank controls were considerably different. (3) The 50%-75% breast milk intake group had the highest rate, the longest duration, and the highest amplitude of bowel sounds, while the >75% breast milk intake group had the highest frequency of bowel sounds. (4) Compared with neonates without hyperbilirubinemia, there was no significant difference in the five parameters of bowel sounds in hyperbilirubinemia infants; nor was there a significant effect of phototherapy and non-phototherapy status on the parameters of bowel sounds during bowel sound monitoring in hyperbilirubinemia patients. (5) A mild transient skin rash appeared on the skin of three infants. No other adverse events occurred. Conclusion: The acoustic recording and analysis system appears useful for monitoring bowel sounds using a continuous, invasive, and real-time approach. Neonatal bowel sounds are affected by various feeding types rather than hyperbilirubinemia and phototherapy. Potential influencing factors and the significance of their application in neonatal intestinal-related disorders require further research.

Ginsenoside Rg5: A Review of Anticancer and Neuroprotection with Network Pharmacology Approach.

Ginsenoside Rg5 (G-Rg5) is a rare ginsenoside isolated from ginseng (Panax ginseng C.A. Meyer), and this compound is increasingly known for its potent pharmacological activities. This study aimed to provide a comprehensive review of the main activities and mechanisms of G-Rg5 by adopting network pharmacological analysis combined with a summary of published articles. The 100 target genes of G-Rg5 were searched through available database, subjected to protein-protein interaction (PPI) network generation and then core screening. The results showed that G-Rg5 has promising anticancer and neuroprotective effects. By summarizing these two pharmacological activities, we found that G-Rg5 exerts its therapeutic effects mainly through PI3K/AKT, MAPK signaling pathways, and the regulation of apoptosis and cell cycle. And these results were corroborated by KEGG analysis. Likewise, molecular docking of the related proteins was performed, and the binding energies were all less than [Formula: see text]7.0[Formula: see text]kJ/mol, indicating that these proteins had excellent binding capacity with G-Rg5. The network pharmacology results revealed many potential G-Rg5 mechanisms, which need to be further explored. We expect that the network pharmacology approach and molecular docking techniques can help us gain a deeper understanding of the therapeutic mechanisms of different ginsenosides and even the ginseng plant, for further developing their therapeutic potential as well as clinical applications.

Influences of miR-378a-3p on the Pathogenesis of Allergic Rhinitis via GzmB-Mediated Inflammatory Reaction.

Methods: Totally, 24 BALB/c mice were assigned to the AR group, control group, GzmB group, and blank group (each n = 6). The blank group was normally fed without treatment, and the other three groups were treated by ovalbumin (OVA) to induce AR models, in which the GzmB group was intranasally injected with lentiviral vector suppressing GzmB expression during the second immunization, while the control group was given the GzmB-blank vector. The times of AR pathological behaviours such as sneezing and scratching the nose of mice were observed and counted. The nasal lavage fluid of each mouse was acquired, and then, the mouse was executed by cervical dislocation, followed by collection of blood and nasal mucosa tissues. Then, ELISA was adopted for quantifying immunoglobulin E (IgE), interleukin (IL)-4, IL-6, and histamine (HA), and nasal mucosa tissues were treated by HE and TUNEL staining to observing their histopathological manifestations. PCR and western blot (WB) were adopted for quantifying GzmB and miR-378a-3p. Additionally, with NP69 cells, dual luciferase reporter (DLR) assay was carried out for determining the targeting association of GzmB with miR-378a-3p. Another 24 mice were assigned to the AR group, GzmB group, miR-378a-3p group, and GzmB+ miR-378a-3p group (each n = 6). The AR and GzmB groups were treated as above. The miR-378a-3p group was intervened by lentiviral vector suppressing miR-378a-3p, while the GzmB+ miR-378a-3p group was given GzmB and lentiviral vector suppressing miR-378a-3p meantime. A rescue assay was conducted through repeating the above tests. Results: The times of sneezing and rubbing the nose and the levels of IgE, IL-4, IL-6, and HA were similar between the control and AR groups (all P > 0.05), and these items of the two groups were all higher than those of the blank and GzmB groups (all P < 0.05). However, no notable difference was observed in IL-4 and IL-6 levels between the GzmB and blank groups (both P > 0.05), while higher levels of other detection results were found in the former group than in the latter (all P < 0.05). The staining results revealed obvious congestion, oedema, and necrosis structures in the nasal mucosa epithelium of the control and AR groups and also revealed a large number of infiltrating eosinophils and notable increase of apoptotic nasal mucosa epithelial cells. The GzmB group showed notably improved nasal mucosa tissues, and its infiltration and apoptosis of eosinophils were more notable than those of the blank group, but notably weaker than those of the AR and control groups. Additionally, the PCR and WB results revealed similar miR-378a-3p and GzmB levels in nasal mucosa between the control and AR groups (both P > 0.05), and a notable decrease of miR-378a-3p and a notable increase of GzmB in both groups (both P < 0.05). The DLR assay revealed notably suppressed fluorescence activity of GzmB-WT in NP69 cells after transfection of miR-378a-3p mimics (P < 0.05) and notably down regulated GzmB protein after increase of miR-378a-3p (P<0.05). Finally, the rescue assay revealed that downregulating miR-378a-3p aggravated the pathological changes of AR (P < 0.05) and also completely reversed the impacts of inhibiting GzmB on the pathological behaviours of AR mice. Conclusions: MiR-378a-3p can accelerate the pathological development of AR through targeted inhibition on the release of pro-inflammatory factors such as IgE and HA activated by GzmB, so it is a promising molecular target of AR therapy and offers a novel research direction for the complete cure of AR.

Total Triterpenes of Wolfiporia cocos (Schwein.) Ryvarden & Gilb Exerts Antidepressant-Like Effects in a Chronic Unpredictable Mild Stress Rat Model and Regulates the Levels of Neurotransmitters, HPA Axis and NLRP3 Pathway.

Purpose: Wolfiporia cocos is frequently used in traditional Chinese medicine to treat depression. However, antidepressant-like effects of the main active ingredients of Wolfiporia cocos, total triterpenes of Wolfiporia cocos (TTWC), are not well studied. This study aimed to investigate those effects and explore their specific mechanisms of action in depth. Methods: Chemical components of TTWC were analyzed using LC-MS. Depression-like behavior in rats were induced by chronic unpredictable mild stress (CUMS). The suppressive effects of TTWC (60, 120, 240 mg/kg) against CUMS-induced depression-like behavior were evaluated using the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT). Levels of 5-hydroxytryptamine (5-HT), glutamate (GLU), corticotropin-releasing hormone (CRH), interleukin-1 beta (IL-1beta), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in different groups were determined by ELISA. Western blotting (WB) was used to detect the expression of NLRP3, ASC, pro-caspase-1, caspase-1, pro-IL-1beta, IL-1beta, pro-IL-18, and IL-18 in the prefrontal cortex. Additionally, the mRNA levels of NLRP3, ASC, caspase-1, IL-1beta and IL-18 were detected by RT-PCR. Results: A total of 69 lanostane-type triterpene acids of TTWC were identified. The results showed that TTWC exhibited an antidepressant-like effect in CUMS rats, reversed the decreased sugar preference in the SPT, reduction of immobility time in the FST, reduced the rest time, increased the total moving distance in the OFT. TTWC increased 5-HT levels and decreased GLU levels in the hippocampus. Moreover, TTWC decreased CRH levels in serum, indicating the regulation of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, reduced serum levels of IL-1beta, IL-18, IL-6, and TNF-alpha. The WB results implied that TTWC inhibited the expression of NLRP3, ASC, caspase-1, IL-1beta, and IL-18 in the prefrontal cortex and enhanced the expression of pro-caspase-1, pro-IL-1beta, and pro-IL-18. Although most of the results were not significant, PCR results showed that TTWC inhibited the expression of NLRP3, ASC, caspase-1, IL-1beta, and IL-18 in the prefrontal cortex. Conclusion: TTWC treatment exerted an antidepressant-like effect and regulates neurotransmitters, HPA axis and NLRP3 signaling pathway. These results indicated the potential of TTWC in preventing the development of depression.

Rabeprazole plus amoxicillin dual therapy is equally effective to bismuth-containing quadruple therapy for Helicobacter pylori eradication in central China: A single-center, prospective, open-label, randomized-controlled trial.

BACKGROUND: Antibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High-dose dual therapy has recently shown encouraging results in H. pylori eradication, but it has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first-line therapy for H. pylori eradication, and factors that affect the curing rate. METHODS: This is a single-center, prospective, open-label, randomized-controlled trial. Naive patients (n=292) were randomly treated with bismuth-containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by 13 C-urea breath test. RESULTS: In per-protocol (PP) analysis, H. pylori eradication rate was 91.2% in BQT group, 89.6% in RADT, and 51.0% in RFDT group. In intention-to-treat (ITT) analysis, infection was eradicated in 86.7% of patients in BQT group, 85.8% in RADT, and 48.1% in RFDT groups, respectively. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group. CONCLUSIONS: Rabeprazole-amoxicillin dual therapy is equally effective to the bismuth-containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non-smoking condition, which deserves future stratified analysis for refinement and optimization.

Two new dammarane-type triterpenoids from the steamed roots of Panax notoginseng.

Two new dammarane-type triterpenoids, notoginsenoside SY3 (1) and notoginsenoside SY4 (2), were isolated from the steamed roots of Panax notoginseng. Their structures were determined to be 3ß, 12ß, 20(S)-trihydroxy-27-anordammar-23(24)(E)-ene-3-O-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranoside (1) and 3ß, 12ß, 20(S)-trihydroxy-25-methoxyldammar-23(24)(E)-ene-3-O-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranoside (2) by IR, HRESIMS and NMR experiments.

[Current status of readmission of neonates with hyperbilirubinemia and risk factors for readmission].

OBJECTIVE: To investigate the current status of readmission of neonates with hyperbilirubinemia and risk factors for readmission. METHODS: From January 2017 to December 2019, a total of 85 infants who were readmitted due to hyperbilirubinemia were enrolled as the study group. A total of 170 neonates with hyperbilirubinemia but without readmission during the same period of time were randomly selected as the control group. The medical data were compared between the two groups. Multivariate logistic regression was used to assess the risk factors for readmission due to hyperbilirubinemia. RESULTS: The readmission rate was 2.30%, and the interval between readmission and initial admission was 5 days. Compared with the control group, the study group had significantly higher levels of total bilirubin and indirect bilirubin at discharge (P<0.05) and a significantly longer duration of phototherapy during the first hospitalization (P<0.05). The univariate analysis showed that compared with the control group, the study group had significantly lower birth weight, gestational age, and age on initial admission (P<0.05) and a significantly higher proportion of infants with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency or hemolytic disease (P<0.05). The multivariate analysis showed that low gestational age (OR=1.792, P<0.05), young age on initial admission (OR=1.415, P<0.05), and G-6-PD deficiency (OR=2.829, P<0.05) were independent risk factors for readmission of neonates with hyperbilirubinemia. CONCLUSIONS: The infants with hyperbilirubinemia who have lower gestational age, younger age on initial admission, and G-6-PD deficiency have a higher risk of readmission due to hyperbilirubinemia. It is thus important to strengthen the management during hospitalization and after discharge for these infants to prevent the occurrence of readmission.

Sacha inchi (Plukenetia volubilis L.) shell extract alleviates hypertension in association with the regulation of gut microbiota.

Dysbiosis of gut microbiota has been implicated in the pathogenesis of hypertension. A definite relationship between gut microbiota and hypertension remains intriguing. Here, we show that the Sacha inchi (Plukenetia volubilis L.) shell extract (SISE) intervention significantly reduced systolic blood pressures in spontaneous hypertensive rats (SHR), attenuated the oxidative damage and modulated plasma calcium homeostasis and left ventricular hypertrophy in both SHR and high-salt diet Wistar-Kyoto rats. SISE reshaped the gut microbiome and metabolome, particularly by improving the prevalence of Roseburia and dihydrofolic acid levels in the gut. Transcriptome analyses showed that the protective effects of SISE were accompanied by the modulation of renal molecular pathways, beneficial for cardiovascular functions such as the L-type voltage-dependent calcium channel (LTCC), a key regulator of calcium signaling. Overall, the results have shown that dietary SISE can alleviate hypertension regulating the gut microbiota, and Ca2+ signaling might be a potential target for spontaneous hypertension.

Sacha inchi oil alleviates gut microbiota dysbiosis and improves hepatic lipid dysmetabolism in high-fat diet-fed rats.

Dietary ω-3 polyunsaturated fatty acids (PUFAs) are beneficial for humans against the development of hyperlipidaemia, but the underlying mechanisms are still poorly understood. Here, we demonstrated that oral consumption of sacha inchi oil, which is rich in α-linolenic acid, alleviated dyslipidemia, hepatic steatosis and inflammatory infiltration in high-fat diet (HFD)-fed rats. Sacha inchi oil administration reversed gut microbiota dysbiosis and altered the gut microbiota metabolome and in particular prevented bile acid dysmetabolism caused by a HFD. Sacha inchi oil intake ameliorated hepatic lipid dysmetabolism in HFD-fed rats, via potentiating the biosynthesis and reuptake of bile acids, reducing the de novo lipogenesis, promoting fatty acid beta-oxidation, and alleviating the dysregulation of glycerolipid, glycerophospholipid, and sphingolipid metabolisms. The results showed that dietary sacha inchi oil can alleviate gut microbiota dysbiosis and reduce lipid dysmetabolism in HFD rats, and provide novel insights into the molecular mechanisms by which plant-derived ω-3 PUFAs prevent the development of hyperlipidaemia.

Association Between Lifestyle Factors, Vitamin and Garlic Supplementation, and Gastric Cancer Outcomes: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The associations of lifestyle factors with gastric cancer (GC) are still underexplored in populations in China. Long-term nutritional supplementation may prevent GC in high-risk populations, but the possible effect modification by lifestyle factors remains unknown. Objective: To evaluate how lifestyle factors, including smoking, alcohol intake, and diet, may change the risk of GC incidence and mortality and whether the effects of vitamin and garlic supplementation on GC are associated with major lifestyle factors. Design, Setting, and Participants: This is a secondary analysis of the Shandong Intervention Trial, a masked, randomized, placebo-controlled trial that aimed to assess the effect of vitamin and garlic supplementations and Helicobacter pylori treatment on GC in a factorial design with 22.3 years of follow-up. The study took place in Linqu County, Shandong province, China, a high-risk area for GC. Data were collected from Jully 1995 to December 2017. Overall, 3365 participants aged 35 to 64 years identified in 13 randomly selected villages who agreed to undergo gastroscopy were invited to participate in the trial and were included in the analysis. Data analysis was conducted from March to May 2019. Interventions: Participants received vitamin and garlic supplementation for 7.3 years, H pylori treatment for 2 weeks (among participants with H pylori ), or placebo. Main Outcomes and Measures: The primary outcomes were GC incidence and GC mortality (1995-2017). We also examined the progression of gastric lesions (1995-2003) as a secondary outcome. Results: Of the 3365 participants (mean [SD] age, 47.1 [9.2] years; 1639 [48.7%] women), 1677 (49.8%) were randomized to receive active vitamin supplementation, with 1688 (50.2%) receiving placebo, and 1678 (49.9%) receiving active garlic supplementation, with 1687 (50.1%) receiving placebo. Overall, 151 GC cases (4.5%) and 94 GC deaths (2.8%) were identified. Smoking was associated with increased risk of GC incidence (odds ratio, 1.72; 95% CI, 1.003-2.93) and mortality (hazard ratio [HR], 2.01; 95% CI, 1.01-3.98). Smoking was not associated with changes to the effects of vitamin or garlic supplementation. The protective effect on GC mortality associated with garlic supplementation was observed only among those not drinking alcohol (never drank alcohol: HR, 0.33; 95% CI, 0.15-0.75; ever drank alcohol: HR, 0.92; 95% CI, 0.55-1.54; P for interaction = .03), and significant interactions were only seen among participants with H pylori (never drank alcohol: HR, 0.31; 95% CI, 0.12-0.78; ever drank alcohol: HR, 0.91; 95% CI, 0.52-1.60; P for interaction = .04). No significant interactions between vitamin supplementation and lifestyle factors were found. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, smoking was associated with an increased risk of GC incidence and mortality. Not drinking alcohol was associated with a stronger beneficial effect of garlic supplementation on GC prevention. Our findings provide new insights into lifestyle intervention for GC prevention, suggesting that mass GC prevention strategies may need to be tailored to specific population subgroups to maximize the potential beneficial effect. Trial Registration: ClinicalTrials.gov Identifier: NCT00339768.

Effects of Helicobacter pylori treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial.

OBJECTIVE: To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN: Blinded randomized placebo controlled trial. SETTING: Linqu County, Shandong province, China. PARTICIPANTS: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339768.

[Chemotactic response of ginseng endophyte to ginseng root exudates].

The ginseng endophytic bacteria F1 is a potential biocontrol agent for ginseng bacterial soft rot. In this paper,the chemotactic response of ginseng endophytic bacteria F1 on 8 kinds of sugar and amino acids was detected by capillary method to explore its biocontrol mechanism. The chemotactic response of F1 strain to 4 kinds of better chemotaxis substances such as glucose,glycine,L-rhamnoseand L-glutamic acid under parameters( concentration,time,temperature and pH) was studied. The results showed that under the same experimental conditions( incubation temperature 25 ℃,incubation time 60 min,chemotaxis concentration 1 mg·L~(-1)),ginseng endophytic bacteria F1 showed different degrees of response to the eight substances tested. The phenomenon of positive chemotaxis of the measured sugars and amino acids was obvious,and the chemotactic response to total ginsenosides was low. The degree of chemotaxis response is positively correlated with the chemotaxis index within a certain range of parameters,but as the temperature,p H,time,concentration and other factors continue to increase,the chemotaxis effect decreases,and F1 optimizes the chemotaxis of the four substances. The parameters are as follows: glucose: 25 ℃,10 mg·L~(-1),45 min,pH 7; glycine: 30 ℃,10 mg·L~(-1),75 min,pH7; L-rhamnose: 30 ℃,1 mg·L~(-1),30 min,pH 6; L-glutamic acid: 25 ℃,0. 1 mg·L~(-1),45 min,pH 8. The chemotactic response is more sensitive to low concentrations of chemotactic substances.