A Bacterial Responsive Microneedle Dressing with Hydrogel Backing Layer for Chronic Wound Treatment.

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.

Design, synthesis, and evaluation of pirfenidone-NSAIDs conjugates for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal, chronic and progressive lung disease that threaten public health like many cancers. In this study, targeting the significant driving factor, inflammatory response, of the IPF, several conjugates of pirfenidone (PFD) with non-steroidal anti-inflammatory drugs (NSAIDs), along with their derivatives, were designed and synthesized to enhance the anti-IPF potency of PFD. Among these compounds, the (S)-ibuprofen-PFD conjugate 5b exhibited the most potent anti-proliferation activity against NIH3T3 cells, demonstrating up to a 343-fold improvement compared to PFD (IC50 = 0.04 mM vs IC50 = 13.72 mM). Notably, 5b exhibited superior activity in inhibiting the migration of macrophages induced by TGF-ß compared to PFD. Additionally, 5b demonstrated significant suppression of TGF-ß-induced migration of NIH3T3 cells and induction of apoptosis in NIH3T3 cells. Mechanistic studies revealed that 5b reduced the expression of collagen I and α-SMA by inhibiting the TGF-ß/SMAD3 pathway. In a bleomycin-induced pulmonary fibrosis model, treatment with 5b (40 mg/kg/day, orally) exhibited a more pronounced effect on reducing the degree of histopathological changes in lung tissue and alleviating collagen deposition compared to PFD (100 mg/kg/day, orally). Moreover, 5b could block the expression of collagen I, α-SMA, fibronectin, and pro-inflammatory factors (IL-6, IFN-γ, and TNF-α) compared to PFD, while demonstrating low toxicity in vivo. These preliminary results indicated that the hybridization of PFD with NSAIDs represented an effective modification approach to improve the anti-IPF potency of PFD. Consequently, 5b emerged as a promising candidate for the further development of new anti-IPF agents.

Comprehensive insight into adsorption of chlortetracycline hydrochloride by room-temperature synthesized water-stable Zr-based metal-organic gel/sodium alginate beads.

Chlortetracycline hydrochloride (CTC) is one of the prevailing antibiotic pollutants that harm both environmental ecosystem and human health. Herein, Zr-based metal-organic gels (Zr-MOGs) with lower-coordinated active sites and hierarchically porous structures are fabricated via a facile straightforward room-temperature strategy for CTC treatment. More importantly, we incorporated the powder Zr-MOGs into low-cost sodium alginate (SA) matrix to achieve shaped Zr-based metal-organic gel/SA beads for enhancing the adsorption ability and ameliorating the recyclability. The Langmuir maximum adsorption capacities of Zr-MOGs and Zr-MOG/SA beads could reach 143.9 mg/g and 246.9 mg/g, respectively. What's more, in the manual syringe unit and continuous bead column experiments, Zr-MOG/SA beads could achieve an eluted CTC removal ratio as high as 96.3% and 95.5% in the river water sample, respectively. On top of that, the adsorption mechanisms were put forward as a combination of pore filling, electrostatic interaction, hydrophilic-lipophilic balance, coordination, π-π interaction as well as hydrogen bonding interaction. This study outlines a workable strategy for the facile preparation of candidate adsorbents for wastewater treatment.

Obstacle-induced giant jammed aggregation of active semiflexible filaments.

Filaments driven by bound motor proteins and chains of self-propelled colloidal particles are a typical example of active polymers (APs). Due to deformability, APs exhibit very rich dynamic behaviors and collective assembling structures. Here, we are concerned with a basic question: how APs behave near a single obstacle? We find that, in the presence of a big single obstacle, the assembly of APs becomes a two-state system, i.e. APs either gather nearly completely together into a giant jammed aggregate (GJA) on the surface of the obstacle or distribute freely in space. No partial aggregation is observed. Such a complete aggregation/collection is unexpected since it happens on a smooth convex surface instead of, e.g., a concave wedge. We find that the formation of a GJA experiences a process of nucleation and the curves of the transition between the GJA and the non-aggregate state form hysteresis-like loops. Statistical analysis of massive data on the growing time, chirality and angular velocity of both the GJAs and the corresponding nuclei shows the strong random nature of the phenomenon. Our results provide new insights into the behavior of APs in contact with porous media and also a reference for the design and application of polymeric active materials.

Syringin Prevents Aß25-35-Induced Neurotoxicity in SK-N-SH and SK-N-BE Cells by Modulating miR-124-3p/BID Pathway.

Alzheimer's disease (AD) is a neurodegenerative disorder disease, disturbing people's normal life. Syringin was mentioned to antagonize Amyloid-ß (Aß)-induced neurotoxicity. However, the action mechanism is still not fully elucidated. This study aimed to explore a molecular mechanism of syringin in defending Aß-induced neurotoxicity. SK-N-SH and SK-N-BE cells were treated with amyloid ß-protein fragment 25-35 (Aß25-35) to induce cell neurotoxicity. The injury effects were distinguished by assessing cell viability and cell apoptosis using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of Cleaved-caspase3 (Cleaved-casp3), B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and BH3 interacting domain death agonist (BID) at the protein level was determined by western blot. The expression of miR-124-3p and BID was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-124-3p and BID was predicted by the online database starBase and confirmed by dual-luciferase reporter assay plus RNA pull-down assay. Aß25-35 treatment inhibited cell viability and induced cell apoptosis, while the addition of syringin recovered cell viability and suppressed cell apoptosis. MiR-124-3p was significantly downregulated in Aß25-35-treated SK-N-SH and SK-N-BE cells, and BID was upregulated. Nevertheless, the addition of syringin reversed their expression. BID was a target of miR-124-3p, and its downregulation partly prevented Aß25-35-induced injuries. Syringin protected against Aß25-35-induced neurotoxicity by enhancing miR-124-3p expression and weakening BID expression, and syringin strengthened the expression of miR-124-3p to diminish BID level. Syringin ameliorated Aß25-35-induced neurotoxicity in SK-N-SH and SK-N-BE cells by regulating miR-124-3p/BID pathway, which could be a novel theoretical basis for syringin to treat AD.

Downregulation of lncRNA XIST Represses Tumor Growth and Boosts Radiosensitivity of Neuroblastoma via Modulation of the miR-375/L1CAM Axis.

Neuroblastoma (NB) is a heterogeneous tumor that is common in infants and young children. Long non-coding RNA X-inactive specific transcript (XIST) is implicated in NB advancement. Nevertheless, the role and regulatory mechanism by which XIST in NB are not fully elucidated. Expression levels of XIST, microRNA-375-5p (miR-375), and L1 cell adhesion molecular (L1CAM) were examined through quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, proliferation, and colony formation of NB cells were determined with flow cytometry, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), or cell colony formation assays. Cell apoptotic rate was detected with flow cytometry assay. The relationship between XIST or L1CAM and miR-375 was verified via dual-luciferase reporter assay. The level of L1CAM protein was examined through western blotting. The role of XIST in vivo was confirmed through xenograft assay. XIST and L1CAM were upregulated while miR-375 was downregulated in NB tissues and cells. XIST depletion repressed tumor growth in vivo and elevated radiosensitivity, arrested cell cycle progression, and impeded proliferation of NB cells in vitro. Mechanistically, XIST modulated L1CAM expression through competitively binding to miR-375. Furthermore, miR-375 inhibitor recovered XIST inhibition-mediated effects on the radiosensitivity and malignant behaviors of NB cells. Also, L1CAM overexpression reversed the effects of miR-375 enhancement on the cell cycle progression, proliferation, and radiosensitivity of NB cells. XIST downregulation repressed tumor growth and boosted radiosensitivity of NB via modulating the miR-375/L1CAM axis, indicating that XIST was a promising target for NB treatment.

[Risk factors for elevated serum total bile acid in preterm infants].

OBJECTIVE: To study the risk factors for elevated serum total bile acid (TBA) in preterm infants. METHODS: A retrospective analysis was performed for the clinical data of 216 preterm infants who were admitted to the neonatal intensive care unit. According to the presence or absence of elevated TBA (TBA >24.8 µmol/L), the preterm infants were divided into elevated TBA group with 53 infants and non-elevated TBA group with 163 infants. A univariate analysis and an unconditional multivariate logistic regression analysis were used to investigate the risk factors for elevated TBA. RESULTS: The univariate analysis showed that there were significant differences between the elevated TBA group and the non-elevated TBA group in gestational age at birth, birth weight, proportion of small-for-gestational-age infants, proportion of infants undergoing ventilator-assisted ventilation, fasting time, parenteral nutrition time, and incidence of neonatal respiratory failure and sepsis (P<0.05). The unconditional multivariate logistic regression analysis showed that low birth weight (OR=3.84, 95%CI: 1.53-9.64) and neonatal sepsis (OR=2.56, 95%CI: 1.01-6.47) were independent risk factors for elevated TBA in preterm infants. CONCLUSIONS: Low birth weight and neonatal sepsis may lead to elevated TBA in preterm infants.

[Y chromosome microdeletion in azoospermia and severe oligozoospermia patients with or without varicocele:A comparative study].

Objective: To compare the incidences of Y chromosome microdeletion between patients with azoospermia or severe oligozoospermia with varicocele( VC) and those without VC and investigate the etiopathogenisis of their infertility. Methods: We included 137 VC patients in group A(70 with azoospermia as group A1 and 67 with severe oligozoospermia as group A2),135 non-VC patients in group B(69 with azoospermia as group B1 and 66 with severe oligozoospermia as group B2),and 30 normal fertile men as controls in group C. We detected Y chromosome microdeletion in different groups using multiplex PCR. Results: Y chromosome microdeletion was detected in 23(16. 8%) of the patients in group A, another 23(17. 0%) in group B,and 0 in group C. The rates of Y chromosome microdeletion were 22. 9% in group A1,10. 4% in group A2,20. 3% in group B1,and 13. 6% in group B2,and the microdeletion rate in the patients with severe oligozoospermia( groups A1 and B1) was 23. 3%(31 /133). No statistically significant difference was found between groups A and B( P > 0. 05). Conclusion: There are no significant differences in the rate of Y chromosome microdeletion between varicocele and non-varicocele patients with azoospermia or severe oligozoospermia, and Y chromosome microdeletion is one of the causes of azoospermia and severe oligozoospermia with varicocele.

Cross-language translation priming asymmetry with Chinese-English bilinguals: a test of the Sense Model.

The present study aimed to test the Sense Model of cross-linguistic masked translation priming asymmetry, proposed by Finkbeiner et al. (J Mem Lang 51:1-22, 2004), by manipulating the number of senses that bilingual participants associated with words from both languages. Three lexical decision experiments were conducted with Chinese-English bilinguals. In Experiment 1, polysemous L2 words and their L1 Chinese single-sense translation equivalents were selected as primes and targets. In Experiment 2, single-sense L1 words and their L2 translation equivalents with polysemous senses severed as primes and targets. We found translation priming effects in the L1-L2 direction, but not in the L2-L1 direction. In Experiment 3, presentation time of the L2 priming stimulus was prolonged, and significant translation priming effects were observed in the L2-L1 direction. These findings suggest that the Sense Model does not adequately explain cross-language translation priming asymmetry. The sense numbers of primes and targets, as well as the activation proportion of these senses between them, were possibly not the primary reason for cross-language translation priming asymmetry. The revised hierarchical model (Kroll and Stewart in J Mem Lang 33:149-174, 1994) and the BIA+ model (Dijkstra and van Heuven in Bilingualism Lang Cognit 5:175-197, 2002) better explain the cross-language translation priming asymmetry we found.

Complement system in Anti-CD20 mAb therapy for cancer: A mini-review.

The complement system is an important part of innate immunity. Through complement-dependent cytotoxicity (CDC), it plays an important role in the clearance of invading pathogens but also cancerous host cells. Therapy with anti-CD20 monoclonal antibodies (mAbs), for example, rituximab and ofatumumab, is a well-established treatment for lymphoid malignancies, and CDC is one of the main mechanisms underlying their anti-cancer activity. However, there are still some issues with the clinical application of anti-CD20 antibodies. On the one hand, anti-CD20 can cause some clinical side effects; on the other hand, anti-CD20 has low potency in some patients, and increasing the dosage does not enhance its effectiveness in these patients. Previous studies have reported that a gain-of-function in a certain complement component can boost the cytolytic activity of anti-CD20 mAbs. Through reviewing the literature on complement system control and anti-CD20 mAbs, this article aims to provide a thorough understanding of the potential of targeting complement components in lymphoma therapy.

Inhaled pulmonary surfactant biomimetic liposomes for reversing idiopathic pulmonary fibrosis through synergistic therapeutic strategy.

Idiopathic pulmonary fibrosis (IPF) stands as a highly heterogeneous and deadly lung disease, yet the available treatment options remain limited. Combining myofibroblast inhibition with ROS modulation in damaged AECs offers a comprehensive strategy to halt IPF progression, but delivering drugs separately to these cell types is challenging. Inspired by the successful application of pulmonary surfactant (PS) replacement therapy in lung disease treatment, we have developed PS nano-biomimetic liposomes (PSBs) to utilize its natural transport pathway for targeting AECs while reducing lung tissue clearance. In this collaborative pulmonary drug delivery system, PSBs composed of DPPC/POPG/DPPG/CHO (20:9:5:4) were formulated for inhalation. These PSBs loaded with ROS-scavenger astaxanthin (AST) and anti-fibrosis drug pirfenidone (PFD) were aerosolized for precise quantification and mimicking patient inhalation. Through aerosol inhalation, the lipid membrane of PSBs gradually fused with natural PS, enabling AST delivery to AECs by hitchhiking with PS circulation. Simultaneously, PFD was released within the PS barrier, effectively penetrating lung tissue to exert therapeutic effects. In vivo results have shown that PSBs offer numerous therapeutic advantages in mice with IPF, particularly in terms of lung function recovery. This approach addresses the challenges of drug delivery to specific lung cells and offers potential benefits for IPF patients.

A Study on the Applicability of Aromatic Parameters in the Maturity Evaluation of Lacustrine Source Rocks and Oils Based on Pyrolysis Simulation Experiments.

Aromatic maturity parameters were evaluated via closed-system pyrolysis experiments using a Mesozoic lacustrine source rock from the Yingen-Ejinaqi Basin, thereby ensuring a uniform source. Pulverized rock aliquots (200 mg) were reacted with water at temperatures ranging from 250 to 550 °C at 5 °C/min, and the aromatic fractions of expelled oil and extracts of the solid residue were analyzed by GC-MS. The experiments showed that the relative abundance of aromatic hydrocarbons in the oil and extractable organic matter (EOM) of source rock had different evolutionary characteristics. With the increase in the thermal evolution degree, the relative abundance of aromatic hydrocarbons in the EOM showed the characteristics of ″increased early (Ro < 0.80), unchanged middle (Ro = 0.80-2.00%), decreased lately (Ro > 2.00%)″. While the relative abundance of aromatic hydrocarbons in the expelled oils continuously increased, as the Ro values increased from 0.62 to 2.39%, the relative abundance of aromatic hydrocarbons gradually increased from 8 to 46%. With increased maturity, the relative abundance of 1-3-ring aromatic hydrocarbons continuously decreased, as observed in the phenanthrene homologs. Meanwhile, the relative abundance of 4+-ring aromatic hydrocarbons continuously increased, as seen in chrysene homologs. It was suggested that the effects of maturity on the composition of aromatic hydrocarbons might not be sufficiently obvious. The effective application range of the alkylnaphthalene-related maturity parameters (2-/1-methylnaphthalenes, (2,6- + 2,7-)/1,5-dimethylnaphthalenes, 2,3,6-/(1,4,6- + 1,3,5-) trimethylnaphthalenes, and (2,3,6- + 1,3,7-)/(1,4,6- + 1,3,5- + 1,3,6-) trimethylnaphthalenes) and the alkyldibenzothiophene maturity parameters (4-/1-methyldibenzothiophenes, 4,6-/(1,4- + 1,6-) dimethyldibenzothiophenes, and (2,6- + 3,6-)/(1,4- + 1,6-) dimethyldibenzothiophenes) was 0.84-2.06% Ro. The alkylphenanthrene-related maturity parameters had a wide application range for lacustrine source rocks with an Ro < 2.06%. These parameters included 1.5 × (2- + 3-)/(phenanthrene +1- + 9-) methylphenanthrenes, 3 × 2-/(phenanthrene + 1- + 9-) methylphenanthrenes, (2- + 3-)/(1- + 9-) methylphenanthrenes, 2-/1-methylphenanthrenes, (3- + 2-)/(1- + 2- + 3- + 9-) methylphenanthrenes, 2-/(1- + 2- + 3- + 9-) methylphenanthrenes, and 2,7-/1,8-dimethylphenanthrenes. In addition, the effective applicable range of the methylnaphthalene-related maturity parameter 3-/1-methylchrysenes was an Ro value less than 1.79%. The results clarified the validity scope of some aromatics' maturity parameters and provided a theoretical basis for the scientific application of these parameters.

[Effect of Panax notoginseng saponins on expression of alpha-secretase mRNA in brains of senescence-accelerated SAMP8 mice].

OBJECTIVE: To study the effect of Panax notoginseng saponins (PNS) on expression of alpha-aecretase mRNA in the brains of senescence-accelerated SAMP8 mice. METHOD: SAMP8 mice were randomly divided into the control group, the PNS high-dosage group (200 mg x kg(-1)), the PNS low-dosage group (100 mg x kg(-1)) and the huperzine A group (0.3 mg x kg(-1)), with eight mice in each group. The control group and each administration group were orally administered with the same volume of double distilled water once for consecutively two months. The expression of alpha-secretase (ADAM 9, ADAM10, ADAM17) mRNA was assayed by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). RESULT: The expression of ADAM9 mRNA in PNS high-dosage group and huperzine A group were significantly higher than that of the control group (P < 0.05). The expression of ADAM10 in the PNS high-dosage group, the PNS low-dosage group and the huperzine A group showed no significant difference from the control group. CONCLUSION: PNS can up-regulate expressions of ADAM9 mRNA and down-regulate expressions of ADAM10 mRNA in the brains of SAMP8 mice.

Psychological experience of inpatients with acute pancreatitis: a qualitative study.

OBJECTIVE: This study aimed to better understand the psychological experiences of inpatients with acute pancreatitis (AP). DESIGN: We used a qualitative descriptive study design to capture patients with AP's thoughts, feelings and behavioural responses. SETTING: We conducted this study in the gastroenterology departments of two tertiary hospitals in Eastern China. PARTICIPANTS: We used a convenience sampling approach to recruit 28 inpatients with AP from 1 August 2020 to 25 December 2020. The interviews were audio-recorded and transcribed verbatim. We employed an adapted version of Colaizzi's qualitative analysis approach to examine the data. RESULTS: We extracted three themes and eight subthemes regarding the participants' psychological experiences: (1) feeling that their disease is unpredictable (the inability to recognise the disease, uncertainty about the illness and fear of progression or recurrence); (2) various kinds of stress and support (feeling different degrees of stress, perceiving social support, seeking and craving social support); and (3) developing self-adaptability in the disease process (treating one's illness negatively or positively). CONCLUSIONS: Cognitive and emotional responses vary in patients with AP during hospitalisation. Moreover, patients with distinct conditions demonstrate significant differences in their responses and coping mechanisms. Healthcare providers need to mobilise social support and formulate comprehensive intervention strategies according to patients' individual characteristics.

A multi-modal open dataset for mental-disorder analysis.

According to the WHO, the number of mental disorder patients, especially depression patients, has overgrown and become a leading contributor to the global burden of disease. With the rising of tools such as artificial intelligence, using physiological data to explore new possible physiological indicators of mental disorder and creating new applications for mental disorder diagnosis has become a new research hot topic. We present a multi-modal open dataset for mental-disorder analysis. The dataset includes EEG and recordings of spoken language data from clinically depressed patients and matching normal controls, who were carefully diagnosed and selected by professional psychiatrists in hospitals. The EEG dataset includes data collected using a traditional 128-electrodes mounted elastic cap and a wearable 3-electrode EEG collector for pervasive computing applications. The 128-electrodes EEG signals of 53 participants were recorded as both in resting state and while doing the Dot probe tasks; the 3-electrode EEG signals of 55 participants were recorded in resting-state; the audio data of 52 participants were recorded during interviewing, reading, and picture description.

Evaluation of the effects of 20 nonsynonymous single nucleotide polymorphisms of CYP2C19 on S-mephenytoin 4'-hydroxylation and omeprazole 5'-hydroxylation.

CYP2C19 is a highly polymorphic enzyme that affects the metabolism of a wide range of therapeutic drugs. Almost all the identified alleles of CYP2C19 are derived from nonsynonymous single nucleotide polymorphisms (nsSNPs). The objective of this study was to functionally characterize 20 nsSNPs of CYP2C19, distributed throughout the entire coding region, most of which have not been thoroughly characterized. cDNAs of these variants were constructed and expressed in yeast cells. All variants had similar levels of apoprotein and holoprotein expression, except for CYP2C19.16 and D360N, which had significantly lower holoprotein levels than the wild-type (WT) CYP2C19 enzyme, and CYP2C19.5B, which showed only apoprotein. The activity of the CYP2C19 variants was investigated using two substrates, S-mephenytoin and omeprazole, and six different kinetic parameters were measured. CYP2C19.5B, CYP2C19.6, and CYP2C19.8 were found to be catalytically inactive. The entire dataset of the remaining 17 variants, together with the WT, was analyzed by multivariate analysis. This analysis indicated that CYP2C19.9, CYP2C19.10, CYP2C19.16, CYP2C19.18, CYP2C19.19, A161P, W212C, and D360N were substantially altered in catalytic properties in comparison with the WT, with each of these variants exhibiting either dramatically decreased catalytic activities or higher K(m) values. These results not only generally confirmed the function of previously reported variants but also identified additional reduced-function variants. These findings will greatly extend our understanding of CYP2C19 genetic polymorphisms in humans as well as facilitate the structure-function study of the CYP2C19 protein.

Evaluation of the effects of 18 non-synonymous single-nucleotide polymorphisms of CYP450 2C19 on in vitro drug inhibition potential by a fluorescence-based high-throughput assay.

To comprehensively understand the effects of CYP2C19 genetic polymorphisms on inhibition-based drug-drug interactions (DDIs), 18 human CYP2C19 non-synonymous single-nucleotide polymorphic variants and the wild-type isoform (CYP2C19.1A) were expressed in yeast cells. Using a fluorescence-based high-throughput method, the kinetic constants of these variants, as well as the inhibition constants for 10 drugs, were determined. CYP2C19.5B and CYP2C19.6 showed no activity towards CEC (3-cyano-7-ethoxycoumarin) O-deethylation. CYP2C19.8, CYP2C19.9, CYP2C19.10, CYP2C19.16, CYP2C19.19, E122A and A161P* (an allele containing both A161P and I331V) exhibited significantly reduced catalytic activities compared with CYP2C19.1A. The inhibition assay showed that the CYP2C19 genotype significantly affected the in vitro drug inhibition potential. Although the effect on drug inhibition potential is genotype- and inhibitor-dependent, there was an obvious trend: drugs tended to exhibit higher IC50 values (i.e. decreased inhibition potential) towards variants with reduced activity compared with variants with normal activity. This indicated that patients with reduced-function alleles may be less susceptible to CYP2C19-related DDIs. In this study, we provided the first in vitro evidence of CYP2C19 genotype-dependent effects on drug inhibition potential. This work greatly extends our understanding of the functional consequences of CYP2C19 genetic polymorphisms, and thus should prove valuable for CYP2C19 genotype-based therapy.

25(OH)-Vitamin D alleviates neonatal infectious pneumonia via regulating TGFß-mediated nuclear translocation mechanism of YAP/TAZ.

Neonatal infectious pneumonia (NIP) is a common infectious disease that develops in the neonatal period. The purpose of our study was to explore the potential roles of 25(OH)-Vitamin D (25-OH-VD) and its anti-inflammatory mechanism in NIP. The results showed that serum 25-OH-VD level was negatively correlated with the severity of NIP, whereas Spearman's correlation analysis showed a significant positive correlation between the severity of NIP and the levels of pneumonia markers procalcitonin (PCT) and interleukin-6 (IL-6). The expression of vitamin D receptor (VDR) was down-regulated, while the transforming growth factor ß (TGFß), nuclear YAP, and TAZ were up-regulated in the peripheral blood mononuclear cells (PBMCs) of neonates with severe pneumonia. Neonates with 25-OH-VD deficiency were associated with an increased risk of NIP. In BEAS-2B cells, down-regulation of nuclear YAP and TAZ was found in the lipopolysaccharide (LPS) + VD group relative to the LPS-induced group. Additionally, positive rate of nuclear YAP, as detected by immunocytochemistry (ICC), and the nuclear translocation of nuclear YAP/TAZ by IFA in the LPS+VD group showed an intermediate level between that of the control and LPS-induced groups. Furthermore, the expressions of VDR and CYP27B1 were significantly increased in the LPS+VD group as compared to those in the LPS-induced group. The anti-inflammatory mechanism in NIP was achieved due to the 25-OH-VD mediating TGFß/YAP/TAZ pathway, which suggested that using 25-OH-VD might be a potential strategy for NIP treatment.

Impact of Fatty Pancreas on Postoperative Pancreatic Fistulae: A Meta-Analysis.

BACKGROUND: Soft pancreas is widely recognized as an important risk factor for the development of postoperative pancreatic fistula (POPF). Although fatty pancreas (FP) has not been formally defined as a cause of pancreatic fistula, existing research has shown that it can increase the incidence of POPF by increasing pancreatic tenderness; therefore, it may be a potential risk factor. This study aimed to discern whether FP was associated with POPF. METHOD: Two reviewers independently performed literature searches from five electronic databases. According to the established inclusion criteria, we extracted necessary data from the studies that met the criteria for further analysis. We pooled the odds ratios (ORs) from individual studies using a random-effects model to investigate the associations between POPF and the prognosis of FP. RESULT: A total of 11 studies involving 2484 individuals were included. The pooled prevalence of POPF was 18% (95% CI: 12-24%). Body mass index (BMI) was associated with a significantly increased risk of POPF (OR=3.55; 95% CI: 1.83, 6.86; P=0.0002; I²=0). FP was obviously associated with the occurrence of POPF (OR=3.75; 95% CI: 1.64, 8.58; P=0.002; I²=78). CONCLUSION: FP is closely associated with the development of POPF, and the early identification of these high-risk patients can help to reduce the incidence of POPF. SYSTEMATIC REVIEW REGISTRATION: The Registration URL link is (https://www.crd.york.ac.uk/PROSPERO/). The ID is "CRD42021265141".