Structural characterization of polysaccharide from the peel of Trichosanthes kirilowii Maxim and its anti-hyperlipidemia activity by regulating gut microbiota and inhibiting cholesterol absorption.

The peel of Trichosanthes kirilowii Maxim, is considered one of the primary sources for Trichosanthis pericarpium in traditional Chinese medicine, exhibiting lipid-lowering properties. The impact on hyperlipidemia mice of the crude polysaccharide from the peel of T. Kirilowii (TRP) was investigated in this study. The findings revealed that TRP exhibited a significant improvement in hepatic lipid deposition. Moreover, it significantly decreased serum levels of TC, TG, and LDL-C, while concurrently increasing HDL-C. 16S rRNA amplicon sequencing technique revealed that TRP group exhibited an increased relative abundance of Actinobacteria, a down-regulated relative abundance of Ruminiclostridium, and an up-regulated relative abundance of Ileibacterium. Therefore, TRP might play a role in anti-hyperlipidemia through regulation of the intestinal milieu and enhancement of microbial equilibrium. Consequently, targeted fractionation of TRP resulted in the isolation of a homogeneous acidic polysaccharide termed TRP-1. The TRP-1 polysaccharide, with an average molecular weight of 1.00 × 104 Da, and was primarily composed of Rha, GlcA, GalA, Glc, Gal and Ara. TRP-1 possessed a backbone consisting of alternating connections between â†’ 6)-α-Galp-(1 â†’ 4)-α-Rhap-(1 â†’ 6)-α-Galp-(2 â†’ 6)-ß-Galp-(1 â†’ 6)-α-Galp-(2 â†’ 6)-ß-Galp-(1 â†’ units and branched chain containing â†’ 6)-α-Glcp-(1→, 2,4)-ß-Glcp-(1, and â†’ 4)-α-GlapA-(1→. Both TRP and TRP-1 exhibited significant disruption of cholesterol micelles, highlighting their potential as lipid-lowering agents that effectively inhibit cholesterol absorption pathways.

Genome editing of PAR2 through targeted delivery of CRISPR-Cas9 system for alleviating acute lung inflammation via ERK/NLRP3/IL-1ß and NO/iNOS signalling.

Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases, immune cell infiltration and protease-driven tissue damages. It is an urgent need to explore potential drug strategies for mitigating lung inflammation. Protease-activated receptor 2 (PAR2) as a vital molecular target principally participates in various inflammatory diseases via intracellular signal transduction. However, it has been rarely reported about the role of PAR2 in lung inflammation. This study applied CRISPR-Cas9 system encoding Cas9 and sgRNA (pCas9-PAR2) for PAR2 knockout and fabricated an anionic human serum albumin-based nanoparticles to deliver pCas9-PAR2 with superior inflammation-targeting efficiency and stability (TAP/pCas9-PAR2). TAP/pCas9-PAR2 robustly facilitated pCas9-PAR2 to enter and transfect inflammatory cells, eliciting precise gene editing of PAR2 in vitro and in vivo. Importantly, PAR2 deficiency by TAP/pCas9-PAR2 effectively and safely promoted macrophage polarization, suppressed pro-inflammatory cytokine releases and alleviated acute lung inflammation, uncovering a novel value of PAR2. It also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/pCas9-PAR2 was mainly dependent on ERK-mediated NLRP3/IL-1ß and NO/iNOS signalling. Therefore, this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases.

Multifaceted complications and surgical management of bronchobiliary fistula with associated pneumonia and intrahepatic stones: A case report.

Background: Bronchobiliary fistulas (BBFs), primarily stemming from choledocholithiasis, present considerable diagnostic and treatment challenges. Their prolonged nature can lead to life-threatening situations without timely management, often complicated by lung abscesses. Case presentation: A 64-year-old man, presenting with fever, chills, and a cough initially misdiagnosed as a common cold, developed severe respiratory distress and delirium upon admission. Urgent intensive care unit (ICU) admission was prompted by a computed tomography (CT) scan revealing a right lung abscess. Enhanced CT scans and elevated bilirubin levels confirmed the biliary origin of the BBFs. Comprehensive treatment included laparoscopic partial hepatectomy, choledochojejunostomy, stone extraction, choledochoscopy, T-tube drainage, and BBFs closure. The patient was discharged with a T-tube. Follow-up CT after two months showed no recurrence. Conclusions: Managing BBFs, especially with concurrent lung abscesses in choledocholithiasis patients, remains challenging but feasible. Early diagnosis and intervention are crucial to improving survival rates and quality of life, highlighting the need for vigilance. This case underscores the importance of early detection and comprehensive treatment for successful outcomes in such complex conditions.

Rosmarinic acid alleviates septic acute respiratory distress syndrome in mice by suppressing the bronchial epithelial RAS-mediated ferroptosis.

Activating angiotensin-converting enzyme 2 (ACE2) is an important player in the pathogenesis of septic-related acute respiratory distress syndrome (ARDS). Rosmarinic acid (RA) as a prominent polyphenolic secondary metabolite derived from Rosmarinus officinalis modulates ACE2 in sepsis remains unclear, although its impact on ACE inhibition and septic-associated lung injury has been explored. The study investigated the ACE2 expression in lipopolysaccharide (LPS)-induced lungs in mice and BEAS2B cells. Additionally, molecular docking, protein-protein interaction (PPI) network analysis, and western blotting were employed to predict and evaluate the molecular mechanism of RA on LPS-induced ferroptosis in vivo and in vitro. LPS-induced glutathione peroxidase 4 (GPX4) downregulation, ACE/ACE2 imbalance, and alteration of frequency of breathing (BPM), minute volume (MV), and the expiratory flow at 50% expired volume (EF50) were reversed by captopril pretreatment in vitro and in vivo. RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement, and decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice. Molecular docking showed RA was able to interact with ACE and ACE2. Moreover, combined with different pharmacological inhibitors to block ACE and ferroptosis, RA still significantly inhibited inflammatory cytokines Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine 2 (CXCL2) levels, as well as improved lung function, and enhanced GPX4 expression. Particularly, the anti-ferroptosis effect of RA in LPS-induced septic ARDS is RAS-dependent.

Gellan gum and pullulan-based films with triple functionalities of antioxidant, antibacterial and freshness indication properties for food packaging.

The objective of this research was to fabricate pH-responsive and active films based on gellan gum (GG) and pullulan (PL) with extracts of Broussonetia papyrifera fruits (BPFE) and leaves (BPLE) by a casting method. Results indicated that the extracts had good compatibility with GG and PL, which were uniformly distributed throughout the matrix. The incorporation of BPFE and BPLE increased the thickness, UV-vis barrier property, mechanical strength, thermal stability and moisture content of the films, while decreasing the water contact angle. Notably, the films exhibited enhanced antioxidant properties, with maximum radical scavenging rates of 77.45 % using 2,2 Diphenyl-1-picrylhydrazyl and 66.21 % using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid). The antibacterial capability of the films also increased significantly after adding BPLE and BPFE. The results of XRD and FTIR showed that BPFE was bound to GG and PL by hydrogen bond. The release behavior of BPFE from the films agreed best with the first-level kinetic model. Furthermore, the films displayed obvious color responses to ammonia gas and different pH environments. Simultaneously, the films were applied to monitor the freshness of Pelteobagrus fulvidraco fish. The color parameters of the films demonstrated high correlations with the freshness indexes measured through standard laboratory procedures.

Characterization of an agmatine N-acetyltransferase from Bactrocera dorsalis that modulates ovary development.

Agmatine N-acetyltransferase (AgmNAT), which catalyzes the formation of N-acetylagmatine from acetyl-CoA and agmatine, is a member of the GCN5-related N-acetyltransferase family. So far, knowledge of the physiological roles of AgmNAT in insects is limited. Here, we identified one gene encoding protein homologous to that of Drosophila AgmNAT using sequence information from an activity-verified Drosophila AgmNAT in a BLAST search of the Bactrocera dorsalis genome. We expressed and purified B. dorsalis AgmNAT in Escherichia coli and used the purified enzyme to define the substrate specificity for acyl-CoA and amine substrates. Our application of the screening strategy to BdorAgmNAT led to the identification of agmatine as the best amine substrate for this enzyme, with the highest kcat/Km value. We successfully obtained a BdorAgmNAT knockout strain based on a wild-type strain (WT) using the CRISPR/Cas9 technique. The ovary development of the BdorAgmNAT knockout mutants was delayed for 10 days compared with the WT specimens. Moreover, mutants had a much smaller mature ovary size and laid far fewer eggs than WT. Loss of function of BdorAgmNAT caused by RNAi with mature WT females did not affect their fecundity. These findings indicate that BdorAgmNAT is critical for oogenesis. Our data provide the first evidence for AgmNAT in regulating ovary development.

Dipterocarpoidae genomics reveal their demography and adaptations to Asian rainforests.

Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status.

Diagnosis, treatment, and prognosis of stage IB non-small cell lung cancer with visceral pleural invasion.

With the increasing implementation of early lung cancer screening and the increasing emphasis on physical examinations, the early-stage lung cancer detection rate continues to rise. Visceral pleural invasion (VPI), which denotes the tumor's breach of the elastic layer or reaching the surface of the visceral pleura, stands as a pivotal factor that impacts the prognosis of patients with non-small cell lung cancer (NSCLC) and directly influences the pathological staging of early-stage cases. According to the latest 9th edition of the TNM staging system for NSCLC, even when the tumor diameter is less than 3 cm, the final T stage remains T2a if VPI is present. There is considerable controversy within the guidelines regarding treatment options for stage IB NSCLC, especially among patients exhibiting VPI. Moreover, the precise determination of VPI is important in guiding treatment selection and prognostic evaluation in individuals with NSCLC. This article aims to provide a comprehensive review of the current status and advancements in studies pertaining to stage IB NSCLC accompanied by VPI.

Evaporation and drying characteristics of the sessile ferrofluid droplet under a horizontal magnetic field.

In this study, the evaporation characteristics and drying patterns of various sessile ferrofluid droplets on certain substrate under horizontal magnetic fields of controlled intensities are reported. The effects of droplet concentration and magnetic field intensity on the duration of each evaporation stage and drying patterns of droplets have been systematically investigated. It turned out that a plateau appears at the initial stage of evaporation in the absence of magnetic field and it was found that the plateau value is positively correlated with the concentration of ferrofluid droplets. Under the external magnetic field, the evaporation time of droplets decreases, the stage of contact line retreat extends, the stage of late pinning mode shortens, and the deposition area of ferrofluid droplet decreases compared to that of without magnetics field. The deposition area increases gradually and becomes more uniform with the increase of magnetic field. The decrease of friction force which is due to the decrease of the number of nanoparticles at the contact line under external magnetic field is the main reason for the observed phenomena. We found that the coffee ring and the uniform deposition inside the droplet will be destroyed when the magnetic field intensity is higher than a critical value. Our work has a significant reference value for the evaporation of sessile magnetic fluid droplets under the applied magnetic field, especially when the drying pattern needs to be precisely controlled, such as in spray or biomedicine.

Re-evaluation of systematic reviews of acupuncture and moxibustion for children with cerebral palsy / 中国针灸

OBJECTIVE@#To assess the methodological quality, report quality and evidence quality of the Meta-analysis and systematic reviews of acupuncture and moxibustion for children with cerebral palsy, aiming to provide decision-making basis for clinical treatment.@*METHODS@#The systematic reviews and Meta-analysis of acupuncture and moxibustion for children with cerebral palsy were searched in CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed and EMbase. The retrieval time was from the database establishment to June 30th, 2022. AMSTAR 2 (a measurement tool to assess systematic reviews) was used to evaluate the methodological quality， and PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and GRADE was used to evaluate the quality of evidence.@*RESULTS@#A total of 14 systematic reviews were included, including 37 primary outcome indexes. According to AMSTAR 2 evaluation results, there were 4 low quality studies, 10 very low quality studies, and low scores on items 2, 4, 7, 10 and 16. PRISMA scores ranged from 15 to 25, and the main reporting problems reflected in structured abstracts, program and registration, retrieval, and funding sources, etc. According to the GRADE classification results, there were 3 high quality evidences, 7 medium quality evidences, 10 low quality evidences and 17 very low quality evidences. The main downgrading factors were limitations, imprecision and publication bias.@*CONCLUSION@#Acupuncture and moxibustion has a certain effect for cerebral palsy in children, but the quality of methodology, reporting and evidence in the included literature is poor, and the comparison of curative effect between different acupuncture and moxibustion methods is unclear.

Mild and moderate postpartum depression treated with acupuncture of / 中国针灸

OBJECTIVE@#To observe the clinical therapeutic effect on mild and moderate postpartum depression treated with acupuncture of @*METHODS@#A total of 116 patients with mild and moderate postpartum depression were divided into an acupuncture group (103 cases) and a non-acupuncture group (13 cases) according to treatment regimen provided. In the acupuncture group, acupuncture of @*RESULTS@#The total effective rate of the acupuncture A group was 100.0% (31/31), better than 76.9% (10/13) in the non-acupuncture group and 58.1% in the acupuncture B group (18/31) (@*CONCLUSION@#Acupuncture of

"Thirteen acupoints for regulating menstruation and promoting pregnancy" for diminished ovarian reserve: a prospective cohort study / 中国针灸

OBJECTIVE@#To evaluate the clinical effect of acupuncture at "thirteen acupoints for regulating menstruation and promoting pregnancy" on diminished ovarian reserve (DOR) and its influence on ovarian reserve function.@*METHODS@#A total of 32 patients with DOR were treated by acupuncture at "thirteen acupoints for regulating menstruation and promoting pregnancy". Acupoints group 1: Baihui (GV 20), Shenting (GV 24), Benshen (GB 13), Zhongwan (CV 12), Tianshu (ST 25), Guanyuan (CV 4), Zigong (EX-CA 1), Dahe (KI 12), Zusanli (ST 36), Sanyinjiao (SP 6), Taichong (LR 3); acupoints group 2: Baihui (GV 20), Shenshu (BL 23), Ciliao (BL 32). Acupoints group 1 and group 2 were alternately used, and acupoints group 1 was used for the first time. The needles were stayed for 30 min each time, once every 1 or 2 days, 3 times a week, 36 times (3 months) as a course of treatment. The treatment could be continued until the patient was pregnant or the patient given up acupuncture, and the acupuncture was uninterrupted during menstruation. The changes of modified Kupperman scale score, serum sex hormones, anti-müllerian hormones (AMH), ovarian peak systolic velocity (PSV), resistive index (RI) and antral follicle count (AFC) were compared before and after treatment, and the clinical effect and pregnancy rate were observed.@*RESULTS@#The total score of modified Kupperman scale after treatment was lower than that before treatment (<0.05); The total effective rate was 90.6% (29/32) and the pregnancy rate was 15.6% (5/32). After treatment, the levels of follicle stimulating hormone (FSH), FSH/ luteinizing hormone (LH) were lower than before treatment, ovarian PSV was higher than before treatment, RI was lower than before treatment, and AFC was more than before treatment (<0.05).@*CONCLUSION@#Acupuncture at "thirteen acupoints for regulating menstruation and promoting pregnancy" can effectively improve the ovarian reserve function of DOR patients.

Observation on therapeutic effect of " acupuncture" on premature ovarian insufficiency of kidney deficiency / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of " acupuncture" and oral estradiol and dydrogesterone tablets (femoston) on premature ovarian insufficiency of kidney deficiency.@*METHODS@#A total of 50 patients with premature ovarian insufficiency of kidney deficiency were randomized into an observation group and a control group, 25 cases in each one.In the observation group, " acupuncture" was applied at Baihui (GV 20), Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Zhongji (CV 3), Yaoyangguan (GV 3), Yaoshu (GV 2), Mingmen (GV 4), etc. once every 2 days, 1 month as a course. In the control group, femoston was prescribed for oral administration, one tablet per time, once a day, 1 month as a course. Both of the two groups were given consecutive treatment for 3 courses. Before and after treatment, the clinical symptoms, menstrual improvement as well as the changes of estradiol (E), luteotrophic hormone (LH) and follicle-stimulating hormone (FSH) in serum were observed in the two groups.@*RESULTS@#After treatment, the clinical symptoms and menstrual conditions were improved (<0.01), the levels of FSH and LH were significantly reduced (<0.01), and the levels of E were significantly increased in the two groups (<0.01). There were no significant difference in menstrual improvement rate and menstrual improvement time between the observation group and the control group (<0.05), the recurrence rate of menopause and clinical symptom score improvement in the observation group were superior to the control group (<0.05). In the observation group, the level of E in serum was lower and the levels of FSH and LH in serum were significantly lower than those in the control group (<0.05, <0.01). In the observation group, the rate of adverse reaction was 4.0% (1/25), which was lower than 36.0% (9/25) in the control group (<0.05).@*CONCLUSION@#" acupuncture" has better therapeutic effect for premature ovarian insufficiency of kidney deficiency. It is superior to femoston in improving clinical symptoms and recurrence rate of menopause as well as reducing the levels of FSH and LH.

Experimental study of the function of nuclear factor-κB-dependent epithelial to mesenchymal transition in pancreatic cancer cells under hypoxic conditions / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the function of nuclear factor (NF)-κB in the epithelial to mesenchymal transition induced by hypoxia in pancreatic cancer cells.</p><p><b>METHODS</b>For cultured pancreatic cancer cells (BxPC-3 and Panc-1) under hypoxic and normoxic conditions, the differences in the morphology were observed by optical microscope. The expression of markers of epithelial and mesenchymal phenotypes, E-cadherin, vimentin and N-cadherin, were determined by Western blot. NF-κB P65 activity was measured by electrophoretic mobility shift assay. Invasion and gemcitabine resistance of pancreatic cancer cells were evaluated in matrigel invasion assay and cell counting kit-8 assay. Both molecular and pharmacologic means of inhibiting NF-κB P65 were used in these hypoxic cells and then the above resulting phenotypes were compared with those of the control-treated cells.</p><p><b>RESULTS</b>After cultured pancreatic cancer cells under hypoxic conditions for 48 h, normoxic cells exhibited a polygonal shape and formed tight clusters of cells, whereas hypoxic cells took on an elongated, fibroblastoid morphology associated with a more highly invasive character and resistance to gemcitabine; hypoxic cells exhibited an suppression of E-cadherin and increase in vimentin and N-cadherin expression. NF-κB P65 activity was elevated in hypoxic cells. On the contrary, on molecular or pharmacologic inhibition of NF-κB P65, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and reversed their highly invasive and drug resistant phenotype.</p><p><b>CONCLUSIONS</b>Pancreatic cancer cells underwent epithelial to mesenchymal transition exposed to hypoxia, exhibited highly invasive and drug resistant phenotype. Inhibition of NF-κB P65 under hypoxic conditions, pancreatic cancer cells regained expression of E-cadherin, lost expression of N-cadherin, and reversed their highly invasive and drug resistant phenotype.</p>

Clinical features and prognosis of early-onset preeclampsia / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To explore the clinical features and prognosis of early-onset preeclampsia.</p><p><b>METHODS</b>A total of 115 cases of early-onset preeclampsia were recruited from January 1999 to December 2004 and the data analyzed in terms of the incidence, manifestation, maternal and fetal complications.</p><p><b>RESULT</b>The early-onset preeclampsia accounted for 13.4% of all preeclampsia diagnosed. The perinatal mortality was 13.3% in early-onset preeclampsia. Dysfunction and hepatic dysfunction were the main maternal complications. The gestational ages at admission and at delivery were significantly correlated with perinatal prognosis (P<0.001). Most cases received regular treatment had good prognosis.</p><p><b>CONCLUSION</b>Early-onset preeclampsia is a severe type of preeclampsia.</p>

Causally Associations of Blood Lipids Levels with COVID-19 Risk: Mendelian Randomization Study

BackgroundCoronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). It has been found that coronary artery disease (CAD) is a comorbid condition for COVID-19. As the risk factors of CAD, whether blood lipids levels are causally related to increasing susceptibility and severity of COVID-19 is still unknown. DesignWe performed two-sample Mendelian Randomization (MR) analyses to explore whether dyslipidemia, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), triglyceride (TG) and total cholesterol (TC) were causally related to COVID-19 risk and severity. The GWAS summary data of blood lipids involving in 188,578 individuals and dyslipidemia in a total of 53,991 individuals were used as exposures, respectively. Two COVID-19 GWASs including 1,221 infected patients and 1,610 severe patients defined as respiratory failure were employed as outcomes. Based on the MR estimates, we further carried out gene-based and gene-set analysis to explain the potential mechanism for causal effect. ResultsThe MR results showed that dyslipidemia was casually associated with the susceptibility of COVID-19 and induced 27% higher odds for COVID-19 infection (MR-IVW OR = 1.27, 95% CI: 1.08 to 1.49, p-value = 3.18 x 10-3). Moreover, the increasing level of blood TC will raise 14 % higher odds for the susceptibility of COVID-19 (MR-IVW OR = 1.14, 95% CI: 1.04 to 1.25, p-value = 5.07 x 10-3). Gene-based analysis identified that ABO gene was associated with TC and the gene-set analysis found that immune processes were involved in the risk effect of TC. ConclusionsWe obtained three conclusions: 1) Dyslipidemia is casually associated with the susceptibility of COVID-19; 2) TC is a risk factor for the susceptibility of COVID-19; 3) The different susceptibility of COVID-19 in specific blood group may be partly explained by the TC concentration in diverse ABO blood groups.