Your preoperative rehabilitation assistant: A study protocol for the impact of a telemedicine-supported preoperative home rehabilitation program on the prognosis of patients undergoing thoracoscopic surgery.

Background: Reduced cardiorespiratory fitness levels are associated with increased short-term complications after surgery, and potentially exert long-lasting effects on the postoperative lives, work and educational pursuits of patients. Currently, research suggests that lifestyle interventions, such as preoperative physical exercise undertaken by patients themselves, may improve patients' cardiopulmonary fitness and reduce post-operative complications. This study aims to investigate the effectiveness and feasibility of a remote medical supervision model for prehabilitation exercise in patients undergoing thoracoscopic lung tumour resection surgery. Methods/Design: All enrolled patients will participate in a 4-week pre-operative exercise intervention to improve their cardiorespiratory fitness. During this period, patients will wear wearable devices and exercise at home based on exercise prescriptions. The exercise prescription comprises aerobic exercise (three times a week or more), muscle strengthening exercise (twice a week or more), and respiratory muscle exercise (once a day). The primary aim is to investigate whether baseline VO2max could be improved following a 4-week preoperative exercise program. Secondary objectives include changes in forced expiratory volume in 1 s and forced vital capacity, degree of acceptance of the technology, quality of life, handgrip strength, postoperative complication rate and length of hospital stay. Discussion: This study aims to evaluate the influence of preoperative prehabilitation exercises in a telemedicine active supervision mode in patients undergoing thoracoscopic lung tumour resection. As such, results of this trial might have some impact on future implementations of group- and home-based prehabilitation exercises in lung cancers. Trial registration: This study was approved by the Medical Ethics Committee of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (approval number: TJ-IRB20220564) with registration at ClinicalTrials.gov (identifier: NCT05608759).

Integrated gut microbiota and serum pharmacochemistry reveal the mechanisms of wine steaming in alleviating rhubarb diarrhea.

BACKGROUND: Long-term use of rhubarb (RH) can cause adverse gastrointestinal reactions (such as diarrhea), whereas RH steaming with wine (PRH) can alleviate RH-induced diarrhea. However, the potential material basis and mechanisms by which wine steaming alleviates diarrhea caused by RH remain unclear. PURPOSE: To reveal the potential material basis and underlying mechanisms of wine steaming in alleviating diarrhea caused by RH from the perspective of small intestinal flora and immune function. METHODS: The major anthraquinone/anthrone components were detected using high-performance liquid chromatography (HPLC). Constipation model mice were replicated using loperamide hydrochloride and were administered RH and PRH for six consecutive weeks. Histopathological observation (duodenum, jejunum, and ileum) was performed using hematoxylin-eosin (HE) staining, and the serum levels of inflammatory cytokines, immunoglobulin G (IgG), and immunoglobulin A (IgA) were examined. CD4+, CD8+, and Treg cells counts in peripheral blood were determined using flow cytometry; The protein expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa-B (NF-κB) was determined using immunohistochemistry (IHC) and western blot (WB). The small intestine contents and feces were analyzed by 16 S rRNA sequencing and the contents of short chain fatty acids (SCFAs) in feces were determined using gas chromatography-mass spectrometry (GC-MS). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the blood absorption compounds and endogenous metabolites. RESULTS: The levels of the major anthraquinone/anthrone components were decreased in PRH. RH and PRH both increased the wet fecal weight at 12 h (WFW-12) and fecal water rate (FWR), alleviated the dry and black fecal morphology, and relieved small intestine injuries in the second week. In the fourth week, although RH and PRH alleviated the abnormal levels of indicators in the model mice (fecal water rate, immune cells percentage, and TLR4/NF-κB expression), minor small intestinal damage was observed. Compared to that at the fourth week, RH and PRH increased the levels of WFW-12, FWR, inflammatory cytokines, and TLR4/NF-κB expression, and decreased the levels of IgG/IgA and immune cells with extended administration (sixth week). Further, damage to the small intestine worsened (severe ileal damage) and different degrees of loose stools were observed in RH- and PRH-administered mice in the sixth week. Compared with those in the control group, the levels of WFW-12, FWR, inflammatory cytokines, TLR4/NF-κB expression, IgG/IgA, and immune cell percentage were significantly different in the RH-H and PRH-H mice at the sixth week (except for CD8+in PRH-H). Further, RH and PRH disturbed the gut microbiota (GM) (Lactobacillus and Dubosiella decreased, Aerococcus and Corynebacterium increased) and obviously reduced the content of SCFAs (acetic acid, butyric acid, and isobutyric acid). However, almost all the results indicated a lower impact of PRH than that of RH. Metabolic pathways mainly involved in glycerophospholipid metabolism were identified along with a total of 21 blood absorption components, including anthraquinones, anthrones, flavanols, and tannins. The correlation analysis showed a positive correlation of pathogenic bacteria (Aerococcus and Corynebacterium) with inflammatory cytokines, TLR4/NF-κB, LysoPC(20:0/0:0), and PE (16:0/20:4(8Z,11Z,14Z,17Z)) and a negative correlation with immune cells and SCFAs (acetic acid and isobutyric acid); however, the opposite results were observed for beneficial bacteria (Lactobacillus and Dubosiella). CONCLUSION: Overall, PRH can alleviate RH-induced diarrhea by recovering the GM imbalance and abnormal levels of GM-mediated SCFAs, alleviating the decrease in cellular immune function and abnormal expression of TLR4/NF-κB, thereby suppressing the release of inflammatory factors, possibly, through its lower content of anthraquinones. This study explored for the first time the processing mechanism of wine steaming in alleviating RH-induced diarrhea from the aspects of small intestinal flora and small intestinal immune function.

The TET3 inflammasome senses unique long HSV-1 proteins for virus particle budding from the nucleus.

Inflammasomes play important roles in resisting infections caused by various pathogens. HSV-1 is a highly contagious virus among humans. The process by which HSV-1 particles bud from the nucleus is unique to herpes viruses, but the specific mechanism is still unclear. Here, we screened genes involved in HSV-1 replication. We found that TET3 plays an essential role in HSV-1 infection. TET3 recognizes the UL proteins of HSV-1 and, upon activation, can directly bind to caspase-1 to activate an ASC-independent inflammasome in the nucleus. The subsequent cleavage of GSDMD in the nucleus is crucial for the budding of HSV-1 particles from the nucleus. Inhibiting the perforation ability of GSDMD on the nuclear membrane can significantly reduce the maturation and spread of HSV-1. Our results may provide a new approach for the treatment of HSV-1 in the future.

Joint Association of Combined Healthy Lifestyle Factors and Hearing Loss with Cognitive Impairment in China.

BACKGROUND: Hearing loss and lifestyle factors have been associated with cognitive impairment. We aimed to explore the joint association of combined healthy lifestyle factors and hearing loss with cognitive impairment, which has been scarcely studied. METHODS: This baseline study used data from the CHOICE-Cohort study (Chinese Hearing Solution for Improvement of Cognition in Elders). Hearing loss was assessed by the better-ear pure-tone average (BPTA). A composite healthy lifestyle score was built based on never smoking, never drinking, regular physical activity, and balanced diet. Cognitive impairment was diagnosed by the Mini-Mental State Examination (MMSE) score of less than 24. RESULTS: We included 17057 participants aged 60 years or older in China (mean age 69.8 [SD 6.2] years, 55.7% female). Among the participants, 48.3% (n=8234) had mild hearing loss, and 25.8% (n=4395) had moderate or greater hearing loss. The proportion of participants with healthy lifestyle scores of 0-1, 2, 3, and 4 was 14.9% (n=2539), 29.3% (n=5000), 37.4% (n=6386), and 18.4% (n=3132), respectively. 29.6% (n=5057) participants had cognitive impairment. When compared to those with normal hearing and healthy lifestyle (scores of 3-4), participants with hearing loss plus unhealthy lifestyle (scores of 0-2) exhibited approximately twofold increased risk of cognitive impairment (OR=1.92, 95% CI 1.70-2.18). Conversely, the risk was greatly attenuated by adherence to healthy lifestyle in individuals with hearing loss (OR=1.57, 95% CI 1.40-1.76). CONCLUSIONS: Our findings demonstrated adherence to a broad range of healthy lifestyle factors was associated with a significantly lower risk of cognitive impairment among participants with hearing loss.

Lipocalin-2 aggravates blood-brain barrier dysfunction after intravenous thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway.

BACKGROUND: Disruption of the blood-brain barrier (BBB) is a major contributor to hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT). However, the clinical therapies aimed at BBB protection after IVT remain limited. METHODS: One hundred patients with AIS who underwent IVT were enrolled (42 with HT and 58 without HT 24 h after IVT). Based on the cytokine chip, the serum levels of several AIS-related proteins, including LCN2, ferritin, matrix metalloproteinase-3, vascular endothelial-derived growth factor, and X-linked inhibitor of apoptosis, were detected upon admission, and their associations with HT were analyzed. After finding that LCN2 was related to HT in patients with IVT, we clarified whether the modulation of LCN2 influenced BBB dysfunction and HT after thrombolysis and investigated the potential mechanism. RESULTS: In patients with AIS following IVT, logistic regression analysis showed that baseline serum LCN2 (p = 0.023) and ferritin (p = 0.046) levels were independently associated with HT. A positive correlation between serum LCN2 and ferritin levels was identified in patients with HT. In experimental studies, recombinant LCN2 (rLCN2) significantly aggravated BBB dysfunction and HT in the thromboembolic stroke rats after thrombolysis, whereas LCN2 inhibition by ZINC006440089 exerted opposite effects. Further mechanistic studies showed that, LCN2 promoted endothelial cell ferroptosis, accompanied by the induction of high mobility group box 1 (HMGB1) and the inhibition of nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Ferroptosis inhibitor ferrostatin-1 (fer-1) significantly restricted the LCN2-mediated BBB disruption. Transfection of LCN2 and HMGB1 siRNA inhibited the endothelial cell ferroptosis, and this effects was reversed by Nrf2 siRNA. CONCLUSION: LCN2 aggravated BBB disruption after thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway, this may provide a promising therapeutic target for the prevention of HT after IVT.

Piperidine-based ionic liquid additive with electrostatic shielding and redox activity enabling advanced lithium-oxygen batteries.

Here, we propose a piperidine-based ionic liquid additive. The electrostatic shielding effect of the piperidine cation (PP13+) effectively inhibits the growth of lithium dendrites. Simultaneously, the redox activity of the bromine anion synergistically reduces the overpotential. This approach significantly improves the cycling performance of lithium-oxygen batteries.

The Use of Multifamily Discharge Preparation Groups in the Discharge Process of Patients with Schizophrenia.

Background: After acute treatment, patients with schizophrenia return to their original living environment for further rehabilitation, which not only determines the quality of life of the patients and their families but also has an important impact on society. However, patients often find it difficult to adapt to changes in the environment when they are discharged from the hospital. This may be related to the incompleteness of China's mental health service system, as many services for schizophrenia patients are only in the treatment stage. In China, schizophrenia is traditionally associated with poor moral quality, and patients find it difficult to obtain support. Many patients have trouble reintegrating into the community after treatment. Schizophrenic multifamily teams gather families affected by the same illness and pain together to promote healing together in an environment that allows mutual sharing, understanding and transparency, maximizes the use of family resources for support, improves discharge readiness, and better deals with post-discharge recovery. Methods: The multifamily group intervention method was used to improve the motivation of the patients' family motivation as well as the discharge readiness and self-efficacy of the patient. Results: After the intervention, the motivation of the family and discharge readiness of the patient were improved compared with that of the baseline period; however, the improvement was not significant. The self-efficacy of the patients was significantly improved (P=0.042). Conclusions: In the discharge preparation of schizophrenia patients, multifamily teams can be used to help patients and their families share resources, enhance support and prepare for discharge. Patients will have better support following discharge for recovery in the community. Additional consideration should be given to the impact of the environment on patient services, and the evaluation of the service process is key to continuously improving the service effect.

Determining nine fasciolicides and three metabolite residues in milk and infant formula using solid-phase extraction and liquid chromatography-tandem mass spectrometry.

A new sensitive method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for nine fasciolicides (closantel, rafoxanide, oxyclozanide, niclosamide, nitroxinil, ioxynil, 4-nitro-3-(trifluoromethyl)phenol, salicylanilide, and triclabendazole) and three metabolite residues (ketotriclabnedazole, triclabendazole sulfone, and triclabendazole sulfoxide) in milk and infant formula was established. The samples were extracted and purified through solid-phase extraction and analyzed using LC-MS/MS. The proposed method demonstrated high accuracy (the average recoveries ranged from 70.5 % to 107.4 %) and high sensitivity (the limits of quantification ranged from 1.0 to 25.0 µg/kg). This method was successfully applied to determine nine fasciolicides and three metabolite residues in 45 milk and infant formula, providing technical support for the safety and quality evaluation of dairy products.

Elucidating the interaction of rhizosphere microorganisms and environmental factors influencing the quality of Polygonatum kingianum Coll. et Hemsl.

Polygonatum kingianum Collett & Hemsl., is one of the most important traditional Chinese medicines in China. The purpose of this study is to investigate the relationship between herb quality and microbial-soil variables, while also examining the composition and structure of the rhizosphere microbial community in Polygonatum kingianum, the ultimate goal is to provide a scientific approach to enhancing the quality of P. kingianum. Illumina NovaSeq technology unlocks comprehensive genetic variation and biological functionality through high-throughput sequencing. And in this study it was used to analyze the rhizosphere microbial communities in the soils of five P. kingianum planting areas. Conventional techniques were used to measure the organic elements, pH, and organic matter content. The active ingredient content of P. kingianum was identified by High Performance Liquid Chromatography (HPLC) and Colorimetry. A total of 12,715 bacterial and 5487 fungal Operational Taxonomic Units (OTU) were obtained and taxonomically categorized into 81 and 7 different phyla. Proteobacteria, Bacteroidetes, and Acidobacteriae were the dominant bacterial phyla Ascomycota and Basidiomycota were the dominat fungal phyla. The key predictors for bacterial community structure included hydrolysable nitrogen and available potassium, while for altering fungal community structure, soil organic carbon content (OCC), total nitrogen content (TNC), and total potassium content (TPOC) were the main influencing factors. Bryobacter and Candidatus Solibacter may indirectly increase the polysaccharide content of P. kingianum, and can be developed as potential Plant Growth Promoting Rhizobacteria (PGPR). This study has confirmed the differences in the soil and microorganisms of different origins of P. kingianum, and their close association with its active ingredients. And it also broadens the idea of studying the link between plants and microorganisms.

Efficacy of ultrasound-guided second serratus anterior plane block on postoperative quality of recovery and analgesia after video-assisted thoracic surgery: a randomized, triple-blind, placebo-controlled study.

Background: Despite widespread application of minimally invasive video-assisted thoracic surgery (VATS), postoperative pain following this procedure is still a constant clinical challenge. Serratus anterior plane (SAP) block is one of the regional analgesic techniques with promising outcomes. However, due to the limited duration of action, optimal analgesia is often not achieved with a single injection. We tested whether in patients who have been subjected to routine SAP block under preoperative anesthesia, the addition of a second SAP block 24 hours after surgery, improves quality of recovery, lowers postoperative opioid consumption, and reduces the prevalence of chronic pain. Methods: The present study is a single institutional, prospective, randomized, triple-blinded, placebo-controlled study. Ninety patients undergoing VATS from January 2022 to April 2022 were randomized at 1:1 ratio to receive ultrasound-guided second SAP block with 15 mL 0.375% ropivacaine (SAP block group) or 15 mL normal saline (control group) 24 hours after both groups received routine SAP block with 15 mL 0.375% ropivacaine. The primary outcome was quality of patient recovery, measured using 40-item quality of recovery questionnaire (QoR-40) at postoperative day 2 (POD 2). Secondary outcomes included: postoperative pain scores at rest, postoperative opioid consumptions, number of times that patient controlled analgesia (PCA) pump button was pressed, perioperative complications and adverse effects, prevalence of chronic pain at 2nd and 3rd month postoperatively, and length of hospital stay (LOS). Results: A total of 83 patients completed the study: 43 patients in SAP block group and 40 patients in the control group. The global QoR-40 scores on POD 2 and POD 3 were significantly higher among SAP block group patients (180.07±11.34, 182.09±8.20) compared with the control group (172.18±6.15, 177.50±6.94) (P=0.01, P=0.008) respectively. Postoperative pain scores, opioid consumptions and incidence of postoperative nausea and vomiting were significantly lower among patients in SAP block group versus control group. There were no statistically significant differences in perioperative complications and LOS between the two groups. The prevalence of chronic pain at the 2nd and 3rd month postoperatively for patients in SAP block group and control group was 16.3%, 14%, and 32.5%, 27.5% respectively. Conclusions: In patients undergoing VATS, application of ultrasound-guided second SAP block 24 hours after surgery improved postoperative quality of life, reduced opioid consumption and related side effects, and lowered the prevalence of chronic pain.

Cellular senescence: A novel therapeutic target for central nervous system diseases.

The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro, is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury).

[Analysis of current situation of outcome indicators in randomized controlled trials on traditional Chinese medicine in treatment of Alzheimer's disease].

This study aims to analyze the current situation of outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment for Alzheimer's disease(AD), so as to provide a reference for establishing a core indicator set in this field. The researchers systematically searched CNKI, Wanfang, VIP, Sino Med, EMbase, PubMed, Medline, and Cochrane Library. Independent screening of literature and extraction of information was conducted according to the inclusion and exclusion criteria. In addition, the Ro B 2. 0 tool was used for bias risk assessment. A total of 78 RCTs were included, involving 6 379 patients,with 122 kinds of outcome indicators. According to functional attributes, the outcome indicators could be categorized into seven groups:TCM diseases(3 kinds, 13 times), symptoms and signs(26 kinds, 196 times), physical and chemical tests(68 kinds, 149 times),qua-lity of life(1 kind, 2 times), long-term prognosis(2 kinds, 2 times), economic evaluation(0 kind), safety events(21 kinds,194 times), and other indicators(1 kind, 1 time). The results show that the literature evaluation of RCTs of TCM treatment for AD is generally risky, and there are some problems in the selection of outcome indicators, such as lack of TCM characteristics, insignificant distinction between primary and secondary outcome indicators, lack of long-term prognosis and economic evaluation indicators, and non-standard safety event reports. It is suggested that future researchers should establish a core indicator set for AD that highlights the characteristics of TCM and then work to improve the quality of clinical trials.

Prediction of pure carbon crystals with intrinsic antiferromagnetism: polymerized from C20 fullerenes.

Pure carbon materials with magnetic properties have attracted considerable research interest due to their advantages over traditional magnetic materials. Nevertheless, such materials are exceedingly rare. Disrupting the Kekulé valence structures in carbon materials potentially leads to the emergence of magnetism. In this study, using first principles calculations, we developed a range of pure carbon allotropes derived from the smallest fullerene C20 which potentially disrupts the Kekulé valence structures after polymerization. The results indicate that some of the allotropes disrupting the Kekulé valence structures exhibit intrinsic antiferromagnetic ordering, and the magnetism originates from the presence of isolated three-fold coordinated C atoms. The other allotropes adhering to the Kekulé valence structures show non-magnetism with all three-fold coordinated C atoms forming dimers. In all magnetic polymers, magnetism arises from unpaired electrons on the isolated three-fold coordinated carbon atoms, with magnetic moments of about 0.40µB at these sites. The adsorption of dopant atoms can significantly alter the magnetic properties of polymers, for instance, the C20-71 polymer with Immm symmetry undergoes a transition from non-magnetic to anti-magnetic ordering upon adsorption of hydrogen atoms. Electronic calculations indicate that these polymers display a range of electronic properties, encompassing both metallic and semiconducting characteristics. Notably, certain magnetic phases exhibit superhard properties, with the hardness value exceeding 40 GPa. This study presents a potential method for designing magnetic carbon materials. Specifically, certain compounds address the gap in magnetic superhard materials composed of light elements, and can be utilized in the field of spintronics where traditional superhard materials are unsuitable.

Single-cell sequencing: Current applications in various tuberculosis specimen types.

Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis (M.tb) and responsible for millions of deaths worldwide each year. It has a complex pathogenesis that primarily affects the lungs but can also impact systemic organs. In recent years, single-cell sequencing technology has been utilized to characterize the composition and proportion of immune cell subpopulations associated with the pathogenesis of TB disease since it has a high resolution that surpasses conventional techniques. This paper reviews the current use of single-cell sequencing technologies in TB research and their application in analysing specimens from various sources of TB, primarily peripheral blood and lung specimens. The focus is on how these technologies can reveal dynamic changes in immune cell subpopulations, genes and proteins during disease progression after M.tb infection. Based on the current findings, single-cell sequencing has significant potential clinical value in the field of TB research. Next, we will focus on the real-world applications of the potential targets identified through single-cell sequencing for diagnostics, therapeutics and the development of effective vaccines.

Hla protein expression and artesunate prevented mice from further damage caused by Staphylococcus aureus pneumonia.

The laboratory standard MRSA strain WHO-2 and clinical isolate S1 were used to establish a pneumonia infection model. The results showed that methicillin increased the expression of Hla and PVL protein at subminimum inhibitory concentration, while artesunate decreased the secretion of Hla and PVL protein. Artesunate alone reduced hemolysin expression and reversed methicillin-induced increases in Hla and PVL proteins. In addition, the study found that the combination of artesunate and methicillin had the best therapeutic effect, with survival rates of 70 % and 40 % at seven days, respectively (corresponding to the WHO-2 and S1 strains). The combination treatment was able to reduce cell mortality, showing a 65 % and 46 % reduction in cell mortality, respectively. The study also found that the combination therapy decreased the expression of alpha-hemolysin and pantone valentin leukin in the culture medium and significantly reduced the activation of NF-kB. This is caused by a significant decrease in the expression of inflammatory factors.

Supramolecular interactions in cocrystals of benzoic acid derivatives with selective COX-2 inhibitor etoricoxib.

The structures of three 1:1 cocrystal forms of etoricoxib {ETR; systematic name: 5-chloro-2-(6-methylpyridin-3-yl)-3-[4-(methylsulfonyl)phenyl]pyridine, C18H15ClN2O2S} have been synthesized and characterized by single-crystal X-ray diffraction; these are etoricoxib-benzoic acid (1/1), C18H15ClN2O2S·C7H6O2 (ETR-Bz), etoricoxib-4-fluorobenzoic acid (1/1), C18H15ClN2O2S·C7H5FO2 (ETR-PFB), and etoricoxib-4-nitrobenzoic acid (1/1), C18H15ClN2O2S·C7H5NO4 (ETR-PNB). Powder X-ray diffraction and thermal differential scanning calorimetry-thermogravimetry (DSC-TG) techniques were also used to characterize these multicomponent systems. Due to the influence of the corresponding acids, ETR shows different conformations. Furthermore, the energetic contributions of the supramolecular motifs have been established by energy framework studies of the stabilizing interaction forces and are consistent with the thermal stability of the cocrystals.

Liver injury protection of Artemisia stechmanniana besser through PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia stechmanniana Besser, one of the most prevalent botanical medicines in Chinese, has been traditionally used for hepatitis treatment. However, the bioactive components and pharmacological mechanism on alcohol-induced liver injury remains unclear. AIM OF THE STUDY: To investigate the effect of A. stechmanniana on alcohol-induced liver damage, and further explore its mechanism. MATERIALS AND METHODS: Phytochemical isolation and structural identification were used to determine the chemical constituents of A. stechmanniana. Then, the alcohol-induced liver damage animal and cell model were established to evaluate its hepato-protective potential. Network pharmacology, molecular docking and bioinformatics were integrated to explore the mechanism and then the prediction was further supported by experiments. Moreover, both compounds were subjected to ADMET prediction through relevant databases. RESULTS: 28 compounds were isolated from the most bioactive fraction, ethyl acetate extract A. stechmanniana, in which five compounds (abietic acid, oplopanone, oplodiol, hydroxydavanone, linoleic acid) could attenuate mice livers damage caused by alcohol intragastration, reduce the degree of oxidative stress, and serum AST and ALT, respectively. Furthermore, abietic acid and hydroxydavanone exhibited best protective effect against alcohol-stimulated L-O2 cells injury among five bioactive compounds. Network pharmacology and bioinformatics analysis suggested that abietic acid and hydroxydavanone exhibiting drug likeliness characteristics, were the principal active compounds acting on liver injury treatment, primarily impacting to cell proliferation, oxidative stress and inflammation-related PI3K-AKT signaling pathways. Both of them displayed strong binding energies with five target proteins (HRAS, HSP90AA1, AKT1, CDK2, NF-κB p65) via molecular docking. Western blotting results further supported the predication with up-regulation of protein expressions of CDK2, and down-regulation of HRAS, HSP90AA1, AKT1, NF-κB p65 by abietic acid and hydroxydavanone. CONCLUSION: Alcohol-induced liver injury protection by A. stechmanniana was verified in vivo and in vitro expanded its traditional use, and its two major bioactive compounds, abietic acid and hydroxydavanone exerted hepatoprotective effect through the regulation of PI3K-AKT signaling pathway.

Clinical features associated with maternal uniparental disomy for chromosome 6.

BACKGROUND: Maternal uniparental disomy for chromosome 6 (upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat) has been previously reported to cause intrauterine growth restriction (IUGR), but the specific clinical phenotype has not been defined. Based on clinical data from two new cases and patients from the literature, specific phenotypes and mechanisms will be discussed further. CASE PRESENTATION: In case 1, a maternal isodisomy mixed with a heterodisomy was found on chromosome 6, including a regional absence of heterozygosity between 6q23.3 and 6q27. In case 2, a homozygous SCUBE3 mutation and upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat, involving the 6p21.1-25.1 region were found. Clinical data related to upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat were also reviewed. Of all the 21 reported cases with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat (including our 2 cases), 18 (85.7%) presented IUGR. CONCLUSIONS: The phenotypes of the two newly identified patients with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat further suggest that IUGR is associated with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and case 2 is the first reported upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat patient with a homozygous SCUBE3 gene mutation. However, the specific phenotypes involved in upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and the related mechanisms need to be further studied.

Prognostic Nutritional Index as a Prognostic Indicator for the Occurrence of Postoperative Complications in Patients with Esophageal Squamous Cell Carcinoma Following Neoadjuvant Immunochemotherapy.

Background & Aims: The objective of this study was to evaluate the prognostic nutritional index (PNI) as a predictor of short-term postoperative complications in esophageal squamous cell carcinoma patients undergoing neoadjuvant immunochemotherapy. Methods: Clinical data were collected from 77 patients undergoing radical esophageal cancer surgery after neoadjuvant immunochemotherapy at Tongji Hospital from January 2022 to January 2023. The receiver operating characteristic curve (ROC) was utilized to establish the optimal cut-off point for the PNI. Subsequently, patients were stratified into low and high PNI groups according to this cut-off point, and comparisons were made between the two groups in terms of clinical data and postoperative complications. Results: Out of the 77 patients included in the study, 31 were categorized in the low PNI group and 46 in the high PNI group, with a defined cutoff point of 47.38. Significant statistical variances were noted in the occurrence rates of general complications (P < 0.001), pulmonary infections (P < 0.001), and anastomotic fistula (P = 0.034) between the two groups. The low PNI group displayed elevated rates of these complications in comparison to the high PNI group. Conclusion: The research findings indicate that preoperative nutritional assessment using the PNI can effectively predict short-term postoperative complications in esophageal squamous cell carcinoma patients who have undergone neoadjuvant therapy. Furthermore, the results suggest that implementing nutritional interventions for patients with moderate-to-severe malnutrition, as indicated by preoperative PNI evaluation, may help reduce the incidence of postoperative complications.