Tryptophan in the mouse diet is essential for embryo implantation and decidualization.

Introduction: Nutritional deficiency occurs frequently during pregnancy and breastfeeding. Tryptophan (Trp), an essential amino acid which is critical for protein synthesis, serves as the precursor for serotonin, melatonin, and kynurenine (Kyn). The imbalance between serotonin and kynurenine pathways in Trp metabolism is closely related to inflammation and depression. This study assessed the effects of Trp deficiency on mouse early pregnancy. Methods: Embryo implantation and decidualization were analyzed after female mice had been fed diets containing 0.2% Trp (for the control group), 0.062% Trp (for the low Trp group) and 0% Trp (for the Trp-free group) for two months. The uteri of the mice were collected on days 4, 5, and 8 of pregnancy for further analysis. Results: On day 8 of pregnancy, the number of implantation sites were found to be similar between the control and the low Trp groups. However, no implantation sites were detected in the Trp-free group. On day 5 of pregnancy, plane polarity- and decidualization-related molecules showed abnormal expression pattern in the Trp-free group. On day 4 of pregnancy, there was no significant difference in uterine receptivity molecules between the low-Trp group and the control group, but uterine receptivity was abnormal in the Trp-free group. At implantation sites of the Trp-free group, IDO and AHR levels were markedly elevated. This potentially increased levels of Kyn, 2-hydroxy estradiol, and 4-hydroxy estradiol to affect decidualization. Conclusions: Trp-free diet may impair decidualization via the IDO-KYN-AHR pathway.

Biodistribution and preclinical safety profile of legubicin: A novel conjugate of doxorubicin and a legumain-cleavable peptide linker.

Legubicin is a novel conjugate of doxorubicin and a legumain-cleavable peptide linker. It has been developed to ameliorate the side effects of doxorubicin. Biodistribution in tumor-bearing mice, acute tolerance, and potential systemic toxic effects in Sprague-Dawley rats and beagle dogs of legubicin were assessed. Legubicin exists mainly as a protein complex in plasma after entering the circulation. Compared with conventional doxorubicin at an equal molar dose in mice, we found higher exposure to doxorubicin in tumor (approximately 1.7-fold increase) while lower exposure in normal tissues (an ~3.26-, 3.46-, and 1.29-fold reduction in heart, kidney, and plasma, respectively) in tumor-bearing mice after intravenous injection of legubicin. The acute maximum tolerance dose (MTD) of legubicin was >16 mg/kg doxorubicin equivalent in female rats, 11 mg/kg doxorubicin equivalent in male rats (LD50 of conventional doxorubicin is 10.51 mg/kg), and >8 mg/kg doxorubicin equivalent in dogs (MTD of conventional doxorubicin is 1.5 mg/kg). Four-week repeat-dose toxicity studies of intravenous legubicin were conducted in rats (5, 10, and 25 mg/kg/dose once weekly) and dogs (3/1.5, 10/5, and 20/10 mg/kg/dose once weekly); the dose levels were reduced from the second dose due to intolerable legubicin-associated toxicity at 20 mg/kg. Major organs of toxicity included the gastrointestinal tract, lymphoid and hematopoietic organs, kidney, skin, liver, reproductive organs, and peripheral nerves, which are all associated with doxorubicin. However, cardiotoxicity was only noted at MTD dose levels. Altogether, our results confirm an improved safety profile of legubicin over conventional doxorubicin and support its clinical benefit for treating cancer.

Head-to-head comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT for the evaluation of tonsil cancer and lymph node metastases: a single-centre retrospective study.

BACKGROUND: This study aimed to compare the diagnostic value of [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT imaging for primary lesions and metastatic lymph nodes in patients with tonsil cancer. METHOD: Twenty-one tonsil cancer patients who underwent [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT scans within two weeks in our centre were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of the two tracers were compared by using the Mann‒Whitney U test. In addition, the sensitivity, specificity, and accuracy of the two methods for diagnosing metastatic lymph nodes were analysed. RESULTS: In detecting primary lesions, the efficiency was higher for [68 Ga]Ga-DOTA-FAPI-04 PET/CT (20/22) than for [18F]FDG PET/CT (9/22). Although [68 Ga]Ga-DOTA-FAPI-04 uptake (SUVmax, 5.03 ± 4.06) was lower than [18F]FDG uptake (SUVmax, 7.90 ± 4.84, P = 0.006), [68 Ga]Ga-DOTA-FAPI-04 improved the distinction between the primary tumor and contralateral normal tonsillar tissue. The TBR was significantly higher for [68 Ga]Ga-DOTA-FAPI-04 PET/CT (3.19 ± 2.06) than for [18F]FDG PET/CT (1.89 ± 1.80) (p < 0.001). In lymph node analysis, SUVmax and TBR were not significantly different between [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT (7.67 ± 5.88 vs. 8.36 ± 6.15, P = 0.498 and 5.56 ± 4.02 vs. 4.26 ± 3.16, P = 0.123, respectively). The specificity and accuracy of [68 Ga]Ga-DOTA-FAPI-04 PET/CT were higher than those of [18F]FDG PET/CT in diagnosing metastatic cervical lymph nodes (all P < 0.05). CONCLUSION: The availability of [68 Ga]Ga-DOTA-FAPI-04 complements the diagnostic results of [18F]FDG by improving the detection rate of primary lesions and the diagnostic accuracy of cervical metastatic lymph nodes in tonsil cancer compared to [18F]FDG.

Crown ether-like octanuclear molybdenum(V) clusters for cation binding and gas adsorption.

Octanuclear polyoxomolybdenum-based porous materials, Na8[Mo8O8(µ2-O)8(µ2-OH)8(3-apz)4]2·26H2O (1, 3-Hapz = 3-aminopyrazole), K8[Mo8O8(µ2-O)8(µ2-OH)8(3-apz)4]2·7H2O (2) and (NH4)4[Mo8O8(µ2-O)8(µ2-OH)4(3-apz)8]·20.5H2O (3), have been successfully synthesized by a hydrothermal method and fully characterized. X-ray structural analyses show that microporous materials 1-3 contain round pores formed by octanuclear molybdenum-oxygen groups connected sequentially with pore sizes of 4.0, 4.0, and 4.8 Å, respectively. Both 1 and 2 are composed of two {Mo8} rings, which are connected by strong intramolecular hydrogen bonds between bridging hydroxy groups and oxygen atoms to form dimeric structures. The central pores in 1 and 2 are occupied by Na+ and K+, respectively, while they are empty in 3. This reflects the structural expansion and contraction effects induced by different cations. Through intermolecular stacking, 1-3 also exhibit channels with sizes of 14.0 × 6.4, 4.6 × 2.6, and 5.4 × 5.4 Å, respectively, which were used for the studies of gas adsorption. The results show that 1-3 can selectively adsorb CO2 and O2, including the empty hole in 3, while they show little or no affinity for gases H2, N2, and CH4. Moreover, an additional polyoxomolybdenum-based species (Mo8O26)n·4n(3-H2apz) (4) has been obtained with protonated 3-aminopyrazole in the absence of a reducing agent, which can serve as an intermediate for the polyoxomolybdenum-based porous products.

The phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity of Forsythiae Fructus: An updated systematic review.

Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications.

Developing and validating a nomogram for penile cancer survival: A comprehensive study based on SEER and Chinese data.

OBJECTIVE: The primary aim of this study was to create a nomogram for predicting survival outcomes in penile cancer patients, utilizing data from the Surveillance, Epidemiology, and End Results (SEER) and a Chinese organization. METHODS: Our study involved a cohort of 5744 patients diagnosed with penile cancer from the SEER database, spanning from 2004 to 2019. In addition, 103 patients with penile cancer from Sun Yat-sen Memorial Hospital of Sun Yat-sen University were included during the same period. Based on the results of regression analysis, a nomogram is constructed and validated internally and externally. The predictive performance of the model was evaluated by concordance index (c-index), area under the curve, decision curve analysis, and calibration curve, in internal and external datasets. Finally, the prediction efficiency is compared with the TNM staging model. RESULTS: A total of 3154 penile patients were randomly divided into the training group and the internal validation group at a ratio of 2:1. Nine independent risk factors were identified, including age, race, marital status, tumor grade, histology, TNM stage, and the surgical approach. Based on these factors, a nomogram was constructed to predict OS. The nomogram demonstrated relatively better consistency, predictive accuracy, and clinical relevance, with a c-index over 0.73 (in the training cohort, the validation cohort, and externally validation cohort.) These evaluation indexes are far better than the TNM staging system. CONCLUSION: Penile cancer, often overlooked in research, has lacked detailed investigative focus and guidelines. This study stands as the first to validate penile cancer prognosis using extensive data from the SEER database, supplemented by data from our own institution. Our findings equip surgeons with an essential tool to predict the prognosis of penile cancer better suited than TNM, thereby enhancing clinical decision-making processes.

The HLA-I landscape confers prognosis and antitumor immunity in breast cancer.

Breast cancer is a highly heterogeneous disease with varied subtypes, prognoses and therapeutic responsiveness. Human leukocyte antigen class I (HLA-I) shapes the immunity and thereby influences the outcome of breast cancer. However, the implications of HLA-I variations in breast cancer remain poorly understood. In this study, we established a multiomics cohort of 1156 Chinese breast cancer patients for HLA-I investigation. We calculated four important HLA-I indicators in each individual, including HLA-I expression level, somatic HLA-I loss of heterozygosity (LOH), HLA-I evolutionary divergence (HED) and peptide-binding promiscuity (Pr). Then, we evaluated their distribution and prognostic significance in breast cancer subtypes. We found that the four breast cancer subtypes had distinct features of HLA-I indicators. Increased expression of HLA-I and LOH were enriched in triple-negative breast cancer (TNBC), while Pr was relatively higher in hot tumors within TNBCs. In particular, a higher Pr indicated a better prognosis in TNBCs by regulating the infiltration of immune cells and the expression of immune molecules. Using the matched genomic and transcriptomic data, we found that mismatch repair deficiency-related mutational signature and pathways were enriched in low-Pr TNBCs, suggesting that targeting mismatch repair deficiency for synthetic lethality might be promising therapy for these patients. In conclusion, we presented an overview of HLA-I indicators in breast cancer and provided hints for precision treatment for low-Pr TNBCs.

Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study.

BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Genetic interactions reveal distinct biological and therapeutic implications in breast cancer.

Co-occurrence and mutual exclusivity of genomic alterations may reflect the existence of genetic interactions, potentially shaping distinct biological phenotypes and impacting therapeutic response in breast cancer. However, our understanding of them remains limited. Herein, we investigate a large-scale multi-omics cohort (n = 873) and a real-world clinical sequencing cohort (n = 4,405) including several clinical trials with detailed treatment outcomes and perform functional validation in patient-derived organoids, tumor fragments, and in vivo models. Through this comprehensive approach, we construct a network comprising co-alterations and mutually exclusive events and characterize their therapeutic potential and underlying biological basis. Notably, we identify associations between TP53mut-AURKAamp and endocrine therapy resistance, germline BRCA1mut-MYCamp and improved sensitivity to PARP inhibitors, and TP53mut-MYBamp and immunotherapy resistance. Furthermore, we reveal that precision treatment strategies informed by co-alterations hold promise to improve patient outcomes. Our study highlights the significance of genetic interactions in guiding genome-informed treatment decisions beyond single driver alterations.

Lipase and pH-responsive diblock copolymers featuring fluorocarbon and carboxyl betaine for methicillin-resistant staphylococcus aureus infections.

The emergence of multidrug-resistant bacteria along with their resilient biofilms necessitates the development of creative antimicrobial remedies. We designed versatile fluorinated polymer micelles with surface-charge-switchable properties, demonstrating enhanced efficacy against Methicillin-Resistant Staphylococcus Aureus (MRSA) in planktonic and biofilm states. Polymethacrylate diblock copolymers with pendant fluorocarbon chains and carboxyl betaine groups were prepared using reversible addition-fragmentation chain transfer polymerization. Amphiphilic fluorinated copolymers self-assembled into micelles, encapsulating ciprofloxacin in their cores (CIP@FCBMs) for antibacterial and antibiofilm applications. As a control, fluorine-free copolymer micelles loaded with ciprofloxacin (CIP@BCBMs) were prepared. Although both CIP@FCBMs and CIP@BCBMs exhibited pH-responsive surface charges and lipase-triggered drug release, CIP@FCBMs exhibited powerful antimicrobial and antibiofilm activities in vitro and in vivo, attributed to superior serum stability, higher drug loading, enhanced fluorination-facilitated cellular uptake, and lipase-triggered drug release. Collectively, reversing surface charge, on-demand antibiotic release, and fluorination-mediated nanoparticles hold promise for treating bacterial infections and biofilms.

[Clinical comparative study on resection and non-resection of the fifth metatarsal to rheumatoid forefoot deformity].

OBJECTIVE: To explore clinical effect of the fifth metatarsal head excision and non-excision in rheumatoid arthritis (RA) forefoot deformity reconstruction. METHODS: Retrospective analysis was performed on 50 patients (76 feet) with moderate to severe forefoot deformity caused by RA treated from May 2015 to January 2019. According to degeneration of the fifth metatarsophalangeal joint,the fifth metatarsal head was retained or excised by wind-like forefoot reconstruction,and divided into the fifth metatarsal head preservation group (preservation group) and the fifth metatarsal head resection group (resection group). Twenty-four female patients in preservation group,aged from 47 to 81 years old with an average of (60.37±8.60) years old;the course of disease ranged from 13 to 22 years with an average of (19.00±3.06) years;body mass index (BMI) ranged from 21 to 28 kg·m-2 with an average of (23.53±2.47) kg·m-2;six patients (6 feet) with moderate hallux valgus deformity and 18 patients (30 feet) with severe hallux valgus deformity;treated with the first metatarsophalangeal joint fusion combined with the second th the fourth metatarsophalangeal joint arthroplasty and the fifth metatarsophalangeal joint cleanup. Twenty-six female patients in resection group were female,aged from 30 to 80 years old with an average of (58.53±13.70) years old;the course of disease ranged from 8 to 25 years with an average of (17.94±3.92) years;BMI raged from 20 to 28 kg·m-2 with an average of (24.60±2.03) kg·m-2;4 patients (4 feet) with moderate bunion valgus deformity and 22 patients (36 feet) with severe bunion valgus deformity;treated by the first metatarsophalangeal joint fusion combined with the second th the fifth metatarsophalangeal joint resection of the metatarsophalangeal head. Operation time and postoperative complications between two groups were observed,hallux valgus angle (HVA),intermetatarsal angles between the first and the second metatarsals (IMAFS),intermetatarsal angles between the first and fifth metatarsals (IMAFF),Japanese Society for Surgery of Foot (JSSF) score before surgery and at the latest follow-up were compared. RESULTS: Fifty patients were followed-up from 14 to 46(25.30±8.83) months in resection group and 12 to 48 with an average of (24.30±11.12) months in preservation group,while no significant difference between two groups (P>0.05). There were no significant difference in operation time and postoperative complications between two groups (P>0.05). JSSF scores,HVA,IMAFS and IMAFF in fesection group were improved from (45.09±3.35) points,(38.90±13.67) °,(12.88±1.72) °,(32.50±2.99) ° before operation to (81.60±3.27) points,(15.40±0.90),(9.06±2.27) °,(22.20±1.98) ° at the latest follow-up (P<0.05);preservation group were improved from (47.09±3.96) points,(43.30±12.65) °,(13.99±3.13) °,(33.20±6.14) ° to (83.10±3.66) points,(15.20±1.54) °,(8.99±1.02) °,(24.70±1.88) °,respectively. There were no significant difference in JSSF score,HVA,IMAFS and IMAFF between two groups before operation and the latest follow-up (P>0.05). At the latest follow-up,there were statistically significant differences in pain and deformity in JSSF scores between two groups (P<0.05). CONCLUSION: Both rheumatoid anterior foot reconstruction and anterior foot reconstruction fifth metatarsophalangeal joint debridement showed significant improvement in clinical efficacy and imaging results. Compared with rheumatoid prefoot reconstruction,the fifth metatarsophalangeal joint reconstruction for the treatment of moderate and severe deformity of rheumatoid prefoot showed better improvement in pain,but worse improvement in deformity. For the moderate to severe deformity of the forefoot caused by rheumatoid disease,patients with mild to moderate degenerative deformity of the articular surface of the fifth metatarsal phalanges may be considered for use.

Anoikis-related lncRNA signature predicts prognosis and is associated with immune infiltration in hepatocellular carcinoma.

Anoikis is a programmed cell death process triggered when cells are dislodged from the extracellular matrix. Numerous long noncoding RNAs (lncRNAs) have been identified as significant factors associated with anoikis resistance in various tumor types, including glioma, breast cancer, and bladder cancer. However, the relationship between lncRNAs and the prognosis of hepatocellular carcinoma (HCC) has received limited research attention. Further research is needed to investigate this potential link and understand the role of lncRNAs in the progression of HCC. We developed a prognostic signature based on the differential expression of lncRNAs implicated in anoikis in HCC. A co-expression network of anoikis-related mRNAs and lncRNAs was established using data obtained from The Cancer Genome Atlas (TCGA) for HCC. Cox regression analyses were conducted to formulate an anoikis-related lncRNA signature (ARlncSig) in a training cohort, which was subsequently validated in both a testing cohort and a combined dataset comprising the two cohorts. Receiver operating characteristic curves, nomograms, and decision curve analyses based on the ARlncSig score and clinical characteristics demonstrated robust predictive ability. Moreover, gene set enrichment analysis revealed significant enrichment of several immune processes in the high-risk group compared to the low-risk group. Furthermore, significant differences were observed in immune cell subpopulations, expression of immune checkpoint genes, and response to chemotherapy and immunotherapy between the high- and low-risk groups. Lastly, we validated the expression levels of the five lncRNAs included in the signature using quantitative real-time PCR. In conclusion, our ARlncSig model holds substantial predictive value regarding the prognosis of HCC patients and has the potential to provide clinical guidance for individualized immunotherapy. In this study, we obtained 36 genes associated with anoikis from the Gene Ontology and Gene Set Enrichment Analysis databases. We also identified 22 differentially expressed lncRNAs that were correlated with these genes using data from TCGA. Using Cox regression analyses, we developed an ARlncSig in a training cohort, which was then validated in both a testing cohort and a combined cohort comprising data from both cohorts. Additionally, we collected eight pairs of liver cancer tissues and adjacent tissues from the Affiliated Tumor Hospital of Nantong University for further analysis. The aim of this study was to investigate the potential of ARlncSig as a biomarker for liver cancer prognosis. The study developed a risk stratification system called ARlncSig, which uses five lncRNAs to categorize liver cancer patients into low- and high-risk groups. Patients in the high-risk group exhibited significantly lower overall survival rates compared to those in the low-risk group. The model's predictive performance was supported by various analyses including the receiver operating characteristic curve, nomogram calibration, clinical correlation analysis, and clinical decision curve. Additionally, differential analysis of immune function, immune checkpoint, response to chemotherapy, and immune cell subpopulations revealed significant differences between the high- and low-risk groups. Finally, quantitative real-time PCR validated the expression levels of the five lncRNAs. In conclusion, the ARlncSig model demonstrates critical predictive value in the prognosis of HCC patients and may provide clinical guidance for personalized immunotherapy.

A review of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology of Abri Herba (Ji-Gu-Cao).

Abri Herba (AH, known as 'Ji-Gu-Cao' in China) has a long-term medicinal history of treating cholecystitis, acute and chronic hepatitis and non-alcoholic fatty liver (NAFL) in China or other Asian countries. This review aimed to provide a comprehensive analysis of AH in terms of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology. The information involved in the study was collected from a variety of electronic resources, and >100 scientific studies have been used since 1962. Until now, 95 chemical compounds have been isolated and identified from AH and the seeds of Abrus cantoniensis Hance (ACH), including 47 terpenoids, 26 flavonoids and 4 alkaloids. The pharmacological activities of AH extracts and their pure compounds have been explored in the aspects of anti-hyperlipidaemia, hepatoprotection, anti-tumour, anti-viral, anti-bacterial, anti-inflammatory and analgesic, immunomodulation, antioxidant and others. The pharmacokinetics and excretion kinetics of AH in vivo and 15 traditional and clinical prescriptions containing AH have been sorted out, and the potential therapeutic mechanism and drug metabolism pattern were also summarised. The pods of ACH are toxic, with a median lethal dose (LD50) of 10.01 ± 2.90 g/kg (i.g.) in mice. Interestingly, the toxicity of ACH's pods and seeds decreased after boiling. However, the toxicity mechanism of pods of ACH is unclear, limiting its clinical application. Clinical trials in the future should be used to explore its safety. Meanwhile, as one of the relevant pharmacological activities, the effects and mechanism of AH on anti-hyperlipidaemia and hepatoprotection should be further studied, which is of great significance for understanding its mechanism of action in the treatment of NAFL disease and improving its clinical application.

Can 18F-FES PET Improve the Evaluation of 18F-FDG PET in Patients With Metastatic Invasive Lobular Carcinoma?

PURPOSE: Invasive lobular carcinoma (ILC) exhibits a low affinity for 18F-FDG. The estrogen receptor (ER) is commonly expressed in ILCs, suggesting a potential benefit of targeting with the ER probe 18F-FES in this patient population. The objective of this study was to evaluate the diagnostic performance of 18F-FES imaging in patients with metastatic ILC and compare it with that of 18F-FDG. METHODS: We conducted a retrospective analysis of 20 ILC patients who underwent concurrent 18F-FES and 18F-FDG PET/CT examinations in our center. 18F-FES and 18F-FDG imaging were analyzed to determine the total count of tracer-avid lesions in nonbone sites and their corresponding organ systems, assess the extent of anatomical regions involved in bone metastases, and measure the SUVmax values for both tracers. RESULTS: Among 20 ILC patients, 65 nonbone lesions were found to be distributed in 13 patients, and 16 patients were diagnosed with bone metastasis, which was distributed in 54 skeletal anatomical regions. The detection rate of 18F-FDG in nonbone lesions was higher than that of 18F-FES (57 vs 37, P < 0.001). 18F-FES demonstrated a superior ability to detect nonbone lesions in 4 patients, whereas 18F-FDG was superior in 5 patients (P > 0.05). Among 9/16 patients with bone metastasis, 18F-FES demonstrated a significant advantage in the detection of bone lesions compared with 18F-FDG (P = 0.05). Furthermore, patients with only 18F-FES-positive lesions (12/12) were administered endocrine regimens, whereas patients lacking 18F-FES uptake (2/3) predominantly received chemotherapy. CONCLUSIONS: 18F-FES is more effective than 18F-FDG in detecting bone metastasis in ILC, but it does not demonstrate a significant advantage in nonbone lesions. Additionally, the results of examination with 18F-FES have the potential to guide patient treatment plans.

Absence of association between Pfnfs1 mutation and in vitro susceptibility to lumefantrine in Plasmodium falciparum.

Artemether-lumefantrine (AL) is the most widely used antimalarial drug for treating uncomplicated falciparum malaria. This study evaluated whether the K65Q mutation in the Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) gene was associated with alternated susceptibility to lumefantrine using clinical parasite samples from Ghana and the China-Myanmar border area. Parasite isolates from the China-Myanmar border had significantly higher IC50 values to lumefantrine than parasites from Ghana. In addition, the K65 allele was significantly more prevalent in the Ghanaian parasites (34.5%) than in the China-Myanmar border samples (6.8%). However, no difference was observed in the lumefantrine IC50 value between the Pfnfs1 reference K65 allele and the non reference 65Q allele in parasites from the two regions. These data suggest that the Pfnfs1 K65Q mutation may not be a reliable marker for reduced susceptibility to lumefantrine.

Unveiling the Causal Association between Non-Infectious Respiratory Disorders and Sepsis through Mendelian Randomization Analysis.

BACKGROUND: The association between sepsis and non-infectious respiratory diseases is well-documented, yet the specific causal link between the two remains unclear. In order to explore this relationship further, we employed a Mendelian randomization (MR) analysis utilizing data from the UK Biobank and FinnGen Biobank. METHODS: We analyzed the summary statistics of a genome-wide association study (GWAS) summary statistics for chronic obstructive pulmonary disease (COPD), asthma, pulmonary embolism (PE), idiopathic pulmonary fibrosis (IPF), obstructive sleep apnea (OSA), lung cancer, sepsis, and sepsis-related mortality. We employed the inverse-variance weighted (IVW) method and four additional MR methods. Heterogeneity and horizontal pleiotropy were assessed using the Cochrane's Q test, MR-Egger intercept, and MR-PRESSO test. A sensitivity analysis was also performed. RESULTS: MR analysis showed associations between COPD and lung cancer with increased sepsis risk (odds ratio (OR)IVW 1.138, P = 0.006; (OR)IVW 1.123, P = 0.031; respectively) and sepsis mortality ((OR)IVW 1.350, P = 0.022; (OR)IVW 1.312, P = 0.022; respectively). Asthma exhibited a potential protective effect against sepsis mortality((OR)IVW = 0.300, P = 0.039), while PE demonstrated a risk effect ((OR)IVW = 1.148, P = 0.032). No causal association was observed between asthma, PE, and sepsis ( P > 0.05). IPF and OSA were not significantly associated with sepsis or sepsis-related mortality ( P > 0.05). Heterogeneity and horizontal pleiotropy were not evident for asthma or lung cancer ( P > 0.05). However, horizontal pleiotropy was suggested for COPD by the MR-Egger regression ( P < 0.05), but not by the MR-PRESSO test ( P > 0.05). IPF and OSA were not significantly associated with sepsis or sepsis-related mortality ( P > 0.05). CONCLUSIONS: Our MR analysis offers new insights into potential links between noninfectious respiratory diseases and the risk of sepsis. However, additional investigation into the underlying mechanisms and clinical studies are necessary to confirm these findings.

The role of perioperative sedative anesthetics in preventing postoperative delirium: a systematic review and network-meta analysis including 6679 patients.

OBJECTIVE: Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate whether there is an effective sedative that can prevent postoperative delirium while also examining the safety of using sedatives during the perioperative period. METHODS: The net-meta analysis was used to compare the incidence of postoperative delirium among four sedatives: sevoflurane, propofol, dexmedetomidine, and midazolam. Interventions were ranked according to their surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 41 RCT studies involving 6679 patients were analyzed. Dexmedetomidine can effectively reduce the incidence of postoperative delirium than propofol (OR 0.47 95% CI 0.25-0.90), midazolam (OR 0.42 95% CI 0.17-1.00), normal saline (OR 0.42 95% CI 0.33-0.54) and sevoflurane (OR 0.39 95% CI 0.18-0.82). The saline group showed a significantly lower incidence of bradycardia compared to the group receiving dexmedetomidine (OR 0.55 95% CI 0.37-0.80). In cardiac surgery, midazolam (OR 3.34 95%CI 2.04-5.48) and normal saline (OR 2.27 95%CI 1.17-4.39) had a higher rate of postoperative delirium than dexmedetomidine, while in non-cardiac surgery, normal saline (OR 1.98 95%CI 1.44-2.71) was more susceptible to postoperative delirium than dexmedetomidine. CONCLUSION: Our analysis suggests that dexmedetomidine is an effective sedative in preventing postoperative delirium whether in cardiac surgery or non-cardiac surgery. The preventive effect of dexmedetomidine on postoperative delirium becomes more apparent with longer surgical and extubation times. However, it should be administered with caution as it was found to be associated with bradycardia.

The predictive significance of chromobox family members in prostate cancer in humans.

PURPOSE: The Chromobox (CBX) family proteins are crucial elements of the epigenetic regulatory machinery and play a significant role in the development and advancement of cancer. Nevertheless, there is limited understanding regarding the role of CBXs in development or progression of prostate cancer (PCa). Our objective is to develop a unique prognostic model associated with CBXs to improve the accuracy of predicting outcomes of patients with PCa. METHODS: Data from TCGA and GEO databases were analyzed to assess differential expression, prognostic value, gene pathway enrichment, and immune cell infiltration. COX regression analysis was utilized to identify the independent prognostic factors that impact disease-free survival (DFS). The expression of CBX2 and FOXP3+ cells infiltration was verified by immunohistochemical staining of clinical tissue sections. In vitro proliferation, migration and invasion assay were conducted to examine the function of CBX2. RNA-seq was employed to examine the CBX2 related pathway enrichment. RESULTS: CBX2, CBX3, CBX4, and CBX8 were upregulated, while CBX6 and CBX7 were downregulated in PCa tissues. CBXs expression varied by stage and grade. Elevated expression of CBX1, CBX2, CBX3, CBX4 and CBX8 is correlated with poor outcome. CBX2 expression, T stage, and Gleason score were independent prognostic factors. The expression level of CBX2 in PCa tissues was significantly higher than that in adjacent normal tissues. More Treg infiltration was observed in the group with high CBX2 expression. CBX2 expression affected PCa cell growth, migration, and invasion. CONCLUSIONS: CBX2 is involved in the development and advancement of PCa, suggesting its potential as a reliable prognostic indicator for PCa patients.

Pollution characteristics, sources, and health risks of phthalate esters in ambient air: A daily continuous monitoring study in the central Chinese city of Nanchang.

In recent years, the atmospheric pollution caused by phthalate esters (PAEs) has been increasing due to the widespread use of PAE-containing materials. Existing research on atmospheric PAEs lacks long-term continuous observation and samples from cities in central China. To investigate the pollution characteristics, sources, and health risks of PAEs in the ambient air of a typical city in central China, daily PM2.5 samples were collected in Nanchang from November 2020 to October 2021. In this study, the detection and quantification of six significant PAE contaminants, namely diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DIBP), Di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DnOP), and diisodecyl phthalate (DIDP), were accomplished using gas chromatography and mass spectrometry. The results revealed that the concentrations of DEP, DnBP, DEHP, and DnOP were relatively high. Higher temperatures promote the volatilization of PAEs, leading to an increase in the gaseous and particulate PAE concentrations in warm seasons and winter pollution scenarios. The results of principal component analysis show that PAEs mainly come from volatile products and polyvinylchloride plastics. Using positive matrix factorization analysis, it is shown that these two sources contribute 67.0% and 33.0% in atmosphere PAEs, respectively. Seasonally, the contribution of volatile products to both gaseous and particulate PAEs substantially increases during warm seasons. The residents in Nanchang exposed to PAEs have a negligible non-cancer risk and a potential low cancer risk. During the warm seasons, more PAEs are emitted into the air, which will increase the toxicity of PAEs and their impact on human health.

Kidney disease in trials of perioperative tranexamic acid.

STUDY OBJECTIVE: To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function. DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: We screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023. PATIENTS: Patients undergoing non-obstetric surgery. INTERVENTIONS: Intravenous tranexamic acid compared to placebo or usual care without tranexamic acid. MEASUREMENT: We summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function. MAIN RESULTS: We evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m2 (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m2 (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min. CONCLUSIONS: The large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown.