HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

The m6A reader IGF2BP2 promotes esophageal cell carcinoma progression by enhancing EIF4A1 translation.

Esophageal squamous cell carcinoma (ESCC) is one of most prevalent cancers worldwide, especially in China. Lacking in depth mechanism study, effective targets and therapeutics are desperately needed in the clinic. RNA-binding proteins (RBPs) mediate the localization, stability, and translation of the target transcripts and fine-tune the physiological functions of the proteins encoded. Bioinformatics analysis revealed that IGF2BPs were highly expressed in ESCC tissues and at least participated in the regulation of cell proliferation of ESCC cells. Biological researches demonstrated that IGF2BP2 promoted the cell proliferation, migration and invasion of ESCC KYSE30 and KYSE450 cells. IGF2BP2 could bind to EIF4A1 mRNA by recognition of m6A sites and enhanced translation of EIF4A1. IGF2BPs, as m6A reader, IGF2BPs were oncogenic genes in ESCC by regulating the expression of EIF4A1 through m6A sites. IGF2BP2, EIF4A1 and their targets could serve as potential biomarkers and therapeutic targets for ESCC, offering promising novel approaches for the diagnosis and treatment of ESCC.

Fucoidan from Apostichopus japonicus ameliorates alcoholic liver disease by regulating gut-liver axis homeostasis.

Long-term and excessive alcohol consumption can lead to the development of alcoholic liver disease (ALD), characterized by oxidative damage, intestinal barrier injury, and disruption of intestinal microbiota. In this study, we extracted fucoidan (Aj-FUC) from Apostichopus japonicus using enzymatic methods and characterized its structure. The ALD model was established in male Balb/c mice using 56° Baijiu, with silymarin as a positive control. Mice were orally administered 100 mg/kg·bw and 300 mg/kg·bw of Aj-FUC for 28 days to evaluate its effects on liver injury in ALD mice and explore its potential role in modulating the gut-liver axis. The results showed significant improvements in histopathological changes and liver disease in the Aj-FUC group. Aj-FUC treatment significantly increased the levels of glutathione (GSH) and glutathione peroxidase (GSH-Px) while weakly reduced the elevation of malondialdehyde (MDA) induced by ALD. It also regulated the Nrf2/HO-1 signaling pathway, collectively alleviating hepatic oxidative stress. Aj-FUC intervention upregulated the expression of ZO-1 and Occludin, thus contributing to repair the intestinal barrier. Additionally, Aj-FUC increased the content of short-chain fatty acids (SCFAs) and regulated the imbalance in gut microbiota. These results suggested that Aj-FUC alleviates ALD by modulating the gut-liver axis homeostasis. It may prove to be a useful dietary supplement in the treatment of alcoholic liver damage.

Effects of UV-B Radiation Exposure on Transgenerational Plasticity in Grain Morphology and Proanthocyanidin Content in Yuanyang Red Rice.

The effect of UV-B radiation exposure on transgenerational plasticity, the phenomenon whereby the parental environment influences both the parent's and the offspring's phenotype, is poorly understood. To investigate the impact of exposing successive generations of rice plants to UV-B radiation on seed morphology and proanthocyanidin content, the local traditional rice variety 'Baijiaolaojing' was planted on terraces in Yuanyang county and subjected to enhanced UV-B radiation treatments. The radiation intensity that caused the maximum phenotypic plasticity (7.5 kJ·m-2) was selected for further study, and the rice crops were cultivated for four successive generations. The results show that in the same generation, enhanced UV-B radiation resulted in significant decreases in grain length, grain width, spike weight, and thousand-grain weight, as well as significant increases in empty grain percentage and proanthocyanidin content, compared with crops grown under natural light conditions. Proanthocyanidin content increased as the number of generations of rice exposed to radiation increased, but in generation G3, it decreased, along with the empty grain ratio. At the same time, biomass, tiller number, and thousand-grain weight increased, and rice growth returned to control levels. When the offspring's radiation memory and growth environment did not match, rice growth was negatively affected, and seed proanthocyanidin content was increased to maintain seed activity. The correlation analysis results show that phenylalanine ammonialyase (PAL), cinnamate-4-hydroxylase (C4H), dihydroflavonol 4-reductase (DFR), and 4-coumarate:CoA ligase (4CL) enzyme activity positively influenced proanthocyanidin content. Overall, UV-B radiation affected transgenerational plasticity in seed morphology and proanthocyanidin content, showing that rice was able to adapt to this stressor if previous generations had been continuously exposed to treatment.

Early GnRH-agonist therapy does not negatively impact the endometrial repair process or live birth rate.

Study objective: To investigate whether different timings of GnRH-a downregulation affected assisted reproductive outcomes in infertile women with moderate-to-severe intrauterine adhesions (IUAs) accompanied by adenomyosis. Design: A retrospective case series. Setting: An assisted reproductive technology center. Patients: The study reviewed 123 infertile women with moderate-to-severe IUAs accompanied by adenomyosis undergoing their first frozen-thawed embryo transfer (FET) cycles between January 2019 and December 2021. Measurements and main results: The majority of patients had moderate IUA (n=116, 94.31%). The average Basal uterine volume was 73.58 ± 36.50 cm3. The mean interval from operation to the first downregulation was 21.07 ± 18.02 days (range, 1-79 days). The mean duration of hormone replacement therapy (HRT) was 16.93 ± 6.29 days. The average endometrial thickness on the day before transfer was 10.83 ± 1.75 mm. A total of 70 women achieved clinical pregnancy (56.91%). Perinatal outcomes included live birth (n=47, 67.14%), early miscarriage (n=18, 25.71%), and late miscarriage (n=5, 7.14%). The time interval between uterine operation and the first downregulation was not a significant variable affecting live birth. Maternal age was the only risk factor associated with live birth (OR:0.89; 95% CI: 0.79-0.99, P=0.041). Conclusions: The earlier initiation of GnRH-a to suppress adenomyosis prior to endometrial preparation for frozen embryo transfer did not negatively impact repair of the endometrium after resection.

Effect of veno-arterial extracorporeal membrane oxygenation lower-extremity cannulation on intra-arterial flow characteristics, oxygen content, and thrombosis risk.

PURPOSE: This study aimed to investigate the effects of lower-extremity cannulation on the intra-arterial hemodynamic environment, oxygen content, blood damage, and thrombosis risk under different levels of veno-arterial (V-A) ECMO support. METHODS: Computational fluid dynamics methods were used to investigate the effects of different levels of ECMO support (ECMO flow ratios supplying oxygen-rich blood 100-40 %). Flow rates and oxygen content in each arterial branch were used to determine organ perfusion. A new thrombosis model considering platelet activation and deposition was proposed to determine the platelet activation and thrombosis risk at different levels of ECMO support. A red blood cell damage model was used to explore the risk of hemolysis. RESULTS: Our study found that partial recovery of cardiac function improved the intra-arterial hemodynamic environment, with reduced impingement of the intra-arterial flow field by high-velocity blood flow from the cannula, a flow rate per unit time into each arterial branch closer to physiological levels, and improved perfusion in the lower extremities. Partial recovery of cardiac function helps reduce intra-arterial high shear stress and residence time, thereby reducing blood damage. The overall level of hemolysis and platelet activation in the aorta decreased with the gradual recovery of cardiac contraction function. The areas at high risk of thrombosis under V-A ECMO femoral cannulation support were the aortic root and the area distal to the cannula, which moved to the descending aorta when cardiac function recovered to 40-60 %. However, with the recovery of cardiac contraction function, hypoxic blood pumped by the heart is insufficient in supplying oxygen to the front of the aortic arch, which may result in upper extremity hypoxia. CONCLUSION: We developed a thrombosis risk prediction model applicable to ECMO cannulation and validated the model accuracy using clinical data. Partial recovery of cardiac function contributed to an improvement in the aortic hemodynamic environment and a reduction in the risk of blood damage; however, there is a potential risk of insufficient perfusion of oxygen-rich blood to organs.

Risk Factors Associated with Postoperative Cerebrospinal Fluid Leaks After Intrathecal Drug Delivery System and an External Pump Implantation in Cancer Patients: A Retrospective Study.

INTRODUCTION: To determine risk factors associated with postoperative cerebrospinal fluid leaks (CSFLs) after intrathecal drug delivery system (IDDS) and external pump implantation. METHODS: The clinical data of 248 patients with advanced cancer who underwent IDDS implantation from January 2021 to December 2022 at the Department of Pain Medicine at the Hunan Cancer Hospital were retrospectively reviewed. Information regarding age, gender, height, weight, body mass index (BMI), tumour type, albumin levels, haemoglobin levels, history of diabetes and pre- and postoperative anti-tumour therapy was collected and analysed. RESULTS: Postoperative CSFLs occurred in 7 of 231 patients (3.30%). Statistical analysis indicated that gender, age, height, weight, BMI, tumour type, albumin levels, haemoglobin levels, history of diabetes, pre- and postoperative chemotherapy, pre- and postoperative radiotherapy, preoperative immunotherapy and postoperative targeted therapy were not independent factors for CSFLs. Preoperative targeted therapy [odds ratio (OR): 16.64; 95% confidence interval (CI): 1.42, 195.56; P = 0.01] and postoperative immunotherapy (OR: 13.38; 95% CI: 1.60, 111.65; P = 0.017) were factors associated with an increased postoperative CSFL rate. Of the two locations where CSFLs can occur, the back (puncture site of catheter, n = 4) and the hypochondriac region (location of infusion port implanted, n = 3), back CSFLs occurred earlier than in the hypochondriac region (18.25 ± 6.45 vs 115 ± 62.02 days, P = 0.032). CONCLUSION: Based on the data from our study, the timing of preoperative targeted therapy and postoperative immunotherapy should be considered to prevent the occurrence of CSFLs in cancer pain patients who have an IDDS and external pump.

Efficacy and Safety of Neoadjuvant Subcutaneous Envafolimab in dMMR/MSI-H Locally Advanced Colon Cancer.

BACKGROUND: Neoadjuvant immunotherapy with programmed death-ligand 1 blockade for colon cancer, especially for mismatch repair-deficient (dMMR)/high microsatellite instability (MSI-H) colon cancer, has gained considerable attention recently. OBJECTIVE: This study aimed to assess the safety and efficacy of neoadjuvant subcutaneous envafolimab in patients with dMMR/MSI-H locally advanced colon cancer. METHODS: Patients with dMMR/MSI-H locally advanced colon cancer treated with envafolimab at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital from October 2021 to July 2023 were retrospectively reviewed and analyzed. The primary endpoint was the pathological complete response (CR) rate, and secondary endpoints were treatment-related adverse events and complete clinical response rate. RESULTS: Overall, 15 patients were analyzed. After neoadjuvant immunotherapy with envafolimab, six patients achieved a CR, with five partial responses, and four stable disease. Three patients achieving a complete clinical response chose to accept a "watch and wait" strategy, and surgery was performed in 12 patients. Postoperative pathology results revealed seven patients achieved pathological CRs, and five patients achieved tumor regression grade 2, with 66.7% of the total CR rate. The most common treatment-related adverse events were pruritus and rash (40%), with no severe cases. No recurrences occurred over a 7.9-month follow-up. CONCLUSIONS: Envafolimab yielded promising surgical outcomes and safety in dMMR/MSI-H locally advanced colon cancer, representing a promising treatment modality for this population.

The safety and efficacy of Sotn ureteroscopy for renal and upper ureteral calculi: a prospective multicenter randomized controlled trial.

BACKGROUND: Sotn ureteroscopy is a new lithotripsy procedure developed on the basis of ureteroscopy and includes a rigid ureteral access sheath, standard mirror, lithotripsy mirror, and Sotn perfusion aspirator. Thus, we performed a prospective multicenter randomized controlled trial comparing the safety and efficacy of Sotn ureteroscopy in the treatment of renal and upper ureteral calculi. METHODS: In this study, 224 patients with renal and upper ureteral calculi were randomly divided equally into study and control groups from March 2018 to March 2022. All the patients were approved by the hospital ethics committee (proof number: ZF-2018-164-01 and ZF-2018-165-01) of the Second Affiliate Hospital of Guangzhou University of Chinese Medicine in China. The primary outcome was stone-free rate (SFR) assessed by computed tomography on the 1st day and month after treatment and operation duration. The secondary outcome was postoperative complication rate. RESULTS: In total, for upper ureteral calculi, the SFR of 1 day after operation of the Sotn ureteroscopy group was significantly higher than the rigid ureteroscopy group (83.6% vs. 60%, P=0.006). Moreover, operative time (33.7±1.80 vs. 52.9±2.73 min, P<0.005) of the Sotn ureteroscopy group was significantly lower than the rigid ureteroscopy group. Additionally, the SFR of 1 day after operation and operative time for the study group (Sotn ureteroscopy combined with flexible ureteroscopy) and the control group (flexible ureteroscopy alone) were 63.2% and 36.8% (P=0.005), 65.6±4.06 and 80.3±4.91 (P=0.023), respectively. However, there were no significant differences in the SFR of 1 month after operation, success rate of ureteral access sheath placement, and postoperative complications between the two groups (P>0.05). In subgroups with stone diameters ≥1.5 cm and stone CT values ≥1000 Hounsfield units, Sotn ureteroscopy showed more advantages in terms of the SFR of 1 day after operation. Importantly, complications such as ureteral injury, sepsis, fever, and severe hematuria were not statistically different between the two groups (P>0.05). CONCLUSIONS: For renal and upper ureteral calculi, Sotn ureteroscopy has the advantage of a higher SFR of 1 day after the operation and a shorter operative time, suggesting that the Sotn ureteroscopy may have further potential applications in clinics.

Genetic Prediction of Osteoporosis by Anti-Müllerian Hormone Levels and Reproductive Factors in Women: A Mendelian Randomization Study.

Previous observational studies have suggested that anti-Müllerian hormone (AMH) and reproductive factors are linked to reduced bone mineral density (BMD) and an increased risk of osteoporosis (OP) in women. However, related studies are limited, and these traditional observational studies may be subject to residual confounders and reverse causation, while also lacking a more comprehensive observation of various reproductive factors. Univariate and multivariate two-sample Mendelian randomization analyses were conducted to determine the causal associations of AMH levels and six reproductive factors with BMD and OP, using the random-effects inverse-variance weighted method. Heterogeneity was assessed using Cochran's Q-statistic, and sensitivity analyses were performed to identify causal correlations. Age at menarche (AAM) was negatively associated with total body BMD (TB-BMD) in females aged 45-60 and over 60 years, as well as with heel bone mineral density (eBMD). Conversely, age at natural menopause (ANM) was positively associated with TB-BMD in the same age ranges and with eBMD. ANM was only causally associated with self-reported OP and showed no significant correlation with definitively diagnosed OP. Neither AMH level nor other reproductive factors were significantly associated with a genetic predisposition to BMD at any age and OP. Later AAM and earlier ANM are significantly genetically causally associated with decreased BMD but not with OP. AMH levels, length of menstrual cycle, age at first birth, age at last birth, and number of live births, in terms of genetic backgrounds, are not causally related to BMD or OP.

Microwave ablation for painful chest wall metastases from gastrointestinal stromal tumor: a case report.

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the digestive tract, with the potential to metastasize. Metastases to bone and soft tissue are more frequent in advanced cases, where targeted therapy is the standard treatment. However, around 10-15% of patients develop disease progression despite treatment. Studies have shown the efficacy of ablation in managing bone and soft tissue metastases (1, 2), but there are no reports of ablation for treating GIST bone or soft tissue metastases. Case presentation: In 2022, a 58-year-old man complaining of left back pain was admitted to Sichuan Cancer Hospital. He had undergone radical resection of the primary gastric GIST and vertebral metastases in 2014 and 2018, respectively. In 2019, rib metastases still occurred despite the use of targeted therapy. During the course of radiotherapy, targeted therapy, and immunotherapy, he experienced persistent chest wall pain. In addition, new lesions occurred in the lungs and chest wall in 2022. After a thorough assessment, microwave ablation (MWA) was recommended in response to his demand for immediate pain relief. The large rib metastasis constricted the spleen, so we completed the ablation in two sessions to reduce the risk of complications. He had 17 months of follow-up until September 2023, during which time his discomfort was considerably reduced. Conclusion: For GIST patients with soft tissue and bone metastases, MWA may offer substantial immediate pain alleviation. When other treatment procedures fail to achieve adequate efficacy, it provides an option.

Complete mitochondrial genome of Angelica dahurica and its implications on evolutionary analysis of complex mitochondrial genome architecture in Apiaceae.

Angelica dahurica is a kind of Chinese traditional herbs with economic and ornament value, widely distributed in China. Despite its significance, there have been limited comprehensive investigations on the genome of A. dahurica, particularly regarding mitochondrial genomes. To investigate the conversion between mitochondrial genome and chloroplast genome, a complete and circular mitochondrial genome was assembled using Oxford Nanopore Technologies (ONT) long reads. The mitochondrial genome of A. dahurica had a length of 228,315 base pairs (bp) with 45.06% GC content. The mitochondrial genome encodes 56 genes, including 34 protein-coding genes, 19 tRNA genes and 3 rRNA genes. Moreover, we discovered that 9 homologous large fragments between chloroplast genome and mitochondrial genome based on sequence similarity. This is the first report for A. dahurica mitochondrial genome, which could provide an insight for communication between plastid genome, and also give a reference genome for medicinal plants within the Angelica family.

The role of Cistanches Herba and its ingredients in improving reproductive outcomes: A comprehensive review.

BACKGROUND: Infertility patients account for an astonishing proportion of individuals worldwide. Due to its complex etiology and challenging treatment, infertility has imposed significant psychological and economic burdens on many patients. C. Herba (Cistanche tubulosa (Schenk) Wight and Cistanche deserticola Ma), renowned as one of the most prominent Chinese herbal medicines (CHMs), is abundant in diverse bioactive compounds that exhibit therapeutic effects on many diseases related to oxidative stress (OS) and disorders of sex hormone levels. OBJECTIVE: Due to the limited drugs currently used in clinical practice to improve reproductive outcomes and their inevitable side effects, developing safe and effective new medications for infertility is of significance. This article comprehensively reviewed the phytochemicals of C. Herba, focusing on their efficacy and mechanisms on infertility and their safety for the first time, aiming to offer valuable insights for the development and application of C. Herba, and for developing novel strategies for treating infertility. METHODS: We used "Cistanche" and its known bioactive components in combination with "sperm", "testicles", "epididymis", "ovaries", "uterus", and "infertility" as keywords to search in PubMed, Web of Science, Scopus and CNKI up to November 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline was followed. RESULTS: The therapeutic effects of C. Herba on infertility are mainly attributed to echinacoside (ECH), verbascoside (VB), salidroside (SAL), polysaccharides, and betaine. They can effectively improve spermatogenic dysfunction, gonadal dysfunction and erectile dysfunction (ED) by exerting anti-oxidation, sex hormones regulation and anti-hypoxia. Moreover, they can also improve premature ovarian failure (POF), ovarian and uterine cancer, oocyte maturation by exerting anti-oxidation, anti-apoptosis, and anti-cancer. C. Herba and its active ingredients also exhibit pleasing safety. CONCLUSION: C. Herba is a promising source of natural medicine for infertility. Additionally, compared to current therapeutic drugs, its favorable safety also supports its development as a nutritional supplement. However, high-quality clinical studies are required to validate its effectiveness for the development of novel therapeutic strategies.

A xanthan gum and carbomer-codispersed divalent manganese ion-loaded tannic acid nanoparticle adjuvanted inactivated pseudorabies virus vaccine induces balanced humoral and cellular immune responses.

Adjuvants including aluminum adjuvant (Alum) and oil-water emulsion have been widely used in inactivated pseudorabies virus (PRV) vaccine to improve its performance, however, they are not sufficient to protect from PRV infection because of the weak immune response and poor Th1-type immune response. Divalent manganese ion (Mn2+) has been reported to increase the cellular immune response significantly. In this work, a xanthan gum and carbomer-dispersed Mn2+-loaded tannic acid-polyethylene glycol (TPMnXC) nanoparticle colloid is developed and used as an adjuvant to improve the performance of the inactivated PRV vaccine. The good in vitro and in vivo biocompatibility of the developed TPMnXC colloid has been confirmed by the cell viability assay, erythrocyte hemolysis, blood routine analysis, and histological analysis of mouse organs and injection site. The TPMnXC-adjuvanted inactivated PRV vaccine (TPMnXC@PRV) significantly promotes higher and more balanced immune responses indicating with an increased specific total IgG antibody and IgG2a/IgG1 ratio, efficient splenocytes proliferation, and elevated Th1- and Th2-type cytokine secretion than those of control groups. Wild PRV challenge experiment is performed using mice as a model animal, achieving a protection rate of up to 86.67 %, which is much higher than those observed from the commercial Alum. This work not only demonstrates the high potentiality of TPMnXC in practical applications but also provides a new way to develop the Mn2+-loaded nanoadjuvant for veterinary vaccines.

Adjuvant chemotherapy for stage II and III gastric adenocarcinoma: A retrospective analysis with long-term follow-up.

BACKGROUND: Whether adjuvant chemotherapy should be different for patients with stage II and III gastric cancer is unknown. METHODS: We retrospectively analyzed the effects of adjuvant chemotherapy on the outcomes of 140 and 256 patients with stage II and III gastric cancer, respectively, between January 2008 and December 2018. Chemotherapies were stratified as fluoropyrimidine plus platinum versus fluoropyrimidine alone, tegafur/gimeracil/octeracil (S-1)-containing versus non-S-1-containing regimens, and S-1 plus cisplatin versus S-1 alone. RESULTS: The median age of patients was 67.0 (range 24.6-98.8) years. With a median follow-up of 105 months, recurrence occurred in 32 (22.9%) and 130 (50.8%) patients with stage II and III disease, respectively. Adjuvant chemotherapy was administered as fluoropyrimidine monotherapy to 68 (48.6%) and 73 (28.5%) patients, fluoropyrimidine plus platinum to 9 (6.4%) and 104 (40.6%) patients, and none to 63 (45.0%) and 79 (30.9%) patients with stage II and III gastric cancer, respectively. Doublet chemotherapy was associated with longer disease-free survival (DFS) (26.5 vs. 15.2 months, P = 0.001) and overall survival (OS) (41.2 vs. 22.0 months, P < 0.001) than fluoropyrimidine monotherapy for stage IIIB-IIIC disease. Furthermore, S-1-containing regimens prolonged DFS (57.4 vs. 21.9 months, P = 0.044) and OS (81.4 vs. 28.6 months, P = 0.023) compared with non-S-1-containing chemotherapy in stage III disease. CONCLUSION: Although fluoropyrimidine monotherapy is feasible for stage II-IIIA disease, doublet chemotherapy is significantly associated with longer survival than monotherapy for stage IIIB-IIIC disease. S-1-containing regimens might lead to longer survival than non-S-1-containing chemotherapy in stage III gastric cancer.

Phenolic constituents with potent α-glucosidase inhibitory and cytotoxic activities from Rumex nepalensis var. remotiflorus.

Quantitative analysis of Rumex nepalensis var. remotiflorus revealed that its roots contain rich anthraquinones, which has emodin, chrysophanol, and physcion contents of up to 0.30, 0.67, and 0.98 mg/g, respectively. Further phytochemical study led to the isolation and purification of seven undescribed phenolic constituents, including one flavan derivative with a 13-membered ring, polygorumin A (1), two dianthrone glucosides, polygonumnolides F and G (2, 3), two diphenylmethanones, rumepalens A and B (4, 5), and a pair of epimeric oxanthrone C-glucosides, rumejaposides K and L (6a, 6b) from the roots of R. nepalensis var. remotiflorus. Furthermore, 1 undescribed natural product, 1-ß-D-glucoside-6'-[(2E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate]-3-hydroxy-5-methylphenyl (19), and 21 known phenolic compounds were obtained from the aforementioned plant for the first time. Their structures were elucidated through extensive spectroscopic data analysis. Notably, compounds 1, 4-5, and 7-9 exhibited inhibitory activity on α-glucosidase with IC50 values ranging from 1.61 ± 0.17 to 32.41 ± 0.87 µM. In addition, the isolated dianthrone, chrysophanol bianthrone (14), showed obvious cytotoxicity against four human cancer cell lines (HL-60, SMMC-7721, A-549, and MDA-MB-231) with IC50 values ranging from 3.81 ± 0.17 to 35.15 ± 2.24 µM. In silico target prediction and molecular docking studies demonstrated that the mechanism of the anticancer activity of 14 may be related to the interaction with protein kinase CK2.

The effect of oral motor intervention with different initiation times to improve feeding outcomes in preterm infants: protocol for a single-blind, randomized controlled trial.

BACKGROUND: Premature infants commonly encounter difficulties with oral feeding, a complication that extends hospital stays, affects infants' quality of life, and imposes substantial burdens on families and society. Enhancing preterm infants' oral feeding skills and facilitating their transition from parenteral or nasal feeding to full oral feeding pose challenges for neonatal intensive care unit (NICU) healthcare professionals. Research indicates that oral motor interventions (OMIs) can enhance preterm infants' oral feeding capabilities and expedite the transition from feeding initiation to full oral feeding. Nonetheless, the most suitable timing for commencing these interventions remains uncertain. METHODS: This is a single-blind, randomized controlled trial. Preterm with a gestational age between 29+0 to 34+6 weeks will be eligible for the study. These infants will be randomized and allocated to one of two groups, both of which will receive the OMIs. The intervention commences once the infant begins milk intake during the early OMIs. Additionally, in the late OMIs group, the intervention will initiate 48 h after discontinuing nasal continuous positive airway pressure. DISCUSSION: OMIs encompass non-nutritive sucking and artificial oral stimulation techniques. These techniques target the lips, jaw, muscles, or tongue of premature infants, aiming to facilitate the shift from tube feeding to oral feeding. The primary objective is to determine the ideal intervention timing that fosters the development of oral feeding skills and ensures a seamless transition from parenteral or nasal feeding to full oral feeding among preterm infants. Furthermore, this study might yield insights into the long-term effects of OMIs on the growth and neurodevelopmental outcomes of preterm infants. Such insights could bear substantial significance for the quality of survival among preterm infants and the societal burden imposed by preterm birth. TRIAL REGISTRATION: chictr.org.cn ChiCTR2300076721. Registered on October 17, 2023.

Optimal Glycated Hemoglobin Cutoff for Diagnosis of Diabetes and Prediabetes in Chinese Breast Cancer Women.

Purpose: Glycated hemoglobin (HbA1c) is widely used in diabetes management and now recommended for diagnosis and risk assessment. Our research focused on investigating the optimal cutoff points of HbA1c for diagnosis of diabetes and prediabetes in Chinese breast cancer women, aiming to enhance early detection and tailor treatment strategies. Patients and Methods: This study involved 309 breast cancer women without diabetes history in China. Patients were categorized into groups of newly diagnosed diabetes, prediabetes, and normal glucose tolerance using oral glucose tolerance test (OGTT) according to the 2010 ADA criteria. HbA1c data were collected from all patients. Receiver operating characteristic (ROC) curve analysis was used to assess the effectiveness of the HbA1c screening. Results: Among the 309 breast cancer women without diabetes history, 96 (31.0%) were identified with diabetes and 130 (42.1%) had prediabetes according to OGTT, and the incidence of normal glucose tolerance was only 26.9% (83). ROC curve analysis, using OGTT as a reference, revealed that the area under the curve of 0.903 (P<0.001, 95% CI, 0.867-0.938) for HbA1c alone, indicating high accuracy. The optimal HbA1c cutoff for identifying diabetes was determined to be 6.0%, with a sensitivity of 78.1% and specificity of 86.4%. For prediabetes, the ROC curve for HbA1c alone showed that the area under the ROC curve of 0.703 (P<0.001, 95% CI, 0.632-0.774), with an optimal cutoff of 5.5% (sensitivity of 76.9% and specificity of 51.8%). Conclusion: The prevalence of undiagnosed diabetes is very high in breast cancer women without diabetes history in China. The optimal cutoff points of HbA1c for identifying diabetes and prediabetes are 6.0% and 5.5% in Chinese breast cancer women, respectively.

Maintenance treatment of immunotherapy after microwave ablation plus drug-eluting bead bronchial arterial chemoembolization for advanced non-small cell lung cancer: a retrospective single-center cohort study.

Background: The combination therapy of immunotherapy and drug-eluting bead bronchial artery chemoembolization (DEB-BACE) or microwave ablation (MWA) has been attempted as an effective and safe approach for advanced non-small cell lung cancer (NSCLC). However, the outcomes of immunotherapy plus multiple interventional techniques for advanced NSCLC remain unclear. This retrospective study thus aimed to investigate the effectiveness and safety of the maintenance treatment of programmed cell death protein 1 (PD-1) blockade after MWA plus DEB-BACE for advanced NSCLC. Methods: This retrospective cohort study consists of 95 patients with advanced NSCLC who were treated with DEB-BACE between April 2017 and October 2022 and who were allocated to three groups: group A (MWA + DEB-BACE + PD-1 blockade; n=15), group B (MWA + DEB-BACE; n=25), and group C (DEB-BACE alone; n=55). The adverse events (AEs) were compared between the three groups. The outcomes were compared via Kaplan-Meier methods, including median progression-free survival (PFS) and overall survival (OS). Survival analyses were performed via the univariate and multivariate analyses to investigate the prognostic predictors. Results: The overall incidence of AEs in the groups A-C was 53.3% (8/15), 36.0% (9/25), and 32.7% (18/55), respectively, which did not represent a significant difference (P=0.42). No severe AEs (SAEs) occurred. Group A, compared with group B and group C, had a significantly longer estimated median PFS (33.0 vs. 7.0 vs. 3.0 months; P<0.001) and OS (33.0 vs. 13.0 vs. 6.0 months; P=0.002). PD-1 blockade (P=0.006), tumor number (P=0.01), and DEB-BACE/bronchial artery infusion (BAI) chemotherapy cycles (P=0.04) were identified as the predictors of PFS, while the predictors of OS were PD-1 blockade (P<0.001), number of metastases (P<0.001), tumor diameter (P<0.001), and DEB-BACE/BAI cycles (P=0.02). Conclusions: Compared with that of advanced NSCLC treated with MWA plus DEB-BACE or DEB-BACE alone, the maintenance treatment of immunotherapy after MWA plus DEB-BACE might provide a superior prognosis without increasing the risk of AEs.

Hidden delta degradation due to fluvial sediment decline and intensified marine storms.

Deltas are threatened by erosion due to climate change and reduced sediment supply, but their response to these changes remains poorly quantified. We investigate the abandoned Yellow River delta that has transitioned from rapid growth to ongoing deterioration due to a river avulsion removing the sediment supply. Integrating bathymetric data, process observations, and sediment transport modeling, we find that while the subaerial delta was stabilized by engineering measures, the subaqueous delta continued to erode due to intensified storms, losing 39% of its mass deposited before the avulsion. Long-term observations show that winter storms initiate scouring of the subaqueous delta, contributing up to 70% of seabed erosion. We then analyze 108 global deltas to assess subaqueous delta erosion risks and identify 17 deltas facing similar situations of sediment decline and storm intensification during the past 40 years. Our findings suggest that subaqueous delta erosion must be integrated into delta sustainability evaluations.