Ketosis is an energy metabolism disorder occurring frequently in periparturient dairy cows,primarily attributed to elevated non-esterified fatty acid(NEFA)levels resulting from nega-tive energy balance(NEB).Excessive NEFA will be incompletely oxidated into large amounts of ketone bodies or be re-esterified and deposit in the liver as a consequence of hepatic limited oxida-tive capacity,ultimately leading to ketosis and fatty liver.Hypoxic microenvironments are com-monly found during the progression of various liver diseases.Hypoxia inducible factor-2 alpha(HIF-2 alpha)has been identified as a crucial regulator of lipid metabolism.However,it is still un-clear the association between HIF-2α and disrupted lipid metabolism in the livers of in ketotic cows.This study aims to investigate the effect of high concentrations of NEFA on HIF-2α expres-sion and cellular oxygen homeostasis through bovine liver tissue and primary hepatocytes.In vivo,hepatic triglyceride(TAG)content was assessed to determine the extent of hepatic lipid accumula-tion,and HIF-2α protein and mRNA levels were analyzed by immunohistochemistry staining,Western blot and qRT-PCR assay in liver tissue samples from dairy cows;in vitro,bovine primary hepatocytes were treated with different concentrations of NEFA.Oil Red O staining and TAG con-tent assay were performed to determine hepatocellular steatosis extent,and immunofluorescence staining.Western blot,and qRT-PCR were performed to analyze HIF-2α expression,in addition,lu-minescent oxygen sensor[Ru(dpp)3]Cl2 was added to indicate intracellular oxygen levels.These results showed a significant increase in TAG content and elevated HIF-2α expression in the liver tissue of ketotic cows,and high concentrations of NEFA induced lipid accumulation,upregulation of HIF-2α expression,and intracellular hypoxia in bovine primary hepatocytes.These findings sug-gested that HIF-2α was significantly"activated"in the liver of ketotic cows and high concentration of NEFA-induced bovine primary hepatocytes,and that high concentrations of NEFA induced in-tracellular hypoxia in vitro.This study provides a potential molecular target for further investiga-tion of the mechanism underlying hepatic lipid metabolism disorders in ketotic cows.

As one of the common negative emotions in diabetic patients, diabetes distress not only directly weakens patients' self-efficacy and treatment compliance, but also increases the risk of complications. With the help of mobile applications, chatbots, virtual reality technology and other means, digital health interventions can effectively alleviate the negative emotions of diabetic patients, improve their self-management ability and confidence, and are increasingly widely used in diabetes distress. The purpose of this review is to introduce the specific forms, application effects and future development directions of digital health intervention in diabetes distress, and to promote further research and clinical practice of digital health intervention in diabetes distress.

As one of the common negative emotions in diabetic patients, diabetes distress not only directly weakens patients' self-efficacy and treatment compliance, but also increases the risk of complications. With the help of mobile applications, chatbots, virtual reality technology and other means, digital health interventions can effectively alleviate the negative emotions of diabetic patients, improve their self-management ability and confidence, and are increasingly widely used in diabetes distress. The purpose of this review is to introduce the specific forms, application effects and future development directions of digital health intervention in diabetes distress, and to promote further research and clinical practice of digital health intervention in diabetes distress.

Ketosis is an energy metabolism disorder occurring frequently in periparturient dairy cows,primarily attributed to elevated non-esterified fatty acid(NEFA)levels resulting from nega-tive energy balance(NEB).Excessive NEFA will be incompletely oxidated into large amounts of ketone bodies or be re-esterified and deposit in the liver as a consequence of hepatic limited oxida-tive capacity,ultimately leading to ketosis and fatty liver.Hypoxic microenvironments are com-monly found during the progression of various liver diseases.Hypoxia inducible factor-2 alpha(HIF-2 alpha)has been identified as a crucial regulator of lipid metabolism.However,it is still un-clear the association between HIF-2α and disrupted lipid metabolism in the livers of in ketotic cows.This study aims to investigate the effect of high concentrations of NEFA on HIF-2α expres-sion and cellular oxygen homeostasis through bovine liver tissue and primary hepatocytes.In vivo,hepatic triglyceride(TAG)content was assessed to determine the extent of hepatic lipid accumula-tion,and HIF-2α protein and mRNA levels were analyzed by immunohistochemistry staining,Western blot and qRT-PCR assay in liver tissue samples from dairy cows;in vitro,bovine primary hepatocytes were treated with different concentrations of NEFA.Oil Red O staining and TAG con-tent assay were performed to determine hepatocellular steatosis extent,and immunofluorescence staining.Western blot,and qRT-PCR were performed to analyze HIF-2α expression,in addition,lu-minescent oxygen sensor[Ru(dpp)3]Cl2 was added to indicate intracellular oxygen levels.These results showed a significant increase in TAG content and elevated HIF-2α expression in the liver tissue of ketotic cows,and high concentrations of NEFA induced lipid accumulation,upregulation of HIF-2α expression,and intracellular hypoxia in bovine primary hepatocytes.These findings sug-gested that HIF-2α was significantly"activated"in the liver of ketotic cows and high concentration of NEFA-induced bovine primary hepatocytes,and that high concentrations of NEFA induced in-tracellular hypoxia in vitro.This study provides a potential molecular target for further investiga-tion of the mechanism underlying hepatic lipid metabolism disorders in ketotic cows.

OBJECTIVE: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities. METHODS: The AlCl₃ colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti - oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C₁₈ column (2.0 mm × 150 mm, 5 μm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase (PDB ID: 2CDU) by molecular docking. RESULTS: Combined with the results of activity screening in vitro, the anti - oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatography-mass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory profile. CONCLUSION The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin.

Objective:To evaluate the influence of age factors on dose-effect relationship of oxycodone inhibiting responses to tracheal intubation during induction of general anesthesia in pediatric patients.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ pediatric patients of both sexes, aged 6 months-6 yr, with body mass index of 12-22 kg/m 2, scheduled for elective surgery under general anesthesia with tracheal intubation, were divided into 3 groups: infant group (group I, 6-12 months), young children group (group Y, >1-3 yr) and preschooler group (group P, >3-6 yr). Oxycodone was slowly injected intravenously, 2 min later etomidate 0.3 mg/kg and cisatracurium 0.15 mg/kg were intravenously injected, and 3 min later endotracheal intubation was carried out with a visual laryngoscope in all the children. Mean arterial pressure(MAP) and heart rate (HR) immediately before intubation and peak MAP and HR within 3 min after intubation were recorded. The modified Dixon′s sequential method was used. The initial dose of oxycodone was 0.3 mg/kg in each group. If the response to tracheal intubation was positive, the dose of oxycodone was increased by 0.02 mg/kg in the next child; if the response to tracheal intubation was negative, the dose of oxycodone was decreased by 0.02 mg/kg in the next child. Positive response to tracheal intubation was defined as increase in MAP and/or HR and increase in the peak value exceeding 20% of the pre-intubation level within 3 min after tracheal intubation. The aforementioned process was repeated until 7 negative and positive reactions crossed, and then the test was stopped. The median effective dose (ED 50) and 95% confidence interval of oxycodone were calculated by Probit method. Results:The ED 50 (95% confidence interval) of oxycodone inhibiting responses to the tracheal intubation were 0.280 (0.247-0.301) mg/kg, 0.321 (0.304-0.342) mg/kg and 0.354 (0.342-0.368) mg/kg in I, Y and P groups, respectively. The ED 50 of oxycodone inhibiting responses to the tracheal intubation was gradually increased during induction of general anesthesia with increasing age ( P<0.05). Conclusions:For children aged 6 months to 6 yr, the potency of oxycodone in inhibiting responses to the tracheal intubation during general anesthesia induction gradually decreases with increasing age.

Objective:To assess the efficacy of high-flow nasal cannula oxygen therapy for the respiratory support after tracheal extubation under general anesthesia in neonates.Methods:This was a prospective randomized controlled study. Ninety-four neonates undergoing general surgery under general anesthesia with endotracheal intubation and endotracheal tube removal following surgery from December 2022 to November 2023 in the Third Affiliated Hospital of Zhengzhou University were selected and divided into 2 groups ( n=47 each) by the random number table method: conventional oxygen therapy group (group C) and high-flow nasal cannula oxygen therapy group (group H). After the endotracheal tube was removed, group H underwent high-flow nasal cannula oxygen therapy: oxygen flow was 2 L·kg -1·min -1, the concentration and humidity of oxygen were both 100%, and the temperature was 37 ℃. Group C underwent conventional mask ventilation with the oxygen flow rate 5 L/min, oxygen concentration 100%, ventilation frequency about 25-35 times/min. The outcome measures were recorded from the time after extubation to the time before discharge from the operating theatre. The main outcome measures were the minimum SpO 2 and hypoxemia (SpO 2<90%), choking, laryngospasm and asphyxia. The secondary outcome measures were respiratory rate (immediate extubation, immediate discharge), minimum HR, and time to discharge from the operating theatre. Results:Compared with group C, the lowest SpO 2 was significantly increased, the incidence of hypoxemia and respiratory rate immediately after discharge from the operating room was decreased ( P<0.05), and no significant changes were found in the incidence of choking, laryngospasm and asphyxia, the lowest heart rate, respiratory rate immediately after tracheal extubation and time to discharge from the operating theatre in group H( P>0.05). Conclusions:High-flow nasal cannula oxygen therapy can improve oxygenation and significantly reduce the risk of hypoxemia when used for the respiratory support after tracheal extubation under general anesthesia in neonates.

Lotus medicinal herbs have the effects of resolving blood stasis and stopping bleeding， invigorating the spleen and benefiting the kidneys， restoring coordination between heart and kidney， and tranquilizing the fetus. Lotus root， lotus leaf， lotus seed， Lotus plumule， Shilianzi（Nelumbo nucifera Gaertn） and other lotus herbs are used to treat various female reproductive system diseases. For example， lotus leaf tip with modified Youshi Pangxing Shuangtu Decoction （伍尤氏胖型双土汤）， lotus root section with modified Youshi Shouxing Shuangteng Decoction （尤氏瘦型双藤汤） were used for polycystic ovary syndrome； Youshi Yangchao Formula （尤氏养巢方） （containing lotus seed）， Gengnian Formula （更年方） （containing lotus plumule） for ovarian reserve dysfunction； Lotus seed - Shihu （Dendrobium nobile） as the herb-pair， lotus stamen with ginseng flowers and Sanqi Flower for thin endometrium； Shilianzi（Nelumbo nucifera Gaertn）， lotus leaf tip， lotus stamen， lotus seed， lotus room， lotus root section can be used for premature abortion， and we summarized the characteristics of clinical medication， compounding experience， drug dosage and precautions of each lotus drug in different diseases.

Liver fibrosis is the common consequence of various chronic liver injuries and is mainly characterized by the imbalance between the production and degradation of extracellular matrix, which leads to the accumulation of interstitial collagen and other matrix components. Matrix metalloproteinases (MMPs) and their specific inhibitors, i.e., tissue inhibitors of metalloproteinases (TIMPs), play a crucial role in collagen synthesis and lysis. Through a literature review, this article reviews the experimental studies of liver fibrosis based on MMPs/TIMPs, summarizes the components that may exert an anti-liver fibrosis effect by affecting the expression or activity of MMPs/TIMPs, and attempts to clarify the mechanism of MMPs/TIMPs in regulating collagen homeostasis, so as to provide support for the development of anti-liver fibrosis drugs.

Background::Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods::This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results::A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups ( P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups. Conclusion::HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration::ClinicalTrials.gov: NCT01883180, NCT02673008.