Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

OBJECTIVE To investigate the mechanism of artesunate increasing the sensitivity of hepatocellular carcinoma(HCC)cells to sorafenib in hypoxic microenvironment.METHODS Firstly,hypoxia-resistant HCC cell models were established.NAC(a ROS scavenger),necrostatin-1(a necrosis inhibitor),and ferrostatin-1(a ferroptosis inhibitor)were added to examine the effects of artesunate on the inhibition rate of HCC cells and the primary modes of cell death in hypoxic microenvironment by MTT assays.Intra-cellular levels of GSH,ROS,lipid peroxidation product MDA,and iron ions were measured using corresponding kits.Mitochondrial membrane potential changes were assessed using JC-1 staining.Western blot and qPCR were performed to detect the expression of fer-roptosis-related proteins after the addition of artesunate.RESULTS The sensitivity of HCC cells to sorafenib decreased under hy-poxic microenvironment,but artesunate significantly enhanced this sensitivity.Further analysis revealed that artesunate promoted sor-afenib-induced ferroptosis by increasing ROS levels in HCC cells(P<0.05,P<0.01,P<0.001).Additionally,artesunate was found to inhibit Nrf2 mRNA and protein levels(P<0.05,P<0.01,P<0.001)and downregulate HIF-1α expression(P<0.05,P<0.01,P<0.001).CONCLUSION Artesunate increases intracellular oxidative stress by inhibiting Nrf2 and HIF-1α protein levels,subse-quently induces ferroptosis and enhances the sensitivity of HCC cells to sorafenib in hypoxic microenvironment.

Objective:To systematically search, evaluate, and summarize evidence-based findings related to postoperative oral health management for orthognathic surgery patients, with the goal of providing clinical care professionals with evidence-based guidance for postoperative care, infection prevention, and functional recovery.Methods:Using the "6S" evidence hierarchy model, a systematic search was conducted in databases such as UpToDate, BMJ Best Practice, DynaMed, The Cochrane Library, World Health Organization (WHO), National Institute for Health and Care Excellence (NICE), Guidelines International Network (GIN), Registered Nurses′Association of Ontario (RNAO), Chinese Stomatological Association (CSA), American Association of Oral and Maxillofacial Surgeons (AAOMS), PubMed, and Scopus. The search included literature on postoperative oral health management for orthognathic surgery patients, such as guidelines, clinical decision-making tools, expert consensus, evidence summaries, and systematic reviews, covering publications from database inception to November 12, 2024. Two researchers independently assessed the quality of the included literature and extracted, summarized, and synthesized the evidence.Results:A total of 18 studies were included, consisting of 7 guidelines, 7 systematic reviews, 2 expert consensus documents and 2 randomized controued trials. Twenty-two best evidence statements were summarized, addressing six key areas: oral hygiene and infection prevention, wound care, oral functional recovery, dietary and nutritional support, oral comfort management, and long-term oral health maintenance.Conclusions:This study provides a comprehensive summary of the best available evidence for postoperative oral health management in orthognathic surgery patients. It offers theoretical support for clinical nursing practices and evidence-based recommendations for postoperative care specific to this patient population.

OBJECTIVE To investigate the mechanism of artesunate increasing the sensitivity of hepatocellular carcinoma(HCC)cells to sorafenib in hypoxic microenvironment.METHODS Firstly,hypoxia-resistant HCC cell models were established.NAC(a ROS scavenger),necrostatin-1(a necrosis inhibitor),and ferrostatin-1(a ferroptosis inhibitor)were added to examine the effects of artesunate on the inhibition rate of HCC cells and the primary modes of cell death in hypoxic microenvironment by MTT assays.Intra-cellular levels of GSH,ROS,lipid peroxidation product MDA,and iron ions were measured using corresponding kits.Mitochondrial membrane potential changes were assessed using JC-1 staining.Western blot and qPCR were performed to detect the expression of fer-roptosis-related proteins after the addition of artesunate.RESULTS The sensitivity of HCC cells to sorafenib decreased under hy-poxic microenvironment,but artesunate significantly enhanced this sensitivity.Further analysis revealed that artesunate promoted sor-afenib-induced ferroptosis by increasing ROS levels in HCC cells(P<0.05,P<0.01,P<0.001).Additionally,artesunate was found to inhibit Nrf2 mRNA and protein levels(P<0.05,P<0.01,P<0.001)and downregulate HIF-1α expression(P<0.05,P<0.01,P<0.001).CONCLUSION Artesunate increases intracellular oxidative stress by inhibiting Nrf2 and HIF-1α protein levels,subse-quently induces ferroptosis and enhances the sensitivity of HCC cells to sorafenib in hypoxic microenvironment.

Objective To investigate the current status of breastfeeding motivation in early post-partum women and analyze the influencing factors of breastfeeding motivation.Methods A conven-ience sampling method was used to select 205 hospitalized women within 48 to 72 hours postpartum as the study subjects.The women were surveyed using a general information questionnaire,a breastfeed-ing motivation scale,a breastfeeding knowledge questionnaire,and a short-form scale for breastfeed-ing self-efficacy.Multiple linear regression analysis was conducted to explore the influencing factors of breastfeeding motivation among the women.Results The average score for autonomous motivation to-wards breastfeeding among 205 women was(49.94±7.62),and the average score for controlled mo-tivation was(23.76±3.59).The results of multiple linear regression analysis showed that age,par-ticipation in breastfeeding-related courses during pregnancy,planned duration of breastfeeding,skill dimension score of the short-form scale for breastfeeding self-efficacy,and total score on the breast-feeding knowledge questionnaire were influencing factors for the autonomous motivation score towards breastfeeding(P＜0.05);participation in breastfeeding-related courses during pregnancy,skill di-mension score on the short-form breastfeeding self-efficacy,and total score on the breastfeeding knowledge questionnaire were influencing factors for the controlled motivation score towards breast-feeding(P＜0.05).Conclusion The level of breastfeeding motivation in early postpartum women needs to be improved.Healthcare providers should focus on maternal age and planned duration of breastfeeding,strengthen breastfeeding knowledge education,and enhance maternal breastfeeding self-efficacy to improve maternal breastfeeding motivation and breastfeeding rates.

A 45-year-old male patient with type 2 diabetes developed euglycemic diabetic ketoacidosis(euDKA)after combined use of ertugliflozin and metformin.Four days after medication,the patient developed chest tightness,shortness of breath,fever,accompanied by urinary frequency and dysuria.Laboratory findings showed random blood glucose of 6.5 mmol·L-1,ketone bodies of 3.1 mmol·L-1,and metabolic acidosis on arterial blood gas analysis(pH 7.27,actual bicarbonate 6.9 mmol·L-1).EuDKA was diagnosed,with suspected urinary tract infection.Ertugliflozin was promptly discontinued.Treatments such as fluid resuscitation,low-dose insulin infusion via pump,electrolyte correction,and anti-infective therapy were administred.Symptoms gradually improved,and ketone bodies turned negative after three days.Using the Naranjo's Assessment Scale,the association between euDKA and the suspected drug ertugliflozin was rated as"probable"(score 7).This case suggested that concomitant use of SGLT2 inhibitors and metformin,especially with co-existing infection,may significantly increase the risk of euDKA.Enhanced medication evaluation and monitoring were recommended in clinical practice.

A 45-year-old male patient with type 2 diabetes developed euglycemic diabetic ketoacidosis(euDKA)after combined use of ertugliflozin and metformin.Four days after medication,the patient developed chest tightness,shortness of breath,fever,accompanied by urinary frequency and dysuria.Laboratory findings showed random blood glucose of 6.5 mmol·L-1,ketone bodies of 3.1 mmol·L-1,and metabolic acidosis on arterial blood gas analysis(pH 7.27,actual bicarbonate 6.9 mmol·L-1).EuDKA was diagnosed,with suspected urinary tract infection.Ertugliflozin was promptly discontinued.Treatments such as fluid resuscitation,low-dose insulin infusion via pump,electrolyte correction,and anti-infective therapy were administred.Symptoms gradually improved,and ketone bodies turned negative after three days.Using the Naranjo's Assessment Scale,the association between euDKA and the suspected drug ertugliflozin was rated as"probable"(score 7).This case suggested that concomitant use of SGLT2 inhibitors and metformin,especially with co-existing infection,may significantly increase the risk of euDKA.Enhanced medication evaluation and monitoring were recommended in clinical practice.

Objective:To systematically search, evaluate, and summarize evidence-based findings related to postoperative oral health management for orthognathic surgery patients, with the goal of providing clinical care professionals with evidence-based guidance for postoperative care, infection prevention, and functional recovery.Methods:Using the "6S" evidence hierarchy model, a systematic search was conducted in databases such as UpToDate, BMJ Best Practice, DynaMed, The Cochrane Library, World Health Organization (WHO), National Institute for Health and Care Excellence (NICE), Guidelines International Network (GIN), Registered Nurses′Association of Ontario (RNAO), Chinese Stomatological Association (CSA), American Association of Oral and Maxillofacial Surgeons (AAOMS), PubMed, and Scopus. The search included literature on postoperative oral health management for orthognathic surgery patients, such as guidelines, clinical decision-making tools, expert consensus, evidence summaries, and systematic reviews, covering publications from database inception to November 12, 2024. Two researchers independently assessed the quality of the included literature and extracted, summarized, and synthesized the evidence.Results:A total of 18 studies were included, consisting of 7 guidelines, 7 systematic reviews, 2 expert consensus documents and 2 randomized controued trials. Twenty-two best evidence statements were summarized, addressing six key areas: oral hygiene and infection prevention, wound care, oral functional recovery, dietary and nutritional support, oral comfort management, and long-term oral health maintenance.Conclusions:This study provides a comprehensive summary of the best available evidence for postoperative oral health management in orthognathic surgery patients. It offers theoretical support for clinical nursing practices and evidence-based recommendations for postoperative care specific to this patient population.

ObjectiveTo analyze the epidemiological features and influencing factors of rabies in Shanxi Province，and to provide evidence to further promote the elimination of rabies in Shanxi Province. MethodsThe incidence data of rabies in Shanxi from 2011 to 2022 were collected and subjected to descriptive analysis. ResultsFrom 2011 to 2022， a total of 348 rabies cases were reported in Shanxi Province， with an average annual incidence of 0.080 3/10⁵. The incidence of rabies showed a downward trend overall. The highest incidence was in August. The cases were mainly farmers， mostly males， and most cases were reported between 50 and 69 years old. The data of cases showed that dogs were the main animals attacking human （93.96%）. The incubation period of most cases was 1‒3 months （37.37%）.The main exposure site was hand（51.33%）. Only 2.66% cases with grade Ⅲ exposure were injected with passive immune agents. ConclusionThe incidence of rabies in Shanxi Province continues to decrease， but there are still loopholes in prevention and control measures. It is necessary to strengthen the management and immunization of dogs，health education， and standardized procedures after exposure to maintain the achievements in the prevention and control of rabies.

Objective:To analyze the histopathological characteristics of peri-implant soft tissue in re-constructed jaws and the changes after keratinized mucosa augmentation(KM A)with free gingival graft(FGG).Methods:Twenty patients were enrolled in this study.Five patients of them,who were perio-dontal and systemic healthy and referred for crown lengthening before restoration with healthy keratinized gingiva collected were enrolled as healthy controls.15 patients of them were with fibula or iliac bone flaps jaw reconstruction(10 with fibula flap and 5 with iliac flap),who were referred to FGG and implant exposures before restoration.Soft tissue was collected before FGG in reconstructed jaws,and in 5 patients(3 with fibula flap and 2 with iliac flap)8 weeks after FGG if a second surgery was conducted.Histologi-cal analysis with hematoxylin-eosin stain and immunological analysis to interlukin-1(IL-1),interlukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were performed.Results:Thickness from the bottom of stratum basale to the top of stratum granulosum and thickness of keratinized layer in reconstructed jaws were significantly lower compared with that of natural healthy keratinized gingiva[0.27(0.20,0.30)mmvs.0.36(0.35,0.47)mm,P＜0.05;16.49(14.90,23.37)μm vs.26.37(24.12,31.53)μm,P＜0.05].In the reconstructed area,thickness from the bottom of stratum basale to the top of stra-tum granulosum increased after KMA with FGG[0.19(0.16,0.25)mm vs.0.38(0.25,0.39)mm,P=0.059]and the thickness of keratinized layer significantly increased after KMA with FGG[16.42(14.16,22.35)μm vs.28.57(27.16,29.14)μm,P＜0.05],which was similar to that in the con-trol group.Furthermore,the number of positive cells of IL-1,IL-6 and TNF-α significantly increased after KMA[0.67(0.17,8.93)vs.11.00(9.16,18.00);13.00(8.50,14.14)vs.21.89(15.00,28.12);0.22(0.04,0.63)vs.2.83(1.68,5.00),respectively,P＜0.05]as well as the average optical density value[0.15(0.14,0.17)vs.0.18(0.17,0.21);0.28(0.26,0.33)vs.0.36(0.33,0.37);0.23(0.22,0.29)vs.0.30(0.28,0.42),respectively,P＜0.05],which was similar to that in the healthy keratinized gingiva.Conclusion:The lack of rete pegs and inflammato-ry factors were common in soft tissue with jaw reconstruction.FGG can improve the quality of the epithe-lium and may improve the stability of the mucosa around implants.