In recent years, an increasing number of emerging environmental pollutants have been identified, garnering widespread attention. Many of these pollutants are characterized by their environmental persistence and bioaccumulation, which pose significant threats to both the ecological environment and human health. However, the molecular mechanisms underlying their effects remain unclear, limiting our ability to assess their adverse impacts and develop effective protective measures. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor traditionally known to be activated by dioxins and polycyclic aromatic hydrocarbons (PAHs) and is involved in the metabolism of exogenous chemicals. Recent research has shown that the AHR can be activated by a diverse range of exogenous and endogenous chemicals and participates in various biological processes. Studies have demonstrated that AHR mediates the toxic effects of emerging environmental pollutants such as perfluorooctane sulfonamide (PFOSA) and N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone (6PPDQ). This paper provided an overview of the AHR activation and the toxic effects induced by emerging environmental pollutants, with a focus on how the AHR activation interacts with multiple signaling pathways. The significance of these interactions in environmental risk assessment and toxicological research was also discussed. We aim to provide a scientific basis for environmental protection and risk assessment.

Objective To investigate the effects of an adeno-associated virus(AAV2)vector expressing secretory transforming growth factor-β(TGF-β)type Ⅱ receptor(sTβRⅡ)extracellular domain-IgG2a Fc fusion protein(sTβRⅡ-Fc)on proliferation and migration of triple-negative murine breast cancer 4T1 cells in mice.Methods The pAAV-sTβRⅡ-Fc vector expressing sTβRⅡ-Fc fusion protein constructed by molecular cloning,the capsid protein-expressing vector pAAV2 and the helper vector were co-transfected into HEK 293T cells to prepare the recombinant AAV2-sTβRⅡ virus,which was purified by density gradient centrifugation with iodixanol.Western blotting was used to examine the effects of AAV-sTβRⅡ virus on Smad2/3 phosphorylation in 4T1 cells and on expression levels of E-cadherin,vimentin and p-Smad2/3 in 4T1 cell xenografts in mice.BALB/c mice bearing subcutaneous xenografts of luciferase-expressing 4T1 cells received intravenous injections of AAV-sTβRⅡ virus,AAV-GFP virus or PBS(n=6)through the tail vein,and the proliferation and migration of 4T1 cells were analyzed with in vivo imaging.Ki67 expression in the tumor tissues and sTβRⅡ protein expressions in mouse livers were detected with immunohistochemistry and immunofluorescence staining,and tumor metastases in the vital organs were examined with HE staining.Results The recombinant pAAV-sTβRⅡ-Fc vector successfully expressed sTβRⅡ in HEK 293T cells.Infection with AAV2-sTβRⅡ virus significantly reduced TGF-β1-induced Smad2/3 phosphorylation in 4T1 cells and effectively inhibited proliferation and lung metastasis of 4T1 xenografts in mice(P<0.05).In the tumor-bearing mice,intravenous injection of AAV-sTβRⅡ virus significantly increased E-cadherin expression,reduced vimentin and Ki67 protein expressions and Smad2/3 phosphorylation level in the tumor tissues(P<0.05 or 0.01),and induced liver-specific sTβRⅡ expression without causing body weight loss or heart,liver,spleen or kidney pathologies.Conclusion The recombinant AVV2 vector encoding sTβRⅡ extracellular domain is capable of blocking the TGF-β signaling pathway to inhibit the proliferation and lung metastasis of 4T1 cells in mice.

Objective To investigate the effects of an adeno-associated virus(AAV2)vector expressing secretory transforming growth factor-β(TGF-β)type Ⅱ receptor(sTβRⅡ)extracellular domain-IgG2a Fc fusion protein(sTβRⅡ-Fc)on proliferation and migration of triple-negative murine breast cancer 4T1 cells in mice.Methods The pAAV-sTβRⅡ-Fc vector expressing sTβRⅡ-Fc fusion protein constructed by molecular cloning,the capsid protein-expressing vector pAAV2 and the helper vector were co-transfected into HEK 293T cells to prepare the recombinant AAV2-sTβRⅡ virus,which was purified by density gradient centrifugation with iodixanol.Western blotting was used to examine the effects of AAV-sTβRⅡ virus on Smad2/3 phosphorylation in 4T1 cells and on expression levels of E-cadherin,vimentin and p-Smad2/3 in 4T1 cell xenografts in mice.BALB/c mice bearing subcutaneous xenografts of luciferase-expressing 4T1 cells received intravenous injections of AAV-sTβRⅡ virus,AAV-GFP virus or PBS(n=6)through the tail vein,and the proliferation and migration of 4T1 cells were analyzed with in vivo imaging.Ki67 expression in the tumor tissues and sTβRⅡ protein expressions in mouse livers were detected with immunohistochemistry and immunofluorescence staining,and tumor metastases in the vital organs were examined with HE staining.Results The recombinant pAAV-sTβRⅡ-Fc vector successfully expressed sTβRⅡ in HEK 293T cells.Infection with AAV2-sTβRⅡ virus significantly reduced TGF-β1-induced Smad2/3 phosphorylation in 4T1 cells and effectively inhibited proliferation and lung metastasis of 4T1 xenografts in mice(P<0.05).In the tumor-bearing mice,intravenous injection of AAV-sTβRⅡ virus significantly increased E-cadherin expression,reduced vimentin and Ki67 protein expressions and Smad2/3 phosphorylation level in the tumor tissues(P<0.05 or 0.01),and induced liver-specific sTβRⅡ expression without causing body weight loss or heart,liver,spleen or kidney pathologies.Conclusion The recombinant AVV2 vector encoding sTβRⅡ extracellular domain is capable of blocking the TGF-β signaling pathway to inhibit the proliferation and lung metastasis of 4T1 cells in mice.

Polygoni multiflori radix praeparata is a processed product of Polygoni multiflori radix(Polygonum multiflorum Thunb.),and its main components include stilbene glycosides,anthraquinones,flavonoids,alkaloids,phenolic acids,etc.It has antioxidant,antianemic,anti-tumor,hypoglycemic,anti-inflammatory effects,etc,and is widely used in clinical practice.The processing technology is mainly stewinging with black bean juice,steaming,processing for 9 times and braising and simmering.After processing,the color deepens and the content of composition changes.By consulting domestic and foreign literature,the research on Polygoni multiflori radix praeparata is not comprehensive enough compared with Polygoni multiflori radix.Therefore,this paper mainly summarizes the processing technology,chemical composition and pharmacological activity of Polygoni multiflori radix preparata reported in the past 20 years,and provides a reference for further development of Polygoni multiflori radix preparata.

Objective:To analyze the clinical situation of critically ill children with Montgomery T-tube，aiming to summarize the characteristics of T-tube application in pediatric and the experience of postoperative airway management in PICU.Methods:The etiology，clinical characteristics，complications and ICU admissions of patients with Montgomery T-tube admitted to the Pediatric Hospital of Fudan University from April 2019 to December 2021 were analyzed，and the application of T-tube in patients with critical conditions requiring long-term mechanical ventilation was described in the light of clinical experience.Results:During the study period,seven children were admitted to the PICU after T-tube insertion,including three males and four females,aged 9~75 months.Five children received mechanical ventilation.Among them,there were five cases with congenital laryngeal malformations,one case with tracheoesophageal fistula,and one case with laryngeal papilloma.The main complications were sputum blockage,infection,and granulation proliferation.One child died of secretion blockage,while the other children were successfully evacuated from the T-tube.The longest retention time of the T-tube was 367 days.Five patients experienced hoarseness after removing the T-tube,and upon re-examination with fiberoptic bronchoscopy,no recurrence of subglottic stenosis was observed.There was no respiratory distress or wheezing,and there were no abnormalities observed during regular outpatient follow-up after discharge.After discharge,the quality of life of the six surviving children improved compared to preoperative,and they all resumed oral feeding.There were no complaints of swallowing difficulties or aspiration during outpatient follow-up.But they were all combined with malnutrition.Conclusion:The Montgomery T-tube is a secure and dependable airway stent utilized for airway remodeling and the maintenance of airway patency following interventional surgery.For critically ill children,early management of airway clearance and infection prevention are imperative.

Objective To investigate the attitudes and influencing factors of transplantation-related populations towards kidney xenotransplantation. Methods From June 2022 to January 2023, stratified random sampling was performed from patients awaiting kidney transplantation, patients after kidney transplantation, patients' relatives and medical students. Four hundred subjects were collected from each population and 1600 subjects were investigated using a self-designed questionnaire. Baseline data of the respondents, their attitudes towards kidney xenotransplantation and the reasons of rejecting kidney xenotransplantation were analyzed. The influencing factors of attitudes towards kidney xenotransplantation were also identified. Results A total of 1 493 valid questionnaires were collected, and the questionnaire retrieval rate was 93.31%. About 93.10% of the respondents accepted allogeneic kidney transplantation, and 66.78% had heard of kidney xenotransplantation. Seven hundred and ninety-five respondents suggested that they could accept kidney xenotransplantation "when kidney xenotransplantation and allogeneic kidney transplantation yielded the same results and risks". Six hundred and ninety-eight respondents indicated that they were "unable" or "uncertain" whether they could accept kidney xenotransplantation (χ²=16.409，P=0.001). Among these 698 respondents, the proportion of them who were willing to accept kidney xenotransplantation when they did not meet the conditions of allogeneic kidney transplantation was 10.9%. About 35.8% of respondents were willing to accept kidney xenotransplantation if it yielded less risk and better prognosis compared with allogeneic kidney transplantation. If the time of awaiting kidney xenotransplantation was shorter than that of allogeneic kidney transplantation, 21.2% were willing to accept kidney xenotransplantation. If the cost of kidney xenotransplantation was less than that of allogeneic kidney transplantation, 24.5% of them were willing to accept kidney xenotransplantation. The main reasons of rejecting kidney xenotransplantation included surgical risk and other unknown risks. Multivariate analysis showed that respondents residing in cities and towns for a long period of time, those who accept allogeneic kidney transplantation and those who have heard of kidney xenotransplantation showed more positive attitudes towards kidney xenotransplantation. Conclusions Different transplantation-related populations have different attitudes towards kidney xenotransplantation, and the overall attitudes are positive. Active promotion of kidney xenotransplantation research and carrying out relevant popular science education contribute to improving public attitudes towards the acceptance of kidney xenotransplantation.

Respiratory therapist is a new profession in medicine, who works therapeutically with people suffering from pulmonary disease.Their timely treatments of patients with cardiopulmonary insufficiency can significantly reduce mortality in pediatric intensive care units.This review focused on the responsibilities of respiratory therapists, the importance of respiratory support therapy in children, and the most updated development in China as well as the problems to be solved.

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals ; Alzheimer Disease/metabolism* ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/metabolism* ; Drosophila/physiology* ; Drosophila Proteins/metabolism* ; Resveratrol/pharmacology* ; Sirtuin 1 ; Sleep

Objective:To investigate the clinical epidemiological data of children with prolonged mechanical ventilation (PMV) in pediatric intensive care unit(PICU), and analyze the primary disease of children with PMV as well as the disease characteristics and prognosis of children with PMV under different kinds of primary disease.Methods:The clinical data of hospitalized children with PMV in PICU at Children′s Hospital of Fudan University from January 2019 to December 2020 were retrospectively collected.Results:A total of 46 children with PMV were collected.There were 18 males (39.1%) and 28 females (60.9%). The median age was 37 (8, 86) months and the median body weight was 15 (7, 20) kg.The average pediatric critical illness score at admission was 84.2±7.7, PaO 2/FiO 2 was (245.5±99.8)mmHg.The primary diseases leading to PMV were as follows: there were 14 cases of severe pneumonia, eight cases of severe encephalitis, five cases of bronchopulmonary dysplasia, three cases of upper airway obstruction/craniofacial deformity, three cases of myasthenia, three cases of brain stem tumor, three cases of mitochondrial encephalomyopathy, two cases of spinal muscular atrophy, two cases of Prader-Willi syndrome, one case of dermatomyositis, one case of severe brain injury, and one case of central hypoventilation.The causes of unable to withdraw ventilator were respiratory dysfunction in 24 cases, brain dysfunction in 16 cases, and diaphragm dysfunction in six cases.Compared with neuromuscular diseases, children with PMV caused by respiratory diseases had lower month age, higher preterm birth rate, lower PaO 2/FiO 2 ratio, higher parameters for ventilator treatment, and the differences were statistically significant ( P<0.05). Children with PMV caused by neuromuscular diseases had lower Glasgow coma score and higher coma rate, and the differences were statistically significant ( P<0.05). A total of nine (19.6%) cases underwent tracheotomy.A total of 23 (50.0%) cases were successfully extubated from ventilator, six (13.0%) cases were dependent on invasive ventilator, and six (13.0%) cases were breathing with tracheotomy tube.The median mechanical ventilation time was 33 (28, 40) days, the median PICU hospital stay was 42 (34, 56) days, and the median hospital stay was 51 (41, 65) days.A total of 27 (58.7%) cases were improved and discharged, four (8.7%) cases were transferred to rehabilitation hospital, four (8.7%) cases were transferred to local hospital, and 11 (23.9%) cases died in hospital or at home after giving up. Conclusion:The main causes of PMV in PICU children are respiratory dysfunction, brain dysfunction and diaphragm dysfunction.50.0% of the children with PMV could be discharged from the ventilator, and 23.9% died or died after giving up.

Objective:To summarize the experience of the precise prevention and control strategy of novel coronavirus infection in the pediatric intensive care unit(PICU)during the epidemic of the Omicron variant.Methods:A retrospective analysis was performed on the strategies and management experience of precise prevention and control of novel coronavirus infection in PICU at Pediatric Hospital of Fudan University from March 1 to May 10, 2022.Results:According to the national and Shanghai novel coronavirus infection prevention and control standards, the PICU in our hospital, in accordance with the specialty characteristics of PICU, cooperated with the hospital′s department of infection and medical department to jointly construct a precise ward management strategy for the outbreak of the omicron mutants infection.Precise prevention and control management strategies were formulated from four aspects: the admission process of critically ill children, the division of PICU ward areas and nosocomial infection protection, the reception management system for children′s family members, and the " bubble management" system for PICU staff, and run them for 3 months.During the epidemic, there was no nosocomial infection of novel coronavirus infection in children or medical staff.During the period, a total of 140 critically ill children were admitted, including 87 cases transferred from the general ward in the hospital, 48 cases from the emergency department(non-febrile, 3 cases transferred by the transfer team), four cases from fever clinic, and one case from control ward.Four of the critically ill children had no emergency nucleic acid test report when they were admitted to the PICU.Among the 140 critically ill children, 54 patients received mechanical ventilation, 18 patients received blood purification, and two patients were monitored after liver transplantation.Seventy-eight (55.7%) children had underlying diseases.Conclusion:During the current round of novel coronavirus epidemic in Shanghai, PICU in our hospital formulated the admission and ward management procedures for critically ill children, which ensured the prevention and control of nosocomial infection of novel coronavirus, and at the same time ensured the treatment of critically ill children to the greatest extent.