ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

Diabetes mellitus, characterized by glucose metabolism disorders and marked by insulin deficiency or insulin resistance, has seen a continuous rise in prevalence. In recent years, islet transplantation has matured as a therapeutic approach for diabetes, becoming an important method for glycemic control and the reduction of diabetes-related complications. Donor selection directly influences transplant outcomes, and various research institutions worldwide have proposed multiple scoring systems to optimize donor assessment, such as the University of Alberta scoring system and the North American Islet Donor Score. This article explores the impact of key factors such as donor age, body mass index and ischemia time on islet transplantation. Combining practical experience in pancreatic donor selection from Shanghai Changzheng Hospital, it proposes screening criteria for pancreatic donors suitable for China, aiming to provide new evidence for improving the success rate of islet transplantation.

OBJECTIVE To investigate the epidemiological characteristics of respiratory human adenovirus(H AdV)infections in hospitalized children in Ningbo,and to provide data for formulating infection prevention and control strategies for HAdV.METHODS A total of 65 022 children hospitalized with respiratory infections at the Women and Children's Hospital of Ningbo University from Jul.2019 to Dec.2024 were selected as the study sub-jects.Multiple reverse transcription-polymerase chain reaction(RT-PCR)and capillary electrophoresis were used to detect 11 non-bacterial pathogens.Basic and clinical information of the children was collected for analysis.RESULTS A total of 65 022 specimens were tested,with 4 292 cases tested positive for HAdV positivity,yielding a positive rate of 6.60％.The lowest positive rate was observed in 2023(3.22％),while the highest was in 2024(13.97％).Compared to the years 2019-2023,the overall HAdV positive rate was high in 2024,peaking at 26.80％in Jun.,indicating an outbreak.The total HAdV positive rate was higher in boys(6.82％)than in girls(6.32％)(P=0.006).The highest HAdV positive rate was observed in the 2 to＜6 age group(9.00％),while the lowest was in the 0 to＜1 age group(2.33％).Among the HAdV-positive specimens,2 658 cases(61.93％)were single infections,and 1 634 cases(38.07％)were co-infections.The non-bacterial respiratory pathogens with the highest co-infection rates were human rhinovirus(34.09％),Mycoplasma pneumoniae(20.44％)and human parainfluenza virus(5.75％).CONCLUSIONS A n outbreak of HAdV infections is observed among hospitalized children in Ningbo in 2024.Higher positive rates are found in boys aged 2 to＜6 years,with a certain proportion of co-infections.

Currently,there are practical and technical difficulties in the construction of clinical ques-tions in the development of clinical practice guidelines.Clinicians or guideline developers seldom construct clin-ical questions based the actual case scenario,leading to some information loss between structured and actual clinical connotation.To overcome this challenge,we proposed a case-guided questions construction approach,and carried out case research and verification in the formulation of the guideline.We found that this method could more efficiently and scientifically assist the formulation of clinical questions,and provide reference for clinicians or guideline developers.

BACKGROUND:Current strategies for the treatment of the corticospinal tract after spinal cord injury mainly focus on exercise rehabilitation,drug therapy,transcranial magnetoelectric stimulation,endogenous regulation such as transcription factors and specific signaling pathways.Among them,transcription factors and their specific signaling pathways are the key factors regulating the axonal regeneration of corticospinal tract after spinal cord injury.A large number of preclinical studies have confirmed that the synergy between transcription factors and their signaling pathways has a significant regulatory effect on the axonal regeneration of neurons in the corticospinal tract after spinal cord injury.Therefore,it has broad application prospects to explore new combination therapy strategies targeting transcription factors and specific signaling pathways for spinal cord injury.OBJECTIVE:To systematically summarize the regulatory effects of transcription factors and their signaling pathways on the axonal regeneration of neurons in the corticospinal tract after spinal cord injury and the underlying molecular mechanisms,and explore the application of combined therapy strategies targeting transcription factors and signaling pathways in the neuroplasticity of the corticospinal tract after spinal cord injury,in order to provide a new combination strategy for the treatment of spinal cord injury.METHODS:The search terms included"spinal cord injury,axon regeneration,transcription factors,signaling pathway,corticospinal tract,central nervous system,synergistic system,neuroprotective system"in Chinese and English.A literature retrieval was conducted in WanFang,Web of Science,and PubMed for relevant literature published from database inception to September 2024.Finally,101 articles were included for analysis and summary.RESULTS AND CONCLUSION:(1)The article outlines the biological properties and intervention strategies for axonal regeneration of the corticospinal tract after spinal cord injury,analyses the reasons for focusing on the corticospinal tract after spinal cord injury,and elucidates the response and possibility of regeneration of the corticospinal tract after spinal cord injury.(2)In this study,the combined regulatory strategy of transcription factors centered on Krüppel-like factor 6,Krüppel-like factor 7,and neuronal restriction silencing factor can significantly promote the axonal regeneration of neurons in the corticospinal tract after spinal cord injury.(3)The phosphatidylinositol 3-kinase-protein kinase B-rapamycin target protein signaling pathway and Wnt5a pathway are the classical signaling pathways fortranscription factors to regulate the axonal regeneration of corticospinal tract neurons,and the combined treatment strategy can effectively promote the axonal regeneration and functional reconstruction of corticospinal tract neurons after spinal cord injury.(4)This article discusses the combined treatment strategies of transcription factors and specific signaling pathways in a comprehensive and detailed manner,such as Krüppel-like factor 6 combined with signal transducer and activator of transcription 3,Krüppel-like factor 7 combined with SOX11 transcription factor,combined inhibition of phosphatase and tensin homologs and neuronal restriction silencing factor,etc.,to exert a synergistic effect and promote the axonal regeneration of corticospinal tract neurons after spinal cord injury,which are significantly better than those of single treatment.It can effectively improve functional recovery and provide a reference scheme for the future treatment of axonal regeneration of corticospinal tract neurons after spinal cord injury.However,the specific mechanism of the combination therapy still needs to be further studied,and the current combination strategy is only widely used in animal models but not in clinical practice.(5)The combined therapy strategy based on transcription factors and specific signaling pathways has a significant therapeutic effect on the axonal regeneration of corticospinal tract neurons after spinal cord injury,and it is necessary to further explore the molecular mechanism of joint regulation in the future,in order to provide an effective combined therapy strategy for the rehabilitation and functional reconstruction of spinal cord injury.

Objective To investigate the regulatory effect and mechanism of Yiqi Jiedu Decoction(YQJD)on ionizing radiation-induced macrophage polarization and its correlation with the Toll-like receptor 4(TLR4)/myeloid differentiation primary response protein 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway.Methods Fifty-five specific-pathogen-free male Sprague-Dawley rats were randomly divided into blank(n=30),anduolin(n=10),and YQJD groups(n=15).They were respectively gavaged with deionized water,anduolin suspension(0.345 6 g/kg),and YQJD high-dose(20.88 g/kg)at a dose of 0.01 mL/g body weight once a day for seven consecutive days.2 hours after the last gavage,blood was collected from the abdominal aorta to prepare the control rat,andolin rat,and YQJD high-dose sera.Appropriate amounts of YQJD high-dose and control sera were mixed in a ratio of 1∶1 and 1∶3,respectively,to obtain YQJD medium-and low-dose rat serum.RAW264.7 cells were divided into blank(10%blank rat serum),model(10%blank rat serum),anduolin(10%anduolin rat serum),and YQJD-L,YQJD-M,YQJD-H groups(10%YQJD low-,medium-,and high-dose rat serum).Except for the blank group,the cells in other groups were irradiated with 12 Gy60 Co γ-rays once to establish the macrophage radiation injury model.At 24 h after irradiation,cell viability was detected using the CCK-8 method,and the cell migration rate was measured using the scratch test.Cell morphology was observed using phalloidin staining,tumor necrosis factor-alpha(TNF-α)and interleukin-10(IL-10)levels in the cell supernatant were quantified using enzyme-linked immunosorbent assay,and the proportion of M1 macrophages was detected using flow cytometry.TLR4,MyD88,and NF-κB protein expression were detected using Western blotting.Results Twenty-four hours after irradiation,compared with the blank group,the model group exhibited significantly reduced cell viability and migration rate(P<0.01),increased cell volume and pseudopodia formation,elevated TNF-α and IL-10 levels,an increased proportion of M1 macrophages,and upregulated TLR4,MyD88,and NF-κB protein expression(P<0.05,P<0.01).Compared with the model group,each drug-treated group showed improved cell viability and migration rate(P<0.05,P<0.01),decreased cell volume,more regular cell shape,reduced TNF-α levels,lower M1-type macrophage proportion,and downregulated TLR4,MyD88,and NF-κB protein expression(P<0.05,P<0.01).IL-10 level showed an upward trend.Conclusion YQJD can partially inhibit M1 macrophage polarization and suppress inflammatory responses,which may be related to the TLR4/MyD88/NF-κB signaling pathway.

The incidence of delayed chemotherapy-induced nausea and vomiting is relatively high among pediatric cancer patients. Nausea and vomiting symptoms can exacerbate physical and psychological burdens, potentially leading to aversion and reduced treatment adherence. This paper analyzes and summarizes delayed chemotherapy-induced nausea and vomiting in pediatric cancer patients, covering overview, influencing factors, assessment tools, and non-pharmacological interventions, aiming to provide insights for clinical prevention and intervention strategies targeting delayed chemotherapy-induced nausea and vomiting in pediatric patients.

Objective:To evaluate the role of YTH domain family protein 2 (YTHDF2) in myocardial ischaemia-reperfusion injury (MIRI) in diabetic rats and the relationship with the nuclear factor E2-related factor 2 (NRF2)-ferritinophagy.Methods:This experiment was performed in 2 parts. Part Ⅰ Animal experiment SPF healthy male rats, aged 6-8 weeks, weighing 200-220 g, were used. A type 1 diabetes mellitus (DM) model was established by intraperitoneal injection of 1% streptozotocin at a dose of 65 mg/kg. Thirty-six diabetic rats were divided into 3 groups ( n=12 each) using a random number table method: DM sham operation group (DS group), DM myocardial ischaemia-reperfusion group (DIR group), and YTHDF2 knockdown + DM myocardial ischaemia-reperfusion group (AAV-Y+ DIR group). Another 36 non-diabetic rats were selected and divided into 4 groups using the random number table method: sham operation group (NS group, n=12), myocardial ischaemia-reperfusion group (NIR group, n=12), adeno-associated virus control group (AAV-N group, n=6), and YTHDF2 knockdown group (AAV-Y group, n=6). The MIRI model was established by ligating the left anterior descending branch of the coronary artery for 30 min, followed by reperfusion for 2 h. Adeno-associated virus was employed to knock down YTHDF2. At the end of reperfusion, serum concentrations of creatine kinase isoenzyme MB(CK-MB) and cardiac troponin Ⅰ(cTnI) were measured using enzyme-linked immunosorbent assay. The animals were sacrificed, myocardial tissues were harvested, and the pathological changes were observed with a light microscope to assess the myocardial infarct size. The expression of YTHDF2, NRF2, and nuclear receptor coactivator 4 (NCOA4) was detected by Western blot. Part Ⅱ Cell experiment H9c2 cells were divided into 9 groups ( n=24 each) using the random number table method: control group (NC group), high-glucose group (HG group), hypoxia-reoxygenation group (HR group), high-glucose hypoxia-reoxygenation group (HHR group), transfection control group (siN group), YTHDF2 knockdown group (siY group), YTHDF2 knockdown + high-glucose hypoxia-reoxygenation group (siY + HHR group), NRF2 inhibitor ML385 + high-glucose hypoxia-reoxygenation group (M + HHR group), and YTHDF2 knockdown + NRF2 inhibitor ML385 + high-glucose hypoxia-reoxygenation group (siY + M + HHR group). The cells were transfected with siRNA to knock down YTHDF2, and a high-glucose, hypoxia and reoxygenation injury model was established by subjecting cells to 48 h of high glucose, followed by 4 h of hypoxia and 2 h of reoxygenation. The cell viability and lactic dehydrogenase(LDH) activity were determined, autophagic vesicles were counted, and the expression of YTHDF2, NRF2 and NCOA4 was detected by Western blot. Results:Part Ⅰ Animal experiment At the end of myocardial ischaemia-reperfusion, serum levels of CK-MB and cTnI and the percentage of myocardial infarct size were significantly increased, the expression of YTHDF2 and NCOA4 in myocardial tissues was up-regulated, and the expression of NRF2 was down-regulated in both diabetic and non-diabetic groups ( P<0.05). Compared with NIR group, serum levels of CK-MB and cTnI and the percentage of myocardial infarct size were significantly increased, the expression of YTHDF2 and NCOA4 in myocardial tissues was up-regulated, and the expression of NRF2 was down-regulated in DIR group ( P<0.05). Compared with DIR group, serum levels of CK-MB and cTnI and the percentage of myocardial infarct size were significantly decreased, the expression of YTHDF2 and NCOA4 in myocardial tissues was down-regulated, and the expression of NRF2 was up-regulated ( P<0.05), and the pathological damage was reduced in AAV-Y + DIR group. Part Ⅱ Cell experiment Compared with HG and HR groups, the cell viability was significantly decreased, the activity of LDH was increased, the counts of autophagic vesicle were increased, the expression of YTHDF2 and NCOA4 was up-regulated, and the expression of NRF2 was down-regulated in HHR group ( P<0.05). Compared with HHR group, the cell viability was significantly decreased, the activity of LDH was increased, the counts of autophagic vesicle were increased, the expression of YTHDF2 and NCOA4 was up-regulated, and the expression of NRF2 was down-regulated in M + HHR group, and the cell viability was significantly increased, the activity of LDH was decreased, the counts of autophagic vesicle were decreased, the expression of YTHDF2 and NCOA4 was down-regulated, and the expression of NRF2 was up-regulated in siY + HHR group ( P<0.05), and no statistically significant changes were found in the above indicators in siY + M + HHR group ( P>0.05) Conclusions:YTHDF2 can down-regulate the expression of NRF2, enhance the level of ferritinophagy, and participate in the process of MIRI in diabetic rats.

Objective:To compare the effects of propofol and dexmedetomidine for sedation on the outcome in mechanically ventilated patients with severe pulmonary infection.Methods:Patients with severe pulmonary infection (Clinical Pulmonary Infection Score >7) requiring mechanical ventilation from the Medical Information Mart for Intensive Care Ⅳ database between 2008 and 2020 were selected and divided into propofol group and dexmedetomidine group based on the sedative agent used. The primary outcome was all-cause in-hospital mortality, and secondary outcomes included 90-day all-cause mortality and duration of mechanical ventilation. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders, and logistic regression and linear regression were applied to analyze the effects of the two sedative drugs on the outcomes of mechanically ventilated patients with pulmonary infection. Kaplan-Meier survival curves were used to analyze survival outcomes.Results:A total of 6 204 critically ill patients with pulmonary infection requiring mechanical ventilation were included, with 3 439 cases in propofol group and 2 765 cases in dexmedetomidine group. The baseline characteristics between the two groups were well balanced (standardized mean difference < 0.1) after IPTW adjustment. In the IPTW-adjusted cohort, the in-hospital all-cause mortality and 90-day all-cause mortality were significantly lower in dexmedetomidine group than in propofol group (439.2[18.7%] vs 563.6[24.1%], 618.0[26.3%] vs 733.6[31.3%], P<0.001), the results of Further Kaplan-Meier survival curve analysis showed that the 90-day all-cause mortality was significantly lower in dexmedetomidine group than in propofol group ( P<0.01). Conclusions:Compared with propofol, dexmedetomidine can decrease the mortality rate and improve the prognosis in mechanically ventilated patients with severe pulmonary infection when used for sedation.

Objective Under the guidance of nurses,an intelligent medical waste temporary storage equipment was developed and its application effect was evaluated,aiming to optimize the medical waste recycling process and save human resources.Methods A research and development(R&D)team was established to analyze the issues in the current medical waste temporary storage process.An intelligent medical waste temporary storage device was developed,equipped with functions such as categorized disposal,permission scanning,barcode recognition,intelligent weighing,overflow alarm,and ozone disinfection.From January 19th to February 20th,2023,an intelligent medical waste storage equipment was placed in the medical waste storage room on the 7th to 9th floors of the outpatient clinic of a tertiary hospital in Wuhan city as an experimental group;traditional medical waste storage bins were placed on the 4th and 5th floors of the outpatient department as a control group.The daily disposal indicators and environmental hygiene monitoring indicators of 2 groups of medical waste were compared.Results With the application of the intelligent medical waste temporary storage device,the disinfection rate of medical waste increased from 5.00％to 100％;the overflow rate decreased from 42.52％to 0％;the handover time reduced from 4.98±2.21 minutes to 1.07±0.35 minutes;the standardization rate of handovers rose from 15.83％to 100％.All these differences were statistically significant(P＜0.001).Additionally,the pass rate of bacterial colonies on the inner walls of bins increased from 53.33％to 67.78％,with a statistically significant difference(P=0.012).Conclusion The application of the intelligent medical waste temporary storage equipment significantly improves the efficiency and quality of medical waste management;at the same time,it also plays an active role in improving the storage environment,which can safeguard the environmental hygiene of hospitals and the safety of patients.