In September 2023， the Measures for Scientific and Technological Ethics Review （Trial Implementation） was issued， revising the provisions related to the simplified procedure for ethical review in Chapter 3， Section 3. This revision of these provisions provides systematic guarantees for further optimizing ethical review work， ensuring that ethical review procedure is well-regulated， and improving scientific research efficiency. The “simplified procedure” does not mean reducing the quality and requirements of the review. Instead， based on always following internationally recognized ethical standards and emphasizing not violating national laws and regulations， improving the efficiency of ethical review and subsequent research work， and promoting the development of life sciences and medical research involving humans. In practical work， it introduces numerous new opportunities and challenges for the improvement of ethics review ability， such as new tests on the judgment and decision-making power of ethics committees， how to ensure the reliability and controllability of the conditions related to the simplified review procedure， and how to determine the basic conditions for adopting the simplified review procedure for review. Therefore， to actively respond to the challenges and possible risks brought by the simplified procedure review， efforts should be made to achieve three “unifications”， including the unification of researchers’ moral autonomy and the heteronomy of supervision implemented by relevant departments； the unification of the standard formulation of the simplified procedure review and the review work in practice； and the unification of ethical responsibility and legal responsibility.

Objective To analyze the characteristics of postoperative hospital-acquired infections and drug sensitivity in lung transplant recipients over the past 5 years in a single center. Methods A total of 724 lung transplant recipients at Wuxi People's Hospital from January 2019 to December 2023 were selected. Based on the principles of hospital-acquired infection diagnosis, a retrospective analysis was conducted on the hospital infection situation and infection sites of lung transplant recipients, and an analysis of the distribution of hospital-acquired infection pathogens and their antimicrobial susceptibility test status was performed. Results Among the 724 lung transplant recipients, 275 cases of hospital-acquired infection occurred, with an infection rate of 38.0%. The case-time infection rate decreased from 54.2% in 2019 to 22.8% in 2023, showing a downward trend year by year (Z=30.98, P<0.001). The main infection site was the lower respiratory tract, accounting for 73.6%. The pathogens were mainly Gram-negative bacteria, with the top four being Acinetobacter baumannii (37.1%), Pseudomonas aeruginosa (17.3%), Klebsiella pneumoniae (13.7%), and Stenotrophomonas maltophilia (13.4%), with imipenem resistance rates of 89%, 53%, 58% and 100%, respectively. Gram-positive bacteria were mainly Staphylococcus aureus (3.6%), with a methicillin resistance rate of 67%. Conclusions Over the past 5 years, the hospital-acquired infections in lung transplant recipients have shown a downward trend, mainly involving lower respiratory tract infections, with the main pathogens being Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, all of which have high resistance rates to imipenem.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

BACKGROUND:The mechanism of programmed death receptor-1(PD-1)effect on osteogenic differentiation of bone marrow mesenchymal stem cells in high glucose environment remains unclear. OBJECTIVE:To explore the effect of PD-1 on osteogenic differentiation of rat bone marrow mesenchymal stem cells in high glucose environment and its regulatory mechanism. METHODS:Rat bone marrow mesenchymal stem cells were randomly divided into normal glucose group(5.6 mmol/L),high glucose group(30 mmol/L),PD-1 overexpression group,PD-1 overexpression no-load group,PD-1 knockdown group,PD-1 knockdown no-load group,and PI3K/AKT pathway inhibitor group(PD-1 knockdown+5 μmol/L LY294002).Rat bone marrow mesenchymal stem cells were cultured in high glucose to simulate the diabetic environment in vitro.The mRNA expression of PD-1 and ligand PD-L1 and the mRNA expression of osteogenic markers Runx2 and OSX in rat bone marrow mesenchymal stem cells were detected by qRT-PCR.The osteogenic differentiation ability was observed by alkaline phosphatase staining and alizarin red staining.Cell proliferation was detected by CCK-8 assay.The protein expressions of PD-1,PD-L1,p-PI3K,and p-AKT were detected by western blot assay. RESULTS AND CONCLUSION:(1)The levels of PD-1 and PD-L1 were significantly increased in the high glucose environment in vitro,and the osteogenic differentiation ability of bone marrow mesenchymal stem cells was inhibited in the high glucose environment.(2)Knockdown of PD-1 expression could promote osteogenic differentiation of bone marrow mesenchymal stem cells,increase cell proliferation activity,and activate the PI3K/AKT pathway.(3)After addition of PI3K/AKT pathway inhibitor LY294002,the ability of bone marrow mesenchymal stem cells to differentiate into osteoblasts decreased.The results show that PD-1 is dependent on the PI3K/AKT signaling pathway to inhibit osteogenic differentiation of rat bone marrow mesenchymal stem cells under high glucose environment.

BACKGROUND:U937 cells can be used as a cell model for studying the biological characteristics,signaling pathways,and therapeutic targets of acute myeloid leukemia.Although it has been reported that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia,its biological function in U937 cells remains unclear,and its mechanism of action in the occurrence and development of acute myeloid leukemia needs to be further clarified. OBJECTIVE:To investigate the expression level of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia and its effect on the proliferation and apoptosis of U937 cells. METHODS:RNA-sequencing was used to analyze the bone marrow monocyte samples from acute myeloid leukemia patients,and the differentially expressed gene long non-coding RNA KIAA0125 was screened.The expression of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia was detected by qRT-PCR.The relationship between long non-coding RNA KIAA0125 mRNA expression and prognosis in bone marrow cells of 173 acute myeloid leukemia patients and 70 healthy people was statistically analyzed by GEPIA database.Subsequently,recombinant lentivirus technology and CRISPR/Cas9-SAM technology were used to construct U937 cell lines with knockdown/overexpression of long non-coding RNA KIAA0125.qRT-PCR was used to detect the knockdown/overexpression efficiency of long non-coding RNA KIAA0125.Next,CCK-8 assay,flow cytometry,and western blot assay were used to detect the effects of knockdown/overexpression of long non-coding RNA KIAA0125 on the proliferation and apoptosis of U937 cells.Finally,western blot assay was used to detect the effect of knockdown/overexpressed long non-coding RNA KIAA0125 on Wnt/β-catenin signaling pathway-related proteins. RESULTS AND CONCLUSION:(1)The results of qRT-PCR showed that long non-coding RNA KIAA0125 was highly expressed in peripheral blood of acute myeloid leukemia patients.The results of GEPIA database showed that long non-coding RNA KIAA0125 was highly expressed in bone marrow cells of acute myeloid leukemia patients,and the high expression group had worse overall survival.(2)The knockdown efficiency of long non-coding RNA KIAA0125 in knockdown group was 70%,and the U937 cells that stably down-regulated long non-coding RNA KIAA0125 expression were successfully constructed.The expression of long non-coding RNA KIAA0125 in overexpression group was four times that of vector group,and stable U937 cells were successfully constructed.(3)Knockdown of long non-coding RNA KIAA0125 inhibited the proliferation of U937 cells and promoted their apoptosis.Overexpression of long non-coding RNA KIAA0125 promoted the proliferation of U937 cells but had no significant effect on the apoptosis of U937 cells.(4)Knockdown of long non-coding RNA KIAA0125 inhibited the activity of Wnt/β-catenin signaling pathway,while overexpression of long non-coding RNA KIAA0125 activated Wnt/β-catenin signaling pathway.These results confirm that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia peripheral blood.Long non-coding RNA KIAA0125 may affect the proliferation and apoptosis of U937 cells by regulating the Wnt/β-catenin signaling pathway,and may be a potential prognostic marker for acute myeloid leukemia.

ObjectiveTo study the mechanism of Shexiang Tongxin Dripping pills-containing serum （STDP） in ameliorating angiotensinⅡ （AngⅡ）-induced cell phenotype transformation， proliferation， migration， and dysfunction of vascular smooth muscle cells. MethodsAn AngⅡ-induced proliferation and migration model of vascular smooth muscle cells was established. The cells were treated with STDP at 5%， 10%， and 20% for 24 h. The immunofluorescence assay was employed to detect the expression of α smooth muscle actin （α-SMA） and matrix metalloproteinase-2 （MMP-2）. The cell-counting kit-8 （CCK-8） assay and 5-ethynyl-2'-deoxyuridine （EdU） staining were employed to detect the proliferation of vascular smooth muscle cells， and the scratch assay was employed to detect the migration of the cells. Western blot was employed to determine the expression levels of pathway proteins such as angiotensin-converting enzyme 2 （ACE2）， angiotensin Ⅱ type 2 （AT2）， angiotensin Ⅱ type 1 （AT1）， as well as proliferation and migration proteins such as typeⅠ collagen （ColⅠ） and osteopontin （OPN）. ResultsCompared with the model group， STDP increased the expression of α-SMA， reduced the expression of MMP-2， and inhibited the proliferation and migration of vascular smooth muscle cells （P<0.05）. Furthermore， STDP up-regulated the expression levels of ACE2， AT2， and MAS1， while down-regulating the expression level of AT1， PCNA， ColⅠ， MMP-9， Rock1， Rock2， and SRF （P<0.05）. Compared with the STDP group， the ACE2 inhibitor reversed the regulatory effects of STDP. ConclusionSTDP inhibits the phenotype transformation， proliferation， and migration of vascular smooth muscle cells and regulates the expression of cell proliferation and migration-related proteins to ameliorate the dysfunction of vascular smooth muscle cells. It exerts the effects by up-regulating the expression of proteins in the ACE2-AT2/MAS pathway and down-regulating the expression of proteins in the AT1-Rock signaling pathway.

ObjectiveTo explore the correlation between general anesthesia and mild cognitive impairment in older adults so as to provide new ideas for early prevention and timely intervention of mild cognitive impairment（MCI）. MethodsBased on the baseline survey of the Hubei memory and aging cohort study（2018-2023）， the participants completed a thorough neuropsychological assessment and physical examination， and self-reported a history of general anesthesia and surgery. The association of general anesthesia and MCI in the elderly was analyzed using the logistic regression model. In addition， the stratification and interaction analysis of anesthesia history， anesthesia number and physical intellectual exercise were conducted separately. ResultsA total of 5 069 older adults aged 65 and above were included in this study， including 3 692 city dwellers and 1 377 rural people， among whom were 2 584 women （51%）. Out of the 1 472 participants with history of general anesthesia， 249 people （17.4%） had MCI. After controlling for confounding factors， there was a 39.6% increased risk of MCI in older adults who underwent general anesthesia ［OR=1.396，95%CI（1.169，1.668），P<0.001］， suggesting that general anesthesia may be an independent influence on MCI. For the older adults who had one general anesthesia ［OR=1.235，95%CI（1.001，1.523），P=0.049］， two general anesthesia ［OR=1.779，95%CI （1.292，2.450），P<0.001］， and three OR more general anesthesia ［OR=2.395，95%CI （1.589，3.610），P<0.001］， their risks of MCI were increased by 23.5%， 77.9%， and 139.5%， respectively. Compared with the older adults without a history of general anesthesia who did not exercise， the risk of developing MCI was significantly negatively correlated with the exercise group， cognitive exercise group， and combined exercise and cognitive exercise groups （all P<0.001）. The risk of developing MCI in the exercise group was 60.2% of that in the no exercise group ［OR = 0.602， 95% CI（0.456， 0.795）］， the risk in the cognitive exercise group was 42.4% of that in the no exercise group ［OR = 0.424， 95% CI（0.294， 0.613）］， and the risk in the combined exercise and cognitive exercise group was 27.0% of that in the no exercise group ［OR = 0.270， 95% CI （0.208， 0.353）］. In the older adults with a history of general anesthesia， compared with the no exercise group， the risk of developing MCI was significantly negatively correlated with the cognitive exercise group and the combined exercise and cognitive exercise group （all P < 0.05）. The risk of developing MCI in the cognitive exercise group was 47.7% of that in the no exercise group ［OR=0.477， 95% CI （0.256，0.892）］， the risk in the combined exercise and cognitive exercise group was 34.5% of that in the no exercise group ［OR=0.345， 95% CI （0.220， 0.540）］， while the risk in the exercise-only group did not show a significant difference. ConclusionThe risk of MCI increased significantly in older adults with a history of general anesthesia， and this risk increased with the times of anesthesia. Physical and mental exercise reduces the risk of MCI. it is recommended that older adults with a history of anesthesia incorporate physical and mental exercise into their daily lives to prevent mild cognitive impairment.

Lung transplantation is the only effective treatment for end-stage lung disease. Acute kidney injury is a common complication after lung transplantation, which is related to the occurrence of chronic kidney disease and increased postoperative fatality. The factors and mechanisms affecting the occurrence of acute kidney injury are very complex. Clinically, it has been found that various risk factors during the perioperative period of lung transplantation may lead to the occurrence of acute kidney injury, including preoperative, intraoperative and postoperative factors. Early diagnosis of acute kidney injury after lung transplantation and timely intervention are of great significance to improving patient prognosis. Therefore, this article reviews the definition of acute kidney injury, non-invasive assessment, risk factors, prognosis, and clinical management of acute kidney injury after lung transplantation, aiming to provide a reference for the diagnosis and treatment of acute kidney injury after lung transplantation in clinical practice and to improve the survival rate of lung transplant recipients.

AIM: To investigate the efficacy and safety of dexamethasone versus conbercept in the treatment of diabetic macular edema(DME)with different optical coherence tomography(OCT)subtypes.METHODS: A total of 160 DME patients(160 eyes)admitted to our hospital from January 2021 to March 2023 were prospectively selected, and the patients were randomly divided into dexamethasone intravitreal implant group and conbercept group, with 80 cases(80 eyes)in each group, and DME patients were divided into 51 eyes with serous retinal detachment(SRD), 55 eyes with cystoid macular edema(CME), and 54 eyes with diffuse retinal thickening(DRT)according to OCT characteristics. The best corrected visual acuity(BCVA), central macular thickness(CMT), intraocular pressure and adverse reactions were compared before treatment and at 2, 3 and 6 mo postoperatively.RESULTS: There were differences in BCVA, CMT and intraocular pressure between the two groups at 2, 3 and 6 mo compared with those before operation(all P<0.05). There were differences in BCVA, CMT and intraocular pressure between the dexamethasone intravitreal implant group and the conbercept group in the treatment of patients with different types of DME(all P<0.05). The BCVA of patients with DRT and SRD types in the dexamethasone intravitreal implant group was improved at 3 and 6 mo after treatment compared with that in the conbercept group(all P<0.05). At 6 mo after treatment, the CMT of patients with DRT type in the dexamethasone intravitreal implant group was lower than that in the conbercept group(P<0.05). During the follow-up period, none of the patients experienced adverse events such as cataract exacerbation or retinal detachment.CONCLUSION: Both dexamethasone intravitreal implant and conbercept treatment can improve visual function and macular retinal morphology in patients with different OCT subtypes of DME with good safety, but the dexamethasone intravitreal implant is better than conbercept in the treatment of DRT type.

The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.