OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

Objective:To explore the clinical and genetic characteristics of a child with autosomal recessive primary microcephaly (MCPH).Methods:A case study has been carried out on a boy who had presented at the Inner Mongolia Maternity and Child Health Care Hospital for microcephaly and mental deficiency in September 2022. Prenatal ultrasound images were retrospectively analyzed, and whole exome sequencing and Sanger sequencing were carried out for his family. A literature review was also carried out using keywords such as " ASPM gene", "microcephaly", "prenatal diagnosis", "primary microcephaly", " ASPM", "MCPH5", "MCPH", "autosomal recessive microcephaly", and "prenatal diagnosis on ultrasonography" on the PubMed database, Wanfang Data and China National Knowledge until September 2023. This study was approved by Medical Ethics Committee of the Inner Mongolia Maternity and Child Health Care Hospital (Ethics No. 2021-093-1). Results:The proband had shown progressive reduction in biparietal diameter (BPD) and head circumference (HC) during the fetal period. He was found to harbor compound heterozygous variants of the ASPM gene, which included a paternally derived c. 8044C>T (p.R2682X) and a maternally derived c.8652dup (p.A2885Sfs*35). Both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4; PVS1+ PM2_Supporting+ PM3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). For other fetuses in his family, prenatal ultrasound and genetic testing were all normal. Literature research has identified 11 relevant articles, which included 14 MCPH cases. All of the MCPH5 cases had shown various degrees of reduced BPD/HC on fetal imaging (100%, 15/15). Developmental delay, intellectual disability, and attention deficits were noted in all survived cases, with one case having seizures (12.5%, 1/8). Their genotypes had included homozygotes (46.2%, 6/13) and compound heterozygotes (53.8%, 7/13) for nonsense variants (45%, 9/20) and frameshifting variants (55%, 11/20). Conclusion:The compound heterozygous variants c. 8044C>T (p.R2682X) and c. 8652dup (p.A2885Sfs*35) of the ASPM gene probably underlay the reduced BPD and HC in this proband with MCPH.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Targeted to the junior nursing students in our university, we applied experiential teaching in the course of Obstetrics and Gynecology Nursing to carry out humanistic care infiltration education, which mainly included three parts: aesthetic activities in theoretical class, experiential activities in experimental class and enlightenment after class. After class, compared with the nursing students who were educated by traditional teaching methods, the quality of humanistic care of nursing students who accepted experiential teaching was improved more obviously. It is suggested that the application of experiential teaching is effective in infiltrating humanistic care education in nursing professional courses, which is also in line with the development of nursing discipline.

Objective:To analyze the risk factors of lower extremities deep vein thrombosis after thoracoscopic surgery in elderly patients with lung cancer, establish a nomogram prediction model and conduct internal verification.Methods:A total of 183 elderly patients with lung cancer who underwent thoracoscopic radical resection in Nanchong Central Hospital from February 2018 to February 2022 were selected as the study subjects. According to the presence or absence of deep venous thrombosis of the lower extremities within one month after operation, the patients were divided into lower extremities deep venous thrombosis group ( n=61) and non-deep lower extremities venous thrombosis group ( n=122) . Univariate and multivariate analyses of deep venous thrombosis of lower extremities after thoracoscopic surgery for lung cancer in the elderly were performed, and a nomogram prediction model was constructed according to the multivariate analysis results, and the model was verified. Results:There were statistically significant differences in smoking history ( χ2=13.40, P<0.001) , preoperative chemotherapy ( χ2=8.79, P=0.003) , surgical method ( χ2=7.97, P=0.005) , operation time ( t=7.23, P<0.001) , postoperative bed rest time ( t=10.40, P<0.001) , combined with diabetes ( χ2=6.37, P=0.012) , combined with hyperlipidemia ( χ2=9.58, P=0.002) , preoperative D-dimer ( t=13.08, P<0.001) , preoperative fibrinogen ( t=5.84, P<0.001) and preoperative platelet count ( t=7.01, P<0.001) between the lower extremity deep venous thrombosis group and the non-lower extremity deep venous thrombosis group. The results of multivariate logistic regression analysis showed that preoperative chemotherapy ( OR=2.45, 95% CI: 1.05-5.71, P=0.038) , surgical method ( OR=2.55, 95% CI: 1.14-5.73, P=0.023) , postoperative bed rest time ( OR=1.50, 95% CI: 1.24-1.81, P<0.001) , combined with diabetes ( OR=3.60, 95% CI: 1.05-12.33, P=0.042) , and preoperative D-dimer ( OR=1.01, 95% CI: 1.01-1.01, P<0.001) were all independent risk factors for lower extremity deep vein thrombosis in elderly patients with lung cancer after thoracoscopic surgery. The C-index of nomogram for predicting lower extremity deep vein thrombosis-related factors was 0.86 (95% CI: 0.81-0.93) . The calibration curve showed that the model had a good correlation in predicting lower extremities deep venous thrombosis. Conclusion:Preoperative chemotherapy, surgical method, postoperative bed rest time, combined with diabetes, and postoperative D-dimer level are influence factors for lower extremity deep vein thrombosis in elderly patients with lung cancer after thoracoscopic surgery. The nomogram prediction model established in this study has high accuracy and discrimination for the prediction of lower extremity deep vein thrombosis in elderly patients with lung cancer after thoracoscopic surgery.

Objective:To evaluate early corneal biomechanical change, safety and effectiveness after small-incision lenticule extraction combined with ultraviolet A corneal collagen cross-linking (SMILE-CXL) for myopic eyes and compare with SMILE.Methods:A non-randomized controlled clinical study was performed.Forty-four myopic eyes of 25 patients were included in Hankou Aier Eye Hospital from December 2017 to July 2018.SMILE-CXL or SMILE was carried out for 22 eyes of 12 patients or 22 eyes of 13 patients, respectively, based on the normal posterior surface manifestation of Belin by Pentacam tomography or not.The posterior surface manifestation of Belin was normal in the SMILE group, and the posterior surface of Belin was yellow or red with Corvis biomechanical index and tomographic biomechanical index<0.3 (except keratoconus) in the SMILE-CXL group.The refractive diopter of the eyes was detected before and 6 months after surgery, including spherical diopter, cylindrical diopter and spherical equivalent (SE) with a comprehensive refractometer.The corneal biomechanical parameters of the eyes were detected before and 6 months after surgery with a Scheimpflug-based dynamic tonometry (Corvis ST). The safety index, a ratio of postoperative mean best corrected visual acuity (BCVA) to preoperative mean BCVA, and efficacy index, a ratio of postoperative uncorrected visual acuity (UCVA) to preoperative BCVA, were compared between SMILE-CXL group and SMILE group.BCVA and UCVA were examined using standard chart and converted to logarithm of the minimal angle of resolution (LogMAR) units.This protocol complied with the Declaration of Helsinki and was approved by an Ethics Committee of Hankou Aier Eye Hospital (No.WHS2017052701). Written informed consent was obtained from each patient prior to entering into the cohort.Results:The postoperative UCVA of the eyes in both groups was more than 1.0.There were no significant differences in safety index, efficacy index and SE change between the SMILE-CXL group and SMILE group (all at P≥0.05). At 6 months after surgery, the values of second applanation time (A2T), time from the start until the highest concavity (HC-Time) and DA ratio 2 mm were significantly increased in comparison with before operation in both SMILE-CXL group and SMILE group (all at P<0.05). The changes of A2T, HC-Time and DA ratio 2 mm in the SMILE-CXL group were significantly lowered than those in the SMILE group at the sixth month after surgery ( P=0.001, 0.001, 0.036). The deformation amplitude, maximum corneal velocity during the first applanation (Vin), distance between both non-deformed peaks and integrated radius during the maximum depression were significantly increased, and the central curvature radius at highest concavity, cord length of first applanation, cord length of second applanation, Ambrósio's relational thickness horizontal, stiffness parameter applanation 1 and biomechanical intraocular pressure during the maximum depression were significantly lower at the sixth month after surgery than those before surgery (all at P<0.05). There were no significant differences in the parameters mentioned above between the two groups (all at P<0.05). Conclusions:Compared with SMILE alone, SMILE-CXL shows a comparable safety and efficacy, and better corneal biomechanical properties.

One hundred and twenty nine patients with pelvic organ prolapse (stage Ⅲ to Ⅳ according to POP-Q staging) diagnosed in our hospital from January 2010 to December 2016 were enrolled,among whom 66 cases underwent vaginal hysterectomy plus vaginal anterior and posterior wall repair (TO group),63 cases underwent vaginal hysterectomy plus pelvic floor reconstruction with autologous tissue (AT group).Clinical parameters,perioperative and postoperative complications were analyzed.There was no statistically significant difference in intraoperative blood loss,indwelling urethral catheter time,length of hospital stay,and anal exhaust time between group AT and group TO (P＞O.05).The average operation time of group AT was significantly longer than that of group TO (P＜0.05).The postoperative rotation angle of urethra (UR),posterior vesicourethral angle (RVA),and bladder neck descent (BND) of group AT were significantly reduced (P＜0.05).The BND of group AT was significantly smaller than that of group TO 3 months and 12 months after the surgery (P＜0.05).There was no statistically significant difference in UR before and 12 months after surgery in group TO (P＞0.05),while the BND at 12 months after operation in group TO was increased compared to 3 months after operation (P＜0.05).There were significant differences in scores of PFIQ-7 and PISQ-12 before surgery and 12 month after surgery in both groups (P＜0.05).There was no statistically significant difference between the two groups in the incidence of postoperative recurrence and pressure incontinence (P＜0.05).It is suggested that the stability of pelvic floor anatomical structure after pelvic floor reconstruction with autologous tissue is better than that of the traditional surgery,especially for patients with severe pelvic organ prolapse.

Objective To investigate effects of pirfenidone (PFD) on diabetic nephropathy model in db/db mice and to explore its possible mechanisms.Methods (1) Wild-type mice were as the normal control group,and db/db mice were divided into model group and PFD group,with 6 mice in each group.In the PFD group mice were administered continuously by 250 mg· kg-1· d-1 PFD for 18 weeks,and mice in the other two groups were administered by 0.5％ sodium carboxymethyl cellulose.Blood glucose and 24 h urinary albumin were measured.The pathological changes of renal tissue were evaluated by PAS staining,PASM staining,Masson staining and Sirius red staining.The expression of collagen type Ⅳ in kidney tissues was detected by immunohistochemistry.(2) Mouse mesangial cells (SV40 MES-13 cells) were cultured as research objects.They were divided into control group,hyperosmolar group,high glucose (HG) group,and 50,100,200,400,800,1600 mg/L PFD+HG group.BrdU cell proliferation test was used to evaluate cell proliferation rate.Cells were divided into control group,hyperosmolar group,HG group and PFD+HG group.The mRNA expressions of α-smooth muscle actin (α-SMA),collagen type Ⅰ,collagen type Ⅳ,transforming growth factor-β1 (TGF-β1),interleukin (IL)-1β,IL-6 and monocyte chemotactic protein-1 (MCP-1) were detected by real-time PCR.Results (1) Compared with normal control group,the model mice had higher weight,blood glucose and 24 h urinary albumin,accompanied with glomerular hypertrophy,mesangial area expansion,tubulointerstitial fibrosis and deposition of collagen type Ⅳ (all P ＜ 0.05).Compared with those in model group,in PFD group 24 h urinary albumin decreased,glomerular hypertrophy,mesangial area expansion and tubulointerstitial fibrosis alleviated,and the protein expression of collagen type Ⅳ inhibited (all P＜0.05).(2) Compared with those in HG group,MES-13 cell proliferation rates of 100,200,400,800,1600 mg/L PFD+HG groups decreased (all P ＜ 0.05),and the mRNA expressions of α-SMA,collagen type Ⅰ,collagen type Ⅳ,TGF-β1,IL-1β,IL-6 and MCP-1 reduced in 400 mg/L PFD+HG group (all P ＜ 0.05).Conclusions PFD can inhibit high glucose-induced proliferation and activation of glomerular mesangial cells,decrease the expression of TGF-β1 and proinflammatory factors,as well as reduce the synthesis of collagen,which improve renal fibrosis of db/db mice.

Objective? To investigate the correlation between nursing humanistic care and health behavior ability in elder patients with diabetes mellitus (DM). Methods? From June 2015 to June 2017, a total of 208 elder patients with DM in Affiliated Hospital of Yangzhou University were selected by convenience sampling method. The levels of nursing humanistic care and health behavior ability were evaluated by Nursing Humanistic Care Experience Scale-Noninfectious Chronic Disease Patients Version (NHCES-NCDP) and Self-Rated Abilities for Health Practices Scale (SRAHP). Results? The average score of NHCES-NCDP was (68.64±7.27), and the lowest dimension score was support for individual uniqueness (2.60±0.30). The SRAHP average score was (55.40±4.80), the lowest dimension score was nutrition (12.25±2.00). Pearson correlation analysis showed that the total score and dimension scores of NHCES-NCDP were positively correlated with total score and the dimension scores of SRAHP (P＜ 0.05). Multivariate linear regression showed that the level of nursing humanistic care were the influencing factor for health behavior ability (P＜0.01). Conclusions? The levels of nursing humanistic care and health behavior ability in elder patients with DM is low. Improving the level of nursing humanistic care can improve the patient's health behavior ability.

Objective:To investigate mechanism of imatinib mesylate induced apoptosis of primary CD3+T cells.Methods:The CD3+T cells were stimulated by 0-100 nmol/L imatinib for 24 h,cell apoptosis was detected by flow cytometry;Caspase-3,Caspase-8, A20 and NF-κB expression levels were detected by Real-time quantitative PCR and Western blot.Results: IM significantly increased apoptosis of T cell;Caspase-3 and A20 gene expression levels were upregulated and NF-κB expression level was downregulated both in gene and protein levels.Conclusion:IM increased apoptosis of T cell by upregulating A20 expression.