BACKGROUND:Abnormal extracellular matrix accumulation and excessive proliferation of fibroblasts are the main manifestations of pathological scars.Excessive proliferation of fibroblasts leads to the production of large amounts of collagen-based extracellular matrix.Therefore,to investigate the role of fibroblast fibrosis in the formation of pathological scar will provide a new idea for revealing the mechanism of pathological scar and biological therapy. OBJECTIVE:To investigate the effect of RAS-selective lethal small molecule 3(RSL3)on the fibrosis of human pathological scar fibroblasts. METHODS:Then cases of pathological scar tissue and normal skin tissue samples from the same individuals,provided by the Department of Burn Plastic Surgery,General Hospital of Ningxia Medical University,were collected.Fibroblasts of human pathological scar and human normal skin were extracted and used in the following experiments.The general condition of the pathological scar tissue and the normal skin tissue was detected by hematoxylin-eosin staining.The appearance of fibroblasts from pathological scar and normal skin were observed by inverted microscope.The fibroblasts were verified by immunofluorescence assay.The cells were treated with different concentrations of RSL3(1,3,5,7,9,11,13 μmol/L).The inhibitory concentration of RSL3 on fibroblasts was detected by cell counting kit-8.Control group(without treatment)and RSL3 intervention group(treated with 7 μmol/L RSL3 for 24 hours)were set up.The mRNA and protein expressions of glutathione peroxidase 4,type Ⅰ collagen,type Ⅲ collagen and α-smooth muscle actin were detected by Qrt-PCR and western blot,respectively.Level of malondialdehyde in cells was detected.The residual scratch area was measured by cell scratch test after 24 hours to calculate the percentage of residual scratch area. RESULTS AND CONCLUSION:The expression of glutathione peroxidase 4 in the pathological scar group was higher than that in the normal skin group(Mrna:t=3.252,P<0.01;protein:t=5.075,P<0.01).The expression of glutathione peroxidase 4 in the pathological scar fibroblast group was higher than that in the normal skin fibroblast group(Mrna:t=10.32,P<0.01;protein:t=26.22,P<0.01).Compared with the control group,the expression of glutathione peroxidase 4 was decreased(Mrna:t=2.798,P<0.05;protein:t=4.643,P<0.01),the content of malondialdehyde was increased(t=2.917,P<0.05),the expression of type Ⅰ collagen(Mrna:t=15.84,P<0.01;protein:t=4.610,P<0.01),type Ⅲ collagen(Mrna:t=28.86,P<0.01;protein:t=7.713,P<0.01)and α-smooth muscle actin(Mrna:t=2.671,P<0.05;protein:t=7.417,P<0.01)were decreased in the RSL3 intervention group.Compared with the control group,the migration ability was weakened in the RSL3 intervention group(t=14.06,P<0.01).To conclude,RSL3 can inhibit the expression of glutathione peroxidase 4 and then inhibit the ability of fibrosis and migration of pathological scar fibroblasts.

Objective To analyze the efficacy and adverse reactions of donepezil in the treatment of patients with a continuous disease spectrum of Alzheimer's disease(AD)with pharmacogenomics.Methods Seventy-two patients who took donepezil therapy at the time of initial molecular pa-thology diagnosis of AD continuous disease spectrum in Chinese PLA General Hospital from Jan-uary 2022 to January 2023 were recruited.Cells from the oral buccal mucosa were collected,and MassARRAY nucleic acid mass spectrometry was applied to detect the genotypes of CYP2D6,the gene encoding cytochrome P450 2D6 enzyme,and CHAT,the gene encoding acetylcholine trans-ferase.After 9 months of follow-up,drug efficacy was indirectly determined by neurological func-tion scales,caregiver evaluations,and drug prescribing behaviors,and thus,the 50 patients on donepezil alone were divide into effective group(n=28)and ineffective group(n=22).Seventy-two patients were divided into adverse reaction group(n=12)and no adverse reaction group(n=60).Multivariate logistic regression analysis was used to analyze the correlation between donepezil efficacy and pharmacogenomics.Results The frequencies of CHAT rs3793790 locus carrying G allele and rs2177370 locus carrying A allele were significantly higher in the effective group than the ineffective group(35.71％vs 9.09％,P=0.029;42.86％vs 9.09％,P=0.008).Multivariate lo-gistic regression analysis showed that donepezil was more effective in those who carrying rs3793790 G allele and/or rs2177370 A allele in the CHAT gene than those who carrying neither of the alleles(95％CI:1.20-34.47,P=0.030).There were no statistical differences in the CYP2D6 gene-adjusted activity score and whether or not carrying*10 between the patients with and without adverse reactions(P＞0.0 5).Conclusion In patients with a continuous spectrum of AD,donepezil efficacy is associated with CHAT gene polymorphisms,but there is no correlation between donepezil adverse reactions and CYP2D6 genotype.

Objective To investigate the accuracy and application value of the Tada formula in evalua-ting the meningioma volume based on 3D reconstruction technology.Methods The thin-slice magnetic reso-nance images of 297 patients with meningioma treated in the neurosurgery department of 940 Hospital of PLA Joint logistics Support Force from January 2014 to May 2022 were retrospectively analyzed.The meningioma volume was evaluated by the Tada formula method and three-dimensional reconstruction method respectively.The accuracy of the evaluation of meningeal tumor volume by the Tada formula was analyzed by grouping sta-tistics.Results In the whole sample and the concentrated sample,the obtained meningioma total volumes had no statistical difference between the two methods(P＞0.05),the Spearman correlation coefficients were 0.995 and 0.993 respectively,and the intragroup correlation coefficients(ICC)were 0.992 and 0.989,respec-tively.In the Bland-Altman plot,most of the data points were within the limit of uniformity.Compared with different groups,the Tada formula had a slightly lower accuracy in the volume assessment of meningiomas with higher degree of irregularity,and a better accuracy in the volume assessment of supratentorial meningio-mas than subtentorial meningiomas.Conclusion The Tada formula could accurately evaluate the volume of meningioma,and it could be used as a preliminary method to evaluate meningioma volume in clinic

Objective To analyze the perioperative outcomes of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection. Methods The perioperative clinical data of patients receiving heart valve replacement in the Department of Cardiovascular Surgery, the First Affiliated Hospital of University of Science and Technology of China from November 2022 to February 2023 were retrospectively analyzed. According to whether the patients were infected with SARS-CoV-2, they were divided into a non-infected group and an asymptomatic group. The perioperative data of the patients were compared between the two groups, and the effect of asymptomatic infection on the result of heart valve replacement surgery was analyzed. Results A total of 66 patients were enrolled including 36 males and 30 females with a mean age of 58.0±11.1 years. There were 51 patients in the non-infected group and 15 patients in the asymtomatic group. There were 2 patients of mitral valve replacement, 20 patients of aortic valve replacement, 1 patient of double valve replacement, 3 patients of aortic valve replacement with tricuspid valvoplasty, 22 patients of mitral valve replacement and tricuspid valvoplasty, 18 patients of double valve replacement and tricuspid valvoplasty. Asymptomatic infected patients received more emergency surgery than uninfected patients (26.7% vs. 0.0%, P<0.01). There was no statistical difference in the duration of extracorporeal circulation, aortic occlusion, mechanical ventilation time after the surgery, ICU stay, postoperative drainage volume, or postoperative complications between the two groups. Conclusion Perioperative results of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection and non-infection are almost the same.

Objective To investigate the protective effect of resveratrol on intestinal barrier in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mouse models and its mechanism for regulating TLR4/MyD88/NF-κB signaling to protect dopaminergic neurons.Methods Fifty-two C57BL/6J mice were randomized into control group(n= 12),MPTP group(n=14),MPTP+resveratrol(30 mg/kg)group(n=13),and MPTP+resveratrol(90 mg/kg)group(n=13),and mouse models were established by intraperitoneal MPTP(30 mg/kg)injection for 7 days in the latter 3 groups.Behavioral tests were conducted to evaluate the effect of resveratrol on motor symptoms of the mice.Western blotting was used to detect the expression of TH,α-syn,ZO-1,Claudin-1,TLR4,MyD88,and NF-κB in the brain tissues of the mice.Immunohistochemistry,immunofluorescence,ELISA and transmission electron microscopy were used to verify the effect of resveratrol for suppressing inflammation and protecting the intestinal barrier.Results Compared with those in the normal control group,the mice in MPTP group showed significant changes in motor function,number of dopaminergic neurons,neuroinflammation,levels of LPS and LBP,and expressions of tight junction proteins in the intestinal barrier.Resveratrol treatment significantly improved motor function of the PD mice(P<0.01),increased the number of neurons and TH protein expression(P<0.05),down-regulated the expressions of GFAP,Iba-1,and TLR4,lowered fecal and plasma levels of LPS and LBP(P<0.05),restored the expression levels of ZO-1 and Claudin-1(P<0.01),and down-regulated the expressions of TLR4,MyD88,and NF-κB in the colon tissue(P<0.05).The mice with resveratrol treatment at 30 mg/kg showed normal morphology of the tight junction complex with neatly and tightly arranged intestinal villi.Conclusion Resveratrol repairs the intestinal barrier by inhibiting TLR4/MyD88/NF-κB signaling pathway-mediated inflammatory response,thereby improving motor function and neuropathy in mouse models of MPTP-induced PD.

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Objective To explore the possible mechanisms of myocardial injury induced by simulated weightlessness in space flight and the recovery of myocardium in rats by aerobic exercise intervention.Methods The body weight of rats was weighed using an electronic balance;the cardiac function indexes of rats in each group were detected using echocardiography and isolated cardiac perfusion;and the expression of proteins related to the AMPK/ULK1/Beclin1 pathway in the myocardial tissues of rats in each group was detected using Western Blot.Results(1)When compared with the C1 group,the T1 group not statistically significant in body weight(P?>?0.05),and the wet weight of the flounder muscle,the wet weight-to-weight ratio of the flounder muscle,and the heart weight were all significantly decreased(P??0.05).After 4 weeks of aerobic exercise,when compared to group C2,group R showed a significant rise in the expression of AMPK and ULK1(P??0.05),and a rise in the expression of Beclin1,but not statistically significant(P?>?0.05);and group A showed a slight increase in the expression of AMPK,ULK1 and Beclin1 expression decreased slightly but not statistically significant(P?>?0.05),p-AMPK expression decreased significantly(P??0.05),and a significant decrease in the expression of ULK1(P??0.05);the expression of p-ULK1 decreased significantly(P?

Objectives:To identify the risk factors associated with delirium in intensive care unit (ICU) hospitalization of sepsis patients and construct a clinical prediction model to to provide a reference for the prevention and control of delirium in sepsis patients.Methods:Data were collected of sepsis patients admitted in the Intensive Care Unit in the Second Affiliated Hospital of Soochow University from September 2020 to August 2022.The patients were divided into delirium group and non-delirium group according to whether delirium occurred or not. Comparing of the differences in general and clinical data between the two groups, the independent risk factors for delirium were screened by backward stepwise regression method, and the delirium risk prediction model was constructed and evaluated. An independent risk factor analysis for delirium was conducted using a backward stepwise regression approach to identify significant predictors. A delirium risk prediction model was constructed based on the identified risk factors, followed by a comprehensive evaluation of the model's performance.Results:A total of 381 sepsis patients were included in the study, 114 patients (29.9%) developed delirium during the ICU hospitalization. Univariate analysis revealed statistically significant differences ( P< 0.05) between the delirium and non-delirium groups for several factors including age ≥ 65 years, blood transfusion, use of midazolam, use of adrenaline, APACHEⅡ score>15, SOFA score>4, metabolic acidosis, urea>7.1 mmol/L, coagulation disorders, lactate levels, and platelet count. Multivariate analysis identified age ≥ 65 years, use of midazolam, APACHEⅡ score>15, metabolic acidosis, urea>7.1 mmol/L, and coagulation disorders as independent risk factors for delirium in sepsis patients during ICU hospitalization.The predictive model was evaluated with an area under the ROC curve of 0.813, a non-significant Hosmer-Lemeshow goodness-of-fit test ( P=0.957>0.05), and a Brier score of 0.149 (<0.25), indicating good predictive performance and calibration. Clinical decision and impact curves demonstrated the model's favorable clinical applicability. Conclusions:The occurrence of delirium in ICU sepsis patients closely associate with six factors: age ≥ 65 years, use of midazolam, APACHEⅡ score>15, metabolic acidosis, urea>7.1 mmol/L, and coagulation disorders. This sepsis delirium prediction model has good clinical predictive ability and clinical applicability.

Objective:To explore the clinical effects of free anterolateral thigh perforator flaps in repairing diabetic foot ulcers (DFUs) under a multi-disciplinary team (MDT) cooperation model.Methods:The study was a retrospective observational study. From June 2018 to December 2022, 49 DFU patients who met the inclusion criteria were admitted to the Department of Hand and Foot Microscopy and Wound Repair Surgery of Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), including 28 males and 21 females, aged from 47 to 68 years, with type 2 diabetes history period ranging from 6 months to 21 years. Under a MDT cooperation model, the physicians from department of endocrinology comprehensively assessed the patients, stabilized the patients' general condition, and controlled their complications, the surgeons from department of vascular surgery assessed and improved the patients' lower limb blood supply, the physicians from department of infectious diseases provided anti-infection treatment plans, the physicians from department of anesthesiology and perioperative medicine assessed the patients' perioperative risk and ensured their perioperative safety, and according to the patients' condition, the physicians from departments such as cardiology, neurology, nutrition, and rehabilitation actively and timely participated in the treatment. The surgeons from department of hand and foot microscopy and wound repair surgery prepared the wound base and used free anterolateral thigh perforator flaps to repair the wounds. After once or multiple debridement in the first stage, the wound area ranged from 5.0 cm×4.5 cm to 17.0 cm×10.0 cm. After once or twice vacuum sealing drainage treatment, the free anterolateral thigh perforator flaps were used to repair the wounds with incision area of 6 cm×5 cm to 18 cm×11 cm in the second stage. The descending branches of lateral circumflex femoral artery and the accompanying veins of flaps were anastomosed to the arteries and veins in the recipient sites, respectively. The wounds in the flap donor sites were sutured directly. After surgery, whether the patient's perioperative period was stable, the survival of flaps, the healing of wounds in the flap donor and recipient sites were observed. During the follow-up, the texture and appearance of flaps, whether there was a new ulcer, and the patient's walking ability were observed.Results:All the patients had stable perioperative period. Among them, the flaps in 46 patients survived successfully; the flaps in 2 patients developed complete necrosis, including 1 case whose ulcer was healed after repair of pedicled flap from the lower leg, and 1 case who underwent amputation of the lower leg; the flap in 1 patient developed partial necrosis, which was healed after dressing change and skin grafting. The wounds in the flap donor and recipient sites healed well. During the postoperative follow-up of 6-24 months, the flaps had good texture and appearance with no new ulcers, and the patients had no obvious impairment in daily walk.Conclusions:The MDT cooperation model can sufficiently ensure the perioperative safety of DFU patients. The free anterolateral thigh perforator flaps can repair the DFU wounds achieving good clinical effects with high flap survival rate and decreased amputation rate.