Objective To establish an oxidative stress mouse model of atopic dermatitis (AD) by applying 2,4-dinitrofluorobenzene (DNFB) to the back and post-auricular skin of KM mice, and to evaluate the regulatory role of the RAGE-NLRP3 axis (receptor for advanced glycation end products-NOD-like receptor family, pyrin domain containing 3 axis) in AD-related oxidative stress, thereby providing a potential therapeutic target for AD treatment. Methods Twenty SPF-grade female KM mice were randomly divided into a control group (Control group) and an experimental group (DNFB group), with 10 mice in each group. Mice in the Control group were treated with an acetone-olive oil vehicle (acetone: olive oil = 3:1) on their back and post-auricular skin. Mice in the DNFB group were treated with 0.5% DNFB (prepared by adding 0.5 g DNFB per 100 mL of acetone-olive oil vehicle) on the same areas, once daily for 14 consecutive days. The severity of skin lesions was scored on days 2, 4, 6, 9, 12, and 14 of treatment. On day 14, scratching behavior and ear thickness were evaluated. Ear swelling was evaluated on the final day by measuring bilateral ear thickness three times with a vernier caliper; the three measurements were averaged. HE staining was used to observe morphological and structural changes of cells in the back skin tissues. The mRNA and protein expression levels of RAGE (receptor for advanced glycation end products) in skin tissues were detected by quantitative real-time PCR, Western blot, and immunohistochemical staining. The mRNA expression levels of oxidative stress-related molecules, including NLRP3 (NOD-like receptor family, pyrin domain containing 3), caspase-1 (cysteine-dependent aspartate-specific protease 1), and IL-1β (Interleukin-1β), were detected by quantitative real-time PCR. Results On day 14, the back skin lesion scores of the Control group and DNFB group were (0.20±0.42) and (9.93±1.30) (P<0.000 1), respectively. Scratching behavior scores were (5.00±2.05) and (49.26±8.49) episodes, respectively (P<0.000 1), and ear thicknesses were (213.00±11.87) μm and (765.93±140.47) μm (P<0.000 1), respectively. The DNFB group exhibited marked skin dryness, desquamation, and thickening. HE staining results showed that skin inflammation was obvious in the DNFB group, consistent with the pathological features of AD. Quantitative real-time PCR and Western blot results showed that compared with the Control group, the mRNA expression level of RAGE in skin tissues of the DNFB group was significantly increased (P<0.05), and the protein expression level of RAGE was also significantly increased (P<0.01). Immunohistochemical staining results showed that compared with the Control group, skin tissue sections of the DNFB group exhibited thickened stratum corneum and fibrotic proliferation of fibroblasts in the interstitium under microscopic observation, with a significant increase in RAGE protein expression in the skin tissues (P<0.01). Quantitative real-time PCR results showed that the mRNA expression levels of NLRP3, caspase-1, and IL-1β in skin tissues of the DNFB group were all significantly increased (P<0.01). Conclusion The AD mouse oxidative stress model has been successfully established by topical DNFB application. RAGE may promote the development of AD by regulating the NLRP3 inflammasome and IL-1β release, forming an oxidative-inflammatory cascade, suggesting that it could be a potential therapeutic target for AD.

AIM To investigate the protective effects and the mechanism of corosolic acid on doxorubicin-induced cardiotoxicity in H9c2 cardiomyocytes.METHODS To screen and determine the effective concentration of corosolic acid,the injury models of H9c2 cardiomyocytes established by 1 μmol/L doxorubicin were exposed to 24 h different concentrations of corosolic acid,followed by detections of their cell activity by MTT method;their cell apoptosis morphology by Hoechst 33342 staining method;their cell apoptosis rate by Annexin V-FITC/PI double staining method;their intracellular ROS level by DCFH-DA probe;their intracellular iron level by iron ion colorimetry;and their protein expressions of Bax,Bcl-2,cleaved-caspase3,Nrf2,GPX4 and Ptgs2 by Western blot.RESULTS Upon the doxorubicin-induced injury models of H9c2 cardiomyocytes,corosolic acid improved their viability and survival rate(P<0.05),decreased their levels of ROS and Fe2+ and the apoptosis rate(P<0.05),up-regulated the protein expressions of Bcl-2,Nrf2 and GPX4(P<0.05),and down-regulated the protein expressions of Bax,cleved-caspase 3 and Ptgs2(P<0.05).CONCLUSION Corosolic acid can inhibit the ROS level and apoptosis of doxorubicin-induced injury models of H9c2 cardiomyocytes,and the iron death as well via activating Nrf2/GPX4 pathway.

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart dis-ease,such as acute or chronic myocardial ischemic changes,sometimes make it difficult to locate the ischemic site due to the short death process,the lack of tissue reaction time.In some cases,the de-ceased died of sudden death on the first-episode,resulting in difficulty for medical examiners to make an accurate diagnosis.However,clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process.This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medi-cal research,including plaque rupture,plaque erosion and calcified nodules,as well as the influencing factors leading to plaque instability,and briefly describes the research progress and technique of the atherosclerotic plaques,in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different patho-logic states of coronary atherosclerotic plaques.

Objective To review the occurrence of allergic reactions during therapeutic plasma exchange(TPE)and to explore the risk factors of TPE allergic reactions.Methods The clinical data of 929 patients treated with TPE using plasma components by the Department of Transfusion Medicine in our medical center from 2018 to 2023 were collected.The influen-cing factors of allergic reactions were analyzed by univariate analysis,and the independent risk factors of allergic reactions were analyzed by logistic multivariate regression analysis.Results A total of 4 071 TPEs were performed in 929 patients.A-mong them,198 patients(21.31%)experienced 349 times(8.57%)of allergic reactions,with the incidence of gradeⅠ,Ⅱ and Ⅲ allergic reactions of 16.33%,81.38%and 2.29%,respectively,and no deaths.The univariate analysis showed that the patient′s age,allergy history,diagnosis of immune-related diseases,ICU admission,plasma consumption,total blood volume,maximum blood flow rate and combined use of albumin were related to the occurrence of allergic reactions(P＜0.05).Multivariate regression analysis showed that young patients,a history of allergy,immune-related diseases and non-ICU patients were prone to allergic reactions in TPE,but the treatment options of TPE such as substitute fluid category,plasma consumption and blood flow rate were not related to the occurrence of allergic reactions.Conclusion There are sig-nificant individual differences in the occurrence of allergic reactions for TPE,and young age,history of allergies,immune-related diseases and non-ICU patients are risk factors for allergic reactions in TPE.Identifying patients with risk factors be-fore TPE treatment and giving corresponding preventive measures can reduce the incidence of allergic reactions.

Objective:To discuss the clinical curative effect and feasibility of the combination therapy of the minimally invasive percutaneous quantitative suture technique eight times and Kirschner wire elastic fixation in the treatment of mallet finger.Methods:A retrospective analysis was performed on patients with tendon zone Ⅰ rupture of tendinous mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from July 2021 to June 2023. During the procedure, firstly, the extensor digitalis tendon in the zone Ⅰ was sutured percutaneous with 3-0 thread monofilament sutures in the "quantitative 8-stitch method " according to the pre-marked number sequence of 1 to 8, and fixed at the base of the distal phalanx via a constructed bone tunnel. Secondly, the distal interphalangeal joint (DIPJ) was fixed elastically with Kirschner wire, without damage to the articular surface. Four to five weeks after the operation, the Kirschner wire was removed, and flexion and extension of the affected finger were gradually increased. At the last follow-up, the range of motion (ROM) and the total action motion (TAM) of the finger were recorded, and the healthy side of the ROM and TAM slightly differed. Finger function was evaluated following the American Association of Hand Surgeons TAM system. It was divided into four grades: excellent, good, fair and poor. SPSS 15.0 software was used for statistical analysis. Measurement data conforming to normal distribution were expressed as Mean±SD, and a paired sample t-test was used for comparison between the affected finger and the corresponding healthy finger. Results:A total of 30 patients (30 digits) were enrolled, including 19 males and 11 females with the age of (38.5±4.3) years (14 to 71 years). All were single closed injuries. Time from injury to operation was (1.1±0.4) d (3 h to 7 d). The distance of tendon break was (8.4±0.5) mm (4 to 12 mm). Mallet finger deformities were all corrected postoperatively. There were no complications such as scar, exposed suture, nail tract infection, or nail removal on the dorsal side of the affected finger. All patients were followed up for (7.5±1.3) months (6-13 months). At the last follow-up, the ROM of DIPJ of the affected finger and the corresponding healthy finger were 43.28°±2.03° and 44.15°±1.12°, respectively, with no statistical significance ( t=1.32, P=0.084). TAM of the affected finger and the corresponding healthy finger were 240.15°±5.13° and 242.13°±3.11°, respectively, with no significant difference ( t=2.12, P=0.135). According to TAM system evaluation criteria, excellent in 27 cases, good in 3 cases, excellent and good rate was 100% (30/30). Conclusion:The combination of the minimally invasive percutaneous quantitative suture technique eight times and Kirschner wire elastic fixation has a satisfactory treatment outcome in the mallet finger, and there is no damage to the DIPJ surface. It is a simple, safe, effective method with minimal invasion.

Objective:To discuss the clinical curative effect and feasibility of the combination therapy of the minimally invasive percutaneous quantitative suture technique eight times and Kirschner wire elastic fixation in the treatment of mallet finger.Methods:A retrospective analysis was performed on patients with tendon zone Ⅰ rupture of tendinous mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from July 2021 to June 2023. During the procedure, firstly, the extensor digitalis tendon in the zone Ⅰ was sutured percutaneous with 3-0 thread monofilament sutures in the "quantitative 8-stitch method " according to the pre-marked number sequence of 1 to 8, and fixed at the base of the distal phalanx via a constructed bone tunnel. Secondly, the distal interphalangeal joint (DIPJ) was fixed elastically with Kirschner wire, without damage to the articular surface. Four to five weeks after the operation, the Kirschner wire was removed, and flexion and extension of the affected finger were gradually increased. At the last follow-up, the range of motion (ROM) and the total action motion (TAM) of the finger were recorded, and the healthy side of the ROM and TAM slightly differed. Finger function was evaluated following the American Association of Hand Surgeons TAM system. It was divided into four grades: excellent, good, fair and poor. SPSS 15.0 software was used for statistical analysis. Measurement data conforming to normal distribution were expressed as Mean±SD, and a paired sample t-test was used for comparison between the affected finger and the corresponding healthy finger. Results:A total of 30 patients (30 digits) were enrolled, including 19 males and 11 females with the age of (38.5±4.3) years (14 to 71 years). All were single closed injuries. Time from injury to operation was (1.1±0.4) d (3 h to 7 d). The distance of tendon break was (8.4±0.5) mm (4 to 12 mm). Mallet finger deformities were all corrected postoperatively. There were no complications such as scar, exposed suture, nail tract infection, or nail removal on the dorsal side of the affected finger. All patients were followed up for (7.5±1.3) months (6-13 months). At the last follow-up, the ROM of DIPJ of the affected finger and the corresponding healthy finger were 43.28°±2.03° and 44.15°±1.12°, respectively, with no statistical significance ( t=1.32, P=0.084). TAM of the affected finger and the corresponding healthy finger were 240.15°±5.13° and 242.13°±3.11°, respectively, with no significant difference ( t=2.12, P=0.135). According to TAM system evaluation criteria, excellent in 27 cases, good in 3 cases, excellent and good rate was 100% (30/30). Conclusion:The combination of the minimally invasive percutaneous quantitative suture technique eight times and Kirschner wire elastic fixation has a satisfactory treatment outcome in the mallet finger, and there is no damage to the DIPJ surface. It is a simple, safe, effective method with minimal invasion.

Objective To establish antemortem and postmortem injury models in nude mice,observe the morphological changes of the wounds and the changes of the microbial communities in the wounds at different time points after the injury,and analyze the differences between antemortem and postmor-tem wounds.Methods Abdominal injury models were established in 48 BALB/c nude mice,which were classified into antemortem injury,4 h and 72 h postmortem injury groups,and the gross manifesta-tions and histopathological changes were observed on days 1,3,5,8,11 and 15 after injury.The mi-crobial communities in the wounds were analyzed by 16S rRNA sequencing technology.QIIME 2 soft-ware was used to calculate Shannon and Observed species indices.The Kruskal-Wallis test was used to determine statistical differences in α-diversity between groups.Jaccard similarity coefficients were calculated by using R v4.3.0 software and applied to the principal co-ordinates analysis to demonstrate inter-sample differences.Permutational multivariate analysis of variance(PERMANOVA)was used to analyze the differences between groups in the composition of bacterial colonies,and R2 values were calculated.Results On days 8,11 and 15 after injury,the antemortem and postmortem injuries could not be differentiated by morphological examination;the Shannon index and Observed species index were statistically different between the antemortem injury group and the 72 h postmortem injury group;the Jaccard similarity coefficient of the microbial community was statistically different between the an-temortem injury group and the 72 h postmortem injury group.The PERMANOVA R2 value gradually increased with the extension of time(0.22-0.61).Conclusion Through the analysis of the wound mi-crobial community,the microbial composition of wounds at different time points can be identified and compared,which provides a new perspective and method for the differentiation of antemortem injuries from postmortem injuries,with good application prospects.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*