BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

Objective To investigate the influence of different embryo development rates on the clinical outcomes of assisted reproductive technology(ART).Methods The clinical data of female patients who underwent in vitro fertilization and intracytoplasmic sperm injection embryo transfer in Reproductive Medicine Center of The First Affiliated Hospital of Naval Medical University from Jan.1,2015 to Dec.31,2023 were retrospectively analyzed.A total of 1 556 cycles were included.Group A was transferred on day 3,and they were assigned to subgroups according to the embryo development rates until day 3:subgroup A1(≤6 cell stages),subgroup A2(7-9 cell cleavage stages),or subgroup A3(≥10 cell cleavage stages).Group B was transferred on day 4,and they were assigned to subgroups according to the embryo development rates until day 4:subgroup B1(cleavage stages),subgroup B2(1st or 2nd period blastocyst or morula stages),or subgroup B3(3rd period blastocyst or higher stages).Group C was transferred on day 5,and they were assigned to subgroups according to the embryo development rates until day 5:subgroup C1(1st or 2nd period blastocyst or morula stages),subgroup C2(4th or 5th period blastocyst stages),or subgroup C3(6th period blastocyst stages).Group D was transferred on day 6,and they were assigned to subgroups according to the embryo development rates until day 6:subgroup D1(morula or 1st or 2nd period blastocyst stages),or subgroup D2(5th or 6th period blastocyst stages).The clinical pregnancy and live birth rates were calculated for each group.Results Pairwise comparisons of the subgroups A1,B1,C1 and D1,all with relatively slow development rates,showed that the clinical pregnancy rates were 23.7%,37.3%,26.9%and 35.9%,respectively(P＜0.05),the live birth rates were 16.4%,28.4%,19.2%and 26.9%,respectively(P＜0.05),and the clinical pregnancy rate and live birth rate were both the highest in the B1 group.Pairwise comparisons of the subgroups A2,B2,C2 and D2 with normal development rates,the clinical pregnancy rates were 58.0%,59.4%,62.2%and 61.5%,respectively(P＜0.05),the live birth rates were 47.5%,49.4%,53.8%and 52.3%,respectively(P＜0.05),and the clinical pregnancy rate and live birth rate were both the highest in the subgroup C2.Pairwise comparisons of the subgroups A3,B3 and C3 with relatively fast development rates showed that the clinical pregnancy rates were 62.2%,64.6%and 63.5%,respectively(P＜0.05),the live birth rates were 52.2%,56.9%and 54.1%,respectively(P＜0.05),and the clinical pregnancy rate and live birth rate were both the highest in the subgroup B3.Conclusion The 4th day fast-developing blastocysts have better development potential and clinical outcomes.Embryos with slower development rate should be transferred on the 4th day,and embryos with normal development rate are recommended to be cultured and transferred to the 5th day.

OBJECTIVES: The Charlson comorbidity index reflects overall comorbidity burden and has been applied in cardiovascular medicine. However, its role in predicting in-hospital mortality in patients with acute myocardial infarction (AMI) complicated by ventricular arrhythmias (VA) remains unclear. This study aims to evaluate the predictive value of the Charlson comorbidity index in this setting and to construct a nomogram model for early risk identification and individualized management to improve outcomes. METHODS: Using the open-access critical care database MIMIC-IV (Medical Information Mart for Intensive Care IV), we identified intensive care unit (ICU) patients diagnosed with AMI complicated by VA. Patients were grouped according to in-hospital survival. The predictive performance of the Charlson comorbidity index and other clinical variables for in-hospital mortality was analyzed. Key predictors were selected using the least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable Logistic regression. A nomogram model was constructed based on the regression results. Model performance was assessed using receiver operating characteristic (ROC) curves and calibration plots. RESULTS: A total of 1 492 patients with AMI and VA were included, of whom 340 died and 1 152 survived during hospitalization. Significant differences were observed between survivors and non-survivors in sex distribution, vital signs, comorbidity burden, organ function, and laboratory parameters (all P<0.05). The area under the curve (AUC) of the Charlson comorbidity index for predicting in-hospital mortality was 0.712 (95% CI 0.681 to 0.742), significantly higher than albumin, international normalized ratio (INR), hemoglobin, body temperature, and platelet count (all P<0.001), but comparable to Sequential Organ Failure Assessment (SOFA) score (P>0.05). LASSO regression identified seven key predictors: the Charlson comorbidity index (quartile groups: T1, <6; T2, ≥6-<7; T3, ≥7-<9; T4, ≥9), ventricular fibrillation, age, systolic blood pressure, respiratory rate, body temperature, and SOFA score. Multivariate Logistic regression showed that compared with T1, mortality risk increased significantly in T2 (OR=1.996, 95% CI 1.135 to 3.486, P=0.016), T3 (OR=3.386, 95% CI 2.192 to 5.302, P<0.001), and T4 (OR=5.679, 95% CI 3.711 to 8.842, P<0.001). Age (OR=1.056, P<0.001), respiratory rate (OR=1.069, P<0.001), SOFA score (OR=1.223, P<0.001), and ventricular fibrillation (OR=2.174, P<0.001) were independent risk factors, while systolic blood pressure (OR=0.984, P<0.001) and body temperature (OR=0.648, P<0.001) were protective factors. The nomogram incorporating these predictors achieved an AUC of 0.849 (95% CI 0.826 to 0.871) with high discrimination and good calibration (mean absolute error=0.014). CONCLUSIONS The Charlson comorbidity index is an independent predictor of in-hospital mortality in AMI patients complicated by VA, with performance comparable to the SOFA score. The nomogram model based on the Charlson comorbidity index and additional clinical variables effectively estimates mortality risk and provides a valuable reference for clinical decision-making.
Humans ; Nomograms ; Hospital Mortality ; Myocardial Infarction/complications* ; Male ; Female ; Comorbidity ; Middle Aged ; Aged ; Arrhythmias, Cardiac/complications* ; ROC Curve ; Intensive Care Units

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 ^-/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Objective To explore the effect of tongue pressure resistance feedback training in the rehabilitation of dysphagia in patients with ischemic stroke(IS).Methods A total of 100 pa-tients with dysphagia after IS were randomly divided into control group(receiving conventional reha-bilitation therapy and oral motor training)and experimental group(receiving tongue pressure resist-ance feedback training on the basis of conventional rehabilitation therapy),with 50 patients in each group.The treatment duration was 4 weeks for both groups.During the study,3 patients dropped out due to personal reasons,and ultimately 49 patients in the control group and 48 patients in the experi-mental group completed the study.Before and after treatment,tongue muscle function was measured in both groups;videofluoroscopic swallowing studies(VFSS)were used to measure temporal and kinemat-ic parameters of swallowing;the Rosenbek Penetration-Aspiration Scale(PAS)was used to assess aspi-ration risk;the Stroke and Aphasia Quality of Life Scale(SWAL-QOL)was used to evaluate quality of life;and occurrence of complications in both groups were compared.Results After 4 weeks of treat-ment,peak tongue pressure,mean tongue pressure,and tongue pressure duration increased inboth groups,with these indicators being higher in the experimental group than in the control group;oral transit time,soft palate elevation time,and hyoid bone displacement time shortened,while upper esoph-ageal sphincter(UES)opening time and laryngeal closure time prolonged,hyoid and thyroid cartilage movement(upward and anterior displacement)and UES opening degree increased,and pharyngeal contractile ratio(PCR)decreased in both groups,with these indicators being superior in the experi-mental group compared to the control group;PAS scores decreased and SWAL-QOL scores increased in both groups,with PAS scores being lower and SWAL-QOL scores being higher in the experimental group compared to the control group;the differences between the two groups in the aforementioned indicators were statistically significant(P＜0.05).The complication rate was 4.17％(2/48)in the experimental group and 10.20％(5/49)in the control group,with no statistically significant difference(P＞0.05).Conclusion Tongue pressure resistance feedback training can improve tongue function and swallowing function,effectively reduce the risk of aspiration after swallowing,and enhance the quality of life of patients with dysphagia after IS during their rehabilitation treatment.

Objective To explore the prevalence of knee osteoarthritis and the influencing fac-tors of comorbidities in people aged ≥60 years old in Chengdu area.Methods A retrospective study was conducted for 168 patients aged ≥ 60 years old with knee osteoarthritis in the hospital from May 2021 to June 2023.Relevant materials of patients with knee osteoarthritis were collected,and preva-lence of the disease was analyzed.Patients were divided into comorbidity group(n=92)and non-co-morbidity group(n=76)based on the comorbidity status.Logistic regression analysis was used to ex-plore the influencing factors of comorbidities.Results Among 168 patients aged ≥60 years old with knee osteoarthritis,there were 107 females(63.69％)and 61 males(36.31％);66 patients(39.29％)were aged 60 to 70 years old,and 102 patients(60.71％)were older than 70 years old;81 patients(48.21％)resided in rural area,and 87 patients(51.79％)resided in urban area;92 patients(54.76％)had one comorbidity at least,specifically including 53 cases of dyslipidemia,38 cases of cardiovascular and cerebrovascular diseases,35 cases of hypertension,28 cases of type 2 diabetes,13 cases of chronic kidney disease,and 11 cases of depression.There were significant differences in age,duration of knee osteoarthritis,body mass index,occupation,history of knee surgery,time of daily physical exercise,knee joint function score,and the proportion of cases preferring spicy and greasy food between the comorbidity group and the non-comorbidity group(P＜0.05).Multivariate Logis-tic regression analysis showed that age(OR=1.561,95％ CI,1.183 to 2.078),body mass index(OR=2.439,95％ CI,1.740 to 3.225),occupation(OR=1.446,95％ CI,1.065 to 1.944),duration of knee osteoarthritis(OR=2.680,95％ CI,1.830 to 3.447),history of knee surgery(OR=1.772,95％ CI,1.313 to 2.336),time of daily physical exercise(OR=1.691,95％ CI,1.221 to 2.174),knee joint function score(OR=2.023,95％ CI,1.573 to 2.859),and prefer-ence for spicy and greasy food(OR=1.842,95％ CI,1.195 to 2.841)were influencing factors of comorbidities in patients with knee osteoarthritis(P＜0.05).Conclusion The knee joint function of people aged ≥60 years old in Chengdu area is poor,and the incidence of complications is high.It is necessary to strengthen the health management of patients with knee osteoarthritis,encourage active exercise,maintain a healthy diet and normal body weight,and reduce the impact of knee os-teoarthritis on their qualities of life.

Objective To investigate the correlations of interleukin-1 β(IL-1β)level and per-centage of CD16+CD56+natural killer(NK)cells in peripheral blood with severity of disease in pa-tients with pulmonary tuberculosis.Methods A total of 150 patients with active pulmonary tubercu-losis(APTB)in the Suqian First People's Hospital from January 1,2021 to September 1,2023 were selected as APTB group,and 150 patients with inactive pulmonary tuberculosis(IPTB)in the same period were selected as IPTB group.Level of IL-1 β and percentage of CD16+CD56+NK cells in pe-ripheral blood of patients with different disease severities were compared,and their correlations with severity of disease were analyzed.Results In the APTB group,level of IL-1 β in the peripheral blood was significantly higher than that in the IPTB group,while the percentage of CD16+CD56+NK cells was significantly lower(P＜0.001).In the mild,moderate,and severe groups,level of IL-1 βshowed a significant gradual increasing trend in peripheral blood,while the percentage of CD16+CD56+NK cells showed a significant gradual decreasing trend(P＜0.001).After treatment,the level of IL-1β in the peripheral blood decreased significantly,while the percentage of CD16+CD56+NK cells increased significantly in the APTB group(P＜0.001).Correlation analysis revealed that level of IL-1β in the peripheral blood of patients with pulmonary tuberculosis was positively correlated with severity of disease(r=0.732,P＜0.001),while the percentage of CD16+CD56+NK cells was negatively correlated with severity of disease(r=-0.612,P＜0.001).Conclusion Level of IL-1β in the peripheral blood is elevated while the percentage of CD16+CD56+NK cells is de-creased in patients with pulmonary tuberculosis,which is closely related to the severity of APTB.

Objective:To investigate the expression of complement C3 in serums and tissues of lung adenocarcinoma patients with brain metastases and the mechanism of complement C3 in inducing epithelial mesenchymal transition (EMT).Methods:The retrospective case-control study, cell experiments and animal experiments were conducted. The serum samples from 20 healthy examinees, 20 advanced lung adenocarcinoma patients without brain metastases and 20 advanced lung adenocarcinoma patients with brain metastases at the First People's Hospital of Yancheng from January 2021 to January 2023 were collected, and the expression of complement C3 in serum samples was detected by immunoturbidimetry. At the same time, lung tissue samples were collected from 10 lung adenocarcinoma patients without brain metastases, and lung tissue and brain tissue samples were collected from 10 lung adenocarcinoma patients with brain metastases in the First People's Hospital of Yancheng. Immunohistochemistry was used to detect the expression of complement C3, C3aR, Kruppel like factor 5 (KLF5), and N-cadherin (N-cad) in the tissue samples. Using lentivirus to construct a human lung adenocarcinoma with brain metastases cell line PC14-C3 with stable overexpression of complement C3, with cells infected with empty vector virus as the control group (PC14-Ctrl). Western blotting was used to detect the expression of complement C3, KLF5, N-cad, and E-cadherin (E-cad) in PC14-C3 and PC14-Ctrl cells, and scratch assay was used to assess cell migration ability. Using the random number table method, 12 BALB/c nude mice were evenly divided into PC14-C3 group and PC14-Ctrl group. PC14-C3 cells and PC14-Ctrl cells were subcutaneously inoculated on the ventral side, and the body mass and tumor volume of the nude mice were recorded. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of KLF5, N-cad and E-cad mRNA in various tumor cells and tumor tissues of nude mice.Results:The serum complement C3 levels in healthy individuals, lung adenocarcinoma patients without brain metastases and lung adenocarcinoma patients with brain metastases were (1.14±0.17) g/L, (1.20±0.15) g/L and (1.61±0.21) g/L, respectively. The serum complement C3 level in lung adenocarcinoma patients with brain metastases was higher than that in lung adenocarcinoma patients without brain metastases and healthy individuals, and the differences were statistically significant (both P < 0.001). The results of immunohistochemical testing showed that the proportions of positive expression areas of complement C3, C3aR, KLF5, and N-cad proteins in the lung primary lesions of lung adenocarcinoma patients with brain metastases were higher than those of patients without brain metastases, and the differences were statistically significant (all P < 0.05). The mRNA ( P < 0.05) and protein expression levels of complement C3 in PC14-C3 cells were higher than those in PC14-Ctrl cells, indicating successful transfection. The scratch assay results showed that the migration rate of PC14-Ctrl cells was (37.5±4.1)%, and the migration rate of PC14-C3 cells was (60.4±2.9)%, and the difference was statistically significant ( t = 7.86, P < 0.01). The relative expressions of EMT promoting molecules KLF5 and N-cad mRNA in PC14-C3 cells were higher than those in PC14-Ctrl cells, while the relative expression of EMT inhibiting molecule E-Cad mRNA was lower than that in PC14-Ctrl cells, and the differences were statistically significant (all P < 0.05). On the 26th day of tumor loading, the tumor volume of nude mice in PC14-C3 group was (610±10) mm 3, while that of PC14-Ctrl group was (321±30) mm 3; the body mass of nude mice in PC14-C3 group was lower than that in PC14-Ctrl group [(21.6±0.6) g vs. (23.2±0.6) g], and the differences were statistically significant (both P < 0.05). At the end of the experiment, 5 nude mice died and 1 survived in the PC14-C3 group; 1 nude mouse died and 5 survived in the PC14-Ctrl group. The relative expressions of KLF5 and N-cad mRNA in the tumor tissues of nude mice in PC14-C3 group were higher than those in PC14-Ctrl group, while the relative expression of E-Cad mRNA was lower than that in PC14-Ctrl group, and the differences were statistically significant (all P < 0.05). Conclusions:Lung adenocarcinoma patients with brain metastases have high levels of complement C3 in their serums and primary lesions. Complement C3 may induce EMT and promote the occurrence of lung adenocarcinoma brain metastases by affecting the expressions of KLF5, N-cad and E-cad.

Flap surgery is a complex surgical procedure that has become an effective method for the treatment of many diseases and traumas. Flap survival is closely related to a variety of factors including cellular autophagy, oxidative stress, inflammatory response, mesenchymal stem cells (MSCs) function, and vascular regeneration. Cellular autophagy maintains intracellular homeostasis and plays a key role in reducing oxidative stress and inflammation and promoting injury repair. Excessive oxidative stress and inflammatory responses pose a threat to flaps, affecting their survival and successful transplantation. Endothelial cells are involved in vascular regeneration through proliferation, migration, and production of angiogenic factors, and vascular endothelial growth factor directly promotes blood vessel formation and maintains endothelial cell function.MSCs play an important role in promoting flap survival and tissue repair due to their unique biological properties and multiple mechanisms of action. The multiple roles played by cellular autophagy, oxidative stress, inflammatory response, MSCs function, and vascular regeneration in influencing postoperative flap survival are hereby elaborated. The aim is to provide a basis for the clinical application of regulating the above factors to improve postoperative flap survival, improve the success rate of flap surgery, reduce complications, and bring more hope for the recovery and quality of life of patients.