Macrophage migration inhibitory factor (MIF) is an enzyme-active pleiotropic cytokine that is expressed in various immune cells and tumor cells. MIF plays diverse roles in inflammation and tumor progression. It acts as a cytokine involved in immune response and inflammatory lesions. Additionally, MIF is closely associated with tumor proliferation, metastasis, and other tumor hallmarks, exerting a multifaceted influence on tumor occurrence and progression. MIF not only functions by being secreted into the extracellular space as a cytokine but can also be localized within the cytoplasm and nucleus, exhibiting diverse biological functions. As MIF in promoting tumor progression becomes increasingly recognized, MIF-based therapeutic strategies have become a hot research topic in oncology. Here, we provide a comprehensive review of MIF with different subcellular localization about their pro-tumoral functions. A better understanding of MIF in tumor biology will bring broader perspectives for the development of novel MIF targeting strategies and give promising direction for future tumor treatments.

Objective:To investigate the safety of early whole body computed tomography (WBCT) combined with coronary angiography (CAG) in patients with extracorporeal cardiopulmonary resuscitation (ECPR) and its application value in the diagnosis of cardiac arrest and complications of cardiopulmonary resuscitation (CPR).Methods:This was a retrospective study. Patients who underwent ECPR in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University from January 2017 to July 2021 were enrolled in this research. Patients younger than 18 years or with incomplete clinical data were excluded. The results of WBCT and CAG examinations after ECPR were collected.Results:A total of 89 patients with ECPR, aged (47±17) years, were enrolled in the study, all underwent WBCT examination, and no adverse events such as ECMO and tracheal tube shedding occurred. WBCT found 7 cases of pulmonary embolism, 3 cases of aortic dissection and 2 cases of cerebral hemorrhage. WBCT identified CPR-related complications in 42 cases, including rib fractures ( n=20), pneumothorax ( n=5), mediastinal emphysema ( n=5), subcutaneous emphysema ( n=6), and hematoma or swelling at puncture site ( n=6). Fifty-five patients underwent CAG examination, the most common culprit vessels were the left anterior descending branch disease (58.2%) followed by the left circumflex branch disease (27.3%), the right coronary artery disease (21.8%) and left main artery disease (12.7%). Conclusions:Early WBCT and CAG examinations are of great significance and safety for the guidance of treatment in ECPR patients.

【Objective】 To investigate the efficacy and safety of ultrasound- guided above- knee and below- knee radiofrequency ablation for the treatment of saphenous varicose veins.【Methods】Patients who underwent ultrasound-guided radiofrequency ablation closure in our department from July 2019 to November 2019 were compared in operation time ， recovery time，volume of sclerosant foam，pain score，venous clinical severity score（VCSS），Aberdeen Varicose Veins Questionnaire （AVVQ）， and complications. 【Results】 Fifty- nine patients underwent above- knee radiofrequency ablation and 19 patients underwent below-knee radiofrequency ablation. The average operation time（69.75 vs. 78.95）min， time return to normal activity（2.93 vs. 3.58）min or the volume of foam（28.3 vs. 24.2）mL were similar in both groups. The pain score，VCSS，and AVVQ scores 24 h，1 week，or 4 w postoperative decreased significantly in the two groups. No deep vein thrombosis，pulmonary embolism，or infection occurred in the two groups after surgery. Other complications including phlebitis，pigmentation，bleeding，rash，or paresthesia，showed no difference in rates. And overall incidence of complications were similar between the two groups. 【Conclusions】 Both above-knee and below-knee radiofrequency ablation are safe and effective treatments for great saphenous varicose veins.

Objective Angiotensin Ⅱ (Ang Ⅱ)-induced vascular damage is a major risk of hypertension. However, the underlying molecular mechanism of AngⅡ-induced vascular damage is still unclear. In this study, we explored the novel mechanism associated with Ang II-induced hypertension. Methods We treated 8- to 12-week-old C57BL/6J male mice with saline and Ang Ⅱ(0.72 mg/kg·d) for 28 days, respectively. Then the RNA of the media from the collected mice aortas was extracted for transcriptome sequencing. Principal component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano plot. Functional annotations including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to reveal the molecular mechanism of Ang Ⅱ-induced hypertension. Finally, the differentially expressed genes were validated by using quantitative real-time PCR. Results The result revealed that a total of 773 genes, including 599 up-regulated genes and 174 down-regulated genes, were differentially expressed in the aorta of Ang Ⅱ-induced hypertension mice model. Functional analysis of differentially expressed genes manifested that various cellular processes may be involved in the Ang Ⅱ-induced hypertension, including some pathways associated with hypertension such as extracellular matrix, inflammation and immune response. Interestingly, we also found that the differentially expressed genes were enriched in vascular aging pathway, and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased (P<0.05). Conclusion We identify that vascular aging is involved in Ang Ⅱ-induced hypertension, and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.
Aging ; Angiotensin II ; Animals ; Aorta/physiopathology* ; Blood Pressure/genetics* ; Gene Expression Profiling/methods* ; Gene Ontology ; Hypertension/genetics* ; Male ; Mice, Inbred C57BL ; Reverse Transcriptase Polymerase Chain Reaction

Objective To investigate whether elevated baseline levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) are associated with an increased risk of breast cancer in Kailuan female cohort. Methods Females from Kailuan cohort (2006-2007) were included in this study. Information on check-up, hsCRP and NE were collected at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) of association between baseline hsCRP and NE values and breast cancer risk. Results By December 31, 2015, a total of 18 866 participants were enrolled in this study. During the follow-up, 183 new cases of breast cancer were observed. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of breast cancer were 829/105, 1 211/105 and 1 495/105 in these 3 groups, respectively ( 2=12.08， P=0.002). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significantly increased risk of breast cancer (HR=1.71,95%CI: 1.18-2.47, P=0.005), howerver, we didn’t find the statistically significant association between NE level (<3.70×109/Lvs. ≥3.70×109/L) and the risk of brease cancer (P>0.05). Conclusions Elevated levels of hsCRP at baseline might increase the risk of breast cancer in females.

The clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system is a versatile genome editing tool with high efficiency. A guide sequence of 20 nucleotides (nt) is commonly used in application of CRISPR/Cas9; however, the relationship between the length of the guide sequence and the efficiency of CRISPR/Cas9 in porcine cells is still not clear. To illustrate this issue, guide RNAs of different lengths targeting the EGFP gene were designed. Specifically, guide RNAs of 17 nt or longer were sufficient to direct the Cas9 protein to cleave target DNA sequences, while 15 nt or shorter guide RNAs had loss-of-function. Full-length guide RNAs complemented with mismatches also showed loss-of-function. When the shortened guide RNA and target DNA heteroduplex (gRNA:DNA heteroduplex) was blocked by mismatch, the CRISPR/Cas9 would be interfered with. These results suggested the length of the gRNA:DNA heteroduplex was a key factor for maintaining high efficiency of the CRISPR/Cas9 system rather than weak bonding between shortened guide RNA and Cas9 in porcine cells.
Base Sequence ; Complement System Proteins ; CRISPR-Cas Systems ; DNA ; Genome ; Nucleotides ; RNA, Guide ; Swine

Objective: To assess the feasibility of HEAD-US scale in the clinical application of hemophilic arthropathy (HA) and propose an optimized ultrasound scoring system. Methods: From July 2015 to August 2017, 1 035 joints ultrasonographic examinations were performed in 91 patients. Melchiorre, HEAD-US (Hemophilic Early Arthropathy Detection with UltraSound) and HEAD-US-C (HEAD-US in China) scale scores were used respectively to analyze the results. The correlations between three ultrasound scales and Hemophilia Joint Health Scores (HJHS) were evaluated. The sensitivity differences of the above Ultrasonic scoring systems in evaluation of HA were compared. Results: All the 91 patients were male, with median age of 16 (4-55) years old, including 86 cases of hemophilia A and 5 cases hemophilia B. The median (P₂₅, P₇₅) of Melchiorre, HEAD-US and HEAD-US-C scores of 1 035 joints were 2(0,6), 1(0,5) and 2(0,6), respectively, and the correlation coefficients compared with HJHS was 0.747, 0.762 and 0.765 respectively, with statistical significance (P<0.001). The positive rates of Melchiorre, HEAD-US-C and HEAD-US scale score were 63.0% (95%CI 59.7%-65.9%), 59.5% (95%CI 56.5%-62.4%) and 56.6% (95%CI 53.6%-59.6%) respectively, and the difference was statistically significant (P<0.001). Even for 336 cases of asymptomatic joints, the positive rates of Melchiorre, HEAD-US-C and HEAD-US scale score were 25.0% (95%CI 20.6%-29.6%), 17.0% (95%CI 12.6%-21.1%) and 11.9% (95%CI 8.4%-15.7%) respectively, and the difference was statistically significant (P<0.001). There were significant changes (P<0.05) in the ultrasonographic score of HA before and after onset of hemorrhage in 107 joints of 40 patients. The difference in variation amplitude of HEAD-US-C scores and HEAD-US scores before and after joint bleeding was statistically significant (P<0.001). Conclusion: Compared with Melchiorre, there were similar good correlations between HEAD-US, HEAD-US-C and HJHS. HEAD-US ultrasound scoring system is quick, convenient and simple to use. The optimized HEAD-US-C scale score is more sensitive than HEAD-US, especially for patients with HA who have subclinical state, which make up for insufficiency of sensitivity in HEAD-US scoring system.
Adolescent ; Adult ; Child ; Child, Preschool ; China ; Hemarthrosis ; Hemophilia A ; Hemophilia B ; Humans ; Male ; Middle Aged ; Ultrasonography ; Young Adult

Objective: This research is conducted to analyze the background, the main practices and the results of the synergistic service of health institutions in Changzhou city, as well as to provide references for promoting the construction of integrated medical and health service system.Methods: This paper uses qualitative interviews and questionnaires to collect information and analyzes the data based on synergetic management theory.Results:Changzhou city has tentatively achieved the synergy of its health institutions by introducing relevant policies, setting up healthcare unions at the municipal level, integrating internal resources among healthcare unions, establishing health information platform and feedback mechanism, etc.Conclusion: The regional synergistic service of health institutions can be effectively promoted by introducing policies at the municipal level, promoting the mutual sharing and communication on information, and integrating internal resources among healthcare unions.But, as there still exist problems such as the distribution of benefits is not perfect, the degree of synergy is not close, etc., thus, the government is suggested to expand the implementation scope of the close-type medical service synergy and further improve the distribution policy of benefits.

Objective:To elucidate the factors influencing the differences in the survival rates of esophageal squamous cell carcinoma (ESCC) patients between the rural and urban regions in China. Methods:A total of 36,723 ESCC patients derived from the clinical data-bases containing 500,000 esophageal and gastric cardia carcinoma cases (1973-2015) of the Henan Key Laboratory for Esophageal Can-cer Research of the First Affiliated Hospital, Zhengzhou University, were analyzed. Of these patients, 33,625 were from the rural re-gions (91.6%), comprising 20,906 male patients with an average age of 58.98 ± 8.71 years and 12,719 females with an average age of 59.59 ± 8.53 years. The remaining 3,098 were from the urban regions and composed of 2,089 male patients with an average age of 60.84±9.10 years and 1,009 females with an average age of 62.46 ± 9.14 years. All the patients underwent radical esophagectomy, de-tailed histopathological diagnosis, and TNM staging. Chi square test, Kaplan-Meier, Log-rank, and Cox proportional hazards regression model were used to analyze the differences between ESCC patients from rural regions and those from urban regions and among the risk factors in prognosis. Results:Kaplan-Meier and Log-rank analysis results showed that the ESCC patients from the rural regions had significantly higher overall survival than the urban patients (χ2=12.971, P=0.000). Further analysis showed that rural patients≥50 years old and diagnosed with stage IIa and IIb (middle stage) ESCC had higher survival rates than urban patients in males and females (male:χ2=16.188, P<0.001;female:χ2=5.019, P=0.025). However, the survival rates of rural and urban patients with stage 0,Ⅰa,Ⅰb (early stage) and Ⅲa, Ⅲc, and Ⅳ (late stage) were similar (P>0.05). The results of Cox proportional hazards regression model analysis showed that age, gender, and TNM stages were independent risk factors for rural and urban ESCC patients. When the rural and urban ESCC patients were both considered, the Cox proportional hazards regression model analysis results showed that male ESCC patients≥50 years old, urban residence, and TNM stages were independent risk factors. Conclusion:Rural ESCC patients have significantly high-er overall survival than urban patients. Male, age of≥50 years old, urban residence, and TNM stages were independent risk factors for ESCC patient survival.

Objective:To investigate the clinicopathological characteristics, treatments, and survival of patients with esophageal adeno-squamous carcinoma (EASC). Methods:A total of 494 patients with EASC were selected from the clinical information databases of 500, 000 cases with esophageal and gastric cardiac carcinomas in the Henan Key Laboratory for Esophageal Cancer Research. Among the 494 EASC cases, 361 were males with an average age of 61.47 ± 8.32 years, and 133 were females with an average age of 65.56 ± 8.06 years. SPSS 21.0 software was applied to determine the statistical differences among the different groups. A life-table method was also used to calculate the five-year survival rate. A linear regression model was used to analyze the correlation of changes at different peri-ods. Results:The incidence of EASC in our database was 0.196%(494/251707). EASC occurred predominantly in male patients (male:female=2.71:1.00). The peak age was within 60-69 years in both males and females (39.6%vs. 40.6%). Notably, the incidence of male patients showed a downward trend (R2=0.063), whereas that of female patients showed an upward trend (R2=0.004). The prevalence of EASC was obviously higher in low-incidence areas for esophageal cancer than in high-incidence areas (53.1%vs. 46.9%, P<0.001). Ac-cording to the TNM staging criteria for esophageal cancer, phases II and III patients comprised the majority of cases, which accounted for 40.8%(173/424). The positive lymph node metastasis rate was 47.0%(206/438), and the number of positive lymph node metasta-ses ranged within 1-2 (48.5%, 100/206). In addition, preoperative biopsy was performed in 467 cases, and more than half of the pa-tients (53.96%, 252/467) were diagnosed before the operation. Surgical resection was the predominant treatment method for EASC (88.8%, 419/472). Only 1.9%patients (9/472) underwent radiotherapy and chemotherapy. The five-year survival rate of male patients who were neither smoking nor drinking of alcohol was higher than that of male smokers (26.5%vs. 12.1%). In patients with stagesⅠ,Ⅱ, andⅢ+Ⅳcarcinomas with surgery as lone treatment, the three-year survival rates were 64.7%, 50.9%, and 48.5%, respectively. Correspondingly, these rates were 51.7%, 47.8%, and 33.1%after adjuvant radiotherapy and chemotherapy. Conclusion:EASC is a rare type of esophageal malignant tumor. The preoperative biopsy pathological diagnosis has high misdiagnosis rate. Smoking and drinking of alcohol can influence the prognosis of patients. In EASC patients, lymph node metastasis easily occurs, and a simple surgery is bet-ter than other cancer treatments.