Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Objective:To investigate the impacts of periodontal-orthodontic treatment on periodontal indicators,bone metabolism and serum levels of soluble intercellular adhesion molecule-1(sICAM-1)and monocyte chemotactic protein-1(MCP-1)in patients with an-terior tooth displacement(ATD)caused by periodontitis.Methods:60 patients with ATD caused by periodontitis were included and randomly divided into a reference group(n=30,periodontal basic treatment+periodontal splint treatment)and a study group(n=30,combination of orthodontic treatment with the reference treatment).31 ATD patients who only received periodontal basic treatment were included into the blank control group.The probing depth(PD),plaque index(PLI)and gingival index(GI),tooth looseness,bone me-tabolism indicators osteocalcin(OCN)and osteoprotegerin(OPG),and serum inflammatory indicators(sICAM-1 and MCP-1)were compared among the 3 groups before and after treatment.Results:After 6 months of treatment,the levels of PD,PLI,GI,and serum sICAM-1 and MCP-1 in the 3 groups were lower than those before treatment(P＜0.05),and lower in the study group than in the refer-ence group and blank control group(P＜0.05);the looseness of the affected teeth in the 3 groups was decreased(P＜0.05),and in the study group was less than in the reference group and blank control group(P＜0.05);the levels of OCN and OPG in the 3 groups were higher(P＜0.05)than those before treatment,and in the study group were higher than in the reference group and blank control group(P＜0.05).Conclusion:Periodontal-orthodontic treatment can obviously reduce the levels of inflammatory factors in serum,effectively regulate bone metabolism and improve periodontal health in patients with ATD caused by periodontitis.

Objective To investigate the correlation between blood glucose variability index(GLUCV)and postoperative delirium(POD)in elderly patients undergoing knee arthroplasty.Methods A total of 112 elderly patients undergoing elective knee arthroplasty were analyzed retrospectively,16 males and 96 females,aged 65-80 years,BMI 22.0-28.0 kg/m2,ASA physical status Ⅰ or Ⅱ.They were di-vided into two groups according to whether they had POD within 5 days after operation:POD group and non-POD group.The score of the last preoperative mini-mental state examination(MMSE),operation time,the duration of the intraoperative regional cerebral oxygen saturation(rScO2)value decreased by more than 13％of the rScO2 basic value(△rScO2＞13％),the preoperative hemoglobin(Hb)and C-reactive protein(CRP)concentration,the fingertip blood glucose concentration before entry,before anesthesia induction,5 minutes after anesthesia induction,1 minute after skin incision,and before leaving the chamber were col-lected,and the GLUCV was calculated.The risk factors of POD in elderly patients undergoing knee arthro-plasty were analyzed by univariate and multivariate logistic regression,and the odds ratio(OR)and 95％confidence interval(CI)were calculated.The receiver operating characteristic(ROC)curve was drawn to calculate the area under the curve(AUC)and analyze the predictive value of GLUCV.Results Thirty patients(26.8％)showed POD symptoms within 5 days after surgery.Compared with the non-POD group,the operation time and duration of intraoperative △rScO2＞13％in the POD group were significantly prolonged(P＜0.05),the CRP concentration and GLUCV were significantly increased(P＜0.05).Multi-variate logistic regression analysis showed that prolonged time of △rScO2＞13％(OR=3.542,95％CI 1.380-9.093,P=0.011),elevated CRP concentration(OR=1.984,95％CI 1.078-3.650.P=0.015),and elevated GLUCV(OR=5.257,95％CI 1.690-16.353,P=0.008)were risk factors of POD in elderly patients undergoing knee arthroplasty.ROC curve analysis showed that the area under the AUC of GLUCV in predicting POD in elderly patients undergoing knee arthroplasty was 0.747(95％CI 0.650-0.844,P＜0.001),while the optimal cutoff value was 23.4％,the sensitivity was 71.4％,and the specificity was 63.3％.Conclusion GLUCV is closely related to POD,and GLUCV level has a good pre-dictive effect on POD in elderly patients undergoing knee arthroplasty.

BACKGROUND: Female breast cancer (FBC) has become the most prevalent malignancy worldwide. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of FBC. METHODS: FBC incidence and mortality in 60 selected countries by cancer registry data integrity in 2020 were estimated from the GLOBOCAN database, and their association with the human development index (HDI) was further evaluated. Trends of age-standardized rates of incidence and mortality in 60 countries from 2000 through 2019 were evaluated by joinpoint regression analysis using data of Global Burden of Disease 2019. The association between potential behavioral, metabolic, and socioeconomic risk factor exposure at the nation level retrieved from the World Bank and Global Health Observatory and the incidence and mortality of FBC were evaluated by multivariate linear regression. RESULTS: FBC incidence and mortality varied greatly in the 60 included countries. Higher incidence and mortality rates were typically observed in countries with higher HDIs and vice versa. During 2000 to 2019, significantly increasing trends in incidence and mortality were observed in 26 (average annual percent changes [AAPCs], 0.35-2.96) and nine countries (AAPC, 0.30-1.65), respectively, while significantly decreasing trends in both incidence and mortality were observed in 22 countries, most of which were high-HDI countries. Among the population aged ≥40 years, there were 26 and 11 countries showing significantly increased trends in incidence and mortality, respectively. Ecological analysis showed that countries with higher prevalence rates of high cholesterol and higher health expenditures were more likely to have higher FBC incidence, and countries with higher rates of obesity and poorer universal health coverage were more likely to have higher FBC mortality. CONCLUSIONS Despite decreased or stabilized FBC incidence and mortality rates were observed in some countries with high HDI over the past decades, disease burden became even severer in developing countries, especially for the population aged ≥40 years. Effective targeted preventive programs are strongly encouraged to reduce the FBC disease burden worldwide.
Breast Neoplasms/epidemiology* ; Female ; Global Health ; Humans ; Incidence ; Registries ; Risk Factors

Objective:To investigate the treatment, safety and prognosis of advanced non-small cell lung cancer patients with leptomeningeal metastasis and performance status score more than 3.Methods:The clinical data of 6 NSCLC patients with leptomeningeal metastasis admitted to the People's Hospital of Wuhan University from November 2016 to September 2018 were analyzed retrospectively. The curative effect and adverse reactions were observed, and the prognosis was analyzed.Results:There were 5 females and 1 male among 6 patients. The median age was 57 years old (46-74 years old). All 6 patients were diagnosed as stage Ⅳ lung adenocarcinoma. There were 3 patients with epidermal growth factor receptor (EGFR) exon 21 mutation, 2 patients with exon 19 mutation and one with anaplastic lymphoma kinase (ALK) fusion mutation. The time window of leptomeningeal metastasis occurred after the progression of adenocarcinoma of lung: 3 cases was more than 12 months, the other 3 cases was less than 12 months, and the average was 20.3 month. Performance status score was more than 3 when leptomeningeal metastasis occurred. The brain magnetic resonance imaging of 6 patients showed linear enhancement of leptomeningeal, cancer cells were found in cerebrospinal fluid in one case, 4 cases were treated with a combination of bevacizumab and EGFR-tyrosine kinase inhibitor (EGFR-TKI), 1 case was treated with oral administration of EGFR-TKI, 1 case was treated with oral administration of EGFR-TKI combined with temozolomide. The median overall survival (mOS) was 9 months (2-13 months), and the median progression free survival was 6 months (2-11 months).Conclusion:Lung adenocarcinoma may be prone to leptomeningeal metastasis; for NSCLC patients with leptomeningeal metastasis and performance status score more than 3, a combination of EGFR-TKI and bevacizumab has good tolerance, high safety and considerable curative effect.

Objective To investigate the effect of metoprolol and metoprolol combined with moderate inten-sity aerobic exercise on the sympathetic vasoconstriction response of skeletal muscle, functional sympatholysis and the exercise capacity of hypertensive men. Methods Thirty men with mild ( stage 1) essential hypertension were divi-ded into a drug group and an observation group. The drug group received only metoprolol while the observation group took metoprolol and performed aerobic exercise (intensity 50-70％ of VO2max, 30-45 min/time, 3-5 times/week) for 12 weeks. Before and after the experiment, the subjects' maximum oxygen uptake (VO2max), peak power (PP) as well as a rating of perceived exertion ( RPE) curve during exercise were determined using the graded exercise test. Forearm vascular conductance ( FVC) induced by the cold pressor test was measured using Doppler ultrasound at rest and during a handgrip exercise. Sympathetic vasoconstriction response was manifested by the rate of change in the conductance (％FVC) before and after the cold pressor test. Functional sympatholysis ( the ability of muscle contrac-tions to inhibit sympathetic vasoconstrictor response) was quantified using the difference in the ％FVC values (△％FVC) between the handgrip exercise and at rest. Results After the treatment,％FVC during the handgrip exercise was lower than at rest in the observation group.△％FVC had increased significantly, as had VO2max and PP. The RPE curve during a graded exercise test shifted to the right in the observation group, but there was no significant change in the other observations. In the drug group, PP had decreased significantly and the RPE curve had shifted to the left. Conclusion Metoprolol can better improve functional sympatholysis and enhance exercise capacity when it is com-bined with moderate intensity aerobic exercise. That will alleviate any exercise intolerance in men with mild hyperten-sion caused by taking metoprolol alone.

PURPOSE: Immune suppression is common in patients with advanced breast cancer but the mechanisms underlying this phenomenon have not been sufficiently studied. In this study, we aimed to identify B7 family members that were able to predict the immune status of patients, and which may serve as potential targets for the treatment of breast cancer. We also aimed to identify microRNAs that may regulate the expression of B7 family members. METHODS: The Cancer Genome Atlas data from 1,092 patients with breast cancer, including gene expression, microRNA expression and survival data, were used for statistical and survival analyses. Polymerase chain reaction and Western blot were used to measure messenger RNA and protein expression, respectively. Luciferase assay was used to investigate direct microRNA target. RESULTS: Bioinformatic analysis predicted that microRNA (miR)-93, miR-195, miR-497, and miR-340 are potential regulators of the immune evasion of breast cancer cells, and that they exert this function by targeting CD274, PDCD1LG2, and NCR3LG1. We chose CD274 for further investigations. We found that miR-195, miR-497, and CD274 expression levels were inversely correlated in MDA-MB-231 cells, and miR-195 and miR-497 expressions mimic inhibited CD274 expression in vitro. Mechanistic investigations demonstrated that miR-195 and miR-497 directly target CD274 3′ untranslated region. CONCLUSION: Our data indicated that the level of B7 family members can predict the prognosis of breast cancer patients, and miR-195/miR-497 regulate CD274 expression in triple negative breast cancer. This regulation may further influence tumor progression and the immune tolerance mechanism in breast cancer and may be able to predict the effect of immunotherapy on patients.
Antigens, CD274 ; B7 Antigens ; Blotting, Western ; Breast Neoplasms ; Computational Biology ; Gene Expression ; Genome ; Humans ; Immune Evasion ; Immune Tolerance ; Immunotherapy ; In Vitro Techniques ; Ligands* ; Luciferases ; MicroRNAs ; Polymerase Chain Reaction ; Prognosis ; RNA, Messenger ; Triple Negative Breast Neoplasms* ; Untranslated Regions

OBJECTIVETo compare the difference of the diameters of superior mesenteric vein (SMV) and gastrocolic trunk (GCT) between patients with cecum-ascending colon cancer and normal individuals, and to assess the diagnostic value of the diameters of SMV and GCT in cecum-ascending colon cancer.

METHODSPreoperative imaging data of 60 patients with primary cecum-ascending colon cancer confirmed by postoperative pathology at the First Affiliated Hospital of Sun Yat-sen University from June 2014 to December 2016 were retrospectively analyzed. The diameters of SMV and GCT were measured on preoperative CT images. SMV was measured at about 2 cm below the junction of SMV and splenic vein. GCT was measured at 1 cm near the proximal junction of right colon vein, right gastroepiploic vein and anterior pancreaticoduodenal vein. Another 60 people receiving pelvic CT examination without organ illness were collected as control. The diameter differences of SMV and GCT between cancer group and control group were compared. The diagnostic value of the diameters of SMV and GCT in cecum-ascending colon cancer was evaluated by receiver operating characteristic (ROC) curves.

RESULTSAmong 60 cases of cecum-ascending colon cancer, 36 were males and 24 were females with median age of 48 years (range 28-84); 13 were cecum cancer, 47 were ascending colon cancer; 11 had no lymph node and liver metastasis, 40 had lymph node metastasis, 9 had liver metastasis (all with lymph node metastasis). Compared to control group, the diameters of SMV and GCT in cancer group were significantly longer [SMV:(11.2±1.3) mm vs. (9.5±1.7) mm, t=6.04, P<0.001; GCT:(5.5±0.9) mm vs. (3.5±1.0) mm, t=11.51, P<0.001]. However, there were no statistically significant differences in diameters of SMV and GCT among hepatic metastasis, lymph node metastasis and no metastasis cancer groups (all P>0.05). The ROC curve analysis showed that the area under the curve of SMV diameter was 0.777, and the optimal cut-off point was 10.5 mm in the diagnosis of cecum-ascending colon cancer, with the sensitivity and specificity of 95.0%(57/60) and 46.7%(28/60) respectively. The area under the curve of GCT diameter was 0.923, and the optimal cut-off point was 4.5 mm in the diagnosis of cecum-ascending colon cancer, with sensitivity and specificity of 88.3%(53/60) and 85.0%(51/60) respectively.

CONCLUSIONThe dilation of the SMV and GCT may be used as warning factors for cecum-ascending colon cancer, especially the diameter of GCT.

Adult ; Aged ; Aged, 80 and over ; Cecum ; Colon, Ascending ; pathology ; Colonic Neoplasms ; pathology ; Female ; Humans ; Male ; Mesenteric Veins ; anatomy & histology ; Middle Aged ; Retrospective Studies

Objective To study effects of different types of high-impact exercises on the increment of bone mineral density (BMD) and bone mineral content (BMC) . Methods Thirty-nine male volunteers, including 13 hoopsters, 13 paratroopers, and 13 common college students as the control, were recruited and divided into two subgroups (subgroup 1:20-22 years old; subgroup 2:23-25 years old). Their BMDs and BMCs on calcaneus, first through fifth metatarsus, hip, and lumbar spine (L1-4) were evaluated. Results The BMC of calcaneus, the first and second metatarsals, total lumbar spine, and total hip in the hoopster group was significantly higher than that in the control group and paratrooper group. The hoopster group obtained statistically higher BMD at the lumbar spine, hip, and femoral neck than the other two groups. However, the BMCs and BMDs of the paratrooper group and control group had no significant differences at almost all measured anatomical locations. Conclusions BMC and BMD are not always in positive correlation with vertical ground reaction forces during normal exercises. Compared with parachuting training, playing basketball as a kind of variable load exercise can effectively increase BMC and BMD, and is more beneficial for reducing the risk of osteoporotic fracture.