BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

OBJECTIVES: Nasopharyngeal carcinoma is often diagnosed at a late stage due to its concealed location and exhibits marked regional clustering, posing a significant public health challenge in China. This study aims to analyze the disease burden of nasopharyngeal carcinoma in China using the latest 2021 Global Burden of Diseases (GBD) database, providing epidemiological evidence for precise prevention and control of nasopharyngeal carcinoma. METHODS: Age-standardized incidence rate (ASIR), mortality rate, and disability-adjusted life year (DALY) rate were used as indicators of disease burden. Stratified analyses were conducted by age, sex, socio-demographic index (SDI), and relevant risk factors. The autoregressive integrated moving average (ARIMA) model and Bayesian age-period-cohort (BAPC) model were employed to project ASIR trends through 2050. RESULTS: In 2021, China's age-standardized incidence, mortality, and DALY rates of nasopharyngeal carcinoma were 3.4/100 000, 1.5/100 000, and 48.7/100 000, respectively, all higher than the global average. Across all age groups, Chinese males exhibited higher ASIR, mortality, and DALY rates than females. From 1990 to 2021, the disease burden of nasopharyngeal carcinoma in China decreased gradually with rising SDI. The proportion of nasopharyngeal carcinoma burden attributed to alcohol consumption, smoking, and occupational formaldehyde exposure in China exceeded global levels, especially among males. Projections from both models indicate a rising trend in ASIR for males, females, and the general population in China and globally from 2022 to 2050. CONCLUSIONS Over the past 30 years, the disease burden of nasopharyngeal carcinoma in China has decreased with the increasing SDI values but remains higher than the global average. Furthermore, ASIR is projected to increase over the next 30 years. It is imperative for China to enhance healthcare resource allocation for nasopharyngeal carcinoma prevention, diagnosis, and treatment, particularly among high-risk male populations.
Humans ; China/epidemiology* ; Male ; Nasopharyngeal Carcinoma/mortality* ; Female ; Middle Aged ; Nasopharyngeal Neoplasms/mortality* ; Adult ; Incidence ; Global Burden of Disease ; Disability-Adjusted Life Years ; Aged ; Risk Factors ; Adolescent ; Databases, Factual ; Young Adult ; Cost of Illness ; Child ; Bayes Theorem

Objective To investigate the effects of long non-coding RNA FEZ family zinc finger 1 antisense RNA 1(lncRNA FEZF1-AS1)on enhancer of zeste homolog 2(EZH2)in regulation of proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of pulmonary interstitial cells and its mechanism.Methods The A549 cells human lung adenocarcinoma cell line were divided into control group and model group[model cells were induced into lung interstitial cells after being treated with transforming growth factor β1(TGF-β1)20 ng/mL for 48 h].The protein expression of E-cadherin,N-cadherin and vimentin in each group was detected by Western blot.The expression of lncRNA FEZF1-AS1 and EZH2 in the two groups was detected by RT-qPCR.Cells in the trans-fection group were divided into si NC group,lncRNA FEZF1-AS1+OE vector group and si lncRNA FEZF1-AS1+OE EZH2 group.Cell proliferation was examined by CCK-8 method,cell migration was detected by cell scratch,and cell invasion was detected by Transwell assays.The protein expression of E-cadherin,N-cadherin,vimentin and EZH2 in each group was detected by Western blot.The direct binding effect of FEZF1-AS1 and EZH2 was deter-mined by RNA immuno-precipitation(RIP).Results Compared with the control group,the protein expression level of E-cadherin in the model group was significantly decreased(P＜0.05),and the protein expression of N-cadherin and vimentin was significantly increased(P＜0.05).Compared with the control group,the expression level of lncRNA FEZF1-AS1 and EZH2 genes was significantly increased in the model group(P＜0.05).Compared with si NC group,the proliferation,migration and invasion ability of si lncRNA FEZF1-AS1+OE vector group were decreased,the ex-pression of E-cadherin protein was increased while the expression of N-cadherin,vimentin and EZH2 was decreased(P＜0.05).Compared with si lncRNA FEZF1-AS1+OE vector group,the proliferation,invasion and migration of si lncRNA FEZF1-AS1+OE EZH2 group were increased(P＜0.05).E-cadherin expression was decreased,while N-cad-herin,vimentin and EZH2 expressions were increased(P＜0.05).RIP experiment further confirmed that lncRNA FEZF1-AS1 had direct binding effect with EZH2.Conclusions LncRNA FEZF1-AS1 can promote the proliferation,invasion,metastasis and EMT process of pulmonary fibrosis cells by regulating EZH2.

Objective    To investigate the early clinical results of MitraClip system in domestic patients. Methods     We retrospectively analyzed the clinical data of 36 patients who underwent transcatheter edge-to-edge repair procedure using MitraClip system in Beijing Fuwai Hospital, Shenzhen Fuwai Hospital and Fuwai Yunnan Cardiovascular Hospital between January and June 2021. There were 24 males and 12 females, with a median age of 70 (47-86) years. Ten (27.8%) patients had 3+ mitral regurgitation (MR) and 26 (72.2%) patients had 4+ MR preoperatively. Results    All procedures were successfully performed. The reduction in MR was 2+ at least immediately after surgery, and 91.7% of patients had MR≤2+ at 3 days postoperatively. There was no statistical difference in left ventricular ejection fraction change postoperatively. Forward velocity and peak gradient of mitral valve were increased after the procedure. Mean gradient of mitral valve were increased at 3 days postoperatively than immediately after surgery (P<0.001). Two patients had acute pericardial effusion intraoperatively, and received pericardial puncture and drainage immediately. Conclusion    MitraClip system has been applied well in domestic patients and can significantly improve MR. This sutdy has a good consistency with foreign studies, and the early results are satisfactory.

OBJECTIVES: Pauwels III fracture is a kind of femoral neck fractures, in which the angle of the fracture line in the coronal plane and the upper edge of the acetabulum is more than 50°. Internal fixation for the treatment of femoral neck fractures is largely performed by cannulated compression screw (CCS), dynamic hip screw, or locking plate. This study aims to compare the biomechanical properties of parallel CCS combined with medial buttress plate fixation and F-type CCS fixation in the treatment of Pauwels III femoral neck fracture by finite element modeling and to determinate the most suitable procedure for such fractures. METHODS: A 52-year-old male volunteer, 176 cm in height and 72 kg in weight, with no history of hip joint, was selected. X-ray and CT examination confirmed that the morphology and bone condition of the right hip of the volunteer were normal. A simulation model of Pauwels III femoral neck fracture was established from the collected CT data of the right proximal femur of the volunteer by the finite element method. Four internal fixations were developed to treat the finite element model: Three CCSs in an inverted triangular parallel configuration combined with medial buttress plate model served as Group A, 2 CCSs in a vertical parallel configuration combined with medial buttress plate model served as Group B, 2 CCSs in a horizontal parallel configuration combined with medial buttress model served as Group C, and the "F" shaped CCS model served as Group D. The distribution of stress, the peak stress, the distribution and maximum of displacement of internal fixations and fracture ends in different models were evaluated. RESULTS: For Groups A, B, C, and D, the peak stresses on the internal fixation were 362.74, 586.84, 558.25, and 208.66 mPa, respectively, all of which occurred near the fractures and the stress distribution in Group D was the most uniform. The maximum displacements of internal fixations in Groups A, B, C, and D were 0.39, 0.45, 0.44, and 0.41 mm, respectively; the peak stresses on the fracture ends were 70.62, 98.48, 55.84, and 65.39 mPa, respectively, all of which were concentrated on the base of femoral neck and lateral cortex of the femoral shaft, and the stresses of Groups C and D were more evenly distributed than those of Groups A and B. The maximum displacements of fracture ends in Groups A, B, C, and D were 0.44, 0.52, 0.50, and 0.44 mm, respectively. CONCLUSIONS The biomechanical stability of F-type CCS fixation is similar to that of 3 CCSs in an inverted triangular parallel configuration combined with medial buttress plate, with a better dispersion of stress. F-type CCS fixation may be a well option for the treatment of femoral neck fracture of Pauwels III.
Bone Plates ; Bone Screws ; Femoral Neck Fractures/surgery* ; Finite Element Analysis ; Fracture Fixation, Internal/methods* ; Humans ; Male ; Middle Aged

Objective:To analyze the trend of medication use in patients with ulcerative colitis (UC) in recent ten years in at Xijing Hospital, Air Force Military Medical University.Methods:From 2010 to 2019, the clinical data of 1 425 patients diagnosed with UC in the Department of Gastroenterology at Xijing Hospital, Air Force Medical University, were retrospectively collected. According to the period of medication, the UC patients were divided into year 2010 to 2014 group and year 2015 to 2019 group. The general information and the medication trend of year 2010 to 2014 group and year 2015 to 2019 group were analyzed. And then according to gender and age (<40 years old and ≥40 years old), patients were divided into subgroups and analyzed. Independent sample t test and chi-square test were used for statistical analysis. Results:The number of UC patients of year 2010 to 2014 group and year 2015 to 2019 group was 369 and 1 056, respectively. The percentages of patients in remission of the two groups were 9.5% (35/369) and 12.0% (127/1 056), respectively; the percentages of mild patients were 40.4% (149/369) and 41.6% (439/1 056), respectively; the percentages of moderate patients were 37.4% (138/369) and 28.9% (305/1 056), respectively; the percentages of severe patients were 12.7% (47/369) and 17.5% (185/1 056), respectively. There was no significant difference in the proportion of UC patients with different degrees between year 2010 to 2014 group and year 2015 to 2019 group ( P>0.05). There were no significant differences in the age and proportion of female between the year 2010 to 2014 group and year 2015 to 2019 group ((46.2±15.3) years old vs. (44.6±30.6) years old; 45.8%, 169/369 vs. 44.8%, 473/1 056; both P>0.05). The utilization rates of 5-aminosalicylic acid (5-ASA), glucocorticoid, immunosuppressants, and biological agents of the year 2015 to 2019 group were all higher than those of the year 2010 to 2014 group (96.8%, 1 022/1 056 vs. 90.0%, 332/369; 29.9%, 316/1 056 vs. 14.6%, 54/369; 8.4%, 89/1 056 vs. 2.4%, 9/369; 4.8%, 51/1 056 vs. 0.5%, 2/369, respectively), and the differences were all statistically significant ( χ2=26.766, 33.256, 15.315 and 14.038, all P<0.01). Within each of the year 2010 to 2014 group and the year 2015 to 2019 group, there were no significant differences between the female and male in the age, utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents ((47.2±13.6) years old vs. (45.3±16.5) years old, (43.1±12.9) years old vs. (45.8±39.5) years old, 88.8%, 150/169 vs. 91.0%, 182/200; 96.8%, 458/473 vs. 96.7%, 564/583; 13.6%, 23/169 vs. 15.5%, 31/200; 28.3%, 134/473 vs. 31.2%, 182/583; 2.4%, 4/169 vs. 2.5%, 5/200; 7.0%, 33/473 vs. 9.6%, 56/583; 0 vs. 1.0%, 2/200; 5.3%, 25/473 vs. 4.5%, 26/583; all P>0.05). In the patients aged≥40 years old of the year 2010 to 2014 group, the proportion of females was higher than that of the patients aged <40 years old (50.2%, 121/241 vs. 37.5%, 48/128), and the utilization rate of 5-ASA in patients aged ≥40 years old was lower than that of patients aged <40 years old (85.9%, 207/241 vs. 97.7%, 125/128), and the differences were statistically significant ( χ2=5.438 and 12.824, P=0.020 and P<0.01). In the year 2010 to 2014 group, there were no statistically significant differences in the utilization rates of glucocorticoid, immunosuppressants and biological agents between patients aged ≥40 years old and patients aged <40 years old (13.7%, 33/241 vs. 16.4%, 21/128; 2.1%, 5/241 vs. 3.1%, 4/128; 0 vs. 1.6%, 2/128; all P>0.05). In the year 2015 to 2019 group, the utilization rate of biological agents in patients aged≥40 years old was lower than that in patients aged<40 years old (3.7%, 23/630 vs. 46.5%, 198/426), and the difference was statistically significant ( χ2=4.721, P=0.030). In the year 2015 to 2019 group, there were no statistically significant differences in female proportion, utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents between patients aged≥40 years old and patients aged <40 years old (43.7%, 275/630 vs. 46.5%, 198/426; 96.0%, 605/630 vs. 97.9%, 417/426; 29.7%, 187/630 vs. 30.3%, 129/426; 8.6%, 54/630 vs. 8.2%, 35/426; all P>0.05). Conclusions:Compared with year 2010 to 2014, the number of UC patients remarkably increased in the year 2015 to 2019 in the Department of Gastroenterology, Xijing Hospiatal, Air Force Medical University. The utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents all increased in UC patients. The medication trends of UC patients with different gender were almost the same. The medication trends of UC patients with different age were different.

Objective To evaluate efficacy and safety of acarbose compared with metformin as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled with insulin. Methods This was a randomized, open-labeled, and parallel group study. Ninety-one type 2 diabetic patients ( HbA1C7.5%-11.0%) who were suboptimally controlled despite receiving twice daily injection of insulin (30-60 U/d for at least 8 weeks) were enrolled. They were randomly assigned 1 ∶ 1 ∶ 1 to continuation of insulin, insulin with acarbose (Ins+Aca), and insulin with metformin (Ins+Met) groups to insulin treatment. The levels of HbA1C, oral glucose tolerance test, blood lipids etc were measured at baseline and 12 weeks, and adverse events were recorded. Results The mean HbA1C levelsdecreasedfrom(7.9±0.4)%atbaselineto(7.0±0.3)%atweek12(P＜0.01)intheIns+Acagroupand(7.8 ±0.2)%to(7.0±0.3)%in the Ins+Met group(P＜0.01), while no significant change in HbA1Cin the insulin alone group. Adding acarbose to insulin resulted in similar reductions in HbA1Crelative to metformin (P＝0.431). The achievement rate of HbA1Cbelow 7.0%at week 12 was the same(both 70%) between the Ins+Aca group and the Ins+Met group. Insulin combined with acarbose in improving blood glucose fluctuation effect was more significant than that incombinationwithmetformin(P＜0.01),withstandarddeviation(SD)ofbloodglucose[(1.1±0.5vs2.7±0.6) mmol/L, P＜0.01], postprandial blood glucose fluctuations [(0.5 ± 0.7 vs 2.8 ± 0.4) mmol/L, P＜0.01], the maximumbloodglucosefluctuations[(2.8±0.7vs4.6±0.6)mmol/L,P＜0.01].Theweightlossoccurredinboththe Ins+AcaandtheIns+Metgroups[-(0.5±0.8vs1.0±0.4)kg].Therewasnosignificantchangesinbloodpressure and lipid profile. Hypoglycemic episodes were comparable in all groups. No serious adverse event was noted in any group. Conclusions Adding acarbose or metformin to insulin therapy could achieve improvements in glycemic control with similar reductions in HbA1Clevels and weight, when comparing with insulin treatment alone. Add-on acarbose to insulin therapy may exist more effectively on glucose fluctuation than that of add-on metformin, which may have important clinical implications in those patients with postprandial hyperglycemia, large blood glucose fluctuation, and intolerance to metformin.

BACKGROUNDSIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear.

METHODSThe effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 µmol/L palmitic acid to induce insulin resistance. SIRT3 was knocked down and overexpressed in L6 cells. SIRT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, c-Jun N-terminal kinase 1 (JNK1), and superoxide dismutase 2 (SOD2) were evaluated by Western blotting.

RESULTSOver expression of SIRT3 increased glucose uptake and decreased ROS production in L6-IR cells as well as in L6 cells. Knock-down of SIRT3 induced increased production of ROS while decreased glucose uptake in both L6 and L6-IR cells, and these effects were reversed by N-acetyl-L-cysteine (NAC). Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-κB p65 (1.5-fold) and JNK1 (1.5-fold). Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-κB p65 and JNK1 and the metformin-induced increase in SOD2 (P < 0.05).

CONCLUSIONSUpregulated SIRT3 is involved in the pharmacological mechanism by which metformin promotes glucose uptake. Additionally, SIRT3 may function as an important regulator of oxidative stress and a new alternative approach for targeting insulin resistance-related diseases.

Animals ; Cell Line ; Insulin Resistance ; physiology ; Metformin ; pharmacology ; Muscle Fibers, Skeletal ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Rats ; Sirtuin 3 ; metabolism ; Transcription Factor RelA ; metabolism

Objective To explore the microsurgical method in treating ruptured aneurysms treatment and evaluating the treatment of the complication during or after the operation.Methods 36 cases of patients with intracranial aneurysm were analyzed retrospectively.All of the patients were subarachnoid hemorrhage (SAH) by CT scan on admission.The intracranial aneurysms were confirmed in 35 cases by DSA examination and A2 aneurysm was confirmed by explorative operation in 1 case.The microsurgical treatment was performed in 36 cases at the early or intermediate stage,22 cases were treated in the early stage,the other 14 cases were treated in the intermediate stage (early stage means within 3 days post SAH;intermediate stage means from 4 days to 10 days post SAH).Results After the operation,21 cases were GOS grade Ⅰ,4 cases were COS grade Ⅱ,4 cases were COS grade Ⅲ,4 cases were GOS grade Ⅳ.Of all the patients,CT scan was done after the operation,finding no intracranial bemorrhage,and cerebral infarction was disclosed in 5 cases.3 cases were dead,one suffered occipital lobe infaret after the PCoA aneurysm clipped,brain hernia occurred at last,one's Hunt Hess grade was Ⅴ,ACoA aneurysm was disclosed by DSA examination,severe brain edema occurred after the operation,the other suffered tonsillar hernia one week after the aneurysm clipping,which ruptured after endovascular treatment of ACoA aneurysm 2 years later.DSA examinations were done in 26 cases after operation,declaring 1 ACoA aneurysm was unclipped,1 PCoA aneurysm was incompletely clipped,and 1 PCoA was sacrificed.Conclusions It is a valuable method to clip the ruptured intracranial aneurysms in early and intermediate stage.The cerebral ischemia is the severe complication after clipping.Especially for the PCoA aneurysms,it is very important to protect the PCoA.Further research should be done for the treatment in the case with mother artery arteriosclerosis and thrombosis within the aneurysms.