Objective To explore the promoting effect and its mechanism of shikonin on wound healing and neovascularization of rats with chronic skin ulcer. Methods Fifty of 60 male SD rats were selected to establish the rat model of chronic skin ulcer, of which 40 rats were done successfully and randomly divided into the model group, positive control group, and low- and high-dose shikonin groups (10 rats each). The other 10 rats served as the control group. The wound surfaces in low-and high-dose shikonin group were evenly smeared with 4 mg/cm² and 8 mg/cm² shikonin suspension, in positive control group with 1890 U/cm² recombinant bovine basic fibroblast growth factor gel to smear the wound, and in model group and positive control group were given the equal volume of normal saline for external application. The wound healing was observed on the 3rd,7th and 14th day of intervention. The abdominal aortic blood and wound granulation tissue of rats were taken after intervention, the histopathological changes of wound granulation were observed by HE staining, and the neovascularization was observed by immunohistochemical staining; the content of hydroxyproline (HyP) in granulation tissue was detected by hydrolysis method, the expression of Notch1 pathway related protein in granulation tissue was detected by Western blotting; and the levels of serum inflammatory factors were detected by ELISA. Results The wound healing rate of skin ulcer in each group increased with time and in a time-dependent manner (P<0.05). The wound healing rate decreased in low- and high-dose shikonin groups than in positive control group, and decreased in low-dose shikonin group than in high-dose shikonin group on the 3rd, 7th and 14th day of intervention (P<0.05). HE staining showed that new granulation tissue with a large number of inflammatory cell infiltration could be seen in model group. Compared with model group, old granulation tissue and inflammatory cell infiltration were observed in low- and high-dose shikonin groups and positive control group, and the inflammatory cell infiltration decreased in turn. Compared with that in positive control group, the IOD value of wound granulation tissue decreased in low- and high-dose shikonin groups(104 725.45±2062.45 vs. 197 585.23±2478.42, P<0.05; 149 752.54±2441.86 vs. 197 585.23±2478.42, P<0.05), and the content of HyP decreased [(3.62±0.12) μg/mg vs. (6.48±0.14) μg/mg, P<0.05; (4.94±0.15) μg/mg vs. (6.48±0.14) μg/mg, P<0.05].The IOD value and HyP content of wound granulation tissue were higher in high-dose shikonin group than in low-dose shikonin group (P<0.05). Western blotting results showed that the relative expressions of vascular endothelial growth factor (VEGF) and transforming growth factor β₁ (TGF-β₁) in wound granulation tissue increased, and of Notch1 protein decreased in low- and high-dose shikonin groups than in model group (P<0.05), while the relative expression of VEGF and TGF-β₁ increased and of Notch1 protein decreased in wound granulation tissue of high-dose shikonin group than in low-dose shikonin group (P<0.05). ELISA results showed that the levels of serum IL-8 and TNF-α decreased in positive control group and low- and high-dose shikonin groups than in model group (P<0.05), but increased in low- and high-dose shikonin groups than in positive control group (P<0.05), and decreased in the high-dose shikonin group than in low-dose shikonin group (P<0.05). Conclusion Shikonin may promote the wound healing and neovascularization of rats with chronic skin ulcer by regulating Notch1 signaling pathway.

Objective To investigate the effect of activating peroxisome proliferator-activated receptor γ (PPARγ) on the expression of activator protein-1 (AP-1) and inflammatory response in lung tissues of mice infected with Mycobacterium tuberculosis(MTB). Methods A total of 50 healthy SPF C57BL/6 male mice aged 6 to 8 weeks were randomly divided into five groups (10 each group): control group, MTB group, MTB+Rosiglitazone group, MTB+GW9662 group, and MTB+ Rosiglitazone+GW9662 group. Lung tissue samples of mice were collected to detect the bacteria load. The protein and mRNA expression levels of PPARγ and AP-1 in lung tissues were detected by Western blotting and real-time fluorescent quantitative PCR (RT-qPCR). The contents of tumor necrosis factor (TNF)-α, interleukin (IL)-10 and IL-6 in lung tissues were determined by enzyme-linked immunosorbent assay (ELISA). The pathological changes in the lung tissue of mice were observed by HE staining. Results Compared with MTB infection alone, PPARγ agonist rosiglitazone significantly increased the bacteria load in lung tissue of MTB-infected mice (P<0.05).Compared with control group, the expression of PPARγ and the content of inflammatory cytokines in the lung tissues of MTB infected mice were significantly increased, while the expression of AP-1 was significantly decreased, and the differences were statistically significant (P<0.05). When giving PPARγ agonist rosiglitazone at the same time as MTB infection, the expression level of AP-1 in lung tissue of mice was significantly decreased compared with MTB group (P<0.05). In addition, in MTB+Rosiglitazone group, the contents of IL-6 and TNF-α were (160.71±20.36) pg/ml and (343.55±58.48) pg/ml, respectively, both of which were down-regulated compared with MTB group [(232.59±21.73) pg/ml and (511.99±69.83) pg/ml]. Interestingly, the content of IL-10 in MTB+Rosiglitazone group [(105.97±10.38) pg/ml], significantly higher than that in MTB group [(83.25±9.00) pg/ml,P<0.05]. GW9662, a PPARγ antagonist, could reverse the above effects of rosiglitazone. Conclusion Activation of PPARγ can down-regulate the expression of AP-1 in the lung tissues of MTB-infected mice, thereby inhibiting the lung tissues inflammatory and affecting the clearance of MTB.

Objective To evaluate the diagnostic value of magnetic resonance imaging (MRI) and mammography (MG)in clustered calcification of breast lesions. Methods The imaging and pathological data of 62 patients with clustered calcification breast lesions in the Chinese PLA General Hospital was retrospectively analyzed to compare the diagnostic efficacy of MRI and MG. Results Of 62 clustered calcification lesions, 20 were benign according to pathologic result, and 42 were malignant. In MRI examination, 14 cases (22.6%) were classified as 1-3, 11 cases (17.7%) as 4, and 37 cases (59.7%) as 5. In MG examination, 10 cases (16.1%) were classified as 1-3, 30 cases (48.4%) as 4, and 22 cases (35.5%) as 5. The consistency between MRI and MG was poor (Kappa=0.346). The diagnostic efficacy of MRI (AUC=0.940, 95%CI 0.850-1.000) was higher than that of MG (AUC=0.800,95%CI 0.686-0.914), and the sensitivity, accuracy, positive predictive value, negative predictive value of MRI (85.7%, 88.7%, 97.3%,76.0%) were higher than those of MG (50.0%, 64.5%, 95.5%, 47.5%). Conclusion For clustered calcification of breast lesions, the diagnostic value of MRI is higher than that of MG.

Objective To report a case of refractory Takayasu arteritis (TAK) treated with tofacitinib (TOF) and evaluated by contrast-enhanced ultrasound, and perform a literature review to better understand this disorder. Methods The data of a case of TAK treated with TOF were analyzed retrospectively, the treatment and follow-up experience summarized by searching the database(CNKI, Wanfang Data, PubMed) and the literature results analyzed comprehensively. Results The patient, a 28-year-old female with a 10-year history of TAK, presented with fever, neck pain and joints pain. Ultrasonography revealed intimal thickening and stenosis of the carotid artery. Laboratory tests demonstrated an elevated erythrocyte sedimentation rate (ESR) and a C-reactive protein (CRP) level. The symptoms were improved after glucocorticoid (GC) treatment. However, it relapsed during the course of GC tapering, even with the combination of disease modifying anti-rheumatic drugs (DMARDs) and tocilizumab. The DMARDs and tocilizumab were not used continuously due to poor response and adverse drug reactions. As disease progressing, left subclavian aneurysm appeared. The treatment of this patient is a big challenge. After adjusting the treatment with tofacitinib (10 mg/d, then adjust to 7.5 mg/d) and GC (methylprednisolone 14 mg/d, then reduce to 8 mg/d), the patient was successfully relieved without any serious adverse events. Contrast-enhanced ultrasound showed that the thickness of arterial wall decreased (the thickness of left common carotid artery decreased from 8.9 mm to 1.2 mm, and the thickness of left subclavian artery decreased from 7.4 mm to 0.8 mm), the contrast intensity decreased (the total score decreased from 5 to 1), and the aneurysm disappeared. By March 2021 (searching CNKI, Wanfang Data and PubMed), a total of 10 cases of TAK patients treated with TOF. Nine patients were women. Seven patients improved and GC reduced. Only one patient had adverse reactions. Conclusions Janus kinase inhibitor is expected to be a new drug for the treatment of TAK. Contrast-enhanced ultrasound can detect the thickness of the vessel wall and the enhancement of the thickened wall in real time. Contrast-enhanced ultrasound will be an effective tool for evaluating vascular inflammation.

Objective To investigate the changes of serum markers of cardiovascular disease risk in patients with acromegaly and the effect of six months of treatment with long-acting octreotide on them. Methods The clinical data of 63 patients with acromegaly (acromegaly group) and 69 healthy people (control group) treated in the First Affiliated Hospital of Chongqing Medical University from May 2012 to January 2021 were collected and analyzed retrospectively. According to the blood glucose level, the patients with acromegaly were divided into three subgroups: normal glucose metabolism (NGT) group (n=25), Impaired glucose regulation (IGR) group (n=11) and diabetes mellitus (DM) group (n=27). The age, body mass index (BMI), blood pressure, growth hormone (GH), blood glucose, blood lipid, high-sensitivity C-reactive protein (hs-CRP), fibrinogen and plasma atherogenic index(AIP) between acromegaly group and control group and three glucose metabolism subgroups were compared, and the relationship between age, BMI, blood pressure, fibrinogen, hs-CRP, blood lipid and AIP was analyzed by Spearman correlation analysis.In addition, 16 of 63 patients with acromegaly who finally completed 6-month long-acting octreotide treatment were studied longitudinally, and the changes of the indexes above were compared before and after treatment. Results Compared with the control group, the levels of BMI, blood pressure, fibrinogen, fasting blood glucose (FPG), triglyceride (TG), lipoprotein a [Lp (a)]and AIP were significantly higher, and of hs-CRP, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were significantly lower (P<0.05) in acromegaly group. For subgroup analysis, the TG level was significantly higher in DM group than that in IGR group and NGT group (P<0.05), while the difference between IGR group and NGT group was not statistically significant; The AIP level was significantly higher in DM group than that in NGT group (P<0.05), and no significant difference existed among the other groups. In correlation analysis, AIP was positively correlated with BMI, fibrinogen, FPG, TG, apolipoprotein B (Apo B), non-high density lipoprotein cholesterol (Non-HDL-C), TC/HDL-C, LDL-C/HDL-C, APO B/APO A-1, and Non-HDL-C/HDL-C, but negatively correlated with HDL-C and apolipoprotein A-1 (Apo A-1). After subgroup analysis, AIP was still correlated with the indexes mentioned above, and the difference was statistically significant (P<0.05). The levels of TG and AIP decreased significantly, but of hs-CRP increased significantly (P<0.05) in patients with acromegaly after 6 months of long-acting octreotide treatment compared with that before treatment. Conclusions The cardiovascular risk of patients with acromegaly is increased. Long acting octreotide treatment can reduce the risk of cardiovascular disease in patients with acromegaly.

Kidney diseases have become an important public health problem worldwide that threatens human health. In addition to traditional risk factors such as advanced age, hypertension, and diabetes, environmental pollution, especially the air pollution and climate change, are also major risk factors for chronic kidney disease. The exposure of airborne particulate matter or gaseous pollutants has been found to be closely associated with the incidence of chronic kidney disease, decline of kidney function, and poor prognosis of patients. As the main manifestation of global climate change, climate warming could also lead to acute kidney injury and nephrolithiasis. This paper reviews the progress in the epidemiological research of the impacts of air pollution and climate change on kidney diseases, in order to provide reference for air pollution control, climate governance, and the development of prevention and control strategies for kidney diseases.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease of the respiratory tract that seriously affects lung ventilation function and gas exchange function. Mitochondria is the center of energy supply and signal induction in cells, which determine the survival and/or death of cells. The cell mitochondrial quality control mechanisms mainly include mitophagy, biosynthesis and dynamics (fusion/fission) and other regulatory processes. These cellular processes maintain the stability of quality and function of mitochondria by degrading aged and damaged mitochondria, replenishing new mitochondria, and promoting the exchange of mitochondrial contents. Recent studies have shown that mitochondrial quality control plays an important role in IPF. In IPF, the dysregulation of mitochondrial quality control leads to mitochondrial dysfunction, increased production of reactive oxygen species, inducing apoptosis, enhanced mitochondrial fusion, and decreased mitochondrial autophagy and biosynthesis. This review describes the research progress on abnormal mitochondrial quality control in IPF.

Lymph node noncompliance is an indicator. If multiple lymph node stations are not detected in each group of lymph nodes submitted for inspection, the specimen is regarded as lymph node noncompliance. Under the background that the incidence of advanced gastric cancer has been increasing year by year, more and more surgeons have begun to pay attention to the surgical effect of radical gastric cancer surgery and the prognostic quality of life of patients. A large number of domestic and foreign experimental studies have shown that the sequence of lymph node metastasis of gastric cancer is roughly from the lesser curvature of the stomach to the lymph nodes around the abdominal aorta. In addition, during the process of lymph node metastasis, there may be lymph nodes that do not appear in the specified location, or due to the factors such as the patient's advanced age, different surgical procedures, thick abdominal fat, deep tumor invasion, and more intraoperative bleeding, the D2 lymph node may be used for gastric cancer. During the resection operation and postoperative pathological sorting, certain errors occurred. Although radical resection of D2 lymph nodes has become a standard surgical approach for the treatment of advanced gastric cancer, a variety of congenital anatomical factors or human error factors will still cause a decrease in the detection rate of postoperative lymph nodes. Therefore, adequate D2 anatomy is still a research focus and difficulty for surgeons. This article discusses the research progress of lymph node noncompliance in D2 radical resection of advanced gastric cancer.

Intracranial aneurysm (IA), characterized by distended blood vessels within the arteries, is a common vascular anomaly that frequently leads to cerebral blood vessel rupture, causing subarachnoid hemorrhage (SAH) with serious consequences.It has been found that, in addition to genetic factors, inflammatory responses induced by altered hemodynamics play a key role in the formation and rupture of IA. Subsequently, vascular inflammation can trigger a series of biochemical responses involving a variety of cells, including vascular smooth muscle cells, macrophages, lymphocytes, mast cells, and neutrophils, and involving several signaling pathways, including the PGE2-EP2-NF-κB signaling pathway, the JAK/STAT3/NF-κB signaling pathway, PI3K/Akt (PKB) signaling pathway, and AMPK/ACC signaling pathway. However, no clear conclusions have been made regarding the specific pathogenesis of IA, and immunotherapies targeting the pathogenesis of IA are still under basic research and not widely used in clinical practice. This review describes the cells, cytokines, and signaling pathways involved in the development of IA, in the hope that it will contribute to the understanding of the pathogenesis of IA and inspire the development and use of immunological drugs.

Female urethral stricture is considered to be one of the important causes of female lower urinary tract symptoms, but it is relatively rare in clinical practice and lacks relevant diagnostic and therapeutic guidelines. In the past, urethral dilation was used as the first-line treatment option for this disease. However, due to its low success rate, high recurrence rate of stricture, and with the development of research on the structure of the female urethra, a variety of urethroplasty procedures have been applied. The success rate of urethroplasty is high, but it is not clear which procedure is more superior. This article reviews the research progress in the etiology, diagnosis and treatment of female urethral stricture to provide a reference for urologists to carry out a variety of treatment methods, and to promote the clinical application of related diagnosis and treatment.