Impaired angiogenesis is one of the crucial factors that impede the wound healing process in diabetic foot ulcers (DFUs). In this study, we found that 20(S)-protopanaxadiol (PPD), an aglycone of ginsenosides in Panax notoginseng, stimulated angiogenesis and benefited wound healing in genetically diabetic mice. In HUVECs, PPD promoted cell proliferation, tube formation and VEGF secretion accompanied by increased nuclear translocalization of HIF-1α, which led to elevated VEGF mRNA expression. PPD activated both PI3K/Akt/mTOR and Raf/MEK/ERK signaling pathways in HUVECs, which were abrogated by LY294002 and PD98059. Furthermore, these two pathways had crosstalk through p70S6K, as LY294002, PD98059 and p70S6K siRNA abolished the angiogenic responses of PPD. In the excisional wound splinting model established in db/db diabetic mice, PPD (0.6, 6 and 60 mg ml−1) accelerated wound closure, which was reflected by a significantly reduced wound area and epithelial gaps, as well as elevated VEGF expression and capillary formation. In addition, PPD activated PI3K/Akt/ERK signaling pathways, as well as enhanced p70S6K activity and HIF-1α synthesis in the wounds. Overall, our results revealed that PPD stimulated angiogenesis via HIF-1α-mediated VEGF expression by activating p70S6K through PI3K/Akt/mTOR and Raf/MEK/ERK signaling cascades, which suggests that the compound has potential use in wound healing therapy in patients suffering from DFUs.
Animals ; Capillaries ; Cell Proliferation ; Diabetic Foot ; Ginsenosides ; Humans ; Mice* ; Panax notoginseng ; Phosphotransferases* ; Ribosomal Protein S6 Kinases, 70-kDa ; RNA, Messenger ; RNA, Small Interfering ; Splints ; Ulcer ; Vascular Endothelial Growth Factor A* ; Wound Healing* ; Wounds and Injuries*

BACKGROUNDMorphological changes of the vasculature system in patients with myopia have been observed by Doppler ultrasound and fundus fluorescein angiography (FFA); however, these studies have limitations. Doppler ultrasound provides low-resolution images which are mainly obtained from visualized large vessels, and FFA is an invasive examination. Optic coherence tomography (OCT) angiography is a noninvasive, high-resolution measurement for vascular density. The purpose of this study was to investigate the change of vascular density in myopic eyes using OCT angiography.

METHODSThis cross-sectional study includes a total of 91 eyes from 47 participants including control, moderate, and high myopia that were evaluated by OCT angiography. Patients with myopia were recruited from the Refractive Department, Shenzhen Aier Eye Hospital, from August 5, 2015 to April 1, 2016. Emmetropic eyes were from healthy volunteers. The vascular density at macula and optic disc regions, ganglion cell complex (GCC) thickness, and retinal nerve fiber layer (RNFL) thickness were measured. Their relationships with axial length (AL) and refractive error were analyzed. One-way analysis of variance (ANOVA), Pearson's correlation, and generalized estimating equation were used for statistical analysis.

RESULTSBoth superficial and deep macular vascular density were highest in control (25.64% ± 3.76% and 37.12% ± 3.66%, respectively), then in moderate myopia (21.15% ± 5.33% and 35.35% ± 5.50%, respectively), and lowest in high myopia group (19.64% ± 3.87% and 32.81% ± 6.29%, respectively) (F = 13.74 and 4.57, respectively; both P < 0.001). Both superficial (β = -0.850 and 0.460, respectively) and deep (β = -0.766 and 0.396, respectively) macular vascular density were associated with AL and spherical equivalent (all P < 0.001). Superficial macular vascular density was associated with GCC thickness (β = 0.244, P = 0.040), independent of spherical equivalent. The vascular density in optic disc region had no difference among the three groups, and it was not associated with AL, spherical equivalent, or RNFL thickness.

CONCLUSIONOur results suggested that with the increase of myopia, the vascular density decreased in macular region, but not in optic disc region.

Adult ; Cross-Sectional Studies ; Eye ; blood supply ; Female ; Fluorescein Angiography ; Humans ; Macula Lutea ; pathology ; physiopathology ; Male ; Middle Aged ; Myopia ; pathology ; physiopathology ; Optic Disk ; pathology ; physiopathology ; Prospective Studies ; Retina ; pathology ; physiopathology ; Retinal Ganglion Cells ; pathology ; Tomography, Optical Coherence ; Young Adult

OBJECTIVETo compare the osteogenic differentiation potential and osteoclast capacity between stem cells from human exfoliated deciduous teeth (SHED) in the physiological root resorption period and dental pulp stem cells (DPSCs).

METHODSSHED and DPSCs were isolated, purified and cultured in vitro. The two stem cells were examined with ALP staining at 14 days and with alizarin red staining at 21 days of osteogenic induction, and the expressions of the genes associated with osteogenesis and osteoclastogenesis were detected using real-time PCR.

RESULTSThe isolated SHED and DPSCs both showed an elongate spindle-shaped morphology. After osteogenic induction of the cells, Alizarin red staining visualized a greater number of mineralized nodules in SHED than in DPSCs (P<0.05), and SHED also exhibited a stronger ALP activity than DPSCs (P<0.05). RT-PCR test results showed that the two stem cells expressed RANKL,OCN, ALP, OPG and Runx2 mRNA after osteogenic induction, but the expression levels of Runx2, OCN and ALP were lower in DPSCs than in SHED (P<0.05), and the ratio of RANKL/OPG was significantly higher in SHED (P<0.05).

CONCLUSIONSCompared with DPSCs, SHED has not only the ability of osteogenic differentiation but also an osteoclast capacity, which sheds light on the regulatory role of SHED in physiological root resorption bone remodeling.

Alkaline Phosphatase ; metabolism ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Dental Pulp ; cytology ; Humans ; Osteoclasts ; cytology ; Osteogenesis ; Osteopontin ; metabolism ; RANK Ligand ; metabolism ; Real-Time Polymerase Chain Reaction ; Stem Cells ; cytology ; Tooth, Deciduous ; cytology

The safety and effectiveness of a novel Chinese one-shot dilation technique based on stimulated diuresis for percutaneous nephrolithotomy (PCNL) were investigated. After the feasibility of the Chinese one-shot dilation based on stimulated diuresis was verified by an animal study, this technique was applied in the clinical practice. A total of 67 patients in our department underwent the modified PCNL from July 2014 to June 2015. After the renal infundibulum was distended by stimulated diuresis, the kidney was punctured under the ultrasonographic guidance via the fornix of the target calyx. The working channel was dilated using a special designed pencil-shaped fascial dilator. The successful access rate, nephrostomy tract creation time, pre- and postoperative hemoglobin values and serum creatinine concentrations, stone-free rate and complications were recorded and analyzed. The renal infundibulum was successfully distended in all of the patients by the diuresis treatment. Under the ultrasonographic guidance, the successful access rate was 100% and the mean tract creation time was 2.0 min (range: 1.5-5.0 min). The stone-free rate right after surgery was 91.0%. Although the postoperative hemoglobin was significantly reduced (P<0.01), transfusion was not clinically necessary. There was no significant difference in serum creatinine concentrations before and after operation (P>0.05). No severe complication occurred during or after the PCNL. It was suggested that this Chinese one-shot dilation technique based on stimulated diuresis is an efficient and safe innovation for PCNL, and is even helpful for those patients with non-dilated pelvicaliceal systems.
Adult ; Aged ; Animals ; Creatinine ; blood ; Diuresis ; Female ; Hemoglobins ; metabolism ; Humans ; Kidney ; surgery ; Male ; Middle Aged ; Nephrostomy, Percutaneous ; adverse effects ; methods ; Postoperative Complications ; Surgery, Computer-Assisted ; adverse effects ; methods ; Swine ; Ultrasonography

OBJECTIVETo evaluate the sensitivity and specificity of CD8CD28/CD8CD28T lymphocyte balance in predicting the gastrointestinal hemorrhage (GH) in patients with inflammatory bowel disease (IBD).

METHODSForty-nine IBD patients, including 30 with ulcerous colitis (UC) and 19 with Crohn's disease (CD), were enrolled to test peripheral blood CD8CD28and CD8CD28T cells using flow cytometry. All the patients were followed up for one year. The receiver-operating characteristic (ROC) curves were used to test the efficiency of CD8CD28/CD8CD28T lymphocyte balance to predict GH. The differences in lasting time of remission (LTR) under different factors were compared using Kaplan-Meier survival analysis, and the correlation between CD8T lymphocytes and the factors were analyzed.

RESULTSThe utilization rates of immunosuppressant, steroids, and biological agent (BA) were significantly higher in CD patients than in UC patients (P=0.003, 0.043 and 0.002, respectively). The frequencies of CD8CD28T cells were obviously higher in UC patients than those in CD patients (t=3.022, P=0.004). CD8CD28T cells, CD8CD28T cells, and especially CD8CD28/CD8CD28ratio (area under curve of 0.977, P=0.000; cut-off value of 1.14 [13.95%/12.24%] with a sensitivity of 93.3% and a specificity of 91.2%) showed good efficiencies in predicting GH (P<0.01). The mean and median of LTR of IBD patients who did not receive BA or surgical treatment were significantly longer (Χ=9.730, P=0.002; Χ=15.981, P=0.000). CD8CD28/CD8CD28ratio was significantly related to both BA (P=0.009) and surgery (P=0.038).

CONCLUSIONBoth decreased CD8CD28T cells and elevated CD8CD28T cells are closely correlated with GH, and their ratio can predict the occurrence of GH with a high sensitivity and specificity and is correlated with BA and surgery at the cut-off value of 1.14.

OBJECTIVETo investigate distinctive features in drug-resistant mutations (DRMs) and interpretations for reverse transcriptase inhibitors (RTIs) between proviral DNA and paired viral RNA in HIV-1-infected patients.

METHODSForty-three HIV-1-infected individuals receiving first-line antiretroviral therapy were recruited to participate in a multicenter AIDS Cohort Study in Anhui and Henan Provinces in China in 2004. Drug resistance genotyping was performed by bulk sequencing and deep sequencing on the plasma and whole blood of 77 samples, respectively. Drug-resistance interpretation was compared between viral RNA and paired proviral DNA.

RESULTSCompared with bulk sequencing, deep sequencing could detect more DRMs and samples with DRMs in both viral RNA and proviral DNA. The mutations M184I and M230I were more prevalent in proviral DNA than in viral RNA (Fisher's exact test, P<0.05). Considering 'majority resistant variants', 15 samples (19.48%) showed differences in drug resistance interpretation between viral RNA and proviral DNA, and 5 of these samples with different DRMs between proviral DNA and paired viral RNA showed a higher level of drug resistance to the first-line drugs. Considering 'minority resistant variants', 22 samples (28.57%) were associated with a higher level of drug resistance to the tested RTIs for proviral DNA when compared with paired viral RNA.

CONCLUSIONCompared with viral RNA, the distinctive information of DRMs and drug resistance interpretations for proviral DNA could be obtained by deep sequencing, which could provide more detailed and precise information for drug resistance monitoring and the rational design of optimal antiretroviral therapy regimens.

Adult ; Antiviral Agents ; pharmacology ; China ; DNA, Viral ; genetics ; metabolism ; Drug Resistance, Viral ; genetics ; Female ; HIV Infections ; drug therapy ; HIV-1 ; drug effects ; genetics ; metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Mutation ; Proviruses ; genetics ; metabolism ; RNA, Viral ; genetics ; metabolism ; RNA-Directed DNA Polymerase

BACKGROUNDNontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population.

METHODSA nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH.

RESULTSNONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, χ2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, χ 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH.

CONCLUSIONSOur findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.

Adult ; Age Distribution ; Aged ; Asian Continental Ancestry Group ; China ; epidemiology ; Female ; Femur Head Necrosis ; epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Young Adult

China ; Humans ; Organ Transplantation ; legislation & jurisprudence

The quality of Chinese medicinal materials relates greatly to the clinical curative effect and security. In order to ensure the quality and safety of Chinese medicinal materials, a systematic and operable traceability system needs to be established. It can realize the whole process of quality and safety management of Chinese medicinal materials "from production to consumption" through recording and inquiring information and recalling defective products, which is an important direction for the future development of traditional Chinese medicine. But it is still at the exploration and trial stage. In this paper, a framework of Chinese medicinal materials' quality and safety traceability system was established on the basis of the domestic and international experience about the construction of food and agricultural products traceability systems. The relationship between traceability system of Chinese medicinal materials' quality and GAP, GMP, GSP was analyzed, and the possible problems and the corresponding solutions were discussed.
China ; Drugs, Chinese Herbal ; chemistry ; standards ; Humans ; Medicine, Chinese Traditional ; standards ; Quality Control

OBJECTIVETo study the clinicopathological characteristics of papillary cystadenoma of the epididymis.

METHODSUsing routine pathology and immunohistochemistry, we observed the surgically obtained samples from 2 cases of papillary cystadenoma of the epididymis, analyzed their pathological features and clinical presentations, and reviewed the related literature.

RESULTSThe 2 patients were both adult males. The tumors typically manifested as painless swelling in the epididymis, with occasionally dull pain and tenesmus in 1 of the cases. Pathologically, the lesions exhibited three morphological features, i. e., dilated ducts and small cysts surrounded by fibrous connective tissue, adenoid papillary hyperplasia into the cysts embraced by fibrovascular stroma, and acidophil substance present in the cysts. Immunohistochemistry showed that the tumors were strongly positive for CK8/18, CK7, and EMA, but negative for CK20, CEA, MC, Calretenin, P53, P63, SMA, VHL, and CD10, with the positive rate of Ki-67 <1%. Follow-up visits revealed good prognosis in both cases.

CONCLUSIONPapillary cystadenoma of the epididymis is a rare benign tumor in the male urogenital system, which may be accompanied by the VHL syndrome. Surgery is the first choice for its treatment.

Adult ; Cystadenoma, Papillary ; chemistry ; pathology ; Epididymis ; Genital Neoplasms, Male ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Male ; von Hippel-Lindau Disease