BACKGROUND:Topical administration of tranexamic acid can be used for anti-skin pigmentation,but its large polarity makes it difficult to break through the cuticle barrier and cell membrane when administered topically,and the subcutaneous accumulation concentration is not easy to reach the effective therapeutic concentration.OBJECTIVE:To design functionalized self-assembled micelles to enhance the anti-pigmentation effect of tranexamic acid.METHODS:The plant polyphenol derivative epigallocatechin gallate palmitate and metformin were used as carrier materials.The self-assembled micelles with synergistic anti-pigging activity and enhanced drug permeability were prepared by hydrogen bonding and electrostatic interaction.The nanoscale properties and stability of self-assembled drug-loaded micelles were tested,and their transdermal permeability was evaluated,and their biocompatibility and cellular effects were investigated.RESULTS AND CONCLUSION:(1)Functional self-assembled drug-carrying micelles with average particle size of(176.27±5.23)nm,polydispersity coefficient of 0.23±0.02,and the Zeta potential of(-25.67±0.98)mV had good stability.The mass concentrations of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(20.03±0.12)and(6.67±0.08)mg/mL,respectively.The drug loadings of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(19.97±0.12)％and(6.65±0.08)％,respectively.(2)In vitro transdermal results showed that the self-assembled drug-carrying micelles had higher penetration and intradermal retention per unit skin area,and could penetrate and diffuse to deeper parts of the skin.(3)MTT assay results demonstrated that undrug-loaded self-assembled micelles containing tranexamic acid 50-250 μg/mL had no toxic effects on mouse fibroblasts and mouse skin melanoma cells.The self-assembled drug-carrying micelles containing tranexamic acid 500 μg/mL had a slight toxic effect on mouse skin melanoma cells.The self-assembled drug-carrying micelles containing 50-500 μg/mL of tranexamic acid did not cause hemolysis and had good biological safety.(4)In vitro cell culture results showed that self-assembled drug-carrying micelles containing 500 μg/mL tranexamic acid could significantly inhibit the tyrosinase activity and melanin release of mouse skin melanoma cells,and the inhibitory effect was stronger than that of tranexamic acid solution or metformin solution alone.These results indicated that functionalized self-assembled micelles could synergize with tranexamic acid to inhibit tyrosinase activity,reduce melanin synthesis,and enhance the anti-skin pigmentation effect of tranexamic acid.

Renal cell carcinoma in a transplanted kidney is rare, and partial nephrectomy in transplanted kidney is even more uncommon. A patient with papillary transplanted renal cell carcinoma who underwent partial nephrectomy was reported. The patient was admitted to the hospital due to the discovery of transplanted kidney mass, and the enhanced examination of CTU found a lesion in the upper pole of the transplanted kidney in the right iliac fossa, which may be renal cancer, with a diameter of about 2 cm. After open partial nephrectomy of the transplanted kidney, the postoperative pathology showed that the tumor was papillary renal cell carcinoma. The antirejection drugs were used after surgery. During the follow-up period of 16 months, there was no recurrence of transplanted kidney tumor.

Renal cell carcinoma in a transplanted kidney is rare, and partial nephrectomy in transplanted kidney is even more uncommon. A patient with papillary transplanted renal cell carcinoma who underwent partial nephrectomy was reported. The patient was admitted to the hospital due to the discovery of transplanted kidney mass, and the enhanced examination of CTU found a lesion in the upper pole of the transplanted kidney in the right iliac fossa, which may be renal cancer, with a diameter of about 2 cm. After open partial nephrectomy of the transplanted kidney, the postoperative pathology showed that the tumor was papillary renal cell carcinoma. The antirejection drugs were used after surgery. During the follow-up period of 16 months, there was no recurrence of transplanted kidney tumor.

BACKGROUND:Topical administration of tranexamic acid can be used for anti-skin pigmentation,but its large polarity makes it difficult to break through the cuticle barrier and cell membrane when administered topically,and the subcutaneous accumulation concentration is not easy to reach the effective therapeutic concentration.OBJECTIVE:To design functionalized self-assembled micelles to enhance the anti-pigmentation effect of tranexamic acid.METHODS:The plant polyphenol derivative epigallocatechin gallate palmitate and metformin were used as carrier materials.The self-assembled micelles with synergistic anti-pigging activity and enhanced drug permeability were prepared by hydrogen bonding and electrostatic interaction.The nanoscale properties and stability of self-assembled drug-loaded micelles were tested,and their transdermal permeability was evaluated,and their biocompatibility and cellular effects were investigated.RESULTS AND CONCLUSION:(1)Functional self-assembled drug-carrying micelles with average particle size of(176.27±5.23)nm,polydispersity coefficient of 0.23±0.02,and the Zeta potential of(-25.67±0.98)mV had good stability.The mass concentrations of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(20.03±0.12)and(6.67±0.08)mg/mL,respectively.The drug loadings of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(19.97±0.12)％and(6.65±0.08)％,respectively.(2)In vitro transdermal results showed that the self-assembled drug-carrying micelles had higher penetration and intradermal retention per unit skin area,and could penetrate and diffuse to deeper parts of the skin.(3)MTT assay results demonstrated that undrug-loaded self-assembled micelles containing tranexamic acid 50-250 μg/mL had no toxic effects on mouse fibroblasts and mouse skin melanoma cells.The self-assembled drug-carrying micelles containing tranexamic acid 500 μg/mL had a slight toxic effect on mouse skin melanoma cells.The self-assembled drug-carrying micelles containing 50-500 μg/mL of tranexamic acid did not cause hemolysis and had good biological safety.(4)In vitro cell culture results showed that self-assembled drug-carrying micelles containing 500 μg/mL tranexamic acid could significantly inhibit the tyrosinase activity and melanin release of mouse skin melanoma cells,and the inhibitory effect was stronger than that of tranexamic acid solution or metformin solution alone.These results indicated that functionalized self-assembled micelles could synergize with tranexamic acid to inhibit tyrosinase activity,reduce melanin synthesis,and enhance the anti-skin pigmentation effect of tranexamic acid.

Objective:To evaluate the in vivo osteogenic activity of titanium implants with strontium loaded TiO 2 nanotubes (NTSr). Methods:The strontium loaded titanium nanotubes were formed on pure titanium implants through anodization and hydrothermal treatment, and the unmodified titanium (Control) and sheer TiO 2 nanotubes (NT) were set to be control groups and treatment group. Inductively coupled plasma mass spectrometry (ICP-MS) was used to evaluate the Sr release at 28 days. Field emission scanning electron microscopes (FE-SEM) was used to view the micro-topography, atomic force microscope was used to exam the surface roughness, and nano-indenter was used to evaluate the hardness of three groups ( n=3). Three groups of implant samples were inserted into the distal femoral metaphysis of New Zealand rabbits ( n=4 at each time point). After 4 weeks and 12 weeks, samples were harvested. Micro-CT scanning, immunofluorescent and histological examinations were carried out. Results:The strontium ions could be released slowly for at least 28 days [the Sr concentration at 28 Day was (2.6±1.5) ng/ml]. NTSr coating exhibited a nanoscale tube array (the diameter was about 70 nm), and the surface roughness of implant was increased with the nanobube coating [Control (34.8±5.3) nm, NT (66.2±4.3) nm, NTSr (85.7±10.6) nm, F=37.59, P<0.001]. The surface roughness (Ra) of NT and NTSr groups was higher than the control group ( P<0.05). Comparing to Control implants, NTSr implants exhibited a better osteogenic ability [the bone volume/total volume (BV/TV) value was Control (24.7±1.1)% vs. NTSr (37.7±1.9)% at 4 weeks ( P<0.05), and Control (40.7±0.9)% vs. NTSr (51.9±2.1)% at 12 weeks ( P<0.05)]. The fluorescent examination revealed that NTSr coating can also accelerated the generation of new bone tissue (bone tissue area% labelled by alizarin red at day 7 was Control (19.2±2.9)% vs. NT (35.4±3.7)% vs. NTSr (40.9±0.9)% ( F=42.74, P<0.01). The results in the NT and NTSr group were statistically higher than that in the control group ( P<0.05). Conclusions:The strontium loaded TiO 2 nanotubes can enhance new bone formation around titanium implants.

Glomus tumor of kidney is very rare in clinic. One case with glomus tumor of the kidney was reported. CT demonstrated a well-defined mass located at the lower pole of the left kidney. The mass densely enhanced in arterial phase and constantly enhanced in venous and portal phase. Laparoscopic enucleation of left renal tumor was successfully performed. The pathological diagnosis was glomus tumor of the kidney. Recurrence and metastasis were not seen after 35 months follow-up.

Objective To objectively study the current progress of China Healthcare Improvement Initiative, and its effectiveness and shortcomings for further improvement. Methods Questionnaires were customized by expert consultation and pre-investigation, and distributed by the National Health Commission in April 2018 to the hospitals.Data of 5 469 hospitals were recovered and analyzed with a statistics software for descriptive analysis.Results Implementation progress of the five working systems varied with regions, and rooms of improvement were found in such aspects as outpatient appointment, clinical pathway management and social work system.In 2017, the proportion of outpatient appointments of 5 469 hospitals averaged 19.1%.Progress of the ten major service models also varied, as defects were found in such service models as continuous medical service, intelligent service, and interconnection service.In 2017, only 6.7% of the 5 469 hospitals had put in place hierarchical integrated clinical pathways within their medical alliances.Conclusions Improvement of the medical services calls for not only the efforts of medical institutions themselves, but also top-level design by the local health authorities. In particular, an online information platform should be established for the whole region, to unify the information standards and processes, and corresponding mechanisms and system support are needed.

Objective To explore the changes of serum vascular endothelial growth factor ( VEGF) and endostatin (ES) in patients with polycystic ovary syndrome (PCOS) and their effects on the ovarian stromal blood flow. Methods From January 2015 to January 2017,sixty cases diagnosed with polycystic ovary syndrome in the Eighth Affiliated Hospital of Sun Yat?sen University were selected into the observation group,and other 60 cases of healthy women with normal menstrual cycle in the same period were selected as the control group. Then, the levels of serum VEGF and ES of the two groups were observed, the patients in the early ovarian follicular blood flow changes were monitored by transvaginal color Doppler ultrasound to observe the bilateral ovaries and the hemodynamic indexes. Hemodynamic indexes (pulsatility index and resistance index) were compared,and the effects of serum VEGF and endostatin levels on ovarian interstitial blood flow were analyzed. Results The PI and RI of the observation group were(1. 3±0. 2) and (0. 5±0. 1),the PI and RI of the control group were (2. 4±0. 4)and(1. 0±0. 1),the differences were statistically significant(t=2. 378,2. 578,P=0. 023,0. 014);the levels of VEGF and ES in the observation group were (1083±167)ng/L and (278±23)ng/L,the levels of VEGF and ES in the control group were (625±71) ng/L and (172±21)ng/L,the differences were statistically significant( t=2. 123,2. 892,P=0. 042,0. 008);there was negative correlation among VEGF and PI and RI ( r=-0. 770,-0. 782,P<0. 01);there was negative correlation among ES and PI and RI ( r=-0. 751,-0. 799,P<0. 01);there was positive correlation between VEGF and ES ( r=0. 552,P<0. 01) . Conclusion The serum levels of VEGF and ES are significantly increase in patients with polycystic ovary syndrome, the imbalance between the two expressions may play an important role in the increase of ovarian stromal blood flow.

OBJECTIVE:To explore losses and gains (L&G) and L&G ratio induced by Essential Medicine System in a county. METHODS:By choosing a county in western China as sample area,field investigation was used to collect outpatient and inpatient visits,outpatient and inpatient income,drug income,total length of stay and medical insurance reimbursement criteria in primary medical institutions (township health centers,village health rooms) of the county during 2009-2015. By setting the year 2009 as the baseline year,the drug cost reimbursed by medical insurance was simulated and calculated when Essential Medicine System were not implemented;L&G and L&G ratio of medical insurance were calculated by comparing with actual drug cost reimbursed by medical insurance. RESULTS:The year 2012,in which the sample county fully implemented the Essential Medicine System was the turning year. Medical insurance funds lost in primary medical institutions of the county during 2010-2011(lost 437000,915000 yuan,respectively),but gained during 2012 to 2015(gained 199000,494000,858000,1290000 yuan, respectively);the L&G ratio increased from -0.67％ to 1.21％. For reimbursed outpatient drug cost and inpatient cost,L&G of medical insurance were different. For reimbursed drug cost of village health room and township health center,L&G of medical insurance were also different. CONCLUSIONS:The implementation of Essential Medicine System benefits to medical insurance within the county and Medical insurance funds can be saved.