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Objective To evaluate the efficacy,safety and economy of teriparatide in the treatment of osteoporosis.Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,WanFang Data,VIP databases and websites related to health technology evaluation were systematically searched to collect high-quality clinical evidence and economic evaluation literature of teriparatide in the treatment of osteoporosis from the inception to January 20,2023.Two researchers independently identified studies,extracted data,assessed the quality of included studies,and descriptive analyzed and summarised the results.Results A total of 25 literatures were included,involving 3 HTA reports,15 systematic review/Meta-analyses and 7 economic studies were included.In terms of effectiveness,the evaluation results showed that teriparatide could improve bone mineral density in patients with osteoporosis,reduce the incidence of vertebral/non-vertebral fractures in primary and secondary osteoporosis and prevent the fractures in postmenopausal osteoporosis compared to bisphosphonates and placebos.In terms of safety,teriparatide was proven to be safe with no elevated risk of adverse drug reactions.In terms of economic cost,teriparatide has a higher cost and economic disadvantage compared with bisphosphonates,however,for people with severe postmenopausal osteoporosis and high risk of fracture,teriparatide can be considered as a potential cost-effect treatment option.Conclusion Teriparatide is effective and safe in the treatment of osteoporosis,but it is not cost-effective advantages compared with the existing other anti-osteoporosis medications.
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Objective:To compare the parameters for infra-acetabular screw placement between men and women using a digital Chinese anatomical model of the pelvis and acetabulum.Methods:The normal pelvic CT data were collected from the 163 adult patients who had been admitted to the Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2018 to December 2021. There were 61 males and 102 females with an age of 53.0 (45.0, 60.0) years. Mimics 21.0 software was used to reconstruct the three dimensional pelvis which was then imported into Autodesk maya 2022 software before the model was flattened. Polygonal modeling tools were used to create a cylinder to simulate an infra-acetabular screw for length and angle measurements of the screw. The diameters of the infra-acetabular screws were measured by axial fluoroscopy in Mimics 21.0 software. The maximum diameters and maximum lengths of the infra-acetabular bone channel were compared between males and females, and the angles between the axis of the infra-acetabular screw and the anterior pelvic plane and the median sagittal plane were also compared between genders.Results:The maximum diameters of the left and right infra-acetabular corridors were 5.24 (4.26, 6.38) mm and 5.04 (4.50, 6.57) mm in males, and 3.99 (3.81, 4.51) mm and 3.89 (3.65, 4.90) mm in females; the maximum lengths of the left and right infra-acetabular corridors were (98.43±4.42) mm and (98.01±5.08) mm in males and 87.73 (84.22, 90.98) mm and 87.51 (84.59, 90.15) mm in females. The left and right angles between the infra-acetabular screw axis and the median sagittal plane were -0.98°±4.79° and -1.08°±4.91° in men, and 6.20° (3.34°, 11.16°) and 6.44° (3.77°, 11.85°) in women. The differences in the above data between men and women were statistically significant ( P<0.05). There was no statistically significant difference between men and women in the angle between the infra-acetabular screw axis and the anterior pelvic plane ( P>0.05). Conclusions:The length and diameter of the infra-acetabular corridor in males are greater than those in females, the angle between the infra-acetabular corridor and the sagittal plane in males is smaller than that in females, and the infra-acetabular corridor in males is more parallel to the sagittal plane. Therefore, the fluoroscopy angle should be adjusted for males to reduce the difficulty in screw placement when an infra-acetabular screw is placed during surgery.
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Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.
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Objective: We investigate symptoms of anxiety and depression among women with asthma prior to fertility treatment. Methods: This is a cross-sectional study of women screened for eligibility to the PRO-ART study (RCT of omalizumab versus placebo in asthmatic women undergoing fertility treatment (NCT03727971)). All participants were scheduled for in vitro fertilization (IVF) treatment at four public fertility clinics in Denmark. Data on demographics and asthma control (ACQ-5) were obtained. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS-A and D, respectively) and defined as being present on both subscales if a score >7 was obtained. Spirometry, diagnostic asthma test, and measurement of fractional exhaled nitric oxide (FeNO) were conducted. Results: A total of 109 women with asthma were included (mean age 31.8 ± 4.6 and BMI 25.5 ± 4.6). Most women had male factor infertility (36.4%) or unexplained infertility (35.5%). Twenty-two percent of the patients reported uncontrolled asthma (ACQ-5 score > 1.5). The mean HADS-A and HADS-D scores were 6.0 ± 3.8 (95% CI 5.3-6.7) and 2.5 ± 2.2 (95% CI 2.1-3.0), respectively. Thirty (28.0%) women reported anxiety symptoms, and four (3.7%) had concomitant depressive symptoms. Uncontrolled asthma was significantly associated with both depressive (p = 0.04) and anxiety symptoms (p = 0.03). Conclusions: More than 25% of women with asthma prior to fertility treatment had self-reported symptoms of anxiety, and just below 5% had self-reported depressive symptoms, possibly related to uncontrolled asthma.
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Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.
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Pelvic and acetabular fractures are one of the serious traumatic diseases, leading to a high rate of disability and fatality. Their operative principles are anatomical repositioning and rigid fixation to achieve early functional exercise and avoid complications. The updating modern technology has made precision and minimally invasion a trend in orthopedic surgery. An increasingly number of new technologies has been applied in clinical surgery, such as three-dimensional printing, three-dimensional navigation, and orthopedic robotics, each with its own characteristics. Of them, three-dimensional printing technology is more advantageous in terms of reducing surgical cost and risk, enhancing surgical efficiency, achieving surgical precision and reducing radiation exposure, as evidenced by a large number of clinical case reports and randomized controlled trials. This paper summarizes the current situation and assesses the prospects of three-dimensional printing technology in the diagnosis and treatment of pelvic and acetabular fractures in order to provide reference for orthopedic colleagues.
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Photothermal therapy has the characteristics of minimal invasiveness, controllability, high efficiency, and strong specificity, which can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment. However, due to the limited tissue penetration of infrared light, it is difficult to promote and apply in clinical practice. The eye is the only transparent tissue in human, and infrared light can easily penetrate the eye tissue, so it is expected that photothermal therapy can be used to treat fundus diseases. Here in, a new nano-platform assembled by liposome and indocyanine green (ICG) was used to treat retinoblastoma. ICG was assembled in liposomes to overcome some problems of ICG itself. For example, ICG is easily quenched, self-aggregating and instability. Moreover, liposomes can prevent free ICG from being cleared through the systemic circulation. The construction of the nano-platform not only ensured the stability of ICG in vivo, but also realized imaging-guide photothermal therapy, which created a new strategy for the treatment of retinoblastoma.
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【Objective】 To compare the clinical efficacy and sagittal parameters of oblique lateral interbody fusion (OLIF) combined with posterior percutaneous internal fixation and percutaneous transforaminal endoscope-assisted posterior lumbar interbody fusion (PT-Endo-TLIF) in treating degenerative lumbar spondylolisthesis. 【Methods】 A retrospective analysis was made on 43 patients with Meyerding Ⅰ and Ⅱ° degenerative lumbar spondylolisthesis treated in our hospital from September 2017 to January 2020. Among them 23 cases were treated by OLIF, and the other 20 cases were treated by PT-Endo-TLIF. We observed and recorded the operation time, average length of hospital stay, and intraoperative blood loss, and postoperative complications of the patients. The patients were followed up 3 day, 6 and 12 months after the operation. The lumbar sagittal parameters of the two groups were compared by X-ray, CT and MRI examinations. The patients’ lower back pain was recorded for visual analogue scale (VAS), and Oswestry disability index (ODI) was used to evaluate the clinical efficacy. 【Results】 Both groups of patients successfully completed the operation and follow-up, with the average follow-up time of 12 months. The average amount of intraoperative blood loss and operation time were significantly lower in OLIF group than in PT-Endo-TLIF group (P<0.05). Intervertebral height increased significantly in the two groups after operation compared with pre-operation (P<0.05). Compared with pre-operation, lumbar lordosis angle, lower lumbar lordosis angle and lumbar lordosis distribution index increased in both groups (P<0.05), with no significant difference between them (P>0.05). The inclination angle of L4 vertebral body and the distance between L1 vertical line and S1 in both groups were decreased compared with those before surgery (P<0.05), but there was no significant difference between the two groups (P>0.05). The inclination angle of L5 vertebral body in the two groups was increased compared with that before surgery (P<0.05), but there was no statistical significance between both groups (P>0.05). 【Conclusion】 OLIF surgical technique has the comparative advantages of definite curative effect, less trauma, fewer surgical complications, shorter operation time, less bleeding, and good recovery of the height of intervertebral space, which is suitable for its application among clinicians.
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Objective:To evaluate the changes in glucose metabolism in the prefrontal cortex during long-term cognitive dysfunction induced by neuropathic pain in developing rats.Methods:SPF healthy male Sprague-Dawley rats, aged 4 weeks, weighing 80-100 g, were used in this study.The model of neuropathic pain was established by using spared nerve injury in anesthetized rats.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before establishing the model (T 0) and 1, 3, 7, 14, 28, 42 and 56 days after establishing the model (T 1-7). According to the results of MWT compared between T 5 and T 0, the rats were divided into neuropathic pain group (group NP) and non-neuropathic pain group (group NNP). Open field test and novel object recognition test were performed at T 7 to assess anxiety-like behavior and cognitive function.Positron emission tomography/computed tomography imaging was performed to determine the standard uptake value of 18F-fluorodeoxyglucose in the prefrontal cortex.Then the rats were sacrificed, and prefrontal cortex was removed for determination of the expression of glucose transporter 3 using Western blot and immunofluorescence. Results:Compared with the baseline at T 0, the MWT at T 1-2 in group NNP and at T 1-7 in group NP were significantly decreased ( P<0.05). Compared with group NNP, the MWT at T 1-7 were significantly decreased, the time of staying at the central region at T 7 was shortened, the percentage of time for exploring the novel object was decreased, the percentage of novel object exploration was decreased, the standard uptake value of 18F-fluorodeoxyglucose in prefrontal cortex was decreased, and the expression of glucose transporter 3 in prefrontal cortex was down-regulated in group NP ( P<0.05). Conclusion:Long-term cognitive dysfunction induced by neuropathic pain may be related to decreased glucose metabolism in the prefrontal cortex of the developing rats.
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Objective:To evaluate the role of P2X 7 receptor in microglia in the medial prefrontal cortex (mPFC) in neuropathic pain (NP) and the relationship with autophagy in rats. Methods:Sixty-four healthy SPF male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 4 groups ( n=16 each) using a random number table method: sham operation group (S group), NP group, sham operation+ P2X 7 receptor blocking group (SP group), and NP+ P2X 7 receptor blocking group (NP+ P group). The NP model was established by ligation of the sciatic nerve.Fourteen days later a cannula was placed in the mPFC with a brain stereotactic instrument, P2X 7 receptor blocker A-740003 0.5 μg/0.5 μl was injected into bilateral mPFC for 3 consecutive days starting from the 14th day in SP and NP+ P groups, and DMSO 0.5 μl was injected instead of A-740003 in S and NP groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 3, 7 and 10 days after establishing the model and 14, 15 and 16 days after administration.Then the rats were sacrificed, and the mPFC was removed for determination of the expression of P2X 7 receptor and mRNA and autophagy-related proteins Beclin1 and LC3Ⅱ/Ⅰ (by quantitative real-time polymerase chain reaction or by Western blot) and co-expression of P2X 7R and microglia (by immunofluorescence) and the number of autophagosomes in mPFC (with a transmission electron microscope). Results:Compared with group S, MWT was significantly decreased, and TWL was shortened at 3, 7 and 10 days after establishing the model, the expression of P2X 7 receptor and mRNA, Beclin1 and LC3Ⅱ/Ⅰ was up-regulated at 30 min after administration on 16 days after establishing the model, and the number of cells co-expressing P2X 7 receptor and IBA-1 and the number of autophagosomes were increased in NP and NP+ P groups ( P<0.05), and no significant change was found in the indexes mentioned above in group SP ( P>0.05). Compared with group NP, MWT was significantly increased, and TWL was prolonged at 30 min after administration on 14, 15 and 16 days after establishing the model, the expression of P2X 7 receptor and mRNA, Beclin1 and LC3Ⅱ/Ⅰ was down-regulated, and the number of cells co-expressing P2X 7 receptor and Iba-1 and the number of autophagosome were decreased in group NP+ P ( P<0.05). Conclusion:Up-regulation of P2X 7 receptor expression in microglia in mPFC is involved in the process of NP in rats, which is associated with the promotion of autophagy.
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BackgroundPatients with pre-existing cirrhosis are considered at increased risk of severe coronavirus disease 2019 (COVID-19) but the clinical course in these patients has not yet been reported. This study aimed to provide a detailed report of the clinical characteristics and outcomes among COVID-19 patients with pre-existing cirrhosis. MethodsIn this retrospective, multicenter cohort study, we consecutively included all adult inpatients with laboratory-confirmed COVID-19 and pre-existing cirrhosis that had been discharged or had died by 24 March 2020 from 16 designated hospitals in China. Demographic, clinical, laboratory and radiographic findings on admission, treatment, complications during hospitalization and clinical outcomes were collected and compared between survivors and non-survivors. FindingsTwenty-one patients were included consecutively in this study, of whom 16 were cured and 5 died in hospital. Seventeen patients had compensated cirrhosis and hepatitis B virus infection was the most common etiology. Lymphocyte and platelet counts were lower, and direct bilirubin levels were higher in patients who died than those who survived (p= 0{middle dot}040, 0{middle dot}032, and 0{middle dot}006, respectively). Acute respiratory distress syndrome and secondary infection were both the most frequently observed complications. Only one patient developed acute on chronic liver failure. Of the 5 non-survivors, all patients developed acute respiratory distress syndrome and 2 patients progressed to multiple organ dysfunction syndrome. InterpretationLower lymphocyte and platelet counts, and higher direct bilirubin level might represent poor prognostic indicators in SARS-CoV-2-infected patients with pre-existing cirrhosis.
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Objective To evaluate the effectiveness of reactive oxygen species (ROS)-responsive nanomedicine in suppressing corneal neovascularization (CNV) in vivo.Methods ROS-responsive nanomedicine (ROS-TK-5/siVEGF),which consists of vascular endothelial growth factor (VEGF) small interfering RNA (siRNA) and thioketal linkage was synthesized by the Michael addition.The cumulative release of siVEGF from nanomedicine under oxidant conditions was assessed by agarose gel electrophoresis.Thirty-nine VEGFR2-1uc-KI transgenic mice were used in this study,of which 30 mice were randomly divided into a normal control group,a PBS control group,an ROS-TK-5/NC group,an ROS-TK-5/siVEGF group,and a ranibizumab group,with 6 mice in each group.The ROS levels in the corneal tissue after alkali burning were tested by dihydroethidium (DHE) staining in the other 9 mice.In each group,alkali-burned mice were subconjunctivally injected with 10 μl of a different formula every two days.The effectiveness of nanomedicine in attenuating CNV was evaluated by slit-lamp microscopy and an in vivo imaging system (IVIS) at 7,14,and 21 days after alkali burning.The use and care of the animals complied with the Statement of the Association for Research in Vision and Ophthalmology (ARVO) and the Guidelines of the Animal Experimental Committee of Liberation Army General Hospital.The study protocol was approved by the Ethics Committee of Liberation Army General Hospital (No.2018-X14-82).Results After treathrent with an aqueous solution without ROS,only 5%-10% of the siVEGF was released from the nanoparticles within 10 hours.In contrast,about 70% of the siVEGF was released from the nanoparticles after treatment with 10 mmol/L H2O2 within 10 hours.The relative fluorescent intensities in the corneal stromal layer at 7 days and 14 days after alkali burning were 5.403±0.306 and 2.930±0.255,respectively,which was significantly greater than those in the normal control group (1.003±0.015) (both at P<0.05).The CNV areas were statistically different among the four groups at various time points (Fgroup =49.855,P<0.01;Ftime =65.556,P<0.01).The CNV area was significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared with the PBS control and ROS-TK-5/NC groups at 7 days and 14 days after modeling,and the CNV area was more effectively reduced in the ROS-TK-5/siVEGF group than the ranibizumab group at 7 days and 14 days after modeling (all at P<0.05).At day 21 after modeling,the CNV area was significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared to the PBS control and ROS-TK-5/NC groups (all at P< 0.05).IVIS showed that the corneal fluorescent intensity was statistically different among the four groups at various times (Fgroup =27.193,P =0.003;Ftime =51.062,P < 0.01).The corneal fluorescent intensities were significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared to the PBS control and ROS-TK-5/NC groups at 7 days and 14 days after modeling;in addition,the corneal fluorescent intensity was more effectively reduced in the ROS-TK-5/siVEGF group in comparison with the ranibizumab group at 7 days and 14 days after modeling (all at P< 0.05).At 21 days after modeling,the corneal fluorescent intensity was significantly reduced in the ROS-TK-5/ siVEGF and ranibizumab groups compared to the PBS control and ROS-TK-5/NC groups (all at P < 0.05).Conclusions ROS-TK-5/siVEGF nanomedicine effectively attenuates alkali burn-induced CNV formation and appears to have a better effect in comparison with ranibizumab at an early stage.
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Objective@#To evaluate the effectiveness of reactive oxygen species (ROS)-responsive nanomedicine in suppressing corneal neovascularization (CNV) in vivo.@*Methods@#ROS-responsive nanomedicine (ROS-TK-5/siVEGF), which consists of vascular endothelial growth factor (VEGF) small interfering RNA (siRNA) and thioketal linkage was synthesized by the Michael addition.The cumulative release of siVEGF from nanomedicine under oxidant conditions was assessed by agarose gel electrophoresis.Thirty-nine VEGFR2-luc-KI transgenic mice were used in this study, of which 30 mice were randomly divided into a normal control group, a PBS control group, an ROS-TK-5/NC group, an ROS-TK-5/siVEGF group, and a ranibizumab group, with 6 mice in each group.The ROS levels in the corneal tissue after alkali burning were tested by dihydroethidium (DHE) staining in the other 9 mice.In each group, alkali-burned mice were subconjunctivally injected with 10 μl of a different formula every two days.The effectiveness of nanomedicine in attenuating CNV was evaluated by slit-lamp microscopy and an in vivo imaging system (IVIS) at 7, 14, and 21 days after alkali burning. The use and care of the animals complied with the Statement of the Association for Research in Vision and Ophthalmology (ARVO) and the Guidelines of the Animal Experimental Committee of Liberation Army General Hospital.The study protocol was approved by the Ethics Committee of Liberation Army General Hospital (No.2018-X14-82).@*Results@#After treathrent with an aqueous solution without ROS, only 5%-10% of the siVEGF was released from the nanoparticles within 10 hours.In contrast, about 70% of the siVEGF was released from the nanoparticles after treatment with 10 mmol/L H2O2 within 10 hours.The relative fluorescent intensities in the corneal stromal layer at 7 days and 14 days after alkali burning were 5.403±0.306 and 2.930±0.255, respectively, which was significantly greater than those in the normal control group (1.003±0.015) (both at P<0.05). The CNV areas were statistically different among the four groups at various time points (Fgroup=49.855, P<0.01; Ftime=65.556, P<0.01). The CNV area was significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared with the PBS control and ROS-TK-5/NC groups at 7 days and 14 days after modeling, and the CNV area was more effectively reduced in the ROS-TK-5/siVEGF group than the ranibizumab group at 7 days and 14 days after modeling (all at P<0.05). At day 21 after modeling, the CNV area was significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared to the PBS control and ROS-TK-5/NC groups (all at P<0.05). IVIS showed that the corneal fluorescent intensity was statistically different among the four groups at various times (Fgroup=27.193, P=0.003; Ftime=51.062, P<0.01). The corneal fluorescent intensities were significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared to the PBS control and ROS-TK-5/NC groups at 7 days and 14 days after modeling; in addition, the corneal fluorescent intensity was more effectively reduced in the ROS-TK-5/siVEGF group in comparison with the ranibizumab group at 7 days and 14 days after modeling (all at P<0.05). At 21 days after modeling, the corneal fluorescent intensity was significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared to the PBS control and ROS-TK-5/NC groups (all at P<0.05).@*Conclusions@#ROS-TK-5/siVEGF nanomedicine effectively attenuates alkali burn-induced CNV formation and appears to have a better effect in comparison with ranibizumab at an early stage.
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The Notch signaling pathway plays an important role in cell fate and homeostasis.Various studies have proved that the Notch signaling pathway has strong effects on corneal wound healing and the maintenance of corneal homeostasis.Limbal stem cells inhibit differentiation and proliferation by inhibiting the Notch signaling pathway.Physiologic downregulation promotes cell migration and wound coverage in the early stage of corneal epithelial repair, and physiologic upregulation in the late stage of corneal epithelial repair is related to preventing excessive stratification of corneal epithelial cells and maintaining cell differentiation.Fibrosis is correlated with Notch after corneal stromal injury.The Notch signaling pathway is directly involved in the endothelial-to-mesenchymal transition induced by transforming growth factor-β after corneal endothelial injury.In addition, there are interactions between the Notch signaling pathway and 14-3-3 sigma, epidermal growth factor receptor, Sirt6, microRNA, and matrix metalloproteinases in maintaining corneal epithelial homeostasis, corneal epithelial differentiation, corneal stromal excessive inflammatory response, corneal neovascularization, etc.This review summarizes the function of the Notch signaling pathway in corneal wound healing.
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Objective To evaluate the ocular pharmacokinetics of a novel antibody, MIL60, tar-geting vascular endothelial growth factor ( VEGF) after subconjunctival injection. Methods After subcon-junctival injection of MIL60 in rabbits, aqueous humour, vitreous from both eyes and peripheral blood were collected of each rabbit to analyze the concentration of MIL60 with ELISA. Results After subconjunctival administration, MIL60 could penetrate into the injected eye′s anterior chamber and vitreous, and maintained at an effective concentration in the aqueous or vitreous for about 10. 7 or 6. 8 days. Moreover, MIL60 could be found in the uninjected eye. Conclusion After subconjunctival injection, MIL60 could maintain at a therapeutic concentration in injected eyes. The pharmacokinetics analysis of MIL60 might provide some basis and guidance for its application in humans in the near future.
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Objective To investigate the effects of Wuzhi capsules on tacrolimus concentration in heart transplant recipients and provide evidence for individualized dose optimization of tacrolimus.Methods Forty heart transplant recipients receiving Wuzhi capsules were enrolled in this study.Tacrolimus trough concentration was compared before and after coadminstration of Wuzhicapsules.Furthermore,polymorphisms of CYP3A4 * 1G and CYP3A5 * 3 were also detected to clarify correlations between genotypes and effects of Wuzhi capsule.Results Dose-normalized concentration of tacrolimus after coadministartion with Wuzhi capsules was 2.02-fold higher than before,the results of which was not associated with CYP3A4 * 1G and CYP3A5 * 3 genotypes.Wuzhi capsule could significantly decrease the total bilimbin (T-BiL),but not other hepatic and renal function.Conclusion Dose-normalized concentration of tacrolimus in heart transplant recipients is remarkably increased by Wuzhi capsule.The elevated trough levels rarely result in hepatic and renal toxicity.Wuzhi capsule is a safe,effective,and stable drug to increase the trough concentration of tacrolimus.
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Stem cells are a group of self-renewal cells with the potential to differentiate into a variety of cell lineages. Embryonic stem cells can differentiate into more than 200 types of cell lineages belonging to endodermal, mesodermal and ectodermal tissues. Corneal epithelial cells derive from epidermal ectoderm during embryonic development. When the ocular surface is severely damaged, corneal epithelium with proliferation potential is essential for its reconstruction. Recent studies are focused on differentiation of bioactive corneal epithelial cells. This review summarizes signaling pathways including Notch, Wnt, bone morphogenetc protein or fibroblast growth factor pathways that are involved in regu?lating the development of embryonic ectoderm and corneal epithelial cells revealed in previous studies.
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Objective To investigate the entry points for clinical work of intensive care unit (ICU) pharmacists.Methods Through combination with daily work and referring the domestic and foreign literature,the characteristics of ICU medications were discussed to find out the entry point for clinical work of ICU pharmacists.Results ICU patients particularly need individualized pharmaceutical care because of the special pathophysiological characteristics and medicine use.Conclusion ICU pharmacists should provide pharmaceutical care based on Pharmacokinetics/pharmacodynamics knowledge and focus on the drug dosage adjustment,drug interactions and adverse event prevention.
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Objective To analyze the anatomic factors of the central retinal artery occlusion or the ophthalmic artery occlusion after the injection of facial cosmetic surgery.Methods Retrospectively analyzed 3 patients who occurred severely ocular complications just after facial cosmetic injection in last 2 years.The diagnosis of central retinal artery occlusion was confirmed by fundus examination and fundus fluoresce-in angiography.Analysis the blood vessel distribution of the injection site and characteristics of peri-orbit vascular anastomosis.Results All the 3 cases presented no light perception,with eye pain or (and)the eyeball pain.The fundus test and fundus fluorescein angiographies showed central retinal artery obstruction.Facial cosmetic injection pressure significantly exceeded the ophthalmic artery systolic pressure 2 seconds after injection (P <0.05).Dorsal nasal artery and angular artery were anastomotic,and the angular artery was usually anastomotic with lateral nasal branches of the posterior ciliary artery.The filler can enter the ophthalmic artery by the branches of the anastomosis,which can make ophthalmic artery occlusion,central retinal artery occlusion or get occlusion of their branches.Conclusion The injectant may get into the orbital artery and retrograde to the ophthalmic artery,which resulting in ophthalmic artery occlusion,or get into central retinal artery and posterior ciliary artery,which resulting in serious ocular complications.
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BACKGROUND:J2 takes functional domain (MHC CD4-D1/) of complex conjugate of CD4 molecule and MHC class II molecule as a target, and is a smal molecule compound obtained by computer screening from a chemical data containing hundreds of thousands of organic compounds. In the previous study, J2 was used in mouse models of skin transplantation and keratoplasty by oral and intraperitoneal injection. Results verified that J2 could prolong the survival time of grafts, and suppress occurrence of rejection. To better play the role of a drug targeting and to reduce systemic toxicity, J2 wil be further utilized in local treatment of keratoplasty rejection. OBJECTIVE:To investigate the inhibitory effect of new immunosuppressive agent J2 on CD4+ and CD8+T cel immune functions in rat models receiving alogenic penetrating keratoplasty. METHODS:Alogeneic penetrating keratoplasty model was established using the adult female Wistar rats as donors and Sprague-Dawley rats as recipients. Group A: normal Sprague-Dawley rats were injected with 0.05 mL placebo subconjunctivaly. Surgery rats were randomly divided into three groups. Group B: alograft rats were injected with 0.05 mL placebo subconjunctivaly after autologous keratoplasty. Group C: alograft rats were injected with 0.05 mL placebo subconjunctivaly. Group D: alograft rats were injected with 1% J2-nanosuspension 0.05 mL subconjunctivaly. The distribution of T cel subsets in peripheral blood was detected using flow cytometry at 3 days, 1, 2 and 3 weeks after transplantation and compared among groups. RESULTS AND CONCLUSION: There was no significant difference in total CD3+ T cels, CD4+ T cels, CD8+ T cels and CD4+/CD8+ in peripheral blood lymphocytes in group B at various time points. At 3 days and 1 week after surgery in group C, no significant difference in total CD3+ T cels, CD4+ T cels and CD8+ T cels was detected. At 1 and 2 weeks, the number of total CD3+ T cels, CD4+ T cels and CD8+ T cels increased, showing significant differences (P < 0.05). In group D, no significant hyperplasy was found in CD4+ T cels and CD8+ T cels at 1 and 2 weeks. The horizontal comparison of the same time point: the total CD3+ T lymphocytes of group D was significantly less than group C at 3 days, 1 and 2 weeks after operation (P < 0.05), whereas there was no significant difference at 3 weeks between the group D and group C. The number of CD4+ T lymphocytes in group D was less than in group C at 3 days and 1 week, but with no significant difference. The ratio of CD4+/CD8+ had no significant difference in group D compared with group C at 3 days, 1 and 3 weeks. J2 inhibits T lymphocyte proliferation and then inhibits T cel-mediated corneal alograft rejection.