BACKGROUND: The application of polymerized 2-hydroxyethyl methacryate (PHEMA) in many organs of living body shows good biocompatibility.OBJECTIVE: To observe the biocompatibility and fibrovascular condition of methl-methacrylate (MMA) modified PHEMA hydrogel orbital implant.DESIGN: Single sample observation.SETTING: Department of Ophthalmology, the General Hospital of Chinese PLA; Institute of Polymer Science,Department of Chemical Engineering, Tinghua university.MATERIALS: Twenty-five New Zealand rabbits of either gender and clean grade, weighing 2.0 to 2.5 kg, were provided by the Animal Experimental Center, General Hospital of Chinese PLA. The animals were observed at postoperative 2, 4,8, 12 and 24 weeks, 5 at each time point. The experiment was permitted by ethics committee. MMA modified PHEMA hydrogel orbital implant was provided by Institute of Polymer Research, Department of Chemical Engineering, Tinghua University. The experiment was permitted by ethics committee.METHODS: This experiment was carried out in the laboratory of Department of Ophthalmology, the General Hospital of Chinese PLA from March to October 2003. The right eye served as operation eye. When the rabbits were anesthetized,their eyelids were open with eyelid retractor. Bulbar conjunctiva was open along the edge of limbus of cornea for isolating fascia. Oculorotatory muscle was isolated and pre-set suture line was made, then muscle was cut off. When optical nerve was cut off, eyeball was completely excised. A MMA modified PHEMA hydrogel orbital implant with the diameter of 14 mm was implanted into the fossa orbitalis of rabbits. Single photon emission computed tomography (SPECT) was performed at postoperative 2, 4, 8, 12 and 24 weeks. The hydrogel orbital implant was taken out at postoperative 2, 4, 8,12 and 24 weeks for light microscope, immunohistochemical and electron microscope examinations.MAIN OUTCOME MEASURES: Vascularization of hydrogel orbital implant was observed in vivo by isotope tracing observation at different time points. Vascularization of hydrogel orbital implant was observed ex vivo by light microscope,immunohistochemical and electron microscope observations.RESULTS: All 25 New Zealand rabbits were involved in the final analysis. ①SPECT examination showed that isotope increased around the implants at week 2, and extended gradually at weeks 4 and 8. The radiotracer accumulated evenly in the implants from surrounding to the center at week 12. ②Light microscopic examination of the prostheses revealed fiber vessels grew from the surrounding to the center. At week 2,fibrovascular tissue grew in the hole of implant. Long or round cells with deeply dyed nucleuses were found in the hole, being fibroblasts. The vascular structure in the hole of the implant was clear, and vascular wall and blood cells were found. The inflammatory cells were mainly neutrophils and lymphocytes, and occasionally large macrophages. ③Scanning electron microscope showed that fibrovascular tissue grew in the hole of the implant, and was dense and intercrossed at week 12. ④ Conjunctiva split appeared postoperatively in 1 of 25 cases, and healed well after two times of operation. Conjunctival congestion lessened and conjunctiva healed within postoperative 7 days in the remaining 24 animals.CONCLUSION: MMA modified PHEMA hydrogel orbital implant has good histocompatibility and fast vascularization process, and is easy to be operated with fewer complications. So, it is a safe and practicable new type orbital implant.

AIM: To investigate the influences of native and oxidized lipoprotein(a) on human arterial smooth muscle cell (SMC) proliferation, change of intracellular free calcium concentration ([Ca 2+ ] i) and the protective effect of sodium ferulate(SF). METHODS: Lp(a) was oxidized by Cu 2+ and the extent of oxidation was assessed by the MDA content.Human SMC were incubated in culture media with SF for 12 h, then exposed to Lp(a) and oxidized-Lp(a), respectively. MTT colorimetry and flow cytometry were used to evaluated the proliferation of SMC and flurorescent indicator Fura-2/AM was used to determined [Ca 2+ ] i. RESULTS: ox-Lp(a) significantly promoted proliferation of SMC and increased[Ca 2+ ] i compared with Lp(a). SF(40,80 mg/L) remarkedly inhibited SMC proliferation and decreased the rising of [Ca 2+ ] i induced by ox-Lp(a) in a dose-dependent manner, but no effect on SMC proliferation and the increase in [Ca 2+ ] i induced by Lp(a).CONCLUSION: ox-Lp(a) induces the strong growth-promoting effect in SMC through increasing in [Ca 2+ ] i, which might be one of the cellular mechanisms responsible for the higher atherogenic potential of ox-Lp(a) compared with Lp(a), and this process can be prevented by inhibiting of oxidation by SF.

Objective:To retrospectively analyze the survival outcomes of the surgical management of primary small cell carcino-ma of the esophagus. Methods:The medical records were reviewed for patients diagnosed with esophageal carcinoma and underwent esophagectomy from January 2000 to December 2009 at the Department of Thoracic Surgery of the Henan Cancer Hospital. We fo-cused on the clinical data of patients with small cell carcinoma of the esophagus. The Kaplan-Meier approach with log-rank test was used for survival analysis. Results:A total of 5,062 patients underwent esophagectomy with curative intent at the Department of Thorac-ic Surgery of the Henan Cancer Hospital;among which, 57 (1.1%) were diagnosed with small cell carcinoma of esophagus. The most common surgical approach was trans-left thoracic incision esophagectomy. Cervical esophagogastrostomy was performed for all pa-tients. The most common chemotherapy regimen was EP. The overall 5-year survival rate was 12.5%, and the median survival time was 45 months. Among the various stages, the 5-year survival rate and survival time were 25% and 50 months for Stage I, 5.9% and 43 months for Stage II, and 4.3%and 43 months for StageⅢ. Subgroup analysis showed that cases treated with surgery alone had poorer overall median survival time compared with those cases that underwent surgery plus chemotherapy (23.2 months vs. 60.7 months, re-spectively;P<0.01). Even for Stage I patients, thesurgery plus chemotherapysubgroup was associated with a significantly longer me-dian survival time than the surgery alone subgroup (81.9 months vs. 22.3 months, P<0.01). Conclusion:For patients with primary small cell carcinoma of the esophagus, surgery alone cannot provide the optimal prognosis. Surgery combined with systemic chemother-apy can improve the survival time.

Renal transplantation is one of the most effective treatment methods for end-stage renal diseases. However, some recipients present with fatigue symptoms after renal transplantation. Fatigue not only affects the quality of life, but also reduces the compliance of recipients with immunosuppressive agents. To strengthen the attention of medical staff to the fatigue, make early diagnosis and deliver effective interventions for renal transplant recipients, the current situation, risk factors and intervention methods of fatigue in renal transplant recipients were reviewed in this article.

ObjectiveTo observe the protective effect of Chaihu Jia Longgu Mulitang （CLMT） on dopaminergic neurons in Parkinson's disease with depression （PDD） model rats， and to explore the mechanism based on adenosine monophosphate-activated protein kinase/mammalian target of rapamycin （AMPK/mTOR） signaling pathway. MethodAmong the 80 male SD rats， 10 were randomly selected as normal group and the rest were treated with long-term low-dose subcutaneous injection of rotenone in the neck and back combined with chronic unpredictable mild stress （CUMS） to establish PDD rat model. The successfully modeled PDD rats were randomly divided into model group， western medicine group （madopar 0.032 g·kg^-1+fluoxetine hydrochloride 0.002 g·kg^-1）， CLMT low-dose， medium-dose and high-dose groups （5， 10 and 20 g·kg^-1）， 10 rats in each group. Normal group and model group were administrated with the same amount of normal saline by gavage for 4 consecutive weeks. Behavioral changes of rats in each group were evaluated by open field test and pole climbing test. The content of dopamine （DA） and 5-hydroxytryptamine （5-HT） in cerebrospinal fluid was determined by high performance liquid chromatography （HPCL）. The pathological changes of dopaminergic neurons in substantia nigra of rats were observed by hematoxylin-eosin （HE） staining. The positive expression of tyrosine hydroxylase （TH） and expression of α-synuclein in substantia nigra were detected by immunohistochemistry （IHC） and immunofluorescence （IF）， repsectively. The protein expression of microtubule-associated protein 1 light chain 3 （LC3）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， mammalian target of rapamycin （mTOR） and phosphorylated mTOR （p-mTOR） was detected by Western blot. ResultCompared with the conditions in normal group， the total horizontal distance and the activity time in the central region in open field test and the content of DA and 5-HT in cerebrospinal fluid were decreased （P<0.05， P<0.01）， and the time of pole climbing was shortened （P<0.01）， with increased score （P<0.01） in model group. Compared with model group， CLMT high-dose group and western medicine group increased the total horizontal distance and activity time in the central region and the content of DA and 5-HT （P<0.05， P<0.01）， and extended the time of climbing pole （P<0.05）， with decreased score （P<0.05， P<0.01）. Compared with those in normal group， the number of dopaminergic neurons in the substantia nigra was reduced， with narrowed and loosely arranged cell body. The fluorescence expression of α-synuclein was enhanced （P<0.01）， and the positive expression of TH was decreased （P<0.01） in model group. Compared with model group， CLMT high-dose group and western medicine group showed elevated number of dopaminergic neurons in the substantia nigra， with enlarged cell body， and decreased fluorescence expression of α-synuclein， and enhanced the positive expression of TH （P<0.05， P<0.01）. Compared with normal group， model group had lowered expression of LC3Ⅱ/Ⅰ， p-AMPK/AMPK in striatum （P<0.05， P<0.01） and increased expression of p-mTOR/mTOR （P<0.01）. Compared with those in model group， LC3Ⅱ/Ⅰ and p-AMPK/AMPK expression were increased （P<0.05， P<0.01） and p-mTOR /mTOR expression was decreased （P<0.01） in CLMT high-dose group and western medicine group. ConclusionCLMT exerts a neuroprotective effect by inhibiting rotenone neurotoxicity. It enhances the level of DA， and thus improves the depression condition in rats with Parkinson's disease. The underlying mechanism may be related to the regulation of AMPK/mTOR signaling pathway， activation of autophagy， and promotion of degrading α-synuclein.

Severe open injury of lower limbs is complex and difficult to cure in a short time,which can lead to serious infection,amputation and so on.For the treatment of open injury,wound repair is extremely important.A variety of new technologies such as new dressings,platelet-rich plasma(PRP),and vacuum sealing drainage(VSD)have recently been applied to lower limb wound repair,which can not only improve the functional prognosis and aesthetic effect,but also improve the quality of wound healing.This review will summarize the research progress of wound repair methods for open injury of lower limbs,so as to further guide clinical application.

Cardiovascular and cerebrovascular diseases are one of the major diseases endangering human health， and its morbidity and mortality are still in the rising stage in our country. Traditional Chinese medicine （TCM） injections play an important role in the prevention and treatment of cardiovascular and cerebrovascular diseases due to their advantages of rapid onset， remarkable curative effect， and convenient use. Among them， Danhong injection （DHI）， a Chinese medicine injection for promoting blood circulation and removing blood stasis， is widely used in the clinical treatment of cardio-cerebrovascular diseases. DHI is composed of Salviae Miltiorrhizae Radix et Rhizoma （Danshen in Chinese） and Carthami Flos （Honghua in Chinese）， and mainly contains phenolic acids， tanshinones and flavonoids. A large number of studies have shown that DHI has a significant effect in the treatment of ischemic cardio-cerebrovascular diseases， is a representative drug of co-therapy of brain and heart of TCM， its pharmacological effects related to many aspects such as anti-inflammatory， anti-oxidation， anti-coagulation. At the same time， Other studies have also explained the protective effects of DHI on cardiovascular and cerebrovascular diseases through the overall regulation and intervention of multiple targets and pathways. However， DHI has a wide range of clinical applications， there are still many unknown pharmacological effects to be further explored. Therefore， this article summarizes the current researches on the chemical components of DHI， the multi-target and multi-path pharmacological mechanisms of DHI in the treatment of cardiovascular and cerebrovascular diseases， and introduces the latest pharmacological research progress， so as to provide theoretical guidance for clinical rational drug use and subsequent in-depth research.

ObjectiveTo investigate the effect of baicalein （BAI） on SH-SY5Y cell injury in lipopolysaccharide （LPS）-activated BV-2 cells conditioned medium and its mechanism. MethodThe BV-2 cells were activated with 1 mg∙L^-1 of LPS to establish the conditioned medium of the LPS group， and a blank group and groups of BAI with low， medium， and high concentrations （4， 8， 16 μmol∙L^-1） were established. SH-SY5Y cells were cultured with the conditioned medium of each group. The cell viability of BV-2 cells in each group after the intervention was determined by cell counting kit-8 （CCK-8）. The content of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the supernatant of BV-2 cells in each group was determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of α-synuclein （α-syn） and tyrosine hydroxylase （TH） in SH-SY5Y cells was observed by immunohistochemical （IHC） staining， and the nuclear transfer of nuclear factor kappa-B p65 protein （NF-κB p65， p65） in SH-SY5Y cells was observed by immunofluorescence （IF）. The protein expression of Toll-like receptor 4（TLR4）， p65， phosphorylated p65 （p-p65）， and Myeloid differentiation factor 88 （MyD88） in SH-SY5Y cells was observed by Western blot. ResultAs compared with the blank group， the viability of BV-2 cells in the LPS group was significantly decreased （P<0.01）， and the content of TNF-α， IL-6， and IL-1β in the cell supernatant was significantly increased （P<0.01）. As compared with the LPS group， the cell viability was significantly increased in groups of BAI with low， medium， and high concentrations （P<0.01）， and TNF-α in the cell supernatant was significantly decreased （P<0.01）. The content of IL-6 in the cell supernatant was decreased in the BAI group with high concentration （P<0.05）， and the content of IL-1β in the cell supernatant was significantly decreased in the BAI groups with medium and high concentrations （P<0.01）. The results of conditioned medium cultured SH-SY5Y cells showed that as compared with the blank group， the protein expression of p65 in the LPS group entered into the nucleus and accumulated， and the protein expression of TH was significantly decreased （P<0.01）， while that of α-syn， TLR4， MyD88， and p-p65 was increased （P<0.05， P<0.01）. Compared with the LPS group， the protein expression of p65 in SH-SY5Y cells in BAI groups with low， medium， and high concentrations gradually dispersed into the cytoplasm and had the enhanced protein expression of TH （P<0.01） but the lowered protein expression of α-syn （P<0.01）. The protein expression of TLR4， MyD88， and p-p65 was decreased in the BAI group with high concentration （P<0.05， P<0.01）， the protein expression of p-p65 and MyD88 was decreased in the BAI group with medium concentration， and the protein expression of MyD88 was decreased in the BAI group with low concentration （P<0.05）. There was no significant difference in the protein expression of p65 among groups. ConclusionBAI can inhibit the activation of BV-2 cells， thereby inhibiting the inflammatory response caused by LPS and further inhibiting the damage of inflammation to SH-SY5Y cells. The mechanism may be related to the regulation of the TLR4/MyD88/NF-κB signaling pathway and reduction of the inflammatory response， thus playing a neuroprotective role.

This study was aimed to obtain the incidence of adverse drug reaction (ADR) of Diemailing Kudiezi injection, explore its characteristics, related risk factors and application in real world. A prospective single cohort study was conducted from 25 hospitals (including Chinese medicine hospitals and Western medicine hospitals) for 4 years. 30 233 consecutive inpatients using Diemailing Kudiezi injection were observed. Their general information was analyzed by using statistic frequency description. Association rules were used to analyze the correlation between comorbidities or drug combinations; the influential factors for ADRs were initially screened by using cross contingency method and Chi-square test, and then Group LASSAO method was used for further analysis. 54 patients with adverse drug events and 30 patients with ADRs were reported among 30 233 patients, with a total ADR incidence of 0.099%[95%CI (0.06%, 0.13%)]. There were 27 patients identified as the "general" ADR, one patients with "severe" ADR (anaphylactic shock) and two patients with new ADRs. ADR occurred most in 30 min after using Diemailing Kudiezi injection, in a total of 16 patients. The most ADRs were palpitation, vomiting, chills, pruritus and rash, 6 times for each symptom. Diemailing Kudiezi injection was well tolerated in the general population. The overall incidence of adverse reactions was rare, with high safety. However, the real incidence of ADRs may be underestimated in this study, and the blood samples were not obtained for the patients, so further mechanism studies shall be conducted.

OBJECTIVE: To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China. METHODS: A prospective, multicenter and registry study was carried out in 2,558 patients at 7 representative clinical sub-centers during November 3, 2016 to February 17, 2019. A questionnaire was used to collect information of patients regarding CM syndromes and constitutions and associated risk factors. Additionally, stroke recurrence was defined as a primary outcome indicator. RESULTS: A total of 327 (12.78 %) patients endured recurrence events, 1,681 (65.72%) were men, and the average age was 63.33 ± 9.45 years. Totally 1,741 (68.06%) patients suffered first-ever ischemic stroke, 1,772 (69.27%) patients reported to have hypertension, and 1,640 (64.11%) of them reported dyslipidemia, 1,595 (62.35%) patients exhibited small-artery occlusion by The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Specifically, 1,271 (49.69%) patients were considered as qi-deficient constitution, and 1,227 (47.97%) patients were determined as stagnant blood constitution. There were 1,303 (50.94%) patients diagnosed as blood stasis syndrome, 1,280 (50.04%) patients exhibited phlegm and dampness syndrome and 1,012 (39.56%) patients demonstrated qi deficiency syndrome. And 1,033 (40.38%) patients declared intracranial artery stenosis, and 478 (18.69%) patients reported carotid artery stenosis. The plaque in 1,508 (41.36%) patients were of mixed. Particularly, 41.09% of them demonstrated abnormal levels of glycated hemoglobin levels. CONCLUSIONS Recurrence in minor and small-artery stroke cannot be ignored. Hypertension, dyslipidemia, abnormal HbA1c, intracranial artery stenosis and carotid plaque were more common in stroke patients. Particularly, phlegm-dampness and blood stasis syndromes, as well as qi deficiency and blood stasis constitutions, were still the main manifestations of stroke. (Trial registration at ClinicalTrials.gov No. NCT03174535).
Aged ; Constriction, Pathologic ; Female ; Hospitals ; Humans ; Hypertension ; Ischemic Stroke ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Prospective Studies ; Stroke/epidemiology* ; Syndrome