Objective To investigate the effect and mechanism of oxycodone on the treatment of cancerous neuropathic pain in advanced colon cancer.Methods 80 cases of advanced colon cancer in department of anorectal of Shaoxing Second Hospital of Zhejiang Province from March 2015 to March 2016 were selected and randomly divided into two groups with 40 cases in each group.The control group were treated with routine clinical treatment, and the experiment group were treated with oxycodone treatment on the basis of the control group.The levels of pain score, quality of life score, serum β-EP, calcitonin gene related peptide (CGRP) and prostaglandin E2(PGE2), clinical efficacy and adverse reaction incidence rate changes were compared between two groups before and after treatment.Results Compared with before treatment, levels of the pain score, serum β-EP, CGRP and PGE2 decreased in two groups after treatment, after treatment, the experiment group pain score (2.38 ±0.34), quality of life score (28.39 ± 3.97), serumβ-EP (228.71 ±34.92), CGRP (22.46 ±3.15), PGE2 level (2.45 ±0.35) and the incidence of adverse reactions was 17.50%, were lower than that of the control group the pain score (3.51 ±0.51), the quality of life score (33.53 ±4.76), serum β-EP (246.67 ±34.83), CGRP (30.36 ±4.25), PGE2(3.36 ±0.47) and the incidence of adverse reactions was 40.00%, the difference was statistically significant (P<0.05), the total effective rate of the experiment group was 87.50%, higher than that of the control group, the total effective rate was 60.00%, the difference was statistically significant (P<0.05).Conclusion Oxycodone can effectively reduce pain in patients with advanced colon cancer neuropathic pain score, improve the quality of life, and has high clinical efficacy and safety.

Objective To study the effect o f levamisole against the invasion of Schistosoma japonicum cercariae. Methods Mice infected wit h Schistosoma cercariae were administered orally with levamisole hydrochloride or alkali levamisole two days before the infectio n at a dose of 26.25 mg/kg for 7 days. The liniments of levamisole hydrochlorid e and alkali levamisole were embrocated on the mouse skin two days, one day and 0 day before the infection respectively, and the concentrations of the drug were 1%, 2%, 3%, 5% and 7% respectively. The experimental animals were dissected 4 we eks after the treatment and adult worms were collected. Results The worm reduction rates of mice administered orally with leva misole hydrochloride or alkali levamisole were both 0. The worm reduction rates were both 100% when the mice were embrocated with 5% levamisole hydrochloride on the infection day or with 7% levamisole hydrochloride one day before the infect ion. The worm reduction rates were all 100% when the mice were embrocated with 2 %, 3% or 5% alkali levamisole one day before the infection. Conc lusions Levamisole liniments can prevent from S . japonicum cercaria infection, and alkali levamisole is better th an levamisole hydrochloride. When levamisole is given orally, no effect was show n.

ObjectiveTo observe the effe ct of varnish“Fangyouling” preventing skin invasion from Schist osoma cercariae. MethodsThe“Fangyouling” was made from niclo s amide and permeable improver, and the concentration of the drug was 1%-2%. Exper imenta l mice and rabbits were spread with “Fangyouling” on the abdomen skin without h air at day 1,2,3,4,5,6,7 respectively before infection, compaired with cont rol group. ResultsThe worm reduction rates of mice which were spread with drug 1-4 days and 5-7 days before infection were 100 % and 99 7%-88 1%. The worm reduction rates of rabbits which were spread with dr ug 3-7 days before infection were 86 4%-80 1%. ConclusionThe“Fangyouling” has long efficiency on preventing Schistosoma cercariae from invading skin.

Nuclear factor erythroid-2 related factor 2 ( Nrf2 ) is an important nuclear transcription factor which protects cells a-gainst oxidative stress injury. Upon exposure to reactive oxygen species ( ROS) or electrophilic stress, Nrf2 can translocate into the nucleus, and then bind to the antioxidant response element ( ARE) , regulating the expression of several antioxidant enzymes and phase Ⅱ detoxifying enzymes which aimed at the detoxifica-tion and elimination of harmful exogenous chemicals, resulting in the facilitation of hepatoprotection. Oxidative stress is the com-mon pathogenesis of many liver diseases, while the Nrf2-ARE signaling pathway is extremely important in the prevention and progression of many liver diseases. Nrf2 has more recently been implicated as a new therapeutic target in treating liver diseases. Here, we focus on the most common liver diseases and the devel-opment of these conditions where activation of Nrf2 may alleviate disease progression, so as to provide reference for related re-search in the future.

Pigment epithelium derived factor (PEDF) has been proven to be an effective drug for the treatment of choroidal neovascularization (CNV). However, the lack of ideal administration route is the biggest bottleneck preventing PEDF from wider clinical use. In this study, we developed a novel PEDF-carrying system which employed immuno-nano-liposomes (INLs) under ultrasound exposure. PEDF-loaded INLs were prepared by conjugating nanoliposomes to the peptide ATWLPPR specifically targeting the receptor-2 for vascular endothelial growth factor (VEGFR-2) and reversely encapsuling PEDF. RF/6A cells were incubated with PEDF-loaded INLs. CNV models of BN rats were injected with PEDF-loaded INLs. MTT assay was used to evaluate the cytotoxicity of the INLs on RF/6A cells. Flow cytometry was conducted to detect the apoptotic rate of cells. Laser scanning confocal microscopy was employed to observe the binding and transmitting process of PEDF-loaded INLs and to calculate the area of CNV in the rat model. The results showed that the PEDF-loaded INLs could exclusively bind to CNV but not to the normal choroidal vessels. The CNV area was significantly decreased in PEDF treatment groups in comparison with control group (P<0.05). Moreover, PEDF-loaded INLs exposed under ultrasound were more efficient in reducing the CNV area (P<0.05). It was concluded that INLs in combination with ultrasonic exposure can transmit PEDF into cytoplasma with high specificity and efficiency, which strengthens the inhibitory effects of PEDF on CNV and reduces its side effects. PEDF-loaded INLs possibly represent a new treatment paradigm for patients with ocular neovascularization.

Objective:To evaluate the cerebral blood flow circulation time (CCT) by contrast-enhanced ultrasound, and to explore the change rule of CCT in different degree of intracranial pressure, so as to provide a new method for non-invasive monitoring of intracranial pressure.Methods:Ten patients with hemorrhagic stroke or acute craniocerebral trauma with increased intracranial pressure were selected from Tangdu Hospital, the Air Force Military Medical University from January to December 2019. Contrast-enhanced ultrasound was performed when the invasive intracranial pressure (iICP) increased (>20 mmHg, iICP increased group) and decreased to normal (≤20 mmHg, iICP normal group), CCT was measured and analyzed. The differences of CCTs between different iICP groups were compared and the relationship between CCT and iICP was analyzed.Results:①The CCT on the lesion sides of the same patients in the iICP increased group was significantly longer than in the iICP normal group[(9.34±2.58)s vs (6.48±1.91)s, P=0.002]. ②When iICP was increased in patients with hemorrhagic stroke or acute craniocerebral trauma, the CCTs of the diseased side and the non-pathological side were not statistically significant [(9.34±2.58)s vs (9.01±3.22)s, P=0.809]. ③Pearson correlation analysis and Spearman rank correlation analysis showed that there were no correlations between patient′s breathing, heart rate, carbon dioxide partial pressure, body temperature, GCS score and CCT (all P>0.05). Age, mean arterial pressure and CCT were moderately correlated ( r=0.518, 0.463 and P=0.023, 0.046, respectively). ④Logistic regression analysis showed that CCT was an independent risk factor related to intracranial hypertension( OR=0.7, 95% CI=0.47-0.95, P=0.036). The area under ROC curve (AUC) predicted by logistic regression was 0.750(0.588~0.912). Conclusions:Contrast-enhanced ultrasound noninvasive assessment of CCT can reflect the intracranial pressure in patients with hemorrhagic stroke or acute traumatic brain injury, and CCT has a predictive value for intracranial hypertension. When the patient has limited conditions for invasive intracranial pressure monitoring, or when the invasive monitoring probe is pulled out but still needs to evaluate intracranial pressure, the change of CCT can provide an effective reference for clinical diagnosis and treatment.

Objective To investigate the changes in cerebral hemodynamic parameters in patients with migraine and different grades of patent foramen ovale(PFO)using contrast-enhanced transcranial Doppler(cTCD)foaming test and contrast-enhanced transthoracic echocardiography(cTTE).Methods A total of 85 patients with migraine in our hospital were enrolled,and cTCD and cTTE were used in combination to determine whether a subject had right to left shunt(PFO-RLS)caused by PFO,which was graded according to the grading criteria(grades 0,Ⅰ,Ⅱ,and Ⅲ).Meanwhile,TCD was used to observe the ultrasound parameters of the middle cerebral artery before and after Valsalva maneuver(VM),in-cluding peak systolic blood flow velocity(Vs),mean blood flow velocity(Vm),peak diastolic blood flow velocity(Vd),resistance index,and pulsatility index,and these ultrasound parameters were compared between grade 0 PFO-RLS and grade Ⅰ/Ⅱ/Ⅲ PFO-RLS.Results Among the 85 subjects,13 patients had migraine with grade 0 PFO-RLS,34 patients had migraine with grade I PFO-RLS,17 patients had migraine with grade Ⅱ PFO-RLS,and 21 patients had migraine with grade Ⅲ PFO-RLS.The results before VM showed that compared with the patients with migraine and grade 0 PFO-RLS,the patients with migraine and grade Ⅱ PFO-RLS had significant increases in Vs,Vm,and Vd(P<0.05),and the results after VM showed that compared with the patients with migraine and grade 0 PFO-RLS,the patients with migraine and grade Ⅲ PFO-RLS had significant increases in Vm and Vd(P<0.05).Conclusion There are different changing trends of cerebral blood flow in patients with migraine and different grades of PFO-RLS,and the characteristic changes in cere-bral blood flow can provide a certain clinical theoretical basis for the etiological diagnosis and treatment of patients with mi-graine.

Pigment epithelium derived factor (PEDF) has been proven to be an effective drug for the treatment of choroidal neovascularization (CNV). However, the lack of ideal administration route is the biggest bottleneck preventing PEDF from wider clinical use. In this study, we developed a novel PEDF-carrying system which employed immuno-nano-liposomes (INLs) under ultrasound exposure. PEDF-loaded INLs were prepared by conjugating nanoliposomes to the peptide ATWLPPR specifically targeting the receptor-2 for vascular endothelial growth factor (VEGFR-2) and reversely encapsuling PEDF. RF/6A cells were incubated with PEDF-loaded INLs. CNV models of BN rats were injected with PEDF-loaded INLs. MTT assay was used to evaluate the cytotoxicity of the INLs on RF/6A cells. Flow cytometry was conducted to detect the apoptotic rate of cells. Laser scanning confocal microscopy was employed to observe the binding and transmitting process of PEDF-loaded INLs and to calculate the area of CNV in the rat model. The results showed that the PEDF-loaded INLs could exclusively bind to CNV but not to the normal choroidal vessels. The CNV area was significantly decreased in PEDF treatment groups in comparison with control group (P<0.05). Moreover, PEDF-loaded INLs exposed under ultrasound were more efficient in reducing the CNV area (P<0.05). It was concluded that INLs in combination with ultrasonic exposure can transmit PEDF into cytoplasma with high specificity and efficiency, which strengthens the inhibitory effects of PEDF on CNV and reduces its side effects. PEDF-loaded INLs possibly represent a new treatment paradigm for patients with ocular neovascularization.
Animals ; Choroidal Neovascularization ; drug therapy ; Drug Delivery Systems ; Eye Proteins ; therapeutic use ; Female ; Liposomes ; administration & dosage ; Male ; Nanoparticles ; administration & dosage ; Nerve Growth Factors ; therapeutic use ; Peptides ; administration & dosage ; Rats ; Rats, Inbred BN ; Serpins ; therapeutic use ; Ultrasonics ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

To evaluate the accuracy of transcranial color‐code sonography ( TCCS) in non‐invasive assessment of intracranial pressure( ICP ) . TCCS was used to monitor the cerebral hemodynamic parameters of patients with acute severe traumatic brain injury after decompressive craniectomy and make estimation of the non‐invasive intracranial pressure ( ICPtccs) . Methods A total of 91 patients with acute severe traumatic brain injury involved in this retrospective study were divided into the ICP normal group( ≤22 mm Hg ) and the ICP increased group ( ＞22 mm Hg ) . T he correlation and consistency of middle cerebral artery blood flow parameters and ICPtccs with invasive intracranial pressure ( iICP ) were analyzed . According to Glasgow score ( GCS) ,Patients( GCS 3－8) were divided into acute extremely severe traumatic brain injury( GCS 3 －5) and acute severe traumatic brain injury ( GCS 6 －8 ) . A comparison was made of ROC ( ICPtccs) curve and the area under the curve( AUC) between the two groups were cornpared . Results①No statistical differences were found in cerebral hemodynamic parameters between the side with and without decompressive craniectomy in patients with acute severe traumatic brain injury ( all P ＞0 .05 ) . ②M onitored resistive index ( RI) ,pulsatility index ( PI) and ICPtccs between the normal ICP group and the increased ICP group showed statistically significant differences ( all P ＜ 0 .05 ) ,w hile monitored systolic velocity ,diastolic velocity and mean velocity presented no statistically significant difference ( all P ＞0 .05) . T he correlations between RI ,PI with iICP were low ( r＝ 0 .247 ,0 .221 ; all P ＜ 0 .05 ) ,w hile there was a moderate correlation between ICPtccs and iICP( r ＝0 .417 , P ＜0 .001 ) . ③Bland‐Altman plot showed an overestimation of 2 .3 mm Hg ( 95% CI 0 .00－4 .59 mm Hg ) for ICPtccs compared to iICP . ④T he AUC of Glasgow score ( GCS 3－5 and GCS 6－8) in the two groups were 0 .759 ,0 .781 ( all P ＜0 .05) . All the cut‐off points of ICPtccs were 19 mm Hg ,with a sensitivity of 83 .33% ,81 .82% and a specificity of 64 .86% , 75 .68% ,respectively . Pairwise comparison of two AUCs showed no statistical difference ( P ＝ 0 .476) . ICPtccs presented the same ability to estimate ICP in patients with acute severe and extremely severe traumatic brain injury . TCCS could accurately assess the elevation of ICP in 72 .52% patients with acute severe traumatic brain injury . Conclusions TCCS can be used as a non‐invasive screening tool to assess w hether ICP of patients with acute severe traumatic brain injury is elevated and to semi‐quantitatively estimate ICP ,showing useful clinical value .