Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".

Objective To evaluate the value of three-dimensional (3D) ultrasonic imaging of vascular volume in assessing postoperative acute rejection(AR) of renal transplant patients. Methods Color Doppler flow imaging(CDFI) and 3D vascular volumetric parameters were collected and analyzed in 30 cases with stable renal function (control group) and 13 cases with AR of kidney transplantation (AR group). The diagnostic performances of each ultrasonic parameter were compared by receiver operating characteristic (ROC) curve. Results The parameters of resistance index(RI) and pulsatility index(PI) in AR group were significantly higher than those in control group( P <0.005 and P <0. 05, respectively). Analysis of the areas under ROC curve showed that the area under VFI curve was the largest;no significant difference( P > 0. 05) was found compared the area under VFI curve to those areas under VI,FI and MG curves;Comparing the area under VFI curve to those under RI, V and PI,there were significant differences( P <0. 05). Taking VFI≤18. 78% as the critical value, the sensitivity and specificity for the diagnosis of AR of transplanted kidneys were 70. 0% and 93. 3% ,and the positive and negative predictive values were 60. 8% and 93. 4%, respectively. Conclusions The sensitivity and specifity of 3D vascular volumetric imaging parameter VFI in the diagnosis of transplanted kidneys with AR were higher than those of blood flow parameters RI and PL VFI with the optimal critical value of ≤18. 78% might be a useful index for the early diagnosis of transplanted kidneys with AR.

Objective To explore the association between the C46T polymorphism of coagulation factor Ⅻ (FⅫ) gene and the involvement of FⅫ activity (FⅫ:C) in patients with unexplained recurrent spontaneous abortion (URSA), and to elucidate its role in the pathogenesis of URSA. Methods This study included 203 patients with URSA (URSA group) and 171 healthy women with at least one child and no history of infertility or miscarriage (control group) in the southern area of Zhejiang Province. The C 46T polymorphism of the FⅫ gene was analyzed with matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS) in all subjects. The values of prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, FⅫ:C and other coagulant parameters were determined. The frequency distribution of the wild-type (CC), heterozygote (CT), homozygote (TT) genotypes and C and T alleles were compared between the patients and controls. A comprehensive analysis of association was conducted between C46T genotypes and the FⅫ:C levels in URSA patients. Results The CC, CT, TT genotypes of the FⅫgene were observed in 7 (3.4%, 7/203), 83 (40.9%, 83/203) and 113 (55.7%, 113/203) patients with URSA versus 7 (4.1%, 7/171), 46 (26.9%, 46/171) and 118 (69.0%, 118/171) controls. The frequency of CT in the patients with URSA was significantly higher than that in controls, but the frequency of TT in the patients was lower than that in controls (χ2=7.939, OR=1.884, 95%CI:1.210-2.935, P<0.05). The frequencies of allele C and allele T were observed in 97 (23.9%, 97/406) and 309 (76.1%, 309/406) patients with URSA versus 60 (17.5%, 60/342) and 282 (82.5%, 282/342) controls. The distribution frequency of allele T in URSA group was lower than that in control group (χ2=4.510, OR=1.475, 95%CI:1.029-2.115, P<0.05). The FⅫ:C levels in the patients were (102±13)%in CC genotype, (78±11)%in CT genotype and (59± 9)%in TT genotype, respectively. The differences of the FⅫ:C levels between the CC and CT, CT and TT, CC and TT genotypes in the patients were significant (all P<0.05). Conclusions The low level of FⅫ:C maybe result from the T allele of the FⅫgene in URSA patients. The CT genotype might be relative to the pathogenesis of URSA in a Chinese Han female population from the southern area of Zhejiang province.

Aim Toinvestigatetheanalgesiceffectsof epidural osthole application on the mechanical allodyn-ia and the ERK/MAPK signaling pathway and the expression of COX-2 mRNA in the spinal dorsal horn.Methods 125adultmaleSDratswererandomizedin-to five groups( n=25 each) :Blank, Sham, NP, Ost and vehicle. At postoperative day 6, 1mg/rat osthole 50 μl was injected epidurally into group Ost and the same volume of vehicle was given into group vehicle. The mechanical pain threshold was measured by 50%MWT at 1 day before operation and the 3 rd,6 th,7 th, 14 th,21 st day after operation. After the measurement of pain threshold on postoperative day 14 , the L4-6 segment of spinal dorsal horn was removed for determi-nation of the expression of ERK, pERK and COX-2 mRNAbyWesternblotandRT-PCR.Results Com-pared with blank group, the mechanical pain threshold was only down-regulated at day 1 after operation in sham group, the expression of pERK and COX-2 mR-NA in sham group showed no significant difference ( P>0. 05 ); the mechanical pain threshold was signifi-cantly down-regulated after operation in NP, Ost and vehicle groups( P<0. 05 ) and the expression of pERK and COX-2 mRNA was significantly increased ( P <0. 05). Compared with vehicle group, the pain thresh-old in Ost group was significantly increased after drug administration( P<0. 05 ) and the expression of pERK and COX-2 mRNA was significantly reduced ( P <0. 05 ) . The expression of ERK showed no significant difference among each group(P>0. 05). The correla-tion analysis on pERK1/2 and COX-2 mRNA revealed the Pearson correlation coefficient was 0 . 878 and 0 . 910 , suggesting a strong positive correlation between pERKandCOX-2mRNA.Conclusions Ostholead-ministrated in the early stage after surgery can alleviate the nucleus pulposus-induced radicular inflammatory pain probably by inhibiting the expression of pERK and COX-2 mRNA in spinal dorsal horn.

In this study, the buffering capacity of amphiphilic pH-sensitivity copolymer poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (PEOZ-CHMC) was evaluated. The ammonium sulfate gradient method was used to prepare doxorubicin hydrochloride (DOX x HCl)-loaded liposomes (DOX-L), and then the post-insertion method was used to prepare PEOZ-CHMC and polyethylene glycol-distearoyl phosphatidyl ethanolamine (PEG-DSPE) modified DOX x HCl-loaded liposomes (PEOZ-DOX-L and PEG-DOX-L). The physico-chemical properties, in vitro drugs release behavior, cellular toxicity and intracellular delivery of liposomes were evaluated, separately. The results showed that PEOZ-CHMC has a satisfactory buffering capacity. The sephadex G-50 column centrifugation method and dynamic light scattering were used to determine the encapsulation efficiency (EE) and particle size of liposomes. The EE and particle size of DOX-L were (97.3 ± 1.4) % and 120 nm, respectively, and the addition of PEOZ-CHMC or PEG-DSPE had no influence on EE and particle size. The zeta potentials of three kinds of liposomes were negative. The release behavior of various DOX liposomes in vitro was investigated by dialysis method. In phosphate buffer solution (PBS) at pH 7.4, DOX x HCl was released from PEOZ-DOX-L in a sustained manner. While in PBS at pH 5.0, the release rate of DOX x HCl from PEOZ-DOX-L increased significantly, which suggested DOX x HCl was released from PEOZ-DOX-L in a pH-dependent manner. The intracellular delivery of liposomes was investigated by confocal laser scanning microscopy (CLSM). The CLSM images indicated that PEOZ-DOX-L showed efficient intracellular trafficking including endosomal escape and release DOX x HCl into nucleus, as well as the DOX-L and PEG-DOX-L had no this effect. The cytotoxicity of liposomes against MCF-7 cells was detected by using MTT assay. The results showed that antiproliferative effects of PEOZ-DOX-L enhanced with pH value decreased, whereas DOX-L and PEG-DOX-L did not have any significant difference in inhibitions at different pH conditions. Therefore, the problems of the inhibition of cellular uptake of liposomes and the failed endosomal escape of pH-sensitive liposomes by PEG chain can be overcome by the pH-sensitive liposomes constructed by PEOZ-CHMC.

Objective To compare the efficacy of dexmedetomidine versus remifentanil in combination with sevoflurane for gynecological laparoscopy. Methods Forty ASA Ⅰ or Ⅱ patients aged 18-64 yr with body mass index of 18-30 kg/m2 undergoing gynecological laparoscopy were randomly assigned to one of two groups ( n =20 each): dexmedetomidine group (group D) and remifentanil group (group R). Starting from 5 min before induction of anesthesia, dexmedetomidine was infused at 0.05 μg · kg - 1 · min- 1 in group D and remifentanil at 0.1 μg· kg- 1· min-1 in group R for 10 min, then dexmedetomidine infusion rate was increased to 0. 3 μg· kg-1 · h-1 and remifentanil infusion rate was increased to 0.15 μg· kg-1 · min-1 . Anesthesia was induced with propofol 1.5-2.0 mg/kg and fentanyl 2 μg/kg. Tracheal intubation was facilitated with cis-atracurium 0.15 mg/kg. Anesthesia was maintained with sevoflurane and fentanyl 1 μg/kg and intermittent iv boluses of cis-atracurium. Narcotrend index was maintained at 40-50. Blood sample was taken from external jugular vein for blood gas analysis and determination of serum concentrations of corticosteroid, norepinephrine and epinephrine before administration, at 5 min after intubation, at 10 min of aeroperitoneum and at 5 min after extubation. The pH value and concentrations of lactic acid and glucose were recorded. The time for recovery of spontaneous breathing, eye-opening time, extubation time, orientation time and perioperative side-effects were recorded. Numeric rating scale was used to assess the intensity of pain during 2 h after operation. The analgesics used were also recorded. Results The serum concentrations of norepinephrine and epinephrine were significanfly lower at 10 min of aeroperitoneum, the time for recovery of spontaneous breathing was shorter, eye-opening time longer and the incidence of shivering and nausea and vomiting lower, the percentage of patients requiring rescue opioids lower in group D than in group R ( P ＜ 0.05). Conclusion The efficacy of dexmedetomidine combined with sevoflurane anesthesia is better than remifentanil combined with sevoflurane anesthesia for gynecological laparoscopy.

Mercury-containing preparations are widely used in surgery department of traditional Chinese medicine and have made remarkable achievements. But they are toxic to human kidney, nerve, immune, etc. Smilacis Glabrae Rhizoma is sweet, tasteless and neutral in nature and able to enter liver and stomach channels and detoxify mercury poisoning. This article summarizes the mercury poisoning and the detoxification effect of Smilacis Glabrae Rhizoma in ancient records, pharmaceutical studies and clinical application, in order to provide ideas and methods for the safe use of mercury-containing preparations in surgery department of traditional Chinese medicine.
Drugs, Chinese Herbal ; therapeutic use ; Humans ; Inactivation, Metabolic ; Liliaceae ; chemistry ; Liver ; drug effects ; metabolism ; Medicine, Chinese Traditional ; Mercury Compounds ; adverse effects ; pharmacokinetics ; therapeutic use ; Mercury Poisoning ; prevention & control ; Plants, Medicinal ; chemistry ; Rhizome ; chemistry ; Stomach ; drug effects ; metabolism

Objective: To investigate the clinical characteristics and outcomes of ulcerative colitis (UC) with cytomegalovirus (CMV) infection. Methods: The related data of 300 patients with UC who were treated in the department of gastroenterology of the First Affiliated Hospital of Xiamen University from January 2013 to October 2017 were analyzed retrospectively. Eighty cases with CMV infection were included into the observation group while 220 cases without CMV infection were enrolled into the control group. The disease characteristics, clinical features, treatment and outcomes were compared between the two groups. Results: For disease characteristics, course of disease in observation group was significantly shorter than that in the control group (t=18.498, P<0.05). The previous application rates of glucocorticoid and immunosuppressant in the observation group were significantly higher than those in the control group (χ²=31.241, 10.381, P<0.05). The incidence rates of glucocorticoid dependence and glucocorticoid resistance in the observation group were significantly higher than those in the control group (χ²=17.513, 64.927, P<0.05). For clinical characteristics, the incidence rates of fever, abdominal pain and weight loss in the observation group were significantly higher than those in the control group (χ²=25.112, 20.633, 13.000, P<0.05). Colonoscopy showed that the ulcer rate in observation group was significantly higher than that in the control group (χ²=15.496, P<0.05). For outcomes, the improvement rate of the observation group was significantly lower than that of the control group (55.00% vs. 79.55%) (χ²=17.933, P<0.05). Conclusions The clinical symptoms of patients with UC and CMV infection are more obvious, the disease was more serious, the ulcer rate is higher and the clinical outcomes were worse than those of uninfected patients.

OBJECTIVE: To explore the genetic etiology and clinical outcome of a child with steroid-resistant nephrotic syndrome and diffuse mesangial sclerosis. METHODS: Genomic DNA was extracted from peripheral blood leukocytes of the proband and his parents. Targeted capture - next generation sequencing and Sanger sequencing were carried out. Candidate variant was verified by segregation analysis in his family. RESULTS: A heterozygous missense variant of the TRPC6 gene, namely c.325G>A (p.Gly109Ser), was detected in the proband. The same variant was not detected in either parent. According to the guidelines for the interpretation of sequence variants developed by American College of Medical Genetics and Genomics, the variant was predicted as pathogenic. CONCLUSION The missense variant of the TRPC6 gene probably underlay the diffuse mesangial sclerosis in this patient. Above finding has expanded the phenotypic spectrum of the TRPC6 gene.
Child ; Genomics ; Humans ; Mutation, Missense ; Nephrotic Syndrome/genetics* ; Sclerosis ; TRPC6 Cation Channel/genetics*

Objective To evaluate the effects of chronic disease management on carotid atherosclerosis. Methods From May 2016 to October 2016, 500 subjects with carotid atherosclerosis diagnosed by ultrasound at the Physical examination center of the First Hospital of Jilin University were enrolled. The participants were aged 55?65(60.7±3.5) years. They were divided into the control group (n=250) and intervention group (n=250) using a random number table; a total of 20patients, 13 in the control group and 7 in the intervention group, were lost to follow-up at the end of the study. The control group only received anti-atherosclerosis treatment, while the intervention group underwent additional chronic disease management, and a 1-year follow-up study was conducted. The health of all the subjects was assessed at the beginning of the study and after the study, based on the health file. The chi-square test, two independent sample t-tests, and rank sum test were used to evaluate the effect of chronic disease management on carotid atherosclerosis. Results After 1 year of intervention, the proportion of patients with an unhealthy lifestyle (smoking, excessive drinking, high-salt diet intake, high-fat diet intake, lack of exercise, and overweight/obesity) decreased in the intervention group(10.3%, 13.1%, 7.8%, 8.6%, 6.2%, 28.0%, vs. 28.8%, 35.0%, 21.0%, 22.6%, 13.2%, 39.5%; χ2=26.49, 33.01, 17.09, 18.03, 6.80, 7.21; P<0.05), while the drug compliance increased(44.4% vs. 35.4%, χ2=4.15, P<0.05), and the total cholesterol (TC), triglyceride (TG), low density lipoproteincholesterol (LDL-C), fasting plasma glucose (FPG), uric acid (UA) and blood pressure (BP) compliance rate also increased (91.8%, 73.3%, 83.1%, 83.1%, 52.3%, 76.5%, 74.1%, 60.5%, vs. 67.5%,72.8%,28.0%,58.8%, respectively; χ2=26.86, 8.92, 15.97, 7.49, 29.81, 17.39, respectively; P<0.05); all indicators, except the drug compliance control rate, were better than those in the control group. After 1 year of intervention, the degree of carotid atherosclerosis in the intervention group was significantly reduced compared to that in the control group. Conclusions Chronic disease management could effectively interfere the control risk factors of atherosclerosis, such as smoking, drinking, obesity or overweight, BP, levels of FPG, blood lipids, and UA, improve drug compliance, delay the progression of atherosclerosis and provide a basis for the construction of the atherosclerosis management model.