Calcineurin inhibitors,such as cyclosporin A and tacroli mus,are widely-used i mmuno-suppressive drugs clinically.However,renal toxicity,hyperglycae mia and other side-effects can occur over long-term use.Isolation of novel calcineurin inhibitors fro m medicinal plants in recent years has pro-vided a new approach to the development of new immunosuppressive drugs with high efficiency and low toxicity.Recnt studies have shown that medicinal plant extracts, such as isogarcinol, quercetin, kae mpferol,phenylethanoid glycosides,ere mophilane sesquiterpenes A and B,pisiferdiol,as well as extracts fro m Smilax china L and Jasminum humile L,have obvious inhibitory effect on calcineurin.

Calcineurin (CaN) serves as a key enzyme in human immune regulation. The most important target of this enzyme is the transcription factors of nuclear factors of activated T cells (NFATc). The discovery of the immunosuppressive function of CaN inhibitors (CNIs),ciclosporin A (CsA) and tacrolimus (FK506),has helped overcome the immune rejection of organ transplantion and changed organ transplantion fundamentally. Both of these drugs are still widely used in clinical and basic research,but their therapeutic effects are limited by their serious side effects,including renal tox?icity and neurotoxicity. Therefore,the development of new CNIs with higher specificity and fewer side effects in the clinic is a focus of research. In this paper,the newly discovered and synthesized CNIs in recent decades,including the CsA and FK506 derivatives,direct inhibitors of CaN,as well as the inhibitors that specifically interfere with CaN-NFATc interaction,were summarized.

OBJECTIVE To investigate the clinical characteristics,treatment and prognosis of laryngotracheal stenosis due to relapsing polychondritis (RP).METHODS The clinical data of 6 patients with laryngotracheal stenosis due to RP were reviewed retrospectively.RESULTS From 1996 to 2006,6 patients with laryngotracheal stenosis due to RP were managed in our hospital.Respiratory tract lesions were diffuse and extensive.Of them,4 patients accepted laryngotracheal reconstruction using surgical flaps with or without pedicle,2 accepted dilation of trachea in thoracic segments.Five patients were cured without recurrence.CONCLUSION Treatment of laryngotracheal stenosis due to RP is very difficult.If the surgical opportunity and methods were selected correctly according to each patient,good results can also be obtained.

Objective To compare wedge biopsy and disposable automatic biopsy gun biopsy for the diagnosis of pancreatic cancer. Methods The clinical data of 217 patients with unresectable pancreatic cancer undergoing palliative operation and biopsy were retrospectively analyzed in our hospital from March 25,2006 to March 25,2011.Group A(wedge biopsy) consisted of 120 cases and B( disposable automated biopsy gun biopsy) of 97 cases.The success rate of biopsy,the positive rate of biopsy,the accuracy of diagnosis and the incidence of postoperative complications were calculated. Results The success rate,positive rate,diagnostic accuracy and the incidence of postoperative hemorrhage of group A and B were 100％,97.5％,97.5％,1.7％ and 100％,99％,99％,1.0％,respectively ( all P ＞ 0.05 ).The incidence of postoperative pancreatic leakage in group A and B were 11.7％ and 2.1％ (P =0.007 ).Conclusions Intra-operative biopsy for the diagnosis of pancreatic cancer using disposable automated biopsy gun biopsy has significantly decreased the incidence of post-biopsy pancreatic leakage as compared with wedge biopsy.

Minocycline is the second generation semisynthetic tetracycline antibiotics.A variety of animal models and clinical trials have shown that it has neuroprotective effect.Its mechanism is associated with inhibiting apoptosis, alleviating inflammatory reaction, reducing infarct volume, and alleviating vascular injury.This article reviews the neuroprotective effect of minocycline in preclinical phase and early clinical trials of acute ischemic stroke.

BACKGROUND:Kinesin II family member 3A (KIF3A), as an important member of the kinesin-2 family, not only holds some general characters of kinesin including the regulation of intracel ular transport and mediation of microtubule movement, but also possesses its own specific features.
OBJECTIVE:To review the research progress of the function of KIF3A recently.
METHODS:A computer-based online research for relative literatures published from January 1996 to July 2016 was performed in PubMed and CJFD databases using the English retrieval words of“KIF3A;kinesin;molecular motor”and Chinese keywords of“kinesin;microtubule;function;molecular motor;spinal cord injury”, respectively. A total of 92 articles were retrieved, and 62 eligible articles were included according to the inclusion criteria.
RESULTS AND CONCLUSION:KIF3A is involved in new bone formation regulation, in the control of nephron number, cell survival and gene expression, in sperm formation and in the inhibition of prostate cancer and glioblastoma process:In the meanwhile, whether KIF3A is involved in spinal nerve injuries is discussed. All provide valuable new information and new ideas for further in-depth study on the KIF3A.

Objective:To investigate the difference of radiofrequency ablation combined with ethanol ablation and radiofrequency ablation in the treatment of benign cystic solid thyroid nodule.Methods:A total of 80 patients who visited the Thyroid Surgery Department of the First Affiliated Hospital of Zhengzhou University from January 2015 to July 2018 were selected. All selected patients are required to meet the following criteria: (1)Color doppler ultrasonography of the neck revealed a cystic solid thyroid nodule greater than 20 mm in diameter. (2) The results of fine needle aspiration cytology of thyroid nodules were benign. (3)The patients is to undergo radiofrequency ablation of thyroid nodule. According to the condition and patients′ wishes, radiofrequency ablation (Group A, n=40) and combined ethanol and radiofrequency ablation(Group B, n=40) were performed respectively to observe the changes of nodule volume and maximum diameter at 3, 6 and 12 months after surgery.The difference of intraoperative radiofrequency ablation energy, postoperative complications and patient satisfaction at 12 months after operation were also observed. The respective clinical effects of the two groups and the difference of curative effects between the two groups were analyzed. Two-factor repeated measurement analysis of variance or independent sample t test was used to compare the measurement data in line with normal distribution between groups. Friedman′s rank sum test was used for comparison of measurement data groups that did not conform to normal distribution, and Bonferroni correction was used for pairwise comparison. Chi-square test was used to compare the counting data between groups. Results:On the 12th months after operation, the volume reduction of of nodules in group B was greater than that of group A, and the difference was statistically significant[(7.0±5.1) mL vs (5.5±4.9) mL, P<0.05]. The maximum diameter reduction of nodules in group B was greater than that of group A and the difference was statistically significant [(1.5±0.6) cm vs (1.4±0.8) cm, P<0.05]. During the period of 6 to 12 months after operation, the trend of nodular shrinkage in group B was more obvious than that in group A ( P<0.05). The radiofrequency ablation energy of group was lower than that of group A, and the difference was statistically significant [(2.37±1.18) kJ vs (3.89±1.17) kJ, P<0.05]. Voice reduction occurred in 2 cases and recovered within 2 weeks.Local bleeding occurred in 1 case during the operation, which was stopped after ablation. There was no statistical significance in the satisfaction of patients in group A and group B (87.5% vs 90%, P>0.05). Conclusion:Compared with radiofrequency ablation, radiofrequency ablation combined with ethanol ablation for benign cystic solid thyroid nodules can achieve better nodule reduction effect and reduce the ablation energy.

Objective:To assess the prognostic value of modified Charlson comorbidity index (mCCI) combined with serum albumin for long-term prognosis in peritoneal dialysis (PD) patients.Methods:From January 1, 2007 to June 30, 2015, patients who started PD in Nanjing Drum Tower Hospital were enrolled in this retrospective cohort study. Clinical data including gender, age, underlying diseases, laboratory examination and prognosis were collected. The mCCI at the beginning of PD was calculated. Whether the duration of PD exceeded 5 years was used as an indicator to evaluate the prognosis. The patients were divided into≥5 years group and<5 years group according to the duration of PD, and the data were compared between the two groups. Cox regression model was constructed to analyze the influencing factors of all-cause death in PD patients. Multivariate logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the predictive value of mCCI and serum albumin levels on whether patients could maintain long-term PD.Results:Of the 183 patients included [males 106(57.9%), females 77(42.1%); (53.35±16.50) years old; 162 cases (88.5%) with hypertension, 55 cases (30.1%) with diabetes], 97 cases had PD duration for ≥5 years and 86 cases less than 5 years. The overall 5-year technical survival rate was 65.1%. At the beginning of PD, compared with the dialysis age≥5 years group, the patients in the dialysis age less than 5 years group had older age, higher mCCI, lower serum albumin level, and higher C-reactive protein (CRP) level (all P<0.05), but there were no significant differences in gender, education level, electrolyte, mean arterial pressure, high densitv lipoprotein (HDL), low-density lipoprotein (LDL) and PD adequacy index between the two groups (all P>0.05). Multivariate logistic regression analysis showed that increased age ( OR=1.022, 95% CI 1.000-1.043, P=0.046), increased mCCI ( OR=1.620, 95% CI 1.300-2.018, P<0.001) and decreased serum albumin ( OR=0.807, 95% CI 0.730-0.893, P<0.001) were independent predictors for the duration of PD<5 years. ROC curve analysis showed that the area under ROC curves ( AUC) of mCCI, serum albumin level and combined prediction probability of the two for the duration of PD<5 years were 0.647(95% CI 0.568-0.727), 0.655(95% CI 0.577-0.734), and 0.767(95% CI 0.700-0.835), respectively, indicating that the accuracy of combined parameters to predict survival outcome was higher than that of any single parameter. Multivariate Cox analysis showed that increased age ( HR=1.073, 95% CI 1.046-1.100, P<0.001), increased mCCI ( HR=1.198, 95% CI 1.044-1.375, P=0.010) and decreased serum albumin ( HR=0.904, 95% CI 0.843-0.969, P=0.004) were independent influencing factors for all-cause death in PD patients. Conclusions:Old age, high mCCI and low serum albumin level are influencing factors for dialysis age<5 years and all-cause death in PD patients. mCCI combined with serum albumin level can improve the accuracy of predicting the long-term dialysis in PD patients.

Objective:To investigate the effect of the musculo-periosteum flap of the sternocleidomastoideus with clavicular periosteum on the reconstruction of extensiveness laryngotracheal defect. Method: Retrospectively studied 49 patients, who admited in our department from 1996 to 2005 years for severe laryngotracheal defect. There were 28 males and 21 females aged from 15 to 69 years old (mean age was 47 years old). The causes of laryngotracheal defect were laryngotracheal stenosis(31 cases) and surgery for thyroid carcinoma invading trachea (18 cases). All of 49 cases were treated with the graft of musculo-periosteum flap of the sternocleidomastoideus with clavicular periosteum and placed a silicon T-tube stenting for 3 to 6 months. Result; All of 49 cases were successfully decannulated with recuperative normal airway patency and effective phonation. The follow up ranged from 2 to 10 years, and the effect of operation was steady. Conclusion:The musculo-periosteum flap of the sternocleidomastoideus with clavicular periosteum is an ideal graft for the reconstruction of cervical extensiveness tracheal defect.

Objective To detect the expression of Mcl-1 gene in gastric cancer cell lines SGC7901 and MGC-803, and to screen the most effective Mcl-1-targeted siRNA sequence. Methods Mcl-1 expression was evaluated in human gastric cancer cell lines SGC7901 and MGC-803 by RT-PCR. Four segments of siRNAs (siRNA1, siRNA2, siRNA3 and siRNA4) targeting Mcl-1 mRNA and a no-sense control segment were designed by bioinformatic technology . Mcl-1 specific siRNAs were transfected transiently into SGC7901 and MGC-803 cells by using lipofectamine 2000 . After transfected 24 , 48 and 72 h , quantitative real-time PCR was applied to detect the mRNA expression of Mcl-1 and western-blot analysis was applied to detect the protein expression. Results Mcl-1 gene was expressed in both SGC7901 and MGC-803 cells. Overall, siRNA1 exhibited the best inhibitory effect after being transfected for 48h. The inhibition rate of mRNA level in SGC7901 group and MGC-803 group was 73.8%and 67.6%, and the inhibition rate of protein level in SGC7901 group and MGC-803 group was 79.3%and 96.1%. Conclusion Mcl-1 specific siRNA sequences were successfully designed, and siRNA1 was selected as the most effective sequence, which can simultanandeously inhibit the expression of Mcl-1 in GC7901 and MGC-803 cells.