OBJECTIVE To explore the safety and efficacy of tocilizumab in the treatment of refractory anti-N-methyl-D-aspartate receptor encephalitis in children, and to provide reference for the treatment of this disease. METHODS The clinical manifestations, diagnosis and treatment, safety and efficacy of tocilizumab in a case of refractory anti-NMDAR encephalitis in Children’s Hospital, Zhejiang University School of Medicine were analyzed retrospectively, and the relevant literature was reviewed. RESULTS The clinical symptoms of the patient were not improved after 2 doses of methylprednisolone, immunoglobulin and 6 doses of rituximab. After 6 doses of tocilizumab, the modified Rankin scale(mRS) score was improved without adverse reactions. CONCLUSION Tocilizumab, as a escalation second-line immunotherapy, is effective and well tolerated in the treatment of refractory anti-NMDAR encephalitis. It is one of the potential therapeutic means.

To explore the clinical and genetic features of Aicardi-Goutières syndrome (AGS) caused by IFIH1 gene mutation.

Structural valve degeneration (SVD) and bioprosthetic valve failure (BVF) seriously limits the service life of biological valves. Exploring the molecular mechanism and pathological process of SVD and BVF is an important way to improve valve durability and prognosis of patients with biological valves replacement. In this review, we systematically summarized the definition, pathogenesis, related molecular pathways and prevention strategies of SVD and BVF. This review is expected to provide a theoretical basis for the study of the mechanism of SVD and BVF and the development of clinical intervention targets.

【Objective】 To investigate the effect of allogeneic platelet-rich on the healing and regeneration of diabetic foot wounds. 【Methods】 A total of 86 patients with diabetic foot ulcer treated in our hospital from January 2019 to June 2020 were selected for this study. They were divided into 2 groups by the random number table method, with 43 patients in each group. The control group was given conventional treatment according to the Guidelines for the Diagnosis and Treatment of Diabetic Foot in China, and the observation group was further treated with platelet-rich gel (APG) from the allogeneic blood bank.The clinical efficacy, general conditions, wound conditions, inflammatory factors, serum levels of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF) and hyaluronic acid (HA) were compared between the two groups. 【Results】 The total effective rate of patients in the observation group was 93.02%, higher than 76.73% in the control group (P<0.05). The wound healing time (15.08±3.19 vs 17.38±4.02) d and hospitalization time (16.12±4.03 vs 18.27±5.11) d in the observation group were shorter than those in the control group (P<0.05). Before treatment, there were no significant differences in hsCRP (4.25±0.39 vs 4.10±0.41) mg/L, TNF-α (5.70±1.29 vs 5.81±1.33) μ g/L and IL-6 (96.38±24.02 vs 99.64±25.17) mg/L between the two groups (P>0.05). After treatment, hsCRP (2.35±0.50 vs 2.83±0.44) mg/L, TNF-α(3.15±0.82 vs 4.02±1.07) μ g/L and IL-6 (50.82±18.54 vs 72.93±20.25) mg/L in the observation group were lower than those in the control group (P < 0.05). Before treatment, there were no significant differences in TGF-β 1 (5.66±1.25 vs 5.81±1.31) ng/L, VEGF (11.03±3.62 vs 10.83±3.72) μ g/L and ha (71.19±20.84 vs 70.82±21.03) mg/L between the two groups (P>0.05). After treatment, the levels of TGF-β 1 (17.29±4.09 vs 14.03±3.72) ng/L, VEGF (43.03±14.17 vs 37.04±11.05) and ha (177.96±39.08 vs 151.94±36.17) in the observation group were higher than those in the control group (P<0.05). 【Conclusion】 On the basis of conventional treatment, allogeneic blood bank concentrated platelet APG can effectively improve the curative effect of diabetic foot wound and shorten the wound healing time and hospitalization time. The mechanism may be related to reducing the level of inflammatory factors and increasing TGF-β 1, VEGF and HA.

OBJECTIVE: To explore the genetic basis of a patient presenting with dysmorphism, intellectual disability, psychomotor delay and hypoplasia of corpus callosum by using next generation sequencing. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his family members and subjected to exome sequencing. Suspected variants were verified with Sanger sequencing. RESULTS: The patient was found to carry a heterozygous c.1357delAinsGGA variant in exon 11 of the TCF4 gene, which was verified as de novo by Sanger sequencing. The variant may result in a truncated protein and affect its function. CONCLUSION The heterozygous c.1357delAinsGGA variant the TCF4 gene probably underlies the disease in the proband.
Facies ; Genetic Testing ; Humans ; Hyperventilation/genetics* ; Intellectual Disability/genetics* ; Male ; Transcription Factor 4/genetics*

AIM: To study the bioequivalence of rosuvastatin calcium tablets produced by two different manufacturers on a fasting and postprandial basis in Chinese healthy subjects. METHODS: A single-center, randomized, balanced, open, two-sequence, two-cycle, double-crossover, and single-dose trial design was used in this study. Each of the fasting group and the postprandial group was enrolled in 52 healthy subjects. Fasting/postprandial oral rosuvastatin calcium tablets 10 mg test preparation or reference preparation, the validated LC-MS/MS method was used to determine the concentration of rosuvastatin calcium tablets in plasma, and the pharmacokinetic parameters were calculated. Human bioequivalence and safety evaluation of two rosuvastatin calcium tablets were evaluated. RESULTS: The t

Objective: To evaluate the predictive value of 3 different risk stratification models including the risk adjustment in congenital heart surgery-1 (RACHS-1), Aristotle basic complexity (ABC), and Society of Thoracic Surgeons-European Association for cardiothoracic surgery congenital heart surgery mortality score (STAT) risk scoring system for death and major complications in patients after congenital heart surgeries. Methods: A total of 3 578 patients (age<18 years old) received surgery for congenital heart diseases from January to December 2015 in Fuwai hospital were enrolled, and the clinical data were retrospectively analyzed. The congenital heart disease patients were 1.7 (0.8, 4.5) years old, and the male accounted for 54.3% (1 943 cases).Death after surgery and major complications including use of extracorporeal membrane oxygenation, bedside thoracotomy, peritoneal dialysis for renal failure, bedside hemofiltration for renal failure, tracheotomy, reoperation for mediastinum infection, reoperation for heart in hospital were observed. The area under the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive value for mortality after surgery and major complications with RACHS-1, ABC, and STAT risk scoring systems. Results: The mortality after surgery was 0.4% (14/3 578) , and the rate of major complications was 3.2% (113/3 578) . For mortality after surgery, areas under the ROC curve were 0.682 (95%CI 0.570-0.795, P=0.002), 0.722 (95%CI 0.612-0.832, P<0.001), and 0.753 (95%CI 0.659-0.847, P<0.001) with RACHS-1, ABC and STAT risk scoring systems, respectively. For major complications, areas under the ROC curve were 0.709 (95%CI 0.667-0.751, P<0.001), 0.743 (95%CI 0.702-0.784, P<0.001), and 0.731 (95%CI 0.693-0.770, P<0.001) with RACHS-1, ABC and STAT risk scoring systems, respectively. Conclusion STAT risk scoring system is superior to RACHS-1 and ABC risk scoring systems on predicting death after surgery, and ABC risk scoring system is superior to RACHS-1 and STAT risk scoring systems on predicting major complications in Chinese patients with congenital heart disease in the single center.

OBJECTIVE:To investigate effectiveness and safety of rh-endostatin in the treatment of keloid.METHODS:Sixty-four keloid patients in Nanchong Central Hospital during Jan.2015-Jan:2016 were divided into observation group and control group by random number table,with 32 cases in each group.Both group received fractional CO2 laser treatment.After surgery,control group was given antioxidant drug and antibiotics routinely.Observation group was additionally given Rh-endostatin injection 0.1-0.2 mg/cm2 via keloid body,once a month,for twice,on the basis of control group.Clinical efficacy,symptom score after laser treatment and 2 months after laser treatment,wound healing time,wound pigmentation area and keloid area before and after treatment,the occurrence of ADR were compared between 2 groups.RESULTS:There was no statistical significance in total re sponse rate (93.75％ vs.87.50％) and the incidence of ADR (15.63％ vs.12.50％) between observation group and control group (P＞0.05).There was no statistical significance in symptom score of control group between after laser treatment and after 2 months of treatment (P＞0.05).The erythema,edema and pigmentation scores of observation group were significantly lower than before treatment and control group,with statistical significance (P＜0.05);there was no statistical significance in skin itching and burning sensation score between 2 groups (P＞0.05).The wound incrustation time,decrustation time and wound healing time of observation group were significantly shorter than those of control group,with statistical significance (P＜0.05).Pigmentation area and keloid area of 2 groups were significantly smaller than before,and the observation group was significantly smaller than the control group,with statistical significance (P＜0.05).CONCLUSIONS:Rh-endostatin can alleviate erythema,edema,pigmenta tion and other symptoms effectively,shorten healing time,and inhibit pigmentation and keloid regeneration effectively with good safety.

BACKGROUND: Inhibiting the degradation of extracellular matrix in the intervertebral disc can delay the degenerative process of intervertebral disc. Matrix metalloproteinases-3 (MMP3) is considered as a key enzyme for degradation of extracelular matrix components such as type II collagen and aggrecan.
OBJECTIVE:To construct the short hairpin RNA lentiviral vector targeting human MMP3 gene and to detect its efficiency of gene silence by infecting human degenerative nucleus pulposus cells.
METHODS:According to the human MMP3 mRNA (NM_002422.4) sequence, four groups of the short hairpin RNA gene sequences targeting MMP3 were designed, synthesized and annealed to form double stranded DNA fragments, which were connected with the LV3 vectors digested by BamHI andEcoRI enzymes, and then transfected into the competent cels. The positive clones were identified by PCR, and analyzed by sequencing. The packaging and titer of lentivirus were determined after transfecting 293T cells. Human degenerative nucleus pulposus cels were infected with lentivirus vector, and the transfection efficiency of each group was observed under inverted fluorescence microscope. The interfering efficiency was detected by real time-PCR and western blot at 72 and 96 hours.
RESULTS AND CONCLUSION:The ds-oligo DNA was successfully inserted into the lentiviral vector as confirmed by electrophoresis and sequence analysis. The recombinant lentivirus was harvested from 293T cels with a viral titer of 1-5 ×108 TU/mL. RNA interference targeting the GCC AGG CTT TCC CAA GCA AAT sequences with the highest interfering efficiency in MMP3 gene at 72 and 96 hours resulted in suppression of MMP3 mRNA expression by 98% and 72%, respectively; and at 96 hours, the interfering efficiency of protein expression was 57.2%. The recombinant lentivirus vector containing RNA interference targeting MMP3 gene is successfuly constructed, which lays a foundation for further studies on the MMP3 function and gene therapy.

Objective: To compare the long term prognosis between revascularization (REV) and medical therapy (MP) in patients with three-vessel disease (3VD) with or without left main (LM) lesion.
Methods: A total of 4,875 consecutive patients with elective coronary angiography (CAG) diagnosed 3VD with or without LM lesion treated in our hospital from 2007-01 to 2008-12 were retrospectively studied. The patients were divided into 2 groups: MT group,n=705 (14.5%) and REV group,n=4170 (85.5%). The all cause mortality and the rate of revascularization during follow-up period were compared between 2 groups by inverse-probability-weighting approach with propensity score.
Results: There were 3962/4875 (81.3%) patients with simple 3VD (right, left anterior descending and left circumlfex coronary arteries) and 913 (18.7%) with 3VD+LM lesion. The in-hospital mortality was similar between 2 groups (OR=0.7, 95% CI 0.3-1.4,P=0.30). With the longest 2-year follow-up study, the adjusted all cause mortality and the rate of revascularization in MT group were both higher than those in REV group (HR=8.3, 95% CI 6.7-11.1,P<0.001) and (HR=1.4, 95% CI 1.1-1.6,P<0.001). No matter the patients with simple 3VD or 3VD+LM lesion, compared with REV group, MT group had the higher all cause mortality, for 3VD+LM lesion (HR=10.4, 95% CI 7.1-15.4,P<0.001) and for simple 3VD (HR=7.1, 95% CI 5.3-10.0,P<0.001).
Conclusion: In real world, the long term prognosis by revascularization treatment was superior to medical treatment in patients with either simple 3 vessel coronary disease or 3 vessel combining LM disease.