Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective Observe the effect of Liuwei Anshen Capsule on sleep improvement of aged sleep deprivation zebrafish model.Methods Sixty 18-month-old female zebrafish were randomly divided into blank group,model group,Liuwei Anshen group,and melatonin group.The zebrafish in the blank group were raised under normal lighting conditions,and the other three groups were constructed with continuous lighting for 3 days.Zebrafish in Liuwei Anshen group were treated with Liuwei Anshen capsule water solution 0.000 50 mg·mL-1 for 3 days on the basis of model group,and zebrafish in melatonin group were treated with melatonin aqueous solution 0.2 mg·mL-1 on the basis of model group for 3 days.After 3 days,the zebrafish behavior system was used to detect the resting time of zebrafish in each group.qRT-PCR method was used to detect cyclin 1a(per1a),cyclin2(per2),circadian motor output cycle 1a(clock1a),cryptochrome 1b(cry1b),and 5-hydroxyindoleacetic acid(5-htiaa)in each group of zebrafish and follicle-stimulating hormone beta(fshβ)gene expression levels.Western blot was used to detect the expression levels of estrogen receptorα(Esrα),Fshβand luteinizing hormone(Lh)in zebrafish in each group.HE staining was used to observe the ovary of zebrafish in each group.Results Compared with the zebrafish in the blank group,the resting time of the zebrafish in the model group decreased significantly(P<0.01)during the 24 hours of observation.After the intervention of Liuwei Anshen Capsule and melatonin,the resting time of the zebrafish was significantly increased.(P<0.01).Compared with the zebrafish in the blank group,the mRNA expressions of zebrafish circadian clock genes per1a,per2,clock1a,cry1b,5-htiaa,and fshβ all showed a downward trend after sleep deprivation(P<0.05,P<0.01).After the intervention of Liuwei Anshen Capsules,the mRNA expressions of per1,clock1a,cry1b,5-htiaa and fshβ were all up-regulated(P<0.05,P<0.01).Compared with the zebrafish in the blank group,the protein expressions of Esrα and Lh in the zebrafish of the model group were up-regulated(P<0.05),the expression of Fshβ protein was down-regulated(P<0.05),after the intervention of Liuwei Anshen Capsules,the above proteins did not change significantly.The ovarian tissue cells of the zebrafish in the blank group had normal morphology and a large number of primary oocytes,while the ovarian tissue cells of the zebrafish in the model group were damaged in morphology and the number of primary oocytes decreased,after the intervention of Liuwei Anshen Capsule and melatonin,the cell morphology of zebrafish ovarian tissue was still damaged to varying degrees,but the whole was relatively intact,and the number of primary oocytes increased.Conclusion The insomnia of aged zebrafish may be caused by multiple factors.Liuwei Anshen capsule has significant effects on estrogen level of rhythm gene and ovarian function of sleep-deprived aged zebrafish.

Objective To explore the influence of erythropoietin (EPO) on infection induced neonatal rat brain injury at different starting time and its related mechanism.Methods Postnatal day 2 (P2) newborn SD rats were randomly divided into 4 groups:control group (group A),lipopolysaccharide (LPS) group (group B),the early EPO group(group C)and the later EPO group(group D).Pups in group A,B and C were injected different drugs intraperitoneally(group A for saline,group B for 0.6 mg/kg of LPS,and group C for 0.6 mg/kg of LPS and 5 000 U/kg of EPO) once a day for consecutive 5 days(P2-P6).LPS in group D were injected 0.6 mg/kg of LPS intraperitoneally once a day for consecutive 5 days(P2 P6),and with 5 000 U/kg of EPO once a day for consecutive 5 days(P7-P1 1).Rats in each group were given different drugs starting at corresponding time by intraperitoneal injection for 5 consecutive days.Every 10 newborn rats in group A and B were selected randomly on P2(6 h after intraperitoneal injection of drugs for the first time),P7 and P12,the brains were divided into the left and the right hemispheres marked by sagittal suture,using enzyme-linked immunosorbent assay method to evaluate the erythropoietin receptor(EPOR) protein level with the right cerebral hemisphere and reverse transcription-polymerase chain reaction (RT-PCR) method was used to investigate EPOR mRNA level of the left cerebral hemisphere.Immunohistochemical method was adopted to evaluate the expression of myelin basic protein(MBP),glial fibrillary acidic protein(GFAP) and EPOR at specified time point,and HE dyeing for the pathological changes of brain damage in different groups.Results HE staining of the group A presented the normal structure in the neonatal rat brain.Reduced numbers of hippocampal pyramidal cells,expansion of the lateral ventricles and periventricular leukomalacia were found in group B.No leukomalacia or lateral ventricles's expansion in EPO administrated groups and it was more obvious in group C.The EPOR protein and mRNA of group B was increased compared with the group A.The EPOR protein and mRNA levels had a tendency to decline with the increase of age.The MBP expression of group B(107.46 ±3.65)was significantly reduced compared with the group A(146.78 ± 3.13) (P ＜ 0.05),and the expression of EPO groups increased in contrast to the group B,moreover,the group C (126.25 ± 4.42) increased more obviously than that of group D(117.35 ± 3.42) (P ＜ 0.05).The GFAP expression of group B(141.46 ± 11.92 at P7 and 149.48 ± 13.59 at P12) increased significantly than group A(120.63 ± 13.32 at P7 and 119.74 ± 12.48 at P12) (P ＜0.05),the EPO group expressed lower than group B at the P12,and the group C (134.59 ± 12.19) decreased than the group D(137.27 ± 13.87) (P ＞ 0.05).Conclusions EPO shows a protective effect on the cerebral white matter injury caused by postpartum infection,it is superior to administer EPO at early time than later time.The mechanism of the protective effect may be connected with the fact that the infection can induce the expression of brain EPOR and the EPOR expression level has a tendency to decline with the increase of age.

Objective To assess the vaIue of speckle tracking imaging (STI) in quantifying the regional myocardial strain in systemic lupus erythematosus (SLE) group.Methods ① Sixty subjects were divided into SLE group and normal group.High frame rate two-dimensional images were recorded from the apical two-chamber view,long-axis view and four-chamber view of the left ventricle (LV).Peak systolic strain of each view of 18 segments were measured by automated functional imaging (AFI) software of 2-DSE.All parameters were compared between the two groups.② Twenty cases were randomly taken from the normal group.The same observer at different times and two observers measure the strain of left ventricular respectively.The results of the measurement between the two groups were compared with unpaired t test and its relevance was analyzed using Pearson's correlation analysis.ResultsLeft ventricular two-dimensional longitudinal strain gradually increased from the base to apex in the normal group.There were statistically differences between the apical segments and the basal,middle segments of every left ventricular wall (P＜0.05).The same wall segment time to peak myocardial systolic peak strain was consistent.Left ventricular two-dimensional longitudinal strain gradually increased from the base to apex in the SLE group,except for the anterio-septal and anterior wall [ (-18.7±4.2)％,(-16.3±9.4)％,(-18.1±10.5)％ vs (-19.0±9.0)％,(-18.6±7.9)％,(-17.7±1.4)％ ].There was no statistically significant difference between the apical segments and the basal,middle segments of every left ventricular wall(P＞0.05).All parameters of S were significantly higher in the normal group than those of the SLE group.The difference was statistically signoficant (P＜0.05).The time to peak systolic peak strain of every segments was not consistent.The results from the same observer at different times and peak systolic myocardial strain measurements by the two observers were correlated well(P＜0.01).Conclusion The myocardial function assessment by STI technology in the SLE patients is significantly different from that of the normal control:SLE patients with left ventricular myocardial damage can be manifested as reduced regional myocardial systolic peak strain.