Effect of Combined Frequency Stimulation on The Electrophysiology of Granule Neurons in The Hippocampal Dentate Gyrus Area of Hindlimb Unloading Mice / 生物化学与生物物理进展

ObjectiveIn recent years, the negative impact of microgravity on astronauts’ nervous systems has received widespread attention. The repetitive transcranial magnetic stimulation (rTMS) technology has shown significant positive effects in the treatment of neurological and psychiatric disorders. The potential benefits of combined frequency stimulation (CFS) which combines different frequency stimulation patterns in ameliorating neurological dysfunctions induced by the microgravity environment, still require in-depth investigation. Exploring the therapeutic effects and electrophysiological mechanisms of CFS in improving various neurological disorders caused by microgravity holds significant importance for neuroscience and the clinical application of magnetic stimulation. MethodsThis study employed 40 C57BL/6 mice, randomly divided into 5 groups: sham group, hindlimb unloading (HU) group, 10 Hz group, 20 Hz group, and combined frequency stimulation (10 Hz+20 Hz, CFS) group. Mice in all groups except the sham group received 14 d of simulated microgravity conditions along with 14 d of repetitive transcranial magnetic stimulation. The effects of CFS on negative emotions and spatial cognitive abilities were assessed through sucrose preference tests and water maze experiments. Finally, patch-clamp techniques were used to record action potentials, resting membrane potentials, and ion channel dynamics of granule neurons in the hippocampal dentate gyrus (DG) region. ResultsCompared to the single-frequency stimulation group, behavioral results indicated that the combined frequency stimulation (10 Hz+20 Hz) significantly improved cognitive impairments and negative emotions in simulated microgravity mice. Electrophysiological experiments revealed a decrease in excitability of granule neurons in the hippocampal DG region after HU manipulation, whereas the combined frequency stimulation notably enhanced neuronal excitability and improved the dynamic characteristics of voltage-gated Na+ and K+ channels. ConclusionThe repetitive transcranial magnetic stimulation with combined frequencies (10 Hz+20 Hz) effectively ameliorates cognitive impairments and negative emotions in simulated microgravity mice. This improvement is likely attributed to the influence of combined frequency stimulation on neuronal excitability and the dynamic characteristics of Na+ and K+ channels. Consequently, this study holds the promise to provide a theoretical basis for alleviating cognitive and emotional disorders induced by microgravity environments.

The relationship between gut microbiota characteristics and peripheral blood lymphocytes in patients with primary Sj?gren′s syndrome / 中华风湿病学杂志

Objective:By detecting the species and distribution of fecal flora in patients with pSS, we investigated the relationship between the alterations of the gut microbiome and its metabolic characteristics with peripheral lymphocyte subsets, and their potential role in the occurrence and development of pSS.Methods:A total of 101 pSS patients who were hospitalized in the department of rheumatology of the Second Hospital of Shanxi Medical University, and 101 age and sex-matched healthy control (HC) in the health check-up center of Shanxi Provincial People′s Hospital from January 2019 to January 2020 were enrolled for 16s rDNA-Amplicon sequencing. The statistical analysis was performed in R software 4.0.3. The Alpha diversity were compared by Wilcoxon test, and Beta diversity were compared by ANOSIM analysis between pSS patients and HC. The difference flora was analyzed by t test. The levels of peripheral lymphocyte subsets pSS patients were detected by flow cytometry. Then the relationship between characteristic flora and clinical indicators such as lymphocyte subsets, erythrocyte sedimentation rate, C-reactive protein, unstimulated whole saliva and stimulated whole saliva were analyzed using Pearson′s correlation analysis. Results:Patients with pSS exhibited a significant reduction in the richness (Chao1, ACE) and diversity (Shannon,Simpson) of gut microbiota compared with those of HC, and there was statistical significant difference in gut microbiota composition (ANOSIM, r=0.09, P=0.001). At the phylum level, the relative abundance of Firmicutes decreased and the relative abundance of Proteobacteria increased in pSS patients. At the genus level, the proportion of Escherichia-shigella ( P<0.001), Lactobacillus ( P<0.001), Bifidobacterium ( P<0.001), Subdoligranulum ( P<0.001), Alistipes ( P<0.001) and [ Eubacterium]_ coprostanoligenes (P=0.002) were increased. The proportion of Faecalibacterium ( P<0.001), Prevotella ( P<0.001), Roseburia ( P<0.001), Megamonas ( P<0.001), Agathobacter ( P<0.001), Lachnospira ( P<0.001), Lachnospira_NK4A136 ( P=0.006), [ Eubacterium] _eligens ( P<0.001) were significantly reduced. PICRUST analysis showed significant enrichment of amino acid metabolism taurine and hypotaurine metabolism ( P<0.001), fatty acid metabolism such as propanoate metabolism ( P<0.001), glutathione metabolism ( P=0.002), lipoic acid metabolism ( P=0.003), lipopolysaccharide biosynthesis and biosynthesis of siderophore group nonribosomal peptides ( P=0.005) and Aminobenzoate degradation ( P=0.002) in patients with pSS. The Pearson correlation results showed that there were significant different in the abundances of the key gut microbiota between the HC and pSS groups, and they were closely related to unstimulated whole saliva, the absolute number of Treg cells and Th17 cells. Conclusion:The dysbiosis and metabolism changes of the pSS intestinal microbiota may contribute to immune homeostasis imbalance, and may be involved in the occurrence and development of pSS.

Efficacy of posterior staged correction in the treatment of severe kyphoscoliosis / 中华骨科杂志

Objective:To analyze the efficacy of posterior staged correction in the treatment of severe kyphoscoliosis.Methods:Retrospective analysis was conducted on 61 patients with severe kyphoscoliosis who underwent one-stage posterior Ponte osteotomy followed by Halo-femoral traction and two-stage posterior correction in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between January 2010 and January 2020. There were 23 males and 38 females with an average age of 22.0(18.0, 25.5) years. The etiologies were idiopathic in 26 cases, congenital in 17 cases, neuromuscular in 16 cases and Marfan syndrome with kyphoscoliosis in 2 cases. The curves were thoracic in 49 cases, thoracolumbar in 3 cases and double major in 9 cases. The apical vertebrae were T 5 level in 1 case, T 7 level in 2 cases, T 8 level in 9 cases, T 9 level in 15 cases, T 10 level in 23 cases, T 11 level in 8 cases, T 12 level in 1 case, and L 1 level in 2 cases. The flexibility of main curve was 13.5%±8.6%. The Cobb angle of main curve, global kyphosis (GK), coronal trunk shift (CTS), sagittal vertical axis (SVA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were assessed at pre-operation, post-traction, post-operation and the last follow-up. The quality of life was evaluated using the MOS item short form health survey (SF)-36 questionnaire, and the complications during peri-operation and long-term follow-up were recorded. Results:All 61 patients were followed up for 25.0 (24.0, 26.5) months. The Cobb angle of main curve and GK were 121.4°±13.9° and 86.8°±20.0° at pre-operation, 94.1°±18.7° and 66.9°±15.3° at post-traction, 78.5°±20.3° and 54.7°±13.6° at post-operation and 79.5°±20.1° and 53.2°±11.3° at the last follow-up, respectively. The differences were statistically significant ( F=210.54, P<0.001; F=93.74, P<0.001). There was no significant difference between the last follow-up and post-operation ( P>0.05). There was no significant correction loss of SVA, TK, LL, PI, PT or SS at the last follow-up when compared with those at post-operation ( P>0.05). The CTS was 17.1±9.8 mm at pre-operation, 17.5±11.4 mm at post-operation, 11.1 (5.9, 23.3) mm at the last follow-up and the difference was statistically significant (χ 2=6.70, P=0.035). The difference between the last follow-up and post-operation was statistically significant ( P=0.032). The scores of physical functioning 80.0 (75.0, 85.0), general health 82.0 (69.5, 87.0) and social functioning 75.0 (62.5, 75.0) in SF-36 at the last follow-up were significantly improved compared with those at pre-operation ( Z=-2.11, P=0.035; Z=-3.64, P<0.001; Z=-2.07, P=0.039). During the traction process, the complications included pin track infection in 1 case, deep vein thrombosis of the lower extremity in 2, misplacement of pedicle screws in 3, coronal decompensation at immediate post-operation in 2, sagittal decompensation at immediate post-operation in 1, and 1 patient had broken rod at 3 years follow-up, respectively. Conclusion:The posterior staged correction could provide satisfying radiographic and clinical outcomes in patients with severe kyphoscoliosis, which could be well maintained during 2 years follow-up. Therefore, the posterior staged correction is a safe and effective treatment for severe kyphoscoliosis.

Study on the relationship between intestinal flora analysis and CD4 +T lymphocyte subsets in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To explore the characteristics of intestinal microbiota in patients with systemic lupus erythematosus (SLE), and further explore the relationship between microbiota and CD4 +T lymphocyte subsets and disease activity. Methods:Fecal samples were collected from 96 patients with SLE, and 96 sex- and age-matched healthy controls (HCs). The gut microbiota were investigated via 16s rRNA sequencing. Flow cytometry was used to detect peripheral CD4 +T lymphocyte subsets of Th1, Th2, Th17 and Treg cells. Indicators of disease activity such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3 and C4, Systemic lupus erythematosus disease activity index(SLEDAI) for each patient were recorded. Differential abundance analysis was carried out using the edgeR algorithm. The Wilcoxon rank-sum test was used to compare alpha diversity indices, bacterial abundances, and the F/B ratio between groups. R (version 4.0.1) was used for comparative statistics, and Pearson′s correlation analysis was used to assess the correlations between the relative abundances of bacterial genera and serum levels of ESR, CRP, C3 and C4 in the samples. Results:The alpha estimators of richness (ACE and Chao 1) were significantly reduced in SLE feces samples compared with those of HCs ( P<0.01). Bacterial diversity estimators, including the Shannon ( P<0.01) and Simpson′s ( P<0.01) indices, were also significantly lower in SLE. Significant differences in gut microbiota composition between SLE and HCs were found using the edgeR algorithm. Compared with HC, 24 species of bacteria were significantly different in SLE patients at the genus level ( P<0.05). Moreover, there was a significant positive correlation between CRP and Coprococcus ( r=0.30, P=0.014), C4 and Corynebacterium ( r=0.31, P=0.013) and Faecalibacterium( r=0.25, P=0.048), Hemoglobin and Morganella( r=0.41, P=0.001), as well as SLIDA and Corynebacterium( r=0.25, P=0.047). In terms of lymphocyte subsets, there was significant positive correlation between B cells, Treg cells and Eubacterium eligens group, as well as CD8 +T, CD4 +T, NK cells and Corynebacterium. In additional, Th1 was positively correlated with Shigella Escherichia coli ( r=0.52, P=0.008), and Th2 was positively correlated with Dielma ( r=0.51, P<0.001). Conclusion:The abundance and diversity of intestinal flora in SLE patients were significantly reduced, and the differentially expressed bacteria were closely related to the CD4 +T lymphocyte subsets and disease activity indicators of patients.

Comparison of the infectivity and stability of Asian versus African lineage Zika virus in glial cells / 中国人兽共患病学报

Infection of pregnant women by Asian lineage Zika virus(ZIKV)is more likely to cause microcephaly in infants than African lineage ZIKV.To further clarify the differences in infectivity and stability between Asian and African lineage ZIKV,we selected Asian lineage SZ01 and African lineage MR766 strains for study in glial cells.First,we examined the differ-ence in infectivity between SZ01 and MR766 on U251 and U87 astrocytes,and T98G glioblastoma cells,by using CCK8 assays.Subsequently,we examined the tolerance of SZ01 and MR766 to 37 ℃ and 40 ℃ in the free and infected cell states,by using qRT-PCR or viral plaque assays.Finally,we examined the effect of repeated freezing and thawing on the stability of SZ01 and MR766 with viral plaque assays.ZIKV had higher infectivity in U251 and U87 than T98G,and SZ01 was more infectious to as-trocytes than MR766.SZ01 tolerated 40 ℃ better than MR766 in the free state.SZ01 proliferated faster than MR766 in glial cells at 40 ℃.The tolerance of SZ01 to repeated freezing and thawing was higher than that of MR766.The above findings sug-gest that the infectivity and stability of Asian lineage ZIKV are significantly higher than those of African lineage ZIKV,possi-bly because of its persistent infection and pathogenicity.

Pelvic fixation for posterior lumbosacral hemivertebra resection and long fusion in adult spinal deformity / 中华骨科杂志

Objective:To evaluate whether pelvic fixation is needed in patients undergoing posterior lumbosacral hemivertebra (LSHV) resection and long fusion.Methods:All 32 adult spinal deformity patients with posterior hemivertebra (HV) resection and long segment fixation treated from April 2005 to August 2019 were analyzed retrospectively, including 12 males and 20 females with a mean age of 32.9±8.8 years. According to the state of coronal balance distance (CBD), there were 15 cases of type A (preoperative CBD≤ 30 mm), 1 case of type B (preoperative CBD>30 mm and C 7 plumb line offset to the concave side), and 16 cases of type C (preoperative CBD>30 mm and C 7 plumb line offset to the convex side). The clinical and imaging data before operation, immediately after operation and at the last follow-up were collected, and the short-term and long-term complications related to operation were recorded. The improvement of Cobb angle and coronal balance of primary curve and compensatory curve were evaluated on the whole spine frontal and lateral X-ray films, and the change of coronal balance type after operation was evaluated. According to the mode of distal internal fixation, the patients were divided into two groups: PF group (pelvic fixation): distal fixation to iliac or sacroiliac; NPF group (non-pelvic fixation): distal fixation to L 5 or S 1. Results:All 32 patients were followed up with an average time of 3.9±2.6 years (range 2-11 years). The Cobb angle of primary curve in PF and NPF groups were 42.6°±13.5° and 41.3°±10.9° respectively before operation, and corrected to 13.1°±5.4° and 17.7°±5.8° respectively after operation. It maintained at 13.4°±5.1°and 18.5°±6.7° in the two groups at the last follow-up, respectively ( FPF=32.58, FNPF=28.64, P<0.001). The correction rates were 69.3%±11.8% and 57.6%±10.3%, respectively ( t=2.14, P=0.012). The compensatory curves of in the two groups were corrected from 54.9°±14.8° and 46.8°±13.6° before operation to 17.3°±9.6° and 15.4°±8.4° after operation. It also maintained at 18.5°±8.8°and 17.6°±9.5° in the two groups at the last follow-up, respectively ( FPF=42.97, FNPF=38.56, P<0.001). The correction rates were 68.4%±16.7% and 67.2%±14.9%, respectively ( t=0.17, P=0.849) in the two groups. In PF group, the primary and compensatory curve were similar (69.3%±11.8% vs. 68.4%±16.7%, t=0.15, P=0.837), while the correction rate of compensatory curve in NPF group was significantly higher than that of the primary curve (67.2%±14.9% vs. 57.6%±10.3%, t=2.13, P=0.013). Coronal decompensation occurred in 12 patients (12/32, 37.5%). The CBD in PF and NPF groups was corrected from 33.3±11.2 mm and 28.8±8.1 mm preoperatively to 18.5±3.5 mm and 27.1±6.8 mm postoperatively, respectively, and it showed no significant change at the last follow-up ( FPF=41.61, P<0.001; FNPF=0.38, P=0.896). While the CBD in PF group was significantly better than that in NPF group ( t=3.23, P=0.002; t=2.94, P=0.008). The incidence of coronal decompensation in PF group was 0%, which was significantly lower than 50% (12/24) in NPF group (χ 2=6.40, P=0.014). In addition, 6 cases in PF group were type C coronal decompensation before operation, and the coronal balance was corrected to type A after surgery (100%). Among 10 patients with type C coronal decompensation in NFP, 4 (40%) patients returned to type A after operation, and the difference was statistically significant (6/6 vs. 4/10, χ 2=5.76, P=0.034). Conclusion:Coronal decompensation (12/32, 37.5%) is not rare in patients after posterior LSHV resection and long fusion. Attention should be paid to the match of the corrections between lumbosacral deformity and compensatory curve, which is of great significance in coronal balance reconstruction. Pelvic fixation is helpful to reduce the incidence of postoperative coronal decompensation, especially for the type C patients.

Effect of postoperative trunk shift on long-term shoulder imbalance after single segment hemivertebra resection in children: risk factors and prognosis / 中华骨科杂志

Objective:To investigate the risk factors of long-term shoulder imbalance in patients presented postoperative shoulder imbalance who underwent single segment hemivertebra resection, and the role of postoperative trunk shift in shoulder imbalance.Methods:All of 30 patients who presented shoulder imbalance after hemivertebrae resection and short fusion from July 2006 to December 2018 were reviewed in this study, including 16 males and 14 females, aged 4.53±2.05 years (range, 2-8 years). Among them, 10 cases were thoracic hemivertebra, 12 thoracolumbar hemivertebra and 8 lumbar hemivertebra. According to the vertical height difference at the highest point of soft tissue shadows on both shoulders in the final follow-up upright posteroanterior radiograph, which was shoulder imbalance (SI), they were divided into two groups: Group B (balance, shoulder imbalance less than 10 mm) and Group IB (imbalance, shoulder imbalance more than 10 mm). Several radiographic parameters were measured preoperatively, 3 months after surgery and at the final follow-up, such as SI, distance between C 7 plumbline and center sacral vertical line (C 7PL-CSVL), Cobb angle of main curve, cobb angle of proximal curve (CAPC), Cobb angle of distal curve (CADC), upper instrumented vertebra offset (UO), lower instrumented vertebra offset (LO), upper instrumented vertebra slope (US), lower instrumented vertebra slope (LS), T1 tilt and sagittal vertical axis (SVA). Results:The mean follow-up period was 54.3±33.7 months (range, 24-132 months). A mean of 3.1 segments were fused. 7 cases (70%) of thoracic, 6 cases (50%) of thoracolumbar and 3 cases of lumbar hemivertebrae (37.5%) with shoulder imbalance at 3 months after surgery remained imbalanced at the last follow-up. Thirteen cases presented coronal imbalance postoperative (C 7PL-CSVL>2 cm), among 6 cases whose trunk shafted to the side of the higher shoulder postoperatively, 5 cases presented aggravated SI at final follow-up, and among 7 cases whose trunk shafted to the side of the lower shoulder postoperatively, 6 cases presented aggravated SI at final follow-up, while the difference had statistical significance ( P=0.029). The static analysis indicated that postoperative and long-term C 7PL-CSVL, long-term lowest instrumented vertebra and long-term T 1 tilt were risk factors of shoulder imbalance at final follow-up. Conclusion:A proportion of congenital scoliosis patients who presented shoulder imbalance after hemivertebra resection plus short fusion are less likely to achieve shoulder balance at the final follow-up. Long-term shoulder imbalance is often presented in the patients whose trunk shafted to the side of the higher shoulder postoperatively.

The expression changes of lncRNA in patients with systemic lupus erythematosus and its correlation with regulatory T cells / 中华风湿病学杂志

Objective:To explore the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T cells (Tregs) by detecting the lncRNAs expression profiles in patients with systemic lupus erythematosus (SLE), then analyze the correlation between Tregs and lncRNAs and the clinical features of SLE patients. We also predict the mechanism by which lncRNAs regulate the differentiation and development of Tregs, and provid new approach for the treatment of SLE.Methods:Peripheral blood of 9 active SLE patients was collected and mononuclear cells (PBMCs) were extracted. The lncRNAs expression profiles of PBMCs was analyzed by whole transcriptome sequencing. Nine healthy people served as controls to screen the differentially expressed lncRNAs, and to analyze the correlation between lncRNAs and Tregs number. Pearson test was used to analyze the correlation between lncRNA and the number of Tregs, and the correlation between Treg-associated lncRNAs and systemic lupus erythematosus disease activity index(SLEDAI) score, erythrocyte sedimentation rate (ESR), C3, C4 in SLE patients. The targeted genes of Treg asso-ciated lncRNAs were predicted with miRcode and Targetscan databases and co-expression network.Results:There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs ( P<0.05) and 106 low expressed lncRNAs ( P<0.05). The expression of ANKRD44-AS1 ( r=0.74, P=0.022), LINC00200 ( r=0.70, P=0.037), AP001363.2 ( r=0.78, P=0.014) and LINC02824 (r=0.79, P=0.011) were positively correlated with the number of Tregs, and the expression of AP000640.1 ( r=-0.72, P=0.028), AC124248.1 ( r=-0.77, P=0.016), LINC00482 ( r=-0.83, P=0.005) and MIR503HG ( r=-0.96, P<0.001) were negatively correlated with the number of Tregs. Among these eight Tregs associated lncRNAs, the expression of LINC00482 ( r=-0.73, P<0.001) and MIR503HG ( r=-0.76, P<0.001) were negatively correlated with C3. LINC00200, ANKRD44-AS1 and AP000640.1 related to Tregs regulated the expression of STAT5, PLD1, HOPX and RUNX3 through competitively binding of miRNA or transregulatory mechanism, thereby regulating the differentiation and development of Tregs. Conclusion:The lncRNAs expression profiles are changed in SLE patients, the differentially expressed lncRNAs are associated with abnormal number and function of Tregs in SLE patients, and Treg associated lncRNAs are associated with SLE disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Tregs function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism.

Molecular Characteristics and Potent Immunomodulatory Activity of Fasciola hepatica Cystatin

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

Influences of Quadriceps Femoris Spasticity on Obstacle Crossing for Stroke Patients / 中国康复理论与实践

Objective:To observe the effect of quadriceps femoris spasticity on the movement parameters in stroke patients during obstacle crossing. Methods:From October, 2017 to November, 2018, 20 stroke patients were divided into spasticity group (n = 11) and non-spasticity group (n = 9) based on the score of modified Ashworth Scale (MAS) of quadriceps femoris. A 10-camera 3D motion analysis system and two force plates were used to synchronously measure the movement parameters of the patients during obstacle crossing of 15 cm high, such as step length, step width, anterior-posterior velocity of the center of mass (COMAPV) and medio-lateral velocity of the center of mass, toe-obstacle distance of unaffected limb, toe-obstacle clearance of affected limb, heel-obstacle distance, double support phase, and the swing phases of affected and unaffected limb. Results:Compared with the non-spasticity group, the COMAPV decreased as both affected and unaffected limb above the obstacle in the spasticity group (F > 10.006, P < 0.01), as well as the toe-obstacle distance and step length before obstacle crossing (F > 13.456, P < 0.01); while, the double support phase and the step width after obstacle crossing increased (F > 4.533, P < 0.05). Conclusion:The quadriceps femoris spasticity may make the strategy of obstacle crossing more carefully for stroke patients, and less efficiently.

The status of peripheral CD4 + T subsets in patients with rheumatism and their changes after immuno-modulatory combination therapies / 中华风湿病学杂志

Objective:To examinethe absolute numbers of cluster of differentiation (CD4) + T cell subsets in peripheral blood of patients with rheumatism and further to develop a new immunomodulatory therapies which aimed to restore their imbalanced CD4 + T lymphocyte subpopulation. Methods:A total of 6 395 rheumatic patients [4 430 females, 1 965 males, mean age (49±15) years] and 206 healthy controls (HCs) were enrolled in this retrospective cross-sectional study, which included rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), Psoriatic arthritis (PsA), systemic sclerosis (SSc), primary Sj?gren′s syndrome (pSS), Be?het's disease (BD), dermatomyositis/polymyositis (DM/PM), gout and vasculitis. Some patients received treatment combined with immunoregulatory drugs (IMiDs) such as low-dose interleukin (IL)-2, rapamycin, metformin, retinoic acid and coenzyme Q10. The absolute numbers of T helper cell (Th)1, Th2, Th17 and regulatory T cell (Treg) in peripheral blood (PB) of these individuals were measured by Flow Cytometery (FCM). Independent sample t test and paired sample t test were used to compare the levels of CD4 + T cell subsets in PB of patients and HCs, before and after treatment respectively, and P<0.05 was considered statistically significant. Results:Compared with HCs, the mean absolute number of Treg was significantly decreased [(31±15) cell/μl vs (27±17) cell/μl, t=3.407, P<0.01] and the ratio of Th17/Treg was increased in all patients [(0.3±0.2) vs ( 0.4±0.7), t=-9.508, P<0.01]. There was a significant increase in the number of Th17 in patients with AS [(10±8) cell/μl, t=-5.403, P<0.01], PsA[ (11±11) cell/μl, t=-3.829, P<0.01], SSc [(7±6) cell/μl, t=3.114, P<0.01], BD [(11±9) cell/μl), t=-4.774, P<0.01] and gout [(11±9) cell/μl, t= -4.604, P<0.01) , and we observed lower level of Treg in patients with RA[(28±15) cell/μl, t=3.032, P<0.01], SLE [(21±21) cell/μl, t=6.836, P<0.01], AS [(28±15) cell/μl, t=2.216, P<0.05], SSc [(27±16) cell/μl, t=3.698, P<0.05], BD [(27±17) cell/μl, t=2.502, P<0.05], DM/PM [(27±22) cell/μl, t=2.974, P<0.01) and gout [(28±15) cell/μl, t=2.079, P<0.05). After IMiDs combination treatment, the levels of CD4 + T subsets were increased. Interestingly, the expansion of Treg was much more dramatical than those of other effector T cells, resulting in a decrease in ratios of Th17/Treg, especially in SLE [(0.6±1.0) vs (0.5±0.4), t=3.157 , P<0.01]. Conclusion:Impaired balance of pro- and anti-inflammatory immune cells, especially insufficiency of Treg, might be a cornerstone of the pathogenesis of rheumatism. The new immunomodulatory therapies could relatively specifically promote Treg proliferation and restored patients' autoimmune tolerance, which isexpected to provide a new strategy for the treatment of rheumatism.

Molecular detection and genetic diversity of bovine papillomavirus in dairy cows in Xinjiang, China

Background@#Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. @*Objectives@#The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. @*Methods@#122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. @*Results@#Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. @*Conclusions@#Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Molecular detection and genetic diversity of bovine papillomavirus in dairy cows in Xinjiang, China

Background@#Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. @*Objectives@#The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. @*Methods@#122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. @*Results@#Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. @*Conclusions@#Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Posterior column osteotomy for the treatment of "Lenke 5-like" lumbar congenital scoliosis / 中华骨科杂志

Objective:To explore the efficacy and correction mechanism of posterior column osteotomy for treatment of "Lenke 5-like" lumbar congenital scoliosis.Methods:From April 2008 to September 2019, 16 patients with lumbar congenital scoliosis underwent posterior column osteotomy were retrospectively reviewed including 6 males and 10 females, aged 23.9±11.7 years (range, 14-48 years). Among them, 8 cases were unsegmentation, 5 malformation and 3 mixed type. The average segments of PCO were 5.3. Posterior column osteotomy was adapted after the insertion of pedicle screws, then removed spinous process, ligaments, superior and inferior facet and corrected the deformity with the rods. The pre- and post-operative and last follow-up radiographic parameters were measured: Cobb angle of lumbar curve, distance between C 7 plumbline and center sacral vertical line (C7PL-CSVL), deformity angle (DA), disc correction angle (DCA) of instrumented segments, disc angle above upper instrumented vertebra (DAAU), lower instrumented vertebra disc angle (LDA), upper instrumented vertebra slope (US), lower instrumented vertebra slope (LS), lower instrumented vertebra offset (LO) and sagittal parameters such as thoracic kyphosis (TK), lumbar lordosis(LL) and thoracic junctional kyphosis (TJK). The Scoliosis Research Society-22 questionnaire (SRS-22) were conducted at preoperation and the final follow up to evaluate the clinical outcomes. Results:The mean follow-up period was 16.69±7.65 months (range, 12-36 months). The coronal DA was 26.74°±10.59° while the sagittal DA was 14.70°±11.63°. The pre- and post-operative Cobb angle were 51.19°±12.91° and 23.25°±12.86° while the correction rate was 57.17%±16.31% and reached 24.26°±13.19° in the last follow-up. The improvement of DAAU, LDA, US, LS, and LO pre- and post-operative had statistical significance ( P<0.001). The pre- and post-operative and the last follow-up C 7PL-CSVL were 27.13±17.08 mm, 21.81±12.80 mm and 20.24±15.02 mm. The pre-operative, postoperative and last follow-up DAAU were -4.35°±2.12°, 1.36°±2.34° and 1.60°±2.45°. The pre- and post-operative LDA were -7.03°±4.40° and 2.42°±3.39°, and the last follow-up LDA was 2.81°±2.98°. US and LS decreased from pre-operative 12.01°±8.33° and 21.46°±5.79° to 2.84°±7.52° and 11.64°±6.06°. The mean US and LS were 4.22°±6.56° and 11.56°±6.02° in the last follow-up. LO decreased after surgery and keep unchanged in the last follow-up, which were 12.71°±6.43°, 6.31°±5.17° and 7.01°±4.73°, respectively. For the sagittal plane parameters, the changes of TK, LL, and TJK reached statistical significance through the surgery. LL increased from 33.69°±14.01° to 44.28°±10.07° through the surgery and reached 41.97°±6.69° at the last follow-up while TK increased from 13.41°±12.37° to 23.52°±8.10°, TJK decreased from 29.02°±20.74° to 16.20°±12.62° after the surgery and reached 16.07°±13.33° at the last follow-up. The pre-operative, post-operative and last follow-up thoracic kyphosis were 13.41°±12.37°, 23.52°± 8.10°, and 24.21°±7.39°. There was no statistical significance of the change of C 7PL-CSVL, SVA, SSA and PI-LL through the surgery ( P>0.05). At the final follow-up, the self-image and psychologic status scores of SRS-22 were significantly higher than that before surgery ( t=15.457, P<0.001; t=14.726, P<0.001), and there was no significant difference in the rest of the domain ( P>0.05). Conclusion:"Lenke5-like" lumbar congenital scoliosis could obtain satisfactory correction of coronal and sagittal deformities with the treatment of posterior column osteotomy, while there was no significant loss of correction during follow-up. The incidence of surgical complications is low.

Mid-term outcomes of one-stage posterior-only jumping hemivertebra resections and short fusions for children with congenital scoliosis secondary to multiple hemivertebrae / 中华骨科杂志

Objective:To evaluate the safety and efficacy of one-stage posterior-only jumping hemivertebra (HV) resection combined with respective short fusions in the treatment of congenital scoliosis (CS) caused by multiple HVs.Methods:All of 13 consecutive patients with multiple HVs treated surgically from January 2010 to December 2017 were retrospectively reviewed, including 4 males and 9 females with a mean age of 3.7±1.2 years. One child had 4 HVs, and the rest had 2 HVs. The responsible HVs causing local scoliosis/kyphosis deformity or coronal plane deviation were selected as the target of resection. The distal HV was removed firstly and then the proximal one was resected; both of the fixation vertebraes were horizontalized during surgery. The clinical and imaging data of the children before the initial operation, immediately after the operation and at the latest follow-up were collected, and the short-term and long-term complications related to surgery were recorded. The data were evaluated on the whole-standing spine anteroposterior and lateral films, including the corrections of proximal and distal main curves, coronal balance, local kyphosis, and the improvement of spinal growth height (upper and lower internal fixation length, T 1-S 1 length). At the same time, the re-progression of coronal and sagittal deformities of the spine during growth was recorded (coronal decompensation: emerging postoperative curve progression more than 20°; kyphosis progression: kyphosis aggravation between upper and lower internal fixation more than 40°) and internal-fixation-related complications (screw cutting, screw malposition) were recorded. Results:Dual HVs were resected in each child, of which 8 (61.5%) were located on contralateral side of the spine, and 5 (38.5%) were located on ipsilateral side of the spine. The follow-up time was 6.2±3.3 years (range 2.0-10.5 years) after surgery. The Cobb angles of proximal and distal main curves were 36.7°±11.8° and 35.2°±7.8° respectively before surgery and were corrected to 9.7°±6.6° and 6.1°±4.1° respectively after surgery ( F=31.249, F=93.83, P< 0.001) ( t=6.888, t=10.954, P<0.001), and the correction rates was 73.6%±19.6% and 82.7%±11.7%, respectively. They were maintained at 14.3°±5.4° and 8.0°±4.6° at the latest follow-up, showing the correction rates loss of 15.8%±26.9% and 6.9%±7%, respectively. The coronal balance improved from 17.2±14.8 mm pre-operatively to -0.2±15.7 mm postoperatively ( t=2.703, P=0.008), and it remained at 0±18.4 mm at the final follow-up ( F=4.137, P=0.024). The T 1-S 1 length was corrected to 273.8±27.3 mm postoperatively, slightly increased compared with pre-operation 256.3±24.0 mm, ( t=0.680, P=0.527), and significantly increased to 333.2±33.4 mm at the latest follow-up ( t=2.986, P<0.001; F=6.704, P=0.003). Seven patients had local kyphosis before operation, which was significantly improved from 32.2°±13.6° to 6.1°±9.8° with a correction rate of 93.4%±27.0% after surgery ( t=3.355, P=0.004), which showed no significant loss of correction at the latest follow-up (5.4°±10.4°) ( F=11.187, P=0.002). Six patients (46.2%) developed coronal decompensation (Curve magnitude >20 °), with an average of 21.7°±1.9°. Two cases (15.4%) had progressive kyphosis between the thoracic regional internal fixations at 3 months after surgery, which were 68° and 58° respectively. After bracing, both coronal decompensation and sagittal kyphosis were improved. At the last follow-up, the coronal decompensation was improved to 14.7±8.9° and the kyphosis was alleviated to 55° and 46°, respectively. Conclusion:Posterior-only skipping hemivertebra resection and short fusion is a safe, effective procedure yielding significantly improvement of the growth imbalance and reginal spinal deformities of CS with multiple HVs. The mid-term follow-up results showed that the progress of the scoliosis was common during the growth period, which could be further controlled by supplementary brace treatment.

Analysis of Serum Transcriptome Characteristics of Patients with Yin and Yang Syndromes of Acute Ischemic Stroke / 中国实验方剂学杂志

Objective:To obtain the regulatory relationship between genes by screening the differentially expressed long non-coding ribonucleic acid(lncRNA), microRNA(miRNA) and messenger RNA(mRNA) in serum of patients with Yin and Yang syndromes of acute ischemic stroke, and to discuss the material basis and biological mechanism of formation of Yin and Yang syndromes of acute ischemic stroke from the transcriptome level. Method:The microarray chips were adopted to detect expression of lncRNA, mRNA and miRNA in serum of ischemic stroke patients with Yin and Yang syndromes and non-stroke subjects(10 cases each). Differential expression profiles related to Yin and Yang syndromes were selected by conjoint analysis. Further, the obtained differential genes were subjected to antisense lncRNA and mRNA co-expression analysis, gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) functional pathway analysis, and the intergenic regulatory relationship was obtained to predict the target genes of lncRNA. Partial differential genes in 40 patients(10 with Yang syndrome and 30 with Yin syndrome) were verified by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR). Result:The expression of 227 lncRNA, 54 mRNA and 4 miRNA were closely related to Yang syndrome, 394 lncRNA and 206 mRNA were closely related to Yin syndrome. Antisense lncRNA RP11-647P12.1 and RP11-677M14.2 may regulate the expression of neuron-derived neurotrophic factor(NDNF) and neurogranin(NRGN) by up-regulating the expression level in Yang syndrome. The differential expression of mRNA between Yin syndrome and Yang syndrome was mainly related to neurotransmitter receptor activity regulation, endocrine hormone regulation, inflammatory response, renin-angiotensin system and other pathways. Conclusion:There are differences in the expression profiles of lncRNA, miRNA and mRNA between Yin syndrome and Yang syndrome in acute ischemic stroke, which may be regulated by multiple pathways, such as blood pressure regulation, adrenergic receptor regulation, renin-angiotensin system and γ-aminobutyric acid(GABA). The transcriptome characteristics provide scientific basis for studying the biological basis of Yin syndrome and Yang syndrome in acute ischemic stroke.

Characteristic profiles of biofilm, enterotoxins and virulence of Staphylococcus aureus isolates from dairy cows in Xinjiang Province, China

As an important zoonotic pathogen, Staphylococcus aureus has led to serious mastitis and endometritis in infected dairy cows. In this study, a total of 164 strains of S. aureus were isolated from dairy cows in Xinjiang Province, China, and subjected to assays to determine drug susceptibility and biofilm (BF) formation ability. Enterotoxin-related genes were detected, and the transcription levels of genes related to BF formation were determined by using reverse transcription-quantitative polymerase chain reaction. Moreover, the pathogenicity of isolates with different BF formation abilities was determined by measuring their hemolysis activity, half lethal dose (LD₅₀) and organ bacterial load. The results showed that 86.0% of S. aureus isolates could form BF. Among them, 42.1% of the strains had weak BF formation ability, and most strains with a strong BF formation ability were ica gene carriers. The S. aureus isolates displayed multidrug resistance and their drug resistance was positively correlated with their BF formation ability. Moreover, 96.3% of the S. aureus isolates carried enterotoxin genes. Among them, the detection rates of the novel enterotoxin genes were higher than those of conventional enterotoxin genes. Furthermore, isolates with a strong BF formation ability had higher LD50 but lower hemolysis ability and organ bacterial load than those of the isolates with weak or no BF ability. However, isolates without BF ability produced more severe pathological changes than those of isolates with strong BF formation ability. These findings suggest that higher BF ability and presence of novel enterotoxin genes are important characteristics of S. aureus isolates from dairy cows in Xinjiang Province, China, and such isolates may pose potential threats to food safety.

Eccrine Chromhidrosis: A Case Report And Review Of Literature

Chromhidrosis is a rare disorder characterized by colored sweat and/or stained skin. Eccrine chromhidrosis is an orphan disease in which water-soluble pigments are excreted through the eccrine glands. This article provides a highly doubtful eccrine chromhidrosis case and the literature review for eccrine chromhidrosis. We recommend an investigative algorithm for dermatologists, hepatologist, and general practitioners to enhance diagnostic capability without mistake among similar and differential diseases. Most importantly, the exact etiology should be determined, which further decides the treatment plan. Systemic treatment of liver diseases or bacteremia was reported particularly effective. Results and prognosis were excellent and without recurrence.

A Meta-analysis on Acupuncture and Moxibustion Treatment of Schizophrenia / 针刺研究

OBJECTIVE: To evaluate the clinical efficacy and security of acupuncture therapy combined with conventional antipsychotics in the treatment of schizophrenia. METHODS: We first comprehensively retrieved papers about acupuncture or moxibustion treatment of schizophrenia published from the time of establishment of the database to April of 2017 in Chinese databases such as Chinese National Knowledge Infrastructure(CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang, and Chinese BioMedical Literature (CBM) by using keywords "acupuncture""moxibustion""acupuncture ＋moxibustion""acupuncture ＋medication""electroacupuncture""filiform needle""scalp-acupuncture""auricular acupuncture"， etc. Then, according to the principles and methods of evidence-based medicine, papers conformed to the included standards were enrolled to Meta-analysis by using Review Manager 5.3 software. RESULTS: A total of 618 studies were identified, with only 17 articles (containing 1 542 patients) conformed to our included standards and analyzed finally. In regard to the total effective rate of acupuncture or moxibustion for schizophrenia, the combined OR＝3.09, 95% CI (2.31, 4.13), the diamond was on the right side of the vertical line (suggesting being effective), OR checked by Z test (Z＝7.61, P<0.000 01). In regard to the untoward effect, the combined OR＝0.34, 95% CI (0.16, 0.75), the diamond was on the left side of the vertical line (suggesting less adverse effects), OR checked by Z test (Z＝2.67，P＝0.008). Sensitivity analysis: the combined standardized mean difference (SMD)＝－0.61, 95% CI(－0.88, －0.34), the diamond was on the left side of the vertical line (suggesting having more profits than simple medication), SMD checked by Z test (Z＝4.39, P<0.000 1)．. CONCLUSION: Acupuncture and moxibustion combined with conventional antipsychotics is significantly better than that of antipsychotics alone in the treatment of schizophrenia and has less side effects. But, high quality clinical studies with rigorous experimental design and large sample size are needed to provide more reliable evidence.

The Experiences of Drug List Formulation Procedure Based on Pharmaeconomics and the Enlightenment to China / 中国卫生经济

Objectives: To analyze the role of pharmaeconomics during drug list formulation procedure and the enlightenment to China. Methods: Using literature review and comparative analysis method, it compared the drug list formulation procedure of WHO, Australia, UK, Tailand and the role of pharmaeconomics. Results: Using pharmaeconomics method was common in international experience. The methodology of pharmaeconomics was also well developed. Conclusions: To improve China drug selection procedure, China should enhance government policy invest in pharmaeconomics usage and support the research, break down the grey benefit relation between medicine and medical.