ObjectiveNon-invasive magnetic stimulation technology has been widely used in the treatment of Alzheimer’s disease (AD), but there is a lack of convenient and timely methods for evaluating and providing feedback on the effectiveness of the stimulation, which can be used to guide the adjustment of the stimulation protocol. This study aims to explore the possibility of heart rate variability (HRV) in diagnosing AD and guiding AD magnetic stimulation intervention techniques. MethodsIn this study, we used a 40 Hz, 10 mT pulsed magnetic field to expose AD mouse models to whole-body exposure for 18 d, and detected the behavioral and electroencephalographic signals before and after exposure, as well as the instant electrocardiographic signals after exposure every day. ResultsUsing one-way ANOVA and Pearson correlation coefficient analysis, we found that some HRV indicators could identify AD mouse models as accurately as behavioral and electroencephalogram(EEG) changes (P<0.05) and significantly distinguish the severity of the disease (P<0.05), including rMSSD, pNN6, LF/HF, SD1/SD2, and entropy arrangement. These HRV indicators showed good correlation and statistical significance with behavioral and EEG changes (r>0.3, P<0.05); HRV indicators were significantly modulated by the magnetic field exposure before and after the exposure, both of which were observed in the continuous changes of electrocardiogram (ECG) (P<0.05), and the trend of the stimulation effect was more accurately observed in the continuous changes of ECG. ConclusionHRV can accurately reflect the pathophysiological changes and disease degree, quickly evaluate the effect of magnetic stimulation, and has the potential to guide the pattern of magnetic exposure, providing a new idea for the study of personalized electromagnetic neuroregulation technology for brain diseases.

  Objective  To summarize the clinical manifestations, pathological features and gene mutation diversity of Blau syndrome/early-onset sarcoidosis.  Methods  We collected general data, clinical manifestations, and auxiliary examination results from 8 patients who were diagnosed of Blau syndrome/early-onset sarcoidosis and treated in our hospital from January 2011 to December 2022, and then summarized and analyzed their characteristics and diversity.  Results  Among the 8 patients, 4 were males and 4 were females. The onset age was 3 to 8 months old. Rash was the first symptom in 7 patients(87.5%). 6 patients(75.0%) had papules and erythema.3 cases(37.5%) had arthritis. 2 cases(25.0%) had uveitis and other eye inflammation. 4 cases (50.0%) also showed intermittent fever. 3 cases (37.5%) showed symptoms in nerve and respiratory system, and hypertension respectively. The skin histopathology of 8 patients showed non-caseous granuloma formation. In laboratory detection, CRP and TNF-α were significantly increased before treatment, while IL-6, IL-8, TNF-α and IL-2 receptor(IL-2R) were significantly decreased in 5 patients after glucocorticoid therapy. The results of genetic testing showed that 4 of the 7 patients had p.R334W(c.1000C > T) mutation, 1 had p.H313R(c.938A > G) and p.R471C(c.1411C > T)double mutation, and 1 had p.476_477del (c.1427_1429delcct).  Conclusions  Blau syndrome/early-onset sarcoidosis has significant features in clinical manifestations, histopathology and gene mutation, but it also has diversity.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown. METHODS: In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot. RESULTS: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC. CONCLUSIONS These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

This study is to observe whether platycodin D has the guiding role in treatment of mouse lung cancer with doxorubicin and explore its guiding mechanism. In vitro, platycodin D and doxorubicin(alone or in combination) were added into Lewis lung cancer(LLC) cells to detect the cell proliferation and doxorubicin uptake. Cell morphological changes were analyzed by cell holographic analysis system; cell gap junctional intercellular communication(GJIC) was tested by fluorescent yellow tracer; lyso-tracker red was used to examine lysosomal function; LC-3 B(Light chain 3 beta)and P62(heat shock 90-like protein)staining were used to test auto-phagy and autophagic degradation respectively; and P-glycoprotein(P-gp) expression was examined by Western blot. In vivo, lung solid tumor was formed in mouse LLC cells via intravenous injection. Platycodin D and doxorubicin(alone or in combination) were used to treat tumor-bearing mice for four weeks, and then the tumor size was examined, mouse survival time was recorded, doxorubicin uptake in lung tissues was tested, and lung tissues were stained for observation by HE(hematoxylin-eosin) and immunohistochemistry. The results showed that platycodin D at the experimental concentration had no effect on LLC cell proliferation but decreased LLC cell volume, promoted the cells to uptake doxorubicin and enhanced the inhibitory action of doxorubicin on cell proliferation. Platycodin D could promote GJIC and lysosomal function, increase autophagy and autophagic degradation and suppress P-gp expression. Platycodin D at the experimental dose in this study had no effect on LLC lung solid tumors in mice, increased doxorubicin uptake in lung tissues and enhanced the therapeutic efficacy of doxorubicin on lung solid tumors. Platycodin D could improve the extracellular matrix deposition in lung solid tumors, decreased the lung mucin 5 AC secretion and pulmonary vessel permeability. In summary, platycodin D had the guiding role in treating mouse lung cancer with doxorubicin, and its guiding mechanism may be associated with the promotion of cell communication, lysosomal function, and improvement of extracellular environment.
Animals ; Cell Line, Tumor ; Doxorubicin ; Lung Neoplasms/drug therapy* ; Mice ; Saponins ; Triterpenes

Objective To investigate the effect of open surgical drainage approach for the treatment of walled-off pancreatic necrosis ( WOPN) in severe acute pancreatitis. Methods Clinical data of 154 WOPN patients admitted in the First Affiliated Hospital of Xinjiang Medical University from January 2005 to October 2016 were retrospectively analyzed. Traditional open debridement necrosectomy was performed in 83 patients from January 2005 to October 2012 ( debridement group) , and small abdominal incision with low-position open surgical drainage was performed in 71 patients from October 2012 to October 2016 ( drainage group ) . The clinical outcomes of two groups were analyzed and compared. Results 43 cases (51. 8％) in debridement group had postoperative intraperitoneal reinfection, while there were only 13 cases with postoperative intraperitoneal reinfection (18. 3％) in drainage group;18 cases (21. 7％) in debridement group had surgery-related digestive tract fistula, while there were only 4 cases with surgery-related digestive tract fistula (5. 6％) in drainage group; the differences were statistically significant (χ2 = 18. 55, P=0. 001; χ2 = 11. 35, P=0. 002). 15 patients (18. 1％) in debridement group and only 2 patients (2. 8％) in drainage group died. The mortality in drainage group were obviously lower than that in debridement group, and the difference was statistically significant (χ2 = 9. 07, P<0. 05 ). 62 cases ( 74. 7％) in debridement group and 55 cases (77. 5％) in drainage group were cured directly, respectively. No significant difference was found between two groups. However, 3 cases (3. 6％) in debridement group and 12 cases (16. 9％) in drainage group were cured by the way of small intestinal fistula in the late stage of intubation, and the latter was higher than the former with statistically significant(χ2 =5. 989,P=0. 014). Conclusions Compared with open debridement necrosectomy, the abdominal infection rate, digestive tract fistula rate and mortality of open surgical drainage were all significantly reduced , which may be a better treatment for WOPN.

OBJECTIVE: To investigate the effects of exosomes from human umbilical cord mesenchymal stem cells on the development of Treg and TH17 cells. METHODS: Exosomes from the serum-free-culture supernatants of hUC-MSC were harvested by ultracentrifugation. The electron microscopy, nanoparticle tracking analysis and western blot were used to identify the hUC-MSC-exosomes, such as the morphology, the paticle chameter, and the protein content. The PBMC stimulated with anti-CD3/CD28 were incubated with the exosomes for five days, and then the percentage changes of Treg and TH17 cells were analyzed by using flow cytometry. RESULTS: The hUC MSC-derived exosomes were saucer-like in morphology the averge diameter was approximately 142 nm. They were identified as positive for CD9 and CD63. Flow cytometry showed that the proportion of CD4CD25Foxp3 Treg cells in the PBMC were significantly higher, but the proportion of CD4IL17A T cells in the hUC-MSC-exosome group was obviously lower than that in the group without the hUC-MSC-exosom (control group) (P<0.05). CONCLUSION The hUC-MSC-exosomes have an immunomodulatory effect on T cells in vitro by increasing the ratio of Treg and reducing the ratio of TH17 cells, expecting the hUC-MSC-exosom as a novel cell-free target for immunotherapy.
Exosomes ; Humans ; Leukocytes, Mononuclear ; Mesenchymal Stem Cells ; T-Lymphocytes, Regulatory ; Th17 Cells ; Umbilical Cord

Objective: To investigate the effects of artesunate treatment on chronic graft-versus-host disease (cGVHD). Methods: Recipient BALB/c mice received 8 × 10(6) bone marrow cells with 8×10(6) spleen cells from B10D2 mice. Artesunate solubilized in acetone was injected intraperitoneally every day at the dose of 1 mg/kg at Day 28 after BMT. The clinical scores, survival and histopathological damage were analyzed. The frequency of Th17 and Tregs in PB and spleens from the mice were evaluated by flow cytometry. In addition, CD4(+) T cells from the spleens of mice were cultured in vitro, then stimulated with artesunate, the frequency of Th17 and Tregs in these splenocytes were evaluated by flow cytometry. Results: Artesunate administration diminished clinical and histopathological damage, and improved the survival of cGVHD mice[(46.57±7.83)% vs (55.71±6.99)%, χ(2)=5.457, P=0.020]; Artesunate contributed to Tregs development [(4.45±0.04)% vs (8.40±0.23)%, t=15.679, P<0.001; (6.62±0.24)% vs (10.48±0.48)%, t=6.587, P=0.003] while decreased Th17 cells [(1.51±0.18)% vs (0.58±0.19)%, t=7.233, P<0.001; (1.48±0.38)% vs (0.71±0.18)%, t=3.653, P=0.011] expressions in both PB and spleens, and decreased the Th17/Treg ratio (0.34±0.05 vs 0.09±0.03, t=7.621, P=0.002; 0.19±0.03 vs 0.06±0.02, t=6.993, P=0.002). Moreover, artesunate suppressed the Th17 cells expressions [(0.82±0.37) % vs (3.39±1.22) %, t=4.044, P=0.007] and contributed to Tregs development [(34.63±1.29) % vs (14.28±1.69) %, t=19.119, P<0.001], and also decreased the Th17/Treg ratio (0.24±0.09 vs 0.02±0.01, t=4.780, P=0.003) in vitro. Conclusions: Artesunate suppressed the Th17 cells expressions and contributed to Tregs development, which provided new sights into the development of a novel drug for cGVHD, e.g., artemisinin.
Animals ; Artesunate ; Graft vs Host Disease ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes, Regulatory ; Th17 Cells

OBJECTIVEVery early-onset coronary artery disease (CAD) is a great challenge in cardiovascular medicine throughout the world, especially regarding its early diagnosis. This study explored whether circulating microRNAs (miRNAs) could be used as potential biomarkers for patients with very early-onset CAD.

METHODSWe performed an initial screening of miRNA expression using RNA isolated from 20 patients with angiographically documented very early-onset CAD and 20 age- and sex-matched normal controls. For further confirmation, we prospectively examined the miRNAs selected from 40 patients with very early-onset CAD and 40 angiography-normal controls.

RESULTSA total of 22 overexpressed miRNAs and 22 underexpressed miRNAs were detected in the initial screening. RT-qPCR analysis of the miRNAs obtained from the initial screening revealed that four miRNAs including miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p exhibited significantly decreased expression in patients compared with that in controls (P<0.05). The areas under the receiver operating characteristic curve for these miRNAs were 0.824 (95% CI, 0.731-0.917; P<0.001), 0.758 (95% CI, 0.651-0.864; P<0.001), 0.753 (95% CI, 0.643-0.863; P<0.001), and 0.782 (95% CI, 0.680-0.884; P<0.001), respectively, in the validation set.

CONCLUSIONTo our knowledge, this is an advanced study to report about four serum miRNAs (miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p) that could be used as novel biomarkers for the diagnosis of very early-onset CAD.

Aged ; Biomarkers ; blood ; Case-Control Studies ; Coronary Artery Disease ; blood ; diagnosis ; genetics ; Early Diagnosis ; Female ; Humans ; Male ; MicroRNAs ; blood ; genetics ; Middle Aged

Objective To investigate anxiety of clinicians in tertiary hospitals,and discuss the fac-tors that influence clinicians'anxiety in order to provide reference for further effective intervention measures. Methods 427 clinicians from various departments in tertiary hospitals selected by cluster sampling method were investigate by self-rating anxiety scale ( SAS) .Statistical software SPSS 17.0 was used to analyze data for multivariate logistic regression analysis of its relevant influencing factors.Results 38.2%of the clini-cians had anxiety symptoms (55.0%was mild anxiety,26.1%was moderate anxiety,18.9%was severe anxi-ety) .Factors like education (χ2=7.3, P=0.03) ,job title (χ2=53.24, P<0.01) ,divisions (χ2=46.46, P<0.01) ,work experience (χ2=9.78, P=0.04) ,work overtime (χ2=4.29, P=0.03) ,worry of medical mal-practice (χ2=9.54, P<0.01),doctor-patient relationship tension (χ2=7.50, P<0.01),fear for personal safety (χ2=10.27, P<0.01) ,job promotion competition (χ2=11.40, P<0.01) ,labor and payment situation (χ2=6.36, P=0.01) ,colleagues'understanding and support (χ2=15.77, P=0.01) ,work environment (χ2=21.85, P<0.01) and leaders'attention (χ2=7.17, P=0.01) had significant differences between anxiety and non-anxiety clinicians.Multivariate logistic regression analysis revealed that factors like divisions ( com-pared with internal medicine,OB&GYNβ=0.98,surgeryβ=0.95,pediatricsβ=0.86,emergencyβ=0.69) , work overtime (β=0.18),fear for personal safety (β=0.86),fear of medical malpractice (β=0.79) and doctor-patient relationship tension (β=0.28) had a negative impact on anxiety,while factors like education ( compared with bachelors,mastersβ=-1.38,doctorsβ=-1.65) ,job title ( compared with primary,intermedi-ateβ=-0.33,highβ=-0.45,advancedβ=-0.59) ,work experience (β=-0.18 ) and work environment (β=-0.32) were protective factors.Conclusion There is a certain degree of anxiety among clinicians in tertiary hospitals,resulting in a heavy psychological burden on them.Active measures should be taken to improve the clinicians'psychological health.

OBJECTIVETo compare efficacy differences between fire filiform needle combined with mild moxibustion and gabapentin combined with sham acupuncture for postherpetic neuralgia (PHN).

METHODSOne hundred cases of PHN were randomly divided into a needle group and a medicine group, 50 cases in each one. In the needle group, pricking method of fire filiform needle was given at the Ashi points, and then mild moxibustion was applied for 15 min. In the medicine group, the oral administration of gabapentin capsule and sham acupuncture at non-acupoints in the distal end of lesions were applied. The treatment was required for 21 days in both groups. The visual analogue score (VAS) was recorded before treatment and on the 1st day, 2nd day, 3rd day, 6th day, 9th day and 12th day of treatment. The most severity of pain within last 24 h, preset severity of pain, immediate analgesia effect and starting time of pain relief were observed, also the efficacy was assessed and improvement of symptoms was observed in the follow-up visit.

RESULTSThe total effective rate was 94.0% (47/50) in the fire filiform needle group, which was superior to 86.0% (43/50) in the medicine group (P < 0.05). Compared with medicine group, the VAS of the most severity of pain within last 24 h was obviously reduced after the 2nd treatment in the fire filiform needle group while that of present severity of pain was relieved after the 1st treatment (both P < 0.05). The immediate analgesia effect in the fire filiform needle group was obviously superior to that in the medicine group in the first three times of treatment (all P < 0.05). The average time of pain relief was (3.91 +/- 0.82) days in the fire filiform needle group, which was significantly earlier to (6.53 +/- 1.13) days in the medicine group (P < 0.05). 26 cases were cured in the fire filiform needle group in the follow-up visit, which was superior to 2 cases in the medicine group (P < 0.05). The improvement of VAS, pain range and sleep quality in the needle group were also superior to those in the medicine group (all P < 0.05). The direct medical cost in the fire filiform needle group was (232.32 +/- 48.108) yuan, which was significantly lower than (466.00 +/- 41.09) yuan in the medicine group (P < 0.05). There was only one case of adverse effect in the medicine group during the treatment.

CONCLUSIONThe fire filiform needle combined with mild moxibustion could obviously relieve the pain in PHN patients, which has superior immediate analgesia effect and pain relieving time compared with gabapentin, which also has less adverse effects and cheap cost.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Combined Modality Therapy ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Neuralgia, Postherpetic ; therapy ; Pain Measurement ; Treatment Outcome