OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

Exosomal circular RNA (circRNAs) are pivotal in cancer biology, and tumor pathophysiology. These stable, non-coding RNAs encapsulated in exosomes participated in cancer progression, tumor growth, metastasis, drug sensitivity and the tumor microenvironment (TME). Their presence in bodily fluids positions them as potential non-invasive biomarkers, revealing the molecular dynamics of cancers. Research in exosomal circRNAs is reshaping our understanding of neoplastic intercellular communication. Exploiting the natural properties of exosomes for targeted drug delivery and disrupting circRNA-mediated pro-tumorigenic signaling can develop new treatment modalities. Therefore, ongoing exploration of exosomal circRNAs in cancer research is poised to revolutionize clinical management of cancer. This emerging field offers hope for significant breakthroughs in cancer care. This review underscores the critical role of exosomal circRNAs in cancer biology and drug resistance, highlighting their potential as non-invasive biomarkers and therapeutic targets that could transform the clinical management of cancer.

Objective: To determine the active components of Eupolyphaga sinensis Walker (Tu Bie Chong) and explore the mechanisms underlying its fracture-healing ability. Methods: A modified Einhorn method was used to develop a rat tibial fracture model. Progression of bone healing was assessed using radiological methods. Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site. Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration. The Transwell assay was used to explore the invasion capacity of the cells. Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells (HUVECs). qRT-PCR was used to evaluate the changes in gene transcription levels. Results: Tu Bie Chong fraction 3 (TF3) significantly shortened the fracture healing time in model rats. X-ray results showed that on day 14, fracture healing in the TF3 treatment group was significantly better than that in the control group (P = .0086). Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group. In vitro, TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs (all P < .01). Transwell assays showed that TF3 promoted the migration of HUVECs, but inhibited the migration of MC3T3-E1 cells. Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules. Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA, SPOCD1, NGF, and NGFR in HUVECs. In MC3T3-E1 cells, the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment. Conclusion TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.

Objective To investigate the effect of iTBS stimulation on walking function in patients with stroke.Methods Fifty patients with post-stroke walking dysfunction who met the inclusion criteria were selected for 3-week rehabilitation treatment,and were randomly divided into iTBS group(n=25)and sham group(n=25).The iTBS group was treated with conventional rehabilitation therapy combined with iTBS stimulation of contral-esional cerebellum,and the sham group was treated with conventional rehabilitation therapy plus iTBS stimulation of contralesional cerebellum.Relevant indicators were analyzed before treatment and at 21 days of treatment.Lower limb motor function scores of the two groups were compared before and after treatment.Fugl-Meyer motor function lower limb activity score,Berg Balance Scale score,Brunnstrom stage(lower limb),hamstring/quadriceps(H/Q)on the affected side,Modified Barthel index(MBI),gait analysis parameters,and TMS-MEP were used to evaluate the effectiveness of cerebellar iTBS in the rehabilitation of walking dysfunction after stroke.Results After 21 days of treatment,the improvements of Brunnstrom stage,Holden grade,Berg score,FMA score,6-minute walking dis-tance,NIHSS score and MBI score in iTBS group were significantly better than those in sham group(P<0.05).Af-ter treatment,the H/Q in iTBS group was significantly higher thanbefore(P<0.05),but there was no significant difference between the two groups(P>0.05).Stride speed,stride frequency,stride width,single support phase on the affected side and GDI score in iTBS group were significantly improved compared with sham group(P<0.05),and there was no significant difference in stride length between the two groups after treatment(P>0.05).The amplitude of MEP in the affected cerebral cortex of iTBS group was lower after treatment than before(P<0.05).Conclusion Contralesional cerebellar iTBS combined with routine rehabilitation could improve lower limb walk-ing function and daily living ability of stroke patients.

Objective To explore the development and validation of a prediction model for severe communi-ty-acquired pneumonia in adults based on peripheral blood inflammatory indicators.Methods Venous blood samples of 204 community-acquired pneumonia in adults patients admitted to 7 hospitals in Chongqing area from April 2021 to August 2022 were collected to detect C-reactive protein(CRP),peripheral white blood cell count(WBC),neutrophil to lymphocyte ratio(NLR),cytokines,lymphocyte subgroups and neutrophil CD64 index.All of patients were divided into a training group and a validation group according to the time of admis-sion.Univariate and multivariate Logistic regression were used to analyze the data of the training group,the characteristic factors of severe progression for pneumonia were selected to construct the nomogram model,and the data of the validation group was used to verify the model.The receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA)were used to evaluate the prediction ability of the model for severe community-acquired pneumonia in adults.Results Logistic regression analysis showed that age,CRP,WBC,interleukin(IL)-4/interferon gamma ratio and IL-6/IL-10 ratio were independent risk factors for severe community-acquired pneumonia in adults.The area under the ROC curve of the nomogram model in the training group and the validation group was 0.893 and 0.880,respectively.The calibration curve and DCA results shown that the model had a good prediction effect for severe community-acquired pneumonia in adults.Conclusion The inflammatory indicators included in this model are simple and easy to obtain clinically.This model with good differentiation and accuracy,it can be used as a practical tool to predict severe community-ac-quired pneumonia in adults,and has certain clinical application value.

Objective To study the effects of intramedullary pressure on the fluid flow behavior in bones.Methods Multi-scale models of macro bone tissue and macro-meso osteon groups were established using the COMSOL Multiphysics software.Considering the interrelationship of different pore scales,such as the bone marrow cavity,Haversia canal,and bone lacunar-canaliculus,the pore pressure and flow rate of hollow bone tissues and bone tissues with intramedullary pressure were compared,and the effects of the amplitude and frequency of intramedullary pressure on the pressure and flow velocity of the liquid in the bone were analyzed.Results When intramedullary pressure was considered,the pore pressure in bone tissues with intramedullary pressure was 6.4 kPa higher than that in hollow bone tissues.The flow pressure increased significantly with an increase in the intramedullary pressure amplitude,but the flow velocity remained unchanged.The frequency of intramedullary pressure had little effect on pore pressure and flow velocity.Conclusions The multi-scale pore model established in this study can accurately analyze bone fluid flow behavior.These results are of great significance for an in-depth understanding of force conduction in the bone.

To identify the bitter compounds of real-world Xiaoer Ganmao Oral Liquid sugar-free intermediates, an integrated strategy has been developed by using ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSⁿ) method and BitterX database prediction. The chromatographic operating conditions were as follows, chromatographic column: Acquity UPLC BEH C₁₈ (100 mm × 2.1 mm, 1.7 μm), mobile phase: 0.1% formic acid-water solution (A)-acetonitrile (B) with gradient elution. The data were collected in positive and negative ion modes, respectively. The accurate molecular mass and structural information of the target compounds were obtained based on quasi-molecular ions and fragmentation ions provided by high-resolution mass spectrometry. The compounds were identified by combining retention time, reference substances, reports, and other relevant data, and a total of 57 constituents including flavonoids, alkaloids, and phenylpropanoids were finally identified. Further, the BitterX database was used to predict binding probability of compounds to bitter receptors and identify potential bitter critical quality attributes, finally 33 potential bitter compounds, including kukoamine A and linarin, were predicted. This study comprehensively characterized the material basis of Xiaoer Ganmao Oral Liquid sugar-free intermediates, it provides an effective method for bitter compound screening and a reference for further improving the undesirable taste of Xiaoer Ganmao Oral Liquid.

An epidemiological investigation was conducted on a cluster epidemic of COVID-19 in the vaccinated population in Beijing in 2022, and serum samples were collected from 21 infected cases and 61 close contacts (including 20 cases with positive nucleic acid in the isolation observation period). The results of antibody detection showed that the IgM antibody of two infected persons was positive, and the IgG antibody positive rates of patients who were converted, not converted to positive and infected persons were 36.84% (7/19), 63.41% (26/41) and 71.43% (15/21), respectively. About 98.78% of patients had been vaccinated with the SARS-CoV-2 inactivated vaccine. The positive rate of IgG antibody in patients immunized with three doses of vaccine was 86.00% (43/50), which was higher than that in patients with one or two doses [16.12% (5/31)]. The antibody level of M (Q₁, Q₃) in patients immunized with three doses was 4.255 (2.303, 7.0375), which was higher than that in patients with one or two doses [0.500 (0.500, 0.500)] (all P values<0.001). The antibody level of patients who were vaccinated less than three months [7.335 (1.909, 7.858)] was higher than that of patients vaccinated more than three months after the last vaccination [2.125 (0.500, 4.418)] (P=0.007). The positive rate and level of IgG antibody in patients who were converted to positive after three doses were 77.78% (7/9) and 4.207 (2.216, 7.099), respectively, which were higher than those in patients who were converted after one or two doses [0 and 0.500 (0.500, 0.500)] (all P values<0.05).
Humans ; COVID-19 ; SARS-CoV-2 ; Disease Outbreaks ; COVID-19 Vaccines ; Immunoglobulin G ; Antibodies, Viral

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve