Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features. Using single-nucleus RNA sequencing, we identified cell-specific transcriptomic changes in the nucleus accumbens (NAc), particularly in astrocytes, of adolescent macaques exhibiting depressive-like behaviors. The level of diacylglycerol kinase beta was significantly reduced in neurons and glial cells of depressed macaques, while FKBP5 levels increased in glial cells. Disruption of GABAergic synapses and disruption of D-glutamine and D-glutamate metabolism were linked to depressive phenotypes in medium spiny neurons (MSNs) and subtypes of astrocytes. Communication pathways between astrocytes and D1/D2-MSNs were also disrupted, involving factors like bone morphogenetic protein-6 and Erb-B2 receptor tyrosine kinase-4. Bulk transcriptomic and proteomic analyses corroborated these findings, and FKBP5 upregulation was confirmed by qRT-PCR, western blotting, and immunofluorescence in the NAc of rats and macaques with chronic unpredictable mild stress. Our results highlight the specific roles of different cell types in adolescent depression in the NAc, offering potential targets for new antidepressant therapies.
Animals ; Nucleus Accumbens/metabolism* ; Male ; Transcriptome ; Depression/genetics* ; Astrocytes/metabolism* ; Neurons/metabolism* ; Rats

Objective To observe the value of amide proton transfer(APT)imaging for assessing central nervous system damages in stable chronic obstructive pulmonary disease(COPD)and the correlations with MR spectroscopy(MRS)and lung function parameters.Methods Thirty-nine stable COPD patients(COPD group)and 34 healthy subjects(control group)were prospectively enrolled.Images of plain head MR,3D-APT and thalami MRS were acquired,and parameters of lung function were obtained.The basic data,outcomes of voxel-based morphometry(VBM)analysis,APT values in multiple brain regions and thalami MRS metabolite parameters were compared between groups,and the correlations of thalamus APT values with thalamus MRS metabolites parameters and lung function parameters were explored.Results Lung function parameters in COPD group were lower than those in control group,while cerebrospinal fluid volume(CSFV)and total brain volume(TIV)in COPD group were lager than those in control group(all P＜0.05).Compared with those in control group,APT values of bilateral thalami,right temporal lobe and right occipital lobe in COPD group were higher,and the peak value of N-acetyl aspartate(NAA)of bilateral thalami and NAA/creatin of right thalamus in COPD group were lower(all P＜0.05).Within COPD group,APT values of bilateral thalami were positively correlated(r=0.641),while APT values of left thalamus showed negative correlation(r=-0.435)with NAA values left thalamus and negative correlation(r=-0.432)with the forced expiratory volume in the first one second after bronchodilator administration(FEV1)(all P＜0.05).Conclusion APT values of central nervous system elevated and NAA values decreased in COPD patients.There were negative correlations between left thalamus APT and NAA values,also between APT values of left thalamus and FEV1.

Purpose The feasibility and application value of 3D amide proton transfer weighted(APTw)imaging is used to evaluate central nervous system injury in stable chronic obstructive pulmonary disease(COPD)patients.Materials and Methods A total of 36 COPD patients who attended the First Affiliated Hospital of Henan University of Chinese Medicine from January 2022 to August 2023 were selected along with 31 age-and gender-matched healthy volunteers.All subjects underwent pulmonary function tests,routine blood tests,Montreal cognitive assessment scale(MoCA)assessment and 3.0T MRI scan.The APT values of each brain region were measured independently and assessed for consistency by two observers,and the differences in APT values of each brain region were compared between the two groups to explore the correlation between the APT values of multiple brain regions and the pulmonary function,blood indices,and MoCA scores.Results The measurement consistency of APT values in multiple brain regions among observers was good(ICC>0.75).The APT values of brain regions in the COPD group were higher than those in the healthy control group,with statistically significant differences between the bilateral pallidum(t=2.490,2.168),the right thalamus(t=2.754),the nucleus accumbens(t=2.137),the temporal lobe gray matter(t=3.533)and the occipital lobe gray matter(t=2.345)compared with those in the healthy control group(all P<0.05);the APT values of the multiple brain regions were in a negative correlation(r=-0.390--0.084),with a stronger correlation between bilateral pallidum(r=-0.390,-0.370,both P<0.05);lung function indexes(forced vital capacity,forced expiratory volume in one second,forced expiratory volume in one second/forced vital capacity,forced expiratory volume in one second/prediction)in the COPD group showed a negative correlation trend with the APT values of the multibulbar areas(r=-0.339--0.010,all P>0.05),while white blood cell count,red blood cell count,hemoglobin concentration and platelet count showed a positive correlation trend with multi brain APT values(r=0.084-0.587).Conclusion As a novel MRI technology,APTw has potential application value in early detection of central nervous system damage in COPD patients and non-invasive monitoring of disease progression.

BACKGROUND: Osteopenia has been well documented in adolescent idiopathic scoliosis (AIS). Bone marrow stem cells (BMSCs) are a crucial regulator of bone homeostasis. Our previous study revealed a decreased osteogenic ability of BMSCs in AIS-related osteopenia, but the underlying mechanism of this phenomenon remains unclear. METHODS: A total of 22 AIS patients and 18 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Bone marrow blood was collected for BMSC isolation and culture. Osteogenic and adipogenic induction were performed to observe the differences in the differentiation of BMSCs between the AIS-related osteopenia group and the control group. Furthermore, a total RNA was extracted from isolated BMSCs to perform RNA sequencing and subsequent analysis. RESULTS: A lower osteogenic capacity and increased adipogenic capacity of BMSCs in AIS-related osteopenia were revealed. Differences in mRNA expression levels between the AIS-related osteopenia group and the control group were identified, including differences in the expression of LRRC17 , DCLK1 , PCDH7 , TSPAN5 , NHSL2 , and CPT1B . Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed several biological processes involved in the regulation of autophagy and mitophagy. The Western blotting results of autophagy markers in BMSCs suggested impaired autophagic activity in BMSCs in the AIS-related osteopenia group. CONCLUSION Our study revealed that BMSCs from AIS-related osteopenia patients have lower autophagic activity, which may be related to the lower osteogenic capacity and higher adipogenic capacity of BMSCs and consequently lead to the lower bone mass in AIS patients.
Humans ; Adolescent ; Scoliosis/genetics* ; Cell Differentiation/physiology* ; Osteogenesis/genetics* ; Bone Diseases, Metabolic/genetics* ; Kyphosis ; Autophagy/genetics* ; Bone Marrow Cells ; Cells, Cultured ; Doublecortin-Like Kinases

BACKGROUND: Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients. METHODS: Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes. RESULTS: Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality. CONCLUSION: Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients. CLINICAL TRIAL REGISTRATION Chinese Clinical Trail Registry, No. ChiCTR2100044625.
Humans ; Blood Pressure ; Pulmonary Disease, Chronic Obstructive/therapy* ; Cohort Studies ; Respiration, Artificial ; Inpatients ; Hospital Mortality

Objective:To evaluate the feasibility and clinical efficacy of deformed complex vertebral osteotomy (DCVO) technique on the treatment of angular kyphosis of cured spinal tuberculosis.Methods:A retrospective study was performed on patients with angular kyphosis of cured spinal tuberculosis who underwent the DCVO technique or posterior vertebral column resection (PVCR) technique from Jan, 2007 to Jan, 2019. 33 patients were included, 18 males and 15 females, the average age was 39.5±15.0 years old (ranged 9-78 years old). The vertebral deformity in thoracic vertebrae 14 cases, thoracolumbar vertebrae 16 cases, and lumbar vertebrae 3 cases. 20 cases underwent the DCVO technique, while 13 cases underwent PVCR technique. For DCVO group, the multiple malformed vertebrae were considered a malformed complex, and a larger range and angle wedge osteotomy was performed within the complex using the DCVO technique. PVCR technique would resect the whole deformed vertebrae, and subsequently brought the two separated spinal columns together with instruments and titanium mesh. The intro-operative blood loss, operating time and complications were recorded. The radiological measurements included preoperative and postoperative spinopelvic parameters, which including thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and segmental kyphosis. The recovery of neurological function was evaluated by Frankle classification.Results:All patients were followed up for 7-72 months. Comparing with the cases underwent PVCR technique, the DCVO group has a significantly lower blood loss (1315.00±462.57 ml), operating time (293.00±83.86 min) and complications rate (1.5%). At the time of preoperation, postoperation and last follow-up, the deformity angle of DCVO group was 96.80°±6.32°, 29.10°±6.96°and 29.05°±6.49°, which gained an average 69.9% correction rate. The statistical analysis suggested that deformity angle was enormously corrected. And there was an insignificant difference between DCVO group and PVCR group. Meanwhile, the preoperative, postoperative and follow-up TK of DCVO group was 96.96°±29.13°, 37.15°±4.88° and 37.00°±3.89°respectively, whosecorrection rate was 67.1%; LL was 66.70°±21.21°, 42.25°±5.53° and 41.90°±4.98°, which have a significant difference between pre-operation and post-operation/follow-up ( F=23.997, P<0.001) ; SVA was 75.95±18.63 mm, 16.30±6.88 mm and 16.55±7.30 mm. PI was 47.50°±6.12°, 47.35°±5.54°and 47.90°±5.93°, PT was 37.25°±9.63°, 18.50°±1.99° and 19.00°±1.65°; SS was 10.25°±8.27°, 29.15°±5.91° and 28.85°±5.77°. The sagittal and spinopelvic parameters of two groups improved significantly at postoperation and follow-up. No obviously difference of spinal parameters was found between two groups at preoperation and postoperation. Both groups have cases with dysneuria. And all of these cases achieved different degrees of recovery at follow-up. Conclusion:The use of DCVO technique for the treatment of post-tubercular angular kyphosis is safe and efficiency. DCVO leads a better clinical outcomes and lower complication rate than VCR technique.

Objective To explore the changes and significance of Klotho protein levels in different stages of chronic kidney disease (CKD). Methods From March 2015 to December 2017,176 patients with CKD admitted to nephrology department of Inner Mongolia People＇s Hospital were selected as the study object (CKD group), and 80 healthy patients in our hospital were selected as the control group in the same period. The serum Klotho levels of CKD patients and control group at different stages were detected by double antibody sandwich ELISA, and the differences between each group were compared. Results The serum Klotho level of CKD group (( 4. 84 ± 1. 87) μg／L) was significantly lower than that of the control group ((9. 11± 3. 14) μg／L) ( t＝ 13. 82, P＜0. 01) . One-way anova showed that estimated renal glomerular filtration rate (eGFR),serum albumin (ALB),hemoglobin ( Hb),blood calcium ( Ca) and serum Klotho were gradually decreased,while phosphorus (P) and creatinine (Cr) in serum were gradually increased,and the difference was statistically significant among the five stages( all P＜0. 01). Spearman correlation analysis showed that Klotho level was positively correlated with eGFR and Ca,and negatively correlated with CKD stage,Cr and P (r＝0. 369,0. 160,－0. 200,－0. 250,－0. 230,all P＜0. 05). The multiple linear regression equation showed that Klotho level was positively and independently correlated with eGFR ( t＝ 3. 89, P＜0. 001),and negatively correlated with CKD staging independently (t＝－4. 12,P＜0. 001). Conclusion The expression level of serum Klotho protein in patients with CKD is lower than that of healthy people,and it decreases with the increase of CKD stages,which is closely related to the deterioration of renal function. It can be used as a reference index to evaluate the incidence and severity of CKD.

Environmental problems are the most serious challenges in the 21st century. With the rapid development of modern industry and agriculture, ecological and environmental deterioration have become the most important factors to restrict the sustainable development of social economy. Microbial cells have strong ability for environmental remediation, but their evolution speed is slower than the speed of emerging pollutants. Therefore, the treatment using the synthetic biology is in urgent need. Full understanding of the microbial degradation characteristics (pathways) of refractory organic pollutants with the help of abundant microbial and gene resources in China is important. Using synthetic biology to redesign and transform the existing degrading strain will be used to degrade particular organic pollutants or multiple organic pollutants. For the complex pollutants, such as wastewater, based on the establishment of metabolic or regulation or resistance related gene modules of typical organic pollutants, artificial flora could be designed to solve the complex pollutants. The rational design and construction of engineering bacteria for typical environmental organic pollutants can effectively promote microbial catabolism of emerging contaminants, providing technical support for environmental remediation in China.

Objective: To discuss the conversion coefficient of morphine injection with continuous intravenous pump delivery or subcutaneous injection for the patients with advanced cancer pain demanding high dose of opioids.Methods: Using a retrospective survey, the patients with advanced cancer pain demanding high dose of opioids with poor efficacy were divided into 3∶1 group and 2.5∶1 group, and the conversion coefficient of 3∶1 or 2.5∶1 was used for the opioids equivalently conversed to intravenous or subcutaneous injection of morphine.After the conversion, the degree of pain relief, the analgesic efficiency in the conversion process, titration time, daily oral morphine equivalent amount at stable pain, morphine related adverse reactions and the other indicators were studied to evaluate the analgesic effect of morphine injection with different conversion coefficient.Results: There was no statistical significant difference between the two groups in the degree of pain relief, the effective rate of analgesia and the daily oral akministration amount of morphine at sable pain(P>0.05).The adjustment times for morphine in the two groups was (1.57±0.93) and (1.0±0.00), respectively, and the difference was statistically significant (P<0.05).The daily oral administration amount of morphine at stable pain in the two groups respectively was (226.67±69.74) mg and (258.67±101.34) mg;the morphine related adverse reactions were mainly constipation, and there was no significant difference in the incidence (P>0.05).Conclusion: Giving morphine injection to the patients with terminal cancer pain demanding high dose of opioids with poor effect, the use of PCA pump through intravenous or subcutaneous injection can effectively relieve pain.Using the conversion coefficient of 2.5:1 can quickly complete the titration process, and safely achieve the effective analgesia.

Objective To evaluate the clinical efficacy and feasibility of using the expanding pedicle subtraction osteotomy (E-PSO) technique for the treatment of congenital severe thoracic angular kyphotic deformity.Methods We retrospectively reviewed a cohort of 13patients with congenital severe kyphosis admitted to our hospital from January 2010 to June 2015 including 5 males and 8 females,the average age is (34.9±20.5) years old (ranged 15-55 years old).The vertebral deformity in T7～83 cases,T8～93 cases,T9～102 cases,T10～114 cases,T9～111 case.All cases were treated by E-PSO technique.The multi-malformed vertebrae are considered as a complexus.And the osteotomy was performed within the complexus.The superior and inferior endplate of the complexus were reserved.After the osteotomy was completed,alternately pressed tightly closed the upper and lower parts.Results All cases were followed up for 10-42 months,with an average of 32 months.At the time of preoperation,postoperation andthe last follow-up,the deformity angle was 107.0°±3.5°,23.5°± 1.5° and 23.5°±0.2°;TK was 98.1°±7.6°,28.9°±3.0° and 29.5°±0.1 °,LL was 94.1 °± 1.5°,43.7°± 1.3° and 44.1 °±5.3°;SVA was (-0.6±39) mm,(1.6±7.9) mm and (6±0.7) mm,respectively;PI was 28.9°±1.6°,31.7±12.3°and 31.9°±2.1°;PT was 17.7°±1.9°,13.4°±3.4°and 13.1°±4.2°,SS was 11.3°±0.4°,18.2°±1.1° and 18.7°±2.1°,respectively.The sagittal parameters and spinopelvic parameters except SVA were significantly improved in the post-operation and the last follow-up compared with the pre-operation according to the image data.No significant loss of correction occurred during the follow-up,and there was no statistical difference.The preoperative VAS score was (5.7± 1.4) points,ODI score was (19.8±12.7) points.The last follow-up VAS score was (1.9±0.7) points,the ODI score was (9.2±0.7) points.No case of nerve damage,infection and other complications,and no dissection,displacement and rupture of internal fixation were found during the follow-up.Conclusion The use of E-PSO technique for the treatment of congenital severe thoracic kyphotic kyphosis is feasible and can achieve better curative effect.