Background The activity in precuneus within default mode network has been reported to be associated with antidepressant response,whereas the relationship between the functional network of precuneus and early response to antidepressant medications remains unclear.Objective To investigate the relationship between precuneus functional connectivity(FC)and early efficacy of antidepressant treatment in patients with major depressive disorder,so as to find a neurobiomarker to predict the early efficacy of antidepressants.Methods A consecutive sample of 47 patients with major depressive disorder who attended the Mental Health Center,West China Hospital of Sichuan University from July 2017 to February 2019 and fulfilled the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)were recruited.Baseline resting-state functional magnetic resonance imaging scan findings and clinical assessments were recorded in participants.All patients treated with antidepressants for two weeks.Improvement was defined as 20%or greater reduction in baseline 16-item Quick Inventory of Depressive Symptoms Self-Report Scale(QIDS-SR16)by treatment exit,and patients were then classified into early improved group(n=27)and non-improved group(n=20).FC values of precuneus and whole brain were calculated using bilateral precuneus as seed region,and baseline precuneus FC values were compared between two groups.Pearson correlation analysis was utilized to explore the correlation between FC values in brain regions with statistically significant differences and QIDS-SR16 total scores and reduction rates.Results FC values between the left precuneus and left precentral gyrus and between the right precuneus and right fusiform gyrus in early improved group were both higher than those in non-improved group(GRF correction,P<0.01).The FC valves between the left precuneus and the left precentral gyrus and between the right precuneus and the right fusiform gyrus were positively correlated with QIDS-SR16 reduction rate(r=0.475,0.297,P<0.05).Conclusion Weakened FC between the left precuneus and left precentral gyrus and between the right precuneus and right fusiform gyrus are related to poor early efficacy to antidepressant treatment,and FC of precuneus may be a potential predictor of early response to antidepressants.

Objective: The main objective of this study was to analyze the efficacy and feasibility of surgical management for patients with thoracic spinal tuberculous spondylitis (STB) by using posterior-only transforaminal debridement and interbody fusion (PTDIF) with preservation of posterior ligamentous complex (PLC) and noninferior of PTDIF compared with conventional posterior-only debridement and interbody fusion (CPDIF). Methods: From January 2019 to January 2022, a prospective, randomized, controlled trial was conducted in which patients with thoracic STB were enrolled and assigned to undergo either the PTDIF group (group A) or CPDIF group (group B) in a 1:1 ratio. The clinical efficacy was evaluated on average operation time, blood loss, hospitalization durations, visual analogue scale, Oswestry Disability Index scores, erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), and neurological function recovery using the American Spinal Injury Association’s impairment scale and operative complications. Radiological measurements included kyphosis correction, loss of correction. The outcomes were compared between the groups at preoperation, postoperaion, and final follow-up. Results: All 65 patients were completely cured during the follow-up. The intraoperative blood loss and operation time in group B were more than that in group A. All patients were pain-free at the final follow-up visit. ESR, CRP returned to normal limits in all patients 3 months after surgery. All patients had improved neurological signs. No significant difference was found in kyphosis angle correction, loss of correction between the 2 groups. Conclusion PTDIF, with preservation of PLC, achieved debridement, decompression, and reconstruction of the spine’s stability, similar to CPDIF in the surgical treatment of thoracic STB. PTDIF has less surgical trauma with less intraoperative blood loss and operation time.

Objective: The main objective of this study was to analyze the efficacy and feasibility of surgical management for patients with thoracic spinal tuberculous spondylitis (STB) by using posterior-only transforaminal debridement and interbody fusion (PTDIF) with preservation of posterior ligamentous complex (PLC) and noninferior of PTDIF compared with conventional posterior-only debridement and interbody fusion (CPDIF). Methods: From January 2019 to January 2022, a prospective, randomized, controlled trial was conducted in which patients with thoracic STB were enrolled and assigned to undergo either the PTDIF group (group A) or CPDIF group (group B) in a 1:1 ratio. The clinical efficacy was evaluated on average operation time, blood loss, hospitalization durations, visual analogue scale, Oswestry Disability Index scores, erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), and neurological function recovery using the American Spinal Injury Association’s impairment scale and operative complications. Radiological measurements included kyphosis correction, loss of correction. The outcomes were compared between the groups at preoperation, postoperaion, and final follow-up. Results: All 65 patients were completely cured during the follow-up. The intraoperative blood loss and operation time in group B were more than that in group A. All patients were pain-free at the final follow-up visit. ESR, CRP returned to normal limits in all patients 3 months after surgery. All patients had improved neurological signs. No significant difference was found in kyphosis angle correction, loss of correction between the 2 groups. Conclusion PTDIF, with preservation of PLC, achieved debridement, decompression, and reconstruction of the spine’s stability, similar to CPDIF in the surgical treatment of thoracic STB. PTDIF has less surgical trauma with less intraoperative blood loss and operation time.

Objective: The main objective of this study was to analyze the efficacy and feasibility of surgical management for patients with thoracic spinal tuberculous spondylitis (STB) by using posterior-only transforaminal debridement and interbody fusion (PTDIF) with preservation of posterior ligamentous complex (PLC) and noninferior of PTDIF compared with conventional posterior-only debridement and interbody fusion (CPDIF). Methods: From January 2019 to January 2022, a prospective, randomized, controlled trial was conducted in which patients with thoracic STB were enrolled and assigned to undergo either the PTDIF group (group A) or CPDIF group (group B) in a 1:1 ratio. The clinical efficacy was evaluated on average operation time, blood loss, hospitalization durations, visual analogue scale, Oswestry Disability Index scores, erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), and neurological function recovery using the American Spinal Injury Association’s impairment scale and operative complications. Radiological measurements included kyphosis correction, loss of correction. The outcomes were compared between the groups at preoperation, postoperaion, and final follow-up. Results: All 65 patients were completely cured during the follow-up. The intraoperative blood loss and operation time in group B were more than that in group A. All patients were pain-free at the final follow-up visit. ESR, CRP returned to normal limits in all patients 3 months after surgery. All patients had improved neurological signs. No significant difference was found in kyphosis angle correction, loss of correction between the 2 groups. Conclusion PTDIF, with preservation of PLC, achieved debridement, decompression, and reconstruction of the spine’s stability, similar to CPDIF in the surgical treatment of thoracic STB. PTDIF has less surgical trauma with less intraoperative blood loss and operation time.

Objective: The main objective of this study was to analyze the efficacy and feasibility of surgical management for patients with thoracic spinal tuberculous spondylitis (STB) by using posterior-only transforaminal debridement and interbody fusion (PTDIF) with preservation of posterior ligamentous complex (PLC) and noninferior of PTDIF compared with conventional posterior-only debridement and interbody fusion (CPDIF). Methods: From January 2019 to January 2022, a prospective, randomized, controlled trial was conducted in which patients with thoracic STB were enrolled and assigned to undergo either the PTDIF group (group A) or CPDIF group (group B) in a 1:1 ratio. The clinical efficacy was evaluated on average operation time, blood loss, hospitalization durations, visual analogue scale, Oswestry Disability Index scores, erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), and neurological function recovery using the American Spinal Injury Association’s impairment scale and operative complications. Radiological measurements included kyphosis correction, loss of correction. The outcomes were compared between the groups at preoperation, postoperaion, and final follow-up. Results: All 65 patients were completely cured during the follow-up. The intraoperative blood loss and operation time in group B were more than that in group A. All patients were pain-free at the final follow-up visit. ESR, CRP returned to normal limits in all patients 3 months after surgery. All patients had improved neurological signs. No significant difference was found in kyphosis angle correction, loss of correction between the 2 groups. Conclusion PTDIF, with preservation of PLC, achieved debridement, decompression, and reconstruction of the spine’s stability, similar to CPDIF in the surgical treatment of thoracic STB. PTDIF has less surgical trauma with less intraoperative blood loss and operation time.

Objective: The main objective of this study was to analyze the efficacy and feasibility of surgical management for patients with thoracic spinal tuberculous spondylitis (STB) by using posterior-only transforaminal debridement and interbody fusion (PTDIF) with preservation of posterior ligamentous complex (PLC) and noninferior of PTDIF compared with conventional posterior-only debridement and interbody fusion (CPDIF). Methods: From January 2019 to January 2022, a prospective, randomized, controlled trial was conducted in which patients with thoracic STB were enrolled and assigned to undergo either the PTDIF group (group A) or CPDIF group (group B) in a 1:1 ratio. The clinical efficacy was evaluated on average operation time, blood loss, hospitalization durations, visual analogue scale, Oswestry Disability Index scores, erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), and neurological function recovery using the American Spinal Injury Association’s impairment scale and operative complications. Radiological measurements included kyphosis correction, loss of correction. The outcomes were compared between the groups at preoperation, postoperaion, and final follow-up. Results: All 65 patients were completely cured during the follow-up. The intraoperative blood loss and operation time in group B were more than that in group A. All patients were pain-free at the final follow-up visit. ESR, CRP returned to normal limits in all patients 3 months after surgery. All patients had improved neurological signs. No significant difference was found in kyphosis angle correction, loss of correction between the 2 groups. Conclusion PTDIF, with preservation of PLC, achieved debridement, decompression, and reconstruction of the spine’s stability, similar to CPDIF in the surgical treatment of thoracic STB. PTDIF has less surgical trauma with less intraoperative blood loss and operation time.

BackgroundFunctional near-infrared spectroscopy （fNIRS） is a new generation of imaging tool that can be used to assist the diagnosis of psychiatric disorders. However， whether the patterns of prefrontal cortex activation observed by fNIRS are specific for different psychiatric disorders remains to be explored. ObjectiveTo investigate the characteristics of prefrontal cortex activation in patients with depression， anxiety disorder， bipolar disorder and schizophrenia in verbal fluency task （VFT） using fNIRS. MethodsFrom September to December 2021， 39 patients with schizophrenia， 205 patients with depressive disorder， 212 patients with anxiety disorder and 77 patients with bipolar disorder meeting the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited in the outpatient and inpatient department of West China Hospital， Sichuan University. fNIRS was used to monitor the prefrontal cortex hemodynamic changes of patients under VFT， and the clinical symptoms of patients were assessed by Symptom Checklist 90 （SCL-90） and Hypomania Checklist-32 items（HCL-32）. Differences in mean oxyhemoglobin （HbO₂） concentration and the initial slope from 2 to 7 second during VFT were compared among patients with different diseases， and the correlation between mean HbO₂ concentration/initial slope and clinical symptoms was analyzed by partial correlation analysis. ResultsThe concentration of HbO₂ in channel 4 （Z=2.828， P=0.028） and channel 6 （Z=2.912， P=0.022） in patients with depression were significantly higher than those in patients with schizophrenia. Patients with anxiety had significantly higher changes in mean HbO₂ concentration in channel 4 （Z=3.154， P=0.010）， channel 5 （Z=3.021， P=0.015）， channel 6 （Z=2.980， P=0.017） and of all channels （Z=2.881， P=0.024） than those of schizophrenia patients. There was a statistically significant difference in the initial slope of channel 3 between patients with depressive disorder and those with bipolar disorder （Z=2.691， P=0.039）. Among patients with bipolar disorder， the anger-hostility scores of SCL-90 were negatively correlated with the mean HbO₂ concentration changes in channel 4 （r=-0.505， P=0.004）， channel 6 （r=-0.390， P=0.004）， channel 15 （r=-0.546， P=0.002）， channel 16 （r=-0.550， P=0.002） and the mean HbO₂ concentration changes of all channels （r=-0.491， P=0.006）. ConclusionPatients with schizophrenia had lower activation in frontopolar and orbitofrontal region than patients with depression and anxiety disorder， and the initial slope of the right frontopolar， inferior frontal and orbitofrontal region in patients with depression is higher than patients with bipolar disorder. In addition， patients with bipolar disorder had less activation in the frontopolar and orbitofrontal lobe， the insular cover of Broca's area and the upper outer frontal cortex， and were more irritable and hostile. ［Funded by 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project， West China Hospital， Sichuan University （number， ZYJC21083）］

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: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies

OBJECTIVE: To construct a polylactic acid-glycolic acid-polyethylene glycol (PLGA-PEG) nanocarrier (N-Pac-CD133) coupled with a CD133 nucleic acid aptamer carrying paclitaxel for eliminating lung cancer stem cells (CSCs). METHODS: Paclitaxel-loaded N-Pac-CD133 was prepared using the emulsion/solvent evaporation method and characterized. CD133⁺ lung CSCs were separated by magnetic bead separation and identified for their biological behaviors and gene expression profile. The efficiency of paclitaxel-loaded N-Pac-CD133 for targeted killing of lung cancer cells was assessed in vitro. SCID mice were inoculated with A549 cells and received injections of normal saline, empty nanocarrier linked with CD133 aptamer (N-CD133), paclitaxel, paclitaxel-loaded nanocarrier (N-Pac) or paclitaxel-loaded N-Pac-CD133 (n=8, 5 mg/kg paclitaxel) on days 10, 15 and 20, and the tumor weight and body weight of the mice were measured on day 40. RESULTS: Paclitaxel-loaded N-Pac-CD133 showed a particle size of about 100 nm with a high encapsulation efficiency (>80%) and drug loading rate (>8%), and was capable of sustained drug release within 48 h. The CD133⁺ cell population in lung cancer cells showed the characteristic features of lung CSCs, including faster growth rate (30 days, P=0.001) and high expressions of tumor stem cell markers OV6(P < 0.001), CD133 (P=0.001), OCT3/4 (P=0.002), EpCAM (P=0.04), NANOG (P=0.005) and CD44 (P=0.02). Compared with N-Pac and free paclitaxel, paclitaxel-loaded N-Pac-CD133 showed significantly enhanced targeting ability and cytotoxicity against lung CSCs in vitro (P < 0.001) and significantly reduced the formation of tumor spheres (P < 0.001). In the tumor-bearing mice, paclitaxel-loaded N-Pac-CD133 showed the strongest effects in reducing the tumor mass among all the treatments (P < 0.001). CONCLUSION CD133 aptamer can promote targeted delivery of paclitaxel to allow targeted killing of CD133⁺ lung CSCs. N-Pac-CD133 loaded with paclitaxel may provide an effective treatment for lung cancer by targeting the lung cancer stem cells.
Animals ; Cell Line, Tumor ; Drug Carriers ; Lung ; Mice ; Mice, SCID ; Nanoparticles ; Neoplasms ; Neoplastic Stem Cells ; Paclitaxel/pharmacology* ; Polyethylene Glycols/pharmacology*