PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Purpose::This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects.Methods::Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct 3-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean ± standard deviation and compared using independent sample t-tests. Results::In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment.Conclusion::Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.

Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province,and provide for the initial diagnosis and treatment of clinical bloodstream infection(BSI).Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacterial antimicrobial resistance surveillance method was imple-mented according to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS).Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 soft-ware and SPSS 27.0 software.Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021,including 107 135(51.7％)Gram-positive bacteria and 99 919(48.3％)Gram-negative bacteria.There was no change in the top 6 pathogenic bacteria from 2012 to 2021,with Escherichia coli(n=51 537,24.9％)ranking first,followed by Staphylococcus epidermidis(n=29 115,14.1％),Staphylococcus aureus(n=17 402,8.4％),Klebsiella pneu-moniae(17 325,8.4％),Pseudomonas aeruginosa(n=4 010,1.9％)and Acinetobacter baumannii(n=3 598,1.7％).The detection rate of methicillin-resistant Staphylococcus aureus(MRSA)decreased from 30.3％in 2015 to 20.7％in 2021,while the detection rate of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)showed an upward trend year by year(57.9％-66.8％).No Staphylococcus was found to be resistant to vancomy-cin,linezolid,and teicoplanin.Among Gram-negative bacteria,constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9％-53.9％and 14.2％-19.5％,respectively,both showing an upward trend(both P＜0.001).Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6％-5.1％and 3.0％-4.5％,respectively,both showing a downward trend year by year(both P＜0.001).From 2012 to 2021,resistance rates of Escherichia coli to imipenem and ertapenem were 1.0％-2.0％and 0.6％-1.1％,respectively;presenting a downward trend(P＜0.001).The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4％-13.7％and 4.8％-6.4％,respectively,presenting a downward trend(both P＜0.001).The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1％-15.6％and 34.7％-45.7％,respectively.The trend of resistance to carbapenem antibiotics was relatively stable,but has de-creased compared with 2012-2016.The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0％-65.4％,showing a downward trend year by year.Conclusion The constituent ra-tio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year,while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years,and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.

Objective To investigate changes in the distribution and antimicrobial resistance of bacteria isolated from cerebrospinal fluid(CSF)specimens in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021 were collected according to China Antimicrobial Resistance Surveillance Sys-tem(CARSS)technical scheme.Data of bacteria isolated from CSF specimens and antimicrobial susceptibility tes-ting results were analyzed with WHONET 5.6 and SPSS 20.0 software.Results A total of 11 837 bacterial strains were isolated from CSF specimens from member units of Hunan Province Antimicrobial Resistance Surveillance Sys-tem from 2012 to 2021.The top 5 strains were coagulase-negative Staphylococcus(n=6 397,54.0％),Acineto-bacter baumannii(n=764,6.5％),Staphylococcus aureus(n=606,5.1％),Enterococcus faecium(n=465,3.9％),and Escherichia coli(n=447,3.8％).The detection rates of methicillin-resistant coagulase-negative Staphyloco-ccus(MRCNS)and methicillin-resistant Staphylococcus aureus(MRSA)were 58.9％-66.3％and 34.4％-62.1％,respectively.No Staphylococcus spp.were found to be resistant to vancomycin,linezolid,and teicoplanin.The de-tection rate of Enterococcus faecium was higher than that of Enterococcus faecalis,and the resistance rates of En-terococcus f aecium to penicillin,ampicillin,high concentration streptomycin and levofloxacin were all higher than those of Enterococcus faecalis(all P=0.001).Resistance rate of Streptococcus pneumoniae to penicillin was 85.0％,at a high level.Resistance rate of Escherichia coli to ceftriaxone was＞60％,while resistance rates to enzyme inhibitors and carbapenem antibiotics were low.Resistance rate of Klebsiella pneumoniae to ceftriaxone was＞60％,to en-zyme inhibitors piperacillin/tazobactam and cefoperazone/sulbactam was＞30％,to carbapenem imipenem and me-ropenem was about 30％.Resistance rates of Acinetobacter baumannii to most tested antimicrobial agents were＞60％,to imipenem and meropenem were 59.0％-79.4％,to polymyxin B was low.Conclusion Among the bac-teria isolated from CSF specimens,coagulase-negative Staphylococcus accounts for the largest proportion,and the overall resistance of pathogenic bacteria is relatively serious.Bacterial antimicrobial resistance surveillance is very important for the effective treatment of central nerve system infection.

Background Results of genetic testing for antipsychotic drugs can guide the rational use of drugs in clinical practice and help improve the clinical symptoms of patients with schizophrenia.However,there is currently limited evidence in China regarding the impact of genetic testing results on medication adherence,social function and drug side effects of antipsychotic drug treatment.Objective To explore the improvement of clinical symptoms,medication adherence and social function in patients with schizophrenia under the guidance of antipsychotic drug gene testing results and examine the safety of drug treatment,so as to provide references for ifor precise treatment of schizophrenia patients.Methods Patients with acute schizophrenia who received hospitalization at Dazhou Minkang Hospital from July 2019 to August 2021 as well as met the diagnostic criteria of the International Classification of Diseases,tenth edition(ICD-10)were selected as research subjects(n=144).Based on random number table,subjects were divided into study group and control group,with 72 cases in each group.Control group received drug treatment based on the doctor's clinical experience,while study group received drug treatment based on the results of gene testing for antipsychotic drug.Both treatments lasted for 12 weeks.At baseline as well as 2,4,8 and 12 weeks after treatment,Positive and Negative Syndrome Scale(PANSS),8-item Morisky Medication Adherence Scale(MMAS-8),Social Functional Rating Scale(SFRS)and Treatment Emergent Symptom Scale(TESS)were adopted for assessment.Result Time effect and group effect of the reducing rate of PANSS,MMAS-8 and SFRS scores in the groups were statistically significant(Ftime=95.251,6.650,14.101,Fgroup=38.055,58.175,128.221,P<0.01).The interaction effect of the reduction rates of MMAS-8 scores in two groups was statistically significant(Finteraction=5.837,P<0.01).The group effect and interaction effect of the severity scores of drug side effects and patient pain scores in two groups were statistically significant(Fgroup=7.553,81.533,Finteraction=8.693,9.322,P<0.01).Conclusion In terms of improving clinical symptom relief,medication adherence,social function and drug side effects,medication for patients with schizophrenia guided by genetic testing of antipsychotic drugs may be more effective than that relying on medication based on clinical experience.

Objective:To compare the characteristics of background mucosa, lesion features, and the efficiency of endoscopic submucosal dissection(ESD)between elderly and non-elderly patients with early gastric cancer(EGC).Methods:This study retrospectively collected data on patients with EGC who underwent ESD treatment at Beijing Hospital from April 2020 to December 2022.The clinical characteristics, background mucosa, lesion features, ESD outcomes, and pathological results of the patients were analyzed to compare the differences between elderly and non-elderly patients.Results:A total of 100 patients with EGC were selected, comprising 57 patients in the elderly group and 43 patients in the non-elderly group, with a total of 111 lesions identified(64 lesions in the elderly group and 47 lesions in the non-elderly group).The proportion of patients with a history of chronic atrophic gastritis was significantly higher in the elderly group(89.5%、51/57)compared to the non-elderly group(74.4%、32/43), with a statistically significant difference( P=0.047).Additionally, the difference in the extent of atrophy between elderly patients with EGC and their non-elderly counterparts was statistically significant( P=0.022).Among these patients, the proportion of those classified as Kimura-Takemoto C0 to C1 in the elderly group(15.6%、10/64)was lower than that in the non-elderly group(40.4%、19/47).In contrast, the proportion of patients classified as C2 to C3 in the elderly group(65.6%、42/64)was higher than that in the non-elderly group(51.1%、24/47), and the proportion of those classified as O1 to O3 in elderly patients(12.5%、8/64)was also higher than in the non-elderly group(4.3%、2/47).Furthermore, the difference in the extent of intestinal metaplasia between elderly and non-elderly patients with early gastric cancer was statistically significant( P=0.007).The overall proportion of total intestinal metaplasia in elderly patients(85.9%、55/64)was significantly higher than that in non-elderly patients(61.7%、29/47).Notably, the proportion of patients exhibiting extensive intestinal metaplasia(intestinal metaplasia present in both the gastric antrum and gastric body)was greater in the elderly group(43.8%、28/64)compared to the non-elderly group(23.4%、11/47).The Kyoto gastric cancer risk endoscopic score for elderly patients with EGC was(2.43±1.28)points, significantly higher than that of the non-elderly group(1.72±1.41)points, with a statistically significant difference observed( t=2.778, P=0.006).No statistically significant differences were observed in the proportions of total resection rates, R0 resections, curative resections, or postoperative complications following ESD when comparing elderly patients with EGC to their non-elderly counterparts. Conclusions:The proportion of extensive atrophy and intestinal metaplasia was higher in the background mucosa of elderly patients with EGC, and correspondingly, the Kyoto endoscopic gastric cancer risk score was elevated.Therefore, endoscopic examinations for elderly patients with chronic atrophic gastritis should be conducted with greater care and comprehensiveness.

Osteoarthritis (OA) is a type of highly prevalent heterogeneous degenerative disease that leads to joint pain, deformity, the destruction of articular cartilage, and eventual disability. The current treatment strategies for OA often suffer from systemic side effects, poor anti-inflammatory efficacy, and persistent pain. To address these issues, we develop light-inducible nanomedicine that enables the co-delivery of anti-inflammatory drug (diacerein, DIA) and small interfering RNA (siRNA) targeting nerve growth factor (NGF) for pain relief to enhance the therapeutic efficacy of OA. The nanomedicine is based on poly(β-amino-ester)-coated gold nanocages (AuNCs), which is further incorporated with the phase-change material (lauric acid/stearic acid, LA/SA). Following intra-articular (IA) injection in vivo, the nanomedicine displays high degree of drug accumulation and retention in the joint lesion of OA mouse models. The photothermal effect, induced by AuNCs, not only promotes DIA and siRNA release, but also upregulates the expression of heat shock protein 70 (HSP-70) to resist the apoptosis of chondrocytes in the inflammatory condition. The internalization of both DIA and siRNA results in strong anti-inflammatory and pain-relieving effects, which greatly contribute to the joint repair of OA mice. This study offers a promising combination strategy for OA treatment.

Humans ; Asthma/drug therapy* ; Biological Therapy