Objective To investigate the effect of exosomal miR-146a-5p expression on gray matter volume in patients with major depressive disorder(MDD).Methods A total of 113 MDD patients(MDD group)and 107 healthy controls(HC)(HC group)were selected.Peripheral blood was collected and exosomes were isolated to quantify miR-146a-5p expression.Brain high-resolution T1 WI images of MDD and HC were obtained via MR,and gray matter volume was computed via SPM12 software.The interaction effect of"Depression×miR-146a-5p expression"on gray matter volume was analyzed using SPM's Flexible factorial design,and the between-group difference was assessed by extracting the mean value,thus to analyze whether MDD-related gray matter volume abnormalities were dependent on miR-146a-5p expression.Results Exosomal miR-146a-5p expression was significantly elevated in MDD group compared to HC group.Voxel-based factorial analysis revealed a relationship between high miR-146a-5p expression in MDD group and reduced gray matter volume in the anterior and posterior cingulate cortices(independent voxel threshold P＜0.001,AlphaSim corrected),and a significantly reduced gray matter volume as compared with HC group was detected in the two regions.Conclusion The exosomal miR-146a-5p is overexpressed in patients with MDD and may be associated with specific cortical atrophy in patients with MDD.

Abstract: Objective　To analyze the risk factors for HIV/AIDS mortality after receiving antiviral treatment in Tongchuan City, and to provide a scientific basis for implementing precision treatment in Tongchuan City. Methods　A retrospective cohort study was conducted to collect general demographic characteristics and survival-related information of HIV/AIDS individuals who received antiviral treatment in Tongchuan City from 2005 to 2023. Mortality table analysis was used to assess the cumulative survival rate, Cox regression model was used to analyze survival influencing factors, and a nomogram was constructed to predict the prognosis of antiviral treatment. Results A total of 410 HIV/AIDS patients underwent antiviral treatment, with the shortest observation period being 0 months and the longest 222 months, and the median survival time was 71 months (QR: 64-106); among the 362 cases followed up, there were 39 AIDS-related deaths. The cumulative survival rates after 1, 5, and 10 years of antiretroviral therapy were 96.2%, 91.3%, and 83.0%, respectively. Multivariate Cox analysis showed that patients with a higher level of education (college degree or above) (HR=0.349, 95%CI: 0.159-0.769) and without clinical symptoms (HR=0.357, 95%CI: 0.178-0.715) had a lower risk of death after antiretroviral treatment, whereas patients with a CD4 cell count <200 cells/μL group (HR=9.383, 95% CI: 2.879-30.578) had a higher risk of death. Based on the above three influencing factors, a nomogram model was constructed. Internal validation showed that the model's discriminative ability with a C-index of 0.859 (95% CI: 0.762-0.956), and the calibration curve indicated good consistency, demonstrating the model's good predictive ability. Conclusions　Tongchuan City should expand health education on AIDS prevention and control, strengthen HIV monitoring, carry out education on compliance with antiviral treatment among HIV/AIDS individuals, conduct timely CD4 cell count detection, and use the constructed nomogram model to assist in precise diagnosis and treatment in clinical practice.

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.
Humans ; Male ; Animals ; Mice ; Semen/metabolism* ; Dyneins/metabolism* ; Cilia/metabolism* ; Mutation ; Ciliary Motility Disorders/genetics*

Objective: To analyze the short-term effect of individual atmospheric PM_2.5 exposure on the diversity, enterotype, and community structure of gut microbiome in healthy elderly people in Jinan, Shandong province. Methods: The present panel study recruited 76 healthy elderly people aged 60-69 years old in Dianliu Street, Lixia District, Jinan, Shandong Province, and followed them up five times from September 2018 to January 2019. The relevant information was collected by questionnaire, physical examination, precise monitoring of individual PM_2.5 exposure, fecal sample collection and gut microbiome 16S rDNA sequencing. The Dirichlet multinomial mixtures (DMM) model was used to analyze the enterotype. Linear mixed effect model and generalized linear mixed effect model were used to analyze the effect of PM_2.5 exposure on gut microbiome α diversity indices (Shannon, Simpson, Chao1, and ACE indices), enterotype and abundance of core species. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 352 person-visits. The age of 76 subjects was (65.0±2.8) years old with BMI (25.0±2.4) kg/m². There were 38 males accounting for 50% of the subjects. People with an educational level of primary school or below accounted for 10.5% of the 76 subjects, and those with secondary school and junior college or above accounting for 71.1% and 18.4%. The individual PM_2.5 exposure concentration of 76 subjects during the study period was (58.7±53.7) μg/m³. DMM model showed that the subjects could be divided into four enterotypes, which were mainly driven by Bacteroides, Faecalibacterium, Lachnospiraceae, Prevotellaceae, and Ruminococcaceae. Linear mixed effects model showed that different lag periods of PM_2.5 exposure were significantly associated with a lower gut α diversity index (FDR<0.05 after correction). Further analysis showed that PM_2.5 exposure was significantly associated with changes in the abundances of Firmicutes (Megamonas, Blautia, Streptococcus, etc.) and Bacteroidetes (Alistipes) (FDR<0.05 after correction). Conclusion: Short-term PM_2.5 exposure is significantly associated with a decrease in gut microbiome diversity and changes in the abundance of several species of Firmicutes and Bacteroidetes in the elderly. It is necessary to further explore the underlying mechanisms between PM_2.5 exposure and the gut microbiome, so as to provide a scientific basis for promoting the intestinal health of the elderly.
Aged ; Humans ; Male ; Middle Aged ; Feces/microbiology* ; Gastrointestinal Microbiome ; Particulate Matter ; RNA, Ribosomal, 16S/genetics* ; Female

OBJECTIVE: To investigate the effectiveness of sequential plate internal fixation in the correction of Madelung deformity after ulnar osteotomy and shortening. METHODS: The clinical data of 13 patients with Madelung deformity admitted between September 2015 and July 2021 were retrospectively analyzed. There were 5 males and 8 females with an average age of 18.3 years ranging from 17 to 23 years. The disease duration ranged from 12 to 24 months, with an average of 17 months. Three cases had a clear history of trauma. All patients had external radial deviation deformity and limited movement of the ulnar deviation, and the ulnar impact pain was significant during ulnar deviation movement; 9 patients had limited wrist joint supination movement, and the supination movement was normal. In the first stage, ulnar osteotomy and shortening combined with external fixator were used to correct wrist deformity in 13 patients. After operation, bone transfer was performed 6 times per day, with adjustments made every 4 hours, which was 1 mm per day. After the osteotomy was in place, the ulnar plate internal fixation was performed to reconstruct the ulnar stability in the second stage. The Cooney wrist joint score was used to assess the pain, function, range of motion, flexion and extension range of motion, and grip strength of the wrist joint before operation and before the removal of internal fixator. The subjective feeling and appearance satisfaction of patients were recorded. RESULTS: After the second-stage operation, all the 13 patients were followed up 10-22 months, with an average of 15 months. The deformity of wrist joint disappeared after operation, and the flexion, extension, and ulnar deviation were basically normal. There was no complication such as ulnar impingement sign, nonunion or infection. Wrist function, pain, and range of motion were significantly improved after operation, except for 1 patient who had no significant improvement in rotation and pain. The ulnar internal fixator was removed at 10-18 months after the second-stage operation. The scores of pain, function, range of motion, flexion and extension range of motion, and grip strength in the Cooney wrist score before removal of internal fixator significantly improved when compared with those before operation ( P<0.05). Subjective and appearance satisfaction of patients were excellent in 9 cases, good in 3 cases, and fair in 1 case. CONCLUSION Ulnar osteotomy and shortening with sequential plate internal fixation for correction of Madelung deformity, with mild postoperative pain, can effectively avoid bone nonunion, improve wrist joint function, and have significant effectiveness.
Male ; Female ; Humans ; Adolescent ; Retrospective Studies ; Ulna/surgery* ; Osteochondrodysplasias ; Radius Fractures/surgery* ; Wrist Joint/surgery* ; Osteotomy ; Range of Motion, Articular ; Treatment Outcome

OBJECTIVE: To explore clinical effect of intermittent flap opening technique in L-shaped incision of calcaneal fracture. METHODS: From January 2017 to January 2019, 48 patients with Sanders typeⅡ to Ⅳ calcaneal fractures were treated by open reduction and internal fixation. According to different flap opening techniques, the patients were divided into control group and observation group, 24 patients in each group. In observation group, there were 17 males and 7 females, aged from 20 to 60 years old with an average of(45.12±9.56) years old;7 patients were typeⅡ, 10 patients were type Ⅲ and 7 patients were type Ⅳ according to Sanders classification;3 patients were C0, 16 patients were C1 and 5 patients were C2 according to Tscherne-Gotzen soft-tissue assessment;treated with intermittent flap technique. In control group, there were 19 males and 5 females aged from 20 to 60 years old with an average of (47.32±10.67) years old;7 patients were typeⅡ, 11 patients were type Ⅲ and 6 patients were type Ⅳ according to Sanders classification;2 patients were C0, 18 patients were C1 and 4 patients were C2 according to Tschemc-Gotzen soft-tissue assessment;treated with static flap opening technique. Operation time, flap retraction time, changes of Böhler angle and Gissane angle before and after operation at 3 days, and occurrence of incision complications were observed and compared between two groups. RESULTS: All patients were followed up from 3 to 6 months with an average of(4.52±1.01) months. There were no significant differences in operation time, changes of Böhler angle and Gissane angle before and after operation at 3 days between the two groups(P>0.05);there was statistical difference in flap retraction time between two groups(P<0.05). Occurrence of incision complications in observation group was significantly lower than that in control group (P<0.05). CONCLUSION Intermittent flap opening technique is superior to static opening technique in reducing incision complications of lateral "L" approach of calcaneus. Single Kirschner wire opening does not affect the exposure, reduction and fixation of fracture during operation.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Surgical Wound ; Treatment Outcome ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods* ; Calcaneus/surgery* ; Ankle Injuries ; Foot Injuries ; Knee Injuries

Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.

Objective:To explore the curative effect of wide pedicled with double-vessel flap of posterior lateral calf in repair of soft tissue defect in hind foot.Methods:From January 2018 to June 2021, 12 patients with soft tissue defects on hind foot were reconstructed with double-vessel flaps pedicled perforator of peroneal artery and sural nerve nutrient vessels in the Department of Trauma Orthopaedics, No.940 Hospital of Chinese People's Liberation Army Joint Service Support Force. The patients were 8 males and 4 females, aged 9-45(27.17±12.14) years old. Time after injury to admission was 6-24(10.17±4.80) hours. Six patients were with simple soft tissue defects, 2 with tendon defects, 3 with bone defects and 1 with postoperative infection due to an open fracture. The sizes of soft tissue defect ranged from 4 cm×5 cm-8 cm×12 cm. Soft tissue defects were reconstructed by transfer of posterolateral calf flaps, and the bone defects were repaired by phase I or phase II bone grafts or antibiotic cement and membrane induction according to the wound surface. For larger bone defects, stage-II bone transport was carried out to restore the length of the hind foot. Defects of Achilles tendon were reconstructed by direct suture or tendon transposition. Foot functions were evaluated by American Orthopaedic Foot and Ankle Surgery(AOFAS) ankle-posterior sufficient scale, visual analogue scale(VSA) score and flap healing. All patients were included in postoperative follow-up regularly through outpatient clinic or via WeChat.Results:All 12 patients had postoperative follow-up that lasted for 6-24(12.92±6.22) months. One flap developed dark purple colour with swelling at the distal end of the flap 3 days after surgery. It eventually healed after removed some sutures from the pedicle together with blood-letting on the flap surface. Three flaps developed local infection, and they were cured after debridement, dressing change and the use of sensitive antibiotics. The remaining 8 patients had achieved good appearance of flaps and normal ankle function. According to AOFAS, scores of ankle-posterior sufficiency scale increased from 14-45(25.25±5.42) before surgery up to 65-96(75.92±7.73) at the final follow-up. Of the 12 patients, 8 were in excellent, 2 in good and 2 in fair. The VAS scores decreased from 5-8(6.55±1.13) before surgery down to 0-4(1.55±1.37) at the final follow-up. The difference had statistics significance( P<0.01). All patients had satisfactory recovery of ankle function, with the extension at 15-20 degrees and plantar flexion of 30-40 degrees. The donor site healed well and all skin grafts survived. Conclusion:The double-vessel flap pedicled with perforating branch of peroneal artery and nutrient vessels of sural nerve can be used for reconstruction of soft tissue defect of hind foot. It achieved good surgical effects with reliable blood supply, smooth venous return, strong anti-infection ability, satisfactory appearance at donor site and flap itself, as well as a good recovery of foot function.

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.
Animals ; Mice ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; Molecular Docking Simulation ; Arthritis, Rheumatoid/genetics* ; Tumor Necrosis Factor-alpha ; NF-kappa B ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional

ObjectiveTo observe the myocardial injury in tumor-bearing mice， and to explore the role and mechanism of park2 gene-encoded E3 ubiquitin protein ligase Parkin-mediated mitophagy in myocardial injury of tumor-bearing mice. MethodsPCR and Western Blot were used to verify park2^-/- mice， the tumor-bearing animal models were constructed by subcutaneous transplantation， small animal ultrasound imaging system was used to monitor cardiac structure and function， the changes in left ventricular internal dimensions （LVD）， left ventricular volume （LVV） ， ejection fraction （EF）， fractional shortening （FS）， and left ventricular wall thickness （LVW） were measured. Morphological changes of hearts were analyzed by pathological techniques. Fluo-3， Rhod-2， DHE-ROS and JC-1 probes were used for the detection of mitochondrial damage indicators. qPCR technology was used to evaluate mitochondriogenesis related factors tfam and nrf1， mitochondrial fusion related factors opa1 and mfn2， mitochondrial fission related factor fis1， and mitophagy related gene park2. Expression of LC3 Ⅱ， LC3 Ⅰ and Parkin was assessed by Western Blot. ResultsThe small animal ultrasound imaging revealed that B16 melanoma-bearing mice had a significant reduction in cardiac function（P<0.01）. Transmission electron microscopy （TEM） showed increased numbers of mitochondria and mitochondria vacuolization in tumor-bearing mice（P=0.023）. Further molecular analysis indicated that tumor-bearing state could cause mitochondrial damage in cardiomyocytes and activate mitophagy. There was significantly increased mortality in tumor-bearing park2^-/- mice （P<0.05）. Mitophagy was inhibited in park2^-/- mice and more severe mitochondrial damage was noted （P<0.05）. ConclusionE3 ubiquitin protein ligase Parkin plays a protective role in cardiomyocyte injury at a tumor-bearing state， which is associated with E3 ubiquitin protein ligase Parkin-mediated mitophagy.