1.Screening of biomarkers for fibromyalgia syndrome and analysis of immune infiltration
Yani LIU ; Jinghuan YANG ; Huihui LU ; Yufang YI ; Zhixiang LI ; Yangfu OU ; Jingli WU ; Bing WEI
Chinese Journal of Tissue Engineering Research 2025;29(5):1091-1100
BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.
2.Association of perceived social support and emotional regulation among college students
GU Manli, XU Jida, JIANG Maomin, LI Zhixiang, ZHANG Honglai
Chinese Journal of School Health 2024;45(1):82-86
Objective:
To understand the current situation of college students emotional regulation and its correlation with perceived social support, so as to provide a reference for improving emotional regulation ability among college students.
Methods:
From September 15 to October 15, 2022, a total of 15 560 students from 27 colleges and universities in Guangdong, Jiangsu, Shandong, Shanghai, Anhui, Hebei, Yunnan, Shanxi and Gansu were enrolled by stratified random sampling method. The Perceived Social Support Scale (PSSS) and the Emotion Regulation Questionnaire (ERQ) were used to investigate, and multiple stepwise regression was used to explore the relationship between perceived social support and emotion regulation of college students.
Results:
The scores of emotion regulation, cognitive reappraisal and expression inhibition were 44(40, 50), 24(20, 28) and 20(19, 24) respectively. There were significant differences in the scores of emotion regulation, cognitive reappraisal and expression inhibition by age, grade, household registration, only child status,cost of living, and sleep ( H/Z =77.72, 49.73, -5.10, -9.77, 7.68, 168.27 ; 204.55, 317.32, -5.96, -7.60, 131.20, 968.08; 82.18, 148.04, -2.30, -8.03, 64.82, 188.08, P <0.05). In addition, the multiple stepwise regression found that family support, friend support, and other support in perceived social support all had a positive impact on the emotional regulation state of college students ( β =0.137,0.207,0.090), and family support and friend support had a significant positive effect on expression inhibition( β =0.079,0.053) and cognitive reappraisal( β =0.153,0.296)( P <0.01).
Conclusion
The perceived social support can directly affect the emotional regulation of college students, and improving the emotional regulation ability has a positive significance to promote the mental health level among college students.
3.The Impact of Generative Artificial Intelligence on the Development, Evaluation, and Application of Clinical Practice Guidelines
Xufei LUO ; Han LYU ; Zaiwei SONG ; Hui LIU ; Zhixiang WANG ; Haodong LI ; Ye WANG ; Di ZHU ; Lu ZHANG ; Yaolong CHEN
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1173-1181
Generative artificial intelligence (GAI) refers to AI technology capable of generating new content such as text, images, or audio from training data. GAI tools not only demonstrate rapid and efficient potential in literature screening, data extraction, and literature appraisal in systematic reviews, but can also be used for guideline evaluation and dissemination, enhancing the readability and promotion efficiency of guidelines. However, the accuracy of content generated by GAI tools, the rationality of cited evidence, the level of evidence, and the reliability of data still need verification. Additionally, data privacy protection and ethical issues are challenges that need to be addressed. This article aims to overview the current status of GAI tools in the formulation, evaluation, dissemination, and implementation of guidelines, explore the feasibility and new models of GAI tools in the field of guidelines, and improve the efficiency and quality of guideline formulation to better serve guideline developers and users.
4.Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation
Rong FU ; Ren LIN ; Zhiping FAN ; Fen HUANG ; Na XU ; Li XUAN ; Yifei HUANG ; Hui LIU ; Ke ZHAO ; Zhixiang WANG ; Ling JIANG ; Min DAI ; Jing SUN ; Qifa LIU
Chinese Journal of Hematology 2024;45(1):62-67
Objectives:To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared.Results:A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods ( P=0.008) . Conclusions:mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.
5.Comparison in Efficacy of Arthroscopic Surgery and Nonsurgical Therapies in Treatment of Meniscus-related Injuries:A Systematic Review and Meta-analysis
Zhixiang LIU ; Hongpeng LI ; Qipei JI
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2024;53(3):380-388
Objective To explore the short-term and long-term efficacy of arthroscopic surgery,different non-surgical ther-apy and sham operation intervention in the treatment of meniscus related injuries,and to compare their advantages and disadvan-tages,so as to provide guidance for clinical practice.Methods Randomized controlled trials on arthroscopic surgery,meniscecto-my and other surgical and non-surgical treatments for knee meniscus injury were searched in PubMed,Embase,Cochrane Librar-y and Web of Science,and the search time was from its inception to July 2023.Two researchers independently screened the liter-ature according to the established literature ranking criteria,and the Cochrane Risk of Bias Assessment Tool was used to evalu-ate the risk of bias of the included literature,while the PEDro Scale Evaluation Tool was used to evaluate the quality of the liter-ature of the randomized controlled trials,and the collected data were quantitatively analyzed using RevMan 5.3 software.Results From the qualitative analysis,it was clear that surgical therapies might be more appropriately applied to patients without osteo-arthritis and without mechanical symptoms,and that meniscal suture repair surgery had a more favorable long-term outcome compared with traditional partial meniscectomy.Quantitative analysis showed that there was no statistical significance between arthroscopic surgery and other non-surgical therapies in several short and long term efficacy(all P>0.05).For example,MD=0.15,95%CI:-4.05~4.35,I2=0%in the short-term comparison of Lysholm knee score;MD=-1.30,95%CI:-3.16~0.57,I2=0%;Short-term VAS score MD=-0.18,95%CI:-0.59~0.23,I2=45%;MD=-0.01,95%CI:-0.20~0.19,I2=36%.In addition,in the subgroup analysis of degenerative meniscus injury alone,the difference in clinical efficacy between the two therapies was also not statistically significant(all P>0.05).Conclusion There is no practical difference between surgi-cal therapy and non-surgical therapy in the short-term and long-term outcomes.For single type injury,such as degenerative me-niscus injury,there is no practical difference between the two therapies.
6.Role of macrophages in pulmonary blood-air barrier impairment induced by PM2.5 exposure
Mengfei YAO ; Guozhen WANG ; Xiaonan HOU ; Duo TANG ; Zijia LIU ; Chao SHENG ; Yuchen ZHENG ; Qi ZONG ; Wenke LI ; Zhixiang ZHOU
Journal of Army Medical University 2024;46(8):849-858
Objective To investigate the role of macrophages in the process of fine particulate matter (PM2.5)exposure induced damage to pulmonary blood-air barrier.Methods Eighteen male BALB/C mice (aged of 10 weeks,weighing 24~27 g)were randomly divided into control group and low-and high-dose PM2.5 exposure groups (receiving 1 .8 and 16.2 mg/kg,respectively),with 6 mice in each group.The control group received tracheal instillations of normal saline on days 1,4,and 7,whereas the exposure groups were administered corresponding dose of PM2.5 exposure at the same time points.In 24 h after last exposure,pathological changes in the lung tissues were observed,and the contents of total protein (TP ),lactate dehydrogenase (LDH ),and alkaline phosphatase (AKP ) in bronchoalveolar lavage fluid (BALF ),and F4/80 protein level in lung tissue were measured to evaluate the blood-air barrier damage and macrophage infiltration within the lung tissues.Additionally,an in vitro model of the blood-air barrier was established using A549 alveolar epithelial cells and EA.hy926 vascular endothelial cells.In combination with a THP-1 macrophage model,the supernatant PM2.5 supernatant,macrophage supernatant,and PM2.5-macrophage supernatant were incubated with the barrier model for 24 h,respectively.Transmembrane electrical resistance (TEER),sodium fluorescein permeability of the barrier model,and LDH release from the barrier cells were measured to ascertain the extent of macrophage-mediated enhancement in barrier damage induced by PM2.5 exposure.Furthermore,the expression of inflammatory cytokines,such as TNF-α,IL-1β,IL-6,and IL-8 in the macrophages after PM2.5 exposure was analyzed with quantitative real-time PCR (qPCR)and enzyme-linked immunosorbent assay (ELISA).Results PM2.5 exposure induced lung tissue damage in mice in a dose-dependent manner,significantly elevated the contents of TP,LDH and AKP in the BALF and caused marked infiltration of macrophages into the lung tissue,especially the high-dose exposure when compared with the mice from the control group (P<0.01 ).In vitro barrier model exposure experiments showed that in comparison with the treatment of 150 and 300 μg/mL PM2.5 and macrophage supernatant,the same doses of PM2.5-macrophage supernatant resulted in notably decreased TEER and significantly enhanced permeability in the barrier model (P<0.01 ),and markedly increased LDH release from epithelial and endothelial barrier cells (P<0.01 ).Additionally,the exposure of 150 and 300μg/mL PM2.5 led to a significant up-regulation of TNF-α,IL-1β,IL-6,and IL-8 in the macrophages (P<0.01 ).Conclusion Macrophages deteriorate PM2.5-induced functional impairment of the pulmonary blood-air barrier.
7.Exploring the effect of PRDX4 on proliferation and apoptosis of esophageal squamous cell carcinoma cells based on the PI3K/AKT signaling pathway
Zhang CUICUI ; Li ZHIXIANG ; Li QUAN ; Lan WENHUA ; Yu YANG ; Wang AIYING ; Liu BIN
Chinese Journal of Clinical Oncology 2024;51(10):500-505
Objective:Studying the effect of PRDX4 on esophageal squamous cell carcinoma cells(esophageal carcinoma,ESCC)proliferation and apoptosis as well as its potential mechanism.Methods:The University of Alabama at Birmingham cancer data analysis portal(UALCAN),gene expression profiling interactive analysis(GEPIA)and the Cancer Genome Atlas(TCGA)databases were used to predict PRDX4 expres-sion in ESCC and its relationship with pathological features and prognosis.The cancer and adjacent tissues of 60 patients with ESCC who un-derwent radical resection in the Affiliated Hospital of Weifang Medical College from August 2010 to August 2023 were selected as research samples.The expression level of PRDX4 in the patients was detected by immunohistochemistry(IHC).The extracted cancer and adjacent tis-sues were homogenized to analyze its mRNA expression.The expression levels of PRDX4 mRNA and related signaling proteins in ESCC cells were analyzed by real-time quantitative PCR and Western blot.Cell Counting Kit-8(CCK-8)assay and flow cytometry were used to analyze the effect of PRDX4 on cell proliferation and apoptosis.Finally,a subcutaneous tumor model in nude mice was constructed to validate the in vitro experimental results.Results:The data from the GEPIA and UALCAN showed that PRDX4 expression was abnormally increased and re-lated to the pathology stage,grade,and survival rate of patients.After knockdown and overexpression of PRDX4 in an ESCC cell line,the ex-pression of PRDX4,phos-phosphatidylinositol 3-kinase(p-PI3K),phos-protein kinase B(p-AKT),cyclinD1,and survivin protein decreased and increased,respectively;cell proliferation and apoptosis were positively regulated.Compared with the sh-NC group,tumor volume and weight in the sh-PRDX4 group were decreased.Conclusions:PRDX4 regulates the proliferation and apoptosis of ESCC cells by activating the PI3K/AKT signaling pathway.
8.The Porous SilMA Hydrogel Scaffolds Carrying Dual-Sensitive Paclitaxel Nanoparticles Promote Neuronal Differentiation for Spinal Cord Injury Repair
Zhixiang LI ; Tao ZHOU ; Zhengqi BAO ; Min WU ; Yingji MAO
Tissue Engineering and Regenerative Medicine 2024;21(6):809-827
BACKGROUND:
In the intricate pathological milieu post-spinal cord injury (SCI), neural stem cells (NSCs) frequently differentiate into astrocytes rather than neurons, significantly limiting nerve repair. Hence, the utilization of biocompatible hydrogel scaffolds in conjunction with exogenous factors to foster the differentiation of NSCs into neurons has the potential for SCI repair.
METHODS:
In this study, we engineered a 3D-printed porous SilMA hydrogel scaffold (SM) supplemented with pH-/ temperature-responsive paclitaxel nanoparticles (PTX-NPs). We analyzed the biocompatibility of a specific concentration of PTX-NPs and its effect on NSC differentiation. We also established an SCI model to explore the ability of composite scaffolds for in vivo nerve repair.
RESULTS:
The physical adsorption of an optimal PTX-NPs dosage can simultaneously achieve pH/temperature-responsive release and commendable biocompatibility, primarily reflected in cell viability, morphology, and proliferation.An appropriate PTX-NPs concentration can steer NSC differentiation towards neurons over astrocytes, a phenomenon that is also efficacious in simulated injury settings. Immunoblotting analysis confirmed that PTX-NPs-induced NSC differentiation occurred via the MAPK/ERK signaling cascade. The repair of hemisected SCI in rats demonstrated that the composite scaffold augmented neuronal regeneration at the injury site, curtailed astrocyte and fibrotic scar production, and enhanced motor function recovery in rat hind limbs.
CONCLUSION
The scaffold’s porous architecture serves as a cellular and drug carrier, providing a favorable microenvironment for nerve regeneration. These findings corroborate that this strategy amplifies neuronal expression within the injury milieu, significantly aiding in SCI repair.
9.pH/Temperature Responsive Curcumin-Loaded Micelle Nanoparticles Promote Functional Repair after Spinal Cord Injury in Rats via Modulation of Inflammation
Taibao QIAN ; Zhixiang LI ; Lijun SHANG ; Sutao HUANG ; Guanglin LI ; Weiwei ZHENG ; Yingji MAO
Tissue Engineering and Regenerative Medicine 2023;20(6):879-892
BACKGROUND:
The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration.
METHODS:
In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso–Beattie– Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining.
RESULTS:
The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements.
CONCLUSION
Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.
10.Effectiveness of transcutaneous lower eyelid blepharoplasty with a skin flap reserving the pretarsal fullness
Jianwu CHEN ; Yuzhi WANG ; Xiaoyu CHENG ; Liming ZHANG ; Qi LI ; Zhixiang CHEN ; Yanhong WU
Chinese Journal of Plastic Surgery 2023;39(10):1088-1093
Objective:To evaluate the effectiveness of transcutaneous lower eyelid blepharoplasty with a skin flap reserving the pretarsal fullness.Methods:From November 2017 to April 2022, a retrospective analysis was performed to assess the reserving of pretarsal fullness after the transcutaneous lower blepharoplasty with a skin flap in the Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command, PLA. A subciliary incision was made below the ciliary margin and a skin flap was elevated at the surface of pretarsal orbicularis. The muscle was partially split at the position of pretarsal crease, leaving the pretarsal orbicularis oculi muscle and the pretarsal crease intact. Preseptal dissection was proceeded down to the level of arcus marginalis, exposing the orbital fat pads. For patient with tear trough deformity or volume deficiency in the medial cheek, retaining ligament laxity and fat repositioning were routinely performed. The muscle wound was closed edge to edge and the excess skin was excised conservatively. Postoperative complications were recorded. Face-Q scale was used for surgical decision and postoperative satisfaction evaluation. The scores range from 0 to 100, with higher scores indicating less regret the operation or greater satisfaction. The preoperative and postoperative digital photographs were used to evaluate the change of pretarsal fullness.Results:256 patients were included, of whom 233 cases were women and 23 cases were men. The age was (43.0±10.2) years. 24 cases had concomitant lateral canthoplasty due to hypotonia of lower eyelid, 22 had concomitant upper blepharoplasty, and 21 cases had brow lift surgery to correct upper eyelid relaxation. All patients had follow-up for (3.7±4.1) months, most patients were satisfied with the operation results. A total of 211 patients maintained a natural pretarsal fullness postoperatively, with the rate of 82.4%. The Face-Q satisfaction score was (75.8±18.6) and the surgical decision score was (80.3±15.4), indicating that most patients did not regret the operation. Postoperative complications included 8 cases of eyelid bags undercorrection, of whom 4 patients underwent secondary resection. 7 patients experienced infraorbital bulge for the uneven placement of the fat pad, 2 of them required revision surgery. Hematoma occurred in 4 cases and was resolved by hematoma clearance. Other complications included 3 cases of ectropion and 2 cases of minimal tear trough correction. Lower eyelid ectropion was corrected in one case.Conclusion:Reserving the pretarsal fullness in transcutaneous lower eyelid blepharoplasty with a skin flap provides excellent aesthetic results and high patient satisfaction. This technique is simple and effective.


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