OBJECTIVE: To observe the clinical efficacy of Fu's subcutaneous needling based on "multi-joint muscle spiral balance chain" theory for cervical vertigo (CV) and its effect on blood flow velocity of vertebral artery. METHODS: A total of 60 patients with CV were randomized into a Fu's subcutaneous needling group and a medication group, 30 cases in each one. In the Fu's subcutaneous needling group, Fu's subcutaneous needling was delivered at Dazhui (GV14), the flexible tube was retained for 5 min after sweeping manipulation, and the treatment was given once every other day, 3 times a week for 3 weeks. In the medication group, betahistine mesylate tablet and diclofenac sodium dual-release enteric capsule were taken orally for continuous 3 weeks. Before treatment, after treatment, and in follow-up of one month after treatment completion, the scores of dizziness handicap inventory (DHI) and visual analogue scale (VAS) were observed; before and after treatment, the blood flow velocity of vertebral artery was measured by transcranial Doppler, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment and in follow-up, each item scores and total scores of DHI were decreased compared with those before treatment in the two groups (P<0.05); the VAS scores after treatment in the two groups, as well as the VAS score in follow-up of the Fu's subcutaneous needling group, were decreased compared with those before treatment (P<0.05). In the Fu's subcutaneous needling group, after treatment and in follow-up, the physical scores and the total scores of DHI, and the VAS scores were lower than those in the medication group (P<0.05); in follow-up, the emotional and functional scores of DHI were lower than those in the medication group (P<0.05). After treatment, the mean blood flow velocity (Vm) of the left vertebral artery (LVA) and the right vertebral artery (RVA) was increased compared with that before treatment in the two groups (P<0.05), and the Vm of LVA and RVA in the Fu's subcutaneous needling group was higher than that in the medication group (P<0.05). The total effective rate was 100.0% (30/30) in the Fu's subcutaneous needling group, which was superior to 73.3% (22/30) in the medication group (P<0.05). CONCLUSION Fu's subcutaneous needling based on the "multi-joint muscle spiral balance chain" theory can effectively alleviate the vertigo and neck pain, and improve the blood flow velocity of vertebral artery in CV patients, and has a long-term therapeutic effect.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/instrumentation* ; Vertebral Artery/physiopathology* ; Adult ; Vertigo/physiopathology* ; Aged ; Blood Flow Velocity ; Treatment Outcome ; Acupuncture Points ; Young Adult

OBJECTIVE: To review clinical application and research progress of different types of intelligent responsive hydrogels in repairing articular cartilage injury. METHODS: The animal experiments and clinical studies of different types of intelligent responsive hydrogels for repairing articular cartilage injury were summarized by reviewing relevant literature at home and abroad. RESULTS: The intrinsic regenerative capacity of articular cartilage following injury is limited. Intelligent responsive hydrogels, including those that are temperature-sensitive, light-sensitive, enzyme-responsive, pH-sensitive, and other stimuli-responsive hydrogels, can undergo phase transitions in response to specific stimuli, thereby achieving optimal functionality. These hydrogels can fill the injured cartilage area, promote the proliferation and differentiation of chondrocytes, and expedite the repair of the damaged site. With advancements in cartilage tissue engineering materials research, intelligent responsive hydrogels offer a novel approach and promising potential for the treatment of cartilage injuries. CONCLUSION Intelligent responsive hydrogel is a kind of flexible, controllable, efficient, and stable polymer, which has similar structure and functional properties to articular cartilage, and has become one of the important biomaterials for cartilage repair. However, there is still a lack of unified treatment standards and simple and efficient preparation technology.
Hydrogels/therapeutic use* ; Cartilage, Articular/injuries* ; Tissue Engineering/methods* ; Humans ; Animals ; Chondrocytes/cytology* ; Biocompatible Materials/chemistry* ; Tissue Scaffolds/chemistry*

Objective To investigate the gene expression and regulatory mechanisms of mouse embryonic fibroblasts (MEFs) under inflammatory conditions, aiming to elucidate the role of MEFs in inflammatory responses and provide a foundation for discovering anti-inflammatory drugs that act by modulating MEF function. Methods MEFs cultured in vitro were divided into the following groups: lipopolysaccharides (LPS)-treated group, inflammatory conditioned medium (CM)-treated group, and control group, which were treated with LPS, CM, and equal volume solvent, respectively. Transcriptome sequencing was used to analyze the effects of two stimuli on gene expression profile of MEFs. Real time fluorescence quantitative PCR (RT-qPCR) was employed to verify the transcription levels of highly expressed genes of MEFs induced by CM. ELISA was performed to determine the concentrations of cytokines in cell supernatants. Finally, the regulatory effects of CM on the activation of signaling pathways in MEFs were analyzed by immunoblotting. Results Transcriptome analysis showed that both LPS and CM induced the transcription of a large number of genes in MEFs. Compared with LPS, CM potentiated the mRNA transcription of some acute phase proteins, inflammatory cytokines, chemokines, matrix metalloproteinases (MMP), prostaglandin synthetases, and colony-stimulating factors. The transcriptome analysis was verified by RT-qPCR. The results of ELISA showed that CM treatment significantly increased the secretion of interleukin 6 (IL-6), C-C motif chemokine ligand (CCL2), and C-X-C motif chemokine ligand (CXCL1) by MEFs compared with LPS. Mechanism study showed that both LPS and CM induced the phosphorylation of nuclear factor-κB p65 (NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), extracellular regulated protein kinases 1/2 (ERK1/2), and TANK-binding kinase (TBK) in MEFs, and CM strongly stimulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in MEFs. Conclusion Both LPS and CM can induce transcription and protein secretion of various inflammation-related genes in MEFs. CM can partly enhance LPS-induced activation of MEFs, and the mechanism may be related to the enhancement effect of CM on the activation STAT3 signaling pathway.
Animals ; Fibroblasts/immunology* ; Mice ; Lipopolysaccharides/pharmacology* ; Inflammation/metabolism* ; Signal Transduction/drug effects* ; Gene Expression Regulation/drug effects* ; Cytokines/genetics* ; Culture Media, Conditioned/pharmacology* ; Cells, Cultured

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.

Clonal hematopoiesis of indeterminate potential (CHIP) refers to the clonal expansion phenomenon of hematopoietic stem cells caused by gene mutations, which has been considered as a potential pathogenetic basis for various diseases. The latest research reveals a possible relationship between CHIP and lymphoma. This article summarizes and explores the role and mechanism of CHIP mediated by TET2 and DNMT3A in lymphoma, and reviews the treatment strategies targeting these genes and related inflammatory pathways, aiming to provide new ideas and methods for the treatment of lymphoma.

BACKGROUND:Currently,there are various rat models of lumbar disc herniation used in experiments,each with its own advantages and disadvantages.The most common modeling methods include autologous nucleus pulposus transplantation and annulus fibrosus puncture models.OBJECTIVE:To establish two autologous nucleus pulposus transplantation models(with spinous process and mastoid process excision and with transverse process and mastoid process excision)as well as an annulus fibrosus puncture model,and to compare and evaluate the characteristics of the three models.METHODS:Forty male adult Sprague-Dawley rats were randomly divided into four groups(n=10 per group):sham surgery group,spinous process group,transverse process group,and annulus fibrosus puncture group.In the sham surgery group,surgical preparation was performed,the skin was incised,and the spinous process was exposed,and then sutured.In the spinous process group,L5 spinous process and transverse process were excised,and two pieces of tail nucleus pulposus were placed in the intervertebral foramen.In the transverse process group,L5 transverse process and transverse process were excised,and two pieces of tail nucleus pulposus were placed in the intervertebral foramen.In the annulus fibrosus puncture group,the transverse process was excised and annulus fibrosus puncture and intervertebral disc injection of interleukin 1β were then performed.Thermal paw withdrawal latencies were tested before and after modeling.Lumbar spine MRI was performed 2 weeks after modeling.Pathological changes in the intervertebral discs were observed using hematoxylin-eosin staining and safranin-O-fast green staining.Immunofluorescence was used to observe CD68+positive expression.RESULTS AND CONCLUSION:(1)Thermal withdrawal threshold testing results showed that compared with the sham surgery group,pain sensitivity and tolerance time of rats decreased significantly after modeling(P<0.05).(2)Lumbar spine MRI images showed that the spinous process and transverse process groups had obvious protrusion of nucleus pulposus tissue,which more closely resembled MRI images of patients with common lumbar disc herniation.(3)Hematoxylin-eosin staining revealed that compared with the sham surgery group,nucleus pulposus tissues in the model groups showed varying degrees of degeneration,inflammatory cell infiltration,and degradation of spinal cord cells,with the appearance of cystic changes,among which the annulus fibrosus puncture group had the most severe pathological changes.(4)Safranin-O-fast green staining showed that compared with the sham surgery group,the boundaries of nucleus pulposus tissues in the three model groups were blurred,with extensive inflammatory reactions and varying degrees of degeneration in the annulus fibrosus.(5)CD68+immunofluorescence staining results showed that compared with the sham surgery group,the expression of CD68+in the model groups was higher and more widespread,with the annulus fibrosus puncture model showing the highest expression.All the three methods could be used to effectively establish rat models of lumbar disc herniation,with the annulus fibrosus puncture model established after excision of the transverse process being superior to the autologous nucleus pulposus transplantation model(spinous process+mastoid process),and the first two models being superior to the autologous nucleus pulposus transplantation model(transverse process+mastoid process).

Objective To differentiate disguised visual acuity,(VA)by analyzing discrepancies across diversified visual acuity tests.Methods Volunteers were recruited,and VA(V,and V2)was measured before and after the experiment.Volunteers independently selected an experimental VA(Vt)and were assigned to either the disguised group or the control group.A specially designed heterogeneous optotype chart and a single-optotype chart with variable test distances were used to measure VA(t1,t2,t3),while a standard logarithmic VA chart was used to measure VA(t4).Based on the maximum VA discrepancy(△t),t4 was classified as"real"(≤ 1 line),"disguised"(≥ 2 lines),or"suspicious"(＞1 and＜2 lines with anomaly).Results A total of 126 valid cases were collected,including 30 in the control group and 96 in the disguised group,with VA ranging from 0.2～1.5.All 88 opinions classified as"disguised"were from the disguised group,and all 29 classified as"real"were from the control group.Of the 7 cases deemed"suspicious,"6 were from the disguised group.The sensitivity,specificity,and overall diagnostic accuracy were 91.7％,96.7％(P＜0.0001),and 92.9％(P＜0.0001),respectively.In the disguised group,38 cases exhibited unexplained identifying anomalies.Conclusion A VA discrepancy of ≥ 2 lines is a reliable indicator for detecting disguised visual acuity.Identifying anomalies may serve as a novel and sensitive marker for recognizing visual disguise.

Objective To study the basic features,judicial identification and trial characteristics of medical malpractice cases related to gastrointestinal endoscopy,enhance the awareness of risks of gastrointestinal endoscopy among medical staffand patients.,emphasize the importance of preoperative education and provide judicial identification and trial personnel with ideas for handling such cases,ensuring standardization and consistency in handling similar cases.Methods A total of 100 medical dispute cases involving gastrointestinal endoscopy from May 2010 to May 2024 were included from the China Judgments Online database.The analysis focused on document types,years,regions,court levels,details of judicial expertise,the proportion of court decision responsibility.Results The number of cases has increased significantly since 2017,with the highest incidence in 2020 and 2021(collectively accounting for 39%);Regions with the most disputes included Fujian,Guangdong,Shandong,Shanghai,Liaoning,Beijing,Jiangsu,collectively accounting for 58%of cases.The primary method of forensic expertise was medical damage identification,accounting for 82.0%of cases;Among these,4 cases underwent reappraisal,all of which resulted in modifications to the original expertise.Male patients outnumbered female patients,with"Digestive tract discomfort"being the main reason for consultation(63%).The most common medical injury was digestive tract perforation(37%),among which colon perforation was the most common;Of the 100 cases,60 cases were found to have errors in gastrointestinal endoscopy,and the medical errors were concentrated in"Improper operation during Operation"(42 cases),The contributory roles of various negligence types in the damage consequence ranged from"no causation"to"complete causation"in varing proportions.Notably,negligence categories such as"improper intraoperative manipulation"and"delayed treatment due to untimely examination"consistently demonstrated contributory roles of"secondary causation or higher."Regarding court rulings,the majority of cases(23 cases)assigned liability proportions of 31%-50%,followed by 20 cases with liability proportions of 71%-100%.

Objective To investigate the expression and mechanistic role of the M2-type pyruvate kinase(PKM2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in the development of experimental autoim-mune uveitis(EAU).Methods Eighteen 4-to 5-week-old C57BL/6J mice were selected and randomly divided into a control group(normal breeding,set as the 0-day state post-modeling),Experimental Group A,and Experimental Group B(both established as stable EAU mouse models using the interphotoreceptor retinoid-binding protein peptide 651-670,com-plete Freund's adjuvant,and pertussis toxin,designated as the 14-day and 21-day states post-modeling,respectively),with 6 mice in each group.The anterior segment of the mice was observed using a slit-lamp microscope,fundus findings were collected using a fundus camera,and clinical and histopathological scores were evaluated after hematoxylin-eosin stai-ning.The protein expression level of serum interleukin(IL)-17A was detected by ELISA.The expression level of PKM2 protein in retinal tissue was detected by immunohistochemistry.The protein expression levels of PKM2,phosphorylated STAT3(p-STAT3),and STAT3 in mouse retinal tissue were detected by Western blot.Results The clinical scores of the anterior segment and fundus,as well as the retinal histopathological scores in Experimental Group A and Experimental Group B,were all significantly higher than those in the control group(all P＜0.05).The serum IL-17A protein expression levels in the control group,Experimental Group A,and Experimental Group B were(69.05±0.45)ng·L-1,(75.06±0.46)ng·L-1,and(72.04±0.82)ng·L-1,respectively.The optical density values of PKM2 protein expression in retinal tissue were(18.51±2.59)％,(37.35±4.67)％,and(29.75±2.17)％,respectively.The expression levels of serum IL-17A protein,retinal PKM2 protein,and retinal STAT3 and p-STAT3 proteins in Experimental Group A and Experimental Group B were all significantly higher than those in the control group(all P＜0.05).Conclusion The expression levels of key factors in the PKM2/STAT3 signaling pathway are positively correlated with the severity of EAU,indicating that this sig-naling pathway,as a positive regulator of the immune response,is involved in the pathological process of EAU.

Objective To investigate the expression and role of T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)in the pathogenesis of experimental autoimmune uveitis(EAU).Methods A total of 12 male C57BL/6J mice,aged 4 to 5 weeks,were selected and divided into the control group(n=3)and the experimental group(n=9)using a random number table.The control group(modeling time point:0 days after modeling)received no treatment,while the experimental group was induced to establish an EAU model(divided into three subgroups according to the modeling time points:7 days,14 days,and 21 days after modeling,with 3 mice in each subgroup).Firstly,the interphotoreceptor retinoid-binding protein 651-670 and complete Freund's adjuvant were fully mixed and emulsified.Then,the emulsion was subcutaneously injected into the two thighs,tail base,and neck of mice in the experimental group(each mouse received 200 μL of immune emulsion containing 500 pg of interphotoreceptor retinoid-binding protein 651-670).Subsequently,each mouse in the experimental group was also intraperitoneally injected with 1 μg of pertussis toxin.The anterior segment and fundus of mice in each group were observed and photographed under a slit-lamp microscope.The clinical and histopatho-logical scoring of these mice was conducted according to the Caspi grading scale based on the severity of inflammation.The serum levels of IFN-γ and IL-17 were measured using the enzyme-linked immunosorbent assay(ELISA),while the mRNA expression of Tim-3 in the spleen and ocular tissues was detected using the real-time quantitative polymerase chain reaction(RT-qPCR).Western blot was employed to detect the protein expression of Tim-3,and immunohistochemistry was used to examine the protein expression of Tim-3 in the spleen tissue.Statistical analysis was performed using GraphPad Prism 9.0.Results The clinical scores of the anterior segment,fundus,and histopathology of the mice increased over time after modeling,with statistically significant differences among these groups(P＜0.05).The serum levels of IFN-γ and IL-17 in the mice also increased over time after modeling,with statistically significant differences among these groups(P＜0.05).The relative mRNA expression of Tim-3 in the spleen and ocular tissues of the mice decreased over time after modeling,with statistically significant differences among these groups(P＜0.05).The protein expression of Tim-3 in the ocular and spleen tissues showed the same pattern as its mRNA expression.Conclusion The expression of Tim-3 decreases with the exacerbation of inflammation in the progression of EAU,suggesting that Tim-3 may play a negative immunoregulatory role in the development of uveitis.