Irritable bowel syndrome （IBS） is a functional bowel disorder characterized primarily by abdominal pain and altered defecation habits. In recent years， traditional Chinese medicine （TCM） has made progress in multiple aspects of IBS research and treatment， including syndrome distribution， development of TCM formulas， clinical efficacy evaluation， external therapies， and psychosocial regulation. However， it still faces challenges such as over-reliance on symptomatic manifestations rather than biomarkers for diagnostic criteria， and the lack of high-quality evidence-based data supporting the efficacy of TCM formulas in treating IBS. This paper proposed that TCM diagnosis and treatment of IBS should adhere to the strategy of integrating the holistic concept with syndrome differentiation and treatment， combining TCM external therapies such as acupuncture， moxibustion and acupoint application）， and emphasizing individualized diagnosis and treatment for psychosomatic abnormalities. Future research should integrate multi-omics technologies， artificial intelligence and other methods to deepen the understanding of the pathogenesis of IBS and the mechanisms of TCM formulas， so as to promote the standardization and internationalization of TCM in the diagnosis and treatment of IBS.

ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.

Objective:To explore the therapeutic effect of anterior chamber puncture combined with laser peripheral iridectomy (LPI) on patients with acute primary angle closure glaucoma (PACG).Methods:A total of 85 patients (85 eyes) with acute PACG treated in the Qingdao Huangdao District Traditional Chinese Medicine Hospital from January 2019 to December 2022 were selected and divided into the study group (43 cases, treated with anterior chamber puncture combined with LPI) and the control group (42 cases, treated with drug antihypertensive combined with LPI) by random number table method. The best corrected visual acuity, intraocular pressure, corneal edema grade, central anterior chamber depth, angle opening range and postoperative complications were compared between the two groups.Results:Before surgery, there were no statistical differences in the best corrected visual acuity and intraocular pressure between the two groups ( P>0.05), and at 3, 6 and 12 months after surgery, the best corrected visual acuity and intraocular pressure in the two groups were significantly lower than those before surgery, and the study group were lower than those in the control group: (0.41 ± 0.09) logMAR vs. (0.47 ± 0.10) logMAR, (0.26 ± 0.05) logMAR vs. (0.31 ± 0.06) logMAR, (0.30 ± 0.07) logMAR vs. (0.34 ± 0.08) logMAR; (14.3 ± 3.6) mmHg(1 mmHg = 0.133 kPa) vs. (16.5 ± 3.2) mmHg, (15.0 ± 3.9) mmHg vs. (17.6 ± 3.6) mmHg, (17.4 ± 3.5) mmHg vs. (20.0 ± 3.8) mmHg, there were statistical differences ( P<0.05). Before surgery, there were no statistical differences between the two groups in central anterior chamber depth and angle opening range ( P>0.05), and at 3, 6 and 12 months after surgery, the central anterior chamber depth and angle opening range were higher in the both groups and the study group were higher than those in the control group: (2.94 ± 0.46) mm vs. (2.72 ± 0.45) mm, (3.01 ± 0.50) mm vs. (2.89 ± 0.48) mm, (2.93 ± 0.44)mm vs. (2.81 ± 0.47) mm; (244.0 ± 26.0)° vs. (236.1 ± 29.5)°, (256.5 ± 27.4)° vs. (248.3 ± 30.3)°, (250.7 ± 29.0)° vs. (241.5 ± 25.4)°, there were statistical differences ( P<0.05). There was no significant difference in preoperative corneal edema grade between the two groups ( P>0.05), and the corneal edema grade in the study group was lower than that in the control group at 3 d after operation, there was statistical difference ( P<0.05). The complication rate was 4.65%(2/43) in the study group and 14.29% (6/42) in the control group, there was no statistical difference ( χ2 = 2.31, P>0.05). Conclusions:The combination of anterior chamber puncture and LPI surgery is beneficial for controlling intraocular pressure, improving vision, and restoring anterior chamber depth in PACG patients, and its clinical efficacy is certain.

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.

BACKGROUND:Spine osteoarthritis is a chronic inflammatory disease of the spine,articular ligaments,and tendons,and is the main cause of chronic low back pain.Artificial tiger bone powder has anti-inflammatory and pain-relieving biological effects,so it is expected to provide a new strategy for targeted therapy of spinal osteoarthritis.OBJECTIVE:To investigate the mechanism of artificial tiger bone meal in regulating the expression level of interleukin-23/interleukin-17 immune axis in improving spine osteoarthritis in rats.METHODS:Sixty SD rats were randomly divided into blank control group,model group,artificial tiger bone meal low-,medium-and high-dose groups,with 12 rats in each group.Except for the blank control group,osteoarthritis models were established in the other groups by injecting 0.1 mL of iodoacetic acid into the joint cavity of the lumbar vertebral joint capsule of the rats.15 days after modeling,the artificial tiger bone meal low,medium and high dose groups were treated by intragastric administration of 120,240 and 480 mg/kg per day respectively.The blank control group and model group were given the same volume of normal saline by gavage.After 21 days of treatment,the expression levels of interleukin-17,interleukin-23,matrix metalloproteinase-3,and chemokine receptor-6 in rat spinal articular cartilage were measured by western blot assay.The expression levels of related inflammatory factors in rat serum were detected by ELISA.The degree of joint injury and degeneration in rats was observed by hematoxylin-eosin staining and safranin O-fast green staining.RESULTS AND CONCLUSION:(1)The results of western blot assay showed that the expression levels of interleukin 17,interleukin 23,matrix metalloproteinase 3,and chemokine receptor 6 in the articular cartilage of rats in the artificial tiger bone meal high-dose group were significantly lower than those in the model group(P＜0.05).(2)ELISA results showed that compared with the model group,the artificial tiger bone meal medium-and high-dose groups had a significant down-regulating effect on the levels of serum interleukin 17,tumor necrosis factor α,interleukin 1β,and matrix metalloproteinase 3(P＜0.05).(3)Hematoxylin-eosin staining and saffron O-solid green staining showed that the infiltration and proliferation of synovial inflammatory cells in each treatment group of artificial tiger bone meal were significantly improved compared with the model group,and the pathological inflammation Osteoarthritis Research Society International score and Mankin's score in the medium-and high-dose groups of artificial tiger bone meal were significantly reduced(P＜0.05).(4)It is suggested that artificial tiger bone meal could significantly improve the inflammation and degeneration of spinal facet joints caused by iodoacetic acid chemical stimulation.Among them,the effect of the high-dose group was more significant.The mechanism may be to inhibit the expression of interleukin-23/interleukin-17 immune axis-related inflammatory factors and improve the immune microenvironment of articular cartilage.

Objective:To summarize the clinical features of Chlamydia pneumoniae pneumonia (CPP) in children. Methods:Case series study. Clinical data of 10 children with CPP hospitalized in Department No.2 of Respiratory Medicine of Beijing Children′s Hospital, Capital Medical University from January 2019 to August 2024 were retrospectively collected, including general information, clinical manifestations, chest imaging, laboratory examination and treatment. The clinical features and prognosis were summarized.Results:Among the 10 children with CPP, 7 were male and 3 were female. The age of onset was 11.2 (10.3, 13.1) years. The course were 17 (7, 23) days. Cough occurred in 9 cases with wet cough in 7 cases, while moderate and high fever occurred in 6 cases. Besides, chest pain occurred in 4 cases, rash and hemoptysis occurred in 1 case respectively. High density mass shadow was found in 7 cases chest CT imaging, accompanied by air bronchogram sign, surrounded by halo sign, 6 cases of which were distributed under the pleura, while patchy consolidation in the remaining 3 cases. Pulmonary embolism was present in 2 cases. Among the 10 children with CPP, bilateral lung involvement was found in 3 cases and unilateral lung involvement in 7 cases. The white blood cell count was 10.21 (7.45, 11.64)×10 9/L and the proportion of neutrophils was 0.69 (0.63, 0.71). C-reactive protein increased in 7 cases, with the level of 33 (16, 77) mg/L. D-dimer increased slightly in 3 cases (0.393, 0.396, 0.739 mg/L). Serum Chlamydia pneumoniae-IgM antibody test was positive in 6 cases. Chlamydia pneumoniae nucleic acid test by bronchoalveolar lavage fluid (BALF) next-generation sequencing was positive in 6 cases. Both serum IgM antibody and BALF nucleic acid tests were positive in 2 cases. Among the 10 children with CPP, azithromycin alone was used in 5 cases, while glucocorticoid was added in 1 case. Due to poor response to azithromycin in 4 cases, doxycycline was replaced in 3 cases and minocycline was replaced in 1 case, while glucocorticoid was added in 2 cases. Moxifloxacin combined with glucocorticoid therapy was adopted in 1 case with long course after the poor response to azithromycin and doxycycline. All patients were cured finally. Conclusions:CPP mostly occurs in elderly children. The main clinical manifestations include cough, fever and chest pain. The common chest imaging feature is subpleural high-density mass shadow with halo sign. Pulmonary embolism is present in a few cases. Nucleic acid detection and (or) serology is helpful for etiological diagnosis. Some cases need glucocorticoid therapy.

Objective To explore the clinical efficacy of Du's bone-setting manipulation reduction combined with proximal femoral nail antirotation(PFNA)in the treatment of femoral intertrochanteric fracture.Methods A total of 79 femoral intertrochanteric fracture patients who underwent PFNA surgery in Sichuan Second Hospital of Traditional Chinese Medicine from January 2018 to December 2023 were selected.40 patients who underwent Du's bone-setting manipulation reduction combined with PFNA were included in manipulation group,and 39 patients who used a traction bed followed by PFNA were included in traction group.The operation time,intraoperative blood loss,recovery of neck-shaft angle and anteversion angle of femur,and fracture healing time of two groups of patients were compared.Results The operation time and fracture healing time of patients in manipulation group were significantly shorter than those in traction group,intraoperative blood loss was significantly less than that in traction group,and the Harris score of hip joint and the excellent and good rate of reduction were significantly higher than those in traction group(P＜0.05).There was no statistically significant difference in postoperative hospital stay,the degree of recovery of neck-shaft angle and anteversion angle of femur between two groups of patients(P＞0.05).Conclusion Du's bone-setting manipulation reduction combined with PFNA in the treatment of femoral intertrochanteric fracture has the advantages of short operation time,less intraoperative blood loss,short fracture healing time and good functional recovery of the affected limb.

Objective:To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA.Methods:A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children′s Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children′s Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00).Results:There was a statistically significant difference in the gender and age distribution between the two groups of children ( P<0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes ( P> 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children′s samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β; production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. Conclusion:DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.

OBJECTIVES: To investigate the role and mechanism of copper overload-mediated endoplasmic reticulum stress (ERS) in vascular endothelial injury in Kawasaki disease (KD). METHODS: Four-week-old male C57BL/6 mice were randomly divided into four groups: control, KD, KD plus copper chelator tetrathiomolybdate (TTM), and KD plus ERS inhibitor AMG PERK 44 (AMG) (n=20 per group). A KD mouse model was established using Candida albicans extract. Human umbilical vein endothelial cells (HUVECs) were divided into control (intervention with healthy children's serum), KD (intervention with KD patients' serum), and KD+TTM (intervention with KD patients' serum plus 20 µmol/L TTM). Copper deposition in mouse heart tissue was assessed using rubeanic acid staining. Vascular pathological changes were observed using hematoxylin-eosin staining and measurement of abdominal aortic diameter and area. ERS activation was detected by transmission electron microscopy and immunofluorescence. HUVEC viability, apoptosis, and functional changes were evaluated using CCK8, flow cytometry, cell scratch assay, and angiogenesis experiments. ERS marker protein expression levels were measured by Western blot. RESULTS: Compared to the KD group, the KD+TTM and KD+AMG groups showed reduced copper deposition in the vascular wall, decreased swelling of coronary endothelial cells and endoplasmic reticulum, reduced inflammatory cell infiltration, and less abdominal aortic lesion expansion. The abdominal aortic diameter and area, and the fluorescence intensity of ERS marker proteins (GRP78 and CHOP) were significantly lower (P<0.05). Compared to the KD group, the KD+TTM group exhibited increased cell viability, tube number, and scratch healing rate, along with decreased apoptosis rate and expression of ERS marker proteins (GRP78, CHOP, ATF6, and p-PERK) (P<0.05). CONCLUSIONS Copper overload aggravates vascular endothelial injury in KD by activating the ERS pathway. TTM can exert protective effects on the endothelium by regulating copper metabolism and inhibiting the ERS pathway.
Endoplasmic Reticulum Stress ; Copper/toxicity* ; Male ; Mucocutaneous Lymph Node Syndrome/metabolism* ; Animals ; Humans ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Mice ; Human Umbilical Vein Endothelial Cells ; Apoptosis ; Endothelium, Vascular/injuries*

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma