BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

OpenSim is an open source, free motion simulation and gait analysis software, which can be used to dynamically simulate and analyze the complex motion of the human body, and is widely used in human biomechanical research. Since OpenSim can analyze multi-dimensional motion data such as muscle strength, joint torque, and muscle synergistic activation during human movement, it can be used to study the biomechanical mechanism of musculoskeletal imbalance diseases and various treatment methods in TCM orthopedics, and has a broad application prospect in the field of TCM orthopedics. By the analysis of the basic characteristics, elements, analysis process, and application prospects of OpenSim, it is concluded that OpenSim musculoskeletal model has a large application space in the field of traditional Chinese medicine orthopedic, which is helpful to explain the pathogenesis and mechanism of diseases, and promote the precision diagnosis and treatment of orthopedics diseases;the application of OpenSim musculoskeletal model can solve the problem that the previous research paid attention to the bone malalignment and not enough attention to the tendon, and provide a new method for the research of orthopedic diseases. At present, there are still problems in the promotion and application of OpenSim, such as large equipment requirements and high operation threshold. Therefore, multidisciplinary cooperation, clinical research, and data sharing are the basic research strategies in this field.
Humans ; Biomechanical Phenomena ; Orthopedics ; Traumatology ; Software ; Medicine, Chinese Traditional ; Musculoskeletal System ; Models, Biological

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

OBJECTIVE: To examine the mechanistic of organochlorine-associated changes in lung function. METHODS: This study investigated 76 healthy older adults in Jinan, Shandong Province, over a five-month period. Personal exposure to organochlorines was quantified using wearable passive samplers, while inflammatory factors and thyroid hormones were analyzed from blood samples. Participants' lung function was evaluated. After stratifying participants according to their thyroid hormone levels, we analyzed the differential effects of organochlorine exposure on lung function and inflammatory factors across the low and high thyroid hormone groups. Mediation analysis was further conducted to elucidate the relationships among organochlorine exposures, inflammatory factors, and lung function. RESULTS: Bis (2-chloro-1-methylethyl) ether (BCIE), was negatively associated with forced vital capacity (FVC, -2.05%, 95% CI: -3.11% to -0.97%), and associated with changes in inflammatory factors such as interleukin (IL)-2, IL-7, IL-8, and IL-13 in the low thyroid hormone group. The mediation analysis indicated a mediating effect of IL-2 (15.63%, 95% CI: 0.91% to 44.64%) and IL-13 (13.94%, 95% CI: 0.52% to 41.07%) in the association between BCIE exposure and FVC. CONCLUSION Lung function and inflammatory factors exhibited an increased sensitivity to organochlorine exposure at lower thyroid hormone levels, with inflammatory factors potentially mediating the adverse effects of organochlorines on lung function.
Environmental Exposure ; Hydrocarbons, Chlorinated/metabolism* ; China ; Ethyl Ethers/metabolism* ; Environmental Monitoring ; Thyroid Hormones/blood* ; Lung/physiology* ; Inhalation Exposure/statistics & numerical data* ; Air Pollution/statistics & numerical data* ; Air Pollutants/metabolism* ; Humans ; Male ; Female ; Middle Aged ; Aged

ObjectivesTo observe the clinical effectiveness， safety， and potential mechanism of Yisui Shengxue Pills （益髓生血丸） as adjuvant treatment for myelosuppression after chemotherapy for malignant tumours with qi and yin deficiency syndrome. MethodsEighty patients of myelosuppression after chemotherapy for malignant tumours with qi and yin deficiency syndrome were randomly divided into trial group and control group， with 40 cases in each group. Both groups received conventional western medicine treatment， while the control group added placebo taken orally， and the trial group received Yisui Shengxue Pills orally， and both groups were treated for 21 consecutive days. Granulocyte colony stimulating factor （G-CSF）， granulocyte-macrophage colony stimulating factor （GM-CSF）， soluble intercellular cell adhesion molecule-1 （sICAM-1）， Jagged 1 （Jagl）， Notch homolog 2 （Notch2）， cell fate determinant membrane associated protein 1 （Numb1）， neutrophils， platelet count， white blood cell count， hemoglobin， cluster of differentiation 4⁺ （CD4⁺）， and cluster of differentiation 8⁺ （CD8⁺） were detected before and after treatment； myelosuppression grade and TCM syndrome scores of the two groups were evaluated before and after treatment， and clinical effectiveness and adverse events of the two groups were compared. ResultsThe difference in myelosuppression grading between the two groups after treatment was statistically significant （P＜0.05）. Compared with this group before treatment， plasma G-CSF， GM-CSF， sICAM-1， Numb1 expression， platelet count， neutrophil count， leukocyte count， haemoglobin， CD4⁺ level decreased， Jagl， Notch2 expression and CD8⁺ level increased， and fatigue， spontaneous sweating， palpitation， night sweating， insomnia， scanty complexion， mouth erosion， vexing heat in chest， palms and soles scores all reduced （P＜0.05）. Compared with the control group after treatment， plasma G-CSF， GM-CSF， sICAM-1， Numb1 expression， platelet count， neutrophil count， leukocyte count， haemoglobin， CD4+ levels increased， Jagl， Notch2 expression and CD8⁺ levels decreased， and fatigue， spontaneous sweating， palpitations， night sweating， insomnia， pale face， mouth erosion， and vexing heat in chest， palms and soles scores decreased in trial group （P＜0.05）. The total effective rate of the trial group was 95.00%， which was significantly higher than that of the control group， which was 80.00% （P＜0.05）. Comparison of the incidence of liver function damage and renal function damage between the two groups showed no statistically significant difference （P＞0.05）， and the incidence of gastrointestinal damage in the trial group was lower than that in the control group （P = 0.02）. ConclusionYisui Shengxue Pills as adjuvant treatment for myelosuppression after chemotherapy for malignant tumours with qi and yin deficiency syndrome can improve the myelosuppression and clinical symptoms， improve the clinical effectiveness， and has a good synergistic and toxicity-reducing effect， and its mechanism of action may be related to the regulation of the Notch signalling pathway and the reduction of immune function impairment.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Objective:To explore the drug resistance of pathogens in puerperal infection of pregnant women with diabetes mellitus (GDM), and analyze the influence of puerperal infection on the expression of toll like receptor 4 (TLR4) inflammatory pathway in peripheral blood monocytes.Methods:A retrospective selection was conducted on 120 GDM postpartum women who underwent regular prenatal check ups and delivery at the 903th Hospital of the PLA (People′s Liberation Army) Joint Logistic Support Force from January 2020 to October 2022. The postpartum infection status, pathogenic characteristics of the infected pathogens, and drug resistance of the mothers were analyzed; According to the postpartum infection situation, the parturients were divided into an infected group and an uninfected group. Logistic regression analysis was used to analyze the relevant factors affecting postpartum infection, and the TLR4 protein and mRNA expression levels of peripheral blood mononuclear cells in the two groups were compared.Results:Among 120 GDM pregnant women, 21 cases (17.50%) developed post infection, including 8 cases (38.10%) of incision infection, 6 cases (28.57%) of uterine cavity infection, 4 cases (19.05%) of urinary system infection, and 3 cases (14.28%) of blood infection; A total of 43 pathogenic bacteria were detected, including 26 Gram negative bacteria (60.46%), 14 Gram positive bacteria (32.56%), and 3 fungi (6.98%). Among the main Gram negative bacteria, escherichia coli had the highest resistance rate to ceftazidime and tetracycline, and had not developed resistance to meropenem; Pseudomonas aeruginosa had the highest resistance rate to ceftazidime and gentamicin. Among the main Gram positive bacteria, staphylococcus aureus had the highest resistance rate to penicillin G and ceftazidime, and had not developed resistance to vancomycin; Enterococcus faecalis had the highest resistance rate to clindamycin. The results of multivariate logistic regression analysis showed that postpartum hemorrhage, premature rupture of membranes, and poor control of prenatal blood sugar were independent risk factors for postpartum infection in GDM mothers (all P<0.05). The expression rate of TLR4 protein, relative expression level of TLR4 mRNA, and levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, and IL-10 in the infected group were significantly higher than those in the non infected group (all P<0.05). Conclusions:The distribution and drug resistance of pathogenic bacteria in postpartum infections of GDM mothers have certain characteristics. Postpartum hemorrhage, premature rupture of membranes, and poor control of prenatal blood sugar are independent risk factors affecting postpartum infections in GDM mothers; The TLR4 inflammatory pathway in peripheral blood mononuclear cells may be involved in the occurrence and development of postpartum infection in GDM mothers.

BACKGROUND:There is currently no anatomic locking plate suitable for the anteromedial platform,so the medial locking plate of the tibial plateau is usually placed forward to fix anteromedial compression fractures caused by hyperextension varus injury.Due to the inability of the locking screw to achieve vertical fixation of the fracture line,coupled with the influence of the patellar ligament,the clinical results are still unsatisfactory. OBJECTIVE:To compare the biomechanical performance of a new type of plate with traditional internal fixation methods in treating hyperextension varus tibial plateau fractures through finite element analysis. METHODS:CT data of 20 cases of hyperextension varus tibial plateau fractures were collected,and their morphological characteristics,such as medial posterior tibial slope,the medial articular fracture angle,surface area,and anterior cortical height were measured.A 24-year-old male volunteer with a height of 175 cm and a weight of 65 kg was selected,and his tibial CT data were imported into Mimics 21.0 software to generate a 3D model.Then,internal fixation models were imported into SolidWorks 2017 software.New type of plate,medial locking plate,posterior medial locking plate,and 6.5 mm hollow screws fixed data models were established based on the measured morphological data.Ansys 17.0 software was used to load stress on the four fixation models and compare their biomechanical performance. RESULTS AND CONCLUSION:(1)With the increase of axial load,the peak stresses of different internal fixation models approximately increased proportionally.At 500 N,the peak stress values were as follows:screw group(6.973 7 MPa)