Objective To investigate the effect of dexmedetomidine(Dex)on bone loss in tail-suspended rats and primarily explore its regulatory mechanism on bone metabolism.Methods A total of 30 male rats were randomly divided into a control group,a model group,and a Dex group,with 10 animals in each group.Rat model of osteoporosis was established by hind limb suspension for 4 weeks.Dex at a dose of 10 μg/kg was given intraperitoneally,once every other day from the day of tail suspension.And equal amount of normal saline was given to the control and model group.Bone histological staining was used to observe the trabecular bone area fraction.Biomechanical three-point bending test was employed to measure the maximum load,stiffness,and fracture energy.Dual calcein/alizarin red fluorescence labeling and tartrate resistant acid phosphatase(TRAP)staining were applied respectively to detect the mineral apposition rate and bone formation rate as well as the number of osteoclasts on bone surfaces.Secondly,after primary osteoblasts were isolated from the tibiae of tail-suspended rats and then treated with 1 nmol/L Dex,the proportion of alkaline phosphatase(ALP)-positive osteoblasts and the activity of the enzyme were detected by ALP staining and activity test.qRT-PCR was applied to measure the expression of osteogenic activity-related factors,including osteocalcin(Ocn),Runt related transcription factor 2(Runx2),Osterix protein(Osx),and type 1 collagen(Col1).Results The animal experiments revealed that Dex treatment significantly increased the tibial trabecular bone area fraction,inhibited the decrease in bone mechanical strength,and enhanced the mineralization deposition rate and new bone formation rate of trabecular bone in the tail-suspended rats(all P＜0.001).The in vitro experiments showed that Dex treatment obviously improved ALP activity and the number of ALP-positive osteoblasts in primary osteoblasts isolated from tail-suspended rats(P＜0.01),and up-regulated the expression levels of osteogenic differentiation-related genes,such as Ocn,Runx2,Osx and Col1(P＜0.01).Conclusion Dex exerts anti-bone loss effect in tail-suspended rats,which may be associated with its stimulation on osteoblast-mediated bone formation.

Objective To explore the characteristics of changes in blood test indicators and the combined detection for the differential diagnosis value of early gastric cancer and atrophic gastritis.Methods A total of 44 patients with early gastric cancer admitted to the hospital from January 2023 to March 2024 were selected as the early gastric cancer group.Another 59 patients with atrophic gastritis who were admitted to the hospital during the same period were selected as the atrophic gastritis group.Analyze the characteristics of changes in blood test indicators of the two groups.The receiver operating characteristic(ROC)curve was drawn to eval-uate the clinical value of blood test indicators in differentiating early gastric cancer from atrophic gastritis.Re-sults The levels of white blood cell count(WBC),platelet count(PLT),C-reactive protein(CRP),pro-thrombin time(PT),fibrinogen(Fib),D-dimer(D-D),and carbohydrate antigen 199(CA199)in the early gastric cancer group were significantly higher than those in the atrophic gastritis group,and the differences were statistically significant(P<0.05).The levels of red blood cells(RBC),hemoglobin(HGB),total pro-tein(TP),thrombin time(TT),and ferritin(Fer)in the early gastric cancer group were significantly lower than those in the atrophic gastritis group,and the difference was statistically significant(P<0.05).The re-sults of the ROC curve analysis show that the area under the curve(AUC)for the individual detection and dif-ferential diagnosis of early gastric cancer and atrophic gastritis by WBC,RBC,HGB,PLT,CRP,TP,PT,TT,Fib,D-D,Fer and CA199 were 0.591,0.716,0.764,0.623,0.728,0.671,0.692,0.746,0.721,0.689,0.770 and 0.680,respectively.The AUC of the combined detection of RBC,HGB,CRP,TT,Fib and Fer for the dif-ferential diagnosis of early gastric cancer and atrophic gastritis was 0.857(95%CI:0.772-0.941),which was significantly higher than AUC of the individual detection.Conclusion The combined detection of blood test indicators such as RBC,HGB,CRP,TT,Fib and Fer has certain clinical value in the differential diagnosis of early gastric cancer and atrophic gastritis.

Objective:To understand the current research status, hot issues, and development trends of Taohong Siwu Decoction.Methods:Research literature about Taohong Siwu Decoction was retrieved from Wanfang Data, CBM, CNKI, and Chongqing VIP from January 1, 2014, to August 13, 2024. Excel 2024 software was used to analyze the annual number of publications, the source journals, literature types and the distribution of diseases and syndromes. CiteSpace 6.3.R3 software was used for visualization analysis on the authors, research institutions and key words.Results:A total of 2 519 articles were included, and the annual publication volume showed a fluctuating growth trend. There were 396 source journals, of which Medicine and Health published the most (80 articles); 208 authors were involved, and the core authors included Peng Daiyin of Anhui University of Chinese Medicine, Zhu Fuping of the First Affiliated Hospital of Hunan University of Chinese Medicine, Sun Shaoqiu of the Second Affiliated Hospital of Hunan University of Chinese Medicine and so on. The main research institutions in this field included Hunan University of Chinese Medicine and its affiliated hospitals. The high-frequency keywords included fracture, irregular menstruation, clinical efficacy, chloasma, Wuling Powder, experience of famous doctors, elderly, etc. Keywords could be clustered into 11 modules.Conclusions:The current research hotspots of Taohong Siwu Decoction mainly focus on the exploration of multi-system disease treatment, individualized syndrome differentiation and treatment, pharmacology and metabolic mechanism of Chinese materia medica, etc. Among them, the in-depth study of drug composition and metabolism, network pharmacology and mechanism is the research frontier in this field.

BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.

This study aims to investigate the in vitro mechanisms underlying the beneficial effects of puerarin on hepatic insulin resistance(IR) based on the carbohydrate response element-binding protein(ChREBP)/peroxisome proliferator-activated receptor(PPAR)α/PPARγ axis involved in glucose and lipid metabolism. An IR-HepG2 cell model was established by treating cells with dexamethasone for 48 h, and the cells were then treated with 10, 20, and 40 μmol·L~(-1) puerarin for 24 h. Glucose levels and output in the extracellular fluid were measured by the glucose oxidase method, while cell viability was assessed by the cell counting kit-8(CCK-8) assay. The adenosine triphosphate(ATP) content and glycogen synthesis were evaluated through chemiluminescence and periodic acid-Schiff staining, respectively. Western blot was employed to quantify the protein levels of forkhead box protein O1(FoxO1), phosphorylated forkhead box protein O1 [p-FoxO1(Ser256)], glucagon, phosphofructokinase, liver type(PFKL), pyruvate kinase L-R(PKLR), pyruvate dehydrogenase complex 1(PDHA1), insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase p85(PI3KR1), phosphorylated protein kinase B [p-Akt(Thr308)], glycogen synthase(GYS), glycogen phosphorylase, liver type(PYGL), adiponectin(ADPN), ChREBP, PPARα, and PPARγ. Additionally, the protein levels of acetyl-CoA carboxylase 1(ACC1), phosphorylated ATP citrate lyase [p-ACLY(Ser455)], sterol regulatory element binding protein 1c(SREBP-1c), peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α), carnitine palmitoyltransferase 1α(CPT1α), and glucagon receptor(GCGR) were also determined. Immunofluorescence was employed to visualize the expression and nuclear location of ChREBP/PPARα/PPARγ. Furthermore, quantitative PCR with the antagonists GW6471 and GW9662 was employed to assess Pparα, Pparγ, and Chrebp. The findings indicated that puerarin effectively reduced both the glucose level and glucose output in the extracellular fluid of IR-HepG2 cells without obvious effect on the cell viability, and it increased intracellular glycogen and ATP levels. Puerarin down-regulated the protein levels of FoxO1 and glucagon while up-regulating the protein levels of p-FoxO1(Ser256), PFKL, PKLR, PDHA1, IRS2, PI3KR1, p-Akt(Thr308), GYS, PYGL, ADPN, ACC1, SREBP-1c, p-ACLY(Ser455), PGC1α, CPT1α, and GCGR in IR-HepG2 cells. Furthermore, puerarin up-regulated both the mRNA and protein levels of ChREBP, PPARα, and PPARγ and promoted the translocation into the nucleus. GW6471 was observed to down-regulate the expression of Pparα while up-regulating the expression of Chrebp and Pparγ. GW9662 down-regulated the expression of Pparγ while up-regulating the expression of Pparα, with no significant effect on Chrebp. In summary, puerarin activated the hepatic ChREBP/PPARα/PPARγ axis, thereby coordinating the glucose and lipid metabolism, promoting the conversion of glucose to lipids to exert the blood glucose-lowering effect.
Isoflavones/pharmacology* ; Humans ; PPAR gamma/genetics* ; Hep G2 Cells ; Glucose/metabolism* ; Lipid Metabolism/drug effects* ; PPAR alpha/genetics* ; Liver/drug effects* ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Insulin Resistance

This paper aims to investigate the hypoglycemic effect and mechanism of berberine in improving energy metabolism based on the multi-pathway regulation of brain and muscle aromatic hydrocarbon receptor nuclear translocal protein 1(BMAL1): cyclin kaput complex of day-night spontaneous output cyclin kaput(CLOCK). The dexamethasone-induced hepatic insulin resistance(IR) HepG2 cell model was used; 0.5, 1, 5, 10, 20 μmol·L~(-1) berberine were administered at 15, 18, 21, 24, 30, 36 h. The time-dose effect of glucose content in extracellular fluid was detected by glucose oxidase method. The optimal dosage and time of berberine were determined for the follow-up study. Glucose oxidase method and chemiluminescence method were respectively performed to detect hepatic glucose output and relative content of ATP in cells; Ca~(2+), reactive oxygen species(ROS), mitochondrial structure and membrane potential were detected by fluorescent probes. Moreover, ultraviolet colorimetry method was used to detect the liver type of pyruvate kinase(L-PK) and phosphoenol pyruvate carboxykinase(PEPCK). In addition, pyruvate dehydrogenase E1 subunit α1(PDHA1), phosphate fructocrine-liver type(PFKL), forkhead box protein O1(FoxO1), peroxisome proliferator-activated receptor gamma co-activator 1α(PGC1α), glucose-6-phosphatase(G6Pase), glucagon, phosphorylated nuclear factor-red blood cell 2-related factor 2(p-Nrf2)(Ser40), heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), fibroblast growth factor 21(FGF21), uncoupled protein(UCP) 1 and UCP2 were detected by Western blot. BMAL1:CLOCK complex was detected by immunofluorescence double-staining method, combined with small molecule inhibitor CLK8. Western blot was used to detect PDHA1, PFKL, FoxO1, PGC1α, G6Pase, glucagon, Nrf2, HO-1, NQO1, FGF21, UCP1 and UCP2 in the CLK8 group. The results showed that berberine downregulated the glucose content in extracellular fluid in IR-HepG2 cells in a time-and dose-dependent manner. Moreover, berberine inhibited hepatic glucose output and reduced intracellular Ca~(2+) and ROS whereas elevated JC-1 membrane potential and improved mitochondrial structure to enhance ATP production. In addition, berberine upregulated the rate-limiting enzymes such as PFKL, L-PK and PDHA1 to promote glycolysis and aerobic oxidation but also downregulated PGC1α, FoxO1, G6Pase, PEPCK and glucagon to inhibit hepatic gluconeogenesis. Berberine not only upregulated p-Nrf2(Ser40), HO-1 and NQO1 to enhance antioxidant capacity but also upregulated FGF21, UCP1 and UCP2 to promote energy metabolism. Moreover, berberine increased BMAL1, CLOCK and nuclear BMAL1:CLOCK complex whereas CLK8 reduced the nuclear BMAL1:CLOCK complex. Finally, CLK8 decreased PDHA1, PFKL, Nrf2, HO-1, NQO1, FGF21, UCP1, UCP2 and increased FoxO1, PGC1α, G6Pase and glucagon compared with the 20 μmol·L~(-1) berberine group. BMAL1:CLOCK complex inhibited gluconeogenesis, promoted glycolysis and glucose aerobic oxidation pathways, improved the reduction status within mitochondria, protected mitochondrial structure and function, increased ATP energy storage and promoted energy consumption in IR-HepG2 cells. These results suggested that berberine mediated BMAL1:CLOCK complex to coordinate the regulation of hepatic IR cells to improve energy metabolism in vitro.
Humans ; Berberine/pharmacology* ; Gluconeogenesis/drug effects* ; Hep G2 Cells ; Glucose/metabolism* ; Liver/drug effects* ; Energy Metabolism/drug effects* ; Hypoglycemic Agents/pharmacology* ; ARNTL Transcription Factors/genetics* ; Glycolysis/drug effects* ; Oxidation-Reduction/drug effects*

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

OBJECTIVES: To evaluate the clinical value of CD4⁺ cell percentage (CD4⁺%) and NK cell percentage (NK%) in predicting treatment outcomes in children with aplastic anemia (AA), providing a reference for precise diagnosis and treatment. METHODS: This retrospective study analyzed the clinical data of AA children treated with cyclosporine A at the First Affiliated Hospital of Xinjiang Medical University from January 2019 to April 2024. The study involved 48 AA children as the observation group and 50 children undergoing medical check-ups during the same period as the control group. Lymphocyte subset data were collected from both groups to analyze differences and their relationship with treatment efficacy. Based on hematological responses, the observation group was divided into an effective group of 18 patients (HR group, including complete and partial remission) and an ineffective group of 30 patients (NHR group, including non-remission). RESULTS: Univariate analysis showed that NK% in the observation group was significantly lower than that in the control group (P<0.05). The observation group was followed up for 3 months. The HR group had a lower CD4⁺% than the NHR group (P=0.018) and a higher NK% than the NHR group (P=0.029). Multivariate logistic regression analysis indicated that a high CD4⁺% was a risk factor for poor treatment efficacy (OR=1.062), whereas a high NK% was a protective factor (OR=0.820). The area under the curve for the prediction of HR in pediatric AA by combining CD4⁺% and NK% was 0.812. CONCLUSIONS A higher CD4⁺% at diagnosis is a predictor of poor treatment response, whereas a higher NK% is associated with better outcomes.
Humans ; Anemia, Aplastic/blood* ; Male ; Female ; Killer Cells, Natural ; Child ; Retrospective Studies ; Child, Preschool ; Prognosis ; Adolescent ; CD4-Positive T-Lymphocytes ; Infant

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

OBJECTIVES: To investigate the causal relationship between Helicobacter pylori (Hp) infection and immune thrombocytopenia (ITP) using Mendelian randomization (MR), as well as the association between Hp infection and chronic ITP (cITP) through a clinical study. METHODS: The datasets from genome-wide association studies were used to select the single nucleotide polymorphism loci significantly associated with Hp infection as genetic instrumental variables. The MR analysis model was used to investigate the causal relationship between ITP and Hp infection. A retrospective analysis was conducted on the medical data of 316 children with newly diagnosed ITP at the First Affiliated Hospital of Xinjiang Medical University from January 2020 to December 2023. The children were followed up for 1 year, and a multivariate logistic regression analysis was used to investigate the risk factors for cITP. RESULTS: The inverse variance weighted analysis revealed that Hp infection was significantly associated with an increased risk of ITP (OR=1.280, 95%CI: 1.098-1.492, P=0.002). There was no heterogeneity or pleiotropy in this MR study (P>0.05), and the model was stable. The "leave-one-out" sensitivity analysis verified the reliability of the results. The multivariate logistic regression analysis demonstrated that Hp infection was an independent risk factor for progression to cITP (OR=7.916, 95%CI: 3.327-18.832, P<0.001). CONCLUSIONS Hp infection is a risk factor for the onset of ITP and is an independent risk factor for cITP in children.
Humans ; Helicobacter Infections/complications* ; Purpura, Thrombocytopenic, Idiopathic/etiology* ; Child ; Male ; Female ; Helicobacter pylori ; Prognosis ; Child, Preschool ; Logistic Models ; Retrospective Studies ; Risk Factors ; Polymorphism, Single Nucleotide ; Adolescent ; Infant