BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

The doctor-patient relationship is a set of social relationships based on shared interests， mutual trust， and emotional bonds， to relieve illnesses and promote health. However， the doctor-patient relationship often falls into tensions and conflicts. How to build a trusting and harmonious doctor-patient destiny community has become one of the most important issues of concern to the whole society. Based on the biopsychosocial concept of disease， the emotion management technique （EMT） emphasizes that doctors take the patient’s emotion as a clue in clinical diagnosis and treatment， regard emotions as one of the important indicators for disease diagnosis， understand the emotional events behind the disease， and provide patients with appropriate empathy and emotional management， so as to provide clinical methods for managing diseases and building a trusting and harmonious doctor-patient relationship.

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Nonalcoholic steatohepatitis （NASH） is a chronic liver disease with the main pathological features of hepatic steatosis， inflammatory cell infiltration， and interstitial fibroplasia， and it is an important risk factor for liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. NOD-like receptor protein 3 （NLRP3） inflammasome is the core of innate immunity， and the abnormal activation of NLRP3 inflammasome is closely associated with the development and progression of NASH， which involves multiple links such as inflammatory response and oxidative stress. A large number of studies have shown that the active ingredients of traditional Chinese medicine （TCM） and TCM compound prescriptions can improve oxidative stress， regulate lipid metabolism， and alleviate liver inflammation by regulating NLRP3 inflammasome. TCM treatment applied in clinical practice has achieved a good therapeutic effect， while inflammasome is one of the key pathways or targets for TCM in improving NASH. This article reviews the mechanism of action of NLRP3 inflammasome in NASH and the research advances in TCM intervention of NLRP3 inflammasome， in order to provide ideas for the clinical TCM treatment of NASH， as well as reference targets and research directions for the research and development of new TCM drugs.

Objective:To explore the recovery of abdominal function and and satisfaction rate in patients who received lower abdominal skin flap repair of extensive soft tissue defects in the limbs based on three-dimensional computed tomography angiography(3D-CTA) technology.Methods:A retrospective study was performed to analyze clinical data from patients with extensive skin and soft tissue defects in the limbs, who were admitted to Shandong Provincial Third Hospital between March 2017 and February 2022. Patients were categorized into two groups: the superficial inferior epigastric artery (SIEA) group and the deep inferior epigastric perforator (DIEP) group, with SIEA flaps and DIEP flaps utilized respectively for tissue defect repair. Based on 3D-CTA imaging, the distribution range and vessel diameters of bilateral SIEA, superficial inferior epigastric veins (SIEV), and DIEP were delineated, facilitating the design and harvest of SIEA and DIEP flaps. Comparisons were drawn between preoperative 3D-CTA findings on the course and distribution of SIEA and SIEV, and intraoperative anatomical observations. In addition, the concordance between vessel diameters and pedicle lengths determined via preoperative 3D-CTA and intraoperative measurements was assessed. The flap survival, wound healing and surveyed patients’ satisfaction with wound repair were analyzed. A customized evaluation scale was utilized to assess abdominal contour one year post-surgery, scoring from 5 to 25, with higher scores indicating better outcomes. The abdominal health module of the BREAST-Q scale evaluated patients’ satisfaction with abdominal function preoperatively, three months postoperatively, and one year postoperatively, scoring from 20 to 100, with increasing scores indicating greater satisfaction. The measurement data that conform to the normal distribution were expressed as Mean±SD, and the comparison between the two groups was performed using independent samples t-test. The comparison were conducted at multiple time points, repeated measures analysis of variance was performed, and for the comparison of scores within the group, paired t-test was applied. Results:A total of 21 patients were included, 3 males and 18 females, with an age range of 21 to 60 years and a mean age of 41 years. The range of skin and soft tissue defects was from 10.0 cm × 5.0 cm to 22.0 cm × 14.0 cm, and the range of skin flap harvesting was from 11.0 cm × 6.0 cm to 23.0 cm × 15.0 cm. There were 11 cases in the SIEA group and 10 cases in the DIEP group. Preoperative 3D-CTA examination showed that the course and distribution of SIEA and SIEV were consistent with intraoperative anatomical observations. There was no statistically significant difference in the comparison of vessel diameters, pedicle lengths, and actual measurements between preoperative 3D-CTA examination and intraoperative measurements (all P > 0.05). No flap necrosis occurred postoperatively, wound healing was uneventful in all cases. At 1 year postoperatively, there was no statistically significant difference in abdominal contour scores between the SIEA and DIEP groups [(21.96±3.51) points vs. (21.62±3.17) points, P > 0.05]. Comparison of preoperative abdominal function satisfaction scores between the SIEA and DIEP groups showed no statistically significant difference [(87.56 ± 5.70) points vs. (85.79 ± 6.33) points, P > 0.05]. However, at 3 months and 1 year postoperatively, the SIEA group had higher scores than the DIEP group [at 3 months postoperatively, (77.62 ± 7.68) points vs. (65.21 ± 8.27) points; at 1 year postoperatively, (86.93 ± 5.65) points vs. (77.59 ± 5.92) points; both P < 0.01], indicating higher abdominal function satisfaction of the SIEA group postoperatively. The scores of both the SIEA and DIEP groups decreased at 3 months postoperatively compared to preoperative scores (both P < 0.01). At 1 year postoperatively, the score of the SIEA group was similar to preoperative levels, with no statistically significant difference ( P > 0.05), while the score of the DIEP group remained lower than preoperative levels ( P < 0.01). Conclusion:Reconstruction of extensive skin and soft tissue defects in the limbs using SIEA flaps, without injury to the deep tissues of the abdominal wall, allows for near-complete restoration of abdominal function and appearance to preoperative levels, with minimal impact on the donor site. Preoperative 3D-CTA reveals the anatomical variations in the vascular supply of SIEA flaps among individuals, achieving comparable wound repair outcomes to other lower abdominal flaps.

Objective:To explore the recovery of abdominal function and and satisfaction rate in patients who received lower abdominal skin flap repair of extensive soft tissue defects in the limbs based on three-dimensional computed tomography angiography(3D-CTA) technology.Methods:A retrospective study was performed to analyze clinical data from patients with extensive skin and soft tissue defects in the limbs, who were admitted to Shandong Provincial Third Hospital between March 2017 and February 2022. Patients were categorized into two groups: the superficial inferior epigastric artery (SIEA) group and the deep inferior epigastric perforator (DIEP) group, with SIEA flaps and DIEP flaps utilized respectively for tissue defect repair. Based on 3D-CTA imaging, the distribution range and vessel diameters of bilateral SIEA, superficial inferior epigastric veins (SIEV), and DIEP were delineated, facilitating the design and harvest of SIEA and DIEP flaps. Comparisons were drawn between preoperative 3D-CTA findings on the course and distribution of SIEA and SIEV, and intraoperative anatomical observations. In addition, the concordance between vessel diameters and pedicle lengths determined via preoperative 3D-CTA and intraoperative measurements was assessed. The flap survival, wound healing and surveyed patients’ satisfaction with wound repair were analyzed. A customized evaluation scale was utilized to assess abdominal contour one year post-surgery, scoring from 5 to 25, with higher scores indicating better outcomes. The abdominal health module of the BREAST-Q scale evaluated patients’ satisfaction with abdominal function preoperatively, three months postoperatively, and one year postoperatively, scoring from 20 to 100, with increasing scores indicating greater satisfaction. The measurement data that conform to the normal distribution were expressed as Mean±SD, and the comparison between the two groups was performed using independent samples t-test. The comparison were conducted at multiple time points, repeated measures analysis of variance was performed, and for the comparison of scores within the group, paired t-test was applied. Results:A total of 21 patients were included, 3 males and 18 females, with an age range of 21 to 60 years and a mean age of 41 years. The range of skin and soft tissue defects was from 10.0 cm × 5.0 cm to 22.0 cm × 14.0 cm, and the range of skin flap harvesting was from 11.0 cm × 6.0 cm to 23.0 cm × 15.0 cm. There were 11 cases in the SIEA group and 10 cases in the DIEP group. Preoperative 3D-CTA examination showed that the course and distribution of SIEA and SIEV were consistent with intraoperative anatomical observations. There was no statistically significant difference in the comparison of vessel diameters, pedicle lengths, and actual measurements between preoperative 3D-CTA examination and intraoperative measurements (all P > 0.05). No flap necrosis occurred postoperatively, wound healing was uneventful in all cases. At 1 year postoperatively, there was no statistically significant difference in abdominal contour scores between the SIEA and DIEP groups [(21.96±3.51) points vs. (21.62±3.17) points, P > 0.05]. Comparison of preoperative abdominal function satisfaction scores between the SIEA and DIEP groups showed no statistically significant difference [(87.56 ± 5.70) points vs. (85.79 ± 6.33) points, P > 0.05]. However, at 3 months and 1 year postoperatively, the SIEA group had higher scores than the DIEP group [at 3 months postoperatively, (77.62 ± 7.68) points vs. (65.21 ± 8.27) points; at 1 year postoperatively, (86.93 ± 5.65) points vs. (77.59 ± 5.92) points; both P < 0.01], indicating higher abdominal function satisfaction of the SIEA group postoperatively. The scores of both the SIEA and DIEP groups decreased at 3 months postoperatively compared to preoperative scores (both P < 0.01). At 1 year postoperatively, the score of the SIEA group was similar to preoperative levels, with no statistically significant difference ( P > 0.05), while the score of the DIEP group remained lower than preoperative levels ( P < 0.01). Conclusion:Reconstruction of extensive skin and soft tissue defects in the limbs using SIEA flaps, without injury to the deep tissues of the abdominal wall, allows for near-complete restoration of abdominal function and appearance to preoperative levels, with minimal impact on the donor site. Preoperative 3D-CTA reveals the anatomical variations in the vascular supply of SIEA flaps among individuals, achieving comparable wound repair outcomes to other lower abdominal flaps.

The increasing incidence of peripheral nerve injuries brought on by trauma or tumors is substantially interfering with people's lives due to the causal sensory and motor dysfunctions.Peripheral nerves have some self-repair ability after injury,but they are limited by the degree of injury and the body's condition.The postoperative recovery of nerve function in patients is not satisfactory,which is closely related to the local inflammatory microenvironment after injury.Melatonin,a compound naturally synthesized in the pineal gland,protects peripheral nervous system cells from oxidative inflammation after injury and regulates their behavior and fate.Therefore,it has good application prospect in nerve tissue engineering.In this paper,we review the synthesis,metabolic processes un-derlying melatonin,mechanism of action as well as the current status of its application in peripheral nerve regeneration as well as poten-tial application for oral diseases.In this way,it further provides a new idea for the clinical treatment of peripheral nerve injury.

Objective:The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored.Methods:A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored.Results:Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS ( P<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS ( P=0.001, HR=6.981, 95% CI 2.186-22.300; P=0.010, HR=6.719, 95% CI 1.572-28.711; P=0.026, HR=3.386, 95% CI 1.158-9.901; P=0.006, HR=0.151, 95% CI 0.039-0.581) . Conclusion:For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.

Objective To investigate the value of serum angiotensin-converting enzyme 2(ACE2),tumor necrosis factor-like weak inducer of apoptosis(TWEAK)and CC motif chemokine ligand 5(CCL5)levels in the diagnosis and severity assessment of attention deficit hyperactivity disorder(ADHD)in children.Methods From October 2022 to October 2023,125 children with ADHD in Hebei Children's Hospital were selected as ADHD group,and 105 healthy children in Hebei Maternal and Child Health Center were selected as control group.According to the Clinical Global Impressions-Severity(CGI-S),the children were separated into a mild to moderate group(n=83)and a severe group(n=42).ELISA was applied to detect levels of ACE2,TWEAK,CCL5,luteinizing hormone(LH),and prolactin(PRL).The combined raven test(CRT)and conners parental symptom questionnaire(PSQ)were applied to score the cognitive and behavioral status of children with disabilities.Spearman correlation was used to analyze the correlation among serum ACE2,TWEAK,and CCL5 with CGI-S,CRT,and PSQ scores in the severe group.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of ACE2,TWEAK,and CCL5 for ADHD and severity.Results The serum ACE2(284.35±92.34 pg/ml)and TWEAK(2.56±0.76 pg/ml)levels in children with ADHD were lower than those in the control group(379.23±106.28 pg/ml,3.52±1.12 pg/ml),while CCL5(7.36±2.37 ng/ml)level was higher than that in the control group(5.24±1.63 ng/ml),and the differences were statistically significant(t=7.244,7.703,7.753,all P＜0.05).The levels of CRT,serum ACE2 and TWEAK in the severe group were lower than those in the mild to moderate group(t=5.318,6.686,6.490),while the levels of PSQ and CCL5 were higher than those in the mild to moderate group(t=5.220,6.134),and the differences were statistically significant(all P＜0.05).Spearman correlation analysis results showed that the serum ACE2 and TWEAK levels in the severe group were negatively correlated with CGI-S and PSQ scores(r=-0.432,-0.453;-0.421,-0.426,all P＜0.001),but positively correlated with CRT scores(r=0.427,0.418,all P＜0.000 1).CCL5 was positively correlated with CGI-S and PSQ scores(r=0.421,0.433,all P＜0.001),but negatively correlated with CRT scores(r=-0.446,P＜0.001).The AUCs for diagnosing ADHD by serum ACE2,TWEAK and CCL5 were 0.814,0.803 and 0.807,respectively,and the AUC of the combined diagnosis of the three was 0.945,which was better than individual diagnosis(Z=5.439,4.258,5.576,all P＜0.001).The AUCs for diagnosing severe ADHD by serum ACE2,TWEAK and CCL5 were 0.853,0.796 and 0.805,respectively,and the AUC of the combined diagnosis of the three was 0.930,which was better than the individual diagnosis(Z=2.604,3.851,3.567,all P＜0.001).Conclusion Serum ACE2 and TWEAK are low expressed in the serum of children with ADHD,while CCL5 is highly expressed.The expression levels of the three are correlated and have high diagnostic value for the occurrence and severity of ADHD.

Objective To observe the efficacy and safety of radiotherapy combined with programmed death receptor-1(PD-1)inhibitors and tyrosine kinase inhibitors(TKIs)for the treatment of microsatellite-stabilized(MSS)-type or mismatch-matched repair-normal(pMMR)-type colorectal cancer with liver metastases(CCLM).Methods Case data of 25 patients with MSS-type CCLM admitted to Jiangsu Provincial Cancer Hospital from April 2021 to August 2023 were retrospectively analyzed.They were divided into observation group(n = 12)and control group(n = 13).The observation group was given radiotherapy combined with PD-1 inhibitor and TKI treatment,and the control group was given TKI monotherapy.The baseline data,treatment effect,progression-free survival,and treatment-related adverse reactions of patients in the two groups were compared.Results The difference in baseline data between the two groups was not statistically significant(P＞0.05),the disease control rate(DCR)of the observation group was higher than that of the control group(P＜0.05),the progression-free survival(PFS)of the patients in the observation group was longer than that of the control group,but the difference was not statistically sig-nificant(P＞0.05),and the difference in the incidence of treatment-related adverse events(TRAE)between the two groups was not statistically significant(P＞0.05).Conclusion The treatment regimen of radiotherapy com-bined with PD-1 inhibitors and TKI drugs improved clinical efficacy and did not increase the incidence of adverse events when compared with TKI alone,which is a treatment regimen worthy of further validation.