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.

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.

Spleen-stomach damp-heat syndrome is currently the most prevalent TCM pattern in patients with chronic atrophic gastritis (CAG), with internal damp-heat accumulation regarded as a key factor contributing to its prolonged and refractory course. This syndrome represents a critical stage in the progressive pathogenesis of CAG, characterized by a deepening pathological evolution. Modern TCM practitioners generally agree that its core pathogenesis lies in "deficiency in root and excess in superficiality, with internal damp-heat retention", and emphasize a treatment strategy that combines eliminating pathogenic factors and reinforcing the body's healthy qi through dynamic syndrome differentiation. Chinese materia medica used in treating CAG with spleen-stomach damp-heat syndrome can effectively relieve clinical symptoms, improve the internal damp-heat environment, mitigate gastric mucosal atrophy and intestinal metaplasia, and delay the inflammation-to-cancer transformation. Its mechanisms may involve eradication of Helicobacter pylori, repair of gastric mucosal injury, regulation of immune inflammatory response and other aspects, which has the advantages of multi-channel and multi-target.

Objective To identify independent predictors of prognosis in MMNS and to examine the expression of CD4,CD8,CD20 and their relationship with prognosis.Methods 87 patients with MMNS were retrospectively an-alyzed to summarize their clinicopathologic characteristics;the expression of CD4,CD8,and CD20 in MMNS were observed by EnVision immunohistochemical staining(IHC)to analyze the relationship between the expression of these markers and prognosis.Results MMNS with sinus,surrounding tissue invasion,larger tumor and higher AJCC stage showed a worse prognosis.No significant correlation was found among sex,age,histological type,melanin granules,mitotic figures and survival rate.The counts of CD4+,CD8+and CD20+TILs in intra-tumoral stroma were positively correlated with the density of TILs at the base of the tumor.CD20+B cells did not have a central tendency to aggregate to form tertiary lymphoid structures,whether in the intratumoral stroma or in the basal stroma of the tumor,the three cell subsets were admixed.There was no statistically significant difference in OS be-tween CD4+,CD8+,and CD20+subsets.Conclusions The number of CD20+B cells was significantly less than that of CD4+and CD8+T cells in both the intratumoral stroma and the basal stroma of the tumor,and tertiary lymphoid structures fail to be formed,which,unlike cutaneous malignant melanoma,might be a cause of the poor prognosis of MMNS.

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

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 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.