Ankylosing spondylitis (AS) is linked to an increased prevalence of myocardial infarction (MI). However, research dedicated to elucidating the pathogenesis of AS-MI is lacking. In this study, we explored the biomarkers for enhancing the diagnostic and therapeutic efficiency of AS-MI. Datasets were obtained from the Gene Expression Omnibus database. We employed weighted gene co-expression network analysis and machine learning models to screen hub genes. A receiver operating characteristic curve and a nomogram were designed to assess diagnostic accuracy. Gene set enrichment analysis was conducted to reveal the potential function of hub genes. Immune infiltration analysis indicated the correlation between hub genes and the immune landscape. Subsequently, we performed single-cell analysis to identify the expression and subcellular localization of hub genes. We further constructed a transcription factor (TF)-microRNA (miRNA) regulatory network. Finally, drug prediction and molecular docking were performed. S100A12 and MCEMP1 were identified as hub genes, which were correlated with immune-related biological processes. They exhibited high diagnostic value and were predominantly expressed in myeloid cells. Furthermore, 24 TFs and 9 miRNA were associated with these hub genes. Enzastaurin, meglitinide, and nifedipine were predicted as potential therapeutic agents. Our study indicates that S100A12 and MCEMP1 exhibit significant potential as biomarkers and therapeutic targets for AS-MI, offering novel insights into the underlying etiology of this condition.
Humans ; Spondylitis, Ankylosing/complications* ; Systems Biology/methods* ; Myocardial Infarction/diagnosis* ; Biomarkers/metabolism* ; MicroRNAs/genetics* ; Gene Regulatory Networks ; Gene Expression Profiling ; Machine Learning

Diabetic cardiomyopathy （DCM） is one of the most common cardiovascular lesions in diabetes mellitus. The development and progression of DCM is closely related to myocardial fibrosis， which has been shown to be an important pathological feature of DCM. Therefore， the treatment targeting myocardial fibrosis can help slow down the DCM progress. In the DCM progress， abnormal transduction of transforming growth factor-β （TGF-β）/Smad signaling pathway is an important mechanism of hyperglycemia-induced myocardial fibrosis. TGF-β is a key factor of myocardial fibrosis and is overexpressed during myocardial fibrosis in DCM， and Smad is a major effector in the downstream of TGF-β. By inducing myocardial apoptosis， TGF-β/Smad signal stimulates the overproduction of myofibroblasts， increase the deposition of extracellular matrix （ECM）， and plays a complex role in the pathogenesis of myocardial fibrosis in diabetic hearts. In recent years， Chinese medicine has played an increasingly important role in the prevention and treatment of DCM， and there has been an increase in the number of studies exploring the effects of Chinese medicine on the intervention of DN progress based on TGF-β/Smad signal. Various pharmacological studies have shown that Chinese medicine is safe and effective in the prevention and treatment of DCM， which has clear effects such as inhibiting the deposition of collagen， anti-myocardial fibrosis， improving cardiac function， and protecting myocardium， and TGF-β/Smad signaling pathway is one of the key pathways in which Chinese medicine， Chinese medicine monomers， and Chinese medicine compounds exert the myocardial protective effect in DCM. Based on this， this paper reviewed the existing pharmacological and experimental research results of Chinese medicine intervention in the TGF-β/Smad signaling pathway to treat DCM in the past decades， hoping to provide references for further in-depth research， development， and application of Chinese medicine in the treatment of DCM.

Diabetic nephropathy （DN）， the most feared microvascular complication of diabetes and one of the most common and serious complications of diabetes， is the major cause of end-stage renal disease worldwide， leading cause of morbidity and mortality in patients with diabetes， and the main non-communicable cause of death worldwide. There are many types of saponins， which are the main bioactive components of various Chinese medicinals. They have various pharmacological activities such as lowering blood glucose and blood lipids， improving insulin resistance， anti-inflammation， anti-oxidative stress， anti-tumor， and immune modulation. In recent years， it has been frequently verified that the saponins in Chinese medicinals have definite effect in regulating DN， showing multi-target， multi-pathway， multi-system， multi-effect characteristics. Thus， they have broad prospects in the prevention and treatment of this disease. There has been an explosion of research on the treatment of DN with saponins in Chinese medicinals in vivo and in vitro， but there is a lack of systematic and comprehensive summary. Therefore， this study summed up the studies of saponins in Chinese medicinals in the intervention of DN and summarized the mechanisms such as improving glucolipid metabolism， inhibiting oxidative stress， anti-inflammation， anti-apoptosis， regulating autophagy， anti-fibrosis， and protecting podocytes， with a view to providing ideas and references for the development of drugs related to DN.

Diabetic peripheral neuropathy （DPN） is a symptom and/or sign of peripheral nerve dysfunction that occurs in patients with diabetes mellitus when other causes are excluded. DPN， one of the most common complications of diabetes mellitus， can lead to disability， foot ulcers， and amputation at a later stage. Its pathogenesis is closely related to high glucose-induced inflammatory damage， oxidative stress， mitochondrial disorders， and apoptosis in neural tissues. The p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway is a key mechanism mediating the expression of inflammatory factors， oxidative factors， and apoptotic factors of neural tissues in DPN. The inflammatory response， oxidative stress damage， and apoptosis， induced by the activation of p38 MAPK phosphorylation by factors such as high glucose， can cause cell lipid peroxidation， protein modification， and nucleic acid damage， which results in axonal degeneration and demyelination changes. The current treatment of DPN with western medicine has obvious shortcomings such as adverse effects and addictive tendencies. In recent years， the research on traditional Chinese medicine （TCM） in the prevention and treatment of DPN has gradually increased， and the exploration of Chinese medicine intervention in the p38 MAPK pathway transduction to improve DPN has advanced. The present study reviewed the relations of the p38 MAPK pathway with insulin resistance and peripheral neuropathy and summarized the molecular biological mechanisms involved in the pathological process of DPN， such as inflammation regulation， oxidative stress， polyol pathway regulation， and Schwann cell apoptosis in the past 10 years. In addition， the literature on Chinese medicine monomers， Chinese patent medicines， and Chinese medicine compounds in inhibiting inflammatory reactions， oxidative injury， and apoptosis of DPN peripheral nerves based on the p38 MAPK pathway， resisting axonal degeneration and demyelination changes， improving sensory and motor abnormalities， relieving peripheral pain sensitization， and facilitating nerve conduction mechanism to provide references for the development of new drugs for clinical prevention and treatment of DPN.

Diabetic kidney disease （DKD）， a major microvascular complication of diabetes mellitus， serves as the most common cause of end-stage renal disease worldwide. The progression of DKD is closely related to oxidative stress， inflammatory response， apoptosis， and fibrosis in renal tissues activated by high glucose. Numerous studies have shown that the transduction of the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway is involved in the pathological process of DKD in renal tissues， activating various pathological mechanisms， such as oxidation， inflammation， apoptosis， and fibrosis. Therefore， blocking the transduction of the p38 MAPK signaling pathway is beneficial to alleviating DKD. At present， the main treatment principles of western medicine are glucose lowering， lipid lowering， and blood pressure lowering， as well as medications with new drugs renal sodium-glucose co-transporter 2 （SGLT2）， mineralocorticoid receptor， and endothelin receptor， but the progression of DKD still cannot be stopped. The treatment of DKD by traditional Chinese medicine （TCM） has the advantages of simplicity， low cost， and convenience， and the symptoms and root causes can be both treated. In recent years， the basic research on Chinese medicine intervention in DKD has greatly advanced， and p38 MAPK is the key factor of Chinese medicine intervention in DKD. The present study searched and reviewed the literature on the Chinese medicine intervention in the p38 MAPK signaling pathway in DKD treatment in the past decade. The results showed that p38 MAPK interacted with transforming growth factor-β₁ （TGF-β₁）， cysteinyl aspartate-specific protease-3 （Caspase-3）， nuclear factor-κB （NF-κB）， and other factors to activate fibrosis， inflammation， oxidative stress， and apoptosis. By acting on p38 MAPK and its upstream and downstream factors， Chinese medicine blocked the pathological processes of DKD and inhibited the pathological injury of DKD and the deterioration of renal function. This study is expected to provide new ideas and directions for the prevention and treatment of DKD with Chinese medicine.

Objective:To develop an online interactive cytopathological training program, and to evaluate it for improving the cytopathological diagnostic ability of endoscopists in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreas.Methods:A total of 5 500 cytopathological images were collected from 194 patients with pancreatic solid mass who underwent EUS-FNA in Nanjing Drum Tower Hospital from August 2018 to August 2019. The cell type in each cytopathological picture was labeled by senior cellular pathologists, which was used to build a learning and testing platform for online interactive cytopathological training. Five endoscopists without cytopathological background were invited to participate in this training. Sensitivity, specificity, positive predictive value and negative predictive value of endoscopists in differential diagnosis of cancer and non-cancer before and after training were compared to evaluate the effect of the online interactive cytopathological training program on improving the ability of endoscopists in diagnosis of cytopathology.Results:A cytopathological training platform for endoscopists to learn and take online test was successfully built. Before training, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of diagnosis of cancer and non-cancer for endoscopists were 0.55 (95% CI: 0.53-0.58), 0.32 (95% CI: 0.30-0.35), 0.43 (95% CI: 0.41-0.45), 0.44 (95% CI: 0.41-0.47) and 0.43 (95% CI: 0.42-0.45), respectively. After training, the above indicators were 0.96 (95% CI: 0.95-0.97), 0.70 (95% CI: 0.68-0.73), 0.74 (95% CI: 0.72-0.76), 0.95 (95% CI: 0.94-0.96) and 0.81 (95% CI: 0.80-0.83), respectively, which were significantly improved compared with those before ( P<0.001). Conclusion:The online interactive cytopathological training program can improve the understanding and diagnostic ability of endoscopists in pancreatic cytopathology, help to implement rapid on-site evaluation in the process of EUS-FNA, and improve the diagnostic efficiency of EUS-FNA.

Objective:To analyze and summarize the characteristics of liver pathology and their relation to clinical markers and further explore noninvasive markers of liver fibrosis in children with chronic hepatitis B.Methods:Data of 80 hospitalized children with chronic hepatitis B who underwent liver biopsy without antiviral treatment from 2011 to 2020 were retrospectively analyzed. Inflammation and liver fibrosis characteristics were analyzed in children of different ages and genders. Variables with good correlation with liver fibrosis stage were selected to establish a non-invasive diagnostic score of liver fibrosis in children. Measurement data was used to compare the t-test or rank sum test. Mantel-Haenszel χ2 test was used for bidirectional ordered grouping data. Spearman’s rank correlation test was used for rank correlation analysis. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of the newly established diagnostic score in children with liver fibrosis. Results:The median age of the children was 6.4 years. HBV DNA level was high (P50 = 7.6 log 10 IU/ml), and serum alanine aminotransferase (ALT) in P50 was 171 U/L (< ULN: 5 cases, ULN-2ULN: 10 cases, > 2 ULN: 65 cases). Pathological analysis showed that the incidence of liver tissue inflammation was 97.5%, and the proportion of patients with G≥2 was 42.5%, while S≥2 was 36.3%. The incidence rate of liver fibrosis and liver cirrhosis was 81.3%, and 1.3%, respectively. The changes in liver tissue inflammation and fibrosis were gradually aggravated with the increase of age, and the proportion of high-grade inflammation and liver fibrosis in male children was higher than that in female children. Serum levels of glutamyl transpeptidase (GGT), γ-glutamyltransferase/platelet ratio (GPR) and HBeAg had a good correlation with fibrosis stage ( rs = 0.397, 0.389, and - 0.311) in children with chronic hepatitis B. The combination of GGT, GPR and HBeAg can establish a non-invasive diagnostic score for evaluating liver fibrosis in children. When the score is less than 1.5, it can be diagnosed as S0, and 1.5 ≤ score < 3.5, it can be diagnosed as S1; 3.5 ≤ score < 5.5, the diagnosis of fibrosis is S2; score≥ 5.5, the diagnosis of fibrosis is S≥3. The sensitivity and specificity were 80%, 83%, 86%, and 53%, 55%, 67%, respectively. Conclusion:The incidence of liver tissue inflammation in children with chronic hepatitis B with elevated and fluctuating transaminase levels is high, and the pathological changes of liver tissue aggravate with the age of the children. GGT, GPR and HBeAg have a good correlation with liver fibrosis in children with chronic hepatitis B. Therefore, combining the above-mentioned markers to establish a new noninvasive diagnostic score has certain diagnostic value for liver fibrosis stage S0-S3 in children with chronic hepatitis B.

Objective To determine the diagnostic value of endoscopic ultrasound-guided fine needle aspiration ( EUS-FNA ) for gastrointestinal lesions with inconclusive endoscopic biopsies. Methods A retrospective analysis was performed in 65 patients who were found to have gastrointestinal lesions with inconclusive endoscopic biopsies and underwent EUS-FNA in Drum Tower Hospital. Diagnostic value of EUS-FNA was determined by comparing with surgical histopathology and follow-up results. Results This study included 41 males ( 63％) and 24 females ( 37％) with median age of 60 years. The most common lesion was diffuse infiltrative lesions ( 37, 56. 9％) , followed by submucosal protrusion types ( 17, 26. 2％) . Fifty-four cases ( 83. 1％) were malignant lesions, and 11 cases ( 16. 9％) were benign. The overall sensitivity, specificity, and accuracy of EUS-FNA for gastrointestinal lesions with inconclusive biopsies were 76. 8％ ( 95％CI: 65. 7％-87. 8％) , 100. 0％ ( 95％CI: 66. 4％-100. 0％) , and 80. 0％( 95％CI: 70. 3％-89. 7％) , respectively. Sub-group analysis showed the sensitivity, specificity, and accuracy of EUS-FNA for diffuse infiltrative lesions were 70. 6％ ( 95％CI: 55. 3％-85. 9％, 100. 0％( 95％CI:29. 2％-100. 0％) , and 73. 0％ ( 95％CI: 58. 7％-87. 3％) , respectively. For submucosal protrusions, the sensitivity, specificity, and accuracy of EUS-FNA were 68. 8％ ( 95％CI: 46. 0％ -91. 5％) , 100. 0％ ( 95％CI: 2. 5％-100. 0％) , and 70. 6％ ( 95％CI: 44. 0％-89. 7％) , respectively. Conclusion EUS-FNA has moderate diagnostic value for endoscopic biopsy-inconclusive gastrointestinal lesions. It can be an alternative option when standard methods, such as endoscopic mucosal forceps biopsy, fail to provide a definitive diagnosis.

Finite element method (FEM) was used to investigate the biomechanical properties of three types of surgical fixations of U-shaped sacral fractures. Based on a previously established and validated complete lumbar-pelvic model, three models of surgical fixations of U-shaped sacral fractures were established: ① S1S2 passed through screw (S1S2), ② L4-L5 pedicle screw + screw for wing of ilium (L4L5 + IS), and ③ L4-L5 pedicle screw + S1 passed through screw + screw for wing of ilium (L4L5 + S1 + IS). A 400 N force acting vertically downward, along with torque of 7.5 N·m in different directions (anterior flexion, posterior extension, axial rotation, and axial lateral bending), was exerted on the upper surface of L4. Comparisons were made on differences in separation of the fracture gap and maximum stress in sitting and standing positions among three fixation methods. This study showed that: for values of separation of the fracture gap produced by different operation groups in different positions, L4L5 + S1 + IS was far less than L4L5 + IS and S1S2. For internal fixators, the maximum stress value produced was: L4L5 + IS > L4L5 + S1 + IS > S1S2. For the intervertebral disc, the maximum stress value produced by S1S2 is much larger than that of L4L5 + S1 + IS and L4L5 + IS. In a comprehensive consideration, L4L5 + S1 + IS could be prioritized for fixation of U-shaped sacral fractures. The objective of this research is to compare the biomechanical differences of three different internal fixation methods for U-shaped sacral fractures, for the reference of clinical operation.
Biomechanical Phenomena ; Finite Element Analysis ; Fracture Fixation ; methods ; Humans ; Lumbar Vertebrae ; Pedicle Screws ; Sacrum ; injuries ; Spinal Fractures ; surgery ; Spinal Fusion

Objective To observe the difference of anoreetal dynamics between Milligan-Morgan hemorrhoidectomy plus internal sphinctemtomy and simple Milligan-Morgan bemorrhoidectomy in the treatment of annulus mixed hemorrhoids.Method Measured the anal resting pressure,maximal anal contractive pressure,rectal sensation thresholds,maximal rectal tolerable dose and maximal rectal compliance 1 day before and 3 months after Milligan-Morgan hemorrhoidectomy plus internal sphincterotomy (therapy group,50 cases)and simple Milligan-Morgan bemorrhoidectomy(control group,52 cases)by anorectal manometric device made in Sweden.Results The anal resting pressures of therapy group and eontrol group reduced signifieanfly 3 months after operation compared with that 1 day before operation(P＜ 0.01 or ＜ 0.05),but there was significant difference between the two groups in 3 months after operation(P＜0.05).The maximal anal contractive pressure,reetal sensation thresholds,maximal rectal tolerable dose and maximal rectal compliance were no significant difference between the two groups in 3 months after operation (P ＞0.05).Conclusion Anal sphineterotomy can change the high anal pressure significantly in the treatment of annulus hemorrhoids without copracrasia,it is a proper operation method.