ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

Objective:To evaluate long-term outcomes of endoscopic papillectomy (EP) for duodenal papillary adenomas and to identify risk factors for incomplete resection.Methods:Clinical data of 180 patients diagnosed as having duodenal papillary adenoma via postoperative pathology after EP in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2010 to December 2022 were retrospectively analyzed. Patients were divided into two groups based on their postoperative margin status: the complete resection group (negative resection margins) and the incomplete resection group (positive/uncertain resection margins). Recurrence rates were compared between the two groups, and logistic regression analysis was performed to identify risk factors for incomplete resection.Results:Among the 180 patients included in the study, 137 underwent complete resection, and 43 had incomplete resections. Recurrence rate was significantly higher in the incomplete resection group than that in the complete resection group (30.2% VS 15.3%, χ2=4.75, P=0.029). logistic regression analysis indicated that high-grade intraepithelial neoplasia was an independent risk factor for incomplete resection ( OR=2.43, 95% CI:1.12-5.26, P=0.024). Conclusion:Patients with incomplete resection after EP have a higher recurrence rate in the long-term follow-up. High-grade intraepithelial neoplasia is an independent risk factor for incomplete resection. Close surveillance and aggressive management are warranted for patients with positive or uncertain resection margins to mitigate the recurrence risk.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Objective To investigate the effectiveness of new-generation snapshot freeze(NG SSF)technology for improving image quality of coronary CT angiography(CCTA)in patients with different heart rate(HR).Methods CCTA data of 164 patients obtained with a 256-row CT scanner and voltages of 80,100 and 120 kV,respectively,in one cardiac cycle were retrospectively analyzed.Smart electrocardiogram(ECG)gating technology was used to calculate patient's HR and choose automatic exposure phase.For these with HR≤65 beats/min(low HR group),the exposure time window was set between 70%—80%R-R interval,for 65 beats/min＜HR≤85 beats/min(medium HR group)was set between 40%—80%R-R interval,while for those HR＞85 beats/min(high HR group)was set between 40%—60%R-R interval.Standard reconstruction(STD),the first-generation snapshot freeze(SSF1)and NG SSF were performed to reconstruct CCTA images,respectively.Subjective scoring of each segment of right coronary artery(RCA),left anterior descending(LAD)and left circumflex artery(LCX)shown on CCTA were performed based on Likert scale.Results In low HR group,the scores of middle and distal segments of LAD and all segments of RCA and LCX on NG SSF CCTA were significantly higher than on STD,and of middle segment of RCA and distal segment of LAD were both higher than on SSF1(all P＜0.05).In medium HR group,the scores of all branches on NG SSF CCTA were significantly higher than on STD or SSF1 CCTA(all P＜0.05).In high HR group,the scores of coronary branches showed on NG SSF CCTA were all significantly higher than on STD CCTA,while of the proximal and distal segments of RCA,middle and distal segments of LAD and all segments of LCX were significantly higher than on SSF1 CCTA(all P＜0.05).Conclusion NG SSF could effectively enhance image quality of prospective ECG-gated CCTA in patients with varying HR.

Objective To investigate the effectiveness of new-generation snapshot freeze(NG SSF)technology for improving image quality of coronary CT angiography(CCTA)in patients with different heart rate(HR).Methods CCTA data of 164 patients obtained with a 256-row CT scanner and voltages of 80,100 and 120 kV,respectively,in one cardiac cycle were retrospectively analyzed.Smart electrocardiogram(ECG)gating technology was used to calculate patient's HR and choose automatic exposure phase.For these with HR≤65 beats/min(low HR group),the exposure time window was set between 70%—80%R-R interval,for 65 beats/min＜HR≤85 beats/min(medium HR group)was set between 40%—80%R-R interval,while for those HR＞85 beats/min(high HR group)was set between 40%—60%R-R interval.Standard reconstruction(STD),the first-generation snapshot freeze(SSF1)and NG SSF were performed to reconstruct CCTA images,respectively.Subjective scoring of each segment of right coronary artery(RCA),left anterior descending(LAD)and left circumflex artery(LCX)shown on CCTA were performed based on Likert scale.Results In low HR group,the scores of middle and distal segments of LAD and all segments of RCA and LCX on NG SSF CCTA were significantly higher than on STD,and of middle segment of RCA and distal segment of LAD were both higher than on SSF1(all P＜0.05).In medium HR group,the scores of all branches on NG SSF CCTA were significantly higher than on STD or SSF1 CCTA(all P＜0.05).In high HR group,the scores of coronary branches showed on NG SSF CCTA were all significantly higher than on STD CCTA,while of the proximal and distal segments of RCA,middle and distal segments of LAD and all segments of LCX were significantly higher than on SSF1 CCTA(all P＜0.05).Conclusion NG SSF could effectively enhance image quality of prospective ECG-gated CCTA in patients with varying HR.

Objective:To evaluate long-term outcomes of endoscopic papillectomy (EP) for duodenal papillary adenomas and to identify risk factors for incomplete resection.Methods:Clinical data of 180 patients diagnosed as having duodenal papillary adenoma via postoperative pathology after EP in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2010 to December 2022 were retrospectively analyzed. Patients were divided into two groups based on their postoperative margin status: the complete resection group (negative resection margins) and the incomplete resection group (positive/uncertain resection margins). Recurrence rates were compared between the two groups, and logistic regression analysis was performed to identify risk factors for incomplete resection.Results:Among the 180 patients included in the study, 137 underwent complete resection, and 43 had incomplete resections. Recurrence rate was significantly higher in the incomplete resection group than that in the complete resection group (30.2% VS 15.3%, χ2=4.75, P=0.029). logistic regression analysis indicated that high-grade intraepithelial neoplasia was an independent risk factor for incomplete resection ( OR=2.43, 95% CI:1.12-5.26, P=0.024). Conclusion:Patients with incomplete resection after EP have a higher recurrence rate in the long-term follow-up. High-grade intraepithelial neoplasia is an independent risk factor for incomplete resection. Close surveillance and aggressive management are warranted for patients with positive or uncertain resection margins to mitigate the recurrence risk.

Aim To establish a quantitative immunofluorescent bioactivity assay(ICW)for insulin glargine based on CHO-IN-SRB 1284 transgenic cells,and to study its equivalence with in-sulin bioassay of Ch.P.Methods The cells were diluted 25 times with 1.5 × 108 L-1 cell density plates and 1 500 μmol·L-1 insulin glargine,and then diluted with a 3-fold gradient se-ries.The cells were stimulated in microporous plates for 20 min.After fixation,permeation and antibody incubation.Quantitative immunofluorescence biological activity was detected by odyssey two-color infrared fluorescence imaging system.Results There was a good dose-effect relationship between the concentration of insulin glargine in ICW and its relative potency.The method had good specificity,and the relative accuracy,intermediate preci-sion and linearity met the requirements.The relative deviation of biological activity results of 7 batches of insulin glargine samples measured by the two methods was less than 10％.The results were analyzed by SPSS and SAS software,which showed that the methods were correlated and equivalent.Conclusions The quantitative immunofluorescence assay for the biological activity of insulin glargine can be established.The method has good spe-cificity,high accuracy and precision,and has correlation and e-quivalent with biotiter assay,which can be applied to in vitro ef-ficacy evaluation and quality control of insulin glargine.

Humans ; Asthma/drug therapy* ; Biological Therapy