Objective:To explore the mechanisms of " TongduAnshen " couplet medicines Notopterygii Rhizoma et Radix-Ziziphi Spinosae Semen(TDAS)on chronic unpredictable mild stress(CUMS)model rats.Methods:The rat model of depression were prepared using isolated and CUMS method.The depression-like behavior was detected by sucrose preference test(SPT),the open field test(OFT)and forced swimming test(FST).The pathological changes of hippocampal neurons were observed by HE and Nissl staining.The levels of 5-hydroxytryptamine(5-HT),interleukin 18(IL-18)and interleukin 1 β(IL-1β)were detected by enzyme linked immunosorbent assay(ELISA).The protein expression of NLRP3,ASC,caspase-1 in hippocampus were determined by Western blot.Results:The depression-like behavior of rats in the TDAS-L,TDAS-M and TDAS-H groups was significantly improved(P＜0.05 orP＜0.01);HE and Nissl staining showed that the neurons were arranged neatly,the number of shrunken cells were reduced,the extent of the injury was reduced;the contents of 5-HT in hippocampus of rats increased(P＜0.05 or P＜0.01),the contents of IL-18 and IL-1β in serum decreased(P＜0.01);the expressions of NLRP3,ASC and caspase-1 in hippocampus were decreased(P＜0.01).Conclusion:TDAS can improve depression-like behavior in chronic unpredictable mild stress rats,and its mechanism may be increase the contents of 5-HT,inhibit the expression of NLRP3 signaling pathway,and reduce the content of inflammatory factors.

In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A-G (1-7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10-27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC₅₀ values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L^-1, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
Mice ; Animals ; Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Inula/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure ; NF-kappa B/immunology* ; NF-E2-Related Factor 2/immunology* ; Macrophages/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha/immunology* ; I-kappa B Kinase/genetics*

To explore the value of general information and rapid laboratory tests obtained from the emergency department in the early diagnosis and prevention of young patients with acute myocardial infarction and acute myocarditis, in order to prevent the disease from progressing to a critical stage. This study employs a retrospective observational study, compiling clinical data from young patients diagnosed with acute myocardial infarction or acute myocarditis who were admitted to the Department of Cardiology or Emergency Department of the Second Affiliated Hospital of Soochow University from January 2015 to September 2024. Demographic information and laboratory test results from both the outpatient and emergency departments were retrieved. The acute myocardial infarction group comprised 267 patients (257 males, 10 females) aged 23-44 ys, while the acute myocarditis group included 134 patients (93 males, 41 females) aged 18-44 ys. A comparative analysis of the clinical data between the two groups was conducted, encompassing variables such as age, gender, comorbidities, high-risk factors, emergency blood routine tests, high-sensitivity C-reactive protein levels, coagulation profiles, renal function tests, NT-proBNP levels, myocardial injury markers, electrocardiogram readings, blood pressure, and heart rate. The results showed that:Compared with the young myocarditis group, the myocardial infarction group was older (ys)[38(35, 42) vs 30(25, 37), U=7 893, P<0.001], more male [257(96.3%) vs 93(69.4%), χ2=57.95, P<0.001], more smoking [211(79.0%) vs 38(28.4%), χ2=97.32, P<0.001], drinking history [125(46.8%) vs 22(16.4%), χ2=35.51, P<0.001], family history of coronary heart disease [45(16.9%) vs 3(2.2%), χ2=18.09, P<0.001], hypertension [100(37.5%) vs 12(9.0%), χ2=36, P<0.001] and diabetes [42(15.7%) vs 4(3.0%), χ2=14.27, P<0.001]. Systolic blood pressure (mmHg)[126(114, 144) vs 119(101, 126), U=11 389.50, P<0.001], diastolic blood pressure (mmHg)[80(70, 93) vs 72(62, 81), U=12 220.50, P<0.001], total white blood cell count (10 9/L)[11.3(9.2, 14.1) vs 8.5(6.6, 11.2), U=10 825.50, P<0.001], hemoglobin (g/L)[157(147, 166) vs 143(129, 154), U=9 404.50, P<0.001], platelet count (10 9/L)[244(206, 297) vs 207(173, 253), U=11 680, P<0.001], uric acid (μmol/L)[380(315, 446) vs 347(265, 412), U=14 805.50, P=0.005], ST segment elevation [204(76.4%) vs 57(42.5%), χ2=73.03, P<0.001] and Q wave formation [76(28.5%) vs 17(12.7%), χ2=12.47, P<0.001] in ECG were higher than those in myocarditis group. The duration of onset (hs) [6(3, 25) vs 48(24, 73), U=27911, P<0.001], heart rate (beats/min)[82(74, 92) vs 92(78, 103), U=22 347, P<0.001], D-dimer (μg/ml)[0.23(0.17, 0.51) vs 0.61(0.30, 1.38), U=25 806, P<0.001], High-sensitivity troponin T/99th percentile upper reference limit [5(1, 36) vs 16(8, 39), U=22 577, P<0.001], NT-proBNP (pg/ml) [204(64, 644) vs 824(189, 4 043), U=25 134, P<0.001], C-reactive protein (mg/L)[6(3, 9) vs 24(6, 55), U=26 349.50, P<0.001] and body temperature (℃) [36.50(36.30, 36.60) vs 37.35(36.50, 38.50), U=26 961, P<0.001] were significantly lower than those in myocarditis group, the symptoms of chest pain in myocardial infarction group was significantly higher than those in myocarditis group [262(98.1%) vs 83(61.9%), χ2=97.24, P<0.001], and the history of prodromal infection [12(4.5%) vs 112(83.6%), χ2=261.26, P<0.001], syncope [11(4.1%) vs 18(13.4%), χ2=11.53, P<0.001] and shock [6(2.2%) vs 22(16.4%), χ2=27.59, P<0.001] in myocardial infarction group were significantly lower than those in myocarditis group. With acute myocardial infarction as the target outcome, 8 influencing factors selected by LASSO regression, and 5 independent influencing factors were found after multiple Logistic regression, those were age ( OR=1.21, 95% CI: 1.12-1.31; P<0.001), pre-infection ( OR=0.02, 95% CI: 0.01-0.06; P<0.001), body temperature ( OR=0.37, 95% CI: 0.18-0.77; P=0.008), chest pain ( OR=26.75, 95% CI: 5.87-121.81; P<0.001) and white blood cell count ( OR=1.27, 95% CI: 1.12-1.44; P<0.001). Younger age, high body temperature and pre-infection are independent predictors for acute myocarditis, while chest pain and elevated white blood cell count are independent predictors for acute myocardial infarction. The five influencing factors selected by multivariate logistic regression and their combined diagnostic model were subjected to ROC analysis. The AUC reached 0.969, sensitivity reached 0.940 and specificity reached 0.925. Calibration curve and decision curve analysis(DCA) demonstrate that the model possesses excellent clinical application value. In conclusion, age, chest pain, pre-infection, body temperature and white blood cell count were independent factors in distinguishing acute myocardial infarction and acute myocarditis in young people. The clinical differential diagnosis model based on 5 independent factors may has high efficiency and good clinical practicability.

Objective:To study the feasibility of design and harvest of free medial sural artery perforator flap with the "two-point and two-line method".Methods:From September 2022 to June 2023, Suzhou Ruihua Orthopaedic Hospital implemented the "two-point and two-line method" to guide preoperative perforator positioning and flap design. Thirty medial sural artery perforator flaps were successfully harvested with the method, and 21 wounds of hand and 9 of foot and ankle were reconstructed with the flaps. The size of soft tissue defects were 2.5 cm×2.5 cm-7.0 cm×14.5 cm, and the flaps size were 3.0 cm×3.0 cm-7.5 cm×15.0 cm. All donor sites were directly closed or by skin grafting. All patients were entered in 6-15 months of postoperative outpatient follow-up, and the recovery of donor and recipient sites was assessed by the comprehensive evaluation scales. The sensory function of the flaps was evaluated using the sensory function evaluation standard of British Medical Research Council (BMRC).Results:All perforators were successfully located with 47 perforators in total, and all of them were musculocutaneous perforator. It was found that there was 1 perforator in 14 flaps, 2 perforators in 15 flaps and 3 perforators in 1 flap. All 30 flaps survived after surgery, beside 2 flaps that had arterial insufficiency but survived successfully after surgical exploration. All donor sites healed in one stage. Comprehensive evaluation scale of flap was employed to evaluate the flaps and the scores were 84 points to 96 points with an average score of 92.5 points. The excellent and good grades were achieved in 27 flaps and 3 flaps, respectively, with a combined excellent and good rate at 100%. Sensation of the flaps was evaluated by BMRC with 1 flap of S 1, 17 of S 2 and 12 of S 3. Conclusion:The "two-point and two-line method" has been used in design of the perforator flap of medial sural artery. This method is simple and accurate, and is feasible and ideal in design of flaps before surgery.

Objective:To explore the mechanisms of " TongduAnshen " couplet medicines Notopterygii Rhizoma et Radix-Ziziphi Spinosae Semen(TDAS)on chronic unpredictable mild stress(CUMS)model rats.Methods:The rat model of depression were prepared using isolated and CUMS method.The depression-like behavior was detected by sucrose preference test(SPT),the open field test(OFT)and forced swimming test(FST).The pathological changes of hippocampal neurons were observed by HE and Nissl staining.The levels of 5-hydroxytryptamine(5-HT),interleukin 18(IL-18)and interleukin 1 β(IL-1β)were detected by enzyme linked immunosorbent assay(ELISA).The protein expression of NLRP3,ASC,caspase-1 in hippocampus were determined by Western blot.Results:The depression-like behavior of rats in the TDAS-L,TDAS-M and TDAS-H groups was significantly improved(P＜0.05 orP＜0.01);HE and Nissl staining showed that the neurons were arranged neatly,the number of shrunken cells were reduced,the extent of the injury was reduced;the contents of 5-HT in hippocampus of rats increased(P＜0.05 or P＜0.01),the contents of IL-18 and IL-1β in serum decreased(P＜0.01);the expressions of NLRP3,ASC and caspase-1 in hippocampus were decreased(P＜0.01).Conclusion:TDAS can improve depression-like behavior in chronic unpredictable mild stress rats,and its mechanism may be increase the contents of 5-HT,inhibit the expression of NLRP3 signaling pathway,and reduce the content of inflammatory factors.

To explore the value of general information and rapid laboratory tests obtained from the emergency department in the early diagnosis and prevention of young patients with acute myocardial infarction and acute myocarditis, in order to prevent the disease from progressing to a critical stage. This study employs a retrospective observational study, compiling clinical data from young patients diagnosed with acute myocardial infarction or acute myocarditis who were admitted to the Department of Cardiology or Emergency Department of the Second Affiliated Hospital of Soochow University from January 2015 to September 2024. Demographic information and laboratory test results from both the outpatient and emergency departments were retrieved. The acute myocardial infarction group comprised 267 patients (257 males, 10 females) aged 23-44 ys, while the acute myocarditis group included 134 patients (93 males, 41 females) aged 18-44 ys. A comparative analysis of the clinical data between the two groups was conducted, encompassing variables such as age, gender, comorbidities, high-risk factors, emergency blood routine tests, high-sensitivity C-reactive protein levels, coagulation profiles, renal function tests, NT-proBNP levels, myocardial injury markers, electrocardiogram readings, blood pressure, and heart rate. The results showed that:Compared with the young myocarditis group, the myocardial infarction group was older (ys)[38(35, 42) vs 30(25, 37), U=7 893, P<0.001], more male [257(96.3%) vs 93(69.4%), χ2=57.95, P<0.001], more smoking [211(79.0%) vs 38(28.4%), χ2=97.32, P<0.001], drinking history [125(46.8%) vs 22(16.4%), χ2=35.51, P<0.001], family history of coronary heart disease [45(16.9%) vs 3(2.2%), χ2=18.09, P<0.001], hypertension [100(37.5%) vs 12(9.0%), χ2=36, P<0.001] and diabetes [42(15.7%) vs 4(3.0%), χ2=14.27, P<0.001]. Systolic blood pressure (mmHg)[126(114, 144) vs 119(101, 126), U=11 389.50, P<0.001], diastolic blood pressure (mmHg)[80(70, 93) vs 72(62, 81), U=12 220.50, P<0.001], total white blood cell count (10 9/L)[11.3(9.2, 14.1) vs 8.5(6.6, 11.2), U=10 825.50, P<0.001], hemoglobin (g/L)[157(147, 166) vs 143(129, 154), U=9 404.50, P<0.001], platelet count (10 9/L)[244(206, 297) vs 207(173, 253), U=11 680, P<0.001], uric acid (μmol/L)[380(315, 446) vs 347(265, 412), U=14 805.50, P=0.005], ST segment elevation [204(76.4%) vs 57(42.5%), χ2=73.03, P<0.001] and Q wave formation [76(28.5%) vs 17(12.7%), χ2=12.47, P<0.001] in ECG were higher than those in myocarditis group. The duration of onset (hs) [6(3, 25) vs 48(24, 73), U=27911, P<0.001], heart rate (beats/min)[82(74, 92) vs 92(78, 103), U=22 347, P<0.001], D-dimer (μg/ml)[0.23(0.17, 0.51) vs 0.61(0.30, 1.38), U=25 806, P<0.001], High-sensitivity troponin T/99th percentile upper reference limit [5(1, 36) vs 16(8, 39), U=22 577, P<0.001], NT-proBNP (pg/ml) [204(64, 644) vs 824(189, 4 043), U=25 134, P<0.001], C-reactive protein (mg/L)[6(3, 9) vs 24(6, 55), U=26 349.50, P<0.001] and body temperature (℃) [36.50(36.30, 36.60) vs 37.35(36.50, 38.50), U=26 961, P<0.001] were significantly lower than those in myocarditis group, the symptoms of chest pain in myocardial infarction group was significantly higher than those in myocarditis group [262(98.1%) vs 83(61.9%), χ2=97.24, P<0.001], and the history of prodromal infection [12(4.5%) vs 112(83.6%), χ2=261.26, P<0.001], syncope [11(4.1%) vs 18(13.4%), χ2=11.53, P<0.001] and shock [6(2.2%) vs 22(16.4%), χ2=27.59, P<0.001] in myocardial infarction group were significantly lower than those in myocarditis group. With acute myocardial infarction as the target outcome, 8 influencing factors selected by LASSO regression, and 5 independent influencing factors were found after multiple Logistic regression, those were age ( OR=1.21, 95% CI: 1.12-1.31; P<0.001), pre-infection ( OR=0.02, 95% CI: 0.01-0.06; P<0.001), body temperature ( OR=0.37, 95% CI: 0.18-0.77; P=0.008), chest pain ( OR=26.75, 95% CI: 5.87-121.81; P<0.001) and white blood cell count ( OR=1.27, 95% CI: 1.12-1.44; P<0.001). Younger age, high body temperature and pre-infection are independent predictors for acute myocarditis, while chest pain and elevated white blood cell count are independent predictors for acute myocardial infarction. The five influencing factors selected by multivariate logistic regression and their combined diagnostic model were subjected to ROC analysis. The AUC reached 0.969, sensitivity reached 0.940 and specificity reached 0.925. Calibration curve and decision curve analysis(DCA) demonstrate that the model possesses excellent clinical application value. In conclusion, age, chest pain, pre-infection, body temperature and white blood cell count were independent factors in distinguishing acute myocardial infarction and acute myocarditis in young people. The clinical differential diagnosis model based on 5 independent factors may has high efficiency and good clinical practicability.

Objective:To study the feasibility of design and harvest of free medial sural artery perforator flap with the "two-point and two-line method".Methods:From September 2022 to June 2023, Suzhou Ruihua Orthopaedic Hospital implemented the "two-point and two-line method" to guide preoperative perforator positioning and flap design. Thirty medial sural artery perforator flaps were successfully harvested with the method, and 21 wounds of hand and 9 of foot and ankle were reconstructed with the flaps. The size of soft tissue defects were 2.5 cm×2.5 cm-7.0 cm×14.5 cm, and the flaps size were 3.0 cm×3.0 cm-7.5 cm×15.0 cm. All donor sites were directly closed or by skin grafting. All patients were entered in 6-15 months of postoperative outpatient follow-up, and the recovery of donor and recipient sites was assessed by the comprehensive evaluation scales. The sensory function of the flaps was evaluated using the sensory function evaluation standard of British Medical Research Council (BMRC).Results:All perforators were successfully located with 47 perforators in total, and all of them were musculocutaneous perforator. It was found that there was 1 perforator in 14 flaps, 2 perforators in 15 flaps and 3 perforators in 1 flap. All 30 flaps survived after surgery, beside 2 flaps that had arterial insufficiency but survived successfully after surgical exploration. All donor sites healed in one stage. Comprehensive evaluation scale of flap was employed to evaluate the flaps and the scores were 84 points to 96 points with an average score of 92.5 points. The excellent and good grades were achieved in 27 flaps and 3 flaps, respectively, with a combined excellent and good rate at 100%. Sensation of the flaps was evaluated by BMRC with 1 flap of S 1, 17 of S 2 and 12 of S 3. Conclusion:The "two-point and two-line method" has been used in design of the perforator flap of medial sural artery. This method is simple and accurate, and is feasible and ideal in design of flaps before surgery.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Abdominal aortic aneurysm (AAA) is a type of aneurysmal aortic disease with a high mortality rate. Endovascular aneurysm repair (EVAR) is an effective treatment for this condition,but endoleaks can occur intraoperatively or years after the procedure,necessitating lifelong monitoring. Type Ⅱ endoleak (T2EL) is a major complication of EVAR,primarily caused by persistent retrograde perfusion of the aneurysm sac from collateral vessels such as the inferior mesenteric artery (IMA) and lumbar arteries (LA). The occurrence of T2EL is closely related to patient anatomical factors (e.g.,the diameter,number,and patency of collateral vessels),surgical factors (e.g.,the degree of stent graft adherence to the arterial wall),and systemic factors such as hypertension. Persistent T2EL may lead to aneurysm sac enlargement and increased risk of rupture,thereby adversely affecting patient prognosis. In recent years,prophylactic embolization of the IMA and LA has shown certain advantages in reducing the incidence of T2EL,aneurysm sac enlargement,and reintervention rates,contributing positively to improving treatment outcomes and quality of life of the patients. Here,the authors reviewed literature published between January 2002 and July 2024 on the epidemiology of endoleaks following EVAR and the use of IMA and LA embolization during EVAR to prevent T2EL. The current research was summarized to discuss the clinical value of prophylactic IMA and LA embolization in patients at high risk of T2EL.

Abdominal aortic aneurysm (AAA) is a type of aneurysmal aortic disease with a high mortality rate. Endovascular aneurysm repair (EVAR) is an effective treatment for this condition,but endoleaks can occur intraoperatively or years after the procedure,necessitating lifelong monitoring. Type Ⅱ endoleak (T2EL) is a major complication of EVAR,primarily caused by persistent retrograde perfusion of the aneurysm sac from collateral vessels such as the inferior mesenteric artery (IMA) and lumbar arteries (LA). The occurrence of T2EL is closely related to patient anatomical factors (e.g.,the diameter,number,and patency of collateral vessels),surgical factors (e.g.,the degree of stent graft adherence to the arterial wall),and systemic factors such as hypertension. Persistent T2EL may lead to aneurysm sac enlargement and increased risk of rupture,thereby adversely affecting patient prognosis. In recent years,prophylactic embolization of the IMA and LA has shown certain advantages in reducing the incidence of T2EL,aneurysm sac enlargement,and reintervention rates,contributing positively to improving treatment outcomes and quality of life of the patients. Here,the authors reviewed literature published between January 2002 and July 2024 on the epidemiology of endoleaks following EVAR and the use of IMA and LA embolization during EVAR to prevent T2EL. The current research was summarized to discuss the clinical value of prophylactic IMA and LA embolization in patients at high risk of T2EL.