OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

[Objective] To explore the clinical significance and application value of establishing a database for red blood cell alloantibody detection. [Methods] Patients who were scheduled for blood transfusion in our hospital from January 1, 2020 to May 1, 2024 were selected as the research subjects. A red blood cell alloantibody detection database was established using Microsoft Office Excel software to register the detection data of patients' alloantibodies and antibodies of undetermined specificity (AUS). A retrospective analysis was conducted on the clinical characteristics, antibody distribution, antibody decay and repeat positivity of the patients in the database. The LISS-IAT method was routinely used for antibody screening and identification. [Results] Among the alloantibodies, the Rh blood group system had the highest detection rate, followed by antibodies of the MNS blood group system and the Lewis blood group system. The predominant antibody in the Rh blood group system was anti-E. In the univariate analysis, the positivity of antibody was significantly associated with the patient's gender, age, blood transfusion history, pregnancy history and type of disease (all P<0.001). In the database, 48 patients experienced antibody decay, accounting for 15.24%(48/315), with an average time span of antibody decay ranging from 22 to 1 324 days. Six cases showed repeat positivity after decay, which were related to blood transfusions. The shortest interval between blood transfusions that led to antibody repeat positivity was 3 days, and the longest interval was 427 days. Among 58 cases with AUS, 3 converted into alloantibodies, among which 2 were anti-E and 1 was anti-Lea. [Conclusion] Establishing a red blood cell alloantibody detection database is an effective way to guide ambiguous cross-matching in clinical practice and is also an effective measure for the management of transfusion risks.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

AIM:To investigate the safety and efficacy of selecting implantable collamer lens(ICL)size for postoperative vaults using sulcus to sulcus(STS)and other data measured by ultrasound biomicroscopy(UBM), and to explore the relevant factors affecting vaults.METHODS: Prospective case observational study. A total of 95 patients(188 eyes)with ametropia who underwent ICL size optimization and 90 patients(174 eyes)without ICL size optimization, from January to December 2022 and underwent regular follow-up for 6 mo were selected. Patients were divided into an optimized group and a standard group based on whether ICL size optimization was performed. The patients were followed up at 1 d, 1 wk, 1, 3, and 6 mo, and uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), refraction state, intraocular pressure(IOP), corneal status, anterior chamber depth(ACD), angle opening, vaults and corneal endothelial cell count were collected.RESULTS: No significant difference in spherical equivalent, UCVA and BCVA was found between the two groups(all P >0.05). The safety index was 1.21±0.24 and 1.19±0.21 at 6 mo for the two groups, respectively, while the efficacy index were 1.18±0.22 and 1.07±0.26. The vaults at 6 mo for the two groups was 407.77±159.31 and 467.16±250.07 μm, respectively. In the optimization group, 92.0% of eyes achieved the desired vaults postoperatively, while 74.1% of eyes in the standard group reached the desired vaults. Both groups exhibited a slight downward trend in vaults over time, with no significant differences between the two groups(F=3.478, P=0.063). However, the standard group experienced 6 eyes of ICL replacement and 2 eyes of ICL removal due to acute angle-closure glaucoma induced by angle closure.CONCLUSION: Selecting the ICL size and determining the implantation orientation based on sulcus to sulcus(STS)and other data measured by UBM provides good safety, efficacy, and predictability for postoperative vaults.

AIM:To investigate the safety and efficacy of selecting implantable collamer lens(ICL)size for postoperative vaults using sulcus to sulcus(STS)and other data measured by ultrasound biomicroscopy(UBM), and to explore the relevant factors affecting vaults.METHODS: Prospective case observational study. A total of 95 patients(188 eyes)with ametropia who underwent ICL size optimization and 90 patients(174 eyes)without ICL size optimization, from January to December 2022 and underwent regular follow-up for 6 mo were selected. Patients were divided into an optimized group and a standard group based on whether ICL size optimization was performed. The patients were followed up at 1 d, 1 wk, 1, 3, and 6 mo, and uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), refraction state, intraocular pressure(IOP), corneal status, anterior chamber depth(ACD), angle opening, vaults and corneal endothelial cell count were collected.RESULTS: No significant difference in spherical equivalent, UCVA and BCVA was found between the two groups(all P >0.05). The safety index was 1.21±0.24 and 1.19±0.21 at 6 mo for the two groups, respectively, while the efficacy index were 1.18±0.22 and 1.07±0.26. The vaults at 6 mo for the two groups was 407.77±159.31 and 467.16±250.07 μm, respectively. In the optimization group, 92.0% of eyes achieved the desired vaults postoperatively, while 74.1% of eyes in the standard group reached the desired vaults. Both groups exhibited a slight downward trend in vaults over time, with no significant differences between the two groups(F=3.478, P=0.063). However, the standard group experienced 6 eyes of ICL replacement and 2 eyes of ICL removal due to acute angle-closure glaucoma induced by angle closure.CONCLUSION: Selecting the ICL size and determining the implantation orientation based on sulcus to sulcus(STS)and other data measured by UBM provides good safety, efficacy, and predictability for postoperative vaults.

Objective: The effects and molecular mechanisms of micheliolide on cytokine expression in myeloproliferative neoplasm cell lines were explored based on the signal transducer and activator of transcription 3 (STAT3)/nuclear factor-kappa B (NF-κB) signaling pathways. Methods: The UKE-1 and SET-2 cell lines were investigated, and micheliolide concentrations were screened using the CCK-8 assay. The UKE-1 and SET-2 cells were divided into the control and micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. Each group received 1 mL of micheliolide solution at final concentrations of 2.5, 5.0, and 10.0 μmol/L, respectively, whereas the control group only received an equal volume of culture medium. The inhibition rates of interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α), and chemokine ligand 2 (CCL2) mRNA expression in cells from each group were detected using real-time fluorescent PCR (RT-PCR). Western blotting was used to measure STAT3 and phosphorylated STAT3 (p-STAT3) protein expression levels in cells from each group. Reversal experiments with reduced glutathione and dithiothreitol were performed using UKE-1 cells, which were divided into the control group, micheliolide, micheliolide + glutathione, micheliolide + dithiothreitol, and glutathione + dithiothreitol groups. Western blotting was used to detect the STAT3 and p-STAT3 protein expression levels in the cells of each group. UKE-1 cells were stimulated with TNF-α (5 μg/L) to replicate a pathological model of excessive cytokine secretion. Subsequently, UKE-1 cells were divided into the control, model, and three micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. RT-PCR was used to measure the indicators above. An enzyme-linked immunosorbent assay (ELISA) was used to detect the CCL2 content in the cell culture media of each group. Western blotting was performed to assess the protein expression levels of STAT3, p-STAT3, and proteins related to the NF-κB signaling pathway. Results: Compared with the control group, the proliferation inhibition rates of UKE-1 cells at 24, 48, and 72 h increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, 10.0, and 20.0 μmol/L. Similarly, the proliferation inhibition rates of SET-2 at 48 and 72 h increased in the micheliolide-treated groups at concentrations of 5.0, 10.0, and 20.0 μmol/L (P<0.05). Concentrations of 2.5, 5.0, and 10.0 μmol/L were selected for further studies to exclude the potential influence of high micheliolide concentrations on subsequent result owing to reduced cell numbers. Compared with the control group, the inhibition rates of TNF-α mRNA expression in UKE-1 and SET-2 cells increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. Similarly, the inhibition rates of IL-1β mRNA expression in UKE-1 and SET-2 cells also increased in the micheliolide-treated groups at concentrations of 5.0 and 10.0 μmol/L. Additionally, the inhibition rate of CCL2 mRNA expression in UKE-1 and SET-2 cells increased in the micheliolide-treated group at a concentration of 10 μmol/L (P<0.05). Compared with the model group, the inhibition rates of TNF-α, IL-1β, and CCL2 mRNA expression in UKE-1 cells increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L after stimulation with TNF-α (P<0.05). ELISA showed that compared with the control group, the CCL2 content in UKE-1 cells increased in the model group. Compared with the model group, the CCL2 content in UKE-1 cells decreased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L (P<0.05). Western blotting showed that compared with the control group, the p-STAT3 protein expression levels in UKE-1 and SET-2 cells were downregulated in the micheliolide-treated groups at concentrations of 5.0 and 10.0 μmol/L, and the protein expression level of STAT3 in SET-2 was also downregulated (P<0.05). Compared with the control group, the p-STAT3 expression level in UKE-1 cells decreased in the micheliolide group in the reductive glutathione and dithiothreitol reversal experiments. Compared with the micheliolide group, the p-STAT3 protein expression levels in UKE-1 cells increased in the micheliolide + dithiothreitol and micheliolide + glutathione groups (P<0.05). Compared with the control group, the model group showed increased p-STAT3, p-IκKα/β, p-IκBα, and p-NF-κB p65 protein expression and decreased IκBα protein expression after stimulation with TNF-α. Compared with the model group, the micheliolide-treated groups showed decreased p-IκKα/β, p-IκBα, p-STAT3, and p-NF-κB p65 protein expression at concentrations of 2.5, 5.0, and 10.0 μmol/L, whereas the micheliolide-treated groups showed increased IκBα protein expression at concentrations of 5.0 and 10.0 μmol/L (P<0.05). Conclusion Micheliolide potently suppresses IL-1β, TNF-α, and CCL2 mRNA expression in UKE-1 and SET-2 cells, as well as CCL2 secretion by UKE-1 cells, which may be associated with STAT3 phosphorylation suppression and NF-κB signaling pathway activation.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

[摘 要] 目的：探索甲硫氨酸腺苷转移酶2（MAT2A）对食管鳞状细胞癌（ESCC）细胞的作用，以及MAT2A抑制剂PF9366对ESCC细胞的抑制作用及其分子机制。方法：选用人ESCC细胞KYSE450、KYSE510、KYSE180和KYSE410及正常食管上皮细胞（NEEC），通过ELISA实验验证S-腺苷甲硫氨酸（SAM）在细胞中的产生情况。分别用0、5、10和25 μmol/L PF9366处理KYSE450、KYSE510细胞，通过ELISA实验、MTS实验、平板克隆形成实验检测PF9366对ESCC细胞甲硫氨酸（MET）活性和细胞增殖的抑制效果，采用RNA-seq实验观察PF9366对KYSE450细胞下游促癌信号通路的影响。构建KYSE450、KYSE510细胞移植瘤小鼠模型，观察PF9366对荷瘤小鼠移植瘤生长的影响。结果：ESCC细胞中的MET活性显著高于NEEC（均P < 0.01）。使用PF9366后，KYSE450、KYSE510细胞SAM活性均显著降低（均P < 0.01），细胞的增殖能力显著降低（均P < 0.01），其抑制作用呈现出明显的剂量依赖性（均P < 0.05）。RNA-seq分析表明，PF9366处理后的ESCC细胞中，有20个与肿瘤发生和发展相关的信号通路被下调。荷瘤小鼠实验表明，PF9366能显著抑制ESCC细胞小鼠移植瘤的生长（均P < 0.000 1）。结论：MAT2A抑制剂PF9366能抑制ESCC细胞中SAM的产生、抑制细胞增殖并激活下游关键促癌信号网络，提示MET代谢关键酶MAT2A是治疗ESCC的潜在靶点。

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.