OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Objective To evaluate the value of modified percutaneous endoscopic gastrostomy(PEG)for patients with amyotrophic lateral sclerosis(ALS)and dysphagia.Methods From January 2018 to December 2023,47 patients with ALS were treated with modified PEG in our hospital.The surgery was performed under local anesthesia.The patients were placed in a semi-seated position,and the surgeon performed surgery with an ultra-fine endoscope through oral entrance to the stomach.Results The modified PEG were successfully completed in all the 47 cases.The operation time was5-20 min[mean,(10.3±1.7)min].The postoperative hospitalization lasted for2-8 d(mean,2.8 d).Postoperative complications occurred in6 cases(12.8%),including aspiration pneumonia in4 cases(8.5%)and incision infection in2 cases(4.3%).The body mass index was17.06±0.89 before PEG and 18.15±0.81 at 3 months after PEG,with significant difference(t=-10.373,P=0.000).Conclusion For ALS patients with dysphagia,modified PEG is feasible,which significantly improves nutritional status of patients.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective:A retrospective study was conducted to investigate the safety of Percutaneous Endoscopic Gastrostomy(PEG)in elderly patients with Amyotrophic Lateral Sclerosis(ALS)and to identify the factors influencing major complications.The aim is to establish a more robust foundation for optimizing both the procedure and its timing, thereby enhancing the evidence base for refining the surgical approach.Methods:We retrospectively collected clinical data from elderly ALS patients(≥60 years old)who underwent PEG at Peking University Third Hospital between January 2006 and January 2024.This dataset includes information on general health conditions, the progression of ALS, comorbidities, surgical details, and related complications.Additionally, we analyzed the postoperative complications experienced by the included patients, focusing specifically on the risk factors associated with aspiration pneumonia.Results:A total of 140 patients were included in the study, with a mean age of 68.2±5.9 years.Among these, 69 were male(49.3%)with a mean age of 68.4±6.5 years, and 71 were female(50.7%)with a mean age of 67.7±6.0 years.Successful outcomes were observed in 139 cases(99.3%).One case was not completed due to respiratory arrest caused by intraoperative aspiration.Postoperative complications occurred in 36 cases(25.7%), which included 9 cases of wound infection(6.4%), 1 case of abdominal infection(0.7%), 21 cases of aspiration pneumonia(15.0%), 1 case of local fistula leakage(0.7%), 2 cases of transient fever(1.4%), and 2 cases of death during hospitalization(1.4%).Both univariate and multivariate analyses indicated that an onset duration of ≤1 year( P=0.020)and a half-sitting position( P=0.022)significantly influenced the occurrence of aspiration pneumonia, acting as protective factors( β<0, OR<1). Conclusions:PEG is a safe method for providing enteral nutrition to elderly patients with ALS.While most complications associated with the procedure are mild and can be managed, Aspiration pneumonia remains a common and serious complication.However, early surgical intervention and the use of a semi-seated position during the procedure can help reduce the incidence of aspiration pneumonia.

BACKGROUND: Endoscopic sphincterotomy (EST) is widely used to treat common bile duct stones (CBDS); however, long-term studies have revealed the increasing incidence of recurrent CBDS after EST. Loss of sphincter of Oddi function after EST was the main cause of recurrent CBDS. Reparation of the sphincter of Oddi is therefore crucial. This study aims to investigate the effectiveness and safety of endoclip papilloplasty (ECPP) for repairing the sphincter of Oddi and elucidate its mechanism. METHODS: Eight healthy Bama minipigs were randomly divided into the EST group and the ECPP group at a 1:1 ratio, and bile samples were collected before endoscopy and 6 months later. All minipigs underwent transabdominal biliary ultrasonography for the diagnosis of cholelithiasis 6 months after endoscopy. The biliary microbiota composition and alpha and beta diversity were analyzed by 16S ribosomal RNA gene sequencing. Differential metabolites were analyzed by bile acid metabolomics to explore the predictive indicators of cholelithiasis. RESULTS: Three minipigs were diagnosed with cholelithiasis in the EST group, while none in the ECPP group showed cholelithiasis. The biliary Firmicutes/Bacteroidota (F/B) ratio was increased after EST and decreased after ECPP. The Chao1 and observed species index significantly decreased 6 months after EST ( P  = 0.017 and 0.018, respectively); however, the biliary α-diversity was similar before and 6 months after ECPP. The β-diversity significantly differed in the EST group before and 6 months after EST, as well as in the ECPP group before and 6 months after ECPP (analysis of similarities [ANOSIM]: R  = 0.917, P  = 0.040; R  = 0.740, P  = 0.035; respectively). Glycolithocholic acid (GLCA) and taurolithocholic acid (TLCA) accumulated in bile 6 months after EST. CONCLUSIONS ECPP has less impact on the biliary microenvironment than EST and prevents duodenobiliary reflux by repairing the sphincter of Oddi. The bile levels of GLCA and TLCA may be used to predict the risk of cholelithiasis.
Animals ; Swine, Miniature ; Swine ; Cholelithiasis/prevention & control* ; Sphincterotomy, Endoscopic/methods* ; Sphincter of Oddi/surgery* ; Female ; Male

As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.

Objective:To investigate the inhibitory effect of astragaloside Ⅳ(AS-Ⅳ)on cisplatin(CDDP)-induced liver injury in the mice,and to elucidate its possible mechanism.Methods:Forty male C57BL/6 mice with body weights of 18-22 g were randomly divided into control group,model group,AS-Ⅳ group and adenosine 5'-monophosphate-activated protein kinase(AMPK)inhibitor(Compound C)+AS-Ⅳ group.The mice in control group and model group were gavaged with the same volume of normal saline,and the drug was administered continuously for 9 d.The mice in AS-Ⅳ group and Compound C+AS-Ⅳ group were given AS-Ⅳ aqueous solution(150 mg·kg-1·d-1),respectively.On the 6th day of experiment,the mice in Compound C+AS-Ⅳ group were intraperitoneally injected with Compound C(20 mg·kg-1),and on the 7th day,except for control group,the mice in other groups were intraperitoneally injected with 20 mg·kg-1 CDDP to establish the mouse liver injury models,and the mice were sacrificed 48 h later.Serum and liver tissues were collected,and the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in the serum of the mice,as well as the activities of superoxide dismutase(SOD)and catalase(CAT)and the levels of malondialdehyde(MDA)in the liver tissue of the mice in various groups were detected by kits.The pathomorphology of liver tissue of the mice in various groups were detected by HE staining.The expression levels of glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and ferroptosis inhibitory protein 1(FSP1)proteins in liver tissue of the mice in various groups were detected by immunohistochemical staining,and the expression levels of nuclear factor-E2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and AMPK proteins in liver tissue of the mice in various groups were detected by Western blotting method.Results:Compared with control group,the levels of AST and ALT in serum of the mice in model group were increased(P＜0.01),the activities of SOD and CAT in the liver tissue were significantly decreased(P＜0.01),and the MDA level was increased(P＜0.01);compared with model group,the levels of AST and ALT in serum of the mice in AS-Ⅳ group were decreased(P＜0.01),the MDA level in the liver tissue was decreased(P＜0.01),and the activities of SOD and CAT were increased(P＜0.01);compared with AS-Ⅳ group(P＜0.01),the levels of AST and ALT in serum of the mice in Compound C+AS-Ⅳ group were increased(P＜0.01),the level of MDA in liver tissue was increased(P＜0.05),and the activities SOD and CAT were decreased(P＜0.01).The HE staining results showed that compared with control group,the liver damage degree of the mice in model group was enhanced,the hepatocyte arrangement was disordered,and some hepatocyte edema were increased;compared with model group,the liver morphology of the mice in AS-Ⅳ group returned to normal;compared with AS-Ⅳ group,the hepatocyte arrangement of the mice in Compound C+AS-Ⅳ group was disordered and the edges were blurred.The immunohistochemistry results showed that compared with control group,the expression levels of GPX4,FTH1 and FSP1 proteins in liver tissue of the mice in model group were decreased(P＜0.05);compared with model group,the expression levels of GPX4,FTH1 and FSP1 proteins in liver tissue of the mice in AS-Ⅳ group were increased(P＜0.05);compared with AS-Ⅳ group,the expression levels of GPX4,FTH1 and FSP1 proteins in liver tissue of the mice in Compound C+AS-Ⅳ group were decreased(P＜0.05 or P＜0.01).The Western blotting results showed that compared with control group,the expression levels of Nrf2,HO-1 and AMPK proteins in liver tissue of the mice in model group were decreased(P＜0.01);compared with model group,the expression levels of Nrf2,HO-1 and AMPK proteins in liver tissue of the mice in AS-Ⅳgroup were increased(P＜0.01);compared with AS-Ⅳ group,the expression levels of Nrf2,HO-1 and AMPK proteins in liver tissue of the mice in Compound C+AS-Ⅳ group were decreased(P＜0.01).Conclusion:AS-Ⅳ can alleviate the CDDP-induced liver injury,and its mechanism may be related to the regulation of AMPK/Nrf2/HO-1 signal pathway and ferroptosis by AS-Ⅳ.

ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.