Acute myocardial infarction and acute upper gastrointestinal bleeding are both critical internal medicine conditions. The incidence of acute upper gastrointestinal bleeding in patients with acute myocardial infarction ranges from 5.31% to 8.90%, with a mortality rate as high as 20.50% to 35.70%. The pathogenesis may be related to the use of antiplatelet and anticoagulant drugs, as well as stress-induced injury. In treatment, the contradiction between antiplatelet/anticoagulation therapy and bleeding has made this disease a significant challenge in modern medicine. Therefore, re-exploring the etiology, pathogenesis, treatment principles, and methods of traditional Chinese medicine(TCM) for acute myocardial infarction and acute upper gastrointestinal bleeding is of great clinical importance. The research team has been working year-round in the coronary care unit(CCU), managing a large number of such severe patients. By revisiting classic texts and delving into the foundational theories of TCM and historical medical literature, it has been found that this disease falls under the category of "distant blood" in the Synopsis of the Golden Chamber. In terms of etiology, it is primarily associated with weakness of healthy Qi and damage caused by drug toxicity. In terms of pathogenesis, in the acute stage, it mainly manifests as insufficient spleen Yang, deficiency of spleen Qi, and failure of the spleen to control blood. In the remission stage, it is characterized by deficiency of both heart Qi and spleen blood. For treatment, during the acute stage, Huangtu Decoction is used to warm Yang and restrain blood, while in the remission stage, Guipi Decoction is administered to tonify Qi and nourish blood. During the treatment process, for patients with acute myocardial infarction complicated with acute upper gastrointestinal bleeding, it is crucial to flexibly apply the treatment principles of "Nil per os" in western medicine and "where there is stomach Qi, there is life; where there is no stomach Qi, there is death" in TCM. Early intervention with Huangtu Decoction can also prevent bleeding, with large doses being key to achieving hemostasis. It is important to address the pathogenesis of heat syndrome in addition to the core pathogenesis of Yang deficiency bleeding and to emphasize the follow-up treatment with Guipi Decoction for a successful outcome.
Humans ; Gastrointestinal Hemorrhage/etiology* ; Myocardial Infarction/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Acute Disease

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Retinopathy of prematurity (ROP) is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia. Here, we investigated the potential effects of alamandine, a novel heptapeptide in the renin-angiotensin system (RAS), on hypoxia-induced retinal neovascularization and its underlying mechanisms. In vivo, the C57BL/6J mice with oxygen-induced retinopathy (OIR) were injected intravitreally with alamandine (1.0 μmol/kg per eye). In vitro, human retinal microvascular endothelial cells (HRMECs) were utilized to investigate the effects of alamandine (10 μg/mL) on proliferation, apoptosis, migration, and tubular formation under vascular endothelial growth factor (VEGF) stimulation. Single-cell RNA sequencing (scRNA-seq) matrix data from the Gene Expression Omnibus (GEO) database and RAS-related genes from the Molecular Signatures Database (MSigDB) were sourced for subsequent analyses. By integrating scRNA-seq data across multiple species, we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group. Next, alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice. In vitro, alamandine effectively mitigated VEGF-induced proliferation, scratch wound healing, and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α (HIF-1α)/VEGF pathway. Further, coincubation with D-Pro⁷ (Mas-related G protein-coupled receptor D (MrgD) antagonist) hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro. Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway, providing a potential therapeutic agent for OIR prevention and treatment.
Animals ; Retinal Neovascularization/prevention & control* ; Mice, Inbred C57BL ; Vascular Endothelial Growth Factor A/metabolism* ; Humans ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Oligopeptides/therapeutic use* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Endothelial Cells/drug effects* ; Retinopathy of Prematurity/drug therapy* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Renin-Angiotensin System/drug effects* ; Cells, Cultured

The current status of exoskeletons was introduced in enhancing individual soldier's battlefield rescue capabilities,promoting the integrated use of battlefield rescue equipment,protecting medical personnel on the battlefield and assisting injured soldiers in rehabilitation training.The challenges of exoskeletons faced in human-machine interaction,power supply endurance,heavy overall structure,restricted movement and high cost were analyzed when applied to medical service support,and some suggestions were proposed accordingly including enhancing technology research and development,integrated application,communication and cooperation and personnel training.References were provided for the application of exoskeletons in China's medical service support.[Chinese Medical Equipment Journal,2024,45(3):71-75]

Objective To evaluate the efficacy,safety and economy of centrally procured ceftazidime injection for treating pulmonary infections,and to provide a reference for clinical therapeutic decisions.Methods Based on the active monitoring and drug evaluation functions of the China Hospital Pharmacovigilance System(CHPS),a retrospective analysis was conducted.Electronic medical records of 203 patients treated with ceftazidime injection for pulmonary injections in our hospital from February 2021 to August 2022 were collected.Patients were divided into two groups based on the type of ceftazidime used,the centrally procured ceftazidime group(102 cases)and the non-centrally procured ceftazidime group(101 cases).Efficacy was evaluated by the effectiveness rate,safety by the incidence of adverse reactions,and economy by cost-effectiveness analysis.Differences between the two groups were compared.Results Treatment efficiency was 90.20%in the centrally procured group and 91.09%in the non-centrally procured group,with no statistically significant difference(P>0.05).The incidence of adverse reactions was 10.78%in the centrally procured group and 5.94%in the non-centrally procured group,with no statistically significant difference(P>0.05).The average cost-effectiveness ratio(C/E)was 1.56±0.86 in the centrally procured group and 18.96±9.38 in the non-centrally procured group,indicating a smaller C/E value for the centrally procured group.Sensitivity analysis results were consistent with the cost-effectiveness analysis results.Conclusion Centrally procured ceftazidime injection has equivalent efficacy and safety compared to non-centrally procured ceftazidime,with improved economic value.Therefore,the centrally procured variant should be given priority when using ceftazidime for the treatment of pulmonary infections.

Objective:To understand the current status of gastroscopy in diagnosing gastric lesions in general population, and to recommend the optimal age for the first gastroscopy and intervals for repeated gastroscopy.Methods:The gastroscopy records of residents aged 18-80 years in Yinzhou District of Ningbo, Zhejiang Province, between April 2010 and December 2021 were analyzed retrospectively. The detections of gastric lesions across different years, age and genders were described. Goodness of fit tests were applied to compare the differences in detection rates of different lesions in first-time endoscopy in different age groups and different populations. Generalized additive models were used to fit the trend of age specific gastric lesion detection rate explore the optimal age for gastroscopy. The appropriate gastroscopy intervals were determined according to the progress of the gastric lesions detected in repeated gastroscopy.Results:A total of 237 751 participants with 344 398 gastroscopy records were included in analyses. A total of 5 597 cases of chronic atrophic gastritis (CAG), 9 796 cases of intestinal metaplasia (IM), 165 cases of low-grade intraepithelial neoplasia (LGIN), 52 cases of high-grade intraepithelial neoplasia (HGIN) and 435 cases of gastric cancer were detected by the first gastroscopy. The overall detection rate of gastric lesions increased significantly in age group 45-70 years, and remained stable after 70 years old, with LGIN and HGIN showing notable increases at 50 and 55 years old, respectively. Repeated gastroscopy detected CAG, IM, LGIN, and HGIN at a higher rate compared with the first gastroscopy. Normal/superficial gastritis progressed in 3-5 years, whereas CAG or more severe lesions progressed in 1-6 years.Conclusion:Gastroscopy is recommended for general population aged 45 years and above. Furthermore, gastroscopy can be performed every 3-5 years for individuals with normal endoscopy results and once a year for patients with CAG or more severe gastric lesions.

ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group， model group， Tamiflu group， and BD-77 groups of 75 and 37.5 g·L^-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group， model group， chloroquine phosphate group， and BD-77 groups of 75， 37.5， 18.75， and 9.375 g·L^-1， with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect related inflammatory factors in lung tissue， and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group， the lung index of mice in each infection group was significantly increased （P<0.01）， and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the lung tissue of mice infected with human coronavirus 229E were all significantly increased （P<0.01）. BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 （P<0.05， P<0.01）， cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 （P<0.01）， and lower the contents of IL-6， IL-10， and TNF-α in the lung tissue of mice infected with human coronavirus 229E （P<0.01）. Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway， TNF signaling pathway， NOD-like signaling pathway， IL-17 signaling pathway， Forkhead box protein O （FoxO） signaling pathway， transforming growth factor-β （TGF-β） signaling pathway， and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism， enhancing the immune function of the host， and attenuating inflammatory responses.

The prevalence of cardiovascular diseases in China has shown a rising trend. With the patient number of about 8.9 million, heart failure has brought a heavy burden to public health and wellness. Despite the modern medical research progress in the pathogenesis and clinical treatment of heart failure, the patients with heart failure still suffer from recurrent episodes of dyspnea(requiring repeated hospital admissions), diuretic resistance, elevated creatinine levels due to prolonged diuretic use, and poor prognosis, among other major clinical and scientific issues. In traditional Chinese medicine(TCM), heart failure belongs to the category of "heart water". The research team has found that because of the changes in the modern disease spectrum, the differences between ancient and modern physical constitutions, and the use of anti-heart failure drugs in modern medicine, the pathological process of heart failure has been altered, and the symptoms of some patients have become unobvious. As a result, the etiology and pathogenesis of heart failure have undergone major changes. The disease causes include external pathogen attack, emotional disorders, excessive labor injury, medication-induced damage, dietary disorders, water-dampness stagnation, and endowment insufficiency. These causes are closely related to the infection aggravation-induced heart failure, cardiac and psychological diseases, and heart volume overload in modern medicine. The pathogeneses of heart failure include edema due to Yang deficiency and water retention turning into heat in the acute stage and liver depression and Qi stagnation, heart Qi deficiency, kidney Yang deficiency, Qi deficiency in lung and spleen, phlegm and water retention, and internal obstruction due to blood stasis in the remission stage. The corresponding treatment strategies were recommended as follows: Zhenwu Decoction for edema due to Yang deficiency, Mufangji Decoction for water retention turning into heat, Chaihu Longgu Muli Decoction for liver depression and Qi stagnation, Guizhi Decoction for heart Qi insufficiency, Shenqi Pills and Yougui Pills for kidney Yang deficiency, Yupingfeng Powder, Lizhong Decoction, Buzhong Yiqi Decoction, and Guipi Decoction for Qi deficiency in lung and spleen, Fangji Huangqi Decoction, Wuling Powder, Linggui Zhugan Decoction, and Tingli Dazao Xiefei Decoction for internal obstruction due to phlegm and water retention, Guizhi Fuling Pills and Danggui Shaoyao Powder for internal obstruction due to blood stasis. The clinical treatment should follow the principle of considering both pathogenesis and pathology as well as both medicine nature and mechanism. The TCM concept of secondary prevention with TCM formulas for replenishing deficiency should be adopted. The treatment based on the principle and concept above will improve the patients' quality of life, reduce the number of hospital admissions, ameliorate diuretic resistance, and improve the clinical outcomes.
Humans ; Heart Failure/etiology* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: To discover the relationship between matrix remodeling associated 7 (MXRA7) and acute B lymphoblastic leukemia (B-ALL), and explore the effect of MXRA7 on the biological functions of B-ALL cell line REH. METHODS: The expression of MXRA7 in blood diseases was searched and analyzed through BloodSpot database. Real-time qPCR was used to detect the expression level of MXRA7 in B-ALL cell line 697 and REH cells. Lentivirus-mediated shRNA interference technology was utilized to knock down the expression of MXRA7 in REH cells. The effects of MXRA7 on the biological functions of REH cells were studied by in vitro experiments. Cell proliferation was detected by CCK-8 assay, cell cycle was detected by PI staining, cell apoptosis was detected by Annexin V and 7-AAD staining, and the expression of apoptosis pathway related proteins was detected by Western blot. RESULTS: Database analysis showed that MXRA7 was highly expressed in B-ALL patients, and real-time qPCR results showed that MXRA7 was also highly expressed in cell lines 697 and REH cells. Knockdown of MXRA7 in REH cells inhibited the cell proliferation and increased the percentage of G₀/G₁ phase cells. After treatment with cytarabine, the apoptotic ratio was increased in MXRA7-impaired REH cells, and the activation of caspase-3 and caspase-9 were also increased. CONCLUSION Knockdown of MXRA7 can reduce the malignancy of REH cells by inhibiting the cell proliferation and increasing the sensitivity of REH cells to cytarabine. These results indicate MXRA7 may be as a novel target for the treatment of B-ALL, and the potential usefulness of MXRA7 in B-ALL deserves further investigation.
Humans ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cytarabine ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism*

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies