In the present study, a mouse model of coronary artery ligation was employed to evaluate the effects of Jiming Powder on mitophagy in the mouse model of myocardial infarction and elucidate its underlying mechanisms. A mouse model of myocardial infarction post heart failure was constructed by ligating the left anterior descending branch of the coronary artery. The therapeutic efficacy of Jiming Powder was assessed from multiple perspectives, including ultrasonographic imaging, hematoxylin-eosin(HE) staining, Masson staining, and serum cardiac enzyme profiling. Dihydroethidium(DHE) staining was employed to evaluate the oxidative stress levels in the hearts of mice from each group. Mitophagy levels were assessed by scanning electron microscopy and immunofluorescence co-localization. Western blot was employed to determine the levels of key proteins involved in mitophagy, including Bcl-2-interacting protein beclin 1(BECN1), sequestosome 1(SQSTM1), microtubule-associated protein 1 light chain 3 beta(LC3B), PTEN-induced putative kinase 1(PINK1), phospho-Parkinson disease protein(p-Parkin), and Parkinson disease protein(Parkin). The results demonstrated that compared with the model group, high and low doses of Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd) and markedly improved the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improving the cardiac function in post-myocardial infarction mice. Jiming Powder effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactate dehydrogenase(LDH), thereby protecting ischemic myocardium. HE staining revealed that Jiming Powder attenuated inflammatory cell infiltration after myocardial infarction. Masson staining indicated that Jiming Powder effectively inhibited ventricular remodeling. Western blot results showed that Jiming Powder activated the PINK1-Parkin pathway, up-regulated the protein level of BECN1, down-regulated the protein level of SQSTM1, and increased the LC3Ⅱ/LC3Ⅰ ratio to promote mitophagy. In conclusion, Jiming Powder exerts therapeutic effects on myocardial infarction by inhibiting ventricular remodeling. The findings pave the way for subsequent pharmacological studies on the active components of Jiming Powder.
Animals ; Myocardial Infarction/physiopathology* ; Mitophagy/drug effects* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Protein Kinases/genetics* ; Male ; Ubiquitin-Protein Ligases/genetics* ; Humans ; Disease Models, Animal ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

This study employed a mouse model of coronary artery ligation to assess the effect and mechanism of Jiming Powder on mitochondrial autophagy in mice with myocardial infarction. The mouse model of heart failure post-myocardial infarction was established by ligating the left anterior descending coronary artery. The pharmacological efficacy of Jiming Powder was evaluated through echocardiographic imaging, hematoxylin-eosin(HE) staining, and Masson staining. The levels of malondialdehyde(MDA), Fe~(2+), reduced glutathione(GSH), and superoxide dismutase(SOD) in heart tissues, as well as MDA immunofluorescence of heart tissues, were measured to assess lipid peroxidation and Fe~(2+) levels in the hearts of mice in different groups. Ferroptosis levels in the groups were evaluated using scanning electron microscopy and Prussian blue staining. Western blot analysis was conducted to detect the levels of key ferroptosis-related proteins, including nuclear factor erythroid 2-related factor 2(NRF2), ferritin heavy chain(FTH), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), heme oxygenase 1(HO-1), and Kelch-like ECH-associated protein 1(KEAP1). The results showed that compared with the model group, both the high-and low-dose Jiming Powder groups exhibited significantly reduced left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd), while the left ventricular ejection fraction(EF) and left ventricular fractional shortening(FS) were significantly improved, effectively enhancing cardiac function in mice post-myocardial infarction. HE staining revealed that Jiming Powder attenuated myocardial inflammatory cell infiltration post-infarction, and Masson staining indicated that Jiming Powder effectively reduced fibrosis in the infarct margin area. Treatment with Jiming Powder reduced the levels of MDA and Fe~(2+), indicators of lipid peroxidation post-myocardial infarction, while increasing GSH and SOD levels, thus protecting ischemic myocardium. Western blot results demonstrated that Jiming Powder reduced KEAP1 protein accumulation, activated the NRF2/HO-1/GPX4 pathway, and up-regulated the protein expression of FTH and SLC7A11, exerting an inhibitory effect on ferroptosis. This study reveals that Jiming Powder exerts a therapeutic effect on myocardial infarction by inhibiting ferroptosis through the NRF2/HO-1/GPX4 pathway, providing a foundation for subsequent research on the pharmacological effects of Jiming Powder.
Animals ; Ferroptosis/drug effects* ; Myocardial Infarction/physiopathology* ; NF-E2-Related Factor 2/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Heme Oxygenase-1/genetics* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Disease Models, Animal

Objective To investigate the clinical safety of Chinese medicine combined with immune checkpoint inhibitors(ICIs)for the treatment of non-small cell lung cancer(NSCLC)at stage Ⅲ-Ⅳ,and to explore the influencing factors of immune-related adverse events(irAEs)in the treatment of stage Ⅲ-Ⅳ NSCLC with ICIs.Methods A retrospective analysis was carried out for the investigation of the distribution of traditional Chinese medicine(TCM)syndromes,related medication information and the occurrence of irAEs in the hospitalized patients diagnosed as stage Ⅲ-Ⅳ NSCLC and treated with Chinese medicine combined with ICIs in the Oncology Department of Guangdong Provincial Hospital of Chinese Medicine(University-town Branch)from September 1,2019 to August 31,2022.And the levels of adverse reactions and their possible influencing factors were analyzed.Results(1)The treatment for the 90 NSCLC patients involved 4 regimens,namely ICIs monotherapy,ICIs combined with chemotherapy,ICIs combined with anti-angiogenic drugs,and ICIs combined with chemotherapy and anti-angiogenic drugs.Among them,ICIs combined with chemotherapy and anti-angiogenic drugs were used most frequently for 52 cases(49.1%).A total of 8 kinds of ICIs drugs were used,of which Tislelizumab accounted for the highest proportion(43 cases,40.6%).(2)All of the patients were classified into 5 syndrome types,namely qi deficiency and phlegm-stasis syndrome,phlegm-stasis obstructing the collateral syndrome,qi and yin deficiency syndrome,qi and blood deficiency syndrome,and phlegm-heat accumulation syndrome.Among them,qi deficiency and phlegm-stasis syndrome was the most common type(80 cases,88.9%).(3)The overall incidence of irAEs was 38.9%(35/90),and irAEs being or above grade 3(G3)level in the patients only accounted for 5.6%(5/90).The initial irAEs usually occurred at the immunotherapy course 1-3(17 cases,48.6%).The incidence of irAEs being or above G3 level in the patients treated with ICIs monotherapy was higher than that in the patients treated with the combined therapy(33.3%vs 3.6%).(4)The Eastern Cooperative Oncology Group(ECOG)performance status(PS)score of 0-1(OR=8.218,95%CI:1.607-42.023,P = 0.011)and adrenal metastasis(OR=4.497,95%CI:1.237-16.354,P=0.022)were the independent risk factors for irAEs in patients with stageⅢ-Ⅳ NSCLC treated by ICIs(P＜0.05).Conclusion Chinese medicine has the potential to reduce the incidnence of adverse reactions of ICIs in the treatment of stage Ⅲ-Ⅳ NSCLC.PS score of 0-1 and adrenal metastasis may be the independent risk factors for irAEs in patients with stage Ⅲ-Ⅳ NSCLC treated by ICIs.

Protein drugs play an extremely important role in the prevention and treatment of diseases. But the properties of macromolecules hinder their effects on intracellular targets. Among the existing delivery strategies, penetrating peptides are more suitable for clinical research and treatment, and have gradually become the most important tool to deliver protein drugs. Therefore, the development of safe and effective penetrating peptide delivery vehicles is of great significance to the basic research and clinical application of biomedicine. In this paper, a self-releasing intracellular transporter LCA2 based on the enterotoxin A2 domain is designed. This carrier is composed of three parts: a linker, self-releasing enzyme sensitive sites (Cs), and the transmembrane domain LTA2. The fluorescent protein mCherry was used as the model protein to detect the properties of LCA2. The results of electrophoresis showed that the high-purity mCherryLCA2 fusion protein was obtained from the engineered bacteria containing pET24a(+)-ma2 recombinant plasmids, and mCherry could be effectively separated from LCA2 by low concentration trypsin. It was observed under a fluorescence microscope that LCA2 could transport mCherry into different types of cells. Flow cytometry has detected that the transport capacity of LCA2 has certain cellular differences. Confocal microscope fluorescence analysis and Western blotting results showed that the mCherry was transported to the endoplasmic reticulum by the LCA2 carrier, separated from LCA2 by cleavage of enzyme sensitive sites and released into the cell. The CCK-8 results showed that there was no significant change in cell viability within the dose range of 5-40 μg/ mL. These results demonstrate that LCA2 is a safe and effective self-releasing delivery vehicle, which can transport and release active proteins or protein drugs into cells.

OBJECTIVETo evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations.

METHODSA randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival (PFS)] and secondary endpoints [median survival time (MST), objective response rate (ORR), disease control rate (DCR) and safety] were observed.

RESULTSNo patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months (95% CI 3.30-21.69) vs. 8.4 months (95% CI 6.30-10.50; log-rank P<0.01), MST of 21.5 months (95% CI 17.28-25.73) vs. 18.3 months (95% CI 17.97-18.63; log-rank P<0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively (P>0.05). The most common toxic effects in the GF group and G group were rash or acne (42.8% vs. 57.1%, P>0.05), diarrhea (11.5% vs. 31.4%, P<0.05), and stomatitis (2.9% vs. 8.7%, P>0.05).

CONCLUSIONPatients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.

OBJECTIVETo investigate the inhibitive effect and the underlying mechanism of Xiaoji Decoction (, XJD) in human lung cancer A549 cells.

METHODSA549 cells in logarithmic proliferation were cultivated in RPMI-1640 containing 10% low, medium or high dosages of XJD serum. The inhibitive effect of XJD in A549 cell proliferation was assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The pro-apoptotic effect of XJD in A549 cells was observed by fluorescence microscope via Hoechst 33258 staining. The role of the Akt signaling pathway was observed by examining the presence of p-Akt protein by Western blot and the mRNA expression of downstream proteins such as Bcl-2/Bcl-XL-associated death promoter (BAD) and caspase-9 by real time polymerase chain reaction.

RESULTSMTT assay revealed that XJD could inhibit A549 proliferation in a dose- and time-dependent manner. Hoechst 33258 staining showed that XJD induced the typical nuclear apoptotic morphology after XJD treatment. Moreover, XJD could reduce the phosphorylation of Akt and increase the mRNA expression of BAD and caspase-9.

CONCLUSIONSXJD can inhibit the proliferation of A549 cells in a dose- and time-dependent manner through signaling Akt pathway via up-regulating the expression of BAD and caspase-9. XJD may provide a novel therapeutic model for lung cancer and deserve further study.

Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Lung Neoplasms ; enzymology ; pathology ; Male ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction

OBJECTIVETo evaluate the influence of Shenfu Injection (SHF) on the quality of life of patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy.

METHODSA total of 133 patients with NSCLC receiving at least two cycles of chemotherapy with taxol plus cisplatin (TP)/vinorelbine plus cisplatin (NP) or gemcitabine plus cisplatin (GP) were randomized into SHF pre-treatment group (with SHF given only in the first cycle) and SHF post-treatment group (with SHF given only in the second cycle). The Quality of Life Questionnaire-Core 30 (QLQ-C30) and the Functional Living Index-Cancer (FLIC) were used to evaluate the quality of life of the patients after the treatments.

RESULTSBoth of the groups showed improved quality of life after the treatments (P<0.01), but the improvements were more obvious in SHF pre-treatment group (P<0.05). SHF showed favorable effects in relieving such adverse effects as fatigue, nausea, vomiting and diarrhea associated with the chemotherapy.

CONCLUSIONSHF can improve the quality of life in NSCLC patients receiving chemotherapies.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cisplatin ; administration & dosage ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Nausea ; prevention & control ; Paclitaxel ; administration & dosage ; Phytotherapy ; Quality of Life ; Surveys and Questionnaires ; Vinblastine ; administration & dosage ; analogs & derivatives ; Vomiting ; prevention & control

Objective To investigate the clinical features of aortic dissection (AD) and emergency treatments. Methods Data from 784 patients with aortic dissection were collected in the Department of Emergency from January 2000 through December 2009. A retrospective analysis was carried out to determine the survival rate, mortality rate and treatment efficiency. Results Pain was the most common onset symptom (77.7% , 609/784). The majority of patients (86.5%) had essential hypertension (678/784). All the patients with preoperative diagnosis of aortic dissection underwent emergency medical intervention by internists resulting in 81.5% survival rate (639/784) and 18.5% mortality rate (145/784). There were 157 patients without improvement (20.0% ) and the total efficiency rate was (83. 1% ). The efficiency rate of conventional treatment was 76.4% , while the efficiency rate of triple four-procedure treatment was 89. 8% (P<0.05). Of them, 139 patients (17. 7% ) died in the hospital. Among them,. 26 patients died within 24 hours (18.4% ) and 47 cases died within 48 hours (33. 8% ) and 66 patients died within 72 hours (47.2% ). There were 92 patients who refused treatments after diagnosis, and among them, 81 patients died within 72 hours (88.04% ). The difference in mortality rate between two groups was significant (P<0.05). Conclusions The diagnosis of aortic dissection depends on detailed history, physical examination and CT or MRI imaging. Analgesia, sedation and control of blood pressure are essential for emergency treatments. Early diagnosis and effective emergency treatments are the critical strategy for the early surgical intervention and time window for further treatment to improve the survival rate of AD.

OBJECTIVETo observe the effect of Shenfu Injection (SFI) for attenuating the toxicity of chemotherapy in treating non-small-cell lung cancer (NSCLC), by the regimens of combined Cisplatin (DDP) with new chemotherapeutic agents, Taxol (TXT), Vinorelbine (NVB) and Gemcitabine (GEM), respectively.

METHODSOne hundred and thirty-three patients with NSCLC, who were scheduled to be treated by at least 2 cycles of chemotherapy, with regimen TP (45 cases), NP (42 cases) and GP (46 cases), were enrolled. They were randomized into 2 groups: 67 cases in the SFI pre-treated group and 66 cases in the SFI post-treated group, on them SFI was administered for 10 successive days on the 1st, 2nd, 3rd day of the 1st and the 2nd cycle, respectively. The effects of SFI on toxicity of the three regimens were observed through a self-controlled crossover design.

RESULTSThe hemato-toxicity (the toxicity on leukocyte, neutrophil, hemoglobin and platelet) and the digestive toxicity (represented as vomiting, constipation or diarrhea) of chemotherapy revealed in the treated stage (the cycle treated with SFI) were all less than those in the control stage (the cycle untreated with SFI), no matter when SFI was applied, all showed statistical significance (P < 0.05 or P < 0.01). Besides, SFI showed a better toxicity attenuating effect on patients of qi-deficiency and phlegm-dampness type (P < 0.01).

CONCLUSIONSFI can relieve the hemato-toxicity and the digestive toxicity of chemotherapy by regimen of combining DDP with TXT, NVB or GEM, and the effect is more significant on patients of qi-deficiency and phlegm-dampness type.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cisplatin ; administration & dosage ; adverse effects ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Phytotherapy

Objective To study the status on economic burden of diarrhea in Zhejiang province so as to provide evidence for allocation of health resource as well as decision-making on health issues. Methods Multi-phases stratified random cluster sampling was used to select samples in the population. Data was collected on the incidence of diarrhea in the last two weeks as well as on the related cost due to medical care etc. Results The overall incidence (person per year) of diarrhea was 0.26, with 0.29 in the rural and 0.22 in the urban areas respectively. The incidence of diarrhea in children less than 5 was 0.66 (person per year), higher than in any of the age groups. The average direct cost of medical treatment was 69.23 Yuan with average direct cost of non-medical care was 8.29 Yuan for every person, while the indirect cost was 48.43 Yuan. in conclusion, the average disease burden of diarrhea in the province was 1.697 billion Yuan per year, which accounted for 1%o of the GDP, with 1.217 billion Yuan in rural area and 0.480 billion Yuan in the urban areas respectively. The direct cost of medical care was 0.886 billion Yuan (52.21%) and the direct cost due to non-medical care was 0.124 billion Yuan (7.31%). The indirect cost appeared to be 0.480 billion Yuan (40.48%). Factors that affecting the cost would relate to: severity of diarrhea, medical insurance, location of residential area, age and education background of the patients, etc. Conclusion Programs on diarrhea prevention and control should be strengthened to reduce the economic burden caused by this disease while special attention should be paid to those children who are under 5 years of age and living in the rural areas.