This study aims to establish the S_(180) tumor-bearing mice model, and to investigate the influence of Shenqi Erpi Granules(SQEPG) on immune function, as well as the drug's tumor-suppressive effect and mechanism. SPF grade KM mice(half male and half female) were randomly divided into 6 groups: a control group, a model group, a cyclophosphamide group(50 mg·kg~(-1)), as well as SQEPG groups in low-, medium-, and high-dose(5.25, 10.5, 21 g·kg~(-1)). The control group and the model group were given distilled water, and the other 4 groups were given the corresponding drugs by gavage. The administration continued for 10 days before the mice were sacrificed. The antitumor and immune regulation effects of SQEPG were evaluated. The effect of SQEPG on delayed type hypersensitivity reaction(DTH), carbon clearance index, and serum hemolysin antibody level was observed to reflect the effect on the immune function of tumor-bearing mice. Tumor weight was recorded to calculate the tumor suppression rate and the immune organ index. Hematoxylin-eosin(HE) staining was used to detect morphological changes in tumor tissues. Flow cytometry was employed to detect the percentage of CD4~+ and CD8~+ T-cells in the spleen tissues and the tumor tissue apoptosis levels. Immunohistochemistry was conducted to detect the KI67 protein expression level of tumor tissues. ELISA resorted to the detection of the following expression levels in tumor tissues: tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), interferon-γ(IFN-γ). Western blot was performed to detect the expression levels of caspase-3, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinases 4(CDK4), G_1/S-specific cyclin D1(cyclin D1), and vascular endothelial growth factor A(VEGFA). The results showed that, compared with the model group, the SQEPG could increase the swelling of the auricle of the tumor-bearing mice; significantly increase the phagocytic index of carbon granule contour(P<0.05 or P<0.01), and the middle dose of SQEPG could significantly increase the antibody level of hemolysin(P<0.05); different doses of SQEPG significantly inhibit the growth of the tumor, and decrease the mass of the tumor tissues(P<0.05 or P<0.01); the low dose of SQEPG significantly decreased spleen index(P<0.05), low and high doses of SQEPG increased thymus index, while medium doses of SQEPG decreased thymus index. High doses of SQEPG significantly elevated the levels of CD4~+ and CD8~+ T-cells in the spleens of the homozygous mice(P<0.01 or P<0.001), and increased the apoptosis rate of the cells of the tumor tissues(P<0.05); Meanwhile, high-dose SQEPG elevated the levels of immunity factors such as IL-2, IFN-γ and TNF-α in the serum of tumor-bearing mice(P<0.01); medium-and high-dose SQEPG significantly lowered the rate of positive expression of KI67 protein in tumor tissues(P<0.01). Compared with the model group, high-dose SQEPG significantly up-regulated the expression of caspase-3 and Bax proteins in tumor tissues(P<0.05), and significantly down-regulated the expression of CDK4, cyclin D1, and VEGFA proteins(P<0.05 or P<0.01). In conclusion, SQEPG has the effect of improving immune function and inhibiting tumor growth in tumor-bearing mice. Its mechanism of tumor-suppressive effects may be related to apoptosis promotion, cell cycle progression block, and tumor cell proliferation inhibition.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Apoptosis/drug effects* ; Sarcoma 180/genetics* ; Humans

OBJECTIVE: To explore the effect of nano-hydroxyapatite/collagen composite (nHAC) on bone graft fusion after anterior cervical discectomy and fusion (ACDF) in patients with cervical spondylosis and low bone mass. METHODS: A retrospective analysis was conducted on 47 patients with low bone mass who underwent ACDF from 2017 to 2021. They were divided into the nHAC group and the allogeneic bone group according to different bone graft materials. The nHAC group included 26 cases, with 8 males and 18 females;aged 50 to 78 years old with an average of (62.81±7.79) years old;the CT value of C₂-C₇ vertebrae was (264.16±36.33) HU. The allogeneic bone group included 21 cases, with 9 males and 12 females;aged 54 to 75 years old with an average of (65.95±6.58) years old;the CT value of C₂-C₇ vertebrae was (272.39±40.44) HU. The visual analogue scale (VAS), neck disability index (NDI), and Japanese Orthopaedic Association (JOA) spinal cord function score were compared before surgery, 1 week after surgery, and at the last follow-up to evaluate the clinical efficacy. Imaging assessment included C₂-C₇ Cobb angle, surgical segment height, intervertebral fusion, and whether the cage subsidence occurred at 1 week after surgery and the last follow-up. RESULTS: The follow-up duration ranged from 26 to 39 months with an average of (33.27±3.34) months in the nHAC group and 26 to 41 months with an average of (31.86±3.57) months in the allogeneic bone group. At 1 week after surgery and the last follow-up, the VAS, NDI scores, and JOA scores in both groups were significantly improved compared with those before surgery, with statistically significant differences (P<0.05). At 1 week after surgery, the C₂-C₇ Cobb angles in the nHAC group and the allogeneic bone group were (14.26±10.32)° and (14.28±8.20)° respectively, which were significantly different from those before surgery (P<0.05). At the last follow-up, the C₂-C₇ Cobb angles in both groups were smaller than those at 1 week after surgery, with statistically significant differences (P<0.05). At 1 week after surgery, the height of the surgical segment in the nHAC group was (31.65±2.55) mm, and that in the allogeneic bone group was (33.63±3.26) mm, which were significantly different from those before surgery (P<0.05). At the last follow-up, the height of the surgical segment in both groups decreased compared with that at 1 week after surgery, with statistically significant differences (P<0.05). At the last follow-up, 39 surgical segments were fused and 6 cages subsided in the nHAC group;40 surgical segments were fused and 7 cages subsided in the allogeneic bone group;there was no statistically significant difference between the two groups (P>0.05). Compared with the CT value of vertebrae without cage subsidence, the CT value of vertebrae with cage subsidence in both groups was significantly lower, with a statistically significant difference (P<0.05). CONCLUSION The application of nHAC in ACDF for patients with low bone mass can achieve effective fusion of the surgical segment. There is no significant difference in improving clinical efficacy, intervertebral fusion, and cage subsidence compared with the allogeneic bone group. With the extension of follow-up time, the C₂-C₇ Cobb angle decreases, the height of the surgical segment is lost, and the cage subsides in both the nHAC group and the allogeneic bone group, which may be related to low bone mass. Low bone mass may be one of the risk factors for cervical spine sequence changes, surgical segment height loss, and cage subsidence after ACDF.
Humans ; Male ; Female ; Middle Aged ; Spondylosis/physiopathology* ; Spinal Fusion/methods* ; Cervical Vertebrae/surgery* ; Aged ; Diskectomy ; Durapatite ; Retrospective Studies ; Collagen/chemistry*

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

BACKGROUND:Currently,there have been studies on the regulatory mechanism of lncRNA\miRNA\mRNA co-expression network on the occurrence and development of osteoarthritis.Our research group has screened qualified NONHSAT248596.1 and miR-146a-5p through the database in the previous stage,but the corresponding in vivo experiments to verify the above regulatory mechanisms are still lacking. OBJECTIVE:To explore the role of NONHSAT248596.1 in regulating competitive endogenous RNA of miR-146a-5p in cartilage degeneration mediated by stromal cell derived factor type 1/chemokine receptor 4 axis in vivo. METHODS:The models of osteoarthritis were established in 36 New Zealand rabbits by injecting stromal cell derived factor 1 solution into the knee joint of the right hind limb.According to the random number table method,they were divided into four groups.lncRNA group,miRNA group,ceRNA group and control group were injected with lentivirus vector overexpressing NONHSAT248596.1,lentivirus vector overexpressing miR-146a-5p,lentivirus vector overexpressing miR-146a-5p+NONHSAT248596.1 and empty lentivirus vector into the molded knee joint,respectively.At 4,8 and 12 weeks of modeling,cartilage tissues and subchondral bone tissues of the knee joint were taken for relevant detection. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and safranin fast green staining showed different degrees of degeneration in the four groups.At 4 weeks,the cartilage tissue of the lncRNA group showed swelling of chondrocytes,loss of cell polarity,destruction of extracellular matrix,surface erosion,fracture formation and partial or full layer loss of cartilage tissue.The degree of cartilage injury was gradually aggravated with time.The progression of articular cartilage inflammation in the miRNA group was the slowest among the four groups.qRT-PCR showed that at the same time point,mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in cartilage tissue of the lncRNA group were higher than those of the other three groups(P＜0.05).The mRNA expression levels of miR-146a-5p,aggrecan and type Ⅱ collagen were lower than those of the other three groups(P＜0.05).The mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in the miRNA group were lower than those in the ceRNA group and control group at 8 and 12 weeks after the model construction(P＜0.05).The mRNA expressions of miR-146a-5p,aggrecan and type Ⅱ collagen were higher than those of the ceRNA group and control group(P＜0.05).Western blot assay showed that at the same time point,the expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the lncRNA group were always lower than those of the other three groups(P＜0.05).The expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the miRNA group at 8 and 12 weeks after modeling were higher than those of the ceRNA group and control group(P＜0.05).The results showed that miR-146a-5p,as the target of NONHSAT248596.1,could be inhibited by the effect of its ceRNA.After acting on miR-146a-5p,NONHSAT248596.1 regulates the stromal cell derived factor type 1/chemokine receptor 4 axis to affect the expression of matrix metalloprotein,type Ⅱ collagen,and aggrecan in osteoarthritis chondrocytes,resulting in the degradation of extracellular matrix and the loss of proteoglycan.

Objectives:To evaluate the tricuspid valve(TV)geometric remodeling in patients with idiopathic pulmonary arterial hypertension(IPAH)by three-dimensional transthoracic echocardiography. Methods:Two-dimensional and three-dimensional transthoracic echocardiography were performed in 30 IPAH patients and 15 healthy controls,and the geometry parameters of TV were obtained by four-dimensional auto tricuspid valve quantitative(4D Auto-TVQ)in the right ventricular-focused apical view.Pulmonary arterial hypertension was determined by right heart catheterization within 48 hours of echocardiography. Results:The 4-chamber diameter,tricuspid annular(TA)perimeter,TA area,maximal tenting height,coaptation point height and tenting volume were larger in IPAH patients than those in healthy controls(all P＜0.05),2-chamber diameter was similar between two groups.In IPAH group,maximal tenting height and coaptation point height were moderately correlated with right ventricular end-diastolic volume(r=0.710,r=0.515,both P＜0.05),while TA perimeter,4-chamber diameter and TA area were moderately correlated with right atrial end-systolic volume(r=0.712,r=0.558,r=0.545,all P＜0.05). Conclusions:IPAH patients have larger maximal tenting height,coaptation point height and tenting volume,TA enlargement is mainly visible in 4-chamber diameter.TV tenting height is associated with right ventricular volume,but TA size is associated with right atrial volume in IPAH patients.

OBJECTIVE To evaluate the clinical efficacy of modified Zhujing Pills in the treatment of dry age-related macular degeneration(AMD)of liver and kidney insufficiency type.METHODS 64 patients with dry AMD of liver and kidney insufficiency type were randomly divided into an experimental group and a control group,32 patients each.The control group was given oral treat-ment with Laishiding capsules,and the experimental group was given oral treatment with modified Zhujing Pills granules.The treatment course for both groups was 3 months.Before and after treatment,the patients in the two groups were observed for TCM syndrome scores,visual acuity,fundus autofluorescence(AF),changes in drusen area within 5 mm of the fovea,and plasma superoxide dis-mutase(SOD),glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)levels.RESULTS After treatment,the scores of TCM syndromes in the experimental group were significantly reduced(P＜0.05,P＜0.01),and the efficacy of TCM syn-dromes was better than that of the control group(P＜0.01);the visual acuity of the patients in the experimental group was significantly improved,AF was significantly weakened and the area of drusen was reduced(P＜0.05,P＜0.01),which were better than those in the control group(P＜0.05);the plasma SOD and GSH-Px activities of the experimental group were increased,and the MDA level was significantly lowered(P＜0.05,P＜0.01),which were better than the control group(P＜0.05).CONCLUSION Modified Zhujing Pills can reduce fundus AF intensity,decrease macular drusen area,improve visual acuity,and reduce TCM syndrome scores in pa-tients with dry AMD.The therapeutic mechanism may be related to its antioxidant effect.

Objective To investigate the clinical efficacy of mitral valve repair technique in the treatment of rheumatic mitral valve lesions. Methods The clinical data of patients diagnosed with rheumatic mitral valve lesions and undergoing mitral valve repair under extracorporeal circulation in our department from 2021 to 2022 were retrospectively analyzed. Results A total of 100 patients were collected, including 78 females and 22 males with an average age of 52 years. There were no secondary open heart or death in the whole group. Extracorporeal circulation time was 136.3±33.1 min, aortic cross-clamping time was 107.6±27.5 min, ventilator use time was 12.9±5.9 h, ICU stay was 2.6±1.4 d, and vasoactive medication use was 823.4±584.4 mg. Before and after the surgery, there were statistical differences in the left ventricular end diastolic diameter, left atrial end systolic diameter, effective mitral valve orifice area, shortening rate of left ventricular short axis, mitral E-peak blood flow velocity, mean mitral transvalvular pressure difference, mitral pressure half-time, and cardiac function graded by New York Heart Association (P＜0.05). While there was no statistical difference in left ventricular ejection fraction or left ventricular end-diastolic volume (P>0.05). Conclusion Overall repair of rheumatic mitral valve lesions can significantly improve the cardiac function and hemodynamics of the patients, and is a good choice for patients with rheumatic mitral valve lesions.

OBJECTIVE To investigate the metabolic changes in MEG-01 megakaryocytes after treatment with linezolid （LZD） from metabolomic perspective and its impact on the the proliferation of cells and generation of platelet precursors. METHODS MEG-01 cells were seeded in proliferation medium and divided into blank control group （untreated）， solvent control group （4‰DMSO）， and 100， 200， 400， 800 μg/mL LZD groups. The proliferation status of cells in each group was observed under the microscope； cell proliferation and viability were assessed. Cells were also seeded in differentiation medium and divided into blank control group （untreated）， solvent control group （4‰DMSO）， and 400 μg/mL LZD group； after 14 days of culture， platelet precursor generation was observed under the microscope； immunofluorescence staining was performed to count the proportion of cells producing pseudopodia， the relative length of pseudopodia was measured， and the expression levels of CD41 and CD42b mRNA were assessed. Cells from the solvent control group and the 400 μg/mL LZD group， cultured in differentiation medium for 14 days， were extracted and subjected to non-targeted metabolomics and targeted energy metabolomics analysis using liquid chromatography-tandem mass spectrometry. The relative content of pyruvate in cells， after being cultured for 14 days with the addition of pyruvate （10 mmol/L） or LZD （400 μg/mL）+pyruvate （10 mmol/L）， was measured and observed， as well as its effects on cell proliferation and platelet precursor generation. RESULTS 400 μg/mL LZD could significantly inhibit the proliferation of MEG-01 cells and the generation of platelet precursors （P＜0.01）. Non-targeted metabolomic analysis of MEG-01 cells after 400 μg/mL LZD treatment revealed significant changes in energy metabolism-related pathways such as mTOR signaling pathway， alanine， aspartate and glutamate metabolism， and central carbon metabolism in cancer. Targeted energy metabolomic analysis further showed that the relative contents of adenosine triphosphate， guanosine triphosphate， and pyruvate in MEG-01 cells were significantly reduced （P＜0.01）， while the relative contents of lactate were significantly increased （P＜0.01）. Compared with the LZD group， the relative content of pyruvate， cell count， the proportion of cells producing pseudopodia and the relative length of pseudopodia were significantly increased in the LZD+pyruvate group （P＜0.01）. CONCLUSIONS LZD may reduce pyruvate production by inhibiting mitochondrial energy metabolism， thereby suppressing megakaryocyte proliferation and platelet precursor production， ultimately leading to the occurrence of thrombocytopenia.

OBJECTIVE To explore the material basis of the anti-inflammatory effect of the petroleum ether extract from Melastoma dodecandrum by establishing its fingerprint and combining it with cellular pharmacodynamics experiments. METHODS HPLC method was adopted； the fingerprints of 20 batches of petroleum ether extract from M. dodecandrum were drawn using The Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）； similarity evaluation and common peak identification were carried out. The lipopolysaccharide-induced inflammation model of mice mononuclear macrophages （RAW264.7） was established； the inhibitory rates of nitric oxide （NO） and tumor necrosis factor α （TNF-α） were used as indexes to investigate the anti-inflammatory activity of the petroleum ether extract from M. dodecandrum； grey correlation degree method and partial least square regression analysis were adopted to study the spectrum-effect relationship. Molecular docking was used to validate the binding activity of the anti-inflammatory active ingredients with TNF-α and iNOS protein receptor. RESULTS There were 19 common peaks in the fingerprint of the petroleum ether extract from M. dodecandrum， the similarity of 20 batches of samples ranged from 0.603-0.990， and five components were identified， such as vitexin （peak 5）， isovitexin （peak 6）， ellagic acid （peak 7）， quercetin （peak 9） and luteolin （peak 10）. The grey correlation degree between 19 common peaks of the petroleum ether extract from M. dodecandrum and the inhibition rates of NO and TNF-α were all greater than 0.7； peaks 19， 13， 9 （quercetin）， 12， 5 （vitexin）， 6 （isovitexin）， 8， 7 （ellagic acid）， 18， 1 were positively correlated with NO inhibition rate， and peaks 8， 10 （luteolin）， 13， 15， 3， 19， 17， 7 （ellagic acid）， 18， 1 were positively correlated with inhibition rate of TNF-α. The binding energies of vitexin， isovitexin and quercetin with iNOS protein receptor were less than －5.0 kcal/mol. CONCLUSIONS Vitexin， isovitexin and quercetin may be the basis of the anti-inflammatory effect of the petroleum ether extract from M.dodecandrum.

Objective To observe the influence of dapagliflozin tablets on myocardial enzymes,mitral valve blood flow and major adverse cardiovascular events(MACE)in patients with acute myocardial infarction(AMI)complicated with type 2 diabetes mellitus(T2DM)after interventional therapy.Methods AMI patients with T2DM were divided into control group and treatment group by cohort method.The control group was given aspirin tablets 300 mg and ticagrelor 180 mg orally,qd,until the day of interventional treatment.After interventional therapy,aspirin tablets 100 mg,qd,oral ticagrelor tablets 90 mg each time,once in the morning and once in the evening.On the basis of the treatment in the control group,the patients in the treatment group were given dapagliflozin tablets 5-10 mg,qd,every morning after admission.After 3 months of continuous treatment,the clinical efficacy,blood glucose control effect[fasting plasma glucose(FPG),2 hour postprandial blood glucose(2 h PG)],myocardial enzymes indicators[creatine kinase(CK),creatine kinase isoenzyme-MB(CK-MB)],ventricular remodeling indicators[left ventricular ejection fraction(LVEF),left ventricular end systolic diameter(LVESD)],adverse drug reactions and MACE were compared between the two groups.Results There were 55 cases in the control group and 59 cases in the treatment group.After treatment,the total effective rates of the treatment group and the control group were 88.14％(52 cases/59 cases)and 72.73％(40 cases/55 cases),respectively,the difference was statistically significant(P＜0.05).After treatment,the FPG of the treatment group and the control group were(7.29±0.71)and(7.81±0.75)mmol·L-1,respectively;the 2 h PG were(8.66±1.33)and(9.59±1.38)mmol·L-1,respectively;the CK were(145.68±29.82)and(163.68±42.16)U·L-1,respectively;the CK-MB were(8.21±2.37)and(10.33±3.08)U·L-1,respectively;the LVEF were(57.63±8.74)％and(51.41±6.49)％,respectively;LVESD were(33.26±5.33)and(39.51±5.38)mm,respectively.The above indexes in the treatment group were significantly different from those in the control group(all P＜0.05).During the treatment,the adverse drug reactions in the treatment group mainly included nausea and vomiting,diarrhea,constipation.The adverse drug reactions in the control group mainly included hypoglycemia,diarrhea,headache.The total incidence of adverse drug reactions in the treatment group and the control group was 6.68％(4 cases/59 cases)and 9.09％(5 cases/55 cases),respectively,and the difference was not statistically significant(P＞0.05).After 3 months of follow-up,the total incidence of MACE in the treatment group and the control group was 5.08％and 18.18％,respectively,the difference was statistically significant(P＜0.05).Conclusion Dapagliflozin has a significant efficacy in the treatment of AMI patients with T2DM,and it can enhance the effect of blood glucose control,reduce the myocardial injury,inhibit the ventricular remodeling,and reduce the risk of MACE,with high safety.