Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases: A case report.

BACKGROUND: Small cell lung cancer (SCLC) is a common and aggressive subtype of lung cancer. It is characterized by rapid growth and a high mortality rate. Approximately 10% of patients with SCLC present with brain metastases at the time of diagnosis, which is associated with a median survival of 5 mo. This study aimed to summarize the effect of bevacizumab on the progression-free survival (PFS) and overall survival of patients with brain metastasis of SCLC. CASE SUMMARY: A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks. The patient was diagnosed with limited-stage SCLC. He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo. CONCLUSION: The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Finite element modeling and analysis of effect of preexisting cervical degenerative disease on the spinal cord during flexion and extension.

Recent studies have emphasized the importance of dynamic activity in the development of myelopathy. However, current knowledge of how degenerative factors affect the spinal cord during motion is still limited. This study aimed to investigate the effect of various types of preexisting herniated cervical disc and the ligamentum flavum ossification on the spinal cord during cervical flexion and extension. A detailed dynamic fluid-structure interaction finite element model of the cervical spine with the spinal cord was developed and validated. The changes of von Mises stress and maximum principal strain within the spinal cord in the period of normal, hyperflexion, and hyperextension were investigated, considering various types and grades of disc herniation and ossification of the ligamentum flavum. The flexion and extension of the cervical spine with spinal canal encroachment induced high stress and strain inside the spinal cord, and this effect was also amplified by increased canal encroachments and cervical hypermobility. The spinal cord might evade lateral encroachment, leading to a reduction in the maximum stress and principal strain within the spinal cord in local-type herniation. Although the impact was limited in the case of diffuse type, the maximum stress tended to appear in the white matter near the encroachment site while compression from both ventral and dorsal was essential to make maximum stress appear in the grey matter. The existence of canal encroachment can reduce the safe range for spinal cord activities, and hypermobility activities may induce spinal cord injury. Besides, the ligamentum flavum plays an important role in the development of central canal syndrome.Significance. This model will enable researchers to have a better understanding of the influence of cervical degenerative diseases on the spinal cord during extension and flexion.

The biomechanical effect of different types of ossification of the ligamentum flavum on the spinal cord during cervical dynamic activities.

Ossification of the ligamentum flavum (OLF) is thought to be an influential etiology of myelopathy, as thickened ligamentum flavum causes the stenosis of the vertebral canal, which could subsequently compress the spinal cord. Unfortunately, there was little information available on the effects of cervical OLF on spinal cord compression, such as the relationship between the progression of cervical OLF and nervous system symptoms during dynamic cervical spine activities. In this research, a finite element model of C1-C7 including the spinal cord featured by dynamic fluid-structure interaction was reconstructed and utilized to analyze how different types of cervical OLF affect principal strain and stress distribution in spinal cord during spinal activities towards six directions. For patients with cervical OLF, cervical extension induces higher stress within the spinal cord among all directions. From the perspective of biomechanics, extension leads to stress concentration in the lateral corticospinal tracts or the posterior of gray matter. Low energy damage to the spinal cord would be caused by the high and fluctuating stresses during cervical movements to the affected side for patients with unilateral OLF at lower grades.

Effect of Different Types of Ossification of the Posterior Longitudinal Ligament on the Dynamic Biomechanical Response of the Spinal Cord: A Finite Element Analysis.

Ossification of the posterior longitudinal ligament (OPLL) has been identified as an important cause of cervical myelopathy. However, the biomechanical mechanism between the OPLL type and the clinical characteristics of myelopathy remains unclear. The aim of this study was to evaluate the effect of different types of OPLL on the dynamic biomechanical response of the spinal cord. A three-dimensional finite element model of the fluid-structure interaction of the cervical spine with spinal cord was established and validated. The spinal cord stress and strain, cervical range of motion (ROM) in different types of OPLL models were predicted during dynamic flexion and extension activity. Different types of OPLL models showed varying degrees of increase in stress and strain under the process of flexion and extension, and there was a surge toward the end of extension. Larger spinal cord stress was observed in segmental OPLL. For continuous and mixed types of OPLL, the adjacent segments of OPLL showed a dramatic increase in ROM, while the ROM of affected segments was limited. As a dynamic factor, flexion and extension of the cervical spine play an amplifying role in OPLL-related myelopathy, while appropriate spine motion is safe and permitted. Segmental OPLL patients are more concerned about the spinal cord injury induced by large stress, and patients with continuous OPLL should be noted to progressive injuries of adjacent level.

Biomarkers and factors in small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.

OBJECTIVE: The aim of this meta-analysis was to summarize the available results of immunotherapy predictors for small cell lung cancer (SCLC) and to provide evidence-based information for their potential predictive value of efficacy. METHODS: We searched PubMed, EMBASE, Web of Science, The Cochrane Library, and ClinicalTrials (from January 1, 1975 to November 1, 2021). The hazard ratios (HR) and its 95% confidence intervals (CIs) and tumor response rate of the included studies were extracted. RESULTS: Eleven studies were eventually included and the pooled results showed that programmed cell death ligand 1 (PD-L1) positive: objective response rate (ORR) (relative risk [RR] = 1.39, 95% CI [0.48, 4.03], p = 0.54), with high heterogeneity (p = 0.05, I2  = 56%); disease control rate [DCR] (RR = 1.31, 95% CI [0.04, 38.57], p = 0.88), with high heterogeneity (p = 0.04, I2  = 75%); overall survival (OS) (HR = 0.89, 95% CI [0.74, 1.07], p = 0.22); and progression-free survival (PFS) (HR = 0.83, 95% CI [0.59, 1.16], p = 0.27), with high heterogeneity (p = 0.005, I2  = 73.1%). TMB-High (TMB-H): OS (HR = 0.86, 95% CI [0.74, 1.00], p = 0.05); PFS (HR = 0.71, 95% CI [0.6, 0.85], p < 0.001). Lactate dehydrogenase (LDH) >upper limit of normal (ULN): OS (HR = 0.95, 95% CI [0.81, 1.11], p = 0.511). Asian patients: OS (HR = 0.87, 95% CI [0.72, 1.04], p = 0.135); White/Non-Asian patients: OS (HR = 0.83, 95% CI [0.76, 0.90], p < 0.001). Liver metastasis patients: OS (HR = 0.93, 95% CI [0.83, 1.05], p = 0.229); PFS (HR = 0.84, 95% CI [0.67, 1.06], p = 0.141). Central nervous system (CNS) metastasis patients: OS (HR = 0.91, 95% CI [0.71, 1.17], p = 0.474); PFS (HR = 1.03, 95% CI [0.66, 1.60], p = 0.903). CONCLUSION: The available research results do not support the recommendation of PD-L1 positive and TMB-H as predictors for the application of immune checkpoint inhibitors (ICIs) in SCLC patients. LDH, baseline liver metastasis and CNS metastasis may be used as markers/influencing factors for predicting the efficacy of ICIs in SCLC patients. Non-Asian SCLC patients had better efficacy with ICIs in our results.

Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense.

Unlike reported pyridine hybrids, 2S (1a) and 2R-alanginenmine A (1b) from Alangium chinense featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (±)-alanginenmine A (1) have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds 1a and 1b exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of 1a, might be the main cause for its better anti-HIV-1 protease activity than 1b. This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.

Meta-analysis of gemcitabine plus nab-paclitaxel combined with targeted agents in the treatment of metastatic pancreatic cancer.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GA) is a commonly used first-line treatment regimen for metastatic pancreatic cancer, and many studies will add a novel targeted agent to this regimen for improving patient survival rate. However, the clinical effectiveness of GA is the most controversial issue. AIM: To compare the efficacy and safety of GA regimen with a targeted agent and GA regimen. METHODS: Up to 1 December 2021, the eligible randomized controlled trials (RCTs) relating to GA and GA with a targeted agent were searched on PubMed, EMBASE and Cochrane Library for eligible data. We screened out appropriate studies for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and toxicity, which had been pooled and finally analyzed by using Stata version 15.1. In addition, we use Reference Citation Analysis (https://www.referencecitationanalysis.com/) to collect the latest related literature to improve the latest cutting-edge research results. RESULTS: Seven RCTs involving 1544 patients (848 men and 696 women) were included. There were no significant differences between GA with a targeted agent and GA in PFS [hazard ratio (HR): 1.18 95% confidence interval (CI): 0.91-1.53], OS (HR: 1.12 95%CI: 0.99-1.27), and ORR (HR: 0.96 95%CI: 0.71-1.29). There was no notable difference in the two groups in grade 3/4 toxicity (fatigue, anemia, vomiting and neutropenia), whereas the incidence of grade 3/4 diarrhea considerably increased in GA with a targeted drug. CONCLUSION: Adding a novel targeted agent to the GA regimen did not improve survival rate of patients with metastatic pancreatic cancer.

Cutaneous metastasis from esophageal squamous cell carcinoma: A case report.

BACKGROUND: Esophageal cancer is a common cause of cancer-related death worldwide. Cutaneous metastasis of esophageal squamous cell carcinoma is rare, particularly in diffuse skin metastasis. CASE SUMMARY: In this case report, we describe an 82-year-old male who was diagnosed with esophageal squamous cell carcinoma. The tumor was staged as T4N3M1 (Stage IVB). The pathological findings revealed poorly differentiated squamous cell carcinoma of the esophagus. Four months after diagnosis, the patient began chemotherapy, and symptoms were relieved after four cycles of chemotherapy. After that, the patient returned home without a systematic physical examination. One year after diagnosis, the patient realized that the skin of the abdominal wall was hard and rough without pain, and the color became darker than normal skin. Thirteen months after diagnosis, a biopsy of the patient's abdominal lesion revealed that the skin metastasis was derived from the esophagus. Then the patient received two cycles of apatinib combined with docetaxel, but the abdominal lesion worsened. Two cycles of nivolumab were administered, but the patient eventually died of multiple organ failure. CONCLUSION: This report highlights cutaneous metastasis as a late and untreatable metastasis of esophageal cancer.

Diagnosis and guidance of treatment of breast cancer cutaneous metastases by multiple needle biopsy: A case report.

BACKGROUND: Breast cancer patients have a high skin metastasis rate. However, reports on treatment of cutaneous metastases of breast cancer are scarce. CASE SUMMARY: We report the treatment process for one breast cancer case with bone, lung, and skin metastases. The patient was a 43-year-old woman with advanced breast cancer and skin metastasis. She underwent pathological diagnosis by needle biopsy to guide the treatment. When the disease progressed, a new pathological diagnosis was determined by needle biopsy to guide the treatment. The patient received chemotherapy, endocrine therapy, and photodynamic dynamic therapy, followed by sonodynamic therapy. CONCLUSION: Repeated puncture should be performed for advanced breast cancer with skin metastasis, in order to obtain the pathology and directly determine diagnosis when the disease progresses. The treatment should focus on controlling the systemic metastasis, rather than the local disease.

Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway.

OBJECTIVE: To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD). METHODS: The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA. RESULTS: Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P<0.05 or P<0.01), and led to neuronal repair in the hippocampus. There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups, nor between the 4-VO+TAK-242 and 4-VO+EA groups (P>0.05). CONCLUSIONS: EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.

Research progress on the treatment of advanced prostate cancer with Olaparib.

Prostate cancer (PCa) is one of the most common malignancies in men worldwide, and metastatic castrate-resistant prostate cancer (mCRPC) has shown a poor prognosis. Although chemotherapy and androgen deprivation therapy (ADT) have improved clinical outcomes, the median survival (MS) of patients with mCRPC is still less than 2 years. With the development of poly adenosine diphosphate-ribose polymerase inhibitor (PARPi), the treatment strategy for patients with mCRPC has markedly evolved. Olaparib, a type of PARPi that can selectively induce synthetic lethality in cancer cells with homologous recombination (HR) deficiencies, was the first type of PARPi approved for treating patients with mCRPC harboring mutations in HR repair (HRR) genes. This review discusses and summarizes the latest progress on therapeutic mechanisms, monotherapy, combination therapy, and adverse events of Olaparib.

The biomechanical effect of preexisting different types of disc herniation in cervical hyperextension injury.

OBJECTIVE: Preexisting severe cervical spinal cord compression is a significant risk factor in cervical hyperextension injury, and the neurological function may deteriorate after a slight force to the forehead. There are few biomechanical studies regarding the influence of pathological factors in hyperextension loading condition. The aim of this study is to analyze the effects of preexisting different types of cervical disc herniation and different degrees of compression on the spinal cord in cervical hyperextension. METHOD: A 3D finite element (FE) model of cervical spinal cord was modeled. Local type with median herniation, local type with lateral herniation, diffuse type with median herniation, and diffuse type with lateral herniation were simulated in neutral and extention positions. The compressions which were equivalent to 10%, 20%, 30%, and 40% of the sagittal diameter of the spinal cord were modeled. RESULTS: The results of normal FE model were consistent with those of previous studies. The maximum von Mises stresses appeared in the pia mater for all 32 loading conditions. The maximum von Mises stresses in extension position were much higher than in neutral position. In most cases, the maximum von Mises stresses in diffuse type were higher than in local type. CONCLUSION: Cervical spinal cord with preexisting disc herniation is more likely to be compressed in hyperextension situation than in neutral position. Diffuse type with median herniation may cause more severe compression with higher von Mises stresses concentrated at the anterior horn and the peripheral white matter, resulting in acute central cord syndrome from biomechanical point of view.

[Effect of electrothermal acupuncture on moderate to severe cancer pain with yin-cold stagnation: a randomized controlled trial].

OBJECTIVE: To observe the effectiveness and safety of electrothermal acupuncture therapy for patients of moderate to severe cancer pain with yin-cold stagnation. METHODS: A total of 60 patients of moderate to severe cancer pain with yin-cold stagnation were randomized into an observation group and a control group, 30 cases in each one. In the control group, opioid painkillers (oxycodone hydrochloride prolonged-release tablet or morphine sulfate sustained-release tablet) were taken. On the basis of the control group, electrothermal acupuncture was applied at Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Hegu (LI 4), Sanyinjiao (SP 6) in the observation group, 30 min each treatment, once a day for 5 days. Before and after treatment, the scores of pain numerical rating scale (NRS) and Karnofsky performance scale (KPS) were observed in the two groups. The pain remission rate, reduction of opioid painkillers and safety were compared. RESULTS: The variation of NRS scores in the observation group were larger than the control group 3, 5 days into treatment (P<0.01, P<0.05). The variation of KPS score in the observation group was larger than the control group after treatment (P<0.05). The pain remission rate was 100.0% (30/30) in the observation group, higher than 86.7% (26/30) in the control group (P<0.05). The reduction of opioid painkillers in the observation group was larger than the control group (P<0.01). There was no adverse reaction during the treatment in the two groups. CONCLUSION: On the basis of the conventional western medication for analgesia, electrothermal acupuncture could relieve pain, reduce the dose of opioid painkillers and improve the quality of life in patients of moderate to severe cancer pain with yin-cold stagnation, has a better safety.

The Effectiveness and Safety of Cinobufotalin Injection as an Adjunctive Treatment for Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

Cinobufotalin injection is a water-soluble preparation extracted from the skin secretion of Bufo bufo gargarizans Cantor or B. melanotictus Schneider, which has been widely used as an adjuvant treatment in lung cancer patients. This study aimed to evaluate the clinical efficacy and safety of cinobufotalin (PubChem CID: 259776) injection as an adjunctive treatment for lung cancer. We designed a meta-analysis that performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We aim to include randomized controlled trials by systematically searching the PubMed, EMBASE, CNKI, Wanfang database, VIP, CBM, the Cochrane Central Register of Controlled Trials, and Chinese Clinical Trial Registry from inception to Mar 1, 2020, comparing the difference between the use of cinobufotalin injection as an adjunctive treatment and a control group without cinobufotalin injection. The objective response rate (ORR) and quality of life (QOL) will be defined as the primary outcomes, and the disease control rate (DCR) and adverse events will be defined as the secondary outcomes. We included 21 articles with 1735 cases of lung cancer patients. Comparison results show that combining with cinobufotalin injection can improve ORR (OR = 1.77, 95% CI [1.43, 2.21], P < 0.001), with low heterogeneity (P = 0.94, I 2 = 0%); DCR (OR = 2.20, 95% CI [1.70, 2.85], P < 0.001), with low heterogeneity (P = 0.60, I 2 = 0%); KPS score (OR = 3.10, 95% CI [2.23, 4.32], P < 0.001), with low heterogeneity (P = 0.85, I 2 = 0%); and the effect of pain relief (OR = 2.68, 95% CI [1.30, 5.55], P = 0.008), with low heterogeneity (P = 0.72, I 2 = 0%). Low-to-moderate evidence shows that cinobufotalin injection combined with chemotherapy can significantly increase ORR, DCR, QOL, and the effect of pain relief. Meanwhile, cinobufotalin injection did not bring additional adverse events such as hematological toxicity, gastrointestinal toxicity, cardiotoxicity, hepatotoxicity, and nephrotoxicity; however, multicenter, large-sample, high-quality clinical research results are still needed to reveal the therapeutic effect of cinobufotalin injection in small-cell lung cancer (PROSPERO registration number: CRD42020170052).

Impact Behavior of Hydrophilic Micron Particles on a Planar Gas-Liquid Interface.

The behavior of hydrophilic micron particles impacting on the gas-liquid interface has been further experimentally studied using a high-speed camera at different surface tensions and dynamic viscosities of liquids. The results show that the impact behavior exhibits suspension and submergence modes, whose boundary cannot be clearly identified because the overlap between the impact velocity ranges occurs because of the unstable pinning of the three-phase contact line on the surface of hydrophilic particles. The liquid properties have little effect on the wettability of hydrophilic particles but greatly influence the hydrodynamic and capillary force exerted on the particles, leading to the expansion of the suspension mode range. In addition, the penetration probability changes little with the decrease in surface tension, while it significantly reduces with the increase in dynamic viscosity. A penetration probability model is predicted as an exponential function of the inertial and supporting forces, and the experimental values agree well with the predicted values. The outcomes of this research will be helpful for understanding the mechanism of particle-interface interaction and providing guidance for enhancing the separation of hydrophilic fine ash via a bubble scrubbing system.

Prohibitin, relocated to the front ends, can control the migration directionality of colorectal cancer cells.

Directional migration is a cost-effective movement allowing invasion and metastatic spread of cancer cells. Although migration related to cytoskeletal assembly and microenvironmental chemotaxis has been elucidated, little is known about interaction between extracellular and intracellular molecules for controlling the migrational directionality. A polarized expression of prohibitin (PHB) in the front ends of CRC cells favors metastasis and is correlated with poor prognosis for 545 CRC patients. A high level of vascular endothelial growth factor (VEGF) in the interstitial tissue of CRC patients is associated with metastasis. VEGF bound to its receptor, neuropilin-1, can stimulate the activation of cell division cycle 42, which recruits intra-mitochondrial PHB to the front end of a CRC cell. This intracellular relocation of PHB results in the polymerization and reorganization of filament actin extending to the front end of the cell. As a result, the migration directionality of CRC cells is targeted towards VEGF. Together, these findings identify PHB as a key modulator of directional migration of CRC cells and a target for metastasis.

MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis.

Growth and invasion of metastatic colorectal cancer (CRC) cells in the liver depend on microenvironment. Here, we showed that human hepatic sinusoidal endothelial cells (HHSECs) induce chemotaxis and outgrowth of CRC cells. Macrophage migration inhibitory factor (MIF), released by HHSECs, stimulated chemotaxis of CRC cells. MIF secreted by HHSECs, but not by CRC cells themselves, promoted migration and epithelial-mesenchymal transition (EMT) and facilitated proliferation and apoptotic resistance of CRC cells. In orthotopic implantation models in nude mice, exogenous MIF stimulated growth of CRC cells and metastasis. Furthermore, MIF accelerated mobility of CRC cells by suppressing F-actin depolymerization and phosphorylating cofilin. Noteworthy, MIF levels were correlated with the size of hepatic metastases. We suggest that HHSECs and paracrine MIF promote initial migration and proliferation of CRC cells in the hepatic sinusoids to generate liver metastases.

[Clinical evaluation of the efficacy of external therapies of traditional Chinese medicine in treatment of cancer pain].

There lack scientific methods for evaluating the treatment of cancer pain with external therapies of traditional Chinese medicine (TCM). The level of clinical study in this field needs to be improved. The authors assert that when external therapies of TCM are applied to treat cancer pain, different types of cancer pain should be distinguished and treatment should be applied according to such a differentiation. Under this framework scientific evaluation can be conducted. The authors also assert that the findings of randomized, blinded and controlled trials should be given particular attention, and it is necessary to include titration of morphine into clinical trails of external therapies for the treatment of cancer pain, not only complying with the three-ladder principle for treating cancer pain suggested by the World Health Organization, but also not influencing the effect evaluation of external therapies of TCM on cancer pain. Patient diaries recording pain were revised as observation indexes. The primary indicator of efficacy was the pain intensity score and the secondary indicators were the equivalent of morphine and the remission rate of pain. The time to onset, remission duration and comparison of assessment of pain influence can mirror the characteristics of external therapies of TCM on cancer pain.

Inhibition of cyclooxygenase-2 enhances myocardial damage in a mouse model of viral myocarditis.

To determine critical role of cyclooxygenase-2 (COX-2) for development of viral myocarditis, a mouse model of encephalomyocarditis virus-induced myocarditis was used. The virus was intraperitoneally given to COX-2 gene-deficient heterozygote mice (COX-2+/-) and wild-type mice (WT). We examined differences in heart weights, cardiac histological scores, numbers of infiltrating or apoptotic cells in myocardium, cardiac expression levels of COX-2, tumor necrosis factor-alpha (TNF-alpha), and adiponectin mRNA, immunoreactivity of COX-2, TNF-alpha, and adiponectin in myocytes, cardiac concentrations of TNF-alpha and adiponectin, prostaglandin E2 (PGE2) levels in hearts, and viral titers in tissues between COX-2+/- and WT. We observed significantly decreased expression of COX-2 mRNA and reactivity in hearts from COX-2+/- on day 8 after viral inoculation as compared with that from WT, together with elevated cardiac weights and severe inflammatory myocardial damage in COX-2+/-. Cardiac expression of TNF-alpha mRNA, reactivity, and protein on day 8 was significantly higher in COX-2+/- than in WT, together with reciprocal expression of adiponectin mRNA, reactivity, and protein in hearts. Significantly reduced cardiac PGE2 levels on day 8 were found in COX-2+/- compared with those in WT. There was no difference in local viral titers between both groups on day 4. Infected WT treated with a selective COX-2 inhibitor, NS-398, also showed the augmented myocardial damage on day 8. These results suggest that inhibition of COX-2 may enhance myocardial damage through reciprocal cardiac expression of TNF-alpha and adiponectin in a mouse model of viral myocarditis.

[Pingfei Mixture's two-way adjustment to cell proliferation in mice with tumor].

OBJECTIVE: To study the antineoplastic mechanism of Pingfei Mixture. METHODS: Thirty C57BL mice bearing Lewis pulmonary carcinoma were randomly divided into 3 groups: saline control group, Pingfei Mixture group and cisplatin group. Fifteen days later, tumor tissues and spleens were taken out and made into unicellular suspension. Argyrophil staining was taken to carcinoma cells and cultured T cells. KL-2 style cell image analysis system was used to analyze the rate between AgNORs and nuclear region (I.S). RESULTS: There were dense brownish-black granules in tumor cell nuclear of saline control group. The brownish-black granules of Pingfei Mixture group and cisplatin group were less than those of saline control group. The differences of T cell I.S in these three groups were significant. The I.S of Pingfei Mixture was higher than that of the other groups, and the I.S of the cisplatin group was the lowest. CONCLUSION: Pingfei Mixture can inhibit tumor cell proliferation, although the effect is inferior to cisplatin. Pingfei Mixture can also promote T cell proliferation and its effect was superior to cisplatin.