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Tumor microenvironment possesses immunosuppression characteristics via the mechanism of inducing tumor cell immune escape. The interaction between tumor cells and tumor microenvironment is an important factor affecting tumor genesis and development. As an important part of tumor microenvironment, cancer-associated fibroblasts interact directly or indirectly with tumor cells and produce various cytokines to regulate tumor immune microenvironment. In recent years, hyperthermia has become an auxiliary means of anti-tumor therapy. With the development of research on tumor hyperthermia and tumor microenvironment, a large number of studies have found that hyperthermia can regulate cancer-associated fibroblasts in tumor microenvironment. In this article, recent research progresses of the effects of hyperthermia on cancer-associated fibroblasts and related cells and cytokines in tumor microenvironment were reviewed, providing a new way for clinical application of hyperthermia combined with immune or targeted therapy.
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Objective:To investigate the regulation and possible mechanism of hyperthermia (HT) on the ferroptosis of squamous cell carcinoma of the tongue cell line CAL-27.Methods:Half maximal inhibitory concentration (IC 50) of Fer-1, an inhibitor of ferroptosis, was detected by CCK-8 assay and used for subsequent experiments. CAL-27 cells were divided into the HT, control, Fer-1 and HT+ Fer-1 groups according to experimental design. Reactive oxygen species (ROS) levels and iron ion concentration were determined by corresponding detection kits. The p53 and TfR1 mRNA levels were detected by real-time reverse transcription PCR. Cell migration was detected by cell scratch test and cell apoptosis was detected by flow cytometry. Results:HT significantly up-regulated the ROS levels ( P<0.01) and iron ion concentration ( P<0.001), and significantly increased the expression levels of p53 and TfR1 mRNA (both P<0.01). The cell migration ability was decreased ( P<0.001), whereas cell apoptosis rate was increased by HT ( P<0.01). In the HT+Fer-1 group, the ROS levels ( P<0.001), iron ion concentration ( P<0.001), expression levels of p53 and TfR1 mRNA (both P<0.01) were significantly down-regulated, the cell migration ability was recovered ( P<0.01), and cell apoptosis rate was decreased ( P<0.01) compared with those in the HT group, respectively. Conclusions:HT may induce the ferroptosis of CAL-27 cell line, inhibit cell migration ability and promote cell apoptosis by activating the p53/TfR1 pathway.
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Vascular endothelial growth factor (VEGF) plays an important role in promoting tumor vascular growth and changing vascular wall permeability. With the in-depth study of tumor hyperthermia and tumor microenvironment, more and more studies have shown that hyperthermia exerts multiple regulatory effects on VEGF in tumor microenvironment. Combined with current research progress in China and abroad, this article reviews the effect of hyperthermia on VEGF and its related cells and factors in tumor microenvironment, aiming to provide new ideas for the clinical application of tumor hyperthermia combined with immune or targeted therapy.
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Objective:To observe the effect of hyperthermia combined with paclitaxel on the proliferation, apoptosis and cycle of human tongue squamous cell carcinoma cell line CAL-27, and to explore the underlying mechanism.Methods:The working concentration of paclitaxel was determined by CCK-8 assay, and the cultured CAL-27 cells were divided into the control, paclitaxel, 42℃ hyperthermia and combined treatment groups. The ability of cell proliferation was detected by colony formation assay, and the cell cycle and apoptosis were determined by flow cytometry. The expression levels of AKT, p-AKT, Bcl-2 and Bax proteins in each group were measured by Western blot.Results:Compared with the control group, the proliferation was significantly inhibited and the apoptosis of CAL-27 cells was significantly promoted in the combined treatment, hyperthermia and paclitaxel groups (all P<0.05), and the anti-proliferation and apoptosis-promoting effect in the combined treatment group was significantly better than those in the hyperthermia and paclitaxel groups (all P<0.05). Western blot showed that hyperthermia combined with paclitaxel could significantly up-regulate the expression level of Bax protein and significantly down-regulate the expression levels of P-AKT and Bcl-2 in CAL-27 cells (all P<0.05). Conclusions:Hyperthermia combined with paclitaxel can play a synergistic role in inhibiting proliferation and promoting apoptosis of tongue squamous cell carcinoma CAL-27 cells. The mechanism may be related to the inhibition of AKT activation and the activation of Bax/Bcl-2 apoptosis signaling pathway.
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Objective@#To examine the effect of early comprehensive interventions on the physical growth and nerve development among premature infants, so as to provide insights into the follow-up management of premature infants after discharge from hospital.@*Methods@#A total of 130 premature infants delivered in Shaoxing Municipal Maternal and Child Health Care Hospital from 2019 to 2021 were selected and divided into high- and low-risk groups according to gestational age and birth weight, while 306 full-term normal infants in the same hospital during the study period served as controls. All premature infants were given early comprehensive interventions until age of 12 months, including nutritional support and parental guidance of children's feeding and development, and all normal infants received periodical health checkup according to the basic public health service program. All infants received periodical measurements of height, weight and head circumference, and the 12-month intellectual and motor development ability was measured using the Bayley Scales of Infant Development revised in Chinese cities was used to assess. Infants' physical growth, mental development index (MDI) and motor development index (PDI) were compared among groups.@*Results@#There were 130 premature infants with gestational ages of 28 to 36 weeks and birth weight of 1 200 to 3 440 g, including 79 male infants, and there were 80 infants in the low-risk group and 50 infants in the high-risk group. The full-term infants had a gestational age of 37 to 42 weeks, and birth weights of 2 500 to 4 000 g, including 162 male infants. There were significant differences in height (Wald χ2=28.664, P<0.001) and head circumference growth (Wald χ2=19.312, P=0.013) among the three groups as revealed by the generalized estimating equation; however, no significant differences were seen in the 12-month weight (F=0.639, P=0.528), height (F=1.051, P=0.350) or head circumference (F=0.318, P=0.728) among the three groups. The percentages of abnormal MDI were 2.00%, 0 and 1.31% among the high-risk premature infants, low-risk premature infants and full-term infants at ages of 12 months (χ2=1.319, P=0.517), while the percentages of abnormal PDI were 20.00%, 7.50% and 5.56% among the three groups at ages of 12 months (χ2=12.818, P=0.002).@*Conclusions@#Following implementation of early comprehensive interventions, the premature infants have favorable physical growth and comparable MDI with full-term infants; however, a high percentage of abnormal PDI is seen in high-risk premature infants. An improvement in the motor development among high-risk premature infants is recommended to be emphasized during the management of premature infants.
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In recent years, tumor hyperthermia has become a hot research topic as an adjuvant therapy to traditional tumor therapy. Hyperthermia can directly induce tumor cell necrosis or apoptosis, or inhibit tumor progression by destroying tumor blood vessels. Meantime, it can also activate the response of immune cells and cytokines in the immune system of the host, thereby regulating the immune state of tumor microenvironment. Multiple combined effects influence the tumor progression. A thorough understanding of the biological mechanism of hyperthermia is beneficial to the development of novel therapeutic methods. In this paper, the biological mechanism of hyperthermia in killing tumors was mainly reviewed.
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With the in-depth study of tumor hyperthermia and tumor immune microenvironment (TIME), the role of hyperthermia in TIME has captivated increasing attention from scholars in recent years. Based upon recent research progress at home and abroad, the effect and mechanism of hyperthermia on several major immune cells and immune-related cytokines in the TIME were reviewed in this article. Comprehensive and deep understanding of the regulation of hyperthermia on the TIME could provide new ideas and methods for tumor treatment.
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In current study, adefovir dipivoxil (AD)-acetaminophen (AP) cocrystal (molar ratio, 1:1) was prepared by slow evaporation from acetonitrile, followed by physicochemical characterizations using differential scanning calorimetry, powder X-Ray diffraction and Fourier transform infrared spectroscopy. Molecular modeling showed that the phosphoester group of AD was connected with the amide group of AP through hydrogen bonds. In comparison to crystalline AD, the solubility and dissolution rate of AD from AD-AP cocrystal were significantly enhanced by 1.5-fold and 1.6-fold, respectively. In addition, based on the rat single-pass intestinal perfusion study, the permeabilities of AD in various intestinal sections (i.e., duodenum, jejunum, ileum and colon) were significantly improved (e.g., about 3-fold enhancement in duodenum) after cocrystallization with AP by inhibiting P-glyprotein mediated efflux of AD, which will benefit absorption in vivo and subsequent oral bioavailability of poorly permeable drug AD.
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OBJECTIVE: Cellular, animal, and human epidemiological studies suggested that benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also clearly linked to carcinogenesis. However, no human studies have examined benzodiazepine-associated carcinogenesis as assessed by changes in cancer biomarkers. METHODS: A total of 19 patients were recruited, and received a 6-week treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2 (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen activator inhibitor (PLGF), placental growth factor, transforming growth factor (TGF)-α, tumor necrosis factor (TNF)-α, urokinase-type plasminogen (uPA), vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D. RESULTS: Six cancer biomarkers were significantly increased in all patients as a whole. The subgroup analysis revealed a distinct pattern of change. Overweight patients showed a significant increase in 11 cancer biomarkers, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D. However, normal-weight patients did not show any changes in cancer biomarkers. CONCLUSION: Adiposity may have primed the carcinogenic potential, leading to lorazepam-associated carcinogenesis in overweight patients. Epidemiological studies addressing this issue should consider the potential modulator contributing to benzodiazepine-associated carcinogenesis.
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Animals , Humans , Adiposity , Angiopoietin-2 , Benzodiazepines , Biomarkers, Tumor , Carcinogenesis , Carrier Proteins , CD40 Ligand , Epidemiologic Studies , Epidermal Growth Factor , Fas Ligand Protein , Heparin-binding EGF-like Growth Factor , Interleukin-18 , Interleukin-8 , Interleukins , Lorazepam , Mortality , Obesity , Overweight , Plasminogen , Plasminogen Activators , Transforming Growth Factors , Tumor Necrosis Factor-alpha , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor C , Vascular Endothelial Growth Factor DABSTRACT
Objective To observe and analyze the clinical outcomes of perfluoropropane (C3 Fs) injection and laser photocoagulation on myopic foveoschisis.Methods A total of 14 patients (18 eyes) diagnosed as myopic foveoschisis were enrolled in this retrospective study.All patients received intraocular tamponade of 0.5-0.7 mL C3 F8,and after 1 week,underwent macular photocoagulation.These patients were given the best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination for central foveal thickness (CFT) and maximal macular thickness (MMT) before and after treatment.Results OCT examination showed that the mean CFT decreased significantly from (494.00 ±454.80) iμm before treatment to (193.61 ± 97.42) μm at the last follow-up,with statistical significance (P =0.01),and the mean MMT decreased from (687.33 ± 385.15)pμn to (331.06 ± 109.31)μm at the same duration,approaching significant difference (P =0.001).The foveoschisis healed completely and partially in 14 eyes at the last follow-up,the mean CFT decreased significantly from (567.36 ±493.01) μm before treatment to (171.43 ± 90.84) μm after treatment,with statistical significance (P =0.006),and the mean MMT decreased from (744.14 ± 417.38)μm to (303.86 ± 8.62)prn at the same duration,approaching significant difference (P =0.002).Patients' BCVA before treatment was (0.94 ± 0.39) logMAR,of which 13 eyes had BCVA < 0.6 logMAR,and increased to (0.92 ± 0.36) logMAR at the last follow-up,with no significant difference (P =0.78).The foveoschisis healed completely and partially in 14 eyes,and the BCVA was (1.04 ± 0.37) logMAR before treatment,up to (0.90 ± 0.34) logMAR after treatment,and the difference was not statistically significant (P =0.16).At the last follow-up,the vision of 4 eyes was increased by 2 lines and above,and unchanged in 10 eyes.All patients had no visual symptoms such as dark spots and no increase in intraocular pressure after treatment.Conclusion Intraocular C3 F8 tamponade and macular photocoagulation can be an satisfying alternative treatment for patients with myopic foveoschisis.
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Objective To analyze the specific peptide of cystatin C (CysC) and its characteristics by bioinformatics technology,and verify the predicted results by mass spectrometry.Methods Online software was applied to analyze the physicochemical properties and homology of CysC peptides hydrolyzed by trypsin and predict the associated parameters of ionized fragmentation of specific peptide by mass spectrometry.Precursor ion scan and product ion scan were conducted on the samples of synthetic specific peptide.The recombinant human CysC and serum samples were analyzed by mass spectrometry after trypsin digestion.The results of analysis were compared with the outcomes predicted by bioinformatics.Results T3 (ALDFAVGEYNK) was considered as the specific peptide of CysC by software analysis.When selecting[M + 2H] 2 + for product ion scan,almost all the y and b ions of fragmentation were observed using tandem mass spectrometry (MS/MS),showing consistency with Skyline predictions.Moreover,both the peptides from the human recombinant CysC and serum sample following the trypsin digestion were eluted at the same time with the isotope-labeled T3 * under the fixed conditions.Conclusion Bioinformatics technology could be available for picking out the specific peptides of target protein quickly and efficiently and predicting the ionized fragmentation precisely by mass spectrometry scanning.
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Introduction: The phenotype and genotype of cancer cells portray hallmarks of cancer which may have clinical value. Cancer cell lines are ideal models to study and confirm these characteristics. We previously established two subtracted cDNA libraries with differentially expressed genes from an acute myeloid leukaemia patient with poor prognosis (PP) and good prognosis (GP). Objective: To compare gene expression of the leukaemia associated genes with selected biological characteristics in leukaemia cell lines and normal controls. Methodology: Expression of 28 PP genes associated with early fetal/embryonic development, HOX-related genes, hematopoiesis and aerobic glycolysis/ hypoxia genes and 36 GP genes involved in oxidative phosphorylation, protein synthesis, chromatin remodelling and cell motility were examined in B-lymphoid (BV173, Reh and RS4;11) and myeloid (HL-60, K562) leukaemia cell lines after 72h in culture as well as peripheral blood mononuclear cells from healthy controls (N=5) using semi-quantitative polymerase chain reaction (PCR) method. Cell cycle profiles were analysed on flow cytometry while MTT cytotoxicity assay was used to determine drug resistance to epirubicin. Results: Genes expressed significantly higher in B-lymphoid leukaemia cell lines compared to healthy controls were mostly of the GP library i.e. oxidative phosphorylation (3/10), protein synthesis (4/11), chromatin remodelling (3/3) and actin cytoskeleton genes (1/5). Only two genes with significant difference were from the PP library. Cancer associated genes, HSPA9 and PSPH (GP library) and BCAP31 (PP library) were significantly higher in the B-lymphoid leukemia cell lines. No significant difference was observed between myeloid cell lines and healthy controls. This may also be due heterogeneity of cell lines studied. PBMC from healthy controls were not in cell cycle. G2/M profiles and growth curves showed B-lymphoid cells just reaching plateau after 72 hour culture while myeloid cells were declining. IC50 values from cytotoxicity assay revealed myeloid cell lines had an average 13-fold higher drug resistance to epirubicin compared to B-lymphoid cell lines. Only CCL1, was expressed at least two-fold higher in myeloid compared to B-lymphoid cell lines. In contrast, MTRNR2, EEF1A1, PTMA, HLA-DR, C6orf115, PBX3, ENPP4, SELL, and IL3Ra were expressed more than 2-fold higher in B-lymphoid compared to myeloid cell lines studied here. Conclusion: Thus, B-lymphoid leukaemia cell lines here exhibited active, proliferating characteristics closer to GP genes. Higher expression of several genes in B-lymphoid compared to myeloid leukaemia cell lines may be useful markers to study biological differences including drug resistance between lineages.
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NeoplasmsABSTRACT
<p><b>BACKGROUND</b>Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice. Antipsychotic medications concurrent with antidepressant treatment are frequently used in major depression, but few studies have investigated trends and patterns of their use over time. This study aimed to examine the prescription patterns of antipsychotic medications for major depression in China from 2002 to 2012 and their association with treatment satisfaction and quality of life (QOL).</p><p><b>METHODS</b>A total of 3655 subjects with major depression treated in 45 Chinese psychiatric hospitals/centers nationwide were interviewed between 2002 and 2012. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects, satisfaction with treatment and QOL were recorded using a standardized protocol and data collection.</p><p><b>RESULTS</b>The frequency of antipsychotic use was 24.9% in the whole sample; the corresponding figures were 17.1%, 20.3%, and 32.8% in 2002, 2006, and 2012, respectively (χ2 = 90.3, df = 2, P < 0.001). Multiple logistic regression analyses revealed that patients on concurrent antipsychotics had significantly more delusions or hallucinations, longer illness duration, greater side effects, and more likely to be treated as inpatients and in major hospitals (i.e., Level-III hospital). Antipsychotic use was associated with lower treatment satisfaction while there was no significant difference with respect to physical and mental QOL between the antipsychotic and nonantipsychotic groups.</p><p><b>CONCLUSIONS</b>Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients' and relatives' satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.</p>
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Adult , Female , Humans , Male , Middle Aged , Antipsychotic Agents , Therapeutic Uses , Depressive Disorder, Major , Drug Therapy , Personal Satisfaction , Psychotropic Drugs , Therapeutic Uses , Quality of LifeABSTRACT
OBJECTIVE: Clozapine is one of the most commonly used antipsychotic drugs in China. To date, few studies have investigated the patterns the prescription of clozapine nationwide. The present study examined these patterns in China in 2006 and identified the demographic and clinical characteristics associated with the use of clozapine. METHODS: Using a standardized protocol and data collection procedure, we surveyed 5,898 patients with schizophrenia in 10 provinces with differing levels of economic development. RESULTS: Overall, clozapine had been prescribed for 31.9% (n=1,883) of the patients; however we found considerable variation among the 10 provinces. The frequency of clozapine use was highest in Sichuan (39.3%) and lowest in Beijing (17.3%). The mean daily dose of clozapine was 210.36+/-128.72 mg/day, and 25.1% of the patients were treated with clozapine in combination with other antipsychotics. Compared with the group not receiving clozapine, clozapine-user had been treated for longer durations and had experienced a greater number of relapses and hospitalizations. Furthermore, those in the clozapine-user had lower family incomes, were less able to seek psychiatric services, and more likely to be male and have a positive family history of schizophrenia. A multiple logistic regression analysis revealed that age, sex, professional help-seeking behaviors, duration of illness, economic status, educational level, and clinical manifestations were associated with the use of clozapine. CONCLUSION: Clozapine use is common in China. However, use of the antipsychotic varies among provinces, and demographic and clinical factors play important roles in the prescription of clozapine.
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Humans , Male , Antipsychotic Agents , China , Clozapine , Data Collection , Educational Status , Hospitalization , Logistic Models , Prescriptions , Recurrence , Sampling Studies , SchizophreniaABSTRACT
Alcohol withdrawal syndrome (AWS) is a rare complication associated with oral cancer operation. This article reported a case of AWS after resection of squamous cell cancer of the right floor of mouth combined with radical neck dissection and trapezius myocutaneous flap reconstruction. The discussion included diagnosis, treatment and prevention of AWS.
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Female , Humans , Alcohols , Carcinoma, Squamous Cell , Mouth Neoplasms , Neck Dissection , Plastic Surgery Procedures , Substance Withdrawal Syndrome , Surgical FlapsABSTRACT
OBJECTIVE: To investigate the patterns of antipsychotic use in China and to analyze the factors that influence antipsychotic prescriptions. METHODS: A standardized survey was conducted from May 20 to 24 2002 in five different regions of China with varying economic levels. The patterns of antipsychotic medication use were analyzed in a sample of 4,779 patients with schizophrenia. The survey gathered information on demographic characteristics, clinical profiles, and antipsychotic medications prescribed. Multiple logistic regression was used to analyze factors related to patterns of antipsychotic medication use. RESULTS: A plurality of patients with schizophrenia was treated with clozapine (39%); this was followed by risperidone, sulpride, chlorpromazine, perphenazine, and haloperidol. More than 56.3% of patients were treated with only one atypical antipsychotic. The mean daily dose of chlorpromazine was 365+/-253 mg (mean+/-standard deviation), and 6.5% of patients were treated with depot injections of typical antipsychotic medications. A total of 73.7% (n=3,523) of patients with schizophrenia received monotherapy, 24.8% (n=1,183) received two antipsychotics, 1.1% (n=52) received three antipsychotics, and one received four different antipsychotics. Patients often simultaneously received other classes of medications including anticholinergic agents, benzodiazepines, beta-blockers, antidepressants, and mood stabilizers. Economic status and clinical symptoms were the main factors that contributed to the patterns of antipsychotic prescription. CONCLUSION: The present study suggests that atypical antipsychotic medications, especially clozapine, are the primary psychiatric treatments of choice in the management of schizophrenia in China. Moreover, the economic status and clinical profile of the patient are the major factors affecting the prescription of antipsychotic medication.
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Humans , Antidepressive Agents , Antipsychotic Agents , Benzodiazepines , China , Chlorpromazine , Cholinergic Antagonists , Clozapine , Haloperidol , Logistic Models , Perphenazine , Prescriptions , Risperidone , SchizophreniaABSTRACT
Objective To seek the factors affecting distortion product otoac oustic emisson in newborn hearing screening. Methods All newborns in our hospital received hearing sc reening by DPOAE and wer e investigated for the factors such as: birth history, pregnancy history, family history, the social position of the family. All data were analysed by SPSS. Results 82.8%(3 242/3 944) newborns passed the hearing sc reening. Pass rates were h igher in right ears, female baby, monocyesis, normal or high birth weight and fo rceps delivery. The Results of the first hearing screening were correlated with birth weight,sex and fetus number by logistic regression. Conclusion The factors suc h as sex, ways of labor, fetus number, fetus age, and birth weight can affect t he results of first hearing screening significantly.
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By using ~3H—TdR incorporation and CTLL—2 cell line,we observed effects of RU486,anantagonist of type Ⅱ glucocorticoid receptor,on dexamethasone inhibition of lymphocyte prolifer-ation and interleukin—2(IL—2)production in rat spleen.It was shown that RU486 obviouslyantagonized the inhibitory actions of dexamethasone on lymphocyte proliferation and IL—2 pro-duction.By means of dot hybridization and Northern blot analysis,effects of dexamethasone andRU486 on IL—2 gene expression were investigated in lymphocytes of rat spleen.The datademonstrated that dexamethasone markedly decreased IL—2 mRNA production,RU486 alonedidn't affect IL-2 mRNA levels,but obviously reversed dexamethasone-mediated downregala-tion of IL—2 mRNA production in ConA—activated lymphocytes.These results suggest thatthe above effects of dexamethasone may be mediated by glucocorticoid receptor in lymphocytesof rat spleen.