Breaking Physical Barrier of Fibrotic Breast Cancer for Photodynamic Immunotherapy by Remodeling Tumor Extracellular Matrix and Reprogramming Cancer-Associated Fibroblasts.

Cancer-associated fibroblasts (CAFs) assist in breast cancer (BRCA) invasion and immune resistance by overproduction of extracellular matrix (ECM). Herein, we develop FPC@S, a photodynamic immunomodulator that targets the ECM, to improve the photodynamic immunotherapy for fibrotic BRCA. FPC@S combines a tumor ECM-targeting peptide, a photosensitizer (protoporphyrin IX) and an antifibrotic drug (SIS3). After anchoring to the ECM, FPC@S causes ECM remodeling and BRCA cell death by generating reactive oxygen species (ROS) in situ. Interestingly, the ROS-mediated ECM remodeling can normalize the tumor blood vessel to improve hypoxia and in turn facilitate more ROS production. Besides, upon the acidic tumor microenvironment, FPC@S will release SIS3 for reprograming CAFs to reduce their activity but not kill them, thus inhibiting fibrosis while preventing BRCA metastasis. The natural physical barrier formed by the dense ECM is consequently eliminated in fibrotic BRCA, allowing the drugs and immune cells to penetrate deep into tumors and have better efficacy. Furthermore, FPC@S can stimulate the immune system and effectively suppress primary, distant and metastatic tumors by combining with immune checkpoint blockade therapy. This study provides different insights for the development of fibrotic tumor targeted delivery systems and exploration of synergistic immunotherapeutic mechanisms against aggressive BRCA.

The involvement of RNA N6-methyladenosine and histone methylation modification in decidualization and endometriosis-associated infertility.

Defective decidualization of endometrial stromal cells (ESCs) in endometriosis (EM) patients leads to inadequate endometrial receptivity and EM-associated infertility. Hypoxia is an inevitable pathological process of EM and participates in deficient decidualization of the eutopic secretory endometrium. Enhancer of zeste homology 2 (EZH2) is a methyltransferase which catalyses H3K27Me3, leading to decreased expression levels of target genes. Although EZH2 expression is low under normal decidualization, it is abundantly increased in the eutopic secretory endometrium of EM and is induced by hypoxia. Chromatin immunoprecipitation-PCR results revealed that decidua marker IGFBP1 is a direct target of EZH2, partially explaining the increased levels of histone methylation modification in defected decidualization of EM. To mechanism controlling this, we examined the effects of hypoxia on EZH2 and decidualization. EZH2 mRNA showed decreased m6 A modification and increased expression levels under hypoxia and decidualization combined treatment. Increased EZH2 expression was due to the increased expression of m6 A demethylase ALKBH5 and decreased expression of the m6 A reader protein YTHDF2. YTHDF2 directly bind to the m6 A modification site of EZH2 to promote EZH2 mRNA degradation in ESCs. Moreover, selective Ezh2 depletion in mouse ESCs increased endometrial receptivity and improved mouse fertility by up-regulating decidua marker IGFBP1 expression. This is the first report showing that YTHDF2 can act as a m6 A reader to promote decidualization by decreasing the stability of EZH2 mRNA and further increasing the expression of IGFBP1 in ESCs. Taken together, our findings highlight the critical role of EZH2/H3K27Me3 in decidualization and reveal a novel epigenetic mechanism by which hypoxia can suppress EM decidualization by decreasing the m6 A modification of EZH2 mRNA.

Clinical data, survival, and prognosis of 426 cases of oropharyngeal cancer: a retrospective analysis.

OBJECTIVE: To determine factors influencing survival and prognosis of HPV-related and non-related oropharyngeal cancer. METHODS: Subjects were determined from the three hospitals in Anhui province of China between 2015 and 2020. Paraffin-embedded specimens from participants' tissues were analyzed, and the subjects were classified as P16 + and P16 - cases using immunohistochemical staining for P16 protein. RESULTS: A total of 426 patients with oropharyngeal cancer were recruited in this study; 108 cases were found to be P16 + . The subjects were treated with the three regimens: surgery/radiotherapy/chemotherapy (SRCT), radiotherapy/chemotherapy (RCT), and surgery/chemotherapy (SCT). There were no statistically significant differences in the survival rates within the P16 + or P16 - groups between the three treatment regimens (P > 0.05). The 1-, 3-, and 5-year survival rates for P16 + and P16 - groups were statistically different (P < 0.05). Multivariate analysis showed that age, physical health status, smoking, and alcohol abuse were independent risk factors affecting the prognosis of P16 + cases, while pathological grading and TNM staging were independent risk factors affecting the P16 - cases. CONCLUSION: The etiology, pathogenesis, survival status, and prognostic factors of HPV-related oropharyngeal cancer are very different from those of traditional oropharyngeal cancer. Thus, HPV-related oropharyngeal cancer could be classified as a separate type of disease. This distinction could be of great significance for treatment, prevention, and prognostication of oropharyngeal cancer.

Platelet-rich plasma alleviates knee arthritis in rats by inhibiting p65.

Knee osteoarthritis (KOA) is a chronic joint disease characterized by the degeneration of articular cartilage. In this study, we explored the potential therapeutic effects of platelet-rich plasma (PRP) and identified molecular targets for treating KOA. A rat model of KOA was established via the Hulth method and primary knee joint chondrocytes were isolated to evaluate the effects of PRP and shRNA targeting p65 (sh-p65). ELISA was used to detect inflammatory factors, including IL-6, IL-1ß, and TNF-α. HE staining, Safranin O/Fast Green staining and Masson staining were performed to evaluate the morphology of articular cartilage, followed by detection of p65, COL2A1, ACAN, MMP13, and ADAMTS5 expression. The proliferation and apoptosis of primary knee chondrocytes were detected by the CCK-8 assay and TUNEL staining, respectively. Treatment with either PRP or sh-p65 decreased IL-6, IL-1ß, and TNF-α levels in the peripheral blood of KOA rats and chondrocyte culture supernatants, increased COL2A1 and ACAN levels, and decreased MMP13 and ADAMTS5 expression. Furthermore, administration of PRP or sh-p65 exerted protective effects on articular cartilage, enhanced the vitality of knee joint chondrocytes, and inhibited apoptosis. Collectively, PRP inhibited inflammation, promoted chondrocyte proliferation and cartilage matrix secretion, and induced cartilage regeneration by suppressing p65 expression; these effects allow PRP to alleviate KOA progression. P65-based targeted therapy administered in combination with PRP might be a promising strategy for treating KOA.

Integrative analysis of transcriptomic and metabolomic profiles reveals abnormal phosphatidylinositol metabolism in follicles from endometriosis-associated infertility patients.

Endometriosis is a common gynecological disorder that causes female infertility. Our recent research found that excessive oxidative stress in ovaries of endometriosis patients induced senescence of cumulus granulosa cells. Here, we analyzed the transcriptomic and metabolomics profiles of follicles in a mouse model of endometriosis and in patients with endometriosis and investigated the potential function of changed metabolites in granulosa cells. RNA-sequencing indicated that both endometriosis lesions and oxidative stress in mice induced abnormalities of reactive oxidative stress, steroid hormone biosynthesis, and lipid metabolism. The mouse model and women with endometriosis showed altered lipid metabolism. Nontargeted metabolite profiling of follicular fluid from endometriosis and male-factor infertility patients by liquid chromatography mass spectrometry identified 55 upregulated and 67 downregulated metabolites. These differential metabolites were mainly involved in steroid hormone biosynthesis and glycerophospholipid metabolism. Phosphatidylinositol (PI 16:0/18:2) was significantly elevated in follicular fluid from endometriosis patients compared with controls (p < 0.05), while lysophosphatidylinositol (LPI 18:2, 20:2, 18:1, 20:3 and 18:3) was reduced (p < 0.05). Upregulated PI and downregulated LPI correlated with oocyte retrieval number and mature oocyte number. LPI inhibited cellular reactive oxidative stress induced by hemin in granulosa cells. Cell proliferation inhibition, senescence, and apoptosis induced by hemin were partially reversed by LPI. Moreover, LPI administration rescued hemin blocking of cumulus-oocyte complex expansion and stimulated expression of ovulation-related genes. Transcriptomic Switching mechanism at 5' end of the RNA transcript sequencing and western blot revealed that LPI effects on granulosa cells were associated with its regulation of MAPK-ERK1/2 signaling, which was suppressed in the presence of hemin. In conclusion, our results revealed the dysregulation of lipid metabolism in endometriotic follicles. LPI may represent a novel agent for in vitro follicular culture that reverses the excessive oxidative stress from endometriotic lesions. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

[Analysis of the effect of free posterior lateral peroneal artery perforator flap of lower leg in repairing oropharyngeal cancer].

Objective:To analyze the clinical effect of free posterior lateral peroneal artery perforator flap of lower leg in repairing postoperative defect of oropharyngeal carcinoma. Methods:Thirty-six patients with oropharyngeal carcinoma admitted to the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Bengbu Medical College from June 2016 to June 2019 were analyzed and followed up, eighteen patients were treated with free posterior lateral peroneal artery perforator flap of the lower leg to repair the postoperative defects（experimental group）, and eighteen patients were treated with free forearm flap（control group）. The survival rate of the transplanted flap, the wound stageⅠhealing rate and average hospitalization time were compared between the two groups. Kaplan-Meier method was used to calculate the 1-year and 3-year survival rates of patients after operation, and log-rank test was used to compare the difference between the survival curves of the two groups; The recovery of swallowing and palatopharyngeal closure function of patients in the two groups at 3, 6, 12 and 18 months after operation was calculated and statistically analyzed through the water swallow test and the air blowing method. Results:There was one case of skin flap necrosis in both the experimental group and the control group, and the survival rate was 94.4%. The wound stageⅠhealing rate in the surgical area was 94.4% in both groups. The wound healing rates of the donor area in the experimental group and the control group were 100.0% and 94.4% respectively. The average hospitalization time of the experimental group and the control group was 16.9 days and 17.2 days, respectively, with no significant difference （P>0.05）. The overall survival rates of all patients at 1-year and 3-year were 91.2% and 66.5% respectively; The 1-year and 3-year survival rates of the experimental group and the control group were 94.1%, 69.3% and 88.2%, 63.7%, respectively, and there was no significant difference between the two groups （P>0.05）. The 1-year and 3-year survival rates of P16+ and P16 - patients were 100.0%, 80.0% and 85.7%, 64.3%, respectively, and there was no significant difference between the two groups （P>0.05）. There was no significant difference in the evaluation of swallowing and velopharyngeal closure function between the two groups at 3 and 6 months after operation （P>0.05）, but there was a significant difference at 12 and 18 months after operation （P<0.05）. Conclusion:The anatomic position of the perforating vessels of the free posterior lateral peroneal artery perforator flap of the lower leg is constant, and it can be prepared into single leaf, multi leaf, chimeric and other flaps according to the tissue defect space. And the concealed supply area can be directly drawn to suture. At the same time, the skin flap has strong plasticity. Therefore, the skin flap can be used as a common skin flap to repair the defects after the operation of oropharyngeal carcinoma.

Recent advances in bacterial therapeutics based on sense and response

Intelligent drug delivery is a promising strategy for cancer therapies. In recent years, with the rapid development of synthetic biology, some properties of bacteria, such as gene operability, excellent tumor colonization ability, and host-independent structure, make them ideal intelligent drug carriers and have attracted extensive attention. By implanting condition-responsive elements or gene circuits into bacteria, they can synthesize or release drugs by sensing stimuli. Therefore, compared with traditional drug delivery, the usage of bacteria for drug loading has better targeting ability and controllability, and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs. This review mainly introduces the development of bacterial-based drug delivery carriers, including mechanisms of bacterial targeting to tumor colonization, gene deletions or mutations, environment-responsive elements, and gene circuits. Meanwhile, we summarize the challenges and prospects faced by bacteria in clinical research, and hope to provide ideas for clinical translation.

Decreased Expression of EZH2 in Granulosa Cells Contributes to Endometriosis-Associated Infertility by Targeting IL-1R2.

The mechanism by which endometriosis, a common gynecological disease characterized by chronic pelvic pain and infertility, causes infertility remains elusive. Luteinized unruptured follicle syndrome, the most common type of ovulatory dysfunction, is a cause of endometriosis-associated infertility involving reduced numbers of retrieved and mature oocytes. Ovulation is controlled by luteinizing hormone and paracrine signals produced within the follicle microenvironment. Generally, interleukin (IL)-1ß is elevated in endometriosis follicular fluid, whereby it amplifies ovulation signals by activating extracellular-regulated kinase 1/2 and CCAAT/enhancer binding protein ß pathways. However, this amplification of ovulation by IL-1ß does not occur in patients with endometriosis. To illuminate the mechanism of ovulatory dysfunction in endometriosis, we analyzed the effect of oxidative stress and IL-1ß expression on endometriosis follicles. We found that oxidative stress decreased EZH2 expression and reduced H3K27Me3 levels in endometriosis ovarian granulosa cells (GCs). Selective Ezh2 depletion in mice ovarian GCs reduced fertility by disturbing cumulus-oocyte complex expansion and reducing epidermal growth factor-like factor expression. Gene expression and H3K27Me3 ChIP-sequencing (ChIP-Seq) of GCs revealed IL-1 receptor 2 (IL-1R2), a high-affinity IL-1ß-receptor that suppresses IL-1ß-mediated inflammatory cascades during ovulation, as a crucial target gene of the EZH2-H3K27Me3 axis. Moreover, IL-1ß addition did not restore ovulation upon Ezh2 knockdown, indicating a vital function of IL-1R2 in endometriosis. Thus, our findings show that reducing EZH2 and H3K27Me3 in GCs suppressed ovulatory signals by increasing IL-1R2 expression, which may ultimately contribute to endometriosis-associated infertility.

Development and Validation of Diagnostic Models for Hand-Foot-and-Mouth Disease in Children.

OBJECTIVE: To find risk markers and develop new clinical predictive models for the differential diagnosis of hand-foot-and-mouth disease (HFMD) with varying degrees of disease. METHODS: 19766 children with HFMD and 64 clinical indexes were included in this study. The patients included in this study were divided into the mild patients' group (mild) with 12292 cases, severe patients' group (severe) with 6508 cases, and severe patients with respiratory failure group (severe-RF) with 966 cases. Single-factor analysis was carried out on 64 indexes collected from patients when they were admitted to the hospital, and the indexes with statistical differences were selected as the prediction factors. Binary multivariate logistic regression analysis was used to construct the prediction models and calculate the adjusted odds ratio (OR). RESULTS: SP, DP, NEUT#, NEUT%, RDW-SD, RDW-CV, GGT, CK/CK-MB, and Glu were risk markers in mild/severe, mild/severe-RF, and severe/severe-RF. Glu was a diagnostic marker for mild/severe-RF (AUROC = 0.80, 95% CI: 0.78-0.82); the predictive model constructed by temperature, SP, MOMO%, EO%, RDW-SD, GLB, CRP, Glu, BUN, and Cl could be used for the differential diagnosis of mild/severe (AUROC > 0.84); the predictive model constructed by SP, age, NEUT#, PCT, TBIL, GGT, Mb, ß2MG, Glu, and Ca could be used for the differential diagnosis of severe/severe-RF (AUROC > 0.76). CONCLUSION: By analyzing clinical indicators, we have found the risk markers of HFMD and established suitable predictive models.

Different Numbers of Long-Pulse 1064-nm Nd-YAG Laser Treatments for Onychomycosis: A Pilot Study.

PURPOSE: To examine the benefits of different numbers of 1064-nm Nd-YAG laser treatments in patients with onychomycosis. METHODS: This was a pilot study of patients with onychomycosis who were divided into three groups: four treatment sessions (group A), eight sessions (group B), and 12 sessions (group C). Only infected nails of degrees II-III (Scoring Clinical Index for Onychomycosis) were included. Treatment was given once a week using a long-pulse Nd-YAG 1064-nm laser. Patients were followed at 8, 16, and 24 weeks after the first treatment. Side effects were recorded. RESULTS: Treatments were completed for 442 nails in 102 patients. The efficacy rates at 8, 16, and 24 weeks were 35.5%, 38.7%, and 37.4% for group A; 31.4%, 41.7%, and 44.0% for group B; and 27.7%, 50.0%, and 55.4% for group C, respectively. There was a significant difference in the efficacy rate at 24 weeks (P = 0.016) between groups A and C, but not for groups A vs. B, or for groups B vs. C. No difference in the efficacy rate at 8 or 16 weeks was observed among the three groups. In all three groups, the efficacy was better for degree II nails than for degree III nails (all P = 0.016) between groups A and C, but not for groups A vs. B, or for groups B vs. C. No difference in the efficacy rate at 8 or 16 weeks was observed among the three groups. In all three groups, the efficacy was better for degree II nails than for degree III nails (all. CONCLUSIONS: The 1064-nm Nd-YAG laser had clinical benefits against onychomycosis. Higher numbers of treatments provided better long-term (24-week) benefits, but had no impact on the short-term outcomes. The efficacy of laser treatment on degree II onychomycosis was better than for degree III.

The effect of arbuscular mycorrhizal fungi and biochar on the growth and Cd/Pb accumulation in Zea mays.

A greenhouse pot experiment was conducted to assess the effects of biochar (BC) and arbuscular mycorrhizal fungus (AMF)-Funneliformis mosseae (Fm), Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on the plant growth and Cd/Pb accumulation by corn grown in the soils artificially contaminated with 5 mg Cd and 300 mg Pb kg-1 soil. The single AMF inoculation and combined usage of AMF and BC evidently improved the P contents of maize. Furthermore, the combined use of AMF and BC produced pronounced positive effect on corn growth, and the shoot biomass in Gv + BC group was 9.85-fold higher than that of the control. Meanwhile, the single BC addition and combined utilization of AMF and BC significantly reduced Cd and Pb concentrations in maize, and the greater reduces were found in the combined utilization, and the lowest Cd concentration of shoot was appeared in Gv + BC group. The single BC addition and combined application of AMF and BC significantly increased soil pH, and reduced soil diethylenetriaminepentaacetic acid (DTPA)-extractable Cd/Pb. This study demonstrated a synergistic effect between AMF (Gv, Fm, Ri) and BC on improving maize growth and decreasing Cd/Pb accumulation in maize, and the combined use of Gv and BC brought the most pronounced effect, which could provide a feasible strategy for safe production of maize from Cd/Pb-polluted soils.

Additive Effects of VDBP and 1,25(OH)2D3 on the Viability and Apoptosis of Rheumatoid Arthritis Synovial Fibroblasts.

Aim: This study is to investigate the additive effect of Vitamin D-binding protein (VDBP) and 1,25(OH)2D3 on the viability and apoptosis of synovial cells from patients with rheumatoid arthritis (RA). Methods: Synovial tissues and synovial fluid of patients with RA and osteoarthritis (OA) were collected. The expression of VDBP was analyzed with immunohistochemistry and ELISA. CCK-8 assay was applied to detect cell viability. Flow cytometry was used to analyze cell cycle and apoptosis. Results: Immunohistochemical results showed that the expression of VDBP in the synovium of RA patients was significantly lower than that of OA (P<0.05). Similarly, ELISA results presented a lower expression of VDBP in the synovial fluid of RA patients. The results of CCK-8 assay showed that both 1,25(OH)2D3 and VDBP significantly inhibited the viability of rheumatoid arthritis synovial fibroblasts (RASF) (P<0.05). The treatment with 1,25(OH)2D3+VDBP led to more significantly inhibited viability of RASF, compared with 1,25(OH)2D3 alone (P<0.05). The results of flow cytometry showed that 1,25(OH)2D3 and VDBP both promoted the apoptosis of RASF (P<0.05) and 1,25(OH)2D3+VDBP led to a higher proportion of RASF apoptosis, compared with 1,25(OH)2D3 alone (P<0.05). However, 1,25(OH)2D3 and VDBP had no significant effect on the cell cycle of RASF. Additionally, 1,25(OH)2D3 promoted the expression of VDBP in RASF, but not concentration-dependently. Conclusion: VDBP is reduced in the synovial tissue and synovial fluid of RA patients and can inhibit viability of RASF and promote the apoptosis of RASF. The 1,25(OH)2D3 can upregulate the expression of VDBP in RASF. Additionally, VDBP can enhance the effects of 1,25(OH)2D3 on viability and apoptosis of RASF.

The role of salvage radiotherapy in re-treatment of esophageal squamous cell carcinoma with regional lymph node oligo-recurrence after surgery / 中华放射肿瘤学杂志

Objective:To evaluate the role of salvage radiotherapy in the re-treatment of patients with regional lymph node oligo-recurrence after radical surgery for esophageal squamous cell carcinoma.Methods:Clinical data of patients diagnosed with thoracic esophageal squamous cell carcinoma treated with radical surgery and developed regional lymph node oligo-recurrence ( n=1-3) from January 2013 to January 2016 were retrospectively analyzed. A total of 74 cases with intact clinical data were extracted for analysis. The survival analysis was performed by Kaplan-Meier method. Group comparison was conducted by Log-rank method. Results:The median overall survival (OS) after recurrence was 9(2.5-43) months, and the median progression-free survival time (PFS) was 4(1-33) months. There were 47 cases in the salvage radiotherapy group and 27 cases in the non-radiotherapy group, and the objective response rates were 77%(36/47) and 30%(8/27), respectively. Patients in the salvage radiotherapy group had better OS ( P=0.042) and PFS ( P=0.01) compared with their counterparts in the non-radiotherapy group. Among the patients who received salvage radiotherapy, involved field irradiation and elective nodal irradiation yielded similar OS ( P=0.963) and PFS ( P=0.599), and patients treated an irradiation dose ≥ 60Gy had better OS ( P=0.001) and PFS ( P=0.001) compared with those with dose< 60Gy. Conclusions:Local salvage radiotherapy is an effective treatment of esophageal squamous cell carcinoma with regional lymph node oligo-recurrence after radical surgery. Salvage radiotherapy has better OS and PFS compared with non-radiotherapy. Prospective clinical studies should be carried out to standardize the target and dose of radiotherapy, and to further clarify the effect of radiotherapy.

Analysis of recurrence pattern of neoadjuvant therapy combined with surgical treatment for esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective To evaluate the recurrence pattern and identify the risk factors of esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.Methods Clinical data of 275 patients with thoracic esophageal squamous cell carcinoma treated with neoadjuvant therapy combined with surgery from December 2011 to December 2015 were retrospectively analyzed.The follow-up data of the enrolled patients were complete and analyzable.The recurrence pattern,recurrence time,recurrence location and influencing factors after neoadjuvant therapy in combination with surgery were analyzed.The recurrence rate was calculated by Kaplan-Meier method.The multivariate analysis was performed by Cox regression model.Results The median follow-up time was 32 (3-84) months,and the median time of the first recurrence was 10.6(2.0-69.1) months.The 1-,2-and 3-year recurrence rates were 32.0％,45.1％ and 52.3％,respectively.A total of 152 cases (55.3％) had recurrence.Among them,77 cases (50.6％) had local-regional recurrence (LRR),34 cases (23.4％) had distant metastasis (DM),33 cases (21.7％) had LRR+DM and 8 cases (6.0％) had recurrence in unknown site.Among the patients with LRR,lymph node recurrence was the most common (n =98,89.1％).For DM patients,lung metastasis (n =33,49.3％),liver metastasis (n=16,23.9％),bone metastasis (n=14,20.9％) and non-regional lymph node metastasis (n=14,20.9％) were commonly observed.The multivariate analysis showed that postoperative T stage (P=0.008),N stage (P＜0.001) and the number of lymph node dissection (P＜0.001) were the independent risk factors for recurrence after treatment.Conclusions The recurrence rate after neoadjuvant therapy remains relatively high for esophageal squamous cell carcinoma,and the regional lymph node is the most common site of recurrence.Postoperative pathological T staging,N staging and the number of lymph node dissection are the independent risk factors for recurrence after treatment.

Prognostic analysis of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgical treatment / 中华放射肿瘤学杂志

Objective To evaluate the clinical efficacy and prognostic factors of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.Methods From December 2011 to December 2015,152 cases of recurrent thoracic esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery were retrospectively analyzed.The overall survival (OS) after treatment failure,clinical efficacy and prognostic factors of different salvage treatments were analyzed.OS was calculated by Kaplan-Meier method.Prognostic analysis was performed by using multivariate Cox regression model.Results The median interval of the first recurrence was 10.6(2.0 to 69.1) months.The median OS after recurrence was 8.0(0.8 to 43.3) months.The 1-,2-and 3-year OS rates after recurrence were 36.0％,15.1％ and 5.2％,respectively.The median OS of patients with locoregional recurrence alone,distant metastasis alone and locoregional recurrence combined with distant metastasis was 11.3(1.8 to 43.3) months,6.7(1.2 to 28.6) months and 5.1 (0.8 to 22.9) months,respectively.Multivariate analysis demonstrated that neoadjuvant chemotherapy (P=0.009),ypTNM stage (P=0.012),comprehensive treatment after recurrence (P=0.000) and locoregional recurrence (P=0.026) were independently correlated with the OS of patients with recurrent esophageal squamous cell carcinoma.Conclusions Neoadjuvant therapy,ypTNM stage,recurrence pattern and postrecurrence treatment are the independent risk factors for clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.Clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy is not satisfactory.After recurrence,combined treatment mode should be adopted according to the site of recurrence and neoadjuvant treatment mode to maximize the benefits of salvage treatment.

Prognostic analysis of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgical treatment / 中华放射肿瘤学杂志

Objective@#To evaluate the clinical efficacy and prognostic factors of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.@*Methods@#From December 2011 to December 2015, 152 cases of recurrent thoracic esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery were retrospectively analyzed. The overall survival (OS) after treatment failure, clinical efficacy and prognostic factors of different salvage treatments were analyzed. OS was calculated by Kaplan-Meier method. Prognostic analysis was performed by using multivariate Cox regression model.@*Results@#The median interval of the first recurrence was 10.6(2.0 to 69.1) months. The median OS after recurrence was 8.0(0.8 to 43.3) months. The 1-, 2-and 3-year OS rates after recurrence were 36.0%, 15.1% and 5.2%, respectively. The median OS of patients with locoregional recurrence alone, distant metastasis alone and locoregional recurrence combined with distant metastasis was 11.3(1.8 to 43.3) months, 6.7(1.2 to 28.6) months and 5.1(0.8 to 22.9) months, respectively. Multivariate analysis demonstrated that neoadjuvant chemotherapy (P=0.009), ypTNM stage (P=0.012), comprehensive treatment after recurrence (P=0.000) and locoregional recurrence (P=0.026) were independently correlated with the OS of patients with recurrent esophageal squamous cell carcinoma.@*Conclusions@#Neoadjuvant therapy, ypTNM stage, recurrence pattern and post-recurrence treatment are the independent risk factors for clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery. Clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy is not satisfactory. After recurrence, combined treatment mode should be adopted according to the site of recurrence and neoadjuvant treatment mode to maximize the benefits of salvage treatment.

Germacrone alleviates collagen-induced arthritis via regulating Th1/Th2 balance and NF-κB activation.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. The imbalance of T helper type 1 (Th1) and Th2 immune responses contributes to the pathogenesis of this disease. Germacrone is a major bioactive component isolated from Rhizoma Curcuma with multiple bioactivities including anti-inflammation. However, the role and mechanism of germacrone in RA are still unknown. Collagen-induced arthritis (CIA) model was established in male DBA/1 J mice by two immunizations with chicken collagen II. Germacrone was orally administered once per day starting on the day of second immunization for 3 weeks. Arthritis scoring was evaluated every 3 days after second immunization. H&E staining was used for histopathological examination. Levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-4 in serum and synovial tissues of mice were detected by ELISA. Th1 and Th2 cell percentage in mouse spleens was analyzed by flow cytometry. IκB and phosphorylation of NF-κB p65 (p-p65) expression in mouse synovial tissues was assayed by Western blot. We found germacrone treatment significantly reduced arthritis score and inflammation in CIA mice. Levels of TNF-α and IFN-γ were elevated, and IL-4 reduced, in the serum and synovial tissues of CIA mice. Germacrone partially reversed levels of these cytokines. Moreover, germacrone decreased the ratio of Th1 to Th2 cells in mouse spleens. Additionally, germacrone remarkably enhanced IκB expression, but suppressed p-p65 level in CIA mice. Taken together, these results suggest that germacrone alleviated the progression of arthritis that might be related to the regulation of Th1/Th2 balance and inactivation of NF-κB pathway.

Combined application of arbuscular mycorrhizal fungi and steel slag improves plant growth and reduces Cd, Pb accumulation in Zea mays.

Little attention has been paid to the combined use of arbuscular mycorrhizal fungus (AMF) and steel slag (SS) for ameliorating heavy metal polluted soils. A greenhouse pot experiment was conducted to study the effects of SS and AMF-Funneliformis mosseae (Fm), Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on plant growth and Cd, Pb uptake by maize grown in soils added with 5 mg Cd kg-1 and 300 mg Pb kg-1 soil. The combined usage of AMF and SS (AMF + SS) promoted maize growth, and Gv + SS had the most obvious effect. Meanwhile, single SS addition and AMF + SS decreased Cd, Pb concentrations in maize, and the greater reductions were found in combined utilization, and the lowest Cd, Pb concentrations of maize appeared in Gv + SS. Single SS amendment and AMF + SS enhanced soil pH and decreased soil diethylenetriaminepentaacetic acid (DTPA)-extractable Cd, Pb concentrations. Furthermore, alone and combined usage of AMF and SS increased contents of soil total glomalin. Our research indicated a synergistic effect between AMF and SS on enhancing plant growth and reducing Cd, Pb accumulation in maize, and Gv + SS exerted the most pronounced effect. This work suggests that AMF inoculation in combination with SS addition may be a potential method for not only phytostabilization of Pb-Cd-contaminated soil but maize safety production.