[Comparative analysis of clinical efficacy between posterior percutaneous endoscopic discectomy and anterior cervical discectomy and fusion in the treatment of cervical spondylotic radiculopathy].

OBJECTIVE: To explore the clinical efficacy of posterior percutaneous endoscopic discectomy(PPECD) in the treatment of cervical spondylotic radiculopathy. METHODS: A total of 56 patiens with single segment cervical spondylotic radiculopathy from December 2017 to October 2020, were randomly divided into observation group and control group. In observation group, there were 16 males and 11 females, including 8 cases of C4,5, 13 cases of C5,6 and 6 cases of C6,7 performed posterior percutaneous endoscopic discectomy, aged from 34 to 61 years old with an average of (51.15±6.29) years old. In control group, there were 19 males and 10 females with single segment cervical spondylotic radiculopathy including 10 cases of C4,5, 14 cases of C5,6 and 5 cases of C6,7 performed anterior cervical discectomy and fusion, aged from 40 to 65 years old with an average of (53.24±5.31) years old. The operative time, intraoperative blood loss, postoperative time of lying in bed and length of postoperative hospital stay were recorded. Visual analogue scale(VAS) and neck disability index(NDI) were used to evaluate the clinical efficacy. Cervical plain films or MRIs, CTs were taken for re-visiting patients. RESULTS: All patients were followed up more than 2 years. The observation group patients were followed up, the duration ranged from 24 to 42 months with an average of (30.48±4.91) months. The control group patients were followed up, the duration ranged from 25 to 47 months, with an average of (32.76±4.53) months. Compared with control group, operative time, intraoperative blood loss, postoperative time of lying in bed and length of postoperative hospital stay were decreased(P<0.05). Compared with pre-operation, VAS of neck and upper limb and NDI at the latest follow-up between two groups were significantly improved(P<0.05). Compared with control group, VAS of neck and upper limb at 1 day after operation in observation group were significantly reduced(P<0.05). There was no significant difference in VAS of neck and upper limb and NID at 1, 3 months and the latest follow-up after operation between two groups(P>0.05). In the observation group, one patient's deltoid muscle strength was weakened to grade 4 after operation, and returned to normal after 12 weeks of conservative treatment. In control group, there was 1 case of postoperative adjacent spondylosis with symptoms of spinal compression after 2 years operation, then underwent cervical artificial intervertebral disc replacement. And there was 1 case of dysphagia after operation in control group and improved after 1 year. There was no significant difference in incidence of complications between two groups. CONCLUSION: PPECD has advantages of shortening operative time, decreasing intraoperative blood loss, reducing postoperative time of lying in bed and length of postoperative hospital stay. However, applicable age range of patients and long-term clinical efficacy needs further study.

Phosphatidylserine released from apoptotic cells in tumor induces M2-like macrophage polarization through the PSR-STAT3-JMJD3 axis.

BACKGROUND: Understanding how the tumor microenvironment is shaped by various factors is important for the development of new therapeutic strategies. Tumor cells often undergo spontaneous apoptotic cell death in tumor microenvironment, these apoptotic cells are histologically co-localized with immunosuppressive macrophages. However, the mechanism by which tumor cell apoptosis modulates macrophage polarization is not fully understood. In this study, we aimed to explore the tumor promoting effects of apoptotic tumor cells and the signal pathways involved. METHODS: Apoptotic cells and macrophages in tumors were detected by immunohistochemical staining. Morphological analysis was performed with Giemsa staining. Lipids generated from apoptotic cells were detected by liquid chromatography-mass spectrometry. Phosphatidylserine-containing liposomes were prepared to mimic apoptotic cells. The expression of protein was determined by real-time PCR, immunohistochemistry enzyme-linked immunosorbent assay and Western blotting. Mouse malignant ascites and subcutaneous tumor models were designed for in vivo analysis. Transgenic mice with specific genes knocked out and inhibitors specific to certain proteins were used for the mechanistic studies. RESULTS: The location and the number of apoptotic cells were correlated with that of macrophages in several types of carcinomas. Phosphatidylserine, a lipid molecule generated in apoptotic cells, induced polarization and accumulation of M2-like macrophages in vivo and in vitro. Moreover, sustained administration of phosphoserine promoted tumor growth in the malignant ascites and subcutaneous tumor models. Further analyses suggested that phosphoserine induced a M2-like phenotype in macrophages, which was related to the activation of phosphoserine receptors including T-cell immunoglobin mucin 4 (TIM4) and the FAK-SRC-STAT3 signaling pathway as well as elevated the expression of the histone demethylase Jumonji domain-containing protein 3 (JMJD3). Administration of specific inhibitors of these pathways could reduce tumor progression. CONCLUSIONS: This study suggest that apoptotic cell-generated phosphoserine might be a notable signal for immunosuppressive macrophages in tumors, and the related pathways might be potential therapeutic targets for cancer therapy.

Atractylenolide inhibits apoptosis and oxidative stress of HTR-8/SVneo cells by activating MAPK/ERK signalling in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a severe hypertension-related disorder occurring during pregnancy that leads to significant mortality and morbidity in both the foetus and mother. Atractylenolide (ATL), a traditional Chinese natural agent isolated from the herb Atractylodes macrocephala, exhibits a series of pharmacological activities, including anti-oxidative stress and anti-inflammatory effects. PURPOSE: The impacts of ATL on apoptosis and oxidative stress in HTR-8/SVneo cells during PE development was investigated. STUDY DESIGN: We identified ATL by an overlap analysis of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database using the keyword 'gestational hypertension' and Traditional Chinese Medicine (Batman-TCM) database using the keyword 'Atractylodes macrocephala'. METHODS: Cell viability, proliferation, and migration were detected by CCK-8, EdU, and transwell assays. Flow cytometry and 2',7'-dichlorodihydrofluorescein diacetate were used to assess apoptosis and reactive oxygen species (ROS) levels. RESULTS: EdU and CCK-8 assays demonstrated that ATL significantly enhanced the viability of HTR-8/SVneo cells. Transwell assays showed that ATL remarkably induced the migration of HTR-8/SVneo cells. Moreover, ROS production in HTR-8/SVneo cells was induced by H2O2, whilst ATL alleviated this H2O2-induced ROS production and apoptosis in cells. CONCLUSION: ATL attenuated apoptosis and oxidative stress in HTR-8/SVneo cells in PE by activating the MAPK/ERK signalling pathway. ATL has potential to be utilized as a potential therapeutic candidate for PE.

Nested Case-Control Study of Corin Combined with sFlt-1/PLGF in Predicting the Risk of Preeclampsia.

BACKGROUND: Preeclampsia (PE), a serious pregnancy disorder, is responsible for maternal and fetal mortality worldwide. At present, numerous candidate biomarkers have been studied to predict PE. OBJECTIVE: To explore the role of Corin in PE risk prediction and then evaluate the predictive ability of soluble vascular endothelial growth factor receptor-1 (sFlt-1), placenta growth factor (PLGF), and sFlt-1/PLGF after the addition of Corin. METHODS: A total of 135 pregnant women from Affiliated Hospital of Shandong University of Traditional Chinese Medicine participated in this study in their first trimester. A nested case-control study was conducted and all subjects were divided into PE groups (n=46) and controls (n=89). The levels of PLGF, sFlt-1, sFlt-1/PLGF ratio, and Corin of the two groups at 12-16 weeks of gestation were measured and analyzed. Receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to evaluate the predictive ability of various biomarkers. RESULTS: The concentrations of sFlt-1, sFlt-1/PLGF, and Corin in PE group were significantly higher than that in controls, while the concentration of PLGF in the PE group was lower. The area under curve (AUC) of sFlt-1, PLGF and sFlt-1/PLGF for predicting PE was 0.786, 0.719 and 0.866, respectively. Combined with Corin, the prediction ability of the above biomarkers could be improved to 0.876, 0.847, and 0.897, respectively. Corin in combination with sFlt-1/PLGF resulted in improvements with 12.6% being reclassified and a resulting NRI of 0.142 (0.020~0.263) and IDI of 0.087 (0.037~0.137). CONCLUSION: The addition of Corin to sFlt-1, PLGF and sFlt-1/PLGF can improve the ability of each marker to predict PE risk. Corin in combination with sFlt-1/PLGF can be used as ideal markers to identify the pregnant women who subsequently develop PE, which will help in risk stratification and better therapeutic management.

A straightforward strategy toward large BN-embedded π-systems: synthesis, structure, and optoelectronic properties of extended BN heterosuperbenzenes.

A straightforward strategy has been used to construct large BN-embedded π-systems simply from azaacenes. BN heterosuperbenzene derivatives, the largest BN heteroaromatics to date, have been synthesized in three steps. The molecules exhibit curved π-surfaces, showing two different conformations which are self-organized into a sandwich structure and further packed into a π-stacking column. The assembled microribbons exhibit good charge transport properties and photoconductivity, representing an important step toward the optoelectronic applications of BN-embedded aromatics.

[Simultaneous determination of chlorogenic acid, scutellarin, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid in different parts of Erigeron breviscapus by high-performance liquid chromatography].

OBJECTIVE: A high-performance liquid chromatographic (HPLC) method was developed for simultaneous determination of chlorogenic acid, scutellarin, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid in different parts of Erigerontis Herba. METHOD: The four constituents were measured on an Agilent Zorbax SB-C18 column (4.6 mm x 450 mm, 5 microm) with a gradient elution of acetonitrile (A) -0.3% phosphoric acid solution (B) (0-10 min, 12%-15% A, 10-32 min, 15% A, 32-33 min, 15%-20% A, 33-50 min, 20%-22% A) at wavelength of 335 nm and 327 nm, and a flow rate of 1.0 mL x min(-1) and the column temperature was 30 degrees C. RESULT: Linearity of each standard was established in the concentration range of 0.050 1-1.002 microg for chlorogenic acid, 0.165 9-3.318 microg for chlorogenic acid, 0.049 7-0.994 microg for 3,5-dicaffeoylquinic acid, 0.048 7-0.974 p.g for 4,5-dicaffeoylquinic acid respectively, with correlation coefficient r > 0.999 6. Average recoveries (n = 6) of 4 compounds were 98.53% with a RSD of 0.94%, 99.68% with a RSD of 0.49%, 98.78% with a RSD of 1.1%, 99.06% with a RSD of 0.81%, respectively. CONCLUSION: The developed method is simple, accurate, and precise, it can be used for the quantitative analysis of Erigeron breviscapus.

Combination of Caspy2 and IP-10 gene therapy significantly improves therapeutic efficacy against murine malignant neoplasm growth and metastasis.

It has been shown that Caspy2, a zebrafish active caspase, can efficiently suppress the growth of malignant tumor. The present study was designed to test whether combined gene therapy with IP-10, a potent antitumor chemokine, and Caspy2 would improve therapy efficacy. Recombinant plasmid expressing both Caspy2 and IP-10 genes was mixed with DOTAP-cholesterol nanoparticles. Immunocompetent mice bearing CT26 colon carcinoma, B16-F10 melanoma, and 4T1 breast carcinoma were treated with the complex. We found that the combined gene therapy more efficiently inhibited tumor growth, while efficiently prolonging the survival of tumor-bearing animals, compared with monotherapy. Moreover, a significant reduction in spontaneous lung metastasis could be observed in the 4T1 breast carcinoma model. Infiltration of CD8(+) T lymphocytes was also observed. In addition, apoptotic cells were widely detected by TUNEL assay and caspase-3 immunostaining in coadministered tumor tissues. The combination treatment also successfully inhibited angiogenesis and tumor cell proliferation as assessed by CD31 and Ki-67 immunostaining, respectively. Furthermore, depletion of CD8(+) T lymphocytes could significantly abrogate the antitumor activity, whereas the depletion of CD4(+) cells or natural killer cells showed partial abrogation. Rechallenged CT26 tumors were rejected in all of the surviving mice treated by combination therapy. Our results suggest that combined therapy with Caspy2 and IP-10 can significantly enhance antitumor activity by acting as an immune response initiator, apoptosis inducer, and angiogenesis inhibitor, which may be important for further applications in clinical cancer therapy.

In vitro study on role of Hsp70 expression in DNA damage of human embryonic lung cells exposed to Benzo[a]pyrene.

OBJECTIVE: Benzo[a]pyrene (B[a]P), a ubiquitous environmental pollutant, is a potent procarcinogen and mutagen that can elicit tumors, leading to malignancy. Heat shock proteins (Hsp) have been shown to protect cells against damages caused by various stresses including exposure to numerous chemicals. Whether Hsps, or more specifically Hsp70, are involved in repair of B[a]P-induced DNA damage is currently unknown. METHODS: We assessed the potential role of the inducible form of Hsp70 in B[a]P-induced DNA damage of human embryonic lung (HEL) cells using immunoblot and the comet assay (i.e., the single cell gel electrophoresis assay). RESULTS: Exposure to B[a]P induced a dose-dependent decrease in the level of Hsp70, but a dose-dependent +-increase in DNA damage both in untreated (control) HEL cells and in cells preconditioned by a heat treatment. Heat preconditioning prior to B[a]P exposure potentiated the effect of B[a]P at a low dose (10 micromol/L), but appeared to be protective at higher doses. There was a negative correlation between Hsp70 level and DNA damage in the non-preheated as well as in the preconditioned cells. CONCLUSION: These data suggest that exposure of HEL cells to B[a]P may induce a dose-dependent reduction in the levels of the inducible Hsp70. The detailed mechanisms for the reduction of Hsp70 levels by B[a]P and the role of Hsp70 in DNA damage under different concentrations of B[a]P remains to be determined.

Effect of manganese on heat stress protein synthesis of new-born rats.

AIM: To study the effect of manganese (Mn) on heat stress protein 70 (HSP70) synthesis in the brain and liver of new-born rats whose mother-rats were exposed to Mn. METHODS: 32 female rats were randomly divided into four groups. One group was administrated with physiological saline only as control group, the other three groups were administrated with 7.5, 15 and 30 mg x kg(-1) manganese chloride (MnCl2) by intraperitioneal injection every two days for two weeks. After delivery, the mother-rats received MnCl2 unceasingly for a week with the same method. Then the contents of Mn Zn Cu and Fe in the livers of the new-born rats were determined by atomic absorption spectroscopy; The level of HSP70 in the brains and the livers of the new-born rats as detected by Western-dot-blotting, and the SOD activities were measured simultaneously. RESULTS: The contents of Mn in the livers of new-born rats of the experimental groups(respective 1.38+/-0.18, 2.73+/-0.65,3.44+/-0.89 microg x g(-1)) were significantly increased compared with the control group(0.88+/-0.18 microg x g(-1); P<0.01); The contents of Fe in the livers of new-born rats of 15 and 30 mg x kg(-1) experimental groups (426+/-125, 572+/-175 microg x g(-1), respectively) were significantly increased compared with the control group(286+/-42 microg x g(-1); P<0.05); the levels of Zn in the livers of the new-born rats of three experimental groups(254+/-49, 263+/-47, 213+/-28 microg x g(-1), respectively) were lower than those of the control group(335+/-50 microg x g(-1); respective P<0.05, P<0.01); and the levels of Cu showed no significant difference among the four groups(three experimental groups: 75+/-21, 68+/-241 and 78+/-18 microg x g(-1); control group: 83+/-9 microg x g(-1); P<0.05). There was a significant increase in the levels of HSP70 in the brains of new-born rats of the 30 mg x kg(-1) group (19.5 x 10(3)+/- 1.3 x 10(3)A;control group:14.3 x 10(3)+/-1.4 x 10(3)A; P<0.01) and the levels of HSP70 in the livers of new-born rats of three experimental groups(respective 19.6 x 10(3)+/- 3.9 x 10(3)A,18.5 x 10(3)+/-3.8 x 10(3)A, 22.4 x 10(3)+/-1.9 x 10(3)A) also increased than control group(13.3 x 10(3)+/-1.0 x 10(3)A;P<0.01), but the SOD activities showed no significant difference among brains of the four groups (experimental groups: 5.04+/-0.43, 4.83+/-0.48, 4.60+/-0.84 ku x g(-1); control group: 4.91+/-0.37 ku x g(-1); P<0.05). The SOD activities in the livers of 15 mg x kgP< group(5.41+/-0.44 ku x gP<) was lower than the control group(5.95+/-0.36 ku x gP<; P<0.05). CONCLUSION: While mother-rats were exposed to manganese, the metabolisms of Mn Zn and Fe of new-born rats in the livers were influenced and were situated in a stress status, thus HSP70 syntheses is induced in the brains and livers of new-born rats, but the mechanism of this effect in the developmental toxicity of Mn remains to be further studied.