Effect of Lactate on Immune Cells in Tumor Microenvironment and Progress of Related Target Therapy / 肿瘤防治研究

The relationship between tumor metabolism and immunity is complex and diverse. To date, the role of tumor-specific metabolic reprogramming in shaping the specific tumor microenvironment in tumor immunotherapy remains unclear. Lactic acid is the main product of glycolysis, and the aerobic glycolysis of tumor cells causes lactic acid to accumulate in the microenvironment. Recent studies have shown that the accumulation of lactic acid in the tumor microenvironment hinders anti-tumor immunity, especially affects the function, differentiation, and metabolism of immune cells, and participates in tumor immune escape, thus promoting tumor. This article reviews the effects of lactate accumulation in the tumor microenvironment on dendritic cells, T cells, NK cells, tumor-associated macrophages, and myeloid-derived suppressor cells. Targeted intervention of lactate production and efflux by tumor cells is expected to become a new strategy for tumor immunotherapy.

The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications

Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs' roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.

Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with brain metastases / 肿瘤研究与临床

Brain metastasis is a common complication of non-small cell lung cancer (NSCLC) patients. About 25%-55% of patients with NSCLC will develop brain metastases, and the occurrence of brain metastasis predicts a poor prognosis. Traditionally, radiotherapy, chemotherapy, targeted therapy and surgery are the main treatment options for NSCLC patients with brain metastases. In recent years, with the emergence of immune checkpoint inhibitors (ICI), the survival of NSCLC patients with brain metastases has been significantly improved. This article reviews the research progress of ICI treatment for NSCLC patients with brain metastases in order to provide new treatment strategies.

Application of Internet diversified rehabilitation medicine education in newly diagnosed breast cancer patients / 国际外科学杂志

Objective:To explore the influence of Internet diversified rehabilitation medicine education on self-efficacy and quality of life in newly diagnosed breast cancer patients.Methods:A prospective study was performed in 130 newly diagnosed breast cancer patients admitted to Beijing Friendship Hospital, Capital Medical University from February 2020 to February 2021. According to the method of randomly number table, these patients were divided into control group and intervention group, 65 cases in each group.The control group was treated with routine treatment scheme, and the intervention group added the intervention of Internet diversified education of rehabilitation medicine on the basis of routine treatment scheme. Compared the general data of the two groups, the General Self-Efficacy Scale (GSES) and the cancer patients′ Quality of Life Questionnaire-Core 30 (QLQ-C30) were used to compare the self-efficacy levels of the two groups before operation, 4 months and 8 months after operation, evaluate the quality of life. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups; Chi-square test was used for comparison of enumeration data between groups. Results:Before operation, there was no significant difference in general data, GSES score and QLQ-C30 score between the two groups ( P> 0.05). Four months after operation, GSES scores [(27.39±4.68) score vs (25.91±3.18)score], somatic function [(65.50±4.34) score vs (63.07±5.42) score], cognitive function [(67.63±10.32) score vs (63.29 ± 11.36) score], role function [(50.82±10.80) score vs (45.59±13.94) score], and total quality of life [(63.47 ± 6.98) score vs (59.26±7.98)score] were compared between the intervention group and the control group, the difference was statistically significant ( P< 0.05). There was no significant difference in the scores of emotional function [(57.60±11.72) score vs (55.53±10.61) score] and social function [(49.86±12.11) score vs (46.13±10.25) score] ( P> 0.05). Eight months after operation, the GSES score [(28.82±3.31) score vs (26.73 ± 3.06) score] of patients in the intervention group and the control group, and the scores of functional areas and overall quality of life in QLQ-C30 score were significantly different ( P< 0.01). Conclusion:the Internet diversified rehabilitation medicine education has a significant effect on improving the self-efficacy of new breast cancer patients, and can improve the quality of life of patients.

Progress of granzyme-induced apoptosis in tumor cells / 肿瘤研究与临床

Granzyme exists in the cytotoxic granules and belongs to a highly homologous serine protease family. Granzyme is synthesized and released from natural killer cells and cytotoxic lymphocytes. It induces multiple programmed death with the participation of perforin and is an important medium for immune cells to exert anti-tumor effects. This article reviews the granzyme-mediated tumor cell death and the relationship between granzyme and kinds of ways of cell apoptosis, in order to provide new theoretical basis and therapeutic strategies for tumor therapy.

Progress of JMJD5 in tumors / 肿瘤研究与临床

JMJD5 belongs to the protein family of JMJD and is closely related to tumorigenesis. JMJD5 plays a carcinogenic role in some tumors, such as oral cancer, prostate cancer, breast cancer, colon cancer and atypical meningiomas, JMJD5 promotes the proliferation, migration and invasion of cancer cells. However, JMJD5 not only plays a carcinogenic role in some tumors, but also plays an anticancer role. For example, in bladder cancer, JMJD5 inhibits the metastasis of bladder cancer; in liver cancer, on the one hand JMJD5 promotes the replication of hepatitis B virus (HBV), and on the other hand it inhibits the growth of cancer cells; in lung cancer, on the one hand JNJD5 promotes the proliferation of cancer cells, and on the other hand it inhibits the metastasis of cancer cells by promoting the stabilization of microtubules. This article will focus on the mechanisms of JMJD5 in tumors, in order to provide a new target for tumor prevention and treatment.

Evaluation value of dualGenergy CT in intracranial hemorrhage after mechanical thrombectomy for stroke / 实用放射学杂志

Objective To investigate the value of dual-energy CT in differentiating intracranial hemorrhage (ICH)from extravasation of contrast medium in patients with acute ischemic stroke (AIS)after mechanical thrombectomy.Methods AIS patients who underwent mechanical thrombectomy from January 2018 to July 2018 were prospectively included.They all underwent dual-energy CT immediately within 1 h after surgery.Virtual non-contrast (VNC),iodine overlay maps (IOM)and mixed energy images (MIX)were obtained and evaluated respectively. Follow-up was performed 48 hours after surgery with dual-energy CT,which was used as a reference standard and compared with the previous evaluation results.Results Among the 34 patients with complete data,6 cases had no obvious high-density shadow on the MIX image.Among the remaining 28 patients with high-density shadow,14 cases had immediate dual-energy CT diagnosis of bleeding,all of which were confirmed as bleeding during follow-up.Twelve cases were diagnosed as extravasation of contrast medium,of which 1 case had secondary hemorrhage transformation during follow-up,and the rest were all extravasation of contrast medium.Two cases were diagnosed as bleeding with extravasation,and both were confirmed during follow-up.The sensitivity was 93%.The specificity was 1 00%.The positive predictive value was 1 00%.The negative predictive value was 9 2% (P＜ 0.05).Conclusion Dual-energy CT can accurately differentiate ICH from extravasation of contrast agent in AIS patients after mechanical thrombectomy,which is of great value in ICH evaluation after surgery.

Epidemiological analysis of malaria prevalence in Nanjing City from 2010 to 2015 / 中国血吸虫病防治杂志

Objective To analyze the epidemiological characteristics of malaria in Nanjing City,so as to provide the evi?dence for further formulating and adjusting the malaria prevention and control strategy. Methods The data of malaria situation, malaria cases and epidemiological investigations were collected from the Internet Reporting System in Nanjing City from 2010 to 2015 and analyzed statistically. Results A total of 137 confirmed malaria cases were reported in Nanjing City from 2010 to 2015,including 102 falciparum malaria cases(74.45%),33 vivax malaria cases(24.09%),one ovale malaria case(0.73%) and one quartan malaria case(0.73%). Among the 137 malaria cases,126 cases(91.97%)were imported from foreign coun?tries,2 cases(1.46%)were infected locally,and nine cases(6.57%)were imported from other provinces in China. Among the 126 overseas imported cases,117 cases were imported from African countries and 9 from Asian countries. These malaria cases were majorly young men working as migrant workers,laborers and technical persons. About 19.30%of the cases went to hospital on onset day,and 55.65%were confirmed by medical institutions as malaria in the same day. The majority of diagnosis institu?tions were municipal hospitals(74.45%). Conclusions The number of malaria cases in Nanjing City is declining year by year. The local infections are eliminating gradually. However,the situation of imported malaria from overseas is still serious. There?fore,the surveillance work and health education still should be strengthened,so as to reduce the risk of imported malaria.

Effect of Zhu Lian Acupuncture Exciting Method on Nerve Cell Apoptosis and the Expressions of PI3K, AKt and Caspase-3 Proteins in Young Rats with Hypoxic-ischemic Brain Damage / 上海针灸杂志

Objective To investigate the effect of different time intervention of Zhu Lian acupuncture exciting method on nerve cell apoptosis and tissue expressions of PI3K (phosphatidylinositol 3-kinase), AKt (serine/threonine kinase) and Caspase-3 (cysteinyl aspartate specific proteinase-3) proteins in young rats with hypoxic-ischemic brain damage.Methods Fifty 7-day-old rats were randomized into groups A (acupuncture exciting methodⅠ), B (acupuncture exciting methodⅡ), C (model), D (sham operation) and E (normal control), 10 rats each. Groups A and E began to receive acupuncture in 24 hours after model making and group B, at 8 days after model making. Groups C and D were not given acupuncture. Every group of animals was sacrificed at 21 days after model making. Nerve cell apoptosis was examined using In situ end labeling (TUNEL) technique. Cerebral expressions of PI3K, AKt and Caspase-3 proteins were determined by immunohistochemical method.Results The number of apoptotic cells was significantly smaller in groups A and B than in group C (P<0.01,P<0.05) and decreased significantly in group A compared with group B (P<0.05). The expressions of PI3K and AKt proteins increased significantly and the expression of Caspase-3 protein decreased significantly in groups A and B compared with group C; there were statistically significant differences (P<0.01,P<0.05). PI3K expression increased significantly and Caspase-3 protein expression decreased significantly in group A compared with group B (P<0.05); there were statistically significant differences (P<0.05).Conclusions Zhu Lian acupuncture exciting method can inhibit nerve cell apoptosis, stimulate the expression of PI3K/AKt signaling pathway, increase PI3K and AKt activities and reduce the expression of Caspase-3 protein in young rats with hypoxic-ischemic brain damage. Early intervention of Zhu Lian acupuncture exciting method is of important significance in producing a protective effect on brain nerves in young rats with hypoxic-ischemic brain damage.

Influence ofZhulian acupuncture exciting method on hypoxic ischemic brain damage in rats to oxidative stress / 国际中医中药杂志

Objective To observate theZhulian acupuncture exciting method in different time of hypoxia ischemia brain injury in rat brain tissue malondialdehyde (MDA), monoamine oxidase (MAO), nitric oxide (NO) and glutathione peroxidase (GSH-PX) content.Methods 7 days old rats were randomly divided into a excitation method acupuncture group I, a excitation method acupuncture group II, a model group, a sham operation group, a normal control group, 10 rats in each group. Excitation method acupuncture group I and normal control group were given stimulation ofZhulian acupuncture exciting method one type technique from 24 h model manipulation, excitation method acupuncture II group from the beginning of the eighth day given Stimulation ofZhulian acupuncture exciting method one type technique. The sham operation group and the model group were not treated by acupuncture. The animals were sacrificed at the twenty-first day after making the model, determined brain tissue MDA、MAO、NO and GSH-PX Content.Results Compared with the model group, MDA (3.4 ± 0.87 nmol/mgvs. 5.50 ± 1.58 nmol/mg) content decreased in the excitation method acupuncture group I (P<0.05). The NO (12.43 ± 3.47μmol/mgvs. 17.10 ± 5.82μmol/mg) content decreased in the excitation method acupuncture group II (P<0.05). MAO (32.12 ± 11.15 U/mg, 31.01 ± 9.92 U/mgvs. 40.90 ± 11.02 U/mg) content were decreased in both excitation method acupuncture group I and group II (P<0.05), while the GSH-PX (2.61 ± 1.20 U/mg, 2.61 ± 1.37 U/mgvs. 1.43 ± 0.49 U/mg) content were increased (P<0.01). ConclusionZhulian acupuncture exciting method one type technique can decrease the content of MDA, MAO and NO reduce the content of hypoxic-ischemic brain injury in rat brain tissue, increase the content of GSH-PX, promote the removal of immature rats with hypoxic ischemic brain damage brain tissue metabolism, and protect brain function.

Determination on Human Plasma Protein Binding Rate of Ginkgolide A, B and K in Diterpene Ginkgolides Meglumine Injection / 世界科学技术-中医药现代化

This paper was aimed to study the human plasma protein binding rate of diterpene ginkgolides meglumine injection.The equilibrium dialysis was used to determine the human plasma protein binding rate of ginkgolide A (GA),ginkgolide B (GB) and ginkgolide K (GK) in diterpene ginkgolides meglumine injection.The LC-MS/MS method was used for the content determination of ginkgolides.And then,the plasma protein binding rate was calculated.The results showed that there was no interference from other ingredients for the determination of ginkgolides.The calibration curve of the analytes was in good linearity in certain range of contents.The precision and stability of the analytes met the methodology requirements.After 8 h incubation,the human plasma protein binding rate of GA,GB and GK achieved balance.The human plasma protein binding rate of GA (0.34,1.70 and 8.51μg·mL-1) was 84.03%-88.11%; the human plasma protein binding rate of GB (0.62,3.09 and 15.5μg·mL-1) was 41.21%-53.56%; the human plasma protein binding rate of GK (0.04,0.20 and 1.01μg·mL-1) was 45.24%-59.59%.It was concluded that the method was simple,rapid and sensitive,which met the analysis requirement for biological samples.GA had a high plasma protein binding rate; GB and GK had medium plasma protein binding rate.

Study on Induction of Rat Liver Microsomes Cytochrome P450 Enzymes byRe-Du-Ning Injection / 世界科学技术-中医药现代化

This study was aimed to investigate the induction effect ofRe-Du-Ning (RDN) Injection on rat liver microsome CYP450 enzymes. SD rats were randomly divided into the solvent control group, positive control group as well as the low, middle and high dose group of RDN (1, 2, 4 mL·kg-1·d-1). After drugs were administrated continuously for 7 days, the rats were sacrificed. The liver was weighed and prepared to microsomes. Meanwhile, the liver coefficients of rats were calculated. And the protein content was detected by BCA method. Finally, activities of five important subtypes of CYP450 enzymes such as CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A1/2 were measured by the“cocktail” method. The results showed that the levels of liver coefficients, microsome yield rate and activities of CYP450 subtypes increased significantly in the positive control group compared with the solvent control group (P < 0.01). There was no significant difference on the levels of liver coefficients, microsome yield and protein content between the low and middle dose group of RDN. However, there was significant difference on the levels of liver coefficients and microsome yield in the high dose group (P < 0.05). In terms of the influence on enzyme activity, RDN Injection can significantly induce the activities of CYP1A2 with dose dependence. It can induce the activities of CYP2C9 and CYP2C19 at the middle and high dose. However, there was no obvious influence on the activities of CYP3A1/2 and CYP2D6. It was concluded that the positive control group can obviously induce activities of CYP450, which can be used in the evaluation of induction experiments. RDN Injection had induction effect on CYP1A2, CYP2C9 and CYP2C19. But it had no influence on the activities of CYP3A1/2 and CYP2D6.

Determination of Five Heavy Metals in Chuanxiong Rhizoma and Gastrodiae Rhizoma by ICP-MS / 世界科学技术-中医药现代化

This article is aimed to provide a method for the simultaneous analysis of five heavy metals, including Cu, As, Pb, Cd, and Hg, in Chuanxiong Rhizoma and Gastrodiae Rhizoma through ICP-MS. Five heavy metals were determined by an inductively coupled plasma-mass spectrometry method after microwave-assisted digestion. The linear correlation coefficients were all better than 0.999. The lowest limits of quantification for all target elements were 0.003 0.134 ug·L-1, while the recovery values ranged from 80.04% 118.34%. This method was accurate, convenient, rapid, and highly sensitive, and can be applied to determine five heavy metals, including Cu, As, Pb, Cd, and Hg in Chuanxiong Rhizoma and Gastrodiae Rhizoma.

Simultaneous Determination of Five Saponins in Yao-Bi-Tong Capsules by QAMS / 世界科学技术-中医药现代化

This study was aimed to establish a quality evaluation method, quantitative analysis of multi-components with a single-marker (QAMS) to determine the contents of five saponins in Yao-Bi-Tong (YBT) capsules. Ginseno-side Rg1 was used as the internal standard; the relative correction factor (RCF) of notoginsenoside R1, ginsenoside Re, ginsenoside Rb1 and ginsenoside Rd were calculated and evaluated. The contents of 5 saponins were determined by the external standard method and QAMS, respectively. Rationality, feasibility and repeatability of the QAMS method were verified by comparing the results obtained from two different methods. The results showed that RCFs of notoginsenoside R1, ginsenoside Re and ginsenoside Rb1 to ginsenoside Rg1 against YBT capsules were 0.999, 1.228, 0.990 and 1.094, respectively, indicating good reproducibility. These results of two methods had no significant dif-ference. It was concluded that the QAMS method can be accurately, rapidly and reasonably used as a new quality assessment model for ginsenosides in YBT capsules.

Determination of Macroporous Resin Residues in Ginkgo Leaf Tablets by Headspace Capillary Gas Chromatography / 世界科学技术-中医药现代化

This study was aimed to establish the determination method of nineorganic solvent residues of macrop-orous resin. Headspace capillary gas chromatography (GC) was used in the content determination of hexane, benzene, methyl-benzene, o-xylene, m-xylene, p-xylene, styrene, diethyl-benzene and divinyl-benzene of macroporousresin residues in Ginkgo leaf tablets. The results showed that ninemacroporous resin residues in Ginkgo leaf tablets were completely separated. The calibration curves were in good linearity (r=0.9992-0.9998). The average recoveries were 80%-110%. It was concluded that themethod was accurate, quick, and sensitive, which can be used to determine the macroporous resin residues in Ginkgo leaf tablets.

The clinic significant of determination of T-lymphocyte subsets in patients with pulmonary tuberculosis combined with diabetes / 中国综合临床

Objective To investigate the clinical diagnostic significance of detecting T in peripheral blood lymphocyte subsets (CD4+,CD8+ and the ratio of pulmonary tuberculosis with diabetes) and explore drug therapy of the five thymus peptide combined anti-tuberculosis on the diabetes complicated with pulmonary tuberculosis.Methods Eighty cases of pulmonary tuberculosis complicated with diabetes mellitus were selected as our treatment subject,who were treated with anti-tuberculosis drug treatment and five thymus peptide regulating immunity treatment.T lymphocyte subsets (CD4 +,CD8 + and their ratio) were detected.Meanwhile acid-fast bacilli and image detection were performed.Another 80 cases were as our control group that treated with anti-tuberculosis drug.Results Following the thymus peptide five treatment for 1,2,and 6 months,T lymphocyte subsets were (CD4+:(34.34 ± 7.32) ％,(39.23 ± 6.62) ％,(41.06 ± 7.13) ％),(CD8+:(31.42 ±8.91)％,(32.52 ±8.58)％,(32.12 ±8.59)％),(CD4+/CD8+:(1.23 ±0.31),(1.34 ±0.30),(1.36 ± 0.32),higher than that of before treatment (30.26 ± 8.25) ％,(30.36 ± 9.86) ％,(1.13 ± 0.42) CD4 +.Through 2 months treatment,CD4+,CD4+/CD8+ of patient in treatment groups were different with that of control group (P ＜ 0.01 or P ＜ 0.05).80 patients after anti-TB plus application thymopentin regulating immunity for 2 months,normal sputum negative conversion rate of CD4+ was 97.2％ and improvement rate was 98.0％.However cases with high CD4+ T lymphocyte subsets showed 78.6％ negative rate of acid-fast bacilli and 88.0 ％ cured rate,and there was significant difference (x2 =4.764,7.680,respectively,P ＜ 0.05).Conclusion Thymic peptide five might have the ability of improving the cellular immune function in patients with pulmonary tuberculosis and diabetes.The prognosis is better when T lymphocyte subsets CD4+ of patient was back to normal through treatment.

Fingerprint Analysis of Terpene Lactones in Ginkgo Biloba Tablets by HPLC-ELSD Coupled with Chemometrics / 世界科学技术-中医药现代化

This study was aimed to establish a high performance liquid chromatography (HPLC) method coupled with Evaporative Light-scattering Detector (ELSD) in order to develop the determination of fingerprint of terpene lactones in Ginkgo biloba tablets. An Agilent Extend-C18 (4.6 mm í 250 mm, 5 μm) was employed as the analysis column and the normal propyl alcohol-tetrahydrofuran-water (1:15:84) as mobile phase. The column temperature was 30℃. And the flow rate was 1.0 mL·min-1. HPLC coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS) was used to identify the common peaks. The fingerprint was further evaluated by chemometrics methods including principal component analysis (PCA), similarity analysis (SA) and hierarchical clus-tering analysis (HCA). The results showed that the precision, stability and repeatability of this method were favorable. Five common peaks were identified by LC/Q-TOF MS as ginkgolide J ( M ) , C , A , B and bilobalide , respectively . Fourteen batches of Ginkgo biloba tablets were determined. With the aid of PCA, SA and HCA, the common pattern of the fingerprint of terpene lactones was established. Samples were divided into 4 clusters by their quality differ-ence. It was concluded that the method established in this paper can be used for quality evaluation of terpene lac-tones in G ink go b ilob a tablets.

Repair of rabbit bone defect with composite of calcium phosphate bone cement and calcium phosphate cement mixed with different ratio of minimal morselized bone in vivo / 中华创伤杂志

ObjectiveTo explore the effect of the calcium phosphate cement (CPC) /calcium polyphosphate fiber (CPPF) composites mixed with different proportion of minimal morselized bone on repair of bone defect in vivo. MethodsA total of 36 New Zealand white rabbits were completely randomly designed into A, B, C, D groups and their bilateral radial bone defect model was prepared. The minimal morselized bone (300-500 μm in diameter) was made from the iliac of those rats. The CPPF and CPC were evenly mixed into CPC/CPPF composites which were divided into four groups in accordance with the CPPF weight O, 10％, 30％ and 50％ in CPC/CPPF composite. The CPC/CPPF composites of the four groups was mixed with the minimal morselized bone with ratio of 6:4 and then the mixture was implanted the bone defect of the rabbits in four groups. The gross, X-ray and histological observations were done at four and eight weeks. The biomechanical test was performed at eight weeks. Results When CPPF occupies 30％ of the CPC/CPPF composite, the maximum compressive load and bending loads were better than those in the other groups ( P ＜ 0.05 ), when the histological observation showed the most tight link between the artificial composite and the bone interface and the closest similarity between material degradation rate and the ossification rate, with the best osteogenesis and the optimal ratio.ConclusionThe repair of bone defect can attain the optimal outcome through adding a certain ratio of minimal morselized bone into the CPC/CPPF to adjust the degradation rate of composites.

CT Diagnosis of Superior Mesenteric Vein Thrombosis / 实用放射学杂志

Objective To explore the diagnostic value of helical CT in superior mesenteric vein(SMV) thrombosis.Methods Characteristic CT appearances of SMV thrombosis verified by clinic in 13 patients were retrospectively analysed.Precontrast and postcontrast CT scan were performed in all patients.After the data were acquired,they were transferred to workstation for maximum intensity projection of muti-plane.Results Hyperaemia and edema of the mesentery could be seen in all patients.After administration of contrast material,the filling defects of SMV could be showed in 8 cases,and the distal SMV was occluded in other patients.The thrombi could be directively showed by CT,but distended bowel loops,bowel wall thicking with or without the target sign,absent or poor enhancement of the bowel wall,and the pneumatosis at interbowel were showed by CT,the later two findings were more important and specific signs of ischemic bowel.There was not directively relation between bowel necrosis and the thrombus was whether or not localized at main SMV.Conclusion Helical CT is a important modality for the diagnosis of SMV thrombosis.