Research Progress of Pseudogenes in Hepatocellular Carcinoma / 肿瘤防治研究

Pseudogenes were initially thought to have no function and were called by aliases, such as "junk genes." With the emergence of large-scale genomics projects and more and more experimental studies, pseudogenes have been shown to play an important role in the occurrence and development of solid tumors, especially playing an important regulatory role in the occurrence and develepment of liver cancer, such as regulating the proliferation, apoptosis, invasion, metastasis, and immunity of liver cancer cells. Recent studies showed that pseudogenes can act as regulators of oncogenes and tumor suppressors in hepatocellular carcinoma (HCC) and can thus serve as prognostic markers and even therapeutic targets for this cancer type. In this review, we systematically summarize the mechanisms and functions of different pseudogenes in HCC and present their future prospects as therapeutic targets.

Prognostic Value of Hematological Indicators in Children and Adolescents with Nasopharyngeal Carcinoma / 肿瘤防治研究

Objective To explore the prognostic value of pretreatment hematological indicators in children and adolescents with nasopharyngeal carcinoma. Methods We performed a retrospective analysis on the medical records of 79 children and adolescents (≤20 years old) with nasopharyngeal carcinoma. Before treatment, all patients underwent hematological tests, and patients received intensity-modulated radiotherapy alone or intensity-modulated radiotherapy combined with chemotherapy, targeted, and other comprehensive treatment modes. The follow-up endpoints were overall survival (OS) and progression-free survival (PFS). Results Age≤14 years, no concurrent chemotherapy, pretreatment hematological indicators (high NLR, high PLR, high LDH, and high LAR) were associated with poor OS and PFS in children and adolescents with nasopharyngeal carcinoma (all P < 0.05). No concurrent chemotherapy and high LAR before treatment were independent adverse prognostic factors for OS in children and adolescents with nasopharyngeal carcinoma. Conclusion High NLR, high PLR, high LDH, and high LAR of pretreatment hematological indicators are associated with poor OS and PFS. Meanwhile, high LAR before treatment is an independent adverse prognostic factor for OS in children and adolescents with nasopharyngeal carcinoma.

Erratum: Author correction to "DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis" Acta Pharmaceutica Sinica B 12 (2022) 262-273

[This corrects the article DOI: 10.1016/j.apsb.2021.03.043.].

DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis

Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan (CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA (dsDNA) from the intestine, leading to cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination (HR) repair and downregulate dsDNA‒cGAS‒STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.

Distribution characteristics and ecological risk assessment of heavy metals in farmland around Changqing Oilfield / 环境与职业医学

Background With the change of the national energy development layout, Qingyang has seen a situation where oil exploitation and agriculture go hand in hand, which may lead to local soil pollution if not taken seriously. Objective To evaluate the distribution characteristics, possible sources, and ecological risks of heavy metals in farmland soils around the main production areas of Changqing Oilfield. Methods A total of 60 farmland soil samples were collected from Zhengning County, Zhenyuan County, and Qingcheng County of Qingyang City, and the contents of heavy metals such lead (Pb), mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As) in farmland soil were detected according to GB 15618-2018 Soil environmental quality—Risk control standard for soil contamination of agricultural land (on trial). The soil background value of Gansu Province was used as the denominator in the calculation of pollution index, and the pollution characteristics and ecological characteristics of selected five heavy metals in farmland soil were evaluated by single-factor pollution index (Pi), Nemerow comprehensive pollution index (PN), and potential ecological risk index. Results The levels of Pb, As, and Hg in farmland soils around Changqing Oilfield, the levels of Cr and Cd in Qingcheng County, and the level of Cd in Zhengning County were higher than the corresponding soil background values of Gansu Province, but lower than the national soil environmental quality standard. The single-factor pollution indexes (Pi) were: Hg, 2.14; Pb, 1.24; As, 1.13; Cr, 0.78; Cd, 0.67, which indicated that Hg were graded as moderate pollution, Pb and As were slight pollution, and Cd and Cr were not polluted. The Nemerow comprehensive pollution indexes (PN) were: Cr, 0.92; Cd, 1.08; As, 1.20; Pb, 1.68; Hg, 3.85, which indicated that Cr was graded as no pollution, Cd, Pb and As were mild pollution, and Hg was severe pollution. The variation coefficients of Hg and Cd in Zhenyuan County and that of Hg in Qingcheng County were 60.00%, 50.00%, and 50.00%, respectively, which were all greater than 50%, indicating that the pollution of above heavy metals in the location was subject to human activities. The potential ecological risk indexes (Er) of Pb, Cr, Cd, As, and Hg were 6.20, 1.55, 20.05, 11.28, and 81.64, respectively, indicating that Hg was graded as strong ecological risk, and the other four heavy metals were mild ecological risk. The comprehensive potential ecological risk index (RRI) was 124.48. Combined with the potential ecological risk index of Hg, the comprehensive potential ecological risk of the five heavy metals in local farmland soils was considered to be at a strong ecological risk level. Conclusion Although the average values of selected five heavy metals in farmland soils surrounding the main production areas of Changqing Oilfield are qualified with the national soil environmental quality standards, they exceed corresponding soil background values of Gansu Province, and there are signs of human influence and potential ecological risks of different degrees.

Research on the equity and spatial accessibility of oral medical resources in Wuhan / 公共卫生与预防医学

Objective To analyze the equity of the allocation of oral medical resources and the accessibility of health service capabilities in Wuhan. Methods The equity of oral medical resources was calculated with Gini coefficient and Theil index, accessibility was assessed by two-step floating catchment area model, and the spatial autocorrelation was used to study the high-low clustering of accessibility. Results The Gini coefficient of oral medical resources based on population level was around 0.3, and the Gini coefficient of oral medical resources based on geographic area was greater than 0.6. Theil index calculation results were similar. In terms of overall accessibility, the area with poor accessibility was 2,428 square kilometers, reaching 28.38% of the total area, while the area with better accessibility accounted for 14.18%. Conclusion The allocation of oral medical care resources based on population distribution was fairer and better than that based on geographic area. Moreover, the geographical accessibility varies greatly between regions, showing the characteristics of high-high cluster and low-low cluster.

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.

Design,synthesis and biological evaluation of phenylsulfonamide-based IDO1 inhibitors / 中国药科大学学报

Based on the reported IDO1 inhibitor U-3i,11 phenylsulfonamide derivatives were designed and syn-thesized by adopting bioisosterism and molecular docking technology.The inhibitory activities of the target compounds against IDO1 were determined by the HeLa cell-based kynurenine assay.The results demonstrated that most compounds showed different degrees of inhibitory effects on IDO1.Among them,compounds 3b and 3e displayed the most potent activity and could reverse IDO1-mediated immune suppression,which might be worth of further investigation.

Asiatic acid inhibits lung cancer cell growthandby destroying mitochondria

Asiatic acid (AA), a pentacyclic triterpene found in, displays significant anti-proliferative effects on cancer cellsalthough the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer bothand. Using the MTT assay, AA was found to induce apoptosis in a dose- and time-dependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3 (LC3) and decreased the expression of p62. Furthermore, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species (ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen (PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth bothandand that the associated apoptosis is mediated through mitochondrial damage.

Effect of low-frequency pulsed electromagnetic fields on proliferation and osteogenic ability of human adipose-derived stem cells in a three-dimensional scaffold / 中国组织工程研究

BACKGROUND:Nowadays increasing experimental findings have proved that the low-frequency pulsed electromagnetic fields (LPEMF) can induce osteogenic differentiation of a variety of stem cells in the two-dimensional scaffold. However, little is reported on the LPEMF effect on the proliferation and osteogenic differentiation of stem cells in the three-dimensional scaffold.OBJECTIVE:To investigate the effect of LPEMF on the proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs) in the 3D Insert-PCL scaffold.METHODS:Passage 3 hASCs were directly cultured in the 3D Insert-PCL scaffolds folowed by LPEMF (50 Hz, 1 mT) exposure, 2 hours per day, for continuous 14 days (experimental group) or no intervention (control group). After 7 days of culture, Live/Dead staining was used to observe cell survival. After 1, 3, 5, 7 days of culture, MTT assay was used to detect cell proliferation. After 7 and 14 days of culture, the osteogenic differentiation of hASCs was assessed through the alkaline phosphatase (ALP) staining and qRT-PCR.RESULTS AND CONCLUSION: Live/dead cell staining proved that the hASCs had a good growth in the 3D Insert-PCL scaffolds as well as a high survival rate. The absorbance values of hASCs in the two groups were increased gradualy with time, and the absorbance value in the experimental group was significantly higher than that in the control group at 1 and 3 days after culture (P < 0.05). The ALP activity in the experimental group was stronger than that in the control group at 7 and 14 days after culture. qRT-PCR findings showed that at 7 days after culture, the mRNA levels of ALP and type Ⅰ collagen were significantly higher in the experimental group than the control group (P < 0.01), while at 14 days after culture, the mRNA levels of osteopontin, Runt-related transcription factor, ALP and type Ⅰ collagen were significantly higher in the experimental group than the control group (P < 0.05). To conclude, the LPEMF exposure can promote the proliferation and osteogenic differentiation of hASCs cultured on the the 3D Insert-PCL scaffold.

Antibacterial and antioxidant properties of various solvents extracts of Abutilon theophrasti Medic. leaves

This paper described the extraction procedure of six extracts from Abutilon theophrasti Medic. leaves and evaluated antioxidant and antibacterial activity of different extracts by hydroxyl radical, DPPH radical scavenging, broth micro-dilution and agar-well diffusion methods. The six extracts were prepared by the two extraction procedures: [I] water was the extraction solvent; [II] 90% alcohol extract was extracted by petroleum ether, chloroform, ethyl acetate and n-butanol in turn. Extract yields were 7.34%, 7.31%, 0.45%, 0.12%, 2.70% and 5.68% for extract I to VI. It was revealed that the various extracts had effective antibacterial activity against four test strains from Staphylococcus aureus [ATCC 25923], Streptococcus [ATCC 49619], Escherichia coli [ATCC 25922] and Salmonella [ATCC 01303]; meanwhile, the six extracts demonstrated potent antioxidant activity, achieved by hydroxyl radical and DPPH radical scavenging assay. Minimum inhibitory concentrations [MICs] for the bacterial species ranged from 2.21 to 539.46 mg/ml, diameter of inhibition zone ranged from 2.08 to 15.05mm. The scavenging ·OH and DPPH· rates were 62.37% to 81.86% with the concentration 0.06 to 1.89mg/ml and 37.80% to 81.23% with the concentration 1.07 to 35.52mg/ml. According to the results, these extracts have antioxidant and antibacterial activity. In view of all the facts collectively, the six extracts will become natural and nontoxic antioxidant and antibacterial agent, and be applied in food and pharmaceutical industries for the prevention or treatment caused by microorganisms and free radicals

Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.

Association between rs689466 in COX-2 gene and aspirin resistance in cerebral infarction patients / 实用医学杂志

Objective To investigate the association of single nucleotide polymorphisms (SNPs) in COX-2 with aspirin resistance in Chinese cerebral infarction patients. Methods A total of 150 Chinese cerebral infarction patients were recruited. Platelet aggregation response was measured by light transmission aggregometry method and four SNPs located in COX2 gene were genotyped by sequencing method. Results Sixty patients of the total were classified as aspirin non-responders. For clinical variables , concentrations of high homocysteine and the frequency of recurrence cerebral infarction were significantly higher in aspirin non-responders when compared with aspirin responders. Univariate analysis of SNPs showed that rs20417 , rs689465 and rs689466 were significantly associated with aspirin resistance. Multivariate analysis indicated that after adjusting other SNPs and clinical risk factors, rs20417 and rs689466 were still significantly associated with aspirin resistance. Conclusions Rs689466 is significantly associated with aspirin resistance in Chinese cerebral infarction patients even after the adjustment of rs20417. By combining rs689466 , rs20417 and other clinical risk factors , we may better classify the aspirin non-responders from aspirin responders.

Application of the problem-based learning teaching method in clinical teaching of orthopedics / 中华医学教育探索杂志

Objective To evaluate the application effect of the problem based learning in clinical teaching of orthopedics. Methods We chose sixty five-year program students of Peking univ-ersity health science center as research object. All students were randomly divided into experimental and control groups, with thirty students in each group. Experimental group was given PBL teaching combined with lecture based learning (section-based learning, LBL), while the control group only received the LBL teaching. Two groups were given 8 hours of teaching experiments. After the end of the study, the teaching effect of the two groups was evaluated by the theory course and clinical skills. The questionnaire was distributed to the 2 groups. The scores of both experimental group students and control group students in theory courses and clinical skills were analyzed using SPSS 19.0 software using t-test and x2 test. Result The score of the experimental group was (53.7 ±3.2) in the knowl-edge-based grades exam, while the control group was (52.3±2.2), showing no obvious difference when compared to the control group's grades (P>0.05). The score of the experimental group was (24.0±1.5) in the hands-on technique grades exam, while the control group was (22.3±1.6). The difference in grades showed statistical significance (P<0.05). Feedback survey results showed that the experimental group's teaching satisfaction degree was also significantly higher than the control group, and the dif-ference was statistically significant (P<0.05). Conclusions The application of PBL in clinical teach-ing in orthopedic clinical teaching can improve students' learning interest and self-study ability, and helps to develop students' clinical thinking ability. But the role of PBL teaching in improving students' medical knowledge level is not obvious.

A comparative study of intensity-modulated radiotherapy with concurrent PF or TP chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To investigate the survival data and acute toxicities in patients with locoregionally advanced nasopharyngeal carcinoma who receive intensity-modulated radiotherapy (IMRT)with concurrent chemotherapy using nedaplatin plus 5-fluorouracil (PF) or taxol plus nedaplatin (TP).Methods A retrospective analysis was performed on the clinical data of 152 patients with stage Ⅲ or Ⅳa nasopharyngeal carcinoma who were admitted to our hospital in 2009-2010.Of the 152 patients,80 received IMRT with concurrent PF chemotherapy,and 72 received IMRT with concurrent TP chemotherapy;there were at least 2 cycles of concurrent chemotherapy in both groups.The Kaplan-Meier method was used to calculate the survival rates,and the log-rank test was used to analyze the survival difference ; the chisquare test was used to compare the acute toxicities in the two groups.Results The follow-up rate was 100％.The 2-year relapse-free survival rate,distant metastasis-free survival rate,progression-free survival rate,and disease-specific death rate for the IMRT/PF group were 95％,82％,81％,and 13％,respectively,versus 97％,83％,79％,and 12％ for the IMRT/TP group (x2 =0.03,0.02,0.62,and 0.22,P=0.861,0.881,0.431,and 0.638).The incidence rates of leukopenia (grade ≥3),neutropenia (grade ≥ 3),thrombocytopenia (grade ≥ 3),ALT elevation (grade ≥ 2),and oral mucositis (grade ≥3) for the IMRT/PF group were 33％,23％,14％,8％,and 12％,respectively,versus 60％,47％,28％,18％,and 25％ for the IMRT/TP group (x2 =11.33,10.29,4.59,3.94,and 3.94,P =0.001,0.001,0.032,0.047,and 0.047).Conclusions Compared with IMRT with concurrent PF chemotherapy,IMRT with concurrent TP chemotherapy does not lead to significantly better survival and results in more acute toxicities in the patients with locoregionally advanced nasopharyngeal carcinoma.

Study of human cytomegalovirus infections and hepatic impairment in chronic hepatitis C patients / 中国医师进修杂志

Objective To explore the infections of human cytomegalovirus (HCMV) in chronic hepatitis C patients and the hepatic impairment in chronic hepatitis C patients co-infected with HCMV.Methods HCMV-DNA was determined by fluorescence quantitative-PCR (FQ-PCR) in 95 patients with chronic hepatitis C (observation group) and 95 healthy controls(control group) and HCMV active infections were analyzed.HCV-RNA was determined by FQ-PCR in observation group,and the difference of HCMV-DNA positive rate between high HCV-RNA(＞ 104 copies/ml) and low HCV-RNA(≤ 104 copies/ml) was analyzed.Alanine aminotransferase (ALT),aspartate aminotransferase (AST) were determined by rate method in two groups and the hepatic impairment was analyzed.Results Twenty-five cases with positive HCMV-DNA in observation group,the positive rate was 26.3％(25/95).Five cases with positive HCMV-DNA in control group,the positive rate was 5.3％(5/95).There was significant difference between two groups for HCMV-DNA (x2 =14.29,P ＜0.01).Twenty-one cases with positive HCMV-DNA in 43 cases of high HCV-RNA patients,the positive rate was 48.8％(21/43).Four cases with positive HCMV-DNA in 52 cases of low HCV-RNA patients,the positive rate was 7.7％(4/52).There was significant difference between the two (x2 =19.90,P ＜ 0.01).ALT,AST in observation group was higher than that in control group (P ＜ 0.01).ALT,AST in chronic hepatitis C patients positive for HCMV-DNA was higher than that in chronic hepatitis C patients negative for HCMV-DNA significantly (P ＜ 0.01).Conclusions HCMV in chronic hepatitis C patients becomes active again and co-infects easily.When chronic hepatitis C patients co-infect HCMV actively,hepatic is further injured.

STUDY ON PHYSIOLOGICAL AND BIOCHEMICAL PROPERTIES OFα-ACETOLACTATE DECAROBOXYLASES FROM DIFFERENT MICROBES / 微生物学通报

The enzyme activity of α－Acetolactate Decaroboxylases (ALDC)from different microbes was studied, the results demonstrated that it was quite different among them. There were diversities of their enzyme reaction velocities. It was clear that the enzyme activity was affected by the pH of the enzyme reaction system, for example, the optimum pH of ALDC from Lactococcus lactis was 6.6, while for Aerobacter Aerogenes it was 5.8. Addition leucine,valine and isoleucine into enzyme reaction system obviously affected the enzyme activity of ALDC from different microbes.