Management of anticoagulant therapy in a patient with complex venous thromboembolism complicated with acute renal insufficiency / 中国药房

OBJECTIVE To provide a reference for the safe use of drugs in patients with complex venous thromboembolism （VTE） and acute renal insufficiency. METHODS Clinical pharmacists participated in the management of anticoagulant therapy for a patient with complex VTE complicated with acute renal insufficiency， and evaluated the patient as high-risk thrombosis and bleeding based on their medical history， laboratory test results， etc.； combined with the complexity of thrombosis and renal insufficiency， clinical pharmacists suggested that enoxaparin sodium should be used in the acute stage of thrombosis （5 to 21 days after onset）， and then warfarin should be adopted for oral anticoagulation treatment. Because the patient’s anticoagulation was not up to the standard （the target range of the international normalized ratio was 2-3）， clinical pharmacists suggested increasing the warfarin dose， detecting the warfarin metabolism genotype， and adjusting the warfarin dose according to the genotype； at the same time， clinical pharmacists developed an anticoagulation monitoring plan to ensure the safety of anticoagulation treatment. RESULTS Doctors had adopted all the recommendations of clinical pharmacists. The patient did not experience adverse events such as bleeding or worsening of thromboembolism during anticoagulation in the hospital. When the anticoagulation met the standards， the patient was allowed to be discharged with medication. CONCLUSIONS By participating in the anticoagulation treatment management of patients with complex VTE and acute renal insufficiency， clinical pharmacists have assisted doctors in formulating personalized anticoagulation plans to promote the compliance with the anticoagulation treatment standard and ensure the safety and effectiveness of medication for patients.

Enlightening from optimizing post-authorization safety monitoring system of SARS-CoV-2 vaccines in major economies worldwide / 中华预防医学杂志

Ongoing global pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has promoted the unprecedented rapid development and large-scale rolling out of different platform-based COVID-19 vaccines worldwide. How to effectively respond to the expected scale increasing adverse events after vaccination campaign of COVID-19 vaccines is a common problem faced by the world. A lot of countries and regions around the world have arranged in advance at different levels, optimizing the original vaccine safety monitoring system from the perspectives of strengthening the foundation and capabilities, promoting internal and external cooperation, upgrading methods, as well as improving transparency and public communication, which has ensured the good and efficient operation of the system and can provide reference for the construction of relevant fields in China.

Management strategy of antithrombotic therapy in thrombocytopenia patients with atrial fibrillation and atherosclerosis and a literature review / 中国药房

OBJECTIVE To provide reference for the management of antithrombotic therapy in thrombocytopenia patients with atrial fibrillation and atherosclerosis. METHODS The clinical pharmacist participated in the treatment of a thrombocytopenia patient with atrial fibrillation and atherosclerosis， and analyzed the causes of thrombocytopenia according to the patient’s medical history and laboratory examination results. At the same time， the risk of thrombosis-bleeding was evaluated according to the relevant guidelines， and the clinicians were assisted in formulating individual antithrombotic therapy plan and pharmaceutical care plan for the patient. The literature on antithrombotic therapy related to thrombocytopenia was collected and analyzed by retrieving CNKI. RESULTS Thrombocytopenia was considered as primary thrombocytopenia in this patient， and the main risk of bleeding was age ≥65 years old， bleeding tendency， and combined use of antithrombotic drugs. After the clinical pharmacist assessed the risk of thrombosis and bleeding， the clinician was recommended to give full dose of Bemiheparin sodium injection + Dronedarone hydrochloride tablets + Metoprolol succinate sustained-release tablets. In view of thrombocytopenia， the clinician gave Compound zaofan pill， Caffeic acid tablet and Sheng xuexiaoban capsule， but the patient developed diarrhea after the medication. The clinical pharmacist suggested stopping Sheng xuexiaoban capsule， and the clinician adopted the clinical pharmacist’s suggestion. When the patient was discharged from hospital， the clinical pharmacist suggested that the antithrombotic therapy plan for discharge was anticoagulation alone or selective anticoagulation. The clinician chose selective anticoagulation treatment considering that the patient’s current thrombocytopenia， urinary occult blood （+） and fecal occult blood were weakly positive， and ordered the patient to take Metoprolol succinate sustained-release tablets + Atorvastatin calcium tablets at discharge. Literature analysis showed that the causes of thrombocytopenia of patients with thromboembolism mainly included heparin induced-thrombocytopenia， immune thrombocytopenia， etc. All patients were improved after symptomatic treatment. CONCLUSIONS By participating in the management of antithrombotic therapy for the thrombocytopenia patient with atrial fibrillation and atherosclerosis， clinical pharmacists can help effectively control the patient’s condition and ensure the safety and effectiveness of drug use.

Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

The impact of lipids on the cancer-immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy

Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.

The characteristics and correlations of vaginal flora in women with cervical lesions / 中华肿瘤杂志

Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.

A study on using comprehensive geriatric assessment to improve the teaching level of doctor-patient communication from the perspective of Johari Window / 中华医学教育探索杂志

Based on the theory of "Johari Window", this study introduced how to stimulate information content obtained in doctor-patient communication and how to apply the comprehensive geriatric assessment creatively from the four modules of open area, blind area, hidden area and unknown area in the model. It helped students to gain the trust and cooperation of patients, rapidly narrow down the blind area, hidden area and unknown area, guide patients to actively extend the open area, improve the teaching quality of doctor-patient communication in a scientific way.

Comparison of the predictive performance of Logistic regression, BP neural network and support vector machine model for the risk of acute exacerbation of readmission in elderly patients with chronic obstructive pulmonary disease within 30 days / 中华危重病急救医学

Objective:To compare the effectiveness of Logistic regression, BP neural network and support vector machine models in the prediction of 30-day risk of readmission in elderly patients with an exacerbation of chronic obstructive pulmonary disease (COPD) and to provide a scientific basis for the screening and prevention of high-risk patients with readmission.Methods:The COPD patient survey questionnaire was made, including the general data questionnaire, modified Medical Research Council dyspnea scale (mMRC), activities of daily living (ADL), the geriatric depression scale, the mini nutritional assessment-short form (MNA-SF) and COPD assessment test (CAT). Elderly COPD patients were selected from the department of respiratory medicine of 13 general hospitals in Ningxia from April 2019 to August 2020 by convenience sampling method, and they were followed up 30 days after discharge. To explore the risk factors of patient readmission, Logistic regression model, BP neural network model and support vector machine models were constructed based on the risk factors. According to the ratio of the training set to the testing set of 7∶3, the model was divided into the training set sample and the testing set sample. The prediction efficiency of the model was compared by the precision rate, recall rate and accuracy rate, F1 index and the area under the receiver operator characteristic curve (AUC).Results:A total of 1 120 patients were investigated, including 879 non-readmission patients and 241 readmission patients. Univariate regression analysis showed that there were statistically significant differences in age, education level, smoking status, proportion of diabetes and coronary heart disease, hospitalization times of acute exacerbation of COPD in the past 1 year, seasonal factors and long-term home oxygen therapy, regular medication, proportion of rehabilitation exercise, course of disease, ADL, depression status, mMRC, nutritional status between non-readmission patients and readmission patients. Binary Logistic regression analysis showed that education level, smoking status, coronary heart disease, hospitalization times of acute exacerbation of COPD in the past 1 year, seasonal factors, whether long-term home oxygen therapy, whether regular medication, nutritional status were the risk factors for 30-day acute exacerbation of readmission in elderly patients with COPD. The training set showed that the accuracy rate of Logistic regression model, BP neural network model and support vector machine models were 70.95%, 76.51% and 84.78%, respectively. The recall rates were 79.55%, 86.36% and 88.64%, respectively. The accuracy rates were 87.81%, 90.81% and 93.82%, respectively. F1 indexes were 0.75, 0.81 and 0.87, respectively. The AUC were 0.850, 0.893 and 0.921, respectively. The testing set showed that the precision rate of Logistic regression model, BP neural network model and support vector machine model were 78.38%, 80.65% and 88.57%, respectively. The recall rates were 70.73%, 60.98% and 75.61%, respectively. The accuracy rates were 85.82%, 84.40% and 90.07%, respectively. F1 indexes were 0.74, 0.69 and 0.82, respectively. The AUC were 0.814, 0.775 and 0.858, respectively.Conclusion:Comparing with Logistic regression and BP neural network, support vector machine model has better prediction effect, and can effectively predict the risk of acute exacerbation of readmission in elderly patients with COPD within 30 days.

Evidence summary of intermittent pneumatic compression devices in preventing venous thromboembolism for trauma patients / 中国实用护理杂志

Objective:To summarize the best evidence for intermittent pneumatic compression devices in preventing venous thromboembolism for trauma patients.Methods:According to "6S" evidence model, computer evidence retrieval was carried out. Guidelines, clinical decisions, evidence summaries, expert consensuses, and systematic reviews regarding intermittent pneumatic compression in preventing of venous thromboembolism for trauma patients were considered. The retrieval time limit was from the establishment of the database to October 31, 2021. Two researchers independently appraised articles, and extracted data for eligible studies.Results:A total of 21 articles were enrolled, including 13 guidelines, 1 clinical decision, 1 evidence summary, 2 expert consensuses, 4 systematic reviews. Totally 27 items of best evidence were summarized from four aspects: pretherapeutic evaluation, contraindications and applicable conditions, therapeutic strategies, training and education.Conclusions:This study summarized the best evidence of using intermittent pneumatic compression devices to prevent venous thromboembolism for trauma patients, which can provide evidence-based practice bases for nurses to implement scientific and effective standardized management of mechanical thromboprophylaxis. It is necessary to select evidence according to clinical practice and patients ′ wishes, so as to improve the effectiveness of using IPC in preventing thrombosis.

Three new triterpenoid saponins from Aralia echinocaulis / 中草药·英文版

Objective: To study the active ingredients in the root bark of Aralia echinocaulis. Methods: Three triterpenoid saponins were separated from the 70% ethanol extracts and purified by column chromatography and their structures were determined by spectroscopic analysis. Compound 1 and 3 were evaluated for antioxidant activity by the in vitro DPPH free radical scavenging ability and the protective effect of OH

A nested case-control study on the relationship between red blood cell folate and the prognosis of low-grade cervical intraepithelial neoplasia / 中华预防医学杂志

Objective: To evaluate the relationship between red blood cell folate (RBC folate) and the prognosis of low-grade cervical intraepithelial neoplasia (CIN 1). Methods: In the married women cohort established in 2014, 564 women with CIN 1 diagnosed by pathology were recruited. The demographic characteristics and factors of cervical intraepithelial neoplasia were collected. Meanwhile, the infection status of human papillomavirus (HPV) was detected by molecular diversion hybridization, and the level of RBC folate was measured by chemical photoimmunoassay. After 24 months of follow-up, pathological examination was performed again to observe the prognosis of participants. The women with reversal were taken as the control group,and those with continuous and progressive CIN 1 were taken as the case group respectively. The relationship between RBC folate and CIN 1 outcome was evaluated by logistic regression model. Results: 453 women completed the follow-up, aged (49.72±6.84) years old. CIN 1 was reversed in 342 women, continued in 58 cases and progressed in 53 cases. The RBC folate level M (Q1,Q3) were 399.01 (307.10, 538.97) ng/ml, 316.98 (184.74, 428.49) ng/ml and 247.14 (170.54, 348.97) ng/ml, respectively. With the decrease of RBC folate, the risk of continuous and progressive CIN 1 increased (all P<0.001), while the risk of reversal CIN 1 decreased gradually (P<0.001). Combined with high-risk human papillomavirus (HR-HPV) infection status, low level of RBC folate could increase the risk of CIN 1 progression regardless of HR-HPV infection (HR-HPV infection: OR=21.34, 95%CI: 3.98-114.54; HR-HPV uninfection: OR=11.15, 95%CI: 2.34-53.13). Conclusion: Low level of RBC folate could increase the risk of CIN 1 persistence and progression regardless of HR-HPV infection.

Echinacoside Alleviates Cognitive Impairment in Cerebral Ischemia Rats through α 7nAChR-Induced Autophagy / 中国结合医学杂志

OBJECTIVES@#To evaluate the effect of echinacoside (ECH) on cognitive dysfunction in post cerebral stroke model rats.@*METHODS@#The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery (MCAO). The rats were randomly divided into 3 groups by a random number table: the sham group (sham operation), the MCAO group (received operation for focal cerebral ischemia), and the ECH group (received operation for focal cerebral ischemia and ECH 50 mg/kg per day), with 6 rats in each group. The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze. The expression of α7nAChR in the hippocampus was detected by immunohistochemistry. The contents of acetylcholine (ACh), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and catalase (CAT) were evaluated by enzyme linked immunosorbent assay. The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining, respectively.@*RESULTS@#ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content (both P<0.01). Compared with MCAO rats, administration of ECH revealed shorter escape latency and long retention time at 7, 14 and 28 days (all P<0.01), increased the α7nAChR protein expression, ACh content, and ChAT activity, and decreased AChE activity in MCAO rats (all P<0.01). ECH significantly decreased MDA content and increased the GSH content, SOD, and CAT activities compared with MCAO rats (all P<0.05). ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats (all P<0.01).@*CONCLUSION@#ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats.

Relationship between hypertriglyceridemic waist phenotype and abnormal blood pressure in children and adolescents in Yinchuan City / 中国学校卫生

Objective@#To investigate the relationship between hypertriglyceridemic waist (HTW) phenotype and abnormal blood pressure in children and adolescents in Yinchuan City, Ningxia, and to provide scientific basis for early identification and prevention of hypertension.@*Methods@#A cluster sampling method was adopted to select 1 566 children and adolescents in Yinchuan. All participants completed questionnaire survey, physical measurement and biochemical examination.@*Results@#In general, after adjusting for age, smoking, drinking, and family history of hypertension, compared with the normal triglyceride normal waist (NWNT) phenotype, the enlarged waist (EW) and HTW phenotypes both increased the risk of abnormal blood pressure ( OR EW =2.62, 95% CI =1.87-3.67; OR HTW =3.97, 95% CI =2.30-6.86); the risk of abnormal blood pressure in boys with EW and HTW phenotypes was that of boys with NTNW phenotype, respectively 3.80 times (95% CI =2.35-6.15) and 3.32 times (95% CI =1.59-6.92) of girls EW and HTW phenotypes. The risk of abnormal blood pressure in girls with EW and HTW phenotypes was that of girls with NTNW phenotype, respectively 1.72 times (95% CI =1.06-2.82) and 4.62 times(95% CI =1.97-10.85).@*Conclusion@#The hypertriglyceridemic waist phenotypes among children and adolescents in Yinchuan is significantly correlated with increased risk of abnormal blood pressure. More attention should be paid to triglyceride level and waist circumference among children and adolescents.

Early assessment of the safety and immunogenicity of a third dose (booster) of COVID-19 immunization in Chinese adults / 医学前沿

Inducing durable and effective immunity against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) via vaccination is essential to combat the current pandemic of coronavirus disease 2019 (COVID-19). It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time, which calls for an additional vaccination regime, as known as booster immunization, to restore immunity among previously vaccinated populations. Here we report a pilot open-label trial of a third dose of BBIBP-CorV, an inactivated SARS-CoV-2 vaccine (Vero cell), on 136 participants aged between 18 to 63 years. Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28. While systemic reactogenicity was either absent or mild, SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks, surpassing the peak antibody titers elicited by the initial two-dose immunization regime. Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination. Furthermore, in an exploratory study, a newly developed recombinant protein vaccine, NVSI-06-08 (CHO Cells), was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals. Together, these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity, providing support for further trials of booster vaccination in larger populations.

Normocalcemic with elevated post-operative parathormone in primary hyperpara-thyroidism: 9 case reports and literature review / 北京大学学报(医学版)

OBJECTIVE@#To summarize and analyze the clinical characteristics of primary hyperpara-thyroidism (PHPT) with normocalcemic parathormone elevation (NPE) after surgical treatment, so as to improve the therapeutic ability and standardized post-operative follow-up of PHPT patients.@*METHODS@#Nine patients who were diagnosed with PHPT in the Department of Endocrinology of China-Japan Friendship Hospital from August 2017 to November 2019 were selected as the subjects. They all developed NPE within 6 months after surgical treatment. The clinical features and outcomes were collected and analyzed retrospectively, in addition, the related literature was reviewed.@*RESULTS@#Clinical features: among the 9 patients, 6 were middle-aged and elderly females and 3 were male. The main clinical manifestations were bone pain, kidney stones, nausea and fatigue except for one case of asymptomatic PHPT. Pre-operative examination showed high serum calcium [(3.33±0.48) mmol/L], low serum phosphorus [0.76 (0.74, 0.78) mmol/L], high 24-hour urinary calcium [8.1(7.8, 12.0) mmol/24 h], obviously elevated intact PTH [(546.1±257.7) ng/L], vitamin D deficiency [25-hydroxyvitamin D3 (21.0±5.7) nmol/L]. Serum levels of bone alkaline phosphatase [7 patients 41.3(38.6, 68.4) μg/L, 2 patients >90 μg/L] and N-terminal midcourse osteocalcin (>71.4 μg/L) were significantly elevated. The estimated glomerular filtration rate decreased in 2 patients. Imaging examination: 7 patients had osteoporosis. Renal calculi were found in 3 patients by renal ultrasound. Imaging examination of parathyroid glands found definite lesions in all the patients, including 2 cases of multiple lesions and 7 cases of single lesions.@*TREATMENT AND OUTCOME@#two patients underwent parathyroidectomy, while other patients were treated with microwave thermal ablation. PTH increased 1 month after therapy [(255.0±101.4) ng/L], and no recurrent lesions were found by parathyroid ultrasound. After combined treatment with cal-cium and vitamin D for six months, PTH decreased significantly and the level of serum calcium remained normal at anytime during the follow-up period.@*CONCLUSION@#The occurrence of postoperative NPE may be related to the higher pre-operative PTH, vitamin D deficiency and lower creatinine clearance. However, NPE may not predict recurrent hyperthyroidism or incomplete parathyroidectomy. Adequate calcium and vitamin D supplementation after surgery seems to be beneficial for patients with NPE. Post-operative follow-up of PHPT patients should be standardized to prevent and treat post-operative NPE.

EGFR exon 20 insertion mutation in non-small cell lung cancer: classification and clinical treatment research / 药学学报

In recent years, targeted therapy has become the standard treatment for advanced non-small cell lung cancer (NSCLC), but this treatment method has very limited effect on patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation. This insertion mutation is the third most common mutation in EGFR. It shrinks the drug binding pocket and gives tumors inherent resistance to available EGFR tyrosine kinase inhibitors (TKIs), resulting in the limited efficiency of the first and second generation of EGFR tyrosine. So far, no targeted therapy has been approved for NSCLC patients with EGFR exon 20 insertion mutations, and there are still no drugs that have met clinical needs. In this case, new treatment strategies using new EGFR TKIs or bispecific antibodies may establish new treatment standards for these patients in the future. In this review, we will summarize all relevant exon 20 insertions reported so far on the structure of EGFR and its influence on EGFR inhibitor sensitivity, as well as the treatment strategies of exon 20 insertions in NSCLC patients, hoping to be a clinical treatment for reference.

Brain tissue microstructure parameters estimation method based on proximal gradient network / 生物医学工程学杂志

Diffusion tensor imaging technology can provide information on the white matter of the brain, which can be used to explore changes in brain tissue structure, but it lacks the specific description of the microstructure information of brain tissue. The neurite orientation dispersion and density imaging make up for its shortcomings. But in order to accurately estimate the brain microstructure, a large number of diffusion gradients are needed, and the calculation is complex and time-consuming through maximum likelihood fitting. Therefore, this paper proposes a kind of microstructure parameters estimation method based on the proximal gradient network, which further avoids the classic fitting paradigm. The method can accurately estimate the parameters while reducing the number of diffusion gradients, and achieve the purpose of imaging quality better than the neurite orientation dispersion and density imaging model and accelerated microstructure imaging via convex optimization model.

Bat-related coronavirus / 第二军医大学学报

The outbreak of coronavirus disease 2019 (COVID-19) in Dec. 2019 sounded another alarm for humanbeing, with the first being the outbreak of severe acute respiratory syndrome (SARS) in 2003. Researchers found that the natural host of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of COVID-19, may be the Rhinolophus sinicus. There have been four outbreaks of coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV], swine acute diarrhea syndrome coronavirus [SADS-CoV] and SARS-CoV-2) worldwide since the beginning of 21st century, and they have caused huge threats and losses to human health, public health, economic development, and social stability. A large amount of evidence suggests that the natural host of all these four coronaviruses may be bats. This article reviews the species and global geographic distribution of bat-related coronaviruses, and the above-metioned four coronaviruses causing severe outbreaks.

The role of human papillomavirus 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein E2 in cervical carcinogenesis and their interaction effect / 中华预防医学杂志

Objective@#To investigate the role of human papillomavirus (HPV) 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein (hnRNP) E2 and their interaction effects in the progression of the cervical cancer.@*Methods@#Women with normal cervix (NC), low cervical intraepithelial neoplasia (CIN Ⅰ) and high cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) from the cervical lesions cohort in Jiexiu County of Shanxi Province from June 2014 to September 2014, and patients with cervical squamous cell carcinoma (SCC) treated at the Second Hospital of Shanxi Medical University in the same period were enrolled in this study. There were 257 participants, about 67 NC cases (26.07%), 69 CIN Ⅰ cases (26.85%), 68 CIN Ⅱ/Ⅲ cases (26.46%), and 53 SCC cases (20.62%), respectively. The information of demographic characteristics, life health habits and cervical lesions were collected by using the structured questionnaire. Cervical exfoliated cells and cervical biopsy tissues were collected to detect the infection of HPV16 and the protein expression levels of hnRNP E2, HPV16 E2 and E6. According to the median-value of the protein expression levels of hnRNP E2, HPV16 E2 and E6 and E2/E6 ratio in the NC group, the study participants were divided into the high and low expression groups/ratio groups. The multivariate logistic regression model was used to analyze the correlation between HPV16 early gene E2 and E6, hnRNP E2 and cervical cancer. The interaction effect was analyzed by using the generalized multifactor dimensionality reduction (GMDR) model.@*Results@#The ages of NC, CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups were (47.00±9.07), (47.64±7.35), (46.37±8.67) and (51.26±8.03) years old, respectively. The multivariate logistic regression model analysis showed that the HPV16 E2 low expression, E6 high expression and E2/E6 low ratio could increase the risk of CIN Ⅱ/Ⅲ, about OR (95%CI) values 11.11 (1.63-75.56), 8.00 (1.28-50.04), and 9.75 (1.22-77.72), respectively and SCC, about OR (95%CI) values 14.22 (2.11-95.88), 10.33 (1.67-64.00), and 12.38 (1.56-97.91), respectively. The hnRNP E2 low expression could increase the risk of CIN Ⅱ/Ⅲ and SCC, about OR (95%CI) values 3.35 (1.39-8.10) and 5.53 (1.54-19.88). The result of GMDR showed that there were interaction effects of the hnRNP E2 low expression, HPV16 E2 low expression and HPV16 E6 high expression in both CIN Ⅱ/Ⅲ and SCC groups.@*Conclusion@#The HPV16 E2 low expression, HPV16 E6 high expression and hnRNP E2 low expression could increase the risk of high-grade cervical intraepithelial neoplasia and cervical cancer, and they might have an important interaction effect in the progression of the cervical cancer.

Epigenetic strategies synergize with PD-L1/PD-1 targeted cancer immunotherapies to enhance antitumor responses

Immunotherapy strategies targeting the programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer. However, owing to the heterogeneity of tumors and individual immune systems, PD-L1/PD-1 blockade still shows slow response rates in controlling malignancies in many patients. Accumulating evidence has shown that an effective response to anti-PD-L1/anti-PD-1 therapy requires establishing an integrated immune cycle. Damage in any step of the immune cycle is one of the most important causes of immunotherapy failure. Impairments in the immune cycle can be restored by epigenetic modification, including reprogramming the environment of tumor-associated immunity, eliciting an immune response by increasing the presentation of tumor antigens, and by regulating T cell trafficking and reactivation. Thus, a rational combination of PD-L1/PD-1 blockade and epigenetic agents may offer great potential to retrain the immune system and to improve clinical outcomes of checkpoint blockade therapy.