Elements for Ethic Review of Clinical Trials for Rare Disease Drugs / 罕见病研究

In the past decade, with the implementation of policies to promote the research and development of rare disease drugs, the increase in the number of clinical trials for rare disease drugs has posed new challenges to ethical review. Clinical trials of rare disease drugs involve vulnerable populations with a small number of patients, scattered populations, and relative concentration in certain disease areas. The trials are mainly conducted in the early stages, often requiring small sample sizes, single arm designs, and more new technologies such as cellular and gene therapy. In addition to meeting the general requirements of clinical trials for common diseases, ethical review should also give special attention to the special characteristics of rare diseases in risk benefit assessment, research design, informed consent, trial operation, etc. Ethical review of clinical trials for rare diseases should effectively promote the development of new drugs for rare diseases and protect the rights and interests of participants.By analyzing the characteristics of clinical trials for rare diseases drugs, this paper presents the points of special concern during the review, aiming to improve the level of ethical review for clinical trials of drugs related to rare diseases.

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions / 医学前沿

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

Operation and Reflection on Exemption from Ethical Review / 中国医学伦理学

Ethical review is an important protective measure for research participants when conducting life sciences and medical research involving humans. "Exemption from ethical review" was proposed in The Measures for Ethical Review of Human Life Sciences and Medical Research Involving Humans issued in February 2023. To implement the exemption from ethical review within the permitted scope of laws and regulations, and to protect the privacy and rights of research participants when utilizing their data information and biological samples, multiple factors need to be considered, including the person responsible for exemption from ethical review, the conditions for exemption from ethical review, and the specific process for exemption from ethical review. As with other review procedures, exemption from ethical review also required the development of corresponding systems, implementation of responsibilities, and reliance on the construction of subject protection systems. It is hoped that this discussion can provide considerations for the implementation of exemption from ethical review.

Guidelines for Ethical Review Project Entrustment of Life Science and Medical Research Involving Humans / 中国医学伦理学

The seventh article of Measures for the Ethical Review of Biomedical Research Involving Humans (2016) stipulated that medical and health institutions without an ethics committee shall not carry out biomedical research involving Humans. The Opinions on Strengthening the Governance of Ethics in Science and Technology, issued in March 2022, clearly stated that the institutions that do not meet the conditions for establishing a scientific and technological ethics (review) committee should entrust other institutions to conduct the review. The fourteenth article of Measures for Ethical Review of Life Science and Medical Research Involving Humans (2023) proposes that if an institution, which carries out life science and medical research involving humans, has not established an ethics committee or its ethics committee is not competent for ethics review, it can entrust a competent ethics committee or regional ethics committee in writing to carry out ethical review. Most medical institutions at or above the second level in China have set up ethics committees. While most universities and colleges, scientific research institutions, enterprises and grass-roots medical and health institutions have not set up ethics committees, which lack a working system to protect the safety and interests of the participants, and is difficult to conduct life sciences and medical research involving humans. At present, there is a need for some research institutions that do not have the conditions to establish ethics committees to entrust their projects of life science and medical research involving humans to other institutions for ethical review. The entrusted review is still in the exploratory stage, and there is no relevant specification. The hasty implementation of entrusted review may not achieve the goal of effectively protecting the safety and interests of the participants, and even cause legal disputes. Based on the thematic discussion, with reference to the relevant laws and regulations, departmental rules, ethical standards, and the experience of the ethics committees of some domestic institutions in implementing the entrusted review, the guideline was formulated for the reference of the current entrusted review to ensure the safety and interests of the participants.

Effects of electroacupuncture at Neiguan (PC6) on arrhythmia during myocardial infarction in a rat model of myocardial ischemia-reperfusion / 针灸推拿医学（英文版）

Objective: To observe the effects of electroacupuncture (EA) at Neiguan (PC6) on arrhythmia during acute myocardial ischemia-reperfusion and the expression of connexin 43 (Cx43) in rats. Methods: A total of 40 Sprague-Dawley male rats were used. Ten rats were randomly selected as the blank group, and the remaining 30 rats were randomly divided into a model group and an EA group, with 15 rats in each group. Before modeling, rats in the EA group received one session of EA intervention at bilateral Neiguan (PC6) for 30 min; the other groups were treated with the same grasping and anesthesia for 30 min without intervention. PowerLab physiological recorder was used to record electrocardiograph within 30 min of infarction. After the experiment, cardiac tissue and serum were collected from rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of myocardial tissue in the ventricular infarction area of rats in each group. The expression of Cx43 protein in the myocardium of each group was detected by Western blotting (WB). Enzyme-linked immunosorbent assay (ELISA) was used to determine the activity of Na+-K+-ATPase in myocardial tissue and the serum content of endogenous digitalis-like factor (EDLF) in rats. Results: There was no statistical difference in arrhythmia score between the EA group and the model group, but the total duration and average duration of arrhythmia in the EA group were decreased (P<0.01). HE staining showed that compared with the blank group, myocardial cells in the model group were disorganized and seriously damaged. The pathological changes in the EA group were similar to those in the model group, but the damage was relatively minor. The results of WB showed that compared with the blank group, the Cx43 expression in myocardial tissue of the model group was decreased (P<0.01); compared with the model group, the Cx43 expression in the EA group was increased (P<0.01); compared with the blank group, the Na+-K+-ATPase activity in myocardial tissue of the model group was significantly decreased (P<0.01); compared with the model group, the Na+-K+-ATPase activity in the EA group was increased (P<0.01). ELISA results showed that compared with the blank group, the serum EDLF content in the model group was significantly increased (P<0.01); compared with the model group, the EDLF content in the EA group was decreased (P<0.01). Conclusion: EA at Neiguan (PC6) can delay and reduce the onset of arrhythmia during myocardial infarction in the rat model of myocardial ischemia-reperfusion. Its mechanism of action may be related to the regulation of the Cx43 expression in myocardial tissue, improvement of the activity of Na+-K+-ATPase in myocardial tissue, and increase in the content of serum EDLF.

Cognitive dysfunction status and risk prediction of patients with coronary heart disease / 中国实用护理杂志

Objective:To understand the current situation of cognitive dysfunction in patients with coronary heart disease, and explore the risk prediction model of the onset of cognitive dysfunction in patients with coronary heart disease.Methods:A total of 448 patients with coronary heart disease admitted to the North China University of Science and Technology Affiliated Hospital from January 2019 to June 2020 were prospectively selected as study subjects. Patients with coronary heart disease were divided into the cognitive dysfunction group ( n=185) and the normal cognitive function group ( n=263) according to whether they were accompanied by cognitive dysfunction. Demographic characteristics, cognitive function, disease history, blood pressure, blood glucose, blood lipid and vascular lesions were compared between the two groups. Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive function. Logistic regression was used to analyze the risk factors of cognitive dysfunction in coronary heart disease patients, and the prediction model of the above risk factors was constructed. The value of the prediction model was evaluated by C-index and cilibration curve. Results:The language, abstraction, visual space and execution, delayed memory and total scores of the cognitive dysfunction group were 1.81 ± 0.59, 1.12 ± 0.33, 3.01 ± 0.90, 2.61 ± 0.79 and 22.32 ± 1.70, respectively, which were lower than those of the normal cognitive function group (2.68 ± 0.47, 1.82 ± 0.38, 4.54 ± 0.50, 4.77 ± 0.42, 27.67 ± 0.76), and the differences were statistically significant ( t values were 17.39-40.00, all P<0.05). The age, fasting blood glucose, systolic blood pressure, proportion of alcohol drinking, proportion of diabetes mellitus in the cognitive dysfunction group were (62.86 ± 5.21) years, (6.19 ± 0.89) mmol/L, (144.00 ± 17.16) mmHg (1 mmHg=0.133 kPa), 36.76% (68/185), 16.22% (30/185), respectively, which were higher than (58.77 ± 5.63) years, (5.46 ± 0.95) mmol/L, (133.74 ± 15.90) mmHg, 27.38% (72/263), 6.84% (18/263) in the normal cognitive function group, the differences were statistically significant ( t=7.81, 8.25, 6.42, χ2=4.45, 9.97, all P<0.05). The rates of single vessel, double vessel and three vessel lesions in the cognitive dysfunction group were 49.73% (92/185), 27.03% (50/185) and 23.24% (43/185), respectively, and those in normal cognitive function group were 46.39% (122/263), 39.92% (105/263) and 13.69% (36/263), respectively ( χ2=11.10, P<0.05) . Logistic regression analysis showed that age, fasting blood glucose, systolic blood pressure and number of vascular lesions were independent risk factors for coronary heart disease patients with cognitive impairment ( OR values were 1.038-2.216, all P<0.05). The correction curve of the prediction model composed of age, fasting blood glucose, systolic blood pressure and number of vascular lesions was in good agreement with the ideal curve, and the C-index of the model was 0.807 for the diagnosis of cognitive dysfunction in patients with coronary heart disease. Conclusions:The cognitive dysfunction of patients with coronary heart disease is mainly manifested in language, abstraction, visual space and execution and delayed memory. The prediction model composed of age, fasting blood glucose, systolic blood pressure and number of vascular lesions has a certain degree of discrimination and accuracy for patients with coronary heart disease complicated by cognitive dysfunction, and can be used for the screening of coronary heart disease complicated by cognitive dysfunction.

Progress in pulmonary enteric adenocarcinoma / 中华肿瘤杂志

Pulmonary enteric adenocarcinoma (PEAC), as a rare histologic subtype of primary lung adenocarcinoma, is defined as an adenocarcinoma in which the enteric component exceeds 50%. It is named after its shared morphological and immunohistochemical features with colorectal cancer. While with such similarity, the differential diagnosis of PEAC and lung metastatic colorectal cancer is a great challenge in the clinic. PEAC may originate from the intestinal metaplasia of respiratory basal cells stimulated by risk factors such as smoking. Current studies have found that KRAS is a relatively high-frequency mutation gene, and other driver gene mutations are rare. In terms of immunohistochemistry, in pulmonary enteric adenocarcinoma, the positive rate was 88.2% (149/169) for CK7, 78.1% (132/169) for CDX2, 48.2% (82/170) for CK20 and 38.8% (66/170) for TTF1. As for clinical features, the average age of onset for pulmonary enteric adenocarcinoma was 62 years, male patients accounted for 56.5% (35/62), smokers accounted for 78.8% (41/52), and 41.4% (24/58) of the primary lesion was located in the upper lobe of the right lung. In terms of treatment, conventional non-small cell lung cancer (NSCLC) regimens rather than colorectal cancer regimens are now recommended. There is still an urgent need for more basic and clinical research, in-depth exploration of its molecular feature and pathogenesis from the level of omics and other aspects, to help diagnosis and differential diagnosis, and find the optimal chemotherapy regimen, possibly effective targeted therapy and even immunotherapy.

Impact of co-infection of streptococcus pneumoniae and pneumococcal vaccination on the clinical outcomes of coronavirus disease 19 / 中华预防医学杂志

Coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has spread all over the world. Streptococcus pneumoniae as a common pathogen of community-acquired pneumonia shares similar high-risk susceptible populations with COVID-19. Streptococcus pneumoniae co-infection is a key risk factor for severe COVID-19 and death. Pneumococcal vaccination has a beneficial impact on reducing the incidence and mortality of COVID-19. The vaccination rate of streptococcus pneumoniae is still low in China. Streptococcus pneumoniae vaccination may be one of effective strategies in the management of COVID-19 for high-risk population such as the elderly and those who have underlying chronic diseases.

Challenges of Investigator-initiated Clinical Trials to Support the New Drug Development / 中国肺癌杂志

A large number of investigator-initiated clinical trials (IIT) were conducted in China, some of them should play an important supporting role in new drug development. Due to the large number, small scale and uneven quality of IIT in China, especially a big gap between the IIT and industry-sponsored trials in terms of protocol design, quality management and ethical review, many IIT can't be used to support the new drug development. Therefore, it is necessary for regulatory authorities, sponsors, research institutions, ethics committees and researchers to improve their understanding of the role of IIT. In order to support the new drug development with high-quality IIT, formulating supervising system, establishing an effective quality management system, enhancing the training of researchers and improving the ability of ethical review should be implemented effectively.
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Multicenter Randomized Controlled Clinical Trial of Longmu Zhuanggu Granule in Treatment of Children Recurrent Respiratory Infection with Lung-Spleen Qi Deficiency Syndrome / 中国实验方剂学杂志

Objective:To evaluate the clinical efficacy and safety of Longmu Zhuanggu granule for the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency. Method:This multicenter stratified， block-randomized， double-blind， double-dummy， positive drug （pidotimod granule） parallel controlled， and non-inferiority trail intended to included 240 children patients and divided them into the experimental group （<italic>n</italic>=120） and the control group （<italic>n</italic>=120） at the ratio of 1∶1. Patients in both groups were treated for eight successive weeks and followed up for 12 months. The cure rates， numbers of respiratory infections， average courses of disease， curative effects of traditional Chinese medicine （TCM） syndrome， curative effects of individual symptoms， curative effects of immune indexes， and safety indexes between the two groups were observed and compared. Result:A total of 237 subjects were collected from 10 research centers， including 119 cases in the control group and 118 in the experimental group. There were 236 cases enrolled into the full analysis set （FAS）， 210 into the per-protocol set （PPS）， and 236 into the safety set （SS）. The baseline data of the two groups were not significantly different from each other， indicating that they were comparable. The cure rates of the experimental group and control group were 75.21% （88/117） and 73.95%（88/119）， respectively， with the 95% confidence interval （CI） of difference between the two groups being 1.26% （-9.85%，12.37%） for FAS and 3.81% （-6.28%，13.90%） for PPS. The 95% CI fell within the 10% non-inferiority margin， implying that non-infertility test of the cure rate in the treatment of endpoint disease was valid， and the conclusions of FAS and PPS analysis were consistent. There was no significant difference in the number or course of upper respiratory infection， bronchitis， and pneumonia. The difference in curative effects of TCM syndrome between the two groups after four weeks of treatment was not remarkable. After eight weeks of treatment， the total effective rate of the experimental group was 84.62%（99/117）， statistically higher than 78.15%（93/119） of the control group（<italic>χ</italic>²=-3.26，<italic>P</italic><0.05）. There were no significant differences in the disappearance rates of individual symptoms between the two groups after four weeks of treatment. After eight weeks of treatment， the experimental group and control group exhibited the disappearance rates of 67.50%（54/80） and 47.37%（36/76） for shortness of breath and laziness to speak， 75.00%（54/72） and 53.33%（40/75） for poor appetite， 54.55%（60/110） and 37.84%（42/111） for hyperhidrosis， respectively， with obviously better outcomes observed in the experimental group （<italic>P</italic><0.05，<italic>P</italic><0.01）. The inter-group comparison revealed significant differences in immune indexes after eight weeks of treatment. As demonstrated by comparison with the situations before treatment， IgA， IgG， IgM， and CD4 did not change significantly after treatment. Except for CD8 in the experimental group (<italic>P</italic><0.05), there was no significant difference in other immune indexes before and after treatment There was no significant difference in the incidence of adverse reactions. Conclusion:Longmu Zhuanggu granule is not inferior to pidomod granule in the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency， and it exhibits good safety， implying its promising clinical application value.

Research on the relationship between smartphone addiction and mental health of medical freshmen / 中华医学教育探索杂志

Objective:To understand the current situation of smartphone addiction and mental health of medical freshmen, and conduct research on the relationship between smartphone addiction and mental health, so as to provide evidence for the prevention and intervention of smartphone addiction among medical freshmen.Methods:A stratified random sampling method was used to select 279 freshmen in the medical profession of Binzhou Medical University as the research objects, and the revised smartphone addiction scale (SAS-C) and mental health symptom self-rating checklist scale (SCL-90) were selected for testing. SPSS 19.0 was used for t test. Results:A percentage of 29.71 medical freshmen had smartphone addiction problems, which was generally above average. The SCL-90 total scores and the scores of somatization, interpersonal sensitivity, depression, anxiety, hostility, psychosis and other factors in the smartphone addiction group were significantly higher than those in non-smartphone addiction group. The total score of smartphone addiction in medical professional freshmen was significantly correlated with the total score of SCL-90. In addition to the interference factors of daily life, other factors had positive correlation with various factors of SCL-90. Interpersonal sensitivity and obsessive-compulsive symptoms had a significant predictive effect on smartphone addiction (β=0.24, 0.26, P < 0.01), which were important variables affecting mobile phone addiction of medical freshmen. Conclusion:Many medical freshmen have the problem of smartphone addiction, which may cause a series of psychological problems, especially obsessive-compulsive symptoms, interpersonal sensitivity, anxiety and psychosis.

Effect of electroacupuncture on expression of IL-23/IL-17 axis and TLR4 in infarcted tissue in rats with myocardial infarction / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on expression of interleukin (IL) -23/IL-17 axis and Toll-like receptor 4 (TLR4) in the infarcted tissue in rats with myocardial infarction (MI), and to explore the mechanism of EA on alleviating MI injury.@*METHODS@#Forty male SD rats were randomly divided into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The MI models were established by ligation of left anterior descending coronary artery in the model group and EA group, while only threading was performed in the sham-operation group and sham-operation plus EA group. The rats in the sham-operation plus EA group and EA group were treated with EA at "Neiguan" (PC 6), disperse-dense wave, 2 Hz/100 Hz, 2 mA, once a day, 20 min each time, for 3 days. After the intervention, the ejection fraction (EF) was measured by echocardiography to evaluate the cardiac function; the infarct area was measured by TTC staining; the HE staining was used to observe the morphological changes of myocardial tissue; the levels of IL-23 and IL-17 in infarcted tissue were detected by ELISA; the protein expression of TLR4 in infarcted tissue was detected by Western blot.@*RESULTS@#Compared with the sham-operation group, the EF was decreased (@*CONCLUSION@#EA may alleviate the excessive inflammatory response after MI by inhibiting the expression of IL-23/IL-17 axis in MI rats, and TLR4 may be involved during the process.

Effect of electroacupuncture at "Neiguan" (PC 6) on cardiac function and inflammatory factors of acupoint area in rats with acute myocardial ischemia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function and cardiomyocyte apoptosis in rats with acute myocardial ischemia (AMI), and to explore the correlation between myocardial protective effect of EA and inflammatory factors i.e. interleukin-1β (IL-1β) and interleukin-17 (IL-17) of "Neiguan" (PC 6) area.@*METHODS@#A total of 40 male SD rats with normal ultrasonic cardiogram were randomized into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The AMI model was established by ligating the left anterior descending (LAD) branch of the coronary artery in the model group and the EA group, while the threading without ligating was adopted in the sham-operation group and the sham-operation plus EA group. In the sham-operation plus EA group and the EA group, EA at bilateral "Neiguan" (PC 6) was applied, with disperse-dense wave, 2 Hz/100 Hz in frequency and 2 mA in density, once a day, 20 min a time for 3 days. The cardiac ejection fraction (EF) and fractional shortening (FS) were measured by ultrasonic cardiogram to evaluate the cardiac function, the cardiomyocyte apoptosis was detected by TUNEL staining, the infiltration of inflammatory factors of "Neiguan" (PC 6) area was observed by H.E. staining, the expression of inflammatory factors IL-1β and IL-17 of "Neiguan" (PC 6) area was detected by immunofluorescence staining.@*RESULTS@#Compared with the sham-operation group, EF and FS were decreased (@*CONCLUSION@#Electroacupuncture at "Neiguan" (PC 6) can improve the cardiac function and reduce the apoptosis of cardiomyocyte in rats with acute myocardial ischemia, its mechanism may be related to the regulation of the inflammatory factors of "Neiguan" (PC 6) area.

Relationship between Stress Hyperglycemia and Catheter-related Urinary Tract Infection in Stroke Patients / 中国医学科学院学报

Objective To verify the relationship between catheter-related urinary tract infection(CAUTI)and stress hyperglycemia during catheter retention in stroke patients. Methods We used nosocomial infection monitoring system to track the status of CAUTI in stroke patients in a hospital.The study cohort was all the patients who received retention catheterization from January 2016 to March 2020.According to the nested case-control design,multivariate logistic regression analysis was performed to explore the relationship between stress hyperglycemia and CAUTI in stroke patients with indwelling catheter. Results A total of 322 cases of CAUTI and 644 cases of non-CAUTI were enrolled in this study.The length of stay in the case group was(20.68 ± 3.73)d,significantly longer than that[(13.00 ± 4.01)d]in the control group(t=29.473,P <0.001).Compared with non-stress hyperglycemia,stress hyperglycemia posed a higher risk of CAUTI in the stroke patients with indwelling catheter(OR=2.020,95% CI=1.447-2.821,P=0.000)and led to the higher incidence of CAUTI in one thousand days(P<0.001). Conclusion Stress hyperglycemia in the stroke patients with indwelling catheter can significantly increase the risk of CAUTI.

Clinical manifestation and genetic analysis of a child with early infantile epileptic encephalopathy 42 / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic characterization of a child with early infantile epileptic encephalopathy.@*METHODS@#The proband was subjected to history taking and was diagnosed based on his clinical manifestation, magnetic resonance imaging (MRI) and whole exome sequencing (WES). Sanger sequencing was carried out to determine the origin of pathogenic variant.@*RESULTS@#The proband unconsciously tilts his head to one side with squint, which revealed an abnormal discharge. MRI indicated suspicious abnormal signal shadow in the left posterior frontal cortex in addition with inflammation signs in the right maxillary sinus and ethmoid sinus. WES revealed that the proband has carried a heterozygous c.5789G>A variant in the CACNAIA gene. The result of Sanger sequencing was in keeping with that of WES. Neither of his parents has carried the same variant.@*CONCLUSION@#The heterozygous c.5789G>A variant of the CACNAIA gene probably underlay the early infantile epileptic encephalopathy 42 in the proband, which has a de novo origin.

Synergistic killing effects of Stattic and arsenic trioxide on acute myeloid leukemia THP1 cell line and underlying mechanism / 西安交通大学学报(医学版)

【Objective】 To investigate the effects and mechanism of STAT3 inhibitor Stattic combined with arsenic trioxide (ATO) on the survival and apoptosis of acute myeloid leukemia (AML) THP1 cells. 【Methods】 CCK8 assay was used to detect the effects of Stattic combined with ATO on cell viability, flow cytometry was used to detect cellular apoptosis and ROS levels, and Caspase 3/7 Glo assay was used to determine Caspase 3/7 activity. qPCR was used to detect mRNA expression levels of GCLM, GCLC and HO-1 genes, and Western blotting was used to detect protein expression levels of P-STAT3, STAT3 and Nrf2. 【Results】 Stattic significantly inhibited the level of phosphorylated STAT3, aggravated the inhibitory effect of ATO on THP1 cell viability, and enhanced the apoptosis and reactive oxygen species (ROS) induced by ATO. Stattic significantly inhibited the expression of ATO-upregulated Nrf2 and the expression of Nrf2 downstream genes including HO-1, GCLM and GCLC. 【Conclusion】 Stattic can enhance the effects of ATO-mediated viability inhibition and apoptosis. The mechanism may be related to the increased ROS via inhibition of Nrf2 and Nrf2 downstream gene expression.

Individualized treatment recommendations for lung cancer patients at different stages of treatment during the outbreak of 2019 novel coronavirus disease epidemic / 中华肿瘤杂志

In order to achieve the overall victory of the 2019 novel coronavirus disease epidemic in this 'war’, especially to prevent the disease recurrence from rebounding during the resumption of labor, the government has not loosened any control of personnel mobility, which has obviously affected the normal examination and treatment of lung cancer patients under the influence of this epidemic. During the epidemic period, cancer patients with low immunity levels face the double ordeals of disease and epidemic situation. Compared with the general population, they are more likely to be infected with the new coronavirus. Among the infected cancer patients, lung cancer is the most common type. It is necessary to provide more appropriate individualized treatment recommendations for patients with lung cancer based on the epidemic situation of the patient's location and in combination with the patient's own condition. Through active prevention of infection, timely conversion of treatment strategies, online and offline joint control, and positive psychological counseling, we significantly hope to help patients with lung cancer to survive this difficult period.

Efficacy, safety and common adverse reactions of Apatinib monotherapy in elderly patients with advanced colorectal cancer failing standard regimens / 中华老年医学杂志

Objective:To investigate the efficacy, safety and common adverse reactions of Apatinib monotherapy in elderly patients with advanced colorectal cancer(CRC)who failed to respond to standard regimens.Methods:This was a retrospective study.A total of 106 elderly patients with advanced CRC who had failed standard regimens from January 2015 to December 2019 were included.Patients enrolled in this study received Apatinib with an initial dosage of 500 mg or 250 mg.The objective response rate(ORR)and disease control rate(DCR)were assessed after treatment with apatinib.The progression-free survival(PFS)and overall survival(OS)were evaluated during the follow-up period.Additionally, adverse reactions during treatment with apatinib were recorded.Results:The efficacy was assessed by using the best overall response during apatinib treatment.Of 106 patients, there were 9 patients with partial response(PR), 68 patients with stable disease(SD)and 29 patients with progressive disease(PD). The ORR was 8.5% and the DCR was 72.6%.The median PFS was 3.6 months and the median OS was 10.1 months.Relatively common adverse reactions in these patients were hypertension(63 patients, 59.4%)and hand-foot syndrome(HFS)(51 patients, 48.1%)during apatinib treatment.The median PFS of patients with hypertension and of patients without hypertension were 5.0 months and 3.0 months, respectively( P=0.008). The median PFS of patients with and without HFS were 5.4 months and 3.0 months, respectively( P=0.013). Conclusions:Preliminary evidence suggests that Apatinib monotherapy has good efficacy and safety in elderly patients with advanced CRC who have failed standard regimens, and patients with adverse reactions such as hypertension and HSF still have a good prognosis.

Acupoint selection rules in treating gastroesophageal reflux disease with acupuncture in China based on data mining / 中国针灸

OBJECTIVE@#To analyze the rules of acupoint selection in the treatment of gastroesophageal reflux disease in China using data mining technology.@*METHODS@#The published literature of treating gastroesophageal reflux disease with acupuncture was retrieved from electronic databases from January 1, 1983 to December 1, 2019, including SinoMed, CNKI, Wanfang and VIP database. Acupuncture prescription database was established, and the rules of acupoint selection were explored by statistical software SPSS 20.0 and SPSS Modeler 18.0.@*RESULTS@#A total of 92 articles were included into this analysis, involving 92 acupuncture prescriptions, 76 acupoints. The total frequency of using these acupoints reached 549 times. Zhongwan (CV 12) was the most frequently used acupoint; the often selected meridians were conception vessel, stomach meridian, governor vessel, bladder meridian; the acupoints located at the abdomen, lower limbs and back were commonly selected; crossing points in the specific acupoints were commonly selected; the most frequently used group was Zusanli (ST 36)-Zhongwan (CV 12) and Neiguan (PC 6).@*CONCLUSION@#Treating gastroesophageal reflux disease by acupuncture in China is dominated by

Progress on clinical trials of cancer drugs in China, 2019 / 中华肿瘤杂志

Objective@#To deliver macro understanding of the latest research progress on clinical trials and approved products of cancer drugs in China in 2019.@*Methods@#The number of clinical trials and related investigational products by domestic and foreign enterprises in 2019 were acquired in the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, while listed drugs were obtained in the China Food and Drug Administration Query System for Domestic and Imported Drug. Characteristics on stage, scope, indication of those trials, classification and mechanism of involved products, as well as listed anticancer drugs were summarized and depicted.@*Results@#There were 474 cancer drug trials registered in China in 2019, accounting for 21.8% of the total, and 397 (83.8%) were initiated by domestic pharmaceutical enterprises. Overall, international multicenter trials accounted for 13.1%, and phase I trials accounted for 47.3%. Compared with global enterprises, the proportion of international multi-center trials initiated by domestic companies is lower (4.8% vs. 55.8%, P<0.001), and the proportion of phase I clinical trials and bioequivalence trials is higher (51.9% vs. 23.4%, 19.4% vs. 1.3%, P<0.001). An accumulative of 27 cancer types were involved for all the cancer drug trials, and lung cancer, solid tumor, and breast cancer were the most common cancer types, with 103, 95 and 49 trials, respectively. For the three cancer types unique to Chinese population, gastric, liver and esophageal cancer, the total number of initiated trials was 47. For all those trials, there were 335 cancer drug varieties, with 86.0% developed by domestic pharmaceutical enterprises, including 300 therapeutic drugs, 30 adjunctive drugs and 5 preventive drugs. In terms of mechanism, targeted drugs and immune drugs were the most popular, accounting for 74.6% and 20.3%, respectively. In addition, 17 anticancer drugs targeting on 11 cancer types were approved in China in 2019.@*Conclusions@#Clinical trials on cancer drugs in China have ushered a booming era, with large number of innovative agents represented by targeted drugs and immune drugs under clinical development or putting into clinical practice. Those local enterprises are playing more and more critical roles. Strengthening clinical research and development on Chinese unique cancer types is the key direction of future work.