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.

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.

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.

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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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.

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.

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.

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.

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.

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.

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.

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.

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.

Clinical observation on gastroesophageal reflux asthma treated with needling technique / 中国针灸

OBJECTIVE@#To compare the clinical effect on gastroesophageal reflux asthma between the needling technique of acupuncture (acupuncture for promoting the circulation of the governor vessel and reducing the reversed ) and omeprazole enteric capsules (OME).@*METHODS@#A total of 60 patients with gastroesophageal reflux asthma were randomized into an acupuncture group and a western medication group, 30 cases in each one. The basic treatment for anti-bronchial asthma was provided in both of the groups. Additionally, OME was prescribed for oral administration in the western medication group, twice a day, 20 mg each time, for 8 weeks. In the acupuncture group, the needling technique of acupuncture was added. The needles were inserted at the sites inferior to the spinous processes of T to T. Acupuncture was given once in the morning on Tuesday, Thursday and Saturday respectively, totally for 8 weeks. Separately, before and after treatment, the score of reflux disease diagnostic questionnaire (RDQ), the score of asthma control test (ACT) and the tenderness threshold at the sites inferior to the spinous processes of T to T were observed and the clinical effect was evaluated in the two groups.@*RESULTS@#①The remarkably effective and curative rate was 46.7% (14/30) in the acupuncture group, higher than 3.3% (1/30) in the western medication group (<0.01). The asthma control rate was 66.7% (20/30) in the acupuncture group, higher than 13.3% (4/30) in the western medication group (<0.01). ②RDQ score after treatment was lower than that before treatment in either group (<0.05). The decrease range of RDQ score in the acupuncture group was larger than that of the western medication group (<0.05). After treatment, ACT score was increased as compared with that before treatment in either group (<0.05) and the increase range of ACT score in the acupuncture group was larger than that of the western medication group (<0.05). ③The tenderness thresholds at the sites inferior to the spinous processes of T to T and T to T were all increased after treatment as compared with those before treatment in the acupuncture group separately (<0.05). In the western medication group, the thresholds were only increased at the sites inferior to the spinous processes of T, T and T after treatment as compared with those before treatment separately (<0.05). After treatment, the tenderness thresholds at T to T in the acupuncture group were all higher than the western medication group (<0.05).@*CONCLUSION@#The needling technique of acupuncture effectively relieves the symptoms of gastroesophageal reflux asthma and improves the quality of life in the patients and its effect is better than omeprazole enteric capsules.

Professor 's concept and experience in the diagnosis and treatment of gastroesophageal reflux disease / 中国针灸

In view of the five major misunderstandings in the clinical understanding of gastroesophageal reflux disease in traditional Chinese medicine, that is, wrong main symptoms, wrong position of the disease, wrong character of the disease, treating acid with acid, and attaching importance to drugs and neglecting acupuncture-moxibustion in treatment, Professor has proposed the corresponding solving strategies, which includes grasping the main disease, carefully examining the disease position, distinguishing the character of disease, and no acid suppression for acid regurgitation. In addition, Professor highly values the external treatment of traditional Chinese medicine. In particular, the acupuncture therapy of " (promote the circulation of the governor vessel and reduce the reversed )" based on many years of clinical experience provides new ideas and methods for the diagnosis and treatment of gastroesophageal reflux disease in traditional Chinese medicine.

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

Cathepsin B Affects the Activation of Nucleotide-binding Domain and Leucine-rich-repeat-containing Family and Pyrin Domain-containing 3 Inflammasome via Transient Receptor Potential Mucolipin-1 / 中国医学科学院学报

Objective To explore the effects of cathepsin B(CTSB)on the activation of nucleotide-binding domain and leucine-rich-repeat-containing family and pyrin domain-containing 3(NLRP3)inflammasome via transient receptor potential mucolipin-1(TRPML1)in cell oxidative stress model and specific gene silencing cell model. Methods BV2 cells cultured in vivo were treated separately or simultaneously with hydrogen peroxide(HO),calcium-sensitive receptor agonist gadolinium trichloride(GdCl),and CTSB inhibitor CA-074Me,and interleukin-1(IL-1)beta and caspase-1 protein were detected by enzyme-linked immunosorbent assay.The growth activity of BV2 cells in each group was measured by MTT.BV2 cells were treated with different concentrations of HO.Cystatin C mRNA and TRPML1 mRNA in BV2 cells were detected by real-time quantitative polymerase chain reaction and the proteins of TRPML1,CTSB,cathepsin D(CTSD),cathepsin L(CTSL)and cathepsin V(CTSV)were detected by Western blot.Specific small interfering RNA was designed for TRPML1 gene target sequence.TRPML1 gene silencing cell lines(named Tr-si-Bv2 cells)were established in BV2 cells and treated with or without HO.TRPML1,CTSB and transcription factor EB(TFEB)proteins in Tr-si-Bv2 cells or control cells were detected by Western blot. Results After treatment with HO,the expression of caspase-1 protein and NLRP3 mRNA in BV2 cells was increased,and IL-1beta protein in BV2 cells was significantly increased after treatment with GdCl(P=0.0036).After treatment with CA-074Me,the doses of NLRP3 mRNA(P=0.037),caspase-1(P=0.021),and IL-1β(P= 0.036)were significantly reduced.Cells in the HO group and HO+GdCl group grew more slowly.The expressions of CTSB mRNA and TRPML1 mRNA,or CTSB and TRPML1 proteins in BV2 cells in the treatment group with 200 μmol/L of HO concentration were similar.HO-induced CTSB protein expression was inhibited after silencing TRPML1 gene.The changes of other cathepsins were not affected for the different concentration of HO.In the BV2 cells treated with TRPML1 gene silencing,the expression of CTSB protein was significantly reduced and the difference was statistically significant(P=0.021)between the HO +siRNA treatment group and the HO treatment group.Conclusion CTSB regulates the activation of NLRP3 inflammasome in the oxidative stress model of microglia cells,probably mediated by calcium channel protein TRPML1.

Suggestions for promoting domestic clinical trials of medicinal products for rare diseases / 国际药学研究杂志

Regardless of rare or common diseases, it is a common desire to shorten the time period of drug devel-opment. This is of particular importance for rare diseases because the most of rare diseases are lack of sufficient therapeu-tic methods. The incentive policy for the development of rare disease drugs(also called orphan drugs)was first adopted by the United States in the Orphan Drug Act in 1983, and correspondingly, most of clinical trials of the orphan drugs are seen in the United States. The clinical trials of orphan drugs are also increasingly on the rise in China. The main target diseases of the major portion of orphan drugs in clinical trials are mainly the rare cancers, and most of them are in the phaseⅡtrials. The clinical trial is a particular step in the orphan drug development. Besides the need of policy support, it still suffers from severe challenges in the clinical trial design and the clinical trial implementation, including the insuffi-ciency in the understanding of natural history and mechanism of the diseases, the impossibility to conduct the random-ized controlled clinical trial, the requirement for innovated design and more sensitive outcome measures to evaluate effi-cacy, the difficulty in enrolling patients to participate in the trials, and the ethical conflict. The solutions to these prob-lems will require the joint efforts of all parties involving the government, pharmaceutical companies, medical institu-tions, and patient organizations.

Expression of autophagy-associated protein light chain 3B in human pulpitis and periapical periodontitis / 中国组织工程研究

BACKGROUND: Role of autophagy in pulpitis, periapical periodontitis and alveolar bone destruction and the underling mechanisms have not been fully elucidated. OBJECTIVE: To investigate the expression of autophagy-related protein light chain 3B in human pulpitis and periapical periodontitis, in order to explore the rule of autophagy. METHODS: The healthy first premolar or surgically removed third premolar was selected from the patients undergoing orthodontics after their consent informs. The dental pulp cells were treated with 1 mg/L lipopolysaccharide for 0, 6, 12, 24 and 48 hours to induce inflammation. The expression of light chain 3B in normal and lipopolysaccharide-stimulated dental pulp cells was detected by western blot assay. The dotted accumulation of light chain 3B was observed by immunofluorescence. The expression level of light chain 3B in specimens of human chronic periapical periodontitis tissues was tested by real-time RT-PCR. RESULTS AND CONCLUSION: The expression of light chain 3B in dental pulp cells stimulated by lipopolysaccharide for 6, 12, 24 and 48 hours was higher than that in normal dental pulp cells. The expression of light chain 3B increased with time, and peaked at 24 hours. Dotted accumulation of light chain 3B increased with lipopolysaccharide simulation time prolonged. The expression level of light chain 3B in specimens of human chronic periapical periodontitis tissues was higher than that in normal periapical tissues. These results indicate that the expression of light chain 3B is increased in human pulpitis and periapical periodontitis, and morphology also shows an increase of autophagy, suggesting that autophagy may be associated with the occurrence and development of pulpitis and periapical periodontitis.

Effects of electroacupuncture at different time during reperfusion on the expression of Bcl-2 and Beclin1 in myocardial tissue in rats with myocardial ischemia reperfusion injury / 中国针灸

OBJECTIVE@#To compare the effects of electroacupuncture (EA) at different time during reperfusion on the expression of autophagy-related protein Bcl-2 and Beclin1 in myocardial tissue in rats with myocardial ischemia reperfusion injury (MIRI), and to explore the autophagy-related mechanism of EA on protecting MIRI.@*METHODS@#A total of 72 SD rats were randomly divided into a sham operation group, a model group, a RA group, a RB group, a RC group and a RD group, 12 rats in each group. Except the sham operation group, the rats in the remaining groups were treated with ligating the left anterior descending artery (LAD) for 30 minutes followed by reperfusion to establish the model of MIRI. The rats in the sham operation group were treated with crossing a line through the LAD. The rats in the model group did not receive treatment. The rats in the RA group, RB group, RC group and RD group were treated with EA at "Neiguan" (PC 6) for 20 min, starting at 0 h, 0.5 h, 1 h, 2 h after reperfusion. Evans Blue-TTC double-staining was employed to evaluate myocardial infarct size; the serum CK-MB was detected by ELISA and the expression of Bcl-2 and Beclin1 protein in myocardial tissue were detected by Western blot.@*RESULTS@#Compared with the model group, the percentage of myocardial infarct size in the RB group, RC group and RD group was decreased significantly (all 0.05); the increasing of Bcl-2 in the RB group was more significant than that in RC group (0.05).@*CONCLUSION@#EA at different time during reperfusion could reduce myocardial infarct size in rats with MIRI, and EA at 0.5 h after reperfusion has best efficacy; this protective effect may be achieved by increasing Bcl-2 expression and reducing Beclin1 expression to inhibit overautophagy during reperfusion.