The main sources of natural drugs include various biological species such as plants, animals, and microorganisms. The accurate identification of these species is the bedrock of natural drug development. We propose a novel method of species identification in this paper: analysis of whole-genome (AGE), a molecular diagnostic method used to identify species by finding species-specific sequences from the whole genome and precisely recognizing the specific target sequences. We elaborate that the principle for species identification based on AGE is that the genome sequences of diverse species must differ and divide the implementation strategy of the method into two levels of research and application. Based on our analysis of its characteristics, the method would have the potential advantages of reliable principle, high specificity, and wide applicability. Moreover, three crucial concerns related to building method systems including genome acquisition, bioinformatics analysis, and database construction, are further discussed. In summary, we offer theoretical underpinnings and methodological guidance for the development of bioinformatics software and commercial kits, indicating AGE has great application potential in objects, subjects, and industries.

Ethical review runs through the whole process of drug clinical trials, and is a critical step to ensure the rights and interests of subjects. This paper analyzed and discussed the role and positioning of ethical review in new drug clinical trials, cleared the principles of ethical review, identified the responsibilities of ethical review, and clarified the authority of ethical review approval documents. The ethical review should primarily focus on the ethics of the clinical trials, not replace other professional institutions to review the clinical trials’ legality and scientific nature. Ethical approval is only one of the necessary conditions for conducting clinical trials, not the only factor. It is recommended to strengthen the publicity and popularization of scientific and technological ethics awareness, improve the clinical trial approval mechanism, and optimize the phrasing of ethical review approval documents. It is warranted to further optimize the quality of ethical review, improve the construction of ethical review system, ultimately achieve the unity of promoting innovation and preventing risks, so as to effectively realize the benign interaction between high-quality development of scientific and technological innovation and high-level safety.

Objective: To explore the related factors of negative conversion time (NCT) of nucleic acid in children with COVID-19. Methods: A retrospective cohort study was conducted. A total of 225 children who were diagnosed with COVID-19 and admitted to Changxing Branch of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 3^rd to May 31^st 2022 were enrolled in the study. The infection age, gender, viral load, basic disease, clinical symptoms and information of accompanying caregivers were retrospectively analyzed. According to age, the children were divided into<3 years of age group and 3-<18 years of age group. According to the viral nucleic acid test results, the children were divided into positive accompanying caregiver group and negative accompanying caregiver group. Comparisons between groups were performed using Mann-Whitney U test or Chi-square test. Multivariate Logistic regression analysis was used to analyze the related factors of NCT of nucleic acid in children with COVID-19. Results: Among the 225 patients (120 boys and 105 girls) of age 2.8 (1.3, 6.2) years, 119 children <3 years and 106 children 3-<18 years of age, 19 cases were diagnosed with moderate COVID-19, and the other 206 cases were diagnosed with mild COVID-19. There were 141 patients in the positive accompanying caregiver group and 84 patients in the negative accompanying caregiver group.Patients 3-<18 years of age had a shorter NCT (5 (3, 7) vs.7 (4, 9) d, Z=-4.17, P<0.001) compared with patients <3 years of age. Patients in the negative accompanying caregiver group had a shorter NCT (5 (3, 7) vs.6 (4, 9) d,Z=-2.89,P=0.004) compared with patients in the positive accompanying caregiver group. Multivariate Logistic regression analysis showed that anorexia was associated with NCT of nucleic acid (OR=3.74,95%CI 1.69-8.31, P=0.001). Conclusion: Accompanying caregiver with positive nucleic acid test may prolong NCT of nucleic acid, and decreased appetite may be associated with prolonged NCT of nucleic acid in children with COVID-19.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Young Adult ; China/epidemiology* ; COVID-19/genetics* ; Nucleic Acids ; Retrospective Studies

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

With the implementation of the national biomedical innovation strategy, new requirements for ethical review of clinical trials have been put forward, and more attention has been paid to the ethical pre-review. Based on the current situation of clinical trials and ethical review of new drugs in China, this paper discussed the concept, advantages and necessity of ethical pre-review, sorted out the problems and challenges in the implementation of ethical pre-review at this stage, and put forward the following suggestions on how to better implement ethical pre-review in clinical trials under the pharmaceutical innovation strategy: the complete definition of "ethical pre-review" should be made clearly; ethical review should be carried out on the basis of necessary reference; the scope of application of ethical pre-review should be clarified; after the ethical pre-review, the statement of the approval document should be standardized and accurate.

Air Pollution ; Asthma/drug therapy* ; China ; Humans ; Treatment Adherence and Compliance

【Objective】To investigate the differences of lung involvement between dengue and severe dengue.【Methods】227 dengue patients admitted in The Third Affiliated Hospital of Sun Yat-sen University from July 2014 to October 2018 were enrolled. The clinical characteristics，treatment and outcome of the patients were analyzed to explore the differences of lung involvement between dengue and severe dengue （SD）. 【Results】 The rate of old age ，smoking ，hypertension，diabetes and cerebrovascular disease was higher in dengue with lung involvement group（DWLI）than dengue without lung involvement group（DWOLI）（χ2 were 25.146，3.847，10.326，7.177，and 5.355，P was 0.050 for smoking，the others were < 0.05）. The rate of cough and breathlessness was higher in DWLI（χ2 were 11.465 and 6.068，P were 0.001 and 0.014），as well as in SD subgroup（χ2 were 4.585 and 6.717，P were 0.032 and 0.010）. C-reactive protein and procalcitonin were increased in DWLI（Z were - 2.591 and - 3.033，P were 0.010 and 0.002）. The rate of pleural effusion was higher in SD subgroup（χ2 = 4.987，P = 0.026）. Bilateral lung infiltration was correlated with SD（χ2 = 5.910，P =0.015）. The rate of acute liver injury，acute kidney injury and multi-organ dysfunction syndrome（MODS）was higher in DWLI（χ2 were 7.044，7.059，and 11.315，P were 0.008，0.008 and 0.001）. The rate of anti-virus，anti-bacteria and combined therapy was higher in DWLI（χ2 were 13.156，32.845，and 12.684，P all were < 0.001）.【Conclusion】Dengue patients who were with old age，smoking，or suffered from underlying disease of hypertension，diabetes and cerebrovascular disease were vulnerable to lung involvement. Cough，breathlessness，pleural effusion and bilateral lung infiltration were signs of severe dengue. Attention should be paid to dengue with lung involvement.

Objective To translate the English version of nursing home survey on patient safety culture (NHSPSC) into Chinese one, and to test the reliability and validity of Chinese version of NHSPSC. Methods The items of NHSPSC were translated into Chinese version using a standard procedure of double-back translation and cross-culture adapted. A total of 237 staff members of nursing home were recruited to examine the reliability and validity of Chinese version of NHSPSC. Results The Chinese version of NHSPSC consisted of 36 items. The Cronbach′s α coefficient was 0. 847 for the total scale and Cronbach′s α of each factors ranged from 0. 632 to 0. 832. The test-retest reliability was 0. 822. The correlation coefficient between each dimension score ranged from 0. 151 to 0. 728 and the correlation coefficient between each dimension and the total score ranged from 0. 294 to 0. 779. The content validity index was 0. 873. Twelve factors were extracted by factor analysis which could explain 63. 156% of the total variance. Conclusions The Chinese version of NHSPSC is reliable and valid, which can be used to evaluate the patient safety culture in nursing homes.

Objective To optimize clinical dosage regimen of sparfloxa-cin through series of pharmacokinetic/pharmacodynamic ( PK/PD ) val-ues.Methods The minimum inhibitory concentration ( MIC ) of spar-floxacin to 479 isolated bacteria were measured by two -fold agar dilution method.To perform pharmacokinetic test after those healthy volunteers were given a single oral dose of 0.1 , 0.2 , 0.3 g of Sparfloxacin , respec-tively.Based on PK/PD theory, calculation of AUC0-24 h/MIC values af-ter three dosages were done.Estimated value of AUC 0-24 h/MIC≥125 was expected to be the target value ( for streptococcus pneumoniae AUC0-24 h/MIC≥50).The Monte Carlo simulation was repeated 1 ×104 times, and the cumulative fraction of response ( CFR) value was calculat-ed according to the respective probability distributions and different AUC0-24 h/MIC and MIC values.The dosage achieving a CFR above 90 percent was recognized as the optimal dosage regimen.Results Given dose of 0.1 g, the pharmacodynamics value CFR was above 90%only to salmonella genera.Given dose of 0.2 g, the pharmacodynamics value CFR was above 90%to Nitrate negative bacillus, Streptococcus pneumoni-ae, Acinetobacter and Methicillin -sensitive Staphylococcus aureus (MSSA).For other strains, oral dose of 0.3 g was needed to not only achieve satisfactory clinical curative effect but also effectively prevent the drug resistance.And for infections caused by Methicillin -resistant Staphylococcus aureus (MRSA), enhanced drug dose should be considered to achieve satisfactory clinical efficacy.Conclusion For infection caused by salmonella genera, oral dose of 0.1 g was a appropriate dosage regimen.For infection caused by Nitrate negative bacillus, Strepto-coccus pneumoniae, Acinetobacter and MSSA, oral dose of 0.2 g was a proper dosage regimen.For infection caused by others, oral dosage regimen of 0.3 g could achieve the expected satisfactory clinical efficacy.And for infections caused by MRSA, an increasing dosage , such as 0.4 mg, could achieve satisfactory clinical curative effect.

OBJECTIVETo evaluate the value of normalization window of tumor vasculature (NWTV) in patients with unresectable gastric cancer undergoing neoadjuvant chemotherapy.

METHODSFrom October 2010 to March 2011, 93 patients with unresectable advanced or locally advanced gastric carcinoma were prospectively collected and randomly divided to Group A(n=30), Group B(n=29), and Group C(n=34). Group A received FOLFOX4 as conventional neoadjuvant chemotherapy. Group B received FOLFOX4 plus bevacizumab. The treatment was adjusted in Group C according to the hypothesis of NWTV with neoadjuvant chemotherapy delivered 5 days after bevacizumab treatment. The efficacy, drug toxicity and clinical outcome were assessed and compared between the three groups.

RESULTSThere were no significant differences among the 3 groups in demographics(P>0.05). All the patients completed the neoadjuvant chemotherapy. Efficacy and toxicity between the three groups were comparable(P>0.05). The rates of tumor downstaging in the three groups were 56.7%(17/30), 72.4%(21/29), 85.3%(29/34), respectively, with a significantly lower downstaging rate in Group C as compared to Group A(P<0.05). R0 resection rates were 23.3%(7/30), 27.6%(8/29), 52.9% (18/34), respectively, with significantly higher R0 resection rate in Group C as compared to Group A and Group B(All P<0.05). There was no perioperative death in this cohort. Postoperative complications were comparable among the 3 groups(P>0.05).

CONCLUSIONSAnti-angiogenesis agent can improve the efficacy of neoadjuvant chemotherapy in unresectable gastric cancer. Furthermore, administration according to NWTV may achieve better outcomes.

Adolescent ; Adult ; Aged ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bevacizumab ; Female ; Fluorouracil ; therapeutic use ; Humans ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neovascularization, Pathologic ; drug therapy ; Organoplatinum Compounds ; therapeutic use ; Prospective Studies ; Stomach Neoplasms ; blood supply ; drug therapy ; Treatment Outcome ; Young Adult