Objective To establish the reference intervals of neutrophil to lymphocyte ratio(NLR),mono-cyte to lymphocyte ratio(MLR)and platelet to lymphocyte ratio(PLR)in different genders and age groups in northern Chinese adults.Methods The data were analyzed according to the Clinical and Laboratory Stand-ards Institute C28-A3.Outliers were checked and judged according to the Dixon method.Subgroups were di-vided according to gender or age factors,and reference intervals were established for different subgroups.Ref-erence intervals were expressed as two-sided 95％percentiles.Results The reference intervals of NLR,MLR and PLR were 0.90-3.82,0.09-0.33 and 71.20-246.87,respectively.The results showed that NLR and PLR in men were lower than those in women(P＜0.001),while MLR in men was significantly higher than that in women(P＜0.001).Linear trend plots showed that NLR,MLR and PLR changed significantly in dif-ferent genders and age groups.In men,NLR and MLR increased with age,while PLR gradually increased and reached the peak before 50 years old,and gradually decreased after 50 years old.In women,NLR and MLR showed the lowest values at 50-＜60 years old,while PLR reached the peak at about 50 years old.The refer-ence intervals established by the model set were verified,and the percentages beyond the reference intervals were less than 10％in different genders and age groups.Conclusion The reference intervals of NLR,MLR and PLR in different genders and age groups of healthy adults in northern China are established in the study.

In the era of evidence-based medicine, it is necessary to explore the unique advantages of traditional Chinese medicine (TCM) based on standardized technical methods and operating procedures in order to achieve the modernization and internationalization of TCM and benefit all humanity. The proposal of a three-pronged evidence system combining TCM theory, human experience and experimental evidence marks an important progress in the thinking method of the TCM evaluation system. The multi-evidence body integrated through appropriate methods provides a strong support for the clinical guideline recommendations and evidence-based health decision-making in TCM. Based on the current methodological progress of international evidence synthesis and grading, this paper proposes a novel approach for integrating multi-evidence in TCM: the MERGE framework. The aim is to establish a solid foundation for the development of this methodology and provide guidance for the advancement of evidence-based medicine framework in TCM.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

Ulcerative colitis （UC） is a commonly seen digestive system disease with unclear pathogenesis. The condition is complex and variable， often chronic， and has a long treatment period with no specific cure. Currently， the treatment of UC often involves the use of corticosteroids， aminosalicylates， and biologics in western medicine， which provide fast-acting and definite efficacy in the short term. However， with prolonged medication， some patients may develop drug resistance and worsening of the disease， leading to the occurrence of colon cancer. Research has found that oxidative stress is one of the important pathogenic factors in UC and influences its onset and development. Oxidative stress is a state of imbalance between oxidative products and the antioxidant system in the body， characterized by overexpression of oxidative products such as malondialdehyde （MDA）， reactive oxygen species （ROS）， nitric oxide （NO）， or deficiency of antioxidant enzymes such as superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH）. It is worth noting that traditional Chinese medicine （TCM）， as a unique characteristic medicine of China， has achieved significant efficacy in the treatment of UC. Studies have shown that TCM effectively inhibits the occurrence of UC by suppressing the accumulation of metabolites and antagonizes the development of UC by enhancing the antioxidant system. Therefore， using TCM to regulate the oxidative balance as a diagnostic and therapeutic approach may be a new method and direction for the treatment of UC in the future. Based on the above research， this article summarized the mechanisms of key pathogenic proteins in oxidative stress and the occurrence and development of UC， and compiled the effective ingredients of Chinese medicine， single drugs， prescriptions， and acupuncture and moxibustion in regulating upstream and downstream target proteins of oxidative stress. These interventions can reduce pathological damage to the intestinal mucosa， lower the colon injury index， enrich the intestinal microbiota， increase colon length， and improve clinical symptoms of UC. The article is expected to expand the application of TCM in the treatment of UC and provide a reliable scientific theoretical basis.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

This paper introduced the Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C), illustrated the comparison with the QUADAS-2, and using QUADAS-C together with QUADAS-2 to present QUADAS-C results through systematic reviews. Like the domain for QUADAS-2, QUADAS-C retained four domains, including patient selection, index test, reference standard, flow, and timing, and comprised additional questions for each QUADAS-2 part. Unlike the QUADAS-2 tool, the starting question of each domain for QUADAS-C was designed to summarize the risk of biased information captured by QUADAS-2. QUADAS-C only dealt with the risk of bias but did not include the part of concerns regarding applicability. The answers to signaling questions for each domain of QUADAS-C would lead to a 'low''high' or 'unclear' risk of biased judgment for the original study.

OBJECTIVE：To provide reference for pharmaceutical enterprises to better fulfill their social responsibilities . METHODS：Taking the pharmaceutical enterprises listed in Shanghai and Shenzhen stock markets as the research objects ，the social responsibility texts and environmental protection texts of the included enterprises from 2017 to 2019 were classified and analyzed according to the three dimensions of time ，ownership and drug production type by using ROST Content Mining 6.0 software. The semantic network and node centrality were analyzed. RESULTS ：From the social responsibility texts of the included enterprises，it could be seen that from the perspective of time dimension ，the included enterprises paid more attention to “employees”，“social responsibility ”and“development”in 2017-2019，and the high-frequency words in the three years were relatively stable. From the perspective of ownership ，state-owned holding enterprises paid more attention to “development”and “targeted poverty reduction ”，while private holding enterprises paid more attention to “employees”，and collective holding enterprises paid more attention to “social responsibility ”. From the perspective of drug production type ，the word frequency of “targeted poverty reduction ”of TCM pharmaceutical enterprises was higher. From the environmental protection texts of the included enterprises，it could be seen that from the time dimension ，the included enterprises paid more and more attention to environmental protection in recent years ，and the description of environmental protection in the texts was more detailed. From the perspective of ownership，private holding enterprises paid more attention to environmental protection than collective holding enterprises and state-owned enterprises. From the perspective of drug production type ，due to the different types of drugs ，chemical drugs ，TCM， biological drugs and active pharmaceutical ingredients enterprises had their own characteristics in pollutants and their treatment processes. The results of semantic network and node centrality analysis showed that ，“development”，“protection” and “targeted poverty reduction ”were three high-frequency words with high centrality in the semantic analysis network of social responsibility text ，the middle centrality was 5.555，1.695，1.521 respectively；“emission”and“testing”were two key words with high centrality in the semantic analysis network of environmental protection texts ，the middle centrality was 3.856， 1.914 respectively，which further reflected that the included enterprises paid more attention to the above issues in terms of social responsibility performance and environmental protection. CONCLUSIONS ：The listed pharmaceutical enterprises have a broad consensus on social responsibility in China ，and have well fulfilled their social responsibility ，which is well combined with the current social hot spots. For environmental protection ，as a high pollution industry ，the pharmaceutical enterprises also performs the responsibility of environmental protection.

The outbreak of pneumonia caused by novel coronavirus (COVID-19) at the end of 2019 was a major public health emergency in human history. In a short period of time, Chinese medical workers have experienced the gradual understanding, evidence accumulation and clinical practice of the unknown virus. So far, National Health Commission of the People's Republic of China has issued seven trial versions of the "Guidelines for the Diagnosis and Treatment of COVID-19". However, it is difficult for clinicians and laymen to quickly and accurately distinguish the similarities and differences among the different versions and locate the key points of the new version. This paper reports a computer-aided intelligent analysis method based on machine learning, which can automatically analyze the similarities and differences of different treatment plans, present the focus of the new version to doctors, reduce the difficulty in interpreting the "diagnosis and treatment plan" for the professional, and help the general public better understand the professional knowledge of medicine. Experimental results show that this method can achieve the topic prediction and matching of the new version of the program text through unsupervised learning of the previous versions of the program topic with an accuracy of 100%. It enables the computer interpretation of "diagnosis and treatment plan" automatically and intelligently.
Betacoronavirus ; China ; Coronavirus Infections ; diagnosis ; therapy ; Humans ; Machine Learning ; Pandemics ; Pneumonia, Viral ; diagnosis ; therapy ; Practice Guidelines as Topic

Objective To investigate the levels of trace elements in preschool children in Guangzhou and their relationships with nutritional status, and to provide a scientific basis for guiding children's nutritional diet and timely and reasonable supplementation of trace elements. Methods A cross-sectional study was used to perform physical examinations and collect blood samples from 5 002 children who were examined in the Department of Pediatric Health of a Maternal and Child Health Hospital in Guangzhou in 2018. The levels of trace elements including iron, zinc and copper were detected by atomic absorption spectrometer. Results The median (upper and lower quartile) levels of iron, zinc and copper for preschool children in a district of Guangzhou were 7.80 (7.39, 8.19) mmol / L, 69.0 (61.0, 76.5) μmol / L, 18.6 (15.9, 21.4) μmol / L. There was no significant difference in the levels of iron, zinc and copper between different genders (P>0.05). The levels of iron and zinc increased significantly with the age of children (P=0.000). There was no significant difference in the level of copper in different ages (P>0.05). The prevalence rates of iron, zinc and copper deficiency in preschool children were 14.93%, 21.93% and 0.24%, respectively, and there was no significant difference between different genders (P>0.05).There were no significant differences in the prevalence of iron and copper deficiency in different ages (P>0.05), while the zinc deficiency rate decreased with the age of children (P = 0.000). (P<0.05). The levels of iron and zinc in overweight children, and those suffering from malnutrition,and obesity were lower than those in normal children. There was no statistically significant difference in the levels of copper in children with different nutritional status (P>0.05). The prevalence rates of iron and zinc deficiency in children with malnutrition, overweight and obesity were higher than those in normal children. There was no significant difference in the prevalence of copper deficiency in children with different nutritional status (P>0.05). Conclusion The prevalence of iron, zinc deficiency is high in preschool children in Guangzhou. Preschool children with malnutrition, overweight and obesity are more prone to iron and zinc deficiency.

Objective: To know the detection rate of hereditary thrombocytopenia (HT) in children with chronic thrombocytopenia and its clinical and laboratory characteristics for an early clinical identification and diagnosis of HT in future. Methods: Data of the children with thrombocytopenia, who had been treated in Beijing Children′s Hospital from April 2016 to May 2018 and whose present history lasted for more than 1 year and had poor response to immunotherapy were retrospectively collected.HT was screened in these patients by adopting next generation sequencing (NGS). Finally, clinical and laboratory characteristics of these children with HT were summarized and analyzed. Results: A total of 161 children with chronic thrombocytopenia were included.Forty-three cases (26.7%) were found to have gene mutations.The genetic rules of the mutant gene, the family verification and the clinical manifestations of the proband and some related laboratory tests were analyzed and 24 cases (14.9%) can be diagnosed as HT.Among the HT patients, the proportion of males and females was 159, and the median onset of age was 0.58 years, which was significantly lower than that of non-HT cases (the median onset of age was 4.36 years), and the difference was statistically significant (P<0.001); the proportion of mucosal hemorrhage and visceral hemorrhage (31.8% and 13.7%) of HT was significantly higher than non-HT cases (15.3% and 0.6%), and the difference was statistically significant (P<0.001). Fifty percent of (12/24 cases) cases of HT had positive family history; according to the ave-rage platelet volume and platelet morphology in peripheral blood smear, HT could be divided into small platelet HT, po-sitive platelet HT and large platelet HT.Some cases had well response to immunotherapy but seemed easy to relapse du-ring the withdrawal period, while the others responded poorly to therapy.Different clinical manifestations of HT suggest different pathogenesis, which can be divided into the related types of megakaryocyte differentiation defect, megakaryocyte maturation defect, platelet release defect and platelet survival time shortening. Conclusions The pathogenesis and cli-nical phenotype of HT was different.Some of them were effective for immunotherapy, which were easily confused with immune thrombocy-topenla(ITP). It is clinically necessary to perform NGS in children with thrombocytopenia at early onset, abnormal platelet morphology, prolonged disease course or severe mucosal/visceral hemorrhage, in order to recognize HT timely to avoid delay in diagnosis and poor prognosis.