Objective To analyze the research hotspots and trends in the field of cancer pain drugs based on literature.Methods This article included research literature related to cancer pain and drugs published in the China National Knowledge Infrastructure(CNKI)and Web of Science databases.The visual analysis of the literature was performed by software of VOS-viewer 1.6.18 and CiteSpace 6.2.R3,including drawing the graphs and comparing the number of published articles,journals,institutions,authors and keywords were also analyzed.Results A total of 4 774 literatures were included.The journals with the largest number of articles published were the Chinese Journal of Pain Medicine and the Journal of Pain and Symptom Management.The authors with the highest number of articles published were Liu Duanqi and Bruera Eduardo.The institutions with the highest number of publications were Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,and the University of Texas Anderson Cancer Center.The most frequent keyword was cancer pain.The keywords with the strongest citation bursts included Clinical efficacy average daily cost,and primary care.Conclusion Since the beginning of the 21st century,the research on cancer pain drugs has gradually heated up,and the number of papers has shown an upward trend.From 2019 to 2022,the research on cancer pain drugs at home and abroad mainly focused on the clinical efficacy and average daily cost.This article has clarified the research hotspots of cancer pain drugs in recent years to a certain extent and has certain reference significance for future research.

OBJECTIVES: To summarize the clinical features of liver damage in children in the acute stage of Kawasaki disease (KD), and to investigate the clinical value of liver damage in predicting coronary artery lesion and no response to intravenous immunoglobulin (IVIG) in children with KD. METHODS: The medical data were collected from 925 children who were diagnosed with KD for the first time in Beijing Children's Hospital from January 1, 2016 to December 31, 2017. According to the presence or absence of abnormal alanine aminotransferase (ALT) level on admission, the children were divided into a liver damage group (n=284) and a non-liver damage group (n=641). A logistic regression analysis was used to investigate the clinical value of the indicators including liver damage in predicting coronary artery lesion and no response to IVIG in children with KD. RESULTS: Compared with the non-liver damage group, the liver damage group had a significantly earlier admission time and significantly higher serum levels of inflammatory indicators (P<0.05). The liver damage group had a significantly higher incidence rate of coronary artery lesion on admission than the non-liver damage group (P=0.034). After initial IVIG therapy, the liver damage group had a significantly higher proportion of children with no response to IVIG than the non-liver damage group (P<0.001). In children with KD, coronary artery lesion was associated with the reduction in the hemoglobin level and the increases in platelet count, C-reactive protein, and ALT (P<0.05), and no response to IVIG was associated with limb changes, the reduction in the hemoglobin level, the increases in platelet count, C-reactive protein, and ALT, and coronary artery lesion (P<0.05). CONCLUSIONS Compared with those without liver damage, the children in the early stage of KD with liver damage tend to develop clinical symptoms early and have higher levels of inflammatory indicators, and they are more likely to have coronary artery lesion and show no response to IVIG treatment.
C-Reactive Protein/analysis* ; Child ; Coronary Vessels/pathology* ; Hemoglobins/analysis* ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Liver Diseases ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Retrospective Studies

OBJECTIVE: To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children. METHODS: Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae. RESULTS: Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus. CONCLUSION 2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.
Child ; Cladribine/adverse effects* ; Cytarabine ; Histiocytosis, Langerhans-Cell/drug therapy* ; Humans ; Recurrence ; Retrospective Studies

Objective:Under the guidance of evidence-based theory, the discharge preparation intervention plan for stroke patients was constructed, in order to provide a reference for improving the discharge preparation of stroke patients.Methods:To retrieve the relevant guidelines, consensus, literature and quality evaluation, summarize relevant evidence and evaluate the first draft of the intervention plan, implement two rounds of expert enquiry, according to the expert score and opinions, and improve the entries after the group discussion to form the final intervention plan.Results:In the two rounds of correspondence, the expert positive coefficient was 100%, the expert authority coefficient was 0.81 and 0.84 respectively, and the Kendall harmony coefficient of each entry was 0.165 and 0.453 respectively. The difference was statistical significant ( P<0.05). The ultimate in intervention plan included 6 primary entry, 23 secondary entries. Conclusions:The discharge preparation intervention plan for stroke patients constructed in this study is scientific, reliable and feasible, and is of great significance to improving the discharge preparation of stroke patients.

OBJECTIVE: To recognize the spatial and temporal characteristics of iodine deficiency disorders (IDD), China national IDD surveillance data for the years of 1995-2018 were analyzed. METHODS: Time series analysis was used to describe and predict the IDD related indicators, and spatial analysis was used to analyze the spatial distribution of salt iodine levels. RESULTS: In China, the median urinary iodine concentration increased in 1995-1997, then decreased to adequate levels, and are expected to remain appropriate in 2019-2022. The goiter rate continually decreased and is expected to be maintained at a low level. Since 2002, the coverage rates of iodized salt and the consumption rates of qualified iodized salt (the percentage of qualified iodized salt in all tested salt) increased and began to decline in 2012; they are expected to continue to decrease. Spatial epidemiological analysis indicated a positive spatial correlation in 2016-2018 and revealed feature regarding the spatial distribution of salt related indicators in coastal areas and areas near iodine-excess areas. CONCLUSIONS Iodine nutrition in China showed gradual improvements. However, a recent decline has been observed in some areas following changes in the iodized salt supply in China. In the future, more regulations regarding salt management should be issued to strengthen IDD control and prevention measures, and avoid the recurrence of IDD.
China/epidemiology* ; Iodine ; Prevalence ; Sodium Chloride, Dietary ; Spatial Analysis ; Time Factors

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

The research on endophytes of medicinal plants mainly relies on the traditional culture and isolation methods. Because of their functions such as promoting host growth, improving stress resistance, promoting the accumulation of medicinal active ingredients or directly producing medicinal active ingredients, the endophytes of medicinal plants have gradually attracted wide attention. However, it was found that the strains isolated by traditional methods were not the true dominant endophytes of medicinal plants by comparing the results of traditional culture isolation with high-throughput sequencing. The blind and random nature of traditional methods leads to the lack of standards in terms of medium selection, culture time and interaction between species. On the contrary, high-throughput sequencing technology is an emerging molecular biology technology developed in recent decades. Due to its high resolution level and indepen-dent culture, it can be used for thorough analysis of the community structure and diversity of environmental microorganisms. Therefore, we proposed the strategy of using high-throughput sequencing technology to guide the traditional culture and isolation of endophytes from medicinal plants. Firstly, the endophytic structure and diversity of medicinal plants were completely clear by high-throughput sequencing technology, and the dominant endophytes of the host were unequivocal. Then according to the characteristics of each dominant endophytes design or query suitable medium for its growth to culture and isolation. Finally, the function of the isolates was studied. This method can prevent researchers from missing out on the important functional strains of the host, expand the research scope of endophytes of medicinal plants, and facilitate the in-depth excavation and utilization of endophytes of medicinal plants.
Endophytes/genetics* ; High-Throughput Nucleotide Sequencing ; Plants, Medicinal ; Research Design

Objective:To explore the distribution characteristics of traditional Chinese medicine （TCM） syndromes of abnormal uterine bleeding associated with ovulatory dysfunction （AUB-O）. Method:A clinical and epidemiological investigation was conducted in 6 688 patients with AUB-O from the provincial， municipal， and county/district hospitals in 29 provinces， autonomous regions， and municipalities across China to identify the distribution characteristics of their TCM syndromes. Result:The AUB-O patients nationwide were mainly differentiated into the kidney Qi deficiency syndrome （17.34%）， the spleen Qi deficiency syndrome （13.25%）， the Qi and blood deficiency syndrome （12.62%）， the Qi deficiency and blood stasis syndrome （8.45%）， and the kidney Yin deficiency syndrome （6.88%）. AUB-O resulted from Qi deficiency， Yin deficiency， and blood deficiency， often involving the kidney， spleen and liver. The analysis of the regional distribution of TCM syndromes in AUB-O patients revealed that kidney Qi deficiency， spleen Qi deficiency， and Qi and blood deficiency were the shared syndromes. However， due to regional discrepancy， the TCM syndrome varied widely from one geographic region to another. The kidney Qi deficiency syndrome was more frequently seen in North China， Northwest China， Southwest China， and East China， but less frequently in central China， Northeast China， and South China. The spleen Qi deficiency syndrome occurred most frequently in central China， while the East China had the highest frequency of Qi and blood deficiency syndrome. The spleen and kidney deficiency syndrome was mostly present in central China， North China， and Southwest China， the Qi deficiency （kidney deficiency） and blood stasis syndrome in Northwest China， South China， and North China， the kidney Yin deficiency syndrome in East China， Northwest China， and Northeast China， the deficiency-heat syndrome in Southwest China and East China， the kidney Yang deficiency syndrome in South China， the liver depression and blood heat syndrome in Northeast China， and the liver depression and spleen deficiency syndrome in central China. The diagnostic criteria for the kidney Qi deficiency， spleen Qi deficiency， Qi and blood deficiency， Qi deficiency and blood stasis， and kidney Yin deficiency syndromes were not significantly different from the previous ones. The distinctive symptoms for the kidney Qi deficiency syndrome were irregular vaginal bleeding， heavy menstrual flow， or shortened menstrual cycle， back soreness and pain， and forgetfulness， while those for the spleen Qi deficiency syndrome mainly included the shortened menstrual cycle， mental fatigue， lack of strength， poor appetite， loose stool， and white tongue coating. The Qi and blood deficiency syndrome were mainly manifested as the shortness of breath， laziness to speak， pale complexion， dizziness， and palpitation. The Qi deficiency and blood stasis syndrome were mainly judged by the scanty menstrual flow frequently or occasionally accompanied by blood clots， mental fatigue， lack of strength， and dark purple tongue. The ovulatory bleeding， dizziness， tinnitus， vexing heat in chest， palms and soles， and night sweat were the characteristic signs for the kidney Yin deficiency syndrome. Conclusion:There exist certain rules in the geographical distribution of TCM syndromes of AUB-O patients， which has provided a reference for the clinical treatment of AUB-O in accordance with the local conditions.

Objective:To investigate the predictive value of neutrophil to lymphocyte ratio (NLR) for hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS).Methods:Consecutive patients with AIS without performing intravenous thrombolysis and mechanical thrombectomy admitted to the Cerebrovascular Disease Treatment Center, the Affiliated Brain Hospital of Nanjing Medical University from December 2015 to December 2020 were enrolled. The clinical, imaging and laboratory examination data were collected. HT was defined as the first imaging examination of AIS patients without finding bleeding signs, but the imaging reexamination after hospitalization found intracranial hemorrhage. Multivariate logistic regression analysis was used to determine the independent correlation between NLR and HT. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of NLR for HT. Results:A total of 805 patients with AIS were included. The median age was 67 years (interquartile range, 63-71 years), the median National Institutes of Health Stroke Scale (NIHSS) score was 4 (interquartile range, 2-9), the median NLR was 3.84 (interquartile range, 2.66-5.30). Seventy-ywo patients (8.9%) had HT. There were significant differences in age, baseline systolic blood pressure, baseline NIHSS score, time from onset to admission, time from onset to blood collection, time from onset to imaging reexamination, NLR, atrial fibrillation, history of previous stroke and transient ischemic attack and stroke etiology between the HT group and the non-HT group (all P<0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for HT in patients with AIS after adjusting for confounding factors (odds ratio 1.355, 95% confidence interval 1.099-1.672; P=0.005). The ROC curve analysis showed that the area under the curve of NLR predicting HT was 0.852, and the optimal cut-off value was 4.75. Its sensitivity and specificity of predicting HT were 88.3% and 71.8% respectively. Conclusion:High NLR is an independent risk factor for HT in patients with AIS during hospitalization, and had better predictive value for HT risk.