Data mining and analysis of oxaliplatin-related adverse events of nervous system / 中国药房

OBJECTIVE To provide reference for clinically safe drug use by mining oxaliplatin-related adverse drug events （ADE） of the nervous system. METHODS Oxaliplatin-related neurologic ADE data reported by the FDA adverse event reporting system （FAERS） between January 1st， 2004 and December 31st， 2022 were collected. The reporting odds ratio and proportional reporting ratio were used for data mining. The data were classified statistically by using systematic organ classification， high-level group term （HLGT） and preferred term （PT） in the MedDRA （version 26.0）. RESULTS A total of 7 266 cases of oxaliplatin- related ADE， which were classified as various neurological， were retrieved， and 100 PT were identified. Of these， fifty-seven PT were unspecified adverse reaction signals in the manual. Among these reports， males （46.85%） were more than females （42.98%）， the age of patients was 45-＜75 years （65.22%）， the number of reports was highest in Italy （16.32%）， and the severe type was hospitalization or prolonged hospitalization （38.16%）. The top 5 PT reports in the list of case number were peripheral neuropathy， paresthesia， neurotoxicity， loss of consciousness and dysarthria. The top 5 PT reports in the list of signal intensities were cold- induced paresthesia， neuromuscular rigidity， acute polyneuropathy， neuronal neuropathy， axonal and demyelinating polyneuropathy. A total of 13 HLGT were involved， with neurological diseases （not classified separately） having the highest number of signals （29）. CONCLUSIONS When using oxaliplatin in clinical practice， it is not only necessary to monitor the high incidence of acute and chronic peripheral neuropathy， but also to pay attention to the patient’s consciousness state and neurological symptoms. We should pay attention to the rare types of adverse reactions， such as guillain-barre syndrome， Lhermitte sign， posterior reversible encephalopathy syndrome， and hyperammoniacal encephalopathy， so as to ensure the safety of medication.

Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial / 中华内科杂志

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

The mechanism of S100A7 inducing the migration and invasion in cervical cancer cells / 中华肿瘤杂志

Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.

Current situation and strategies of asthma self-management in adolescents / 国际儿科学杂志

Asthma is a common chronic respiratory disease in children.Adolescent asthma is characterized by high prevalence rate, high mortality and poor disease control.The optimal adolescent asthma management is crucial to improve asthma control, as well as reduce the burden of asthma including mortality.The key of the management in adolescents with asthma is the self-management, which involves individual, family and social aspects.The imbalance between physical development and psychological development in adolescents leads to many challenges in the self-management in adolescents with asthma.This review elaborates the current situation, influence factors and promotional strategies of self-management in adolescents with asthma so as to achieve the optimal asthma self-management.

A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges / 神经科学通报·英文版

Major depressive disorder (MDD) is a highly heterogeneous mental disorder, and its complex etiology and unclear mechanism are great obstacles to the diagnosis and treatment of the disease. Studies have shown that abnormal functions of the visual cortex have been reported in MDD patients, and the actions of several antidepressants coincide with improvements in the structure and synaptic functions of the visual cortex. In this review, we critically evaluate current evidence showing the involvement of the malfunctioning visual cortex in the pathophysiology and therapeutic process of depression. In addition, we discuss the molecular mechanisms of visual cortex dysfunction that may underlie the pathogenesis of MDD. Although the precise roles of visual cortex abnormalities in MDD remain uncertain, this undervalued brain region may become a novel area for the treatment of depressed patients.

A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges / 神经科学通报·英文版

Major depressive disorder (MDD) is a highly heterogeneous mental disorder, and its complex etiology and unclear mechanism are great obstacles to the diagnosis and treatment of the disease. Studies have shown that abnormal functions of the visual cortex have been reported in MDD patients, and the actions of several antidepressants coincide with improvements in the structure and synaptic functions of the visual cortex. In this review, we critically evaluate current evidence showing the involvement of the malfunctioning visual cortex in the pathophysiology and therapeutic process of depression. In addition, we discuss the molecular mechanisms of visual cortex dysfunction that may underlie the pathogenesis of MDD. Although the precise roles of visual cortex abnormalities in MDD remain uncertain, this undervalued brain region may become a novel area for the treatment of depressed patients.

Application of self-efficacy theory in nursing intervention of breastfeeding for patients with gestational diabetes mellitus / 中国实用护理杂志

Objective:To explore the intervention effect of nursing guided by self-efficacy theory on postpartum breastfeeding of patients with gestational diabetes mellitus.Methods:A total of 140 patients with gestational diabetes mellitus in Qingdao Women and Children ′s Hospital were selected as study subjects by convenient sampling method. They were divided into two groups according to the time of diagnosis. Seventy patients recruited from August to September 2019 were named as the control group, while those 70 patients from May to June 2020 were set as the intervention group. The control group took routine care and the intervention group received breastfeeding intervention based on self-efficacy theory. The rate of delayed onset of lactogenesisⅡ(DOLⅡ), breastfeeding knowledge, exclusive breastfeeding rate and breastfeeding self-efficacy in different time were compared. Results:The rate of DOLⅡ in the intervention group was 11.43% (8/70), which was lower than 25.71% (18/70) in the control group, the difference was statistically significant ( χ2=4.72, P<0.05). The score of breastfeeding knowledge in the intervention group at postpartum day 3 was 16.0 (15.0, 17.0) , which was higher than that in the control group 14.0(13.0, 16.0), the difference was statistically significant ( Z=-3.55, P<0.05). The rates of exclusive breastfeeding at postpartum day 3, month 1 and month 3 was 78.57% (55/70), 68.57% (48/70), 61.43% (43/70) in the intervention group and 61.43% (43/70), 45.71% (32/70), 37.14% (26/70) in the control group, the differences were statistically significant ( χ2=4.90, 6.60, 8.26, all P<0.05). The total scores of breastfeeding self-efficacy before intervention, 3 days, 1 month and 3 months postpartum were (48.34 ± 5.37), (50.00 ± 6.06), (52.54 ± 5.41), (52.92 ± 5.62) points in the control group and (48.96 ± 4.30), (53.32 ± 5.94), (56.91 ± 5.03), (59.11 ± 4.70) points in the intervention group. The total score of breastfeeding self-efficacy of patients in the two groups was analyzed by repeated measures of variance, and the differences in time effect, between-group effect and interaction effect were statistically significant ( Ftime=81.61, Fbetween-group=31.31, Finteraction=10.23, all P<0.05). Conclusions:Breastfeeding nursing intervention based on self-efficacy theory can improve the knowledge level of breastfeeding in patients with gestational diabetes mellitus, reduce the rate of DOLⅡ, enhance the sense of self-efficacy of breastfeeding and promote exclusive breastfeeding.

Non-pharmaceutical interventions for respiratory virus infection in children and its effect / 中华实用儿科临床杂志

With the emergence of new respiratory virus, it is more apparent for the vulnerability of population to respiratory viral infection.Non-pharmaceutical interventions (NPIs) for respiratory virus infection have become the main way to prevent corona virus disease 2019.Some studies had proven its effectiveness.In addition, the NPIs also significantly reduced the incidence and hospitalization rate of other respiratory disease in children.NPIs for respiratory virus infection in children have its particularity and challenge.In daily life, it is important to guide children how to do the NPIs, so as to protect susceptible children and reduce the disease burden in children′s health system.Therefore, the aerosol transmission, the specificity of the NPIs in children, and the impact on childhood respiratory diseases are described in this article, to improve the prevention of common respiratory diseases in children.

Two cardenolide glycosides from the seed fairs of Asclepias curassavica and their cytotoxic activities / 中国天然药物

Two cardenolide glycosides, corotoxigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (1) and coroglaucigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (2), were isolated from the seed fairs of Asclepias curassavica. The structures of 1-2 were determined based on the combination of the analysis of their MS, NMR spectroscopic data and acid hydrolysis. The inhibitory effects of compounds 1 and 2 on human colorectal carcinoma cells (HCT116), non-small cell lung carcinoma cells (A549) and hepatic cancer cells (SMMC-7721) were evaluated. The results showed that both compounds 1 and 2 significantly inhibited the viability, proliferation, and migration of A549, HCT116 and SMMC-7721 cells, suggesting that compounds 1 and 2 can be applied in the treatment of lung, colon and liver cancers in clinical practice. This study may not only provide a scientific basis for clarifying the active ingredients in A. curassavica, but also help to understand its antitumor activity, which can promote the application of A. curassavica in clinical treatment of various cancers.

Accurate quantification of 3'-terminal 2'-O-methylated small RNAs by utilizing oxidative deep sequencing and stem-loop RT-qPCR / 医学前沿

The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive, convenient, and reliable methods for quantifying RNA modifications. In particular, a subset of small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), are modified at their 3'-terminal nucleotides via 2'-O-methylation. However, quantifying the levels of these small RNAs is difficult because 2'-O-methylation at the RNA 3'-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase. These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays. In this study, we profiled 3'-terminal 2'-O-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment. We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach. Likewise, stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3'-terminal 2'-O-methyl piRNAs in human seminal plasma. In summary, this study established a standard procedure for quantifying the levels of 3'-terminal 2'-O-methyl miRNAs in plants and piRNAs. Accurate measurement of the 3'-terminal 2'-O-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.

Survival and disease burden trend analysis of occupational pneumoconiosis from 1963 to 2020 in Shizuishan City / 中华劳动卫生职业病杂志

Objective: To understand the survival status and its influencing factors of occupational pneumoconiosis patients in Shizuishan City, and to analyze the disease burden of occupational pneumoconiosis and its trend, so as to provide scientific basis for formulating comprehensive prevention and treatment measures of occupational pneumoconiosis. Methods: A retrospective survey was conducted during July to December 2020 to explore the survival status of occupational pneumoconiosis patients who had been reported from 1963 to 2020 in Shizuishan City. The Kaplan-Meier method and Life-table method were used for survival analysis, and Cox proportional hazards regression model was used to analyze the influencing factors of survival time. The disability adjusted life years (DALY) was applied to analyze the disease burden of occupational pneumoconiosis and its temporal trend. Results: From 1963 to 2020, a total of 3263 cases of occupational pneumoconiosis were reported in Shizuishan City, of which 1467 died, so that the fatality rate was 44.96%. The median survival time was 26.71 years, average age of death was (70.55±10.92) years old. There were significant differences in the survival rates of occupational pneumoconiosis patients among different types, diagnosis age, exposure time, industry, initial diagnosis stage and whether upgraded (P<0.05) . As the survival time increased, the survival rate of patients decreased gradually. When the survival time was ≥50 years, the cumulative survival rate of patients was 4.20%. Cox regression analysis suggested that the type of pneumoconiosis, industry, diagnosis age, exposure time, initial diagnosis stage and whether upgraded were the influencing factors for the survival time of patients with occupational pneumoconiosis (P<0.05) . The total DALY attributable to occupational pneumoconiosis from 1963 to 2020 in Shizuishan City was 48026.65 person years, of which the years of life lost (YLL) was 15155.39 person years, and the average YLL was 10.33 years/person, and the years lost due to disability (YLD) was 32871.26 person years, and the average YLD was 10.07 years/person. The DALY attributed to coal worker's pneumoconiosis and silicosis were 39408.51 person years and 6565.02 person years, respectively, and they accounted for 82.06% and 13.67% of the total disease burden in Shizuishan City, respectively. The DALY caused by occupational pneumoconiosis in the age group of 40-49 years old and the first diagnosis of stage I occupational pneumoconiosis were higher, which were 20899.71 and 36231.97 person years, respectively. The average YLL and average YLD showed a volatility downtrend over time. Conclusion: The disease burden of occupational pneumoconiosis cannot be ignored in Shizuishan City, and timely targeted measures should be taken for key populations and key industries. It is recommended that life-cycle health management and hierarchical medical should be taken to improve the life quality of patients and prolong their lifes.

Total serum IgE in people immunized with human diploid cell rabies vaccines with different production processes / 中华微生物学和免疫学杂志

Objective:To investigate the effects of different production processes on sensitization responses to human diploid cell rabies vaccines.Methods:This study randomly collected 360 serum samples in clinical trials of four rabies vaccines with different production processes. Total IgE levels at different time points were detected by ELISA. SPSS19.0 software was used for statistical analysis.Results:Total IgE test results showed that the seropositive rate was 20% (6/30) for all four vaccines. The lowest mean value of total IgE was 9 IU/ml and the highest was 210 IU/ml. Repeated measures analysis of variance showed that there was no significant difference in total IgE levels at different sampling time points ( P=0.284), and the total IgE level in people injected with multistep concentrated human diploid cell rabies vaccine was significantly below that in people immunized with Vero cell rabies vaccine ( P=0.024). Conclusions:Increasing the immune dosage of human rabies vaccine could not result in a rise in total IgE. Human diploid cell rabies vaccines had good safety as the production process could remove most of allergenic impurities.

Application of CT radiomics analysis to predict symptomatic radiation pneumonitis for lung cancer / 中华放射医学与防护杂志

Objective:To build a predictive model for symptomatic radiation pneumonitis(RP) using the pretreatment CT radiomics features, clinical and dosimetric data of lung cancer patients by using machine learning method.Methods:A retrospective analysis of 103 lung cancer patients who underwent radiotherapy in the Affiliated Hospital of Jiangnan University from November 2018 to April 2020 was performed. Total normal lung tissues were segmented as an interested volume in pretreatment CT images, and then 250 radiomics features were extracted. The correlations of RP and clinical or dosimetric features were firstly investigated with univariate analysis. Then all clinical data, dosimetric data and CT radiomics features were collected and considered as predictors for modeling of RP grade ≥ 2. Features were selected through LASSO machine learning method, and the predictive model was built. Finally, nomogram for risk of RP were obtained according to the selected features.Results:The result of univariate analysis showed that symptomatic RP was significantly correlated with lung dosimetric parameters including mean lung dose (MLD), V20 Gy and V30 Gy( t=2.20, 2.34 and 2.93, P<0.05). Four features, including lung dose volume percentage V30 Gyand three radiomics features, entropy feature of GLCM, mean and median feature of wavelet histogram were selected among all clinical, dosimetric features and radiomics features. AUC of the predicted model obtained from selected features reached 0.757. For convenient clinical use, the nomogram were obtained, and then personalized RP risk prediction and early intervention could be performed according to this nomogram. Conclusions:Pretreatment CT radiomics and dosimetric features can be used in predicting symptomatic RP, which will be useful for advanced intervention treatment.

Mediating effect of transition shock between spiritual climate and intention to stay among newly graduated nurses / 中国实用护理杂志

Objective:To investigate the status and their relationship of new nurses ′ transition shock, spiritual climate and nurses ′ intention to stay on the job, to explore the mediating effect of transition shock between spiritual climate and intention to stay among newly graduated nurses. Methods:A convenient sampling method was used from October to December in 2019 to investigate 231 new graduate nurses from four hospitals in Qingdao City with the general data questionnaire, the New Nurses ′ Transition Shock Scale, the Nurses ′ Intention to Stay on the Job Scale and the Spiritual Climate Scale. Results:The total score of new nurse retention intend was (20.65 ± 4.30) points, spiritual climate score was (63.20 ± 19.28), and transition shock score was (82.92 ± 22.33) points. Transition shock was negatively correlated with spiritual climate and intention to stay ( r values were -0.451, -0.548, P<0.01) ; spiritual climate was positively correlated with intention to stay ( r value was 0.450, P<0.01). Transition shock played a partial mediating role in spiritual climate and intention to stay (37%). Conclusions:Spiritual climate of the work environment can directly or indirectly affect the intention to stay through the transition shock among newly graduate nruses. Managers can take appropriate intervention measures to improve the spirit climate of the department, alleviate the impact of new nurses ′ transformation and stabilize nursing team.

Clinical Efficiency of Rituximab Combined with Autologous Hematopoietic Blood Stem Cell Transplantation for Treatment of CD20 / 中国实验血液学杂志

METHODS@#From January 2005 to December 2013, 83 patients with refractory/recurrent CD20@*RESULTS@#All the patient achieved complete response. The median follow.up time was 39 months. Both the two groups collected peripheral blood stem cells successfully, and had no difference in hematopoietic reconstitution time. Three patients in treatment group and six patients in control group relapsed and the three year overall survival and EFS in treatment group was significantly higher than that in control group, that is（93.0% vs 73.1%, P=0.037） and （89.5% vs 65.4%, P=0.034）, respectively. Subgroup analysis showed that: compared with the treatment group in which using R in the whole courses(before and after transplantation, and collection of stem cells) was superior to the control group in both OS and EFS, with the OS 97% vs 87.5% (P>0.05) and EFS 97% vs 76.2% (P=0.05) respectively. While stratified by the different courses of rituximab, the OS was 88.9% (1-2 courses, 9 cases), 93.1% (3-4 courses, 29 cases), 94.7%(more than 5 courses,19 cases), and EFS was 77.8%, 89.7% and 94.7%, respectively.@*CONCLUSION@#For the patients with refractory/recurrent CD20

Progress in antitumor activity of baicalin / 药学学报

Flavonoids baicalin is the main bioactive component extracted from Scutellaria baicalensis Georgi. Baicalin has high medicinal value and shows extensive pharmacological effects including antitumor, antibiosis, anti-inflammatory, antioxidation, neuro-protection, and significant potential in tumor treatment. Recent studies have shown that baicalin suppresses the growth of many kinds of human cancer. The underlying mechanisms include induction of apoptosis, induction of cell cycle arrest, inhibition of tumor metastasis, suppression of angiogenesis, and so on. This article reviewed the research progress of baicalin on its antitumor pharmacology and possible mechanisms at home and abroad, and provided the basis for its further research.

Resistance to thyroid hormone syndrome due to p.Cys446Ser variant of THRbeta gene in a pedigree / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with resistance to thyroid hormone syndrome (RTH).@*METHODS@#Exons 7 to 10 of the THRbeta gene were sequenced for the proband and members of his pedigree.@*RESULTS@#Three patients from the pedigree were identified. All have presented with palpitation, fatigue, goiter, elevated free thyroid hormone and free triiodothyronine, and normal or elevated thyrotropin. Genetic testing revealed that the proband, his mother, second sister and one of her daughters had carried a heterozygous c.1336T>A variant of the THRbeta gene, which resulted in substitution of Cysteine by Serine at position 446. The variant was unreported previously. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.1336T>A(p.Cys446Ser) variant of THRbeta gene was predicted to be lilely pathogenic(PM1+PM2+PM5+PP3).@*CONCLUSION@#The c.1336T>A variant, identified in the exon 10 of the THRbeta gene, probably underlay the RTH in this pedigree. Genetic testing has validated the clinical diagnosis for this pedigree.

Chinese herbal medicines for prevention and treatment of colorectal cancer: From molecular mechanisms to potential clinical applications / 中西医结合学报

Worldwide, colorectal cancer (CRC) is one of the most common malignant tumors, leading to immense social and economic burdens. Currently, the main treatments for CRC include surgery, chemotherapy, radiotherapy and immunotherapy. Despite advances in the diagnosis and treatment of CRC, the prognosis for CRC patients remains poor. Furthermore, the occurrence of side effects and toxicities severely limits the clinical use of these therapies. Therefore, alternative medications with high efficacy but few side effects are needed. An increasing number of modern pharmacological studies and clinical trials have supported the effectiveness of Chinese herbal medicines (CHMs) for the prevention and treatment of CRC. CHMs may be able to effectively reduce the risk of CRC, alleviate the adverse reactions caused by chemotherapy, and prolong the survival time of patients with advanced CRC. Studies of molecular mechanisms have provided deeper insight into the roles of molecules from CHMs in treating CRC. This paper summarizes the current understanding of the use of CHMs for the prevention and treatment of CRC, the main molecular mechanisms involved in these processes, the role of CHMs in modulating chemotherapy-induced adverse reactions, and CHM's potential role in epigenetic regulation of CRC. The current study provides beneficial information on the use of CHMs for the prevention and treatment of CRC in the clinic, and suggests novel directions for new drug discovery against CRC.

Establishment of an early warning score model in children with hand-foot-mouth disease / 中华实用儿科临床杂志

Objective:To construct an early warning score model for the identification of hand-foot-mouth disease (HFMD) in children using the decision tree, and to provide scientific evidence for early recognition of critical HFMD in clinical practice.Methods:The medical records of 2 488 children with severe and critical HFMD hospi-talized in Qingdao Women and Children′s Hospital from January 2014 to December 2016 were retrospectively analyzed.Multivariate Logistic regression analysis was made to screen the independent risk factors of critical HFMD.An early warning score model for identifying children with HFMD was established by using the chi- square automatic interactive detection method in the decision tree, and the effectiveness of the model was evaluated by the receiver operating characteristic curve (ROC). Results:The multivariate Logistic regression analysis identified 5 independent risk factors of critical HFMD, including age<3 years old, blood sugar≥8.0 mmol/L, body temperature≥39.0 ℃, limb shaking and trembling, and hand-foot herpes.Two risk factors, i.e., blood sugar and body temperature, were included in the tree chart through the decision tree, and scoring criteria were established according to the tree chart.Combining the early warning scoring system for children, the warning model were finally set up, which consisted of 5 dimensions and inclu-ded 9 evaluation indicators: consciousness, skin color, heart rate, capillary refill time, respiratory frequency, participation of respiratory muscles, oxygen therapy, blood sugar and body temperature.Each dimension ranged from 0 to 3 points, totaling 0-15 points.The area under the ROC, sensitivity, specificity, maximum Youden index, and cut-off value of the model were 0.911, 0.910, 0.774, 0.684, and 6.5, respectively. Conclusions:The early warning score model established in this paper can accurately identify critical HFMD, with high sensitivity and specificity.

Prognostic value of PD-L1 expression level in metastatic renal cell carcinoma / 中华泌尿外科杂志

Objective:To explore the prognostic value of PD-L1 expression level in patients with metastatic renal cell carcinoma (mRCC).Methods:The clinicopathological and survival data of patients with mRCC in our hospital from Jan 2014 to Apr 2016 were retrospectively analyzed including 46 males and 15 females. The median age of these patients was 56 years(range: 29-75 years), with 41 patients ≤60 years and 20 patients >60 years. The baseline data before the systemic therapy showed 36 patients(59.0%)had 1 metastatic organ and 25 patients (41.0%) had equal or more than 2 organs to be metastasized. Among them, 17 patients(27.9%)had lung metastasis and 54 patients(88.5%)had liver metastasis. Abnormal baseline LDH occurred in 4 patients and 52 patients had normal LDH. Favorite and intermediate risk patients categorized by MSKCC risk stratification accounted for 59.6%(34 patients)and 40.4%(23 patients), respectively. Six patients(9.8%)experienced distant metastasis at initial diagnosis, with 4 of them undergoing primary site resection, and the other 55 patients undergoing radical nephrectomy. PD-L1 expression was detected by the immunohistochemical staining method. PD-L1 staining rate ≥1% detected on the tumor cell membrane was defined as positive expression. The correlation between PD-L1 expression and clinicopathological characteristics were compared. Kaplan-Meier method and log-rank test were used to compare the differences about DFS and OS under different factors. Cox proportional hazards regression model is used for multivariable analysis of survival data.Results:The detailed pathological types of the 61 patients with renal cell carcinoma were classified as 53 clear cell carcinomas, 3 papillary carcinomas, 1 collecting duct carcinoma, 2 translocation renal cell carcinomas and 2 being unclassified. There were 4, 20, 19 and 9 patients categorized as WHO/ISUP nuclear grade 1, 2, 3 and 4, and 26, 12, 20 and 2 patients were categorized as T 1, T 2, T 3 and T 4 stage, respectively. Five patients had regional lymph node metastasis(N+), and the other 56 patients had no regional lymph node metastasis(N-). The numbers of patients categorized as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ diseases according to TNM staging system were 20, 11, 21 and 8, respectively. The total PD-L1 positive rate was 24.6%(15/61). The corresponding PD-L1 expression rate of patients with WHO/ISUP nuclear grade 1-4 were 0(0 patient), 5.0%(1 patient), 31.6%(6 patients)and 44.4%(4 patients), respectively; With the increasing WHO/ISUP nuclear grade, the positive rate of PD-L1 gradually escalated with a linear correlation ( P=0.006). The PD-L1 expression of the normal and abnormal LDH group were 19.2%(10 patients)and 75.0%(3 patients), respectively, with significant difference( P=0.035). Univariate analysis of disease-free survival time(DFS)showed that the prognostic factors include PD-L1( P=0.045), age group( P=0.014), WHO/ISUP nuclear grade( P<0.001), T stage( P=0.015), N stage( P=0.026)and TNM stage( P=0.005). However multivariate analysis only suggested WHO/ISUP nuclear grade as the independent prognostic factors for DFS( HR=1.8, 95% CI 1.1-2.9, P=0.018). Either in univariate or multivariate analysis, PD-L1 was not a prognostic factor for overall survival (OS)of mRCC patients(univariate analysis: P=0.154; multivariate analysis: P=0.902). The independent prognostic factors of OS include WHO/ISUP nuclear grade( HR=3.0, 95% CI 1.1-8.0, P=0.033)and MSKCC risk stratification( HR=5.9, 95% CI 1.2-29.7, P=0.03). Conclusions:This study showed that the higher the WHO/ISUP nuclear grade of patients with mRCC, the higher the positive rate of PD-L1. PD-L1 expression was not the independent prognostic factor for DFS or OS of mRCC.