Research progress on bone metabolism and molecular mechanisms in accelerated aging SAMP6 mice / 中国药理学通报

Senile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. The pathogenesis of SOP is complex and not well understood. Currently, the rapid aging model mouse, senescence accelerated mouse prone 6 (SAMP6), is an ideal model for studying the mechanisms of SOP development and exploring its prevention and treatment. This model exhibits characteristics including increased bone fragility, degradation of bone microstructure, loss of bone matrix, and abnormal metabolism and dysfunction of bone cells, faithfully replicating the process of SOP occurrence and progression at both macroscopic and microscopic levels.

Effect of Plasmacytoid Dendritic Cell Dose in Grafts on CMV Infection after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation between plasmacytoid dendritic cell (pDC) dose in grafts and the occurrence of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 80 children who received allo-HSCT in Children's Hospital of Soochow University from August 20, 2020 to June 11, 2021 were retrospectively analyzed. Proportions of DC subsets and T-cell subsets in grafts were detected by flow cytometry in order to calculate infused cell dose of each cell. Weekly monitoring of CMV-DNA copies in peripheral blood for each child were performed after transplantation. The last follow-up date was December 31, 2021.@*RESULTS@#All the children gained hematopoietic reconstitution. CMV infection was observed in 51 children (63.8%±5.4%) within the first 100 days after transplantation, including 2 cases developing CMV disease. Univariate analysis indicated that infused doses of DC and pDC were significantly associated with CMV infection within 100 days after allo-HSCT (P <0.05). Multivariate analysis indicated that a high dose infusion of pDC was an independent protective factor for CMV infection within 100 days after allo-HSCT (P <0.05). By the end of follow-up, 7 children died of transplantation-related complications, including 2 deaths from CMV disease, 2 deaths from extensive chronic graft-versus-host disease, and 3 deaths from capillary leak syndrome. The overall survival rate was 91.2%.@*CONCLUSION@#The pDC in grafts may be associated with early infection of CMV after allo-HSCT, while a high infused pDC dose may serve as a protective factor for CMV infection after transplantation.

Association between Serum Uric Acid to HDL-Cholesterol Ratio and Nonalcoholic Fatty Liver Disease Risk among Chinese Adults / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this case-control study was to explore the association between serum uric acid to high density lipoprotein cholesterol ratio (UHR) and the risk of nonalcoholic fatty liver disease (NAFLD) in Chinese adults.@*METHODS@#A total of 636 patients with NAFLD and 754 controls were enrolled from the Affiliated Hospital of Qingdao University, China, between January and December 2016. All patients completed a comprehensive questionnaire survey and underwent abdominal ultrasound examination and a blood test. NAFLD was diagnosed using ultrasonography after other etiologies were excluded. Logistic regression and restricted cubic spline model were conducted to evaluate the relationship of UHR with NAFLD risk.@*RESULTS@#The multivariable adjusted odds ratio (95% confidence interval, CI) for NAFLD in the highest versus lowest quartile of UHR was 3.888 (2.324-6.504). In analyses stratified by sex and age, we observed significant and positive associations between UHR and the risk of NAFLD in each subgroup. In analyses stratified by body mass index (BMI), a significant and positive association was found only in individuals with a BMI of ≥ 24 kg/m2. Our dose-response analysis indicated a linear positive correlation between UHR and the risk of NAFLD.@*CONCLUSION@#UHR is positively associated with the risk of NAFLD and may serve as an innovative and noninvasive marker for identifying individuals at risk of NAFLD.

Perceived exercise benefits and barriers and their association with physical activity time in Chinese Han children and adolescents aged 9 to 18 years / 中华流行病学杂志

Objective: To analyze the perceived exercise benefits and barriers and their association with physical activity time in Chinese Han children and adolescents aged 9-18 years. Methods: Data were extracted from the 2019 Chinese National Survey on Students' Constitution and Health and a total of 163 656 children and adolescents aged 9-18 years in Han ethnic group were included in the analysis. Mann-Whitney U test and Kruskal-Wallis test were used to compare the perceived exercise benefits score, perceived exercise barriers score and perceived exercise benefits to barriers ratio in the children and adolescents with different demographic characteristics and physical activity time. The differences in physical activity time in subgroups were compared with χ2 tests. log-binomial regression model was used to evaluate the association between physical activity time and perceived exercise benefits and barriers. Results: The M (Q1,Q3) of the perceived exercise benefits score, perceived exercise barriers score, and perceived exercise benefits to barriers ratio in the children and adolescents were 4.11 (3.78, 4.78), 2.70 (2.10, 3.20) and 1.55 (1.22, 2.07), respectively. Children and adolescents living in urban area, boys, those at younger age and those with physical activity time ≥1 hour had higher perceived exercise benefits score and perceived exercise benefits to barriers ratio, but lower perceived exercise barriers score (all P<0.001). The prevalence of physical activity time ≥1 hour was 41.4% in the children and adolescents. In the log-binomial model with two variables of perceived exercise benefits score and perceived exercise barriers score, for each 1-point increase in the perceived exercise benefits, the possibility of physical activity time ≥1 hour increased by 11% (OR=1.11, 95%CI: 1.10-1.12), and for each 1-point increase in the perceived exercise barriers, the possibility of physical activity time ≥1 hour decreased by 15% (OR=0.85, 95%CI: 0.84-0.85). In the log-binomial model with variable of perceived exercise benefits to barriers ratio, for each 1-point increase in the perceived exercise benefits to barriers ratio, the possibility of physical activity time ≥1 hour increased by 12% (OR=1.12, 95%CI: 1.11-1.12). Conclusion: The perceived exercise benefits and barriers are significantly associated with physical activity time in children and adolescents in China.

Trend of the detection rate of myopia among Chinese Han children and adolescents aged 7-18 years from 2010 to 2019 / 中华预防医学杂志

Objective: To analyze the trend of the detection rate of myopia among Chinese Han children and adolescents aged 7-18 years from 2010 to 2019. Methods: Data from the Chinese National Survey on Students' Constitution and Health in 2010, 2014 and 2019 were used, and about 213 833, 212 742 and 209 942 Han students aged 7-18 years were included in this study. The χ² test was used to compare the differences in the prevalence of myopia among the subgroups in the survey year, and logistic regression was used to compare the differences in the prevalence of myopia between different years. A curve-fitting method was used to obtain the growth rate of myopia among Han Chinese students from 2010 to 2019, and the differences in the change of myopia between different age groups were analyzed. Results: In 2019, the overall detection rate of myopia among Chinese Han children and adolescents aged 7-18 was 60.1%. The detection rate of urban students (62.7%) was higher than that of rural students (57.4%) and the detection rate of girls (63.5%) was higher than that of boys (56.7%). In 2019, the regional disparities were large in the detection rate of myopia in various provinces, with the lowest in Guizhou (49.6%) and the highest in Zhejiang (71.3%). The detection rate of myopia showed an upward trend from 2010 to 2019, from 55.5% in 2010 to 57.1% in 2014, and finally to 60.1% in 2019. The gap in the detection rate of myopia between urban and rural children and adolescents gradually shrank. The average annual growth rate of myopia detection rate from 2014 to 2019 was 0.6 percentage points per year, higher than that from 2010 to 2014 about 0.4 percentage points per year. The peak age of the growth rate of myopia detection rate decreased from 12 years in 2010 to 10 years in 2014, and finally to 7 years in 2019. Conclusions: The detection rate of myopia among Chinese Han children and adolescents is still at a high level, and the peak age of the growth rate of myopia detection rate continues to advance.

Long-term trend of the age of spermarche and its association with nutritional status among Chinese Han boys aged 11-18 from 2010 to 2019 / 中华预防医学杂志

Objective: To analyze the long-term trend of the age of spermarche among Chinese Han boys aged 11 to 18 from 2010 to 2019 and its association with nutritional status. Methods: The data from Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019 were used. The age, residence and spermarche of the participants were collected by questionnaire, and their height and weight were measured. A total of 184 633 Han boys aged 11‒18 years with complete data on spermarche, height, and weight were included in this study. The probability regression method was used to calculate the median age (95%CI) at spermarche in different areas, and the trend of age at spermarche in different groups was compared. The multivariate logistic regression model was used to analyze the association between nutritional status and spermarche of Chinese Han boys aged 11‒18 years. Results: The median age of spermarche (95%CI) was 13.85 (13.45-14.22) years old among Chinese Han boys aged 11‒18 years in 2019, with 0.18 years earlier than that in 2010. The median age at spermarche in urban and rural boys was 13.89 and 13.81 years, respectively. Compared with that in 2010, the age at spermarche in urban and rural boys was 0.08 and 0.27 years earlier, respectively. After adjusting for age, province and urban/rural areas, compared with normal weight, spermarche was negatively associated with wasting and positively associated with overweight and obesity, with OR (95%CI) about 0.73 (0.67-0.80), 1.09 (1.02-1.17) and 1.09 (1.01-1.18), respectively. Conclusion: The age of spermarche generally shows an advanced trend among Chinese Han boys and is associated with nutritional status.

Trends of age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019 / 中华预防医学杂志

Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were-0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and-0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were-0.071 years and 0.006 years, respectively, while those in rural areas were-0.082 years and-0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were-0.064, -0.099, -0.091, -0.080, -0.096 and-0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and-0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.

The Psychosomatic Traits of "People with the Five Elements in Traditional Chinese Medicine": A Qualitative Study / 生物医学与环境科学（英文）

OBJECTIVE@#To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of "people with the five elements in traditional Chinese medicine (TCM)."@*METHODS@#Data collected from the literature review, two sessions of brainstorming of experts with related experience in "people with the five elements in TCM" from October 2020 to December 2020, and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed. Triangulation was used in this study, and theming and synthesizing were used to analyze the data.@*RESULTS@#A total of 31 experts and 30 interviewees participated in this study. The median age of the experts and interviewees were 48.0 and 38.5 years, respectively; 51.66% and 54.8% of experts and interviewees, respectively, were men. The descriptors of facial diagrams of "people with the five elements in TCM" were complexion, shape, distribution state of facial bones, convergence trend of facial muscles, and facial expression. A theoretical model of "people with the five elements in TCM" was shaped based on these findings.@*CONCLUSION@#The study suggests a possibility for bridging the gap between personality and bodily state, identifying an avenue for personality research from the perspective of TCM.

Impaired cognitive map in transgenic animals relevant to Alzheimer's disease: from neurons to network / 生理学报

Alzheimer's disease (AD) is a typical cognitive disorder with an increasing incidence in recent years. AD is also one of the main causes of disability and death of the elderly in current aging society. One of the most common symptoms of AD is spatial memory impairment, which occurs in more than 60% of patients. This memory loss is closely related to the impairment of cognitive maps in the brain. The entorhinal grid cells and the hippocampal place cells are important cellular basis for spatial memory and navigation functions in the brain. Understanding the abnormal firing pattern of these neurons and their impaired coordination to neural oscillations in transgenic rodents is crucial for identifying the therapeutic targets for AD. In this article, we review recent studies on neural activity based on transgenic rodent models of AD, with a focus on the changes in the firing characteristics of neurons and the abnormal electroencephalogram (EEG) rhythm in the entorhinal cortex and hippocampus. We also discuss potential cell-network mechanism of spatial memory disorders caused by AD, so as to provide a scientific basis for the diagnosis and treatment of AD in the future.

Exploring the application value of the modified Delphi method in the development process of acupuncture and moxibustion guideline recommendations based on the WFAS Clinical Practice Guideline for Female Urinary Incontinence / 中国针灸

Taking the recommendations development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) standard Clinical Practice Guideline for Female Urinary Incontinence as an example, this study analyzed the consensus expert composition, specific consensus process, and results in the development of the guideline's recommendations. It systematically examined the advantages of using the modified Delphi method in the formation of recommendations for acupuncture and moxibustion clinical practice guideline, with the aim of providing reference for the development of acupuncture and moxibustion guidelines in the same field.

Effect of Shao's five-needle therapy pretreatment on airway inflammatory response in asthmatic rats based on ROS/TXNIP/NLRP3 pathway / 中国针灸

OBJECTIVES@#To explore the possible mechanism of Shao's five-needle therapy pretreatment on relieving airway inflammatory response in asthmatic rats.@*METHODS@#Forty SPF-grade SD rats were randomly divided into a blank group, a model group, an acupuncture group, and a medication group, with 10 rats in each group. Except the blank group, asthma model was established by aerosol inhalation of ovalbumin in the other 3 groups. The rats in the acupuncture group were treated with acupuncture at "Dazhui" (GV 14) and bilateral "Feishu" (BL 13) and "Fengmen" (BL 12), with each session lasting for 20 min. Acupuncture was given before each motivating, once daily for 7 consecutive days. The rats in the medication group were treated with intraperitoneal injection of dexamethasone sodium phosphate solution before each motivating, once daily for 7 days. General situation of the rats was observed in each group; ELISA method was used to detect the levels of inflammatory cytokines interleukin (IL)-1β and IL-18 in serum; immunofluorescence staining method was performed to assess the expression of reactive oxygen species (ROS) in lung tissues; Western blot method was used to measure the protein expression of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in lung tissues.@*RESULTS@#The rats in the blank group exhibited normal behavior, while those in the model group showed signs of respiratory distress, ear scratching, cheek rubbing, and dysphoria. Compared with the model group, the rats in the acupuncture group and the medication group showed stable respiration and relatively agile responses. Compared with those in the blank group, the serum levels of IL-18 and IL-1β were elevated (P<0.01), the expression intensity of ROS was increased, and the protein expressions of TXNIP, NLRP3, ASC and Caspase-1 in lung tissues were increased (P<0.01) in the model group. Compared with those in the model group, the serum levels of IL-18 and IL-1β were reduced (P<0.01), the expression intensity of ROS was lowered, and the protein expressions of TXNIP, NLRP3, ASC and Caspase-1 in lung tissues were reduced (P<0.01) in the acupuncture group and the medication group. Compared with the medication group, the protein expression of ASC in lung tissue was reduced in the acupuncture group (P<0.05).@*CONCLUSIONS@#Pretreatment of Shao's five-needle therapy could alleviate airway inflammatory response in asthmatic rats by reducing ROS levels and decreasing the aggregation and activation of pathway-related proteins in the ROS/TXNIP/NLRP3 pathway, ultimately leading to decreased secretion of IL-1β and IL-18. This mechanism may contribute to the effectiveness of Shao's five-needle therapy in preventing and treating asthma.

Influencing Factors and Prediction Model of Performance of Needle Visualization in Fine Needle Aspiration of Thyroid Nodules / 中国医学科学院学报

Objective To investigate the influencing factors and establish a model predicting the performance of needle visualization in fine-needle aspiration (FNA) of thyroid nodules. Methods This study prospectively included 175 patients who underwent FNA of thyroid nodules in the Department of Ultrasound in China-Japan Friendship Hospital and compared the display of the needle tips in the examination of 199 thyroid nodules before and after the application of needle visualization.We recorded the location,the positional relationship with thyroid capsule,ultrasonic characteristics,and the distribution of the soft tissue strip structure at the puncture site of the nodules with unclear needle tips display before using needle visualization.Furthermore,according to the thyroid imaging reporting and data system proposed by the American College of Radiology,we graded the risk of the nodules.Lasso-Logistic regression was employed to screen out the factors influencing the performance of needle visualization and establish a nomogram for prediction. Results The needle tips were not clearly displayed in the examination of 135 (67.8%) and 53 (26.6%) nodules before and after the application of needle visualization,respectively,which showed a significant difference (P<0.001).Based on the positional relationship between the nodule and capsule,anteroposterior/transverse diameter (A/T) ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site,a nomogram was established to predict the probability of unclear display of the needle tips after application of needle visualization.The C-index of the prediction model was 0.75 (95%CI=0.67-0.84) and the area under the receiver operating characteristic curve was 0.72.The calibration curve confirmed the appreciable reliability of the prediction model,with the C-index of 0.70 in internal validation. Conclusions Needle visualization can improve the display of the needle tip in ultrasound-guided FNA of thyroid nodules.The nomogram established based on ultrasound features such as the positional relationship between the nodule and capsule,A/T ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site can predict whether needle visualization is suitable for the examination of nodules.

Nomogram-Based Prediction of Risk of Cervical Lymph Node Metastasis in Differentiated Thyroid Carcinoma / 中国医学科学院学报

Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group (n=444) and a validation group (n=125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P<0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95%CI=0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

Application of meridian and acupoint diagnosis of three yin meridians of foot in the treatment for gynecological diseases with acupuncture and moxibustion / 中国针灸

With three representative types of gynecological diseases (dysmenorrhea, pelvic inflammation, polycystic ovary syndrome) as examples, the application methods of meridian and acupoint diagnosis for gynecological diseases treated with acupuncture and moxibustion are discussed. During clinical diagnosis and treatment, it is recommended to examine the patient's leg segment along the three yin meridians of foot, aiming to explore the positive reactions of the meridians and acupoints (color, shape, skin temperature, sensory abnormalities, etc.). Acupuncture and moxibustion treatment at this positive reaction place can improve the clinical efficacy. Meridian and acupoint diagnosis could provide basis for meridian syndrome differentiation, thus guiding the selection of acupoint prescriptions; it is also helpful to clarify the deficiency, excess, cold and heat of the disease nature, thus guiding the selection of acupuncture and moxibustion methods. In addition, it is an auxiliary method to estimate the prognosis and outcome of the disease.

Recent Research Progress on CircRNA in Hematological Malignancies--Review / 中国实验血液学杂志

Most hematological tumors have high-grade malignancy and low cure rate, requiring new molecular markers for detection and evaluation. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed-loop structures, which participate in gene transcription and translation by binding to microRNAs and proteins. In recent years, with the deepening research on circRNAs, circRNAs have been found to play an important role in hematological malignancies. In this review, the latest research progress on the function and molecular mechanism of circRNAs in hematological malignancies was systematically summarized, and it was found that circRNAs may be potential new biomarkers and therapeutic targets in hematological malignancies.

Trend of age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019 / 中华预防医学杂志

Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were -0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and -0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were -0.071 years and 0.006 years, respectively, while those in rural areas were -0.082 years and -0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were -0.064, -0.099, -0.091, -0.080, -0.096 and -0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and -0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.

Infiltration and significance of M1 macrophage in breast cancer: an analysis of METABRIC database and clinical validation / 中华肿瘤杂志

Objective: To investigate the differences of immune microenvironment between stage T1N3 and stage T3N0 breast cancer patients and explore the relationship between M1 macrophage infiltration and lymph node metastasis in breast cancer. Methods: Clinical information and RNA-sequencing (RNA-Seq) expression data of stage T1N3 (n=9) and stage T3N0 (n=11) breast cancer patients were extracted from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Using CIBERSORT, the proportions of 22 types of immune cells were calculated, and then the differences of immune cell infiltration between stage T1N3 and T3N0 patients were compared. From 2011 to 2022, pathologic specimens were collected from breast cancer patients who underwent curative resection at the Cancer Hospital, Chinese Academy of Medical Sciences, including 77 at stage T1N3 and 58 at stage T3N0.The METABRIC database analysis results were verified by examining the density of M1 macrophages in tissues using dual-staining immunohistochemistry. Results: METABRIC data analysis showed M1 macrophage was the highest proportion, 15.85% in stage T1N3 breast cancer; M2 macrophage was the highest proportion, 13.07% in stage T3N0 breast cancer.M1 macrophage proportions were statistically different between patients with stage T1N3 and stage T3N0 (P=0.010). The dual-staining immunohistochemistry analysis of breast cancer tissues showed M1 macrophage density (median) of 62.0 and 38.0 cells/mm(2) for stage T1N3 and T3N0, respectively. The difference was statistically significant (P=0.002). Conclusion: The density of M1 macrophages is notably higher in stage T1N3 patients and is associated with lymph node metastasis.

Preliminary study of PPARA regulate the ferroptosis of hepatocellular carcinoma to prevent disease deterioration / 中华预防医学杂志

To explore whether PPARA is involved in the process of ferroptosis in hepatoma cells, peroxisome proliferator activated receptor (PPARA) was comprehensively analyzed in hepatocellular carcinoma (HCC) through public database and experimental data, including the expression, the functions and the potential roles of tumor progression. The research design is experimental research,data analysis based on bioinformatics and cell experiment. From January 2022 to August 2022, relevant cell experiments were conducted in the Basic Medical Laboratory of the General Hospital of the Southern Theatre of the Chinese People's Liberation Army. The expression and the correlation with clinicopathologic features of PPARA in HCC were analyzed by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. To study the protein expression of PPARA in HCC and normal tissues through the Human Protein Atlas (HPA). The protein-protein interaction (PPI) network between PPARA and the core factor of ferroptosis was constructed based on Search Tool for the Retrival of Interacting Genes/Protein (STRING) database, then, the correlation between PPARA and the core gene Glutamate-cysteine Ligase Catalytic Subunit (GCLC) was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). Assessed the expression of PPARA in HCC cell lines SK-HEP-1, SMMC-7721, MHCC-97H, BEL-7402 and normal liver cell L02 by Western Blot (WB) and the changes of PPARA expression after 48h treatment with ferroptosis inducer Erastin were observed. Single factor analysis of variance was used to compare the expression of PPARA between groups in GEPIA database. The expression of PPARA in GSE25097 and GSE112790 data was compared by rank sum test. Survival analysis was performed using time series test method. The difference of PPARA expression between clinical and pathological features was compared using the Kruskal-Wallis test. The correlation between the expression of GCLC and PPARA was compared by the method of Spearman correlation. The expression of PPARA in cell lines was compared by paired T test. The results showed that the RNA and protein expression of PPARA in HCC was lower than that in normal tissues (P<0.05). PPARA alterations were correlated with patient clinicopathological features and prognosis (P<0.05). The PPI constructed by STRING database suggests that PPARA interact with the key factors of ferroptosis, such as NFE2 like bZIP transcription factor 2 (NFE2L2), Heme Oxygenase 1 (HMOX1), Tumor Protein P53 (TP53), GCLC, Dipeptidyl Peptidase 4 (DPP4), Citrate Synthase (CS), Arachidonate 15-Lipoxygenase (ALOX15) and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4). Furthermore, the PPARA was significantly associated with GCLC validated via GEPIA database(R=0.6, P<0.05). The expression of PPARA increased after treatment with ferroptosis inducer Erastin for 48 h by WB. In conclusion, the expression of PPARA is lower in HCC with a poor prognosis. PPARA interacts with GCLC in regulating ferroptosis in HCC.

Systemic lupus erythematosus associated macrophage activation syndrome with neuropsychiatric symptoms: A report of 2 cases / 北京大学学报(医学版)

Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.

Related factors of endogenous erythropoietin and its association with 10-year risks of cardiovascular disease in a community-based Chinese study / 北京大学学报(医学版)

OBJECTIVE@#To investigate the associated factors of endogenous erythropoietin (EPO) and its association with 10-year risks of atherosclerotic cardiovascular disease in a Chinese community-based general population.@*METHODS@#The participants of this study were from an atherosclerosis cohort survey which was established by the Department of Cardiology, Peking University First Hospital in 2011. The cohort survey was performed in the Gucheng and Pingguoyuan communities of Shijingshan district in Beijing, China. The inclusion criteria of this study were: (1) endogenous EPO was measured; (2) health questionnaire data and other clinical data were complete; (3) participatants who had cardiovascular or cerebrovascular diseases (defined as self-reported coronary heart disease, stroke or transient ischemic attack) or anemia or estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m2) at baseline were excluded. Multivariate linear regression model was used to examine the associated factors of endogenous EPO. The participants were grouped into low (< 5%), moderate (5%-10%) and high risk (≥10%) groups, based on predicted 10-year cardiovascular disease risk using the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) equations.@*RESULTS@#A total of 4 013 participants were included. Mean age of them was (55.9±8.2) years, 62.2% (n=2 496) of them were female, and 46.3% (n=1 859), 70.9% (n=2 845), 21.9% (n=879) had hypertension, dyslipidemia and diabetes, individually. The average body mass index was (26.1±3.3) kg/m2. The median of EPO level was 12.8 (9.3-17.4) IU/L and 25.1% (n=998) were at high 10-years risk of cardiovascular disease. Hemoglobin (β=-0.05, 95%CI: -0.07 to -0.04) and eGFR ≥90 mL/(min·1.73 m2) (β=-0.05, 95%CI: -0.07 to -0.04) were associated with lower in transformed EPO levels while hypertension (β=0.08, 95%CI: 0.05 to 0.12) and obesity (β=0.14, 95%CI: 0.09 to 0.18) were associated with higher in transformed EPO levels in multivariate linear regression analyses. Ten-year cardiovascular disease risks were positively associated with in transformed EPO levels (β=0.07, 95%CI: 0.05 to 0.09). The participants at moderate and high cardiovascular disease risks had significant higher EPO levels than the low risk group (all P < 0.05).@*CONCLUSION@#In community-based Beijing populations, endogenous EPO was associated with hemoglobin, renal function, obesity and hypertension. Individuals at high 10-years cardiovascular disease risks have higher endogenous EPO levels. Endogenous EPO may be a potential risk marker of cardiovascular disease.