Single-Cell RNA Sequencing Shows T-Cell Exhaustion Landscape in the Peripheral Blood of Patients with Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure

Background/Aims@#The occurrence and development of hepatitis B virus-associated acute-onchronic liver failure (HBV-ACLF) is closely related to the immune pathway. We explored the heterogeneity of peripheral blood T cell subsets and the characteristics of exhausted T lymphocytes, in an attempt to identify potential therapeutic target molecules for immune dysfunction in ACLF patients. @*Methods@#A total of 83,577 T cells from HBV-ACLF patients and healthy controls were screened for heterogeneity by single-cell RNA sequencing. In addition, exhausted T-lymphocyte subsets were screened to analyze their gene expression profiles, and their developmental trajectories were investigated. Subsequently, the expression of exhausted T cells and their capacity in secreting cytokines (interleukin 2, interferon γ, and tumor necrosis factor α) were validated by flow cytometry. @*Results@#A total of eight stable clusters were identified, among which CD4 + TIGIT + subset and CD8 + LAG-3 + subset, with high expression of exhaust genes, were significantly higher in the HBV-ACLF patients than in normal controls. As shown by pseudotime analysis, T cells experienced a transition from naïve T cells to effector T cells and then exhausted T cells. Flow cytometry confirmed that the CD4 + TIGIT + subset and CD8 + LAG-3 + subset in the peripheral blood of the ACLF patients were significantly higher than those in the healthy controls. Moreover, in vitro cultured CD8 + LAG-3 + T cells were significantly fewer capable of secreting cytokines than CD8 + LAG-3- subset. @*Conclusions@#Peripheral blood T cells are heterogeneous in HBV-ACLF. The exhausted T cells markedly increase during the pathogenesis of ACLF, suggesting that T-cell exhaustion is involved in the immune dysfunction of HBV-ACLF patients.

Epidemic characteristics and trend of brucellosis in China from 2004 to 2018 / 中华地方病学杂志

Objective:To analyze the epidemic characteristics of brucellosis in China from 2004 to 2018, in order to understand the development trend of brucellosis.Methods:The surveillance data of brucellosis in China from 2004 to 2018 were collected from National Public Health Science Data Center. Joinpoint regression was used to analyze the trend of brucellosis incidence in China and various provinces. Overall trends were estimated by the average annual percentage change (AAPC). Seasonal and trend decomposition using loess (STL) was used to analyze the seasonal characteristics of brucellosis in China and various provinces. The age-related thermodynamic diagram of incidence rate was used to analyze the characteristics of age-onset changes.Results:From 2004 to 2018, a total of 524 980 brucellosis cases and 16 deaths were reported nationwide, with a incidence rate of 2.61/100 000 and a case fatality rate of (3.05 × 10 -3)%. The incidence of brucellosis in China was on the rise (AAPC = 11.58%, 95% CI: 7.91% - 15.25%, P < 0.001). There was no significant trend of change in Inner Mongolia Autonomous Region, Shanxi and Shaanxi provinces ( P > 0.05). Tibet Autonomous Region showed a downward trend (AAPC = - 55.19%, P < 0.001). All other provinces were showing an upward trend (AAPC > 0, P < 0.05). The peak incidence in China occurred from April to June. In terms of provinces, the peak incidence in Hainan, Sichuan, Guizhou, Fujian and Anhui provinces occurred from April to August, the peak incidence in Chongqing and Shanghai cities occurred from June to August, and the peak incidence in other provinces was generally from April to June. There were reports of brucellosis cases in all age groups nationwide, and the age distribution showed an inverted "V" shape. The peak incidence occurred in the 50 - 54 years old (5.43/100 000), followed by the 60 - 64 years old (4.94/100 000). From 2004 to 2018, the top 3 age groups of incidence rate changed from 40 - 44, 50 - 54 and 35 - 39 years old in 2004 to 50 - 54, 60 - 64 and 55 - 59 years old in 2018. Conclusions:The incidence of brucellosis is on the rise nationwide and in most provinces from 2004 to 2018. The high incidence age is gradually changing to the elderly population.

Myocardial specific overexpression of Sirt1 inhibits recovery of cardiac function in mice with myocardial ischemia / 中国药理学通报

Aim To investigate the effect of overexpression of silent information regulator 1 (Sirtl) on cardiac function in mice with myocardial ischemia. Methods Myocardial specific Sirtl overexpression transgenic mice (Sirtl-Tg) and littermate control mice (C57BL/6J), half male and half female, were randomly divided into control sham operation group (Con), control model group (Con +ISO), Sirtl overexpression sham operation group (Sirtl-Tg) and Sirtl overexpression model group (Sirtl-Tg + ISO). Isoproterenol (ISO) was injected subcutaneously into the back of the neck at 100 mg • kg

Clinical characteristics of elderly-onset gouty arthritis and risk factors for tophi / 中华内分泌代谢杂志

Objective:To analyze the clinical characteristics of elderly-onset gouty arthritis and risk factors of tophi.Methods:A total of 1 239 gout patients were retrospective selected in the outpatient department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from 2016 to 2022. According to age of onset, they were divided into the young and middle-aged group(aged<60) consisted of 826 cases, and the elderly group(aged≥60) consisted of 413 cases. Compare the clinical characteristics of elderly with Young and Middle-aged patients.Results:The systolic blood pressure, fasting blood glucose, creatinine, regular exercise, comorbidities, and tophi in the elderly group was higher than that in the middle-aged and young group. The proportion of diastolic blood pressure, serum triglycerides, eGFR, serum uric acid, alcohol consumption rate, and family history of gout was lower than that of young and middle-aged group( P<0.05); In the elderly-onset group, the initial site of arthritis was commonly observed in the first metatarsophalangeal joint. The proportion of the first attack with the upper limb joint was higher in old age group than in young and middle age group( P<0.05). Renal underexcretion type was the main subtype in the elderly group, and the proportion of overproduction type was higher than that of the young and middle-aged group( P<0.05). The logistic regression analysis showed that age, urea nitrogen, disease duration≥10 years and family history of gout were risk factors for tophi in elderly patients( P<0.05). Conclusion:The elderly-onset gout has unique clinical characteristics, characterized by a higher prevalence of tophi, a higher rate of complications. An initial site of arthritis commonly observed in the first metatarsophalangeal joint and the predominant type of uric acid excretion is renal excretion impairment. Early diagnosis and treatment, control of blood uric acid levels, smoking cessation and alcohol, regular exercise should be applied to prevent or delay the formation of tophi.

Clinical characteristics and risk factors for primary gout patients with multiple subcutaneous tophi / 中华内分泌代谢杂志

Objective:To investigate the clinical characteristics and risk factors of multiple tophi among gout patients.Methods:Gout patients treated at Affiliated Hospital of Qingdao University from September 2017 to September 2021 were included retrospectively. According to the number of tophi, the patients were divided into the multiple tophi group, the single tophi group and the non-tophi group. Clinical data were collected, biochemical indices and urine pH value were determined. One- way ANOVA or Chi-square test was used to compare groups, and multivariate logistic regression was used to analyze the risk factors. Results:The age, disease course, blood pressure, serum uric acid, urea nitrogen, and the rate of family history, smoking, drinking, gout attacks≥2 twice per year, hypertension, cardio-cerebrovascular diseases, kidney stones in the multiple tophi group were significantly higher than those in the single tophi group and the non-tophi group. The glomerular filtration rate, urine pH value and the rate of regular exercise were significantly lower than those of single tophi group and non-tophi group. In the multiple tophi group, 245 cases(44.46%) were involved in the interphalangeal joint or metacarpophalangeal joint, 212 cases(38.47%) were involved in other joints of the upper limb, which was second only to the first metatarsophalangeal joint(349 cases, 63.33%). Logistic regression analysis showed that the course of disease, urea nitrogen, serum uric acid, positive family history, drinking, gout attacks ≥twice per year and hypertension were the risk factors for multiple tophi in gout patients. Conclusion:Patients with a long disease course, elevated uric acid, high urea nitrogen, positive family history, alcohol consumption, frequent gout flare and hypertension are more likely to develop multiple tophi.

Effect of acupuncture exercise therapy synchronizing isokinetic muscle strength training for postoperative rehabilitation of meniscectomy under arthroscopy / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture exercise therapy synchronizing isokinetic muscle strength training on the motor function, stability and proprioception of knee joint, as well as the anxiety emotion in patients after meniscectomy under arthroscopy.@*METHODS@#A total of 70 patients after meniscectomy under arthroscopy were randomized into an observation group (35 cases, 2 cases were eliminated， 2 cases dropped off) and a control group (35 cases, 2 cases were eliminated, 1 case dropped off). Acupuncture was applied at Chize (LU 5), Neixiyan (EX-LE 4), Dubi (ST 35),Yanglingquan (GB 34), etc. on the affective side in the two groups. After 30 min, the needles of the knee joint area were withdrew, while the needle at elbow was continuously retained, the observation group was given acupuncture exercise therapy synchronizing isokinetic muscle strength training, and the control group was given conventional acupuncture exercise therapy. The treatment was given once a day, 7-day treatment was taken as one course, and totally 4 courses were required in the two groups. Before and after treatment, the knee joint Lysholm score, the knee joint isokinetic muscle strength flexion/extension ratio (H/Q), joint position sense measurement (JPS) and Hamilton anxiety scale (HAMA) score were compared in the two groups.@*RESULTS@#After treatment, the knee joint Lysholm scores and H/Q were increased compared with those before treatment in the two groups (P<0.001), and the knee joint Lysholm score and H/Q in the observation group were higher than those in the control group (P<0.001); the JPS and HAMA scores were decreased compared with those before treatment in the two groups (P<0.001), the JPS and HAMA score in the observation group were lower than those in the control group (P<0.05).@*CONCLUSION@#Acupuncture exercise therapy synchronizing isokinetic muscle strength training can effectively improve the motor function, stability and proprioception of knee joint, as well as the anxiety emotion in patients after meniscectomy under arthroscopy.

Development of needle-thread integrative embedding needle / 中国针灸

The needle-thread integrative embedding needle consists of needle handle, needle core, thread, locker and needle guard. The thread is fixed in the core by the locker. With the needle inserted into acupoint, the locker is separated from the thread, while the thread is embedded directly into acupoint, to achieve one acupoint with one needle. This type of thread embedding needle is operated simply and safely without cross infection occurrence, easy to carry.

Preparation, properties and antibacterial applications of medical nano-metals and their oxides: a review / 生物工程学报

Antibiotics are playing an increasingly important role in clinical antibacterial applications. However, their abuse has also brought toxic and side effects, drug-resistant pathogens, decreased immunity and other problems. New antibacterial schemes in clinic are urgently needed. In recent years, nano-metals and their oxides have attracted wide attention due to their broad-spectrum antibacterial activity. Nano-silver, nano-copper, nano-zinc and their oxides are gradually applied in biomedical field. In this study, the classification and basic properties of nano-metallic materials such as conductivity, superplasticity, catalysis, and antibacterial activities were firstly introduced. Secondly, the common preparation techniques, including physical, chemical and biological methods, were summarized. Subsequently, four main antibacterial mechanisms, such as cell membrane, oxidative stress, DNA destruction and cell respiration reduction, were summarized. Finally, the effect of size, shape, concentration and surface chemical characteristics of nano-metals and their oxides on antibacterial effectiveness and the research status of biological safety such as cytotoxicity, genotoxicity and reproductive toxicity were reviewed. At present, although nano-metals and their oxides have been applied in medical antibacterial, cancer treatment and other clinical fields, some issues such as the development of green preparation technology, the understanding of antibacterial mechanism, the improvement of biosafety, and the expansion of application fields, require further exploration.

Comparison of the effects of combined model and single model in HFRS incidence fitting and prediction / 公共卫生与预防医学

Objective To compare the prediction effect of combined model and single model in HFRS incidence fitting and prediction, and to provide a reference for optimizing HFRS prediction model. Methods The province with the highest incidence in China (Heilongjiang Province) in recent years was selected as the research site. The monthly incidence data of HFRS in Heilongjiang Province from 2004 to 2017 were collected. The data from 2004 to 2016 was used as training data, and the data from January to December 2017 was used as test data. The training data was used to train SARIMA , ETS and NNAR models, respectively. The reciprocal variance method and particle swarm optimization algorithm (PSO) were used to calculate the model coefficients of SARIMA, ETS and NNAR, respectively, to construct combined model A and combined model B. The established models were used to predict the incidence of HFRS from January to December 2017. The fitted and predicted values of the five models were compared with the training data and test data, respectively. Mean Absolute Percentage Error (MAPE), Mean Absolute Error (MAE), Root Mean Standard Deviation (RMSE), and Mean Error Rate (MER) were used to evaluate the model fitting and prediction effects. Results The optimal SARIMA model was SARIMA(1,0,2)(2,1,1)12. The optimal ETS model was ETS(M, N, M), and the smoothing parameter =0.738，=1*10. The optimal NNAR model was NNAR(13,1,7)12. The residuals of the three single models were white noise (P>0.05). The expression of combined model A was ŷ=0.134*ySARIMA+0.162*yETS+0.704*yNNAR; the expression of combined model B was ŷ=0.246*ySARIMA+0.435*yETS+0.319*yNNAR. The MAPE, MAE, RMSE, and MER fitted by SARIMA, ETS, NNAR, combined model A and combined model B were 24.10%, 0.11, 0.17, 23.29%; 17.14%, 0.08, 0.14, 17.96%; 6.33%, 0.02, 0.03, 4.25%; 9.03%, 0.03, 0.05, 7.51%; 13.16%, 0.06, 0.09, 12.33%, respectively. The MAPE, MAE, RMSE, and MER predicted by the five models were 18.70%, 0.05, 0.06, 19.62%; 23.83%, 0.06, 0.07, 24.49%; 28.30%, 0.07, 0.10, 29.21%; 21.69%, 0.06, 0.08, 22.63%; 17.39%, 0.05, 0.07, 18.76%, respectively. Conclusion The fitting and prediction effects of the combined models are better than the single models. The combined model based on PSO to calculate the weight of the single model is the optimal model.

Correlation analysis between family function and disease benefit in patients with chronic obstructive pulmonary disease / 中国实用护理杂志

Objective:To investigate and analyze the correlation between family function and disease benefit perception among patients with chronic obstructive pulmonary disease (COPD).Methods:A cross-sectional study, convenient sampling method, family function Assessment Scale (APGAR) and disease benefit scale were used to investigate the family function assessment and disease benefit of 172 COPD patients in the respiratory department of Yinchuan First People ′s Hospital from January to April 2021. Results:The total score of family function in COPD patients was (7.74 ± 2.50) points, and the total score of disease benefit was (53.24 ± 7.03) points. There was a positive correlation between family function and disease benefit in COPD patients ( r values were 0.041-0.275, P<0.05). Conclusions:The disease benefit of COPD patients was closely related to family function, and improving the level of family function support can improve the disease benefit of COPD patients.

Construction of a prediction model for lung cancer combined with chronic obstructive pulmonary disease by combining CT imaging features with clinical features and evaluation of its efficacy / 中华放射学杂志

Objective:To assess the effectiveness of a model created using clinical features and preoperative chest CT imaging features in predicting the chronic obstructive pulmonary disease (COPD) among patients diagnosed with lung cancer.Methods:A retrospective analysis was conducted on clinical (age, gender, smoking history, smoking index, etc.) and imaging (lesion size, location, density, lobulation sign, etc.) data from 444 lung cancer patients confirmed by pathology at the Second Affiliated Hospital of Naval Medical University between June 2014 and March 2021. These patients were randomly divided into a training set (310 patients) and an internal test set (134 patients) using a 7∶3 ratio through the random function in Python. Based on the results of pulmonary function tests, the patients were further categorized into two groups: lung cancer combined with COPD and lung cancer non-COPD. Initially, univariate analysis was performed to identify statistically significant differences in clinical characteristics between the two groups. The variables showing significance were then included in the logistic regression analysis to determine the independent factors predicting lung cancer combined with COPD, thereby constructing the clinical model. The image features underwent a filtering process using the minimum absolute value convergence and selection operator. The reliability of these features was assessed through leave-P groups-out cross-validation repeated five times. Subsequently, a radiological model was developed. Finally, a combined model was established by combining the radiological signature with the clinical features. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were plotted to evaluate the predictive capability and clinical applicability of the model. The area under the curve (AUC) for each model in predicting lung cancer combined with COPD was compared using the DeLong test.Results:In the training set, there were 182 cases in the lung cancer combined with COPD group and 128 cases in the lung cancer non-COPD group. The combined model demonstrated an AUC of 0.89 for predicting lung cancer combined with COPD, while the clinical model achieved an AUC of 0.82 and the radiological model had an AUC of 0.85. In the test set, there were 78 cases in the lung cancer combined with COPD group and 56 cases in the lung cancer non-COPD group. The combined model yielded an AUC of 0.85 for predicting lung cancer combined with COPD, compared to 0.77 for the clinical model and 0.83 for the radiological model. The difference in AUC between the radiological model and the clinical model was not statistically significant ( Z=1.40, P=0.163). However, there were statistically significant differences in the AUC values between the combined model and the clinical model ( Z=-4.01, P=0.010), as well as between the combined model and the radiological model ( Z=-2.57, P<0.001). DCA showed the maximum net benifit of the combined model. Conclusion:The developed synthetic diagnostic combined model, incorporating both radiological signature and clinical features, demonstrates the ability to predict COPD in patients with lung cancer.

Evaluation of peripheral blood T-lymphocyte subpopulations features in patients with hepatitis B virus-related acute-on-chronic liver failure based on single-cell sequencing technology / 中华肝脏病杂志

Objective: T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Methods: Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Results: Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets (P = 0.007) and CD8(+)LAG3(+) (P = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. Conclusion: There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.

Epidemiological overview and periodic trends of hemorrhagic fever with renal syndrome in Jingzhou City, Hubei Province from 1962 to 2020 / 中华地方病学杂志

Objective:To analyze the epidemic characteristics and periodicity of hemorrhagic fever with renal syndrome (HFRS) in Jingzhou City, Hubei Province, and provide a basis for scientific prevention and control of HFRS in Jingzhou City.Methods:Retrospective analysis was used to collect HFRS case data and population data of Jingzhou City and 8 counties (cities, districts) within its jurisdiction, including Shashi District, Jingzhou District, Gongan County, Jianli City, Jiangling County, Shishou City, Honghu City, and Songzi City from 1962 to 2020, from the Archives of the Jingzhou Center for Disease Control and Prevention and the Infectious Disease Report Information Management System of the China Disease Control and Prevention Information System; and the epidemic characteristics of HFRS was analyzed in Jingzhou City and 8 counties (cities, districts) within its jurisdiction. The periodicity of HFRS onset was determined using wavelet analysis.Results:From 1962 to 2020, 18 936 HFRS cases were reported in Jingzhou City, with an average incidence rate of 5.95/100 000. There were a total of three epidemic peaks, namely from 1972 to 1973 (24.82/100 000, 24.84/100 000), 1983 (60.08/100 000), and 1995 (14.57/100 000). According to different regions, the high incidence areas of HFRS showed a phased transfer trend: from the 1960s to the 1970s, the Jiangbei area (Honghu City, Jianli City) was the highest incidence area; in the 1980s and 1990s, the high incidence areas were transferred to Jiangnan area (Songzi City, Shishou City, and Gongan County); after 2005, high incidence areas were relocated to Jiangbei area (Honghu City, Jianli City, Jiangling County). The wavelet analysis results showed that there were 12.30 and 21.77 years of HFRS epidemic cycles in Jingzhou City before 2000 ( P < 0.05); among them, the periodicity of Shashi District, Gongan County, Jiangling County, Shishou City, and Honghu City was relatively consistent with that of Jingzhou City, with epidemic cycles of about 12 or 22 years ( P < 0.05). Conclusions:Jingzhou City is currently at the peak of a 22-year epidemic cycle of HFRS, with Jiangbei area as the high incidence areas. The 12-year epidemic cycle in Jingzhou City has ended after 2000.

The investigation of vaccination in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To investigate the prevalence of influenza, pneumococcal, hepatitis B virus (HBV), human papillomavirus (HPV), and varicella zoster virus (VZV) vaccination in patients with systemic lupus erythematosus (SLE), and to analyze the factors related to vaccination.Methods:Data were obtained from 1 203 patients with SLE, via a multi-center web-based survey using an online questionnaire. Data about their social conditions, clinical presentations, willingness for being vaccinated, vaccination within 5 years were collected. Demographic data were shown by descriptive analysis. Chi-square and logistic regression analysis were used to assess the power of related indexes as predictors of vaccination.Results:The vaccination rates of influenza, pneumococcal, HBV, HPV, and VZV were 5.49% (66/1 203), 0.66% (8/1 203), 2.08% (25/1 203), 3.82% (46/1 203), and 0.17% (2/1 203), respectively. Data analysis showed that higher education ( χ2=30.94, P<0.001) and higher income ( χ2=10.70, P=0.001) had greater effects on influenza vaccination. There was a relationship between HPV vaccination and higher education ( χ2=20.96, P<0.001), higher income ( χ2=20.56, P<0.001), younger age ( χ2=8.54, P=0.001), and single ( χ2=5.63, P=0.018). Male ( χ2=10.27, P=0.001) and higher education ( χ2=4.52, P=0.034) were associated with HBV vaccination. The multivariate logistic regression analysis revealed that higher education [ OR (95% CI)=2.14 (1.10, 4.18), P=0.026], having children under 18 years-old [ OR(95% CI)=1.802(1.02, 3.18), P=0.042], and hydroxychloroquine usage [ OR(95% CI)=2.55(1.06, 6.15), P=0.037], had a positive correlation with influenza vaccination. Male [ OR(95% CI)=4.24(1.37, 13.08), P=0.012], had an impact on HBV vaccination. The factors related to HPV vaccination included age <45 [ OR (95% CI)=0.93(0.89, 0.97), P=0.001], higher education [ OR(95% CI)=2.28(1.11, 4.65), P=0.024], higher income [ OR(95% CI)=2.68(1.32, 3.41), P=0.006] and the usage of immunosuppressive agents [ OR(95% CI)=1.92(1.03, 3.59), P=0.041]. Conclusion:The prevalence of vaccination in patients with SLE is low. Patients with higher education and income are more likely to being vaccinated.

Application of TBATS in the prediction of mumps incidence / 公共卫生与预防医学

Objective To explore the applicability of the TBATS in predicting the incidence of mumps. Methods The incidence of mumps of Jiangxi Province from 2004 to 2017 was used as the demonstration data. The incidence of mumps in Jiangxi Province from July to December 2017 was used as test data. The training data from January 2004 to June 2017 were used to train the TBATS and the SARIMA, and predict the value from July to December 2017. The fitted and predicted values were compared with the test data. The MAPE, RMSE, MAE and MER were used to evaluate model fitting and prediction effects. Results SARIMA (1,0,0)(1,1,0)12 with drift was the optimal SARIMA. The MAPE, MAE, RMSE and MER fitted by the TBATS and the SARIMA were 15.06%, 0.21, 0.29, 13.57% and 21.93%, 0.29, 0.41, 18.73%, respectively. The MAPE, MAE, RMSE and MER predicted by the TBATS and the SARIMA were 7.95%, 0.08, 0.11, 7.12% and 15.33%, 0.17, 0.18, 14.93%. Conclusion The TBATS has high accuracy in predicting the incidence of mumps and is worthy of popularization and application.

Effect of Astragali Radix-Curcumae Rhizoma compatibility combined with 5-fluorouracil on Th17/Treg balance and tumor-related mRNA and protein expression in orthotopic xenograft model mice of CT26.WT colorectal carcinoma / 中国中药杂志

Astragali Radix-Curcumae Rhizoma(AR-CR) is a combination commonly used in the clinical treatment of tumors. Based on the T helper 17(Th17)/regulatory T cell(Treg) balance, the present study explored the possible mechanism of AR-CR combined with 5-fluorouracil(5-FU) on the tumor growth of orthotopic xenograft model mice of colorectal carcinoma. Ninety male BALB/c mice were randomly divided into nine groups, i.e., a blank group, a model group, a 5-FU group, high-, medium-, and low-dose AR-CR(2∶1) groups, and high-, medium-, and low-dose AR-CR+5-FU groups, with 10 mice in each group. The orthotopic xenograft model of CT26.WT colorectal carcinoma was induced in mice except those in the blank group. Twenty-four hours after the ope-ration, mice in the blank group and the model group received normal saline by gavage(10 mL·kg~(-1), once per day), and those in the 5-FU group received 5-FU by intraperitoneal injection(25 mg·kg~(-1), once every other day). Mice in the AR-CR groups received AR and CR decoctions by gavage(12, 6, and 3 g·kg~(-1), once a day) and those in the combination groups received AR and CR decoctions and 5-FU(doses and administration methods were the same as above). After intervention for three weeks, all mice were sacrificed and tumor tissues were collected. The tumor mass was weighed and the average tumor weight was calculated. The changing trend of Th17/Treg(%) in the CD4~+T lymphocytes of the spleen tissues of the mice in each group was detected. The mRNA expression in the blood and protein expression in the tumor tissues of transforming growth factor-β(TGF-β), tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), Smad4, N-cadherin, matrix metalloproteinase-7(MMP-7) were detected. The experimental results revealed that compared with the model group, the groups with drug intervention showed reduced tumor mass(P<0.01), decreased CD4~+IL-17~+ in the spleen tissues to varying degrees(P<0.001), and increased proportion of CD4~+Foxp3~+(P<0.001 or P<0.05), indicating that Th17/Treg maintained dynamic balance, and the effect of the combination groups was predominant. Additionally, the mRNA expression in the blood and protein expression in the tumor tissues of TGF-β, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 declined to varying degrees in a dose-dependent manner(P<0.01 or P<0.001). The AR-CR combined with 5-FU can inhibit the tumor growth of orthotopic xenograft model mice of CT26.WT colorectal carcinoma. The mechanism may be related to maintenance of Th17/Treg dynamic balance in the body and down-regulation of TGF-β, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 expression.

Anti-colorectal cancer mechanism of Astragali Radix-Curcumae Rhizoma-Paridis Rhizoma based on network pharmacology and experimental verification / 中国中药杂志

The present study explored the underlying mechanism of Astragali Radix-Curcumae Rhizoma-Paridis Rhizoma(AR-CR-PR) in the treatment of colorectal cancer(CRC) by network pharmacology and molecular docking and animal tests and verified the core targets based on the orthotopic transplantation model in nude mice. The active components of AR-CR-PR were retrieved from databases such as TCMSP. The targets of drugs and the disease were obtained from PubChem, SwissTargetPrediction, TTD, and DrugBank, and the intersection targets were imported into STRING for the analysis of the protein-protein interaction(PPI). Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses were performed through DAVID. AutoDock Vina was used to perform molecular docking and binding ability prediction between the active components and the core targets. The effects of AR-CR-PR on tumor growth, metastasis, and phosphorylation of core target proteins in tumor tissues based on the orthotopic transplantation model in nude mice. As revealed by network pharmacology, AR-CR-PR contained nine core components, such as quercetin, curcumin, and β-ecdysone, and the key targets included protein kinase B(AKT1), mitogen-activated protein kinase 3(MAPK3), MAPK1, and epithelial growth factor receptor(EGFR), which was indicated that the anti-CRC effect of AR-CR-PR was presumedly achieved by regulating tumor cell proliferation, apoptosis, migration, and angiogenesis through PI3 K-AKT, MAPK and other signaling pathways. The results of molecular docking showed that the nine core components had strong binding abilities to AKT1 and MAPK3. The results in vivo showed that AR-CR-PR could reduce the volume of the orthotopic tumor, inhibit liver metastasis, and decrease the phosphorylation of AKT1 and MAPK3 in the CRC model. The mechanism of AR-CR-PR in the intervention of CRC may be related to the activation of PI3 K-AKT and MAPK signaling pathway. This study provides a scientific basis for the clinical application of AR-CR-PR in the treatment of CRC and ideas for modern research on AR-CR-PR.

Validation of the Pollard' s classification criteria (2010) for rheumatoid arthritis patients with fibromyalgia / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the sensitivity and specificity of Pollard' s classification criteria(2010) for the diagnosis of rheumatoid arthritis (RA) patients withfibromyalgia (FM) in Chinese patients, and to assess the clinical features and psychological status of RA-FM patients in a real-world observational setting.@*METHODS@#Two hundred and two patients with rheumatoid arthritis were enrolled from the outpatients in Rheumatology and Immunology Department in Peking University People' s Hospital. All the patients were evaluated whether incorporating fibromyalgia translation occured using the 1990 American College of Rheumatolgy (ACR)-FM classification criteria. Forty two RA patients were concomitant with FM, while the other one hundred and sixty RA patients without FM were set as the control group.@*RESULTS@#There was no significant difference in general demography between the two groups (P>0.05). In this study, the Pollard' s classification criteria (2010) for RA-FM in Chinese patients had a high sensitivity of 95.2% and relatively low specificity of 52.6%. Compared with those patients without FM, RA patients with FM (RA-FM patients) had higher Disease Activity Scale in 28 joints (DAS-28) score (5.95 vs. 4.38, P=0.011) and much more 28-tender joint counts (TJC) (16.5 vs.4.5, P < 0.001).RA-FM patients had worse Health Assessment Questionnaire (HAQ) score (1.24 vs. 0.66, P < 0.001) and lower SF-36 (28.63 vs. 58.22, P < 0.001). Fatigue was more common in RA-FM patients (88. 1% vs. 50.6%, P < 0.001) and the degree of fatigue was significantly increased in RA-FM patients (fatigue VAS 5.55 vs. 3.55, P < 0.001). RA-FM patients also had higher anxiety (10 vs.4, P < 0.001) and depression scores (12 vs.6, P < 0.001). erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), morning stiffness time and 28-swollen joint counts (SJC) showed no difference between these two groups.@*CONCLUSION@#The Pollard' s classification criteria (2010) for RA-FM are feasible in Chinese rheumatoid arthritis patients. The Pollard' s classification criteria is highly sensitive in clinical application, while the relativelylow specificity indicates that various factors need to be considered in combination. RA patients with FM result in higher disease activity, worse function aland psychological status. RA patients with FM also have poorer quality of life. DAS-28 scores may be overestimated in RA patients with FM. In a RA patient thatdoes not reach remission, the possibility of fibromyalgia should be con-sidered.

The relationship between homocysteine, coagulation dysfunction and breast cancer risk / 中华肿瘤杂志

Objective: To investigate the correlation of homocysteine (HCY) and coagulation function index with the risk of breast cancer and its clinicopathological characteristics. Methods: The HCY, coagulation function test index, and clinicopathological information of female breast cancer patients (333 cases) treated in Tianjin Medical University Cancer Hospital from January 2018 to December 2018 were collected, and female patients with benign breast (225 cases) were selected during the same period for the control group. The t-test was used to compare measurement data with normal distribution, D-Dimer data were distributed discreetly and described by median, non-parametric Mann-Whitney U test was used to compare the two groups. The chi-square test was used to compare enumeration data, and the Logistic regression analysis was used for the risk analysis. Results: The levels of HCY, fibrinogen (Fbg), protein C (PC), and median D-Dimer (D-D) in peripheral blood of breast cancer patients group [(13.26±5.24) μmol/L, (2.61±0.83) g/L, (117.55±19.67)%, and 269.68 ng/ml, respectively] were higher than those in the control group [(11.58±0.69) μmol/L, (2.49±0.49) g/L, (113.42±19.82)% and 246.98 ng/ml, respectively, P<0.05]. The prothrombin time (PT), PT(INR), α2-antiplasmin (α2-AP) levels [(10.19±0.63) s, 0.91±0.07 and (110.64±13.93)%, respectively] were lower than those in the control group [(10.58±0.65) s, 0.93±0.01 and (123.81±14.77) %, P<0.05]. The serum levels of PC and median D-D in premenopausal breast cancer patients [(112.57±17.86)% and 242.01 ng/ml, respectively] were higher than those in the control group [(105.31±22.31)% and 214.75 ng/ml, respectively, P<0.05]. The levels of PT(INR), α2-AP [0.91±0.07 and (111.29±12.54)%, respectively] were lower than those of the control group[0.98±0.15 and (120.17±16.35)%, respectively, P<0.05]. The levels of HCY and median D-D in postmenopausal breast cancer patients [(14.25±5.76) μmol/L and 347.53 ng/ml, respectively] were higher than those in the control group [(11.67±2.38) μmol/L and 328.28 ng/ml, P<0.05]. The levels of PT, PT(INR), antithrombin Ⅲ (AT-Ⅲ), α2-AP levels [(10.18±0.66) s, 0.87±0.09, (97.30±12.84)% and (110.13±14.96)%] were lower than those in the control group [(10.38±0.61) s, 0.90±0.08, (102.89±9.12)%, and (127.05±12.38)%, respectively, P<0.05]. The levels of α2-AP and median D-D in T2-4 stage breast cancer patients [(111.69±14.41)% and 289.25 ng/ml, respectively] were higher than those in Tis-1 stage patients [(108.05±12.37)% and 253.49 ng/ml, respectively, P<0.05]. The levels of PT, PT (INR), Fbg, AT-Ⅲ, α2-AP, median D-D [(10.62±0.63) s, 0.95±0.06, (3.04±1.52) g/L, (103.21±9.45)%, (118.72±14.77)% and 331.33 ng/ml, respectively] in breast cancer patients with lymph node metastasis were higher than those of patients without lymph node metastasis [(10.42±0.58) s, 0.93±0.06, (2.52±0.54) g/L, (95.20±13.63)%, (106.91±13.13)% and 263.38 ng/ml, respectively, P<0.05]. In non-menopausal breast cancer patients, the level of HCY [(12.63±4.41) μmol/L] in patients with T2-4 stage was higher than that of patients with Tis-1 stage [(10.70±3.49) μmol/L, P=0.010], and the level of thrombin time [(19.35±0.90) s] of patients with T2-4 stage was lower than that of patients with Tis-1 stage [(19.79±1.23) s, P=0.015]. The levels of PT(INR), Fbg, AT-Ⅲ, α2-AP [0.97±0.56, (3.37±2.34) g/L, (102.38±8.77)% and (120.95±14.06)%] in patients with lymph node metastasis were higher than those of patients without lymph node metastasis [0.94±0.05, (2.36±0.48) g/L, (94.56±14.37)% and (109.51±11.46)%, respectively, P<0.05]. Among postmenopausal breast cancer patients, the levels of AT-Ⅲ and α2-AP in T2-4 stage patients [(98.48±11.80)% and (111.84±15.35)%, respectively] were higher than those in patients with the Tis-1 stage [(94.12±14.98)% and (105.49±12.89)%, respectively, P<0.05]. The levels of AT-Ⅲ and α2-AP in N1-3 stage patients [(103.74±9.94)% and (117.29±15.23)%] were higher than those in N0 stage patients [(95.75±13.01)% and (108.39±14.42)%, P<0.05]. Conclusions: HCY and abnormal coagulation function are related to the risk of breast cancer, T stage and lymph node metastasis in breast cancer patients.

Structurally defined tandem-responsive nanoassemblies composed of dipeptide-based photosensitive derivatives and hypoxia-activated camptothecin prodrugs against primary and metastatic breast tumors

Substantial progress in the use of chemo-photodynamic nano-drug delivery systems (nano-DDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise nanostructures, however, has limited the therapeutic efficacy of the prepared nano-DDS to date. Here, we report a structurally defined tandem-responsive chemo-photosensitive co-nanoassembly to eliminate primary breast tumor and prevent lung metastasis. This both-in-one co-nanoassembly is prepared by assembling a biocompatible photosensitive derivative (pheophorbide-diphenylalanine peptide, PPA-DA) with a hypoxia-activated camptothecin (CPT) prodrug [(4-nitrophenyl) formate camptothecin, N-CPT]. According to computational simulations, the co-assembly nanostructure is not the classical core-shell type, but consists of many small microphase regions. Upon exposure to a 660 nm laser, PPA-DA induce high levels of ROS production to effectively achieve the apoptosis of normoxic cancer cells. Subsequently, the hypoxia-activated N-CPT and CPT spatially penetrate deep into the hypoxic region of the tumor and suppress hypoxia-induced tumor metastasis. Benefiting from the rational design of the chemo-photodynamic both-in-one nano-DDS, these nanomedicines exhibit a promising potential in the inhibition of difficult-to-treat breast tumor metastasis in patients with breast cancer.