Objective To identify the role of RNA-editing enzyme ADAR1 (adenosine deaminase acting on RNA) in EV71 infection and virus mutation.Methods RNAi technology was applied to establish ADAR1 knock-down stable cell lines.Then the cells were served to evaluate the role of ADAR1 in EV71 infection by MTT assay for detecting virus-induced cell viability,virus plaque assay for quantification of the virus titer and the cellular susceptibility to the virus,and Western blot for virus protein expressions.ADAR1-mediated RNA editing can result in the genetic A-G and T-C mutations.To further determine whether the effects of ADAR1 on EV71 infection were correlated with ADAR1-mediated EV71 RNA editing and therefore increased the viral mutations during the infection,the characteristics of EV71 mutation were analyzed based on the different full-length viral genomes from epidemic regions.The viral genome was also sequenced from the infected ADAR1 knock-down cells.Results After ADAR1 knock-down,the cell viability decreased quickly after the virus infection,and formed much more and larger sizes of plaques than the control cells.The virus capsid protein VP1 expressions and virus titer in the cells culture media were both increased in ADAR1 knockdown cells.Statistic analysis showed that A-G and T-C mutations were the major mutations of EV71,which were believed to be the hot sites for RNA-editing.However,the results of viral RNA genomic sequencing data indicated that ADAR1 did not edit EV71 genome directly.Conclusions ADAR1 was a restriction factor for controlling EV71.However,ADAR1 does not directly edit EV71 genome.

Objective To investigate the status of exercise autonomy of chronic obstructive pulmonary disease (COPD) patients at stationary phase in community and to analyze the influencing factors of exercise autonomy so as to guide the external hospital control of COPD. Methods Totals of 124 COPD patients at stationary phase from three target communities in the area of the First Affiliated Hospital of Zhengzhou University were investigated by the method of convenience sampling. We analyzed the status of exercise among them. Non-conditional Logistic stepwise regression was used to determine the influencing factors of exercise autonomy. Results A total of 122 valid questionaires were collected. Among 122 patient, 51 (41.80%) patients never carried out, 33 (27.05%) occasionally carried out and 38 (31.15%) persisted in respiratory function exercise. Besides, 44 (36.07%) patients never carried out, 36 (29.51%) occasionally carried out and 42 (34.43%) persisted in all-round exercise. There were 53 patients with the good exercise autonomy. The frequent hospitalization was the independent protective factor of patients' exercise autonomy (P＜ 0.05). Conclusions COPD patients at stationary phase in community have poor exercise autonomy. Patients with more frequent hospitalization tend to carry out exercise more actively.

Objective To analyze the hepatitis B virus infection with extreme reduction of cholinesterase(CHE)not caused by liver synthesis dysfunction,and to explore its clinical significance.Methods The clinical data of 2 rare cases hospitalized in the 3rd people's hospital of Kunming in July 2021 and February 2022,including liver function,coagulation function,hepatitis B markers,hepatitis B virus volume,and whole exon sequencing,were collected and analyzed,and literature was reviewed.Results CHE was extremely reduced in 2 patients with HBV infection,liver synthesis function was good,and whole exon sequencing showed the presence of butyrylcholinesterase(BCHE)gene mutation.Conclusion The extremely low CHE in this case is not due to liver function disorder.Exon sequencing detected mutations in the BCHE gene in two patients.Screening for BCHE mutations may be necessary in patients with extremely low cholinesterase levels not due to liver dysfunction.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Objective : To study the expression and clinical significance of Wnt signal secretory protein DKK1 in cervical cancer. Methods : Reverse transcription polymerase chain reaction (RT⁃PCR) was used to detect the expression of DKK1 mRNA in 30 pairs of cervical cancer tissues and adjacent normal tissues. The expression of DKK1 protein was detected by immunohistochemistry in 60 cases of cervical cancer and 30 cases of normal cervical tissue , and the relationship between the expression and clinicopathological characteristics of cervical cancer was analyzed. Results : The expression of DKK1 in cervical cancer tissues was lower than that in adjacent tissues and normal cervical tissues (P < 0. 05) . The expression of DKK1 was closely related to clinicopathological stage , tissue differentiation , lymph node metastasis and depth of invasion (P < 0. 05) . Conclusion The expression of DKK1 is low in cervical cancer and plays an important role in the occurrence and development of cervical cancer.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection with an extremely high mortality rate,and it is the main risk factor for acute lung injury(ALI).However,the pathophysiology and pathogenesis of sepsis-associated ALI are not fully understood,and effective drugs are extremely limited.Therefore,it is urgent that we explore the pathogenesis of sepsis-associated ALI and attempt to discover effective intervention measures to improve the prognosis of sepsis-associated ALI patients.In recent years,ferroptosis has been considered closely related to the pathological and physiological processes of sepsis-associated ALI,and inhibiting related cell ferroptosis can effectively slow down the occurrence and development of the disease.In this paper,therapeutic strategies targeting ferroptosis in related cells are reviewed to provide a reference for future research on ferroptosis in sepsis-associated ALI and provide a new perspective on potential treatments.

BACKGROUNDSelf-monitoring of blood glucose (SMBG) by individuals with type 2 diabetes (T2D) is crucial for long-term health, yet numerous cultural, economic and health factors can reduce SMBG. Most studies on SMBG adherence have come out of the US and Europe, and their relevance to Asia is unclear. The aims of the present study were to assess the current state of SMBG in China and analyze demographic and diabetes-related characteristics that may influence it.

METHODSIn this multi-center, cross-sectional study, 5 953 individuals with T2D from 50 medical centers in 29 provinces across China filled out a standardized questionnaire that requested information on demographic characteristics, education level, occupation, income, lifestyle risk factors, duration of diabetes, chronic complications, and frequency of SMBG. Respondents were also asked whether their glycosylated hemoglobin (HbA1c) had been checked in the past 6 months. The most recent values for fasting plasma glucose, 2-hour postprandial blood glucose and HbA1c were recovered from medical records.

RESULTSOnly 1 130 respondents (18.98%) performed SMBG with the recommended frequency, while 4 823 (81.02%) did not. In fact, nearly 2 105 (35.36%) reported never performing SMBG. In the subset of 3 661 individuals on insulin therapy, only 266 (7.27%) performed SMBG at least once a day, while 1 210 (33.05%) never performed it. In contrast, 895 of 2 292 individuals (39.05%) on diet/exercise therapy or oral hypoglycemic therapy never performed it. Multivariate Logistic regression identified several factors associated with SMBG adherence: female gender, higher education level, higher income, longer T2D duration and education about SMBG.

CONCLUSIONSSMBG adherence in our Chinese population with T2D was less frequent than that in developed countries. Several factors influence SMBG adherence: gender, education level, income, T2D duration, therapy regimen and exposure to education about SMBG.

Adult ; Blood Glucose ; metabolism ; Blood Glucose Self-Monitoring ; statistics & numerical data ; China ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; blood ; Female ; Humans ; Male ; Middle Aged

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal-luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in Eubacterium, which is a butyrate-producing genera of bacteria, and a significant increase in Devosia in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to Eubacterium and Devosia may serve as a promising biomarker for the early detection of CRC.

ObjectiveTo evaluate pharmacological effects of Shengmai injection（SMI）on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham group， a model group， a low-dose SMI group（3 mL·kg^-1）， a middle-dose SMI group（6 mL·kg^-1）， a high-dose SMI group（12 mL·kg^-1）， and a Ginaton group（4 mL·kg^-1）according to the random number table method， with 12 rats in each group. The rat model of cerebral ischemia-reperfusion（MCAO/R）was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion， which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores， cerebral infarction area， hematoxylin-eosin （HE） staining， Nissl staining， terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining， and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay （ELISA）， Western blot， and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation（OGD/R）-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly decreased density of Nissl bodies and neurons（P<0.01）. Compared with the model group， the SMI groups exhibited significantly decreased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly increased density of Nissl bodies and neurons （P<0.05）. The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury， and the chloride intracellular channel protein 1 （CLIC1） was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced， compared with those in the model group（P<0.05， P<0.01）， and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 （NLRP3） decreased （P<0.01）. In addition， the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate（P<0.01） and significantly decreased the intracellular chloride ion concentration（P<0.05）. ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.